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Sample records for acidosis

  1. Metabolic acidosis

    Acidosis - metabolic ... Metabolic acidosis occurs when the body produces too much acid. It can also occur when the kidneys are not ... the body. There are several types of metabolic acidosis. Diabetic acidosis develops when acidic substances, known as ...

  2. Metabolic acidosis.

    Lim, Salim

    2007-01-01

    Acute metabolic acidosis is frequently encountered in critically ill patients. Metabolic acidosis can occur as a result of either the accumulation of endogenous acids that consumes bicarbonate (high anion gap metabolic acidosis) or loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic or normal anion gap metabolic acidosis). The cause of high anion gap metabolic acidosis includes lactic acidosis, ketoacidosis, renal failure and intoxication with ethylene glycol, methanol, salicylate and less commonly with pyroglutamic acid (5-oxoproline), propylene glycole or djenkol bean (gjenkolism). The most common causes of hyperchloremic metabolic acidosis are gastrointestinal bicarbonate loss, renal tubular acidosis, drugs-induced hyperkalemia, early renal failure and administration of acids. The appropriate treatment of acute metabolic acidosis, in particular organic form of acidosis such as lactic acidosis, has been very controversial. The only effective treatment for organic acidosis is cessation of acid production via improvement of tissue oxygenation. Treatment of acute organic acidosis with sodium bicarbonate failed to reduce the morbidity and mortality despite improvement in acid-base parameters. Further studies are required to determine the optimal treatment strategies for acute metabolic acidosis.

  3. Proximal renal tubular acidosis

    Renal tubular acidosis - proximal; Type II RTA; RTA - proximal; Renal tubular acidosis type II ... are neutralized by alkaline substances, mainly bicarbonate. Proximal renal tubular acidosis (Type II RTA) occurs when bicarbonate ...

  4. Distal renal tubular acidosis

    ... get better with treatment. When to Contact a Medical Professional Call your health care provider if you have symptoms of distal renal tubular acidosis. Get medical help right away if you develop emergency symptoms ...

  5. Acidosis and Urinary Calcium Excretion

    Alexander, R Todd; Cordat, Emmanuelle; Chambrey, Régine

    2016-01-01

    Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone and inhibi...

  6. Drug-Induced Metabolic Acidosis.

    Pham, Amy Quynh Trang; Xu, Li Hao Richie; Moe, Orson W

    2015-01-01

    Metabolic acidosis could emerge from diseases disrupting acid-base equilibrium or from drugs that induce similar derangements. Occurrences are usually accompanied by comorbid conditions of drug-induced metabolic acidosis, and clinical outcomes may range from mild to fatal. It is imperative that clinicians not only are fully aware of the list of drugs that may lead to metabolic acidosis but also understand the underlying pathogenic mechanisms. In this review, we categorized drug-induced metabolic acidosis in terms of pathophysiological mechanisms, as well as individual drugs' characteristics.

  7. Lactic acidosis, hyperlactatemia and sepsis

    Andrea Montagnani

    2016-12-01

    Full Text Available Among hospitalized patients, lactic acidosis represents the most common cause of metabolic acidosis. Lactate is not just a metabolic product of anaerobic glycolysis but is triggered by a variety of metabolites even before the onset of anaerobic metabolism as part of an adaptive response to a hypermetabolic state. On the basis of such considerations, lactic acidosis is divided into two classes: inadequate tissue oxygenation (type A and absence of tissue hypoxia (type B. Lactic acidosis is characterized by non-specific symptoms but it should be suspected in all critical patients who show hypovolemic, hypoxic, in septic or cardiogenic shock or if in the presence of an unexplained high anion gap metabolic acidosis. Lactic acidosis in sepsis and septic shock has traditionally been explained as a result of tissue hypoxia when whole-body oxygen delivery fails to meet whole body oxygen requirements. In sepsis lactate levels correlate with increased mortality with a poor prognostic threshold of 4 mmol/L. In hemodynamically stable patients with sepsis, hyperlactatemia might be the result of impaired lactate clearance rather than overproduction. In critically ill patients the speed at which hyperlactatemia resolves with appropriate therapy may be considered a useful prognostic indicator. The measure of blood lactate should be performed within 3 h of presentation in acute care setting. The presence of lactic acidosis requires early identification of the primary cause of shock for the best appropriate treatment. Since most cases of lactic acidosis depend on whole-body oxygen delivery failure, the maximization of systemic oxygen delivery remains the primary therapeutic option. When initial resuscitation does not substantially or completely correct lactic acidosis, it is also essential to consider other causes. The treatment of acidosis with buffering agents (specifically bicarbonate is generally advocated only in the setting of severe acidosis. Ongoing

  8. Acidosis, hypoxia and bone.

    Arnett, Timothy R

    2010-11-01

    Bone homeostasis is profoundly affected by local pH and oxygen tension. It has long been recognised that the skeleton contains a large reserve of alkaline mineral (hydroxyapatite), which is ultimately available to neutralise metabolic H(+) if acid-base balance is not maintained within narrow limits. Bone cells are extremely sensitive to the direct effects of pH: acidosis inhibits mineral deposition by osteoblasts but it activates osteoclasts to resorb bone and other mineralised tissues. These reciprocal responses act to maximise the availability of OH(-) ions from hydroxyapatite in solution, where they can buffer excess H(+). The mechanisms by which bone cells sense small pH changes are likely to be complex, involving ion channels and receptors in the cell membrane, as well as direct intracellular effects. The importance of oxygen tension in the skeleton has also long been known. Recent work shows that hypoxia blocks the growth and differentiation of osteoblasts (and thus bone formation), whilst strongly stimulating osteoclast formation (and thus bone resorption). Surprisingly, the resorptive function of osteoclasts is unimpaired in hypoxia. In vivo, tissue hypoxia is usually accompanied by acidosis due to reduced vascular perfusion and increased glycolytic metabolism. Thus, disruption of the blood supply can engender a multiple negative impact on bone via the direct actions of reduced pO(2) and pH on bone cells. These observations may contribute to our understanding of the bone disturbances that occur in numerous settings, including ageing, inflammation, fractures, tumours, anaemias, kidney disease, diabetes, respiratory disease and smoking.

  9. Renal tubular acidosis type 4 in pregnancy.

    Jakes, Adam Daniel; Baynes, Kevin; Nelson-Piercy, Catherine

    2016-03-17

    We describe the clinical course of renal tubular acidosis (RTA) type 4 in pregnancy, which has not been previously published. Renal tubular acidosis type 4 is a condition associated with increased urinary ammonia secondary to hypoaldosteronism or pseudohypoaldosteronism. Pregnancy may worsen the hyperkalaemia and acidosis of renal tubular acidosis type 4, possibly through an antialdosterone effect. We advise regular monitoring of potassium and pH throughout pregnancy to ensure safe levels are maintained.

  10. Acidosis activates complement system in vitro

    Michael Emeis

    1998-01-01

    Full Text Available We investigated the in vitro effect of different form s of acidosis (pH 7.0 on the formation of anaphylatoxins C3a and C5a. Metabolic acidosis due to addition of hydrochloric acid (10 μ mol/ml blood or lactic acid (5.5 μ mol/ml to heparin blood (N=12 caused significant activation of C3a and C5a compared to control (both p=0.002. Respiratory acidosis activated C3a (p=0.007 and C5a (p=0.003 compared to normocapnic controls. Making blood samples with lactic acidosis hypocapnic resulted in a median pH of 7.37. In this respiratory compensated metabolic acidosis, C3a and C5a were not increased. These experiments show that acidosis itself and not lactate trigger for activation of complement components C3 and C5.

  11. Acidosis activates complement system in vitro.

    Emeis, M; Sonntag, J; Willam, C; Strauss, E; Walka, M M; Obladen, M

    1998-01-01

    We investigated the in vitro effect of different forms of acidosis (pH 7.0) on the formation of anaphylatoxins C3a and C5a. Metabolic acidosis due to addition of hydrochloric acid (10 micromol/ml blood) or lactic acid (5.5 micromol/ml) to heparin blood (N=12) caused significant activation of C3a and C5a compared to control (both p=0.002). Respiratory acidosis activated C3a (p=0.007) and C5a (p=0.003) compared to normocapnic controls. Making blood samples with lactic acidosis hypocapnic resulted in a median pH of 7.37. In this respiratory compensated metabolic acidosis, C3a and C5a were not increased. These experiments show that acidosis itself and not lactate trigger for activation of complement components C3 and C5. PMID:9927235

  12. Pharmacologically-induced metabolic acidosis: a review.

    Liamis, George; Milionis, Haralampos J; Elisaf, Moses

    2010-05-01

    Metabolic acidosis may occasionally develop in the course of treatment with drugs used in everyday clinical practice, as well as with the exposure to certain chemicals. Drug-induced metabolic acidosis, although usually mild, may well be life-threatening, as in cases of lactic acidosis complicating antiretroviral therapy or treatment with biguanides. Therefore, a detailed medical history, with special attention to the recent use of culprit medications, is essential in patients with acid-base derangements. Effective clinical management can be handled through awareness of the adverse effect of certain pharmaceutical compounds on the acid-base status. In this review, we evaluate relevant literature with regard to metabolic acidosis associated with specific drug treatment, and discuss the clinical setting and underlying pathophysiological mechanisms. These mechanisms involve renal inability to excrete the dietary H+ load (including types I and IV renal tubular acidoses), metabolic acidosis owing to increased H+ load (including lactic acidosis, ketoacidosis, ingestion of various substances, administration of hyperalimentation solutions and massive rhabdomyolysis) and metabolic acidosis due to HCO3- loss (including gastrointestinal loss and type II renal tubular acidosis). Determinations of arterial blood gases, the serum anion gap and, in some circumstances, the serum osmolar gap are helpful in delineating the pathogenesis of the acid-base disorder. In all cases of drug-related metabolic acidosis, discontinuation of the culprit medications and avoidance of readministration is advised.

  13. Dietary Acid Load and Metabolic Acidosis in Renal Transplant Recipients

    Berg, van den Else; Engberink, M.F.; Brink, E.J.; Baak, van M.A.; Joosten, M.M.; Gans, R.O.B.; Navis, G.; Bakker, S.J.L.

    2012-01-01

    Background and objectives Acidosis is prevalent among renal transplant recipients (RTRs) and adversely affects cardiometabolic processes. Factors contributing to acidosis are graft dysfunction and immunosuppressive drugs. Little is known about the potential influence of diet on acidosis in RTRs. Thi

  14. Chronic Metabolic Acidosis Destroys Pancreas

    Peter Melamed

    2014-11-01

    Full Text Available One primary reason for the current epidemic of digestive disorders might be chronic metabolic acidosis, which is extremely common in the modern population. Chronic metabolic acidosis primarily affects two alkaline digestive glands, the liver, and the pancreas, which produce alkaline bile and pancreatic juice with a large amount of bicarbonate. Even small acidic alterations in the bile and pancreatic juice pH can lead to serious biochemical/biomechanical changes. The pancreatic digestive enzymes require an alkaline milieu for proper function, and lowering the pH disables their activity. It can be the primary cause of indigestion. Acidification of the pancreatic juice decreases its antimicrobial activity, which can lead to intestinal dysbiosis. Lowering the pH of the pancreatic juice can cause premature activation of the proteases inside the pancreas with the potential development of pancreatitis.The acidification of bile causes precipitation of the bile acids, which irritate the entire biliary system and create bile stone formation. Aggressive mixture of the acidic bile and the pancreatic juice can cause erratic contractions of the duodenum’s walls and subsequent bile reflux into the stomach and the esophagus. Normal exocrine pancreatic function is the core of proper digestion. Currently, there is no effective and safe treatment for enhancing the exocrine pancreatic function. Restoring normal acid-base homeostasis can be a useful toolfor pathophysiological therapeutic approaches for various gastrointestinal disorders. There is strong research and practical evidence that restoring the HCO3 - capacity in the blood can improve digestion.

  15. Metabolic acidosis: pathophysiology, diagnosis and management.

    Kraut, Jeffrey A; Madias, Nicolaos E

    2010-05-01

    Metabolic acidosis is characterized by a primary reduction in serum bicarbonate (HCO(3)(-)) concentration, a secondary decrease in the arterial partial pressure of carbon dioxide (PaCO(2)) of approximately 1 mmHg for every 1 mmol/l fall in serum HCO(3)(-) concentration, and a reduction in blood pH. Acute forms (lasting minutes to several days) and chronic forms (lasting weeks to years) of the disorder can occur, for which the underlying cause/s and resulting adverse effects may differ. Acute forms of metabolic acidosis most frequently result from the overproduction of organic acids such as ketoacids or lactic acid; by contrast, chronic metabolic acidosis often reflects bicarbonate wasting and/or impaired renal acidification. The calculation of the serum anion gap, calculated as [Na(+)] - ([HCO(3)(-)] + [Cl(-)]), aids diagnosis by classifying the disorders into categories of normal (hyperchloremic) anion gap or elevated anion gap. These categories can overlap, however. Adverse effects of acute metabolic acidosis primarily include decreased cardiac output, arterial dilatation with hypotension, altered oxygen delivery, decreased ATP production, predisposition to arrhythmias, and impairment of the immune response. The main adverse effects of chronic metabolic acidosis are increased muscle degradation and abnormal bone metabolism. Using base to treat acute metabolic acidosis is controversial because of a lack of definitive benefit and because of potential complications. By contrast, the administration of base for the treatment of chronic metabolic acidosis is associated with improved cellular function and few complications.

  16. Acidosis inhibits mineralization in human osteoblasts.

    Takeuchi, Shoko; Hirukawa, Koji; Togari, Akifumi

    2013-09-01

    Osteoblasts and osteoclasts maintain bone volume. Acidosis affects the function of these cells including mineral metabolism. We examined the effect of acidosis on the expression of transcription factors and mineralization in human osteoblasts in vitro. Human osteoblasts (SaM-1 cells) derived from the ulnar periosteum were cultured with α-MEM containing 50 μg/ml ascorbic acid and 5 mM β-glycerophosphate (calcifying medium). Acidosis was induced by incubating the SaM-1 cells in 10 % CO₂ (pH approximately 7.0). Mineralization, which was augmented by the calcifying medium, was completely inhibited by acidosis. Acidosis depressed c-Jun mRNA and increased osteoprotegerin (OPG) production in a time-dependent manner. Depressing c-Jun mRNA expression using siRNA increased OPG production and inhibited mineralization. In addition, depressing OPG mRNA expression with siRNA enhanced mineralization in a dose-dependent manner. Acidosis or the OPG protein strongly inhibited mineralization in osteoblasts from neonatal mice. The present study was the first to demonstrate that acidosis inhibited mineralization, depressed c-Jun mRNA expression, and induced OPG production in human osteoblasts. These results suggest that OPG is involved in mineralization via c-Jun in human osteoblasts.

  17. Mechanisms in hyperkalemic renal tubular acidosis.

    Karet, Fiona E

    2009-02-01

    The form of renal tubular acidosis associated with hyperkalemia is usually attributable to real or apparent hypoaldosteronism. It is therefore a common feature in diabetes and a number of other conditions associated with underproduction of renin or aldosterone. In addition, the close relationship between potassium levels and ammonia production dictates that hyperkalemia per se can lead to acidosis. Here I describe the modern relationship between molecular function of the distal portion of the nephron, pathways of ammoniagenesis, and hyperkalemia.

  18. Pathogenesis of acidosis in hereditary fructose intolerance.

    Richardson, R M; Little, J A; Patten, R L; Goldstein, M B; Halperin, M L

    1979-11-01

    An 18-yr-old man with a classical history of hereditary fructose intolerance (HFI) developed typical biochemical changes following an oral fructose load: fructosemia, hypoglycemia, hypophosphatemia, hyperuricemia, and metabolic acidosis. Hypokalemia (3.1 meq/liter) was also noted. Three aspects of this case expand the published literature on this syndrome: (1) Metabolic acidosis was found to be due to both lactic acidosis and proximal renal tubular acidosis (RTA). We could quantitate the relative contribution of each, and found that urinary bicarbonate loss due to proximal RTA accounted for less than 10% of the fall in serum bicarbonate. The major cause of the metabolic acidosis was lactic acidosis. (2) Hypokalemia was found to be due to movement of potassium out of the extracellular space rather than to urinary loss. Potassium may have entered cells with phosphate or may have been sequestered in the gastrointestinal tract. (3) The coexistence of proximal RTA and acidemia made it possible to study the effect of acidemia on the urine-blood partial pressure of carbon dioxide (PCO2) gradient in alkaline urine (U-B PCO2). The U-B PCO2 measured during acidemia was much higher at the same urine bicarbonate concentration than in normal controls during alkalemia, providing evidence in humans that acidemia stimulates distal nephron hydrogen-ion secretion.

  19. The genomic analysis of lactic acidosis and acidosis response in human cancers.

    Julia Ling-Yu Chen

    2008-12-01

    Full Text Available The tumor microenvironment has a significant impact on tumor development. Two important determinants in this environment are hypoxia and lactic acidosis. Although lactic acidosis has long been recognized as an important factor in cancer, relatively little is known about how cells respond to lactic acidosis and how that response relates to cancer phenotypes. We develop genome-scale gene expression studies to dissect transcriptional responses of primary human mammary epithelial cells to lactic acidosis and hypoxia in vitro and to explore how they are linked to clinical tumor phenotypes in vivo. The resulting experimental signatures of responses to lactic acidosis and hypoxia are evaluated in a heterogeneous set of breast cancer datasets. A strong lactic acidosis response signature identifies a subgroup of low-risk breast cancer patients having distinct metabolic profiles suggestive of a preference for aerobic respiration. The association of lactic acidosis response with good survival outcomes may relate to the role of lactic acidosis in directing energy generation toward aerobic respiration and utilization of other energy sources via inhibition of glycolysis. This "inhibition of glycolysis" phenotype in tumors is likely caused by the repression of glycolysis gene expression and Akt inhibition. Our study presents a genomic evaluation of the prognostic information of a lactic acidosis response independent of the hypoxic response. Our results identify causal roles of lactic acidosis in metabolic reprogramming, and the direct functional consequence of lactic acidosis pathway activity on cellular responses and tumor development. The study also demonstrates the utility of genomic analysis that maps expression-based findings from in vitro experiments to human samples to assess links to in vivo clinical phenotypes.

  20. Severe metabolic acidosis following assault chemical burn.

    Roock, Sophie D; Deleuze, Jean-Paul; Rose, Thomas; Jennes, Serge; Hantson, Philippe

    2012-04-01

    Assault chemical burns are uncommon in northern Europe. Besides local toxicity, systemic manifestations are possible after strong acid exposure. A 40-year-old woman was admitted 1 h after a criminal assault with sulfuric acid. The total burned surface area was 35%, third degree. Injury was due to sulfuric acid (measured pH 0.9) obtained from a car battery. Immediate complications were obstructive dyspnea and metabolic acidosis. The admission arterial pH was 6.92, with total bicarbonate 8.6 mEq/l and base deficit 23.4 mEq/l. The correction of metabolic acidosis was achieved after several hours by the administration of bicarbonate and lactate buffers. The patient developed several burns-related complications (sepsis and acute renal failure). Cutaneous projections of strong acids may cause severe metabolic acidosis, particularly when copious irrigation and clothes removal cannot be immediately performed at the scene.

  1. Severe metabolic acidosis following assault chemical burn

    Sophie De Roock

    2012-01-01

    Full Text Available Assault chemical burns are uncommon in northern Europe. Besides local toxicity, systemic manifestations are possible after strong acid exposure. A 40-year-old woman was admitted 1 h after a criminal assault with sulfuric acid. The total burned surface area was 35%, third degree. Injury was due to sulfuric acid (measured pH 0.9 obtained from a car battery. Immediate complications were obstructive dyspnea and metabolic acidosis. The admission arterial pH was 6.92, with total bicarbonate 8.6 mEq/l and base deficit 23.4 mEq/l. The correction of metabolic acidosis was achieved after several hours by the administration of bicarbonate and lactate buffers. The patient developed several burns-related complications (sepsis and acute renal failure. Cutaneous projections of strong acids may cause severe metabolic acidosis, particularly when copious irrigation and clothes removal cannot be immediately performed at the scene.

  2. Metabolic Acidosis of CKD: An Update.

    Kraut, Jeffrey A; Madias, Nicolaos E

    2016-02-01

    The kidney has the principal role in the maintenance of acid-base balance. Therefore, a decrease in renal ammonium excretion and a positive acid balance often leading to a reduction in serum bicarbonate concentration are observed in the course of chronic kidney disease (CKD). The decrease in serum bicarbonate concentration is usually absent until glomerular filtration rate decreases to acidosis, high-anion gap acidosis, or both can be found at all stages of CKD. The acidosis can be associated with muscle wasting, bone disease, hypoalbuminemia, inflammation, progression of CKD, and increased mortality. Administration of base may decrease muscle wasting, improve bone disease, and slow the progression of CKD. Base is suggested when serum bicarbonate concentration is  24 mEq/L might be associated with worsening of cardiovascular disease adds complexity to treatment decisions. Further study of the mechanisms through which metabolic acidosis contributes to the progression of CKD, as well as the pathways involved in mediating the benefits and complications of base therapy, is warranted.

  3. Trauma triggering thyrotoxic crisis with lactic acidosis.

    Prosser, Jennifer S; Quan, Dan K

    2015-01-01

    Thyrotoxic crisis (TC) is defined as a life-threatening exacerbation of the hyperthyroid state that causes multiple autonomic and metabolic disturbances. It is considered to be an endocrine emergency that must be urgently diagnosed and treated. We describe a case of TC precipitated by trauma with a resultant lactic acidosis. The patient is a 24-year-old male with a history of hyperthyroidism who presented to the emergency department following a motor vehicle accident. The patient was initially tachycardic and hypertensive, however, was afebrile. Initial laboratory analysis showed an anion gap of 26, lactic acid 7.6, free T4 5.61 and thyroid stimulating hormone < 0.015. A diagnosis of TC was made, and he was treated with intravenous fluids, propranolol, and methimazole with improvement of tachycardia and lactic acidosis. We discuss the features of this case, which reviews the presentations of TC as well as its metabolic sequelae.

  4. Trauma triggering thyrotoxic crisis with lactic acidosis

    Jennifer S Prosser

    2015-01-01

    Full Text Available Thyrotoxic crisis (TC is defined as a life-threatening exacerbation of the hyperthyroid state that causes multiple autonomic and metabolic disturbances. It is considered to be an endocrine emergency that must be urgently diagnosed and treated. We describe a case of TC precipitated by trauma with a resultant lactic acidosis. The patient is a 24-year-old male with a history of hyperthyroidism who presented to the emergency department following a motor vehicle accident. The patient was initially tachycardic and hypertensive, however, was afebrile. Initial laboratory analysis showed an anion gap of 26, lactic acid 7.6, free T4 5.61 and thyroid stimulating hormone < 0.015. A diagnosis of TC was made, and he was treated with intravenous fluids, propranolol, and methimazole with improvement of tachycardia and lactic acidosis. We discuss the features of this case, which reviews the presentations of TC as well as its metabolic sequelae.

  5. Acute isoniazid intoxication: seizures, acidosis and coma.

    Temmerman, W; Dhondt, A; Vandewoude, K

    1999-08-01

    Isoniazid (INH) is the most widely used of the antituberculosis drugs. An acute overdose is potentially fatal and is characterized by the clinical triad of repetitive seizures unresponsive to the usual anticonvulsants, metabolic acidosis with a high anion gap and coma. The diagnosis of INH overdose should be considered in any patient who presents with an unexplained metabolic acidosis and convulsions. The cornerstone of therapy consists in pyridoxine (vitamin B6) and the dose should be equal to the amount of INH ingested. When conservative therapy fails or in case of renal insufficiency, dialysis must be considered. Severe central nervous toxicity can also be caused by chronic ingestion of higher than therapeutic doses of INH. In those cases pyridoxine-therapy can be useful as well. In the present paper a case of acute overdose of INH is reported, followed by a review of the literature.

  6. Distal renal tubular acidosis with hereditary spherocytosis.

    Sinha, Rajiv; Agarwal, Indira; Bawazir, Waleed M; Bruce, Lesley J

    2013-07-01

    Hereditary spherocytosis (HS) and distal renal tubular acidosis (dRTA), although distinct entities, share the same protein i.e. the anion exchanger1 (AE1) protein. Despite this, their coexistence has been rarely reported. We hereby describe the largest family to date with co-existence of dRTA and HS and discuss the molecular basis for the co-inheritance of these conditions.

  7. Understanding lactic acidosis in paracetamol (acetaminophen) poisoning.

    Shah, Anoop D; Wood, David M; Dargan, Paul I

    2011-01-01

    Paracetamol (acetaminophen) is one of the most commonly taken drugs in overdose in many areas of the world, and the most common cause of acute liver failure in both the UK and USA. Paracetamol poisoning can result in lactic acidosis in two different scenarios. First, early in the course of poisoning and before the onset of hepatotoxicity in patients with massive ingestion; a lactic acidosis is usually associated with coma. Experimental evidence from studies in whole animals, perfused liver slices and cell cultures has shown that the toxic metabolite of paracetamol, N-acetyl-p-benzo-quinone imine, inhibits electron transfer in the mitochondrial respiratory chain and thus inhibits aerobic respiration. This occurs only at very high concentrations of paracetamol, and precedes cellular injury by several hours. The second scenario in which lactic acidosis can occur is later in the course of paracetamol poisoning as a consequence of established liver failure. In these patients lactate is elevated primarily because of reduced hepatic clearance, but in shocked patients there may also be a contribution of peripheral anaerobic respiration because of tissue hypoperfusion. In patients admitted to a liver unit with paracetamol hepatotoxicity, the post-resuscitation arterial lactate concentration has been shown to be a strong predictor of mortality, and is included in the modified King's College criteria for consideration of liver transplantation. We would therefore recommend that post-resuscitation lactate is measured in all patients with a severe paracetamol overdose resulting in either reduced conscious level or hepatic failure.

  8. A peculiar cause for metabolic acidosis in the newborn.

    Kisku, Sundeep; Sen, Sudipta; Joseph Thomas, Reju; Dastidar, Arindam; Thomas, Niranjan

    2012-01-01

    Metabolic acidosis is often encountered in a sick neonate and intestinal duplication with heterotopic gastric mucosa is a well-established condition. We present a previously unreported relationship between neonatal metabolic acidosis, resulting from transperitoneal absorption of hydrochloric acid, and a ruptured non- communicating ileal duplication cyst with gastric mucosal heterotopia. The neonate recovered rapidly after resection of the ileal duplication. We present this case to highlight a rare but surgically correctable cause of neonatal metabolic acidosis.

  9. Drug-Induced Metabolic Acidosis [version 1; referees: 3 approved

    Amy Quynh Trang Pham

    2015-12-01

    Full Text Available Metabolic acidosis could emerge from diseases disrupting acid-base equilibrium or from drugs that induce similar derangements. Occurrences are usually accompanied by comorbid conditions of drug-induced metabolic acidosis, and clinical outcomes may range from mild to fatal. It is imperative that clinicians not only are fully aware of the list of drugs that may lead to metabolic acidosis but also understand the underlying pathogenic mechanisms. In this review, we categorized drug-induced metabolic acidosis in terms of pathophysiological mechanisms, as well as individual drugs’ characteristics.

  10. [Lactate acidosis: a rare or common disease?].

    Kubát, K

    1995-05-01

    The authors present a survey of 50 documented cases of metabolic lactic acidosis (MLAC) recorded in the course of 5 years. To this study cases of severe hyperlactataemia (determined minimum lactate level of concentration 4 mmol/l) have been included. The sample consists of patients hospitalized at the Department of Internal Medicine Litomĕrice (hinterland of about 110,000 inhabitants). Liver involvement in 5 cases, cardiogenous shock in 6 cases, sepsis in 2 cases were the cause of lactic acidosis. The administration of biguanids (Adebit, Silubin R, Diformin) seems to be the probable cause in 21 cases, other cases were triggered by rarer causes. Dehydratation (16), vomiting (9), diarrhoea (11) dominate often in the clinical picture. The patients were admitted to the hospital often unconscious, with diagnose of vasculo-cerebral incidence, transitory ischaemic incidence... Quit rarely the typical Kussmaul's respiratory (only 9 cases) was recorded. Hyperlactatemia was usually associated with decrease of blood pH (theta = 7.12, pH less than 7.35 was recorded in 49 cases, pH less than 6.8 in 5 cases) and with decrease of BE value (= Ccoase, theta = -15.3 mmol/l). When the hypochloremia and/or hypocapnia was simultaneously more severe, only in these cases the value of pH was within physiological limits or even increased (10). The conclusions show that MLAC is not a rare disorder, however, its occurrence is depended rather on the clinician's capacity to diagnose this disorder and to indicate lactate examination. Usual signs of acidosis (Kussmaul's respiratory, decrease of pH, decrease of BE) can be missing in many cases.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. [Lactic acidosis and biguanid therapy (author's transl)].

    Thimme, W; Buschmann, H J; Dissmann, W; Amft, R

    1976-09-03

    Ten case histories of patients with lactic acidosis and biguanide therapy are presented. 6 patients received phenformin, 4 buformin. The symptomatology was characterized by somnolence or unconsciousness with hyperventilation, renal insufficiency, signs of infection occasionally with detection of gram negative rods and in later stages circulatory insufficiency with high central venous pressure. Glucose, insulin, bicarbonate, dialysis, antibiotics and katecholamines were the therapeutic measurements. It is the proposal of this communication to call attention again to the potential toxicity of biguanids which makes necessary the strict observation of contraindications.

  12. Distal Renal Tubular Acidosis and Calcium Nephrolithiasis

    Moe, Orson W.; Fuster, Daniel G.; Xie, Xiao-Song

    2008-09-01

    Calcium stones are commonly encountered in patients with congenital distal renal tubular acidosis, a disease of renal acidification caused by mutations in either the vacuolar H+-ATPase (B1 or a4 subunit), anion exchanger-1, or carbonic anhydrase II. Based on the existing database, we present two hypotheses. First, heterozygotes with mutations in B1 subunit of H+-ATPase are not normal but may harbor biochemical abnormalities such as renal acidification defects, hypercalciuria, and hypocitraturia which can predispose them to kidney stone formation. Second, we propose at least two mechanisms by which mutant B1 subunit can impair H+-ATPase: defective pump assembly and defective pump activity.

  13. The syndrome of renal tubular acidosis with nerve deafness.

    Donckerwolcke, R A; Van Biervliet, J P; Koorevaar, G; Kuijten, R H; Van Stekelenburg, G J

    1976-01-01

    Two brothers with renal tubular acidosis and nerve deafness are described. Studies of the physiopathological characteristics of the renal acidification defect show that the defect is limited to the distal tubule. Renal tubular acidosis with nerve deafness is a distinct nosologic entity that is determined by an autosomal recessive trait.

  14. Treatment of acute non-anion gap metabolic acidosis.

    Kraut, Jeffrey A; Kurtz, Ira

    2015-02-01

    Acute non-anion gap metabolic acidosis, also termed hyperchloremic acidosis, is frequently detected in seriously ill patients. The most common mechanisms leading to this acid-base disorder include loss of large quantities of base secondary to diarrhea and administration of large quantities of chloride-containing solutions in the treatment of hypovolemia and various shock states. The resultant acidic milieu can cause cellular dysfunction and contribute to poor clinical outcomes. The associated change in the chloride concentration in the distal tubule lumen might also play a role in reducing the glomerular filtration rate. Administration of base is often recommended for the treatment of acute non-anion gap acidosis. Importantly, the blood pH and/or serum bicarbonate concentration to guide the initiation of treatment has not been established for this type of metabolic acidosis; and most clinicians use guidelines derived from studies of high anion gap metabolic acidosis. Therapeutic complications resulting from base administration such as volume overload, exacerbation of hypertension and reduction in ionized calcium are likely to be as common as with high anion gap metabolic acidosis. On the other hand, exacerbation of intracellular acidosis due to the excessive generation of carbon dioxide might be less frequent than in high anion gap metabolic acidosis because of better tissue perfusion and the ability to eliminate carbon dioxide. Further basic and clinical research is needed to facilitate development of evidence-based guidelines for therapy of this important and increasingly common acid-base disorder.

  15. An unrecognised case of metabolic acidosis following neobladder augmentation cystoplasty

    David Eldred-Evans

    2015-01-01

    Conclusion: Hyperchloremic metabolic acidosis is a well-established complication of urinary diversion. Patient with orthotopic neobladder with high residual urine and large capacity are at even higher risk of metabolic acidosis. This information should be clearly documented in the post-operative discharge documentation to ensure early recognition by non-specialists.

  16. Mechanistic Modeling of the Effects of Acidosis on Thrombin Generation

    2015-08-01

    the compu- tational model using the data on clotting factor composition for 472 subjects from the Leiden Thrombophilia Study. To compare acidosis...trick, MD. The Leiden Thrombophilia Study, completed previously (FRR), was funded by the Netherlands Heart Foundation (89-063). The authors declare... Thrombophilia Study. To compare acidosis-induced relative parameter changes in individual (???virtual???) subjects, we estimated the probabilities of

  17. Sodium bicarbonate therapy in patients with metabolic acidosis.

    Adeva-Andany, María M; Fernández-Fernández, Carlos; Mouriño-Bayolo, David; Castro-Quintela, Elvira; Domínguez-Montero, Alberto

    2014-01-01

    Metabolic acidosis occurs when a relative accumulation of plasma anions in excess of cations reduces plasma pH. Replacement of sodium bicarbonate to patients with sodium bicarbonate loss due to diarrhea or renal proximal tubular acidosis is useful, but there is no definite evidence that sodium bicarbonate administration to patients with acute metabolic acidosis, including diabetic ketoacidosis, lactic acidosis, septic shock, intraoperative metabolic acidosis, or cardiac arrest, is beneficial regarding clinical outcomes or mortality rate. Patients with advanced chronic kidney disease usually show metabolic acidosis due to increased unmeasured anions and hyperchloremia. It has been suggested that metabolic acidosis might have a negative impact on progression of kidney dysfunction and that sodium bicarbonate administration might attenuate this effect, but further evaluation is required to validate such a renoprotective strategy. Sodium bicarbonate is the predominant buffer used in dialysis fluids and patients on maintenance dialysis are subjected to a load of sodium bicarbonate during the sessions, suffering a transient metabolic alkalosis of variable severity. Side effects associated with sodium bicarbonate therapy include hypercapnia, hypokalemia, ionized hypocalcemia, and QTc interval prolongation. The potential impact of regular sodium bicarbonate therapy on worsening vascular calcifications in patients with chronic kidney disease has been insufficiently investigated.

  18. [Chronic kidney diseases, metformin and lactic acidosis].

    Borbély, Zoltán

    2016-04-01

    Chronic kidney disease and diabetes mellitus represent a worldwide public health problem. The incidence of these diseases is gradually growing into epidemic proportions. In many cases they occur simultaneously, what leads to increased morbidity and mortality among the affected patients. The majority of the patients treated for diabetes mellitus are unaware of the presence of renal insufficiency. Vascular hypertrophy and diabetic kidney disease in patients with type 2 diabetes are the most common causes of kidney failure in countries with advanced healthcare systems. Metformin is a basic drug used for the treatment of type 2 diabetes mellitus. It is excreted in an unchanged form by the kidneys. When administered to patients with renal insufficiency, sepsis, dehydration or after the parenteral administration of iodinated contrast agents, metformin can cause lactic acidosis, which is also associated with an increased mortality rate.

  19. Treatment of acute metabolic acidosis: a pathophysiologic approach.

    Kraut, Jeffrey A; Madias, Nicolaos E

    2012-10-01

    Acute metabolic acidosis is associated with increased morbidity and mortality because of its depressive effects on cardiovascular function, facilitation of cardiac arrhythmias, stimulation of inflammation, suppression of the immune response, and other adverse effects. Appropriate evaluation of acute metabolic acidosis includes assessment of acid-base parameters, including pH, partial pressure of CO(2) and HCO(3)(-) concentration in arterial blood in stable patients, and also in central venous blood in patients with impaired tissue perfusion. Calculation of the serum anion gap and the change from baseline enables the physician to detect organic acidoses, a common cause of severe metabolic acidosis, and aids therapeutic decisions. A fall in extracellular and intracellular pH can affect cellular function via different mechanisms and treatment should be directed at improving both parameters. In addition to supportive measures, treatment has included administration of base, primarily in the form of sodium bicarbonate. However, in clinical studies of lactic acidosis and ketoacidosis, bicarbonate administration has not reduced morbidity or mortality, or improved cellular function. Potential explanations for this failure include exacerbation of intracellular acidosis, reduction in ionized Ca(2+), and production of hyperosmolality. Administration of tris(hydroxymethyl)aminomethane (THAM) improves acidosis without producing intracellular acidosis and its value as a form of base is worth further investigation. Selective sodium-hydrogen exchanger 1 (NHE1) inhibitors have been shown to improve haemodynamics and reduce mortality in animal studies of acute lactic acidosis and should also be examined further. Given the important effects of acute metabolic acidosis on clinical outcomes, more intensive study of the pathogenesis of the associated cellular dysfunction and novel methods of treatment is indicated.

  20. Tolerance of hypercapnic acidosis by the European eel, Anguilla anguilla

    McKenzie, DJ; Dalla Valle, AZ; Steffensen, JF;

    2000-01-01

    in tailbeat frequencies, aerobic scope or maximum sustainable swimming speed. The results indicate that the eel is extremely tolerant of hypercapnic acidosis. Acute, severe acidosis and hypoxaemia had no effect on CO or whole animal O2 uptake; chronic acidosis and hypoxaemia had no effect on the ability.......5 ± 2.2 vol%, significantly lower than in the control animals, where pHa was 7.89 ± 0.04 and ca,O2 11.6 ± 1.5 vol%. Exercise performance was studied in a swimming respirometer. Stepwise increases in swimming speed caused similar, exponential increases in O2 uptake in all groups, with no differences...

  1. [Metabolic acidosis in patients with chronic kidney diseases: why and when to treat it?].

    Sofia, A; Cappelli, V; Valli, A; Garibotto, G

    2005-01-01

    Metabolic acidosis is a common complication in patients with advanced chronic renal diseases and dialytic treatments are unable to correct it completely. In hemodialysis (HD) patients, severe metabolic acidosis is associated with an increased risk of death. Evidence from several experimental studies suggests that even mild metabolic acidosis is associated with systemic effects. Acidosis is implicated in endocrine changes and has negative repercussions on bone and protein metabolism. In addition, recent observations suggest that acidosis triggers inflammation and accelerates the progression of chronic kidney diseases. As a contradictory finding, acidosis can reduce circulating leptin. Clinical studies on the nutritional effects of metabolic acidosis correction have shown mildly favorable effects. Taking into account the systemic effects of metabolic acidosis it is suggested that even mild metabolic acidosis is corrected. However, the new findings concerning the systemic effects of acidosis must be evaluated in controlled trials.

  2. Intractable metabolic acidosis in a patient with colovesical fistula.

    Pillinger, Toby; Abdelrahman, Mohamed; Jones, Gregory; D'Souza, Francis

    2012-11-23

    A 58-year-old female presented with urosepsis and faecaluria secondary to a colovesical fistula of diverticular aetiology. A plan was made for surgical repair of the fistula. Preoperatively the patient developed a hyperchloraemic metabolic acidosis, with hyperkalaemia and hyponatraemia. Renal function was normal, and a short synachten test ruled out Addison's disease. Postoperatively her acid-base physiology normalised in the absence of medical management, demonstrating that surgical intervention was responsible for resolution of the patient's metabolic acidosis. The mechanisms by which colovesical pathophysiology causes hyperchloraemic metabolic acidosis are discussed. Although diverticular disease is the most common cause of colovesical fistulae, this is the first report of such fistulae causing metabolic acidosis.

  3. Hemolytic anemia and metabolic acidosis: think about glutathione synthetase deficiency.

    Ben Ameur, Salma; Aloulou, Hajer; Nasrallah, Fehmi; Kamoun, Thouraya; Kaabachi, Naziha; Hachicha, Mongia

    2015-02-01

    Glutathione synthetase deficiency (GSSD) is a rare disorder of glutathione metabolism with varying clinical severity. Patients may present with hemolytic anemia alone or together with acidosis and central nervous system impairment. Diagnosis is made by clinical presentation and detection of elevated concentrations of 5-oxoproline in urine and low glutathione synthetase activity in erythrocytes or cultured skin fibroblasts. The prognosis seems to depend on early diagnosis and treatment. We report a 4 months old Tunisian male infant who presented with severe metabolic acidosis with high anion gap and hemolytic anemia. High level of 5-oxoproline was detected in her urine and diagnosis of GSSD was made. Treatment consists of the correction of acidosis, blood transfusion, and supplementation with antioxidants. He died of severe metabolic acidosis and sepsis at the age of 15 months.

  4. Klinefelter's syndrome with renal tubular acidosis: impact on height.

    Jebasingh, F; Paul, T V; Spurgeon, R; Abraham, S; Jacob, J J

    2010-02-01

    A 19-year-old Indian man presented with a history of proximal muscle weakness, knock knees and gynaecomastia. On examination he had features of rickets and bilateral small testes. Karyotyping revealed a chromosomal pattern of 47,XXX, confirming the diagnosis of Klinefelter's syndrome. He was also found to have hyperchloraemic metabolic acidosis with hypokalaemia, hypophosphataemia, phosphaturia and glycosuria, which favoured a diagnosis of proximal renal tubular acidosis. Patients with Klinefelter's syndrome typically have a tall stature due to androgen deficiency, resulting in unfused epiphyses and an additional X chromosome. However, this patient had a short stature due to associated proximal renal tubular acidosis. To the best of our knowledge, this is the second case of Klinefelter's syndrome with short stature due to associated renal tubular acidosis reported in the literature. This report highlights the need to consider other causes when patients with Klinefelter's syndrome present with a short stature.

  5. Benign duodenocolic fistula. A case presenting with acidosis

    Benn, Marianne; Nielsen, F T; Antonsen, H K

    1997-01-01

    A case of benign duodenocolic fistula as a complication to peptic ulcer disease is presented, the case being interesting for the rarity of the diagnosis and by being complicated with acidosis. The etiology, clinical features, diagnosis, and treatment are reviewed.......A case of benign duodenocolic fistula as a complication to peptic ulcer disease is presented, the case being interesting for the rarity of the diagnosis and by being complicated with acidosis. The etiology, clinical features, diagnosis, and treatment are reviewed....

  6. Acidosis differently modulates the inflammatory program in monocytes and macrophages.

    Riemann, Anne; Wußling, Hanna; Loppnow, Harald; Fu, Hang; Reime, Sarah; Thews, Oliver

    2016-01-01

    Inflammation, ischemia or the microenvironment of solid tumors is often accompanied by a reduction of extracellular pH (acidosis) that stresses the cells and acts on cellular signaling and transcription. The effect of acidosis on the expression of various inflammatory markers, on functional parameters (migration, phagocytic activity) and on signaling pathways involved was studied in monocytic cells and macrophages. In monocytic cell lines acidosis led to a reduction in expression of most of the inflammatory mediators, namely IL-1ß, IL-6, TNF-α, MCP-1, COX-2 and osteopontin. In primary human monocytes MCP-1 and TNF-α were reduced but COX-2 and IL-6 were increased. In RAW264.7 macrophage cell line IL-1ß, COX-2 and iNOS expression was increased, whereas MCP-1 was reduced similar to the effect in monocytic cells. For primary human monocyte-derived macrophages the regulation of inflammatory markers by acidosis depended on activation state, except for the acidosis-induced downregulation of MCP-1 and TNF-α. Acidosis affected functional immune cell behavior when looking at phagocytic activity which was increased in a time-dependent manner, but cellular motility was not changed. Neither ERK1/2 nor CREB signaling was stimulated by the reduction of extracellular pH. However, p38 was activated by acidosis in RAW264.7 cells and this activation was critical for the induction of IL-1ß, COX-2 and iNOS expression. In conclusion, acidosis may impede the recruitment of immune cells, but fosters inflammation when macrophages are present by increasing the level of COX-2 and iNOS and by functionally forcing up the phagocytic activity.

  7. Metabolic Acidosis as a Complication of Bicarbonate Haemodialysis

    Irshad Ahmad Sinval, Bassam Bernieh, Ahdulrahman Osman Mohamad, Mohamed Adnan Abbadi,Mossadeque Ahmed, Ahmad Abdelwahab AItabakh

    1999-01-01

    Twelve episodes ofsevere metabolic acidosis were observed among 10 maintenance dialysis patientsusing Bicarbonate Haemodialysis (HDB). Patients were stable at the start of haemodialysis (HO)and became sick during or following the procedure. The main clinical features observed wereabdominal pain and vomiting, hypotension or shock, and CNS manifestations. Laboratoryinvestigations revealed severe metabolic acidosis in all and hyperkalemia in 4 patients. On fouroccasions, dialysate fluid sample a...

  8. Acidosis and Correction of Acidosis Does Not Affect rFVIIa Function in Swine

    2012-12-15

    normaliza- tion of respiration returned arterial pH to 7.4 and restored PaCO2, PaO2 and BE to baseline (Table 3). Ionized calcium was maintained near...model Control Acidosis Acidosis corrected n=10 pH 7.38±0.01 7.14±0.01 7.43±0.01 PaCO2 (mmHg) 47.3±1.8 43.0±1.8 55.0±3.1 PaO2 (mmHg) 433.6±26.4 400.9±33.1...mmHg) 49.5±1.3 48.2±1.8 94.0±5.2 *# PaO2 (mmHg) 142.8±3.3 133.5±8.6 99.6±9.6 *# HCO3 - (mM) 31.2±0.7 24.3±1.1* 29.5±1.2# BE (mM) 5.8±0.6 -1.5±1.0* -2.1

  9. [D-Lactic acidosis secondary to short bowel syndrome].

    Tapia Guerrero, M J; Olveira, G; Bravo Utrera, M; Colomo Rodríguez, N; Fernández García, J C

    2010-01-01

    The short bowel syndrome appears for the reduction of intestinal absorptive surface due to functional or anatomical loss of part of the small bowel. We present the case of a 35-year-old woman with severe short bowel syndrome secondary to acute intestinal ischemia in adults, who presented at 5 years of evolution episodes of dizziness with gait instability and loss of strength in hands. The diagnosis was D-lactic acidosis. D-lactic acidosis is a rare complication, but important for their symptoms, of this syndrome. It is due to a change in intestinal flora secondary to an overgrowth of lactic acid bacteria that produce D-lactate. D-lactic acidosis should be looked for in cases of metabolic acidosis in which the identity of acidosis is not apparent, neurological manifestations without focality and the patient has short bowel syndrome or patients who have had jejunoileal bypass surgery. Appropriate treatment usually results in resolution of neurologic symptoms and prevents or reduces further recurrences.

  10. Metabolic Acidosis with Ophthalmic Dorzolamide in a Neonate.

    Capino, Amanda C; Dannaway, Douglas C; Miller, Jamie L

    2016-01-01

    Carbonic anhydrase inhibitors are a common cause of normal anion gap metabolic acidosis; however, development is less commonly associated with ophthalmic administration of these agents. We report a case of a premature neonate who was being treated at our institution with betaxolol, dorzolamide, and latanoprost ophthalmic products for suspected bilateral congenital glaucoma. In addition, the patient was also receiving caffeine, ursodiol, and acidified liquid human milk fortifier. The patient developed a normal anion gap metabolic acidosis, and both dorzolamide ophthalmic solution and the acidified human milk fortifier were considered potential causes. Upon discontinuation of the dorzolamide ophthalmic solution and the switching of liquid human milk fortifiers, the normal anion gap metabolic acidosis gradually resolved. As a result of the pH and acidity, the acidified liquid human milk fortifier is thought to be associated with an anion gap acidosis; therefore, dorzolamide is suspected to be the primary cause of a normal gap acidosis. This case demonstrates that systemic effects can occur with ophthalmic administration of dorzolamide in a premature neonate. Ophthalmic agents should not be overlooked as a potential cause of systemic toxicity.

  11. Approach to the Treatment of Chronic Metabolic Acidosis in CKD.

    Raphael, Kalani L

    2016-04-01

    Chronic metabolic acidosis is not uncommon in patients with chronic kidney disease (CKD). Clinical practice guidelines suggest that clinicians administer alkali to maintain serum bicarbonate level at a minimum of 22 mEq/L to prevent the effects of acidosis on bone demineralization and protein catabolism. Small interventional studies support the notion that correcting acidosis slows CKD progression as well. Furthermore, alkaline therapy in persons with CKD and normal bicarbonate levels may also preserve kidney function. Observational studies suggest that targeting a serum bicarbonate level near 28 mEq/L may improve clinical outcomes above and beyond targeting a value ≥ 22 mEq/L, yet values > 26 mEq/L have been reported to be associated with incident heart failure and mortality in the CRIC (Chronic Renal Insufficiency Cohort) Study. Furthermore, correcting acidosis may provoke vascular calcification. This teaching case discusses several uncertainties regarding the management of acidosis in CKD, such as when to initiate alkali treatment, potential side effects of alkali, and the optimum serum bicarbonate level based on current evidence in CKD. Suggestions regarding the maximum sodium bicarbonate dose to administer to patients with CKD to achieve the target serum bicarbonate concentration are offered.

  12. Metabolic acidosis-induced insulin resistance and cardiovascular risk.

    Souto, Gema; Donapetry, Cristóbal; Calviño, Jesús; Adeva, Maria M

    2011-08-01

    Microalbuminuria has been conclusively established as an independent cardiovascular risk factor, and there is evidence of an association between insulin resistance and microalbuminuria, the former preceding the latter in prospective studies. It has been demonstrated that even the slightest degree of metabolic acidosis produces insulin resistance in healthy humans. Many recent epidemiological studies link metabolic acidosis indicators with insulin resistance and systemic hypertension. The strongly acidogenic diet consumed in developed countries produces a lifetime acidotic state, exacerbated by excess body weight and aging, which may result in insulin resistance, metabolic syndrome, and type 2 diabetes, contributing to cardiovascular risk, along with genetic causes, lack of physical exercise, and other factors. Elevated fruits and vegetables consumption has been associated with lower diabetes incidence. Diseases featuring severe atheromatosis and elevated cardiovascular risk, such as diabetes mellitus and chronic kidney failure, are typically characterized by a chronic state of metabolic acidosis. Diabetic patients consume particularly acidogenic diets, and deficiency of insulin action generates ketone bodies, creating a baseline state of metabolic acidosis worsened by inadequate metabolic control, which creates a vicious circle by inducing insulin resistance. Even very slight levels of chronic kidney insufficiency are associated with increased cardiovascular risk, which may be explained at least in part by deficient acid excretory capacity of the kidney and consequent metabolic acidosis-induced insulin resistance.

  13. Obscure Severe Infrarenal Aortoiliac Stenosis With Severe Transient Lactic Acidosis

    Teerapat Nantsupawat MD

    2013-01-01

    Full Text Available A 57-year-old man presented with sudden onset of leg pain, right-sided weakness, aphasia, confusion, drooling, and severe lactic acidosis (15 mmol/L. He had normal peripheral pulses and demonstrated no pain, pallor, poikilothermia, paresthesia, or paralysis. Empiric antibiotics, aspirin, full-dose enoxaparin, and intravenous fluid were initiated. Lactic acid level decreased to 2.5 mmol/L. The patient was subsequently extubated and was alert and oriented with no complaints of leg or abdominal pain. Unexpectedly, the patient developed cardiac arrest, rebound severe lactic acidosis (8.13 mmol/L, and signs of acute limb ischemia. Emergent computed tomography of the aorta confirmed infrarenal aortoiliac thrombosis. Transient leg pain and transient severe lactic acidosis can be unusual presentations of severe infrarenal aortoiliac stenosis. When in doubt, vascular studies should be implemented without delay to identify this catastrophic diagnosis.

  14. The impact of extracellular acidosis on dendritic cell function.

    Vermeulen, Mónica Elba; Gamberale, Romina; Trevani, Analía Silvina; Martínez, Diego; Ceballos, Ana; Sabatte, Juan; Giordano, Mirta; Geffner, Jorge Raúl

    2004-01-01

    Dendritic cells (DCs) are the most efficient antigen-presenting cells. They are activated in the periphery by conserved pathogen molecules and by inflammatory mediators produced by a variety of cell types in response to danger signals. It is widely appreciated that inflammatory responses in peripheral tissues are usually associated with the development of acidic microenvironments. Surprisingly, there are relatively few studies directed to analyze the effect of extracellular acidosis on the immune response. We focus on the influence of extracellular acidosis on the function of immature DCs. The results presented here show that acidosis activates DCs. It increases the acquisition of extracellular antigens for MHC class I-restricted presentation and the ability of antigen-pulsed DCs to induce both specific CD8+ CTL and B-cell responses. These findings may have important implications to our understanding of the mechanisms through which DCs sense the presence of infection or inflammation in nonlymphoid tissues.

  15. Bilateral putaminal necrosis in a comatose patient with metabolic acidosis

    Sudhir Kumar

    2016-01-01

    Full Text Available We present a case of acute-onset coma in a young woman, associated with metabolic acidosis, respiratory distress, and hypotension. Magnetic resonance imaging of the brain done on day 2 of admission showed features of bilateral putaminal necrosis. History of methanol ingestion, though not forthcoming at admission, was confirmed later after the patient regained consciousness. A final diagnosis of methyl alcohol toxicity resulting in severe metabolic acidosis, coma, and bilateral blindness was made. This case is reported to emphasize the point that the finding of bilateral putaminal necrosis in a patient with coma and metabolic acidosis is virtually diagnostic of methyl alcohol toxicity even in the absence of any positive history.

  16. Molecular and pathophysiologic mechanisms of hyperkalemic metabolic acidosis.

    DuBose, T D

    2000-01-01

    In summary, hyperkalemia may have a dramatic impact on ammonium production and excretion. Chronic hyperkalemia decreases ammonium production in the proximal tubule and whole kidney, inhibits absorption of NH4+ in the mTALH, reduces medullary interstitial concentrations of NH4+ and NH3, and decreases entry of NH4+ and NH3 into the medullary collecting duct. The potential for development of a hyperchloremic metabolic acidosis is greatly augmented when renal insufficiency with associated reduction in functional renal mass coexists with the hyperkalemia, or in the presence of aldosterone deficiency or resistance. Such a cascade of events helps to explain, in part, the hyperchloremic metabolic acidosis and reduction in net acid excretion characteristic of several experimental models of hyperkalemic-hyperchloremic metabolic acidosis including: obstructive nephropathy, selective aldosterone deficiency, and chronic amiloride administration (7.9).

  17. Ventilatory response in metabolic acidosis and cerebral blood volume in humans.

    Ven, M.T.P. van de; Colier, W.N.J.M.; Sluijs, M.C. van der; Oeseburg, B.; Folgering, H.T.M.

    2001-01-01

    The relationship between alterations in cerebral blood volume (CBV) and central chemosensitivity regulation was studied under neutral metabolic conditions and during metabolic acidosis. Fifteen healthy subjects (5610 years) were investigated. To induce metabolic acidosis, ammonium chloride (NH(4)Cl)

  18. [End stage of chronic kidney disease and metabolic acidosis].

    Klaboch, J; Opatrná, S; Matoušovic, K; Schück, O

    2012-01-01

    Renal function disorder is inevitably associated with metabolic acidosis. An adult produces approximately 1 mmol of acids/kg of body weight every day (3 mmol/kg in children), derived from metabolization of proteins from food. Development of metabolic acidosis in patients with kidney disease is based on accumulation of acids and insufficient production of bicarbonates; alkaline loss represents a marginal issue here limited to patients with type II renal tubular acidosis only. The prevalence of this disorder increases with declining glomerular filtration (GFR) from 2% in patients with GFR 1.0-1.5 ml/s/1.73 m2 to 39% in patients with GFR inflammation, to progression of tubular interstitial fibrosis that subsequently leads to further GFR reduction. Metabolic acidosis has a number of severe adverse effects on the organism, e.g. deterioration of kidney bone disease through stimulation of bone resorption and inhibition of bone formation, inhibition of vitamin D formation, increased muscle catabolism, reduced albumin production, glucose metabolism disorder, increased insulin resistance, reduced production of thyroid hormones, increased accumulation of β2-microglobulin etc. Non-interventional studies suggest that alkali supplementation may slow down progression of chronic nephropathies. However, this approach, safe and inexpensive, has not been widely implemented in clinical practice yet. With respect to dialyzed patients, abnormal levels of bicarbonates are associated with increased mortality. Both metabolic acidosis and alkalosis, rather regularly seen in a considerable number of patients, have a negative effect on patient survival. Alkali substitution from a dialysis solution is the main pillar of metabolic acidosis management in patients on hemo- as well as peritoneal dialysis. Available technologies allow individualization of the treatment and this should be observed.

  19. Intracellular acidosis enhances the excitability of working muscle.

    Pedersen, Thomas H; Nielsen, Ole B; Lamb, Graham D; Stephenson, D George

    2004-08-20

    Intracellular acidification of skeletal muscles is commonly thought to contribute to muscle fatigue. However, intracellular acidosis also acts to preserve muscle excitability when muscles become depolarized, which occurs with working muscles. Here, we show that this process may be mediated by decreased chloride permeability, which enables action potentials to still be propagated along the internal network of tubules in a muscle fiber (the T system) despite muscle depolarization. These results implicate chloride ion channels in muscle function and emphasize that intracellular acidosis of muscle has protective effects during muscle fatigue.

  20. Type 4 renal tubular acidosis in a kidney transplant recipient

    Manjunath Kulkarni

    2016-02-01

    Full Text Available We report a case of a 66-year-old diabetic patient who presented with muscle weakness 2 weeks after kidney transplantation. Her immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and steroids. She was found to have hyperkalemia and normal anion gap metabolic acidosis. Tacrolimus levels were in therapeutic range. All other drugs such as beta blockers and trimethoprim – sulfamethoxazole were stopped. She did not respond to routine antikalemic measures. Further evaluation revealed type 4 renal tubular acidosis. Serum potassium levels returned to normal after starting sodium bicarbonate and fludrocortisone therapy. Though hyperkalemia is common in kidney transplant recipients, determining exact cause can guide specific treatment.

  1. Type 4 renal tubular acidosis in a kidney transplant recipient.

    Kulkarni, Manjunath

    2016-02-01

    We report a case of a 66-year-old diabetic patient who presented with muscle weakness 2 weeks after kidney transplantation. Her immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and steroids. She was found to have hyperkalemia and normal anion gap metabolic acidosis. Tacrolimus levels were in therapeutic range. All other drugs such as beta blockers and trimethoprim - sulfamethoxazole were stopped. She did not respond to routine antikalemic measures. Further evaluation revealed type 4 renal tubular acidosis. Serum potassium levels returned to normal after starting sodium bicarbonate and fludrocortisone therapy. Though hyperkalemia is common in kidney transplant recipients, determining exact cause can guide specific treatment.

  2. Role of the endocrine pancreas in the kalemic response to acute metabolic acidosis in conscious dogs.

    Adrogué, H J; Chap, Z; ISHIDA, T.; Field, J B

    1985-01-01

    Metabolic acidosis due to organic acids infusion fails to elicit hyperkalemia. Although plasma potassium levels may rise, the increase is smaller than in mineral acid acidosis. The mechanisms responsible for the different effects of organic acid acidosis and mineral acid acidosis remain undefined, although dissimilar hormonal responses by the pancreas may explain dissimilar hormonal responses by the pancreas may explain the phenomena. To test this hypothesis, beta-hydroxybutyric acid (7 meq/k...

  3. [5-0xoproline (pyroglutamic acid) acidosis and acetaminophen- a differential diagnosis in high anion gap metabolic acidosis].

    Weiler, Stefan; Bellmann, Romuald; Kullak-Ublick, Gerd A

    2015-12-01

    Rare cases of high anion gap metabolic acidosis during long-term paracetamol administration in therapeutic doses with causative 5-oxoproline (pyroglutamic acid} accumulation have been reported. Other concomitant risk factors such as malnutrition, alcohol abuse, renal or hepatic dysfunction, comedication with flue/oxacillin, vigabatrin, netilmicin or sepsis have been described. The etiology seems to be a drug-induced reversible inhibition of glutathione synthetase or 5-oxoprolinase leading to elevated serum and urine levels of 5-oxoproline. Other more frequent differential diagnoses, such as intoxications, ketoacidosis or lactic acidosis should be excluded. Causative substances should be stopped. 5-oxoproline concentrations in urine can be quantified to establish the diagnosis. Adverse drug reactions, which are not listed or insufficiently described in the respective Swiss product information, should be reported to the regional pharmacovigilance centres for early signal detection. 5-0 xoproline acidosis will be integrated as a potential adverse drug reaction in the Swiss product information for paracetamol.

  4. Screening renal stone formers for distal renal tubular acidosis

    Osther, P J; Hansen, A B; Røhl, H F

    1989-01-01

    A group of 110 consecutive renal stone formers were screened for distal renal tubular acidosis (RTA) using morning fasting urinary pH (mfUpH) levels followed by a short ammonium chloride loading test in patients with levels above 6.0. In 14 patients (12.7%) a renal acidification defect was noted...

  5. Distal renal tubular acidosis with multiorgan autoimmunity: A case report

    M.J. Van Den Wildenberg (Maria J.); E.J. Hoorn (Ewout); N. Mohebbi (Nilufar); C.A. Wagner (Carsten); A.J.J. Woittiez; P.A.M. de Vries; P. Laverman (Peter)

    2015-01-01

    textabstractA 61-year-old woman with a history of pernicious anemia presented with progressive muscle weakness and dysarthria. Hypokalemic paralysis (serum potassium, 1.4 mEq/L) due to distal renal tubular acidosis (dRTA) was diagnosed. After excluding several possible causes, dRTA was considered au

  6. Metabolic acidosis improves airway conductance in patients with asthma.

    Brijker, F.; Elshout, F.J.J. van den; Bosch, F.H.; Heijdra, Y.F.; Folgering, H.T.M.

    2009-01-01

    The objective was to investigate whether acute metabolic acidosis could cause bronchodilation in patients with asthma. Twelve patients with asthma (8 females, mean age 39 (+/- SD 12) years, forced expiratory volume in 1 second [FEV(1)] 93 [+/-9] % predicted, PC(20) 1.9 (+/-1.0) mg/mL) participated i

  7. Cerebrovascular response to acute metabolic acidosis in humans.

    Ven, M.T.P. van de; Colier, W.N.J.M.; Kersten, B.T.P.; Oeseburg, B.; Folgering, H.T.M.

    2003-01-01

    OBJECTIVES: Evaluation of the cerebrovascular response (delta CBV/delta PaCO2) during baseline metabolic conditions and acute metabolic acidosis. METHODS: 15 healthy subjects, 5 m, 10 f, 56 +/- 10 yrs were investigated. For acidification, NH4Cl was given orally. CBV was measured using Near Infrared

  8. Renal tubular acidosis secondary to jejunoileal bypass for morbid obesity

    Schaffalitzky de Muckadell, O B; Ladefoged, Jens; Thorup, Jørgen Mogens

    1985-01-01

    Renal handling of acid and base was studied in patients with persistent metabolic acidosis 3-9 years after jejunoileal bypass for morbid obesity. Excretion of acid was studied before and after intravenous infusion of NH4Cl and excretion of bicarbonate after infusion of NaHCO3. Bypass patients...

  9. Acidosis, magnesium and acetylsalicylic acid: Effects on thrombin

    Borisevich, Nikolaj; Loznikova, Svetlana; Sukhodola, Aleksandr; Halets, Inessa; Bryszewska, Maria; Shcharbin, Dzmitry

    2013-03-01

    Thrombin, an enzyme from the hydrolase family, is the main component of the blood coagulation system. In ischemic stroke it acts as a serine protease that converts soluble fibrinogen into insoluble strands of fibrin forming blood clots in the brain. It has been found to phosphoresce at room temperature in the millisecond and microsecond ranges. The phosphorescence of thrombin was studied under physiological conditions, in acidosis (decrease of pH from 8.0 to 5.0) and on the addition of salts (magnesium sulfate and sodium chloride) and of acetylsalicylic acid, and its connection with thrombin function is discussed. Acidosis significantly increased the internal dynamics of thrombin. We propose that lactate-acidosis plays a protective role in stroke, preventing the formation of clots. The addition of NaCl and MgSO4 in different concentrations increased the internal dynamics of thrombin. Also, the addition of MgSO4 decreased thrombin-induced platelet aggregation. However, magnesium sulfate and acetylsalicylic acid in the therapeutic concentrations used for treatment of ischemic stroke had no effect on thrombin internal dynamics. The data obtained will help to elucidate the conformational stability of thrombin under conditions modulating lactate-acidosis and in the presence of magnesium sulfate.

  10. Metformin-induced lactic acidosis: a case series

    Silvestre Joana

    2007-10-01

    Full Text Available Abstract Introduction Unlike other agents used in the treatment of type 2 diabetes mellitus, metformin has been shown to reduce mortality in obese patients. It is therefore being increasingly used in higher doses. The major concern of many physicians is a possible risk of lactic acidosis. The reported frequency of metformin related lactic acidosis is 0.05 per 1000 patient-years; some authors advocate that this rate is equal in those patients not taking metformin. Case presentation We present two case reports of metformin-associated lactic acidosis. The first case is a 77 year old female with a past medical history of hypertension and type 2 diabetes mellitus who had recently been prescribed metformin (3 g/day, perindopril and acetylsalicylic acid. She was admitted to the emergency department two weeks later with abdominal pain and psychomotor agitation. Physical examination revealed only signs of poor perfusion. Laboratory evaluation revealed hyperkalemia, elevated creatinine and blood urea nitrogen and mild leukocytosis. Arterial blood gases showed severe lactic acidemia. She was admitted to the intensive care unit. Vasopressor and ventilatory support was initiated and continuous venovenous hemodiafiltration was instituted. Twenty-four hours later, full clinical recovery was observed, with return to a normal serum lactate level. The patient was discharged from the intensive care unit on the sixth day. The second patient is a 69 year old male with a past medical history of hypertension, type 2 diabetes mellitus and ischemic heart disease who was on metformin (4 g/day, glycazide, acetylsalicylic acid and isosorbide dinitrate. He was admitted to the emergency department in shock with extreme bradycardia. Initial evaluation revealed severe lactic acidosis and elevated creatinine and urea. The patient was admitted to the Intensive Care Unit and commenced on continuous venovenous hemodiafiltration in addition to other supportive measures. A

  11. Use of anion gap in the evaluation of a patient with metabolic acidosis.

    Vichot, Alfred A; Rastegar, Asghar

    2014-10-01

    High anion gap (AG) metabolic acidosis, a common laboratory abnormality encountered in clinical practice, frequently is due to accumulation of organic acids such as lactic acid, keto acids, alcohol metabolites, and reduced kidney function. The cause of high AG metabolic acidosis often is established easily using historical and simple laboratory data. Despite this, several challenges in the diagnosis and management of high AG metabolic acidosis remain, including quantifying the increase in AG, understanding the relationship between changes in AG and serum bicarbonate level, and identifying the cause of high AG metabolic acidosis when common causes are ruled out. The present case was selected to highlight the importance of the correction of AG for serum albumin level, the use of actual baseline AG rather than mean normal AG, the relationship between changes in serum bicarbonate level and AG, and a systematic diagnostic approach to uncommon causes of high AG metabolic acidosis, such as 5-oxoproline acidosis (pyroglutamic acidosis).

  12. Acidosis ruminal en bovinos lecheros: implicaciones sobre la producción y la salud animal - Ruminal acidosis in dairy cattle: implications for animal health and production

    Granja Salcedo, Yury Tatiana

    2012-04-01

    Full Text Available ResumenLa acidosis ruminal es un importante problema en la producción de bovinos alimentados con dietas ricas en concentrados, especialmente en vacas de alta producción lechera.AbstractRuminal acidosis is a major problem in the production of cattle fed diets rich in concentrates, especially in cows of high milk production.

  13. Influence of intracellular acidosis on contractile function in the working rat heart

    Jeffrey, F.M.H.; Malloy, C.R.; Radda, G.K. (Univ. of Oxford (England))

    1987-12-01

    The decrease in myocardial contractility during ischemia, hypoxia, and extracellular acidosis has been attributed to intracellular acidosis. Previous studies of the relationship between pH and contractile state have utilized respiratory or metabolic acidosis to alter intracellular pH. The authors developed a model in the working perfused rat heart to study the effects of intracellular acidosis with normal external pH and optimal O{sub 2} delivery. Intracellular pH and high-energy phosphates were monitored by {sup 31}P nuclear magnetic resonance spectroscopy. Hearts were perfused to a steady state with a medium containing 10 mM NH{sub 4}Cl. Acidosis induced a substantial decrease in aortic flow and stroke volume which was associated with little change in peak systolic pressure. It was concluded that (1) for the same intracellular acidosis the influence on tension development was more pronounced with a combined extra- and intracellular acidosis than with an isolated intracellular acidosis, and (2) stroke volume at constant preload was impaired by intracellular acidosis even though changes in developed pressure were minimal. These observations suggest that isolated intracellular acidosis has adverse effects on diastolic compliance and/or relaxation.

  14. Metformin-Associated Acute Kidney Injury and Lactic Acidosis

    David Arroyo

    2011-01-01

    Full Text Available Objectives. Metformin is the preferred oral antidiabetic agent for type 2 diabetes. Lactic acidosis is described as a rare complication, usually during an acute kidney injury (AKI. Material and Methods. We conducted a prospective observational study of metformin-associated AKI cases during four years. 29 cases were identified. Previous renal function, clinical data, and outcomes were recorded. Results. An episode of acute gastroenteritis precipitated the event in 26 cases. Three developed a septic shock. Three patients died, the only related factor being liver dysfunction. More severe metabolic acidosis hyperkalemia and anemia were associated with higher probabilities of RRT requirement. We could not find any relationship between previous renal dysfunction and the outcome of the AKI. Conclusions. AKI associated to an episode of volume depletion due to gastrointestinal losses is a serious complication in type 2 diabetic patients on metformin. Previous renal dysfunction (mild-to-moderate CKD has no influence on the severity or outcome.

  15. A distal renal tubular acidosis showing hyperammonemia and hyperlactacidemia

    C. Ripoli

    2012-08-01

    Full Text Available Introduction: distal renal tubular acidosis (dRTA presents itself with variable clinical manifestations and often with late expressions that impact on prognosis. Case report: A 45-day-old male infant was admitted with stopping growth, difficult feeding and vomiting after meals. Clinical tests and labs revealed a type 1 renal tubular acidosis, even if the first blood tests showed ammonium and lactate increase. We had to exclude metabolic diseases before having a certain diagnosis. Conclusions: blood and urine investigations and genetic tests are fundamental to formulate dRTA diagnosis and to plan follow-up, according to possible phenotypic expressions of recessive and dominant autosomal forms in patients with dRTA.

  16. Pneumoperitoneum and acidosis during arthroscopy with CO2.

    Lotman, D B

    1987-01-01

    Two cases of knee arthroscopy are reported in which the patient sustained both pneumoperitoneum and acidosis. In each case, a pump was used to maintain a set intraarticular pressure of CO2. In neither case was the pneumatic tourniquet inflated. The conclusion is drawn that, to avoid these two complications, arthroscopists should routinely exsanguinate the extremity and inflate the pneumatic tourniquet when using this type of pump.

  17. Blood Parameters Modification at Different Ruminal Acidosis Conditions

    Roberta De Nardi

    2013-09-01

    Full Text Available This study evaluated the reliability of various blood parameters to assess the ruminal acidosis in cattle. Six whole heifers were fed three experimental rations in a 3 x 3 Latin square design. The diets had different starch levels: high (HS, medium (MS or low (CT. Ruminal pH values were continuously measured using wireless sensors. To evaluate the severity of ruminal acidosis, the amount of time per day that the pH was below 5.8, 5.5 and 5.0 was recorded. Blood samples were analyzed for complete blood count, venous blood gas and biochemical profile at 8:00 and 12:00 h. The data were analyzed according to a mixed model. Feeding on CT, MS and HS led to significant differences in DMI (7.7 vs. 6.9 vs. 5.1 kg/d; P < 0.01 which modified the amount of time per day that the pH was below 5.0 (0 vs. 12 vs. 92 min; P < 0.10. Feeding MS and HS diets led to inflammation as indicated by the significant increment of white blood cells when compared to the CT ones and to blood concentration due to the osmotic pressure at ruminal level. Furthermore a significant decrease of bicarbonate level, CO2 partial pressure and oxyhemoglobin was observed as consequence of the activation of metabolic processes aimed to prevent metabolic acidosis. No differences were observed on blood sampling time, suggesting that one daily blood sample was enough to evaluate the metabolic variations related to ruminal acidosis.

  18. Molecular and pathophysiologic mechanisms of hyperkalemic metabolic acidosis.

    DuBose, T D

    2000-01-01

    In summary, hyperkalemia may have a dramatic impact on ammonium production and excretion. Chronic hyperkalemia decreases ammonium production in the proximal tubule and whole kidney, inhibits absorption of NH4+ in the mTALH, reduces medullary interstitial concentrations of NH4+ and NH3, and decreases entry of NH4+ and NH3 into the medullary collecting duct. The potential for development of a hyperchloremic metabolic acidosis is greatly augmented when renal insufficiency with associated reducti...

  19. Renal adaptation to metabolic acidosis in senescent rats

    Prasad, R.; Kinsella, J.L.; Sacktor, B. (National Institutes of Health, Baltimore, MD (USA))

    1988-12-01

    In this study, the authors compared results obtained in senescent rats with young rats given an equivalent acid load. They examined the renal changes by giving equivalent acid loads for 48 h to both 6- and 24-mo-old rats. The basal excretion of ammonium was the same in both groups, whereas titratable acids, phosphate, and Ca{sup 2+} excretions were increased in the senescent animal. After administration of the acid load, ammonium, phosphate, Ca{sup 2+}, and titratable acid excretions increased in both age groups, but there were greater absolute increases in ammonium and titratable acid excretions in the young rats. The total acid excreted by the 24-mo rats was reduced 50 (day 1) and 25% (day 2) compared with the young rats, which was reflected by the more severe acidosis in those animals. The portion of total acid excreted as titratable acids in senescent animals was also increased during acidosis when compared with the young animals. In isolated proximal tubule brush-border membrane vesicles, acidosis increased Na{sup +}-H{sup +} exchange and decreased Na{sup +}-dependent phosphate transport in both age groups. They also found that the basal activity of the Na{sup +}-H{sup +} exchanger was not changed with age but the Na{sup +} dependent phosphate transporter was less in the 24-mo rat. The results suggest that physiological regulation of these renal processes remains intact in the aged rat but the responses may be reduced or delayed in the senescent animal.

  20. Thyroid hormones changes in infants and children with metabolic acidosis.

    Tahirović, H F

    1991-10-01

    The influence of the acidotic state on the thyroxine (T4) peripheral metabolism was studied in two different forms of metabolic acidosis, ie infantile diarrhea and diabetic ketoacidosis. The serum concentrations of T4, free T4 (FT4), triiodothyronine (T3), reverse T3 (rT3), thyrotropin (TSH) and thyroxine-binding globulin (TBG) were measured and compared to healthy control groups. Lower T4 and T3 and higher rT3 serum concentrations were found in both tested groups of patients in relation to the control groups. In infants with severe metabolic acidosis FT4 values were lower than those observed in the control group. In addition, serum TBG levels were lower in diabetic patients as compared to control subjects. Despite the reduced serum T3 and T4 concentrations in both groups of patients, TSH concentrations, were within the normal range. Therefore, we concluded that acidosis caused either by diarrhea (not so far described) or by diabetes mellitus (well documented up to now) affects the thyroid hormones metabolism in a similar way, at least as far as the thyroid hormones blood levels are concerned.

  1. Complement and contact activation in term neonates after fetal acidosis

    Sonntag, J.; Wagner, M.; Strauss, E.; Obladen, M.

    1998-01-01

    AIMS—To evaluate complement and contact activation after fetal acidosis.
METHODS—Fifteen term neonates with hypoxic-ischaemic encephalopathy after umbilical arterial pH 7.20. Determinations of the complement function and C1-inhibitor activity were performed as kinetic tests 22-28 hours after birth. C1q, C1-inhibitor, and factor B concentrations were determined by radial immunodiffusion and those of C3a, C5a, and factor XIIa by enzyme immunoabsorbent assay.
RESULTS—Median complement function (46 vs 73 %), C1q (4.3 vs 9.1 mg/dl), and factor B (5.2 vs 7.7 mg/dl) decreased after fetal acidosis. The activated split products C3a (260 vs 185 µg/l), C5a (5.0 vs 0.6 µg/l), and factor XIIa (3.2 vs 1.3 µg/l) increased in the neonates after fetal acidosis. No differences were found in the concentration and activity of C1-inhibitor.
CONCLUSIONS—Complement and contact activation occurred in the newborns with hypoxic-ischaemic encephalopathy. Activation of these systems generates mediators which can trigger inflammation and tissue injury.

 PMID:9577283

  2. More sensitivity of cortical GABAergic neurons than glutamatergic neurons in response to acidosis.

    Liu, Hua; Li, Fang; Wang, Chunyan; Su, Zhiqiang

    2016-05-25

    Acidosis impairs brain functions. Neuron-specific mechanisms underlying acidosis-induced brain dysfunction remain elusive. We studied the sensitivity of cortical GABAergic neurons and glutamatergic neurons to acidosis by whole-cell recording in brain slices. The acidification to the neurons was induced by perfusing artificial cerebral spinal fluid with lower pH. This acidification impairs excitability and synaptic transmission in the glutamatergic and GABAergic neurons. Acidosis impairs spiking capacity in the GABAergic neurons more than in the glutamatergic neurons. Acidosis also strengthens glutamatergic synaptic transmission and attenuates GABAergic synaptic transmission on the GABAergic neurons more than the glutamatergic neurons, which results in the functional impairment of these GABAergic neurons. This acidosis-induced dysfunction predominantly in the cortical GABAergic neurons drives the homeostasis of neuronal networks toward overexcitation and exacerbates neuronal impairment.

  3. METABOLIC ACIDOSIS--AN UNDERESTIMATED PROBLEM AFTER KIDNEY TRANSPLANTATION?.

    Katalinić, Lea; Blaslov, Kristina; Đanić-Hadžibegović, Ana; Gellineo, Lana; Kes, Petar; Jelaković, Bojan; Basić-Jukić, Nikolina

    2015-12-01

    Despite prolonged survival and better quality of life as compared to dialysis, kidney transplantation frequently presents with a complex set of medical issues that require intensive management to protect graft function. Metabolic acidosis has an impact on several metabolic complications such as mineral and muscle metabolism, nutritional status and anemia. It may also have an effect on graft function, possibly through the stimulation of adaptive mechanisms aimed at maintaining acid-base homeostasis. We investigated current practice in the evaluation of metabolic acidosis at one of the largest transplant centers in the Eurotransplant region. Adult renal transplant recipients having received allograft from January 2011 to August 2012 were included in the investigation. We recorded the frequency of measuring the parameters of venous blood gas analysis, as well as creatinine and urea levels, creatinine clearance, proteinuria, calcium, phosphate and potassium blood levels, body mass index and the time spent on dialysis prior to kidney transplantation. Out of 203 patients who had received renal allograft at our institution during the observed period, 191 (124 males and 67 females, age range from 18 to 77 years) were enrolled in the study. Of these, only 92 (48.167%) patients had parameters of venous blood gas analysis measured at some time after kidney transplantation. Acid-base status was determined more often in males (77 males vs. 22 females, p = 0.001). Patients with pH/blood gas analysis performed were found to have significantly higher creatinine and urea levels and significantly lower creatinine clearance (p Metabolic acidosis is a very important clinical issue that needs to be monitored in every transplant recipient. Its effects on graft function, nutritional status, anemia and bone mass are complex but can be successfully managed. Our study showed metabolic acidosis to be linked with significantly higher creatinine and urea levels, decreased creatinine clearance

  4. Distal renal tubular acidosis without renal impairment after use of tenofovir: a case report

    2016-01-01

    Background Tenofovir, one of antiretroviral medication to treat human immunodeficiency virus (HIV) infection, is known to cause proximal renal tubular acidosis such as Fanconi syndrome, but cases of distal renal tubular acidosis had never been reported. Case presentation A 20-year-old man with HIV infection developed nausea and vomiting without diarrhea after starting antiretroviral therapy. Arterial blood gas revealed non-anion-gap metabolic acidosis and urine test showed positive urine anio...

  5. Functional interaction between responses to lactic acidosis and hypoxia regulates genomic transcriptional outputs

    Tang, Xiaohu; Lucas, Joseph E.; Chen, Julia Ling-Yu; LaMonte, Gregory; Wu, Jianli; Wang, Michael Changsheng; Koumenis, Constantinos; Chi, Jen-Tsan

    2011-01-01

    Within solid tumor microenvironments, lactic acidosis and hypoxia each have powerful effects on cancer pathophysiology. However, the influence that these processes exert on each other is unknown. Here we report that a significant portion of the transcriptional response to hypoxia elicited in cancer cells is abolished by simultaneous exposure to lactic acidosis. In particular, lactic acidosis abolished stabilization of HIF-1α protein which occurs normally under hypoxic conditions. In contrast,...

  6. In-vitro activation of complement system by lactic acidosis in newborn and adults

    Friederike Hecke

    2001-01-01

    Full Text Available Introduction: Complement activation occurs secondary to a variety of external stimuli. Lactic acidosis has been previously shown to activate the complement factors C3a and C5a. In the present investigation we examined the differential effect of lactic acidosis on anaphylatoxin levels in cord and adult blood. Furthermore we aimed to determine if the entire complement cascade could be activated by lactic acidosis.

  7. Hemodynamic consequences of severe lactic acidosis in shock states: from bench to bedside

    Kimmoun, Antoine; Novy, Emmanuel; Auchet, Thomas; Ducrocq, Nicolas; Levy, Bruno

    2015-01-01

    Lactic acidosis is a very common biological issue for shock patients. Experimental data clearly demonstrate that metabolic acidosis, including lactic acidosis, participates in the reduction of cardiac contractility and in the vascular hyporesponsiveness to vasopressors through various mechanisms. However, the contributions of each mechanism responsible for these deleterious effects have not been fully determined and their respective consequences on organ failure are still poorly defined, part...

  8. Postoperative metabolic acidosis following the minimally invasive radiofrequency maze procedure

    Raymond Patrick Hom

    2016-01-01

    Full Text Available Purpose: Atrial fibrillation (AF is the most common arrhythmia treated in the world. While medical treatment with antiarrhythmic drugs remains the primary treatment modality, symptomatic refractory AF often requires treatment with a catheter or surgical ablation. One minimally invasive therapy is the Mini-Maze procedure, which utilizes epicardial radiofrequency ablation via a subxiphoid approach to rid the heart of arrhythmogenic atrial foci without a median sternotomy or cardiopulmonary bypass. The goal of this retrospective cohort study was to identify clinical factors associated with metabolic acidosis following the Mini-Maze procedure. Materials and Methods: After Institutional Review Board approval, we studied patients undergoing the Mini-Maze procedure, off-pump coronary artery bypass grafting or patients conventional Cox-Maze on cardiopulmonary bypass. The first base deficit value obtained in the Intensive Care Unit was used as a measure of metabolic acidosis. Using logistic regression with Akaike information criteria, we analyzed preoperative, intraoperative, and postoperative data to determine the factors associated with changes in base deficit. Results: A multivariable model using stepwise selection demonstrated that diabetes mellitus and weight were associated with a decrease in the base deficit by 2.87 mEq/L (95% CI: −5.55-−0.19 and 0.04 mEq/L (95%CI: −0.08, 0.004, respectively. Furthermore, creatinine was associated with a 1.57 mEq/L (95% CI: 0.14, 2.99 increase in the base deficit. Conclusion: The Mini-Maze procedure was not associated with postoperative metabolic acidosis. Instead, nondiabetic patients and patients with higher creatinine were associated with greater base deficits after undergoing cardiac surgery.

  9. Acidosis slows electrical conduction through the atrio-ventricular node

    Ashley Muir Nisbet

    2014-06-01

    Full Text Available Acidosis affects the mechanical and electrical activity of mammalian hearts but comparatively little is known about its effects on the function of the atrio-ventricular node (AVN. In this study, the electrical activity of the epicardial surface of the left ventricle of isolated Langendorff-perfused rabbit hearts was examined using optical methods. Perfusion with hypercapnic Tyrode’s solution (20% CO2, pH 6.7 increased the time of earliest activation (Tact from 100.5+7.9 to 166.1+7.2ms (n=8 at a pacing cycle length (PCL of 300ms (37oC. Tact increased at shorter PCL, and the hypercapnic solution prolonged Tact further: at 150ms PCL, Tact was prolonged from 131.0+5.2 to 174.9+16.3ms. 2:1 AVN block was common at shorter cycle lengths. Atrial and ventricular conduction times were not significantly affected by the hypercapnic solution suggesting that the increased delay originated in the AVN. Isolated right atrial preparations were superfused with Tyrode’s solutions at pH 7.4 (control, 6.8 and 6.3. Low pH prolonged the atrial-Hisian (AH interval, the effective and functional refractory periods and Wenckebach cycle length significantly. Complete AVN block occurred in 6 out of 9 preparations. Optical imaging of conduction at the AV junction revealed increased conduction delay in the region of the AVN, with less marked effects in atrial and ventricular tissue. Thus acidosis can dramatically prolong the AVN delay, and in combination with short cycle lengths, this can cause partial or complete AVN block and is therefore implicated in the development of brady-arrhythmias in conditions of local or systemic acidosis.

  10. Effects of intracellular acidosis on endothelial function: an overview.

    Crimi, Ettore; Taccone, Fabio Silvio; Infante, Teresa; Scolletta, Sabino; Crudele, Valeria; Napoli, Claudio

    2012-04-01

    The endothelium represents the largest functional organ in the human body playing an active role in vasoregulation, coagulation, inflammation, and microvascular permeability. Endothelium contributes to maintain vascular integrity, intravascular volume, and tissue oxygenation promoting inflammatory network response for local defense and repair. Acid-basis homeostasis is an important physiologic parameter that controls cell function, and changes in pH can influence vascular tone by regulating endothelium and vascular smooth muscle cells. This review presents a current perspective of the effects of intracellular acidosis on the function and the basic regulatory mechanisms of endothelial cells.

  11. Severe lactic acidosis after an iatrogenic propylene glycol overdose.

    Zosel, Amy; Egelhoff, Elizabeth; Heard, Kennon

    2010-02-01

    Propylene glycol is a diluent found in many intravenous and oral drugs, including phenytoin, diazepam, and lorazepam. Propylene glycol is eliminated from the body by oxidation through alcohol dehydrogenase to form lactic acid. Under normal conditions, the body converts lactate to pyruvate and metabolizes pyruvate through the Krebs cycle. Lactic acidosis has occurred in patients, often those with renal dysfunction, who were receiving prolonged infusions of drugs that contain propylene glycol as a diluent. We describe a 50-year-old man who experienced severe lactic acidosis after receiving an accidental overdose of lorazepam, which contains propylene glycol. The patient was acutely intoxicated, with a serum ethanol concentration of 406 mg/dl. He had choked on a large piece of meat and subsequently experienced pulseless electrical activity with ventricular fibrillation cardiac arrest. He was brought to the emergency department; within 2 hours, he was admitted to the intensive care unit for initiation of the hypothermia protocol. The patient began to experience generalized tonic-clonic seizures 12 hours later, which resolved after several boluses of lorazepam. A lorazepam infusion was started; however, it was inadvertently administered at a rate of 2 mg/minute instead of the standard rate of 2 mg/hour. Ten hours later, the administration error was recognized and the infusion stopped. The patient's peak propylene glycol level was 659 mg/dl, pH 6.9, serum bicarbonate level 5 mEq/L, and lactate level 18.6 mmol/L. Fomepizole was started the next day and was continued until hospital day 3. Continuous renal replacement therapy was started and then replaced with continuous venovenous hemofiltration (CVVH) for the remainder of the hospital stay. The patient's acidosis resolved by day 3, when his propylene glycol level had decreased to 45 mg/dl. Fomepizole was discontinued, but the patient's prognosis was poor (anoxic brain injury); thus care was withdrawn and the patient died

  12. Renal histology and immunopathology in distal renal tubular acidosis.

    Feest, T G; Lockwood, C M; Morley, A R; Uff, J S

    1978-11-01

    Renal biospy studies are reported from 10 patients with distal renal tubular acidosis (DRTA). On the biopsies from 6 patients who had associated immunological abnormalities immunofluorescent studies for immunoglobulins, complement, and fibrin were performed. Interstitial cellular infiltration and fibrosis were common findings in patients with and without immunological abnormalities, and were usually associated with nephrocalcinosis and/or recurrent urinary infection. No immune deposits were demonstrated in association with the renal tubules. This study shows that DRTA in immunologically abnormal patients is not caused by tubular deposition of antibody or immune complexes. The possibility of cell mediated immune damage is discussed.

  13. A Fatal Case of Metformin-associated Lactic Acidosis.

    Ozeki, Toshikazu; Kawato, Rui; Watanabe, Mitsuru; Minatoguchi, Shun; Murai, Yukari; Ryuge, Akihiro; Takasugi, Koji; Hamada, Takuya; Oyama, Yukako; Nomura, Atsushi; Tomino, Tatsuhito; Shimizu, Hideaki; Fujita, Yoshiro

    2016-01-01

    A 72-year-old woman with a history of type 2 diabetes mellitus was brought to the ER with metformin-associated lactic acidosis. She received continuous hemofiltration and hemodialysis, but the laboratory analyses showed no improvement. She died 11 hours after admission. Metformin is minimally bound to proteins and is readily dialyzable, but a prolonged period of dialysis is required, because metformin has a very large distribution volume and is distributed to multiple compartments. The peak blood metformin level was 432 mg/L in this case, which is one of the highest metformin concentrations ever reported, and eight hours of hemodialysis were not sufficient to reduce the serum level.

  14. Metformin-associated lactic acidosis in a patient with normal kidney function.

    van Sloten, T T; Pijpers, E; Stehouwer, C D A; Brouwers, M C G J

    2012-06-01

    The existence of metformin-induced lactic acidosis has been questioned, in particular in the absence of specific risk factors such as impaired renal function. This report describes the presence of lactic acidosis in a patient with normal kidney function and normal doses of metformin. Subsequent positive rechallenge with metformin confirms causality.

  15. A perspective on Serum Lactic acid, Lactic Acidosis in a Critical Care Unit

    Agela A.Elbadri

    2013-06-01

    Full Text Available Breast cancer is one of the major surgical problems encountered in Libya. Lactic acidosis is a universal complication in breast cancer patients and can be considered a possible prognostic marker. Therefore, it will be beneficial to correctly understand and review the biochemistry underlying lactic acidosis and its possible significance as a prognostic marker in critical care patients, including breast cancer.

  16. Metformin and lactic acidosis : cause or coincidence? A review of case reports

    Stades, AME; Heikens, JT; Erkelens, DW; Holleman, F; Hoekstra, JBL

    2004-01-01

    Objective. Metformin has been associated with the serious side-effect lactic acidosis. However, it remains unclear whether the use of metformin was a cause or a coincidence in lactic acidosis. Design. A literature search of the Index Medicus (1959-66) and of the databases Embase, Medline, Medline Ex

  17. Reality of severe metformin-induced lactic acidosis in the absence of chronic renal impairment.

    Bruijstens, L.A.; Luin, M. van; Buscher-Jungerhans, P.M.; Bosch, F.H.

    2008-01-01

    BACKGROUND: Lactic acidosis in metformin use is a widely recognised but rare side effect. Case reports usually describe elderly patients with conditions which in themselves can cause lactic acidosis or with known contraindications to metformin. We present cases of an elderly woman, a younger woman a

  18. Everything you need to know about distal renal tubular acidosis in autoimmune disease

    T. Both (Tim); R. Zietse (Bob); E.J. Hoorn (Ewout); P.M. van Hagen (Martin); V.A.S.H. Dalm (Virgil); J.A.M. van Laar (Jan); P.L.A. van Daele (Paul)

    2014-01-01

    textabstractRenal acid-base homeostasis is a complex process, effectuated by bicarbonate reabsorption and acid secretion. Impairment of urinary acidification is called renal tubular acidosis (RTA). Distal renal tubular acidosis (dRTA) is the most common form of the RTA syndromes. Multiple pathophysi

  19. Anoxia and Acidosis Tolerance of the Heart in an Air-Breathing Fish (Pangasianodon hypophthalmus).

    Joyce, William; Gesser, Hans; Bayley, Mark; Wang, Tobias

    2015-01-01

    Air breathing has evolved repeatedly in fishes and may protect the heart during stress. We investigated myocardial performance in the air-breathing catfish Pangasianodon hypophthalmus, a species that can withstand prolonged exposure to severe hypoxia and acidosis. Isometric ventricular preparations were exposed to anoxia, lactic acidosis, hypercapnic acidosis, and combinations of these treatments. Ventricular preparations were remarkably tolerant to anoxia, exhibiting an inotropic reduction of only 40%, which fully recovered during reoxygenation. Myocardial anoxia tolerance was unaffected by physiologically relevant elevations of bicarbonate concentration, in contrast to previous results in other fishes. Both lactic acidosis (5 mM; pH 7.10) and hypercapnic acidosis (10% CO2; pH 6.70) elicited a biphasic response, with an initial and transient decrease in force followed by overcompensation above control values. Spongy myocardial preparations were significantly more tolerant to hypercapnic acidosis than compact myocardial preparations. While ventricular preparations were tolerant to the isolated effects of anoxia and acidosis, their combination severely impaired myocardial performance and contraction kinetics. This suggests that air breathing may be a particularly important myocardial oxygen source during combined anoxia and acidosis, which may occur during exercise or environmental stress.

  20. [Metformin-associated lactic acidosis and acute kidney injury].

    Greco, Paolo; Regolisti, Giuseppe; Antoniotti, Riccardo; Maccari, Caterina; Parenti, Elisabetta; Corrado, Silvia; Fiaccadori, Enrico

    2016-01-01

    Metformin is recommended as the treatment of choice in patients with type 2 diabetes mellitus because of its efficacy, general tolerability and low cost. Recent guidelines have extended the use of metformin to patients with Chronic Kidney Disease (CKD) up to stage III. However, in the recent literature, cases of MALA (metformin-associated lactic acidosis) are increasingly reported. MALA is the most dangerous side effect of the drug, with an incidence rate of 2-9 cases per 100000 person-years of exposure. We report on two patients with accidental metformin overdose, severe lactic acidosis and acute kidney injury. In both cases, the usual dose of metformin was inappropriate with respect to the level of kidney dysfunction (CKD stage III). As both patients met the criteria for renal replacement therapy in metformin poisoning, they were treated effectively with sustained low-efficiency dialysis until normalization of serum lactate and bicarbonate values. Clinical status and kidney function improved and both patients could be discharged from the hospital.

  1. Ruminal Acidosis in Feedlot: From Aetiology to Prevention

    Joaquín Hernández

    2014-01-01

    Full Text Available Acute ruminal acidosis is a metabolic status defined by decreased blood pH and bicarbonate, caused by overproduction of ruminal D-lactate. It will appear when animals ingest excessive amount of nonstructural carbohydrates with low neutral detergent fiber. Animals will show ruminal hypotony/atony with hydrorumen and a typical parakeratosis-rumenitis liver abscess complex, associated with a plethora of systemic manifestations such as diarrhea and dehydration, liver abscesses, infections of the lung, the heart, and/or the kidney, and laminitis, as well as neurologic symptoms due to both cerebrocortical necrosis and the direct effect of D-lactate on neurons. In feedlots, warning signs include decrease in chewing activity, weight, and dry matter intake and increase in laminitis and diarrhea prevalence. The prognosis is quite variable. Treatment will be based on the control of systemic acidosis and dehydration. Prevention is the most important tool and will require normalization of ruminal pH and microbiota. Appropriate feeding strategies are essential and involve changing the dietary composition to increase neutral detergent fiber content and greater particle size and length. Appropriate grain processing can control the fermentation rate while additives such as prebiotics or probiotics can help to stabilize the ruminal environment. Immunization against producers of D-lactate is being explored.

  2. Ruminal acidosis in feedlot: from aetiology to prevention.

    Hernández, Joaquín; Benedito, José Luis; Abuelo, Angel; Castillo, Cristina

    2014-01-01

    Acute ruminal acidosis is a metabolic status defined by decreased blood pH and bicarbonate, caused by overproduction of ruminal D-lactate. It will appear when animals ingest excessive amount of nonstructural carbohydrates with low neutral detergent fiber. Animals will show ruminal hypotony/atony with hydrorumen and a typical parakeratosis-rumenitis liver abscess complex, associated with a plethora of systemic manifestations such as diarrhea and dehydration, liver abscesses, infections of the lung, the heart, and/or the kidney, and laminitis, as well as neurologic symptoms due to both cerebrocortical necrosis and the direct effect of D-lactate on neurons. In feedlots, warning signs include decrease in chewing activity, weight, and dry matter intake and increase in laminitis and diarrhea prevalence. The prognosis is quite variable. Treatment will be based on the control of systemic acidosis and dehydration. Prevention is the most important tool and will require normalization of ruminal pH and microbiota. Appropriate feeding strategies are essential and involve changing the dietary composition to increase neutral detergent fiber content and greater particle size and length. Appropriate grain processing can control the fermentation rate while additives such as prebiotics or probiotics can help to stabilize the ruminal environment. Immunization against producers of D-lactate is being explored.

  3. Acidosis láctica grave asociada a intoxicación por metformina Severe lactic acidosis associated to metformin intoxication

    M. S. Holanda Peña

    2007-02-01

    Full Text Available La metformina es una biguanida ampliamente utilizada en el tratamiento de la diabetes mellitus tipo II. Entre los efectos secundarios derivados de su empleo destaca por su baja frecuencia de presentación pero potencial gravedad la acidosis láctica. El diagnóstico de la misma se basa generalmente en la coexistencia de la acidosis láctica en un paciente en tratamiento con metformina con uno o mas factores de riesgo para la presentación de la misma. El desarrollo de acidosis láctica en relación con el tratamiento con metformina conlleva una mortalidad que oscila entre 50-80%.Metformin is a biguanide extensively used in the treatment of type II diabetes mellitus. Between the nocive effects of the metformin emphasizes tha lactic acidosis because of its low frecuency but potential severity. The diagnosis of the poisoning due to metformin is based on the coexistence of lactic acidosis and one or more of the risk factors. The development of lactic acidosis in metformin poisoning is associated to a range of 50-80% of mortality.

  4. Acidosis y coma en el Diabético

    Alfredo Jácome Roca

    1992-12-01

    Full Text Available

    Definición. La cetoacidosis diabética (CADy la alcohólica, la acidosis láctica y el síndrome hiperosmolar hiperglucémico (SHH a menudo se sobreponen en grado considerable, por lo que los revisaremos en conjunto. Definiremos la cetoacidosLs diabética como la descompensación grave de la diabetes, la emergencia endocrina más común caracterizada por un desequilibrio ácido-básico, de líquidos y electrolitos, asociado a una diuresis osmótica y catabolismo de las grasas por hiperglucemia insulino- deficiente.

    El síndrome hiperosmolar hiperglucémico es de comienzo lento y se caracteriza por trastorno del estado de conciencia, deshidratación profunda e hiperglucemia sin cetoacidosis. La cetoacidosLs alcohólica es un desequilibrio ácido-básico con deshidratación en alcohólicos, mujeres por lo común, no necesariamente diabéticas, aunque puede haber moderada hiperglucemia. La acidos Ls láctica puede ser complicación de un estado de shock y/o deshidratación severa, o de ingesta abundante de alcohol, lo que también puede llevar a hiperuricemia y gota.

    Signos y síntomas. Malestar general, astenia, anorexia, náusea, vómito, dolor abdominal con somnolencia, estupor y/o coma, pueden ser manifestaciones de cualquiera de las entidades arriba mencionadas.

    Sin embargo, aunque tanto en CADcomo en SHH hay signos de deshidratación (sequedad de mucosa con piel seca sin turgencia, ojos hundidos, en el primero hay náusea, vómito y respiración acidótica (rápida y profunda, lo que generalmente falta en el segundo. ElCADes de niños y adultos jóvenes o maduros, con función cardio-renal aceptable mientras que el SHHes más de ancianos, a menudo hipertensos con fallas renal o cardíaca, hemiparéticos, que pueden consultar por convulsiones focales. No siempre el paciente es reconocido como diabético, sobre todo en SHH.

    Lapoliuria y la polidipsia caracterizan a la acidosis diabética y al s

  5. Clinical significance of the fractional excretion of anions in metabolic acidosis.

    Kim, H Y; Han, J S; Jeon, U S; Joo, K W; Earm, J H; Ahn, C; Kim, S; Lee, J S; Kim, G H

    2001-06-01

    The fractional excretion of anions has been proposed as a new index for the differential diagnosis of metabolic acidosis, identifying the properties of the conjugate base by examining the renal handling of the anion. Here, we investigated clinical significance of the fractional excretion of anions in pathophysiologic diagnosis of metabolic acidosis by measuring urine ammonium (NH4+) excretion, the ratio of A plasma anion gap/delta plasma HCO3- concentration (deltaAG/deltaHCO3-), and fractional excretion of anions in three different groups of metabolic acidosis: acid overproduction (8 patients with lactic acidosis, 8 with diabetic ketoacidosis, 3 with hippuric acidosis following glue sniffing), acid underexcretion (10 patients with chronic renal failure) and normal controls (10 normal volunteers who underwent 3-day NH4Cl loading). As expected, urine NH4+ excretion was higher in overproduction acidosis than in acid-loaded normal controls (88.1 +/- 12.3 vs. 54.0 +/- 3.7 mmol/day, p anions had no difference between overproduction acidosis and chronic renal failure (41.2 +/- 42.8% vs. 41.0 +/- 8.1%). However, the fractional excretion of anions showed significant differences between the subgroups in acid overproduction (lactic acidosis, 4.7 +/- 0.3%; diabetic ketoacidosis, 45.8 +/- 3.1%; hippuric acidosis, 126.0 +/- 14.4%; p anions and the ratio of plasma deltaAG/deltaHCO3- (r2 =-0.89, p anions may provide a useful clue to the differential diagnosis of metabolic acidosis caused by acid overproduction.

  6. Ethylene glycol toxicity presenting with non-anion gap metabolic acidosis.

    Soghoian, Sari; Sinert, Richard; Wiener, Sage W; Hoffman, Robert S

    2009-01-01

    Ethylene glycol classically produces an elevated anion gap metabolic acidosis. We report a series of patients with ethylene glycol toxicity with a component of non-anion gap metabolic acidosis without known associated confounding factors. A retrospective review of Poison Control Center records were searched more than 8 years (2000-2007) for ethylene glycol and antifreeze. Cases were reviewed and excluded for miscoding, information calls, animal exposures, or non-ingestion exposures. The bicarbonate gap, or delta ratio (DR), was calculated using the formula: DR = (AG - 12)/[24 - measured serum where anion gap (AG) = [Na(+)] - [Cl(-)] - , all in mEq/l. Non-anion gap metabolic acidosis was considered present when the DR metabolic acidosis at presentation. Their calculated anion gap was 14-28, and measured serum ranged from 2-20 mEq/l. A normal anion gap was present in two patients who presented with non-anion gap metabolic acidosis. The DR ranged from 0.28-0.95. Seven out of 14 patients with non-anion gap metabolic acidosis had elevated serum [Cl(-)]. In the other cases, no explanation for the non-anion gap metabolic acidosis could be determined. The absence of a significant anion gap elevation in the setting of metabolic acidosis after ethylene glycol ingestion without other confounding factors (such as ethanol, lithium carbonate or bromide) has not previously been recognized. Clinicians should be aware of the potential for non-anion gap metabolic acidosis in patients with ethylene glycol toxicity, and should not exclude the diagnosis in patients who present with a non-anion gap metabolic acidosis. Further study is needed to determine the mechanisms by which this occurs.

  7. Metabolic acidosis increases fibroblast growth factor 23 in neonatal mouse bone.

    Krieger, Nancy S; Culbertson, Christopher D; Kyker-Snowman, Kelly; Bushinsky, David A

    2012-08-01

    Fibroblast growth factor 23 (FGF23) significantly increases with declining renal function, leading to reduced renal tubular phosphate reabsorption, decreased 1,25-dihydroxyvitamin D, and increased left ventricular hypertrophy. Elevated FGF23 is associated with increased mortality. FGF23 is synthesized in osteoblasts and osteocytes; however, the mechanisms by which it is regulated are not clear. Patients with chronic kidney disease have decreased renal acid excretion leading to metabolic acidosis, which has a direct effect on bone cell activity. We hypothesized that metabolic acidosis would directly increase bone cell FGF23 production. Using cultured neonatal mouse calvariae, we found that metabolic acidosis increased medium FGF23 protein levels as well as FGF23 RNA expression at 24 h and 48 h compared with incubation in neutral pH medium. To exclude that the increased FGF23 was secondary to metabolic acidosis-induced release of bone mineral phosphate, we cultured primary calvarial osteoblasts. In these cells, metabolic acidosis increased FGF23 RNA expression at 6 h compared with incubation in neutral pH medium. Thus metabolic acidosis directly increases FGF23 mRNA and protein in mouse bone. If these results are confirmed in humans with chronic kidney disease, therapeutic interventions to mitigate acidosis, such as bicarbonate administration, may also lower levels of FGF23, decrease left ventricular hypertrophy, and perhaps even decrease mortality.

  8. [Does acidosis in brain play a role in Alzheimer's disease?].

    Pirchl, Michael; Humpel, Christian

    2009-01-01

    Alzheimer's disease is characterized by beta-amyloid plaques, tau pathology, cell death of cholinergic neurons, inflammatory processes and cerebrovascular damage. The reasons for the development of this chronic disease are not known yet. We hypothesize that chronic long lasting mild damage of the cerebrovascular brain capillaries cause hypoperfusion, acidosis and neurodegeneration, and induces a cell death cascade with beta-amyloid dysfunction and tau-pathology and inflammation. Vascular risk factors, such as hyperhomocysteinemia or hypercholesterolemia, may play a role in this process. The accumulation of chronic silent strokes may cause cognitive defects as seen in vascular dementia and Alzheimer's disease. This summary tries to link the different events, which occur in Alzheimer's disease, focusing on the cerebrovascular hypothesis.

  9. Acute starvation in pregnancy: a cause of severe metabolic acidosis.

    Patel, A; Felstead, D; Doraiswami, M; Stocks, G M; Waheed, U

    2011-07-01

    We report a case of starvation-induced metabolic ketoacidosis in a previously healthy 29-year-old, nulliparous woman at 32 weeks of gestation. She was admitted to hospital with mild preeclampsia associated with persistent nausea and vomiting that progressed to severe preeclampsia requiring urgent control of hypertension before caesarean delivery. Prolonged and severe vomiting limited oral caloric intake and led to starvation ketoacidosis, characterised by ketonuria and a raised anion gap metabolic acidosis that required intensive care support. Despite significant metabolic derangement the patient appeared clinically well. Intravascular volume was replenished. Fluid restriction used as part of our preeclampsia treatment regimen delayed the therapeutic administration of sufficient dextrose, which rapidly corrected her metabolic derangement when commenced after delivery. Electrolyte supplementation was given to prevent re-feeding syndrome. Both mother and baby were discharged without sequelae.

  10. Acidosis Activates Endoplasmic Reticulum Stress Pathways through GPR4 in Human Vascular Endothelial Cells

    Lixue Dong

    2017-01-01

    Full Text Available Acidosis commonly exists in the tissue microenvironment of various pathophysiological conditions such as tumors, inflammation, ischemia, metabolic disease, and respiratory disease. For instance, the tumor microenvironment is characterized by acidosis and hypoxia due to tumor heterogeneity, aerobic glycolysis (the “Warburg effect”, and the defective vasculature that cannot efficiently deliver oxygen and nutrients or remove metabolic acid byproduct. How the acidic microenvironment affects the function of blood vessels, however, is not well defined. GPR4 (G protein-coupled receptor 4 is a member of the proton-sensing G protein-coupled receptors and it has high expression in endothelial cells (ECs. We have previously reported that acidosis induces a broad inflammatory response in ECs. Acidosis also increases the expression of several endoplasmic reticulum (ER stress response genes such as CHOP (C/EBP homologous protein and ATF3 (activating transcription factor 3. In the current study, we have examined acidosis/GPR4- induced ER stress pathways in human umbilical vein endothelial cells (HUVEC and other types of ECs. All three arms of the ER stress/unfolded protein response (UPR pathways were activated by acidosis in ECs as an increased expression of phosphorylated eIF2α (eukaryotic initiation factor 2α, phosphorylated IRE1α (inositol-requiring enzyme 1α, and cleaved ATF6 upon acidic pH treatment was observed. The expression of other downstream mediators of the UPR, such as ATF4, ATF3, and spliced XBP-1 (X box-binding protein 1, was also induced by acidosis. Through genetic and pharmacological approaches to modulate the expression level or activity of GPR4 in HUVEC, we found that GPR4 plays an important role in mediating the ER stress response induced by acidosis. As ER stress/UPR can cause inflammation and cell apoptosis, acidosis/GPR4-induced ER stress pathways in ECs may regulate vascular growth and inflammatory response in the acidic

  11. Effect of acidosis on skeletal muscle metabolism with and without propranolol.

    Barclay, J K; Graham, T E; Wolfe, B R; Van Dijk, J; Wilson, B A

    1990-07-01

    Does the stimulatory effect of circulating catecholamines counteract the inhibitory effect of acidosis on skeletal muscle metabolism? To investigate this possibility, we studied gastrocnemii in dogs breathing either air (n = 10) or 4% carbon dioxide in air (n = 10) at rest and during contractions. In five dogs from each group, we infused propranolol into the arterial supply of the right and left muscles for 40 min. After 30 min of infusion, the left muscle was stimulated at 3 Hz for 10 min. During the 10th min of contractions, we removed and froze both muscles in liquid nitrogen. Oxygen uptake and blood flow to the left muscle prior to or during stimulation was not affected by acidosis either with or without propranolol. Glycogen concentration in resting muscle was unaffected by acidosis with or without propranolol. There was an acidosis related decrease of approximately 50% in the glycolytic intermediates (glucose 6-phosphate, fructose 1,6-diphosphate, alpha-glycerol phosphate, and dihydroxyacetone phosphate) in unstimulated muscles without beta-blockade. At rest, acidosis decreased muscle lactate by 50% with and 64% without propranolol, but lactate release was decreased only with acidosis without propranolol (1.4-0.1 mumols/kg.s). Acidosis without propranolol had no effect on the changes in glycogen concentration or the change in the concentration of glycolytic intermediates resulting from contractions. In beta-blocked muscle, the difference between stimulated and unstimulated concentrations of glycogen and glycolytic intermediates including lactate was 20-50% smaller with acidosis. Thus, with beta-blockade, the acidotic effects at rest disappeared and an inhibition of the metabolic adjustment to contractions appeared, indicating that circulating catecholamines do modify some metabolic effects of acidosis.

  12. Metabolic acidosis-induced hypercalcemia in an azotemic patient with primary hyperparathyroidism.

    Rastegar, Mandana; Levine, Barton S; Felsenfeld, Arnold J

    2014-06-01

    A 58-year-old man with Stage 3b chronic kidney disease and primary hyperparathyroidism treated with cinacalcet was admitted for acute cholecystitis. A cholecystostomy tube was placed, estimated glomerular filtration rate decreased, metabolic acidosis developed and ionized calcium increased from 1.33 to 1.76 mM despite cinacalcet administration. A sodium bicarbonate infusion corrected the metabolic acidosis restoring ionized calcium to normal despite no improvement in renal function. The correlation between the increase in serum bicarbonate and decrease in ionized calcium was r = -0.93, P metabolic acidosis increasing calcium efflux from bone while renal failure decreased the capacity to excrete calcium.

  13. Fatal lactic acidosis possibly related to ganciclovir therapy in a renal transplant patient?

    Wittebole, Xavier; Morelle, Johann; Vincent, Marie-Françoise; Hantson, Philippe

    2015-01-01

    Ganciclovir is widely prescribed in renal transplant patients for the prevention or treatment of herpes and cytomegalovirus (CMV) infections. Side-effects are usually represented by hematological disorders, and particularly leucopenia. We report a case of severe and fatal lactic acidosis developing in a 76-year-old renal transplant woman, a few days after ganciclovir has been introduced to treat CMV pneumonia. Usual etiologies of lactic acidosis were ruled out. A high lactate/pyruvate molecular ratio was suggestive of a respiratory chain dysfunction. With the analogy to nucleoside analogues-related lactic acidosis, we suggest that ganciclovir may exceptionally be responsible for respiratory chain dysfunction and subsequent lactic acidosis, and we discuss potential risk factors in our patient. PMID:25810616

  14. /sup 32/P studies into phosphate metabolism of cattle with metabolic acidosis

    Lachmann, G.; Pfueller, K.; Bier, H.; Mueller, D.; Rummel, G. (Karl-Marx-Universitaet, Leipzig (German Democratic Republic). Sektion Tierproduktion und Veterinaermedizin)

    1984-03-01

    Phosphorus balance and intraveneous injection of /sup 32/P into three bulls showed that hay diet was followed by excretion of only small amounts of phosphorus in the urine (1.5 g/die), with renal net base excretion being 35 mmol/l. Yet, the amounts of phosphorus excretion in urine were high (16.3 g/die) in conditions of metabolic acidosis due to cereal diet, with renal net acid excretion being 78 mmol/l. No negative balance was observed during three weeks of acidosis, in spite of high phosphaturia, since in cattle with acidosis the increase in renal excretion was offsetted by depression of endogenic fecal phosphorus. Endogenic fecal phosphorus accounted for 43% of phosphorus intake with hay diet but only for 7% with cereal diet. Hence, hyperphosphaturia is ruled out as a cause for the genesis of osteopathies in a condition of metabolic acidosis.

  15. Life threatening hyperkalemia and acidosis secondary to trimethoprim-sulfamethoxazole treatment.

    Margassery, S; Bastani, B

    2001-01-01

    We present a 77-year-old male with moderate chronic renal insufficiency from diabetic nephropathy who developed severe metabolic acidosis and life threatening hyperkalemia on treatment with regular dose of trimethoprim-sulfamethoxazole (TMP-SMZ) for urinary tract infection. The metabolic acidosis and hyperkalemia resolved upon appropriate medical intervention and discontinuation of TMP-SMZ. While hyperkalemia has commonly been reported with high dose of TMP-SMZ, severe metabolic acidosis is quite uncommon with regular dose TMP-SMZ. We emphasize that patients with renal tubular acidosis (RTA), renal insufficiency, aldosterone deficiency, old age with reduced renal mass and function, and angiotensin converting enzyme (ACE)-inhibitor therapy are at high risk of developing these severe and potentially life threatening complications.

  16. Acidosis-induced p38 MAPK activation and its implication in regulation of cardiac contractility

    Ming ZHENG; Rong HOU; Rui-ping XIAO

    2004-01-01

    AIM: To determine the possible role of pH in mediating activation of p38 mitogen-activated protein kinase (MAPK) and the consequent function of activated p38 MAPK in regulating cardiac contractility. METHODS: Adult rat cardiomyocytes were isolated and cultured. Low pH media was used to induce intracellular acidosis and contraction of single cardiomyocyte was measured. RESULTS: Phosphorylation of p38 MAPK was increased during ischemia, and pHi was decreased. Intracellular acidosis activated p38 MAPK to a similar level as ischemia. Inhibition of p38 MAPK activation by SB203580, a specific inhibitor of p38 MAPK, reversed acidosis-mediated reduction of myocyte contractility. CONCLUSION: In adult rat cardiomyocytes, intracellular acidification activated p38 MAPK and decreased cardiac contractility. Pretreatment of cardiomyocytes with SB203580 completely blocked p38 MAPK activation and partially reversed acidosis-mediated decline of cardiac contractility.

  17. ACIDOSIS LÁCTICA TIPO B1 SECUNDARIA A LINFOMA DE BURKITT.

    Jiménez Brenes, Natalia; Rojas Vega, Jason; Barguil Meza, Ibrahim

    2011-01-01

    Lactic acidosis is a rare complication of malignant neoplasms first described in patients with acute leukemia in 1963. Since then, there hasbeen seen more often, particularly in hematological malignancies and rarely in solid tumors. Wereport the case of a 53 years old male with lactacidosis B1 and gastric Burkitt lymphoma whowas admitted to the hospital with constitutionalsymptoms, weight loss, diarrhea and melena.Arterial blood gases revealed a metabolic acidosis with increased anion gap (pH...

  18. Enterolobium contortisiliquum is a cause of acute ruminal acidosis in sheep.

    Pupin, Rayane C; Leal, Paula V; Lima, Stephanie C; Melo, Gleice Kelli A; Pott, Arnildo; Araújo, Marcelo A; Barros, Claudio S L; Lemos, Ricardo A A

    2017-02-01

    The ingestion of pods of Enterolobium contortisiliquum is associated with digestive disturbances, photosensitivity and abortion in domestic ruminants. This experiment was designed to test the hypothesis that digestive disturbances in this toxicosis are really caused by acute ruminal acidosis. Three sheep fed large doses (10-15 g/kg/body weight [bw]) of E. contortisiliquum pods developed ruminal acidosis and were treated with sodium bicarbonate to try to control this metabolic disturbance, thus providing additional evidence of the involvement of ruminal acidosis in the pathogenesis of toxicosis. Two of the sheep died, and one recovered after treatment. In the two sheep that developed severe signs of ruminal acidosis, the values of blood lactate were 18 mg/dL and 196.88 mg/dL, indicating metabolic acidosis as the cause of death. Additionally, four sheep developed elevated serum levels of aspartate aminotransferase and gamma glutamyl transferase, indicating that the pods had hepatotoxic effects. Necropsy findings included the accentuation of the hepatic lobular pattern and multiple focally extensive red areas in the rumen mucosa and on the surface of the liver. Repeated ingestion of small doses induced tolerance but did not induce cumulative effects. Histopathologically, the epithelial mucosa of the rumen and reticulum exhibited swollen and vacuolated epithelia with intraepithelial pustules. Focal ulceration of the mucosa was also observed. Multifocal vacuolar degeneration of hepatocytes and scattered individual hepatocellular necrosis were evident in the liver. We concluded that the main clinical manifestation of intoxication by E. contortisiliquum pods in sheep was acute ruminal lactic acidosis and metabolic acidosis. Ingestion of repeated sublethal doses could stimulate proliferation of the ruminal fauna that degrades the sugar present in the pods, and thereby prevent the occurrence of ruminal acidosis. The plant is also hepatotoxic, and no abortions were

  19. Hyperchloremic metabolic acidosis following total gut irrigation with normal saline in pediatric patients: A rare occurrence

    Indu Bala

    2017-01-01

    Full Text Available Use of 0.9% sodium chloride for total gut irrigation (TGI through nasogastric route is an effective method of bowel preparation in children undergoing colorectal surgeries. TGI with normal saline (NS can result in nausea, vomiting, abdominal distension, and mild electrolyte imbalance; however, hyperchloremic metabolic acidosis has not been documented. We report two cases of hyperchloremic metabolic acidosis in children posted for colorectal surgery following TGI with NS who were successfully managed.

  20. Tubulointerstitial Nephritis Complicated by Fanconi Syndrome and Renal Tubular Acidosis Associated with three autoimmune diseases

    Io, Kumiko; Obata, Yoko; Nishino, Tomoya; Hirose, Misaki; Yamashita, Hiroshi; Uramatsu, Tadashi; Ichikawa, Tatsuki; Hayashi, Tomayoshi; Kawakami, Atsushi; Taguchi, Takashi; Kohno, Shigeru

    2013-01-01

    A 45-year-old woman experiencing back pain showed signs of metabolic acidosis and electrolyte imbalances. The results of blood and urine tests indicated Fanconi syndrome and renal tubular acidosis. An x-ray showed vertebral fractures, which were thought to responsible for the back pain. In addition, the patient had proteinuria and renal dysfunction; therefore, renal biopsy was performed, and tubulointerstitial nephritis (TIN) was diagnosed. While investigating TIN, primary biliary cirrhosis a...

  1. Metabolic Acidosis Treatment as Part of a Strategy to Curb Inflammation

    Tales Rubens de Nadai

    2013-01-01

    Full Text Available Abnormalities in systemic acid-base balance may induce significant changes in the immune response, and they may play a significant role in the development or maintenance of immune dysfunction. Different forms of acidosis (metabolic and respiratory and even different types of metabolic acidosis (hyperchloremic and lactic may produce different effects on immune function. If alkalization has, or not, some effect on inflammation control is still a matter of speculation. Studies concerning these subjects are limited justifying this paper.

  2. Metabolic Acidosis Treatment as Part of a Strategy to Curb Inflammation

    Tales Rubens de Nadai; Mariane Nunes de Nadai; Agnes Afrodite Sumarelli Albuquerque; Marco Tulio Menezes de Carvalho; Andrea Carla Celotto; Paulo Roberto Barbosa Evora

    2013-01-01

    Abnormalities in systemic acid-base balance may induce significant changes in the immune response, and they may play a significant role in the development or maintenance of immune dysfunction. Different forms of acidosis (metabolic and respiratory) and even different types of metabolic acidosis (hyperchloremic and lactic) may produce different effects on immune function. If alkalization has, or not, some effect on inflammation control is still a matter of speculation. Studies concerning these...

  3. Metabolic acidosis treatment as part of a strategy to curb inflammation.

    de Nadai, Tales Rubens; de Nadai, Mariane Nunes; Albuquerque, Agnes Afrodite Sumarelli; de Carvalho, Marco Tulio Menezes; Celotto, Andrea Carla; Evora, Paulo Roberto Barbosa

    2013-01-01

    Abnormalities in systemic acid-base balance may induce significant changes in the immune response, and they may play a significant role in the development or maintenance of immune dysfunction. Different forms of acidosis (metabolic and respiratory) and even different types of metabolic acidosis (hyperchloremic and lactic) may produce different effects on immune function. If alkalization has, or not, some effect on inflammation control is still a matter of speculation. Studies concerning these subjects are limited justifying this paper.

  4. Medullary nephrocalcinosis, distal renal tubular acidosis and polycythaemia in a patient with nephrotic syndrome

    Karunarathne Suneth

    2012-07-01

    Full Text Available Abstract Background Medullary nephrocalcinosis and distal renal tubular acidosis are closely associated and each can lead to the other. These clinical entities are rare in patients with nephrotic syndrome and polycythaemia is an unusual finding in such patients. We describe the presence of medullary nephrocalcinosis, distal renal tubular acidosis and polycythaemia in a patient with nephrotic syndrome due to minimal change disease. Proposed mechanisms of polycythaemia in patients with nephrotic syndrome and distal renal tubular acidosis include, increased erythropoietin production and secretion of interleukin 8 which in turn stimulate erythropoiesis. Case presentation A 22 year old Sri Lankan Sinhala male with nephrotic syndrome due to minimal change disease was investigated for incidentally detected polycythaemia. Investigations revealed the presence of renal tubular acidosis type I and medullary nephrocalcinosis. Despite extensive investigation, a definite cause for polycythaemia was not found in this patient. Treatment with potassium and bicarbonate supplementation with potassium citrate led to correction of acidosis thereby avoiding the progression of nephrocalcinosis and harmful effects of chronic acidosis. Conclusion The constellation of clinical and biochemical findings in this patient is unique but the pathogenesis of erythrocytosis is not clearly explained. The proposed mechanisms for erythrocytosis in other patients with proteinuria include increased erythropoietin secretion due to renal hypoxia and increased secretion of interleukin 8 from the kidney. This case illustrates that there may exist hitherto unknown connections between tubular and glomerular dysfunction in patients with nephrotic syndrome.

  5. Functional interaction between responses to lactic acidosis and hypoxia regulates genomic transcriptional outputs.

    Tang, Xiaohu; Lucas, Joseph E; Chen, Julia Ling-Yu; LaMonte, Gregory; Wu, Jianli; Wang, Michael Changsheng; Koumenis, Constantinos; Chi, Jen-Tsan

    2012-01-15

    Within solid tumor microenvironments, lactic acidosis, and hypoxia each have powerful effects on cancer pathophysiology. However, the influence that these processes exert on each other is unknown. Here, we report that a significant portion of the transcriptional response to hypoxia elicited in cancer cells is abolished by simultaneous exposure to lactic acidosis. In particular, lactic acidosis abolished stabilization of HIF-1α protein which occurs normally under hypoxic conditions. In contrast, lactic acidosis strongly synergized with hypoxia to activate the unfolded protein response (UPR) and an inflammatory response, displaying a strong similarity to ATF4-driven amino acid deprivation responses (AAR). In certain breast tumors and breast tumor cells examined, an integrative analysis of gene expression and array CGH data revealed DNA copy number alterations at the ATF4 locus, an important activator of the UPR/AAR pathway. In this setting, varying ATF4 levels influenced the survival of cells after exposure to hypoxia and lactic acidosis. Our findings reveal that the condition of lactic acidosis present in solid tumors inhibits canonical hypoxia responses and activates UPR and inflammation responses. Furthermore, these data suggest that ATF4 status may be a critical determinant of the ability of cancer cells to adapt to oxygen and acidity fluctuations in the tumor microenvironment, perhaps linking short-term transcriptional responses to long-term selection for copy number alterations in cancer cells.

  6. Differential diagnosis of nongap metabolic acidosis: value of a systematic approach.

    Kraut, Jeffrey A; Madias, Nicolaos E

    2012-04-01

    Nongap metabolic acidosis is a common form of both acute and chronic metabolic acidosis. Because derangements in renal acid-base regulation are a common cause of nongap metabolic acidosis, studies to evaluate renal acidification often serve as the mainstay of differential diagnosis. However, in many cases, information obtained from the history and physical examination, evaluation of the electrolyte pattern (to determine if a nongap acidosis alone or a combined nongap and high anion gap metabolic acidosis is present), and examination of the serum potassium concentration (to characterize the disorder as hyperkalemic or hypokalemic in nature) is sufficient to make a presumptive diagnosis without more sophisticated studies. If this information proves insufficient, indirect estimates or direct measurement of urinary NH(4)(+) concentration, measurement of urine pH, and assessment of urinary HCO(3)(-) excretion can help in establishing the diagnosis. This review summarizes current information concerning the pathophysiology of this electrolyte pattern and the value and limitations of all of the diagnostic studies available. It also provides a systematic and cost-effective approach to the differential diagnosis of nongap metabolic acidosis.

  7. Osteomalacia complicating renal tubular acidosis in association with Sjogren's syndrome.

    El Ati, Zohra; Fatma, Lilia Ben; Boulahya, Ghada; Rais, Lamia; Krid, Madiha; Smaoui, Wided; Maiz, Hedi Ben; Beji, Soumaya; Zouaghi, Karim; Moussa, Fatma Ben

    2014-09-01

    Renal involvement in Sjogren's syndrome (SS) is not uncommon and may precede other complaints. Tubulointerstitial nephritis is the most common renal disease in SS and may lead to renal tubular acidosis (RTA), which in turn may cause osteomalacia. Nevertheless, osteomalacia rarely occurs as the first manifestation of a renal tubule disorder due to SS. We herewith describe a 43-year-old woman who was admitted to our hospital for weakness, lumbago and inability to walk. X-ray of the long bones showed extensive demineralization of the bones. Laboratory investigations revealed chronic kidney disease with serum creatinine of 2.3 mg/dL and creatinine clearance of 40 mL/min, hypokalemia (3.2 mmol/L), hypophosphatemia (0.4 mmol/L), hypocalcemia (2.14 mmol/L) and hyperchloremic metabolic acidosis (chlorine: 114 mmol/L; alkaline reserve: 14 mmol/L). The serum alkaline phosphatase levels were elevated. The serum levels of 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D were low and borderline low, respectively, and the parathyroid hormone level was 70 pg/L. Urinalysis showed inappropriate alkaline urine (urinary PH: 7), glycosuria with normal blood glucose, phosphaturia and uricosuria. These values indicated the presence of both distal and proximal RTA. Our patient reported dryness of the mouth and eyes and Schirmer's test showed xerophthalmia. An accessory salivary gland biopsy showed changes corresponding to stage IV of Chisholm and Masson score. Kidney biopsy showed diffuse and severe tubulo-interstitial nephritis with dense lymphoplasmocyte infiltrates. Sicca syndrome and renal interstitial infiltrates indicated SS as the underlying cause of the RTA and osteomalacia. The patient received alkalinization, vitamin D (Sterogyl ®), calcium supplements and steroids in an initial dose of 1 mg/kg/day, tapered to 10 mg daily. The prognosis was favorable and the serum creatinine level was 1.7 mg/dL, calcium was 2.2 mmol/L and serum phosphate was 0.9 mmol/L.

  8. Pyruvate carboxylase deficiency: An underestimated cause of lactic acidosis

    F. Habarou

    2015-03-01

    Full Text Available Pyruvate carboxylase (PC is a biotin-containing mitochondrial enzyme that catalyzes the conversion of pyruvate to oxaloacetate, thereby being involved in gluconeogenesis and in energy production through replenishment of the tricarboxylic acid (TCA cycle with oxaloacetate. PC deficiency is a very rare metabolic disorder. We report on a new patient affected by the moderate form (the American type A. Diagnosis was nearly fortuitous, resulting from the revision of an initial diagnosis of mitochondrial complex IV (C IV defect. The patient presented with severe lactic acidosis and pronounced ketonuria, associated with lethargy at age 23 months. Intellectual disability was noted at this time. Amino acids in plasma and organic acids in urine did not show patterns of interest for the diagnostic work-up. In skin fibroblasts PC showed no detectable activity whereas biotinidase activity was normal. We had previously reported another patient with the severe form of PC deficiency and we show that she also had secondary C IV deficiency in fibroblasts. Different anaplerotic treatments in vivo and in vitro were tested using fibroblasts of both patients with 2 different types of PC deficiency, type A (patient 1 and type B (patient 2. Neither clinical nor biological effects in vivo and in vitro were observed using citrate, aspartate, oxoglutarate and bezafibrate. In conclusion, this case report suggests that the moderate form of PC deficiency may be underdiagnosed and illustrates the challenges raised by energetic disorders in terms of diagnostic work-up and therapeutical strategy even in a moderate form.

  9. Hyperkalemic distal renal tubular acidosis caused by immunosuppressant treatment with tacrolimus in a liver transplant patient: case report.

    Riveiro-Barciela, M; Campos-Varela, I; Tovar, J L; Vargas, V; Simón-Talero, M; Ventura-Cots, M; Crespo, M; Bilbao, I; Castells, L

    2011-12-01

    Nephrotoxicity is one of the most common side effects of long-term immunosuppressive therapy with calcineurin inhibitors. We describe a case of distal renal tubular acidosis secondary to tacrolimus administration. A 43-year-old man with end-stage liver disease due to hepatitis C and B virus infections and alcoholic cirrhosis received a liver transplantation under immunosuppressive treatment with tacrolimus and mycophenolate mofetil. In the postoperative period, the patient developed hyperkalemic hyperchloremic metabolic acidosis, with a normal serum anion gap and a positive urinary anion gap, suggesting distal renal tubular acidosis. We excluded other causes of hyperkalemia. Administration of intravenous bicarbonate, loop diuretics, and oral resin exchanger corrected the acidosis and potassium levels. Distal renal tubular acidosis is one of several types of nephrotoxicity induced by tacrolimus treatment, resulting from inhibition of potassium secretion in the collecting duct. Treatment to correct the acidosis and hyperkalemia should be promptly initiated, and the tacrolimus dose adjusted when possible.

  10. Topiramate and severe metabolic acidosis: case report Acidose metabólica grave por topiramato: relato de caso

    2005-01-01

    Topiramate infrequently induces anion gap metabolic acidosis through carbonic anhydrase inhibition on the distal tubule of the nephron - a type 2 renal tubular acidosis. We report on a 40 years old woman previously healthy that developed significant asymptomatic metabolic acidosis during topiramate therapy at a dosage of 100mg/day for three months. Stopping medication was followed by normalization of the acid-base status within five weeks. This infrequent side effect appears unpredictable and...

  11. Refractory metabolic acidosis in patients with sepsis following hemiarthroplasty for femoral neck fracture: a causative role for paracetamol and flucloxacillin?

    2011-01-01

    The authors report two cases of pyroglutamic acidosis as a result of paracetamol and flucloxacillin therapy in patients with prosthesis infection following hemiarthroplasty for neck of femur fractures. Pyroglutamic acidosis is an important and often unrecognised cause of refractory metabolic acidosis that disproportionately affects older women, and can be caused by drugs such as paracetamol and flucloxacillin in the setting of sepsis, renal failure and malnutrition. Although relatively rare, ...

  12. The effect of sodium bicarbonate on cytokine secretion in CKD patients with metabolic acidosis.

    Ori, Yaacov; Zingerman, Boris; Bergman, Michael; Bessler, Hanna; Salman, Hertzel

    2015-04-01

    The incidence of acidosis increases with the progression of chronic kidney disease (CKD). Correction of acidosis by sodium bicarbonate may slow CKD deterioration. Inflammation, which is common in CKD, may be related to acidosis. Whether the slower rate of GFR decline following the correction of acidosis is related to changes in inflammatory markers is unknown. The current study examined whether correcting CKD-acidosis affected inflammatory cytokines secretion. Thirteen patients with CKD 4-5 and acidosis were tested for cytokines secretion from peripheral-blood mononuclear cells at baseline and after one month of oral sodium bicarbonate. Following treatment with sodium bicarbonate there was no change in weight, blood pressure, serum creatinine, albumin, sodium, calcium, phosphate, PTH, hemoglobin and CRP. Serum urea decreased (134±10-116±8 mg/dl, P=0.002), potassium decreased (5.1±0.4-4.8±0.1 mequiv./l, P=0.064), pH increased (7.29±0.01-7.33±0.01, P=0.008), and serum bicarbonate increased (18.6±0.4 mequiv./l to 21.3±0.3 mequiv./l, P=0.001). The secretion of the anti-inflammatory cytokine IL-10 decreased (2.75±0.25 ng/ml to 2.29±0.21 ng/ml, P=0.041). There was no significant change in the secretion of the other pro-inflammatory and anti-inflammatory cytokines, including IL-1β, IL-2, IL-6, TNFα, IFNγ, IL-1ra. Thus, correcting acidosis in CKD with bicarbonate decreases IL-10 secretion. Its significance needs to be further investigated.

  13. Correction of metabolic acidosis to ameliorate wasting in chronic kidney disease: goals and strategies.

    Chiu, Yi-Wen; Kopple, Joel D; Mehrotra, Rajnish

    2009-01-01

    Metabolic acidosis is an important cause of protein-energy wasting, commonly observed in chronic kidney disease (CKD). This wasting is, in part, a result of the imbalance between protein degradation and synthesis induced by metabolic acidosis. The increase in protein degradation seen with metabolic acidosis is largely secondary to increased activities of the adenosine triphosphate-dependent, ubiquitin-proteasome system and branched-chain ketoacid dehydrogenase. Studies consistently have shown increased protein degradation with lower serum bicarbonate levels and/or arterial pH; however, the evidence for the anti-anabolic effects of metabolic acidosis is less consistent. In contrast to these metabolic studies, many cross-sectional studies have shown a direct relationship between the severity of metabolic acidosis and the adequacy of nutritional status in CKD patients. Moreover, lower serum bicarbonate levels have been associated with better survival in some epidemiologic studies of patients undergoing maintenance hemodialysis. It is likely that these relationships are confounded by the direct association of dietary protein intakes with metabolic acidosis-controlling the survival data for measures of dietary protein intakes, malnutrition, and inflammation shows a rather steep increase in the risk of death with lower serum bicarbonate levels. Two randomized controlled studies have shown that correction of metabolic acidosis is associated with reduction in risk for hospitalization in chronic peritoneal dialysis patients; the studies in maintenance hemodialysis patients have been small and inconsistent. For now, metabolic studies and data from clinical trials lend support to the recommendations made by the Nutrition Workgroup of the Kidney Disease Outcomes Quality Initiative to maintain serum bicarbonate levels of 22 mEq/L or greater in all CKD patients. Limited data suggest that a higher serum bicarbonate level (around 24 mEq/L) may be even more beneficial, particularly

  14. Neuroprotection and acidosis induced by cortical spreading depression

    Kwong KK

    2016-12-01

    Full Text Available Kenneth K Kwong, Suk-tak Chan Department of Radiology, MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, USA We read with interest the article “Cortical spreading depression produces a neuroprotective effect activating mitochondrial uncoupling protein-5” published in Neuropsychiatr Dis Treat by Viggiano et al.1 The authors showed that cerebral spreading depression (CSD triggered uncoupling protein-5 (UCP-5,1 which had been reported to exert a long-term effect upon neuron protection.2 The result is another piece in CSD literature on modifying gene expressions to provide neuroprotection to subsequent ischemic episodes.3,4 Authors' replyGiovanni Messina1,2Emanuela Viggiano1,3Vincenzo Monda1Antonietta Messina1Fiorenzo Moscatelli2Anna Valenzano2Domenico Tafuri4Vincenzo De Luca5Giuseppe Cibelli2Marcellino Monda1 1Section of Human Physiology and Unit of Dietetic and Sport Medicine, Department of Experimental Medicine, Second University of Naples, Caserta, 2Department of Clinical and Experimental Medicine, University of Foggia, Foggia, 3Department of Medicine, University of Padua, Padua, 4Department of Motor Sciences and Wellness, University of Naples “Parthenope,” Napoli, Italy; 5Department of Psychiatry, University of Toronto, Toronto, ON, Canada Thank you for the attention paid to our article entitled: “Cortical spreading depression produces a neuroprotective effect activating mitochondrial uncoupling protein-5”.1 We do agree that cerebral spreading depression (CSD-induced acidosis is an intriguing aspect of the neuroprotection puzzle. It is well known that CSD is involved in the pathophysiology of migraine, cerebral ischemia, subarachnoid hemorrhage, and traumatic brain injury.2–7 View the original paper by Viggiano and colleagues. 

  15. Effect of sodium bicarbonate administration on mortality in patients with lactic acidosis: a retrospective analysis.

    Hyun Jeong Kim

    Full Text Available BACKGROUND: Lactic acidosis is a common cause of high anion gap metabolic acidosis. Sodium bicarbonate may be considered for an arterial pH <7.15 but paradoxically depresses cardiac performance and exacerbates acidosis by enhancing lactate production. This study aimed to evaluate the cause and mortality rate of lactic acidosis and to investigate the effect of factors, including sodium bicarbonate use, on death. METHODS: We conducted a single center analysis from May 2011 through April 2012. We retrospectively analyzed 103 patients with lactic acidosis among 207 patients with metabolic acidosis. We used SOFA and APACHE II as severity scores to estimate illness severity. Multivariate logistic regression analysis and Cox regression analysis models were used to identify factors that affect mortality. RESULTS: Of the 103 patients with a mean age of 66.1±11.4 years, eighty-three patients (80.6% died from sepsis (61.4%, hepatic failure, cardiogenic shock and other causes. The percentage of sodium bicarbonate administration (p = 0.006, catecholamine use, ventilator care and male gender were higher in the non-survival group than the survival group. The non-survival group had significantly higher initial and follow-up lactic acid levels, lower initial albumin, higher SOFA scores and APACHE II scores than the survival group. The mortality rate was significantly higher in patients who received sodium bicarbonate. Sodium bicarbonate administration (p = 0.016 was associated with higher mortality. Independent factors that affected mortality were SOFA score (Exp (B = 1.72, 95% CI = 1.12-2.63, p = 0.013 and sodium bicarbonate administration (Exp (B = 6.27, 95% CI = 1.10-35.78, p = 0.039. CONCLUSIONS: Lactic acidosis, which has a high mortality rate, should be evaluated in patients with metabolic acidosis. In addition, sodium bicarbonate should be prescribed with caution in the case of lactic acidosis because sodium bicarbonate

  16. Haptoglobin and serum amyloid a in subacute ruminal acidosis in goats

    F.H.D. González

    2010-12-01

    Full Text Available Ruminal acidosis is a frequent disorder that occurs in goats as a consequence of feedingmistakes in animals not adapted to a diet of easily fermentable carbohydrates. The subacuteform of the disease is difficult to diagnose because no apparent signs are shownand the acid-base parameters may remain within the normal range. The present studyaimed at testing the hypothesis that haptoglobin (Hp and serum amyloid A (SAA,the two major acute phase proteins in ruminants, may be useful as markers of subacuteacidosis in goats.A subacute acidosis was induced in six Murciano-Granadina goats through a diet of60% mixed feed-40% alfalfa hay offered during 5 days to goats not adapted to eatmixed feed. Two goats were rumen-fistulated to investigate the effect of feeding onruminal pH. Sampling of blood and urine of all animals was done before the inductionof the acidosis, during 5 days after the onset of induction and for 18 days after theinduction (recovery period.Ruminal pH in the fistulated goats dropped to less than 5.5 during the inductionperiod, and half of the goats had diarrhea on the third day after the induction of acidosis.Acid-base parameters showed that the acid-base compensatory mechanisms wereefficient in maintaining the equilibrium. Serum Hp had a moderate increase duringthe induction period, while SAA did not change. These results suggest that Hp mightbe a potential marker for ruminal acidosis in goats.

  17. Calcium citrate improves the epithelial-to-mesenchymal transition induced by acidosis in proximal tubular cells

    Maria José Rodriguez Cabalgante

    2012-12-01

    Full Text Available INTRODUCTION: Epithelial-to-mesenchymal transition (EMT is a key event in renal fibrosis. The aims of the study were to evaluate acidosis induced EMT, transforming-growth-factor (TGF β1 role and citrate effect on it. METHODS: HK2 cells (ATCC 2290 were cultured in DMEM/HAM F12 medium, pH 7.4. At 80% confluence, after 24 hr under serum free conditions, cells were distributed in three groups (24 hours: A Control: pH 7.4, B Acidosis: pH 7.0 and C Calcium citrate (0.2 mmol/L + pH 7.0. Change (Δ of intracellular calcium concentration, basal and after Angiotensin II (10-6M exposition, were measured to evaluate cellular performance. EMT was evaluated by the expression of α-smooth muscle actin (α-SMA and E-cadherin by immunocytochemistry and/or Western blot. TGF-β1 secretion was determined by ELISA in cell supernatant. RESULTS: At pH 7.0 HK2 cells significantly reduced E-cadherin and increased α-SMA expression (EMT. Supernatant TGF-β1 levels were higher than in control group. Calcium citrate decreased acidosis induced EMT and improved cells performance, without reduction of TGF-β production. CONCLUSIONS: Acidosis induces EMT and secretion of TGF-β1 in tubular proximal cells in culture and citrate improves cellular performance and ameliorates acidosis induced EMT.

  18. Effects of hypercapnia and hypercapnic acidosis on attenuation of ventilator-associated lung injury.

    Ismaiel, N M; Henzler, D

    2011-07-01

    Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are associated with impaired gas exchange, severe inflammation and alveolar damage including cell death. Patients with ALI or ARDS typically experience respiratory failure and thus require mechanical ventilation for support, which itself can aggravate lung injury. Recent developments in this field have revealed several therapeutic strategies that improve gas exchange, increase survival and minimize the deleterious effects of mechanical ventilation. Among those strategies is the reduction in tidal volume and allowing hypercapnia to develop during ventilation, or actively inducing hypercapnia. Here, we provide an overview of hypercapnia and the hypercapnic acidosis that typically follows, as well as the therapeutic effects of hypercapnia and acidosis in clinical studies and experimental models of ALI. Specifically, we review the effects of hypercapnia and acidosis on the attenuation of pulmonary inflammation, reduction of apoptosis in alveolar epithelial cells, improvement in sepsis-induced ALI and the therapeutic effects on other organ systems, as well as the potentially harmful effects of these strategies. The clinical implications of hypercapnia and hypercapnic acidosis are still not entirely clear. However, future research should focus on the intracellular signaling pathways that mediate ALI development, potentially focusing on the role of reactive biological species in ALI pathogenesis. Future research can also elucidate how such pathways may be targeted by hypercapnia and hypercapnic acidosis to attenuate lung injury.

  19. Prediction of neonatal metabolic acidosis in women with a singleton term pregnancy in cephalic presentation.

    Westerhuis, Michelle E M H; Schuit, Ewoud; Kwee, Anneke; Zuithoff, Nicolaas P A; Groenwold, Rolf H H; Van Den Akker, Eline S A; Van Beek, Erik; Van Dessel, Hendrikus J H M; Drogtrop, Addy P; Van Geijn, Herman P; Graziosi, Guiseppe C M; Van Lith, Jan M M; Nijhuis, Jan G; Oei, S Guid; Oosterbaan, Herman P; Porath, Martina M; Rijnders, Robert J P; Schuitemaker, Nico W E; Wijnberger, Lia D E; Willekes, Christine; Wouters, Maurice G A J; Visser, Gerard H A; Mol, Ben Willem J; Moons, Karel G M

    2012-03-01

    We sought to predict neonatal metabolic acidosis at birth using antepartum obstetric characteristics (model 1) and additional characteristics available during labor (model 2). In 5667 laboring women from a multicenter randomized trial that had a high-risk singleton pregnancy in cephalic presentation beyond 36 weeks of gestation, we predicted neonatal metabolic acidosis. Based on literature and clinical reasoning, we selected both antepartum characteristics and characteristics that became available during labor. After univariable analyses, the predictors of the multivariable models were identified by backward stepwise selection in a logistic regression analysis. Model performance was assessed by discrimination and calibration. To correct for potential overfitting, we (internally) validated the models with bootstrapping techniques. Of 5667 neonates born alive, 107 (1.9%) had metabolic acidosis. Antepartum predictors of metabolic acidosis were gestational age, nulliparity, previous cesarean delivery, and maternal diabetes. Additional intrapartum predictors were spontaneous onset of labor and meconium-stained amniotic fluid. Calibration and discrimination were acceptable for both models (c-statistic 0.64 and 0.66, respectively). In women with a high-risk singleton term pregnancy in cephalic presentation, we identified antepartum and intrapartum factors that predict neonatal metabolic acidosis at birth.

  20. Acidosis láctica por metformina desencadenada por una insuficiencia renal aguda Metformin-induced lactic acidosis due to acute renal failure

    M.D. Macías-Robles

    2011-04-01

    Full Text Available La acidosis láctica es una complicación grave pero infrecuente asociada al empleo de metformina. Se discuten los mecanismos fisiopatológicos implicados en la acidosis láctica, con especial atención al papel potencial del fármaco. Presentamos un caso severo de este efecto secundario de la metformina en una paciente con diabetes tipo 2 que ingresó en el Servicio de Urgencias Hospitalario por un cuadro de insuficiencia renal aguda. El diagnóstico quedó apoyado por unos niveles séricos elevados de la biguanida, procedimiento escasamente utilizado en la práctica clínica. El tratamiento consiste en suspender la administración del fármaco e iniciar de forma inmediata la hemodiálisis con bicarbonato, lo cual proporciona un tratamiento sintomático y etiológico al eliminar del suero tanto el lactato como el antidiabético oral. Los síntomas de la acidosis láctica por metformina son inespecíficos y el comienzo es sutil, lo que hace necesario un alto nivel de sospecha para establecer un diagnostico precoz.Lactic acidosis is a serious but uncommon side effect of metformin use. We discuss the pathophysiological mechanisms of lactic acidosis with particular regard to the role played by the drug as a potential cause of the entity. We report on a severe case of this kind of drug toxicity in a patient with type 2 diabetes mellitus, admitted to the emergency department with acute renal failure symptoms. The diagnosis was supported by elevated serum levels of the biguanide, a procedure scarcely used in clinical practice. The management of this complication consists in drug discontinuation and hemodialysis with bicarbonate that provides symptomatic and ethiological treatment by removing both the lactate and the hypoglycemic agent from the serum. Since the symptoms of metformin-associated lactic acidosis are unspecific and its onset is subtle, a high level of suspicion is needed to establish an early diagnosis.

  1. Long-term follow-up in distal renal tubular acidosis with sensorineural deafness.

    Peces, R

    2000-11-01

    A 20-year-old man presented with failure to thrive and bilateral genu valgum. On the basis of growth failure, skeletal deformity, hyperchloremic metabolic acidosis with alkaline urine and hypokalemia, nephrocalcinosis, and hearing loss, a diagnosis of distal renal tubular acidosis (DRTA) with sensorineural deafness was made. The genu valgum was treated by corrective osteotomy. Skeletal deformity was corrected and impaired growth improved after sustained therapy of metabolic acidosis with alkali supplementation. During an 8-year follow-up period the patient's glomerular filtration rate remained stable, the nephrocalcinosis did not progress, and his height increased 10 cm. Although nephrolithiasis led to atrophy of the right kidney, at last follow-up, when the patient was 44 years old, his creatinine clearance was 50 ml/min per 1.73 m2 body surface.

  2. in vitro activation of complement and contact system by lactic acidosis

    J. Sonntag

    1998-01-01

    Full Text Available The activation of complement and contact systems occurs in reperfusion injuries with initial tissue hypoxia, and lactic acidosis such as mycardial infarction and birth asphyxia. The aim of our experiment was the formal proof of activation by sole lactic acidosis. Lactic acid was added to blood and plasma samples from 10 healthy volunteers. C5a and factor XIIa were measured by EIA after incubation at 37°C for 1 h. Both concentrations increased (P<0.0001 by Friedman analysis in blood and plasma samples with increasing amount of added lactic acid. Lactic acidosis can activate C5 from the complement system and factor XII from the contact system directly, even in the absence of cellular components.

  3. In vitro activation of complement and contact system by lactic acidosis.

    Sonntag, J; Emeis, M; Strauss, E; Obladen, M

    1998-01-01

    The activation of complement and contact systems occurs in reperfusion injuries with initial tissue hypoxia, and lactic acidosis such as mycardial infarction and birth asphyxia. The aim of our experiment was the formal proof of activation by sole lactic acidosis. Lactic acid was added to blood and plasma samples from 10 healthy volunteers. C5a and factor XIIa were measured by EIA after incubation at 37 degrees C for 1 h. Both concentrations increased (P < 0.0001 by Friedman analysis) in blood and plasma samples with increasing amount of added lactic acid. Lactic acidosis can activate C5 from the complement system and factor XII from the contact system directly, even in the absence of cellular components. PMID:9839699

  4. Autophagic clearance of mitochondria in the kidney copes with metabolic acidosis.

    Namba, Tomoko; Takabatake, Yoshitsugu; Kimura, Tomonori; Takahashi, Atsushi; Yamamoto, Takeshi; Matsuda, Jun; Kitamura, Harumi; Niimura, Fumio; Matsusaka, Taiji; Iwatani, Hirotsugu; Matsui, Isao; Kaimori, Junya; Kioka, Hidetaka; Isaka, Yoshitaka; Rakugi, Hiromi

    2014-10-01

    Metabolic acidosis, a common complication of CKD, causes mitochondrial stress by undefined mechanisms. Selective autophagy of impaired mitochondria, called mitophagy, contributes toward maintaining cellular homeostasis in various settings. We hypothesized that mitophagy is involved in proximal tubular cell adaptations to chronic metabolic acidosis. In transgenic mice expressing green fluorescent protein-tagged microtubule-associated protein 1 light chain 3 (GFP-LC3), NH4Cl loading increased the number of GFP puncta exclusively in the proximal tubule. In vitro, culture in acidic medium produced similar results in proximal tubular cell lines stably expressing GFP-LC3 and facilitated the degradation of SQSTM1/p62 in wild-type cells, indicating enhanced autophagic flux. Upon acid loading, proximal tubule-specific autophagy-deficient (Atg5-deficient) mice displayed significantly reduced ammonium production and severe metabolic acidosis compared with wild-type mice. In vitro and in vivo, acid loading caused Atg5-deficient proximal tubular cells to exhibit reduced mitochondrial respiratory chain activity, reduced mitochondrial membrane potential, and fragmented morphology with marked swelling in mitochondria. GFP-LC3-tagged autophagosomes colocalized with ubiquitinated mitochondria in proximal tubular cells cultured in acidic medium, suggesting that metabolic acidosis induces mitophagy. Furthermore, restoration of Atg5-intact nuclei in Atg5-deficient proximal tubular cells increased mitochondrial membrane potential and ammoniagenesis. In conclusion, metabolic acidosis induces autophagy in proximal tubular cells, which is indispensable for maintaining proper mitochondrial functions including ammoniagenesis, and thus for adapted urinary acid excretion. Our results provide a rationale for the beneficial effect of alkali supplementation in CKD, a condition in which autophagy may be reduced, and suggest a new therapeutic option for acidosis by modulating autophagy.

  5. Extracellular acidosis promotes neutrophil transdifferentiation to MHC class II-expressing cells.

    Pliyev, Boris K; Sumarokov, Alexander B; Buriachkovskaia, Lyudmila I; Menshikov, Mikhail

    2011-01-01

    Inflammation in peripheral tissues is usually associated with local acidosis. In the present study, we demonstrate that extracellular acidification enhances GM-CSF- and IFN-γ-induced expression of HLA-DR, CD80 and CD86 in human neutrophils (neutrophil transdifferentiation), and potentiates antigen-capturing capacities (both endocytosis and phagocytosis) of the transdifferentiated cells. Furthermore, in acidic conditions the transdifferentiated neutrophils have stronger antigen-presenting capacity, inducing more intense proliferation of autologous T lymphocytes in the presence of staphylococcal enterotoxin A. Thus, extracellular acidosis can represent a factor that promotes neutrophil transdifferentiation and potentiates the functional abilities of the transdifferentiated cells in inflammatory foci in vivo.

  6. Propylene Glycol Poisoning From Excess Whiskey Ingestion: A Case of High Osmolal Gap Metabolic Acidosis.

    Cunningham, Courtney A; Ku, Kevin; Sue, Gloria R

    2015-01-01

    In this report, we describe a case of high anion gap metabolic acidosis with a significant osmolal gap attributed to the ingestion of liquor containing propylene glycol. Recently, several reports have characterized severe lactic acidosis occurring in the setting of iatrogenic unintentional overdosing of medications that use propylene glycol as a diluent, including lorazepam and diazepam. To date, no studies have explored potential effects of excess propylene glycol in the setting of alcohol intoxication. Our patient endorsed drinking large volumes of cinnamon flavored whiskey, which was likely Fireball Cinnamon Whisky. To our knowledge, this is the first case of propylene glycol toxicity from an intentional ingestion of liquor containing propylene glycol.

  7. Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes unveiled by valproate

    Neera Chaudhry

    2013-01-01

    Full Text Available Valproic acid (VPA is widely used as an anti-epileptic drug. The primary mechanism of VPA toxicity is interference with mitochondrial beta-oxidation, and it can exacerbate an underlying mitochondrial cytopathy. We report a case of Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes unmasked by use of Sodium Valproate in a 12-year-old boy who presented with headache and seizures. There was precipitation of encephalopathy, myopathy, lactic acidosis, and hepatic damage within two days of valproate use, after withdrawing of which there was a remarkable clinical and biochemical recovery.

  8. Role of the endocrine pancreas in the kalemic response to acute metabolic acidosis in conscious dogs.

    Adrogué, H J; Chap, Z; Ishida, T; Field, J B

    1985-03-01

    Metabolic acidosis due to organic acids infusion fails to elicit hyperkalemia. Although plasma potassium levels may rise, the increase is smaller than in mineral acid acidosis. The mechanisms responsible for the different effects of organic acid acidosis and mineral acid acidosis remain undefined, although dissimilar hormonal responses by the pancreas may explain dissimilar hormonal responses by the pancreas may explain the phenomena. To test this hypothesis, beta-hydroxybutyric acid (7 meq/kg) or hydrochloric acid (3 meq/kg) was infused over 30 min into conscious dogs (n = 12) with chronically implanted catheters in the portal, hepatic, and systemic circulation, and flow probes were placed around the portal vein and hepatic artery. Acid infusion studies in two groups of anesthetized dogs were also done to assess the urinary excretion of potassium (n = 14), and to evaluate the effects of acute suppression of renal electrolyte excretion on plasma potassium and on the release/uptake of potassium in peripheral tissues of the hindleg (n = 17). Ketoacid infusion caused hypokalemia and a significant increase in portal vein plasma insulin, from the basal level of 27 +/- 4 microU/ml to a maximum of 84 +/- 22 microU/ml at 10 min, without changes in glucagon levels. By contrast, mineral acid acidosis of similar severity resulted in hyperkalemia and did not increase portal insulin levels but enhanced portal glucagon concentration from control values of 132 +/- 25 pg/ml to 251 +/- 39 pg/ml at 40 min. A significant decrease in plasma glucose levels due to suppression of hepatic release was observed during ketoacid infusion, while no changes were observed with mineral acid infusion. Plasma flows in the portal vein and hepatic artery remained unchanged from control values in both acid infusion studies. Differences in renal potassium excretion were ruled out as determinants of the disparate kalemic responses to organic acid infusion compared with HCl acidosis. Evaluation of the

  9. Citric acid ingestion: a life-threatening cause of metabolic acidosis.

    DeMars, C S; Hollister, K; Tomassoni, A; Himmelfarb, J; Halperin, M L

    2001-11-01

    We present a case that illustrates the acute (acidosis accompanied by an increase in the plasma anion gap that was not caused by L -lactic acidosis, hyperkalemia, and the abrupt onset of hypotension. A unique feature was a dramatic clinical improvement when ionized calcium was infused. The case illustrates the importance of considering the properties of the conjugate base (anion) of the added acid because, in this instance, the citrate anion had a unique and life-threatening consequence (lower ionized calcium level) that was rapidly reversible.

  10. Activation of GPR4 by acidosis increases endothelial cell adhesion through the cAMP/Epac pathway.

    Aishe Chen

    Full Text Available Endothelium-leukocyte interaction is critical for inflammatory responses. Whereas the tissue microenvironments are often acidic at inflammatory sites, the mechanisms by which cells respond to acidosis are not well understood. Using molecular, cellular and biochemical approaches, we demonstrate that activation of GPR4, a proton-sensing G protein-coupled receptor, by isocapnic acidosis increases the adhesiveness of human umbilical vein endothelial cells (HUVECs that express GPR4 endogenously. Acidosis in combination with GPR4 overexpression further augments HUVEC adhesion with U937 monocytes. In contrast, overexpression of a G protein signaling-defective DRY motif mutant (R115A of GPR4 does not elicit any increase of HUVEC adhesion, indicating the requirement of G protein signaling. Downregulation of GPR4 expression by RNA interference reduces the acidosis-induced HUVEC adhesion. To delineate downstream pathways, we show that inhibition of adenylate cyclase by inhibitors, 2',5'-dideoxyadenosine (DDA or SQ 22536, attenuates acidosis/GPR4-induced HUVEC adhesion. Consistently, treatment with a cAMP analog or a G(i signaling inhibitor increases HUVEC adhesiveness, suggesting a role of the G(s/cAMP signaling in this process. We further show that the cAMP downstream effector Epac is important for acidosis/GPR4-induced cell adhesion. Moreover, activation of GPR4 by acidosis increases the expression of vascular adhesion molecules E-selectin, VCAM-1 and ICAM-1, which are functionally involved in acidosis/GPR4-mediated HUVEC adhesion. Similarly, hypercapnic acidosis can also activate GPR4 to stimulate HUVEC adhesion molecule expression and adhesiveness. These results suggest that acidosis/GPR4 signaling regulates endothelial cell adhesion mainly through the G(s/cAMP/Epac pathway and may play a role in the inflammatory response of vascular endothelial cells.

  11. Severe lactic acidosis associated with juice of the mangosteen fruit Garcinia mangostana.

    Wong, Leslie P; Klemmer, Philip J

    2008-05-01

    The tropical mangosteen fruit has long been prized in Southeast Asia for its traditional healing properties. Mangosteen fruit juice is now available in the United States and marketed for its purported health benefits. We describe a case of severe lactic acidosis associated with the use of mangosteen juice as a dietary supplement.

  12. [Topiramate in monotherapy or in combination as a cause of metabolic acidosis in adults with epilepsy].

    Ruiz-Granados, Velvet J; Márquez-Romero, Juan M

    2015-02-16

    Objetivo. Determinar la frecuencia de acidosis metabolica y sus factores relacionados en pacientes tratados con topiramato solo o como adyuvante para el tratamiento de epilepsia. Pacientes y metodos. Analisis transversal de la gasometria arterial de pacientes epilepticos que recibieron topiramato durante 2010 en la clinica de epilepsia del Centro Medico Nacional 20 de Noviembre en Mexico. Se registraron datos clinicos concernientes a la epilepsia y su tratamiento, asi como de los sintomas comunes de acidosis metabolica. Resultados. Se estudiaron 32 adultos con epilepsia, quienes recibieron topiramato en monoterapia o en combinacion por lo menos durante un mes. Se encontro acidosis metabolica en todos los pacientes (HCO3 < 22 Eq/L); nueve tomaron solo topiramato y 23 tomaron por lo menos dos farmacos antiepilepticos (FAE). Todos los pacientes fueron asintomaticos. No se encontro correlacion entre los niveles de bicarbonato y la dosis del medicamento o la duracion del tratamiento. La dosis fue significativamente mayor en el grupo de monoterapia y el nivel de bicarbonato fue mas bajo en los pacientes que tomaban mas de un FAE. Conclusiones. El uso concomitante de FAE incrementa los efectos conocidos del topiramato sobre los niveles sericos de bicarbonato y la presencia de acidosis metabolica; estos efectos parecen ser independientes del numero de FAE utilizados.

  13. Renal Tubular Acidosis after Jejunoileal Bypass for Morbid Obesity: role of secondary hyperparathyroidism

    Andersen, NN; Ladefoged, NN

    1991-01-01

    The effect of calcium infusion was studied in patients with renal tubular acidosis (RTA) and secondary hyperparathyroidism. Both developed after jejunoileal bypass operation (JIB) for morbid obesity. In three of four cases the acidification defect was abolished, probably due to a decrease of seru...

  14. Re-Evaluation of Acid-Base Prediction Rules in Patients with Chronic Respiratory Acidosis

    Tereza Martinu

    2003-01-01

    Full Text Available RATIONALE: The prediction rules for the evaluation of the acid-base status in patients with chronic respiratory acidosis, derived primarily from an experimental canine model, suggest that complete compensation should not occur. This appears to contradict frequent observations of normal or near-normal pH levels in patients with chronic hypercapnia.

  15. Involvement of organic cation transporter 1 in the lactic acidosis caused bv metformin

    Wang, DS; Kusuhara, H; Kato, Y; Jonker, JW; Schinkel, AH; Sugiyama, Y

    2003-01-01

    Biguanides are a class of drugs widely used as oral antihyperglycemic agents for the treatment of type 2 diabetes mellitus, but they are associated with lactic acidosis, a lethal side effect. We reported previously that biguanides are good substrates of rat organic cation transporter 1 (Oct1; Slc22a

  16. Comparison of potential risks of lactic acidosis induction by biguanides in rats.

    Bando, Kiyoko; Ochiai, Shoko; Kunimatsu, Takeshi; Deguchi, Jiro; Kimura, Juki; Funabashi, Hitoshi; Seki, Takaki

    2010-10-01

    Lactic acidosis has been considered to be a side effect of some biguanides, after phenformin was withdrawn from the market because of its association with lactic acidosis. The potential of lactic acidosis induced by biguanides at human therapeutic exposure levels, however, has not been examined. Then, we compared the risk of lactic acid at doses providing exposure levels comparable to human therapeutic doses. Metformin and phenformin were orally administered to rats for up to 28 days, and plasma drug concentrations and blood lactic acid levels were examined. Metformin did not elevate lactic acid levels at the dose corresponding to higher systemic drug exposure than human therapeutic level, even for repeated doses. In contrast, phenformin elevated lactic acid levels at the dose corresponding to lower exposure than human therapeutic level, and sustained high levels were observed up to 24h post-dose; furthermore, these changes were enhanced by repeated doses. Direct comparison at each rat equivalent dose clearly indicated that lactic acid levels of phenformin were higher than those of metformin. These non-clinical findings suggest that metformin dose not increase lactic acid levels like phenformin does, and therefore may not increase the risk for lactic acidosis at human therapeutic exposure level.

  17. Indicators of induced subacute ruminal acidosis (SARA) in Danish Holstein cows

    Danscher, Anne Mette; Li, Shucong; Andersen, Pia H.;

    2015-01-01

    BACKGROUND: The prevalence of subacute ruminal acidosis (SARA) in dairy cows is high with large impact on economy and welfare. Its current field diagnosis is based on point ruminal pH measurements by oral probe or rumenocentesis. These techniques are invasive and inaccurate, and better markers fo...

  18. Indomethacin abolishes cerebral blood flow increase in response to acetazolamide-induced extracellular acidosis

    Wang, Qian; Paulson, O B; Lassen, N A

    1993-01-01

    by acetazolamide (Az), a drug that induces brain extracellular acidosis, which triggers its effect on CBF. We compared the results to the inhibitory effect of indomethacin on the CBF increase during hypercapnia. Indomethacin but not diclofenac, another potent cyclooxygenase inhibitor, was found to block almost...

  19. Scalp blood lactate for intra-partum assessment of fetal metabolic acidosis

    Heinis, A.M.; Spaanderman, M.E.A.; Gunnewiek, J.M.; Lotgering, F.K.

    2011-01-01

    Objective. To study to what extent the fetal scalp blood lactate concentration during labor correlates with fetal scalp pH and base deficit, and metabolic acidosis at birth, and to suggest lactate cut-off values to serve as indicators for either reassurance or immediate intervention. Design. A retro

  20. TRPA1 and TRPV1 Antagonists Do Not Inhibit Human Acidosis-Induced Pain.

    Schwarz, Matthias G; Namer, Barbara; Reeh, Peter W; Fischer, Michael J M

    2017-01-03

    Acidosis occurs in a variety of pathophysiological and painful conditions where it is thought to excite or contribute to excitation of nociceptive neurons. Despite potential clinical relevance the principal receptor for sensing acidosis is unclear, but several receptors have been proposed. We investigated the contribution of the acid-sensing ion channels, transient receptor potential vanilloid type 1 (TRPV1) and transient receptor potential ankyrin type 1 (TRPA1) to peripheral pain signaling. We first established a human pain model using intraepidermal injection of the TRPA1 agonist carvacrol. This resulted in concentration-dependent pain sensations, which were reduced by experimental TRPA1 antagonist A-967079. Capsaicin-induced pain was reduced by the TRPV1 inhibitor BCTC. Amiloride was used to block acid-sensing ion channels. Testing these antagonists in a double-blind and randomized experiment, we probed the contribution of the respective channels to experimental acidosis-induced pain in 15 healthy human subjects. A continuous intraepidermal injection of pH 4.3 was used to counter the buffering capacity of tissue and generate a prolonged painful stimulation. In this model, addition of A-967079, BCTC or amiloride did not reduce the reported pain. In conclusion, target-validated antagonists, applied locally in human skin, have excluded the main hypothesized targets and the mechanism of the human acidosis-induced pain remains unclear.

  1. Starvation Ketoacidosis: A Cause of Severe Anion Gap Metabolic Acidosis in Pregnancy

    Nupur Sinha

    2014-01-01

    Full Text Available Pregnancy is a diabetogenic state characterized by relative insulin resistance, enhanced lipolysis, elevated free fatty acids and increased ketogenesis. In this setting, short period of starvation can precipitate ketoacidosis. This sequence of events is recognized as “accelerated starvation.” Metabolic acidosis during pregnancy may have adverse impact on fetal neural development including impaired intelligence and fetal demise. Short periods of starvation during pregnancy may present as severe anion gap metabolic acidosis (AGMA. We present a 41-year-old female in her 32nd week of pregnancy, admitted with severe AGMA with pH 7.16, anion gap 31, and bicarbonate of 5 mg/dL with normal lactate levels. She was intubated and accepted to medical intensive care unit. Urine and serum acetone were positive. Evaluation for all causes of AGMA was negative. The diagnosis of starvation ketoacidosis was established in absence of other causes of AGMA. Intravenous fluids, dextrose, thiamine, and folic acid were administered with resolution of acidosis, early extubation, and subsequent normal delivery of a healthy baby at full term. Rapid reversal of acidosis and favorable outcome are achieved with early administration of dextrose containing fluids.

  2. In-vitro activation of complement system by lactic acidosis in newborn and adults.

    Hecke, F; Hoehn, T; Strauss, E; Obladen, M; Sonntag, J

    2001-01-01

    INTRODUCTION: Complement activation occurs secondary to a variety of external stimuli. Lactic acidosis has been previously shown to activate the complement factors C3a and C5a. In the present investigation we examined the differential effect of lactic acidosis on anaphylatoxin levels in cord and adult blood. Furthermore we aimed to determine if the entire complement cascade could be activated by lactic acidosis. METHODS: Cord and adult blood samples (n = 20 each) were collected and incubated for one hour in either untreated condition or with the addition of lactate in two concentrations (5.5 mmol/l vs. 22 mmol/l). Following incubation, levels of C3a, C5a and sC5b-9, and blood gas parameters were determined. RESULTS: Anaphylatoxin (C3a and C5a) and sC5b-9 levels increased with the addition of lactate in a dose-dependent manner in cord and adult blood (C3a: 1 h, 5.5 mmo/l, 22 mmol/l: 418/498/622 microg/l in cord blood; 1010/1056/1381 microg/l in adult blood, p<0,05; similar results were found for C5a and sC5b-9). CONCLUSION: Lactic acidosis leads to an activation of the entire complement system in neonates and in adults. This activation is dose-dependent and more pronounced in adults as compared to neonates. PMID:11324901

  3. Acute isoniazid intoxication: an uncommon cause of convulsion, coma and acidosis.

    Uzman, Sinan; Uludağ Yanaral, Tümay; Toptaş, Mehmet; Koç, Alparslan; Taş, Aytül; Bican, Gülşen

    2013-01-01

    Despite the widespread use, suicidal ingestion of isoniazid is a rare condition in Turkey. We reported a case of acute isoniazid intoxication associated with alcohol intake presenting with convulsion, coma and metabolic acidosis. The patient was treated successfully with intravenous pyridoxine administration. Early recognation and appropriate treatment in the intensive care unit is very important to prevent mortality in patients with acute isoniazid toxicity.

  4. Haptoglobin and serum amyloid a in subacute ruminal acidosis in goats

    F.H.D. González

    2010-01-01

    Full Text Available La acidosis ruminal es un trastorno frecuente en cabras como consecuencia de errores en el manejo alimentario en animales no adaptados a dietas que contienen carbohidratos fácilmente fermentables. La forma subaguda de la enfermedad es de difícil diagnóstico toda vez que no muestra evidencia de signos clínicos claros y los parámetros ácido-básicos pueden permanecer en el rango normal. El presente estudio tuvo por objetivo probar la hipótesis de que la haptoglobina y la proteína amilóide sérica A, las dos proteínas de fase aguda más importantes en rumiantes, pueden ser útiles como marcadores de acidosis subaguda en cabras. Se indujo acidosis ruminal a seis cabras de la raza Murciano-Granadina, no adaptadas al consumo de concentrado, mediante el suministro de una dieta con 60% de concentrado y 40% de heno de alfalfa durante 5 días. Dos cabras fueron sometidas a fistulación ruminal para comprobar el efecto del tratamiento sobre el pH del rumen. A todos los animales se les tomaron muestras de sangre y orina el día anterior a la inducción, durante el período de inducción y hasta 18 días después de la inducción (período de recuperación. El pH ruminal cayó a menos de 5,5 durante el período de inducción de acidosis en las cabras fistuladas, mientras que la mitad de las cabras tuvieron diarrea al tercer día de la inducción de acidosis. Los parámetros gasométricos indicaron que los mecanismos compensatorios fueron eficientes para mantener el equilibrio ácido-básico. La haptoglobina sérica presentó un aumento moderado durante el período de inducción de acidosis, mientras que la amilóide sérica A no presentó cambios. Los resultados sugieren que la haptoglobina puede utilizarse como un potencial indicador de acidosis ruminal en cabras.

  5. Starvation Ketoacidosis as a Cause of Unexplained Metabolic Acidosis in the Perioperative Period

    Mostert, Monique; Bonavia, Anthony

    2016-01-01

    Patient: Female, 24 Final Diagnosis: Starvation ketoacidosis Symptoms: None Medication: — Clinical Procedure: Lumbar laminectomy Specialty: Orthopedics and Traumatology Objective: Unusual clinical course Background: Besides providing anesthesia for surgery, the anesthesiologist’s role is to optimize the patient for surgery and for post-surgical recovery. This involves timely identification and treatment of medical comorbidities and abnormal laboratory values that could complicate the patient’s perioperative course. There are several potential causes of anion and non-anion gap metabolic acidosis in surgical patients, most of which could profoundly affect a patient’s surgical outcome. Thus, the presence of an acute acid-base disturbance requires a thorough workup, the results of which will influence the patient’s anesthetic management. Case Report: An otherwise-healthy 24-year-old female presented for elective spine surgery and was found to have metabolic acidosis, hypotension, and polyuria intraoperatively. Common causes of acute metabolic acidosis were investigated and systematically ruled out, including lactic acidosis, diabetic ketoacidosis, drug-induced ketoacidosis, ingestion of toxic alcohols (e.g., methanol, ethylene glycol), uremia, and acute renal failure. Laboratory workup was remarkable only for elevated serum and urinary ketone levels, believed to be secondary to starvation ketoacidosis. Due to the patient’s unexplained acid-base disturbance, she was kept intubated postoperatively to allow for further workup and management. Conclusions: Starvation ketoacidosis is not widely recognized as a perioperative entity, and it is not well described in the medical literature. Lack of anesthesiologist awareness about this disorder may complicate the differential diagnosis for acute intraoperative metabolic acidosis and lead to a prolonged postoperative stay and an increase in hospital costs. The short- and long-term implications of perioperative

  6. Acidosis downregulates platelet haemostatic functions and promotes neutrophil proinflammatory responses mediated by platelets.

    Etulain, Julia; Negrotto, Soledad; Carestia, Agostina; Pozner, Roberto Gabriel; Romaniuk, María Albertina; D'Atri, Lina Paola; Klement, Giannoula Lakka; Schattner, Mirta

    2012-01-01

    Acidosis is one of the hallmarks of tissue injury such as trauma, infection, inflammation, and tumour growth. Although platelets participate in the pathophysiology of all these processes, the impact of acidosis on platelet biology has not been studied outside of the quality control of laboratory aggregation assays or platelet transfusion optimization. Herein, we evaluate the effect of physiologically relevant changes in extracellular acidosis on the biological function of platelets, placing particular emphasis on haemostatic and secretory functions. Platelet haemostatic responses such as adhesion, spreading, activation of αIIbβ3 integrin, ATP release, aggregation, thromboxane B2 generation, clot retraction and procoagulant activity including phosphatidilserine exposure and microparticle formation, showed a statistically significant inhibition of thrombin-induced changes at pH of 7.0 and 6.5 compared to the physiological pH (7.4). The release of alpha granule content was differentially regulated by acidosis. At low pH, thrombin or collagen-induced secretion of vascular endothelial growth factor and endostatin were dramatically reduced. The release of von Willebrand factor and stromal derived factor-1α followed a similar, albeit less dramatic pattern. In contrast, the induction of CD40L was not changed by low pH, and P-selectin exposure was significantly increased. While the generation of mixed platelet-leukocyte aggregates and the increased chemotaxis of neutrophils mediated by platelets were further augmented under acidic conditions in a P-selectin dependent manner, the increased neutrophil survival was independent of P-selectin expression. In conclusion, our results indicate that extracellular acidosis downregulates most of the haemostatic platelet functions, and promotes those involved in amplifying the neutrophil-mediated inflammatory response.

  7. Chronic metabolic acidosis reduces urinary oxalate excretion and promotes intestinal oxalate secretion in the rat.

    Whittamore, Jonathan M; Hatch, Marguerite

    2015-11-01

    Urinary oxalate excretion is reduced in rats during a chronic metabolic acidosis, but how this is achieved is not clear. In this report, we re-examine our prior work on the effects of a metabolic acidosis on urinary oxalate handling [Green et al., Am J Physiol Ren Physiol 289(3):F536-F543, 2005], offering a more detailed analysis and interpretation of the data, together with new, previously unpublished observations revealing a marked impact on intestinal oxalate transport. Sprague-Dawley rats were provided with 0.28 M ammonium chloride in their drinking water for either 4 or 14 days followed by 24 h urine collections, blood-gas and serum ion analysis, and measurements of (14)C-oxalate fluxes across isolated segments of the distal colon. Urinary oxalate excretion was significantly reduced by 75% after just 4 days compared to control rats, and this was similarly sustained at 14 days. Oxalate:creatinine clearance ratios indicated enhanced net re-absorption of oxalate by the kidney during a metabolic acidosis, but this was not associated with any substantive changes to serum oxalate levels. In the distal colon, oxalate transport was dramatically altered from net absorption in controls (6.20 ± 0.63 pmol cm(-2) h(-1)), to net secretion in rats with a metabolic acidosis (-5.19 ± 1.18 and -2.07 ± 1.05 pmol cm(-2) h(-1) at 4 and 14 days, respectively). Although we cannot rule out modifications to bi-directional oxalate movements along the proximal tubule, these findings support a gut-kidney axis in the management of oxalate homeostasis, where this shift in renal handling during a metabolic acidosis is associated with compensatory adaptations by the intestine.

  8. Extracellular acidosis induces neutrophil activation by a mechanism dependent on activation of phosphatidylinositol 3-kinase/Akt and ERK pathways.

    Martínez, Diego; Vermeulen, Mónica; Trevani, Analía; Ceballos, Ana; Sabatté, Juan; Gamberale, Romina; Alvarez, María Eugenia; Salamone, Gabriela; Tanos, Tamara; Coso, Omar A; Geffner, Jorge

    2006-01-15

    Inflammation in peripheral tissues is usually associated with the development of local acidosis; however, there are few studies aimed at analyzing the influence of acidosis on immune cells. We have shown previously that extracellular acidosis triggers human neutrophil activation, inducing a transient increase in intracellular Ca2+ concentration, a shape change response, the up-regulation of CD18 expression, and a delay of apoptosis. In this study, we analyzed the signaling pathways responsible for neutrophil activation. We found that acidosis triggers the phosphorylation of Akt (the main downstream target of PI3K) and ERK MAPK, but not that of p38 and JNK MAPK. No degradation of IkappaB was observed, supporting the hypothesis that NF-kappaB is not activated under acidosis. Inhibition of PI3K by wortmannin or LY294002 markedly decreased the shape change response and the induction of Ca2+ transients triggered by acidosis, whereas the inhibition of MEK by PD98059 or U0126 significantly inhibited the shape change response without affecting the induction of Ca2+ transients. We also found that acidosis not only induces a shape change response and the induction of Ca2+ transients in human neutrophils but also stimulates the endocytosis of FITC-OVA and FITC-dextran. Stimulation of endocytosis was partially prevented by inhibitors of PI3K and MEK. Together, our results support the notion that the stimulation of human neutrophils by extracellular acidosis is dependent on the activation of PI3K/Akt and ERK pathways. Of note, using mouse peritoneal neutrophils we observed that the enhancement of endocytosis induced by acidosis was associated with an improved ability to present extracellular Ags through a MHC class I-restricted pathway.

  9. Construction and validation of a decision tree for treating metabolic acidosis in calves with neonatal diarrhea

    Trefz Florian M

    2012-12-01

    Full Text Available Abstract Background The aim of the present prospective study was to investigate whether a decision tree based on basic clinical signs could be used to determine the treatment of metabolic acidosis in calves successfully without expensive laboratory equipment. A total of 121 calves with a diagnosis of neonatal diarrhea admitted to a veterinary teaching hospital were included in the study. The dosages of sodium bicarbonate administered followed simple guidelines based on the results of a previous retrospective analysis. Calves that were neither dehydrated nor assumed to be acidemic received an oral electrolyte solution. In cases in which intravenous correction of acidosis and/or dehydration was deemed necessary, the provided amount of sodium bicarbonate ranged from 250 to 750 mmol (depending on alterations in posture and infusion volumes from 1 to 6.25 liters (depending on the degree of dehydration. Individual body weights of calves were disregarded. During the 24 hour study period the investigator was blinded to all laboratory findings. Results After being lifted, many calves were able to stand despite base excess levels below −20 mmol/l. Especially in those calves, metabolic acidosis was undercorrected with the provided amount of 500 mmol sodium bicarbonate, which was intended for calves standing insecurely. In 13 calves metabolic acidosis was not treated successfully as defined by an expected treatment failure or a measured base excess value below −5 mmol/l. By contrast, 24 hours after the initiation of therapy, a metabolic alkalosis was present in 55 calves (base excess levels above +5 mmol/l. However, the clinical status was not affected significantly by the metabolic alkalosis. Conclusions Assuming re-evaluation of the calf after 24 hours, the tested decision tree can be recommended for the use in field practice with minor modifications. Calves that stand insecurely and are not able to correct their position if pushed

  10. Transient Acidosis during Early Reperfusion Attenuates Myocardium Ischemia Reperfusion Injury via PI3k-Akt-eNOS Signaling Pathway

    Xin Qiao

    2013-01-01

    Full Text Available In this paper, we concluded that transient acidosis reperfusion conferred cardioprotection against myocardial ischemia reperfusion injury in isolated rat hearts through activating PI3K-Akt-eNOS pathway.

  11. Rumen microbial and fermentation characteristics are affected differently by bacterial probiotic supplementation during induced lactic and subacute acidosis in sheep

    Lettat Abderzak

    2012-07-01

    Full Text Available Abstract Background Ruminal disbiosis induced by feeding is the cause of ruminal acidosis, a digestive disorder prevalent in high-producing ruminants. Because probiotic microorganisms can modulate the gastrointestinal microbiota, propionibacteria- and lactobacilli-based probiotics were tested for their effectiveness in preventing different forms of acidosis. Results Lactic acidosis, butyric and propionic subacute ruminal acidosis (SARA were induced by feed chalenges in three groups of four wethers intraruminally dosed with wheat, corn or beet pulp. In each group, wethers were either not supplemented (C or supplemented with Propionibacterium P63 alone (P or combined with L. plantarum (Lp + P or L. rhamnosus (Lr + P. Compared with C, all the probiotics stimulated lactobacilli proliferation, which reached up to 25% of total bacteria during wheat-induced lactic acidosis. This induced a large increase in lactate concentration, which decreased ruminal pH. During the corn-induced butyric SARA, Lp + P decreased Prevotella spp. proportion with a concomitant decrease in microbial amylase activity and total volatile fatty acids concentration, and an increase in xylanase activity and pH. Relative to the beet pulp-induced propionic SARA, P and Lr + P improved ruminal pH without affecting the microbial or fermentation characteristics. Regardless of acidosis type, denaturing gradient gel electrophoresis revealed that probiotic supplementations modified the bacterial community structure. Conclusion This work showed that the effectiveness of the bacterial probiotics tested depended on the acidosis type. Although these probiotics were ineffective in lactic acidosis because of a deeply disturbed rumen microbiota, some of the probiotics tested may be useful to minimize the occurrence of butyric and propionic SARA in sheep. However, their modes of action need to be further investigated.

  12. Knock-down of hypoxia-induced carbonic anhydrases IX and XII radiosensitizes tumor cells by increasing intracellular acidosis

    2013-01-01

    The relationship between acidosis within the tumor microenvironment and radioresistance of hypoxic tumor cells remains unclear. Previously we reported that hypoxia-induced carbonic anhydrases (CA) IX and CAXII constitute a robust intracellular pH (pHi)-regulating system that confers a survival advantage on hypoxic human colon carcinoma LS174Tr cells in acidic microenvironments. Here we investigate the role of acidosis, CAIX and CAXII knock-down in combination with ionizing radiation. Fibrobla...

  13. Acidosis activation of the proton-sensing GPR4 receptor stimulates vascular endothelial cell inflammatory responses revealed by transcriptome analysis.

    Lixue Dong

    Full Text Available Acidic tissue microenvironment commonly exists in inflammatory diseases, tumors, ischemic organs, sickle cell disease, and many other pathological conditions due to hypoxia, glycolytic cell metabolism and deficient blood perfusion. However, the molecular mechanisms by which cells sense and respond to the acidic microenvironment are not well understood. GPR4 is a proton-sensing receptor expressed in endothelial cells and other cell types. The receptor is fully activated by acidic extracellular pH but exhibits lesser activity at the physiological pH 7.4 and minimal activity at more alkaline pH. To delineate the function and signaling pathways of GPR4 activation by acidosis in endothelial cells, we compared the global gene expression of the acidosis response in primary human umbilical vein endothelial cells (HUVEC with varying level of GPR4. The results demonstrated that acidosis activation of GPR4 in HUVEC substantially increased the expression of a number of inflammatory genes such as chemokines, cytokines, adhesion molecules, NF-κB pathway genes, and prostaglandin-endoperoxidase synthase 2 (PTGS2 or COX-2 and stress response genes such as ATF3 and DDIT3 (CHOP. Similar GPR4-mediated acidosis induction of the inflammatory genes was also noted in other types of endothelial cells including human lung microvascular endothelial cells and pulmonary artery endothelial cells. Further analyses indicated that the NF-κB pathway was important for the acidosis/GPR4-induced inflammatory gene expression. Moreover, acidosis activation of GPR4 increased the adhesion of HUVEC to U937 monocytic cells under a flow condition. Importantly, treatment with a recently identified GPR4 antagonist significantly reduced the acidosis/GPR4-mediated endothelial cell inflammatory response. Taken together, these results show that activation of GPR4 by acidosis stimulates the expression of a wide range of inflammatory genes in endothelial cells. Such inflammatory response can be

  14. Renal tubular acidosis type IV as a complication of lupus nephritis.

    Sánchez-Marcos, C; Hoffman, V; Prieto-González, S; Hernández-Rodríguez, J; Espinosa, G

    2016-03-01

    Renal tubular acidosis (RTA) is a rare complication of renal involvement of systemic lupus erythematosus (SLE). We describe a 24-year-old male with type IV lupus nephropathy as a presenting manifestation of SLE. He presented with improvement of renal function following induction therapy with three pulses of methylprednisolone and 500 mg biweekly pulses of cyclophosphamide. However, a week after the first pulse of cyclophosphamide, the patient presented with a significant increase in legs edema and severe hyperkalemia. Type IV RTA associated with hyporeninemic hypoaldosteronism was suspected in the presence of metabolic acidosis with a normal anion gap, severe hyperkalemia without worsening renal function, and urinary pH of 5. RTA was confirmed with a transtubular potassium concentration gradient of 2 and low levels of plasma aldosterone, renin, angiotensin II, and cortisol. Intravenous bicarbonate, high-dose furosemide, and fludrocortisone were administered with normalization of potassium levels and renal function.

  15. Rapid Revival of a Patient after very Severe Metabolic Acidosis: A Case Report

    Sajad Ahmadi

    2013-01-01

    Full Text Available Background: Metabolic acidosis is a fatal finding in trauma patients thatcomplicates the process of resuscitation.Case: The case was a 37-year-old man with open fracture in both legs and fracturein second lumbar vertebral (L2. The serial arterial blood gas (ABG test resultsshowed a pH value of 6.7 indicating a very severe and special case of metabolicacidosis. The rate of mortality for such a case was very high. The patient wastreated with sodium bicarbonate and successfully revived after four hours posttreatment and metabolic acidosis was resolved.Conclusion: This indicated that bicarbonate administration is useful for verysevere cases. The good condition of the patient after survival from the severeacademia allowed for extubation.

  16. Alteration in Fecal Microbiota Associated with Grain-induced Subacute Ruminal Acidosis Challenge in Dairy Cows

    Danscher, Anne Mette; Derakshani, Hooman; Li, Shucong

    2014-01-01

    Introduction: High prevalence of subacute rumen acidosis (SARA) in dairy herds has been reported with large impact on production and welfare. The field diagnosis of SARA is currently unclear and primarily based on point measurements of rumen pH, which are inaccurate. Consequently, SARA cases in t...... of the disease. bovine, subacute ruminal acidosis, fecal microbiome, biological marker Host publication information...... in the field are often not detected. Thus, other and better markers of SARA are needed. The purpose of this research was to study the feces microbiome during SARA and assess the possibilities of using feces microbial markers as indicators of SARA. Methods: Six lactating, rumen cannulated, Danish Holstein cows...... value was estimated to R2: 87.0 and Q2: 73.2, respectively. Conclusion: Results confirm that intensive grain feeding changes the feces microbiome. The identification of specific taxa characteristic of SARA could provide new knowledge of the pathogenesis and might be useful as future biological markers...

  17. Sjogren's syndrome with distal renal tubular acidosis presenting as hypokalaemic paralysis.

    Vaidya, Gaurang; Ganeshpure, Swapnil

    2012-10-19

    A young lady with a history of repeated episodes of generalised weakness and fatigue presented to our hospital with similar symptoms and was found to have severe hypokalaemia. She had been previously diagnosed as hypokalaemic periodic paralysis but during this presentation she had also started complaining of the classic sicca-complex of Sjogren's syndrome, which was not present previously. On subsequent investigations she was found to have normal anion-gap metabolic acidosis with positive urine anion gap consistent with the diagnosis of distal renal tubular acidosis (RTA). It was thus concluded that the distal RTA secondary to Sjogren's syndrome was the cause of severe hypokalaemia in our patient. By presenting this case we aim to not only highlight one of the rare presentations of Sjogren's syndrome but also the favourable response of our patient to potassium replacement alone.

  18. Lactic Acidosis Induced by Linezolid Mimics Symptoms of an Acute Intracranial Bleed: A Case Report and Literature Review

    Zuccarini, Nichole Suzzanne; Yousuf, Tariq; Wozniczka, Daniel; Rauf, Anis Abdul

    2016-01-01

    Lactic acidosis is common and most often associated with disturbed acid-base balance. Rarely, it can be a life-threatening medication side effect. Hence, determining the etiology of lactic acidosis early in patients is paramount in choosing the correct therapeutic intervention. Although lactic acidosis as an adverse drug reaction of linezolid is a well-recognized and documented clinical entity, the occurrence of such mimicking an acute intracranial bleed has not been reported to our knowledge. The following case is presented as an example of such an occurrence. A 67-year-old woman presented to the emergency department for lethargy, nausea and syncope. The head CT did not demonstrate any bleeding or mass effect, but lab results were significant for elevated lactic acid. The patient recently underwent left total hip replacement surgery, which was complicated by a methicillin-resistant Staphylococcus aureus (MRSA) infection. She received 6 weeks of oral linezolid therapy. And upon learning that key part of her history, the linezolid was discontinued. Her lactic acid rapidly normalized and she was discharged home. Several publications demonstrate that linezolid induces lactic acidosis by disrupting crucial mitochondrial functions. It is essential that clinicians are aware that linezolid can cause lactic acidosis. And, the important reminder is that adverse drug reactions can often mimic common diseases. If it is not recognized early, ominous clinical consequences may occur. In conclusion, linezolid should be suspected and included in the differential diagnosis if lactic acidosis exists with an uncommon clinical picture. PMID:27635182

  19. The Use of Sodium Bicarbonate in the Treatment of Acidosis in Sepsis: A Literature Update on a Long Term Debate

    Dimitrios Velissaris

    2015-01-01

    Full Text Available Introduction. Sepsis and its consequences such as metabolic acidosis are resulting in increased mortality. Although correction of metabolic acidosis with sodium bicarbonate seems a reasonable approach, there is ongoing debate regarding the role of bicarbonates as a therapeutic option. Methods. We conducted a PubMed literature search in order to identify published literature related to the effects of sodium bicarbonate treatment on metabolic acidosis due to sepsis. The search included all articles published in English in the last 35 years. Results. There is ongoing debate regarding the use of bicarbonates for the treatment of acidosis in sepsis, but there is a trend towards not using bicarbonate in sepsis patients with arterial blood gas pH>7.15. Conclusions. Routine use of bicarbonate for treatment of severe acidemia and lactic acidosis due to sepsis is subject of controversy, and current opinion does not favor routine use of bicarbonates. However, available evidence is inconclusive, and more studies are required to determine the potential benefit, if any, of bicarbonate therapy in the sepsis patient with acidosis.

  20. Role of Ca2+ in protecting the heart from hyperkalemia and acidosis in the rabbit: implications for exercise.

    Leitch, S P; Paterson, D J

    1994-11-01

    Catecholamines can offset the negative effect of acidosis and raised extracellular K+ concentration in the isolated rabbit heart when these factors are changed with similar kinetics and concentrations as those observed in exercise. This effect appears to be mediated by changes in Ca2+ handling in the heart. To test the role of Ca2+ in vivo, we studied the interactive effects of infusions of KCl, lactic acid, norepinephrine (NE), and CaCl2 on cardiovascular performance in the anesthetized rabbit. After propranolol, CaCl2 was given during acidosis and hyperkalemia. Acidosis (arterial pH 7.17 +/- 0.3) markedly reduced cardiac performance, and its effects were exacerbated by hyperkalemia (7.3 +/- 0.4 mM). NE reversed the cardiac response to combined acidosis and hyperkalemia. After propranolol, arterial pH and arterial K+ concentration changed more rapidly with acidosis and hyperkalemia, combined with a faster fall in cardiac performance, but CaCl2 offset these negative hemodynamic effects. The rises in plasma Ca2+, NE, and sympathetic activity during exercise may therefore interact to ameliorate the harmful effects of acidosis and hyperkalemia.

  1. Relationship between rickets and incomplete distal renal tubular acidosis in children

    Oduwole Abiola O

    2010-08-01

    Full Text Available Abstract Background In the Sub Saharan Africa Rickets has now been established to be due primarily to calcium deficiency and sometimes in combination with vitamin D deficiency. The main thrust of management is calcium supplementation with or without vitamin D. An observation was made that some children with nutritional rickets do not respond to this management modality. The recently reported high prevalence of Incomplete Distal Renal Tubular Acidosis (idRTA in adults with osteoporosis as brought to fore the possibility of this being a possible cause of calcium wastage and therefore the poor response in these group of children with rickets. Aim To determine the prevalence of idRTA amongst a cohort of subjects with rickets To show a relationship between rickets and incomplete distal renal acidosis To determine the response of children with rickets and idRTA to addition of Shohl's solution to therapy Methodology Two separate cohorts of children with rickets performed the ammonium chloride loading test to detect those with incomplete renal tubular acidosis. Following identification for idRTA, Shohl's solution was added to therapy of calcium and vitamin D supplementation and their response compared to those without idRTA on calcium and vitamin D supplementation solely. Results 50 children with rickets aged from two to six years of age and composed of 29 females and 21males were investigated. Incomplete renal tubular acidosis was found in 38% of them. Prevalence of idRTA was highest amongst those aged 3-6 years of age. Those with idRTA had worse limb deformities, biochemical and radiological parameters than those who hadn't. Rate of response on those with idRTA treated with Shohl's solution was at par with those without idRTA. Conclusion Incomplete idRTA exist amongst children with rickets and should be looked out for in severe rickets and older children. Treatment of idRTA will lead to optimal response and healing of rickets.

  2. The Effects of Extracellular Acidosis on Neurons and Glia In Vitro

    Goldman, Steven A.; PULSINELLI, WILLIAM A.; Clarke, Wendy Y.; Kraig, Richard P.; Plum, Fred

    1989-01-01

    Cerebral lactic acid, a product of ischemic anaerobic glycolysis, may directly contribute to ischemic brain damage in vivo. In this study we evaluated the effects of extracellular acid exposure on 7-day-old cultures of embryonic rat forebrain. Mixed neuronal and glial cultures were exposed to either lactic or hydrochloric acid to compare the toxicities of relatively permeable and impermeable acids. Neurons were relatively resistant to extracellular HCl acidosis, often surviving 10-min exposur...

  3. Metabolic acidosis and malnutrition-inflammation complex syndrome in chronic renal failure.

    Kalantar-Zadeh, Kamyar; Mehrotra, Rajnish; Fouque, Denis; Kopple, Joel D

    2004-01-01

    Metabolic acidosis, a common condition in patients with renal failure, may be linked to protein-energy malnutrition (PEM) and inflammation, together also known as malnutrition-inflammation complex syndrome (MICS). Methods of serum bicarbonate measurement may misrepresent the true bicarbonate level, since the total serum carbon dioxide measurement usually overestimates the serum bicarbonate concentration. Moreover, the air transportation of blood samples to distant laboratories may lead to erroneous readings. In patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD), a significant number of endocrine, musculoskeletal, and metabolic abnormalities are believed to result from acidemia. Metabolic acidosis may be related to PEM and MICS due to an increased protein catabolism, decreased protein synthesis, endocrine abnormalities including insulin resistance, decreased serum leptin level, and inflammation among individuals with renal failure. Evidence suggests that the catabolic effects of metabolic acidosis may result from an increased activity of the adenosine triphosphate (ATP)-dependent ubiquitin-proteasome and branched-chain keto acid dehydrogenase. In contrast to the metabolic studies, many epidemiologic studies in maintenance dialysis patients have indicated a paradoxically inverse association between mildly decreased serum bicarbonate and improved markers of protein-energy nutritional state. Hence metabolic acidosis may be considered as yet another element of the reverse epidemiology in ESRD patients. Interventional studies have yielded inconsistent results in CKD and ESRD patients, although in peritoneal dialysis patients, mitigating acidemia appears to more consistently improve nutritional status and reduce hospitalizations. Large-scale, prospective randomized interventional studies are needed to ascertain the potential benefits of correcting acidemia in malnourished and/or inflamed CKD and maintenance hemodialysis patients. Until then, all

  4. Characterization of the increased synthesis of rat renal glutaminase during metabolic acidosis

    Tong, J.Y.

    1986-01-01

    The relative rates of glutaminase synthesis were determined by comparing the amount of (/sup 35/S)methionine incorporated into specific immunoprecipitates with that incorporated into total protein. In a normal animal, the rate of glutaminase synthesis constitutes 0.04% of the total protein synthesis. During onset of acidosis, the relative rate of synthesis increases more rapidly than the appearance of increased glutaminase activity. Recovery from chronic acidosis results in a rapid decrease in the relative rate of glutaminase synthesis, but a gradual decrease in glutaminase activity. From the decrease in activity that occurs upon recovery from acidosis, the tube half-life for the glutaminase was estimated to be 3 days. The reticulocyte lysate was used to compare the level of translatable glutaminase mRNA that is present in rat kidney following translatable glutaminase mRNA that is present in rat kidney following onset of acidosis. The initial translate of glutaminase was previously identified as a 72,000 dalton protein that is 4000 daltons larger than the mitochondrial glutaminase. The amount of (/sup 35/S)methionine incorporated into the glutaminase was determined by densitometric tracing of specific immunoprecipitates. The relative rate of glutaminase synthesis was determined by comparing this value with the amount of (/sup 35/S) methionine incorporated into total protein. In order to obtain a more specific immunoprecipitate of the in vitro translate, poly(A)/sup +/RNA was fractionated. The fractionated poly(A)/sup +/RNA was about 25-fold enriched in glutaminase mRNA. The size of glutaminase mRNA was estimated to be between 6.4 Kb and 6.8 Kb. The effect of alteration in acid-base balance on the level of mRNA coding for glutaminase was also determined by using fractionated poly(A)/sup +/RNA from the kidneys of normal, chronic acidotic and recovered rats for in vitro translation.

  5. Metabolic acidosis and changes in water and electrolyte balance after maximal exercise.

    Sejersted, O M; Medbø, J I; Hermansen, L

    1982-01-01

    The purpose of this investigation was to study lactate production and the consequent changes in acid-base status, and in water and electrolyte balance, in response to 1 min of maximal exercise in sprint- and endurance-trained subjects. So far, the results from only two subjects (one sprinter and one marathon runner) have been analysed. The rate of lactate production was higher in the sprinter than in the marathon runner, as shown by peak blood lactate concentrations of 20.8 and 13.3 mM for the two subjects, respectively. Arterial blood pH fell from 7.43 to 7.14 in the sprinter and from 7.44 to 7.23 for the marathon runner. The metabolic acidosis was partly compensated for by a lowering of arterial CO2 tension by 0.0775 kPa per 1 mM drop in base excess. In each subject large changes in water and electrolyte balance occurred. Haematocrit increased dramatically in both subjects, and the calculated decrease in plasma volume was 20% for the marathon runner and 30% for the sprinter. In each subject sodium was removed from the circulation in amounts sufficient to keep the plasma sodium concentration constant. Plasma potassium concentration was unrelated to the state of acidosis, being 2.5 mM above the resting concentration immediately after maximal exercise, and dropping by 3 mM in the subsequent 2-3 min of recovery during prevailing acidosis. The degree of lactic acidosis was large in both subjects, although more severe in the sprinter than in the endurance runner. However, buffer capacity and compensatory mechanisms were largely similar in both subjects.

  6. Cleistanthus collinus induces type I distal renal tubular acidosis and type II respiratory failure in rats

    Maneksh Delinda

    2010-01-01

    Full Text Available Background and Purpose : A water decoction of the poisonous shrub Cleistanthus collinus is used for suicidal purposes. The mortality rate is 28%. The clinical profile includes distal renal tubular acidosis (DRTA and respiratory failure. The mechanism of toxicity is unclear. Objectives : To demonstrate features of C. collinus toxicity in a rat model and to identify its mechanism(s of action. Materials and Methods : Rats were anesthetized and the carotid artery was cannulated. Electrocardiogram and respiratory movements were recorded. Either aqueous extract of C. collinus or control solution was administered intraperitoneally. Serial measurements of blood gases, electrolytes and urinary pH were made. Isolated brush border and basolateral membranes from rat kidney were incubated with C. collinus extract and reduction in ATPase activity was assessed. Venous blood samples from human volunteers and rats were incubated with an acetone extract of C. collinus and plasma potassium was estimated as an assay for sodium-potassium pump activity. Results : The mortality was 100% in tests and 17% in controls. Terminal event in test animals was respiratory arrest. Controls had metabolic acidosis, respiratory compensation , acidic urine and hyperkalemia. Test animals showed respiratory acidosis, alkaline urine and low blood potassium as compared to controls. C. collinus extract inhibited ATPase activity in rat kidney. Plasma K + did not increase in human blood incubated with C. collinus extract. Conclusions and Implications : Active principles of C. collinus inhibit proton pumps in the renal brush border, resulting in type I DRTA in rats. There is no inhibition of sodium-potassium pump activity. Test animals develop respiratory acidosis, and the immediate cause of death is respiratory arrest.

  7. Proximal tubule-specific glutamine synthetase deletion alters basal and acidosis-stimulated ammonia metabolism.

    Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E; Lamers, Wouter H; Chaudhry, Farrukh A; Verlander, Jill W; Weiner, I David

    2016-06-01

    Glutamine synthetase (GS) catalyzes the recycling of NH4 (+) with glutamate to form glutamine. GS is highly expressed in the renal proximal tubule (PT), suggesting ammonia recycling via GS could decrease net ammoniagenesis and thereby limit ammonia available for net acid excretion. The purpose of the present study was to determine the role of PT GS in ammonia metabolism under basal conditions and during metabolic acidosis. We generated mice with PT-specific GS deletion (PT-GS-KO) using Cre-loxP techniques. Under basal conditions, PT-GS-KO increased urinary ammonia excretion significantly. Increased ammonia excretion occurred despite decreased expression of key proteins involved in renal ammonia generation. After the induction of metabolic acidosis, the ability to increase ammonia excretion was impaired significantly by PT-GS-KO. The blunted increase in ammonia excretion occurred despite greater expression of multiple components of ammonia generation, including SN1 (Slc38a3), phosphate-dependent glutaminase, phosphoenolpyruvate carboxykinase, and Na(+)-coupled electrogenic bicarbonate cotransporter. We conclude that 1) GS-mediated ammonia recycling in the PT contributes to both basal and acidosis-stimulated ammonia metabolism and 2) adaptive changes in other proteins involved in ammonia metabolism occur in response to PT-GS-KO and cause an underestimation of the role of PT GS expression.

  8. High anion gap refractory metabolic acidosis as a critical presentation of endosulfan poisoning

    Raj Kumar Sharma

    2011-01-01

    Full Text Available Organochloride insecticides are chlorinated cyclic hydrocarbons. One of such insecticides is endosulfan (6,7,8,9,10-10 hexachloro 1,5,5a,6,9,9a-hexahydro-6-methano-2,4,3-hexadithioxanthiep in 3-oxide and it has been widely used in agriculture since 1960. The uncontrolled use of these compounds in developing countries has resulted in the deaths of animals and humans. Characteristic clinical signs following acute exposure are indicative of CNS disturbances or overstimulation. Mortality and morbidity rates are high and there is no specific antidote. We present an uncommon presentation of endosulfan poisoning in a 32-year-old male with high anion gap severe refractory metabolic acidosis. The patient was treated with continuous renal replacement therapy and was salvaged. Till date, there is no case report from India for endosulfan poisoning with severe metabolic acidosis and hypotension. Through this case report, we emphasize the role of continuous renal replacement therapy as a rescue therapy for endosulfan poisoning with severe refractory metabolic acidosis and hypotension, even though it is a non dialyzable poison.

  9. Profound neonatal hypoglycemia and lactic acidosis caused by pyridoxine-dependent epilepsy.

    Mercimek-Mahmutoglu, Saadet; Horvath, Gabriella A; Coulter-Mackie, Marion; Nelson, Tanya; Waters, Paula J; Sargent, Michael; Struys, Eduard; Jakobs, Cornelis; Stockler-Ipsiroglu, Sylvia; Connolly, Mary B

    2012-05-01

    Pyridoxine-dependent epilepsy (PDE) was first described in 1954. The ALDH7A1 gene mutations resulting in α-aminoadipic semialdehyde dehydrogenase deficiency as a cause of PDE was identified only in 2005. Neonatal epileptic encephalopathy is the presenting feature in >50% of patients with classic PDE. We report the case of a 13-month-old girl with profound neonatal hypoglycemia (0.6 mmol/L; reference range >2.4), lactic acidosis (11 mmol/L; reference range pyridoxine. The diagnosis of α-aminoadipic semialdehyde dehydrogenase deficiency was confirmed based on the elevated urinary α-aminoadipic semialdehyde excretion, compound heterozygosity for a known splice mutation c.834G>A (p.Val278Val), and a novel putative pathogenic missense mutation c.1192G>C (p.Gly398Arg) in the ALDH7A1 gene. She has been seizure-free since 1.5 months of age on treatment with pyridoxine alone. She has motor delay and central hypotonia but normal language and social development at the age of 13 months. This case is the first description of a patient with PDE due to mutations in the ALDH7A1 gene who presented with profound neonatal hypoglycemia and lactic acidosis masquerading as a neonatal-onset gluconeogenesis defect. PDE should be included in the differential diagnosis of hypoglycemia and lactic acidosis in addition to medically refractory neonatal seizures.

  10. The effects of extracellular acidosis on neurons and glia in vitro.

    Goldman, S A; Pulsinelli, W A; Clarke, W Y; Kraig, R P; Plum, F

    1989-08-01

    Cerebral lactic acid, a product of ischemic anaerobic glycolysis, may directly contribute to ischemic brain damage in vivo. In this study we evaluated the effects of extracellular acid exposure on 7-day-old cultures of embryonic rat forebrain. Mixed neuronal and glial cultures were exposed to either lactic or hydrochloric acid to compare the toxicities of relatively permeable and impermeable acids. Neurons were relatively resistant to extra-cellular HCl acidosis, often surviving 10-min exposures to pH 3.8. In the same cultures, immunochemically defined astrocytes survived 10-min HCl exposures to a maximum acidity of pH 4.2. Similarly, axonal bundles defasciculated in HCl-titrated media below pH 4.4, although their constituent fibers often survived pH 3.8. Cell death occurred at higher pH in cultures subjected to lactic acidosis than in those exposed to HCl. Over half of forebrain neurons and glia subjected for 10 min to lactic acidification failed to survive exposure to pH 4.9. Longer 1-h lactic acid incubations resulted in cell death below pH 5.2. The potent cytotoxicity of lactic acid may be a direct result of the relatively rapid transfer of its neutral protonated form across cell membranes. This process would rapidly deplete intracellular buffer stores, resulting in unchecked cytosolic acidification. Neuronal and glial death from extracellular acidosis may therefore be a function of both the degree and the rapidity of intracellular acidification.

  11. Acidosis láctica secundaria a terapia antirretroviral en pacientes con VIH/sida

    Benhard Hasbum-Fernández

    2006-06-01

    Full Text Available La acidosis láctica es una complicación infrecuente de la terapia antirretroviral para VIH. Su aparición se ha relacionado con la administración de análogos nucleósidos de la transcriptasa inversa, en especial estavudina y didanosina. Se presentan los 2 casos que se manejaron en el año 2005 en el Servicio de Medicina del Hospital México. En ambos el desenlace fue fatal, aún cuando se utilizaron todas las medidas terapéuticas recomendadas.Lactic acidosis is a rare complication of antiretroviral treatment for HIV. Its occurrence has been related to the use of transcriptase reverse nucleoside analogues, especially estavudine and didanosine. We present here 2 cases of HIV patients who suffered lactic acidosis and were treated at the Internal Medicine Department of the Hospital Mexico, San Jose, Costa Rica. Both cases had a fatal evolution, despite that both received all the therapeutic measures recommended in the literature.

  12. Early Administration of Glutamine Protects Cardiomyocytes from Post-Cardiac Arrest Acidosis

    Yan-Ren Lin

    2016-01-01

    Full Text Available Postcardiac arrest acidosis can decrease survival. Effective medications without adverse side effects are still not well characterized. We aimed to analyze whether early administration of glutamine could improve survival and protect cardiomyocytes from postcardiac arrest acidosis using animal and cell models. Forty Wistar rats with postcardiac arrest acidosis (blood pH < 7.2 were included. They were divided into study (500 mg/kg L-alanyl-L-glutamine, n=20 and control (normal saline, n=20 groups. Each of the rats received resuscitation. The outcomes were compared between the two groups. In addition, cardiomyocytes derived from human induced pluripotent stem cells were exposed to HBSS with different pH levels (7.3 or 6.5 or to culture medium (control. Apoptosis-related markers and beating function were analyzed. We found that the duration of survival was significantly longer in the study group (p<0.05. In addition, in pH 6.5 or pH 7.3 HBSS buffer, the expression levels of cell stress (p53 and apoptosis (caspase-3, Bcl-xL markers were significantly lower in cardiomyocytes treated with 50 mM L-glutamine than those without L-glutamine (RT-PCR. L-glutamine also increased the beating function of cardiomyocytes, especially at the lower pH level (6.5. More importantly, glutamine decreased cardiomyocyte apoptosis and increased these cells’ beating function at a low pH level.

  13. Abnormalities of acid-base balance and predisposition to metabolic acidosis in Metachromatic Leukodystrophy patients.

    Lorioli, L; Cicalese, M P; Silvani, P; Assanelli, A; Salvo, I; Mandelli, A; Fumagalli, F; Fiori, R; Ciceri, F; Aiuti, A; Sessa, M; Roncarolo, M G; Lanzani, C; Biffi, A

    2015-05-01

    Metachromatic Leukodystrophy (MLD; MIM# 250100) is a rare inherited lysosomal storage disorder caused by the deficiency of Arylsulfatase A (ARSA). The enzymatic defect results in the accumulation of the ARSA substrate that is particularly relevant in myelin forming cells and leads to progressive dysmyelination and dysfunction of the central and peripheral nervous system. Sulfatide accumulation has also been reported in various visceral organs, although little is known about the potential clinical consequences of such accumulation. Different forms of MLD-associated gallbladder disease have been described, and there is one reported case of an MLD patient presenting with functional consequences of sulfatide accumulation in the kidney. Here we describe a wide cohort of MLD patients in whom a tendency to sub-clinical metabolic acidosis was observed. Furthermore in some of them we report episodes of metabolic acidosis of different grades of severity developed in acute clinical conditions of various origin. Importantly, we finally show how a careful acid-base balance monitoring and prompt correction of imbalances might prevent severe consequences of acidosis.

  14. Lentiform fork sign: a magnetic resonance finding in a case of acute metabolic acidosis.

    Grasso, Daniela; Borreggine, Carmela; Perfetto, Francesco; Bertozzi, Vincenzo; Trivisano, Marina; Specchio, Luigi Maria; Grilli, Gianpaolo; Macarini, Luca

    2014-06-01

    We report a 33 year-old woman addicted to chronic unspecified solvents abuse with stupor, respiratory disorders, tetraplegia and severe metabolic acidosis. On admission an unenhanced cranial CT scan showed symmetrical hypodensities of both lentiform nuclei. MR imaging performed 12 hours after stupor demonstrates bilateral putaminal hemorrhagic necrosis, bilateral external capsule, corona radiata and deep cerebellar hyperintensities with right cingulate cortex involvement. DWI reflected bilateral putaminal hyperintensities with restricted water diffusion as to citotoxic edema and development of vasogenic edema in the external capsule recalling a fork. On day twenty, after specific treatments MRI demonstrated a bilateral putaminal marginal enhancement. Bilateral putaminal necrosis is a characteristic but non-specific radiological finding of methanol poisoning. Lentiform Fork sign is a rare MRI finding reported in literature in 22 patients with various conditions characterized by metabolic acidosis. Vasogenic edema may be due to the differences in metabolic vulnerability between neurons and astrocytes. We postulate that metabolic acidosis could have an important role to generate this sign.

  15. Effect of chronic metabolic acidosis on bone density and bone architecture in vivo in rats.

    Gasser, Jürg A; Hulter, Henry N; Imboden, Peter; Krapf, Reto

    2014-03-01

    Chronic metabolic acidosis (CMA) might result in a decrease in vivo in bone mass based on its reported in vitro inhibition of bone mineralization, bone formation, or stimulation of bone resorption, but such data, in the absence of other disorders, have not been reported. CMA also results in negative nitrogen balance, which might decrease skeletal muscle mass. This study analyzed the net in vivo effects of CMA's cellular and physicochemical processes on bone turnover, trabecular and cortical bone density, and bone microarchitecture using both peripheral quantitative computed tomography and μCT. CMA induced by NH4Cl administration (15 mEq/kg body wt/day) in intact and ovariectomized (OVX) rats resulted in stable CMA (mean Δ[HCO3(-)]p = 10 mmol/l). CMA decreased plasma osteocalcin and increased TRAP5b in intact and OVX animals. CMA decreased total volumetric bone mineral density (vBMD) after 6 and 10 wk (week 10: intact normal +2.1 ± 0.9% vs. intact acidosis -3.6 ± 1.2%, P metabolic acidosis induces a large decrease in cortical bone mass (a prime determinant of bone fragility) in intact and OVX rats and impairs bone microarchitecture characterized by a decrease in trabecular number.

  16. Branched-chain amino acid metabolism in rat muscle: abnormal regulation in acidosis

    May, R.C.; Hara, Y.; Kelly, R.A.; Block, K.P.; Buse, M.G.; Mitch, W.E.

    1987-06-01

    Branched-chain amino acid (BCAA) metabolism is frequently abnormal in pathological conditions accompanied by chronic metabolic acidosis. To study how metabolic acidosis affects BCAA metabolism in muscle, rats were gavage fed a 14% protein diet with or without 4 mmol NH/sub 4/Cl x 100 g body wt/sup -1/ x day/sup -1/. Epitrochlearis muscles were incubated with L-(1-/sup 14/C)-valine and L-(1-/sup 14/C)leucine, and rates of decarboxylation, net transamination, and incorporation into muscle protein were measured. Plasma and muscle BCAA levels were lower in acidotic rats. Rates of valine and leucine decarboxylation and net transamination were higher in muscles from acidotic rats; these differences were associated with a 79% increase in the total activity of branched-chain ..cap alpha..-keto acid dehydrogenase and a 146% increase in the activated form of the enzyme. They conclude that acidosis affects the regulation of BCAA metabolism by enhancing flux through the transaminase and by directly stimulating oxidative catabolism through activation of branched-chain ..cap alpha..-keto acid dehydrogenase.

  17. Coma y acidosis metabólica: Intoxicación por metanol

    J Villegas del Ojo

    2011-01-01

    Full Text Available La intoxicación por metanol es un proceso poco frecuente en la actualidad, a pesar de su uso habitual en la industria, laboratorios y hogar. La vía de intoxicación suele ser la oral y, dada su elevada mortalidad, debe considerarse siempre una intoxicación grave. Se presenta el caso clínico de un paciente joven extranjero sin antecedentes, en coma y con acidosis metabólica grave, que evoluciona a muerte encefálica a pesar de establecer medidas de soporte y tratamiento específico (corrección de acidosis, etanol, diálisis instaurado empíricamente a las 12 horas del ingreso, confirmándose posteriormente la intoxicación por metanol. En conclusión, debe destacarse la importancia del diagnostico precoz, dado el amplio periodo de latencia, la escasa sintomatología inicial y la alta mortalidad, sospechándose ante un paciente con acidosis metabólica con anión gap aumentado y alteraciones neurológicas, pues el diagnóstico de certeza es su presencia en plasma, técnica no disponible en la mayoría de los hospitales.

  18. [Case of distal renal tubular acidosis complicated with renal diabetes insipidus, showing aggravation of symptoms with occurrence of diabetes mellitus].

    Liu, Hexing; Tomoda, Fumihiro; Koike, Tsutomu; Ohara, Maiko; Nakagawa, Taizo; Kagitani, Satoshi; Inoue, Hiroshi

    2011-01-01

    We report herein a 27-year-old male case of inherited distal renal tubular acidosis complicated with renal diabetes insipidus, the symptoms of which were aggravated by the occurrence of diabetes mellitus. At 2 months after birth, he was diagnosed as having inherited distal renal tubular acidosis and thereafter supplementation of both potassium and alkali was started to treat his hypokalemia and metabolic acidosis. At the age of 4 years, calcification of the bilateral renal medulla was detected by computed tomography. Subsequently his urinary volume gradually increased and polyuria of approximately 4 L/day persisted. At the age of 27 years, he became fond of sugar-sweetened drinks and also often forgot to take the medicine. He was admitted to our hospital due to polyuria of more than 10 L day, muscle weakness and gait disturbance. Laboratory tests disclosed worsening of both hypokalemia and metabolic acidosis in addition to severe hyperglycemia. It seemed likely that occurrence of diabetes mellitus and cessation of medications can induce osmotic diuresis and aggravate hypokalemia and metabolic acidosis. Consequently, severe dehydration, hypokalemia-induced damage of his urinary concentration ability and enhancement of the renin angiotensin system occurred and thereby possibly worsened his hypokalemia and metabolic acidosis. As normalization of hyperglycemia and metabolic acidosis might have exacerbated hypokalemia further, dehydration and hypokalemia were treated first. Following intensive treatment, these abnormalities were improved, but polyuria persisted. Elevated plasma antidiuretic hormone (12.0 pg/mL) and deficit of renal responses to antidiuretic hormone suggested that the polyuria was attributable to the preexisting renal diabetes insipidus possibly caused by bilateral renal medulla calcification. Thiazide diuretic or nonsteroidal anti-inflammatory drugs were not effective for the treatment of diabetes insipidus in the present case.

  19. The effect of acidosis on the interval-force relation and mechanical restitution in ferret papillary muscle.

    McCall, E; Orchard, C H

    1991-01-01

    1. The effect of a respiratory acidosis on the interval-force relation and on mechanical restitution was investigated in ferret papillary muscles. 2. Acidosis (pH 6.85) decreased developed force over a range of stimulation frequencies (1.0.06 Hz); the percentage decrease was greatest at the lowest stimulation frequencies. Qualitatively similar effects of acidosis on developed force were observed in the presence of the sarcoplasmic reticulum (SR) inhibitor ryanodine. 3. Mechanical restitution curves were constructed by interpolating extra-systoles at different test intervals following a train of steady-state beats. Mechanical restitution in ferret papillary muscle was triphasic: an initial, rapid, exponential increase in force with test intervals to 2 s, a further increase with test intervals between 60 and 90 s and then a slow decline, with a plateau at about 30 min (0.33 Hz, 30 degrees C). 4. Acidosis slowed the initial phase of mechanical restitution. The degree of slowing depended on the steady-state stimulation frequency, being greatest at low frequencies. 5. Inhibition of the SR abolished the initial phase of mechanical restitution, suggesting that this phase depends on Ca2+ release from the SR. 6. The strength of the first contraction after the extra-systole varied inversely with the size of the extra-systole under all conditions studied. 7. It is concluded that acidosis may inhibit the SR by altering the time required for Ca2+ recycling between contractions. This effect may alter Ca2+ release from the SR during acidosis, and may underlie the mechanical alternans (the alternation of small and large contractions) that can occur during acidosis.

  20. Distal renal tubular acidosis as a cause of osteomalacia in a patient with primary Sjögren's syndrome

    Jovelić Aleksandra

    2005-01-01

    Full Text Available Background. One half of the patients with primary Sjögren’s syndrome has extraglandular manifestations, including renal involvement. The most frequent renal lesion is tubulo-interstitial nephritis, which manifests clinically as distal tubular acidosis and may result in the development of osteomalacia. Case report. In a 29 - year-old female patient, with bilateral nephrolithiasis, the diagnosis of primary Sjögren’s syndrome, tubulo-interstitial nephritis, distal renal tubular acidosis, and hypokalemia were established. She was treated for hypokalemia. Two years later she developed bone pains and muscle weakness, she wasn’t able to walk, her proximal muscles and pelvic bones were painful, with radiological signs of pelvic bones osteopenia and pubic bones fractures. The diagnosis of osteomalacia was established and the treatment started with Schol’s solution, vitamin D and calcium. In the following two months, acidosis was corrected, and the patient started walking. Conclusion. In our patient with primary Sjögren’s syndrome and interstitial nephritis, osteomalacia was a result of the long time decompensate acidosis, so the correction of acidosis, and the supplementation of vitamin D and calcium were the integral part of the therapy.

  1. Systemic lupus erythematosus associated with type 4 renal tubular acidosis: a case report and review of the literature

    Young Larry

    2011-03-01

    Full Text Available Abstract Introduction Type 4 renal tubular acidosis is an uncommon clinical manifestation of systemic lupus erythematosus and has been reported to portend a poor prognosis. To the best of our knowledge, this is the first case report which highlights the successful management of a patient with systemic lupus erythematosus complicated by type 4 renal tubular acidosis who did not do poorly. Case presentation A 44-year-old Hispanic woman developed a non-anion gap hyperkalemic metabolic acidosis consistent with type 4 renal tubular acidosis while being treated in the hospital for recently diagnosed systemic lupus erythematosus with multi-organ involvement. She responded well to treatment with corticosteroids, hydroxychloroquine and mycophenolate mofetil. Normal renal function was achieved prior to discharge and remained normal at the patient's one-month follow-up examination. Conclusion This case increases awareness of an uncommon association between systemic lupus erythematosus and type 4 renal tubular acidosis and suggests a positive impact of early diagnosis and appropriate immunosuppressive treatment on the patient's outcome.

  2. Metformin-associated lactic acidosis: Current perspectives on causes and risk.

    DeFronzo, Ralph; Fleming, G Alexander; Chen, Kim; Bicsak, Thomas A

    2016-02-01

    Although metformin has become a drug of choice for the treatment of type 2 diabetes mellitus, some patients may not receive it owing to the risk of lactic acidosis. Metformin, along with other drugs in the biguanide class, increases plasma lactate levels in a plasma concentration-dependent manner by inhibiting mitochondrial respiration predominantly in the liver. Elevated plasma metformin concentrations (as occur in individuals with renal impairment) and a secondary event or condition that further disrupts lactate production or clearance (e.g., cirrhosis, sepsis, or hypoperfusion), are typically necessary to cause metformin-associated lactic acidosis (MALA). As these secondary events may be unpredictable and the mortality rate for MALA approaches 50%, metformin has been contraindicated in moderate and severe renal impairment since its FDA approval in patients with normal renal function or mild renal insufficiency to minimize the potential for toxic metformin levels and MALA. However, the reported incidence of lactic acidosis in clinical practice has proved to be very low (metformin are too conservative, thus depriving a substantial number of type 2 diabetes patients from the potential benefit of metformin therapy. On the other hand, the success of metformin as the first-line diabetes therapy may be a direct consequence of conservative labeling, the absence of which could have led to excess patient risk and eventual withdrawal from the market, as happened with earlier biguanide therapies. An investigational delayed-release metformin currently under development could potentially provide a treatment option for patients with renal impairment pending the results of future studies. This literature-based review provides an update on the impact of renal function and other conditions on metformin plasma levels and the risk of MALA in patients with type 2 diabetes.

  3. Coma, metabolic acidosis, and methemoglobinemia in a patient with acetaminophen toxicity.

    Kanji, Hussein D; Mithani, Shazma; Boucher, Paul; Dias, Valerian C; Yarema, Mark C

    2013-01-01

    We present a case of early coma, metabolic acidosis and methemoglobinemia after substantial acetaminophen toxicity in the absence of hepatic failure. A 77-year-old female presented to the emergency department with a decreased level of consciousness. She was found unresponsive by a family member in her bed, and was reported to be acting normally when she was last seen eight hours earlier. Laboratory results on arrival were: pH 7.19, sodium 139 mmol/L, chloride 106 mmol/L, potassium 3.3 mmol/L, CO2 8 mmol/L, and an anion gap of 25. Both venous lactate (10.2 mmol/L) and methemoglobin (9.4 %) were elevated. The patient's acetaminophen concentration was markedly elevated at 7138 µmol/L (1078 µg/ml). Hepatic enzymes and coagulation tests were normal [alanine transaminase (ALT) 8 U/L, international normalized ratio (INR) 1.0]. Intravenous N-acetylcysteine (NAC) was initiated at a dose of 150 mg/kg over 15 minutes, followed by 50 mg/kg over the next four hours, followed by 100 mg/kg over the next 16 hours. Twenty-four hours after admission, the anion gap metabolic acidosis had resolved, and the methemoglobin was 2.1%. Aminotransferases peaked at 44 U/L and INR peaked at 1.9. A urine 5-oxoproline assay performed five days after admission was negative, suggesting no evidence of a 5-oxoprolinase deficiency. We describe the pathophysiology and discuss the literature on acetaminophen-induced coma and metabolic acidosis in the absence of hepatic injury; and propose mechanisms for associated methemoglobinemia. 

  4. Effect of metabolic acidosis on renal tubular sodium handling in rats as determined by lithium clearance

    Menegon L.F.

    1998-01-01

    Full Text Available Systemic metabolic acidosis is known to cause a decrease in salt and water reabsorption by the kidney. We have used renal lithium clearance to investigate the effect of chronic, NH4Cl-induced metabolic acidosis on the renal handling of Na+ in male Wistar-Hannover rats (200-250 g. Chronic acidosis (pH 7.16 ± 0.13 caused a sustained increase in renal fractional Na+ excretion (267.9 ± 36.4%, accompanied by an increase in fractional proximal (113.3 ± 3.6% and post-proximal (179.7 ± 20.2% Na+ and urinary K+ (163.4 ± 5.6% excretion when compared to control and pair-fed rats. These differences occurred in spite of an unchanged creatinine clearance and Na+ filtered load. A lower final body weight was observed in the acidotic (232 ± 4.6 g and pair-fed (225 ± 3.6 g rats compared to the controls (258 ± 3.7 g. In contrast, there was a significant increase in the kidney weights of acidotic rats (1.73 ± 0.05 g compared to the other experimental groups (control, 1.46 ± 0.05 g; pair-fed, 1.4 ± 0.05 g. We suggest that altered renal Na+ and K+ handling in acidotic rats may result from a reciprocal relationship between the level of metabolism in renal tubules and ion transport.

  5. The deleterious effect of metabolic acidosis on nutritional status of hemodialysis patients

    Tayebeh Soleymanian

    2011-01-01

    Full Text Available One of the main causes of protein-energy malnutrition in patients on maintenance hemodialysis (MHD is metabolic acidosis. The aim of this study was to evaluate the effect of metabolic acidosis on nutritional status in a group of MHD patients with adequately delivered dialysis treatment. Of 165 eligible anuric MHD outpatients with Kt/V ≥ 1 and no underlying inflammatory diseases, 47 subjects were enrolled. In order to evaluate the effect of different parameters on serum albumin, we measured the pre-dialysis serum albumin, blood pH, serum bicarbonate (HCO 3‾ , Kt/V, normalized protein catabolic rate (nPCR and body mass index (BMI in these patients. The mean age of the study patients was 55 ± 13.8 years; there were 22 females and six diabetics. The average Kt/V was 1.22 ± 0.16, pH was 7.40 ± 0.15, serum HCO 3‾ was 23.18 ± 2.38 mEq/L, serum albumin was 4.03 ± 0.56 g/dL, nPCR was 1.00 ± 0.16 g/kg/day, post-dialysis body weight was 58.50 ± 11.50 kg and BMI was 23.47 ± 2.70 kg/m 2 . There was a statistically significant direct correlation between serum albumin and BMI (r = 0.415, P = 0.004, and between serum albumin and serum HCO 3 (r = 0.341, P = 0.019. On multiple regression analysis, the predictors of serum albumin were serum HCO3‾ and BMI (direct effect and nPCR (inverse effect. In 17 patients on MHD with serum HCO3‾ 22 mEq/L (P = 0.046. These data demonstrate that patients on MHD with metabolic acidosis had a lower serum albumin concentration despite adequate dialysis treatment. The inverse effect of nPCR on serum albumin concentration in acidotic MHD patients may be due to hypercatabolism in the setting of metabolic acidosis, leading to deleterious effects on the nutritional status of patients on MHD.

  6. Severe hypophosphatemic osteomalacia with Fanconi syndrome, renal tubular acidosis, vitamin D deficiency and primary biliary cirrhosis.

    Bando, Hironori; Hashimoto, Naoko; Hirota, Yushi; Sakaguchi, Kazuhiko; Hisa, Itoko; Inoue, Yoshifumi; Imanishi, Yasuo; Seino, Susumu; Kaji, Hiroshi

    2009-01-01

    A 49-year-old woman was admitted to our hospital for back pain with marked thoracic and extremity deformities leading to bed-rest for three years. She was diagnosed with hypophosphatemic osteomalacia based on her symptoms, X-ray and bone scintigram, high serum alkaline phosphatase level, and low serum levels of both phosphorus and 1,25 dihydroxyvitamin D(3) with inhibition of phosphorus reabsorption. Fanconi syndrome with renal tubular acidosis, vitamin D deficiency and primary biliary cirrhosis were related to the pathogenesis of osteomalacia in this case. Several causal diseases may be concomitantly responsible for acceleration of the severity of osteomalacia in this patient.

  7. Poliencefalomalacia asociada a acidosis metabólica en bovino de lidia

    2010-01-01

    La polioencefalomalacia o necrosis cerebrocortical es una enfermedad no infecciosa asociada normalmente a rumiantes jóvenes en cría intensiva. Normalmente la causa desconocida, aunque se asocia a alteraciones de la dieta que puedan conducir a acidosis metabólica. Los signos clínicos más frecuentes son los asociados a desórdenes metabólicos generalizados y a alteraciones del sistema nervioso central, aunque también pueden verse afectados diferentes órganos, provocando lesiones como: abscesos h...

  8. Coma y acidosis metabólica: Intoxicación por metanol

    2011-01-01

    La intoxicación por metanol es un proceso poco frecuente en la actualidad, a pesar de su uso habitual en la industria, laboratorios y hogar. La vía de intoxicación suele ser la oral y, dada su elevada mortalidad, debe considerarse siempre una intoxicación grave. Se presenta el caso clínico de un paciente joven extranjero sin antecedentes, en coma y con acidosis metabólica grave, que evoluciona a muerte encefálica a pesar de establecer medidas de soporte y tratamiento específico (corrección de...

  9. Is acidosis the clue to the loss of structure and functioning of the sarcolemma?

    Verkleij, A J; Post, J A; Schneijdenberg, C T

    1990-04-01

    The only way for a tissue or organ to survive ischemia is by reperfusion or restoration of the blood flow. However, if the ischemic period is too long reperfusion leads to a Ca2+ overload of the myocardial cells and thereby to cell death. The question is; what are the key events during ischemia which cause this transition from reversible to irreversible injury. In this article we discuss whether acidosis may play a crucial role by inducing Ca2+ release from the sarcolemma and reorganization of membrane components especially the membrane lipids, i.e. lateral phase separation, resulting in membrane protein clustering and changes in lipid asymmetry.

  10. The need for genetic study to diagnose some cases of distal renal tubular acidosis.

    Heras Benito, Manuel; Garcia-Gonzalez, Miguel A; Valdenebro Recio, María; Molina Ordás, Álvaro; Callejas Martínez, Ramiro; Rodríguez Gómez, María Astrid; Calle García, Leonardo; Sousa Silva, Lisbeth; Fernández-Reyes Luis, María José

    We describe the case of a young woman who was diagnosed with advanced kidney disease, with an incidental finding of nephrocalcinosis of unknown aetiology, having been found asymptomatic throughout her life. The genetic study by panels of known genes associated with tubulointerstitial disease allowed us to discover autosomal dominant distal renal tubular acidosis associated with a de novo mutation in exon 14 of the SLC4A1 gene, which would have been impossible to diagnose clinically due to the advanced nature of the kidney disease when it was discovered.

  11. [Sjögren syndrome associated with renal tubular acidosis type I].

    Górriz, L; Molino, R; Arjona, D; Estripeaut, D

    2000-01-01

    Primary Sjögren's Syndrome complicated with a renal tubular acidosis type 1 and hypocalcemic paralysis, as the principal clinical manifestation, is uncommon. Although the initial manifestations of the nephropathy are not well understood, it is believed that the invasion of mononuclear cells and the high level of circulating antibodies, play an important role in the pathogenesis of the disease. We present a patient with hypocalcemic paralysis as an initial manifestation of a latent Sjögren's disease. The glandular biopsy was normal, suggesting a mayor participation of an immunological humoral factor in the renal lesion.

  12. Acidosis láctica secundaria a terapia antirretroviral en pacientes con VIH/sida

    Benhard Hasbum-Fernández

    2006-06-01

    Full Text Available La acidosis láctica es una complicación infrecuente de la terapia antirretroviral para VIH. Su aparición se ha relacionado con la administración de análogos nucleósidos de la transcriptasa inversa, en especial estavudina y didanosina. Se presentan los 2 casos que se manejaron en el año 2005 en el Servicio de Medicina del Hospital México. En ambos el desenlace fue fatal, aún cuando se utilizaron todas las medidas terapéuticas recomendadas.

  13. Metabolic acidosis in renal transplantation: neglected but of potential clinical relevance.

    Messa, Pier Giorgio; Alfieri, Carlo; Vettoretti, Simone

    2016-05-01

    Chronic metabolic acidosis (CMA) is a common complication of the more advanced stages of chronic kidney diseases (CKD), and is associated with morbidity and mortality of CKD patients and possibly with the progression of renal disease. Nevertheless, there is limited evidence or information on the prevalence, the potential causal factors, the clinical impact and the effects of correction of CMA in kidney transplant recipients. In this review, we briefly look at the more relevant, though scanty, studies which have, over time, addressed the above-mentioned points, with the hope that in the future the interest of transplant nephrologists and surgeons will grow towards this unreasonably neglected issue.

  14. [Pyridoxine for severe metabolic acidosis and seizures due to isoniazid overdose].

    Adler, M; Girsh-Solomonovich, Z; Raikhlin-Eisenkraft, B

    1993-05-16

    A 15-year-old girl took 3 g of isoniazid (15 tablets) in a suicide attempt and was brought unconscious to the emergency room. She was in respiratory failure, with seizures that could not be stopped with diazepam. Severe metabolic acidosis with normal serum lactate developed (pH 6.85), but did not improve after infusion of bicarbonate. Intravenous administration of pyridoxine led to prompt cessation of the seizures and to gradual improvement of acid-base status. She recovered consciousness after several hours and was discharged a week later.

  15. Effects of acute hypercapnia with and without acidosis on lung inflammation and apoptosis in experimental acute lung injury.

    Nardelli, L M; Rzezinski, A; Silva, J D; Maron-Gutierrez, T; Ornellas, D S; Henriques, I; Capelozzi, V L; Teodoro, W; Morales, M M; Silva, P L; Pelosi, P; Garcia, C S N B; Rocco, P R M

    2015-01-01

    We investigated the effects of acute hypercapnic acidosis and buffered hypercapnia on lung inflammation and apoptosis in experimental acute lung injury (ALI). Twenty-four hours after paraquat injection, 28 Wistar rats were randomized into four groups (n=7/group): (1) normocapnia (NC, PaCO2=35-45 mmHg), ventilated with 0.03%CO2+21%O2+balancedN2; (2) hypercapnic acidosis (HC, PaCO2=60-70 mmHg), ventilated with 5%CO2+21%O2+balancedN2; and (3) buffered hypercapnic acidosis (BHC), ventilated with 5%CO2+21%O2+balancedN2 and treated with sodium bicarbonate (8.4%). The remaining seven animals were not mechanically ventilated (NV). The mRNA expression of interleukin (IL)-6 (p=0.003), IL-1β (pacidosis, reduced lung inflammation and lung and kidney cell apoptosis.

  16. Sabiporide improves cardiovascular function, decreases the inflammatory response and reduces mortality in acute metabolic acidosis in pigs.

    Dongmei Wu

    Full Text Available INTRODUCTION: Acute metabolic acidosis impairs cardiovascular function and increases the mortality of critically ill patients. However, the precise mechanism(s underlying these effects remain unclear. We hypothesized that targeting pH-regulatory protein, Na(+/H(+ exchanger (NHE1 could be a novel approach for the treatment of acute metabolic acidosis. The aim of the present study was to examine the impact of a novel NHE1 inhibitor, sabiporide, on cardiovascular function, blood oxygen transportation, and inflammatory response in an experimental model of metabolic acidosis produced by hemorrhage-induced hypovolemia followed by an infusion of lactic acid. METHODS AND RESULTS: Anesthetized pigs were subjected to hypovolemia for 30 minutes. The animals then received a bolus infusion of sabiporide (3 mg/kg or vehicle, followed by an infusion of lactic acid for 2 hours. The animals were continuously monitored for additional 3 hours. Hypovolemia followed by a lactic acid infusion resulted in a severe metabolic acidosis with blood pH falling to 6.8. In association with production of the acidemia, there was an excessive increase in pulmonary artery pressure (PAP and pulmonary vascular resistance (PVR. Treatment with sabiporide significantly attenuated the increase in PAP by 38% and PVR by 67%, as well as significantly improved cardiac output by 51%. Sabiporide treatment also improved mixed venous blood oxygen saturation (55% in sabiporide group vs. 28% in control group, and improved systemic blood oxygen delivery by 36%. In addition, sabiporide treatment reduced plasma levels of TNF-α (by 33%, IL-6 (by 63%, troponin-I (by 54%, ALT (by 34%, AST (by 35%, and urea (by 40%. CONCLUSION: These findings support the possible beneficial effects of sabiporide in the treatment of acute metabolic acidosis and could have implications for the treatment of metabolic acidosis in man.

  17. Down-sizing of neuronal network activity and density of presynaptic terminals by pathological acidosis are efficiently prevented by Diminazene Aceturate.

    de Ceglia, Roberta; Chaabane, Linda; Biffi, Emilia; Bergamaschi, Andrea; Ferrigno, Giancarlo; Amadio, Stefano; Del Carro, Ubaldo; Mazzocchi, Nausicaa; Comi, Giancarlo; Bianchi, Veronica; Taverna, Stefano; Forti, Lia; D'Adamo, Patrizia; Martino, Gianvito; Menegon, Andrea; Muzio, Luca

    2015-03-01

    Local acidosis is associated with neuro-inflammation and can have significant effects in several neurological disorders, including multiple sclerosis, brain ischemia, spinal cord injury and epilepsy. Despite local acidosis has been implicated in numerous pathological functions, very little is known about the modulatory effects of pathological acidosis on the activity of neuronal networks and on synaptic structural properties. Using non-invasive MRI spectroscopy we revealed protracted extracellular acidosis in the CNS of Experimental Autoimmune Encephalomyelitis (EAE) affected mice. By multi-unit recording in cortical neurons, we established that acidosis affects network activity, down-sizing firing and bursting behaviors as well as amplitudes. Furthermore, a protracted acidosis reduced the number of presynaptic terminals, while it did not affect the postsynaptic compartment. Application of the diarylamidine Diminazene Aceturate (DA) during acidosis significantly reverted both the loss of neuronal firing and bursting and the reduction of presynaptic terminals. Finally, in vivo DA delivery ameliorated the clinical disease course of EAE mice, reducing demyelination and axonal damage. DA is known to block acid-sensing ion channels (ASICs), which are proton-gated, voltage-insensitive, Na(+) permeable channels principally expressed by peripheral and central nervous system neurons. Our data suggest that ASICs activation during acidosis modulates network electrical activity and exacerbates neuro-degeneration in EAE mice. Therefore pharmacological modulation of ASICs in neuroinflammatory diseases could represent a new promising strategy for future therapies aimed at neuro-protection.

  18. A Case of Myopathy, Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS) Syndrome with Intracardiac Thrombus [corrected].

    Joo, Jung-Chul; Seol, Myung Do; Yoon, Jin Won; Lee, Young Soo; Kim, Dong-Keun; Choi, Yong Hoon; Ahn, Hyo Seong; Cho, Wook Hyun

    2013-03-01

    Myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) is a multisystem clinical syndrome manifested by mitochondrial myopathy, encephalopathy, lactic acidosis and recurrent stroke-like episodes. A 27-year-old female with MELAS syndrome presented with cerebral infarction. Echocardiography revealed a thrombus attached to the apex of the hypertrophied left ventricle, with decreased systolic function. The embolism of the intracardiac thrombus might have been the cause of stroke. There should be more consideration given to the increased possibility of intracardiac thrombus formation when a MELAS patient with cardiac involvement is encountered.

  19. Recurrent Anion Gap Acidosis: An Unusual Presentation of X-Linked Adrenoleukodystrophy in a Five-year-old Male.

    Schwab, Joel; Pena, Loren; Sigman, Laura; Waggoner, Darrel

    2010-01-01

    We are presenting a five-year-old male with recurrent anion gap acidosis. During his last admission, it was detected that he had elevated VLCFA and the evaluation discovered that he had X-linked Adrenooleukodystrophy. He had the Addisonian only phenotype without any clinical or radiographic CNS findings. We were unable to find any other reports of this presentation of ALD. If the work-up of recurrent anion gap acidosis does not uncover an etiology, X-linked ALD should be considered in the differential diagnosis.

  20. Magnetic resonance imaging detects placental hypoxia and acidosis in mouse models of perturbed pregnancies.

    Gabriele Bobek

    Full Text Available Endothelial dysfunction as a result of dysregulation of anti-angiogenic molecules secreted by the placenta leads to the maternal hypertensive response characteristic of the pregnancy complication of preeclampsia. Structural abnormalities in the placenta have been proposed to result in altered placental perfusion, placental oxidative stress, cellular damage and inflammation and the release of anti-angiogenic compounds into the maternal circulation. The exact link between these factors is unclear. Here we show, using Magnetic Resonance Imaging as a tool to examine placental changes in mouse models of perturbed pregnancies, that T 2 contrast between distinct regions of the placenta is abolished at complete loss of blood flow. Alterations in T 2 (spin-spin or transverse relaxation times are explained as a consequence of hypoxia and acidosis within the tissue. Similar changes are observed in perturbed pregnancies, indicating that acidosis as well as hypoxia may be a feature of pregnancy complications such as preeclampsia and may play a prominent role in the signalling pathways that lead to the increased secretion of anti-angiogenic compounds.

  1. Ruminal lipopolysaccharide concentration and inflammatory response during grain-induced subacute ruminal acidosis in dairy cows.

    Gozho, G N; Krause, D O; Plaizier, J C

    2007-02-01

    The effects of grain-induced subacute ruminal acidosis (SARA) in lactating dairy cows on free ruminal lipopolysaccharide (LPS) and indicators of inflammation were determined. Four mid lactation dairy cows were divided into 2 groups of 2 cows and used in a repeated switchover design. During each period, SARA was induced in 2 animals for 5 subsequent days by replacing 25% of their total mixed ration (dry matter basis) with a concentrate made of 50% wheat and 50% barley. The other 2 cows acted as controls and were fed a total mixed ration diet in which 44% of dry matter was concentrate. On average, inducing SARA did not affect milk composition, increased the duration of rumen pH below 5.6 from 187 to 309 min/d, and increased free ruminal LPS concentration from 24,547 endotoxin units (EU)/mL to 128,825 EU/mL. Averaged across treatments, milk fat yield and milk protein yield were 0.66 and 1.00 kg/d, respectively. Rumen pH and milk fat data suggest that control cows also experienced ruminal acidosis, albeit a milder form of this disease than SARA cows. Serum LPS concentration in both control and SARA cows was less than the detection limit of inflammation including haptoglobin, fibrinogen, serum copper, or white blood cells. These results suggest that grain-induced SARA in mid lactation dairy cows increases the lysis of gram-negative bacteria and activates an inflammatory response.

  2. Magnetic resonance imaging detects placental hypoxia and acidosis in mouse models of perturbed pregnancies.

    Bobek, Gabriele; Stait-Gardner, Tim; Surmon, Laura; Makris, Angela; Lind, Joanne M; Price, William S; Hennessy, Annemarie

    2013-01-01

    Endothelial dysfunction as a result of dysregulation of anti-angiogenic molecules secreted by the placenta leads to the maternal hypertensive response characteristic of the pregnancy complication of preeclampsia. Structural abnormalities in the placenta have been proposed to result in altered placental perfusion, placental oxidative stress, cellular damage and inflammation and the release of anti-angiogenic compounds into the maternal circulation. The exact link between these factors is unclear. Here we show, using Magnetic Resonance Imaging as a tool to examine placental changes in mouse models of perturbed pregnancies, that T 2 contrast between distinct regions of the placenta is abolished at complete loss of blood flow. Alterations in T 2 (spin-spin or transverse) relaxation times are explained as a consequence of hypoxia and acidosis within the tissue. Similar changes are observed in perturbed pregnancies, indicating that acidosis as well as hypoxia may be a feature of pregnancy complications such as preeclampsia and may play a prominent role in the signalling pathways that lead to the increased secretion of anti-angiogenic compounds.

  3. Refeeding syndrome as an unusual cause of anion gap metabolic acidosis.

    Singla, Manish; Perry, Alexandra; Lavery, Eric

    2012-11-01

    Refeeding syndrome is characterized by hypophosphatemia in the setting of malnutrition. It is commonly seen in patients with anorexia, alcoholism, or malignancy, and it is often a missed diagnosis. Because of the potential morbidity associated with missing the diagnosis of refeeding syndrome, it is important to monitor for this disease in any malnourished patient. We present a case of a 49-year-old male with chronic alcohol abuse who presented for alcohol detoxification and was found to have low phosphate, potassium, and magnesium on presentation, in addition to an elevated anion gap of unclear etiology. After extensive workup to evaluate the cause of his elevated anion gap and worsening of his electrolyte abnormalities despite replenishment, it was felt his symptoms were a result of refeeding syndrome. After oral intake was held and aggressive electrolyte replenishment was performed for 24 hours, the patient's anion gap closed and his electrolyte levels stabilized. This case demonstrates a unique presentation of refeeding syndrome given the patient's profound metabolic acidosis that provided a clue toward his eventual diagnosis. The standard workup for an anion gap metabolic acidosis was negative, and it was not until his refeeding syndrome had been treated that the anion gap closed.

  4. Mechanism of potassium depletion during chronic metabolic acidosis in the rat

    Scandling, J.D.; Ornt, D.B.

    1987-01-01

    Pair-fed rats on a normal K diet were given either 1.5% NH/sub 4/Cl or water for 4 days. The acid-fed animals developed metabolic acidosis, negative K balance, and K depletion. Urinary Na excretion and urinary flow were not different between the groups beyond the first day. After the 4 days, isolated kidneys from animals in each of these groups were perfused at normal pH and bicarbonate concentrations. Urinary K excretion was similar between the groups despite the potassium depletion in the acid-fed animals. In contrast, isolated kidneys from animals with comparable K depletion induced by dietary K restriction readily conserved K. Sodium excretion and urinary flow were similar among the three groups of isolated kidneys. Plasma aldosterone concentrations were greater in the acid-fed rats after the 4 days of NH/sub 4/Cl ingestion than in the control animals. Adrenalectomized rats were treated with either normal (4 ..mu..g/day) or high (22 ..mu..g/day) aldosterone replacement while ingesting NH/sub 4/Cl for 4 days. Only in the presence of high aldosterone replacement did the acid-fed adrenalectomized animals develop K depletion. The authors conclude that chronic metabolic acidosis stimulates aldosterone secretion, and that aldosterone maintains the inappropriately high urinary potassium excretion and K depletion seen in this acid-base disorder.

  5. Metabolic acidosis mimicking diabetic ketoacidosis after use of calorie-free mineral water.

    Dahl, Gry T; Woldseth, Berit; Lindemann, Rolf

    2012-09-01

    A previously healthy boy was admitted with fever, tachycardia, dyspnea, and was vomiting. A blood test showed a severe metabolic acidosis with pH 7.08 and an anion gap of 36 mmol/L. His urine had an odor of acetone. The serum glucose was 5.6 mmol/L, and no glucosuria was found. Diabetic ketoacidosis could therefore be eliminated. Lactate level was normal. Tests for the most common metabolic diseases were negative. Because of herpes stomatitis, the boy had lost appetite and only been drinking Diet Coke and water the last days. Diet Coke or Coca-Cola Light is sweetened with a blend containing cyclamates, aspartame, and acesulfame potassium, all free of calories. The etiology of the metabolic acidosis appeared to be a catabolic situation exaggerated by fasting with no intake of calories. The elevated anion gap was due to a severe starvation ketoacidosis, mimicking a diabetic ketoacidosis. Pediatricians should recommend carbohydrate/calorie-containing fluids for rehydration of children with acute fever, diarrhea, or illness.

  6. Lipoyltransferase 1 Gene Defect Resulting in Fatal Lactic Acidosis in Two Siblings

    Véronique Taché

    2016-01-01

    Full Text Available A term male neonate developed severe intractable lactic acidosis on day of life 1 and died the same day at our institution. The family previously lost another term, female newborn on day of life 1 from suspected sepsis at an outside hospital. After performing an autopsy on the neonate who died at our institution, extensive and lengthy neonatal and parental genetic testing, as well as biochemical analyses, and whole exome sequencing analysis identified compound heterozygous mutations in the lipoyltransferase 1 (LIPT1 gene responsible for the lipoylation of the 2-keto dehydrogenase complexes in the proband. These mutations were also identified in the deceased sibling. The clinical manifestations of these two siblings are consistent with those recently described in two unrelated families with lactic acidosis due to LIPT1 mutations, an underrecognized and underreported cause of neonatal death. Conclusions. Our observations contribute to the delineation of a new autosomal recessive metabolic disorder, leading to neonatal death. Our case report also highlights the importance of an interdisciplinary team in solving challenging cases.

  7. Lanthanum carbonate versus sevelamer hydrochloride: improvement of metabolic acidosis and hyperkalemia in hemodialysis patients.

    Filiopoulos, Vassilis; Koutis, Ioannis; Trompouki, Sofia; Hadjiyannakos, Dimitrios; Lazarou, Dimitrios; Vlassopoulos, Dimosthenis

    2011-02-01

    Sevelamer hydrochloride (SH) has been reported to aggravate metabolic acidosis and hyperkalemia. This study was performed to evaluate acid-base status and serum potassium changes after replacing SH with lanthanum carbonate (LC) in hemodialysis patients. SH was prescribed for 24 weeks in 14 stable hemodialysis patients and replaced by LC in a similar treatment schedule. Laboratory tests, including indices of acid-base status, nutrition, bone/mineral metabolism, and dialysis adequacy, were performed monthly during the study. Dialysate bicarbonate, potassium and calcium concentrations remained constant. Serum bicarbonate and pH rose, and serum potassium dropped significantly under LC. Alkaline phosphatase also decreased significantly under LC. No significant differences were observed in the other studied parameters between the two treatment periods. Control of serum phosphate was similar under both phosphate-binders and no differences were observed in calcium, Ca × P product, CRP, or lipid levels. Dialysis adequacy was constantly kept within K/DOQI target-range. Although full compliance to treatment was reported, three patients on LC complained of gastrointestinal upset and/or a metallic taste, and four had difficulty chewing the LC tablet. LC improves metabolic acidosis and hyperkalemia in hemodialysis patients previously under SH. Although both medications are well-tolerated, the gastrointestinal side-effects appear to occur more frequently with LC; a fact that, together with difficulties in chewing the tablet, may result in decreased compliance.

  8. [Higher Brain Dysfunction in Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis and Stroke-Like Episodes (MELAS)].

    Ichikawa, Hiroo

    2016-02-01

    Stroke-like episodes are one of the cardinal features of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), and occur in 84-99% of the patients. The affected areas detected on neuroimaging do not have classical vascular distribution, and involve predominantly the temporal, parietal and occipital lobes. Thus, the neurological symptoms including higher brain dysfunction correlate with this topographical distribution. In association with the occipital lobe involvement, the most frequent symptom is cortical blindness. Other symptoms have been occasionally reported in case reports: visual agnosia, prosopagnosia, cortical deafness, auditory agnosia, topographical disorientation, various types of aphasia, hemispatial neglect, and so on. On the other hand, cognitive decline associated with more diffuse brain impairment rather than with focal stroke-like lesions has been postulated. This condition is also known as mitochondrial dementia. Domains of cognitive dysfunction include abstract reasoning, verbal memory, visual memory, language (naming and fluency), executive or constructive functions, attention, and visuospatial function. Cognitive functions and intellectual abilities may decline from initially minimal cognitive impairment to dementia. To date, the neuropsychological and neurologic impairment has been reported to be associated with cerebral lactic acidosis as estimated by ventricular spectroscopic lactate levels.

  9. Treatment of Metformin Intoxication Complicated by Lactic Acidosis and Acute Kidney Injury: The Role of Prolonged Intermittent Hemodialysis.

    Regolisti, Giuseppe; Antoniotti, Riccardo; Fani, Filippo; Greco, Paolo; Fiaccadori, Enrico

    2017-02-17

    Metformin intoxication with lactic acidosis, a potentially lethal condition, may develop in diabetic patients when the drug dose is inappropriate and/or its clearance is reduced. Diagnosis and therapy may be delayed due to nonspecific symptoms at presentation, with severe anion gap metabolic acidosis and elevated serum creatinine values being the most prominent laboratory findings. Confirmation requires measurement of serum metformin by high-performance liquid chromatography-tandem mass spectrometry, but this technique is available only at specialized institutions and cannot be relied on as a guide to immediate treatment. Thus, based on strong clinical suspicion, renal replacement therapy must be started promptly to achieve efficient drug clearance and correct the metabolic acidosis. However, because metformin accumulates in the intracellular compartment with prolonged treatment, a rebound in serum concentrations due to redistribution is expected at the end of dialysis. We report a case of metformin intoxication, severe lactic acidosis, and acute kidney injury in a diabetic patient with pre-existing chronic kidney disease stage 3, treated effectively with sustained low-efficiency dialysis. We discuss the pathophysiology, differential diagnosis, and treatment options and highlight specific pharmacokinetic issues that should be considered in selecting the appropriate modality of renal replacement therapy.

  10. Drug-induced haemolysis, renal failure, thrombocytopenia and lactic acidosis in patients with HIV and cryptococcal meningitis: a diagnostic challenge.

    Camara-Lemarroy, Carlos R; Flores-Cantu, Hazael; Calderon-Hernandez, Hector J; Diaz-Torres, Marco A; Villareal-Velazquez, Hector J

    2015-12-01

    Patients with HIV are at risk of both primary and secondary haematological disorders. We report two cases of patients with HIV and cryptococcal meningitis who developed severe haemolytic anaemia, thrombocytopenia, renal failure and lactic acidosis while on treatment with amphotericin B and co-trimoxazole.

  11. Proteomic profiling and pathway analysis of the response of rat renal proximal convoluted tubules to metabolic acidosis.

    Schauer, Kevin L; Freund, Dana M; Prenni, Jessica E; Curthoys, Norman P

    2013-09-01

    Metabolic acidosis is a relatively common pathological condition that is defined as a decrease in blood pH and bicarbonate concentration. The renal proximal convoluted tubule responds to this condition by increasing the extraction of plasma glutamine and activating ammoniagenesis and gluconeogenesis. The combined processes increase the excretion of acid and produce bicarbonate ions that are added to the blood to partially restore acid-base homeostasis. Only a few cytosolic proteins, such as phosphoenolpyruvate carboxykinase, have been determined to play a role in the renal response to metabolic acidosis. Therefore, further analysis was performed to better characterize the response of the cytosolic proteome. Proximal convoluted tubule cells were isolated from rat kidney cortex at various times after onset of acidosis and fractionated to separate the soluble cytosolic proteins from the remainder of the cellular components. The cytosolic proteins were analyzed using two-dimensional liquid chromatography and tandem mass spectrometry (MS/MS). Spectral counting along with average MS/MS total ion current were used to quantify temporal changes in relative protein abundance. In all, 461 proteins were confidently identified, of which 24 exhibited statistically significant changes in abundance. To validate these techniques, several of the observed abundance changes were confirmed by Western blotting. Data from the cytosolic fractions were then combined with previous proteomic data, and pathway analyses were performed to identify the primary pathways that are activated or inhibited in the proximal convoluted tubule during the onset of metabolic acidosis.

  12. Impaired renal function is associated with greater urinary strong ion differences in critically ill patients with metabolic acidosis.

    Moviat, M.; Terpstra, A.M.; Hoeven, J.G. van der; Pickkers, P.

    2012-01-01

    PURPOSE: Urinary excretion of chloride corrects metabolic acidosis, but this may be hampered in patients with impaired renal function. We explored the effects of renal function on acid-base characteristics and urinary strong ion excretion using the Stewart approach in critically ill patients with me

  13. Acidosis, acetazolamide, and amiloride: effects on /sup 22/Na transfer across the blood-brain and blood-CSF barriers

    Murphy, V.A.; Johanson, C.E.

    1989-04-01

    Sprague-Dawley rats were given treatments, known to decrease /sup 22/Na movement into choroid plexus and CSF, to investigate their effect on /sup 22/Na transfer across the cerebral capillaries. Acidic salts, acetazolamide, or amiloride was injected intraperitoneally into bilaterally nephrectomized rats, and the rate of /sup 22/Na uptake into parietal cortex, pons-medulla, and CSF was determined at 12, 18, and 24 min. Severe acidosis (arterial pH 7.2), produced by HCl injection, decreased the rate of /sup 22/Na entry into both brain regions and CSF by 25%, whereas mild acidosis (pH 7.3) from NH/sub 4/Cl injection reduced brain entry by 18%, but CSF entry by only 10%. Like HCl acidosis, amiloride reduced transport into both brain and CSF by 22%. Penetration of /sup 22/Na into parietal cortex was unchanged by acetazolamide, but that into CSF was slowed 30%. Since uptake of /sup 22/Na into cortical regions is primarily movement of tracer across the cerebral capillaries when tracer uptake time is less than 30 min, the results indicate that both metabolic acidosis and amiloride decrease Na+ permeativity at the cerebral capillaries as well as at the choroid plexus. Acetazolamide, on the other hand, alters Na+ movement only across the choroidal epithelium.

  14. Acidosis reduces the function and expression of α1D-adrenoceptor in superior mesenteric artery of Capra hircus

    Ipsita Mohanty

    2016-01-01

    Conclusion: (i Adrenergic receptor mediates vasoconstriction in GSMA under normal physiological pHo, and α1Dis the possible subtype involved in this event (ii acidosis attenuates the vasocontractile response due to reduced function and expression of α1D-AR and also increased the release of endothelial-relaxing factors.

  15. Long-term management of sevelamer hydrochloride-induced metabolic acidosis aggravation and hyperkalemia in hemodialysis patients.

    Sonikian, Macroui; Metaxaki, Polyxeni; Iliopoulos, Anastasios; Marioli, Stamatia; Vlassopoulos, Dimosthenis

    2006-01-01

    Sevelamer hydrochloride use in hemodialysis patients is complicated by metabolic acidosis aggravation and hyperkalemia. Rare reports about a short-term correction of this complication have been published. The current authors investigated the long-term correction of metabolic acidosis and hyperkalemia in sevelamer hydrochloride-treated patients at doses adequate to achieve serum phosphate levels within K/DOQI recommendations. The authors followed 20 hemodialysis patients for 24 months in an open-label prospective study. The dialysate bicarbonate concentration was increased stepwise to a maximum 40 mEq/L and adjusted to reach patient serum bicarbonate levels of 22 mEq/L, according to K/DOQI recommendations. Laboratory results for serum bicarbonate, potassium, calcium, phosphate, albumin, alkaline phosphatase, iPTH, cholesterol (HDL-LDL), triglycerides, Kt/V, systolic-diastolic arterial pressure were recorded. Sevelamer hydrochloride-induced metabolic acidosis aggravation and hyperkalemia in hemodialysis patients were corrected, on the long-term, by an increase in dialysate bicarbonate concentration. Further improvement in bone biochemistry was noted with this adequate acidosis correction and parallel sevelamer hydrochloride administration, in sufficiently large doses to achieve K/DOQI phosphate recommendations.

  16. The use of chloride-sodium ratio in the evaluation of metabolic acidosis in critically ill neonates.

    Kurt, Abdullah; Ecevit, Ayşe; Ozkiraz, Servet; Ince, Deniz Anuk; Akcan, Abdullah Baris; Tarcan, Aylin

    2012-06-01

    Acid-base disturbances have been usually evaluated with the traditional Henderson-Hasselbach method and Stewart's physiochemical approach by quantifying anions of tissue acids (TA). It is hypothesized that an increase in tissue acids during metabolic acidosis would cause a compensatory decrease in the plasma chloride (Cl) relative to sodium (Cl-Na ratio) in order to preserve electroneutral balance. Therefore, we aimed to investigate the use of Cl-Na ratio as a bedside tool to evaluate the identifying raised TA in neonates as an alternative to complex calculations of Stewart's physiochemical approach. This retrospective study was conducted between January 2008 and December 2009. Infants were included in the study when blood gas analysis reveals a metabolic acidosis; pH anion gap (AG), albumin-corrected AG (AG(corr)), strong ion difference (SID), unmeasured anions (UMA), and TA were calculated at each episode of metabolic acidosis. A total of 105 metabolic acidosis episodes occurred in 59 infants during follow-up. Hypochloremic metabolic acidosis occurred in 17 (16%) of samples, and all had increased TA. The dominant component of TA was UMA rather than lactate. There was a negative correlation between the Cl-Na ratio and SID, AG(corr), UMA, and TA. Also, there was a positive correlation between Diff(NaCl) and SID, AG(corr), UMA, and TA. Base deficit and actual bicarbonate performed poorly in identifying the TA. In conclusion, our study suggested that Diff(NaCl) and Cl-Na ratio are simple and fast, and may be an alternative method to complex Stewart's physiochemical approach in identifying raised UMA and TA in critically ill neonates.

  17. Local anesthetic failure associated with inflammation: verification of the acidosis mechanism and the hypothetic participation of inflammatory peroxynitrite

    Takahiro Ueno

    2008-11-01

    Full Text Available Takahiro Ueno1, Hironori Tsuchiya2, Maki Mizogami1, Ko Takakura11Department of Anesthesiology, Asahi University School of Dentistry, Mizuho, Gifu, Japan; 2Department of Dental Basic Education, Asahi University School of Dentistry, Mizuho, Gifu, JapanAbstract: The presence of inflammation decreases local anesthetic efficacy, especially in dental anesthesia. Although inflammatory acidosis is most frequently cited as the cause of such clinical phenomena, this has not been experimentally proved. We verified the acidosis mechanism by studying the drug and membrane lipid interaction under acidic conditions together with proposing an alternative hypothesis. Liposomes and nerve cell model membranes consisting of phospholipids and cholesterol were treated at different pH with lidocaine, prilocaine and bupivacaine (0.05%–0.2%, w/v. Their membrane-interactive potencies were compared by the induced-changes in membrane fluidity. Local anesthetics fluidized phosphatidylcholine membranes with the potency being significantly lower at pH 6.4 than at pH 7.4 (p < 0.01, supporting the acidosis theory. However, they greatly fluidized nerve cell model membranes even at pH 6.4 corresponding to inflamed tissues, challenging the conventional mechanism. Local anesthetics acted on phosphatidylserine liposomes, as well as nerve cell model membranes, at pH 6.4 with almost the same potency as that at pH 7.4, but not on phosphatidylcholine, phosphatidylethanolamine and sphingomyelin liposomes. Since the positively charged anesthetic molecules are able to interact with nerve cell membranes by ion-paring with anionic components like phosphatidylserine, tissue acidosis is not essentially responsible for the local anesthetic failure associated with inflammation. The effects of local anesthetics on nerve cell model membranes were inhibited by treating with peroxynitrite (50 μM, suggesting that inflammatory cells producing peroxynitrite may affect local anesthesia

  18. Clinical utility of standard base excess in the diagnosis and interpretation of metabolic acidosis in critically ill patients

    M Park

    2008-03-01

    Full Text Available The aims of this study were to determine whether standard base excess (SBE is a useful diagnostic tool for metabolic acidosis, whether metabolic acidosis is clinically relevant in daily evaluation of critically ill patients, and to identify the most robust acid-base determinants of SBE. Thirty-one critically ill patients were enrolled. Arterial blood samples were drawn at admission and 24 h later. SBE, as calculated by Van Slyke's (SBE VS or Wooten's (SBE W equations, accurately diagnosed metabolic acidosis (AUC = 0.867, 95%CI = 0.690-1.043 and AUC = 0.817, 95%CI = 0.634-0.999, respectively. SBE VS was weakly correlated with total SOFA (r = -0.454, P < 0.001 and was similar to SBE W (r = -0.482, P < 0.001. All acid-base variables were categorized as SBE VS <-2 mEq/L or SBE VS <-5 mEq/L. SBE VS <-2 mEq/L was better able to identify strong ion gap acidosis than SBE VS <-5 mEq/L; there were no significant differences regarding other variables. To demonstrate unmeasured anions, anion gap (AG corrected for albumin (AG A was superior to AG corrected for albumin and phosphate (AG A+P when strong ion gap was used as the standard method. Mathematical modeling showed that albumin level, apparent strong ion difference, AG A, and lactate concentration explained SBE VS variations with an R² = 0.954. SBE VS with a cut-off value of <-2 mEq/L was the best tool to diagnose clinically relevant metabolic acidosis. To analyze the components of SBE VS shifts at the bedside, AG A, apparent strong ion difference, albumin level, and lactate concentration are easily measurable variables that best represent the partitioning of acid-base derangements.

  19. Reversal of severe lactic acidosis with thiamine in a renal allograft recipient

    K Nanda Kumar

    2015-01-01

    Full Text Available A 48-year-old female patient with end-stage renal failure developed unexplained severe lactic acidosis (LA associated with hyperglycemia during robotic-assisted laparoscopic renal transplantation. Initial treatment with sodium bicarbonate and insulin infusion were ineffective in treating acidemia. Postoperatively, intravenous administration of thiamine resulted in rapid improvement of LA and blood sugar levels. Uremia and chronic hemodialysis might be the causes behind the quantitative/qualitative deficiency of thiamine unmasked during the surgical stress. Though a rare entity, acute thiamine deficiency should be considered in the differential diagnosis of unexplained severe LA in patients with chronic kidney disease and hemodialysis who undergo major surgery or admitted to critical illness care units.

  20. Subacute ruminal acidosis in dairy cows: the physiological causes, incidence and consequences.

    Plaizier, J C; Krause, D O; Gozho, G N; McBride, B W

    2008-04-01

    During subacute ruminal acidosis (SARA) rumen pH is depressed for several hours per day due to accumulation of volatile fatty acids and insufficient rumen buffering. Surveys suggested an incidence of SARA of between 19% and 26% in early and mid-lactation dairy cows. Causes of SARA include feeding excessive amounts of non-structural carbohydrates and highly fermentable forages, and insufficient dietary coarse fiber. Consequences of SARA include feed intake depression, reduced fiber digestion, milk fat depression, diarrhea, laminitis, liver abscesses, increased production of bacterial endotoxin and inflammation characterized by increases in acute phase proteins. The increase in endotoxin is similar among methods for SARA induction, but depends on the diet fed before induction. Increases in acute phase proteins vary among methods of SARA induction, even when the methods result in similar rumen pH depressions. This suggests that the inflammatory response might not be solely due to bacterial endotoxin in the rumen.

  1. Subacute ruminal acidosis (SARA) challenge, ruminal condition and cellular immunity in cattle.

    Sato, Shigeru

    2015-02-01

    Subacute ruminal acidosis (SARA) is characterized by repeated bouts of low ruminal pH. Cows with SARA often develop complications or other diseases, and associate physiologically with immunosuppression and inflammation. Ruminal free lipopolysaccharide (LPS) increases during SARA and translocates into the blood circulation activating an inflammatory response. Ruminal fermentation and cellular immunity are encouraged by supplementing hay with calf starter during weaning. SARA calves given a 5-day repeated administration of a bacteria-based probiotic had stable ruminal pH levels (6.6-6.8). The repeated administration of probiotics enhance cellular immune function and encourage recovery from diarrhea in pre-weaning calves. Furthermore, the ruminal fermentation could guard against acute and short-term feeding changes, and changes in the rumen microbial composition of SARA cattle might occur following changes in ruminal pH. The repeated bouts of low ruminal pH in SARA cattle might be associated with depression of cellular immunity.

  2. [Urolithiasis due to renal tubular acidosis associated with Sjögren's syndrome].

    Umekawa, T; Esa, A; Uemura, T; Kohri, K; Kurita, T; Ishikawa, Y; Iguchi, M; Kataoka, K

    1990-03-01

    We encountered 4 patients with urolithiasis due to renal tubular acidosis (RTA) associated with Sjögren's syndrome. Laboratory results about RTA in 4 patients with Sjögrenhs syndrome were not significantly different from those in patients who suffered from urolithiasis due to RTA without Sjögren's syndrome. The incidence of urolitiasis in these cases was suspected to be higher than that in RTA patients without Sjögren's syndrome, because all 4 patients in this study had urolithiasis. When we examine patients with bilateral and multiple urolithiasis, particularly in middle-aged women, we should bear in mind that RTA and Sjögren's syndrome may exist in the background.

  3. Indicators of induced subacute ruminal acidosis (SARA) in Danish Holstein cows

    Danscher, Anne Mette; Li, Shucong; Andersen, Pia H.;

    2015-01-01

    BACKGROUND: The prevalence of subacute ruminal acidosis (SARA) in dairy cows is high with large impact on economy and welfare. Its current field diagnosis is based on point ruminal pH measurements by oral probe or rumenocentesis. These techniques are invasive and inaccurate, and better markers...... for the diagnosis of SARA are needed. The goal of this study was to evaluate clinical signs of SARA and to investigate the use of blood, faecal and urinary parameters as indicators of SARA. Six lactating, rumen cannulated, Danish Holstein cows were used in a cross-over study with three periods. The first and second...... periods included two cows on control diet and two cows on nutritional SARA challenge. The third period only included two cows on SARA challenge. Control diet was a conventional total mixed ration [45.5% dry matter (DM), 17.8% crude protein, 43.8% neutral detergent fibre, and 22.5% acid detergent fibre (DM...

  4. When should MELAS (Mitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes be the diagnosis?

    Paulo José Lorenzoni

    2015-11-01

    Full Text Available ABSTRACTMitochondrial myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS is a rare mitochondrial disorder. Diagnostic criteria for MELAS include typical manifestations of the disease: stroke-like episodes, encephalopathy, evidence of mitochondrial dysfunction (laboratorial or histological and known mitochondrial DNA gene mutations. Clinical features of MELAS are not necessarily uniform in the early stages of the disease, and correlations between clinical manifestations and physiopathology have not been fully elucidated. It is estimated that point mutations in the tRNALeu(UUR gene of the DNAmt, mainly A3243G, are responsible for more of 80% of MELAS cases. Morphological changes seen upon muscle biopsy in MELAS include a substantive proportion of ragged red fibers (RRF and the presence of vessels with a strong reaction for succinate dehydrogenase. In this review, we discuss mainly diagnostic criterion, clinical and laboratory manifestations, brain images, histology and molecular findings as well as some differential diagnoses and current treatments.

  5. Renal tubular acidosis type II associated with vitamin D deficiency presenting as chronic weakness.

    Ali, Yaseen; Parekh, Amila; Baig, Mirza; Ali, Taseen; Rafiq, Tazeen

    2014-08-01

    Chronic vitamin D deficiency, though common in the elderly, is often under diagnosed and when progressing to renal tubular acidosis type II (RTA 2) can cause several simultaneous electrolyte imbalances that may present with weakness and pain as chief symptoms. We present such a case that after months of evaluation and symptomatic treatment did not lead to an effective establishment of the etiology causing chronic weakness and body pain in an elderly female patient. Eventually, after a careful review of the patient's history, repeat physical examinations, laboratory data evaluation, and diagnostic testing led to the establishment of the diagnosis of proximal RTA 2 associated with vitamin D deficiency, which caused the patient to develop several remarkable secondary electrolyte imbalances such as hypokalemia, hypocalcemia, hypophosphatemia, acidemia, hyperparathyroidism, with weakness and body pain.

  6. An unusual case of refractory metabolic acidosis after homeopathic medicinal treatment

    Sameer Saraf

    2014-01-01

    Full Text Available Homeopathy is one of the most frequently used and controversial systems of complementary and alternative medicine (CAM. It is based on the ′principle of similars′, whereby highly diluted preparations of substances that cause symptoms in healthy individuals are used to stimulate healing in patients who have similar symptoms when ill 1. General trends show a rise in the number of individuals utilising naturopathic and homeopathic therapeutic methods 2. The patients who seek homeopathic treatment are primarily those suffering from long-standing, chronic disease 1. Certainly, the CAM can show clinical benefits. However, some of these also involve a considerable risk of sometimes severe side-effects. We here are reporting an unusual case of refractory metabolic acidosis after homeopathic medicinal treatment.

  7. Transient distal renal tubular acidosis following hump nosed viper bite: Two cases from Sri Lanka

    Ranga M Weerakkody

    2016-01-01

    Full Text Available Hump-nosed viper (Hypnale hypnale; HNV is one of the six major snake species in Sri Lanka that cause envenomation. Nephrotoxicity, coagulopathy, and neurotoxicity are wellrecognized features of its envenomation. Type 4 renal tubular acidosis (RTA4 has only once been described previously in this condition, and we report two further cases. Two patients aged 53 and 51 presented following HNV bites with acute kidney injury and microangiopathic hemolytic anemia. Both underwent multiple cycles of hemodialysis until the polyuric phase was reached. Despite polyuria, both patients developed resistant hyperkalemia that needed further hemodialysis. The urinary pH, arterial pH, delta ratio, and transtubular potassium gradient confirmed RTA4. HNV venom has been shown to damage the proximal convoluted tubules in animal studies, but not the distal convoluted tubule, and hence the mechanism of our observation in these two patients is unclear. Unexplained hyperkalemia in recovery phase of HNV bite should raise suspicions of RTA4.

  8. Serum acute phase proteins in cows with SARA (Subacute Ruminal Acidosis suspect

    C. Cannizzo

    2012-02-01

    Full Text Available The aim of this study was to evaluate the variations of Acute Phase Proteins (APPs and other blood constituents during the onset of the sub-acute ruminal acidosis (SARA pathological status. A total of 108 cows from 12 dairy herds were randomly selected and divided into three Groups of 36 animals each. All animals were subjected to a rumenocentesis. Group A was composed by subjects with a rumen pH>5.8, Group B was composed by subjects with a rumen pH ≤5.5≤5.8 and Group C was composed by subjects with a rumen pH<5.5. Blood samples were collected by jugular venipuncture and Haptoglobin (Hp, Serum Amyloid A (SAA, Total Proteins, Albumin and White Blood Cells (WBC were determined. One-way ANOVA showed a statistical significance on Rumen pH, Hp, SAA. SARA seems not stimulate the APPs production from liver.

  9. Esubacute acidosis in rumen of high-yield dairy cows: Prevalence and prevention

    Petrujkić Branko T.

    2008-01-01

    Full Text Available The objective of the investigations presented in this paper was to establish the frequency of the incidence of subacute acidosis in the rumen of cows (SARA in the first three months of lactation and the possibilities for its prevention using a mineral mix based on bentonite, zeolite, magnesium oxide, and sodium bicarbonate (Mix plus. The values obtained for the rumen pH content show that subacute rumen acidosis occurs in in 20 percent of the examined cows in the early stage of lactation. For these investigations, cows in early stages of lactation were chosen and divided into 2 groups. Cows of the experimental group were administered a fodder mix which contained the mineral mix for a buffer effect (Mix plus. The average values of the rumen pH content in the control and the experimental group of cows at the beginning and on the 30th day of the experiment were approximately the same and did not differ significantly (p>0.05. On the 60th day of the experiment, the values for the electrochemical reaction of the rumen content for the control group amounted to an average of 6.219±0.18, and for the experimental group of cows it was 6.772±0.23. The obtained difference was statistically very significant (p<0.001. At the end of the experiment, on the 90th day, the average pH value of the rumen content of cows of the control group was 6.308±0.16, while this value in the experimental group of cows was significantly higher and amounted to 6.676±0.29 (p<0.01.

  10. Equivalent metabolic acidosis with four colloids and saline on ex vivo haemodilution.

    Morgan, T J; Vellaichamy, M; Cowley, D M; Weier, S L; Venkatesh, B; Jones, M A

    2009-05-01

    Colloid infusions can cause metabolic acidosis. Mechanisms and relative severity with different colloids are incompletely understood. We compared haemodilution acid-base effects of 4% albumin, 3.5% polygeline, 4% succinylated gelatin (all weak acid colloids, strong ion difference 12 mEq/l, 17.6 mEq/l and 34 mEq/l respectively), 6% hetastarch (non-weak acid colloid, strong ion difference zero) and 0.9% saline (crystalloid, strong ion difference zero). Gelatin weak acid properties were tracked via the strong ion gap. Four-step ex vivo dilutions of pre-oxygenated human venous blood were performed to a final [Hb] near 50% baseline. With each fluid, base excess fell to approximately -13 mEq/l. Base excess/[Hb] relationships across dilution were linear and direct (R2 > or = 0.96), slopes and intercepts closely resembling saline. Baseline strong ion gap was -0.3 (2.1) mEq/l. Post-dilution increases occurred in three groups: small with saline, hetastarch and albumin (to 3.5 (02) mEq/l, 4.3 (0.3) mEq/l, 3.3 (1.4) mEq/l respectively), intermediate with polygeline (to 12.2 (0.9) mEq/l) and greatest with succinylated gelatin (to 20.8 (1.4) mEq/l). We conclude that, despite colloid weak acid activity ranging from zero (hydroxyethyl starch) to greater than that of albumin with both gelatin preparations, ex vivo dilution causes a metabolic acidosis of identical severity to saline in each case. This uniformity reflects modifications to the albumin and gelatin saline vehicles, in part aimed at pH correction. By proportionally increasing the strong ion difference, these modifications counter deviations from pure saline effects caused by colloid weak acid activity. Extrapolation in vivo requires further investigation.

  11. An autopsy case of death due to metabolic acidosis after citric acid ingestion.

    Ikeda, Tomoya; Usui, Akihito; Matsumura, Takashi; Aramaki, Tomomi; Hosoya, Tadashi; Igari, Yui; Ohuchi, Tsukasa; Hayashizaki, Yoshie; Usui, Kiyotaka; Funayama, Masato

    2015-11-01

    A man in his 40s was found unconscious on a sofa in a communal residence for people with various disabilities. He appeared to have drunk 800 ml of undiluted citric acid from a commercial plastic bottle. The instructions on the label of the beverage specified that the beverage be diluted 20- to 30-fold before consumption. The patient was admitted to an emergency hospital with severe metabolic acidosis (pH, 6.70; HCO3(-), 3.6 mEq/L) and a low ionized calcium level (0.73 mmol/L). Although ionized calcium and catecholamines were continuously administered intravenously to correct the acidosis, the state of acidemia and low blood pressure did not improve, and he died 20 h later. Citric acid concentrations in the patient's serum drawn shortly after treatment in the hospital and from the heart at autopsy were 80.6 mg/ml and 39.8 mg/dl, respectively (normal range: 1.3-2.6 mg/dl). Autopsy revealed black discoloration of the mucosal surface of the esophagus. Microscopically, degenerated epithelium and neutrophilic infiltration in the muscle layer were observed. In daily life, drinking a large amount of concentrated citric acid beverage is rare as a cause of lethal poisoning. However, persons with mental disorders such as dementia may mistakenly drink detergent or concentrated fluids, as in our case. Family members or facility staff in the home or nursing facility must bear in mind that they should not leave such bottles in places where they are easily accessible to mentally handicapped persons.

  12. Diagnostic Challenge in a Patient with Severe Anion Gap Metabolic Acidosis

    Eugene M. Tan

    2015-01-01

    Full Text Available The approach to the patient with acute renal failure and elevated anion and osmolal gap is difficult. Differential diagnoses include toxic alcohol ingestion, diabetic or starvation ketoacidosis, or 5-oxoproline acidosis. We present a 76-year-old female with type 2 diabetes mellitus, who was found at home in a confused state. Laboratory analysis revealed serum pH 6.84, bicarbonate 5.8 mmol/L, pCO2 29 mmHg, anion gap 22.2 mmol/L, osmolal gap 17.4 mOsm/kg, elevated beta-hydroxybutyrate (4.2 mmol/L, random blood sugar 213 mg/dL, creatinine 2.1 mg/dL, and potassium 7.5 mmol/L with no electrocardiogram (EKG changes. Fomepizole and hemodialysis were initiated for presumed ethylene glycol or methanol ingestion. Drug screens returned negative for ethylene glycol, alcohols, and acetaminophen, but there were elevated urine levels of acetone (11 mg/dL. The acetaminophen level was negative, and 5-oxoproline was not analyzed. After 5 days in the intensive care unit (ICU, her mental status improved with supportive care. She was discharged to a nursing facility. Though a diagnosis was not established, our patient’s presentation was likely due to starvation ketosis combined with chronic acetaminophen ingestion. Acetone ingestion is less likely. Overall, our case illustrates the importance of systematically approaching an elevated osmolal and anion gap metabolic acidosis.

  13. Rumen microbiome composition determined using two nutritional models of subacute ruminal acidosis.

    Khafipour, Ehsan; Li, Shucong; Plaizier, Jan C; Krause, Denis O

    2009-11-01

    Subacute ruminal acidosis (SARA) is a metabolic disease in dairy cattle that occurs during early and mid-lactation and has traditionally been characterized by low rumen pH, but lactic acid does not accumulate as in acute lactic acid acidosis. It is hypothesized that factors such as increased gut permeability, bacterial lipopolysaccharides, and inflammatory responses may have a role in the etiology of SARA. However, little is known about the nature of the rumen microbiome during SARA. In this study, we analyzed the microbiome of 64 rumen samples taken from eight lactating Holstein dairy cattle using terminal restriction fragment length polymorphisms (TRFLP) of 16S rRNA genes and real-time PCR. We used rumen samples from two published experiments in which SARA had been induced with either grain or alfalfa pellets. The results of TRFLP analysis indicated that the most predominant shift during SARA was a decline in gram-negative Bacteroidetes organisms. However, the proportion of Bacteroidetes organisms was greater in alfalfa pellet-induced SARA than in mild or severe grain-induced SARA (35.4% versus 26.0% and 16.6%, respectively). This shift was also evident from the real-time PCR data for Prevotella albensis, Prevotella brevis, and Prevotella ruminicola, which are members of the Bacteroidetes. The real-time PCR data also indicated that severe grain-induced SARA was dominated by Streptococcus bovis and Escherichia coli, whereas mild grain-induced SARA was dominated by Megasphaera elsdenii and alfalfa pellet-induced SARA was dominated by P. albensis. Using discriminant analysis, the severity of SARA and degree of inflammation were highly correlated with the abundance of E. coli and not with lipopolysaccharide in the rumen. We thus suspect that E. coli may be a contributing factor in disease onset.

  14. Acidosis and nutritional status in hemodialyzed patients. French Study Group for Nutrition in Dialysis.

    Chauveau, P; Fouque, D; Combe, C; Laville, M; Canaud, B; Azar, R; Cano, N; Aparicio, M; Leverve, X

    2000-01-01

    In a cross-sectional study of more than 30% of French dialysis patients (N = 7,123), we evaluated the relationships between predialysis plasma bicarbonate concentration and nutritional markers. Data including age, gender, cause of end-stage renal disease (ESRD), time on dialysis, body mass index (BMI), blood levels of midweek predialysis albumin, prealbumin, and bicarbonate were collected. Normalized protein catabolic rate (nPCR), dialysis adequacy parameters, and estimation of lean body mass (LBM) were computed from pre- and postbicarbonate-dialysis urea and creatinine levels according to the classical formulas of Garred. Average values (+/- 1 SD) were age 61 +/- 16 years, BMI 23.3 +/- 4.6 kg/m2, dialysis time 12.4 +/- 2.7 h/week, HCO3 22.8 +/- 3.5 mmol/L, albumin 38.7 +/- 5.3 g/L, prealbumin 340 +/- 90 mg/L, Kt/V 1.36 +/- 0.36, nPCR 1.13 +/- 0.32 g/kg BW/day, and LBM 0.86 +/- 0.21% of ideal LBM. A highly significant negative correlation was observed between predialysis bicarbonate levels (within a range of 16-30 mmol/L, 95% of this population) and nPCR confirmed by analysis of variance using bicarbonate classes (p V despite a positive correlation between Kt/V and nPCR. It is likely that a persistent acidosis observed despite standard bicarbonate dialysis was caused by a high dietary protein intake which results in an increased acid load, but also overcomes the usual catabolic effects of acidosis.

  15. Utilidad de la recolección de orina de dos horas para el diagnóstico del tipo de acidosis tubular renal

    Margarita Irene Rocha-Gómez; Samuel Zaltzman-Girshëvich; Silvestre García-de la Puente

    2015-01-01

    La acidosis tubular renal se caracteriza por acidosis metabólica hiperclorémica. El diagnóstico del tipo de acidosis tubular renal se realiza mediante la medición del transporte tubular máximo de bicarbonato y de la capacidad de acidificación urinaria; sin embargo, estas pruebas son invasivas y requieren determinaciones especializadas. Objetivo: comparar la utilidad de la recolección urinaria de dos horas, una prueba relativamente simple y al alcance de muchos laboratorios, con la medició...

  16. Successful recovery from iatrogenic severe hypernatremia and severe metabolic acidosis resulting from accidental use of inappropriate bicarbonate concentrate for hemodialysis treatment

    Guruprasad P Bhosale

    2015-01-01

    Full Text Available Bicarbonate dialysis is the treatment modality of choice for correction of metabolic acidosis in chronic renal failure. However, improper selection of dialysate concentrate can result in life-threatening human errors. We report a case of iatrogenic severe hypernatremia (sodium 207 mEq/L and severe metabolic acidosis (pH 6.65 that resulted due to accidental use of inappropriate bicarbonate concentrate for hemodialysis treatment. There was successful recovery in this patient with no neurological sequelae. To the best of our knowledge, this is the first case report in adults of severe hypernatremia along with severe metabolic acidosis due to error in the preparation of dialysis fluid.

  17. Reduction of beta-amyloid-induced neurotoxicity on hippocampal cell cultures by moderate acidosis is mediated by transforming growth factor beta.

    Uribe-San Martín, R; Herrera-Molina, R; Olavarría, L; Ramírez, G; von Bernhardi, R

    2009-02-18

    Progression of Alzheimer's disease (AD) is associated with chronic inflammation and microvascular alterations, which can induce impairment of brain perfusion because of vascular pathology and local acidosis. Acidosis can promote amyloidogenesis, which could further contribute to neurodegenerative changes. Nevertheless, there is also evidence that acidosis has neuroprotective effects in hypoxia models. Here we studied the effect of moderate acidosis on beta-amyloid (Abeta)-mediated neurotoxicity. We evaluated morphological changes, cell death, nitrite production and reductive metabolism of hippocampal cultures from Sprague-Dawley rats exposed to Abeta under physiological (pH 7.4) or moderate acidosis (pH 7.15-7.05). In addition, because transforming growth factor beta (TGFbeta) 1 is neuroprotective and is induced by several pathophysiological conditions, we assessed its presence at the different pHs. The exposure of hippocampal cells to Abeta induced a conspicuous reduction of neurites' arborization, as well as increased neuronal death and nitric oxide production. However, Abeta neurotoxicity was significantly attenuated when hippocampal cultures were kept at pH 7.15-7.05, showing a 68% reduction on lactate dehydrogenase release compared with cultures exposed to Abeta at pH 7.4 (Pacidosis compared with basal pH media (Pacidosis decreased intracellular TGFbeta1 precursor (latency associated protein-TGFbeta1) and increased up to fourfold TGFbeta1 bioactivity, detecting a 43% increase in the active TGFbeta levels in cultures exposed to Abeta and moderate acidosis. Inhibition of TGFbeta signaling abolished the neuroprotective effect of moderate acidosis. Our results show that moderate acidosis protected hippocampal cells from Abeta-mediated neurotoxicity through the increased activation and signaling potentiation of TGFbeta.

  18. A case of life-threatening lactic acidosis after smoke inhalation - interference between beta-adrenergic agents and ethanol?

    Taboulet, P; Clemessy, J L; Freminet, A; Baud, F J

    1995-12-01

    A 49-year-old male developed bronchospasm and severe lactic acidosis after exposition to fire smoke. The correction of lactic acidosis following beta-adrenergic agents withdrawal, and the transitory increase in lactate after salbutamol reintroduction are consistent with hypersensitivity to salbutamol. However, the plasma lactate concentration (32.6 mmol/l) that we observed 9.5 h after admission is far above those currently seen after administration of beta-adrenergic agents. We searched for causes able to potentiate the adverse effects of these drugs and we noticed that our patient had a high plasma ethanol level (2.4 g/l). Alcohol metabolism in the liver results in generation of high NADH/NAD+ ratios, thus reducing lactate liver clearance. This observation suggests that plasma lactate levels should be monitored closely in alcoholic patients treated with beta-mimetic agents.

  19. Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome mimicking herpes simplex encephalitis on imaging studies.

    Gieraerts, Christopher; Demaerel, Philippe; Van Damme, Philip; Wilms, Guido

    2013-01-01

    We present a case in which mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome mimicked the clinical and radiological signs of herpes simplex encephalitis. In a patient with subacute encephalopathy, on computed tomography and magnetic resonance imaging, lesions were present in both temporal lobes extending to both insular regions with sparing of the lentiform nuclei and in both posterior straight and cingulate gyri. Final diagnosis of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome was based on biochemical investigations on cerebrospinal fluid, electromyogram, muscle biopsy, and genetic analysis. On diffusion-weighted imaging, diffusion restriction was present in some parts of the lesions but not throughout the entire lesions. We suggest that this could be an important sign in the differential diagnosis with herpes simplex encephalitis.

  20. Monitoring of metformin-induced lactic acidosis in a diabetic patient with acute kidney failure and effect of hemodialysis.

    Laforest, Claire; Saint-Marcoux, Franck; Amiel, Jean-Bernard; Pichon, Nicolas; Merle, Louis

    2013-02-01

    Metformin associated lactic acidosis (MALA) is a serious complication occurring especially in elderly patients given high doses of the drug. We report a non-fatal case of MALA with pronounced acidosis (pH 6.76, lactate 30.81 mmol/l) and high metformin concentrations (127 mg/l) in a patient who had developed acute renal failure after undergoing an operation. Multiple measurements of biological parameters and metformin blood concentrations showed the effectiveness of repeated hemodialysis sessions on metformin elimination. Cases previously reported with such a severe MALA were associated with a high mortality rate. We show that close monitoring in an intensive care unit together with prompt and repeated dialysis sessions can lead to a favorable outcome.

  1. Sigmoid volvulus in a patient with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS): a rare occurrence.

    Hallac, Alexander; Keshava, Hari B; Morris-Stiff, Gareth; Ibrahim, Samuel

    2016-03-02

    Mitochondrial diseases are rare and devastating, with a wide spectrum of clinical presentations and systemic symptoms. The majority of the published literature focuses on the neuromuscular manifestations and genetic components of this mitochondrial cytopathy, however, cardiac, renal, endocrine and gastrointestinal manifestations may also be present. The authors report a case detailing a 56-year-old woman's final hospitalisation from the gastrointestinal sequelae of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) (Co Q10 deficiency variant). She presented with abdominal pain and distension associated with lactic acidosis, and was shown on imaging to have a colon perforation. This resulted in emergent surgery at which a necrotic colon secondary to a sigmoid colon was identified. Following four subsequent operations, and the development of multiorgan failure, care was eventually withdrawn. Practitioners of patients with MELAS should be cognisant of the rare but devastating gastrointestinal consequences of mitochondrial diseases.

  2. Acidosis Decreases c-Myc Oncogene Expression in Human Lymphoma Cells: A Role for the Proton-Sensing G Protein-Coupled Receptor TDAG8

    Zhigang Li

    2013-10-01

    Full Text Available Acidosis is a biochemical hallmark of the tumor microenvironment. Here, we report that acute acidosis decreases c-Myc oncogene expression in U937 human lymphoma cells. The level of c-Myc transcripts, but not mRNA or protein stability, contributes to c-Myc protein reduction under acidosis. The pH-sensing receptor TDAG8 (GPR65 is involved in acidosis-induced c-Myc downregulation. TDAG8 is expressed in U937 lymphoma cells, and the overexpression or knockdown of TDAG8 further decreases or partially rescues c-Myc expression, respectively. Acidic pH alone is insufficient to reduce c-Myc expression, as it does not decrease c-Myc in H1299 lung cancer cells expressing very low levels of pH-sensing G protein-coupled receptors (GPCRs. Instead, c-Myc is slightly increased by acidosis in H1299 cells, but this increase is completely inhibited by ectopic overexpression of TDAG8. Interestingly, TDAG8 expression is decreased by more than 50% in human lymphoma samples in comparison to non-tumorous lymph nodes and spleens, suggesting a potential tumor suppressor function of TDAG8 in lymphoma. Collectively, our results identify a novel mechanism of c-Myc regulation by acidosis in the tumor microenvironment and indicate that modulation of TDAG8 and related pH-sensing receptor pathways may be exploited as a new approach to inhibit Myc expression.

  3. Osteomalacia complicating renal tubular acidosis in association with Sjogren′s syndrome

    Zohra El Ati

    2014-01-01

    Full Text Available Renal involvement in Sjogren′s syndrome (SS is not uncommon and may precede other complaints. Tubulointerstitial nephritis is the most common renal disease in SS and may lead to renal tubular acidosis (RTA, which in turn may cause osteomalacia. Nevertheless, osteomalacia rarely occurs as the first manifestation of a renal tubule disorder due to SS. We herewith describe a 43-year-old woman who was admitted to our hospital for weakness, lumbago and inability to walk. X-ray of the long bones showed extensive demineralization of the bones. Laboratory investigations revealed chronic kidney disease with serum creatinine of 2.3 mg/dL and creatinine clearance of 40 mL/min, hypokalemia (3.2 mmol/L, hypophosphatemia (0.4 mmol/L, hypocalcemia (2.14 mmol/L and hyperchloremic metabolic acidosis (chlorine: 114 mmol/L; alkaline reserve: 14 mmol/L. The serum alkaline phosphatase levels were elevated. The serum levels of 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D were low and borderline low, respectively, and the parathyroid hormone level was 70 pg/L. Urinalysis showed inappropriate alkaline urine (urinary PH: 7, glycosuria with normal blood glucose, phosphaturia and uricosuria. These values indicated the presence of both distal and proximal RTA. Our patient reported dryness of the mouth and eyes and Schirmer′s test showed xerophthalmia. An accessory salivary gland biopsy showed changes corresponding to stage IV of Chisholm and Masson score. Kidney biopsy showed diffuse and severe tubulo-interstitial nephritis with dense lymphoplasmocyte infiltrates. Sicca syndrome and renal interstitial infiltrates indicated SS as the underlying cause of the RTA and osteomalacia. The patient received alkalinization, vitamin D (Sterogyl ®, calcium supplements and steroids in an initial dose of 1 mg/kg/day, tapered to 10 mg daily. The prognosis was favorable and the serum creatinine level was 1.7 mg/dL, calcium was 2.2 mmol/L and serum phosphate was 0.9 mmol/L.

  4. Local anesthetic failure associated with inflammation: verification of the acidosis mechanism and the hypothetic participation of inflammatory peroxynitrite

    Tsuchiya, Hironori

    2008-01-01

    Takahiro Ueno1, Hironori Tsuchiya2, Maki Mizogami1, Ko Takakura11Department of Anesthesiology, Asahi University School of Dentistry, Mizuho, Gifu, Japan; 2Department of Dental Basic Education, Asahi University School of Dentistry, Mizuho, Gifu, JapanAbstract: The presence of inflammation decreases local anesthetic efficacy, especially in dental anesthesia. Although inflammatory acidosis is most frequently cited as the cause of such clinical phenomena, this has not been experimentally proved. ...

  5. Local anesthetic failure associated with inflammation: verification of the acidosis mechanism and the hypothetic participation of inflammatory peroxynitrite.

    Ueno, Takahiro; Tsuchiya, Hironori; Mizogami, Maki; Takakura, Ko

    2008-01-01

    The presence of inflammation decreases local anesthetic efficacy, especially in dental anesthesia. Although inflammatory acidosis is most frequently cited as the cause of such clinical phenomena, this has not been experimentally proved. We verified the acidosis mechanism by studying the drug and membrane lipid interaction under acidic conditions together with proposing an alternative hypothesis. Liposomes and nerve cell model membranes consisting of phospholipids and cholesterol were treated at different pH with lidocaine, prilocaine and bupivacaine (0.05%-0.2%, w/v). Their membrane-interactive potencies were compared by the induced-changes in membrane fluidity. Local anesthetics fluidized phosphatidylcholine membranes with the potency being significantly lower at pH 6.4 than at pH 7.4 (p acidosis theory. However, they greatly fluidized nerve cell model membranes even at pH 6.4 corresponding to inflamed tissues, challenging the conventional mechanism. Local anesthetics acted on phosphatidylserine liposomes, as well as nerve cell model membranes, at pH 6.4 with almost the same potency as that at pH 7.4, but not on phosphatidylcholine, phosphatidylethanolamine and sphingomyelin liposomes. Since the positively charged anesthetic molecules are able to interact with nerve cell membranes by ion-paring with anionic components like phosphatidylserine, tissue acidosis is not essentially responsible for the local anesthetic failure associated with inflammation. The effects of local anesthetics on nerve cell model membranes were inhibited by treating with peroxynitrite (50 μM), suggesting that inflammatory cells producing peroxynitrite may affect local anesthesia.

  6. Effect of acidosis on IL-8 and MCP-1 during hypoxia and reoxygenation in human NT2-N neurons.

    Frøyland, Elisabeth; Pedersen, Elena Didenko; Kvissel, Anne-Katrine; Almaas, Runar; Pharo, Anne; Skålhegg, Bjørn Steen; Mollnes, Tom Eirik; Rootwelt, Terje

    2006-10-03

    Inflammation probably plays a significant role in perinatal brain injury. To study the contribution of locally produced cytokines, the effect on cell death of addition of IL-8 and MCP-1 or antibodies to these, and the impact of acidosis, human postmitotic NT2-N neurons were exposed to 3 h of hypoxia and glucose deprivation and reoxygenated for 21 h. After 3 h of hypoxia with neutral medium, IL-8 was significantly increased compared to controls (150 (100-250)% vs. 100 (85-115)%, p=0.023). After 21 h of neutral reoxygenation, both IL-8 (380 (110-710)% vs. 150 (85-260)%, p=0.041) and monocyte chemoattractant protein-1 (MCP-1) (650 (440-2000)% vs. 310 (230-340)%, p=0.007) were significantly increased compared to controls. After 3 h of hypoxia, both IL-8 (p=0.002) and MCP-1 (p=0.008) were significantly lower in cells with acidotic compared with cells with neutral medium. Acidosis during reoxygenation, however, significantly increased IL-8 release, whereas MCP-1 release was diminished. Similar effects of acidosis were seen in normoxic controls. The cells also secreted RANTES and IP-10, but not 8 other cytokines tested. We found no effect on cell death, measured by MTT assay, of addition of IL-8, MCP-1 or antibodies to these. We conclude that human NT2-N neurons release IL-8 and MCP-1 during 21 h of reoxygenation after 3 h of hypoxia. Acidosis led to a differential effect on IL-8 and MCP-1, with increased IL-8 and decreased MCP-1, both during reoxygenation and in normoxic controls. IL-8 and MCP-1 had no effect on cell death.

  7. Acidosis-Induced Changes in Proteome Patterns of the Prostate Cancer-Derived Tumor Cell Line AT-1.

    Ihling, Angelika; Ihling, Christian H; Sinz, Andrea; Gekle, Michael

    2015-09-04

    Under various pathological conditions, such as inflammation, ischemia and in solid tumors, physiological parameters (local oxygen tension or extracellular pH) show distinct tissue abnormalities (hypoxia and acidosis). For tumors, the prevailing microenvironment exerts a strong influence on the phenotype with respect to proliferation, invasion, and metastasis formation and therefore influences prognosis. In this study, we investigate the impact of extracellular metabolic acidosis (pH 7.4 versus 6.6) on the proteome patterns of a prostate cancer-derived tumor cell type (AT-1) using isobaric labeling and LC-MS/MS analysis. In total, 2710 proteins were identified and quantified across four biological replicates, of which seven were significantly affected with changes >50% and used for validation. Glucose transporter 1 and farnesyl pyrophosphatase were found to be down-regulated after 48 h of acidic treatment, and metallothionein 2A was reduced after 24 h and returned to control values after 48 h. After 24 and 48 h at pH 6.6, glutathione S transferase A3 and NAD(P)H dehydrogenase 1, cellular retinoic acid-binding protein 2, and Na-bicarbonate transporter 3 levels were found to be increased. The changes in protein levels were confirmed by transcriptome and functional analyses. In addition to the experimental in-depth investigation of proteins with changes >50%, functional profiling (statistical enrichment analysis) including proteins with changes >20% revealed that acidosis upregulates GSH metabolic processes, citric acid cycle, and respiratory electron transport. Metabolism of lipids and cholesterol biosynthesis were downregulated. Our data comprise the first comprehensive report on acidosis-induced changes in proteome patterns of a tumor cell line.

  8. Phosphate binders and metabolic acidosis in patients undergoing maintenance hemodialysis—sevelamer hydrochloride, calcium carbonate, and bixalomer.

    Sanai, Toru; Tada, Hideo; Ono, Takashi; Fukumitsu, Toma

    2015-01-01

    The serum bicarbonate (HCO3(-)) levels are decreased in chronic hemodialysis (HD) patients treated with sevelamer hydrochloride (SH). We assessed the effects of bixalomer on the chronic metabolic acidosis in these patients. We examined 12 of the 122 consecutive Japanese patients with end-stage renal disease on HD, who orally ingested a dose of SH (≥2250 mg), and an arterial blood gas analysis and biochemical analysis were performed before HD. Patients whose serum HCO3(-) levels were under 18 mmol/L were changed from SH to the same dose of bixalomer. A total of 12 patients were treated with a large amount of SH. Metabolic acidosis (a serum HCO3(-) level under 18 mmol/L) was found in eight patients. These patients were also treated with or without small dose of calcium carbonate (1.2 ± 1.1 g). The dose of SH was changed to that of bixalomer. After 1 month, the serum HCO3(-) levels increased from 16.3 ± 1.4 to 19.6 ± 1.7 mmol/L (P Metabolic acidosis was not observed in four patients (serum HCO3(-) level: 20.3 ± 0.7 mmol/L) likely because they were taking 3 g of calcium carbonate with SH. In the present study, the development of chronic metabolic acidosis was induced by HCl containing phosphate binders, such as SH, and partially ameliorated by calcium carbonate, then subsequently improved after changing the treatment to bixalomer.

  9. Low-flow CO2 removal integrated into a renal-replacement circuit can reduce acidosis and decrease vasopressor requirements

    2013-01-01

    Introduction Lung-protective ventilation in patients with ARDS and multiorgan failure, including renal failure, is often paralleled with a combined respiratory and metabolic acidosis. We assessed the effectiveness of a hollow-fiber gas exchanger integrated into a conventional renal-replacement circuit on CO2 removal, acidosis, and hemodynamics. Methods In ten ventilated critically ill patients with ARDS and AKI undergoing renal- and respiratory-replacement therapy, effects of low-flow CO2 removal on respiratory acidosis compensation were tested by using a hollow-fiber gas exchanger added to the renal-replacement circuit. This was an observational study on safety, CO2-removal capacity, effects on pH, ventilator settings, and hemodynamics. Results CO2 elimination in the low-flow circuit was safe and was well tolerated by all patients. After 4 hours of treatment, a mean reduction of 17.3 mm Hg (−28.1%) pCO2 was observed, in line with an increase in pH. In hemodynamically instable patients, low-flow CO2 elimination was paralleled by hemodynamic improvement, with an average reduction of vasopressors of 65% in five of six catecholamine-dependent patients during the first 24 hours. Conclusions Because no further catheters are needed, besides those for renal replacement, the implementation of a hollow-fiber gas exchanger in a renal circuit could be an attractive therapeutic tool with only a little additional trauma for patients with mild to moderate ARDS undergoing invasive ventilation with concomitant respiratory acidosis, as long as no severe oxygenation defects indicate ECMO therapy. PMID:23883472

  10. Computed tomography and angiography in MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes). Report of 3 cases

    Hasuo, K.; Tamura, S.; Yasumori, K.; Uchino, A.; Masuda, K.; Goda, S.; Ishimoto, S.; Kamikaseda, K.; Wakuta, Y.; Kishi, M.

    1987-07-01

    Among mitochondrial encephalomyopathies, MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes, Pavlakis et al., 1983) is recognized as a distinct syndrome characterized by generalized convulsions and recurrrent stroke-like episodes. The neuroradiological findings of three patients with MELAS are reported here. Retrospective review shows that MELAS should be included in the differential diagnosis of infarct-like lesions of the cerebrum.

  11. Complex III deficiency due to an in-frame MT-CYB deletion presenting as ketotic hypoglycemia and lactic acidosis

    Mari Mori

    2015-09-01

    Full Text Available Complex III deficiency due to a MT-CYB mutation has been reported in patients with myopathy. Here, we describe a 15-year-old boy who presented with metabolic acidosis, ketotic hypoglycemia and carnitine deficiency. Electron transport chain analysis and mitochondrial DNA sequencing on muscle tissue lead to the eventual diagnosis of complex III deficiency. This case demonstrates the critical role of muscle biopsies in a myopathy work-up, and the clinical efficacy of supplement therapy.

  12. Role of extracellular and intracellular acidosis for hypercapnia-induced inhibition of tension of isolated rat cerebral arteries

    Tian, R; Vogel, P; Lassen, N A

    1995-01-01

    The importance of smooth muscle cell pHi and pHo for the hypercapnic vasodilation of rat cerebral arteries was evaluated in vitro. Vessel segments were mounted in a myograph for isometric tension recording; pHi was measured by loading the smooth muscle cells with the fluorescent dye BCECF, and p......Ho was measured with a glass electrode. In all studies, Ca(2+)-dependent basal tension (in the absence of any agonist) and tension in the presence of arginine vasopressin were investigated. Control solution was physiological saline bubbled with 5% CO2 and containing 25 mmol/L HCO3- (pH 7.45 to 7.50). Induction...... of hypercapnic acidosis (10% CO2) or normocapnic acidosis (15 mmol/L HCO3-) caused significant inhibition of smooth muscle tension, and both conditions reduced pHi as well as pHo. N-Nitro-L-arginine significantly inhibited the relaxation to hypercapnic acidosis but had no significant effect on relaxation...

  13. An experimental renal acidification defect in patients with hereditary fructose intolerance. I. Its resemblance to renal tubular acidosis.

    Morris, R C

    1968-06-01

    In three unrelated patients with hereditary fructose intolerance (HFI), but in none of five normal subjects, the experimental administration of fructose invariably induced a reversible dysfunction of the renal tubule with biochemical and physiological characteristics of renal tubular acidosis. During a state of ammonium chloride-induced acidosis, (a) urinary pH was greater than six and the rate of excretion of net acid (titratable acid plus ammonium minus bicarbonate) was inappropriately low, (b) the glomerular filtration rate remained unchanged or decreased modestly, and (c) urinary excretion of titratable acid increased briskly with diuresis of infused phosphate, although urinary pH changed little. The tubular dysfunction, which also includes impaired tubular reabsorption of alpha amino nitrogen and phosphate, persisted throughout administration of fructose and disappeared afterward. The tubular dysfunction was not causally dependent on hypoglucosemia, ammonium chloride-induced acidosis or osmotic diuresis. Rather, it appeared causally related to the fructose-induced metabolic abnormality of patients with HFI. The causal enzymatic defect, the virtual absence of fructose-1-phosphate aldolase, occurs in the kidney as well as in the liver of patients with HFI.

  14. Topiramate and severe metabolic acidosis: case report Acidose metabólica grave por topiramato: relato de caso

    Jayme E. Burmeister

    2005-06-01

    Full Text Available Topiramate infrequently induces anion gap metabolic acidosis through carbonic anhydrase inhibition on the distal tubule of the nephron - a type 2 renal tubular acidosis. We report on a 40 years old woman previously healthy that developed significant asymptomatic metabolic acidosis during topiramate therapy at a dosage of 100mg/day for three months. Stopping medication was followed by normalization of the acid-base status within five weeks. This infrequent side effect appears unpredictable and should be given careful attention.Topiramato pode produzir raramente uma acidose metabólica através da inibição da anidrase carbônica no túbulo distal do néfron - acidose tubular renal do tipo 2. Relatamos o caso de mulher de 40 anos previamente saudável que desenvolveu quadro de acidose metabólica assintomática grave, sem outra etiologia identificável, durante uso de topiramato na dose de 100mg/dia por três meses. Este efeito colateral, embora infrequente, parece ser imprevisível e requer atenção cuidadosa.

  15. Treatment options for mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome.

    Santa, Kristin M

    2010-11-01

    Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare neurodegenerative disease caused by the decreased ability of cells to produce sufficient energy in the form of adenosine 5'-triphosphate. Although it is one of the most common maternally inherited mitochondrial disorders, its exact incidence is unknown. Caused most frequently by an A-to-G point mutation at the 3243 position in the mitochondrial DNA, MELAS syndrome has a broad range of clinical manifestations and a highly variable course. The classic neurologic characteristics include encephalopathy, seizures, and stroke-like episodes. In addition to its neurologic manifestations, MELAS syndrome exhibits multisystem effects including cardiac conduction defects, diabetes mellitus, short stature, myopathy, and gastrointestinal disturbances. Unfortunately, no consensus guidelines outlining standard drug regimens exist for this syndrome. Many of the accepted therapies used in treating MELAS syndrome have been identified through a small number of clinical trials or isolated case reports. Currently, the drugs most often used include antioxidants and various vitamins aimed at minimizing the demands on the mitochondria and supporting and maximizing their function. Some of the most frequently prescribed agents include coenzyme Q(10), l-arginine, B vitamins, and levocarnitine. Although articles describing MELAS syndrome are available, few specifically target education for clinical pharmacists. This article will provide pharmacists with a practical resource to enhance their understanding of MELAS syndrome in order to provide safe and effective pharmaceutical care.

  16. Lactic acidosis and diastolic hypotension after intermittent albuterol nebulization in a pediatric patient

    Tehila A. Saadia

    2015-01-01

    Full Text Available We describe a case of 13-year-old female with intermittent asthma who developed lactic acidosis and diastolic hypotension after receiving intermittent albuterol nebulizer treatment. She presented to the emergency department (ED with sudden onset of shortness of breath and chest pain. She received two albuterol nebulizer treatments at home without symptomatic relief. She was treated in the ED with intermittent albuterol nebulization for a total of 22.5 mg over the next 5 hours. A decrease in diastolic blood pressure from 60 mmHg to 40 mmHg was noted after the treatment. Blood lactate level was 5.9 mmol/L. She recovered from it and was discharged to home but she had recurrence of shortness of breath and presented to the ED two days later. She was treated with albuterol nebulization for a total of 17.5 mg over the next two and half hours and developed diastolic hypotension again, as low as 30 mm Hg. After discontinuation of albuterol nebulization, her BP normalized. Cardiopulmonary and metabolic side effects of continuous albuterol therapy have been reported in the recent medical literature. Our patient, however, developed these adverse effects on intermittent albuterol nebulizer treatment. It is important for the pediatrician to recognize the adverse effects of β2-agonist therapy to avoid carrying out extensive workup for hypotension and hyperlactatemia prolonging hospital stay.

  17. Lactic acidosis, potassium, and the heart rate deflection point in professional road cyclists

    Lucia, A; Hoyos, J; Santalla, A; Perez, M; Carvajal, A; Chicharro, J

    2002-01-01

    Objective: To determine the influence of lactic acidosis, the Bohr effect, and exercise induced hyperkalaemia on the occurrence of the heart rate deflection point (HRDP) in elite (professional) cyclists. Methods: Sixteen professional male road cyclists (mean (SD) age 26 (1) years) performed a ramp test on a cycle ergometer (workload increases of 5 W/12 s, averaging 25 W/min). Heart rate (HR), gas exchange parameters, and blood variables (lactate, pH, P50 of the oxyhaemoglobin dissociation curve, and K+) were measured during the tests. Results: A HRDP was shown in 56% of subjects at about 88% of their maximal HR (HRDP group; n = 9) but was linear in the rest (No-HRDP group; n = 7). In the HRDP group, the slope of the HR-workload regression line above the HRDP correlated inversely with levels of K+ at the maximal power output (r = -0.67; p<0.05). Conclusions: The HRDP phenomenon is associated, at least partly, with exercise induced hyperkalaemia. PMID:11916893

  18. Metabolic Acidosis and Strong Ion Gap in Critically Ill Patients with Acute Kidney Injury

    Cai-Mei Zheng

    2014-01-01

    Full Text Available Purpose. To determine the influence of physicochemical parameters on survival in metabolic acidosis (MA and acute kidney injury (AKI patients. Materials and Methods. Seventy-eight MA patients were collected and assigned to AKI or non-AKI group. We analyzed the physiochemical parameters on survival at 24 h, 72 h, 1 week, 1 month, and 3 months after AKI. Results. Mortality rate was higher in the AKI group. AKI group had higher anion gap (AG, strong ion gap (SIG, and apparent strong ion difference (SIDa values than non-AKI group. SIG value was higher in the AKI survivors than nonsurvivors and this value was correlated serum creatinine, phosphate, albumin, and chloride levels. SIG and serum albumin are negatively correlated with Acute Physiology and Chronic Health Evaluation IV scores. AG was associated with mortality at 1 and 3 months post-AKI, whereas SIG value was associated with mortality at 24 h, 72 h, 1 week, 1 month, and 3 months post-AKI. Conclusions. Whether high or low SIG values correlate with mortality in MA patients with AKI depends on its correlation with serum creatinine, chloride, albumin, and phosphate (P levels. AG predicts short-term mortality and SIG value predicts both short- and long-term mortality among MA patients with AKI.

  19. Impact of hard vs. soft wheat and monensin level on rumen acidosis in feedlot heifers.

    Yang, W Z; Xu, L; Zhao, Y L; Chen, L Y; McAllister, T A

    2014-11-01

    Many feedlot finishing diets include wheat when the relative wheat prices are low. This study was conducted to examine the responses in ruminal pH and fermentation as well as site and extent of digestion from substituting soft or hard wheat for barley grain and to determine whether an elevated monensin concentration might decrease indicators of ruminal acidosis in feedlot heifers. Five ruminally cannulated beef heifers were used in a 5 × 5 Latin square with 2 × 2 + 1 factorial arrangement. Treatments included barley (10% barley silage, 86% barley, 4% supplement, with 28 mg monensin/kg DM) and diets where barley was substituted by either soft or hard wheat with either 28 or 44 mg monensin/kg diet DM. Intake of DM was not affected by grain source, whereas increasing monensin with wheat diets reduced (P type or monensin level. Total VFA concentrations were greater (P type. The molar proportion of propionate was greater (P Feeding soft vs. hard wheat delivered a greater (P feed use by heifers fed wheat-based finishing diets.

  20. Successful Management of Refractory Type 1 Renal Tubular Acidosis with Amiloride

    Chow, Robert; Yim, Kenneth; Jaar, Bernard G.

    2017-01-01

    A 28-year-old female with history of hypothyroidism, Sjögren's Syndrome, and Systemic Lupus Erythematosus (SLE) presented with complaints of severe generalized weakness, muscle pain, nausea, vomiting, and anorexia. Physical examination was unremarkable. Laboratory test showed hypokalemia at 1.6 mmol/l, nonanion metabolic acidosis with HCO3 of 11 mmol/l, random urine pH of 7.0, and urine anion gap of 8 mmol/l. CT scan of the abdomen revealed bilateral nephrocalcinosis. A diagnosis of type 1 RTA likely secondary to Sjögren's Syndrome was made. She was started on citric acid potassium citrate with escalating dosages to a maximum dose of 60 mEq daily and potassium chloride over 5 years without significant improvement in serum K+ and HCO3 levels. She had multiple emergency room visits for persistent muscle pain, generalized weakness, and cardiac arrhythmias. Citric acid potassium citrate was then replaced with sodium bicarbonate at 15.5 mEq every 6 hours which was continued for 2 years without significant improvement in her symptoms and electrolytes. Amiloride 5 mg daily was added to her regimen as a potassium sparing treatment with dramatic improvement in her symptoms and electrolyte levels (as shown in the figures). Amiloride was increased to 10 mg daily and potassium supplementation was discontinued without affecting her electrolytes. Her sodium bicarbonate was weaned to 7.7 mEq daily. PMID:28127482

  1. The role of dietary acid load and mild metabolic acidosis in insulin resistance in humans.

    Williams, Rebecca S; Kozan, Pinar; Samocha-Bonet, Dorit

    2016-05-01

    Type 2 diabetes is increasingly being recognised as a global health crisis (World Health Organisation). Insulin resistance is closely associated with obesity and precedes the development of type 2 diabetes. However, there is now increasing evidence to suggest that diet itself may independently be associated with type 2 diabetes risk. A diet with a high acid load (or high potential renal net acid load, PRAL) can result in a decrease in pH towards the lower end of the normal physiological range, which may in turn lead to the development of insulin resistance. Conversely, reducing dietary acid load (the so called 'alkaline diet') may be protective and prevent the onset of type 2 diabetes. Here, we explore the influence of dietary acid load on the development of mild metabolic acidosis and induction of insulin resistance. Whilst large prospective cohort studies link high dietary acid load or low serum bicarbonate with the development of type 2 diabetes, the effect of a diet with a low acid (or high alkaline) load remains unclear. Further interventional studies are required to investigate the influence of dietary composition on the body's acid/base balance, insulin resistance and incidence of type 2 diabetes.

  2. Nitazoxanide induces in vitro metabolic acidosis in Taenia crassiceps cysticerci.

    Isac, Eliana; de A Picanço, Guaraciara; da Costa, Tatiane L; de Lima, Nayana F; de S M M Alves, Daniella; Fraga, Carolina M; de S Lino Junior, Ruy; Vinaud, Marina C

    2016-12-01

    Nitazoxanide (NTZ) is a broad-spectrum anti-parasitic drug used against a wide variety of protozoans and helminthes. Albendazole, its active metabolite albendazole sulfoxide (ABZSO), is one of the drugs of choice to treat both intestinal and tissue helminth and protozoan infections. However little is known regarding their impact on the metabolism of parasites. The aim of this study was to compare the in vitro effect of NTZ and ABZSO in the glycolysis of Taenia crassiceps cysticerci. The cysticerci were treated with 1.2; 0.6; 0.3 or 0.15 μg/mL of NTZ or ABZSO. Chromatographic and spectrophotometric analyses were performed in the culture medium and in the cysticerci extract. Regarding the glucose concentrations was possible to observe two responses: impair of the uptake and gluconeogenesis. The pyruvate concentrations were increased in the ABZSO treated group. Lactate concentrations were increased in the culture medium of NTZ treated groups. Therefore it was possible to infer that the metabolic acidosis was greater in the group treated with NTZ than in the ABZSO treated group indicating that this is one of the modes of action used by this drug to induce the parasite death.

  3. [Non-fatal hyperkalemia in lactic acidosis due to metformin overdose. Report of one case].

    Díaz, Rienzi; Vega, Jorge; Goecke, Helmuth

    2015-03-01

    We report a 74-year-old man with diabetes mellitus type 2 and hypertension, who recently underwent coronary bypass surgery due to severe triple vessel disease receiving cardiological and combined antidiabetic therapy, including metformin 4 g/day. He was admitted with abdominal pain, nausea, vomiting, diarrhea and loss of consciousness. At admission, he was disoriented and agitated with signs of poor perfusion. His blood pressure was 80/70 mmHg, pulse rate 40 beats/min, respiratory rate 20-breaths/min, and axillary temperature 35 °C. Biochemical profile revealed an extreme hyperkalemia of 15.4 mEq/L (double checked), elevated creatinine, uremia and brain natriuretic peptide; hypoglycemia (blood glucose 68 mg/dl) and normal C Reactive Protein. Arterial blood gases revealed severe lactic acidemia. The electrocardiogram showed sinus bradycardia, simple AV block, widened QRS with prominent T wave and prolonged QT. He was admitted to the Intensive Care Unit (ICU) with the suspicion of lactic acidosis associated with metformin, receiving fluid management, intravenous hypertonic glucose plus insulin and sodium bicarbonate, mechanical ventilation, vasopressor therapy, a temporary pacemaker lead, in addition to continuous venovenous hemodiafiltration. Two days later, the patient experienced a significant clinical improvement with normalization of the acid-base status, plasma lactate and potassium levels. On day 9, diuresis was recovered, creatinine and uremia returned to normal levels and the patient was discharged from the ICU.

  4. Incidence of lactic acidosis toxicity among patients on stavudine or zidovudine containing antiretroviral therapy at Lighthouse clinics

    W Ng'ambi

    2012-11-01

    Full Text Available Although stavudine and zidovudine remain frequently used in low-income countries in Africa, they are associated with long-term toxicities. Lactic acidosis is one of the most serious toxicities in antiretroviral treatment (ART and occurs predominantly in regimens containing stavudine (D4T or zidovudine (AZT. We conducted this study to determine the incidence and risk factors for lactic acidosis among HIV-positive patients that have been on ART for at least 6 months. This study will bridge the gap that exists due to scarcity of data on the extent of toxicities due to long-term use of D4T and AZT. We conducted a retrospective cohort study using routine clinic data from the Lighthouse and Martin Preuss Centre electronic data systems. We used the clinic data collected between 1st January 2004 and 31st December 2011. We included into the analysis all patients that have been on D4T- or AZT-containing ARV drugs for at least 6 months. We analysed the data using Poisson regression of the number of cases of lactic acidosis (LA on gender, age at ART initiation, baseline BMI, and lipodystrophy in order to determine the incidence and risk factors for lactic acidosis. All statistical analyses were done at 5% significance level. We identified 14,854 patients that have ever been on D4T- or AZT-containing ARV drugs for longer than 5 months. Of these, 43% were male and median age was 34 years. The total number of cases of confirmed LA was 342 with observed mortality rate 40% more than the patients without confirmed LA. There were 23.02 cases of LA for every 1000 patient-years on D4T- or AZT-containing ART regimens. The strongest risk factor identified for developing LA was having a baseline BMI >25 with incidence rate ratio (IRR 3.11 (95% CI: 2.49, 3.88. The IRR for patients with a diagnosis of lipodystrophy was 1.77 (95% CI: 1.35, 2.32. Patients aged <30 years at ART initiation had 31% reduced risk of developing LA as compared to patients aged>39 years at ART

  5. Prevalence of Metformin Use and the Associated Risk of Metabolic Acidosis in US Diabetic Adults With CKD: A National Cross-Sectional Study.

    Kuo, Chin-Chi; Yeh, Hung-Chieh; Chen, Bradley; Tsai, Ching-Wei; Lin, Yu-Sheng; Huang, Chiu-Ching

    2015-12-01

    The use of metformin in chronic kidney disease (CKD) population has been intensely debated with conflicting evidence. Large population studies are needed to inform risk assessment and therapeutic decision-making. We evaluated the associations among metformin, metabolic acidosis, and CKD in a 10-year nationally representative noninstitutionalized civilian population in the United States.In this cross-sectional study, a total of 2279 diabetic adults aged 20 years or older in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2012 were included and had measurements of serum bicarbonate, sodium, potassium, and chloride. The exposure was metformin use. The outcome was subclinical and severe metabolic acidosis defined by serum bicarbonate 16mEq/L and by serum bicarbonate 60 mL/min/1.73 m was also observed. In multiple linear regression analysis, metformin was significantly associated with decreased serum bicarbonate levels (β = -0.45, 95% CI: -0.73, -0.17) and increased serum anion gap levels (β = 0.40, 95% CI: 0.19, 0.61). The adjusted odds ratio of subclinical high anion gap and severe metabolic acidosis for metformin users was 1.68 (95% CI: 1.11, 2.55) and 1.31 (0.49, 3.47), respectively. The association between metformin and serum bicarbonate was significantly modified by CKD status. No interaction was found between metformin and CKD stages for serum anion gap and acidosis.Metformin is associated with subclinical metabolic acidosis but not with severe metabolic acidosis. The propensity of serum bicarbonate-lowering effect was intensified in advanced CKD; however, such tendency was not associated with the risk of clinically defined acidosis. Our findings highlight a potential of cautious expansion of metformin use among CKD-3b patients with diabetes meriting further investigations.

  6. Risk factors for mortality in children with diabetic keto acidosis from developing countries.

    Poovazhagi, Varadarajan

    2014-12-15

    Diabetic keto acidosis (DKA) is the major cause for mortality in children with Diabetes mellitus (DM). With increasing incidence of type 1 DM worldwide, there is an absolute increase of DM among children between 0-14 year age group and overall incidence among less than 30 years remain the same. This shift towards younger age group is more of concern especially in developing countries where mortality in DKA is alarmingly high. Prior to the era of insulin, DKA was associated with 100% mortality and subsequently mortality rates have come down and is now, 0.15%-0.31% in developed countries. However the scenario in developing countries like India, Pakistan, and Bangladesh are very different and mortality is still high in children with DKA. Prospective studies on DKA in children are lacking in developing countries. Literature on DKA related mortality are based on retrospective studies and are very recent from countries like India, Pakistan and Bangladesh. There exists an urgent need to understand the differences between developed and developing countries with respect to mortality rates and factors associated with increased mortality in children with DKA. Higher mortality rates, increased incidence of cerebral edema, sepsis, shock and renal failure have been identified among DKA in children from developing countries. Root cause for all these complications and increased mortality in DKA could be delayed diagnosis in children from developing countries. This necessitates creating awareness among parents, public and physicians by health education to identify symptoms of DM/DKA in children, in order to decrease mortality in DKA. Based on past experience in Parma, Italy it is possible to prevent occurrence of DKA both in new onset DM and in children with established DM, by simple interventions to increase awareness among public and physicians.

  7. Risk factors for mortality in children with diabetic keto acidosis from developing countries

    Varadarajan; Poovazhagi

    2014-01-01

    Diabetic keto acidosis(DKA) is the major cause for mortality in children with Diabetes mellitus(DM). With increasing incidence of type 1 DM worldwide, there is an absolute increase of DM among children between 0-14 year age group and overall incidence among less than 30 years remain the same. This shift towards younger age group is more of concern especially in developing countries where mortality in DKA is alarmingly high. Prior to the era of insulin, DKA was associated with 100% mortality and subsequently mortality rates have come down and is now, 0.15%-0.31% in developed countries. However the scenario in developing countries like India, Pakistan, and Bangladesh are very different and mortality is still high in children with DKA. Prospective studies on DKA in children are lacking in developing countries. Literature on DKA related mortality are based on retrospective studies and are very recent from countries like India, Pakistan and Bangladesh. There exists an urgent need to understand the differences between developed and developing countries with respect to mortality rates and factors associated with increased mortality in children with DKA. Higher mortality rates, increased incidence of cerebral edema, sepsis, shock and renal failure have been identified among DKA in children from developing countries.Root cause for all these complications and increased mortality in DKA could be delayed diagnosis in children from developing countries. This necessitates creating awareness among parents, public and physicians by health education to identify symptoms of DM/DKA in children, in order to decrease mortality in DKA. Based on past experience in Parma, Italy it is possible to prevent occurrence of DKA both in new onset DM and in children with established DM, by simple interventions to increase awareness among public and physicians.

  8. Active dry Saccharomyces cerevisiae can alleviate the effect of subacute ruminal acidosis in lactating dairy cows.

    AlZahal, O; Dionissopoulos, L; Laarman, A H; Walker, N; McBride, B W

    2014-12-01

    The objective of the study was to determine the effect of active dry Saccharomyces cerevisiae (ADSC) supplementation on dry matter intake, milk yield, milk components, ruminal pH, and microbial community during a dietary regimen that leads to subacute ruminal acidosis (SARA). Sixteen multiparous, rumen-cannulated lactating Holstein cows were randomly assigned to 1 of 2 dietary treatments that included ADSC (Biomate; AB Vista, Marlborough, UK; 8 × 10(10) cfu/head per day) or control. During wk 1 to 6, all cows received a high-forage (HF) diet (77:23, forage:concentrate). Cows were then abruptly switched during wk 7 to a high-grain (HG) diet (49:51, forage:concentrate) and remained on the HG until the end of wk 10. Feed intake and milk yields were recorded daily. Ruminal pH was recorded continuously using an indwelling system for 1 to 2 d per week during the pre-experimental phase, and wk 6, 7, and 10. Ruminal digesta samples were collected at the end of the experiment and analyzed for relative change in microbial communities using real-time quantitative PCR. Cows were considered to have SARA if the duration below pH 5.6 was ≥300 min/d. Ruminal pH during wk 6 (HF plateau) was not different across treatments (15 ± 46 min/d at pH inflammation within the rumen. Cows supplemented with ADSC had a 2.3-fold increase in Streptococcus bovis and a 12-fold reduction in Megasphaera elsdenii. The reduction in M. elsdenii may reflect lower concentration of lactic acid within the rumen for ADSC cows. In conclusion, ADSC supplementation to dairy cows was demonstrated to alleviate the condition of SARA caused by abrupt dietary changes from HF to HG, and can potentially improve rumen function, as indicated by greater numbers of cellulolytic microorganisms within the rumen.

  9. Consequences and therapy of the metabolic acidosis of chronic kidney disease.

    Kraut, Jeffrey A; Madias, Nicolaos E

    2011-01-01

    Metabolic acidosis is common in patients with chronic kidney disease (CKD), particularly once the glomerular filtration rate (GFR) falls below 25 ml/min/1.73 m(2). It is usually mild to moderate in magnitude with the serum bicarbonate concentration ([HCO(3)(-)]) ranging from 12 to 23 mEq/l. Even so, it can have substantial adverse effects, including development or exacerbation of bone disease, growth retardation in children, increased muscle degradation with muscle wasting, reduced albumin synthesis with a predisposition to hypoalbuminemia, resistance to the effects of insulin with impaired glucose tolerance, acceleration of the progression of CKD, stimulation of inflammation, and augmentation of β(2)-microglobulin production. Also, its presence is associated with increased mortality. The administration of base to patients prior to or after initiation of dialysis leads to improvement in many of these adverse effects. The present recommendation by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF KDOQI) is to raise serum [HCO(3)(-)] to ≥ 22 mEq/l, whereas Caring for Australians with Renal Impairment (CARI) recommends raising serum [HCO(3)(-)] to >22 mEq/l. Base administration can potentially contribute to volume overload and exacerbation of hypertension as well as to metastatic calcium precipitation in tissues. However, sodium retention is less when given as sodium bicarbonate and sodium chloride intake is concomitantly restricted. Results from various studies suggest that enhanced metastatic calcification is unlikely with the pH values achieved during conservative base administration, but the clinician should be careful not to raise serum [HCO(3)(-)] to values outside the normal range.

  10. Fatores de risco maternos associados à acidose fetal Maternal risk factors associated with fetal acidosis

    José Mauro Madi

    2010-09-01

    Full Text Available OBJETIVOS: avaliar os fatores de risco maternos associados à acidose fetal. MÉTODOS: estudo tipo caso-controle composto por 188 recém-nascidos, sendo que 47 compuseram o grupo casos (pH de artéria umbilical OBJECTIVES: to assess maternal risk factors associated with fetal acidosis. METHODS: a case-control type study was conducted of 188 neonates, of whom 47 comprised the case group (umbilical arterial pH <7.0 and 141 the control (umbilical arterial pH E7.1 <7.3. The study included only single-gestation neonates without congenital malformations. Both maternal and fetal variables were taken into consideration. Statistical analysis involved the calculation of the raw and adjusted Odds Ratio, Student's t-test, the chi-squared test and multivariate analysis using Enter-method non-conditional logistic regression. The level of statistical significance was set at p<0.05. RESULTS: in the case group higher percentages of caesarian sections and pre-term births were observed, involving almost five times as much intensive care and twenty-five times more likelihood of Apgar in the 5th minute <7. No association was observed between the groups and fetal presentation, mother's age, history of miscarriage, years of schooling of mother or attendance at prenatal sessions. After multivariate analysis, the only risk factors that remained significant were complications relating to the placenta or the umbilical cord. Deliveries involving complications relating to the placenta or the umbilical cord were three times more likely to involve fetal acidemia. CONCLUSIONS: acidemia among neonates was associated with a higher percentage of caesarians, premature births, a need for intensive care and treatment and an Apgar index of <7 in the 5th minute. After multivariate analysis, complications relating to premature displacement of the placenta and the umbilical cord were the only remaining risk factors associated with fetal acidemia.

  11. Progress in Diagnosing Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like Episodes

    Ying-Xin Wang; Wei-Dong Le

    2015-01-01

    Objective:Mitochondrial myopathy,encephalopathy,lactic acidosis,and stroke-like episodes (MELAS) is a progressive,multisystem affected mitochondrial disease associated with a number of disease-related defective genes.MELAS has unpredictable presentations and clinical course,and it can be commonly misdiagnosed as encephalitis,cerebral infarction,or brain neoplasms.This review aimed to update the diagnosis progress in MELAS,which may provide better understanding of the disease nature and help make the right diagnosis as well.Data Sources:The data used in this review came from published peer review articles from October 1984 to October 2014,which were obtained from PubMed.The search term is "MELAS".Study Selection:Information selected from those reported studies is mainly based on the progress on clinical features,blood biochemistry,neuroimaging,muscle biopsy,and genetics in diagnosing MELAS.Results:MELAS has a wide heterogeneity in genetics and clinical manifestations.The relationship between mutations and phenotypes remains unclear.Advanced serial functional magnetic resonance imaging (MRI) can provide directional information on this disease.Muscle biopsy has meaningful value in diagnosing MELAS,which shows the presence of ragged red fibers and mosaic appearance of cytochrome oxidase negative fibers.Genetic studies have reported that approximately 80% of MELAS cases are caused by the mutation m.3243A>G of the mitochondrial transfer RNA (Leu (UUR)) gene (MT-TL1).Conclusions:MELAS involves multiple systems with variable clinical symptoms and recurrent episodes.The prognosis of MELAS patients depends on timely diagnosis.Therefore,overall diagnosis of MELAS should be based on the maternal inheritance family history,clinical manifestation,and findings from serial MRI,muscle biopsy,and genetics.

  12. Effects of acetate-free citrate-containing dialysate on metabolic acidosis, anemia, and malnutrition in hemodialysis patients.

    Kuragano, Takahiro; Kida, Aritoshi; Furuta, Minoru; Yahiro, Mana; Kitamura, Rie; Otaki, Yoshinaga; Nonoguchi, Hiroshi; Matsumoto, Akihide; Nakanishi, Takeshi

    2012-03-01

    Previously, dialysate contained small amounts of acetate as an alkaline buffer. Recently, acetate-free dialysate (A[-]D) has been available. We evaluated the clinical effect of A(-)D over acetate-containing dialysate (A(+)D) on acid-base balance, anemia, and nutritional status in maintenance hemodialysis (MHD) patients. Twenty-nine patients on MHD were treated with A(+)D for 4 months (first A(+)D), switched to A(-)D for 4 months, and returned to A(+)D for the next 4-month period (second A(+)D). Metabolic acidosis: Serum bicarbonate (HCO3(-) ) levels did not change in patients with normal HCO3(-) levels (≥20 mEq/L) throughout the study. Meanwhile, in patients with initially low HCO3(-) levels, it was significantly increased during the A(-)D period only. Anemia: In patients with target hemoglobin (Hb) ≥10 g/dL, Hb levels were maintained during the study period, even if the dose of erythropoiesis-stimulating agents (ESAs) decreased. In patients with low Hb levels, it was significantly increased in the A(-)D period without increasing ESA or iron doses. Nutritional Condition: In patients with normal albumin levels (≥3.8 g/dL), albumin did not change throughout the study period. However, in patients with lower albumin levels, it was significantly increased during the A(-)D period. These improvements in metabolic acidosis, anemia, and nutrition in the A(-)D period completely dissipated during the second A(+)D period. Hemodialysis (HD) with A(-)D may improve a patient's clinical status with intractable metabolic acidosis, hyporesponsiveness to ESA, and malnutrition that were not normalized in HD with A(+)D.

  13. Acute but not chronic metabolic acidosis potentiates the acetylcholine-induced reduction in blood pressure: an endothelium-dependent effect.

    Celotto, A C; Ferreira, L G; Capellini, V K; Albuquerque, A A S; Rodrigues, A J; Evora, P R B

    2016-02-01

    Metabolic acidosis has profound effects on vascular tone. This study investigated the in vivo effects of acute metabolic acidosis (AMA) and chronic metabolic acidosis (CMA) on hemodynamic parameters and endothelial function. CMA was induced by ad libitum intake of 1% NH4Cl for 7 days, and AMA was induced by a 3-h infusion of 6 M NH4Cl (1 mL/kg, diluted 1:10). Phenylephrine (Phe) and acetylcholine (Ach) dose-response curves were performed by venous infusion with simultaneous venous and arterial blood pressure monitoring. Plasma nitrite/nitrate (NOx) was measured by chemiluminescence. The CMA group had a blood pH of 7.15±0.03, which was associated with reduced bicarbonate (13.8±0.98 mmol/L) and no change in the partial pressure of arterial carbon dioxide (PaCO2). The AMA group had a pH of 7.20±0.01, which was associated with decreases in bicarbonate (10.8±0.54 mmol/L) and PaCO2 (47.8±2.54 to 23.2±0.74 mmHg) and accompanied by hyperventilation. Phe or ACh infusion did not affect arterial or venous blood pressure in the CMA group. However, the ACh infusion decreased the arterial blood pressure (ΔBP: -28.0±2.35 mm Hg [AMA] to -4.5±2.89 mmHg [control]) in the AMA group. Plasma NOx was normal after CMA but increased after AMA (25.3±0.88 to 31.3±0.54 μM). These results indicate that AMA, but not CMA, potentiated the Ach-induced decrease in blood pressure and led to an increase in plasma NOx, reinforcing the effect of pH imbalance on vascular tone and blood pressure control.

  14. Role of CaMKII in post acidosis arrhythmias: a simulation study using a human myocyte model.

    Lascano, Elena C; Said, Matilde; Vittone, Leticia; Mattiazzi, Alicia; Mundiña-Weilenmann, Cecilia; Negroni, Jorge A

    2013-07-01

    Postacidotic arrhythmias have been associated to increased sarcoplasmic reticulum (SR) Ca(2+) load and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) activation. However, the molecular mechanisms underlying these arrhythmias are still unclear. To better understand this process, acidosis produced by CO2 increase from 5% to 30%, resulting in intracellular pH (pHi) change from 7.15 to 6.7, was incorporated into a myocyte model of excitation-contraction coupling and contractility, including acidotic inhibition of L-type Ca(2+) channel (I(CaL)), Na(+)-Ca(2+) exchanger, Ca(2+) release through the SR ryanodine receptor (RyR2) (I(rel)), Ca(2+) reuptake by the SR Ca(2+) ATPase2a (I(up)), Na(+)-K(+) pump, K(+) efflux through the inward rectifier K(+) channel and the transient outward K(+) flow (I(to)) together with increased activity of the Na(+)-H(+) exchanger (I(NHE)). Simulated CaMKII regulation affecting I(rel), I(up), I(CaL), I(NHE) and I(to) was introduced in the model to partially compensate the acidosis outcome. Late Na(+) current increase by CaMKII was also incorporated. Using this scheme and assuming that diastolic Ca(2+) leak through the RyR2 was modulated by the resting state of this channel and the difference between SR and dyadic cleft [Ca(2+)], postacidotic delayed after depolarizations (DADs) were triggered upon returning to normal pHi after 6 min acidosis. The model showed that DADs depend on SR Ca(2+) load and on increased Ca(2+) leak through RyR2. This postacidotic arrhythmogenic pattern relies mainly on CaMKII effect on I(CaL) and I(up), since its individual elimination produced the highest DAD reduction. The model further revealed that during the return to normal pHi, DADs are fully determined by SR Ca(2+) load at the end of acidosis. Thereafter, DADs are maintained by SR Ca(2+) reloading by Ca(2+) influx through the reverse NCX mode during the time period in which [Na(+)]i is elevated.

  15. A patient presenting with metabolic acidosis despite severe vomiting--correct diagnosis by use of the physical-chemical approach.

    Lindner, Gregor; Pfortmüller, Carmen; Exadaktylos, Aristomenis K

    2013-06-01

    We describe the case of a 28-year-old otherwise healthy woman who presents to our emergency department with nausea for 2 days and severe vomiting for 1 day. She has no history of travel, and her medical history is unremarkable. The physical examination shows a soft and nontender abdomen. Laboratory examinations reveal the presence of significant metabolic alkalosis despite the severe vomiting of the patient. Hypochloremic alkalosis would be expected to be present in this patient. We explain how to correctly identify the rare cause of metabolic acidosis present in this patient using the physicochemical approach (Stewarts approach) for the analysis of human acid-base disorders.

  16. Severe lactic acidosis due to thiamine deficiency in a patient with B-cell leukemia/lymphoma on total parenteral nutrition during high-dose methotrexate therapy.

    Svahn, Johanna; Schiaffino, Maria Cristina; Caruso, Ubaldo; Calvillo, Michaela; Minniti, Giuseppe; Dufour, Carlo

    2003-12-01

    An 11-month-old girl with B-cell leukemia/lymphoma developed profound lethargy due to severe lactic acidosis during chemotherapy and total parenteral nutrition (TPN). Initial treatment with NaHCO3 was ineffective. Treatment with a vitamin cocktail (OH-cobalamin, pyridoxine, thiamine, riboflavine, biotin, carnitine) at pharmacologic doses rapidly improved the child's clinical and laboratory status. Lactic acidosis was caused by an impairment of pyruvate dehydrogenase complex, which was due to lack of its necessary cofactor thiamine in the TPN. This case report indicates that lactic acidosis may be a front-line diagnosis in patients on TPN with lethargy and outlines the need for monitoring thiamine supply in TPN.

  17. Effect of collecting duct-specific deletion of both Rh B Glycoprotein (Rhbg) and Rh C Glycoprotein (Rhcg) on renal response to metabolic acidosis.

    Lee, Hyun-Wook; Verlander, Jill W; Handlogten, Mary E; Han, Ki-Hwan; Weiner, I David

    2014-02-15

    The Rhesus (Rh) glycoproteins, Rh B and Rh C Glycoprotein (Rhbg and Rhcg, respectively), are ammonia-specific transporters expressed in renal distal nephron and collecting duct sites that are necessary for normal rates of ammonia excretion. The purpose of the current studies was to determine the effect of their combined deletion from the renal collecting duct (CD-Rhbg/Rhcg-KO) on basal and acidosis-stimulated acid-base homeostasis. Under basal conditions, urine pH and ammonia excretion and serum HCO3(-) were similar in control (C) and CD-Rhbg/Rhcg-KO mice. After acid-loading for 7 days, CD-Rhbg/Rhcg-KO mice developed significantly more severe metabolic acidosis than did C mice. Acid loading increased ammonia excretion, but ammonia excretion increased more slowly in CD-Rhbg/Rhcg-KO and it was significantly less than in C mice on days 1-5. Urine pH was significantly more acidic in CD-Rhbg/Rhcg-KO mice on days 1, 3, and 5 of acid loading. Metabolic acidosis increased phosphenolpyruvate carboxykinase (PEPCK) and Na(+)/H(+) exchanger NHE-3 and decreased glutamine synthetase (GS) expression in both genotypes, and these changes were significantly greater in CD-Rhbg/Rhcg-KO than in C mice. We conclude that 1) Rhbg and Rhcg are critically important in the renal response to metabolic acidosis; 2) the significantly greater changes in PEPCK, NHE-3, and GS expression in acid-loaded CD-Rhbg/Rhcg-KO compared with acid-loaded C mice cause the role of Rhbg and Rhcg to be underestimated quantitatively; and 3) in mice with intact Rhbg and Rhcg expression, metabolic acidosis does not induce maximal changes in PEPCK, NHE-3, and GS expression despite the presence of persistent metabolic acidosis.

  18. Rumen lipopolysaccharide and inflammation during grain adaptation and subacute ruminal acidosis in steers.

    Gozho, G N; Krause, D O; Plaizier, J C

    2006-11-01

    Three rumen-fistulated Jersey steers were gradually adapted to a wheat-barley concentrate over a 4-wk period. Adaptation steps consisted of four 1-wk periods during which steers were fed diets with forage-to-concentrate (F:C) ratios of 100:0, 79:21, 59:41, and 39:61. The forage consisted of chopped hay (CH), and the concentrate consisted of pelleted concentrate containing 50% ground wheat and 50% ground barley. Steers were fed the all-forage diet ad libitum during wk 1. Feed offered in wk 2 to 4 was kept constant at the ad libitum intake during wk 1. On 2 d that were set 3 d apart during wk 5, subacute ruminal acidosis (SARA) was induced in the steers by feeding a diet with an F:C ratio of 24:76 by offering them 0.9 kg of CH at 0900 h followed by 2 meals of 3.0 kg each of wheat-barley pellets (WBP) at 1100 h and 1300 h and 0.9 kg of CH at 1700 h, to depress rumen pH for at least 3 h/d below 5.6. The average concentrate inclusion for the SARA induction diet was 76 +/- 10% DM. During stepwise adaptation, time with pH below 5.6 increased to an average of 121 min/d when the steers were consuming a diet containing 61% DM as WBP. Dietary inclusion of WBP at the rate of 76% DM induced SARA because the steers spent an average of 219 min/d with pH below 5.6. The free ruminal lipopolysaccharide (LPS) concentration increased from 6,310 endotoxin units (EU)/mL with the all-forage diet to 18,197 EU/mL with the 61% concentrate diet. The ruminal LPS concentration increased to 26,915 EU/mL when SARA was induced. Serum haptoglobin increased from 0.53 mg/mL when steers were on the all-forage diet to 1.90 mg/mL with the 61% concentrate diet and were not increased further by inducing SARA. The serum amyloid-A concentration was not affected by increasing dietary concentrate during stepwise adaptation to the concentrate, but increased from 71 to 163 microg/mL when SARA was induced. A gradual increase in dietary concentrate so that the F:C ratio decreased to 39:61 resulted in increased

  19. Ácidosis D-láctica secundaria a síndrome de intestino corto D-Lactic acidosis secondary to short bowel syndrome

    M. J. Tapia Guerrero

    2010-10-01

    Full Text Available El síndrome de intestino corto aparece por la reducción de la superficie absortiva intestinal efectiva por pérdida funcional o anatómica de una parte de intestino delgado. Se presenta el caso de una mujer de 35 años con síndrome de intestino corto severo secundario a isquemia intestinal aguda en la edad adulta, que presenta a los 5 años de evolución episodios de mareos con inestabilidad en la marcha y pérdida de fuerza en las manos, llegándose al diagnóstico de acidosis D-láctica. La acidosis D-láctica representa una complicación infrecuente, pero importante por su sintomatología, de este síndrome. Se debe a un cambio en la flora intestinal debido a un sobrecrecimiento de bacterias acidolácticas, que producen D-lactato. Debe sospecharse en aquellos casos de acidosis sin causa aparente y manifestaciones neurológicas sin focalidad en pacientes con síndrome de intestino corto o intervenidos de by-pass yeyuno-ileal. El tratamiento apropiado resuelve con frecuencia los síntomas neurológicos y previene o reduce las recurrencias.The short bowel syndrome appears for the reduction of intestinal absorptive surface due to functional or anatomical loss of part of the small bowel. We present the case of a 35-year-old woman with severe short bowel syndrome secondary to acute intestinal ischemia in adults, who presented at 5 years of evolution episodes of dizziness with gait instability and loss of strength in hands. The diagnosis was D-lactic acidosis. D-lactic acidosis is a rare complication, but important for their symptoms, of this syndrome. It is due to a change in intestinal flora secondary to an overgrowth of lactic acid bacteria that produce D-lactate. D-lactic acidosis should be looked for in cases of metabolic acidosis in which the identity of acidosis is not apparent, neurological manifestations without focality and the patient has short bowel syndrome or patients who have had jejunoileal bypass surgery. Appropiate treatment

  20. Bone Density Is Directly Associated With Glomerular Filtration and Metabolic Acidosis but Do Not Predict Fragility Fractures in Men With Moderate Chronic Kidney Disease.

    Lima, Guilherme Alcantara Cunha; de Paula Paranhos-Neto, Francisco; Silva, Luciana Colonese; de Mendonça, Laura Maria Carvalho; Delgado, Alvimar Gonçalves; Leite, Maurilo; Gomes, Carlos Perez; Farias, Maria Lucia Fleiuss

    2016-01-01

    Hyperparathyroidism, vitamin D deficiency, increased fibroblast growth factor-23 (FGF-23), and metabolic acidosis promote bone fragility in chronic kidney disease (CKD). Although useful in predicting fracture risk in the general population, the role of dual-energy X-ray absorptiometry (DXA) in CKD remains uncertain. This cross-sectional study included 51 men aged 50-75 yr with moderate CKD. The stage 4 CKD patients had higher levels of parathyroid hormone (pmetabolic acidosis for bone impairment and to the inadequacy of DXA to evaluate bone fragility in CKD patients.

  1. Endolymphatic Sac Enlargement in a Girl with a Novel Mutation for Distal Renal Tubular Acidosis and Severe Deafness

    Rink Nikki

    2012-01-01

    Full Text Available Hereditary distal renal tubular acidosis (dRTA is caused by mutations of genes encoding subunits of the H+-ATPase (ATP6V0A4 and ATP6V1B1 expressed in α-intercalated cells of the distal renal tubule and in the cochlea. We report on a 2-year-old girl with distal RTA and profound speech delay which was initially misdiagnosed as autism. Genetic analysis showed compound heterozygous mutations with one known and one novel mutation of the ATP6V1B1 gene; cerebral magnetic resonance imaging (MRI revealed bilateral enlargement of the endolymphatic sacs of the inner ear. With improved cooperation, audiometric testing showed that hearing loss was most profound on the right, where endolymphatic sac enlargement was greatest, demonstrating a clear link between the degree of deafness and the degree of inner ear abnormality. This case indicates the value of MRI for diagnosis of inner ear involvement in very young children with distal RTA. Although citrate therapy quickly corrects the acidosis and restores growth, early diagnosis of deafness is crucial so that hearing aids can be used to assist acquisition of speech and to provide enough auditory nerve stimulation to assure the affected infants remain candidates for cochlear implantation.

  2. Seizure-induced damage to substantia nigra and globus pallidus is accompanied by pronounced intra- and extracellular acidosis

    Inamura, K.; Smith, M.L.; Hansen, A.J.; Siesjoe, B.K. (Univ. of Lund (Sweden))

    1989-12-01

    Status epilepticus of greater than 30-min duration in rats gives rise to a conspicuous lesion in the substantia nigra pars reticulata (SNPR) and globus pallidus (GP). The objective of the present study was to explore whether the lesion, which encompasses necrosis of both neurons and glial cells, is related to intra- and extracellular acidosis. Using the flurothyl model previously described to produce seizures, we assessed regional pH values with the autoradiographic 5,5-dimethyl(2-14C)oxazolidine-2,4-dione technique. Regional pH values were assessed in animals with continuous seizures for 20 and 60 min, as well as in those allowed to recover for 30 and 120 min after seizure periods of 20 or 60 min. In additional animals, changes in extracellular fluid pH (pHe) were measured with ion-selective microelectrodes, and extracellular fluid (ECF) volume was calculated from the diffusion profile for electrophoretically administered tetramethylammonium. In structures such as the neocortex and the hippocampus, which show intense metabolic activation during seizures, status epilepticus of 20- and 60-min duration was accompanied by a reduction of the composite tissue pH (pHt) of 0.2-0.3 unit. Recovery of pHt was observed upon termination of seizures. In SNPR and in GP, the acidosis was marked to excessive after 20 and 60 min of seizures (delta pHt approximately 0.6 after 60 min).

  3. Nonsense mutation in pseudouridylate synthase 1 (PUS1) in two brothers affected by myopathy, lactic acidosis and sideroblastic anaemia (MLASA).

    Fernandez-Vizarra, Erika; Berardinelli, Angela; Valente, Lucia; Tiranti, Valeria; Zeviani, Massimo

    2009-01-01

    Myopathy, lactic acidosis and sideroblastic anaemia (MLASA) is a rare condition that combines early-onset myopathy with lactic acidosis and sideroblastic anaemia. MLASA has been associated with a missense mutation in pseudouridylate synthase 1 (PUS1), an enzyme located in both nucleus and mitochondria, which converts uridine into pseudouridine in several cytosolic and mitochondrial tRNA positions and increases the efficiency of protein synthesis in both compartments. We examined two Italian brothers with MLSA and sequenced the PUS1 gene. We found combined defects in mitochondrial respiratory chain complexes in muscle and fibroblast homogenates of both patients, and low levels of mtDNA translation products in fibroblast mitochondria. A novel, homozygous stop mutation was present in PUS1 (E220X). The stop mutation in PUS1 is likely to determine the loss of function of the protein, since it predicts the synthesis of a protein missing 208/427 amino acid residues on the C terminus, and was associated with low mtDNA translation.

  4. Underlying mechanism of ASIC1a involved in acidosis-induced cytotoxicity in rat C6 glioma cells

    Xie-chuan WENG; Jian-quan ZHENG; Jin LI; Wen-bin XIAO

    2007-01-01

    Aim:To investigate the underlying mechanism of acid-sensing ion channel (ASIC) la involved in the acidosis-induced cytotoxicity of rat C6 glioma cells. Methods:The stable ASICla-silenced C6 cells built with the RNA interference technology were confirmed by RT-PCR and Western blot analysis. Intracellular calcium ([Ca2+]i) in both the wild-type rat C6 glioma cells and the ASIC I a-silenced C6 cells were analyzed before and after acid application/exposure with the calcium imaging experiment. Results:The rapid extracellular pH drop induced the increase of [Ca2+]i in the wild-type C6 cells,but not in the ASICla-silenced C6 cells. During the prolonged acid exposure,[Ca2+]i was lower in the ASICla-silenced C6 cells than that in the control cells. Conclusion:The resultant toxicity of [Ca2+]i might contribute to the acidosis-induced cytotoxicity.

  5. Short Review of Our Work - “Chronic Metabolic Acidosis Destroys Pancreas” with Focus on the Functional Exocrine Pancreatic Disorders

    linic of San Fran

    2015-07-01

    Full Text Available We deeply appreciate your publishing of our work - “Chronic metabolic acidosis destroys pancreas” in JOP (2014 [1]. We feel that our work can give the food for thought to many young researchers and health practitioners. A short review of our work may generate various questions and ideas for further investigations. In our work, we have focused on negative affects of the chronic metabolic acidosis on pancreatic function including: • Premature activation of the proteases within the pancreas • Diminishing the antimicrobial activity of the pancreatic juice • Suppressing of the flushing out zymogens from the pancreas • Precipitation of the aggressive bile acids • Calcification Authors believe that further research may provide more details of how the acidification destroys the pancreas and causes chronic pancreatitis. We would like to share some of our thoughts on this subject as follows: Descriptions of symptoms of chronic pancreatitis such as pain, malabsorption syndrome, steatorrhea, and weight loss are found in almost all medical books, textbooks, and articles. The medical literature refers to these conditions as “pancreatic insufficiency”. It is known that these symptoms occur when only 10 % of the exocrine pancreatic function is left intact. This is not an “insufficiency.” It is a pancreatic “failure” when the therapeutic opportunities are very limited.

  6. Roux-en-Y gastric bypass surgery reduces bone mineral density and induces metabolic acidosis in rats.

    Abegg, Kathrin; Gehring, Nicole; Wagner, Carsten A; Liesegang, Annette; Schiesser, Marc; Bueter, Marco; Lutz, Thomas A

    2013-11-01

    Roux-en-Y gastric bypass (RYGB) surgery leads to bone loss in humans, which may be caused by vitamin D and calcium malabsorption and subsequent secondary hyperparathyroidism. However, because these conditions occur frequently in obese people, it is unclear whether they are the primary causes of bone loss after RYGB. To determine the contribution of calcium and vitamin D malabsorption to bone loss in a rat RYGB model, adult male Wistar rats were randomized for RYGB surgery, sham-operation-ad libitum fed, or sham-operation-body weight-matched. Bone mineral density, calcium and phosphorus balance, acid-base status, and markers of bone turnover were assessed at different time points for 14 wk after surgery. Bone mineral density decreased for several weeks after RYGB. Intestinal calcium absorption was reduced early after surgery, but plasma calcium and parathyroid hormone levels were normal. 25-hydroxyvitamin D levels decreased, while levels of active 1,25-dihydroxyvitamin D increased after surgery. RYGB rats displayed metabolic acidosis due to increased plasma lactate levels and increased urinary calcium loss throughout the study. These results suggest that initial calcium malabsorption may play a key role in bone loss early after RYGB in rats, but other factors, including chronic metabolic acidosis, contribute to insufficient bone restoration after normalization of intestinal calcium absorption. Secondary hyperparathyroidism is not involved in postoperative bone loss. Upregulated vitamin D activation may compensate for any vitamin D malabsorption.

  7. A grain-based subacute ruminal acidosis challenge causes translocation of lipopolysaccharide and triggers inflammation.

    Khafipour, E; Krause, D O; Plaizier, J C

    2009-03-01

    The effects of a grain-based subacute ruminal acidosis (SARA) challenge on translocation of lipopolysaccharide (LPS) into the peripheral circulation, acute phase proteins in blood and milk, feed intake, milk production and composition, and blood metabolites were determined in 8 lactating Holstein cows. Between wk 1 and 5 of 2 successive 6-wk periods, cows received a total mixed ration ad libitum with a forage to concentrate (F:C) ratio of 50:50. In wk 6 of both periods, the SARA challenge was conducted by replacing 21% of the dry matter of the total mixed ration with pellets containing 50% wheat and 50% barley. Rumen pH was monitored continuously using indwelling pH probes in 4 rumen cannulated cows. Rumen fluid samples were collected 15 min before feed delivery and at 2, 4, 6, 12, 14, 16, 18, and 24 h after feed delivery for 2 d during wk 5 (control) and wk 6 (SARA). Peripheral blood samples were collected using jugular catheters 15 min before feeding and at 6 and 12 h after feeding at the same days of the rumen fluid collections. The SARA challenge significantly reduced average daily pH from 6.17 to 5.97 and increased the duration of rumen pH below pH 5.6 from 118 to 279 min/d. The challenge reduced dry matter intake (16.5 vs. 19 kg/d), milk yield (28.3 vs. 31.6 kg/d), and milk fat (2.93 vs. 3.30%, 0.85 vs. 0.97 kg/d), and tended to increase milk protein percentage (3.42 vs. 3.29%), without affecting milk protein yield (1.00 vs. 0.98 kg/d). The challenge also increased the concentration of free LPS in rumen fluid from 28,184 to 107,152 endotoxin units (EU)/mL. This was accompanied by an increase in LPS in peripheral blood plasma (0.52 vs. <0.05 EU/mL) with a peak at 12 h after feeding (0.81 EU/mL). Concentrations of the acute phase proteins serum amyloid A, haptoglobin, and LPS-binding protein (LBP) in peripheral blood as well as LBP concentration in milk increased (438.5 vs. 167.4, 475.6 vs. 0, 53.1 vs. 18.2, and 6.94 vs. 3.02 microg/mL, respectively) during

  8. Impact of subacute ruminal acidosis (SARA) adaptation and recovery on the density and diversity of bacteria in the rumen of dairy cows

    Hook, S.E.; Steele, M.A.; Northwood, K.S.; Dijkstra, J.; France, J.; Wright, A.G.; McBride, B.W.

    2011-01-01

    Subacute ruminal acidosis (SARA) is characterized by ruminal pH depression and microbial perturbation. The impact of SARA adaptation and recovery on rumen bacterial density and diversity was investigated following high-grain feeding. Four ruminally cannulated dairy cows were fed a hay diet, transiti

  9. Ibuprofen-Induced Hypokalemia and Distal Renal Tubular Acidosis: A Patient’s Perceptions of Over-the-Counter Medications and Their Adverse Effects

    Mark D. Salter

    2013-01-01

    Full Text Available We highlight a case of distal renal tubular acidosis secondary to ibuprofen and codeine use. Of particular interest in this case are the patient’s perception of over-the-counter (OTC medication use, her own OTC use prior to admission, and her knowledge of adverse reactions or side effects of these medications prior to taking them.

  10. The Effects of Lung Protective Ventilation or Hypercapnic Acidosis on Gas Exchange and Lung Injury in Surfactant Deficient Rabbits.

    Helmut D Hummler

    Full Text Available Permissive hypercapnia has been shown to reduce lung injury in subjects with surfactant deficiency. Experimental studies suggest that hypercapnic acidosis by itself rather than decreased tidal volume may be a key protective factor.To study the differential effects of a lung protective ventilatory strategy or hypercapnic acidosis on gas exchange, hemodynamics and lung injury in an animal model of surfactant deficiency.30 anesthetized, surfactant-depleted rabbits were mechanically ventilated (FiO2 = 0.8, PEEP = 7cmH2O and randomized into three groups: Normoventilation-Normocapnia (NN-group: tidal volume (Vt = 7.5 ml/kg, target PaCO2 = 40 mmHg; Normoventilation-Hypercapnia (NH-group: Vt = 7.5 ml/kg, target PaCO2 = 80 mmHg by increasing FiCO2; and a Hypoventilation-Hypercapnia (HH-group: Vt = 4.5 ml/kg, target PaCO2 = 80 mmHg. Plasma lactate and interleukin (IL-8 were measured every 2 h. Animals were sacrificed after 6 h to perform bronchoalveolar lavage (BAL, to measure lung wet-to-dry weight, lung tissue IL-8, and to obtain lung histology.PaO2 was significantly higher in the HH-group compared to the NN-group (p<0.05, with values of the NH-group between the HH- and NN-groups. Other markers of lung injury (wet-dry-weight, BAL-Protein, histology-score, plasma-IL-8 and lung tissue IL-8 resulted in significantly lower values for the HH-group compared to the NN-group and trends for the NH-group towards lower values compared to the NN-group. Lactate was significantly lower in both hypercapnia groups compared to the NN-group.Whereas hypercapnic acidosis may have some beneficial effects, a significant effect on lung injury and systemic inflammatory response is dependent upon a lower tidal volume rather than resultant arterial CO2 tensions and pH alone.

  11. Risk Factor Analysis for Lactic Acidosis%乳酸性酸中毒的危险因素分析

    舒英; 佘宁兰; 龚蓉; 刘蔓莉; 徐争鸣; 王平; 陈泽君; 程弓

    2011-01-01

    Objective To analyze the risk factors of lactic acidosis. Methods The clinical data of 32 patients with lactic acidosis admitted to our hospital from May 2008 to December 2010 were studied retrospectively. Results All patients had type 2 diabetes mellitus. Among them, 27 (84. 6%) were older than 60, 20 (62. 5%) had ingested antidiabetic drugs of biguanides, 12 (37. 5%) were complicated by pulmonary diseases, 9 (28. 1%) by heart diseases, 15 (46. 9%) by renal dysfunction, and 8 (25. 0%) by liver dysfunction. Conclusions Diabetes mellitus, old age, ingesting of biguanides, cardiopulmonary diseases, renal and hepatic dysfunction all contribute to the occurrence of lactic acidosis. During clinical work, we should try to avoid the above-mentioned risk factors.%目的 分析乳酸性酸中毒发生的危险因素,警示临床工作.方法 回顾性分析2008年5月-2010年12月收治的32例乳酸性酸中毒患者的临床资料.结果 32例患者均合并2型糖尿病,其中老年患者27例(占84.6%);20例有服用双胍类降糖药物史(占62.5%);12例合并肺部疾病(占37.5%);9例合并心脏疾病(占28.1%);15例合并肾功能不全(占46.9%);8例合并肝功能异常(占25.0%).结论 糖尿病、老年、使用双胍类药物、合并心肺疾病及肝肾功能不全都是发生乳酸性酸中毒的危险因素.在临床工作中,对高危患者需提高警惕,尽量避免危险因素叠加以减少乳酸性酸中毒的发生.

  12. Comparison of end-tidal carbon dioxide and arterial blood bicarbonate levels in patients with metabolic acidosis referred to emergency medicine

    Taghizadieh, Ali; Pouraghaei, Mahboub; Moharamzadeh, Payman; Ala, Alireza; Rahmani, Farzad; Basiri Sofiani, Karim

    2016-01-01

    Introduction: The routine and gold standard method to diagnose of acid – base disturbance is arterial blood gas (ABG) sampling. Capnography could be used to measure the end-tidal carbon dioxide (ETCO2) levels and ETco2 has a close correlation with the PaCo2. The aim of this study was comparison the ETco2 and arterial blood bicarbonate levels in patients with metabolic acidosis. Methods: In a descriptive-analytical study that performed in Emergency Department of Emam Reza Medical Research and Training Hospital of Tabriz on patients with metabolic acidosis, ETco2 level and blood bicarbonate levels in 262 patients were evaluated. Results: Mean of ETco2 and Hco3 levels in patients with metabolic acidosis were 22.29 ± 4.15 and 12.78 ± 3.83, respectively. In all patients, the significant direct linear relationship was found between ETco2 with Hco3 (r = 0.553, P < 0.001). We had 4 groups of patients with metabolic acidosis, also there is a significant direct linear relationship between the ETCo2 and the Hco3 level of arterial blood in patients with renal failure (P < 0.001 and r = 0.551), sepsis (P < 0.001 and r = 0.431), drug toxicity (P < 0.001 and r = 0.856), and ketoacidosis (DKA) (P < 0.001 and r = 0.559). Conclusion: According to the results of this study, capnography can be used for primary diagnosis of metabolic acidosis in spontaneously breathing patients who referred to the emergency wards, however, the ABG must be considered as the gold standard tool for diagnosis and guiding the treatment. PMID:27777693

  13. Ca++-sensitizing mutations in troponin, P(i), and 2-deoxyATP alter the depressive effect of acidosis on regulated thin-filament velocity.

    Longyear, Thomas J; Turner, Matthew A; Davis, Jonathan P; Lopez, Joseph; Biesiadecki, Brandon; Debold, Edward P

    2014-05-01

    Repeated, intense contractile activity compromises the ability of skeletal muscle to generate force and velocity, resulting in fatigue. The decrease in velocity is thought to be due, in part, to the intracellular build-up of acidosis inhibiting the function of the contractile proteins myosin and troponin; however, the underlying molecular basis of this process remains poorly understood. We sought to gain novel insight into the decrease in velocity by determining whether the depressive effect of acidosis could be altered by 1) introducing Ca(++)-sensitizing mutations into troponin (Tn) or 2) by agents that directly affect myosin function, including inorganic phosphate (Pi) and 2-deoxy-ATP (dATP) in an in vitro motility assay. Acidosis reduced regulated thin-filament velocity (VRTF) at both maximal and submaximal Ca(++) levels in a pH-dependent manner. A truncated construct of the inhibitory subunit of Tn (TnI) and a Ca(++)-sensitizing mutation in the Ca(++)-binding subunit of Tn (TnC) increased VRTF at submaximal Ca(++) under acidic conditions but had no effect on VRTF at maximal Ca(++) levels. In contrast, both Pi and replacement of ATP with dATP reversed much of the acidosis-induced depression of VRTF at saturating Ca(++). Interestingly, despite producing similar magnitude increases in VRTF, the combined effects of Pi and dATP were additive, suggesting different underlying mechanisms of action. These findings suggest that acidosis depresses velocity by slowing the detachment rate from actin but also by possibly slowing the attachment rate.

  14. Rh versus pH: the role of Rhesus glycoproteins in renal ammonia excretion during metabolic acidosis in a freshwater teleost fish.

    Wright, Patricia A; Wood, Chris M; Wilson, Jonathan M

    2014-08-15

    Increased renal ammonia excretion in response to metabolic acidosis is thought to be a conserved response in vertebrates. We tested the hypothesis that Rhesus (Rh) glycoproteins in the kidney of the freshwater common carp, Cyprinus carpio, play a crucial role in regulating renal ammonia excretion during chronic metabolic acidosis. Exposure to water pH 4.0 (72 h) resulted in a classic metabolic acidosis with reduced plasma arterial pH and [HCO3(-)], no change in PCO2 and large changes in renal function. Urine [NH4(+)] as well as [titratable acidity-HCO3(-)] rose significantly over the acid exposure, but the profound reduction (fivefold) in urine flow rates eliminated the expected elevations in renal ammonia excretion. Low urine flow rates may be a primary strategy to conserve ions, as urinary excretion rates of Na(+), Cl(-) and Ca(2+) were significantly lower during the acid exposure relative to the control period. Interestingly, renal Rhcg1 mRNA and protein levels were elevated in acid-exposed relative to control groups, along with mRNA levels of several ion transporters, including the Na(+)/H(+) exchanger, H(+)-ATPase and Na(+)/K(+)-ATPase. Immunofluorescence microscopy showed a strong apical Rhcg1 signal in distal tubules. Taken together, these data show that renal Rh glycoproteins and associated ion transporters are responsive to metabolic acidosis, but conservation of ions through reduced urine flow rates takes primacy over renal acid-base regulation in the freshwater C. carpio. We propose that an 'acid/base-ion balance' compromise explains the variable renal responses to metabolic acidosis in freshwater teleosts.

  15. Clinical, pathological and genetic study of a kindred of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes

    FENG Yan-qing; GUO Ning; HUANG Fan; LI Ling; YAO Xiao-li; LI Xun-hua; ZHANG Cheng; LIANG Xiu-ling

    2005-01-01

    @@ The first description of a syndrome including stroke-like episodes, lactic acidaemia, and ragged red fibres, was reported by Shapira et al in 1975.1 Pavlakis et al2 described further cases, introduced the acronym MELAS (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes), and suggested that this represented a distinct mitochondrial disease phenotype. In 1990, Goto et al3 identified A3243G mutation in the transfer RNA (tRNA) leucine (UUR) gene in some patients with MELAS. Although this mutation has now been established to be the commonest mtDNA defect it is often misdiagnosed. Here we report a kindred of MELAS including a mother and a son. Clinical, pathological and genetic studies are proceeding.

  16. [A case of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episode/Leigh overlap syndrome].

    Matsui, Jun; Takano, Tomoyuki; Ryujin, Fukiko; Anzai, Yuko; Yoshioka, Seiichiro; Takeuchi, Yoshihiro; Goto, Yuichi

    2014-09-01

    We experienced a case in which mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS) was identified as complications following the onset of Leigh syndrome along with a 10191 T>C mutation of the mitochondrial gene. The case pertains to a 26-year-old woman. The disease appeared when she was 11 years old due to divergent strabismus, at which point a diagnosis of juvenile Leigh syndrome was made. Many infraction images not conforming to the vessel region were observed upon a brain MRI which was performed at 26 years of age, thus leading to her being diagnosed with MELAS as a complication. Upoon bibliographical consideration, it was speculated that the clinical features of MELAS/Leigh overlap syndrome clearly differ from Leigh syndrome in terms of age of onset, symptoms, and prognosis. Pleiotropic genetic factors including heteroplasmy were presumed to be involved in the diverse phenotype of overlap syndrome.

  17. Mucosal necrosis of the small intestine in myopathy,encephalopathy, lactic acidosis, and stroke-like episodes syndrome

    Keita Fukuyama; Yasuhide Ishikawa; Tetsuro Ogino; Hidenobu Inoue; Ryoya Yamaoka; Tetsuro Hirose; Tomohiko Nishihira

    2012-01-01

    This report presents a case of massive mucosal necrosis of the small intestine in a patient with mitochondrial myopathy,encephalopathy,lactic acidosis,and stroke-like episodes (MELAS),which particularly affects the brain,nervous system and muscles.A 45-year-old Japanese female,with an established diagnosis of MELAS,presented with vomiting.Computed tomography showed portomesenteric venous gas and pneumatosis intestinalis.She underwent a resection of the small intestine.A microscopic study showed necrosis of the mucosa and vacuolar degeneration of smooth muscle cells in the arterial wall.Immunohistochemistry showed anti-mitochondrial antibody to be highly expressed in the crypts adjacent the necrotic mucosa.The microscopic and immunohistochemical findings suggested the presence of a large number of abnormal mitochondria in MELAS to be closely linked to mucosal necrosis of the small intestine.

  18. Knock-down of hypoxia-induced carbonic anhydrases IX and XII radiosensitizes tumor cells by increasing intracellular acidosis

    Jérôme eDoyen

    2013-01-01

    Full Text Available The relationship between acidosis within the tumor microenvironment and radioresistance of hypoxic tumor cells remains unclear. Previously we reported that hypoxia-induced carbonic anhydrases CAIX and CAXII constitute a robust pHi-regulating system that confers a survival advantage on hypoxic human colon carcinoma LS174Tr cells in acidic microenvironments. Here we investigate the role of acidosis, CAIX and CAXII knock-down in combination with ionizing radiation. Fibroblasts cells (-/+ CAIX and LS174Tr cells (inducible knock-down for ca9/ca12 were analyzed for cell cycle phase distribution and survival after irradiation in extracellular pHo manipulations and hypoxia (1% O2 exposure. Radiotherapy was used to target ca9/ca12-silenced LS174Tr tumors grown in nude mice. We found that diminishing the pHi-regulating capacity of fibroblasts through inhibition of NHE-1 sensitize cells to radiation-induced cell death. Secondly, the pHi-regulating function of CAIX plays a key protective role in irradiated fibroblasts in an acidic environment as accompanied by a reduced number of cells in the radiosensitive phases of the cell cycle. Thirdly, we demonstrate that irradiation of LS174Tr spheroids, silenced for either ca9 or both ca9/ca12, showed a respective 50% and 75% increase in cell death as a result of a decrease in cell number in the radioresistant S phase and a disruption of CA-mediated pHi regulation. Finally, LS174Tr tumor progression was strongly decreased when ca9/ca12 silencing was combined with irradiation in vivo. These findings highlight the combinatory use of radiotherapy with targeting of the pHi-regulating carbonic anhydrases as an anti-cancer strategy.

  19. Evaluación del estado ácido-base en terneros con acidosis ruminal inducida experimentalmente: aplicación de dos modelos de diagnóstico

    Baquero Parrado, Johann Ricardo

    2015-01-01

    Introducción: Durante la lactación del ternero puede alterarse el reflejo de cierre de la gotera esofágica conduciendo a acidosis ruminal por D-lactato con implicaciones fisiológicas importantes como alteraciones en el crecimiento, baja ganancia de peso y pérdidas económicas importantes. Objetivos: Evaluar el estado ácido-base en terneros con acidosis ruminal inducida experimentalmente. Hipótesis: La acidosis metabólica de origen ruminal, en terneros neonatos, puede ser diagnosticada ig...

  20. Experimental acute rumen acidosis in sheep: consequences on clinical, rumen, and gastrointestinal permeability conditions and blood chemistry.

    Minuti, A; Ahmed, S; Trevisi, E; Piccioli-Cappelli, F; Bertoni, G; Jahan, N; Bani, P

    2014-09-01

    Acute acidosis was induced in sheep, and gastrointestinal permeability was assessed by using lactulose as a permeability marker. Metabolism was evaluated by monitoring blood metabolites. Four rams (72.5 ± 4.6 kg BW) were used in a 2 × 2 changeover design experiment. The experimental period lasted 96 h from -24 to 72 h. After 24 h of fasting (from -24 to 0 h) for both controls and acidosis-induced rams (ACID), 0.5 kg of wheat flour was orally dosed at 0 and 12 h of the experimental period to ACID, while the basal diet (grass hay, ad libitum) was restored to control. At 24 h, a lactulose solution (30 g of lactulose in 200 mL of water) was orally administered. Blood samples were collected at -24, 0, 24, 48, and 72 h of the experimental periods for the analysis of metabolic profiles and during the 10 h after lactulose dosage to monitor lactulose changes in blood. In addition, rumen and fecal samples were collected at 24 h of the experimental period. The acidotic challenge markedly reduced (P < 0.01) rumen pH and VFA but increased rumen d- and l-lactic acid (P < 0.01). Concurrently, a decrease of fecal pH and VFA occurred in ACID (P < 0.01), together with an abrupt increase (P < 0.01) of lactate and fecal alkaline phosphatase. Blood lactulose was significantly increased in ACID peaking 2 h after lactulose dosage. Blood glucose, β-hydroxybutyrate, Ca, K, Mg, and alkaline phosphatase showed a significant reduction (P < 0.05) at 24 h, whereas urea and NEFA declined (P < 0.05) from 48 to 72 h. A strong inflammatory acute phase response with oxidative stress in ACID group was observed from 24 to 72 h; higher values of haptoglobin (P < 0.01) were measured from 24 to 72 h and of ceruloplasmin from 48 (P < 0.05) to 72 h (P < 0.01). Among the negative acute phase reactants, plasma albumin, cholesterol, paraoxonase, and Zn concentration also decreased (P < 0.05) in ACID at different time points between 24 and 72 h after acidotic challenge start. A rise (P < 0.05) of reactive

  1. Hemodialysis-refractory metformin-associated lactate acidosis with hypoglycemia, hypothermia, and bradycardia in a diabetic patient with belated diagnosis and chronic kidney disease
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    Zibar, Lada; Zibar, Karin

    2017-01-30

    Metformin is a first-line oral antidiabetic therapy for patients with type 2 diabetes mellitus. Metformin-associated lactate acidosis (MALA) is a well-known, life-threatening, but rare side effect of metformin therapy. Chronic kidney disease (CKD) patients have a much greater risk of MALA. We report the case of a severe refractory MALA despite hemodialysis (HD) treatment, associated with hypoglycemia, hypothermia, and bradycardia in a neglected and thus untimely-recognized CKD patient with type 2 diabetes mellitus. Despite the recent rehabilitation of metformin as a treatment of choice for type 2 diabetes mellitus, the drug should be prescribed with caution as it can be associated with life-threatening refractory acidosis, particularly in CKD patients. Moreover, HD treatment could occasionally be ineffective, resulting in a fatal outcome.
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  2. The Spitzer-Weinstein Syndrome: One Form of Type IV Renal Tubular Acidosis and Its Response to Indapamide: A Case Report

    Hilmi Umut ÜNAL

    2012-05-01

    Full Text Available Spitzer-Weinstein is rare disorder characterized by thiazide responsive hyperkalemia and normal anion gap metabolic acidosis, similar to Gordon syndrome.The hyperfunction of thiazide–sensitive Na-Cl cotransporter (TSC is the main pathophysiological mechanism. We present a 21-year-old male with normal blood pressure, persistently elevated serum potassium, and metabolic asidosis. The diagnosis of Spitzer-Weinstein syndrome was made by clinical pictures and thiazide test. After using 1.5 mg indapamide from a group of thiazide diuretics, his serum potassium decreased from 6.68 mmol/L to 3.54 mmol/L and the daily urine potassium excretion increased from 13.2 mmol to 34.1 mmol. This patient then took indapamide 1.5 mg daily. The persistent hyperkalemia and metabolic acidosis were corrected. Thiazide, a powerful inhibitor of TSC, proved to be a useful tool for the diagnosis and treatment of Spitzer-Weinstein syndrome.

  3. Evaluating in vitro dose-response effects of Lavandula officinalis essential oil on rumen fermentation characteristics, methane production and ruminal acidosis.

    Yadeghari, Shahin; Malecky, Mostafa; Dehghan Banadaky, Mehdi; Navidshad, Bahman

    2015-01-01

    Four in vitro experiments (Exp.) were conducted to evaluate lavender essential oil (LEO) effects at 0 (control), 250 (low dose), 500 (medium dose), 750 and 1000 µL per L (high doses) of incubation medium on rumen gas production kinetics (Exp.1), ruminal digestibility and fermentation (Exp.2), methane production (Exp.3) and rumen acidosis (Exp.4). The asymptote of gas production (A) increased quadratically (p production rate (µ) decreased linearly (p = 0.031) with increasing dose of LEO. A linear and quadratic effect (p production decreased by 11.00 and 44.00 to 60.00% at medium and high doses of LEO (p essential oil decreased also ruminal pH at all included doses (p < 0.05), intensifying rumen acidosis. These results revealed a dose-dependent selective effect (stimulatory at low and medium, and inhibitory at high doses) of LEO on rumen fermentation.

  4. Arrhythmogenic Biophysical Phenotype for SCN5A Mutation S1787N Depends upon Splice Variant Background and Intracellular Acidosis.

    Rou-Mu Hu

    Full Text Available SCN5A is a susceptibility gene for type 3 long QT syndrome, Brugada syndrome, and sudden infant death syndrome. INa dysfunction from mutated SCN5A can depend upon the splice variant background in which it is expressed and also upon environmental factors such as acidosis. S1787N was reported previously as a LQT3-associated mutation and has also been observed in 1 of 295 healthy white controls. Here, we determined the in vitro biophysical phenotype of SCN5A-S1787N in an effort to further assess its possible pathogenicity.We engineered S1787N in the two most common alternatively spliced SCN5A isoforms, the major isoform lacking a glutamine at position 1077 (Q1077del and the minor isoform containing Q1077, and expressed these two engineered constructs in HEK293 cells for electrophysiological study. Macroscopic voltage-gated INa was measured 24 hours after transfection with standard whole-cell patch clamp techniques. We applied intracellular solutions with pH7.4 or pH6.7. S1787N in the Q1077 background had WT-like INa including peak INa density, activation and inactivation parameters, and late INa amplitude in both pH 7.4 and pH 6.7. However, with S1787N in the Q1077del background, the percentages of INa late/peak were increased by 2.1 fold in pH 7.4 and by 2.9 fold in pH 6.7 when compared to WT.The LQT3-like biophysical phenotype for S1787N depends on both the SCN5A splice variant and on the intracellular pH. These findings provide further evidence that the splice variant and environmental factors affect the molecular phenotype of cardiac SCN5A-encoded sodium channel (Nav1.5, has implications for the clinical phenotype, and may provide insight into acidosis-induced arrhythmia mechanisms.

  5. Persistent lactic acidosis in neonatal hypoxic-ischaemic encephalopathy correlates with EEG grade and electrographic seizure burden.

    Murray, D M

    2012-02-03

    BACKGROUND: Predicting at birth which infants with perinatal hypoxic-ischaemic injury will progress to significant encephalopathy remains a challenge. OBJECTIVE: To determine whether lactic acidosis at birth in asphyxiated neonates could predict the grade of EEG encephalopathy by examining the relationship between time taken for the normalisation of lactate, severity of encephalopathy and seizure burden. METHODS: Continuous early video-EEG monitoring was performed in babies at risk for hypoxic-ischaemic encephalopathy. Encephalopathy was graded from the EEG data. Total seizure burden (seconds) was calculated for each baby. Initial blood gas measurements of pH, base deficit and lactate were taken within 30 minutes of delivery. Time to normal serum lactate was determined in hours from birth for each infant. RESULTS: All 50 term infants had raised initial serum lactate (median (lower, upper quartiles) 11.7 (10.2, 14.9)). There were no significant differences between the initial serum lactate, pH and base deficit in infants with normal\\/mildly abnormal (n = 24), moderately abnormal (n = 14), severely abnormal (n = 5) and inactive EEGs (n = 7). Time to normal lactate varied significantly with EEG grade (median (lower, upper quartile) 6.0 (4.1, 9.5) for mild\\/normal EEG, 13.5 (6.8, 23.5) moderate EEG, 41.5 (30.0, 55.5) severe group, 12.0 (8.1, 21.5) inactive group; p<0.001). Time to normal lactate correlated significantly with EEG seizure burden (seconds; R = 0.446, p = 0.002). Mean (SD) time to normal lactate was 10.0 (7.2) hours in infants who did not have seizures and 27.3 (19.0) hours in the 13 infants with electrographic seizures (p = 0.002). CONCLUSIONS: Serum lactate levels in the first 30 minutes of life do not predict the severity of the ensuing encephalopathy. In contrast, sustained lactic acidosis is associated with severe encephalopathy on EEG and correlates with seizure burden.

  6. Atypical Strokes in a Young African American Male: A Case of Mitochondrial Encephalopathy Lactic Acidosis and Stroke-Like Episodes (MELAS Syndrome

    Jully M. Sanchez

    2011-01-01

    Full Text Available Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS syndrome is a rare but important cause of stroke-like symptoms which can often be missed Thambisetty and Newman 2004. We describe a case of a young male presenting with stroke-like episodes, later diagnosed with MELAS in an attempt to improve the understanding about diagnosing MELAS in the appropriate clinical context.

  7. Treatment of metabolic acidosis in patients with stage 3 chronic kidney disease with fruits and vegetables or oral bicarbonate reduces urine angiotensinogen and preserves glomerular filtration rate.

    Goraya, Nimrit; Simoni, Jan; Jo, Chan-Hee; Wesson, Donald E

    2014-11-01

    Alkali therapy of metabolic acidosis in patients with chronic kidney disease (CKD) with plasma total CO2 (TCO2) below 22 mmol/l per KDOQI guidelines appears to preserve estimated glomerular filtration rate (eGFR). Since angiotensin II mediates GFR decline in partial nephrectomy models of CKD and even mild metabolic acidosis increases kidney angiotensin II in animals, alkali treatment of CKD-related metabolic acidosis in patients with plasma TCO2 over 22 mmol/l might preserve GFR through reduced kidney angiotensin II. To test this, we randomized 108 patients with stage 3 CKD and plasma TCO2 22-24 mmol/l to Usual Care or interventions designed to reduce dietary acid by 50% using sodium bicarbonate or base-producing fruits and vegetables. All were treated to achieve a systolic blood pressure below 130 mm Hg with regimens including angiotensin converting enzyme inhibition and followed for 3 years. Plasma TCO2 decreased in Usual Care but increased with bicarbonate or fruits and vegetables. By contrast, urine excretion of angiotensinogen, an index of kidney angiotensin II, increased in Usual Care but decreased with bicarbonate or fruits and vegetables. Creatinine-calculated and cystatin C-calculated eGFR decreased in all groups, but loss was less at 3 years with bicarbonate or fruits and vegetables than Usual Care. Thus, dietary alkali treatment of metabolic acidosis in CKD that is less severe than that for which KDOQI recommends therapy reduces kidney angiotensin II activity and preserves eGFR.

  8. Deficiency of the iron-sulfur clusters of mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase (complex I) in an infant with congenital lactic acidosis.

    Moreadith, R W; Batshaw, M L; Ohnishi, T; Kerr, D.; Knox, B; Jackson, D.; Hruban, R; Olson, J.; Reynafarje, B; Lehninger, A L

    1984-01-01

    We report the case of an infant with hypoglycemia, progressive lactic acidosis, an increased serum lactate/pyruvate ratio, and elevated plasma alanine, who had a moderate to profound decrease in the ability of mitochondria from four organs to oxidize pyruvate, malate plus glutamate, citrate, and other NAD+-linked respiratory substrates. The capacity to oxidize the flavin adenine dinucleotide-linked substrate, succinate, was normal. The most pronounced deficiency was in skeletal muscle, the le...

  9. Differential impacts of elevated CO2 and acidosis on the energy budget of gill and liver cells from Atlantic cod, Gadus morhua.

    Stapp, L S; Kreiss, C M; Pörtner, H O; Lannig, G

    2015-09-01

    Ocean acidification impacts fish and other marine species through increased seawater PCO2 levels (hypercapnia). Knowledge of the physiological mechanisms mediating effects in various tissues of fish is incomplete. Here we tested the effects of extracellular hypercapnia and acidosis on energy metabolism of gill and liver cells of Atlantic cod. Exposure media mimicked blood conditions in vivo, either during normo- or hypercapnia and at control or acidic extracellular pH (pHe). We determined metabolic rate and energy expenditure for protein biosynthesis, Na(+)/K(+)-ATPase and H(+)-ATPase and considered nutrition status by measurements of metabolic rate and protein biosynthesis in media with and without free amino acids (FAA). Addition of FAA stimulated hepatic but not branchial oxygen consumption. Normo- and hypercapnic acidosis as well as hypercapnia at control pHe depressed metabolic stimulation of hepatocytes. In gill cells, acidosis depressed respiration independent of PCO2 and FAA levels. For both cell types, depressed respiration was not correlated with the same reduction in energy allocated to protein biosynthesis or Na(+)/K(+)-ATPase. Hepatic energy expenditure for protein synthesis and Na(+)/K(+)-ATPase was even elevated at acidic compared to control pHe suggesting increased costs for ion regulation and cellular reorganization. Hypercapnia at control pHe strongly reduced oxygen demand of branchial Na(+)/K(+)-ATPase with a similar trend for H(+)-ATPase. We conclude that extracellular acidosis triggers metabolic depression in gill and metabolically stimulated liver cells. Additionally, hypercapnia itself seems to limit capacities for metabolic usage of amino acids in liver cells while it decreases the use and costs of ion regulatory ATPases in gill cells.

  10. Hyperlactatemia and metabolic acidosis in critically ill patient%重症患者的高乳酸血症与代谢性酸中毒

    杜微; 刘大为

    2011-01-01

    高乳酸血症和代谢性酸中毒的关系一直是讨论的热点,涉及到休克复苏、机体内环境稳定及营养支持等方面.一方面重症患者组织低灌注时无氧酵解增加带来的乳酸生成增多会加重代谢性酸中毒,而另一方面乳酸在器官水平和细胞水平被利用会引起血乳酸水平降低进而减轻代谢性酸中毒,最终血乳酸水平取决于两者的平衡.%The relationship between hyperlactatemia and metabolic acidosis, which may involve shock resuscitation,homoiostasis, and nutritional support, remains a hot topic. On one hand, increased production of lac-tate due to anaerobic glycolysis during tissue hypoperfusion can aggravate metabolic acidosis; on the other hand,the utilization of lactate at organ and cell levels may lower blood lactate level, and thus alleviate metabolic acidosis.The ultimate blood lactate level depends on the balance of these two action mechanisms.

  11. The Effect of Osmotherapy and Tight Control of Acidosis on Early Graft Function among Deceased-Donor Kidney Transplant Recipients: A Randomized Controlled Trial

    Etezadi, F.; Najafi Abrandabadi, A. H.; Motaharinia, J.; Mojtahedzadeh, M.; Pourfakhr, P.; Khajavi, M. R.; Gooran, S.; Shariat Moharari, R.; Dehghani, S.

    2017-01-01

    Background: Reperfusion injury and the acid-base status of the transplant are important factors affecting post-transplantation graft function. Objective: We hypothesized that infusing hypertonic saline (HS) or tight control of acid-base status of the blood rushing through renal graft using sodium bicarbonate may have beneficial effects on early graft function. Methods: Candidates for deceased-donor kidney transplant were randomized into three groups. HS group (n=33) received 50 mL/kg normal saline (NS) titrated during operation plus 4 mL/kg of 5% HS just within graft reperfusion phase; bicarbonate group (n=37) was administered 60 mL/kg NS while their metabolic acidosis (base excess ≤5 mEq/L) was tightly corrected every 30 min with sodium bicarbonate; and a control group (n=36) that received 60 mL/kg normal saline while they were administered sodium bicarbonate only, if they encountered severe metabolic acidosis (base excess ≤15 mEq/L). The primary outcome was defined as early post-operative renal function evaluated based on serial serum creatinine levels. The study was registered in Iranian Registry of Clinical Trials (IRCT2013122815841N19). Results: Post-operative early graft function improved significantly during the first 3 days in the intervention groups (pcontrol of metabolic acidosis with sodium bicarbonate infusion improve early renal function during renal transplant surgery.

  12. Deafness and renal tubular acidosis in mice lacking the K-Cl co-transporter Kcc4.

    Boettger, Thomas; Hübner, Christian A; Maier, Hannes; Rust, Marco B; Beck, Franz X; Jentsch, Thomas J

    2002-04-25

    Hearing depends on a high K(+) concentration bathing the apical membranes of sensory hair cells. K(+) that has entered hair cells through apical mechanosensitive channels is transported to the stria vascularis for re-secretion into the scala media(). K(+) probably exits outer hair cells by KCNQ4 K(+) channels(), and is then transported by means of a gap junction system connecting supporting Deiters' cells and fibrocytes() back to the stria vascularis. We show here that mice lacking the K(+)/Cl(-) (K-Cl) co-transporter Kcc4 (coded for by Slc12a7) are deaf because their hair cells degenerate rapidly after the beginning of hearing. In the mature organ of Corti, Kcc4 is restricted to supporting cells of outer and inner hair cells. Our data suggest that Kcc4 is important for K(+) recycling() by siphoning K(+) ions after their exit from outer hair cells into supporting Deiters' cells, where K(+) enters the gap junction pathway. Similar to some human genetic syndromes(), deafness in Kcc4-deficient mice is associated with renal tubular acidosis. It probably results from an impairment of Cl(-) recycling across the basolateral membrane of acid-secreting alpha-intercalated cells of the distal nephron.

  13. Tumor acidosis enhances cytotoxic effects and autophagy inhibition by salinomycin on cancer cell lines and cancer stem cells

    Pellegrini, Paola; Dyczynski, Matheus; Sbrana, Francesca Vittoria; Karlgren, Maria; Buoncervello, Maria; Hägg-Olofsson, Maria; Ma, Ran; Hartman, Johan; Bajalica-Lagercrantz, Svetlana; Grander, Dan; Kharaziha, Pedram; De Milito, Angelo

    2016-01-01

    Sustained autophagy contributes to the metabolic adaptation of cancer cells to hypoxic and acidic microenvironments. Since cells in such environments are resistant to conventional cytotoxic drugs, inhibition of autophagy represents a promising therapeutic strategy in clinical oncology. We previously reported that the efficacy of hydroxychloroquine (HCQ), an autophagy inhibitor under clinical investigation is strongly impaired in acidic tumor environments, due to poor uptake of the drug, a phenomenon widely associated with drug resistance towards many weak bases. In this study we identified salinomycin (SAL) as a potent inhibitor of autophagy and cytotoxic agent effective on several cancer cell lines under conditions of transient and chronic acidosis. Since SAL has been reported to specifically target cancer-stem cells (CSC), we used an established model of breast CSC and CSC derived from breast cancer patients to examine whether this specificity may be associated with autophagy inhibition. We indeed found that CSC-like cells are more sensitive to autophagy inhibition compared to cells not expressing CSC markers. We also report that the ability of SAL to inhibit mammosphere formation from CSC-like cells was dramatically enhanced in acidic conditions. We propose that the development and use of clinically suitable SAL derivatives may result in improved autophagy inhibition in cancer cells and CSC in the acidic tumor microenvironment and lead to clinical benefits. PMID:27248168

  14. Acidosis Mediates the Switching of Gs-PKA and Gi-PKCε Dependence in Prolonged Hyperalgesia Induced by Inflammation.

    Huang, Wei-Yu; Dai, Shih-Ping; Chang, Yan-Ching; Sun, Wei-Hsin

    2015-01-01

    Chronic inflammatory pain, when not effectively treated, is a costly health problem and has a harmful effect on all aspects of health-related quality of life. Previous studies suggested that in male Sprague Dawley rats, prostaglandin E2 (PGE2)-induced short-term hyperalgesia depends on protein kinase A (PKA) activity, whereas long-lasting hyperalgesia induced by PGE2 with carrageenan pre-injection, requires protein kinase Cε (PKCε). However, the mechanism underlying the kinase switch with short- to long-term hyperalgesia remains unclear. In this study, we used the inflammatory agents carrageenan or complete Freund's adjuvant (CFA) to induce long-term hyperalgesia, and examined PKA and PKCε dependence and switching time. Hyperalgesia induced by both agents depended on PKA/PKCε and Gs/Gi-proteins, and the switching time from PKA to PKCε and from Gs to Gi was about 3 to 4 h after inflammation induction. Among the single inflammatory mediators tested, PGE2 and 5-HT induced transient hyperalgesia, which depended on PKA and PKCε, respectively. Only acidic solution-induced hyperalgesia required Gs-PKA and Gi-PKCε, and the switch time for kinase dependency matched inflammatory hyperalgesia, in approximately 2 to 4 h. Thus, acidosis in inflamed tissues may be a decisive factor to regulate switching of PKA and PKCε dependence via proton-sensing G-protein-coupled receptors.

  15. A single nucleotide polymorphism in kidney anion exchanger 1 gene is associated with incomplete type 1 renal tubular acidosis

    Takeuchi, Takumi; Hattori-Kato, Mami; Okuno, Yumiko; Kanatani, Atsushi; Zaitsu, Masayoshi; Mikami, Koji

    2016-01-01

    Various conditions including distal renal tubular acidosis (dRTA) can induce stone formation in the kidney. dRTA is characterized by an impairment of urine acidification in the distal nephron. dRTA is caused by variations in genes functioning in intercalated cells including SLC4A1/AE1/Band3 transcribing two kinds of mRNAs encoding the Cl−/HCO3− exchanger in erythrocytes and that expressed in α-intercalated cells (kAE1). With the acid-loading test, 25% of urolithiasis patients were diagnosed with incomplete dRTA. In erythroid intron 3 containing the promoter region of kAE1, rs999716 SNP showed a significantly higher minor allele A frequency in incomplete dRTA compared with non-dRTA patients. The promoter regions of the kAE1 gene with the minor allele A at rs999716 downstream of the TATA box showed reduced promoter activities compared that with the major allele G. Patients with the A allele at rs999716 may express less kAE1 mRNA and protein in the intercalated cells, developing incomplete dRTA. PMID:27767102

  16. The effects of grain-induced subactue ruminal acidosis on interleukin-6 and acute phase response in dairy cows

    Li, Shucong; Danscher, Anne Mette; Andersen, Pia Haubro

    2014-01-01

    Subacute ruminal acidosis (SARA) resulting from excessive grain feeding to dairy cows is accompanied by an acute phase response. Interleukin 6 (IL-6) has been proposed as a mediator of this response. We tested if the acute phase response associated with grain-induced SARA is mediated by IL-6. Six...... 5, and d 3 before SARA induction and during three SARA days. ELISA kits were used for measurement of IL-6, and the acute phase proteins haptoglobin (Hp), LPS binding protein (LBP), and serum amyloid A (SAA). The SARA challenge tended to increase LBP (7.54 vs. 10.23 mg/L, P = 0.10), and increased...... the SAA (4.24 vs. 11.60 mg/L, P = 0.04) and Hp (3.57 vs. 22.09 mg/L, P = 0.04) in blood plasma, confirming that the challenge caused an acute phase response. Concentrations of IL-6 were not affected by the SARA challenge, and averaged 5.06 ng/mL across treatments. Our data do not confirm that IL-6...

  17. Acidosis Mediates the Switching of Gs-PKA and Gi-PKCε Dependence in Prolonged Hyperalgesia Induced by Inflammation.

    Wei-Yu Huang

    Full Text Available Chronic inflammatory pain, when not effectively treated, is a costly health problem and has a harmful effect on all aspects of health-related quality of life. Previous studies suggested that in male Sprague Dawley rats, prostaglandin E2 (PGE2-induced short-term hyperalgesia depends on protein kinase A (PKA activity, whereas long-lasting hyperalgesia induced by PGE2 with carrageenan pre-injection, requires protein kinase Cε (PKCε. However, the mechanism underlying the kinase switch with short- to long-term hyperalgesia remains unclear. In this study, we used the inflammatory agents carrageenan or complete Freund's adjuvant (CFA to induce long-term hyperalgesia, and examined PKA and PKCε dependence and switching time. Hyperalgesia induced by both agents depended on PKA/PKCε and Gs/Gi-proteins, and the switching time from PKA to PKCε and from Gs to Gi was about 3 to 4 h after inflammation induction. Among the single inflammatory mediators tested, PGE2 and 5-HT induced transient hyperalgesia, which depended on PKA and PKCε, respectively. Only acidic solution-induced hyperalgesia required Gs-PKA and Gi-PKCε, and the switch time for kinase dependency matched inflammatory hyperalgesia, in approximately 2 to 4 h. Thus, acidosis in inflamed tissues may be a decisive factor to regulate switching of PKA and PKCε dependence via proton-sensing G-protein-coupled receptors.

  18. Diffusion and Perfusion Characteristics of MELAS (Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-Like Episode) in Thirteen Patients

    Kim, Ji Hye; Jeon, Tae Yeon; Eo, Hong; Yoo, So Young [Samsung Medical Center, Sungkyunkwan University, School of Medicine, Seoul (Korea, Republic of); Lim, Myung Kwan; Rha, Jung Ho; Shu, Chang Hae [Inha University Hospital, Incheon (Korea, Republic of)

    2011-02-15

    We analyzed the diffusion and perfusion characteristics of acute MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode) lesions in a large series to investigate the controversial changes of the apparent diffusion coefficient (ADC) that were reported in prior studies. We analyzed 44 newly appearing lesions during 28 stroke-like episodes in 13 patients with MELAS. We performed a visual assessment of the MR images including the ADC and perfusion maps, comparison of the ADC between the normal and abnormal areas, comparison of % ADC between the 44 MELAS lesions and the 30 acute ischemic infarcts. In addition, the patterns of evolution on follow-up MR images were analyzed. Decreased, increased, and normal ADCs were noted in 16 (36%), 16 (36%), and 12 (27%) lesions, respectively. The mean % ADC was 102 {+-} 40.9% in the MELAS and 64 {+-} 17.8% in the acute vascular infarcts (p < 0.001), while perfusion imaging demonstrated hyper-perfusion in six acute MELAS lesions. On follow-up images, resolution, progression, and tissue loss were noted in 10, 4, and 17 lesions, respectively. The cytotoxic edema gradually evolves following an acute stroke-like episode in patients with MELAS, and this may overlap with hyper-perfusion and vasogenic edema. The edematous swelling may be reversible or it may evolve to encephalomalacia, suggesting irreversible damage

  19. Severe Encephalopathy, Lactic Acidosis, Vegetative Instability and Neuropathy with 5-Fluorouracil Treatment – Pyrimidine Degradation Defect or Beriberi

    A. Rosen

    2011-08-01

    Full Text Available We present the case of a 19-year-old female with nasopharyngeal carcinoma, who received two courses of chemotherapy with 5-fluorouracil (5-FU in combination with folic acid and cisplatin. Upon developing esophageal strictures in the course of her radiotherapy, she required total parenteral nutrition. In the course of therapy, the patient developed severe multisystem failure with encephalopathy, lactic acidosis, vegetative instability and neuropathy. The treatment with 5-FU can lead to severe toxicity due to enzyme deficiencies in the degradation of pyrimidines, but it can also lead to thiamine deficiency with the classic symptoms of beriberi. Beriberi is a rare disorder, usually attributed to malnutrition or alcoholism. 5-FU has been shown to induce thiamine depletion. Reduced food intake or total parenteral nutrition devoid of vitamin supplements may aggravate symptoms. We were unable to find a genetic cause for increased 5-FU toxicity in our patient, ruling out deficiencies of dihydropyrimidine dehydrogenase, dihydropyrimidinase or β-ureidopropionase and double-strand break repair deficits. We come to the conclusion that, even without any definable enzyme deficiency, treatment with 5-FU can lead to high toxicity due to thiamine deficiency if vitamin supplementation is not undertaken.

  20. Sodium bicarbonate use and the risk of hypernatremia in thoracic aortic surgical patients with metabolic acidosis following deep hypothermic circulatory arrest

    Kamrouz Ghadimi

    2016-01-01

    Full Text Available Objective: Metabolic acidosis after deep hypothermic circulatory arrest (DHCA for thoracic aortic operations is commonly managed with sodium bicarbonate (NaHCO 3 . The purpose of this study was to determine the relationships between total NaHCO 3 dose and the severity of metabolic acidosis, duration of mechanical ventilation, duration of vasoactive infusions, and Intensive Care Unit (ICU or hospital length of stay (LOS. Methods: In a single center, retrospective study, 87 consecutive elective thoracic aortic operations utilizing DHCA, were studied. Linear regression analysis was used to test for the relationships between the total NaHCO 3 dose administered through postoperative day 2, clinical variables, arterial blood gas values, and short-term clinical outcomes. Results: Seventy-five patients (86% received NaHCO 3 . Total NaHCO 3 dose averaged 136 ± 112 mEq (range: 0.0-535 mEq per patient. Total NaHCO 3 dose correlated with minimum pH (r = 0.41, P < 0.0001, minimum serum bicarbonate (r = −0.40, P < 0.001, maximum serum lactate (r = 0.46, P = 0.007, duration of metabolic acidosis (r = 0.33, P = 0.002, and maximum serum sodium concentrations (r = 0.29, P = 0.007. Postoperative hypernatremia was present in 67% of patients and peaked at 12 h following DHCA. Eight percent of patients had a serum sodium ≥ 150 mEq/L. Total NaHCO 3 dose did not correlate with anion gap, serum chloride, not the duration of mechanical ventilator support, vasoactive infusions, ICU or hospital LOS. Conclusion: Routine administration of NaHCO 3 was common for the management of metabolic acidosis after DHCA. Total dose of NaHCO 3 was a function of the severity and duration of metabolic acidosis. NaHCO 3 administration contributed to postoperative hypernatremia that was often severe. The total NaHCO 3 dose administered was unrelated to short-term clinical outcomes.

  1. Differing effects of 2 active dried yeast (Saccharomyces cerevisiae) strains on ruminal acidosis and methane production in nonlactating dairy cows.

    Chung, Y-H; Walker, N D; McGinn, S M; Beauchemin, K A

    2011-05-01

    different strains of S. cerevisiae fed as active dried yeasts vary in their ability to modify the rumen fermentative pattern in nonlactating dairy cows. Because strain 2 tended (when compared with strain 1) to lower CH(4) emissions but increase the risk of acidosis, it may be prudent to further evaluate this strain in cattle fed high-forage diets, for which the risk of acidosis is low but CH(4) emissions are high.

  2. Evaluation of the systemic innate immune response and metabolic alterations of nonlactating cows with diet-induced subacute ruminal acidosis.

    Rodríguez-Lecompte, J C; Kroeker, A D; Ceballos-Márquez, A; Li, S; Plaizier, J C; Gomez, D E

    2014-12-01

    Subacute ruminal acidosis (SARA) increases lipopolysaccharide endotoxin in the rumen, which might translocate into the systemic circulation, triggering a cascade of clinical and immunological alterations. The objective of this study was to characterize the clinical immune and metabolic responses to ruminal-derived lipopolysaccharide in nonlactating cows induced with SARA using 2 challenges, a grain-based SARA challenge (GBSC) or an alfalfa-pellet SARA challenge (APSC). Six dry, nonlactating Holstein cows were used in a 3 × 3 Latin square arrangement of treatments with 4-wk experimental cycles. All cows received the control diet containing 70% forage and 30% mixed concentrates (dry matter basis) for 3 wk. In wk 4, cows received a control diet, GBSC (38% wheat-barley pellets, 32% other mixed concentrate, and 30% forages), or APSC (45% mixed concentrate, 32% alfalfa pellets, and 23% other forages). Total plasma proteins and immunology-related proteins, acute phase proteins, blood cells, serum chemistry, mRNA gene expression of peripheral blood cell surface markers, and selected proinflammatory cytokines were evaluated. Ruminal pH was lower in both groups with induced SARA compared with a control group. Ruminal endotoxins were higher in GBSC; however, plasma endotoxin was not detected in any study group. No significant differences in feed intake, rectal temperature, white blood cell counts, or differentials were found between control and SARA challenge groups; changes in glucose, urea, Ca, and Mg were observed in SARA groups. Total plasma proteins were lower in both SARA groups, and acute phase proteins were higher in GBSC. The expression of CD14, MD2, and TLR4 mRNA in peripheral blood leukocytes was not affected by SARA induction. The induction of SARA as a result of GBSC or APSC challenge was successful; however, LPS was not detected in plasma. Changes in clinical, metabolic, and inflammatory responses were not observed in the SARA-challenged cows, suggesting that

  3. Inflammatory receptors and pathways in human NT2-N neurons during hypoxia and reoxygenation. Impact of acidosis.

    Frøyland, Elisabeth; Skjaeret, Camilla; Wright, Marianne S; Dalen, Marit Lunde; Cvancarova, Milada; Kasi, Cecilie; Rootwelt, Terje

    2008-06-27

    Cytokines are released in response to brain injury and inflammation. By binding to receptors, they can cause, exacerbate or inhibit cellular injury and repair. We studied RNA expression of cytokine receptors and members of inflammatory pathways in human NT2-N neurons during 3 h of hypoxia and glucose deprivation followed by 21 h of reoxygenation, and the impact of acidosis. Right after acidotic hypoxia, RNA of IL-10RA and CXCR4 were significantly increased relative to acidotic control, while Bcl-2 and Bcl-xL were significantly decreased. After 21 h of neutral reoxygenation after neutral hypoxia, there was a significant increase in RNA of CXCR1 (relative quantification (RQ)=4.1, p<0.05), CXCR2 (3.6, p<0.05), CCR2 (3.8, p<0.05), Hsp70 (2.4, p<0.05), HIF-1alpha (1.5, p<0.001), TRAF6 (1.3, p<0.05) and TNFR1 (1.6, p<0.05). After 21 h of acidotic reoxygenation after acidotic hypoxia, we found a significant increase in RNA of IL-1R1, IL-10RA, CXCR4 and Hsp70 compared to control, and a significant decrease in FAS and TRAF6. There was a significant increase in Bax expression and a significant decrease in Bcl-2 and Bcl-xL expression in three out of four pH groups after 21 h of reoxygenation. Acidotic, relative to neutral, hypoxia and reoxygenation also influenced the expression of various genes. We conclude that inflammatory receptors and pathways are activated during hypoxia and reoxygenation in NT2-N neurons, and that this activation is pH dependent. This supports the concept that inflammatory pathways play a role in cerebral hypoxic-ischemic damage, and that they may represent important pharmacological targets.

  4. Gut Microbes manuscript type: Commentary and views submission probiotics, D-Lactic acidosis, oxidative stress and strain specificity.

    Vitetta, Luis; Coulson, Samantha; Thomsen, Michael; Nguyen, Tony; Hall, Sean

    2017-01-12

    The existence of an implicit living microscopic world, composed primarily of bacteria, has been known for centuries. The exact mechanisms that govern the contribution of bacteria to human health and disease have only recently become the subject of intense research efforts. Within this very evident shift in paradigms, the rational design of probiotic formulations has led to the creation of an industry that seeks to progress the engineering of probiotic bacteria that produce metabolites that may enhance human host health and prevent disease. The promotion of probiotics is often made in the absence of quality scientific and clinically plausible data. The latest incursions into the probiotic market of claims have posited the amelioration of oxidative stress via potent antioxidant attributes or limiting the administration of probiotics to those species that do not produce D-Lactic acid (i.e., claims that D-Lactic acid acidosis is linked to chronic health conditions) or are strain-specific (shaping an industry point of difference) for appraising a therapeutic effect. Evidence-based research should guide clinical practice, as there is no place in science and medicine that supports unsubstantiated claims. Extravagant industry based notions continue to fuel the imprimatur of distrust and skepticism that is leveled by scientists and clinicians at an industry that is already rife with scientific and medical distrust and questionable views on probiotics. Ignoring scientifically discordant data, when sorting through research innovations and false leads relevant to the actions of probiotics, drives researcher discomfit and keeps the bar low, impeding the progress of knowledge. Biologically plausible posits are obligatory in any research effort; companies formulating probiotics often exhibit a lack of analytical understanding that then fuels questionable investigations failing to build on research capacity.

  5. Dialysis Disequilibrium Syndrome: Brain death following hemodialysis for metabolic acidosis and acute renal failure – A case report

    Bagshaw Sean M

    2004-08-01

    Full Text Available Abstract Background Dialysis disequilibrium syndrome (DDS is the clinical phenomenon of acute neurologic symptoms attributed to cerebral edema that occurs during or following intermittent hemodialysis (HD. We describe a case of DDS-induced cerebral edema that resulted in irreversible brain injury and death following acute HD and review the relevant literature of the association of DDS and HD. Case Presentation A 22-year-old male with obstructive uropathy presented to hospital with severe sepsis syndrome secondary to pneumonia. Laboratory investigations included a pH of 6.95, PaCO2 10 mmHg, HCO3 2 mmol/L, serum sodium 132 mmol/L, serum osmolality 330 mosmol/kg, and urea 130 mg/dL (46.7 mmol/L. Diagnostic imaging demonstrated multifocal pneumonia, bilateral hydronephrosis and bladder wall thickening. During HD the patient became progressively obtunded. Repeat laboratory investigations showed pH 7.36, HCO3 19 mmol/L, potassium 1.8 mmol/L, and urea 38.4 mg/dL (13.7 mmol/L (urea-reduction-ratio 71%. Following HD, spontaneous movements were absent with no pupillary or brainstem reflexes. Head CT-scan showed diffuse cerebral edema with effacement of basal cisterns and generalized loss of gray-white differentiation. Brain death was declared. Conclusions Death is a rare consequence of DDS in adults following HD. Several features may have predisposed this patient to DDS including: central nervous system adaptations from chronic kidney disease with efficient serum urea removal and correction of serum hyperosmolality; severe cerebral intracellular acidosis; relative hypercapnea; and post-HD hemodynamic instability with compounded cerebral ischemia.

  6. Clinical Analysis of 23 Cases of Diabetic Lactic Acidosis%糖尿病乳酸性酸中毒23例临床分析

    尹延伟; 张中东; 胡爱民

    2012-01-01

    目的:探讨糖尿病乳酸性酸中毒的诱发因素、临床特点,提高对糖尿病乳酸性酸中毒的诊断及治疗水平.方法:对确诊为糖尿病乳酸性酸中毒的23例患者临床诊治资料进行回顾性总结和分析.结果:本组23例糖尿病乳酸性酸中毒患者平时口服双胍类降糖药控制血糖者有20例(87.0%);有明确感染病史的患者19例(82.6%);肾功能不全患者11例(47.8%);心功能不全患者8例(34.8%)及肝功能异常患者5例(21.7%).经积极治疗,23例糖尿病乳酸性酸中毒患者抢救成功18例,死亡5例.结论:糖尿病患者在使用双胍类降糖药,并发感染,器官功能异常等其他情况时能够增加其发生乳酸性酸中毒的风险.糖尿病乳酸性酸中毒发病急,病情严重,死亡率高,其临床表现常被原发疾病的症状、体征所掩盖,临床工作中容易误诊与漏诊,应加以重视.%Objective: To investigate the inducement and clinical features of diabetic lactic acidosis. To improve the diagnosis and treatment of patients with diabetic lactic acidosis. Method:The clinical data of 23 cases for diabetic lactic acidosis were analysed retrospectively. Result:In 23 cases ,20 cases with biguanidestreatment ( 87. 0% ) ;19 cases with a clear history of infection ( 82. 6% ) ; 11 cases with chronic renal insufficiency (47. 8% ) ;8 cases with heart failure(34. 8% ) ; 5 cases with abnormal liver function(21. 7% ). After active treatment, 18 cases with successful rescue, and 5 cases with death. Conclusion: Using biguanides treatment, infection and organ dysfunction can increase the risk of diabetic lactic acidosis for diabetic patients. Diabetic lactic acidosis is an acute disease and has such characteristics as seriously condition and high case mortality rate. Clinical manifestations of diabetic lactic acidosis were usually covered by signs and symptoms of primary diseases, causing missed diagnosis and misdiagnosis frequently. So we should attach importance to this

  7. Protective role of acidic pH-activated chloride channel in severe acidosis-induced contraction from the aorta of spontaneously hypertensive rats.

    Zhiyong Ma

    Full Text Available Severe acidic pH-activated chloride channel (ICl,acid has been found in various mammalian cells. In the present study, we investigate whether this channel participates in reactions of the thoracic aorta to severe acidosis and whether it plays a role in hypertension. We measured isometric contraction in thoracic aorta rings from spontaneously hypertensive rats (SHRs and normotensive Wistar rats. Severe acidosis induced contractions of both endothelium-intact and -denuded thoracic aorta rings. In Wistar rats, contractions did not differ at pH 6.4, 5.4 and 4.4. However, in SHRs, contractions were higher at pH 5.4 or 4.4 than pH 6.4, with no difference between contractions at pH 5.4 and 4.4. Nifedipine, ICl,acid blockers 5-nitro-2-(3-phenylpropylamino benzoic acid (NPPB and 4,4'-diisothiocyanatostilbene-2, 2'-disulfonic acid (DIDS inhibited severe acidosis-induced contraction of aortas at different pH levels. When blocking ICl,acid, the remnant contraction was greater at pH 4.4 than pH 5.4 and 6.4 for both SHRs and Wistar rats. With nifedipine, the remnant contraction was greatly reduced at pH 4.4 as compared with at pH 6.4 and 5.4. With NPPB or DIDS, the ratio of remnant contractions at pH 4.4 and 5.4 (R4.4/5.4 was lower for SHRs than Wistar rats (all 1. Furthermore, patch clamp recordings of ICl,acid and intracellular Ca(2+ measurements in smooth muscle cells confirmed these findings. ICl,acid may protect arteries against excess vasoconstriction under extremely acidic extracellular conditions. This protective effect may be decreased in hypertension.

  8. Estimation of the true incidence of lactic acidosis within the Lighthouse Clinic cohort, and the likely magnitude of missed diagnoses in the region

    Colin Speight

    2014-11-01

    Full Text Available Introduction: Lactic acidosis is one of the most serious side effects associated with ART, most commonly associated with stavudine. Clinical features are non-specific and specialist laboratory capabilities are essential to confirm the diagnosis, making under-diagnosis likely in resource-constrained settings. Lighthouse Trust is a tertiary referral ART centre with over 23,500 patients on ART. The adjacent University of North Carolina Project laboratory, also serving Kamuzu Central Hospital, has been the only site processing lactate tests in Central Zone for many years. Our objective was to quantify the true incidence within our cohort, and estimate the likely degree of historical missed diagnoses from less central ART clinics. Methods: All high lactate results between June 2010 and June 2013 were treated as cases, and cross referenced with the Lighthouse database. Patients transferring in to Lighthouse within one month prior to diagnosis were assumed to have been referred due to their lactic acidosis, and moved to the Central Zone cohort to avoid referral bias. Routinely collected quarterly ART cohort data for both Lighthouse and the entire Central Zone were analyzed. Results: Over the three-year period, from within the Lighthouse cohort, there were 138 cases: 74% were female, median duration on ART was 14 months (IQR 10–26, and 98.5% were attributable to stavudine (only two cases to zidovudine. Over this period, the average number of patients taking stavudine at Lighthouse was 10,960 (3,600 on zidovudine. For the whole Central Zone (minus Lighthouse patients there were 61,000 on stavudine (4,830 on zidovudine, yet only 124 cases of lactic acidosis were apparently diagnosed from within this cohort. Conclusions: Although cases may, of course, also have been missed at Lighthouse, as a tertiary referral centre the rate observed is likely to be closer to the true incidence. Over the three years, with 138 cases from the 10,960 patients taking

  9. Friedrich Nietzsche (1844-1900): a classical case of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome?

    Koszka, Christiane

    2009-08-01

    Friedrich Nietzsche was one of the most influential and profound German philosophers. After prolonged illness, he died at the age of 55 in Weimar, Germany. The interest in his medical biography has always been strong while the cause of his illness and death has remained a mystery, intriguing philosophers as well as physicians. The diagnosis of syphilis proposed in the 19th century has been controversial until today and many other diagnoses have been discussed. This paper suggests that Nietzsche suffered from mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes syndrome.

  10. Liquid extracorporeal carbon dioxide removal: use of THAM (tris-hydroxymethyl aminomethane) coupled to hemofiltration to control hypercapnic acidosis in a porcine model of protective mechanical ventilation

    Tapia, Pablo; Lillo, Felipe; Soto, Dagoberto; Escobar, Leslie; Simon, Felipe; Hernández, Karina; Alegría, Leyla; Bruhn, Alejandro

    2016-01-01

    A promising approach to facilitate protective mechanical ventilation is the use of extracorporeal CO2 removal techniques. Several strategies based on membrane gas exchangers have been developed. However, these techniques are still poorly available. The goal of this study was to assess the efficacy and safety of THAM infusion coupled to hemofiltration for the management of hypercapnic acidosis. A severe respiratory acidosis was induced in seven anesthetized pigs. Five of them were treated with THAM 8-mmol·kg-1·h-1 coupled to hemofiltration (THAM+HF group) at 100 mL·kg-1·h-1. After 18-hours of treatment the THAM infusion was stopped but hemofiltration was kept on until 24-hours. The 2 other animals were treated with THAM but without hemofiltration. After 1-hour of treatment in THAM+HF, PaCO2 rapidly decreased from a median of 89.0 (IQR) (80.0, 98.0) to 71.3 (65.8, 82.0) mmHg (P<0.05), while pH increased from 7.12 (7.01, 7.15) to 7.29 (7.27, 7.30) (P<0.05). Thereafter PaCO2 remained stable between 60-70 mmHg, while pH increased above 7.4. After stopping THAM at 18 hours of treatment a profound rebound effect was observed with severe hypercapnic acidosis. The most important side effect we observed was hyperosmolality, which reached a maximum of 330 (328, 332) mOsm·kg H2O-1 at T18. The animals treated only with THAM developed severe hypercapnia, despite the fact that pH returned to normal values, and died after 12 hours. Control-group had an uneven evolution until the end of the experiment. A combined treatment with THAM coupled to hemofiltration may be an effective treatment to control severe hypercapnic acidosis. PMID:27648139

  11. Protective effect of hypercapnic acidosis in ischemia-reperfusion lung injury is attributable to upregulation of heme oxygenase-1.

    Wu, Shu-Yu; Li, Min-Hui; Ko, Fu-Chang; Wu, Geng-Chin; Huang, Kun-Lun; Chu, Shi-Jye

    2013-01-01

    Hypercapnic acidosis (HCA) has protective effects in animal models of acute lung injury, but the mechanism underlying the effect of HCA is unclear. Heme oxygenase-1 (HO-1) is an antioxidant enzyme that protects tissue from inflammation injury. We investigated whether HO-1 contributes to the protective effects of HCA in ischemia-reperfusion (IR)-induced lung injury. Typical acute lung injury in rats was successfully induced by 40 min of ischemia and 90 min of reperfusion in an isolated perfused lung model. The rat lungs were randomly assigned to the control group, IR group or IR + HCA group with or without zinc protoporphyrin IX (ZnPP), an HO-1 activity inhibitor. At the end of the experiment, bronchoalveolar lavage fluid (BALF) and lung tissues were collected to evaluate the degree of lung injury. In in vitro experiments, HO-1 siRNA transfected A549 cells were exposed to a normoxic or hypoxia-reoxygenation (H/R) environment in the presence or absence of HCA. IR caused significant increases in the pulmonary arterial pressure, lung weight to body weight and wet/dry ratios, lung weight gain, capillary filtration coefficient, lung injury scores, neutrophil infiltration, and concentrations of protein and TNF-α in the BALF. IR also induced degradation of inhibitor of nuclear factor (NF)-κB-α, increased IκB kinase (IKK)-β phosphorylation and nuclear translocation of NF-κB, and up-regulated HO-1 expression and activity. Furthermore, IR decreased Bcl-2 protein expression and increased the number of active caspase-3 stained cells. HCA treatment enhanced HO-1 expression and activity, and accordingly reduced IKK-NF-κB signaling, inhibited apoptosis, and significantly attenuated IR-induced changes. Treatment with ZnPP partially blocked the protective effect of HCA. In addition, HO-1 siRNA significantly reversed HCA-mediated inhibition of NF-κB signaling in A549 cells subjected to H/R. In conclusion, the protective effect of HCA in IR lung injury in rats was mediated in

  12. Protective effect of hypercapnic acidosis in ischemia-reperfusion lung injury is attributable to upregulation of heme oxygenase-1.

    Shu-Yu Wu

    Full Text Available Hypercapnic acidosis (HCA has protective effects in animal models of acute lung injury, but the mechanism underlying the effect of HCA is unclear. Heme oxygenase-1 (HO-1 is an antioxidant enzyme that protects tissue from inflammation injury. We investigated whether HO-1 contributes to the protective effects of HCA in ischemia-reperfusion (IR-induced lung injury. Typical acute lung injury in rats was successfully induced by 40 min of ischemia and 90 min of reperfusion in an isolated perfused lung model. The rat lungs were randomly assigned to the control group, IR group or IR + HCA group with or without zinc protoporphyrin IX (ZnPP, an HO-1 activity inhibitor. At the end of the experiment, bronchoalveolar lavage fluid (BALF and lung tissues were collected to evaluate the degree of lung injury. In in vitro experiments, HO-1 siRNA transfected A549 cells were exposed to a normoxic or hypoxia-reoxygenation (H/R environment in the presence or absence of HCA. IR caused significant increases in the pulmonary arterial pressure, lung weight to body weight and wet/dry ratios, lung weight gain, capillary filtration coefficient, lung injury scores, neutrophil infiltration, and concentrations of protein and TNF-α in the BALF. IR also induced degradation of inhibitor of nuclear factor (NF-κB-α, increased IκB kinase (IKK-β phosphorylation and nuclear translocation of NF-κB, and up-regulated HO-1 expression and activity. Furthermore, IR decreased Bcl-2 protein expression and increased the number of active caspase-3 stained cells. HCA treatment enhanced HO-1 expression and activity, and accordingly reduced IKK-NF-κB signaling, inhibited apoptosis, and significantly attenuated IR-induced changes. Treatment with ZnPP partially blocked the protective effect of HCA. In addition, HO-1 siRNA significantly reversed HCA-mediated inhibition of NF-κB signaling in A549 cells subjected to H/R. In conclusion, the protective effect of HCA in IR lung injury in rats was

  13. (Uncommon) Mechanisms of Branchial Ammonia Excretion in the Common Carp (Cyprinus carpio) in Response to Environmentally Induced Metabolic Acidosis.

    Wright, Patricia A; Wood, Chris M; Hiroi, Junya; Wilson, Jonathan M

    2016-01-01

    Freshwater fishes generally increase ammonia excretion in acidic waters. The new model of ammonia transport in freshwater fish involves an association between the Rhesus (Rh) protein Rhcg-b, the Na(+)/H(+) exchanger (NHE), and a suite of other membrane transporters. We tested the hypothesis that Rhcg-b and NHE3 together play a critical role in branchial ammonia excretion in common carp (Cyprinus carpio) chronically exposed to a low-pH environment. Carp were exposed to three sequential environmental treatments-control pH 7.6 water (24 h), pH 4.0 water (72 h), and recovery pH 7.6 water (24 h)-or in a separate series were simply exposed to either control (72 h) or pH 4.0 (72 h) water. Branchial ammonia excretion was increased by ∼2.5-fold in the acid compared with the control period, despite the absence of an increase in the plasma-to-water partial pressure NH3 gradient. Alanine aminotransferase activity was higher in the gills of fish exposed to pH 4 versus control water, suggesting that ammonia may be generated in gill tissue. Gill Rhcg-b and NHE3b messenger RNA levels were significantly elevated in acid-treated relative to control fish, but at the protein level Rhcg-b decreased (30%) and NHE3b increased (2-fold) in response to water of pH 4.0. Using immunofluorescence microscopy, NHE3b and Rhcg-b were found to be colocalized to ionocytes along the interlamellar space of the filament of control fish. After 72 h of acid exposure, Rhcg-b staining almost disappeared from this region, and NHE3b was more prominent along the lamellae. We propose that ammoniagenesis within the gill tissue itself is responsible for the higher rates of branchial ammonia excretion during chronic metabolic acidosis. Unexpectedly, gill Rhcg-b does not appear to be important in gill ammonia transport in low-pH water, but the strong induction of NHE3b suggests that some NH4(+) may be eliminated directly in exchange for Na(+). These findings contrast with previous studies in larval zebrafish

  14. Deficiency of the iron-sulfur clusters of mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase (complex I) in an infant with congenital lactic acidosis.

    Moreadith, R W; Batshaw, M L; Ohnishi, T; Kerr, D; Knox, B; Jackson, D; Hruban, R; Olson, J; Reynafarje, B; Lehninger, A L

    1984-09-01

    We report the case of an infant with hypoglycemia, progressive lactic acidosis, an increased serum lactate/pyruvate ratio, and elevated plasma alanine, who had a moderate to profound decrease in the ability of mitochondria from four organs to oxidize pyruvate, malate plus glutamate, citrate, and other NAD+-linked respiratory substrates. The capacity to oxidize the flavin adenine dinucleotide-linked substrate, succinate, was normal. The most pronounced deficiency was in skeletal muscle, the least in kidney mitochondria. Enzymatic assays on isolated mitochondria ruled out defects in complexes II, III, and IV of the respiratory chain. Further studies showed that the defect was localized in the inner membrane mitochondrial NADH-ubiquinone oxidoreductase (complex I). When ferricyanide was used as an artificial electron acceptor, complex I activity was normal, indicating that electrons from NADH could reduce the flavin mononucleotide cofactor. However, electron paramagnetic resonance spectroscopy performed on liver submitochondrial particles showed an almost total loss of the iron-sulfur clusters characteristic of complex I, whereas normal signals were noted for other mitochondrial iron-sulfur clusters. This infant is presented as the first reported case of congenital lactic acidosis caused by a deficiency of the iron-sulfur clusters of complex I of the mitochondrial electron transport chain.

  15. Acidosis Acts through HSP90 in a PHD/VHL-Independent Manner to Promote HIF Function and Stem Cell Maintenance in Glioma.

    Filatova, Alina; Seidel, Sascha; Böğürcü, Nuray; Gräf, Sabine; Garvalov, Boyan K; Acker, Till

    2016-10-01

    Hypoxia is a common feature of solid tumors, which controls multiple aspects of cancer progression. One important function of hypoxia and the hypoxia-inducible factors (HIF) is the maintenance of cancer stem-like cells (CSC), a population of tumor cells that possess stem cell-like properties and drives tumor growth. Among the changes promoted by hypoxia is a metabolic shift resulting in acidification of the tumor microenvironment. Here, we show that glioma hypoxia and acidosis functionally cooperate in inducing HIF transcription factors and CSC maintenance. We found that these effects did not involve the classical PHD/VHL pathway for HIF upregulation, but instead involved the stress-induced chaperone protein HSP90. Genetic or pharmacologic inactivation of HSP90 inhibited the increase in HIF levels and abolished the self-renewal and tumorigenic properties of CSCs induced by acidosis. In clinical specimens of glioma, HSP90 was upregulated in the hypoxic niche and was correlated with a CSC phenotype. Our findings highlight the role of tumor acidification within the hypoxic niche in the regulation of HIF and CSC function through HSP90, with implications for therapeutic strategies to target CSC in gliomas and other hypoxic tumors. Cancer Res; 76(19); 5845-56. ©2016 AACR.

  16. 儿童远端肾小管酸中毒1例%1 Case of Children With Distal Renal Tubular Acidosis

    王瑞彬

    2015-01-01

    在儿科临床工作中,如果小儿有烦渴,多饮,多尿,腹泻,乏力,低钾血症,不明原因的代谢性酸中毒,生长发育落后,佝偻病,要考虑到本病,进一步检查血离子,血气,肾功能,尿常规,双肾超声,腕骨 X 线片。注意酸碱度,有无高氯性酸中毒,电解质紊乱,活动性佝偻病,肾结石,肾钙化。%In pediatric clinical work if the child has thirst, polydipsia, polyuria, diarrhea, fatigue, hypokalemia, metabolic acidosis, unexplained, growth retardation, rickets, taking into account the disease, further examination of blood ions, blood gas, kidney function, urine routine, renal ultrasound, Carpale x-ray. Note that the pH is hyperchloremic acidosis, electrolyte disorder, activity of rickets, kidney stones, renal calcification.

  17. Expression of Glutamine Transporter Slc38a3 (SNAT3 During Acidosis is Mediated by a Different Mechanism than Tissue-Specific Expression

    Sarojini Balkrishna

    2014-05-01

    Full Text Available Background: Despite homeostatic pH regulation, systemic and cellular pH changes take place and strongly influence metabolic processes. Transcription of the glutamine transporter SNAT3 (Slc38a3 for instance is highly up-regulated in the kidney during metabolic acidosis to provide glutamine for ammonia production. Methods: Slc38a3 promoter activity and messenger RNA stability were measured in cultured cells in response to different extracellular pH values. Results: Up-regulation of SNAT3 mRNA was mediated both by the stabilization of its mRNA and by the up-regulation of gene transcription. Stabilisation of the mRNA involved a pH-response element, while enhanced transcription made use of a second pH-sensitive Sp1 binding site in addition to a constitutive Sp1 binding site. Transcriptional regulation dominated the early response to acidosis, while mRNA stability was more important for chronic adaptation. Tissue-specific expression of SNAT3, by contrast, appeared to be controlled by promoter methylation and histone modifications. Conclusions: Regulation of SNAT3 gene expression by extracellular pH involves post-transcriptional and transcriptional mechanisms, the latter being distinct from the mechanisms that control the tissue-specific expression of the gene.

  18. Relationship of hyperlactatemia and metabolic acidosis%高乳酸血症与代谢性酸中毒的相互关系

    杜微; 刘大为; 石岩; 隆云; 芮曦; 王小亭

    2011-01-01

    目的 观察重症患者的高乳酸血症与代谢性酸中毒的相关性,以提供更为准确的反映组织灌注的指标.方法 回顾了2009年8月至2010年4月,9个月间所有重症医学科(ICU)患者的血气分析结果.入选标准为患者同时抽取的一份动脉血标本同时送检血气分析、血清电解质、血清白蛋白检查,其中血气分析结果中乳酸升高,满足高乳酸血症标准(Lac≥2 mmol/L)的结果.结果 在这一乳酸升高(Lac≥2)的人群中用传统方法判断代酸,代酸发生率33.9%,用Stewart's方法判断代酸,代酸发生率为56.0%.但该组人群血清pH值不具有典型酸血症的特点(7.42±0.07),存活组中乳酸占代酸的百分比为(33.6±17.9)%,死亡组中乳酸占代酸的百分比为(42.1±18.5)%,P=0.008;存活组中SIG占代酸百分比为(28.6±23.5)%,死亡组中SIG占代酸的百分比(44.9±23.0)%,P=0.000.结论 在ICU乳酸升高的人群中,乳酸并不是引起代酸的主要成分,乳酸和SIG共同组成代酸的主要组分,但乳酸占代酸的百分比和SIG占代酸的百分比升高可能提示预后不佳,这两个指标也许能为临床提供更准确的反映组织灌注的信息.%Objective To investigate the acid-base abnormalities of the patients with hyperlactatemia and explore the relationship of hyperlactatemia and metabolic acidosis so as to seek a more precise index of reflecting organ perfusion. Methods From August 2009 to April 2010, all consecutive patients admitted into intensive care unit received an analysis of blood gas. Those individuals with arterial lactate ≥2 mmol/L were selected. Results In the group of hyperlactatemic patients, the occurrence of metabolic acidosis as judged by the traditional method was less than that by the Stewart's method (33.9% vs 56. 0% ). No typical acidemia was found. And all components of metabolic acidosis were calculated. Lactate and SIG (strong ion gap ) contributed a certain percentage to metabolic acidosis in the

  19. Stroke and Metabolic Acidosis

    2010-01-01

    Paciente de sexo femenino, de 59 años, educadora; llevada a institución hospitalaria por alteración súbita del estado de conciencia. Antecedente de hipotiroidismo en manejo con levotiroxina, 50 microgramos al día. Al examen físico de ingreso se encontraba en mal estado general, FC: 88 x min., TA 170/110, FR: 8 x min., temp.: 35 Cº, Glasgow: 6/15; estuporosa, con apertura ocular al estímulo doloroso, sin respuesta verbal, movimiento de retirada en hemicuerpo izquierdo al estímulo doloroso. Ple...

  20. Renal Tubular Acidosis

    ... Disease Chronic Kidney Disease (CKD) What Is Chronic Kidney Disease? Causes of CKD Tests & Diagnosis Managing CKD Eating Right Preventing CKD What If My Kidneys Fail? Clinical Trials Anemia High Blood Pressure Heart ... Nephropathy Kidney Disease in Children Childhood Nephrotic Syndrome Hemolytic ...

  1. Renal Tubular Acidosis

    ... Looking for Health Lessons? Visit KidsHealth in the Classroom What Other Parents Are Reading Your Child's Development ( ... may involve stopping use of the drug or changing the dosage. If an underlying disease or other ...

  2. Alfalfa pellet-induced subacute ruminal acidosis in dairy cows increases bacterial endotoxin in the rumen without causing inflammation.

    Khafipour, E; Krause, D O; Plaizier, J C

    2009-04-01

    A study was conducted to determine if subacute ruminal acidosis (SARA) induced by feeding alfalfa pellets results in increases in free bacterial lipopolysaccharide (LPS) in rumen fluid and peripheral blood, and acute phase proteins in plasma, and to determine the effect of alfalfa pellet-induced SARA on feed intake, rumen fermentation characteristics, milk production and composition, and blood metabolites. Eight lactating Holstein cows, 4 of which were ruminally cannulated, were used in a 6-wk experiment and were fed once daily at 0900 h. During wk 1, cows received a diet containing 50% of DM as concentrate and 50% of DM chopped alfalfa hay. Between wk 2 and wk 6, alfalfa hay was gradually replaced with alfalfa pellets at the rate of 8% per week to reduce rumen pH. Rumen pH was monitored continuously in the ruminally cannulated cows using indwelling pH probes. Rumen fluid and peripheral blood were sampled 15 min before feed delivery and at 6 h after feed delivery. Based on adopted threshold of SARA of at least 180 min/d below pH 5.6, SARA was induced from wk 3 onwards. Replacing 40% of alfalfa hay with alfalfa pellets quadratically increased the DMI from 18.1 kg/d in wk 1 to 23.4 kg/d in wk 6. This replacement linearly decreased milk yield (32.7 vs. 35.9 kg/d) and milk fat percentage and yield (2.32 vs. 3.22%, and 0.77 vs. 1.14 kg/d, respectively), but increased milk protein percentage and yield (3.80 vs. 3.04%, and 1.23 vs. 1.07 kg/d, respectively). This gradual replacement also linearly increased the daily averages of total volatile fatty acids (90 to 121.9 mM), acetate (53.9 to 66.8 mM), propionate (21.5 to 39.6 mM), and osmolality (277.7 to 293.8 mmol/kg) in the rumen and decreased the acetate to propionate ratio from 2.62 to 1.73. Replacing alfalfa hay with alfalfa pellets linearly increased blood lactate from 1.00 mM in wk 1 to a peak of 3.46 mM in wk 5. Induction of SARA in this study increased free rumen LPS concentration from 42,122 endotoxin unit (EU

  3. Increased feeding frequency increased milk fat yield and may reduce the severity of subacute ruminal acidosis in higher-risk cows.

    Macmillan, K; Gao, X; Oba, M

    2017-02-01

    The objectives of this study were to determine whether feeding behavior is different between cows at higher or lower risk for subacute ruminal acidosis (SARA) and whether increasing feeding frequency could be used to reduce the severity of SARA in higher-risk cows. In preliminary studies, 16 ruminally cannulated lactating cows were fed high-grain diets once per day to increase the risk of SARA. After a 17-d diet adaptation, ruminal pH was measured every 30 s over 24 h. Cows were classified as higher-risk (n = 7) or lower-risk (n = 9) for SARA based on an acidosis index (area of pH Feeding behavior was recorded every 5 min over the same 24 h. The 24-h observation period was analyzed in 3 periods of 8 h after feeding. Although there was no significant difference in overall dry matter intake, higher-risk cows spent more time eating in the first 8-h period after feeding than lower-risk cows (186 vs. 153 min) and less time eating in the third 8-h period (19 vs. 43 min). In the primary experiment, 8 ruminally cannulated lactating cows were fed a high-grain diet once per day (1×; 0800 h) or 3 times per day (3×; 0800, 1500, and 2000 h) in a crossover design with 21-d periods (16 d of treatment adaptation and 5 d of data collection). Rumen pH and feeding behavior were measured over 72 h. Behavior data were summarized separately for the 3 periods (0800 to 1500, 1500 to 2200, and 2200 to 0800 h). Four cows were categorized as higher-risk and 4 as lower-risk, based on their acidosis index. The 3× feeding reduced eating time between 0800 and 1500 h (99 vs. 145 min) and increased eating time between 2200 and 0800 h (76 vs. 43 min) for all cows, regardless of category, compared with 1× feeding. For higher-risk cows, 3× feeding reduced the area below pH 5.8 (51 vs. 98 pH × min/d), but it did not affect rumen pH for the lower-risk cows. Milk yield was not different between groups, but 3× feeding increased milk fat yield (1.22 vs. 1.08 kg/d) for all cows, regardless of

  4. Effect of acarbose on milk yield and composition in early-lactation dairy cattle fed a ration to induce subacute ruminal acidosis.

    McLaughlin, C L; Thompson, A; Greenwood, K; Sherington, J; Bruce, C

    2009-09-01

    Subacute ruminal acidosis reduces lactation performance in dairy cattle and most often occurs in animals fed a high concentrate:forage ration with large amounts of readily fermentable starch, which results in increased production of volatile fatty acids and lactic acid and a reduction in ruminal pH. Acarbose is commercially available (Glucobay, Bayer, Wuppertal, Germany) and indicated for the control of blood glucose in diabetic patients. In cattle, acarbose acts as an alpha-amylase and glucosidase inhibitor that slows the rate of degradation of starch to glucose, thereby reducing the rate of volatile fatty acid production and maintaining rumen pH at higher levels. The ability of acarbose to reverse the reduced feed intake and milk fat percentage and yield associated with a high concentrate:forage ration with a high risk of inducing subacute ruminal acidosis was evaluated in 2 experiments with lactating dairy cattle. In 2 preliminary experiments, the effects of a 70:30 concentrate:forage ration on ruminal pH and lactation were evaluated. Ruminal pH was monitored in 5 Holstein steers with ruminal cannulas every 10 min for 5 d. Ruminal pH was dairy cows, the 70:30 concentrate:forage ration decreased feed intake 5%, milk fat percentage 7%, and milk fat yield 8% compared with a 50:50 concentrate:forage ration but did not affect milk yield. Early lactating dairy cattle were offered the 70:30 concentrate:forage ration with 0 or 0.75 g/d of acarbose added in a crossover design in 2 experiments. In the first experiment, acarbose increased dry matter feed intake (23.1 vs. 21.6 kg/d) and 3.5% fat-corrected milk yield (33.7 vs. 31.7 kg/d) because of an increase in percentage milk fat (3.33 vs. 3.04%) compared with control cows. In the second experiment, cows were fasted for 3 h before the morning feeding to induce consumption of a large meal to mimic conditions that might be associated with unplanned delayed feeding. In this experiment, acarbose also increased feed intake (22

  5. Interaction between bunk management and monensin concentration on finishing performance, feeding behavior, and ruminal metabolism during an acidosis challenge with feedlot cattle.

    Erickson, G E; Milton, C T; Fanning, K C; Cooper, R J; Swingle, R S; Parrott, J C; Vogel, G; Klopfenstein, T J

    2003-11-01

    Two commercial feedlot experiments and a metabolism study were conducted to evaluate the effects of monensin concentrations and bunk management strategies on performance, feed intake, and ruminal metabolism. In the feedlot experiments, 1,793 and 1,615 steers were used in Exp. 1 and 2, respectively, in 18 pens for each experiment (six pens/treatment). Three treatments were evaluated: 1) ad libitum bunk management with 28.6 mg/kg monensin and clean bunk management strategies with either 2) 28.6 or 3) 36.3 mg/kg monensin. In both experiments, 54 to 59% of the clean bunk pens were clean at targeted clean time, or 2200, compared with 24 to 28% of the ad libitum pens. However, only 13% of the pens were clean by 2000 in Exp. 1 (summer), whereas 44% of the pens in Exp. 2 (winter) were clean by 2000. In Exp. 1, bunk management and monensin concentration did not affect carcass-adjusted performance. In Exp. 2, steers fed ad libitum had greater DMI (P 0.13) similar to that of clean bunk-fed steers. Monensin concentration had no effect on carcass-adjusted performance (P > 0.20) in either experiment. A metabolism experiment was conducted with eight fistulated steers in a replicated 4 x 4 Latin square acidosis challenge experiment. An acidosis challenge was imposed by feeding 125% of the previous day's DMI, 4 h later than normal. Treatments consisted of monensin concentrations (mg/kg) of 0, 36.7, 48.9, or 36.7 until challenged and switched to 48.9 on the challenge day and 4 d following. Each replicate of the Latin square was managed with separate bunk management strategies (clean bunk or ad libitum). Feeding any concentration of monensin increased number of meals and decreased DMI rate (%/h) (P < 0.12) for the 4 d following the acidosis challenge. Meal size, pH change, and pH variance were lower (P < 0.10) for steers fed monensin with clean bunk management. However, no monensin effect was observed for steers fed ad libitum. Bunk management strategy has the potential to decrease

  6. El entrenamiento de fuerza reduce la acidosis metabólica y la hipertrofia hepática y renal consecuentes del consumo de una dieta hiperproteica en ratas Resistance training reduces the metabolic acidosis and hepatic and renal hypertrophy caused by the consumption of a high protein diet in rats

    2011-01-01

    Introducción: El consumo de dietas hiperproteicas (HP) podría tener un efecto adverso sobre la acidosis metabólica y la salud hepática y renal. Sin embargo, existen pocos estudios que analicen los efectos del entrenamiento de fuerza sobre los parámetros sensibles de ser alterados por dichas dietas. Material y métodos: Un total de 32 ratas Wistar adultas fueron distribuidas de forma aleatoria en 4 grupos experimentales (n = 8): dieta normoproteica o HP, con o sin entrenamiento de fuerza. Las d...

  7. Predisposition to metabolic acidosis induced by topiramate Predisposição a acidose metabólica induzida por topiramato

    MARIA AUGUSTA MONTENEGRO

    2000-12-01

    Full Text Available RATIONALE: Metabolic acidosis induced by topiramate is a well documented but infrequent adverse event. The objective was to demonstrate the lowering of carbon dioxide serum levels, which is usually asymptomatic but may facilitate the occurrence of metabolic acidosis in patients using topiramate. METHODS: We evaluated, prospectively, the carbon dioxide serum levels of 18 patients seen at the epilepsy clinic of our university hospital, before and 3 months after introducing topiramate. RESULTS: Five patients were female and 13 were male, age ranging from 2 to 16 years old (mean=9.3. Carbon dioxide mean serum levels were 25 and 21.2 mmol/L (normal = 22 to 30, before and 3 months after introducing topiramate, respectively. Dose ranged from 2.08 to 11.76 mg/kg/day (mean=6.7mg/kg/day. Adverse events were anorexia, nausea and somnolence. CONCLUSION: We conclude that the lowering of carbon dioxide serum levels induced by topiramate is mostly asymptomatic, but may facilitate the occurrence of metabolic acidosis. Since patients in use of topiramate have refractory epilepsy, they may need epilepsy surgery, and must be carefully monitored for the risk of metabolic acidosis during surgery.INTRODUÇÃO: Acidose metabólica induzida por topiramato é evento adverso pouco frequente, mas bem documentado. Nosso objetivo foi demonstrar a diminuição dos níveis de dióxido de carbono, muitas vezes assintomática, mas que pode predispor ao aparecimento de acidose metabólica. MATERIAL E MÉTODO: Avaliamos prospectivamente os níveis de dióxido de carbono de 18 pacientes acompanhados no ambulatório de epilepsia infantil da UNICAMP, antes e 3 meses após o início do uso de topiramato. RESULTADOS: Foram avaliados 18 pacientes com idade entre 2 e 16 anos (média = 9,3 anos. Cinco pacientes eram do sexo feminino e 13, do sexo masculino. Os níveis médios de dióxido de carbono antes e após o uso de topiramato foram 25 e 21,2 mmol/L (normal = 22 a 30

  8. Comparison of conventional and diffusion-weighted MRI and proton MR spectroscopy in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like events

    Abe, K.; Hikita, T.; Sakoda, S. [Department of Neurology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871, Osaka (Japan); Yoshimura, H.; Tanaka, H.; Fujita, N. [Department of Radiology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, 565-0871, Osaka (Japan)

    2004-02-01

    The mechanism of neurological disturbances in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is controversial. We studied 12 patients with MELAS using conventional and diffusion weighted MRI (DWI) and MR spectroscopy (MRS), to look at the physiopathology of the stroke-like events. Although conventional MRI showed lesions in all patients, DWI was more sensitive. One patient did not show high signal on DWI 48 h after a from stroke-like episode, but MRS demonstrated a lactate peak in left occipital lobe; 2 weeks after the attack, high signal was demonstrated on the right frontal lobe where MRS had shown a lactate peak. Our findings suggest a possible predictive ability of {sup 1}H-MRS, in showing early MELAS lesions and supports the hypothesis that mitochondrial metabolic dysfunction may precedes abnormalities on DWI. (orig.)

  9. Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes syndrome with hypothyroidism and focal segmental glomerulosclerosis in a paediatric patient.

    Lau, Keith K; Yang, Samuel P; Haddad, Maha N; Butani, Lavjay; Makker, Sudesh P

    2007-01-01

    Herein, we report on a paediatric patient with mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) who was hospitalized for acute on chronic renal insufficiency, seizures and deterioration of the level of consciousness. She also had hypertension, hypothyroidism and nephrotic range proteinuria. Kidney biopsy revealed many sclerotic glomeruli and focal segmental glomerulosclerosis (FSGS). Glomerulopathy is rare in patients with MELAS, and FSGS has been reported only in a few patients. The histopathological features of the renal biopsy suggested that the aetiology of the FSGS may have been secondary to chronic renal injury rather than from a primary immunologic cause. Moreover, our case is unique in that, the coexistence of MELAS, hypothalamic hypothyroidism and FSGS has not been reported in the past. The purpose of this report is to increase the awareness of health-care professionals, especially in the fields of paediatrics, neurology, endocrinology and nephrology, regarding the manifestations and complications of MELAS.

  10. The effects of active dried and killed dried yeast on subacute ruminal acidosis, ruminal fermentation, and nutrient digestibility in beef heifers.

    Vyas, D; Uwizeye, A; Mohammed, R; Yang, W Z; Walker, N D; Beauchemin, K A

    2014-02-01

    The study addressed the importance of yeast (Saccharomyces cerevisiae) viability for reducing the incidence of subacute ruminal acidosis (SARA) and improving total tract nutrient digestibility in beef heifers. Six ruminally cannulated beef heifers (680 ± 50 kg BW) were used in a replicated 3 × 3 Latin square design and were fed a diet consisting of 40% barley silage, 10% chopped grass hay, and 50% barley grain-based concentrate (DM basis). Treatments were 1) no yeast (Control), 2) active dried yeast (ADY; 4 g providing 10(10) cfu/g; AB Vista, Marlborough, UK), and 3) killed dried yeast (KDY; 4 g autoclaved ADY). The treatments were directly dosed via the ruminal cannula daily at the time of feeding. The periods consisted of 2 wk of adaptation (d 1 to 14) and 7 d of measurements (d 15 to 21). Ruminal pH was continuously measured (d 15 to 21) using an indwelling system. Ruminal contents were sampled on d 15 and 17 at 0, 3, 6, 9, and 12 h after feeding. Total tract nutrient digestibility was measured using an external marker (YbCl3) from d 15 to 19. No treatment difference was observed for DMI (P = 0.86). Yeast supplementation (ADY and KDY) tended to increase total tract digestibility of starch (P = 0.07) whereas no effects were observed on digestibility of other nutrients. Both ADY and KDY elevated minimum (P yeast supplementation was effective in reducing time that ruminal pH was below 5.8 (P 0.10); however, the proportion of Ruminococcus flavefaciens in solid fraction of digesta was greater with KDY (P = 0.05). The study demonstrates the positive effects of yeast, irrespective of its viability, in reducing the severity of SARA. However, further studies are required to evaluate the importance of yeast viability for other dietary conditions, particularly when the risk of acidosis is high.

  11. A CHARACTERIZATION OF INFLAMMATORY AND STRUCTURAL MARKERS WITHIN THE RUMEN EPITHELIUM DURING GRAIN-INDUCED RUMINAL ACIDOSIS IN LACTATING DAIRY CATTLE

    L. Dionissopoulos

    2012-01-01

    Full Text Available The objective of this study was to characterize the mRNA and protein expression of inflammatory and structural genes in the rumen epithelium during grain-induced ruminal acidosis in lactating dairy cattle. A total of 16 rumen-fistulated, lactating Holstein dairy cattle (618±35 kg of body weight, 221±32 days in milk were used in a randomized complete block design study. All cattle were initially fed a high-forage diet (HF; 88.9% of dry matter and after a baseline (wk 0 measurement, half of the cattle were randomly assigned and transitioned to a high-concentrate diet (HC; 62.2% of dry matter which was fed for 3 weeks (weeks 1, 2 and 3. Continuous ruminal pH, ruminal LPS and plasma LPS-binding protein were measured each week followed by a rumen papillae biopsy used for mRNA and protein quantification. After the baseline period, ruminal LPS was higher in HC compared to HF cattle (28851±6905 vs. 5771±3042 EU mL-1. There was no difference in mRNA expression of inflammatory and structure genes in rumen papillae between HF and HC cattle during all weeks. With regard to protein expression, there was an up regulation (p = 0.02 of nuclear factor of activated T-cells cytoplasmic 2 expression during weeks 1, 2 and 3; however, all other inflammatory markers within the rumen epithelium were unchanged by treatment. These results suggest that although grain-induced ruminal acidosis leads to characteristic whole-animal inflammatory response, only marginal changes in inflammatory and structural gene and protein expression in the rumen epithelium were detected.

  12. El entrenamiento de fuerza reduce la acidosis metabólica y la hipertrofia hepática y renal consecuentes del consumo de una dieta hiperproteica en ratas Resistance training reduces the metabolic acidosis and hepatic and renal hypertrophy caused by the consumption of a high protein diet in rats

    V. A. Aparicio

    2011-12-01

    Full Text Available Introducción: El consumo de dietas hiperproteicas (HP podría tener un efecto adverso sobre la acidosis metabólica y la salud hepática y renal. Sin embargo, existen pocos estudios que analicen los efectos del entrenamiento de fuerza sobre los parámetros sensibles de ser alterados por dichas dietas. Material y métodos: Un total de 32 ratas Wistar adultas fueron distribuidas de forma aleatoria en 4 grupos experimentales (n = 8: dieta normoproteica o HP, con o sin entrenamiento de fuerza. Las dietas estuvieron basadas en un hidrolizado de proteína de lactosuero (whey. Tras 90 días de diseño experimental los animales fueron sacrificados para los posteriores análisis. Resultados y discusión: El consumo de una dieta HP provocó acidosis metabólica (hipercalcemia e hipocitraturia urinarias, acidificación del pH urinario y niveles elevados de urea plasmática, (P Introduction: High protein (HP diet consumption may adversely affect metabolic acidosis and hepatic and renal health. Despite such potentially adverse effect, there are only few studies analyzing the effects of resistance training on the parameters that could be altered by such diets. Material and methods: A total of 32 adult male Wistar rats were randomly distributed in 4 experimental groups (n = 8: normoprotein or HP diets, with or without resistance training. Diets were based on a whey protein hydrolyzate, and the experimental period lasted for 90 days. Results and discussion: Consumption of HP diets and resistance training significantly affected food intake, body composition and plasmatic levels of total cholesterol and triglycerides. Consumption of HP diets led to a considerable increase in liver and kidney weight (P < 0.001, urinary volume and acidity, as well as in the urinary excretion of Ca, with a parallel reduction in the urinary excretion of citrate (P < 0.05. The buffering action of resistance training on such diet-induced alterations was especially evident in the

  13. L-Arginine Affects Aerobic Capacity and Muscle Metabolism in MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes Syndrome.

    Lance H Rodan

    Full Text Available To study the effects of L-arginine (L-Arg on total body aerobic capacity and muscle metabolism as assessed by (31Phosphorus Magnetic Resonance Spectroscopy ((31P-MRS in patients with MELAS (Mitochondrial Encephalomyopathy with Lactic Acidosis and Stroke-like episodes syndrome.We performed a case control study in 3 MELAS siblings (m.3243A>G tRNA(leu(UUR in MTTL1 gene with different % blood mutant mtDNA to evaluate total body maximal aerobic capacity (VO(2peak using graded cycle ergometry and muscle metabolism using 31P-MRS. We then ran a clinical trial pilot study in MELAS sibs to assess response of these parameters to single dose and a 6-week steady-state trial of oral L-Arginine.At baseline (no L-Arg, MELAS had lower serum Arg (p = 0.001. On 3(1P-MRS muscle at rest, MELAS subjects had increased phosphocreatine (PCr (p = 0.05, decreased ATP (p = 0.018, and decreased intracellular Mg(2+ (p = 0.0002 when compared to matched controls. With L-arginine therapy, the following trends were noted in MELAS siblings on cycle ergometry: (1 increase in mean % maximum work at anaerobic threshold (AT (2 increase in % maximum heart rate at AT (3 small increase in VO(2peak. On (31P-MRS the following mean trends were noted: (1 A blunted decrease in pH after exercise (less acidosis (2 increase in Pi/PCr ratio (ADP suggesting increased work capacity (3 a faster half time of PCr recovery (marker of mitochondrial activity following 5 minutes of moderate intensity exercise (4 increase in torque.These results suggest an improvement in aerobic capacity and muscle metabolism in MELAS subjects in response to supplementation with L-Arg. Intramyocellular hypomagnesemia is a novel finding that warrants further study.Class III evidence that L-arginine improves aerobic capacity and muscle metabolism in MELAS subjects.ClinicalTrials.gov NCT01603446.

  14. Very Low-Protein Diet (VLPD) Reduces Metabolic Acidosis in Subjects with Chronic Kidney Disease: The “Nutritional Light Signal” of the Renal Acid Load

    Di Iorio, Biagio Raffaele; Di Micco, Lucia; Marzocco, Stefania; De Simone, Emanuele; De Blasio, Antonietta; Sirico, Maria Luisa; Nardone, Luca

    2017-01-01

    Background: Metabolic acidosis is a common complication of chronic kidney disease; current guidelines recommend treatment with alkali if bicarbonate levels are lower than 22 mMol/L. In fact, recent studies have shown that an early administration of alkali reduces progression of CKD. The aim of the study is to evaluate the effect of fruit and vegetables to reduce the acid load in CKD. Methods: We conducted a case-control study in 146 patients who received sodium bicarbonate. Of these, 54 patients assumed very low-protein diet (VLPD) and 92 were controls (ratio 1:2). We calculated every three months the potential renal acid load (PRAL) and the net endogenous acid production (NEAP), inversely correlated with serum bicarbonate levels and representing the non-volatile acid load derived from nutrition. Un-paired T-test and Chi-square test were used to assess differences between study groups at baseline and study completion. Two-tailed probability values ≤0.05 were considered statistically significant. Results: At baseline, there were no statistical differences between the two groups regarding systolic blood pressure (SBP), diastolic blood pressure (DBP), protein and phosphate intake, urinary sodium, potassium, phosphate and urea nitrogen, NEAP, and PRAL. VLPD patients showed at 6 and 12 months a significant reduction of SBP (p < 0.0001), DBP (p < 0.001), plasma urea (p < 0.0001) protein intake (p < 0.0001), calcemia (p < 0.0001), phosphatemia (p < 0.0001), phosphate intake (p < 0.0001), urinary sodium (p < 0.0001), urinary potassium (p < 0.002), and urinary phosphate (p < 0.0001). NEAP and PRAL were significantly reduced in VLPD during follow-up. Conclusion: VLPD reduces intake of acids; nutritional therapy of CKD, that has always taken into consideration a lower protein, salt, and phosphate intake, should be adopted to correct metabolic acidosis, an important target in the treatment of CKD patients. We provide useful indications regarding acid load of food and drinks

  15. A new disease-related mutation for mitochondrial encephalopathy lactic acidosis and strokelike episodes (MELAS) syndrome affects the ND4 subunit of the respiratory complex I

    Lertrit, P.; Noer, A.S.; Kapsa, R.; Marzuki, S. (Monash Univ., Clayton, Victoria (Australia)); Jean-Francois, M.J.B.; Thyagarajan, D.; Byrne, E. (St. Vincent' s Hospital, Fitzroy, Victoria (Australia)); Dennett, X. (Univ. of Melbourne, Parkville, Victoria (Australia)); Lethlean, K. (Prince Henry Hospital, Sydney (Australia))

    1992-09-01

    The molecular lesions in two patients exhibiting classical clinical manifestations of MELAS (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes) syndrome have been investigated. A recently reported disease-related A[yields]G base substitution at nt 3243 of the mtDNA, in the DHU loop of tRNA[sup Leu], was detected by restriction-enzyme analysis of the relevant PCR-amplified segment of the mtDNA of one patient but was not observed, by either restriction-enzyme analysis or nucleotide sequencing, in the other. To define the molecular lesion in the patient who does not have the A[yields]G base substitution at nt 3243, the total mitochondrial genome of the patient has been sequenced. An A[yields]G base substitution at nt 11084, leading to a Thr-to-Ala amino acid replacement in the ND4 subunit of the respiratory complex I, is suggested to be a disease-related mutation. 49 refs., 7 figs., 1 tab.

  16. Recoverable, Record-High Lactic Acidosis in a Patient with Glycogen Storage Disease Type 1: A Mixed Type A and Type B Lactate Disorder

    Yonatan Oster

    2016-01-01

    Full Text Available A 17-year-old patient with GSD type 1a (von Gierke disease was hospitalized with an extremely elevated serum lactate following an intercurrent infection and interruption of his frequent intake of carbohydrates. The patient developed shock, oliguric renal failure, and cardiorespiratory failure requiring mechanical ventilation and inotropes. At the peak of metabolic decompensation and clinical instability, serum lactate reached a level of 47.6 mmol/L which was accompanied by a severe anion gap metabolic acidosis with a pH of 6.8 and bicarbonate of 4 meq/L. The patient was stabilized with massive infusions of sodium bicarbonate (45 meq/h and glucose and recovered without the need for dialysis. This patient illustrates pathophysiologic mechanisms involved in the development of extreme mixed type A and type B lactic acidemia, reflecting altered metabolic pathways in GSD type 1, combined with tissue hypoperfusion. The rationale for the specific interventions in this case is outlined.

  17. Mitochondrial myopathy, lactic acidosis, and sideroblastic anemia (MLASA) plus associated with a novel de novo mutation (m.8969G>A) in the mitochondrial encoded ATP6 gene.

    Burrage, Lindsay C; Tang, Sha; Wang, Jing; Donti, Taraka R; Walkiewicz, Magdalena; Luchak, J Michael; Chen, Li-Chieh; Schmitt, Eric S; Niu, Zhiyv; Erana, Rodrigo; Hunter, Jill V; Graham, Brett H; Wong, Lee-Jun; Scaglia, Fernando

    2014-11-01

    Mitochondrial myopathy, lactic acidosis and sideroblastic anemia (MLASA) is a rare mitochondrial disorder that has previously been associated with mutations in PUS1 and YARS2. In the present report, we describe a 6-year old male with an MLASA plus phenotype. This patient had features of MLASA in the setting of developmental delay, sensorineural hearing loss, epilepsy, agenesis of the corpus callosum, failure to thrive, and stroke-like episodes. Sequencing of the mitochondrial genome identified a novel de novo, heteroplasmic mutation in the mitochondrial DNA (mtDNA) encoded ATP6 gene (m.8969G>A, p.S148N). Whole exome sequencing did not identify mutations or variants in PUS1 or YARS2 or any known nuclear genes that could affect mitochondrial function and explain this phenotype. Studies of fibroblasts derived from the patient revealed a decrease in oligomycin-sensitive respiration, a finding which is consistent with a complex V defect. Thus, this mutation in MT-ATP6 may represent the first mtDNA point mutation associated with the MLASA phenotype.

  18. Mutation of the mitochondrial tyrosyl-tRNA synthetase gene, YARS2, causes myopathy, lactic acidosis, and sideroblastic anemia--MLASA syndrome.

    Riley, Lisa G; Cooper, Sandra; Hickey, Peter; Rudinger-Thirion, Joëlle; McKenzie, Matthew; Compton, Alison; Lim, Sze Chern; Thorburn, David; Ryan, Michael T; Giegé, Richard; Bahlo, Melanie; Christodoulou, John

    2010-07-09

    Mitochondrial respiratory chain disorders are a heterogeneous group of disorders in which the underlying genetic defect is often unknown. We have identified a pathogenic mutation (c.156C>G [p.F52L]) in YARS2, located at chromosome 12p11.21, by using genome-wide SNP-based homozygosity analysis of a family with affected members displaying myopathy, lactic acidosis, and sideroblastic anemia (MLASA). We subsequently identified the same mutation in another unrelated MLASA patient. The YARS2 gene product, mitochondrial tyrosyl-tRNA synthetase (YARS2), was present at lower levels in skeletal muscle whereas fibroblasts were relatively normal. Complex I, III, and IV were dysfunctional as indicated by enzyme analysis, immunoblotting, and immunohistochemistry. A mitochondrial protein-synthesis assay showed reduced levels of respiratory chain subunits in myotubes generated from patient cell lines. A tRNA aminoacylation assay revealed that mutant YARS2 was still active; however, enzyme kinetics were abnormal compared to the wild-type protein. We propose that the reduced aminoacylation activity of mutant YARS2 enzyme leads to decreased mitochondrial protein synthesis, resulting in mitochondrial respiratory chain dysfunction. MLASA has previously been associated with PUS1 mutations; hence, the YARS2 mutation reported here is an alternative cause of MLASA.

  19. An experimental renal acidification defect in patients with hereditary fructose intolerance. II. Its distinction from classic renal tubular acidosis; its resemblance to the renal acidification defect associated with the Fanconi syndrome of children with cystinosis.

    Morris, R C

    1968-07-01

    In adult patients with hereditary fructose intolerance (HFI) fructose induces a renal acidification defect characterized by (a) a 20-30% reduction in tubular reabsorption of bicarbonate (T HCO(3) (-)) at plasma bicarbonate concentrations ranging from 21-31 mEq/liter, (b) a maximal tubular reabsorption of bicarbonate (Tm HCO(3) (-)) of approximately 1.9 mEq/100 ml of glomerular filtrate, (c) disappearance of bicarbonaturia at plasma bicarbonate concentrations less than 15 mEq/liter, and (d) during moderately severe degrees of acidosis, a sustained capacity to maintain urinary pH at normal minima and to excrete acid at normal rates. In physiologic distinction from this defect, the renal acidification defect of patients with classic renal tubular acidosis is characterized by (a) just less than complete tubular reabsorption of bicarbonate at plasma bicarbonate concentrations of 26 mEq/liter or less, (b) a normal Tm HCO(3) (-) of approximately 2.8 mEq/100 ml of glomerular filtrate, and (c) during acidosis of an even severe degree, a quantitatively trivial bicarbonaturia, as well as (d) a urinary pH of greater than 6. That the fructose-induced renal acidification defect involves a reduced H(+) secretory capacity of the proximal nephron is supported by the magnitude of the reduction in T HCO(3) (-) (20-30%) and the simultaneous occurrence and the persistence throughout administration of fructose of impaired tubular reabsorption of phosphate, alpha amino nitrogen and uric acid.A reduced H(+) secretory capacity of the proximal nephron also appears operative in two unrelated children with hyperchloremic acidosis, Fanconi's syndrome, and cystinosis. In both, T HCO(3) (-) was reduced 20-30% at plasma bicarbonate concentrations ranging from 20-30 mEq/liter. The bicarbonaturia disappeared at plasma bicarbonate concentrations ranging from 15-18 mEq/liter, and during moderate degrees of acidosis, urinary pH decreased to less than 6, and the excretion rate of acid was normal.

  20. Rumen microbial abundance and fermentation profile during severe subacute ruminal acidosis and its modulation by plant derived alkaloids in vitro.

    Mickdam, Elsayed; Khiaosa-Ard, Ratchaneewan; Metzler-Zebeli, Barbara U; Klevenhusen, Fenja; Chizzola, Remigius; Zebeli, Qendrim

    2016-06-01

    Rumen microbiota have important metabolic functions for the host animal. This study aimed at characterizing changes in rumen microbial abundances and fermentation profiles using a severe subacute ruminal acidosis (SARA) in vitro model, and to evaluate a potential modulatory role of plant derived alkaloids (PDA), containing quaternary benzophenanthridine and protopine alkaloids, of which sanguinarine and chelerythrine were the major bioactive compounds. Induction of severe SARA strongly affected the rumen microbial composition and fermentation variables without suppressing the abundance of total bacteria. Protozoa and fungi were more sensitive to the low ruminal pH condition than bacteria. Induction of severe SARA clearly depressed degradation of fiber (P < 0.001), which came along with a decreased relative abundance of fibrolytic Ruminococcus albus and Fibrobacter succinogenes (P < 0.001). Under severe SARA conditions, the genus Prevotella, Lactobacillus group, Megasphaera elsdenii, and Entodinium spp. (P < 0.001) were more abundant, whereas Ruminobacter amylophilus was less abundant. SARA largely suppressed methane formation (-70%, P < 0.001), although total methanogenic 16S rRNA gene abundance was not affected. According to principal component analysis, Methanobrevibacter spp. correlated to methane concentration. Addition of PDA modulated ruminal fermentation under normal conditions such as enhanced (P < 0.05) concentration of total SCFA, propionate and valerate, and increased (P < 0.05) degradation of crude protein compared with the unsupplemented control diet. Our results indicate strong shifts in the microbial community during severe SARA compared to normal conditions. Supplementation of PDA positively modulates ruminal fermentation under normal ruminal pH conditions.

  1. Hyperkalemia in neonatal diarrheic calves depends on the degree of dehydration and the cause of the metabolic acidosis but does not require the presence of acidemia.

    Trefz, F M; Constable, P D; Sauter-Louis, C; Lorch, A; Knubben-Schweizer, G; Lorenz, I

    2013-01-01

    Hyperkalemia is a clinically important electrolyte imbalance in neonatal diarrheic calves that has previously been associated with skeletal muscle weakness and life-threatening cardiac arrhythmias. The aim of the present retrospective analysis was to identify risk factors for hyperkalemia in a convenience sample of 832 calves (≤ 21 d of age) with a clinical diagnosis of diarrhea admitted to a veterinary teaching hospital. Plasma potassium concentrations were most closely associated with parameters of dehydration and renal function such as serum creatinine [Spearman correlation (rs) = 0.61], urea (rs = 0.51), and inorganic phosphorus concentrations (rs = 0.64). Plasma potassium concentrations were weakly associated with venous blood pH (rs = -0.21). Although venous blood pH was not predictive in a multivariate linear regression analysis, the odds of having hyperkalemia (>5.8 mmol/L) in acidemic calves was found to be 8.6 times as high as in nonacidemic calves [95% confidence interval (CI): 4.8-15.4]. However, the presence of hyperkalemia depended on the nature of an existing acidosis, and the odds for the presence of hyperkalemia in acidemic calves with hyper-D-lactatemia (>3.96 mmol/L) were only 0.15 times as high as in acidemic calves with normal D-lactate concentrations (95% CI, 0.11-0.22). Acidemia in hyperkalemic diarrheic calves was associated with hyponatremia and increased concentrations of inorganic phosphorus, L-lactate, and unidentified strong anions that presumably included uremic anions such as sulfate. We conclude that hyper-D-lactatemia in neonatal diarrheic calves is not usually associated with elevated plasma potassium concentrations. Application of the simplified strong ion acid-base model indicated that dehydration is an important contributor to the pathogenesis of hyperkalemia and acidemia in neonatal calves with diarrhea.

  2. SUSCEPTIBILIDADE DE BOVINOS DAS RAÇAS JERSEY E GIR À ACIDOSE LÁCTICA RUMINAL: II - ACIDOSE METABÓLICAE METABOLIZAÇÃO DO LACTATO-L SUSCEPTIBILITY OF JERSEY AND GIR STEERS TO RUMEN LACTIC ACIDOSIS: II - METABOLIC ACIDOSIS AND L-LACTATE METABOLISM

    Celso Akio Maruta

    2002-02-01

    Full Text Available Quatro garrotes Jersey (J (Bos taurus e quatro Gir (G (Bos indicus foram utilizados para comparar a susceptibilidade de zebuínos e taurinos à acidose láctica ruminal (ALR. Neste trabalho, acompanhou-se o grau da acidose metabólica (AM e a metabolização do lactato-L. A ALR foi induzida com a administração de sacarose intraruminal. Amostras de sangue foram colhidas nos seguintes momentos: zero, 14, 16, 18, 20, 22 e 24 horas. Foram determinadas as concentrações de lactato total, de seus isômeros L e D e o perfil hemogasométrico. Nos momentos mais críticos observados (14ªh a 18ªh, a AM foi severa em ambas as raças, porém, ao término do experimento, esta passou a grau moderado nos garrotes G, mantendo-se severa nos J. Os animais J absorveram, do rúmen, maiores quantidades de lactato-D, o qual apresentou correlação negativa com o pH sangüíneo (r = - 0,78. Por outro lado, o lactato-L foi mais absorvido e utilizado nos bovinos G, contribuindo para a restauração parcial do equilíbrio ácido-básico e gerando alterações nas pCO2 e pO2. Os garrotes zebuínos da raça Gir apresentaram menor susceptibilidade à AM que os taurinos da raça Jersey.In order to compare the susceptibility to acute rumen lactic acidosis (RLA, four Jersey (J (Bos taurus and four Gir (G (Bos indicus steers were used to evaluate the degree of metabolic acidosis (MA and the metabolism of L-lactate during the RLA. The RLA was induced by the administration of sucrose into the rumen. Blood samples were collected at following times: zero, 14th,16th, 18th, 20th, 22nd and 24th h. Total lactic acid and its isomers, and blood gas determination were measured. At the most critical moments (14th to 18th h the MA was severe in both breeds, but the MA became moderate in the G steers and remained severe in the J steers at the end of the trial. Higher amounts of D-lactate was absorbed from the rumen to the blood of the J steers; the higher the D-lactate plasma level, the

  3. Nutritional Models of Experimentally-Induced Subacute Ruminal Acidosis (SARA) Differ in Their Impact on Rumen and Hindgut Bacterial Communities in Dairy Cows

    Plaizier, Jan C.; Li, Shucong; Tun, Hein M.; Khafipour, Ehsan

    2017-01-01

    Effects of subacute ruminal acidosis (SARA) challenges on the bacteria in rumen fluid, cecal digesta, and feces of dairy cows were determined using 16S rRNA gene pyrosequencing and real-time quantitative PCR. Six non-lactating Holstein cows with cannulas in the rumen and cecum were used in a 3 × 3 Latin square arrangement of treatments. During the first 3 wk of each experimental period, cows received a control diet containing 70% forages on a dry matter (DM) basis. In wk 4 of each period, cows received one of three diets: (1) the control diet; (2) a diet in which 34% of the dietary DM was replaced with pellets of ground wheat and barley (GBSC); or (3) a diet in which 37% of dietary DM was replaced with pellets of ground alfalfa (APSC). Rumen fluid, cecal digesta and feces were collected on d 5 of wk 4 of each period and the composition of the bacterial community was studied. Rumen fermentation responses were reported in a companion study. Both SARA-inducing challenges resulted in similar digesta pH depressions (as shown by the companion study), and reduced bacterial richness and diversity in rumen fluid, but GBSC had the larger effect. None of the challenges affected these measures in cecal digesta, and only GBSC reduced bacterial richness and diversity in feces. Only GBSC reduced the abundance of Bacteroidetes in rumen fluid. Abundances of limited number of bacterial genera identified by 16S rRNA gene sequencing in the rumen, cecum and feces were affected by the GBSC. The APSC did not affect any of these abundances. Both challenges increased the abundances of several starch, pectin, xylan, dextrin, lactate, succinate, and sugar fermenting bacterial species in the rumen, cecum, and feces as determined by qPCR. Only GBSC increased that of Megasphaera elsdenii in the rumen. Both challenges decreased the abundance of Streptococcus bovis, and increased that of Escherichia coli, in cecal digesta and feces, with GBSC having the larger effect. These results showed that

  4. Causas de Acidosis Metabólica en el lactante, pre-escolar y escolar y análisis de los resultados del Anion Restante en la orientación etiológica : estudio realizado en el área de urgencias del Hospital de Niños Dr. Roberto Gilbert Elizalde período febrero 2014 - julio 2014.

    Silva Galarza, Rina Johanna

    2014-01-01

    La acidosis metabólica es una alteración patológica, resultado de diversos trastornos; de etiología identificable mediante la utilización del anión restante, que relacionado con la clínica y examen físico del paciente, permiten realizar un diagnóstico y tratamiento oportuno. Objetivo: Identificar las causas de acidosis metabólica en los pacientes en etapa de lactante, preescolar y escolar que acuden al área de urgencias del Hospital Dr. Roberto Gilbert y utilidad del anión restante en la o...

  5. 肾小管性酸中毒骨骼并发症的临床分析%Clinical analysis of bone complications in renal tubular acidosis

    马毓华; 谢静远; 张春丽; 李晓; 沈平雁; 任红; 陈楠

    2013-01-01

    Objectives This study aims to investigate the features of bone complications secondary to renal tubular acidosis(RTA) and to further discuss the differences and characteristics of clinical manifestations between patients with primary RTA (PRTA) or RTA Secondary to Sj? gren's syndrome (SRTA) patients.Methods We retrospectively recruited 109 SRTA patients and 144 PRTA patients who admitted to our clinical center during 1996 and 2010.Baseline demographic,clinical features,laboratory examinations,outcomes and isotope bone density examination were collected and analyzed.Results The study included 144 PRTA and 109 SRTA patients.In PRTA group,there were 63 men and 81 women,the average age was 38 years; In SRTA group,there were 10 men and 99 women,the average age was 42 years..Within the PRTA group,bone pain and joint pain occured in 22 cases (15.3%),reduced bone mass was observed in 3 cases (2.1%),osteoporosis was found in 17 cases (11.8%).While in SRTA group,25 patients (22.9%) were reported to have bone pain and joint pain,and reduced bone mass was found in 10 cases (9.2%),9 cases (8.3%) of the patients had osteoporosis.Accordingly,more patients with bone disease were detected in SRTA group than in PRTA group (37.6% vs 24.3%,p < 0.05).The isotope bone density with lumbar spine T value of 9 PRTA patients is more than the SRTA patients.Additionally,SRTA patients had a lower lumber spine T value than PRTA patients (-0.53 ± 0.97 vs-1.65 ± 1.29,P < 0.05) by isotope bone density test which indicated a higher frequency and more severe bone disease occurred in RTA patients with Sj? gren 's syndrome than primary RTA patients.Conclusions Sjgren's syndrome is the most common cause of secondary RTA,the incidence and severity of bone disease was higher in RTA patients secondary to Sj? gren's syndrome than primary RTA patients,which aroused early diagnosis and clinical attentions.%目的 总结肾小管酸中毒(Renal Tubular Acidosis,RTA)骨骼并发症的特

  6. Metabolic acidosis and ventilatory response

    Langbroek, Aart Jan Mattheüs

    1988-01-01

    In terrestrial vertebrates lung ventilation is nescessary to accmplish exchange of oxygen (O2) and carbon dioxide (CO2) between the gas phase (lung alveoli) and the fluid phase (the blood flowing through the lung capillaries). The ventilatory control system adjusts the arterial carbon dioxide tensio

  7. Uso de bicarbonato e lactato-L para correção da acidose metabólica sistêmica em bovinos com acidose láctica ruminal aguda Use of bicarbonate and lactate L for correction of systemic metabolic acidosis in cattle with acute rumen lactic acidosis

    M.L.R. Leal

    2007-08-01

    Full Text Available Foram utilizados seis novilhos, providos de cânula ruminal, em delineamento experimental cross-over, para comparar a eficiência de soluções de bicarbonato de sódio e lactato-L de sódio na correção da acidose metabólica sistêmica (AMS, causada pela acidose láctica ruminal (ALR. Vinte horas após, quando apresentavam intensa AMS, os animais foram distribuídos aleatoriamente e tratados com cinco litros de 150mMol/l de bicarbonato de sódio ou de lactato-L de sódio, infundidas por via intravenosa, nas quatro horas seguintes. Amostras de sangue, para hemogasometria, foram coletadas no decorrer da infusão a zero, 1, 2, 3, 4, 6 e 8 horas. Ambos os tratamentos elevaram o pH sangüíneo já na primeira hora pós-infusão, corrigindo adequadamente a AMS. O tratamento com lactato-L de sódio aumentou as concentrações de bicarbonato, TCO2 e EAB sangüíneos já na segunda hora pós-infusão; com o bicarbonato essa elevação ocorreu a partir da terceira hora. Não houve diferenças entre tratamentos para pH sangüíneo, bicarbonato, TCO2 e excesso de base. Vinte e quatro horas após o tratamento todos os novilhos apresentaram plena recuperação. O lactato-L pode substituir o bicarbonato na correção da AMS em novilhos com ALR.The efficiency of sodium bicarbonate or l-lactate for correcting systemic metabolic acidosis (SMA caused by rumen lactic acidosis (RLA was evaluated using six rumen-cannulated steers in a cross-over experimental design. RLA was induced by administration of sucrose, intraruminally. Twenty hours later when the animals developed an intense SMA, the steers were randomly distributed and treated intravenously either with 5l of 15 mMol/l sodium bicarbonate or L-lactate solution, infused throughout 4h. Blood samples were colleted throughout the infusion at zero, 1, 2, 3, 4, 6 and 8h, for blood gas analysis. After 1hour, both sodium bicarbonate and L-lactate solutions increased blood pH and corrected adequately the SMA. Blood

  8. Safety Analysis of Vinegar Enema in Hepatic Encephalopathy Complicated with Metabolic Acidosis%食醋灌肠在肝性脑病合并代谢性酸中毒中的安全性分析

    魏晓广; 郑佳

    2016-01-01

    目的:分析食醋灌肠在肝性脑病合并代谢性酸中毒中的安全性。方法选取我院收治的48例肝性脑病合并代谢性酸中毒患者作为研究对象,随机分为两组,各24例。对照组采用乳果糖治疗,观察组采用食醋灌肠进行治疗。对比观察两组患者治疗效果及不良反应发生情况。结果观察组总有效率为91.67%,明显优于对照组70.83%,差异显著(P<0.05);对照组不良反应发生率为25.0%,观察组未见不良反应,组间比较差异显著(P<0.05)。结论对肝性脑病合并代谢性酸中毒患者实施食醋灌肠的方法进行治疗,临床效果显著,且不良反应发生率低,安全有效,值得推广运用。%Objective To analyze the safety of vinegar enema in hepatic encephalopathy complicated with metabolic acidosis. Methods 48 cases of patients with hepatic encephalopathy and metabolic acidosis were randomly divided into two groups, each of 24 cases. The control group was given lactulose treatment, the observation group was treated with vinegar enema treatment. The treatment effect and adverse reaction of the two groups were compared and observed.ResultsThe total effective rate of the observation group was 91.67%, which was significantly better than that of the control group (70.83%), and the difference was signiifcant (P<0.05); The adverse reaction rate of control group was 25.0%, no adverse reaction was observed in the observation group, and the difference was signiifcant (P<0.05).Conclusion In patients with hepatic encephalopathy complicated with metabolic acidosis implementation vinegar enema method of treatment, significant clinical effect and adverse reactions occurred rate is low, and is safe and effective, worthy of popularization and application.

  9. Adult-onset Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke (MELAS)-like Encephalopathy Diagnosed Based on the Complete Sequencing of Mitochondrial DNA Extracted from Biopsied Muscle without any Myopathic Changes.

    Mukai, Masako; Nagata, Eiichiro; Mizuma, Atsushi; Yamano, Mitsuhiko; Sugaya, Keizo; Nishino, Ichizo; Goto, Yu-Ichi; Takizawa, Shunya

    The clinical features of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) are not uniform. We herein report a male patient with unusual MELAS-like encephalopathy who had been experiencing isolated recurrent stroke-like episodes since he was 33 years old without any particular family history. Despite an extensive investigation, he had no other signs suggestive of MELAS. Although the muscle pathology showed a normal appearance, a mitochondrial genome sequence analysis of the biopsied muscle revealed a heteroplasmic m.10158T>C mutation in the mitochondrial complex I subunit gene, MT-ND3. To prevented further deterioration of the higher brain function, the early diagnosis and treatment of mitochondrial stroke-like episodes is important.

  10. Controvérsias acerca da acidose hipercápnica na síndrome do desconforto respiratório agudo Controversies involving hypercapnic acidosis in acute respiratory distress syndrome

    Liliane Nardelli

    2009-12-01

    distress syndrome is the ventilatory support. However, mechanical ventilation can worsen lung injury. In this context, a protective ventilatory strategy with low tidal volume has been proposed. The use of low tidal volume reduced the mortality rate of acute respiratory distress syndrome patients, but result in hypercapnic acidosis. The current article presents a review of literature on the effects of permissive hypercapnia in acute respiratory distress syndrome. To that end, we carried out a systematic review of scientific literature based on established criteria for documental analysis including clinical and experimental articles, using as data bases MedLine, LILACS, SciELO, PubMed, Cochrane. Hypercapnic acidosis has been considered by some authors as a modulator of the inflammatory process of acute respiratory distress syndrome. However, clinical and experimental studies on the effects of hypercapnic acidosis have shown controversial results. Therefore it is important to better elucidate the role of hypercapnic acidosis in acute respiratory distress syndrome.

  11. 急慢性代谢性酸中毒对红细胞内外pH值的影响%Effects of acute or chronic metabolic acidosis on intracellular pH of rat erythrocytes

    王贤东; 袁媛; 王冬; 赫曼; 刘若彬

    2009-01-01

    Objecfive To investigate the effects of acute or chronic metabolic acidosis on intracellular pH of rat erythrocytes.Methods Acute metabolic acidosis in Wistar rats was induced by infusion of 4mmol/kg HCl for 4 hours;Chronic metabolic acidosis rats was induced by addition of 0.28 mol/L NH4CI to drinking water for 7 days.The control groups were given 0.9%NaCl in the same time.At 0,2and 4h after HCl infusion in acute group,and at 0,1,3,5 and 7 days after NH4Cl administration in chronic group,0.5ml blood samples were taken.All blood samples were placed in test tubes with heparin anticoagulant solution.Blood gas was analyzed.Carbonic anhydrase activity in rat erythrocytes was assayed by following the hydration of CO2 according to the method described by Wilbur and Anderson.And after stained by BCECF-AM fluorescent probe,the changes of intracellular pH were observed,and the ability of NHE1 were measured by detected recovery rate of intraeellular pH by laser scanning confocal microscopy.Results Acute metabolic acidosis inhibits NHE1 activity(P<0.05)and no changes in pHi and carbonic anhydrase activity of rat erythrocyte were seen.On the contrast.it was showed increasing activity of NHE 1 and carbonic anhydrase with decreasing phi in rats erythrocytesin chronic metabolic acidosis over five days(P<0.05).Conclusion These results suggest that an acute acid load does not alter pHi while chronic metabolic acidosis does reduce pHi of rat crythrocyte.%目的 观察急性或慢性代谢性酸中毒对大鼠红细胞内pH(pHi)、碳酸酐酶(carbonic and hydrase,CA)和钠-氢交换蛋白Ⅰ(Na+-H+ exchanger Ⅰ,NHE Ⅰ)活性的影响.方法 将24只Wistar大鼠随机分为急性组和慢性组.急性组分为:急性对照组(A组)和急性代谢性酸中毒组(B组);慢性组分为:慢性对照组(C组)和慢性代谢性酸中毒组(D组)(n=6).急性组采用静脉输注4 mmol·kg1-·h-1 HCl 4 h,慢性组采用0.28 mol/L NH4Cl喂饲7 d,构建大鼠急性和慢性代谢性酸

  12. 2型糖尿病患者口服保健品引发乳酸酸中毒的临床分析%Clinical study of type 2 diabetes patients taking health products with lactic acidosis

    刘雪芳; 夏碧文; 蒋婵; 曾炼坤; 李素燕

    2015-01-01

    目的:分析口服保健品的2型糖尿病患者并发乳酸酸中毒的临床特征,探讨2型糖尿病并发乳酸酸中毒危险因素,总结治疗经验,降低病死率。方法采用回顾性分析,将2011年1月~2014年2月我院收治的43例2型糖尿病并乳酸酸中毒患者分为乳酸≥13.0mmol/L 组(A 组,20例),乳酸<13.0mmol/L(B组,23例),比较两组患者临床及实验室指标、治疗方法及转归。结果 A 组死亡率为15%,显著高于 B组(P <0.05);A 组糖尿病病程、白细胞计数、阴离子间隙、血肌酐、尿素氮较 B 组显著性升高(P <0.05);A 组 SO2%、Hb、pH 值、CO2CP、血糖、HbA1C%显著低于 B 组(P <0.05);Pearson 相关性分析显示,补碱量与乳酸、pH 值水平无显著相关性(P >0.05),r 值分别为0.041、0.101。结论警惕“消渴平糖、平糖养胰”等含不明降糖成份的保健品引发糖尿病乳酸酸中毒,糖尿病病程、炎症、肾功能不全、低氧血症为糖尿病患者乳酸升高的危险因素,补碱量与乳酸、pH 值无相关性。%Objective To analyze the clinical characteristics and risk factors of type 2 daibetes patients with lactic acidosis, to summarize the trentment experience and reduce morbidity. Methods 43 cases of T2DM with lactic acidosis of the January 2011- February 2014 in our hospital were divided into lactic acidosis greater than or equal to 13.0mmol/L group (A group, 20cases)and lactate levels less than 13.0mmol/L(group B,23cases) .The clinical and laboratory parameters and treatment and prognosis of two groups were retrospectively analyzed. Results Mortality of group A was 15%, significantly higher than group B, P < 0.05. Diabetes duration white blood cell count, anion gap, serum creatinine and blood urea nitrogen of group A were significantly higher than that in group B, P < 0.05. SO2%, Hb, pH value, CO2cp, blood glucose and HbA1C% of group A were significantly lower

  13. Double effects of propofol on cardiac function of rats with metabolic acidosis%丙泊酚对代谢性酸中毒心脏功能的双重影响

    徐彦秋; 马兰; 曹焕军; 李力兵

    2012-01-01

    Objective To study the effect of propofol on cardiac function of rats with metabolic acidosis. Methods A metabolic acidosis model of in vitro rat heart was established with modified Langendoff apparatus. Twenty-four SD rats were randomly divided into control group, 25mmol/L propofol group(PL group) and 50mmol/L propofol group(PH group), 8 in each group. Metabolic acidosis was induced by perfusion with K-H solution(pH=7.4) for 40min, then with acidic K-H solution(pH=6-5) for 20 min and K-H solution(pH =7.4) for 30min. Propofol was added into the K-H solution 25min after stable perfusion. Heart rate (HR), left ventricular develop pressure(LVDP), left ventricular pressure ± dP/dtmax, perfusion circuit pressure and myocardial water content(MWC) were recorded before acidosis and 1, 5, 10, 20 and 30min after reperfusion. Results The HR, LVDP and left ventricular pressure ± dP/ dtmax were lower in PL and PH groups than in control group and significantly lower in PH group than in control group during the lOmin reperfusion(Pacidosis. The effect of 25mmol/L propofol is better than 50mmol/L propofol on recovery of cardiac function and improvement of cardiac muscle reperfusion and edema.%目的 探讨丙泊酚对代谢性酸中毒心脏功能的影响.方法 应用改良Langendorff装置,制备离体心脏代谢性酸中毒模型.将24只SD大鼠随机分为对照组(C组)、丙泊酚25μmol/L组(PL组)和丙泊酚50μmol/L组(PH组),每组8只.C组用pH=7.4的K-H液平衡灌注40min,然后用pH=6.5的K-H液酸化20min

  14. 艾滋病患者HAART致高乳酸血症及乳酸酸中毒10例临床分析%Analysis on 10 AIDS Patients who have HAART which Occurred High Lactatemia and Lactic Acidosis

    郜桂菊; 林可可; 肖江; 杨涤; 李鑫; 梁洪远; 刘龙; 韩宁; 赵红心

    2012-01-01

    目的 分析艾滋病患者高效抗逆转录病毒治疗(HAART)过程中出现高乳酸血症或乳酸酸中毒的病例特点,进一步认识HAART的毒副作用,探究处理办法.方法 对本院2008年以来收治的10例正在接受HAART治疗的艾滋病患者的临床表现、HAART方案、服用时间、乳酸水平、阴离子间隙(AG)、酸碱值(pH值)及治疗转归进行分析.结果 10例患者服用的HAART方案主要是司他夫定(d4T)、拉米夫定(3TC)、奈韦拉平(NVP),服用时间均在8个月以上.主要临床表现为:乏力3例,食欲不振2例,恶心呕吐1例,双下肢麻木及疼痛5例,体重明显下降2例,且临床表现有交叉.乳酸2.7~10.8mmol/L.,G均升高,pH值<7.35的1例,其余均在正常范围.死亡3例,死亡原因主要是呼吸衰竭1例,循环衰竭2例;好转5例;自动出院2例.结论 以d4T为主的HAART方案容易发生线粒体毒性,表现为高乳酸血症或乳酸酸中毒,一旦发生乳酸酸中毒,死亡率较高,因此应该重视HAART线粒体毒性的副作用,早发现,早治疗,以便改善患者预后.%Objective To retrospectively analyzed the case characteristics of high lactatemia and lactic acidosis in 10 HIV/AIDS patients who have HAART in Beijing Ditan hospital, so as to further understand side effects of HAART, and explore treatment methods. Methods A total of 10 HIV/AIDS inpatients since 2008 were enrolled. Clinical manifestation, HAART regimen, medication time, lactic level, anion gap (AG) , PH value and treatment outcome were retrospectively analyzed. Results These patients had the same HAART regimen, mainly including d4T,3TC and NVP, their medication time were much more 8 months. The main clinical manifestations were fatigue, loss of appetite, nausea and vomiting, numbness and pain in lower limbs, body weight decreased significantly, and multiple clinical manifestations might be seen in one patient; lactic level was between 2. 7 and 10. 8 mmol/L,AG were increased,only one

  15. The analysis on the predictors of the efficacy of Noninvasive positive pressure ventilation in AECOPD patients ;with different degrees of respiratory acidosis%无创正压通气对不同呼酸程度 AECOPD 患者疗效的预测因素分析

    宋丹丹; 代冰; 谭伟; 赵洪文; 康健

    2015-01-01

    Objective To investigate the predictors of the efficacy of Noninvasive positive pressure ventilation (NPPV) in AECOPD patients with different degrees of respiratory acidosis.Methods According to the PH value of the arterial blood gas analysis,72 cases of AECOPD patients were divided into three groups:mild respiratory acidosis,moderate respiratory acidosis and severe respiratory acidosis. The successful cases and the failure cases were compared with each other in three groups mentioned above before the NPPV treatment and 2 hours follow the treatment to find the significant difference between them.Results There was no significant difference between the successful cases and the failure cases in the three groups before the NPPV treatment.After 2 hours′NPPV treatment,comparing with failure cases in the mild respiratory acidosis group,several items were significantly improved in successful group (P <0.05),including the VAS score,SAMU score,heart rate and respiratory rate.In the moderate respiratory acidosis group,the respiratory rate and PaCO 2 were significantly improved in successful group (P <0.05),comparing to the failure cases.No significant differences were found in the severe respiratory acidosis group between the successful cases and the failure cases.Conclusions Different factors should be selected for the AECOPD patients with different degrees of respiratory acidosis to evaluate the prognosis in the early treatment.%目的:探讨无创正压通气对不同呼酸程度慢性阻塞性肺疾病急性加重(AECOPD)患者治疗成败的预测因素。方法根据动脉血气 pH 值将72例 AECOPD 患者分为轻、中、重度呼酸3组,分别比较3组中成功病例与失败病例在无创正压通气治疗前和治疗2 h 后的各项观察指标的差异有无统计学意义。结果无创正压通气治疗前,3组成功病例与失败病例的各项观察指标的差异无统计学意义。无创正压通气治疗2 h 后,轻度呼酸组,成功病例的视

  16. The measurement of urine pH to predict the amount of buffer used in the treatment of acute rumen lactic acidosis in cattle Mensuração do pH de urina para predizer a quantidade de tampão empregado para o tratamento de acidose láctica ruminal aguda em bovinos

    Celso Akio Maruta

    2008-06-01

    Full Text Available The purpose of the present study was to establish a practical, fast, precise and low-cost procedure to estimate the degree of metabolic acidosis in cattle with acute rumen lactic acidosis for further treatment. The rumen acidosis was induced experimentally in 40 crossbreed rumen-cannulated 1.5-year-old steers. The induction caused the development of the most characteristic clinical signs of acute rumen lactic acidosis, severe rumen acidosis and a moderate metabolic acidosis, which was evidenced by low blood pH, and blood bicarbonate concentration and base excess (BE. A highly positive correlation (r=0.80 between urinary pH and BE concentration, and between urinary pH and blood pH (r=0.75 was observed. The BE concentration estimated by urinary pH was similar to that determined by venous blood gas analysis (P>0.99. Furthermore, the results presented by the predictive formula were very significant. In conclusion, urinary pH is a good tool to predict the quantity of buffers needed to treat metabolic acidosis in cattle with acute rumen lactic acidosis.O presente estudo teve como objetivo desenvolver um procedimento de baixo custo, preciso, rápido e prático para estimar o grau de acidose metabólica, para tratar bovinos com quadros de acidose láctica ruminal. A acidose ruminal foi induzida experimentalmente em 40 novilhos mestiços de 1,5 anos de idade, implantados com cânula ruminal. Essa indução causou o surgimento de sinais clínicos muito típicos da enfermidade aguda, com o aparecimento de pronunciada acidose ruminal e acidose metabólica de grau moderado, caracterizado por baixo pH sangüíneo e diminutos teores de bicarbonato e excesso de base (BE no sangue. Verificou-se uma alta correlação positiva (r = 0,80 entre o pH urinário e o BE e entre o pH urinário e o pH sangüíneo (r = 0,75. A concentração de BE estimado pelo pH urinário foi similar à obtida pela análise do hemogasômetro (P = 0,99. Além disso, os resultados

  17. SUSCEPTIBILIDADE DE BOVINOS DAS RAÇAS JERSEY E GIR À ACIDOSE LÁCTICA RUMINAL: I - VARIÁVEIS RUMINAIS E FECAIS SUSCEPTIBILITY OF JERSEY AND GIR STEERS TO RUMEN LACTIC ACIDOSIS: I - RUMINAL AND FAECAL VARIABLES

    Celso Akio Maruta

    2002-02-01

    Full Text Available Quatro garrotes Jersey (J (Bos taurus e quatro Gir (G (Bos indicus, providos de cânula ruminal, foram utilizados para comparar a susceptibilidade à acidose láctica ruminal (ALR aguda. Para a uniformização da microbiota ruminal, os animais receberam uma alimentação padronizada por dois meses antes da indução da ALR. Esta foi realizada com o uso de sacarose administrada diretamente no rúmen, de acordo com peso metabólico corrigido. Amostras de suco ruminal e fezes foram colhidas no decorrer de 24 horas após a indução. Em ambas as amostras, foram determinados o pH e as concentrações de ácido láctico total e dos seus isômeros D e L. Ambas as raças apresentaram marcante e idêntica acidose ruminal, não ocorrendo diferenças no pH e nas concentrações de ácido láctico total, L e D no suco ruminal e nas fezes. Quanto maior foi a concentração de ácido láctico total nas fezes menores foram os valores de pH fecal (r = - 0,65. Devido à grande queda no pH fecal, sugere-se que esse pode ser utilizado para se firmar o diagnóstico de ALR.To compare the susceptibility to acute rumen lactic acidosis (RLA four Jersey (J (Bos taurus and four Gir (G (Bos indicus rumen-cannulated steers were used. In order to standardise the rumen microbiota, the steers were fed a standard diet of hay and concentrates, for two months before the beginning of the induction. The RLA was induced with sucrose administered intraruminally, on a basis of the corrected metabolic weight. Rumen fluid and faecal samples were collected throughout 24h after the induction. The pH and the concentration of total lactic acid and its L and D isomers were determined in all samples. Both breeds developed intense rumen acidosis; similar pH and concentration of total lactic acid and its isomers were found in the rumen fluid and faecal samples. The higher the total lactic acid concentration in the faeces, the lower the faecal pH (r = - 0.65. The faecal pH can be used as a tool

  18. 60 cases obese children Ⅱ diabetes TongZheng acidosis clinical analysis%肥胖儿童2型糖尿病酮症酸中毒60例的临床分析

    谷玉龙

    2012-01-01

    objective To improve the clinical pediatricians to start to in obesity symptoms of child obesity type 2 diabetes TongZheng acidosis (DKA) and tall lipemia (HL) understanding. Methods Retrospective analysis in January 2001 to December 2011 60 cases were 0 -6 years of age FeiPanXing type 2 diabetes TongZheng acidosis and hyperlipidemia obese children clinical data. Results The 60 cases obese children, boys than girls, a ratio of 1.8:1.2, namely, girls for 24 cases, the boy for 36 cases, age: 4.21 + /-1.56 years;before the disease were no diabetes history and related symptoms, there were no history of hyperlipemia;before the disease were no boozing, overeating and cholelith disease history;are obese size, body mass index 29.41 + /-2.07;reached DKA diagnosis standard. Conclusions children with type 2 diabetes FeiPanXing to obesity clinic of, should be routine check blood fat; adjust diet and exercise can relieve the obese child's 2 diabetes symptoms.%目的:提高临床医师对以肥胖为首发症状的儿童2型糖尿病酮症酸中毒(DKA)并高脂血症(HL)的认识.方法:回顾性分析我院2001年1月至2011年12月收治的60例0~6岁2型糖尿病DKA并高脂血症肥胖儿童的临床资料.结果:60例肥胖儿童年龄(4.21±1.56)岁,其中女童24例,男童36例,男:女为1.8∶1.2;病前均无糖尿病史及相关症状,均无高脂血症史;病前均无暴饮、暴食和胆石症史;均为肥胖体型,体质指数(29.41±2.07);均达到DKA诊断标准.结论:儿童肥胖型2型糖尿以肥胖就诊的,应常规查血脂;调整饮食和运动可以缓解肥胖儿童的糖尿病症状.

  19. Premature Children Late-onset Metabolic Acidosis Analysis of 89 Cases%早产儿晚发性代谢性酸中毒89例分析

    郝宝生; 王艳

    2013-01-01

    Objective To study the incidence of late metabolic acidosis among premature infant. Method: Summary of clinical data of 89 cases of LMA patients from Mar 2005 to June 2008 and analysis of the gestational age, birth weight and feeding, timing of occurrence, blood gas analysis and treatment result. Results ① The gestational age 2.5kg accounting for 14.49%; ② breastfeeding 8 cases (11.5%), occurred in 2 ~ 3w 36 cases (52.17%); ③blood gas analysis showed that lower pH, BE negative increase, PCO2 normal or slightly lower, PO2 normal; ④short SB oral treatment I excel ent outcomes. Conclusion:The incidence of late metabolic acidosis among premature infant is higher. The smal er the gestational age at birth, lower birth weight, the higher incidence of LMA;Artificial feeding showed higher incidence; clinical symptoms is not typical, Timely blood gas analysis would be helpful for early diagnosis. Treatment is simple and with early intervention, prognosis is good.%目的了解早产儿晚发性代谢性酸中毒的情况。方法总结2005年3月~2008年6月共89例LMA患儿的资料,对LMA发生的出生胎龄、出生体重、喂养方式、发生时间及血气分析及治疗结果进行分析。结果①出生胎龄2.5kg占14.49%;②母乳喂养8例(11.5%),发生时间在2~3w36例(52.17%);③血气分析结果表明,pH值降低,BE负值增大,PCO2正常或稍低,PO2正常;④治疗予短期SB口服,疗效良好。结论早产儿晚发性代谢性酸中毒发生率较高。出生胎龄越小,出生体重越低,发生率越高;人工喂养发生率高;临床表现不典型,及时进行血气分析以早期明确诊断;本病治疗简单,早期积极干预,预后良好。

  20. Metabolic acidosis and its effect on calcium and phosphorus metabolism in maintenance hemodialysis patients%维持性血液透析患者代谢性酸中毒对钙磷代谢的影响

    黎晓磊; 邵咏红; 孔耀中

    2012-01-01

    分析比较维持性血液透析(MHD)患者的代谢性酸中毒对钙磷代谢的影响.方法:选择MHD患者120例,测定透析前碳酸氢根(HCO3-)、血尿素氮(BUN)、肌酐(CR)、钙(Ca)、磷(P)、碱性磷酸酶(ALP)、甲状旁腺激素(iPTH)及透析后BUN和CR,计算钙磷乘积(Ca×P)、Kt/V.根据HCO3-分为3组:A组(HCO3-< 20 mmol/L)、B组(HCO3-为20~24 mmol/L)和C组(HCO3-≥24 mmol/L),比较3组酸中毒对钙磷紊乱的影响.结果:B、C组的P、ALP及iPTH均低于A组(P<0.05),C组的P、Ca×P低于A、B组(P<0.05).HCO3-浓度与P、iPTH、ALP及Ca×P呈负相关(P<0.05).结论:对于MHD患者,HCO3-< 20 mmol/L较HCO3-≥20 mmol/L者易合并高磷血症、低钙血症,可刺激iPTH的合成,最终导致肾性骨病及转移性钙化.%Objective To evaluate the effect of metabolic acidosis on calcium and phosphorus metabolism in maintenance hemodialysis(MHD) patients. Methods 120 MHD patients were enrolled in the present study. Predialysis laboratory detections including HC03", BUN creatinine, calcium, phosphorus, alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH) were performed. Calcium-phosphate product and Kt/V were also determined. The patients were randomized into 3 groups: group A(HCO3- < 20 mmol/L), group B (20 mmol/L≤HCO-3< 24 mmol/L), group C (HCO3-≥ 24 mmol/L). Results The concentrations of phosphorus, ALP and iPTH were decreased in groups B and C in comparation to that in group A (P < 0.05). Compared with group A and B, the phosphorus and calcium-phosphate product level in group C were decreased (P < 0.05). The serum HCO3" level correlated negatively with the serum phosphorus, iPTH, ALP and calcium-phosphate product (P < 0.05). Conclusions Correction of metabolic acidosis (bicarbonate level -S 20 mmol/L) may prevent the deleterious long-term consequences such as CKD-MBD, but further investigation of the long-term effect still needs to be done.

  1. Clinical Significance of Early Correction of Metabolic Acidosis in Patients with Chronic Kidney Disease%早期纠正慢性肾脏病患者代谢性酸中毒的临床意义

    田秋菊

    2015-01-01

    目的:探讨早期纠正慢性肾脏病患者代谢性酸中毒的临床意义。方法将该院于2014年1月-2014年12月收治的符合慢性肾脏病2、3期且TCO2跃22 mmol/L的80例患者随机分为治疗组和对照组。对照组给予常规治疗,治疗组在对照组的基础上给予NaHCO3片1.0~1.5 g/d,分次口服,同时给予产碱的水果蔬菜。主要观察指标为血尿素氮、血肌酐、血pH值、血TCO2、电解质及血压。结果治疗组血pH值、血TCO2有所提高,血尿素氮、血肌酐略有升高,但差异无统计学意义。对照组血pH值、血TCO2进一步下降,血尿素氮、血肌酐明显升高,差异有统计学意义。两组治疗前后电解质、血压均无明显变化。结论NaHCO3片和产碱的水果蔬菜饮食疗法能纠正血浆TCO2跃22 mmol/L慢性肾脏病患者的代谢性酸中毒,并延缓肾功能进展,具有肾脏保护作用,且不引起电解质紊乱及血压升高。%Objective To study the clinical effect of early correction of metabolic acidosis in patients with chronic kidney disease(CKD). Methods A total of 80 patients from 2014 January to 2014 December in our hospital with CKD at stages II-III and TCO2>22mmol/L were enrolled in the study. The patients were randomly divided into treatment group and control group. The con-trol group was given conventional treatment. The treatment group was given NaHCO3 1.0~1.5 g/d and alkali production of fruits and vegetables based on conventional treatment. The main parameters including serum urea nitrogen, serum creatinine, PH value, TCO2, electrolyte and blood pressure were measured. Results The PH, TCO2, blood urea nitrogen, and serum creatinine slightly im-proved in treatment group, but there was no significant difference. The pH value and TCO2 fell further and serum urea nitrogen and serum creatinine significantly improved. There was significant difference after treatment. There were no obvious changes in electrolytes and

  2. Adaptation to High Grain Diets Proceeds Through Minimal Immune System Stimulation and Differences in Extracellular Matrix Protein Expression in A Model of Subacute Ruminal Acidosis in Non-lactating Dairy Cows

    L. Dionissopoulos

    2012-01-01

    Full Text Available Problem statement: Subacute Ruminal Acidosis (SARA is a metabolic disorder affecting approximately 20% of all dairy cattle in North America. Although the presence of SARA has been described for some time, the etiology of the disorder remains uncertain. For example, many animals diagnosed with SARA seem to remodel and adapt their epithelium to accommodate the stresses imposed by SARA, but not before exacting a significant health and economic toll. Specifically, a search is on in which a desire to identify the system and associated pathways that are causative agents in the progression and development of SARA is evident. We hypothesize that adaptation to SARA is facilitated by the immune system. Approach: In order to answer of this question, 4 mature, non-lactating dairy cattle were transitioned from a High Fiber (HF; 0% grain diet to High Grain (HG; 65% grain diet. Having fed the HG diet for three weeks, the cattle were then transitioned back to the HF diet for an additional three weeks to facilitate adaptation. SARA was diagnosed by pH data only during the first week and not during the remaining weeks, indicating that adaptation to the HG diet took place within one week. Results: In this study, significant (pConclusion: These results indicate that the immune system is involved in the adaptation of the rumen epithelium to a HG diet, but to a lesser extent than was previously thought. This is the first time an attempt has been made to link the immune system and wound healing in the adaptation of the bovine rumen to a HG diet."""

  3. Clinical Analysis of 6 Patients with Type 2 of Diabetes Complicated with Lactic Acidosis and Upper Gastrointestinal Hemorrhage%2型糖尿病乳酸性酸中毒并上消化道出血6例临床分析

    吴满辉; 林小鸿

    2012-01-01

      Objective: To explore the clinical characteristics, prophylaxis and treatment to patients with type 2 of diabetes complicated with lactic acidosis and upper gastrointestinal hemorrhage. Methods: The clinical data of 8 patients with type 2 of diabetes complicated with lactic acidosis were respectively reviewed from Jan. 2000 to Dec. 2011. Results: Among the 8 cases, 6 cases suffered from upper gastrointestinal hemorrhage, and 3 cases manifested melena or haematemesis. 4 cases recovered after 7~14 days treatment and 2 cases died. Conclusions: Early treatment and prophylaxis should be used to patients with type 2 of diabetes complicated with lactic acidosis due to the high occurrence of upper gastrointestinal hemorrhage.%  目的:探讨2型糖尿病乳酸性酸中毒并上消化道出血的特点及防治方法。方法:回顾性分析2000年1月至2011年12月收治的糖尿病乳酸性酸中毒患者8例的临床资料。结果:糖尿病乳酸性酸中毒并上消化道出血的发病率为6/8,其中黑便和呕吐咖啡样物各3例,经治疗7~15天,痊愈4例,死亡2例。结论:糖尿病乳酸性酸中毒并上消化道出血发生率高,需尽早防治。

  4. Efeitos da correção da acidose metabólica com bicarbonato de sódio sobre o catabolismo protéico na insuficiência renal crônica The effects of the correction of metabolic acidosis with sodium bicarbonate on protein catabolism in chronic kidney failure

    Denise MAFRA

    2001-04-01

    Full Text Available A desnutrição protéico-energética constitui problema comum aos pacientes com insuficiência renal crônica, influenciando diretamente na sua morbi-mortalidade. A acidose metabólica tem papel no catabolismo protéico, ativando a via proteolítica proteasoma-ubiquitina, dependente de adenosina trifosfato, e conjuntamente com glicocorticóides induz uma maior atividade na desidrogenase que degrada os aminoácidos de cadeia ramificada. Esta revisão teve como objetivo descrever o mecanismo pelo qual a acidose metabólica nos pacientes com insuficiência renal crônica promove o catabolismo protéico, favorecendo assim a desnutrição, bem como avaliar os efeitos do uso de bicarbonato de sódio na correção da acidose e conseqüentemente redução do catabolismo protéico. Pesquisas mostram melhora da acidose pelo uso de bicarbonato de sódio e conseqüente redução do catabolismo protéico na insuficiência renal crônica, podendo ser esta uma conduta promissora na atenuação da desnutrição nestes pacientes.Protein-Energy Malnutrition is common among patients with chronic kidney failure, thus increasing morbidity and mortality. Several studies have shown that metabolic acidosis is a major cause of muscle protein breakdown, and recently it was attributed to ATP-dependent ubiquitin-proteasome proteolytic pathway. Acidosis, plus glucocorticoids, also respond to increasing branched-chain amino acids oxidation. In this review, the impact of metabolic acidosis on protein and amino acid metabolism is examined in order to understand its effect on lean body mass and the nutritional status of patients with chronic kidney failure. The study also observes whether or not sodium bicarbonate supplementation is beneficial to chronic kidney failure patients. In summary, there is a preliminary evidence suggesting that the correction of acidosis using sodium bicarbonate reduces protein degradation in chronic kidney failure patients, thus emerging as a

  5. 两种连续肾脏替代纠正乳酸酸中毒的临床观察%Clinical investigation of continuous venous-venous hemofiltration and continuous venous-venous hemodialysis on lactic acidosis

    彭绵; 方伟强; 蔡举瑜; 简小莉

    2014-01-01

    Objective To investigate the effect of continuous venous-venous hemofiltration (CVVH) and continuous venous-venous hemodialysis (CVVHD) on patients with lactic acidosis.Methods A total of 137 cases with lactic acidosis were included in this prospective randomized control study.lhe patients were collected from the University of Hong Kong-shenzhen Hospitall and the First Affiliated Hospital of Shantou University Medical College from April 2009 to April 2013.Inclusion criteria were patients with lactic acidosis.Exclusion criteria were patients with end-stage malignancy or terminal stage of illnesses.The patients were randomly divided into two groups:CVVH group and CVVHD group,and patients of both group were intervened with conventional treatments as well.For each group,the lactic acid and blood gas analysis were tested before CRRT,and at 4 hours,8 hours,12 hours,24 hours,and 48 hours of CRRT.The patients' mortality and length of ICU stay time were analysed and recorded.Statistical analysis was performed using SPSS 15.0software.Results When the length of time for treatment was the same,the efficacy between CVVH group and CVVHD group showed no difference in blood lactic acid level [4 h:(11.65 ± 3.39) mmol/L vs.(11.12±2.65) mmol/L; 8 h:(8.78±2.35) mmol/L vs.(8.59±2.09) mmol/L; 12 h:(6.91 ±1.67)mmol/Lvs.(6.74±1.76) mmol/L;24h:(1.66±0.39) mmol/Lvs.(1.51±0.30) mmol/L; 48 h:(0.95 ±0.24) mmol/L vs.(0.66 ±0.20) mmol/L,P > 0.05) and pH value [4 h:(6.93 ±0.14) vs.(7.05±0.09);8h:(7.04±0.10)vs.(7.12±0.05); 12h:(7.13±0.07)vs.(7.20±0.04);24h:(7.30±0.03) vs.(7.38±0.04); 48h:(7.41 ±0.03) vs.(7.46±0.02),P> 0.05].There are also no difference in the hospital mortality (11.4% vs.10.4%,P=0.854) and length ofICU stay time [(9.5 ±2.4) d vs.(8.8 ± 2.9) d,P =0.329].Conclusions Both CVVH and CVVHD can effectively correct hyperlactemia,enhance acid-base balance,contributing no differences in length of ICU stay time and patients' hospital mortality.%目的 比较持

  6. Acid-base disarrangement and gastric intramucosal acidosis predict outcome from major trauma Desarranjo ácido-base e acidose gástrica intramucosal predizem desfecho de trauma grave

    José O. Calvete

    2008-04-01

    Full Text Available INTRODUCTION: This prospective non-interventional study intended to assess the prognostic value of gastric intramucosal acidosis in patients with severe trauma admitted to a medical/surgical ICU. METHODS: Gastric tonometer catheters were introduced to measure air PCO2 level (Tonocap device in forty consecutive critically ill trauma patients. Gastric intramucosal pH, air PCO2 gradient, lactate and acid-base parameters were measured at admission and at 6, 12 and 24 h thereafter. RESULTS: The median age, mean APACHE II and SOFA scores were higher in nonsurvivors than in survivors (p 18 mmHg carried a relative risk of 4.6 for death, slightly higher than a HCO3 INTRODUÇÃO: O objetivo deste estudo prospectivo, não-intervencionista, foi avaliar o valor prognóstico da acidose gástrica intramucosal em pacientes com trauma grave admitidos numa UTI. MÉTODOS: Cateteres tonométricos gástricos foram introduzidos para medir o nível de PCO2 aéreo em 40 pacientes traumatizados. O pH gástrico intramucosal, o gradiente de PCO2 aéreo, o lactato e os parâmetros ácido-base foram medidos na admissão e 6, 12 e 24 h após a admissão. RESULTADOS: A idade mediana, o APACHE II e os escores SOFA médios foram maiores nos não-sobreviventes que nos sobreviventes (p18 mmHg acarretou um risco relativo de 4.6 para óbito, um pouco maior que um HCO3 <20 mEq/L (RR=4.29 ou um excesso de base <-2 mmol/L (RR=3.65. CONCLUSÃO: Bicarbonato, déficit de base, lactato, pH gástrico intramucosal e o gradiente de PCO2 discriminaram os sobreviventes dos não-sobreviventes de trauma. Um gradiente crítico de PCO2 aéreo acarretou o maior risco relativo para óbito após 24 horas de UTI. Fluxo sangüíneo regional inadequado detectado por um gradiente crítico de PCO2 parece contribuir para a morbidade e mortalidade de pacientes traumatizados graves.

  7. Acute renal injury and tubular acidosis caused by intravenous voriconazole%静脉应用伏立康唑致急性肾损伤及肾小管性酸中毒

    周晓明; 陈愉; 冯学威; 赵立

    2012-01-01

    1例80岁男性患者因术后感染给予亚胺培南西司他汀钠、万古霉素、卡泊芬净、米卡芬净及美罗培南,效果不佳,后治疗改为联用美罗培南1.0 g,1次/8 h静脉滴注及伏立康唑200 mg(首日剂量400 mg,1次/12 h),1次/12 h静脉滴注.第5~9天,实验室检查示血清肌酐(SCr)154~208 μmol/L,尿素氮(BUN)24.3~35.9 mmol/L,血清胱抑素C 4.54~5.44 mg/L;血pH值7.18~7.34,氯离子122~130 mmol/L,钾离子3.4~4.1 mmol/L,标准碳酸氢盐波动于12~15 mmol/L,实际碳酸氢盐 13~14 mmol/L,阴离子间隙13~14 mmol/L.尿分析示红细胞3.8~4.8个/HP,蛋白±,pH值保持在5.5.诊断为肾小管性酸中毒、急性肾损伤.第9天,伏立康唑用法改为每晨静脉滴注200 mg,每晚鼻饲给药200 mg.调整用法后第3天患者出现高氯性酸中毒、低钾血症,第11天停用伏立康唑,美罗培南继续应用.停药2 d后,患者血清SCr及BUN水平升至最高,分别达282 μmol/L及49.4 mmol/L,随后逐渐降低,分别于停药后第25天和停药后34天降至正常,血气分析各项指标于停药后第25天基本恢复正常.%An 80-year-old male; patient was given imipenem/cilastatin, vancomycin, caspofungin, micafungin, and meropenem for post-operative infections, but these had no effect. The treatment was then switched to an IV infusion of meropenem 1. 0 g every 8 hours combined with an IV infusion of voriconazole 400 mg every 12 hours on the first day followed by 200 mg every 12 hours. On days 5-9 of treatment, the laboratory tests showed the following levels; serum creatine ( SCr ) 154-208 (xmol/L, blood urea nitrogen ( BUN ) 24.3-35.9 mmol/L, serum cystatin C 4. 54-5.44 mg/L, blood pH 7. 18-7. 34, Cl" 122-130 mmol/L, K*3.4-4. 1 mmol/L, standard bicarbonate 12-15 mmol/L, actual bicarbonate 13-14 mmol/L,anion gap 13-14 mmol/L. Urinalysis revealed the following levels; RBC connt 3. 8-4. 8 cells/HP, protein ?, and pH 5. 5. Acute renal tubular acidosis and acute renal injury were

  8. Topiramate and Metabolic Acidosis in Infants

    J Gordon Millichap

    2002-08-01

    Full Text Available The acid-base metabolism was investigated in 9 infants and toddlers, aged 5 months to 2.3 years (median, 6 months, treated with topiramate (TPM for seizures at Johannes Gutenberg University, Mainz, Germany.

  9. Krebs cycle anions in metabolic acidosis.

    Bowling, Francis G; Morgan, Thomas J

    2005-10-05

    For many years it has been apparent from estimates of the anion gap and the strong ion gap that anions of unknown identity can be generated in sepsis and shock states. Evidence is emerging that at least some of these are intermediates of the citric acid cycle. The exact source of this disturbance remains unclear, because a great many metabolic blocks and bottlenecks can disturb the anaplerotic and cataplerotic pathways that enter and leave the cycle. These mechanisms require clarification with the use of tools such as gas chromatography-mass spectrometry.

  10. Brain carbonic acid acidosis after acetazolamide

    Heuser, D; Astrup, J; Lassen, N A;

    1975-01-01

    In cats in barbiturate anesthesia extracellular pH and potassium were continously recorded from brian cortex by implanted microelectrodes. Implantation of the electrodes preserved the low permeability of the blood-brain-barrier to HCO3-minus and H+ions as indicated by the development of brain aci...

  11. BUTYRATE-MEDIATED GENOMIC CHANGES INVOLVED IN NON-SPECIFIC HOST DEFENSES, MATRIX REMODELING AND THE IMMUNE RESPONSE IN THE RUMEN EPITHELIUM OF COWS AFFLICTED WITH SUBACUTE RUMINAL ACIDOSIS

    Louis Dionissopoulos

    2013-01-01

    Full Text Available Subacute Ruminal Acidosis (SARA is a disorder in cattle which can lead to chronic inflammation in the rumen epithelium, known as rumenitis. Butyrate has been shown to attenuate some of the detrimental effects of inflammatory gastroenteral disorders but the molecular mechanisms mediated by butyrate have not been defined. The objective of this study was to define the inflammatory-related genomic changes responsible for the beneficial effects of butyrate. Experimentally, 16 fistulated dairy cows at mid-lactation were fed a SARA-inducing (45% non-fiber carbohydrate diet beginning 2 days before the beginning of treatment and continuing throughout the experiment. Cows were then evenly divided into treatment groups where a carrier with (n = 8 or without (n = 8 supplemental butyrate (2.5% initial DM intake was deposited into the rumen daily for 7 days. The minimum rumen pH was higher in cows with supplemental butyrate (4.96±0.09 to 5.20±0.05, p = 0.040, but mean pH, maximum pH and the duration for which rumen pH was below 5.6 was unaffected. Free plasma Lipopolysaccharide (LPS concentration was unaffected by treatment as was the concentration of Serum Amyloid A (SAA, although the LPS Binding Protein (LBP concentration was increased by the addition of butyrate to the rumen (6.91±0.29 to 7.93±0.29 μg mL-1, p = 0.024. Of the rumen Short Chain Fatty Acids (SCFA tested, only butyrate showed a pronounced treatment effect, rising from 8.60±0.94 to 21.60±0.94 mM (p≤0.0001. Plasma Beta-Hydroxybutyrate (BHBA concentration also increased (799.50±265.24 to 3261.63±265.24 μM, p≤0.001. Butyrate infusion did not affect milk parameters (total fat, lactose, total protein and LOS; however, when related to dry matter intake, milk production efficiency was increased (p = 0.035. Microarray and qRT-PCR analyses of rumen papillae biopsies collected on day 7 found that butyrate administration affected (p≤0.05 the expression of genes

  12. G14453A mutation in mitochondrial myopathy encephalomyopathy with lactic acidosis and stroke-like episodes%MELAS综合征线粒体基因组G14453A突变分析

    郑雪飞; 张彦春; 张英; 裴珮; 马祎楠

    2015-01-01

    Objective To analyz mitochondrial DNA mutation in one case of mitochondrial myopathy,encephalopathy,lactic acidosis and stroke-like episodes (MELAS).Methods The patient,a 10-years-old boy,clinically diagnosed as MELAS.The clinical information was collected,and the normal mitochondrial mutations (such as A3243G,A8344G,T8993G/C,G13513A etc)were excluded.PCR-sequencing was used to analyz the whole-mitochondrial genome(16.6 kb),and PCR-RFLP was used to confirm the mutations.Results m.G14453A mutation was detected from the patient's peripheral blood and urine,but it was not found in his parents and 100 normal controls.The m.G14453A mutation was confirmed by PCR-RFLP,and mutation ratio of in blood was 56.8% and urine was 72.5%.The activity of complex Ⅰ was decreased(67.6 nmol · min-1 · mg-1).This was the first report that m.G14453A mutation could lead to MELAS in China according www.mitomap.org web and NCBI.Conclusion m.G14453A mutationis one of the causative mutations in MELAS,but the mechanism of the mutation should be studied in future.%目的 分析1例MELAS综合征线粒体基因组突变情况.方法 2012年11月北京大学第一医院儿科临床拟诊为MELAS的1例男性患儿,详细收集该患儿临床资料,排除常见线粒体点突变(如A3243G、A8344G、T8993G/C、G13513A等)后,应用聚合酶链式反应-直接测序法分析16.6 kb的线粒体基因组全序列,并应用聚合酶链式反应-限制性片段长度多态性分析(PCR-RFLP)对突变进行验证.结果 经线粒体基因组全测序后,在患者的外周血和尿沉渣线粒体DNA (mtDNA)均检测出G14453A点突变,父母及100名健康对照的外周血mtDNA未发现携带此突变.经PCR-RFLP方法验证,患者外周血mtDNA中G14453A突变比例为56.8%,尿沉渣mtDNA中G14453A突变比例为72.5%.患者线粒体呼吸链复合物Ⅰ活力降低,为67.6 nmol·min-1·mg-1.参考www.mitomap.org网站及NCBI数据库,本例mtDNA G14453A突变所致MELAS综合征

  13. MELAS综合征的临床、病理和动态影像学表现%Clinical, pathological and dynamic imaging findings of patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes

    贾守强; 张颖颖; 解丙坤; 王敏; 李莹

    2012-01-01

    Objective To investigate the clinical, pathological and dynamic imaging characteristics of patients with mitochondrial myopathy,encephalopathy,lactic acidosis and stroke-like episodes (MELAS). Methods A retrospective analysis was performed on the clinical,pathological and dynamic imaging data of 10 patients with MELAS confirmed by muscle biopsy. Results The clinical manifestations included headache,seizures,nausea,vomiting,nystagrnus and visual disturbances.CT showed less lesions,and MRI could clearly show multiple lesions which mainly located in the temporal,parietal,occipital cortex and sub-cortex,having multifocal,asymmetric,migratory characterstics and not following the distribution of blood vessels.MRA showed no significant stenosis,and the lesion showed hyperperfusion and vasogenic edema,and Lae peak was visible.Muscle biopsy showed ragged red fiber optical microscope (RRF) and strongly SDH-reactive vessel (SSV),and electron microscope showed increased mitochondria number, and abnormal size and shape. Conclusion MELAS has certain clinical and imaging characteristics; by combining the muscle biopsy,we can diagnose the disease early and make differential diagnosis.%目的 探讨线粒体脑肌病伴乳酸血症和脑卒中发作(MELAS综合征)的临床、病理和动态影像学表现特点. 方法 回顾性分析经肌肉活检病理证实的10例MELAS综合征患者的临床、病理及动态影像学资料. 结果 MELAS综合征患者的主要临床表现为头痛、癫痫、恶心呕吐、眼球震颤、视力障碍.CT显示病变较差,MR能清晰显示病变,病变多位于颞叶、顶叶、枕叶皮层及皮层下,呈脑回状,具有多灶性、非对称性、游走性、不按血管分布特点,MRA多无明显血管狭窄,病变区呈现高灌注和血管源性水肿,MRS可见乳酸(Lac)峰.肌肉病理活检光镜下显示破碎红纤维、强阳性血管,电镜下见线粒体数量增多、大小和形态异常. 结论 MELAS综合征的临床和影

  14. Effect of propofol on intracellular pH of erythrocytes in rats with acute or chronic metabolic acidosis%异丙酚对急性和慢性代谢性酸中毒大鼠红细胞内pH的影响

    袁媛; 张诗海; 姚尚龙; 王贤东; 王冬

    2008-01-01

    Objective To investigate the effect of propofol on erythrocyte intracellular pH (phi) in rats with acute or chronic metabolic acidosis. Methods Adult Wistar rats of both sexes weighing 290-330 g were used in this study. In the first part, acute metabolic acidosis was induced by 0.15 mol/L HCI (4 mmol/kg) infusion via tail vein for 4 h and then forty rats were randomly divided into 4 groups ( n = 10) : control group (F) 10% fat emulsion 10 ml·kg-1·h-1 , acetazolamide 20 mg·kg-1·h-1 group (Z), propofol 10mg·kg-1·h-1 group (P1) and propofol 20 mg·kg-1·h-1 group ( P2 ). In the second part, chronic metabolic acidosis was induced by drinking water containing NH4 CI 0.28 mol/L (535 mg/kg) for 5 days and then forty rats were randomly divided into 4 groups ( n = 10) receiving the same drugs respectively as that of the first part. Blood samples were taken from femoral artery immediately before and at 1, 3 and 6 h during drug administration for determination of carbonic anhydrase (CA) activity, phi and sedinm-hydrogan exchanger-1 (NHE-I) activity. Results In the first part, compared with group F, CA activity was significantly decreased after drug administration in group Z ( P 0.05).第二部分与F组比较,Z组、P1组和P2组pHi和CA活性降低(P0.05).结论 静脉输注异丙酚10、20 mg·kg-1·h-1可导致慢性代谢性酸中毒大鼠红细胞phi降低,其机制与抑制CA活性有关;而对急性代谢性酸中毒大鼠红细胞pHi无影响.

  15. 桥本甲状腺炎合并干燥综合征肾小管酸中毒致低钾血症的临诊应对%Approach to the patient with hypokalemia caused by Hashimoto′s thyroiditis associated with primary Sjogren′s syndrome and renal tubular acidosis

    张洪梅; 张伟伟; 李晓永; 陈寒蓓; 杨震; 钮忆欣; 苏青

    2016-01-01

    Hypokalemia is a common clinical symptom. It is quite important to clarify the cause of hypokalemia. Autoimmune thyroid disease and primary Sjogren syndrome ( pSS ) have a common genetic predisposition. The coexistence of both diseases is frequent. Renal tubular acidosis ( RTA) is one of the causes of hypokalemia, which can be primary and secondary to other diseases in etiology. Primary RTA is more common in children. As for adults, RTA is often secondary to pSS. In this paper, we reported a case of hypokalemia caused by Hashimoto’s thyroiditis associated with primary Sjogren’s syndrome and renal tubular acidosis in order to call attention to the special cause and treatment of hypokalemia.%低钾血症临床上较为常见,明确低血钾的原因至关重要。自身免疫性甲状腺疾病及干燥综合征有共同的遗传易感性,往往同时发生,肾小管性酸中毒为低钾血症病因之一,按病因分原发性和继发性,原发性多见于儿童,成人以继发性肾小管酸中毒多见,多继发于原发性干燥综合征。本文详细描述了1例桥本甲状腺炎合并干燥综合征肾小管酸中毒导致低钾血症的诊疗过程,以使临床医生重视低钾血症的病因,及时诊治。

  16. 线粒体脑肌病伴高乳酸血症及卒中样发作综合征的病因及病机研究进展%Research Progress of Mitochondrial Encephalopathy with Lactic Acidosis and Stroke-Like Episodes in Etiopathogenisis and Pathogenesis

    陈燕; 曹秉振

    2011-01-01

    Mitochondrial encephalopathy with lactic acidosis and stroke - like episodes ( MELAS syndrome ) is the most common form of mitochondrial dieases and coused by an A to G transition mutation at position 3243 of the mitochondrial genome. The disease is maternal inheritance , usually involved central nerve system and skeletal muscle. The most frequent clinical manifestations were headache, fatigue or movement intolerance, mental impairment, stroke - like episodes and lactic acidosis.In recent years the pathogenesis, genetic mutation characteristics, pathology, clinical manifestation of MELAS svndrome has made great progress. This review emphatically discusses the etiology and pathogenesis of the disease.%线粒体脑肌病伴高乳酸血症及卒中样发作(MELAS)综合征是人类线粒体疾病中最常见的表现形式,该病主要是由线粒体基因组第3243位点的腺嘌呤突变为鸟嘌呤所致.呈母系遗传,主要累及中枢神经系统和骨骼肌.头痛、抽搐、运动耐受差、智能障碍、脑卒中样发作、血乳酸水平升高为本组患者的主要临床表现.近年来MELAS综合征的发病机制、基因突变特点、病理改变、临床表现等方面取得了较大进展,本文着重讨论该病的病因及发病机制.

  17. Avaliação da acidose metabólica em pacientes graves: método de Stewart-Fencl-Figge versus a abordagem tradicional de henderson-hasselbalch Assessment of metabolic acidosis in critically ill patients: method of Stewart-Fencl-Figge versus the traditional henderson-hasselbalch approach

    Manuela Borges Gavaza Barbosa

    2006-12-01

    of metabolic acidosis giving emphasis to the of Stewart-Fencl-Figge method versus the traditional method of Henderson-Hasselbalch. CONTENTS: Metabolic acidosis is a common issue in critically ill patients, an important cause of myocardial contractility depression and sensible marker of impaired tissue oxygenation. Traditionally, is evaluated by the Henderson-Hasselbalch approach in which an arterial blood sample provides information about the presence and type of acid base disturbance. However, this method is not always capable to explain the causes of the metabolic acidosis and, therefore, several studies have explored mechanisms to improve its interpretation. The Stewart-Fencl-Figge method calculated through a mathematical formula, where in addition to arterial blood gas levels, serum levels of electrolytes, lactate and albumin are used, supplies trustworthy information allowing detection of mixed metabolic abnormalities and quantification of the magnitude of each component, mainly in patients with multiple organic dysfunctions. In these individuals, the presence of unmeasured anions in the plasma is an important mechanism of metabolic acidosis and its early detection fundamental to avoid deleterious effect on the organism. CONCLUSIONS: The traditional Henderson-Hasselbalch approach fails in analyzing the underlying mechanisms of metabolic acidosis and possesses many variables that intervene with its result especially in the critically ill patient. The Stewart-Fencl-Figge method offers a broader analysis of metabolic acidosis, indicating its mechanisms and guiding a better therapeutically strategy. As an alternative, the albumin-corrected and lactate-corrected anion gap seems to be as useful as the Stewart approach in identifying the unmeasured anions.

  18. 15例MELAS综合征的临床、肌肉病理及基因分析%Clinical manifestation, muscle pathology and gene analyses of 15 patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episode

    王娟; 喻绪恩; 吴君仓; 程楠; 王训; 胡纪源; 韩咏竹; 杨任民

    2015-01-01

    Objective To conclude the clinical features,pathologic changes and gene mutations of mitochondrial myopathy,encephalopathy,lactic acidosis and stroke-like episode (MELAS).Methods A restrospective analysis was carried out on the clinical manifeststions,muscle pathologies changes and gene results of 15 patients with MELAS,admitted to our hospital from December 2008 and March 2015.Results In 15 MELAS patients,6 were male and 9 were female.The onset age ranged from 3 to 38 years,with average age of 15.0±9.1 years.Epilepsy as first symptom appeared in 6 patients,headache as first symptom in 4 and vision loss as first symptom in 2.The epilepsy in the course was noted in 14 patients,headache symptoms in 13 and stroke-like onset in 7.Brain MR imaging showed significant abnormality in 13 patients,mainly presented as occipital lobe in 10 patients,temporal lobe in 7 and parietal lobe in 5.The 15 patients were found strongly SDH-reactive blood vessels (SSV) in muscle tissue pathological staining and the SSV of CCO(+),and ragged-red fober in 11 patients.Genetic test indicated mtDNA A3243G mutation in 13 patients.Conclusion The clinical manifestations of MELAS mainly include epilepsy,headache and stroke-like onset;the asymmetry occipital,temporal and parietal lobe damage are showed in the brain MRI;SSV in muscle pathological changes is most common in MELAS;the A3243G mutation in the mitochondrial DNA is the hotspot regin of MELAS.%目的 归纳总结线粒体脑肌病伴乳酸中毒和卒中样发作(MELAS)综合征的临床表现、肌肉病理特点及基因突变热点. 方法 回顾性分析安徽中医药大学神经病学研究所附属医院神经内科自2008年12月至2015年3月收治的经肌肉病理检查和基因检测确诊的15例MELAS综合征患者的临床表现、肌肉病理特点和基因检测情况. 结果 15例患者中男6例,女9例;发病年龄3~38岁,平均(15.0±9.1)岁;以癫痫为首发症状6例,其次头痛4例及视力下降2

  19. Electrophysiological effects of lidocaine on myocardial tissue in guinea-pig left ventricular outflow tract under conditions of hypoxia, acidosis and treatment with epinephrine%利多卡因对低氧、酸中毒及肾上腺素条件下豚鼠左心室流出道心肌组织电活动的影响

    赵兰平; 王雪芳; 杜会博; 薛淑芳; 陈彦静

    2013-01-01

    AIM; To study the electrophysiological effects of lidocaine on the myocardial tissue in guinea-pig left ventricular outflow tract under the conditions of hypoxia, acidosis and treatment with epinephrine. METHODS: The action potentials of pacemaker cells in guinea-pig left ventricular outflow tract were recorded by conventional technique with intracellular microelectrodes. The effects of lidocaine on the spontaneous slow response potentials were investigated under the conditions of hypoxia, acidosis and treatment with epinephrine (EPI). RESULTS: Lidocaine markedly decreased the rate of pacemaker firing ( RPF) , the velocity of diastolic depolarization ( VDD) , the maximal rate of depolarization ( Vmax), the maximal diastolic potential (MDP) and the amplitude of action potential ( APA). Lidocaine also shortened the 50% and 80% of duration of action potential (APD50 and APD80). At the concentrations from 0.1 μmol/L to 10 μmol/L, the effects of lidocaine were more significant. Under the condition of hypoxia and perfusion with deprived glucose content for 15 min, VDD, RPF, Vmax, MDP and APA significantly decreased, and APD50 notably shortened. Under the condition of hypoxia, lidocaine at 1 μmol/L significantly decreased VDD, RPF, Vmax and APA as compared with the cells treated with hypoxia only. Perfusion with pH 6.8 solution for 10 min, VDD, RPF, Vmax and APA significantly decreased, MDP notably increased, and APD50 and APD80 markedly shortened. Under the condition of acidosis for 10 min, lidocaine significantly decreased VDD, RPF and Vmax, and lengthened APD50 and APD80 as compared with the cells under the condition of acidosis alone. Perfusion with EPI at 10 μmol/L for 10 min resulted in significant increases in VDD, RPF, Vmax, MDP and APA, and notable shortenings of APD50 and APD80, were also observed. Compared with 10 μmol/L EPI group, 1 μmol/L lidocaine +10 μmol/L EPI significantly reduced VDD, RPF, MDP and APA, and lengthened APD50, and APD80. CONCLUSION

  20. Unmeasured anions account for most of the metabolic acidosis in patients with hyperlactatemia Ânions não mensuráveis são responsáveis pela maior parte da acidose metabólica de pacientes com hiperlactatemia

    Alexandre Toledo Maciel

    2007-02-01

    Full Text Available PURPOSE: To characterize the different components of metabolic acidosis in patients with hyperlactatemia in order to determine the degree to which lactate is responsible for the acidosis and the relevance that this might have in the outcome of these patients. METHODS: Arterial blood gas, arterial lactate, Na+, K+, Ca2+, Mg2+, Cl-, phosphate, albumin, and creatinine were measured on admission to make a diagnosis of the acid-base disturbances present. Intensive Care Unit and in-hospital mortality were also recorded. RESULTS: A total of 58 patients with hyperlactatemia were included. They usually had a mild acidemia (pH 7.31 ± 0.12 and a significantly high Standard Base Deficit (7.6 ± 6.7 mEq/L. In addition to lactate (4.3 ± 2.3 mEq/L, chloride (106.9 ± 9.5 mEq/L and unmeasured anions (8.6 ± 5.0 mEq/L accounted for the metabolic acidosis. Unmeasured anions were primarily responsible for the acidosis in both Intensive Care Unit survivors and nonsurvivors (44.7% ± 26.0% and 46.0% ± 17.5%, respectively, P = 0.871. Lactate contributed in similar percentages to the acidosis in both groups (23.0% ± 11.8% and 24.2% ± 9.7% in Intensive Care Unit survivors and nonsurvivors, respectively; P = 0.753. Correlation between Standard Base Deficit and lactate was found only in Intensive Care Unit nonsurvivors (r = 0.662, P OBJETIVO: Caracterizar os diferentes componentes da acidose metabólica de pacientes com hiperlactatemia de modo a verificar o quanto o lactato é responsável pela acidose e a relevância que isso possa ter no prognóstico desses pacientes. MÉTODOS: Gasometria arterial com dosagem de lactato, Na+, K+, Ca2+, Mg2+, Cl-, fosfato, albumina e creatinina séricas foram coletados no momento da admissão para fazer o diagnóstico dos possíveis distúrbios ácido-básicos presentes. Mortalidade na UTI e mortalidade hospitalar foram avaliadas. RESULTADOS: Um total de 58 pacientes com hiperlactatemia foram incluídos. Eles tinham na média uma

  1. Protective Effects of Pomegranate Peel Polyphenol Extract against Related Harmful Factors of Subacute Ruminal Acidosis%石榴皮多酚提取物对亚急性瘤胃酸中毒相关有害因子的影响

    杜宇; 王之盛; 董利锋

    2011-01-01

    This study established a in vitro subacute ruminal acidosis ( SARA) model to evaluate the effects of different supplemental levels of pomegranate peel polyphenols extract (PPPE) on related harmful factors of subacute ruminal acidosis. Single factor design was used for the trial, and 3 supplemental levels of PPPE were design, which were 0, 4. 5% and 9.0% of fermentation substrate, respectively. Each supplemental level had 5 replicates. The results showed as follows; with prolonged fermentation time, the pH of fermentation broth was gradually decreased. The PPPE supplementation could retard the pH decreased, and the pH of fermentation broth at the 6th, 12th and 18th h in the group containing 4. 5% PPPE was significantly higher than that in the group containing 9.0% PPPE (P <0.05). The contents of endotoxin and histamine in the fermentation broth were significantly decreased by PPPE supplementation (P <0.05), and showed a dose-dependant effect. After supplemented PPPE, the volatile fatty acid contents were all decreased to different extent, and significant effects were found in some time points (P <0. 05). The results indicate that PPPE supplementation can effectively relieve SARA, and the 4. 5% supplemental level has a better effect.%本文通过建立体外亚急性瘤胃酸中毒(subacute ruminal acidosis,SARA)模型,研究不同添加水平的石榴皮多酚提取物(pomegranate peel polyphenol extract,PPPE)对SARA相关有害因子的影响.试验采用单因素试验设计,PPPE设3个添加水平,即分别为发酵底物质量的0、4.5%和9.0%,每个水平设5个重复.结果表明:随发酵时间的延长,各组发酵液的pH逐渐下降,添加PPPE可减缓pH的下降,且PPPE添加量为4.5%的组发酵液pH在6、12、18 h时显著高于添加量为9.0%的组(P<0.05).添加PPPE显著降低发酵液中内毒素和组胺含量(P<0.05),且呈现剂量效应.添加PPPE后,发酵液中各挥发性脂肪酸含量均有不同程度地降低,并

  2. 儿童线粒体脑肌病伴高乳酸血症和卒中样发作综合征2例报告%Children with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes syndrome:two cases report

    唐志慧; 罗强

    2015-01-01

    ObjectiveTo discuss the clinical features, diagnosis and treatment of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome in children.Methods The clinical features and treatment process of two children with MELAS were retrospectively analyzed.ResultsThe main clinical features of MELAS were stroke-like epi-sodes, seizure, visual anomaly and lactic acidosis. Cephalic MRI ifndings performed during episode periods were in accord with the typical radiographic features of MELAS. Gene testing on the two children and their mothers showed the point mutation of A3243G in mitochondrial genome. The symptoms were improved signiifcantly after energy supply and corticosteroid treatment. Conclusions MELAS syndrome is easy to be misdiagnosed due to the varied clinical features. The diagnosis depends on the musclebiopsy and gene testing. Corticosteroid therapy is effective for MELAS syndrome.%目的:探讨线粒体脑肌病伴高乳酸血症和卒中样发作综合征(MELAS)的诊断与治疗。方法回顾性分析2例MELAS患儿的临床特征及诊疗过程。结果2例患儿主要临床表现为卒中样发作、抽搐、视物模糊、高乳酸血症;发作期头颅磁共振成像结果符合典型的MELAS综合征影像学表现;基因测序存在mtDNA的A3243G点突变;改善供能及皮质激素治疗后症状明显改善。结论 MELAS临床症状复杂多样,血乳酸及头颅磁共振成像检查有助临床诊断,确诊需要肌肉活检或基因检测,皮质激素治疗有效。

  3. 6例线粒体脑肌病伴高乳酸血症和卒中样发作的临床分析%Clinical Features of Mitochondrial Myopathy,Encephalopathy,Lactic Acidosis and Stroke-like Episodes(MELAS):A Report of 6 Cases

    郭章宝; 叶茂斌; 陈博; 徐莉; 薛峥; 卜碧涛; 唐荣华

    2013-01-01

    Objective To examine the clinical characteristics of mitochondrial myopathy,encephalopathy, lactic acidosis and stroke-like episodes(MELAS) in an attempt to facilitate early diagnosis and treatment. Methods Data of clinical manifestations , imaging,pathology and genetics of 6 cases of MELAS were retrospectively analyzed. Results The most common clinical manifestations of MELAS in the 6 patients were limb weakness, stroke-like episodes, seizure, visual anomaly and lactic acidosis. CT or MRI showed that the lesions in the 6 patients were not distributed in accordance with cerebral vessels. The muscle biopsy showed increased mitochondria with irregular appearance and ragged red fibers(RRF). Gene testing on 2 patients showed mtDNA A324 3G mutation. The typical MRS showed increased and inverted lactate peak. Conclusion MELAS is characterized by multiple and complex clinical manifestations and the confirmative diagnosis depends on the results of muscle biopsy and gene testing. Imaging examination(especial MRS) may facilitate early diagnosis of MELAS and differential diagnosis.%目的 分析线粒体脑肌病伴高乳酸血症和卒中样发作(MELAS)的临床特征,为早期诊断和及时治疗提供依据.方法 对6例确诊为MELAS患者的临床表现,影像学、病理及遗传学特征进行回顾性分析.结果 肌无力、卒中样发作、抽搐、视物模糊、血乳酸增高是该组患者的主要临床表现.6例患者CT或MRI检查显示与血管分布不一致的病灶,肌肉活检组织的电镜观察发现线粒体增多、形态不规则,病理均见破碎红纤维(RRF).2例基因检测发现A3243G点突变,典型病例患者磁共振波谱(MRS)可见升高和倒置的乳酸峰.结论 MELAS临床表现多样,确诊有赖于肌肉活检或基因检测,影像学检查(尤其是MRS)对于MELAS的早期诊断和鉴别诊断有一定的价值.

  4. Influência da forma de indução à acidose na determinação da intensidade de lactato mínimo em corredores de longa distância Influence of the acidosis induction manner in the determination of minimal lactate threshold in endurance runners

    Vanessa Santhiago

    2008-08-01

    Full Text Available O objetivo principal deste estudo foi verificar se diferentes formas de indução à acidose interferem na determinação da intensidade do lactato mínimo (LACmin em corredores de longa distância. Desse modo, 14 corredores de provas fundas do atletismo participaram do estudo. Os atletas realizaram três protocolos: 1 teste incremental em esteira rolante, com incrementos de 1km.h-1 a cada três minutos até a exaustão, para a determinação das intensidades de limiar anaeróbio (OBLA, de limiar aeróbio (Laer, consumo máximo de oxigênio (VO2max e intensidade de consumo máximo de oxigênio (vVO2max; 2 teste de lactato mínimo em pista de atletismo (LACminp, que consistiu de dois esforços máximos de 233m na pista de atletismo com intervalo de um minuto entre cada repetição, com oito minutos de recuperação passiva, seguido de um teste incremental semelhante ao do protocolo 1; e 3 teste de lactato mínimo em esteira rolante (LACmine, constituído de dois esforços máximos de um minuto e 45 segundos com intervalo de um minuto, na intensidade de 120% da vVO2max, seguido dos mesmos procedimentos do protocolo 2. Foram coletadas amostras de sangue do lóbulo da orelha ao final de cada estágio em todos os protocolos e no 7º minuto de recuperação passiva dos testes de LACmine e LACminp. A análise de variância (ANOVA mostrou que ocorreram diferenças significativas entre as intensidades de LACmine (13,23 ± 1,78km.h-1 e OBLA (14,67 ± 1,44km.h-1. Dessa maneira, a partir dos resultados obtidos no presente estudo, é possível concluir que a determinação da intensidade correspondente ao lactato mínimo é dependente do protocolo utilizado para a indução à acidose. Além disso, o LACmine subestimou a intensidade correspondente ao OBLA, não podendo ser utilizado para a mensuração da capacidade aeróbia de corredores fundistas.The purpose of this study was to verify if different induction forms to the acidosis can interfere in the

  5. Subdiaphragmatic venous stasis and tissular hypoperfusion as sources of metabolic acidosis during passive portal-jugular and caval-jugular bypasses in dogs Estase venosa subdiafragmática e hipoperfusão tissular como fontes de acidose metabólica durante desvios porta-jugular e cava-jugular passivos em cães

    Antônio Roberto de Barros Coelho

    2000-06-01

    Full Text Available Subdiafragmatic venous decompression during anhepatic stage of canine orthotopic liver transplantation attenuates portal and caval blood stasis and minimize hipoperfusion and metabolic acidosis observed with occlusion of portal and caval veins. During two hours, six dogs submitted to portal-jugular and caval-jugular passive shunts, with maintenance of arterial hepatic flow, were evaluated for pH, carbon dioxide tension (PCO2, base deficit (BD and oxygen tension (PO2 in portal, caval and systemic arterial blood, as well as for increments of BD (DBD in portal and caval blood. With a confidence level of 95%, the results showed that: 1. There were not changes of pH anDBD in portal and systemic arterial blood in the majority of studied times; 2. There was metabolic acidosis in caval blood; 3. The negative increments of BD (DBD were higher in caval blood than in splancnic venous blood at T10, T30 and T105; and, 4. Deoxigenation of portal and caval blood were detected. Acid-base metabolism and oxigenation monitoring of subdiaphramatic venous blood can constitute an effective way to evaluate experimental passive portal-jugular and caval-jugular bypass in dogs.A descompressão venosa subdiafragmática durante a fase anhepática do transplante ortotópico de fígado em cães atenua a estase de sangue nas veias Porta e Cava Inferior e minimiza a hipoperfusão tissular e a acidose metabólica observadas na oclusão dessas veias. Durante duashoras, seis cães submetidos a desvios porta-jugular e cava-jugular passivos, com permanência do fluxo arterial hepático, foram avaliados através de pH, PCO2, DB e PO2 no sangue portal, da Veia Cava Inferior e arterial sistêmico, bem como por incrementos de DB (DDB no sangue portal e da Veia Cava Inferior. Os resultados obtidos permitem concluir com uma confiança de 95% que: 1. Não foram constatadas alterações de pH e DB no sangue portal e arterial sistêmico na maioria dos tempos estudados; 2. Houve acidose

  6. 原发性干燥综合征合并肾小管酸中毒并发骨软化症的临床特征及诊治%Clinical Manifestation and Diagnosis of Osteomalacia in Patients with Primary Sjgren's Syndrom and Renal Tubular Acidosis

    李凤翱; 马中书; 邱明才; 韩红玲; 贾红蔚; 崔瑾; 汤绍芳; 戴晨琳; 高桦; 郑方遒; 朱梅

    2012-01-01

    Objective To summarize the clinical manifestations and treatment of osteomalacia in patients with primary Sjogren's Syndrom and renal tubular acidosis. Methods The clinical data of 20 patients suffered from this disease and admitted in our hospital from 2003 to 2008 were analyzed retrospectively. Results All these 20 patients experienced decayed tooth, tiredness, and boneache. Among them 15 patients had had thirsty feelings and 10 suffered from scheroma. According to the clinical manifestations, bone X - ray findings, and bone mineral density, these 20 patients were divided into severe bone disease group ( n = 10 ) and mild bone disease group ( n = 10 ). The comparison of rheumatic immunological index between these two groups concluded that the positive rates of SSA and SSB and the concentration of globulin in severe group were higher than those in mild group, although the difference was not statistically significant ( P > 0. 05 ). Antinuclear antibody, rheumatoid factor, andγglobulin in severe group were significantly higher than those in mild group ( P <0. 05 ). Infiltration of lympocytes and deposition of immunoglobulin complexes were found both in kidney and muscular biopsy tissues. Tiredness and boneache were resolved after treatment. Conclusion For osteomalacia caused by the combination of primary Sjogren's syndrome and renal tubular acidosis , active immunosuppressive treatment and supplementation of large - dose vitamin D in active form may be feasible in addition to conventional acidity correction and calcium supplementation,%目的 探讨原发性干燥综合征、肾小管酸中毒并发骨软化症的临床特点和治疗效果.方法 回顾性分析天津医科大学总医院内分泌科2003-2008年收治的20例原发性干燥综合征、肾小管酸中毒并发骨软化症患者的临床资料.结果 20例患者均有龋齿、乏力、骨痛,15例患者有口干症状,10例患者有眼干症状.依据临床表现、骨X线和骨密度检查结果,20

  7. Série de treinamento intervalado de alta intensidade como índice de determinação da tolerância à acidose na predição da performance anaeróbia de natação High intensity interval training series as indices of acidosis tolerance determination in swimming anaerobic performance prediction

    Rafael Deminice

    2007-06-01

    Full Text Available O objetivo do presente estudo foi determinar a tolerância à acidose através de uma série de nados intervalados de alta intensidade e relacionar com a velocidade de limiar anaeróbio (VLan, concentração de lactato sanguíneo de pico ([Lac]pico, capacidade de trabalho anaeróbio (CTA, freqüência de braçada (fB, comprimento de braçada (CB e índice de braçada (IB na predição da performance de 100m de natação. Dez nadadores realizaram seis nados máximos de 100m no estilo crawl com intervalo de seis minutos. Amostras de sangue foram coletadas cinco minutos após cada nado para posterior análise de lactacidemia ([Lac]. Através da razão entre [Lac] e os respectivos tempos de execução dos seis nados, determinou-se a tolerância à acidose (TA. O número de braçadas realizadas durante os seis esforços foi anotado para determinação da fB, CB, IB. Um nado máximo de 100m foi utilizado como parâmetro de performance (P100 e amostras de sangue foram coletadas para determinação da concentração de lactato sanguíneo de pico ([Lac]pico. Três esforços progressivos de 400m foram realizados para determinação da VLan correspondente à concentração fixa de 3,5mM de lactato. Esforços máximos de 200 e 400m foram realizados para determinação da CTA por regressão linear (coeficiente linear. Os resultados apresentaram significativas correlações (p The aim of the present study was to determine the acidosis tolerance through one high intensity interval swim serie and to relate with anaerobic threshold speed (ATS, blood lactate peak concentration ([Lac]peak, anaerobic work capacity (AWC, stroke rate (SR, stroke length (SL and stroke index (SI in swimming 100 m performance prediction. Ten swimmers performed six maximal swims along 100 m by crawl style with 6 minutes for a rest. Blood samples were taken 5 minutes before each swim for lactate analyses ([Lac]. Through the division of the [Lac] for the time to complete the 6 swims, was

  8. Mitochondrial myopathy,encephalopathy,lactic acidosis and stroke-like episodes:clinical manifestations and gene mutation analysis%线粒体脑肌病伴有高乳酸血症和卒中样发作综合征的临床及基因突变分析

    林菡; 宋兴旺; 易咏红; 陆雪芬; 廖卫平

    2009-01-01

    Objective To investigate the characteristic clinical manifestations and gene mutations in mitochondrial myopathy,encephalopathy,lactic acidosis and stroke-like episodes(MELAS).Methods The clinical manifestations,imaging data and muscle pathologies of a patient with MELASwere analyzed,and the mutations in the mitochondrial DNA were investigated using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)and gene sequencing.Results MELAS was clinically characterized by such symptoms as recurrent headache and vomiting,stroke-like episodes,epilepsy,intolerance to exercise,short stature,nerve deafness and lactic acidosis.CT scan demonstrated bilateral basal ganglia calcification,and magnetic resonance imaging(MRI)showed abnormal signals in the occipital lobe.Proton magnetic resonance spectroscopy revealed a visible peak of lactic acid in the area with T2-weighted abnormal signals,while a low peak of lactic acid was identified in the area with T2-weighted normal signals.Muscle biopsy did not find any mitochondrial anomalies.A heterozygous A 3243G mutation in the mitochondrial DNA was found in this patient.Conclusion The diagnosis of MELAS relies on a comprehensive analysis of the clinical features,imaging findings,pathological results and genetic analysis.Normal pathological results do not rule out the possibility of MELAS.Mitochondrial DNA mutation analysis should be carried out as a routine procedure for identifying MELAS.%目的 探讨线粒体脑肌病伴有高乳酸血症和卒中样发作综合征(MELAS)的临床及基因突变特征. 方法 对1例MELAS患者的临床表现、影像学、肌肉病理特点进行分析,并用PCR-RFLP结合基因测序方法进行线粒体基因突变分析. 结果 患者主要临床表现为发作性头痛和呕吐、反复卒中样发作、癫痫、运动不耐受、身材矮小、神经性耳聋、乳酸水平升高等.脑CT见双侧基底节多个钙化灶,MRI见枕叶异常信号,1H-MRS见T2WI

  9. 醋酸钠林格注射液纠正失血性休克代谢性酸中毒的临床效果%Analysis of the clinical effect of acetate ringers in correcting metabolic acidosis in patients with hemorrhagic shock

    刘冬; 曹志然; 刘斌

    2015-01-01

    Objective To compare the effects of acetate ringers solution and lactated ringers solution on metabolic acidosis in patients with hemorrhagic shock. Methods 50 patients with hemorrhagic shock were divided equally into 2 groups randomly(n=25): the acetate ringers solution(group A) and lactated ringers group(group L). Changes of arterial blood gas and volume of NaHCO3 before and 1, 2, 3, 4h after induction respectively were observed. Results There were no statistics difference in the ASA grade, operation time, the volume of transfusion during operation and hemorrhage volume of both groups(P﹥0.05). pH in group A changed at time point of T3 respectively compared to group L(P0.05)。A组在T3时间点较L组pH值显著改善(P<0.05);A组T2时间点LAC值较T0点显著降低(P<0.05),L组T2、T3、T4时间点LAC值较T0点明显升高(P<0.05),且在T2、T3、T4时间点LAC值L组较A组显著升高(P<0.05);NaHCO3用量A组比L组减少(P<0.05);BE值两组间比较无显著差异。结论在失血性休克患者液体复苏过程中,醋酸钠林格注射液可使用更少NaHCO3用量、更快速改善血pH值,降低血乳酸水平。

  10. 阿德福韦酯致肾小管酸中毒并低磷骨软化症3例临床分析%Renal tubular acidosis and secondary hypophosphatemic osteomalacia caused by adefovir dipivoxil: 3 cases report

    吴丹; 巴建明; 谷伟军; 金楠; 杨国庆; 母义明; 窦京涛; 吕朝晖

    2012-01-01

    Objective To analyze the clinical characteristics and treatment of 3 patients with renal tubular acidosis ( RTA ) and secondary hypophosphatemic osteomalacia caused by adefovir dipivoxil, and to raise awareness of renal tubular dysfunction caused by adefovir dipivoxil. Methods The clinical data and treatment of 3 patients with RTA and hypophosphatemic osteomalacia caused by adefovir dipivoxil were reviewed and summarized. Results Three patients were hospitalized with the chief complaint of progressive systemic aggravation of bone pain. When they came to our hospital, they all lied in bed and could hardly walk. Laboratory tests showed acidic blood ( pH = 7. 329 - 7. 381 ), alkaline urine ( pH = 6. 5 - 8. 0 ), hypophosphatemia ( 0. 42 - 0. 68 mmol/L ), hypokalemia ( 3. 08 - 3. 5mmol/L ), higher level of alkaline phosphatase ( 185. 1 - 247. 7U/L ), and normal serum calcium and PTH. They all had osteoporosis. Case 1 was diagnosed as renal tubular acidosis, and case 2 and case 3 were diagnosed as Fanconi syndrome because they had glycosuria, proteinuria, and aminoaciduria. All the 3 patients had secondary hypophosphatemic osteomalacia. According to their medical history, laboratory tests, and the history of long-term oral administration of adefovir dipivoxil, we considered that the injury of renal tubular was caused by adefovir dipivoxil. The initial treatment was to withdraw adefovir dipivoxil and to use other antivirals instead.Effective managements including the supplementation of neutral phosphorus mixture, active vitamin D, potassium citrate, and sodium bicarbonate were given according to the different biochemical abnormality. The follow-up showed that their clinical symptoms ameliorated significantly, and bone pain relieved. They could walk without any help. The biochemical indicators gradually returned to normal. Conclusion Impairment of renal function during the treatment of adfovir dipivoxil for patients with hepatitis B is not rare in clinical practice. Renal

  11. 代谢性酸中毒诱导新生大鼠视网膜新生血管缺氧诱导因子-lα的表达及其意义%Expression and significance of hypoxia-inducible factor-1α in retinal neovascularization induced by metabolic acidosis in newborn rats

    张玉真; 王娟; 乔立兴; 蒋犁

    2011-01-01

    Objective To investigate the expression and significance of hypoxia-inducible factor-1α (HIF-1α) in the retinal neovascularization by metabolic acidosis in newborn rats. Methods One hundred and twenty newborn SD rats were randomly divided into acidosis (experiment) and normoxia (control) groups. A total of 60 newborn rats in experiment group underwent tubal feeding day for 6 days and followed by a period of recovery. The rats in the two groups were sacrificed at the 3rd, 5th, 8th, 10th, 13th and 20th day after birth, respectively. The morphologic changes of retinal vessels were estimated by observing the vascular pattern in adenosine diphosphatase stained retina flat mounts. The newborn vessels were quantified by HE staining. Immunohistochemical method was used to detect HIF-1α expression. Results In experiment group, numerous neovascularization and un-perfused area at the periphery of vessels occurred on the 10th day. The result of HE staining showed that in experiment group of 10-day old,the number of neovascular nuclei extending into the vireo was 28.78±7.53, and that of the control group was 1.22±1.48 (t=11.169,P<0.01). The results of immunohistochemistry revealed that the expression of HIF-1α protein were stronger in the experiment group than in the control group on the 8th, 10th and 13th day, and there were significant differences between the two groups (108.87±15.21, 183.68±26.58 and 129.42±9.85 vs 74.98±4.50, 76.38± 3.38 and 74.78±1.86, t=4.625, 9.023 and 9.672,P<0.05). Conclusions HIF-lα might play an important role in retinal neovascularization.%目的 探讨缺氧诱导因子-lα(hypoxia-inducible factor-lα,HIF-lα)在代谢性酸中毒诱导视网膜新生血管中的表达和意义.方法 将120只新生SD大鼠随机分为酸中毒模型组和正常对照组,各60只.酸中毒模型组出生后第2天开始按535 mg/(kg·d)的剂量管饲氯化铵溶液 (质量浓度为50 mg/ml),2次/d,连续6 d,停药进入恢复期.2

  12. Distal renal tubular acidosis in recurrent renal stone formers

    Osther, P J; Hansen, A B; Røhl, H F

    1989-01-01

    Renal acidification ability was examined in 90 recurrent renal stone formers, using fasting morning urinary pH levels followed by a short ammonium chloride loading test in subjects with pH levels above 6.0. Fifteen patients (16.6%) revealed a distal renal tubular acidification defect: one patient...

  13. Acute phase protein response during acute ruminal acidosis in cattle

    Danscher, A. M.; Thoefner, M. B.; Heegaard, Peter M. H.;

    2011-01-01

    acids. In humans, inflammation has been linked to metabolic diseases. In cattle, studies into the possible links between acid-base changes, inflammation/innate immunity and metabolic disease are warranted as this might improve our understanding of the production disease complexes occurring in particular...

  14. Coagulation Changes to Systemic Acidosis and Bicarbonate Correction in Swine

    2011-11-01

    a decrease in respiration successfully lowered arterial pH to 7.1 (Acido- sis, Table 2) and significantly elevated PaCO2 and HCO3 and lowered PaO2 ...PaCO2, PaO2 , and BE to near their prehemorrhage levels. CaCl2 was injected i.v. during reinfusion of citrated blood (1 mg/mL of blood), so that the plasma...3.1* 55.0 3.2 PaO2 (mm Hg) 479.8 26.2 464.5 26.1 455.4 16.6 HCO3 (mmol/L) 33.2 0.7 16.2 1.8* 31.4 1.5 BE (mmol/L) 7.0 0.7 -12.5

  15. A Case Misdiagnosed as Cerebral Infarct:Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis and Stroke-Like Episodes%线粒体脑肌病伴高乳酸血症和卒中样发作误诊为脑梗死

    肖展翅; 吕衍文; 王洪敏; 王佳君; 周刚; 姜华

    2014-01-01

    Objective To explore the diagnostic criteria, misdiagnosis causes and preventive measures of mitochon-drial myopathy, encephalopathy, lactic acidosis and stroke-like episodes ( MELAS) . Methods Clinical data of the MELAS patient misdiagnosed as cerebral infarct was retrospectively analyzed. Results The patient with double eyes vision loss for a day was hospitalized, and diagnosed as cerebral infarction after the body and head MRI examinations, vision of double eyes were mildly better after treatment. By DSA, MRS examinations and genetic testing, the patient was eventually confirmed as MELAS syndrome in stead of cerebral infarction. After 3-month treatment such as improving the metabolism and blood supply of the brain, the patient got better obviously, and MRI showed that the focus of head disappeared. Conclusion Clinical mani-festations being similar to acute cerebral infarction, head MRI showing cerebral infarction and knowledge of doctors being nar-row were the main causes of misdiagnosis. Strengthening learning to understand and mastering relevant knowledge of mitochon-dria encephalo-myopathy can prevent or reduce the misdiagnosis.%目的:探讨线粒体脑肌病伴高乳酸血症和卒中样发作的诊断要点、误诊原因及防范措施。方法对我院近期收治的误诊为脑梗死的线粒体脑肌病伴高乳酸血症和卒中样发作1例的临床资料进行回顾性分析。结果患者因双眼突发视力减退1 d入院,经查体及头颅MRI等相关检查考虑脑梗死,予相应治疗,视力稍好转。后患者行头颅数字减影血管造影及磁共振波谱检查排除脑梗死,最终经基因检查确诊线粒体脑肌病( MELAS综合征)。予改善代谢及脑供血等治疗3个月,患者病情明显好转,头颅MRI检查示病灶消失。结论临床表现与急性脑梗死相似、头颅MRI检查提示脑梗死及接诊医生知识面狭窄是导致本例误诊的主要原因。加强学习、拓宽知识面、了解

  16. Mitochondrial Encephalomyopathies with Lactic Acidosis and Stroke Like Episodes-Clinical, Pathological and Mitochondrial DNA Analysis%粒脑肌病伴高乳酸血症和卒中样发作患者的临床、病理和线粒体DND突变分析

    王康; 焉传祝; 王国相; 焦劲松; 张永庆; 金淼; 顾卫红

    2009-01-01

    目的 能量代谢障碍是青年期卒中的重要病因之一,该研究总结线粒体脑肌病伴高乳酸血症和卒中样发作(mitochondrial encephalomyopathy with lactic acidosis and stroke-like episode.MELAS)患者的临床,病理特征,分析线拉体DNA突变,望能有助于提高对该病的认识、改进青年卒中的诊治.方法 回顾分析15例临床特征和骨骼肌病理符合MELAS的患者.分析线粒体脱氧核糖核酸(mitochondrial DNA,mtONA)突变,多聚酶链反应(polymerase chain reaction,PCR)后直接测序分析mtDNA热点突变,并对未发现热点突变的患者进行全mtDNA序列分析.结果 15例患者的临床表现以头痛和卒中样发作,癫癎发作为主要表现,病灶以皮层尤其枕叶、顶叶为多,磁共振成像(magnetic resonance imaging,MRI)有一定特征,生化检查发现血乳酸、乳酸/丙酮酸此值升高,肌酶轻度升高,病理上以破碎红纤维(ragged-red fibers,RRF)和细胞色素C氧化酶(cytochrome C oxidase,COX)/琥珀酸脱氲酶(Succinate dehydrogenase,SDH)蓝染纤维为主要特征,电镜下显示线粒体增多,线拉体内包涵体.11例由亮氨酸转运核搪核酸(mitochondrial tRNA for leucine,MTTL1,tRNA1)基因突变导致,细胞色素C氧化酶亚单位3(Cytochrome c oxidase subunit 111,C05)基因9469C/T突变,线粒体ATP合成酶亚单位8(Subunit 8 of mitochondrial ATP synthase.ATP8)基因8469A/G突变和细胞色素C氧化酶亚单位1(Cytochrome c oxidase subunit 1,C01 or MTC01)基因62553T/C突变各1例,1例患者无任何mtDNA突变.结论 MELAS是青年期卒中重要原因之一,肌肉活检是临床诊断的主要手段,mtDNA突变分析尤其是热点突变(MTTL1,5245G和MTTL1*5271C)分析对于确诊有重要价值.

  17. Dynamic evolution of brain magnetic resonance imaging findings in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes syndrome%线粒体脑肌病伴高乳酸血症和卒中样发作综合征患者的脑磁共振成像改变动态演变规律

    赵丹华; 王朝霞; 于磊; 肖江喜; 谢晟; 袁云; 黄一宁

    2014-01-01

    Objective To analyze the dynamic evolution of brain MRI in patients with mitochondrial myopathy,encephalopathy,lactic acidosis,and stroke-like episodes (MELAS) syndrome.Methods A retrospective study was performed on 58 MELAS cases with pathologically and (or) molecularly confirmed diagnosis.MRI were repeated within 60 days after the onset of stroke-like episodes (SLE) and the evolution changes of cerebral lesions were accessed.Brain atrophy index (BAI) was calculated in the remission stage from 31 patients with MELAS,and the correlation between BAI,age and disease duration was analyzed.Results The proportion of lesions expansion,migration and shrink within 30 days after the onset of SLE was 64.1% (25/39),10.2% (4/39),17.9% (7/39),respectively,and 13% (3/23),21.7% (5/23),56.5% (13/23),between 30-60 days after the onset of SLE respectively.In the recovery stage of SLE,the BAI in 31 patients with MELAS was 15.2% ±2.8%.The correlation coefficient between BAI and the age,total disease course and duration of encephalopathy was 0.329 (P =0.043),0.405 (P =0.012) and 0.649 (P =0.000).Conclusions Brain atrophy in the studied MELAS patients gradually develops and strokelike lesions shrink with progression of the disease.However,the migration of lesions is persistent.%目的 分析线粒体脑肌病伴高乳酸血症和卒中样发作(MELAS)综合征患者的脑MRI改变动态演变规律.方法 收集经肌肉病理检查和(或)基因检测确诊的58例MELAS患者的资料,于卒中样发作(SLE)后60 d内进行重复脑MRI检查,分析其病灶的演变规律;计算31例患者缓解期头MRI的脑萎缩指数以及与其年龄及病程之间的相关性.结果 SLE后30 d内64.1% (25/39)的病灶扩大,10.2% (4/39)的病灶转移,17.9%(7/39)的病灶缩小.在30 ~60 d内13%(3/23)的病灶扩大,21.7%(5/23)的病灶转移和56.5%(13/23)的病灶缩小.31例患者SLE缓解期脑萎缩指数为15.2%±2.8%,与年龄、总病程、脑内症

  18. 线粒体DNA G13513A突变所致线粒体脑肌病伴高乳酸血症和脑卒中样发作/Leigh重叠综合征%Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes/Leigh overlap syndrome caused by mutation of mitochondrial DNA G13513A

    韩漫夫; 白润涛; 冯宏业; 陶唯宜; 王朝霞; 袁云

    2009-01-01

    Objective To describe the chnical, neuroimagine, pathological and genetic features in a case with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS)/Leigh overlap syndrome.Methods The ease was a 22-year-old woman with recurrent headache, loss of visual acuity and general seizures over 11 years.MRI demonstrated symmetrical high T2-weighted signals in occipital and parietal lobes, in the late stage of the disease, the above imagine changes on MRJ were also shown in the bilateral basal ganglion and brainstem.She died of status epilepticus at age of 22.Brain autopsy and mitochondrial DNA (mtDNA) analysis were performed in the patient.Results The main neuropathological findings were muhifocal and lamilar spongiform in the cortex of the whole brain, the basal ganglion and middle brain.Gliosis, macrophagie reaction and capillary endothelial proliferation were observed in these areas.All 6 layers of the cortex and subcortical white matter in occipital and parietal lobes were severely affected.GI3513A mutation was found in the gene of mitochondria encoded NADH dehydrogenase subunit 5 (MTNDS).Conclusions MELAS/Leigh overlap syndrome presents the symptoms predominantly affecting the cerebral cortex.Neuroimagines suggested that the lesion initially involves the cerebral cortex and in the late stage implicates the basal ganglion and the brainstem, possibly caused by pathological changes of spongiform with capillary proliferation in these areas.%目的 报道1例线粒体DNA G13513A点突变所致线粒体脑肌病伴高乳酸血症和脑卒中样发作(MELAS)/Leigh重叠综合征的临床、影像学、神经病理学改变特点.方法 患者为22岁女性,反复出现头痛、视力下降和肢体抽动11年,因癫疴持续状态而死亡.之前多次MRI检查发现大脑皮质大片长T1长T2异常信号,病灶从枕叶开始,逐渐波及顶叶,疾病后期累及双侧基底节区及脑干灰质核团.对患者进行脑局部尸体解

  19. 线粒体脑肌病伴高乳酸血症和卒中样发作患者的血管自主调节功能%Evaluation of vascular autoregulation in mitochondrial myopathy, encephalopathy, lactic acidosis,and stroke-like episodes patients

    陈靖; 赵丹华; 王朝霞; 彭清; 袁云; 黄一宁

    2012-01-01

    Objective To investigate the cerebral vascular autoregulation in patients with mitochondrial encephalomyopathy with lactic acidosis and strokc-like episodes (MELAS) during the remission of stroke-like episodes,including cerebrovascular CO2 reactivity and vascular endothelial function.Methods Twenty-nine MELAS patients confirmed by genetic analysis were recruited in this study. They underwent the examination at least 2 weeks after the onset of last stroke-like episode.Twenty-eight healthy people were collcctcd as healthy controls. Carotid ultrasound and brain magnetic resonance angiogram (MRA) were done to evaluate the cervical and intracranial appearance of large arteries. Evaluation of vascular autoregulation included: (1) the cerebrovascular CO2 reactivity with breath-holding test by transcranial Doppler and calculating breath holding index (BHI),and ( 2 ) flow-mediatcd dilation ( FMD )and nitroglycerin-mediated dilation with ultrasound assessment of humeral artery.Independent-samples t test was done between the results of two groups.Results Carotid ultrasound and cranial MRA revealed no abnormalities in both MELAS patients and healthy controls.The BHI of MELAS patients was significantly decreased than that of normal controls ( 1.36 ± 0.52 vs 1.81 ±0.26,t =- 3.693,P < 0.01 ),and the FMD of MELAS patients was also significantly lower than that of normal controls (11.0% ±4.8% vs 15.8% ±5.8%,t =-3.390,P <0.01).Conclusion The function of vascular autoregulation,including cerebrovascular CO2 reactivity and FMD,is impaired in MELAS patients.%目的 评价线粒体脑肌病伴高乳酸血症和卒中样发作(MELAS)患者的脑血管二氧化碳(CO2)反应性和血管内皮功能,以分析患者在卒中样发作缓解期的血管自主调节功能变化.方法以经基因诊断证实的29例MELAS为患者组,检查时间距离末次卒中样发作的时间大于2周;健康志愿者28名为对照组.应用颈部血管彩超和头颅磁共振血管成

  20. Caracterização físico-química da acidose metabólica induzida pela expansão volêmica inicial com solução salina a 0,9% em pacientes com sepse grave e choque séptico Physicochemical characterization of metabolic acidosis induced by normal saline resuscitation of patients with severe sepsis and septic shock

    Marcelo Park

    2011-06-01

    Full Text Available OBJETIVO: O objetivo deste estudo foi caracterizar e quantificar a acidose metabólica causada pela expansão volêmica inicial na reanimação de pacientes com sepse grave e choque séptico. MÉTODOS: Uma coleta de sangue para caracterização físico-química do equilíbrio ácido-básico antes e após a expansão volêmica com 30 mL/kg de solução salina a 0,9%. O diagnóstico e a quantificação da acidose metabólica foram feitas com o uso do "standard base excess" (SBE. RESULTADOS: Oito pacientes com 58 ± 13 anos e APACHE II de 20 ± 4 foram expandidos com 2000 ± 370 mL de solução salina a 0,9%. Houve queda do pH de 7,404 ± 0,080 para 7,367 ± 0,086 (P=0,018 associada a elevação da PCO2 de 30 ± 5 mmHg para 32 ± 2 mmHg (P=0,215 e queda do SBE de -4,4 ± 5,6 para -6,0 ± 5,7 mEq/L (P=0,039. Esta queda do SBE foi associada ao poder acidificante de dois fatores: elevação não significativa do "strong ion gap" (SIG de 6,1 ± 3,4 para 7,7 ± 4,0 mEq/L (P=0,134 e queda não significativa do "strong ion diference" aparente inorgânico (SIDai de 40 ± 5 para 38 ± 4 mEq/L (P=0,318. Em contraposição, houve queda da albumina sérica de 3,1 ± 1,0 para 2,6 ± 0,8 mEq/L (P=0,003, que teve um poder alcalinizante sobre o SBE. A elevação do cloro sérico de 103 ± 10 para 106 ± 7 mEq/L (POBJECTIVE: The aim of this study was to characterize and quantify metabolic acidosis that was caused by initial volume expansion during the reanimation of patients with severe sepsis and septic shock. METHODS: A blood sample was drawn for physicochemical characterization of the patient's acid-base equilibrium both before and after volume expansion using 30 mL/kg 0.9% saline solution. The diagnosis and quantification of metabolic acidosis were based on the standard base excess (SBE. RESULTS: Eight patients with a mean age of 58 ± 13 years and mean APACHE II scores of 20 ± 4 were expanded using 2,000 ± 370 mL of 0.9% saline solution. Blood pH dropped

  1. 成人线粒体脑肌病伴高乳酸血症和卒中样发作(MELAS)综合征浅析%Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome in adult:a case report with literature review

    冯全志; 韩彤; 雷静

    2015-01-01

    Objective To investigate the clinical and imaging characteristics of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome in adult, and to enhance the knowledge of this disease and decrease misdiagnose. Methods Relevant literatures were reviewed, and two cases of MELAS syndrome proved by muscle pathology were retrospectively analyzed. Results The two patients presented with the onset of stroke and seizures. Imaging examination: “cerebral infarction”-like lesions asymmetrically involving temporal parietal occipital lobe. CT scan showed patchy low density shadow. On MRI, lesions showed slightly long T1 and T2 signals, hyperintensity on FLAIR and DWI, slightly low signal on ADC map. The lesions involved the territories of middle cerebral artery and the posterior cerebral artery. Brain MRA scan showed supply artery stenosis or occlusion. The perfusion weighted imaging showed abnormal hyperperfusion in the lesion area. Magnetic resonance spectroscopy (TE=135 ms) scan showed obvious inverted lactate peak at lesions. Laboratory tests showed the lactate level of blood and cerebrospinal fluid increased significantly. For biceps brachii biopsy, the scattered and ragged red fibers can be seenon modified Gomori-trichrome. The two cases of last diagnosis is MELAS syndrome. For the mt DNA A3243G of detection, the first case was negative, but the second case was positive. The first patient returned one year later due to second onset, the new lesion involved temporal pole, brain atrophy was seen at the primary lesion area. Conclusion MELAS syndrome is rare in clinic, and clinical and imaging manifestations have certain characteristics. Multi-modality MRI has important value in the diagnosis of the disease. Final diagnosis relies on muscle histological examination.%目的:探讨成人MELAS综合征的临床表现和影像特点,提高对该病的认识,减少误诊。方法复习线粒体脑肌病

  2. Epileptic seizures and electroencephalographic findings in patients with mitochondrial myopathy encephalopathy, lactic acidosis and stroke-like episodes%线粒体脑肌病伴高乳酸血症和卒中样发作的癫痫发作及脑电图特点分析

    张晓; 王朝霞; 刘凤君; 邓馨; 于磊; 王薇薇; 袁云

    2014-01-01

    Objective To investigate the features of epileptic seizures and eletroencepalogram (EEG) in patients with mitochondrial myopathy encephalopathy,lactic acidosis and stroke-like episodes (MELAS).Methods Forty-four patients with MELAS were diagnosed at the First Hospital of Peking University from November 2007 to August 2013.EEG and head MRI were performed on all patients.The types of epileptic seizure and EEG changes were compared between patients in and outside stroke-like episodes.Results Epileptic seizures occurred in 39 of 44 patients (88.6%) with MELAS,while multitype epileptic seizures were presented in 26 cases (66.7%).In stroke-like episodes,22 patients presented with partial seizures,30 with generalized seizures and 17 with status epilepticus.In nonstroke-like episodes,7 patients presented with partial seizures,14 with generalized seizures and 2 with status epilepticus.The frequency of partial seizures,generalized tonic-clonic seizures,status epilepticus were 47.7% (21/44),68.2% (30/44),38.6% (17/44) in stroke-like episodes and 13.6% (6/44),27.3% (12/44),4.5% (2/44) in nonstroke-like episodes,which have statistical significance (x2 =12.022,14.758,15.103;P =0.001,0.000,0.000,respectively).Abnormal EEGs appeared in all patients.The rates of slow alpha frequency,diffuse δ or θ wave,epileptic discharges were 6.8% (3/44),43.2% (19/44),25.0%(11/44) in stroke-like episodes and 31.8% (14/44),59.1% (26/44),22.7% (10/44) in nonstroke-like episodes,respectively.Slow alpha frequency were significantly different between patients in and outside stroke-like episodes (x2 =8.822,P =0.003).Conclusions Epileptic seizures with different types are more common during stroke-like episodes in patients with MELAS.While the rates of epileptic discharges are also common outside the stroke-like episodes.%目的 探讨线粒体脑肌病伴高乳酸血症和卒中样发作(MELAS)患者的癫痫发作及脑电图特点.方法 收集2007年11月至2013年8

  3. 线粒体脑肌病伴乳酸血症和卒中样发作190例的临床特征分析%Clinical features of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes:an analysis of 190 cases

    张哲; 赵丹华; 刘靖; 左越焕; 熊晖; 吕鹤; 张巍; 袁云; 王朝霞

    2016-01-01

    Objective To summarize the clinical features of Chinese patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes ( MELAS).Methods A total of 190 patients with MELAS who presented to Peking University First Hospital between 1997 and 2015 were recruited.Among 190 patients, 175 were identified carrying mitochondrial DNA mutations, and the remaining 15 patients were diagnosed by muscle biopsy.The clinical features, including predisposing factors of stroke-like episodes, the onset symptoms and frequencies of various manifestations were analyzed and reported.Results In our cohort of MELAS patients, the male-to-female ratio was 1.44∶1.The median age of onset was 14 years ( from 7 months to 45 years).The peak onset ages were 8-12 years.The median onset age of the first stroke-like episode was 16 years ( from 1 to 53 years ).There were 66 ( 46.15%) patients who had predisposing factors before the onset, and fatigue and upper respiratory tract infection were the most common predisposing factors of stroke-like episodes in these patients ( 37.88%, 25/66 and 34.85%, 23/66, respectively).Other predisposing factors included emotional agitation, drinking alcohol, trauma, withdrawal of antiepileptic drugs, being frightened, satiation and hunger.Stroke-like episodes appeared in 70.53%(134/190) patients as an onset symptom and developed in all patients with disease progression.The neurological manifestations included seizure ( 89.42%, 169/189 ) , mental retardation or dementia (82.87%, 150/181), headache (74.30%, 133/179), hemianopia or cortical blindness (67.72%, 107/158), exercise intolerance (50.87%, 88/173), hemiplegia or hemianesthesia (47.44%, 74/156), sensorineural deafness (46.20%, 85/184), aphasia (39.47%, 60/152), behaviour disorder (17.71%, 31/175) and ophthalmoplegia ( 9.60%, 17/177 ).The manifestations of extra-nervous systems included hirsutism (67.57%, 100/148), vomiting (65.58%, 101/154), fever (62.07%, 90/145), short stature (45

  4. Heteroplasmy levels of mitochondrial tRNALeu(UUR) A3243G mutation and clinical features in a Chinese family with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome%线粒体脑肌病伴高乳酸血症和脑卒中样发作综合征一家系临床特征及线粒体基因A3243G位点点突变异质性水平

    何振巍; 张朝东

    2010-01-01

    目的 调查1个疑似患有母系遗传性线粒体脑肌病伴高乳酸血症和脑卒中样发作(MELAS)综合征家系的临床表现、生物化学检测数据和影像学资料,并探索其与血细胞线粒体基因突变异质性水平的关联性.方法 收集先证者和11位其母系家系成员的一般情况、抽搐及脑卒中样发作等病史,检测家系成员的血常规和运动前后血浆乳酸水平等生化指标,并做头颅磁共振检查.用聚合酶链反应(PCR)-限制性内切酶片段长度多态和DNA测序法检测其成员是否存在线粒体基因组A3243G点突变,并用荧光实时定量PCR定量该突变的水平.结果 该家系部分成员存在抽搐、脑卒中样发作和高乳酸血症等MELAS综合征典型症状,以及身材矮小、运动不耐受和发热、偏头痛等非典型症状.发作期头颅磁共振成像符合MELAS综合征的典型特点,且普遍存在小脑萎缩.母系亲属均存在线粒体基因的A3243G位点点突变,突变异质性水平越高,症状越典型且严重.结论 该调查家系确诊母系遗传性MELAS综合征,其致病基因为线粒体A3243G点突变.外周血血细胞线粒体基因突变异质性水平与亲缘关系、抽搐早现性和血乳酸值等临床表型存在相关性.%Objective To investigate the clinical manifestation, biochemically detected data, and radiographic features of a pedigree with suspected mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome, and to explore the correlations between the clinical features and the mutant heteroplasmy levels of mitochondrial genome. Methods The personal details, histories of stroke-like episodes and seizures within the proband and 11 members in the maternal lineage of the family were collected. Routine blood examinations and plasma lactate levels before and after movements of these family members were detected, followed by cephalic MRI examinations. Polymerase chain reaction

  5. Disseminated histoplasmosis presenting as diabetic keto-acidosis in an immunocompetent patient.

    Niknam, Negin; Malhotra, Prashant; Kim, Angela; Koenig, Seth

    2017-01-06

    Histoplasma capsulatum causes a spectrum of manifestations from asymptomatic to fatal disseminated disease. Disseminated histoplasmosis is mostly seen in endemic areas among immunocompromised patients such as those with AIDS. Here, we present a patient living in a non-endemic area with previously undiagnosed diabetes mellitus, who presented with septic shock and diabetic ketoacidosis (DKA), and was ultimately diagnosed with disseminated histoplasmosis. The patient rapidly recovered on administration of intravenous liposomal amphotericin followed by oral itraconazole. Uncontrolled diabetes may be a risk factor for disseminated or severe histoplasmosis in otherwise immunocompetent patients.

  6. MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, Stroke) – a Diagnosis Not to be Missed

    Quinn, NM

    2016-09-01

    MELAS is a rare mitochondrial disorder. We report two cases in Irish males where the characteristics were evident, but the diagnosis not made for a considerable period of time. In one of the cases the symptoms were presumed secondary to prematurity. In the other the symptoms were presumed secondary to epilepsy and he had three respiratory arrests secondary to benzodiazepine administration. This report wishes to highlight MELAS as a differential diagnosis in paediatric patients who present with stroke.

  7. Melas (mitochondrial, encephalopathy, lactic acidosis and stroke like episodes: relato de um caso

    Lineu Cesar Werneck

    1987-09-01

    Full Text Available Relato de caso de menino de 12 anos de idade que apresentou diversas crises convulsivas, cefaléia e vômitos de difícil controle, concomitantes a sinais neurológicos focais. Esses episódios eram recorrentes e apresentavam regressão, com permanência de discreto déficit. A investigação revelou aumento do ácido láctico plasmático, lesões semelhantes a infartos cerebrais e calcificações nos gânglios da base. A biópsia muscular mostrou inúmeras fibras granulares (ragged-reds e diminuição da citocromo c oxidase no tecido muscular. É apresentada revisão sobre as desordens mitocondriais com comprometimento do sistema nervoso central e músculos, enfatizando-se o diagnóstico e reconhecimento desta nova entidade, tendo em vista possível tratamento sintomático.

  8. Placental endoplasmic reticulum stress and acidosis: relevant aspects in gestational diabetes.

    Jawerbaum, Alicia

    2016-10-01

    In this issue, Yung and colleagues (doi: 10.1007/s00125-016-4040-2 ) report endoplasmic reticulum stress in the placenta of patients with gestational diabetes mellitus. With the use of a trophoblast-like cell line, these authors identify putative mechanisms involved in, and treatments to prevent the induction of endoplasmic reticulum stress. Here, the relevance and possible implications of these findings and areas for further research are discussed.

  9. Intraoperative acidosis is a new predictor for postoperative pancreatic ifstula after pancreati-coduodenectomy

    Erdem Kinaci; Mert Mahsuni Sevinc; Abdulkerim Ozakay; Savas Bayrak; Ekrem Cakar; Serkan Sari

    2015-01-01

    BACKGROUND: Early diagnosis of postoperative pancreatic ifstula (POPF) is important for proper interventions. The pre-operative, intraoperative and early postoperative biochemical markers have predictive value of POPF. The present study was to evaluate several simple biochemical parameters in the pre-diction of POPF. METHODS: Patients who underwent pancreaticoduodenec-tomy in our center between 2006 and 2015 were reviewed ret-rospectively. Preoperative and early postoperative biochemi-cal parameters were evaluated. Additionally, the relationship between POPF and pH and lactate level at the end of surgery were analyzed, and neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and red cell distribution width-to-platelet ratio (RPR) were calculated for postoperative days (PODs) 1 and 3. Diagnosis and grading of POPF were per-formed according to the standards of the International Study Group on Pancreatic Fistula. The patients were divided into two groups: Group 1 with no ifstula or grade-A ifstula; group 2 with grade-B or -C ifstula. These simple biochemical markers were then compared between the two groups. RESULTS: Serum amylase level was signiifcantly higher at POD3, and pH level was signiifcantly lower at the end of op-eration in group 2 compared with those in group 1. However, the serum amylase was below the upper limit of normal serum level and therefore, the difference was not signiifcant in clini-cal practice. Receiver operating charecteristic curve analysis showed that pH level was a reliable predictor of POPF (area under the curve: 0.713; 95% CI: 0.573-0.853). CONCLUSIONS: A low pH level at the end of pancreaticoduo-denectomy was a risk factor of POPF. NLR, PLR, and RPR had no predictive value of POPF after pancreaticoduodenectomy.

  10. Intraoperative acidosis is a new predictor for postoperative pancreatic ifstula after pancreati-coduodenectomy

    Erdem Kinaci; Mert Mahsuni Sevinc; Abdulkerim Ozakay; Savas Bayrak; Ekrem Cakar; Serkan Sari

    2016-01-01

    BACKGROUND: Early diagnosis of postoperative pancreatic ifstula (POPF) is important for proper interventions. The pre-operative, intraoperative and early postoperative biochemical markers have predictive value of POPF. The present study was to evaluate several simple biochemical parameters in the pre-diction of POPF. METHODS: Patients who underwent pancreaticoduodenec-tomy in our center between 2006 and 2015 were reviewed ret-rospectively. Preoperative and early postoperative biochemi-cal parameters were evaluated. Additionally, the relationship between POPF and pH and lactate level at the end of surgery were analyzed, and neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and red cell distribution width-to-platelet ratio (RPR) were calculated for postoperative days (PODs) 1 and 3. Diagnosis and grading of POPF were per-formed according to the standards of the International Study Group on Pancreatic Fistula. The patients were divided into two groups: Group 1 with no ifstula or grade-A ifstula; group 2 with grade-B or -C ifstula. These simple biochemical markers were then compared between the two groups. RESULTS: Serum amylase level was signiifcantly higher at POD3, and pH level was signiifcantly lower at the end of op-eration in group 2 compared with those in group 1. However, the serum amylase was below the upper limit of normal serum level and therefore, the difference was not signiifcant in clini-cal practice. Receiver operating charecteristic curve analysis showed that pH level was a reliable predictor of POPF (area under the curve: 0.713; 95% CI: 0.573-0.853). CONCLUSIONS: A low pH level at the end of pancreaticoduo-denectomy was a risk factor of POPF. NLR, PLR, and RPR had no predictive value of POPF after pancreaticoduodenectomy.

  11. Pre-hospital transfusion of plasma in hemorrhaging trauma patients independently improves hemostatic competence and acidosis

    Henriksen, Hanne H; Rahbar, Elaheh; Baer, Lisa A

    2016-01-01

    ; nearly half received both RBCs and plasma) whereas 182 patients only received in-hospital blood products (RBCs, Plasma and Platelets) within 6 hours of admission (IH group). PH patients had lower Glasgow coma scale (GCS) scores, more penetrating injuries, lower systolic blood pressures, lower hemoglobin...

  12. Mechanisms of the Effects of Acidosis and Hypokalemia on Renal Ammonia Metabolism

    Han, Ki-Hwan

    2011-01-01

    Renal ammonia metabolism is the predominant component of net acid excretion and new bicarbonate generation. Renal ammonia metabolism is regulated by acid-base balance. Both acute and chronic acid loads enhance ammonia production in the proximal tubule and secretion into the urine. In contrast, alkalosis reduces ammoniagenesis. Hypokalemia is a common electrolyte disorder that significantly increases renal ammonia production and excretion, despite causing metabolic alkalosis. Although the net ...

  13. A truncating PET100 variant causing fatal infantile lactic acidosis and isolated cytochrome c oxidase deficiency.

    Oláhová, Monika; Haack, Tobias B; Alston, Charlotte L; Houghton, Jessica Ac; He, Langping; Morris, Andrew Am; Brown, Garry K; McFarland, Robert; Chrzanowska-Lightowlers, Zofia Ma; Lightowlers, Robert N; Prokisch, Holger; Taylor, Robert W

    2015-07-01

    Isolated mitochondrial complex IV (cytochrome c oxidase) deficiency is an important cause of mitochondrial disease in children and adults. It is genetically heterogeneous, given that both mtDNA-encoded and nuclear-encoded gene products contribute to structural components and assembly factors. Pathogenic variants within these proteins are associated with clinical variability ranging from isolated organ involvement to multisystem disease presentations. Defects in more than 10 complex IV assembly factors have been described including a recent Lebanese founder mutation in PET100 in patients presenting with Leigh syndrome. We report the clinical and molecular investigation of a patient with a fatal, neonatal-onset isolated complex IV deficiency associated with multiorgan involvement born to consanguineous, first-cousin British Asian parents. Exome sequencing revealed a homozygous truncating variant (c.142C>T, p.(Gln48*)) in the PET100 gene that results in a complete loss of enzyme activity and assembly of the holocomplex. Our report confirms PET100 mutation as an important cause of isolated complex IV deficiency outside of the Lebanese population, extending the phenotypic spectrum associated with abnormalities within this gene.

  14. A 44-year-old woman with metabolic acidosis, high anion gap, and delayed neurologic deterioration.

    Vakil, Abhay; Upadhyay, Hinesh; Sherani, Khalid; Cervellione, Kelly; Trepeta, Scott; Patel, Mahendra C

    2015-01-01

    A 44-year-old woman was brought to the ED from John F. Kennedy International Airport. The patient was returning with her son from a 3-month visit to Bangladesh. Her journey started with a 4-h flight from Dhaka, Bangladesh to Dubai, United Arab Emirates. She consumed 240 mL of whiskey during the flight. This was followed by a 14-h flight from Dubai to New York. According to the patient's son, she did not consume any alcohol during the second flight. The patient was in her usual state of health with normal mentation throughout her journey. Upon landing, she started complaining of shortness of breath. After disembarking, she was witnessed to have seizure-like activity with involuntary passage of urine, following which she collapsed. The patient was intubated by emergency medical services in the field.

  15. Rumen Microbiome Composition in Cattle during Grain-Induced Subacute Ruminal Acidosis (SARA)

    Danscher, Anne Mette; Derakshani, Hooman; Li, Shucong

    2014-01-01

    at the genus level. The rumen bacterial communities were altered in response to SARA (P=0.01). The proportion of several taxa was significantly higher in SARA samples, including S24-7, Erysipelotrichales. Lactobacillus, C lostridia, Moryella, Butyrivibrio, Olsenella, and C oprococcus. Microbiome profiling...... of rumen during SARA could provide new knowledge of the pathogenesis and might be used as a biological marker of the disease....

  16. Muscle surface pH: measurement technique and responses to acidosis and alkalosis.

    Kost, G J

    1982-01-01

    The technique of muscle surface pH measurement used clinically was refined for application in animal experimentation. Guidelines for electrode utilization were developed, and sources of error were investigated. In pentobarbital sodium-anesthetized rabbits, during steady-state conditions, the surface pH of the medial gastrocnemius [7.39 +/- 0.05 (SD)] was equal to that of the soleus, and both were lower than femoral venous outflow pH (7.42 +/- 0.04, P less than 0.001), which was lower than arterial pH (7.46 +/- 0.05, P less than 0.001). With acid-base infusions, the same relationship found during steady-state control conditions (arterial greater than venous outflow greater than muscle surface pH) was observed despite large fluctuations in blood pH. Only during forced hypoventilation, when CO2 transiently moved into muscle, did the relationship reverse. In all experiments, muscle surface pH followed venous outflow pH more closely than it followed arterial pH, the soleus more rapidly than the medial gastrocnemius. Results were consistent with the physiological characteristics of the two muscles and demonstrated that muscle surface pH reflects the local pH of the interstitial compartment under the site of electrode placement.

  17. The Ovine Fetal and Placental Inflammatory Response to Umbilical Cord Occlusions With Worsening Acidosis.

    Xu, Alex; Matushewski, Brad; Cao, Mingju; Hammond, Robert; Frasch, Martin G; Richardson, Bryan S

    2015-11-01

    We hypothesized that repetitive umbilical cord occlusions (UCOs) leading to severe acidemia will stimulate a placental and thereby fetal inflammatory response which will be exacerbated by chronic hypoxemia and low-grade bacterial infection. Chronically instrumented fetal sheep served as controls or underwent repetitive UCOs for up to 4 hours or until fetal arterial pH was 55% and pH approaching 7.00 for all 3 UCO groups. Neutrophils, while unchanged within the cotyledon fetal and intermediate zones, were ∼2-fold higher within the zona intima for all 3 UCO groups. However, no differences were observed in macrophage counts among the treatment groups and no cotyledon mast cells were seen. Fetal plasma and amniotic fluid cytokines remained little changed post-UCOs and/or at 1 and 48 hours of recovery in the normoxic-UCO and hypoxic-UCO groups but increased several fold in the LPS-UCO group with IL-6 plasma values at 1 hour recovery highly correlated with the nadir pH attained (r = -.97). As such, repetitive UCOs with severe acidemia can induce a placental inflammatory response and more so with simulated low-grade infection and likely contributing to cytokine release in the umbilical circulation.

  18. Hypercapnic acidosis attenuates the pulmonary innate immune response in ventilated healthy mice.

    Halbertsma, F.J.; Vaneker, M.; Pickkers, P.; Snijdelaar, D.G.; Egmond, J. van; Scheffer, G.J.; Hoeven, J.G. van der

    2008-01-01

    BACKGROUND: Mechanical ventilation with small tidal volumes reduces the development of ventilator-induced lung injury and mortality, but may increase PaCO2. It is not clear whether the beneficial effect of a lung-protective strategy results from reduced ventilation pressures/tidal volumes or is medi

  19. Lactic acidosis in the rectal lumen of patients with septic shock measured by luminal equilibrium dialysis

    Due, V; Bonde, J; Espersen, K;

    2002-01-01

    Gut ischaemia may contribute to morbidity in sepsis, but little is known about the metabolic state of the gut mucosa in such patients.......Gut ischaemia may contribute to morbidity in sepsis, but little is known about the metabolic state of the gut mucosa in such patients....

  20. Mitochondrial myopathy, encephalopathy, lactate acidosis with stroke-like episodes syndrome (MELAS: A case report

    Petrović Igor N.

    2012-01-01

    Full Text Available Introduction. Mitochondrial encephalopathy, lactacidosis and stroke-like episodes (MELAS represent a multisystemic dysfunction due to various mutations in mitochondrial DNA. Here we report a patient with genetically confirmed MELAS. Case Outline. A patient is presented whose clinical features involved short stature, easy tendency to fatigue, recurrent seizures, progressive cognitive decline, myopathy, sensorineural deafness, diabetes mellitus as well as stroke-like episodes. The major clinical feature of migraine type headache was not present. Neuroimaging studies revealed signs of ischemic infarctions localized in the posterior regions of the brain cortex. Electron microscopy of the skeletal muscle biopsy showed subsarcolemmal accumulation of a large number of mitochondria with paracristal inclusions in the skeletal muscle cells. The diagnosis of MELAS was definitively confirmed by the detection of a specific point mutation A to G at nucleotide position 3243 of mitochondrial DNA. Conclusion. When a relatively young patient without common risk factors for ischemic stroke presents with signs of occipitally localized brain infarctions accompanied with multisystemic dysfunction, MELAS syndrome, it is necessary to conduct investigations in order to diagnose the disease.

  1. Lightweight Noninvasive Trauma Monitor for Early Indication of Central Hypovolemia and Tissue Acidosis

    2010-04-01

    equation [7,12]. The light output of the system was assessed with 3 NIST-traceable reflectance standards ( Avian Technologies, LLC, Wilmington, OH...34Simultaneous measurement of hepatic tissue pH, venous oxygen saturation and hemoglobin by near infrared spectroscopy," Shock 15, 106-111 (2001). 7...34Application of fiberoptic sensors for the study of hepatic dysoxia in swine hemorrhagic shock," Crit Care Med 29, 1438-1444 (2001). 10. B. R. Soller

  2. Cold intermittent cardioplegia reduces the acidosis during prolonged cardiac surgery with cardiopulmonary bypass.

    Nollo, Giandomenico; Ferrari, Paolo; Graffigna, Angelo C

    2011-01-01

    The effect on acid-base balance efficacy of intermittent warm and cold blood cardioplegia (IWBC, ICBC) was assessed in 44 patients who underwent cardiac surgery with prolonged aortic cross clamping. With this purpose a customized multi sensor probe was inserted in the coronary sinus, and pH, PO(2), PCO(2) and temperature were continuously measured at 1 Hz sampling rate. The mean cross-clamping time was of 76 ± 26 min on 19 IWBC cases and of 80 ± 24 min on 14 ICBC cases. With IWBC perfusion, at the end of every ischemic period, the lowest pH and PO(2) progressively decreased and the maximal PCO(2) increased. During ICBC the minimum of pH and PO(2) and maximum of PCO2 at the end of different ischemic period during time were constant, also during long cross-clamping time. With IWBC, myocardial ischemia seemed not completely reversed by standardized reperfusions, as reflected by steady deterioration of PCO(2) and pH after each reperfusion.

  3. Metabolic alkalosis reduces exercise-induced acidosis and potassium accumulation in human skeletal muscle interstitium

    Street, D.; Nielsen, Jens Jung; Bangsbo, Jens

    2005-01-01

    Skeletal muscle releases potassium during activity. Interstitial potassium accumulation is important for muscle function and the development of fatigue resulting from exercise. In the present study we used sodium citrate ingestion as a tool to investigate the relationship between interstitial H+ ...

  4. Metabolic acidosis with a high anion: A drug-drug interaction between paracetamol and flucloxacillin

    Jessurun, N.T.; Van Hunse, F.; Van Puijenbroek, E.

    2015-01-01

    Background: Five-oxoproline is a product of disordered glutathione metabolism in the gamma glutamyl cycle: glutathione deficiency removes the feedback inhibition resulting in the formation of γ -glutamylcysteine and elevated concentrations of γ -glutamylcysteine leading to the formation of 5-oxoprol

  5. Umbilical cord blood lactate: a valuable tool in the assessment of fetal metabolic acidosis

    Gjerris, Anne Cathrine Roslev; Staer-Jensen, Jette; Jørgensen, Jan Stener;

    2008-01-01

    The aim of the present study was (1) to evaluate the relationship between umbilical cord arterial blood lactate and pH, standard base excess (SBE), and actual base excess (ABE) at delivery and (2) to suggest a cut-off level of umbilical cord arterial blood lactate in predicting fetal asphyxia usi...

  6. Umbilical cord blood lactate: a valuable tool in the assessment of fetal metabolic acidosis

    Gjerris, A.C.; Staer-Jensen, J.; Jorgensen, J.S.;

    2008-01-01

    OBJECTIVE: The aim of the present study was (1) to evaluate the relationship between umbilical cord arterial blood lactate and pH, standard base excess (SBE), and actual base excess (ABE) at delivery and (2) to suggest a cut-off level of umbilical cord arterial blood lactate in predicting fetal a...

  7. Systemic lupus erythematosus and renal tubular acidosis associated with hyperthyroidism. Case Report.

    Deng, Datong; Sun, Li; Xia, Tongjia; Xu, Min; Wang, Youmin; Zhang, Qiu

    2016-07-01

    A case of a 42-year-old female with hyperthyroidism was subsequently diagnosed to have systemic lupus erythematosus with distal RTA. The clinical examination on admission showed swelling of the knee joints and the urinalysis showed pH 6.5, pro 3+. Her blood routine results were as follows: white blood cells 1.85×109/L, platelets 100×109/L, erythrocyte 3.06×1012/L. The serum potassium was 3.11 mmol/L, 24 hour urinary electrolyte: K 68.87 mmol/24 H, antinuclear antibodies (ANA) 1:1 000, speckled pattern. The anti-double stranded DNA antibody (anti-dsDNA), anti SS-A(52) antibody and anti SS-A(60) antibody were positive. The light microscopy and immunofluorescence showed diffuse proliferative lupus nephritis. These data were compatible with the diagnosis of systemic lupus erythematosus. The diagnosis of hyperthyroidism and distal RTA is clear. This report showed that other autoimmune disease in the diagnosis of hyperthyroidism should not be ignored.

  8. Tolerance of acute hypercapnic acidosis by the European eel ( Anguilla anguilla)

    McKenzie, D J; Taylor, E W; Dalla Valle, A Z;

    2002-01-01

    European eels ( Anguilla anguilla) were exposed sequentially to partial pressures of CO(2) in the water ( PwCO(2)) of 5, 10, 20, 40, 60 then 80 mm Hg (equivalent to 0.66-10.5 kPa), for 30 min at each level. This caused a profound drop in arterial plasma pH, from 7.9 to below 7.2, an increase in a...

  9. Progress in Diagnosing Mitochondrial Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like Episodes

    Ying-Xin Wang

    2015-01-01

    Conclusions: MELAS involves multiple systems with variable clinical symptoms and recurrent episodes. The prognosis of MELAS patients depends on timely diagnosis. Therefore, overall diagnosis of MELAS should be based on the maternal inheritance family history, clinical manifestation, and findings from serial MRI, muscle biopsy, and genetics.

  10. Neonatal lactic acidosis, complex I/IV deficiency, and fetal cerebral disruption

    van Straaten, HLM; van Tintelen, JP; Trijbels, JMF; van den Heuvel, LP; Troost, D; Rozemuller, JM; Duran, M; de Vries, LS; Schuelke, M; Barth, PG

    2005-01-01

    Cerebral developmental abnormalities occur in various inborn errors of metabolism including peroxisomal deficiencies, pyruvate dehydrogenase complex deficiency and others. Associations with abnormalities of the respiratory chain are rare. Here we report male and female siblings with microcephaly, a

  11. Obstruction of endotracheal tube with relevant respiratory acidosis during pediatric cardiac surgery

    Morei, N.M.; Mungroop, H. E.; Michielon, Guido; Scheeren, Thomas

    2014-01-01

    We describe a case of pediatric cardiac surgery in a 21- days old baby, in whom a nasal endotracheal tube (ETT) was inserted. At the end of surgery both ventilatory pressures and end-tidal CO2 increased suggesting airway obstruction. Suctioning of the ETT lumen did not relieve the problem, only ETT

  12. D(—–Lactic Acid Producing Probiotics, D(—–Lactic Acidosis and Infants

    David R Mack

    2004-01-01

    Full Text Available There is mounting evidence that ingestion of selected probiotics can modify disease morbidity for specific conditions affecting humans, and there is growing interest in the amelioration or prevention of disease with probiotics. Modulation in gene expression of the cellular elements of the intestinal mucosa and interbacterial interactions are leading theories as to the mechanism whereby probiotics can effect benefit for the host. Furthermore, gene-environmental interactions are considered to be important in the development of disease in those at genetic risk. With the intestinal tract harbouring large numbers of bacteria, alteration of the microbial environment with probiotic microbes is being considered as a controllable factor that may limit disease expression for those at genetic risk. This reasoning has led to interest in the administration of probiotics to infants. However, there are significant developmental changes occurring in many organ systems from the time of parturition and during the first months of life. Because there is little in the published scientific medical literature regarding the effects of long-term administration of probiotics to infants, potential problems must be considered; one such issue is that of administration of D(--lactate-producing probiotics. An appraisal of the current knowledge of this potential adverse effect is the subject of this communication.

  13. Yeast mediates lactic acidosis suppression after antibiotic cocktail treatment in short small bowel?

    Bongaerts, G.P.A.; Severijnen, R.S.V.M.; Skladal, D.; Bakkeren, J.A.J.; Sperl, W.

    2005-01-01

    During acidotic periods in a girl with a short small bowel, very high D-lactic acid concentrations were measured in blood and urine; the patient's characteristic faecal flora contained mainly lactobacilli, and during antibiotic cocktail treatment also many yeasts. In this case report we sought to un

  14. Genetics Home Reference: SLC4A1-associated distal renal tubular acidosis

    ... a shortage of red blood cells ( anemia ). Hemolytic anemia can lead to unusually pale skin (pallor), extreme tiredness (fatigue), ... breakdown of these abnormal red blood cells may lead to hemolytic anemia. Some people have nonhereditary forms of distal renal ...

  15. Elucidation of how cancer cells avoid acidosis through comparative transcriptomic data analysis.

    Kun Xu

    Full Text Available The rapid growth of cancer cells fueled by glycolysis produces large amounts of protons in cancer cells, which tri mechanisms to transport them out, hence leading to increased acidity in their extracellular environments. It has been well established that the increased acidity will induce cell death of normal cells but not cancer cells. The main question we address here is: how cancer cells deal with the increased acidity to avoid the activation of apoptosis. We have carried out a comparative analysis of transcriptomic data of six solid cancer types, breast, colon, liver, two lung (adenocarcinoma, squamous cell carcinoma and prostate cancers, and proposed a model of how cancer cells utilize a few mechanisms to keep the protons outside of the cells. The model consists of a number of previously, well or partially, studied mechanisms for transporting out the excess protons, such as through the monocarboxylate transporters, V-ATPases, NHEs and the one facilitated by carbonic anhydrases. In addition we propose a new mechanism that neutralizes protons through the conversion of glutamate to γ-aminobutyrate, which consumes one proton per reaction. We hypothesize that these processes are regulated by cancer related conditions such as hypoxia and growth factors and by the pH levels, making these encoded processes not available to normal cells under acidic conditions.

  16. Reincarnation in cultured muscle of mitochondrial abnormalities. Two patients with epilepsy and lactic acidosis.

    Askanas, V; Engel, W K; Britton, D E; Adornato, B T; Eiben, R M

    1978-12-01

    Two unrelated 9-year-old boys failed to thrive from ages 5 and 4 years, and had focal cerebral seizures followed by transcent hemipareses. Histochemistry of their muscle biopsies showed "ragged-red" fibers, which ultrastructurally contained clusters of mitochondria having loss of crisp delineation of crista membranes and contained amorphous inclusion material and parallel-packed cristae and sometimes paracrystalline inclusions. In the patients' cultured muscles, similar mitochondrial abnormalities were present. 2,4-Dinitrophenol, introduced to the medium of cultures of normal human muscle, produced mitochondrial abnormalities similar to those of the patients', and the medium of the patients' muscle cultures worsened the mitochondrial abnormalities. This study, in demonstrating a mitochondrial defect reproducible in the cultured muscle fibers and, therefore, intrinsic to the ragged-red muscle fibers themselves, raises the possibility of a collateral mitochondrial defect in CNS cells as part of a multicellular mitochondriopathy.

  17. Physically effective fiber: method of determination and effects on chewing, ruminal acidosis, and digestion by dairy cows.

    Yang, W Z; Beauchemin, K A

    2006-07-01

    A study was conducted to investigate the effects of physically effective neutral detergent fiber (peNDF) content of dairy cow diets containing corn silage as the sole forage on intake, chewing, ruminal pH, microbial protein synthesis, digestibility, and milk production. A second objective was to compare current methods of measuring peNDF to determine the most suitable approach for use in ration formulation. The experiment was designed as a replicated 3 x 3 Latin square using 6 lactating dairy cows with ruminal cannulas. Diets varied in peNDF content (high, medium, and low) by altering the particle length of corn silage. The physical effectiveness factors (pef) and peNDF contents of the corn silage and diets were determined based on the original (19- and 8-mm sieves) and new Penn State Particle Separator (PSPS; 19-, 8-, and 1.18-mm sieves). A dry-sieving technique that measures the proportion of particles retained on a 1.18-mm sieve was also used. The new PSPS and the 1.18-mm sieve produced similar estimates of pef and peNDF of diets but gave higher values than the original PSPS. There was a much smaller range in pef of corn silage when 3 sieves, rather than 2, were used with the PSPS (range of 0.93 to 0.96 vs. 0.41 to 0.72, respectively). Consequently, increased forage particle length in the diets increased dietary peNDF content and its intake when using the original PSPS; however, the new PSPS and the 1.18-mm sieve failed to detect changes in dietary peNDF and peNDF intake. The peNDF values estimated based on fractional NDF rather than the total NDF content were higher, but the ranking of diets was not changed. Increased intake of peNDF linearly increased digestibility of CP and tended to linearly increase digestibility of fiber in the total tract. As a result, milk yield tended to linearly increase with no effect on milk composition. Ruminal microbial protein synthesis and microbial efficiency were higher with the medium peNDF than with the high or low peNDF diets. Total chewing time and ruminating time were linearly increased with increasing dietary peNDF, whereas influence of dietary peNDF on ruminal pH and fermentation was minimal. This study showed that increasing peNDF content of diets improved fiber digestion. Of the systems used to measure peNDF, the original PSPS provided a good description of dietary particle length and its effects on chewing time and rumen pH, whereas the new PSPS provided a more consistent chewing index, the ratio of total chewing activity to peNDF, across diets varying in chop length of corn silage.

  18. Glucose replacement to euglycemia causes hypoxia, acidosis, and decreased insulin secretion in fetal sheep with intrauterine growth restriction.

    Rozance, Paul J; Limesand, Sean W; Barry, James S; Brown, Laura D; Hay, William W

    2009-01-01

    Nutritional interventions for intrauterine growth restriction (IUGR) have raised concerns for fetal toxicity, the mechanisms of which are unknown. Most of these attempts did not aim to normalize fetal metabolic conditions. Therefore, we used a model of IUGR to determine whether normalization of fetal hypoglycemia for 2 wks would be tolerated and increase insulin concentrations and pancreatic beta-cell mass. IUGR fetuses received either a direct saline infusion (Sal, the control group) or a 30% dextrose infusion (Glu) to normalize glucose concentrations. Neither insulin concentrations (0.11 +/- 0.01 Glu vs. 0.10 +/- 0.01 ng/mL Sal) nor beta-cell mass (65.2 +/- 10.3 Glu vs. 74.7 +/- 18.4 mg Sal) changed. Glucose stimulated insulin secretion (GSIS) was lower in the Glu group. Glu fetuses became progressively more hypoxic: O2 content 1.4 +/- 0.5 Glu vs. 2.7 +/- 0.4 mM Sal, p < 0.05. Partial pressure of carbon dioxide (Paco2) (53.6 +/- 0.8 Glu vs. 51.6 +/- 0.8 Sal, p < 0.05) and lactate (7.74 +/- 3.82 Glu vs. 2.47 +/- 0.55 mM Sal, p < 0.0001) were greater and pH lower (7.275 +/- 0.071 Glu vs. 7.354 +/- 0.003 Sal, p < 0.01) in the Glu group. We conclude that correction of fetal hypoglycemia is not well tolerated and fails to increase insulin concentrations or beta-cell mass in IUGR fetuses.

  19. Effects of acidosis, alkalosis, hyperthermia and hypothermia on haemostasis : results of point of care testing with the thromboelastography analyser

    Ramaker, Albert J. D. W. R.; Meyer, Peter; van der Meer, Jan; Struys, Michel M. R. F.; Lisman, Ton; van Oeveren, Wim; Hendriks, Herman G. D.

    2009-01-01

    In this study we assessed the effects of changes in pH, temperature, and their combination in whole blood on thromboelastographic variables. Blood was collected from six healthy volunteers. Thromboelastograph (TEG series 5000; Haemoscope Corporation, Illinois, USA) channels were set at temperatures

  20. Effect of virginiamycin on ruminal fermentation in cattle during adaptation to a high concentrate diet and during an induced acidosis.

    Coe, M L; Nagaraja, T G; Sun, Y D; Wallace, N; Towne, E G; Kemp, K E; Hutcheson, J P

    1999-08-01

    The objective of Exp. 1 was to compare the effects of virginiamycin (VM; 0, 175, or 250 mg x animal(-1) x d(-1)) and monensin/tylosin (MT; 250/ 90 mg x animal(-1) x d(-1)) on ruminal fermentation products and microbial populations in cattle during adaptation to an all-concentrate diet. Four ruminally cannulated, Holstein steers were used in a 4x4 Williams square design with 21-d periods. Steers were stepped up to an all-concentrate diet fed at 2.5% of BW once daily. Ruminal pH, protozoal counts, and NH3-N and VFA concentrations generally were unaffected by VM or MT. Mean counts of Lactobacillus and Streptococcus bovis were lower (PVirginiamycin seemed to control the growth of ruminal lactic acid-producing bacteria and, therefore, has the potential to moderate ruminal fermentation in situations that could lead to rapid production of lactic acid.

  1. Acidosis and Formaldehyde Secretion as a Possible Pathway of Cancer Pain and Options for Improved Cancer Pain Control.

    Hoang, Ba X; Shaw, D Graeme; Han, Bo; Fang, Josephine Y; Nimni, Marcel

    2015-09-01

    The prevalence of cancer pain in patients with cancer is high. The majority of efforts are spent on research in cancer treatment, but only a small fraction focuses on cancer pain. Pain in cancer patients, viewed predominantly as a secondary issue, is considered to be due to the destruction of tissues, compression of the nerves, inflammation, and secretion of biological mediators from the necrotic tumor mass. As a result, opioid drugs have remained as the primary pharmacological therapy for cancer pain for the past hundred years. This report reviews evidence that cancer pain may be produced by the metabolic effects of two byproducts of cancer-high acidity in the cancer microenvironment and the secretion of formaldehyde and its metabolites. We propose the research and development of therapeutic approaches for preemptive, short- and long-term management of cancer pain using available drugs or nutraceutical agents that can suppress or neutralize lactic acid production in combination with formaldehyde scavengers. We believe this approach may not only improve cancer pain control but may also enhance the quality of life for patients.

  2. Osteopathy of renal tubular acidosis: Case report%肾小管酸中毒性骨病1例

    李欣欣

    2011-01-01

    @@ 患者男,49岁.因"腰腿疼痛3年,加重1个月"来诊.患者既往有慢性乙型肝炎病史,长期服用多种抗病毒药物.入院查体:腰椎及髋部压痛明显,直腿抬高试验及"4"字征(-).实验室检查:HLA B27(-).尿常规检查:尿蛋白(-),尿糖:(+),尿pH值7.00;电解质:TCO2 17.21 mmol/L,K+ 3.26 mmol/L,Cl- 106.00 mmol/L;肾功能检查:Cr 106.00 μmol/L,Bun 6.90 mmol/L.血钙1.92 mmol/L,血磷1.80 mmol/L.

  3. Chloride test - blood

    ... disease Antidiuretic hormone blood test Gastric suction Heart failure - overview Hyperventilation Ions Metabolic acidosis Multiple endocrine neoplasia (MEN) II Proximal renal tubular acidosis Respiratory acidosis Sodium blood test Review Date 5/3/2015 Updated by: Laura J. ...

  4. Fanconi Bickel Syndrome: Novel Mutations in GLUT 2 Gene Causing a Distinguished Form of Renal Tubular Acidosis in Two Unrelated Egyptian Families

    Mohammad Al-Haggar

    2011-01-01

    Full Text Available Background. Fanconi-Bickel syndrome (FBS is an autosomal recessive disorder caused by defects in facilitative glucose transporter 2 (GLUT2 or SLC2A2 gene mapped on chromosome 3q26.1-26.3, that codes for the glucose transporter protein 2. Methods. Two unrelated Egyptian families having suspected cases of FBS were enrolled after taking a written informed consent; both had positive consanguinity, and index cases had evidences of proximal renal tubular defects with hepatomegaly; they were subjected to history taking, signs of rickets as well as anthropometric measurements. Laboratory workup included urinalysis, renal and liver function tests including fasting and postprandial blood sugar; serum calcium, phosphorus, alkaline phosphatase, sodium and potassium, lipid profile, and detailed blood gas. Imaging including bone survey and abdominal ultrasound, and liver biopsy were done to confirm diagnosis. Molecular analysis of the GLUT2 gene was done for DNA samples extracted from peripheral blood leukocyte. All coding sequences, including flanking introns in GLUT2 gene, were amplified using PCR followed by direct sequencing. Results. Two new mutations had been detected, one in each family, in exon 3 two bases (GA were deleted (c.253 254delGA and in exon 6 in the second family, G-to-C substitution at position-1 of the splicing acceptor site (c.776-1G>C or IVS5-1G>A. Conclusion. FBS is a rare disease due to mutation in GLUT2 gene; many mutations were reported, about half were novel mutations; yet none of these mutations is more frequent. A more extensive survey for the most frequent mutations among FBS has to be contemplated to allow for use of molecular screening tests like ARMS.

  5. Infantile diabetics presenting dehydration and acidosis%以脱水及酸中毒为首发表现的婴儿糖尿病

    郭毅; 陈沫; 熊嗣玉

    2004-01-01

    婴幼儿胰岛素依赖型糖尿病临床并不少见,但我们收治的1例情况特殊.患儿父母同患甲状腺功能亢进症(甲亢),经放射免疫治疗后均发生甲状腺功能减退症(甲减),均以左甲状腺素维持治疗.并在治疗期间生育,患儿于1岁时发病。现报告如下:

  6. A patient with acute liver failure and extreme hypoglycaemia with lactic acidosis who was not in coma : causes and consequences of lactate-protected hypoglycaemia

    Oldenbeuving, G.; McDonald, J. R.; Goodwin, M. L.; Sayilir, R.; Reijngoud, D. J.; Gladden, L. B.; Nijsten, M. W. N.

    2014-01-01

    Lactate can substitute for glucose as a metabolic substrate. We report a patient with acute liver failure who was awake despite a glucose level of 0.7 mmol/l with very high lactate level of 25 mmol/l. The hypoglycaemia+hyperlactataemia combination may be considered paradoxical since glucose is the m

  7. pHj, contractility and Ca-balance under hypercapnic acidosis in the myocardium of different vertebrate species

    Gesser, H; Bonefeld-Jørgensen, Eva Cecilie

    1982-01-01

    concentration of hydrogen ions was larger in the turtle than in the trout myocardium. Intracellular Ca-activity, measured by efflux of 45Ca from preloaded heart strips, was unaffected by high CO2 in trout, but was raised in the other three species. Thus the ability to counteract the negative inotropic effect...... of hypercapnia is apparently not due to cellular buffering or extrusion of hydrogen ions. More probably it involves (a) a release of intracellular Ca; (b) a positive inotropic effect of an increase in intracellular Ca-activity....

  8. Brain Injury and Inflammatory Response to Umbilical Cord Occlusions Is Limited With Worsening Acidosis in the Near-Term Ovine Fetus.

    Xu, Alex; Matushewski, Brad; Nygard, Karen; Hammond, Robert; Frasch, Martin G; Richardson, Bryan S

    2016-07-01

    We hypothesized that repetitive umbilical cord occlusions (UCOs) with worsening fetal acidemia will lead to an inflammatory response within the brain and thereby brain injury which will be exacerbated by chronic hypoxemia and low-grade infection. Chronically instrumented fetal sheep served as controls (N = 10) or underwent repeated UCOs for up to 4 hours or until arterial pH was 55% and pH approaching 7.00 for all 3 UCO groups. However, there was no significant effect on measures of brain inflammation or injury, except in the LPS-UCO animals where TUNEL-positive cells were increased in the hippocampus, although small animal numbers in the hypoxic-UCO group may have limited the ability to detect significance in their TUNEL cell findings. We were therefore unable to confirm our working hypothesis since the near-term ovine fetal brain showed remarkable tolerance for these cord occlusion insults and likely involving protective metabolic mechanisms, despite the severe acidemia noted.

  9. Long-term effects of subacute ruminal acidosis (SARA on milk quality and hepatic gene expression in lactating goats fed a high-concentrate diet.

    Haibo Dong

    Full Text Available PURPOSE: The mechanism underlying the decline in milk quality during periods of feeding high-concentrate diets to dairy ruminants is not well documented. The aim of this study was to investigate the metabolic changes in the liver that contribute to the input of substrate precursors to the mammary gland after feeding a high-concentrate diet to lactating goats for a long period. EXPERIMENTAL DESIGN: Eight mid-lactating goats with rumen cannulas were randomly assigned to two groups. For 9 weeks, the treatment group was fed a high-concentrate diet (60% concentrate of dry matter, HC and the control group was fed a low-concentrate diet (40% concentrate of dry matter, LC. Ruminal fluid, plasma, and liver tissues were sampled, microarray techniques and real-time polymerase chain reaction were used to evaluate metabolic parameters and gene expression in liver. RESULTS: Feeding a 60%-concentrate diet for 9 weeks resulted in a significant decrease in rumen pH. Changes in fat and protein content also occurred, which negatively affected milk quality. Plasma levels of leptin (p = 0.058, non-esterified fatty acid (p = 0.071, and glucose (p = 0.014 increased markedly in HC group. Plasma cortisol concentration was significantly elevated in the treatment group (p<0.05. Expression of the glucocorticoid receptor protein gene was significantly down-regulated (p<0.05 in the liver. The expression of genes for interleukin 1β, serum amyloid A, C-reactive protein, and haptoglobin mRNA was significantly increased (p<0.05 in the HC group. GeneRelNet analysis showed that gene expression involved in inflammatory responses and the metabolism of lipids, protein, and carbohydrate were significantly altered by feeding a high-concentrate diet for 9 weeks. CONCLUSIONS: Activation of the acute phase response and the inflammatory response may contribute to nutrient partitioning and re-distribution of energy in the liver, and ultimately lead to a decline in milk quality.

  10. Fanconi Bickel Syndrome: Novel Mutations in GLUT 2 Gene Causing a Distinguished Form of Renal Tubular Acidosis in Two Unrelated Egyptian Families.

    Al-Haggar, Mohammad; Sakamoto, Osamu; Shaltout, Ali; El-Hawary, Amany; Wahba, Yahya; Abdel-Hadi, Dina

    2011-01-01

    Background. Fanconi-Bickel syndrome (FBS) is an autosomal recessive disorder caused by defects in facilitative glucose transporter 2 (GLUT2 or SLC2A2) gene mapped on chromosome 3q26.1-26.3, that codes for the glucose transporter protein 2. Methods. Two unrelated Egyptian families having suspected cases of FBS were enrolled after taking a written informed consent; both had positive consanguinity, and index cases had evidences of proximal renal tubular defects with hepatomegaly; they were subjected to history taking, signs of rickets as well as anthropometric measurements. Laboratory workup included urinalysis, renal and liver function tests including fasting and postprandial blood sugar; serum calcium, phosphorus, alkaline phosphatase, sodium and potassium, lipid profile, and detailed blood gas. Imaging including bone survey and abdominal ultrasound, and liver biopsy were done to confirm diagnosis. Molecular analysis of the GLUT2 gene was done for DNA samples extracted from peripheral blood leukocyte. All coding sequences, including flanking introns in GLUT2 gene, were amplified using PCR followed by direct sequencing. Results. Two new mutations had been detected, one in each family, in exon 3 two bases (GA) were deleted (c.253 254delGA) and in exon 6 in the second family, G-to-C substitution at position-1 of the splicing acceptor site (c.776-1G>C or IVS5-1G>A). Conclusion. FBS is a rare disease due to mutation in GLUT2 gene; many mutations were reported, about half were novel mutations; yet none of these mutations is more frequent. A more extensive survey for the most frequent mutations among FBS has to be contemplated to allow for use of molecular screening tests like ARMS.

  11. 代谢性酸中毒与慢性肾脏病的关系认识%Understanding of relationship between metabolic acidosis and chronic kidney disease

    张景红; 宦红娣

    2011-01-01

    @@ 慢性肾脏病(chronic kidney disease,CKD)的发病率和检出率正逐年增高.来自美国国家卫生和营养调查的流行病学研究显示,CKD的患病率已从10%上升至13%.CKD发病持续增多的主要原因是人口老龄化和2型糖尿病在全球范围内的流行,其中1~4期CKD患者数量超过了CKD 5期患者,且可达后者的50倍[1-2].我国CKD患病率约为10%,有研究提示,2006年有超过36万的CKD患者在接受透析治疗,而之后的3~4年内,这一数值将增加1倍[3].肾脏是调节机体酸碱平衡重要的器官之一,而代谢性酸中毒是CKD患者常见的临床表现.

  12. The role of adrenergic stimulation in maintaining maximum cardiac performance in rainbow trout (Oncorhynchus mykiss) during hypoxia, hyperkalemia and acidosis at 10 degrees C.

    Hanson, Linda M; Obradovich, Shannon; Mouniargi, Janet; Farrell, Anthony P

    2006-07-01

    As rainbow trout approach exhaustion during prolonged exercise, they maintain maximum cardiac output despite the fact their venous blood, which bathes the heart, becomes hypoxic, acidotic and hyperkalemic. Because these factors are individually recognized to have detrimental inotropic and chronotropic effects on cardiac performance, we hypothesized that adrenergic stimulation is critical in maintaining maximum cardiac performance under these collectively adverse conditions in vivo. To test this hypothesis, maximum cardiac performance in the presence and absence of maximal adrenergic stimulation was assessed with in situ rainbow trout hearts using relevant hyperkalemic (5.0 mmol l(-1) K+), acidotic (pH 7.5) and hypoxic challenges. With tonic adrenergic stimulation (5.0 nmol l(-1) adrenaline), hearts produced only 44.8+/-14.6% of their normal maximum cardiac output when exposed under normoxic conditions (20 kPa) to the hyperkalemic, acidotic perfusate, indicating that in vivo there was no refuge from cardiac impairment even if venous blood was fully oxygenated. By contrast, maximum adrenergic stimulation (500 nmol l(-1) adrenaline), fully protected maximum cardiac performance under hyperkalemic and acidotic conditions over a wide range of oxygen availability, from normoxia to 2.0 kPa, a venous oxygen tension close to routine values in vivo. Extending the level of hypoxia to 1.3 kPa resulted in a 43.6+/-2.8% decrease in maximum cardiac output, with hearts failing when tested at 1.0 kPa. Our results suggest that adrenergic stimulation of the trout heart is critical in maintaining maximum performance during prolonged swimming tests, and probably during all forms of exhaustive activity and recovery, when venous blood is hyperkalemic, acidotic and hypoxic.

  13. 1082: Prevalence of Kidney Injury in Burn Patients Requiring Fluid Resuscitation

    2014-12-01

    to kind of acidosis in the immediately postoperative period. The clas- sification evaluated metabolic acidosis by base excess <-4 mmol/L and albumin ...high and normal albumin -corrected anion gap) and to the non-acidosis. Results:The study involved 618 patients. Overall, the acidosis incidence was

  14. Respiratory muscle strength and muscle endurance are not affected by acute metabolic acidemia.

    Nizet, T.; Heijdra, Y.F.; Elshout, F.J.J. van den; Ven, M.J.T. van de; Bosch, F.H.; Mulder, P.H.M. de; Folgering, H.T.M.

    2009-01-01

    Respiratory muscle fatigue in asthma and chronic obstructive lung disease (COPD) contributes to respiratory failure with hypercapnia, and subsequent respiratory acidosis. Therapeutic induction of acute metabolic acidosis further increases the respiratory drive and, therefore, may diminish ventilator

  15. Genetics Home Reference: pseudohypoaldosteronism type 1

    ... and high levels of potassium in the blood (hyperkalemia). Infants with PHA1 can also have high levels of acid in the blood (metabolic acidosis). Hyponatremia, hyperkalemia, or metabolic acidosis can cause nonspecific symptoms such ...

  16. Genetics Home Reference: corticosterone methyloxidase deficiency

    ... levels of potassium in the blood (hyponatremia and hyperkalemia, respectively). Individuals with corticosterone methyloxidase deficiency can also ... acid in the blood (metabolic acidosis). The hyponatremia, hyperkalemia, and metabolic acidosis associated with corticosterone methyloxidase deficiency ...

  17. In Vivo Bleeding Time and In Vitro Thrombelastography Measurements are Better Indicators of Dilutional Hypothermic Coagulopathy Than Prothrombin Time

    2007-06-01

    lation proteins. It is often worsened by massive blood or other fluid transfusion, metabolic acidosis , and hypothermia, or any combination of these...fluid replacement (he- modilution) and hypothermia without massive tissue injury or metabolic acidosis . A mild acidosis (respiratory, pH 7.3) that...massive tissue injury, large hemorrhage that di- lutes and consumes most coagulation factors and hypoperfu- sion, which causes metabolic acidosis and

  18. Where does the lactate come from? A rare cause of reversible inhibition of mitochondrial respiration

    Levy, Bruno; Perez, Pierre; Perny, Jessica

    2010-01-01

    Biguanide poisoning is associated with lactic acidosis. The exact mechanism of biguanide-induced lactic acidosis is not well understood. In the previous issue of Critical Care, Protti and colleagues demonstrated that biguanide-induced lactic acidosis may be due in part to a reversible inhibition of mitochondrial respiration. Thus, in the absence of an antidote, increased drug elimination through dialysis is logical.

  19. Ethyl Pyruvate Provides Therapeutic Benefits to Resuscitation Fluids

    2009-02-01

    described in previous studies [40]. Animals without resuscitation were characterized by uremia, metabolic acidosis and hyperglycemia. Both resuscitation...AnGap) and negative base excess of extracellular fluid (BEecf). Resuscitation with Hextend alone or with ethyl pyruvate improved metabolic acidosis , anion...gap and BEecf . These effects on metabolic acidosis did not correlate with changes in bicarbonate, gases (total and partial CO2), or

  20. Tested Demonstrations.

    Gilbert, George L., Ed.

    1983-01-01

    Discusses a supplement to the "water to rose" demonstration in which a pink color is produced. Also discusses blood buffer demonstrations, including hydrolysis of sodium bicarbonate, simulated blood buffer, metabolic acidosis, natural compensation of metabolic acidosis, metabolic alkalosis, acidosis treatment, and alkalosis treatment. Procedures…