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

Science.gov (United States)

Dong, Lixue; Krewson, Elizabeth A; Yang, Li V

2017-01-27

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 microenvironment.

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

Science.gov (United States)

2012-12-15

acidosis ) with a decrease in respiration ( respiratory aci- dosis) successfully lowered arterial pH to 7.1 (Table 2). Bicarbonate infusion with...in normal, aci- dosis and acidosis -corrected swine for both HCl- and hemorrhage/ respiratory -induced aci- dosis (Figure 2). Infusions of rFVIIa led to...2). Infusion of FVIIa caused no change in aPTT in the Hemorrhage/ Respiratory Model, but deceased ACT in the control, acidosis and acidosis

Metabolic Acidosis or Respiratory Alkalosis? Evaluation of a Low Plasma Bicarbonate Using the Urine Anion Gap.

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Batlle, Daniel; Chin-Theodorou, Jamie; Tucker, Bryan M

2017-09-01

Hypobicarbonatemia, or a reduced bicarbonate concentration in plasma, is a finding seen in 3 acid-base disorders: metabolic acidosis, chronic respiratory alkalosis and mixed metabolic acidosis and chronic respiratory alkalosis. Hypobicarbonatemia due to chronic respiratory alkalosis is often misdiagnosed as a metabolic acidosis and mistreated with the administration of alkali therapy. Proper diagnosis of the cause of hypobicarbonatemia requires integration of the laboratory values, arterial blood gas, and clinical history. The information derived from the urinary response to the prevailing acid-base disorder is useful to arrive at the correct diagnosis. We discuss the use of urine anion gap, as a surrogate marker of urine ammonium excretion, in the evaluation of a patient with low plasma bicarbonate concentration to differentiate between metabolic acidosis and chronic respiratory alkalosis. The interpretation and limitations of urine acid-base indexes at bedside (urine pH, urine bicarbonate, and urine anion gap) to evaluate urine acidification are discussed. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Sodium bicarbonate as prevention of metabolic acidosis in sheep submitted to experimental ruminal acidosis

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Luciane M. Laskoski

2014-09-01

Full Text Available The aim of this study was to evaluate the preventive effect of sodium bicarbonate on systemic acidosis due to ruminal acidosis, which was induced by ingestion of concentrate after prolonged fasting. Fourteen sheep were divided into three experimental groups: control group (Cg, with four sheep, submitted to fasting without development of ruminal acidosis; no-treated group (NTg, with five sheep with rumen acidosis without preventive treatment; and treated group (Tg, with five sheep with rumen acidosis and preventively treated with sodium bicarbonate. Assessments of ruminal pH and arterial hemogasometry were performed for 48 hours after ingestion of the concentrate. There was a reduction in the ruminal pH in all groups, whereas the Cg showed a reduction only after 24 hours. A reduction in the arterial pH, bicarbonate and base excess in all groups was also noted, indicating systemic metabolic acidosis, but the NTg presented the greatest alteration. It is concluded that sodium bicarbonate prevents systemic metabolic acidosis, reducing its severity in sheep subjected to ruminal acidosis.

Acidosis láctica: algunas consideraciones

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Maia Heredero Valdés

2000-09-01

Full Text Available La hiperlactacidemia significa clínicamente problemas para los pacientes. La acidosis láctica es un trastorno ácido-básico consecutivo a la acumulación del ácido láctico, el cual se comporta en el nivel celular, como la contrapartida reducida del ácido pirúvico. Este último, resulta de la degradación de la glucosa en el citosol, proceso que se realiza de manera anaoeróbica y que puede culminar en CO2 H2O si sigue la vía del ácido cítrico de Krebs. El diagnóstico de esta entidad se confirma al medir la concentración sanguínea del lactato, aunque existen diversas características clínicas y de laboratorio que dan indicios de la existencia de este trastorno. Las causas de acidosis láctica se dividen en las producidas por hipoxia hística (tipo A y las no producidas por este trastorno (tipo B; dentro de estas últimas se sitúan las debidas a alteraciones sistémicas, al uso de fármacos o toxinas y a las que acompañan a errores innatos del metabolismo.Hyperlactatemia is a clinical problem for patients. The lactic acidosis is an acid-base disorder following the builup of lactic acid which at cellular level hehaves as a reduced counterpart of the pyruvic acid. The latter results from the degradation of glucose into citosol, a process that is anaerobically carried out and may end up in CO2 H2O if it takes the Krebs? citric acid route. The diagnosis sof this entity is confirmed by measuring blood lactate concentration although there are several clinical and lab characteristics that demonstrate the existance of this disorder. The causes of lactic acidosis are divided into those caused by hystic hypoxia (type A and those not caused by this disorder (type B such as lactic acidosis due to systemic disorders, use of drugs or toxins and acidosis resulting from inborn metabolic errors.

The Postural Tachycardia Syndrome (POTS: Pathophysiology, Diagnosis & Management

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Satish R Raj

2006-04-01

Full Text Available Postural tachycardia syndrome (POTS, characterized by orthostatic tachycardia in the absence of orthostatic hypotension, has been the focus of increasing clinical interest over the last 15 years 1. Patients with POTS complain of symptoms of tachycardia, exercise intolerance, lightheadedness, extreme fatigue, headache and mental clouding. Patients with POTS demonstrate a heart rate increase of ≥30 bpm with prolonged standing (5-30 minutes, often have high levels of upright plasma norepinephrine (reflecting sympathetic nervous system activation, and many patients have a low blood volume. POTS can be associated with a high degree of functional disability. Therapies aimed at correcting the hypovolemia and the autonomic imbalance may help relieve the severity of the symptoms. This review outlines the present understanding of the pathophysiology, diagnosis, and management of POTS.

Missing cells: pathophysiology, diagnosis and management of (pancytopenia in childhood

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Miriam eErlacher

2015-07-01

Full Text Available Peripheral blood cytopenia in children can be due to a variety of acquired or inherited diseases. Genetic disorders affecting a single hematopoietic lineage are frequently characterized by typical bone marrow findings such as lack of progenitors or maturation arrest in congenital neutropenia or a lack of megakaryocytes in congenital amegakaryocytic thrombocytopenia whereas antibody mediated diseases such as autoimmune neutropenia are associated with a rather unremarkable bone marrow morphology. In contrast, pancytopenia is frequently associated with a hypocellular bone marrow and the differential diagnosis includes acquired aplastic anemia, myelodysplastic syndrome, inherited bone marrow failure syndromes such as Fanconi anemia and dyskeratosis congenita and a variety of immunological disorders including hemophagocytic lymphohistiocytosis. Thorough bone marrow analysis is of special importance for the diagnostic work-up of most patients. Cellularity, cellular composition and dysplastic signs are the cornerstones of the differential diagnosis. Pancytopenia in the presence of a normo- or hypercellular marrow with dysplastic changes may indicate myelodysplastic syndrome. More challenging for the hematologist is the evaluation of the hypocellular bone marrow. Although aplastic anemia and hypocellular refractory cytopenia of childhood (RCC can reliably be differentiated on a morphological level the overlapping pathophysiology remains a significant challenge for the choice of the therapeutic strategy. Furthermore, inherited bone marrow failure syndromes are usually associated with the morphological picture of RCC and the recognition of these entities is essential as they often present a multisystem disease requiring different diagnostic and therapeutic approaches. This paper gives an overview over the different disease entities presenting with (pancytopenia, their pathophysiology, characteristic bone marrow findings and therapeutic approaches.

Acidosis in cattle: a review.

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Owens, F N; Secrist, D S; Hill, W J; Gill, D R

1998-01-01

Acute and chronic acidosis, conditions that follow ingestion of excessive amounts of readily fermented carbohydrate, are prominent production problems for ruminants fed diets rich in concentrate. Often occurring during adaptation to concentrate-rich diets in feedyards, chronic acidosis may continue during the feeding period. With acute acidosis, ruminal acidity and osmolality increase markedly as acids and glucose accumulate; these can damage the ruminal and intestinal wall, decrease blood pH, and cause dehydration that proves fatal. Laminitis, polioencephalomalacia, and liver abscesses often accompany acidosis. Even after animals recover from a bout of acidosis, nutrient absorption may be retarded. With chronic acidosis, feed intake typically is reduced but variable, and performance is depressed, probably due to hypertonicity of digesta. Acidosis control measures include feed additives that inhibit microbial strains that produce lactate, that stimulate activity of lactate-using bacteria or starch-engulfing ruminal protozoa, and that reduce meal size. Inoculation with microbial strains capable of preventing glucose or lactate accumulation or metabolizing lactate at a low pH should help prevent acidosis. Feeding higher amounts of dietary roughage, processing grains less thoroughly, and limiting the quantity of feed should reduce the incidence of acidosis, but these practices often depress performance and economic efficiency. Continued research concerning grain processing, dietary cation-anion balance, narrow-spectrum antibiotics, glucose or lactate utilizing microbes, and feeding management (limit or program feeding) should yield new methods for reducing the incidence of acute and chronic acidosis.

Severe Lactic Acidosis in a Patient with B-Cell Lymphoma: A Case Report and Review of the Literature

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Farn Huei Chan

2009-01-01

Full Text Available Lactic acidosis is commonly observed in clinical situations such as shock and sepsis, as a result of tissue hypoperfusion and hypoxia. Lymphoma and leukemia are among other clinical situations where lactic acidosis has been reported. We present a case of a 59-year-old female with lactic acidosis who was found to have aggressive B-cell lymphoma. There have been 29 cases of lymphoma induced lactic acidosis reported thus far; however all reported cases have abnormal vital signs or concomitant medical conditions that may lead to lactic acidosis. The pathogenesis of malignancy-induced lactic acidosis is not well understood; however associated factors include increased glycolysis, increased lactate production by cancer cells, and decreased hepatic clearance of lactate. When it occurs, lactic acidosis is a poor prognostic sign in these patients. Prompt diagnosis and treatment of underlying lymphoma or leukemia remains the only way to achieve complete resolution of lactic acidosis in these patients.

Role of acidosis-induced increases in calcium on PTH secretion in acute metabolic and respiratory acidosis in the dog.

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López, Ignacio; Aguilera-Tejero, Escolástico; Estepa, José Carlos; Rodríguez, Mariano; Felsenfeld, Arnold J

2004-05-01

Recently, we showed that both acute metabolic acidosis and respiratory acidosis stimulate parathyroid hormone (PTH) secretion in the dog. To evaluate the specific effect of acidosis, ionized calcium (iCa) was clamped at a normal value. Because iCa values normally increase during acute acidosis, we now have studied the PTH response to acute metabolic and respiratory acidosis in dogs in which the iCa concentration was allowed to increase (nonclamped) compared with dogs with a normal iCa concentration (clamped). Five groups of dogs were studied: control, metabolic (clamped and nonclamped), and respiratory (clamped and nonclamped) acidosis. Metabolic (HCl infusion) and respiratory (hypoventilation) acidosis was progressively induced during 60 min. In the two clamped groups, iCa was maintained at a normal value with an EDTA infusion. Both metabolic and respiratory acidosis increased (P acidosis, the increase in iCa was progressive and greater (P respiratory acidosis, in which iCa increased by 0.04 mM and then remained constant despite further pH reductions. The increase in PTH values was greater (P respiratory acidosis). In the nonclamped metabolic acidosis group, PTH values first increased and then decreased from peak values when iCa increased by > 0.1 mM. In the nonclamped respiratory acidosis group, PTH values exceeded (P acidosis. In conclusion, 1) both metabolic acidosis and respiratory acidosis stimulate PTH secretion; 2) the physiological increase in the iCa concentration during the induction of metabolic and respiratory acidosis reduces the magnitude of the PTH increase; 3) in metabolic acidosis, the increase in the iCa concentration can be of sufficient magnitude to reverse the increase in PTH values; and 4) for the same degree of acidosis-induced hypercalcemia, the increase in PTH values is greater in metabolic than in respiratory acidosis.

Acetazolamide in cerebral diagnosis: Physiological and pathophysiological aspects

International Nuclear Information System (INIS)

Lerch, H.; Franke, W.G.; Templin, A.

1990-01-01

The sensitivity in the diagnosis of cerebrovascular diseases using radiotracers can be enhanced by the use of the acetazolamide test. In this paper we present and discuss some physiological and pathophysiological aspects of its mechanism. The physiological action of the carboanhydrase inhibitor is like the action of enhanced pCO 2 in the tissue, thus acting at the site of metabolic regulation. The reaction of the vascular bed is influenced in part by subcortical structures. Pathologically the reaction can be disturbed at first by an altered regulation with the vessels being mechanically intact, e.g. in hypoxia or transient ischemia. Secondly, the mechanics of the vessels may be not intact e.g., in atherosclerosis or surrounding edema. Lastly, the vessels have already dilated, e.g. poststenotically. All these facts have to be taken into consideration interpreting an acetazolamid test. (orig.) [de

Restless Legs Syndrome: From Pathophysiology to Clinical Diagnosis and Management

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Shiyi Guo

2017-06-01

Full Text Available Restless legs syndrome (RLS, a common neurological sensorimotor disorder in western countries, has gained more and more attention in Asian countries. The prevalence of RLS is higher in older people and females. RLS is most commonly related to iron deficiency, pregnancy and uremia. The RLS symptoms show a significant circadian rhythm and a close relationship to periodic limb movements (PLMs in clinical observations, while the pathophysiological pathways are still unknown. The diagnostic criteria have been revised in 2012 to improve the validity of RLS diagnosis. Recent studies have suggested an important role of iron decrease of brain in RLS pathophysiology. Dopaminergic (DA system dysfunction in A11 cell groups has been recognized long ago from clinical treatment and autopsy. Nowadays, it is believed that iron dysfunction can affect DA system from different pathways and opioids have a protective effect on DA system. Several susceptible single nucleotide polymorphisms such as BTBD9 and MEIS1, which are thought to be involved in embryonic neuronal development, have been reported to be associated with RLS. Several pharmacological and non-pharmacological treatment are discussed in this review. First-line treatments of RLS include DA agents and α2δ agonists. Augmentation is very common in long-term treatment of RLS which makes prevention and management of augmentation very important for RLS patients. A combination of different types of medication is effective in preventing and treating augmentation. The knowledge on RLS is still limited, the pathophysiology and better management of RLS remain to be discovered.

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

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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.

Lactic acidosis, hyperlactatemia and sepsis

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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

Furosemide/Fludrocortisone Test and Clinical Parameters to Diagnose Incomplete Distal Renal Tubular Acidosis in Kidney Stone Formers.

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Dhayat, Nasser A; Gradwell, Michael W; Pathare, Ganesh; Anderegg, Manuel; Schneider, Lisa; Luethi, David; Mattmann, Cedric; Moe, Orson W; Vogt, Bruno; Fuster, Daniel G

2017-09-07

Incomplete distal renal tubular acidosis is a well known cause of calcareous nephrolithiasis but the prevalence is unknown, mostly due to lack of accepted diagnostic tests and criteria. The ammonium chloride test is considered as gold standard for the diagnosis of incomplete distal renal tubular acidosis, but the furosemide/fludrocortisone test was recently proposed as an alternative. Because of the lack of rigorous comparative studies, the validity of the furosemide/fludrocortisone test in stone formers remains unknown. In addition, the performance of conventional, nonprovocative parameters in predicting incomplete distal renal tubular acidosis has not been studied. We conducted a prospective study in an unselected cohort of 170 stone formers that underwent sequential ammonium chloride and furosemide/fludrocortisone testing. Using the ammonium chloride test as gold standard, the prevalence of incomplete distal renal tubular acidosis was 8%. Sensitivity and specificity of the furosemide/fludrocortisone test were 77% and 85%, respectively, yielding a positive predictive value of 30% and a negative predictive value of 98%. Testing of several nonprovocative clinical parameters in the prediction of incomplete distal renal tubular acidosis revealed fasting morning urinary pH and plasma potassium as the most discriminative parameters. The combination of a fasting morning urinary threshold pH 3.8 mEq/L yielded a negative predictive value of 98% with a sensitivity of 85% and a specificity of 77% for the diagnosis of incomplete distal renal tubular acidosis. The furosemide/fludrocortisone test can be used for incomplete distal renal tubular acidosis screening in stone formers, but an abnormal furosemide/fludrocortisone test result needs confirmation by ammonium chloride testing. Our data furthermore indicate that incomplete distal renal tubular acidosis can reliably be excluded in stone formers by use of nonprovocative clinical parameters. Copyright © 2017 by the American

Distal renal tubular acidosis

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... this disorder. Alternative Names Renal tubular acidosis - distal; Renal tubular acidosis type I; Type I RTA; RTA - distal; Classical RTA Images Kidney anatomy Kidney - blood and urine flow References Bose A, Monk RD, Bushinsky DA. Kidney ...

Trauma triggering thyrotoxic crisis with lactic acidosis

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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.

Review article: the pathophysiology, differential diagnosis and management of rumination syndrome.

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Tack, J; Blondeau, K; Boecxstaens, V; Rommel, N

2011-04-01

Rumination syndrome, characterised by the effortless, often repetitive, regurgitation of recently ingested food into the mouth, was originally described in children and in the developmentally disabled. It is now well-recognised that rumination syndrome occurs in patients of all ages and cognitive abilities. To review a scholarly review on our current understanding of the rumination syndrome. The review was conducted on the basis of a medline search to identify relevant publications pertaining to the pathophysiology, clinical diagnosis and management of rumination syndrome. The Rome III consensus established diagnostic criteria for rumination syndrome in adults, children and infants. A typical history can be highly suggestive but oesophageal (high resolution) manometry/impedance with ingestion of a meal may help to distinguish rumination syndrome from other belching/regurgitation disorders. The pathophysiology is incompletely understood, but involves a rise in intra-gastric pressure, generated by a voluntary, but often unintentional, contraction of the abdominal wall musculature, at a time of low pressure in the lower oesophageal sphincter, causing retrograde movement of gastric contents into the oesophagus. To date, controlled trials in the treatment rumination syndrome are lacking. The mainstay of treatment for rumination syndrome is explanation and behavioural treatment which consists of habit reversal techniques that compete with the urge to regurgitate. Chewing gum, prokinetics, baclofen and even antireflux surgery have been proposed as adjunctive therapies, but high quality studies are generally lacking. Rumination is an under-recognised condition with incompletely understood pathophysiology. Behavioural therapy seems effective, but controlled treatment trials are lacking. © 2011 Blackwell Publishing Ltd.

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

DEFF Research Database (Denmark)

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...

A Quick Reference on Respiratory Acidosis.

Science.gov (United States)

Johnson, Rebecca A

2017-03-01

Respiratory acidosis, or primary hypercapnia, occurs when carbon dioxide production exceeds elimination via the lung and is mainly owing to alveolar hypoventilation. Concurrent increases in Paco 2 , decreases in pH and compensatory increases in blood HCO 3 - concentration are associated with respiratory acidosis. Respiratory acidosis can be acute or chronic, with initial metabolic compensation to increase HCO 3 - concentrations by intracellular buffering. Chronic respiratory acidosis results in longer lasting increases in renal reabsorption of HCO 3 - . Alveolar hypoventilation and resulting respiratory acidosis may also be associated with hypoxemia, especially evident when patients are inspiring room air (20.9% O 2 ). Copyright © 2016 Elsevier Inc. All rights reserved.

Ruminal acidosis: strategies for its control

OpenAIRE

Jaramillo-López, Esaúl; Itza-Ortiz, Mateo F.; Peraza-Mercado, Gwendolyne; Carrera-Chávez, José M.

2017-01-01

ABSTRACT: Ruminal acidosis in ruminants is a metabolic disorder of gastrointestinal origin that occurs in animals with a high feed intake of cereal grains diets, which affect the performance. According to clinical manifestations it can be classified as: a) acute lactic acidosis with prolonged exposure to ruminal pH ≤ 5.0, triggering a systemic acidosis, with clinical manifestations and changes in biochemical patterns, starting the first twelve hours of ruminal acidosis and it takes 48 to 120 ...

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

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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.

Significant Lactic Acidosis from Albuterol

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Deborah Diercks

2018-03-01

Full Text Available Lactic acidosis is a clinical entity that demands rapid assessment and treatment to prevent significant morbidity and mortality. With increased lactate use across many clinical scenarios, lactate values themselves cannot be interpreted apart from their appropriate clinical picture. The significance of Type B lactic acidosis is likely understated in the emergency department (ED. Given the mortality that sepsis confers, a serum lactate is an important screening study. That said, it is with extreme caution that we should interpret and react to the resultant elevated value. We report a patient with a significant lactic acidosis. Though he had a high lactate value, he did not require aggressive resuscitation. A different classification scheme for lactic acidosis that focuses on the bifurcation of the “dangerous” and “not dangerous” causes of lactic acidosis may be of benefit. In addition, this case is demonstrative of the potential overuse of lactates in the ED.

Metabolic acidosis as a risk factor for the development of acute kidney injury and hospital mortality.

Science.gov (United States)

Hu, Jiachang; Wang, Yimei; Geng, Xuemei; Chen, Rongyi; Xu, Xialian; Zhang, Xiaoyan; Lin, Jing; Teng, Jie; Ding, Xiaoqiang

2017-05-01

Metabolic acidosis has been proved to be a risk factor for the progression of chronic kidney disease, but its relation to acute kidney injury (AKI) has not been investigated. In general, a diagnosis of metabolic acidosis is based on arterial blood gas (ABG) analysis, but the diagnostic role of carbon dioxide combining power (CO 2 CP) in the venous blood may also be valuable to non-respiratory patients. This retrospective study included all adult non-respiratory patients admitted consecutively to our hospital between October 01, 2014 and September 30, 2015. A total of 71,089 non-respiratory patients were included, and only 4,873 patients were evaluated by ABG analysis at admission. In patients with ABG, acidosis, metabolic acidosis, decreased HCO 3 - and hypocapnia at admission was associated with the development of AKI, while acidosis and hypocapnia were independent predictors of hospital mortality. Among non-respiratory patients, decreased CO 2 CP at admission was an independent risk factor for AKI and hospital mortality. ROC curves indicated that CO 2 CP was a reasonable biomarker to exclude metabolic acidosis, dual and triple acid-base disturbances. The effect sizes of decreased CO 2 CP on AKI and hospital mortality varied according to age and different underlying diseases. Metabolic acidosis is an independent risk factor for the development of AKI and hospital mortality. In non-respiratory patient, decreased CO 2 CP is also an independent contributor to AKI and mortality and can be used as an indicator of metabolic acidosis.

Gerbode defect: A comprehensive review of its history, anatomy, embryology, pathophysiology, diagnosis, and treatment

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Erfanul Saker

2017-10-01

Full Text Available The purpose of this paper is to survey the literature on Gerbode defect and provide an overview of its history, anatomy, development, pathophysiology, diagnosis, and treatment options. The available literature on this topic, including case reports, was thoroughly reviewed. Gerbode defect is defined as abnormal shunting between the left ventricle and right atrium resulting from either a congenital defect or prior cardiac insults. The pathophysiology underlying the development of Gerbode defect is a disease process that injures the atrioventricular septum and leads to the abnormal shunting of blood. Although the most prevalent cause of Gerbode defect has historically been congenital, an increasing trend towards acquired cases has recently been reported owing to improved diagnostic capabilities and a greater number of invasive cardiac procedures. In conclusion, Gerbode defect is an increasingly recognized condition that warrants further study.

Pathophysiology of incomplete renal tubular acidosis in recurrent renal stone formers: evidence of disturbed calcium, bone and citrate metabolism

DEFF Research Database (Denmark)

Osther, P J; Bollerslev, Jens; Hansen, A B

1993-01-01

Urinary acidification, bone metabolism and urinary excretion of calcium and citrate were evaluated in 10 recurrent stone formers with incomplete renal tubular acidosis (iRTA), 10 recurrent stone formers with normal urinary acidification (NUA) and 10 normal controls (NC). Patients with iRTA had...

Update on Mastocytosis (Part 1): Pathophysiology, Clinical Features, and Diagnosis.

Science.gov (United States)

Azaña, J M; Torrelo, A; Matito, A

2016-01-01

Mastocytosis is a term used to describe a heterogeneous group of disorders characterized by clonal proliferation of mast cells in various organs. The organ most often affected is the skin. Mastocytosis is a relatively rare disorder that affects both sexes equally. It can occur at any age, although it tends to appear in the first decade of life, or later, between the second and fifth decades. Our understanding of the pathophysiology of mastocytosis has improved greatly in recent years, with the discovery that somatic c-kit mutations and aberrant immunophenotypic features have an important role. The clinical manifestations of mastocytosis are diverse, and skin lesions are the key to diagnosis in most patients. Copyright © 2015 Elsevier España, S.L.U. and AEDV. All rights reserved.

Acidosis activates complement system in vitro.

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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 result...

Importance of early audiologic assessment in distal renal tubular acidosis

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Elizabeth Norgett

2010-12-01

Full Text Available Anand P Swayamprakasam1, Elizabeth Stover1, Elizabeth Norgett1, Katherine G Blake-Palmer1, Michael J Cunningham2, Fiona E Karet11Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge, UK; 2Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, MA, USAAbstract: Autosomal recessive distal renal tubular acidosis is usually a severe disease of childhood, often presenting as failure to thrive in infancy. It is often, but not always, accompanied by sensorineural hearing loss, the clinical severity and age of onset of which may be different from the other clinical features. Mutations in either ATP6V1B1 or ATP6V0A4 are the chief causes of primary distal renal tubular acidosis with or without hearing loss, although the loss is often milder in the latter. We describe a kindred with compound heterozygous alterations in ATP6V0A4, where hearing loss was formally diagnosed late in both siblings such that they missed early opportunities for hearing support. This kindred highlights the importance of routine audiologic assessments of all children with distal renal tubular acidosis, irrespective either of age at diagnosis or of which gene is mutated. In addition, when diagnostic genetic testing is undertaken, both genes should be screened irrespective of current hearing status. A strategy for this is outlined.Keywords: sensorineural hearing loss, renal tubular acidosis, recessive, genetics, mutation

Acidosis and Urinary Calcium Excretion

DEFF Research Database (Denmark)

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...

The rumination syndrome in adults: A review of the pathophysiology, diagnosis and treatment

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Papadopoulos V

2007-01-01

Full Text Available Rumination in adults is considered to be the effortless regurgitation of recently ingested food into the mouth, followed by either rechewing and reswallowing or expulsion of the regurgitate. On the basis of the definition of rumination as a unique category of functional gastroduodenal disorders, according to the newly established Rome III classification, a review of the pathophysiology, diagnosis and treatment of the rumination syndrome in adults is presented after systematic and critical approach of all articles that could be retrieved through PubMed using the term "rumination".

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

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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.

An International Consortium Update: Pathophysiology, Diagnosis, and Treatment of Polycystic Ovarian Syndrome in Adolescence.

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Ibáñez, Lourdes; Oberfield, Sharon E; Witchel, Selma; Auchus, Richard J; Chang, R Jeffrey; Codner, Ethel; Dabadghao, Preeti; Darendeliler, Feyza; Elbarbary, Nancy Samir; Gambineri, Alessandra; Garcia Rudaz, Cecilia; Hoeger, Kathleen M; López-Bermejo, Abel; Ong, Ken; Peña, Alexia S; Reinehr, Thomas; Santoro, Nicola; Tena-Sempere, Manuel; Tao, Rachel; Yildiz, Bulent O; Alkhayyat, Haya; Deeb, Asma; Joel, Dipesalema; Horikawa, Reiko; de Zegher, Francis; Lee, Peter A

2017-01-01

This paper represents an international collaboration of paediatric endocrine and other societies (listed in the Appendix) under the International Consortium of Paediatric Endocrinology (ICPE) aiming to improve worldwide care of adolescent girls with polycystic ovary syndrome (PCOS)1. The manuscript examines pathophysiology and guidelines for the diagnosis and management of PCOS during adolescence. The complex pathophysiology of PCOS involves the interaction of genetic and epigenetic changes, primary ovarian abnormalities, neuroendocrine alterations, and endocrine and metabolic modifiers such as anti-Müllerian hormone, hyperinsulinemia, insulin resistance, adiposity, and adiponectin levels. Appropriate diagnosis of adolescent PCOS should include adequate and careful evaluation of symptoms, such as hirsutism, severe acne, and menstrual irregularities 2 years beyond menarche, and elevated androgen levels. Polycystic ovarian morphology on ultrasound without hyperandrogenism or menstrual irregularities should not be used to diagnose adolescent PCOS. Hyperinsulinemia, insulin resistance, and obesity may be present in adolescents with PCOS, but are not considered to be diagnostic criteria. Treatment of adolescent PCOS should include lifestyle intervention, local therapies, and medications. Insulin sensitizers like metformin and oral contraceptive pills provide short-term benefits on PCOS symptoms. There are limited data on anti-androgens and combined therapies showing additive/synergistic actions for adolescents. Reproductive aspects and transition should be taken into account when managing adolescents. © 2017 S. Karger AG, Basel.

Acidosis in the hospital setting: is metformin a common precipitant?

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Scott, K A; Martin, J H; Inder, W J

2010-05-01

Acidosis is commonly seen in the acute hospital setting, and carries a high mortality. Metformin has been associated with lactic acidosis, but it is unclear how frequently this is a cause of acidosis in hospitalized inpatients. The aim of this study is to explore the underlying comorbidities and acute precipitants of acidosis in the hospital setting, including the relationship between type 2 diabetes (T2DM) and metformin use. Retrospective review. Cases of acidosis were identified using the hospital discharge code for acidosis for a 3-month period: October-December 2005. A total of 101 episodes of acidosis were identified: 29% had isolated respiratory acidosis, 31% had metabolic acidosis and 40% had a mixed respiratory and metabolic acidosis. There were 28 cases of confirmed lactic acidosis. Twenty-nine patients had T2DM, but only five of the subjects with T2DM had lactic acidosis; two were on metformin. The major risk factors for development of lactic acidosis were hepatic impairment (OR 33.8, P = 0.01), severe left ventricular dysfunction (OR 25.3, P = 0.074) and impaired renal function (OR 9.7, P = 0.09), but not metformin use. Most cases of metabolic and lactic acidosis in the hospital setting occur in patients not taking metformin. Hepatic, renal and cardiac dysfunction are more important predictors for the development of acidosis.

Statin precipitated lactic acidosis?

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Neale, R; Reynolds, T M; Saweirs, W

2004-09-01

An 82 year old woman was admitted with worsening dyspnoea. Arterial blood gases were taken on air and revealed a pH of 7.39, with a partial pressure of CO2 (pCO2) of 1.2 kPa, pO2 of 19.3 kPa, HCO3 of 13.8 mmol/litre, and base excess of -16.3 mmol/litre: a compensated metabolic acidosis with hyperventilation induced hypocapnia, which is known to be a feature of lactic acidosis. There was also an increased anion gap ((Na140 + K4.0) - (Cl 106 + HCO3 13.8) = 24.2 mEq/litre (reference range, 7-16)), consistent with unmeasured cation. Lactate was measured and found to be raised at 3.33 mmol/litre (reference range, 0.9-1.7). After exclusion of common causes of lactic acidosis Atorvastatin was stopped and her acid-base balance returned to normal. Subsequently, thiamine was also shown to be deficient. The acidosis was thought to have been the result of a mitochondrial defect caused by a deficiency of two cofactors, namely: ubiquinone (as a result of inhibition by statin) and thiamine (as a result of dietary deficiency).

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

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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.

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

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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.

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

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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.

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

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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 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.

Refractory Lactic Acidosis in Small Cell Carcinoma of the Lung

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Daniel J. Oh

2017-01-01

Full Text Available Background. Elevated lactate levels in critically ill patients are most often thought to be indicative of relative tissue hypoxia or type A lactic acidosis. Shock, severe anemia, and thromboembolic events can all cause elevated lactate due to tissue hypoperfusion, as well as the mitochondrial dysfunction thought to occur in sepsis and other critically ill states. Malignancy can also lead to elevation in lactate, a phenomenon described as type B lactic acidosis, which is much less commonly encountered in the critically ill. Case Presentation. We present the case of a 73-year-old Caucasian woman with type 2 diabetes and hypertension who presented with abdominal pain, nausea, vomiting, nonbloody diarrhea, and weight loss over five weeks and was found to have unexplained refractory lactic acidosis despite fluids and antibiotics. She was later diagnosed with small cell carcinoma of the lung. Conclusions. In this case report, we describe a critically ill patient whose elevated lactate was incorrectly attributed to her acute illness, when in truth it was an indicator of an underlying, as yet undiagnosed, malignancy. We believe this case is instructive to the critical care clinician as a reminder of the importance of considering malignancy on the differential diagnosis of a patient presenting with elevated lactate out of proportion to their critical illness.

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

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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.

Otosclerosis update (1). Pathophysiology and diagnosis

International Nuclear Information System (INIS)

Ogawa, Kaoru; Inoue, Yasuhiro; Saito, Hideyuki; Kanzaki, Sho; Okamoto, Yasuhide; Mizutari, Kunio; Suzuki, Takashi; Oishi, Naoki

2009-01-01

Otosclerosis is an otological disease that typicaly causes conductive hearing loss. This disease is an important clinical entity since hearing impairment in these case can be dramatically improved by surgery. In this review paper, we review recent research into the pathophysiology of otosclerosis and summarize clinical features, audiometry and diagnostic imaging examinations in 160 ears with otosclerosis that we treated surgically in our department. (author)

Role of lactate in ischemic acidosis

International Nuclear Information System (INIS)

Nagai, Y.; Naruse, S.; Vink, R.; Weiner, M.W.

1987-01-01

Brain ischemia produces cerebral acidosis that is associated with a rise in lactic acid levels. It is generally thought that the acidosis is due to lactic acid. To investigate this, rats were made hypoglycemic with insulin and the cerebral ischemia was produced. P-31 MR imaging and H-1 MR spectroscopy were used to measure pH and lactate. Hypoclygemia inhibited the rise in lactic acid levels but did not affect pH. Therefore, the fall in pH produced by cerebral ischemia cannot be due to lactic acidosis

Deaths during apprehensions of agitated persons. A review of proposed pathophysiological theories

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Tamsen Fredrik

2014-06-01

Full Text Available The pathophysiology of sudden death during apprehension remains largely unclear. The most frequently discussed mechanisms are excited delirium, positional asphyxia, metabolic acidosis, acute and chronic drug abuse, and autonomic instability. As in most areas of forensic medicine, much of the knowledge comes from case reports, which are of little use in understanding causality. Experimental studies of some aspects have been performed, and they show somewhat divergent results and interpretations. The aim of this review is to summarize the different proposed theories, and to point out important issues for further research.

Colonic lactate metabolism and D-lactic acidosis

DEFF Research Database (Denmark)

Hove, H; Mortensen, P B

1995-01-01

D-Lactic acidosis is seen in patients with intestinal bypass or short bowels in whom colonic produced D-lactate accumulates. An intestinal bypassed patient with D-lactic acidosis had higher fecal D-lactate (122.4 mmol/liter) and L-lactate (90.1 mmol/liter) than described before in humans. D......-Lactate fluctuated between 0.5 and 3.1 mmol/liter in plasma (normal liter) and between 1.1 and 52.8 mmol/liter in urine (normal liter) within a few hours, indicating that the human organism do metabolize and excrete D-lactate. The patient with D-lactic acidosis had a 10-fold increased DL......-lactate in feces (84.0 mmol/liter) and plasma (2.3 mmol/liter) considerably in the patient with D-lactic acidosis. Intestinal prolongation (22 cm ileum) had a temporary effect on fecal and plasma D-lactate, but intestinal continuity was reestablished 26 months later because D-lactic acidosis recurred (plasma 8...

Inborn Errors of Metabolism with Acidosis: Organic Acidemias and Defects of Pyruvate and Ketone Body Metabolism.

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Schillaci, Lori-Anne P; DeBrosse, Suzanne D; McCandless, Shawn E

2018-04-01

When a child presents with high-anion gap metabolic acidosis, the pediatrician can proceed with confidence by recalling some basic principles. Defects of organic acid, pyruvate, and ketone body metabolism that present with acute acidosis are reviewed. Flowcharts for identifying the underlying cause and initiating life-saving therapy are provided. By evaluating electrolytes, blood sugar, lactate, ammonia, and urine ketones, the provider can determine the likelihood of an inborn error of metabolism. Freezing serum, plasma, and urine samples during the acute presentation for definitive diagnostic testing at the provider's convenience aids in the differential diagnosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Distal renal tubular acidosis in two children with acquired hypothyroidism.

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Guerra-Hernández, Norma E; Ordaz-López, Karen V; Vargas-Poussou, Rosa; Escobar-Pérez, Laura; García-Nieto, Víctor M

2018-04-28

Two cases of children diagnosed with renal tubular acidosis (RTA) associated with autoimmune hypothyroidism are presented. Case 1 developed an intestinal ileus at the age of five in the context of a respiratory problem. The tests performed confirmed metabolic acidosis, hyperchloraemia, hypokalaemia and nephrocalcinosis. Case 2 was diagnosed with hypothyroidism at the age of 11, and with RTA two years later. In both patients, the diagnosis of RTA was verified when decreased maximum urinary pCO 2 was found. In case 2, a proximal bicarbonate leak (type 3 RTA) was also confirmed. This was the first case to be published on the topic. The causes of RTA in patients with hypothyroidism are reviewed. The deleterious effect on the kidneys may be due to the absence of thyroid hormone and/or autoantibodies in the cases of autoimmune hypothyroidism. Copyright © 2018 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Diffuse Lymphomatous Infiltration of Kidney Presenting as Renal Tubular Acidosis and Hypokalemic Paralysis: Case Report

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Jhamb, Rajat; Gupta, Naresh; Garg, Sandeep; Kumar, Sachin; Gulati, Sameer; Mishra, Deepak; Beniwal, Pankaj

2007-01-01

We report the case of a 22-year-old woman who presented with acute onset flaccid quadriparesis. Physical examination showed mild pallor with cervical and axillary lymphadenopathy, hepatomegaly, and bilateral smooth enlarged kidneys. Neurological examination revealed lower motor neuron muscle weakness in all the four limbs with hyporeflexia and normal sensory examination. Laboratory investigations showed anemia, severe hypokalemia, and metabolic acidosis. Urinalysis showed a specific gravity of 1.010, pH of 7.0, with a positive urine anion gap. Ultrasound revealed hepatosplenomegaly with bilateral enlarged smooth kidneys. Renal biopsy was consistent with the diagnosis of non-Hodgkin lymphoma (B cell type). Metabolic acidosis, alkaline urine, and severe hypokalemia due to excessive urinary loss in our patient were suggestive of distal renal tubular acidosis. Renal involvement in lymphoma is usually subclinical and clinically overt renal disease is rare. Diffuse lymphomatous infiltration of the kidneys may cause tubular dysfunction and present with hypokalemic paralysis. PMID:18074421

Increased accumulation of N-isopropyl-p-(123I)-iodoamphetamine in two cases with mitochondrial encephalomyopathy with lactic acidosis and strokelike episodes (MELAS)

International Nuclear Information System (INIS)

Morita, K.; Ono, S.; Fukunaga, M.; Morita, R.; Yasuda, T.; Higashi, Y.; Terao, A.

1989-01-01

We present two cases with mitochondrial encephalopathy with lactic acidosis and strokelike episodes (MELAS), which showed both increased and decreased accumulation of N-isopropyl-p-( 123 I)-iodoamphetamine ( 123 I-IMP) in single photon emission computed tomography (SPECT). The increased accumulation of the tracer occurred before low density appeared on conventional computed tomography, suggesting that 123 I-IMP SPECT may be useful in pathophysiological study of MELAS. (orig.)

Sodium Bicarbonate Therapy in Patients with Metabolic Acidosis

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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. PMID:25405229

Sodium Bicarbonate Therapy in Patients with Metabolic Acidosis

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María M. Adeva-Andany

2014-01-01

Full Text Available 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.

Differences in baseline factors and survival between normocapnia, compensated respiratory acidosis and decompensated respiratory acidosis in COPD exacerbation: A pilot study.

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Lun, Chung-Tat; Tsui, Miranda S N; Cheng, Suet-Lai; Chan, Veronica L; Leung, Wah-Shing; Cheung, Alice P S; Chu, Chung-Ming

2016-01-01

Patients with chronic obstructive pulmonary disease (COPD) experiencing acute exacerbation (AE-COPD) with decompensated respiratory acidosis are known to have poor outcomes in terms of recurrent respiratory failure and death. However, the outcomes of AE-COPD patients with compensated respiratory acidosis are not known. We performed a 1-year prospective, single-centre, cohort study in patients surviving the index admission for AE-COPD to compare baseline factors between groups with normocapnia, compensated respiratory acidosis and decompensated respiratory acidosis. Survival analysis was done to examine time to readmissions, life-threatening events and death. A total of 250 patients fulfilling the inclusion and exclusion criteria were recruited and 245 patients were analysed. Compared with normocapnia, both compensated and decompensated respiratory acidosis are associated with lower FEV1 % (P respiratory acidosis, there was no difference in FEV1 (% predicted) (P = 0.15), GOLD stage (P = 0.091), BODE index (P = 0.158) or time to life-threatening events (P = 0.301). High PaCO2 level (P = 0.002) and previous use of non-invasive ventilation (NIV) in acute setting (P respiratory acidosis are associated with poorer lung function and higher risk of future life-threatening events. High PaCO2 level and past history of NIV use in acute settings were predictive factors for future life-threatening events. Compensated respiratory acidosis warrants special attention and optimization of medical therapy as it poses risk of life-threatening events. © 2015 Asian Pacific Society of Respirology.

Incidence, nature, and etiology of metabolic acidosis in dogs and cats.

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Hopper, K; Epstein, S E

2012-01-01

Metabolic acidosis is an important abnormality in ill and injured dogs and cats. To describe the incidence, nature, and etiology of metabolic acidosis in dogs and cats that had arterial or venous blood gases measured for any reason at a university teaching hospital. Dogs and cats at the Veterinary Medical Teaching Hospital. Acid base parameters and electrolyte and lactate concentrations in dogs and cats measured during a 13-month period were retrospectively retrieved from a computer database. Metabolic acidosis was defined as a standardized base excess (SBE) in dogs of acidosis (753 dogs and 134 cats). Primary metabolic acidosis was the most common disorder in dogs, whereas mixed acid base disorder of metabolic acidosis and respiratory acidosis was most common in cats. Hyperchloremic metabolic acidosis was more common than a high anion gap (AG) metabolic acidosis; 25% of dogs and 34% of cats could not be classified as having either a hyperchloremic metabolic acidosis or a high AG metabolic acidosis. Metabolic acidosis was found commonly in this patient population and was associated with a wide variety of disease processes. Mixed acid base disorders occur frequently and routine categorization of metabolic acidosis based on the presence of high AG or hyperchloremia may be misleading in a large proportion of cases. Copyright © 2012 by the American College of Veterinary Internal Medicine.

The frequency and severity of metabolic acidosis related to topiramate.

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Türe, Hatice; Keskin, Özgül; Çakır, Ülkem; Aykut Bingöl, Canan; Türe, Uğur

2016-12-01

Objective We planned a cross-sectional analysis to determine the frequency and severity of metabolic acidosis in patients taking topiramate while awaiting craniotomy. Methods Eighty patients (18 - 65 years) taking topiramate to control seizures while awaiting elective craniotomy were enrolled. Any signs of metabolic acidosis or topiramate-related side effects were investigated. Blood chemistry levels and arterial blood gases, including lactate, were obtained. The severity of metabolic acidosis was defined according to base excess levels as mild or moderate. Results Blood gas analysis showed that 71% ( n = 57) of patients had metabolic acidosis. The frequency of moderate metabolic acidosis was 56% ( n = 45), while that of mild metabolic acidosis was 15% ( n = 12). A high respiratory rate was reported in only 10% of moderately acidotic patients. Conclusions In patients receiving topiramate, baseline blood gas analysis should be performed preoperatively to determine the presence and severity of metabolic acidosis.

The effect of lactic acidosis on the generation and compensation of mixed respiratory-metabolic acidosis in neonatal calves.

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Bleul, U; Götz, E

2013-05-18

Postnatal mixed respiratory-metabolic acidosis is common in calves, and depending on its severity can impair vitality or even cause death. Carbon dioxide accounts for the respiratory component and L-lactate for the metabolic component of the mixed acidosis, but it remains unclear which component determines the severity and duration of the acidosis. In a first attempt to clarify, this was investigated retrospectively in 31 calves during the first two hours of life, and in 13 calves during the first three days of life. Venous blood was collected for blood gas analysis and measurement of acid-base variables and L-lactate concentration. pH Was more strongly correlated with L-lactate concentration (r(2)=0.808) than with partial pressure of CO2 (pCO2, r(2)=0.418). Duration of parturition had a distinct effect on pH and L-lactate concentration but not on pCO2; calves born within six hours of rupture of the allantoic sac had a higher pH and lower L-lactate concentration than calves born after a longer duration of parturition (both Pacidosis than pCO2, and that the duration of metabolic acidosis exceeds that of respiratory acidosis in perinatal asphyxia of calves.

Metabolic acidosis may be as protective as hypercapnic acidosis in an ex-vivo model of severe ventilator-induced lung injury: a pilot study.

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Kapetanakis, Theodoros; Siempos, Ilias I; Metaxas, Eugenios I; Kopterides, Petros; Agrogiannis, George; Patsouris, Efstratios; Lazaris, Andreas C; Stravodimos, Konstantinos G; Roussos, Charis; Armaganidis, Apostolos

2011-04-13

There is mounting experimental evidence that hypercapnic acidosis protects against lung injury. However, it is unclear if acidosis per se rather than hypercapnia is responsible for this beneficial effect. Therefore, we sought to evaluate the effects of hypercapnic (respiratory) versus normocapnic (metabolic) acidosis in an ex vivo model of ventilator-induced lung injury (VILI). Sixty New Zealand white rabbit ventilated and perfused heart-lung preparations were used. Six study groups were evaluated. Respiratory acidosis (RA), metabolic acidosis (MA) and normocapnic-normoxic (Control - C) groups were randomized into high and low peak inspiratory pressures, respectively. Each preparation was ventilated for 1 hour according to a standardized ventilation protocol. Lung injury was evaluated by means of pulmonary edema formation (weight gain), changes in ultrafiltration coefficient, mean pulmonary artery pressure changes as well as histological alterations. HPC group gained significantly greater weight than HPMA, HPRA and all three LP groups (P = 0.024), while no difference was observed between HPMA and HPRA groups regarding weight gain. Neither group differ on ultrafiltration coefficient. HPMA group experienced greater increase in the mean pulmonary artery pressure at 20 min (P = 0.0276) and 40 min (P = 0.0012) compared with all other groups. Histology scores were significantly greater in HP vs. LP groups (p < 0.001). In our experimental VILI model both metabolic acidosis and hypercapnic acidosis attenuated VILI-induced pulmonary edema implying a mechanism other than possible synergistic effects of acidosis with CO2 for VILI attenuation.

Pathophysiologic Changes in Extracellular pH Modulate Parathyroid Calcium-Sensing Receptor Activity and Secretion via a Histidine-Independent Mechanism.

Science.gov (United States)

Campion, Katherine L; McCormick, Wanda D; Warwicker, Jim; Khayat, Mohd Ezuan Bin; Atkinson-Dell, Rebecca; Steward, Martin C; Delbridge, Leigh W; Mun, Hee-Chang; Conigrave, Arthur D; Ward, Donald T

2015-09-01

The calcium-sensing receptor (CaR) modulates renal calcium reabsorption and parathyroid hormone (PTH) secretion and is involved in the etiology of secondary hyperparathyroidism in CKD. Supraphysiologic changes in extracellular pH (pHo) modulate CaR responsiveness in HEK-293 (CaR-HEK) cells. Therefore, because acidosis and alkalosis are associated with altered PTH secretion in vivo, we examined whether pathophysiologic changes in pHo can significantly alter CaR responsiveness in both heterologous and endogenous expression systems and whether this affects PTH secretion. In both CaR-HEK and isolated bovine parathyroid cells, decreasing pHo from 7.4 to 7.2 rapidly inhibited CaR-induced intracellular calcium (Ca(2+)i) mobilization, whereas raising pHo to 7.6 potentiated responsiveness to extracellular calcium (Ca(2+)o). Similar pHo effects were observed for Ca(2+)o-induced extracellular signal-regulated kinase phosphorylation and actin polymerization and for L-Phe-induced Ca(2+)i mobilization. Intracellular pH was unaffected by acute 0.4-unit pHo changes, and the presence of physiologic albumin concentrations failed to attenuate the pHo-mediated effects. None of the individual point mutations created at histidine or cysteine residues in the extracellular domain of CaR attenuated pHo sensitivity. Finally, pathophysiologic pHo elevation reversibly suppressed PTH secretion from perifused human parathyroid cells, and acidosis transiently increased PTH secretion. Therefore, pathophysiologic pHo changes can modulate CaR responsiveness in HEK-293 and parathyroid cells independently of extracellular histidine residues. Specifically, pathophysiologic acidification inhibits CaR activity, thus permitting PTH secretion, whereas alkalinization potentiates CaR activity to suppress PTH secretion. These findings suggest that acid-base disturbances may affect the CaR-mediated control of parathyroid function and calcium metabolism in vivo. Copyright © 2015 by the American Society of

Metabolic acidosis may be as protective as hypercapnic acidosis in an ex-vivo model of severe ventilator-induced lung injury: a pilot study

Directory of Open Access Journals (Sweden)

Patsouris Efstratios

2011-04-01

Full Text Available Abstract Background There is mounting experimental evidence that hypercapnic acidosis protects against lung injury. However, it is unclear if acidosis per se rather than hypercapnia is responsible for this beneficial effect. Therefore, we sought to evaluate the effects of hypercapnic (respiratory versus normocapnic (metabolic acidosis in an ex vivo model of ventilator-induced lung injury (VILI. Methods Sixty New Zealand white rabbit ventilated and perfused heart-lung preparations were used. Six study groups were evaluated. Respiratory acidosis (RA, metabolic acidosis (MA and normocapnic-normoxic (Control - C groups were randomized into high and low peak inspiratory pressures, respectively. Each preparation was ventilated for 1 hour according to a standardized ventilation protocol. Lung injury was evaluated by means of pulmonary edema formation (weight gain, changes in ultrafiltration coefficient, mean pulmonary artery pressure changes as well as histological alterations. Results HPC group gained significantly greater weight than HPMA, HPRA and all three LP groups (P = 0.024, while no difference was observed between HPMA and HPRA groups regarding weight gain. Neither group differ on ultrafiltration coefficient. HPMA group experienced greater increase in the mean pulmonary artery pressure at 20 min (P = 0.0276 and 40 min (P = 0.0012 compared with all other groups. Histology scores were significantly greater in HP vs. LP groups (p Conclusions In our experimental VILI model both metabolic acidosis and hypercapnic acidosis attenuated VILI-induced pulmonary edema implying a mechanism other than possible synergistic effects of acidosis with CO2 for VILI attenuation.

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

International Nuclear Information System (INIS)

Jeffrey, F.M.H.; Malloy, C.R.; Radda, G.K.

1987-01-01

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 2 delivery. Intracellular pH and high-energy phosphates were monitored by 31 P nuclear magnetic resonance spectroscopy. Hearts were perfused to a steady state with a medium containing 10 mM NH 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

Discrete Pathophysiology is Uncommon in Patients with Nonspecific Arm Pain.

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Kortlever, Joost T P; Janssen, Stein J; Molleman, Jeroen; Hageman, Michiel G J S; Ring, David

2016-06-01

Nonspecific symptoms are common in all areas of medicine. Patients and caregivers can be frustrated when an illness cannot be reduced to a discrete pathophysiological process that corresponds with the symptoms. We therefore asked the following questions: 1) Which demographic factors and psychological comorbidities are associated with change from an initial diagnosis of nonspecific arm pain to eventual identification of discrete pathophysiology that corresponds with symptoms? 2) What is the percentage of patients eventually diagnosed with discrete pathophysiology, what are those pathologies, and do they account for the symptoms? We evaluated 634 patients with an isolated diagnosis of nonspecific upper extremity pain to see if discrete pathophysiology was diagnosed on subsequent visits to the same hand surgeon, a different hand surgeon, or any physician within our health system for the same pain. There were too few patients with discrete pathophysiology at follow-up to address the primary study question. Definite discrete pathophysiology that corresponded with the symptoms was identified in subsequent evaluations by the index surgeon in one patient (0.16% of all patients) and cured with surgery (nodular fasciitis). Subsequent doctors identified possible discrete pathophysiology in one patient and speculative pathophysiology in four patients and the index surgeon identified possible discrete pathophysiology in four patients, but the five discrete diagnoses accounted for only a fraction of the symptoms. Nonspecific diagnoses are not harmful. Prospective randomized research is merited to determine if nonspecific, descriptive diagnoses are better for patients than specific diagnoses that imply pathophysiology in the absence of discrete verifiable pathophysiology.

Genetics Home Reference: renal tubular acidosis with deafness

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... adults with renal tubular acidosis with deafness have short stature, and many develop kidney stones. The metabolic acidosis ... enlarged vestibular aqueduct, can be seen with medical imaging. The vestibular aqueduct is a bony canal that ...

A review of the pathophysiology, diagnosis, and management of allergic reactions in the dental office.

Science.gov (United States)

Rochford, Christopher; Milles, Maano

2011-02-01

Since more than 50 million people in the United States have allergies, knowledge of the management of allergic reactions in the dental office is extremely important. Appropriate care may range from a simple referral to a primary care physician to lifesaving measures implemented during acute anaphylactic reactions. The authors present a basic review of the pathophysiology of allergic reactions and provide information detailing the diagnosis and management of allergic reactions that may be encountered in the dental office. Utilizing this information, the dental practitioner and ancillary staff will have a thorough understanding of allergic reactions and be prepared to successfully identify and treat these reactions.

Pathophysiology and Biomarkers in Acute Ischemic Stroke – A Review

African Journals Online (AJOL)

The pathophysiology of ischemic stroke is complex, and majorly involves excitotoxicity, oxidative stress, inflammation, blood-brain barrier dysfunction, apoptosis, etc. Several of the biomarkers are related to these pathophysiologic mechanisms and they may have applications in stroke prediction, diagnosis, assessment, ...

Effects of acute respiratory and metabolic acidosis on diaphragm muscle obtained from rats.

Science.gov (United States)

Michelet, Pierre; Carreira, Serge; Demoule, Alexandre; Amour, Julien; Langeron, Olivier; Riou, Bruno; Coirault, Catherine

2015-04-01

Acute respiratory acidosis is associated with alterations in diaphragm performance. The authors compared the effects of respiratory acidosis and metabolic acidosis in the rat diaphragm in vitro. Diaphragmatic strips were stimulated in vitro, and mechanical and energetic variables were measured, cross-bridge kinetics calculated, and the effects of fatigue evaluated. An extracellular pH of 7.00 was obtained by increasing carbon dioxide tension (from 25 to 104 mmHg) in the respiratory acidosis group (n = 12) or lowering bicarbonate concentration (from 24.5 to 5.5 mM) in the metabolic acidosis group (n = 12) and the results compared with a control group (n = 12, pH = 7.40) after 20-min exposure. Respiratory acidosis induced a significant decrease in maximum shortening velocity (-33%, P Respiratory acidosis impaired more relaxation than contraction, as shown by impairment in contraction-relaxation coupling under isotonic (-26%, P acidosis group. In rat diaphragm, acute (20 min) respiratory acidosis induced a marked decrease in the diaphragm contractility, which was not observed in metabolic acidosis.

Computed tomography and angiography in MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes)

International Nuclear Information System (INIS)

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

1987-01-01

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. (orig.)

Pathophysiology, diagnosis, and management of glaucoma associated with Sturge-Weber syndrome.

Science.gov (United States)

Javaid, Usman; Ali, Muhammad Hassaan; Jamal, Samreen; Butt, Nadeem Hafeez

2018-02-01

Sturge-Weber syndrome (SWS), also known as encephalotrigeminal angiomatosis, is a condition which includes leptomeningeal hemangioma, facial angiomatosis or nevus flammeus, and ocular changes. SWS can lead to severe complications of anterior segment involving conjunctiva and eyelids, whereas posterior segment of the eye may also be affected by diffuse choroidal hemorrhages. This article was written with the objectives to determine the pathophysiology, diagnosis, and treatment of glaucoma associated with this rare and challenging disorder. A detailed literature search was conducted on PubMed, EMBASE, Cochrane Library, and Google Scholar using the key words. Forty-five articles matched our inclusion criteria that were included in this systematic review. Glaucoma is the one of the commonest ocular manifestations of SWS. It is caused by anterior chamber malformations, increased pressure in the episcleral veins, and changes in ocular hemodynamics. Glaucoma associated with SWS is usually congenital but can develop adults as well. The treatment of glaucoma associated with SWS is quite challenging because of early-onset, severe visual field impairment at the time of diagnosis, and unresponsiveness to standard medical treatment. Several surgical procedures have been devised but the long-term control of the intraocular pressure and visual function remain unsatisfactory. Modifications in the filtration surgery techniques and use of newer anti-fibrotic agents have produced good control of intraocular pressure. Management of glaucoma associated with SWS is multi-dimensional and needs both medical and surgical interventions for better control. The treatment should be devised on case to case basis depending upon the intraocular pressure, stage of the disease, and type of glaucoma.

Pediatric Sjogren syndrome with distal renal tubular acidosis and autoimmune hypothyroidism: an uncommon association.

Science.gov (United States)

Agarwal, Amit; Kumar, Pradeep; Gupta, Nomeeta

2015-11-01

A 14-year-old female came with the history of sudden onset weakness; during work up, she was found to have hyperchloremic metabolic acidosis with normal anion gap and normal renal function suggesting the possibility of renal tubular acidosis (RTA). On further evaluation of RTA, she had positive antinuclear antibody, anti-Ro, and anti-La antibodies. On nuclear scan of salivary glands, her left parotid gland was nonfunctional. Her parotid biopsy revealed dilated interlobular ducts engulfed by lymphoid cells. She also had autoimmune hypothyroidism as suggested by raised TSH and positive anti-TPO antibodies. At admission, her serum potassium levels were low and she was treated with intravenous potassium chloride. After she recovered from acute hypokalemic paralysis, she was started on oral potassium citrate along with phosphate supplements, hydroxychloroquine, oral prednisolone and thyroxine supplements. Over the next 6 months, she has significant reduction in the dosage of potassium, bicarbonate and phosphate and gained 3 kg of weight and 3.5 cm of height. As primary Sjogren syndrome itself is rare in pediatric population and its association with renal tubular acidosis is even rarer, we suggest considering Sjogren syndrome as a differential diagnosis during the RTA work-up is worth trying.

Imaging Alzheimer's disease pathophysiology with PET

Directory of Open Access Journals (Sweden)

Lucas Porcello Schilling

Full Text Available ABSTRACT Alzheimer's disease (AD has been reconceptualised as a dynamic pathophysiological process characterized by preclinical, mild cognitive impairment (MCI, and dementia stages. Positron emission tomography (PET associated with various molecular imaging agents reveals numerous aspects of dementia pathophysiology, such as brain amyloidosis, tau accumulation, neuroreceptor changes, metabolism abnormalities and neuroinflammation in dementia patients. In the context of a growing shift toward presymptomatic early diagnosis and disease-modifying interventions, PET molecular imaging agents provide an unprecedented means of quantifying the AD pathophysiological process, monitoring disease progression, ascertaining whether therapies engage their respective brain molecular targets, as well as quantifying pharmacological responses. In the present study, we highlight the most important contributions of PET in describing brain molecular abnormalities in AD.

Metformin-associated lactic acidosis mimicking ischaemic bowel.

Science.gov (United States)

Ali, Sajjad; Labuschagne, Heloise; Azarov, Nickolay; Hindi, Zakaria; Oud, Lavi

2018-02-01

Metformin-associated lactic acidosis (MALA) is a rare complication among patients who are diabetic, commonly presenting with non-specific findings, and developing mostly among those with other risk factors for lactic acidosis. We report the development of MALA in a 67-year-old man with diabetes who presented with progressive abdominal pain and bloody diarrhoea. On presentation the patient was in shock, with signs suggestive of peritonitis, and with severe lactic acidosis, renal failure and non-specific findings on abdominal CT. Neither the patient nor family could provide details of his home pharmaceuticals. Circulatory resuscitation with intravenous crystalloids and vasopressors was commenced, along with empiric broad-spectrum antibiotics. Emergent laparotomy did not show pathological findings. Emergent haemodialysis, initiated postoperatively, resulted in rapid resolution of shock and lactic acidosis. A list of patient's medications, provided afterwards by the family, included metformin. Microbiological studies remained negative and renal function normalised by the time of patient's hospital discharge after 9 days. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Brain carbonic acid acidosis after acetazolamide

DEFF Research Database (Denmark)

Heuser, D; Astrup, J; Lassen, N A

1975-01-01

acidosis by I.V. injection of HCO3-minus. Acetazolamide (25 mg/kg) i.v. was followed by a marked brain acidosis which after 10 min had progressed to a drop in pH of 0.203 plus or minus 0.046 (x bar plus or minus S.D., n equals 8). The slowness ofthe development of acidosis points to a direct effect......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...... of the carbonic anhydrase inhibition on the brain tissue. As a further support for this conclusion was considered the finding of a prolonged response time of brain pH to HCO3-minus i.v. to CO2-minus inhalation, and to hyperventilation after the acetazolamide inhibtion. No changes in brain extracelllular potassium...

[Lactic acidosis in the postictal state].

Science.gov (United States)

van Rooij, Femke J M; Admiraal-van de Pas, Yvonne

2015-01-01

Epilepsy is a neurological disorder with an annual incidence in the Netherlands of 30 per 100,000 people. We present two cases of a patient admitted to the emergency department upon experiencing a generalized seizure. In each case, severe metabolic lactic acidosis was identified through routine laboratory diagnostics. Based on their clinical presentation, we had no reasons to suspect another cause of this severe acidosis apart from the seizure. We repeated arterial blood sample one to two hours later and found that both pH and lactate were normalized. Severe lactic acidosis may occur in patients who experience seizures but otherwise do not require treatment. Taking an arterial blood sample from these patients in the emergency setting will be of limited value, because in most patients hyperlactatemia in the postictal state is self-limiting. In some patients, however, a persistent hyperlactatemia may indicate a serious underlying pathology. It is therefore advisable to repeat an arterial blood sample a few hours later.

Dichloroacetate prevents hypoxic lactic acidosis in rats | Bosco ...

African Journals Online (AJOL)

acidosis, particularly in the cerebral tissue and the cerebrospinal fluid. Assess the efficiency of dichloroacetate in the prevention of hypoxia-induced lactic acidosis. We used adult rats, 3 months old, with a weight of 250-300 grams. Anesthesia was achieved by intraperitoneal injection of pentobarbital (Nembutal®), at the ...

Chronic Pruritus in the Absence of Skin Disease: Pathophysiology, Diagnosis and Treatment.

Science.gov (United States)

Pereira, Manuel P; Kremer, Andreas E; Mettang, Thomas; Ständer, Sonja

2016-08-01

Chronic pruritus arises not only from dermatoses, but also, in up to half of cases, from extracutaneous origins. A multitude of systemic, neurological, psychiatric, and somatoform conditions are associated with pruritus in the absence of skin disease. Moreover, pruritus is a frequently observed side effect of many drugs. It is therefore difficult for physicians to make a correct diagnosis. Chronic pruritus patients frequently present to the dermatologist with skin lesions secondary to a long-lasting scratching behavior, such as lichenification and prurigo nodularis. A structured clinical history and physical examination are essential in order to evaluate the pruritus, along with systematic, medical history-adapted laboratory and radiological tests carried out according to the differential diagnosis. For therapeutic reasons, a symptomatic therapy should be promptly initiated parallel to the diagnostic procedures. Once the underlying factor(s) leading to the pruritus are identified, a targeted therapy should be implemented. Importantly, the treatment of accompanying disorders such as sleep disturbances or mental symptoms should be taken into consideration. Even after successful treatment of the underlying cause, pruritus may persist, likely due to chronicity processes including peripheral and central sensitization or impaired inhibition at spinal level. A vast arsenal of topical and systemic agents targeting these pathophysiological mechanisms has been used to deter further chronicity. The therapeutic options currently available are, however, still insufficient for many patients. Thus, future studies aiming to unveil the complex mechanisms underlying chronic pruritus and develop new therapeutic agents are urgently needed.

Pathophysiology, diagnosis, and treatment of canine hip dysplasia

International Nuclear Information System (INIS)

Cook, J.L.; Tomlinson, J.L.; Constantinescu, G.M.

1996-01-01

Dogs with hip dysplasia are commonly presented to veterinarians for evaluation. Although many causes of the condition have been proposed, a definitive cause has not been established. The multifactorial nature of canine hip dysplasia can confuse client education and management ofthe disease. The basic concept involved is the biomechanical imbalance between the forces on the coxofemoral joint and the associated muscle mass; the result is joint laxity in young, growing dogs. This laxity leads to incongruity; the eventual result is degenerative joint disease. Canine hip dysplasia can affect any breed but is most often reported in large and giant breeds. Understanding the pathophysiology and biomechanics involved with this developmental disease is important in providing clients with diagnostic, therapeutic, and prognostic information. The selection of treatment is influenced by the following factors:the age, health, and intended use of the patient; clinical signs; diagnostic findings; the availability of treatment; and the financial constraints of the owner. This article discusses the current concepts concerning the pathophysiology and biomechanics of canine hip dysplasia and outlines diagnostic and therapeutic options. The objective of the article is to provide practitioners with a reference for decision making and client education

FHR patterns that become significant in connection with ST waveform changes and metabolic acidosis at birth.

Science.gov (United States)

Rosén, Karl G; Norén, Håkan; Carlsson, Ann

2018-04-18

Recent developments have produced new CTG classification systems and the question is to what extent these may affect the model of FHR + ST interpretation? The two new systems (FIGO2015 and SSOG2017) classify FHR + ST events differently from the current CTG classification system used in the STAN interpretation algorithm (STAN2007). Identify the predominant FHR patterns in connection with ST events in cases of cord artery metabolic acidosis missed by the different CTG classification systems. Indicate to what extent STAN clinical guidelines could be modified enhancing the sensitivity. Provide a pathophysiological rationale. Forty-four cases with umbilical cord artery metabolic acidosis were retrieved from a European multicenter database. Significant FHR + ST events were evaluated post hoc in consensus by an expert panel. Eighteen cases were not identified as in need of intervention and regarded as negative in the sensitivity analysis. In 12 cases, ST changes occurred but the CTG was regarded as reassuring. Visual analysis of the FHR + ST tracings revealed specific FHR patterns: Conclusion: These findings indicate FHR + ST analysis may be undertaken regardless of CTG classification system provided there is a more physiologically oriented approach to FHR assessment in connection with an ST event.

The relationship between metabolic acidosis and nutritional parameters in patients on hemodialysis

Directory of Open Access Journals (Sweden)

A D Sajgure

2017-01-01

Full Text Available The progressive loss of kidney function is accompanied by metabolic acidosis. The relationship between metabolic acidosis, nutritional status, and oral bicarbonate supplementation has not been assessed in the Indian chronic kidney disease (CKD population who are on maintenance hemodialysis (MHD. This is a single-center prospective study conducted in the Western part of India. Thirty-five patients, who were receiving MHD were assessed for metabolic acidosis along with various nutritional parameters at the baseline and at the follow-up after 3 months, postcorrection of acidosis with oral sodium bicarbonate supplements. The relationship between the correction of metabolic acidosis with oral bicarbonate supplements and changes in dietary and various nutritional parameters were evaluated. Metabolic acidosis at the baseline evaluation was found in 62.86% cases of the cohort with a mean serum bicarbonate value of 20.18 ± 4.93 mmol/L. The correction of acidosis with increment in the mean dosage of oral sodium bicarbonate supplements from 0.69 ± 0.410 mmol/kg/day at baseline to 1.04 ± 0.612 mmol/kg/day, significantly reduced the prevalence of metabolic acidosis to 23.33% cases at the follow-up. Improvement in serum bicarbonate level showed significant dietary, anthropometric, and nutritional improvements in these patients. Hence, we conclude that correction of metabolic acidosis with optimal oral bicarbonate supplementation plays a pivotal role in the treatment of malnourished CKD patients on MHD.

ACE Inhibitor-Induced Angioedema of the Intestine: Case Report, Incidence, Pathophysiology, Diagnosis and Management

Directory of Open Access Journals (Sweden)

Gavin Oudit

2001-01-01

Full Text Available A case report of fosinopril-induced angioedema of the intestine with a chronic course accompanied by multiple acute exacerbations is described. Angiotensin-converting enzyme (ACE inhibitor-induced angioedema of the intestine (AIAI occurs in a minority of patients taking an ACE inhibitor. The clinical presentation encompasses acute abdominal symptoms, pronounced bowel edema and ascites with occasional facial and/or oropharyngeal swelling. AIAI is diagnosed based on the temporal relationship between the symptomatic presentation and drug use, absence of alternative diagnoses including other causes of angioedema, and the prompt resolution of symptoms upon discontinuation of the ACE inhibitor. Prompt radiological investigation (abdominal computerized tomography and/or ultrasound is critical in making an early diagnosis and in preventing unnecessary surgical intervention. There is a female predominance of AIAI, which may reflect the interaction of estradiol with the various pathways involved in the pathophysiology of AIAI. Management of AIAI consists mainly of conservative measures and discontinuation of the ACE inhibitor. Angiotensin II receptor antagonists should not be considered as appropriate alternatives. Awareness and knowledge of AIAI are important because of the increasing use of ACE inhibitors, current delays in making the diagnosis, obvious management strategies once the diagnosis is made and the dysutility of alternative diagnoses, which may lead to considerable morbidity. AIAI must be considered in patients taking ACE inhibitors who develop gastrointestinal complaints irrespective of the duration of the therapy.

Acute renal response to rapid onset respiratory acidosis.

Science.gov (United States)

Ramadoss, Jayanth; Stewart, Randolph H; Cudd, Timothy A

2011-03-01

Renal strong ion compensation to chronic respiratory acidosis has been established, but the nature of the response to acute respiratory acidosis is not well defined. We hypothesized that the response to acute respiratory acidosis in sheep is a rapid increase in the difference in renal fractional excretions of chloride and sodium (Fe(Cl) - Fe(Na)). Inspired CO(2) concentrations were increased for 1 h to significantly alter P(a)CO(2) and pH(a) from 32 ± 1 mm Hg and 7.52 ± 0.02 to 74 ± 2 mm Hg and 7.22 ± 0.02, respectively. Fe(Cl) - Fe(Na) increased significantly from 0.372 ± 0.206 to 1.240 ± 0.217% and returned to baseline at 2 h when P(a)CO(2) and pH(a) were 37 ± 0.6 mm Hg and 7.49 ± 0.01, respectively. Arterial pH and Fe(Cl) - Fe(Na) were significantly correlated. We conclude that the kidney responds rapidly to acute respiratory acidosis, within 30 min of onset, by differential reabsorption of sodium and chloride.

The pathophysiology of trauma-induced coagulopathy.

Science.gov (United States)

Frith, Daniel; Brohi, Karim

2012-12-01

Transfusion paradigms and protocols have evolved at a rapid pace in the last few years to ameliorate the adverse effects of trauma-induced coagulopathy (TIC). This has occurred despite fragmented and inadequate knowledge of the underlying pathophysiology that they are supposed to treat. This review will collate and assimilate the most recent data about TIC in order to present our state-of-the-art understanding of this condition. TIC was conventionally construed simply as depletion, dysfunction or dilution of procoagulant factors. However, contemporary understanding recognizes it as an imbalance of the dynamic equilibrium between procoagulant factors, anticoagulant factors, platelets, endothelium and fibrinolysis. The endogenous component of TIC (acute traumatic coagulopathy) is not merely a consumptive coagulopathy, but is characterized by isolated factor V inhibition, dysfibrinogenaemia, systemic anticoagulation, impaired platelet function and hyperfibrinolysis. Acute traumatic coagulopathy then becomes exacerbated by hypothermia, acidosis and resuscitation with hypocoagulable fluids. Further improvement in the outcome from trauma-haemorrhage is possible with more refined and tailored haemostatic resuscitation. Achieving this will depend upon a better understanding of the haemostatic defects that develop after injury.

A neglected case of Renal Tubular Acidosis

International Nuclear Information System (INIS)

Derakhshan, A.; Basiratnia, M.; Fallahzadeh, M.H.; Al-Hashemi, G.H.

2007-01-01

In this report, we present a case of a child with distal renal tubular acidosis, severe failure to thrive and profound rickets, who was only 7.8 Kg when presented at 6 years of age. His response to treatment and his follow up for four years is discussed. Although failure to thrive is a common finding in renal tubular acidosis but the physical and x-ray findings in our case were unique. (author)

Age specific fast breathing in under-five diarrheal children in an urban hospital: Acidosis or pneumonia?

Science.gov (United States)

Nuzhat, Sharika; Ahmed, Tahmeed; Kawser, Chowdhury Ali; Khan, Azharul Islam; Islam, S M Rafiqul; Shahrin, Lubaba; Shahunja, K M; Shahid, Abu S M S B; Al Imran, Abdullah; Chisti, Mohammod Jobayer

2017-01-01

Children with diarrhea often present with fast breathing due to metabolic acidosis from dehydration. On the other hand, age specific fast breathing is the cornerstone for the diagnosis of pneumonia following classification of pneumonia recommended by the World Health Organization (WHO). Correction of metabolic acidosis by rehydrating the diarrheal children requires time, which delays early initiation of appropriate antimicrobials for pneumonia and thereby increases the risk of deaths. We need to further investigate the simple clinical features other than fast breathing which might help us in earliest diagnosis of pneumonia in children with diarrhea Thus, the objective of our study was to identify other contributing clinical features that may independently help for early diagnosis of pneumonia in diarrheal children who present with age specific fast breathing. This was an unmatched case-control study. Diarrheal children aged 0-59 months, admitted to Dhaka Hospital of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b) during January 2014 to December 2014 having age specific fast breathing (11-59 months ≥40 breaths/min) were studied. The study children with clinical and radiological pneumonia constituted the cases (n = 276) and those without pneumonia constituted the controls (n = 446). Comparison of clinical features and outcomes between the cases and the controls was made. The distribution of acidosis among the cases and the controls was comparable (35% vs. 41%, p = 0.12). The cases had proportionately higher deaths compared to the controls, however, the difference was not statistically significant (3% vs. 1%; p = 0.23). In logistic regression analysis after adjusting for potential confounders, the cases were independently associated with cough (OR = 62.19, 95% CI = 27.79-139.19; ppneumonia. The results underscore the importance of early identification of these simple clinical features that may help to minimize potential delay due to

An update on pancreatic pathophysiology (do we have to rewrite pancreatic pathophysiology?).

Science.gov (United States)

Hammer, Heinz F

2014-02-01

This review focuses on seven aspects of physiology and pathophysiology of the exocrine pancreas that have been intensively discussed and studied within the past few years: (1) the role of neurohormonal mechanisms like melatonin, leptin, or ghrelin in the stimulation of pancreatic enzyme secretion; (2) the initiation processes of acute pancreatitis, like fusion of zymogen granules with lysosomes leading to intracellular activation of trypsinogen by the lysosomal enzyme cathepsin B, or autoactivation of trypsinogen; (3) the role of genes in the pathogenesis of acute pancreatitis; (4) the role of alcohol and constituents of alcoholic beverages in the pathogenesis of acute pancreatitis; (5) the role of pancreatic hypertension, neuropathy, and central mechanisms for the pathogenesis of pain in chronic pancreatitis; (6) the relation between exocrine pancreatic function and diabetes mellitus; and (7) pathophysiology, diagnosis and treatment of pancreatic steatorrhea.

Metabolic acidosis caused by concomitant use of paracetamol (acetaminophen) and flucloxacillin? A case report and a retrospective study.

Science.gov (United States)

Berbee, J K; Lammers, L A; Krediet, C T P; Fischer, J C; Kemper, E M

2017-11-01

A patient was identified with severe metabolic acidosis, a high anion gap and 5-oxoproline accumulation, probably caused by the simultaneous use of paracetamol (acetaminophen) and flucloxacillin. We wanted to investigate the necessity to control the interaction between both drugs with an automatic alert system. To investigate the relevance of the interaction of paracetamol and flucloxacillin, a retrospective study was conducted. Data on paracetamol and flucloxacillin prescriptions and laboratory data (pH, Na + , HCO 3 - , Cl - , albumin and 5-oxoproline levels) were combined to assess the prevalence of acidosis, calculate the anion gap and analyse 5-oxoproline levels in clinically admitted patients using both drugs simultaneously. In the 2-year study period, approximately 53,000 admissions took place in our hospital. One thousand and fifty-seven patients used paracetamol and flucloxacillin simultaneously, of which 51 patients (4.8%) had a serum pH ≤ 7.35. One patient, the same patient as presented in the case report, had a high anion gap and a toxic level of 5-oxoproline. The prevalence of metabolic acidosis is very low and the only patient identified with the interaction was recognised during normal clinical care. We conclude that automatic alerts based on simultaneous use of paracetamol and flucloxacillin will generate too many signals. To recognise patients earlier and prevent severe outcomes, a warning system (clinical rule) based on paracetamol, flucloxacillin and pH measurement may be helpful. Early calculation of the anion gap can narrow the differential diagnosis of patients with metabolic acidosis and measurement of 5-oxoproline can explain acidosis due the interaction of paracetamol and flucloxacillin.

Postoperative Compensatory Ammonium Excretion Subsequent to Systemic Acidosis in Cardiac Patients.

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Roehrborn, Friederike; Dohle, Daniel-Sebastian; Waack, Indra N; Tsagakis, Konstantinos; Jakob, Heinz; Teloh, Johanna K

2017-01-01

Postoperative acid-base imbalances, usually acidosis, frequently occur after cardiac surgery. In most cases, the human body, not suffering from any severe preexisting illnesses regarding lung, liver, and kidney, is capable of transient compensation and final correction. The aim of this study was to correlate the appearance of postoperatively occurring acidosis with renal ammonium excretion. Between 07/2014 and 10/2014, a total of 25 consecutive patients scheduled for elective isolated coronary artery bypass grafting with cardiopulmonary bypass were enrolled in this prospective observational study. During the operative procedure and the first two postoperative days, blood gas analyses were carried out and urine samples collected. Urine samples were analyzed for the absolute amount of ammonium. Of all patients, thirteen patients developed acidosis as an initial disturbance in the postoperative period: five of respiratory and eight of metabolic origin. Four patients with respiratory acidosis but none of those with metabolic acidosis subsequently developed a base excess > +2 mEq/L. Ammonium excretion correlated with the increase in base excess. The acidosis origin seems to have a large influence on renal compensation in terms of ammonium excretion and the possibility of an overcorrection.

Risk of lactic acidosis in type 2 diabetes patients using metformin

DEFF Research Database (Denmark)

Aharaz, Abdellatif; Pottegård, Anton; Henriksen, Daniel Pilsgaard

2018-01-01

risk of lactic acidosis associated with metformin treatment. Methods This is a population-based combined cohort and case-control study among patients with type 2 diabetes mellitus who were acutely admitted with lactic acidosis at Odense University Hospital, Denmark; in the period from 1st June 2009...... to 1st October 2013. The patients included as cases were all acutely hospitalized with lactic acidosis (pH 2.0 mmol/l). For each case, we identified 24 age- and sex-matched controls sampled from the same cohort with type 2 diabetes mellitus. The use of metformin identified by using......Background Metformin constitutes first-line treatment of type 2 diabetes mellitus. It is presumed to have lactic acidosis as a dangerous, but rare, side effect. Objectives To estimate the incidence rate of lactic acidosis in patients with type 2 diabetes mellitus as well as to estimate the relative...

What is the clinical significance of 5-oxoproline (pyroglutamic acid) in high anion gap metabolic acidosis following paracetamol (acetaminophen) exposure?

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Liss, D B; Paden, M S; Schwarz, E S; Mullins, M E

2013-11-01

Paracetamol (acetaminophen) ingestion is the most frequent pharmaceutical overdose in the developed world. Metabolic acidosis sometimes occurs, but the acidosis is infrequently persistent or severe. A growing number of case reports and case series describe high anion gap metabolic acidosis (HAGMA) following paracetamol exposure with subsequent detection or measurement of 5-oxoproline (also called pyroglutamic acid) in blood, urine, or both. Typically 5-oxoprolinuria or 5-oxoprolinemia occurs in the setting of inborn genetic errors in glutathione metabolism. It is unknown whether 5-oxoprolinemia in the setting of paracetamol exposure reflects an acquired or transient derangement of glutathione metabolism or previously unrecognized genetic defects. We reviewed the published cases of 5-oxoprolinemia or 5-oxoprolinuria among patients with HAGMA in the setting of paracetamol exposure. Our goal was to identify any consistent features that might increase our understanding of the pathophysiology, diagnosis, and treatment of similar cases. We searched the medical literature using PUBMED and EMBASE from inception to 28 August 2013 applying search terms ("oxoproline" OR "pyroglutamic acid" AND "paracetamol" OR "acetaminophen"). The intersection of these two searches returned 77 articles, of which 64 involved human subjects and were in English. Two articles, one each in Spanish and Dutch, were reviewed. An additional Google Scholar search was done with the same terms. We manually searched the reference lists of retrieved articles to identify additional four relevant articles. We focused on articles including measured 5-oxoproline concentrations in urine or blood. Twenty-two articles included quantified 5-oxoproline concentrations. Several additional articles mentioned only qualitative detection of 5-oxoproline in urine or blood without concentrations being reported. Our manual reference search yielded four additional articles for a total of 24 articles describing 43 patients

Lactic Acidosis in a Patient with Type 2 Diabetes Mellitus.

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Weisberg, Lawrence S

2015-08-07

Lactic acidosis occurs when lactate production exceeds its metabolism. There are many possible causes of lactic acidosis, and in any given patient, several causes may coexist. This Attending Rounds presents a case in point. Metformin's role in the pathogenesis of lactic acidosis in patients with diabetes mellitus is complex, as the present case illustrates. The treatment of lactic acidosis is controversial, except for the imperative to remedy its underlying cause. The use of sodium bicarbonate to treat the often alarming metabolic derangements may be quite efficacious in that regard but is of questionable benefit to patients. Renal replacement therapies (RRTs) have particular appeal in this setting for a variety of reasons, but their effect on clinical outcomes is untested. Copyright © 2015 by the American Society of Nephrology.

Metformin-associated lactic acidosis in a peritoneal dialysis patient

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Najlaa Almaleki

2015-01-01

Full Text Available Metformin is one of the commonly used drugs in type-2 diabetes mellitus. It reduces glucose levels by increasing insulin sensitivity, reducing hepatic glucose release and increasing muscle uptake. One of the serious complications associated with metformin use is lactic acidosis, and it is associated with high morbidity and mortality. This is more likely to happen in patients with renal failure due to reduced clearance. International guidelines recommend discontinuing metformin in advanced renal failure. We report a case of metformin-associated lactic acidosis in a patient with end-stage renal disease on peritoneal dialysis. The patient presented with severe lactic acidosis, which was successfully treated with hemodialysis.

Interaction of metabolic and respiratory acidosis with α and β-adrenoceptor stimulation in rat myocardium.

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Biais, Matthieu; Jouffroy, Romain; Carillion, Aude; Feldman, Sarah; Jobart-Malfait, Aude; Riou, Bruno; Amour, Julien

2012-12-01

The effects of acute respiratory versus metabolic acidosis on the myocardium and their consequences on adrenoceptor stimulation remain poorly described. We compared the effects of metabolic and respiratory acidosis on inotropy and lusitropy in rat myocardium and their effects on the responses to α- and β-adrenoceptor stimulations. The effects of acute respiratory and metabolic acidosis (pH 7.10) and their interactions with α and β-adrenoceptor stimulations were studied in isolated rat left ventricular papillary muscle (n=8 per group). Intracellular pH was measured using confocal microscopy and a pH-sensitive fluorophore in isolated rat cardiomyocytes. Data are mean percentages of baseline±SD. Respiratory acidosis induced more pronounced negative inotropic effects than metabolic acidosis did both in isotonic (45±3 versus 63±6%, Prespiratory or metabolic acidosis. The inotropic response to β-adrenergic stimulation was impaired only in metabolic acidosis (137±12 versus 200±33%, Pacidosis. The lusitropic response to β-adrenergic stimulation was not modified by respiratory or metabolic acidosis. Acute metabolic and respiratory acidosis induce different myocardial effects related to different decreases in intracellular pH. Only metabolic acidosis impairs the positive inotropic effect of β-adrenergic stimulation.

Herpes Simplex Virus-1 Encephalitis in Adults: Pathophysiology, Diagnosis, and Management.

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Bradshaw, Michael J; Venkatesan, Arun

2016-07-01

Herpetic infections have plagued humanity for thousands of years, but only recently have advances in antiviral medications and supportive treatments equipped physicians to combat the most severe manifestations of disease. Prompt recognition and treatment can be life-saving in the care of patients with herpes simplex-1 virus encephalitis, the most commonly identified cause of sporadic encephalitis worldwide. Clinicians should be able to recognize the clinical signs and symptoms of the infection and familiarize themselves with a rational diagnostic approach and therapeutic modalities, as early recognition and treatment are key to improving outcomes. Clinicians should also be vigilant for the development of acute complications, including cerebral edema and status epilepticus, as well as chronic complications, including the development of autoimmune encephalitis associated with antibodies to the N-methyl-D-aspartate receptor and other neuronal cell surface and synaptic epitopes. Herein, we review the pathophysiology, differential diagnosis, and clinical and radiological features of herpes simplex virus-1 encephalitis in adults, including a discussion of the most common complications and their treatment. While great progress has been made in the treatment of this life-threatening infection, a majority of patients will not return to their previous neurologic baseline, indicating the need for further research efforts aimed at improving the long-term sequelae.

A case of lactic acidosis complicating assessment and management of asthma

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Veenith Tonny V

2008-04-01

Full Text Available Abstract Introduction Lactic acidosis often occurs in severely unwell patients presenting to Accident and Emergency. It is commonly associated with either hypoxia or decreased tissue perfusion secondary due to cardiovascular collapse or sepsis. Case presentation We present a case of severe lactic acidosis in the presence of normal tissue perfusion and oxygenation in a 31-year-old patient with poorly-controlled asthma. Acidosis promptly reversed on discontinuation of inhaled beta-agonists. Conclusion Lactic acidosis secondary to inhaled beta-agonist administration may be a common scenario which can be misinterpreted very easily and can confuse the clinical picture. Further studies will be needed to establish the exact aetiology of this lactic acid production.

Age specific fast breathing in under-five diarrheal children in an urban hospital: Acidosis or pneumonia?

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Sharika Nuzhat

Full Text Available Children with diarrhea often present with fast breathing due to metabolic acidosis from dehydration. On the other hand, age specific fast breathing is the cornerstone for the diagnosis of pneumonia following classification of pneumonia recommended by the World Health Organization (WHO. Correction of metabolic acidosis by rehydrating the diarrheal children requires time, which delays early initiation of appropriate antimicrobials for pneumonia and thereby increases the risk of deaths. We need to further investigate the simple clinical features other than fast breathing which might help us in earliest diagnosis of pneumonia in children with diarrhea Thus, the objective of our study was to identify other contributing clinical features that may independently help for early diagnosis of pneumonia in diarrheal children who present with age specific fast breathing.This was an unmatched case-control study. Diarrheal children aged 0-59 months, admitted to Dhaka Hospital of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b during January 2014 to December 2014 having age specific fast breathing (11-59 months ≥40 breaths/min were studied. The study children with clinical and radiological pneumonia constituted the cases (n = 276 and those without pneumonia constituted the controls (n = 446. Comparison of clinical features and outcomes between the cases and the controls was made.The distribution of acidosis among the cases and the controls was comparable (35% vs. 41%, p = 0.12. The cases had proportionately higher deaths compared to the controls, however, the difference was not statistically significant (3% vs. 1%; p = 0.23. In logistic regression analysis after adjusting for potential confounders, the cases were independently associated with cough (OR = 62.19, 95% CI = 27.79-139.19; p<0.01 and chest wall indrawing (OR = 31.05, 95%CI = 13.43-71.82; p<0.01 and less often had severe acute malnutrition (OR = 0.33, 95%CI = 0

Life-threatening hypokalemia following rapid correction of respiratory acidosis.

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Hammond, Kendra; You, David; Collins, Eileen G; Leehey, David J; Laghi, Franco

2013-01-01

A 56-year-old woman with a history of paraplegia and chronic pain due to neuromyelitis optica (Devic's syndrome) was admitted to a spinal cord injury unit for management of a sacral decubitus ulcer. During the hospitalization, she required emergency transfer to the intensive care unit (ICU) because of progressive deterioration of respiratory muscle function, severe respiratory acidosis, obtundation and hypotension. Upon transfer to the ICU, arterial blood gas revealed severe acute-on-chronic respiratory acidosis (pH 7.00, PCO2 120 mm Hg, PO2 211 mm Hg). The patient was immediately intubated and mechanically ventilated. Intravenous fluid boluses of normal saline (10.5 L in about 24 h) and vasopressors were started with rapid correction of hypotension. In addition, she was given hydrocortisone. Within 40 min of initiation of mechanical ventilation, there was improvement in acute respiratory acidosis. Sixteen hours later, however, the patient developed life-threatening hypokalemia (K(+) of 2.1 mEq/L) and hypomagnesemia (Mg of 1.4 mg/dL). Despite aggressive potassium supplementation, hypokalemia continued to worsen over the next several hours (K(+) of 1.7 mEq/L). Urine studies revealed renal potassium wasting. We reason that the recalcitrant life-threatening hypokalemia was caused by several mechanisms including total body potassium depletion (chronic respiratory acidosis), a shift of potassium from the extracellular to intracellular space (rapid correction of respiratory acidosis with mechanical ventilation), increased sodium delivery to the distal nephron (normal saline resuscitation), hyperaldosteronism (secondary to hypotension plus administration of hydrocortisone) and hypomagnesemia. We conclude that rapid correction of respiratory acidosis, especially in the setting of hypotension, can lead to life-threatening hypokalemia. Serum potassium levels must be monitored closely in these patients, as failure to do so can lead to potentially lethal consequences

Lactic Acidosis in Prostate Cancer: Consider the Warburg Effect

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Johannes C. van der Mijn

2017-11-01

Full Text Available Lactic acidosis is a commonly observed clinical condition that is associated with a poor prognosis, especially in malignancies. We describe a case of an 81-year-old patient who presented with symptoms of tachypnea and general discomfort. Arterial blood gas analysis showed a high anion gap acidosis with a lactate level of 9.5 mmol/L with respiratory compensation. CT scanning showed no signs of pulmonary embolism or other causes of impaired tissue oxygenation. Despite treatment with sodium bicarbonate, the patient developed an adrenalin-resistant cardiac arrest, most likely caused by the acidosis. Autopsy revealed Gleason score 5 + 5 metastatic prostate cancer as the most probable cause of the lactic acidosis. Next-generation sequencing indicated a nonsense mutation in the TP53 gene (887delA and an activating mutation in the PIK3CA gene (1634A>G as candidate molecular drivers. This case demonstrates the prevalence and clinical relevance of metabolic reprogramming, frequently referred to as “the Warburg effect,” in patients with prostate cancer.

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

OpenAIRE

Granja Salcedo, Yury Tatiana; Ribeiro Junior, Carlos Stefenson; Toro Gomez, Daniela Juliana; Rivera Calderón, Luis Gabriel; Machado, Mirela; Manrique Ardila, Adalberto

2012-01-01

Ruminal acidosis is a major problem in the production of cattle fed diets rich in concentrates, especially in cows of high milk production. During rumen acidosis rumen pH is depressed due to the accumulation of volatile fatty acids and the decline of the mechanisms responsible for rumen buffering. Among the main causes of acidosis include consumption of diets high in fiber carbohydrates and lack of effective fiber added to them. The increase in ruminal acidity and osmolality by the accumulati...

Pathophysiological aspect of metabolic acid-base disorders

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Nešović-Ostojić Jelena

2016-01-01

Full Text Available Maintaing the arterial pH values (in normal range of 7,35-7,45 is one of the main principles of homeostasis. Regulatory responses, including chemical buffering (extracellular, intracellular, sceletal, the regulation of pCO2 by the respiratory system, and the regulation of [HCO3-] by the kidneys, act in concert to maintain normal arterial pH value. The main extracellular chemical buffer is bicarbonate-carbonic acid buffer system. The kidneys contribute to the regulation of hydrogen (and bicarbonate in body fluids in two ways. Proximal tubules are important in bicarbonate reabsorption and distal tubules excrete hydrogen ion (as ammonium ion or titratable acid. There are four simple acid-base disorders: metabolic acidosis and metabolic alkalosis; respiratory acidosis and respiratory alkalosis. Metabolic acidosis can occur because of an increase in endogenous acid production (such as lactate and ketoacids, loss of bicarbonate (as in diarrhea, or accumulation of endogenous acids (as in renal failure. Metabolic acidosis can also be with high and normal (hyperchloremic metabolic acidosis anion gap. Renal tubular acidosis (RTA is a form of hyperchloremic metabolic acidosis which occurs when the renal damage primarily affects tubular function. The main problem in distal RTA is reduced H+ excretion in distal tubule. Type 2 RTA is also called proximal RTA because the main problem is greatly impaired reabsorption of bicarbonate in proximal tubule. Impaired cation exchange in distal tubule is the main problem in RTA type 4. Metabolic alkalosis occurs as a result of net gain of [HCO3-] or loss of nonvolatile acid from extracellular fluids. Metabolic alkalosis can be associated with reduced or increased extracellular volume.

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

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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.

Association of metabolic acidosis with bovine milk-based human milk fortifiers.

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Cibulskis, C C; Armbrecht, E S

2015-02-01

To compare the incidence of metabolic acidosis and feeding intolerance associated with powdered or acidified liquid human milk fortifier (HMF). This retrospective study evaluated infants ⩽ 32 weeks gestational age or ⩽ 1500 g birth weight who received human milk with either powdered or acidified liquid HMF (50 consecutively born infants per group). Primary outcomes tracked were metabolic acidosis (base excess less than -4 mmol l(-1) or bicarbonate less than 18 mmol l(-1)), feeding intolerance (gastric residual > 50% feed volume, > 3 loose stools or emesis per day, abdominal tenderness or distention), necrotizing enterocolitis, late-onset infection, death, length of hospital stay and ability to remain on HMF. Demographics, feeding practices, growth parameters and laboratory data were also collected. Significantly more infants who received acidified liquid HMF developed metabolic acidosis (P acidosis or feeding intolerance than those on powdered HMF (P acidosis and to be switched off HMF than those who received powdered HMF. Growth in the liquid HMF group was no different than the powdered group, despite higher protein intake.

Endocrine and metabolic emergencies in children: hypocalcemia, hypoglycemia, adrenal insufficiency, and metabolic acidosis including diabetic ketoacidosis

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Se Young Kim

2015-12-01

Full Text Available It is important to fast diagnosis and management of the pediatric patients of the endocrine metabolic emergencies because the signs and symptoms of these disorders are nonspecific. Delayed diagnosis and treatment may lead to serious consequences of the pediatric patients, for example, cerebral dysfunction leading to coma or death of the patients with hypoglycemia, hypocalcemia, adrenal insufficiency, or diabetic ketoacidosis. The index of suspicion of the endocrine metabolic emergencies should be preceded prior to the starting nonspecific treatment. Importantly, proper diagnosis depends on the collection of blood and urine specimen before nonspecific therapy (intravenous hydration, electrolytes, glucose or calcium injection. At the same time, the taking of precise history and searching for pathognomonic physical findings should be performed. This review was described for fast diagnosis and proper management of hypoglycemic emergencies, hypocalcemia, adrenal insufficiency, and metabolic acidosis including diabetic ketoacidosis.

A young woman with recurrent kidney stones: questions on hypokalaemic tubular acidosis

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Jill Vanmassenhove

2017-04-01

Full Text Available This paper discusses the diagnostic and therapeutic approach to the problem of a young woman presenting with recurrent kidney stones. In the clinical work-up, a hypokalaemic normal anion gap metabolic acidosis was found. The diagnostic tests to solve this common clinical problem and some therapeutic recommendations are discussed. Question on hypokalaemic tubular acidosis: 1. What is the significance of the plasma anion gap (PAG? 2. How does one appreciate the respiratory component of the acid base status? 3. How does one perform tests for tubular acidification disturbances? 4. What is the pathogenesis of distal tubular acidification ­disturbances? 5. What is the explanation of the hypokalaemia in distal ­tubular acidosis? 6. What is the pathogenesis of nephrolithiasis in distal tubular acidosis? 7. How does one treat a patient with distal tubular acidosis and recurrent nephrolithiasis?

Metabolic acidosis in an infant associated with permethrin toxicity.

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Goksugur, Sevil B; Karatas, Zehra; Goksugur, Nadir; Bekdas, Mervan; Demircioglu, Fatih

2015-01-01

Pyrethroids are broad-spectrum insecticides. Permethrin intoxication due to topical application has not been documented in humans. We report a 20-month-old infant who had used 5% permethrin lotion topically for scabies treatment. Approximately 60 mL (20 mL/day) was used and after the third application he developed agitation, nausea, vomiting, respiratory distress, tachycardia, and metabolic acidosis. His clinical symptoms and metabolic acidosis normalized within 20 hours. His follow-up was unremarkable. Toxicity of permethrin is rare, and although permethrin is a widely and safely used topical agent in the treatment of scabies and lice, inappropriate use may rarely cause toxicity. Moreover, in cases of unexplained metabolic acidosis, topically applied medications should be carefully investigated. © 2014 Wiley Periodicals, Inc.

Pathophysiology of acute small bowel disease with CT correlation

International Nuclear Information System (INIS)

Sarwani, N.; Tappouni, R.; Tice, J.

2011-01-01

The objective of this article is to review the pathophysiology of acute small bowel diseases, and to correlate the mechanisms of disease with computed tomography (CT) findings. Disease entities will be classified into the following: immune mediated and infectious causes, vascular causes, mechanical causes, trauma, and others. Having an understanding of acute small bowel pathophysiology is a useful teaching tool, and can lead to imaging clues to the most likely diagnosis of acute small bowel disorders.

Spasmodic Dysphonia: A Review. Part 2: Characterization of Pathophysiology.

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Hintze, Justin M; Ludlow, Christy L; Bansberg, Stephen F; Adler, Charles H; Lott, David G

2017-10-01

Objective The purpose of this review is to describe the recent advances in characterizing spasmodic dysphonia. Spasmodic dysphonia is a task-specific focal laryngeal dystonia characterized by irregular and uncontrolled voice breaks. The pathophysiology is poorly understood, and there are diagnostic difficulties. Data Sources PubMed, Google Scholar, and Cochrane Library. Review Methods The data sources were searched using the following search terms: ( spasmodic dysphonia or laryngeal dystonia) and ( etiology, aetiology, diagnosis, pathogenesis, or pathophysiology). Conclusion The diagnosis of spasmodic dysphonia can be difficult due to the lack of a scientific consensus on diagnostic criteria and the fact that other voice disorders may present similarly. Confusion can arise between spasmodic dysphonia and muscle tension dysphonia. Spasmodic dysphonia symptoms are tied to particular speech sounds, whereas muscle tension dysphonia is not. With the advent of more widespread use of high-speed laryngoscopy and videokymography, measures of the disruptions in phonation and delays in the onset of vocal fold vibration after vocal fold closure can be quantified. Recent technological developments have expanded our understanding of the pathophysiology of spasmodic dysphonia. Implications for Practice A 3-tiered approach, involving a questionnaire, followed by speech assessment and nasolaryngoscopy is the most widely accepted method for making the diagnosis in most cases. More experimental and invasive techniques such as electromyography and neuroimaging have been explored to further characterize spasmodic dysphonia and aid in diagnosing difficult cases.

Distal renal tubular acidosis and amelogenesis imperfecta: A rare association

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P Ravi

2013-01-01

Full Text Available Renal tubular acidosis (RTA is characterized by a normal anion gap with hyperchloremic metabolic acidosis. Primary distal RTA (type I is the most common RTA in children. Childhood presentation of distal RTA includes vomiting, failure to thrive, metabolic acidosis, and hypokalemia. Amelogenesis imperfecta (AI represents a condition where the dental enamel and oral tissues are affected in an equal manner resulting in the hypoplastic or hypopigmented teeth. We report a 10-year-old girl, previously asymptomatic presented with the hypokalemic paralysis and on work-up found out to have type I RTA. The discoloration of teeth and enamel was diagnosed as AI.

Linezolid-induced lactic acidosis: the thin line between bacterial and mitochondrial ribosomes.

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Santini, Alessandro; Ronchi, Dario; Garbellini, Manuela; Piga, Daniela; Protti, Alessandro

2017-07-01

Linezolid inhibits bacterial growth by targeting bacterial ribosomes and by interfering with bacterial protein synthesis. Lactic acidosis is a rare, but potentially lethal, side effect of linezolid. Areas covered: The pathogenesis of linezolid-induced lactic acidosis is reviewed with special emphasis on aspects relevant to the recognition, prevention and treatment of the syndrome. Expert opinion: Linezolid-induced lactic acidosis reflects the untoward interaction between the drug and mitochondrial ribosomes. The inhibition of mitochondrial protein synthesis diminishes the respiratory chain enzyme content and thus limits aerobic energy production. As a result, anaerobic glycolysis and lactate generation accelerate independently from tissue hypoxia. In the absence of any confirmatory test, linezolid-induced lactic acidosis should be suspected only after exclusion of other, more common, causes of lactic acidosis such as hypoxemia, anemia or low cardiac output. Normal-to-high whole-body oxygen delivery, high venous oxygen saturation and lack of response to interventions that effectively increase tissue oxygen provision all suggest a primary defect in oxygen use at the mitochondrial level. During prolonged therapy with linezolid, blood drug and lactate levels should be regularly monitored. The current standard-of-care treatment of linezolid-induced lactic acidosis consists of drug withdrawal to reverse mitochondrial intoxication and intercurrent life support.

Powerful functional imaging of respiratory nuclear medicine. Is CT imaging alone really sufficient for diagnosis and pathophysiologic assessment of lung diseases?

International Nuclear Information System (INIS)

Suga, Kazuyoshi

2010-01-01

Ventilation (V)-perfusion (Q) single photon emission computed tomography (SPECT) provides important information of functional impairment in various lung diseases, and often sensitively detects CT-undetectable lesions. V·Q SPECT also provides objective and quantitative assessment of severity of lung functional impairment. Functional-morphological correlation on V·Q SPECT-CT fusion images further facilitates these advantages of V·Q SPECT. This article describes clinical feasibility of V·Q SPECT in functional assessment and diagnosis of chronic obstructive pulmonary diseases, pulmonary embolism, pulmonary hypertension, interstitial lung diseases, and lung right-to-left shunt diseases. This article hopefully provides sufficient responses to the crucial query of ''Is CT imaging alone really sufficient for diagnosis and pathophysiological assessment of various lung diseases?'' (author)

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

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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

Extreme lactic acidosis type B associated with metformin treatment

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Vernersson, Einar; Frid, Anders; Sterner, Gunnar

2011-01-01

The elimination of metformin is exclusively through the kidneys and elevated plasma concentrations can cause lactic acidosis. We report a case of severe lactic acidosis (pH 6.60) occuring with ostensibly normal therapeutic doses of metformin in the setting of acute renal failure. Continuous veno-venous haemodiafiltration decreased plasma metformin concentrations from 266 lmol/L at presentation to 68 lmol/L, 21 h later. The patient improved rapidly. PMID:25984205

Complicated pregnancies in inherited distal renal tubular acidosis: importance of acid-base balance.

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Seeger, Harald; Salfeld, Peter; Eisel, Rüdiger; Wagner, Carsten A; Mohebbi, Nilufar

2017-06-01

Inherited distal renal tubular acidosis (dRTA) is caused by impaired urinary acid excretion resulting in hyperchloremic metabolic acidosis. Although the glomerular filtration rate (GFR) is usually preserved, and hypertension and overt proteinuria are absent, it has to be considered that patients with dRTA also suffer from chronic kidney disease (CKD) with an increased risk for adverse pregnancy-related outcomes. Typical complications of dRTA include severe hypokalemia leading to cardiac arrhythmias and paralysis, nephrolithiasis and nephrocalcinosis. Several physiologic changes occur in normal pregnancy including alterations in acid-base and electrolyte homeostasis as well as in GFR. However, data on pregnancy in women with inherited dRTA are scarce. We report the course of pregnancy in three women with hereditary dRTA. Complications observed were severe metabolic acidosis, profound hypokalemia aggravated by hyperemesis gravidarum, recurrent urinary tract infection (UTI) and ureteric obstruction leading to renal failure. However, the outcome of all five pregnancies (1 pregnancy each for mothers n. 1 and 2; 3 pregnancies for mother n. 3) was excellent due to timely interventions. Our findings highlight the importance of close nephrologic monitoring of women with inherited dRTA during pregnancy. In addition to routine assessment of creatinine and proteinuria, caregivers should especially focus on acid-base status, plasma potassium and urinary tract infections. Patients should be screened for renal obstruction in the case of typical symptoms, UTI or renal failure. Furthermore, genetic identification of the underlying mutation may (a) support early nephrologic referral during pregnancy and a better management of the affected woman, and (b) help to avoid delayed diagnosis and reduce complications in affected newborns.

32P studies into phosphate metabolism of cattle with metabolic acidosis

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Lachmann, G.; Pfueller, K.; Bier, H.; Mueller, D.; Rummel, G.

1984-01-01

Phosphorus balance and intraveneous injection of 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. (author)

Acidosis increases the susceptibility of respiratory epithelial cells to Pseudomonas aeruginosa-induced cytotoxicity.

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Torres, Iviana M; Demirdjian, Sally; Vargas, Jennifer; Goodale, Britton C; Berwin, Brent

2017-07-01

Bacterial infection can lead to acidosis of the local microenvironment, which is believed to exacerbate disease pathogenesis; however, the mechanisms by which changes in pH alter disease progression are poorly understood. We test the hypothesis that acidosis enhances respiratory epithelial cell death in response to infection with Pseudomonas aeruginosa Our findings support the idea that acidosis in the context of P. aeruginosa infection results in increased epithelial cell cytotoxicity due to ExoU intoxication. Importantly, enforced maintenance of neutral pH during P. aeruginosa infection demonstrates that cytotoxicity is dependent on the acidosis. Investigation of the underlying mechanisms revealed that host cell cytotoxicity correlated with increased bacterial survival during an acidic infection that was due to reduced bactericidal activity of host-derived antimicrobial peptides. These findings extend previous reports that the activities of antimicrobial peptides are pH-dependent and provide novel insights into the consequences of acidosis on infection-derived pathology. Therefore, this report provides the first evidence that physiological levels of acidosis increase the susceptibility of epithelial cells to acute Pseudomonas infection and demonstrates the benefit of maintaining pH homeostasis during a bacterial infection. Copyright © 2017 the American Physiological Society.

[MELAS: Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-Like Episodes].

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Murakami, Hidetomo; Ono, Kenjiro

2017-02-01

Mitochondrial disease is caused by a deficiency in the energy supply to cells due to mitochondrial dysfunction. Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) is a mitochondrial disease that presents with stroke-like episodes such as acute onset of neurological deficits and characteristic imaging findings. Stroke-like episodes in MELAS have the following features: 1) neurological deficits due to localization of lesions in the brain, 2) episodes often accompany epilepsy, 3) lesions do not follow the vascular supply area, 4) lesions are more often seen in the posterior brain than in the anterior brain, 5) lesions spread to an adjacent area in the brain, and 6) neurological symptoms often disappear together with imaging findings, but later relapse. About 80% of patients with MELAS have an A-to-G transition mutation at the nucleotide pair 3243 in the dihydrouridine loop of mitochondrial tRNALeu(UUR), which causes the absence of posttranscriptional taurine modification at the wobble nucleotide of mitochondrial tRNALeu(UUR) and disrupts protein synthesis. However, the precise pathophysiology of stroke-like episodes is under investigation, with possible hypotheses for these episodes including mitochondrial angiopathy, mitochondrial cytopathy, and neuron-astrocyte uncoupling. With regard to treatment, L-arginine and taurine have recently been suggested for relief of clinical symptoms.

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

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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.

Anemia of Chronic Disease and Iron Deficiency Anemia in Inflammatory Bowel Diseases: Pathophysiology, Diagnosis, and Treatment.

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Murawska, Natalia; Fabisiak, Adam; Fichna, Jakub

2016-05-01

Anemia coexists with inflammatory bowel disease (IBD) in up to two-thirds of patients, significantly impairing quality of life. The most common types of anemia in patients with IBD are iron deficiency anemia and anemia of chronic disease, which often overlap. In most cases, available laboratory tests allow successful diagnosis of iron deficiency, where difficulties appear, recently established indices such as soluble transferrin-ferritin ratio or percentage of hypochromic red cells are used. In this review, we discuss the management of the most common types of anemia in respect of the latest available data. Thus, we provide the mechanisms underlying pathophysiology of these entities; furthermore, we discuss the role of hepcidin in developing anemia in IBD. Next, we present the treatment options for each type of anemia and highlight the importance of individual choice of action. We also focus on newly developed intravenous iron preparations and novel, promising drug candidates targeting hepcidin. Concurrently, we talk about difficulties in differentiating between the true and functional iron deficiency, and discuss tools facilitating the process. Finally, we emphasize the importance of proper diagnosis and treatment of anemia in IBD. We conclude that management of anemia in patients with IBD is tricky, and appropriate screening of patients regarding anemia is substantial.

Acidosis-induced downregulation of hepatocyte mitochondrial aquaporin-8 and ureagenesis from ammonia.

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Molinas, Sara M; Soria, Leandro R; Marrone, Julieta; Danielli, Mauro; Trumper, Laura; Marinelli, Raúl A

2015-08-01

It has been proposed that, during metabolic acidosis, the liver downregulates mitochondrial ammonia detoxification via ureagenesis, a bicarbonate-consuming process. Since we previously demonstrated that hepatocyte mitochondrial aquaporin-8 channels (mtAQP8) facilitate the uptake of ammonia and its metabolism into urea, we studied whether mtAQP8 is involved in the liver adaptive response to acidosis. Primary cultured rat hepatocytes were adapted to acidosis by exposing them to culture medium at pH 7.0 for 40 h. Control cells were exposed to pH 7.4. Hepatocytes exposed to acid medium showed a decrease in mtAQP8 protein expression (-30%, p ammonia was assessed by incubating the cells with (15)N-labeled ammonia and measuring (15)N-labeled urea synthesis by nuclear magnetic resonance. Reduced ureagenesis was found in acidified hepatocytes (-31%, p ammonia in response to acidosis.

The kidney of chicken adapts to chronic metabolic acidosis: in vivo and in vitro studies.

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Craan, A G; Lemieux, G; Vinay, P; Gougoux, A

1982-08-01

Renal adaptation to chronic metabolic acidosis was studies in Arbor Acre hens receiving ammonium chloride by stomach tube 0.75 g/kg/day during 6 days. During a 14-day study, it was shown that the animals could excrete as much as 60% of the acid load during ammonium chloride administration. At the same time urate excretion fell markedly but the renal contribution to urate excretion (14%) did not change. During acidosis, blood glutamine increased twofold and the tissue concentration of glutamine rose in both liver and kidney. Infusion of L-glutamine led to increased ammonia excretion and more so in acidotic animals. Glutaminase I, glutamate dehydrogenase, alanine aminotransferase (GPT), and malic enzyme activities increased in the kidney during acidosis but phosphoenolpyruvate carboxykinase (PEPCK) activity did not change. Glutaminase I was not found in the liver, but hepatic glutamine synthetase rose markedly during acidosis. Glutamine synthetase was not found in the kidney. Renal tubules incubated with glutamine and alanine were ammoniagenic and gluconeogenic to the same degree as rat tubules with the same increments in acidosis. Lactate was gluconeogenic without increment during acidosis. The present study indicates that the avian kidney adapts to chronic metabolic acidosis with similarities and differences when compared to dog and rat. Glutamine originating from the liver appears to be the major ammoniagenic substrate. Our data also support the hypothesis that hepatic urate synthesis is decreased during acidosis.

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

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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. Copyright �

Haptoglobin and serum amyloid a in subacute ruminal acidosis in goats

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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.

Ruminant Nutrition Symposium: Acidosis: new insights into the persistent problem.

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Oba, M; Wertz-Lutz, A E

2011-04-01

The Ruminant Nutrition Symposium titled "Acidosis: New insights into the persistent problem" was held at the Joint Annual Meeting of the American Dairy Science Association, American Society of Animal Science, Poultry Science Association, Asociación Mexicana de Producción Animal, Western Section-ASAS, and the Canadian Society of Animal Science in Denver, Colorado, July 11 to 15, 2010. The objective of the symposium was to provide the ruminant nutrition community with new insights and perspectives from recent research findings on acidosis. Under modern production systems, ruminants are fed high-grain diets to maximize their energy intake and productivity. However, feeding highly fermentable diets often causes excess fermentation and results in accumulation of fermentation acids in the rumen, leading to a decrease in feed intake, poor feed efficiency, liver abscesses, and lameness in feedlot cattle or lactating dairy cows. Although our understanding of nutritional factors (i.e., effects of type and processing method of grains and importance of physically effective fiber) affecting rumen pH have increased substantially over the past few decades, rumen acidosis has continued to be a common problem in the ruminant livestock industry. The symposium program was organized to review recent research findings in acidosis with more emphasis on physiological aspects, and provide novel insights into the persistent problem.

Diagnostic Challenge in a Patient with Severe Anion Gap Metabolic Acidosis

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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.

Haptoglobin and serum amyloid a in subacute ruminal acidosis in goats

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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.

Polyuria, acidosis, and coma following massive ibuprofen ingestion.

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Levine, Michael; Khurana, Amandeep; Ruha, Anne-Michelle

2010-09-01

Ibuprofen was the first over-the-counter nonsteroidal anti-inflammatory drug available in the United States. Despite being a common agent of ingestion, significant toxicity in overdose is rare. We report a case of a massive ibuprofen ingestion who developed polyuria, acidosis, and coma but survived, despite having a serum ibuprofen concentration greater than previous fatal cases. A 19-year-old man ingested 90 g (1,200 mg/kg) ibuprofen. He was initially awake and alert, but his level of consciousness deteriorated over several hours. Seven hours following the ingestion, he was intubated and mechanically ventilated secondary to loss of airway reflexes. He developed a lactic acidosis and polyuria, which lasted for nearly 24 h. His serum creatinine peaked at 1.12 mg/dL. An ibuprofen level drawn 7 h postingestion was 739.2 mg/L (therapeutic 5-49 mg/L). We describe a case of a massive ibuprofen overdose characterized by metabolic acidosis, coma, and a state of high urine output who survived with aggressive supportive care. This case is unique in several ways. First, ibuprofen levels this high have only rarely been described. Second, polyuria is very poorly described following ibuprofen ingestions.

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

NARCIS (Netherlands)

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

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

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

NARCIS (Netherlands)

Stades, A. M. E.; Heikens, J. T.; Erkelens, D. W.; Holleman, F.; Hoekstra, J. B. L.

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

Brain tissue stiffness is a sensitive marker for acidosis.

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Holtzmann, Kathrin; Gautier, Hélène O B; Christ, Andreas F; Guck, Jochen; Káradóttir, Ragnhildur Thóra; Franze, Kristian

2016-09-15

Carbon dioxide overdose is frequently used to cull rodents for tissue harvesting. However, this treatment may lead to respiratory acidosis, which potentially could change the properties of the investigated tissue. Mechanical tissue properties often change in pathological conditions and may thus offer a sensitive generic readout for changes in biological tissues with clinical relevance. In this study, we performed force-indentation measurements with an atomic force microscope on acute cerebellar slices from adult rats to test if brain tissue undergoes changes following overexposure to CO2 compared to other methods of euthanasia. The pH significantly decreased in brain tissue of animals exposed to CO2. Concomitant with the drop in pH, cerebellar grey matter significantly stiffened. Tissue stiffening was reproduced by incubation of acute cerebellar slices in acidic medium. Tissue stiffness provides an early, generic indicator for pathophysiological changes in the CNS. Atomic force microscopy offers unprecedented high spatial resolution to detect such changes. Our results indicate that the stiffness particularly of grey matter strongly correlates with changes of the pH in the cerebellum. Furthermore, the method of tissue harvesting and preparation may not only change tissue stiffness but very likely also other physiologically relevant parameters, highlighting the importance of appropriate sample preparation. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Acetazolamide in cerebral diagnosis: Physiological and pathophysiological aspects. Acetazolamid in der zerebrovaskulaeren Diagnostik: Physiologische und pathophysiologische Aspekte

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Lerch, H.; Franke, W.G.; Templin, A. (Medizinische Akademie ' Carl Gustav Carus' , Klinik fuer Nuklearmedizin, Dresden (Germany) Medizinische Akademie ' Carl Gustav Carus' , Klinik fuer Psychiatrie und Neurologie, Abt. Neurologie, Dresden (Germany))

1990-01-01

The sensitivity in the diagnosis of cerebrovascular diseases using radiotracers can be enhanced by the use of the acetazolamide test. In this paper we present and discuss some physiological and pathophysiological aspects of its mechanism. The physiological action of the carboanhydrase inhibitor is like the action of enhanced pCO{sub 2} in the tissue, thus acting at the site of metabolic regulation. The reaction of the vascular bed is influenced in part by subcortical structures. Pathologically the reaction can be disturbed at first by an altered regulation with the vessels being mechanically intact, e.g. in hypoxia or transient ischemia. Secondly, the mechanics of the vessels may be not intact e.g., in atherosclerosis or surrounding edema. Lastly, the vessels have already dilated, e.g. poststenotically. All these facts have to be taken into consideration interpreting an acetazolamid test. (orig.).

Dietary Treatment of Metabolic Acidosis in Chronic Kidney Disease.

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Siener, Roswitha

2018-04-20

Chronic kidney disease and reduced glomerular filtration rate are risk factors for the development of chronic metabolic acidosis. The prevention or correction of chronic metabolic acidosis has been found to slow progression of chronic kidney disease. Dietary composition can strongly affect acid⁻base balance. Major determinants of net endogenous acid production are the generation of large amounts of hydrogen ions, mostly by animal-derived protein, which is counterbalanced by the metabolism of base-producing foods like fruits and vegetables. Alkali therapy of chronic metabolic acidosis can be achieved by providing an alkali-rich diet or oral administration of alkali salts. The primary goal of dietary treatment should be to increase the proportion of fruits and vegetables and to reduce the daily protein intake to 0.8⁻1.0 g per kg body weight. Diet modifications should begin early, i.e., even in patients with moderate kidney impairment, because usual dietary habits of many developed societies contribute an increased proportion of acid equivalents due to the high intake of protein from animal sources.

Dietary Treatment of Metabolic Acidosis in Chronic Kidney Disease

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Roswitha Siener

2018-04-01

Full Text Available Chronic kidney disease and reduced glomerular filtration rate are risk factors for the development of chronic metabolic acidosis. The prevention or correction of chronic metabolic acidosis has been found to slow progression of chronic kidney disease. Dietary composition can strongly affect acid–base balance. Major determinants of net endogenous acid production are the generation of large amounts of hydrogen ions, mostly by animal-derived protein, which is counterbalanced by the metabolism of base-producing foods like fruits and vegetables. Alkali therapy of chronic metabolic acidosis can be achieved by providing an alkali-rich diet or oral administration of alkali salts. The primary goal of dietary treatment should be to increase the proportion of fruits and vegetables and to reduce the daily protein intake to 0.8–1.0 g per kg body weight. Diet modifications should begin early, i.e., even in patients with moderate kidney impairment, because usual dietary habits of many developed societies contribute an increased proportion of acid equivalents due to the high intake of protein from animal sources.

Hypokalaemia and Renal Tubular Acidosis due to Abuse of Nurofen Plus

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M. J. Blackstock

2012-01-01

Full Text Available Nurofen Plus is a common analgesic containing ibuprofen and codeine. We present a case of a 38-year-old lady who developed renal tubular acidosis with severe hypokalaemia, after chronic abuse of Nurofen Plus tablets. She presented with confusion and profound biochemical abnormalities requiring critical care admission for electrolyte replacement. Ibuprofen causes renal tubular acidosis due to its effects on carbonic anhydrase activity.

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

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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

Acidosis láctica severa y leucemia aguda

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David Loja

2004-03-01

Full Text Available Reportamos el caso de una paciente de 27 años de edad con leucemia linfoblástica aguda, quien presentó acidosis láctica severa como complicación metabólica. Ella acudió con desnutrición severa, anemia marcada y síndrome consuntivo. No había compromiso del sistema reticuloendotelial y un mielograma inicial fue normal. Estos factores retardaron el diagnóstico y obligaron a ampliar el diagnóstico diferencial. La sospecha de neoplasia hematológica asociada a acidosis láctica sin causa aparente permitió reevaluar el caso con un nuevo mielograma y establecer el diagnóstico.

Pulmonary vascular responses during acute and sustained respiratory alkalosis or acidosis in intact newborn piglets.

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Gordon, J B; Rehorst-Paea, L A; Hoffman, G M; Nelin, L D

1999-12-01

Acute alkalosis-induced pulmonary vasodilation and acidosis-induced pulmonary vasoconstriction have been well described, but responses were generally measured within 5-30 min of changing pH. In contrast, several in vitro studies have found that relatively brief periods of sustained alkalosis can enhance, and sustained acidosis can decrease, vascular reactivity. In this study of intact newborn piglets, effects of acute (20 min) and sustained (60-80 min) alkalosis or acidosis on baseline (35% O2) and hypoxic (12% O2) pulmonary vascular resistance (PVR) were compared with control piglets exposed only to eucapnia. Acute alkalosis decreased hypoxic PVR, but sustained alkalosis failed to attenuate either baseline PVR or the subsequent hypoxic response. Acute acidosis did not significantly increase hypoxic PVR, but sustained acidosis markedly increased both baseline PVR and the subsequent hypoxic response. Baseline PVR was similar in all piglets after resumption of eucapnic ventilation, but the final hypoxic response was greater in piglets previously exposed to alkalosis than in controls. Thus, hypoxic pulmonary vasoconstriction was not attenuated during sustained alkalosis, but was accentuated during sustained acidosis and after the resumption of eucapnia in alkalosis-treated piglets. Although extrapolation of data from normal piglets to infants and children with pulmonary hypertension must be done with caution, this study suggests that sustained alkalosis may be of limited efficacy in treating acute hypoxia-induced pulmonary hypertension and the risks of pulmonary hypertension must be considered when using ventilator strategies resulting in permissive hypercapnic acidosis.

Respiratory and metabolic acidosis differentially affect the respiratory neuronal network in the ventral medulla of neonatal rats.

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Okada, Yasumasa; Masumiya, Haruko; Tamura, Yoshiyasu; Oku, Yoshitaka

2007-11-01

Two respiratory-related areas, the para-facial respiratory group/retrotrapezoid nucleus (pFRG/RTN) and the pre-Bötzinger complex/ventral respiratory group (preBötC/VRG), are thought to play key roles in respiratory rhythm. Because respiratory output patterns in response to respiratory and metabolic acidosis differ, we hypothesized that the responses of the medullary respiratory neuronal network to respiratory and metabolic acidosis are different. To test these hypotheses, we analysed respiratory-related activity in the pFRG/RTN and preBötC/VRG of the neonatal rat brainstem-spinal cord in vitro by optical imaging using a voltage-sensitive dye, and compared the effects of respiratory and metabolic acidosis on these two populations. We found that the spatiotemporal responses of respiratory-related regional activities to respiratory and metabolic acidosis are fundamentally different, although both acidosis similarly augmented respiratory output by increasing respiratory frequency. PreBötC/VRG activity, which is mainly inspiratory, was augmented by respiratory acidosis. Respiratory-modulated pixels increased in the preBötC/VRG area in response to respiratory acidosis. Metabolic acidosis shifted the respiratory phase in the pFRG/RTN; the pre-inspiratory dominant pattern shifted to inspiratory dominant. The responses of the pFRG/RTN activity to respiratory and metabolic acidosis are complex, and involve either augmentation or reduction in the size of respiratory-related areas. Furthermore, the activation pattern in the pFRG/RTN switched bi-directionally between pre-inspiratory/inspiratory and post-inspiratory. Electrophysiological study supported the results of our optical imaging study. We conclude that respiratory and metabolic acidosis differentially affect activities of the pFRG/RTN and preBötC/VRG, inducing switching and shifts of the respiratory phase. We suggest that they differently influence the coupling states between the pFRG/RTN and preBötC/VRG.

Management of Sub-acute Ruminal Acidosis in Dairy Cattle for Improved Production: A Review

OpenAIRE

Kafil Hussain; Amjad Ul Islam; Surinder Kumar Gupta

2011-01-01

Sub-acute ruminal acidosis (SARA) is a well-recognized digestive disorder that is an increasing health problem in most dairy herds. Feeding diets high in grain and other highly fermentable carbohydrates to dairy cows increases milk production, but also increases the risk of SARA. Sub-acute ruminal acidosis is defined as periods of moderately depressed ruminal pH, from about 5.5 to 5.0. Sub-acute ruminal acidosis may be associated with laminitis and other health problems resulting in decreased...

Acute phase protein response during acute ruminal acidosis in cattle

DEFF Research Database (Denmark)

Danscher, A. M.; Thoefner, M. B.; Heegaard, Peter M. H.

2011-01-01

The aim of the study was to describe the acute phase protein and leukocyte responses in dairy heifers during acute, oligofructose-induced ruminal acidosis. The study included 2 trials involving oral oligofructose overload (17g/kg BW) to nonpregnant Danish Holstein heifers. Trial 1 included 12...... performed.Heifers receiving oligofructose developed a profound ruminal and systemic acidosis (in Trial 1 and 2 lowest ruminal pH was 4.3±0.2 and 3.8±0.02, respectively, and minimum SBE was −9.3±4.1 and −8.9±2.8, respectively). In Trial 1, SAA concentrations were higher than baseline concentrations on all...... than control heifers at 18 and 24h after overload (max. 13.7±4.3 billions/L). Feeding had no effect on plasma fibrinogen concentrations or WBC in Trial 1.Acute ruminal and systemic acidosis caused by oligofructose overload resulted in distinct acute phase protein and leukocyte responses in dairy...

[Pathophysiology and treatment of orofacial pain.

Science.gov (United States)

Shinoda, Masamichi; Noma, Noboru

"Pain" is one of body defense mechanisms and crucial for the life support. However, orofacial pain such as myofascial pain syndrome, burning mouth syndrome and trigeminal neuralgia plays no part in body defense mechanisms and requires therapeutic intervention. Recent studies have indicated that plastic changes in the activities of trigeminal neurons, satellite glial cells in trigeminal ganglion, secondary neurons, microglia and astrocytes in trigeminal spinal subnucleus following orofacial inflammation and trigeminal nerve injury are responsible for orofacial pain mechanisms. Clinically, it is well known that the etiologic differential diagnosis which consists of careful history-taking and physical examination is essential for therapeutic decision in patients with orofacial pain. This report outlines the current knowledge on the pathophysiology, diagnosis, treatment of orofacial pain.

Nasal flaring as a clinical sign of respiratory acidosis in patients with dyspnea.

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Zorrilla-Riveiro, José Gregorio; Arnau-Bartés, Anna; Rafat-Sellarés, Ramón; García-Pérez, Dolors; Mas-Serra, Arantxa; Fernández-Fernández, Rafael

2017-04-01

To determine whether the presence of nasal flaring is a clinical sign of respiratory acidosis in patients attending emergency departments for acute dyspnea. Single-center, prospective, observational study of patients aged over 15 requiring urgent attention for dyspnea, classified as level II or III according to the Andorran Triage Program and who underwent arterial blood gas test on arrival at the emergency department. The presence of nasal flaring was evaluated by two observers. Demographic and clinical variables, signs of respiratory difficulty, vital signs, arterial blood gases and clinical outcome (hospitalization and mortality) were recorded. Bivariate and multivariate analyses were performed using logistic regression models. The sample comprised 212 patients, mean age 78years (SD=12.8), of whom 49.5% were women. Acidosis was recorded in 21.2%. Factors significantly associated with the presence of acidosis in the bivariate analysis were the need for pre-hospital medical care, triage level II, signs of respiratory distress, presence of nasal flaring, poor oxygenation, hypercapnia, low bicarbonates and greater need for noninvasive ventilation. Nasal flaring had a positive likelihood ratio for acidosis of 4.6 (95% CI 2.9-7.4). In the multivariate analysis, triage level II (aOR 5.16; 95% CI: 1.91 to 13.98), the need for oxygen therapy (aOR 2.60; 95% CI: 1.13-5.96) and presence of nasal flaring (aOR 6.32; 95% CI: 2.78-14.41) were maintained as factors independently associated with acidosis. Nasal flaring is a clinical sign of severity in patients requiring urgent care for acute dyspnea, which has a strong association with acidosis and hypercapnia. Copyright © 2016 Elsevier Inc. All rights reserved.

Cerebral lactic acidosis correlates with neurological impairment in MELAS.

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Kaufmann, P; Shungu, D C; Sano, M C; Jhung, S; Engelstad, K; Mitsis, E; Mao, X; Shanske, S; Hirano, M; DiMauro, S; De Vivo, D C

2004-04-27

To evaluate the role of chronic cerebral lactic acidosis in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). The authors studied 91 individuals from 34 families with MELAS and the A3243G point mutation and 15 individuals from two families with myoclonus epilepsy and ragged red fibers (MERRF) and the A8344G mutation. Subjects were divided into four groups. Paternal relatives were studied as controls (Group 1). The maternally related subjects were divided clinically into three groups: asymptomatic (no clinical evidence of neurologic disease) (Group 2), oligosymptomatic (neurologic symptoms but without the full clinical picture of MELAS or MERRF) (Group 3), and symptomatic (fulfilling MELAS or MERRF criteria) (Group 4). The authors performed a standardized neurologic examination, neuropsychological testing, MRS, and leukocyte DNA analysis in all subjects. The symptomatic and oligosymptomatic MELAS subjects had significantly higher ventricular lactate than the other groups. There was a significant correlation between degree of neuropsychological and neurologic impairment and cerebral lactic acidosis as estimated by ventricular MRS lactate levels. High levels of ventricular lactate, the brain spectroscopic signature of MELAS, are associated with more severe neurologic impairment.

Ruminant Nutrition Symposium: Productivity, digestion, and health responses to hindgut acidosis in ruminants.

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Gressley, T F; Hall, M B; Armentano, L E

2011-04-01

Microbial fermentation of carbohydrates in the hindgut of dairy cattle is responsible for 5 to 10% of total-tract carbohydrate digestion. When dietary, animal, or environmental factors contribute to abnormal, excessive flow of fermentable carbohydrates from the small intestine, hindgut acidosis can occur. Hindgut acidosis is characterized by increased rates of production of short-chain fatty acids including lactic acid, decreased digesta pH, and damage to gut epithelium as evidenced by the appearance of mucin casts in feces. Hindgut acidosis is more likely to occur in high-producing animals fed diets with relatively greater proportions of grains and lesser proportions of forage. In these animals, ruminal acidosis and poor selective retention of fermentable carbohydrates by the rumen will increase carbohydrate flow to the hindgut. In more severe situations, hindgut acidosis is characterized by an inflammatory response; the resulting breach of the barrier between animal and digesta may contribute to laminitis and other disorders. In a research setting, effects of increased hindgut fermentation have been evaluated using pulse-dose or continuous abomasal infusions of varying amounts of fermentable carbohydrates. Continuous small-dose abomasal infusions of 1 kg/d of pectin or fructans into lactating cows resulted in decreased diet digestibility and decreased milk fat percentage without affecting fecal pH or VFA concentrations. The decreased diet digestibility likely resulted from increased bulk in the digestive tract or from increased digesta passage rate, reducing exposure of the digesta to intestinal enzymes and epithelial absorptive surfaces. The same mechanism is proposed to explain the decreased milk fat percentage because only milk concentrations of long-chain fatty acids were decreased. Pulse-dose abomasal fructan infusions (1 g/kg of BW) into steers resulted in watery feces, decreased fecal pH, and increased fecal VFA concentrations, without causing an

Amblyaudia: Review of Pathophysiology, Clinical Presentation, and Treatment of a New Diagnosis.

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Kaplan, Alyson B; Kozin, Elliott D; Remenschneider, Aaron; Eftekhari, Kian; Jung, David H; Polley, Daniel B; Lee, Daniel J

2016-02-01

Similar to amblyopia in the visual system, "amblyaudia" is a term used to describe persistent hearing difficulty experienced by individuals with a history of asymmetric hearing loss (AHL) during a critical window of brain development. Few clinical reports have described this phenomenon and its consequent effects on central auditory processing. We aim to (1) define the concept of amblyaudia and (2) review contemporary research on its pathophysiology and emerging clinical relevance. PubMed, Embase, and Cochrane databases. A systematic literature search was performed with combinations of search terms: "amblyaudia," "conductive hearing loss," "sensorineural hearing loss," "asymmetric," "pediatric," "auditory deprivation," and "auditory development." Relevant articles were considered for inclusion, including basic and clinical studies, case series, and major reviews. During critical periods of infant brain development, imbalanced auditory input associated with AHL may lead to abnormalities in binaural processing. Patients with amblyaudia can demonstrate long-term deficits in auditory perception even with correction or resolution of AHL. The greatest impact is in sound localization and hearing in noisy environments, both of which rely on bilateral auditory cues. Diagnosis and quantification of amblyaudia remain controversial and poorly defined. Prevention of amblyaudia may be possible through early identification and timely management of reversible causes of AHL. Otolaryngologists, audiologists, and pediatricians should be aware of emerging data supporting amblyaudia as a diagnostic entity and be cognizant of the potential for lasting consequences of AHL. Prevention of long-term auditory deficits may be possible through rapid identification and correction. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Understanding lactic acidosis in paracetamol (acetaminophen) poisoning.

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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. © 2010 The Authors. British Journal of Clinical Pharmacology © 2010 The British Pharmacological Society.

Bilateral Proximal Femur Fractures in a Patient with Renal Tubular Acidosis: A Case Report

Directory of Open Access Journals (Sweden)

Charl SS

2018-03-01

Full Text Available The diagnosis of pathological fractures is on the rise. The morbidity involved does not only burden the patient and their families but it has a great toll on the healthcare system as well. Early identification of the patient at risk is an invaluable tool to cut cost and improve the patient’s quality of life. Multiple renal pathologies have been highlighted in relation to the risk of pathological fractures; however, complications in renal tubular acidosis have been rarely documented. Nevertheless, prompt action with adequate and relevant patient education ultimately can reduce the associated morbidity. We present a case of poor control of the disease and its debilitating pathological fracture complications.

Role of Anti-Müllerian Hormone in pathophysiology, diagnosis and treatment of Polycystic Ovary Syndrome: a review.

Science.gov (United States)

Dumont, Agathe; Robin, Geoffroy; Catteau-Jonard, Sophie; Dewailly, Didier

2015-12-21

Polycystic ovary syndrome (PCOS) is the most common cause of chronic anovulation and hyperandrogenism in young women. Excessive ovarian production of Anti-Müllerian Hormone, secreted by growing follicles in excess, is now considered as an important feature of PCOS. The aim of this review is first to update the current knowledge about the role of AMH in the pathophysiology of PCOS. Then, this review will discuss the improvement that serum AMH assay brings in the diagnosis of PCOS. Last, this review will explain the utility of serum AMH assay in the management of infertility in women with PCOS and its utility as a marker of treatment efficiency on PCOS symptoms. It must be emphasized however that the lack of an international standard for the serum AMH assay, mainly because of technical issues, makes it difficult to define consensual thresholds, and thus impairs the widespread use of this new ovarian marker. Hopefully, this should soon improve.

Severe metabolic acidosis in adult patients with Duchenne muscular dystrophy.

Science.gov (United States)

Lo Cascio, Christian M; Latshang, Tsogyal D; Kohler, Malcolm; Fehr, Thomas; Bloch, Konrad E

2014-01-01

Duchenne muscular dystrophy (DMD) leads to progressive paresis, respiratory failure and premature death. Long-term positive pressure ventilation can improve quality of life and survival, but previously unrecognized complications may arise. We analyzed the characteristics of severe metabolic acidosis occurring in 8 of 55 DMD patients, of 20-36 years of age, observed over a 5-year period. All patients were on positive pressure ventilation and were being treated for chronic constipation. Before admission, they had had a reduced intake of fluids and food. Upon examination, they were severely ill, dyspneic and suffering from abdominal discomfort. Metabolic acidosis with a high anion gap was noted in 5 of the 8 patients and with a normal anion gap in the other 3. They all recovered after the administration of fluids and nutrition, the regulation of bowel movements and treatment with antibiotics, as appropriate. Metabolic acidosis is a life-threatening, potentially preventable complication in older DMD patients. Early recognition, subsequent administration of fluids, nutrition and antibiotics and regulation of bowel movements seem to be essential. © 2014 S. Karger AG, Basel.

STUDY OF METABOLIC ACIDOSIS IN PATIENTS UNDERGOING SURGERIES OF OPERATIVE TIME GREATER THAN 2 HOURS DURATION

Directory of Open Access Journals (Sweden)

Sathu T. S

2018-02-01

Full Text Available BACKGROUND Metabolic acidosis is proven complication of major surgery, but very less significance is given to it. Metabolic acidosis has a significant effect in postoperative recovery and morbidity of patients undergoing major surgery. Metabolic acidosis has a say in proper functioning of cardiovascular, renal and pulmonary system, added to severe stress full condition related to postoperative period, it bring about major shift in the speedy recovery of patient. It becomes significantly important that metabolic acidosis in diagnosed as early as possible and corrective measures are taken immediately. MATERIALS AND METHODS Study design is a prospective observational study. 109 patients who underwent elective and emergency surgeries in the department of General Surgery, Govt. Medical College Kottayam was studied for a period of 3 months (2016. On arrival of the patient, a detailed history of the patient was taken, along with emphasis to the multiple factors in the history which could be contributory to postoperative metabolic acidosis such as diabetic status, drug history, history of respiratory, cardiac and renal status. Basic preoperative laboratory investigation was carried out and its values were recorded. A preoperative arterial blood gas analysis (ABG of the patient was done before patient was taken for surgery, values of which were recorded and analysed to rule out existing acidotic status of patient, if the patient is already having metabolic acidosis he was excluded from the study. A second ABG was sent at 2 hours after induction of anaesthesia, values of which was recorded, along with the values of intraoperative fluids, preoperative Hb, duration of surgery, type of surgery, blood transfusion and colloid administration given during the time of anaesthesia. A third ABG was sent within six hours of completion of surgery and the values analysed, with due notes on postoperative care done and the days of ICU stay, for analysis and comparison

Hyperammonemia associated with distal renal tubular acidosis or urinary tract infection: a systematic review.

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Clericetti, Caterina M; Milani, Gregorio P; Lava, Sebastiano A G; Bianchetti, Mario G; Simonetti, Giacomo D; Giannini, Olivier

2018-03-01

Hyperammonemia usually results from an inborn error of metabolism or from an advanced liver disease. Individual case reports suggest that both distal renal tubular acidosis and urinary tract infection may also result in hyperammonemia. A systematic review of the literature on hyperammonemia secondary to distal renal tubular acidosis and urinary tract infection was conducted. We identified 39 reports on distal renal tubular acidosis or urinary tract infections in association with hyperammonemia published between 1980 and 2017. Hyperammonemia was detected in 13 children with distal renal tubular acidosis and in one adult patient with distal renal tubular acidosis secondary to primary hyperparathyroidism. In these patients a negative relationship was observed between circulating ammonia and bicarbonate levels (P urinary tract infection was complicated by acute hyperammonemia and symptoms and signs of acute neuronal dysfunction, such as an altered level of consciousness, convulsions and asterixis, often associated with signs of brain edema, such as anorexia and vomiting. Urea-splitting bacteria were isolated in 28 of the 31 cases. The urinary tract was anatomically or functionally abnormal in 30 of these patients. This study reveals that both altered distal renal tubular acidification and urinary tract infection may be associated with relevant hyperammonemia in both children and adults.

Neonatal metabolic acidosis at birth: In search of a reliable marker.

Science.gov (United States)

Racinet, C; Ouellet, P; Charles, F; Daboval, T

2016-06-01

A newborn may present acidemia on the umbilical artery blood which can result from respiratory acidosis or metabolic acidosis or be of mixed origin. Currently, in the absence of a satisfactory definition, the challenge is to determine the most accurate marker for metabolic acidosis, which can be deleterious for the neonate. We reviewed the methodological and physiological aspects of the perinatal literature to search for the best marker of NMA. Base deficit and pH have been criticized as the standard criteria to predict outcome. The proposed threshold of pathogenicity is not based on convincing studies. The algorithms of various blood gas analyzers differ and do not take into account the specific neonatal acid-base profile. Birth-related neonatal eucapnic pH is described as the most pertinent marker of NMA at birth. The various means of calculating this value and the level below which it seems to play a possible pathogenic role are presented. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

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

Science.gov (United States)

Lorenzoni, Paulo José; Werneck, Lineu Cesar; Kay, Cláudia Suemi Kamoi; Silvado, Carlos Eduardo Soares; Scola, Rosana Herminia

2015-11-01

Mitochondrial 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.

Trimethoprim/Sulfamethoxazole-Induced Severe Lactic Acidosis: A Case Report and Review of the Literature.

Science.gov (United States)

Bulathsinghala, Marie; Keefer, Kimberly; Van de Louw, Andry

2016-04-01

Propylene glycol (PG) is used as a solvent in numerous medications, including trimethoprim/sulfamethoxazole (TMP/SMX) and lorazepam, and is metabolized in the liver to lactic acid. Cases of lactic acidosis related to PG toxicity have been described and always involved large doses of benzodiazepines and PG. We present the first case of severe lactic acidosis after a 3-day course of TMP/SMX alone, involving allegedly safe amounts of PG.A 31-year-old female with neurofibromatosis and pilocytic astrocytoma, receiving temozolomide and steroids, was admitted to the intensive care unit for pneumonia and acute respiratory failure requiring intubation. Her initial hemodynamic and acid-base statuses were normal. She was treated with intravenous TMP/SMX for possible Pneumocystis jirovecii pneumonia and was successfully extubated on day 2. On day 3, she developed tachypnea and arterial blood gas analysis revealed a severe metabolic acidosis (pH 7.2, PCO2 19 mm Hg, bicarbonates 8 mEq/L) with anion gap of 25 mEq/L and lactate of 12.1 mmol/L. TMP/SMX was discontinued and the lactate decreased to 2.9 mmol/L within 24 hours while her plasma bicarbonates normalized, without additional intervention. The patient never developed hypotension or severe hypoxia, and her renal and liver functions were normal. No other cause for lactic acidosis was identified and it resolved after TMP/SMX cessation alone, suggesting PG toxicity.Although PG-related lactic acidosis is well recognized after large doses of lorazepam, clinicians should bear in mind that TMP/SMX contains PG as well and should suspect PG toxicity in patients developing unexplained metabolic acidosis while receiving TMP/SMX.

Autoimmune Hepatitis with Distal Renal Tubular Acidosis and Small Bowel Partial Malrotation.

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Kanaiyalal Modi, Tejas; Parikh, Hardik; Sadalge, Abhishek; Gupte, Amit; Bhatt, Pratin; Shukla, Akash

2015-01-01

Renal tubular acidosis (RTA) is not uncommon in patient with chronic autoimmune hepatitis (AIH), but usually remains latent. Here, we report a case of renal tubular acidosis RTA who presented with AIH. She was also diagnosed to have partial bowel malrotation. A 9-year-old girl, a case of distal RTA, presented with jaundice, abdominal distension and altered sensorium. She was diagnosed to be AIH, which was successfully treated with steroids and azathioprine. Coexistent midgut partial malrotation with volvulus was diagnosed during the treatment. She was treated successfully with anti-tuberculous treatment for cervical lymphadenitis. Autoimmune hepatitis should not be ruled out in each case of RTA presenting with jaundice. Modi TK, Parikh H, Sadalge A, Gupte A, Bhatt P, Shukla A. Autoimmune Hepatitis with Distal Renal Tubular Acidosis and Small Bowel Partial Malrotation. Euroasian J Hepato-Gastroenterol 2015;5(2):107-109.

Distinct mechanisms underlie adaptation of proximal tubule Na+/H+ exchanger isoform 3 in response to chronic metabolic and respiratory acidosis.

Science.gov (United States)

Silva, Pedro Henrique Imenez; Girardi, Adriana Castello Costa; Neri, Elida Adalgisa; Rebouças, Nancy Amaral

2012-04-01

The Na(+/)H(+) exchanger isoform 3 (NHE3) is essential for HCO(3)(-) reabsorption in renal proximal tubules. The expression and function of NHE3 must adapt to acid-base conditions. The goal of this study was to elucidate the mechanisms responsible for higher proton secretion in proximal tubules during acidosis and to evaluate whether there are differences between metabolic and respiratory acidosis with regard to NHE3 modulation and, if so, to identify the relevant parameters that may trigger these distinct adaptive responses. We achieved metabolic acidosis by lowering HCO(3)(-) concentration in the cell culture medium and respiratory acidosis by increasing CO(2) tension in the incubator chamber. We found that cell-surface NHE3 expression was increased in response to both forms of acidosis. Mild (pH 7.21 ± 0.02) and severe (6.95 ± 0.07) metabolic acidosis increased mRNA levels, at least in part due to up-regulation of transcription, whilst mild (7.11 ± 0.03) and severe (6.86 ± 0.01) respiratory acidosis did not up-regulate NHE3 expression. Analyses of the Nhe3 promoter region suggested that the regulatory elements sensitive to metabolic acidosis are located between -466 and -153 bp, where two consensus binding sites for SP1, a transcription factor up-regulated in metabolic acidosis, were localised. We conclude that metabolic acidosis induces Nhe3 promoter activation, which results in higher mRNA and total protein level. At the plasma membrane surface, NHE3 expression was increased in metabolic and respiratory acidosis alike, suggesting that low pH is responsible for NHE3 displacement to the cell surface.

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

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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.

Mechanisms of adaptation to chronic respiratory acidosis in the rabbit proximal tubule.

OpenAIRE

Krapf, R

1989-01-01

The hyperbicarbonatemia of chronic respiratory acidosis is maintained by enhanced bicarbonate reabsorption in the proximal tubule. To investigate the cellular mechanisms involved in this adaptation, cell and luminal pH were measured microfluorometrically using (2",7')-bis(carboxyethyl)-(5,6)-carboxyfluorescein in isolated, microperfused S2 proximal convoluted tubules from control and acidotic rabbits. Chronic respiratory acidosis was induced by exposure to 10% CO2 for 52-56 h. Tubules from ac...

Lactic acidosis occurrence during exercises in the smoke chamber in a 53-year-old firefighter with no significant medical history

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Agata Bronisz

2014-04-01

Full Text Available Lactic acidosis is a form of metabolic acidosis with a high anion gap, reduced rate of arterial blood pH under 7.35 mmol/l, and lactic acid concentration over 7 mmol/l. In the literature we can find some descriptions of the cases of lactic acidosis in patients with severe systemic diseases (cancer, acquired immunodeficiency syndrome, sepsis, diabetes with cardiovascular disease and after organ transplantations. We present the case of lactic acidosis in a patient with no chronic disease - a firefighter in whom lactic acidosis has developed during standard exercises in the smoke chamber.

Friedrich Nietzsche (1844-1900): a classical case of mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome?

Science.gov (United States)

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.

Infusion of sodium bicarbonate in experimentally induced metabolic acidosis does not provoke cerebrospinal fluid (CSF) acidosis in calves.

Science.gov (United States)

Abeysekara, Saman; Zello, Gordon A; Lohmann, Katharina L; Alcorn, Jane; Hamilton, Don L; Naylor, Jonathan M

2012-01-01

In a crossover study, 5 calves were made acidotic by intermittent intravenous infusion of isotonic hydrochloric acid (HCl) over approximately 24 h. This was followed by rapid (4 h) or slow (24 h) correction of blood pH with isotonic sodium bicarbonate (NaHCO(3)) to determine if rapid correction of acidemia produced paradoxical cerebrospinal fluid (CSF) acidosis. Infusion of HCl produced a marked metabolic acidosis with respiratory compensation. Venous blood pH (mean ± S(x)) was 7.362 ± 0.021 and 7.116 ± 0.032, partial pressure of carbon dioxide (Pco(2), torr) 48.8 ± 1.3 and 34.8 ± 1.4, and bicarbonate (mmol/L), 27.2 ± 1.27 and 11 ± 0.96; CSF pH was 7.344 ± 0.031 and 7.240 ± 0.039, Pco(2) 42.8 ± 2.9 and 34.5 ± 1.4, and bicarbonate 23.5 ± 0.91 and 14.2 ± 1.09 for the period before the infusion of hydrochloric acid and immediately before the start of sodium bicarbonate correction, respectively. In calves treated with rapid infusion of sodium bicarbonate, correction of venous acidemia was significantly more rapid and increases in Pco(2) and bicarbonate in CSF were also more rapid. However, there was no significant difference in CSF pH. After 4 h of correction, CSF pH was 7.238 ± 0.040 and 7.256 ± 0.050, Pco(2) 44.4 ± 2.2 and 34.2 ± 2.1, and bicarbonate 17.8 ± 1.02 and 14.6 ± 1.4 for rapid and slow correction, respectively. Under the conditions of this experiment, rapid correction of acidemia did not provoke paradoxical CSF acidosis.

Inhaled β-agonist therapy and respiratory muscle fatigue as under-recognised causes of lactic acidosis.

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Lau, Emily; Mazer, Jeffrey; Carino, Gerardo

2013-10-14

A 49-year-old man with chronic obstructive pulmonary disease (COPD) presented with significant tachypnoea, fevers, productive cough and increased work of breathing for the previous 4 days. Laboratory data showed elevated lactate of 3.2 mEq/L. Continuous inhaled ipratropium and albuterol nebuliser treatments were administered. Lactate levels increased to 5.5 and 3.9 mEq/L, at 6 and 12 h, respectively. No infectious source was found and the lactic acidosis cleared as the patient improved. The lactic acidosis was determined to be secondary to respiratory muscle fatigue and inhaled β-agonist therapy, two under-recognised causes of lactic acidosis in patients presenting with respiratory distress. Lactic acidosis is commonly used as a clinical marker for sepsis and shock, but in the absence of tissue hypoperfusion and severe hypoxia, alternative aetiologies for elevated levels should be sought to avoid unnecessary and potentially harmful medical interventions.

Mitochondrial encephalopathy with lactic acidosis and stroke-like ...

African Journals Online (AJOL)

Laila Selim

2013-04-12

Apr 12, 2013 ... heteroplasmic A3243G mutation was detected in the blood of the patient and his mother. .... mitochondrial defects, such as lactic acidosis or Ragged Red ..... [48] Pulkes T, Eunson L, Patterson V, Siddiqui A, Wood NW, Nelson.

Causes of metabolic acidosis in canine hemorrhagic shock: role of unmeasured ions

OpenAIRE

Bruegger, Dirk; Kemming, Gregor I; Jacob, Matthias; Meisner, Franz G; Wojtczyk, Christoph J; Packert, Kristian B; Keipert, Peter E; Faithfull, N Simon; Habler, Oliver P; Becker, Bernhard F; Rehm, Markus

2007-01-01

Introduction: Metabolic acidosis during hemorrhagic shock is common and conventionally considered to be due to hyperlactatemia. There is increasing awareness, however, that other nonlactate, unmeasured anions contribute to this type of acidosis. Methods: Eleven anesthetized dogs were hemorrhaged to a mean arterial pressure of 45 mm Hg and were kept at this level until a metabolic oxygen debt of 120 mLO2/kg body weight had evolved. Blood pH, partial pressure of carbon dioxide, and concentr...

Renal Tubular Acidosis Secondary to FK506 in Living Donor Liver Transplantation: A Case Report

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Keiko Ogita

2003-10-01

Full Text Available FK506 is an immunosuppressant that is thought to be less nephrotoxic than cyclosporine A. However, complications due to renal tubular acidosis (RTA have recently been reported. We report a case of RTA secondary to FK506 administration in liver transplantation. A 6-month-old girl was treated with FK506 after undergoing living donor liver transplantation for fulminant hepatitis. On postoperative day 17, she demonstrated hyperkalaemia and metabolic acidosis; she was diagnosed to have hyperkalaemic distal RTA with aldosterone deficiency (type IV. Intravenous sodium bicarbonate and furosemide, and intrarectal calcium polystyrenesulfonate were administered to correct the acidosis and promote potassium secretion. Thereafter, the FK506 concentration in whole blood gradually decreased, and the hyperkalaemia and metabolic acidosis following RTA improved. RTA is one type of nephrotoxicity induced by FK506, and it is reversible in mild cases when appropriately treated. The mechanism of RTA induced by FK506 has not yet been clearly elucidated. Surgeons and physicians should therefore be aware of the potential for RTA to occur with FK506 after any organ transplantation. The treatment for acidosis and hyperkalaemia should be started as soon as RTA is diagnosed, and the dosage of FK506 should also be reduced if possible.

Single histidine button in cardiac troponin I sustains heart performance in response to severe hypercapnic respiratory acidosis in vivo.

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Palpant, Nathan J; D'Alecy, Louis G; Metzger, Joseph M

2009-05-01

Intracellular acidosis is a profound negative regulator of myocardial performance. We hypothesized that titrating myofilament calcium sensitivity by a single histidine substituted cardiac troponin I (A164H) would protect the whole animal physiological response to acidosis in vivo. To experimentally induce severe hypercapnic acidosis, mice were exposed to a 40% CO(2) challenge. By echocardiography, it was found that systolic function and ventricular geometry were maintained in cTnI A164H transgenic (Tg) mice. By contrast, non-Tg (Ntg) littermates experienced rapid and marked cardiac decompensation during this same challenge. For detailed hemodymanic assessment, Millar pressure-conductance catheterization was performed while animals were treated with a beta-blocker, esmolol, during a severe hypercapnic acidosis challenge. Survival and load-independent measures of contractility were significantly greater in Tg vs. Ntg mice. This assay showed that Ntg mice had 100% mortality within 5 min of acidosis. By contrast, systolic and diastolic function were protected in Tg mice during acidosis, and they had 100% survival. This study shows that, independent of any beta-adrenergic compensation, myofilament-based molecular manipulation of inotropy by histidine-modified troponin I maintains cardiac inotropic and lusitropic performance and markedly improves survival during severe acidosis in vivo.

Persistent villi hypoperfusion explains intramucosal acidosis in sheep endotoxemia

NARCIS (Netherlands)

Dubin, Arnaldo; Edul, Vanina Siham Kanoore; Pozo, Mario Omar; Murias, Gastón; Canullán, Carlos Manuel; Martins, Enrique Francisco; Ferrara, Gonzalo; Canales, Héctor Saul; Laporte, Mercedes; Estenssoro, Elisa; Ince, Can

2008-01-01

OBJECTIVE: To test the hypothesis that persistent villi hypoperfusion explains intramucosal acidosis after endotoxemic shock resuscitation. DESIGN: Controlled experimental study. SETTING: University-based research laboratory. SUBJECTS: A total of 14 anesthetized, mechanically ventilated sheep.

Reclassification of clinical sleep disorders using traditional models of syndromic, neuroanatomic, pathophysiological and etiological diagnosis.

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Spitzer, A Robert

2014-09-01

Existing classifications of central nervous system sleep disorders do not often provide tools to diagnose the majority of patients complaining of sleep-related symptoms, nor always guide effective treatment. I present a novel classification system that completely separates clinical syndromes from anatomical localization, pathophysiology, and etiology. The clinical syndrome I present can describe the majority of patients, but can be fractionated into individual subgroups for further study. By then separating the anatomy and physiology from the symptoms, an avenue of research becomes available to study the different possible structures that regulate sleep, that may be damaged and cause syndromes of sleep dysfunction. Some of these may produce symptoms that overlap with narcolepsy and some may be distinct. Because the clinical syndrome should be distinguished from anatomy or physiology, I have proposed the term narcoleptiform syndrome for the clinical syndrome. The model also clearly separates etiology from anatomy in a classical neurological manner. This allows etiology, localization and symptoms to be studied separately. It is likely that different etiologies may produce damage in areas that produce similar syndromes. For example, in this model, different causes of damage to the orexin nucleus would result in the same clinical syndrome. This reinforces the concept of studying anatomy, symptoms and etiology separately. By studying the relationship of syndromes or symptoms to anatomic localization and pathophysiology, it should be possible to test novel approaches to treatment based on different underlying structure or function. For example, patients with lesions in the ventrolateral preoptic nucleus or the thalamic intralaminar nuclei may both present with insomnia symptoms but need different treatment; or they might present with symptoms overlapping narcolepsy (a narcoleptiform syndrome) yet need different treatment. In some cases, a single treatment may cross over

Respiratory acidosis in adolescents with anorexia nervosa hospitalized for medical stabilization: a retrospective study.

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Kerem, Nogah C; Riskin, Arieh; Averin, Elvira; Srugo, Isaac; Kugelman, Amir

2012-01-01

To examine the effect of malnutrition due to anorexia nervosa (AN) on venous blood gases of adolescents with AN hospitalized for medical stabilization. This retrospective study included 45 adolescents with recent onset (respiratory acidosis (pH 45 mm Hg) was observed in 78% of the patients on admission and only in 35% at discharge (p = .0003). Positive correlations were found between % of weight loss and pCO(2) on admission and between BMI on admission and the delta pCO(2) during hospitalization. Mild respiratory acidosis is common in adolescents with recently diagnosed AN, hospitalized for medical stabilization. Respiratory acidosis improves with bed rest and refeeding. The clinical significance of these findings should be further evaluated. Copyright © 2011 Wiley Periodicals, Inc.

Alzheimer's disease: pathophysiology and applications of magnetic nanoparticles as MRI theranostic agents.

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Amiri, H.; Saeidi, K.; Borhani, P.; Manafirad, A.; Ghavami, M.; Zerbi, V.

2013-01-01

Alzheimer's disease (AD) is the most common form of dementia. During the recent decade, nanotechnology has been widely considered, as a promising tool, for theranosis (diagnosis and therapy) of AD. Here we first discuss pathophysiology and characteristics of AD with a focus on the amyloid cascade

Metformin-Associated Acute Kidney Injury and Lactic Acidosis

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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.

Prolonged resuscitation of metabolic acidosis after trauma is associated with more complications.

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Weinberg, Douglas S; Narayanan, Arvind S; Moore, Timothy A; Vallier, Heather A

2015-09-24

Optimal patterns for fluid management are controversial in the resuscitation of major trauma. Similarly, appropriate surgical timing is often unclear in orthopedic polytrauma. Early appropriate care (EAC) has recently been introduced as an objective model to determine readiness for surgery based on the resuscitation of metabolic acidosis. EAC is an objective treatment algorithm that recommends fracture fixation within 36 h when either lactate acidosis using EAC. At an adult level 1 trauma center, 332 patients with major trauma (Injury Severity Score (ISS) ≥16) were prospectively treated with EAC. The time from injury to EAC resuscitation was determined in all patients. Age, race, gender, ISS, American Society of Anesthesiologists score (ASA), body mass index (BMI), outside hospital transfer status, number of fractures, and the specific fractures were also reviewed. Complications in the 6-month post-operative period were adjudicated by an independent multidisciplinary committee of trauma physicians and included infection, sepsis, pulmonary embolism, deep venous thrombosis, renal failure, multiorgan failure, pneumonia, and acute respiratory distress syndrome. Univariate analysis and binomial logistic regression analysis were used to compare complications between groups. Sixty-six patients developed complications, which was less than a historical cohort of 1,441 patients (19.9% vs. 22.1%). ISS (p acidosis was associated with a higher complication rate. Identifying the innate differences in the response, regulation, and resolution of acidosis in these critically injured patients is an important area for trauma research. Level 1: prognostic study.

Heart Failure with Preserved Ejection Fraction – Concept, Pathophysiology, Diagnosis and Challenges for Treatment

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Lidija Veterovska Miljkovik

2015-07-01

Full Text Available Heart failure (HF with preserved left ventricular (LV ejection fraction (HFpEF occurs in 40 to 60% of the patients with HF, with a prognosis which is similar to HF with reduced ejection fraction (HFrEF. HFpEF pathophysiology is different from that of HFrEF, and has been characterized with diastolic dysfunction. Diastolic dysfunction has been defined with elevated left ventricular stiffness, prolonged iso-volumetric LV relaxation, slow LV filing and elevated LV end-diastolic pressure. Arterial hypertension occurs in majority cases with HFpEF worldwide. Patients are mostly older and obese. Diabetes mellitus and atrial fibrillation appear proportionally in a high frequency of patients with HFpEF. The HFpEF diagnosis is based on existence of symptoms and signs of heart failure, normal or approximately normal ejection and diagnosing of LV diastolic dysfunction by means of heart catheterization or Doppler echocardiography and/or elevated concentration of plasma natriuretic peptide. The present recommendations for HFpEF treatment include blood pressure control, heart chamber frequency control when atrial fibrillation exists, in some situations even coronary revascularization and an attempt for sinus rhythm reestablishment. Up to now, it is considered that no medication or a group of medications improve the survival of HFpEF patients. Due to these causes and the bad prognosis of the disorder, rigorous control is recommended of the previously mentioned precipitating factors for this disorder. This paper presents a universal review of the most important parameters which determine this disorder.

Distal renal tubular acidosis and hypokalemic paralysis in a patient with hypothyroidism

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Parvaiz Ahmad Koul

2011-01-01

Full Text Available A 43- year- old woman on treatment for primary hypothyroidism presented with 1- day progressive weakness of all her limbs and history of similar episodes in the past. Clinical examination revealed grade 2 hyporeflexive weakness. Investigations revealed features of hypokalemia, metabolic acidosis, alkaline urine, and a fractional bicarbonate excretion of 3.5%, consistent with distal renal tubular acidosis. Antithyroid peroxidase and antithroglobulin antibodies were positive, suggesting an autoimmune basis for the pathogenesis of the functional tubular defect. Bicarbonate therapy resulted in a sustained clinical recovery.

[Liver diseases in high-production cows with ruminal acidosis].

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Ivanov, I B; Mikhaĭlov, G; Pham, T H

1987-01-01

Studied was the relation of the subclinical, recurring, and chronic rumen acidosis, on the one hand, to the disturbed function, resp., injuries of the liver, on the other. Experiments were carried out with a total of 862 high-producing cows, 54 out of which had massive injuries of the liver. Full clinical examination was performed, 22 of the animals being subject to laboratory investigations with regard to the rumen content (pH, infusorial count per 1 cm3 with the differentiation of bacteria, activity with regard to glucose, nitrates, sedimentation, and flotation), blood (whole blood picture, coagulation tests, bilirubin, SGOT, SGPT, serum aldolase, alkaline phosphatase, alkaline reserves, blood sugar), and urine (pH, protein, ketone bodies, sugar, and CSR). It is concluded that three inferences could be drawn, pointing to the relation between recurring rumen acidosis and the liver diseases.

PATHOPHYSIOLOGY, DIAGNOSIS AND TREATMENTOF DUMPING SYNDROME AND ITS RELATION TO BARIATRIC SURGERY.

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Chaves, Yasmin da Silva; Destefani, Afrânio Côgo

The dumping syndrome is frequent in bariatric surgery. It is probably the most common syndrome following partial or complete gastrectomy. Its prevalence in partial gastrectomy can reach up to 50%, thus it can be a significant complication arising from some types of bariatric surgeries. Critical analysis on dumping syndrome, its pathophysiology, diagnosis and treatment. A literature review was performed using the key words: 'dumping syndrome', 'bariatric surgery' and 'rapid dumping syndrome'. Inclusion criteria were: books, original works, case reports and meta-analyzes, and the exclusion criterion was literature review. Concerning the publication time, articles were screened between 1960 and May 2015. The dumping syndrome is complication arising from obesity surgeries, but also can be a result of vagus nerve damage. Diagnosis is done primarily through the use of questionnaires based on scores. The Sigstad score and Arts survey are valid means for assessing the dumping syndrome. Initial therapy consists in the adoption of dietary measures, short acting drugs administration. A síndrome de dumping é frequente após operações bariátricas. É, provavelmente, a mais comum das síndromes que sucedem gastrectomias parciais ou completas. Sua prevalência, em gastrectomias parciais pode chegar a até 50%, tornando-se assim complicação significante em alguns tipos de operações bariátricas. Realizar análise crítica sobre a síndrome de dumping em sua fisiopatologia, diagnóstico e tratamento. Foi realizada revisão bibliográfica utilizando os descritores: 'síndrome de dumping', 'cirurgia bariátrica' e 'síndrome do esvaziamento rápido'. Os critérios de inclusão foram: livros, trabalhos originais, relatos de caso e metanálises; excluíram-se as revisões bibliográficas. Quanto ao tempo de publicação, foram selecionados artigos entre 1960 e maio de 2015. A síndrome de dumping é complicação gastrointestinal oriunda de operações para obesidade, mas tamb

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

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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.

Pyruvate carboxylase deficiency: An underestimated cause of lactic acidosis

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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.

Cluster Headache: Epidemiology, Pathophysiology, Clinical Features, and Diagnosis.

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Wei, Diana Yi-Ting; Yuan Ong, Jonathan Jia; Goadsby, Peter James

2018-04-01

Cluster headache is a primary headache disorder affecting up to 0.1% of the population. Patients suffer from cluster headache attacks lasting from 15 to 180 min up to 8 times a day. The attacks are characterized by the severe unilateral pain mainly in the first division of the trigeminal nerve, with associated prominent unilateral cranial autonomic symptoms and a sense of agitation and restlessness during the attacks. The male-to-female ratio is approximately 2.5:1. Experimental, clinical, and neuroimaging studies have advanced our understanding of the pathogenesis of cluster headache. The pathophysiology involves activation of the trigeminovascular complex and the trigeminal-autonomic reflex and accounts for the unilateral severe headache, the prominent ipsilateral cranial autonomic symptoms. In addition, the circadian and circannual rhythmicity unique to this condition is postulated to involve the hypothalamus and suprachiasmatic nucleus. Although the clinical features are distinct, it may be misdiagnosed, with patients often presenting to the otolaryngologist or dentist with symptoms. The prognosis of cluster headache remains difficult to predict. Patients with episodic cluster headache can shift to chronic cluster headache and vice versa. Longitudinally, cluster headache tends to remit with age with less frequent bouts and more prolonged periods of remission in between bouts.

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

International Nuclear Information System (INIS)

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

1987-01-01

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 4 Cl x 100 g body wt -1 x day -1 . Epitrochlearis muscles were incubated with L-[1- 14 C]-valine and L-[1- 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 α-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 α-keto acid dehydrogenase

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

Energy Technology Data Exchange (ETDEWEB)

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.

Analysis of the clinical backgrounds of patients who developed respiratory acidosis under high-flow oxygen therapy during emergency transport.

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Ogino, Hirokazu; Nishimura, Naoki; Yamano, Yasuhiko; Ishikawa, Genta; Tomishima, Yutaka; Jinta, Torahiko; Takahashi, Osamu; Chohnabayashi, Naohiko

2016-01-01

High-flow oxygen is often administered to patients during emergency transport and can sometimes cause respiratory acidosis with disturbed consciousness, thereby necessitating mechanical ventilation. Although oxygen titration in chronic obstructive pulmonary disease patients during emergency transport reduces mortality rates, the clinical risk factors for respiratory acidosis in emergency settings are not fully understood. Therefore, we analyzed the clinical backgrounds of patients who developed respiratory acidosis during pre-hospital transport. This was a retrospective study of patients who arrived at our hospital by emergency transport in 2010 who received high-flow oxygen while in transit. Respiratory acidosis was defined by the following arterial blood gas readings: pH, ≤7.35; PaCO 2 , ≥45 mmHg; and HCO 3 - , ≥24 mmol/L. The risk factors were identified using multivariable logistic regression analysis. In 765 study patients, 66 patients showed respiratory acidosis. The following risk factors for respiratory acidosis were identified: age, ≥65 years (odds ratio [OR] 1.4; 95% confidence interval [CI], 0.7-2.8); transportation time, ≥10 min (OR 2.0; 95% CI, 1.1-3.7); three digits on the Japan Coma Scale (OR 3.1; 95% CI, 1.7-5.8); percutaneous oxygen saturation, ≤90% (OR 1.6; 95% CI, 0.8-3.0); tuberculosis (OR 4.5; 95% CI, 1.4-15.1); asthma (OR 1.8; 95% CI, 0.6-5.3); pneumonia (OR 1.5; 95% CI, 0.7-3.1); and lung cancer (OR 3.9; 95% CI, 1.5-10.1). These underlying diseases as risk factors included both comorbid diseases and past medical conditions. The factors identified may contribute to the development of respiratory acidosis. Further studies on preventing respiratory acidosis will improve the quality of emergency medical care.

Sjögren syndrome presenting with hypopotassemic periodic paralysis due to renal tubular acidosis

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Ataoglu, Esra Hayriye; Demir, Betul; Tuna, Mazhar; Çavus, Bilger; Cetin, Faik; Temiz, Levent Umit; Ozturk, Savas; Yenigun, Mustafa

2012-01-01

Summary Background: Sjögren syndrome (SS) is an autoimmune-lymphoproliferative disorder characterized by mononuclear cell infiltration of exocrine glands. Clinically, Sjögren syndrome (SS) has a wide spectrum, varying from autoimmune exocrinopathy to systemic involvement. There have been few cases reporting that primary SS developed with distal renal tubular acidosis clinically. Case Report: Here, we present a case with primary Sjögren syndrome accompanied by hypopotassemic paralysis due to renal tubular acidosis. Severe hypopotassemia, hyperchloremic metabolic acidosis, alkaline urine and disorder in urinary acidification test were observed in the biochemical examination of the 16-year-old female patient, who had applied to our clinic for extreme loss of muscle force. After the examinations it was determined that the patient had developed Type 1 RTA (distal RTA) due to primary Sjögren syndrome. Potassium and alkaline replacement was made and an immediate total recovery was achieved. Conclusions: Hypopotassemic paralysis due to primary Sjögren syndrome is a rare but severe disorder that could lead to death if not detected early and cured appropriately. Thus, effective treatment should be immediately initiated in cases where severe hypopotassemia is accompanied by metabolic acidosis, and the cases should also be examined for extraglandular involvement of SS. PMID:23569525

Clinical predictors and outcome of metabolic acidosis in under-five children admitted to an urban hospital in Bangladesh with diarrhea and pneumonia.

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Mohammod J Chisti

Full Text Available BACKGROUND: Clinical features of metabolic acidosis and pneumonia frequently overlap in young diarrheal children, resulting in differentiation from each other very difficult. However, there is no published data on the predictors of metabolic acidosis in diarrheal children also having pneumonia. Our objective was to evaluate clinical predictors of metabolic acidosis in under-five diarrheal children with radiological pneumonia, and their outcome. METHODS: We prospectively enrolled all under-five children (n = 164 admitted to the Special Care Ward (SCW of the Dhaka Hospital of icddr, b between September and December 2007 with diarrhea and radiological pneumonia who also had their total serum carbon-dioxide estimated. We compared the clinical features and outcome of children with radiological pneumonia and diarrhea with (n = 98 and without metabolic acidosis (n = 66. RESULTS: Children with metabolic acidosis more often had higher case-fatality (16% vs. 5%, p = 0.039 compared to those without metabolic acidosis on admission. In logistic regression analysis, after adjusting for potential confounders such as age of the patient, fever on admission, and severe wasting, the independent predictors of metabolic acidosis in under-five diarrheal children having pneumonia were clinical dehydration (OR 3.57, 95% CI 1.62-7.89, p = 0.002, and low systolic blood pressure even after full rehydration (OR 1.02, 95% CI 1.01-1.04, p = 0.005. Proportions of children with cough, respiratory rate/minute, lower chest wall indrawing, nasal flaring, head nodding, grunting respiration, and cyanosis were comparable (p>0.05 among the groups. CONCLUSION AND SIGNIFICANCE: Under-five diarrheal children with radiological pneumonia having metabolic acidosis had frequent fatal outcome than those without acidosis. Clinical dehydration and persistent systolic hypotension even after adequate rehydration were independent clinical predictors of metabolic acidosis among the children

Clinical predictors and outcome of metabolic acidosis in under-five children admitted to an urban hospital in Bangladesh with diarrhea and pneumonia.

Science.gov (United States)

Chisti, Mohammod J; Ahmed, Tahmeed; Ashraf, Hasan; Faruque, A S G; Bardhan, Pradip K; Dey, Sanjoy Kumer; Huq, Sayeeda; Das, Sumon Kumar; Salam, Mohammed A

2012-01-01

Clinical features of metabolic acidosis and pneumonia frequently overlap in young diarrheal children, resulting in differentiation from each other very difficult. However, there is no published data on the predictors of metabolic acidosis in diarrheal children also having pneumonia. Our objective was to evaluate clinical predictors of metabolic acidosis in under-five diarrheal children with radiological pneumonia, and their outcome. We prospectively enrolled all under-five children (n = 164) admitted to the Special Care Ward (SCW) of the Dhaka Hospital of icddr, b between September and December 2007 with diarrhea and radiological pneumonia who also had their total serum carbon-dioxide estimated. We compared the clinical features and outcome of children with radiological pneumonia and diarrhea with (n = 98) and without metabolic acidosis (n = 66). Children with metabolic acidosis more often had higher case-fatality (16% vs. 5%, p = 0.039) compared to those without metabolic acidosis on admission. In logistic regression analysis, after adjusting for potential confounders such as age of the patient, fever on admission, and severe wasting, the independent predictors of metabolic acidosis in under-five diarrheal children having pneumonia were clinical dehydration (OR 3.57, 95% CI 1.62-7.89, p = 0.002), and low systolic blood pressure even after full rehydration (OR 1.02, 95% CI 1.01-1.04, p = 0.005). Proportions of children with cough, respiratory rate/minute, lower chest wall indrawing, nasal flaring, head nodding, grunting respiration, and cyanosis were comparable (p>0.05) among the groups. Under-five diarrheal children with radiological pneumonia having metabolic acidosis had frequent fatal outcome than those without acidosis. Clinical dehydration and persistent systolic hypotension even after adequate rehydration were independent clinical predictors of metabolic acidosis among the children. However, metabolic acidosis in young diarrheal children had no impact on the

Effect of metabolic and respiratory acidosis on intracellular calcium in osteoblasts.

Science.gov (United States)

Frick, Kevin K; Bushinsky, David A

2010-08-01

In vivo, metabolic acidosis {decreased pH from decreased bicarbonate concentration ([HCO(3)(-)])} increases urine calcium (Ca) without increased intestinal Ca absorption, resulting in a loss of bone Ca. Conversely, respiratory acidosis [decreased pH from increased partial pressure of carbon dioxide (Pco(2))] does not appreciably alter Ca homeostasis. In cultured bone, chronic metabolic acidosis (Met) significantly increases cell-mediated net Ca efflux while isohydric respiratory acidosis (Resp) does not. The proton receptor, OGR1, appears critical for cell-mediated, metabolic acid-induced bone resorption. Perfusion of primary bone cells or OGR1-transfected Chinese hamster ovary (CHO) cells with Met induces transient peaks of intracellular Ca (Ca(i)). To determine whether Resp increases Ca(i), as does Met, we imaged Ca(i) in primary cultures of bone cells. pH for Met = 7.07 ([HCO(3)(-)] = 11.8 mM) and for Resp = 7.13 (Pco(2) = 88.4 mmHg) were similar and lower than neutral (7.41). Both Met and Resp induced a marked, transient increase in Ca(i) in individual bone cells; however, Met stimulated Ca(i) to a greater extent than Resp. We used OGR1-transfected CHO cells to determine whether OGR1 was responsible for the greater increase in Ca(i) in Met than Resp. Both Met and Resp induced a marked, transient increase in Ca(i) in OGR1-transfected CHO cells; however, in these cells Met was not different than Resp. Thus, the greater induction of Ca(i) by Met in primary bone cells is not a function of OGR1 alone, but must involve H(+) receptors other than OGR1, or pathways sensitive to Pco(2), HCO(3)(-), or total CO(2) that modify the effect of H(+) in primary bone cells.

Metabolic acidosis in a patient with metformin overdose

African Journals Online (AJOL)

gas findings taken at room temperature at this time are shown in Table 1. Calculation of the anion gap was not possible because ... Arterial blood gas findings on 30% oxygen at this time revealed a metabolic acidosis as shown in .... is ideal in acute overdose for effective removal of both metformin and circulating lactate.

Influence of acidosis and hypoxia on liver ischemia and reperfusion injury in an in vivo rat model

NARCIS (Netherlands)

Heijnen, Bob H. M.; Elkhaloufi, Yasser; Straatsburg, Irene H.; van Gulik, Thomas M.

2002-01-01

The contribution of acidosis to the development of reperfusion injury is controversial. In this study, we examined the effects of respiratory acidosis and hypoxia in a frequently used in vivo liver ischemia and reperfusion (I/R) injury rat model. Rats were anesthetized with intraperitoneal

The Pathophysiology of Insomnia

Science.gov (United States)

Levenson, Jessica C.; Kay, Daniel B.

2015-01-01

Insomnia disorder is characterized by chronic dissatisfaction with sleep quantity or quality that is associated with difficulty falling asleep, frequent nighttime awakenings with difficulty returning to sleep, and/or awakening earlier in the morning than desired. Although progress has been made in our understanding of the nature, etiology, and pathophysiology of insomnia, there is still no universally accepted model. Greater understanding of the pathophysiology of insomnia may provide important information regarding how, and under what conditions, the disorder develops and is maintained as well as potential targets for prevention and treatment. The aims of this report are (1) to summarize current knowledge on the pathophysiology of insomnia and (2) to present a model of the pathophysiology of insomnia that considers evidence from various domains of research. Working within several models of insomnia, evidence for the pathophysiology of the disorder is presented across levels of analysis, from genetic to molecular and cellular mechanisms, neural circuitry, physiologic mechanisms, sleep behavior, and self-report. We discuss the role of hyperarousal as an overarching theme that guides our conceptualization of insomnia. Finally, we propose a model of the pathophysiology of insomnia that integrates the various types of evidence presented. PMID:25846534

[A clinical case of development of lactic acid acidosis in a diabetic patient taking metformin].

Science.gov (United States)

Cesur, Mustafa; Cekmen, Nedum; Cetinbas, Riza R; Badalov, Pavel; Erdemli, Ozcan

2006-01-01

Metformin is a biguanide. Due to its effects in suppressing the hepatic production of endogenous glucose and in increasing insulin sensitivity in adipose tissue and skeletal muscle, the agent is used particularly in type 2 diabetes mellitus and metabolic syndrome, in which insulin resistance is especially pronounced. Lactic acidosis is one of the most important side effects of metformin. A male patient, born in 1923, was admitted to the emergency unit of our hospital for sudden vertigo, weakness, dyspnea, cyanosis, and lethargy. His history data showed that the patient had been suffering from type 2 diabetes mellitus for 10 years and taking Glargin (insulin), 12 U/kg, once daily and Glucophage (metformin), 850 mg thrice daily. The patient's general condition was fair; stupor, time and spatial orientation were absent. Analysis of arterial blood gases showed the presence of metabolic acidosis, hypokalemia, hypoxemia, and hypercapnia. Thereafter the patient was transferred to the intensive care unit of the hospital; intubated and connected to a T-bird ventilation apparatus. On the following day, an analysis of arterial blood gases indicated the proximity of the results to their physiological parameters. Ventilation was stopped; and monitoring of the patient continued by following the T-shape type of ventilation discontinuation. There were no X-ray signs of pneumonia or pulmonary edema. On the same day, the patient was extubated and oxygen inhalation in a dose of L/min was continued through a mask. On day 4 since therapy was initiated, the patient's vital signs, serum sugar and lactate levels became normal. By determining a new treatment regimen, the patient was discharged from the intensive care unit. Dyspnea, acidosis, and hypoxia developed in the patient resulted from lactic acidosis caused by the use of metformin. It should be remembered that dyspnea, acidosis, and hypoxia, which suddenly developed in metformin-treated patients with type 2 diabetes mellitus, may be

[A case of mFOLFOX6-induced lactic acidosis in a patient with colon cancer].

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Ito, Atene; Kawamoto, Kazuyuki; Park, Taebun; Ito, Tadashi

2014-11-01

Leucovorin calcium, 5-fluorouracil, and oxaliplatin (FOLFOX) therapy is a standard chemotherapy regimen used to treat colorectal cancer. Peripheral nerve disorder and myelosuppression are frequently reported treatment-related adverse events. With modified FOLFOX6 (mFOLFOX6) therapy, adverse events of an altered mental state with reversible posterior leukoencephalopathy and hypoammonemia have been reported, while lactic acidosis is uncommon. We describe a case of mFOLFOX6 - induced lactic acidosis in a 64-year-old man with colorectal cancer who underwent pelvic exenteration following chemotherapy. Postoperative histopathological analysis revealed residual cancer. Following the commencement of mFOLFOX6 therapy, the patient experienced emesis, hiccupping, and an altered mental state. Laboratory testing revealed only severe lactic acidosis, while diagnostic imaging was unrevealing. All symptoms quickly improved upon the administration of intravenous infusion of sodium bicarbonate.

Mitochondrial Encephalomyopathy With Lactic Acidosis and Stroke-Like Episodes-MELAS Syndrome.

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Henry, Caitlin; Patel, Neema; Shaffer, William; Murphy, Lillian; Park, Joe; Spieler, Bradley

2017-01-01

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a rare inherited disorder that results in waxing and waning nervous system and muscle dysfunction. MELAS syndrome may overlap with other neurologic disorders but shows distinctive imaging features. We present the case of a 28-year-old female with atypical stroke-like symptoms, a strong family history of stroke-like symptoms, and a relapsing-remitting course for several years. We discuss the imaging features distinctive to the case, the mechanism of the disease, typical presentation, imaging diagnosis, and disease management. This case is a classic example of the relapse-remitting MELAS syndrome progression with episodic clinical flares and fluctuating patterns of stroke-like lesions on imaging. MELAS is an important diagnostic consideration when neuroimaging reveals a pattern of disappearing and relapsing cortical brain lesions that may occur in different areas of the brain and are not necessarily limited to discrete vascular territories. Future studies should investigate disease mechanisms at the cellular level and the value of advanced magnetic resonance imaging techniques for a targeted approach to therapy.

Analysis of the clinical backgrounds of patients who developed respiratory acidosis under high‐flow oxygen therapy during emergency transport

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Ogino, Hirokazu; Yamano, Yasuhiko; Ishikawa, Genta; Tomishima, Yutaka; Jinta, Torahiko; Takahashi, Osamu; Chohnabayashi, Naohiko

2015-01-01

Aim High‐flow oxygen is often administered to patients during emergency transport and can sometimes cause respiratory acidosis with disturbed consciousness, thereby necessitating mechanical ventilation. Although oxygen titration in chronic obstructive pulmonary disease patients during emergency transport reduces mortality rates, the clinical risk factors for respiratory acidosis in emergency settings are not fully understood. Therefore, we analyzed the clinical backgrounds of patients who developed respiratory acidosis during pre‐hospital transport. Methods This was a retrospective study of patients who arrived at our hospital by emergency transport in 2010 who received high‐flow oxygen while in transit. Respiratory acidosis was defined by the following arterial blood gas readings: pH, ≤7.35; PaCO 2, ≥45 mmHg; and HCO 3 −, ≥24 mmol/L. The risk factors were identified using multivariable logistic regression analysis. Results In 765 study patients, 66 patients showed respiratory acidosis. The following risk factors for respiratory acidosis were identified: age, ≥65 years (odds ratio [OR] 1.4; 95% confidence interval [CI], 0.7–2.8); transportation time, ≥10 min (OR 2.0; 95% CI, 1.1–3.7); three digits on the Japan Coma Scale (OR 3.1; 95% CI, 1.7–5.8); percutaneous oxygen saturation, ≤90% (OR 1.6; 95% CI, 0.8–3.0); tuberculosis (OR 4.5; 95% CI, 1.4–15.1); asthma (OR 1.8; 95% CI, 0.6–5.3); pneumonia (OR 1.5; 95% CI, 0.7–3.1); and lung cancer (OR 3.9; 95% CI, 1.5–10.1). These underlying diseases as risk factors included both comorbid diseases and past medical conditions. Conclusions The factors identified may contribute to the development of respiratory acidosis. Further studies on preventing respiratory acidosis will improve the quality of emergency medical care. PMID:29123744

Oedema disease is associated with metabolic acidosis and small intestinal acidosis

NARCIS (Netherlands)

Nabuurs, M.J.A.; Weijgert, van de E.; Grootendorst, A.F.; Niewold, T.A.

2001-01-01

Limited information is available about the pathogenesis and pathophysiology of oedema disease (OD). Oedema disease is caused by specific enterotoxemic Escherichia coli (SLTIIv-toxin producing) strains; however, the same strains are also found in non-afflicted pigs. Furthermore, it is unclear how the

INDUCED METABOLIC ACIDOSIS BY AMMONIUM CHLORIDE: ACTION MECHANISMS, DOSE AND EFFECTS ON ATHLETIC PERFORMANCE

OpenAIRE

Correia-Oliveira, Carlos Rafaell; Kiss, Maria Augusta Peduti Dal’Molin

2018-01-01

ABSTRACT The relationship between metabolic acidosis and athletic performance has been investigated over the years through manipulation of the blood and muscle pH. Among the pH manipulation manners, the ammonium chloride (NH4Cl) is the most widely used chemical component when is intentioned to induce a blood acidosis status prior to exercise. However, there is a lack of studies investigating the action of this substance on athletic performance as only two studies were performed in the last 15...

Acidosis y coma en el Diabético

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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

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

Science.gov (United States)

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.

Ruminal acidosis: a review with detailed reference to the controlling agent Megasphaera elsdenii NCIMB 41125

OpenAIRE

Meissner, H.H.; Henning, P.H.; Horn, C.H.; Leeuw, K-J.; Hagg, F.M.; Fouché, G.

2010-01-01

Ruminal acidosis is discussed with reference to causes and economic and health implications. Distinction is made between the acute form which with proper adaptation to high energy diets is seldom encountered and the more problematic chronic or sub-acute form, commonly referred to as sub-acute ruminal acidosis (SARA). Apart from stepwise transition from roughage to concentrates, methods adopted to reduce SARA include grain treatment to reduce starch degradation, feed additives such as buffers ...

Diet-Induced Low-Grade Metabolic Acidosis and Clinical Outcomes: A Review

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Renata Alves Carnauba

2017-05-01

Full Text Available Low-grade metabolic acidosis is a condition characterized by a slight decrease in blood pH, within the range considered normal, and feeding is one of the main factors that may influence the occurrence of such a condition. The excessive consumption of acid precursor foods (sources of phosphorus and proteins, to the detriment of those precursors of bases (sources of potassium, calcium, and magnesium, leads to acid-base balance volubility. If this condition occurs in a prolonged, chronic way, low-grade metabolic acidosis can become significant and predispose to metabolic imbalances such as kidney stone formation, increased bone resorption, reduced bone mineral density, and the loss of muscle mass, as well as the increased risk of chronic diseases such as type 2 diabetes mellitus, hypertension, and non-alcoholic hepatic steatosis. Considering the increase in the number of studies investigating the influence of diet-induced metabolic acidosis on clinical outcomes, this review gathers the available evidence evaluating the association of this disturbance and metabolic imbalances, as well as related mechanisms. It is necessary to look at the western dietary pattern of most countries and the increasing incidence of non-comunicable diseases for the balance between fruit and vegetable intake and the appropriate supply of protein, mainly from animal sources, so that it does not exceed the daily recommendations.

Role of hepcidin-ferroportin axis in the pathophysiology, diagnosis, and treatment of anemia of chronic inflammation.

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Langer, Arielle L; Ginzburg, Yelena Z

2017-06-01

Anemia of chronic inflammation (ACI) is a frequently diagnosed anemia and portends an independently increased morbidity and poor outcome associated with multiple underlying diseases. The pathophysiology of ACI is multifactorial, resulting from the effects of inflammatory cytokines which both directly and indirectly suppress erythropoiesis. Recent advances in molecular understanding of iron metabolism provide strong evidence that immune mediators, such as IL-6, lead to hepcidin-induced hypoferremia, iron sequestration, and decreased iron availability for erythropoiesis. The role of hepcidin-ferroportin axis in the pathophysiology of ACI is stimulating the development of new diagnostics and targeted therapies. In this review, we present an overview of and rationale for inflammation-, iron-, and erythropoiesis-related strategies currently in development. © 2017 International Society for Hemodialysis.

Early optimal parenteral nutrition and metabolic acidosis in very preterm infants.

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Francesco Bonsante

Full Text Available It is currently recognized that an optimized nutritional approach, consisting of an early and substantial supply of protein and energy by parenteral route, may be beneficial for very low birth weight infants and recent guidelines endorse this strategy. However, the impact of the enhanced parenteral nutrition (PN on acid-basic balance has never been investigated. The aim of the present study is to assess the effect of nutrient intake on acid-base homeostasis in a large population of preterm infants on PN.This observational study described the acid-base profile of very preterm infants (≤29 week's gestation receiving PN during the first week of life. For this purpose three different cohorts of infants who received increasing (group 1 to group 3 nutritional intakes were considered. Nutrition data were recorded daily and correlated to acid-base data (pH, base excess, and lactate. The outcome measure to assess metabolic acidosis was the base excess (BE.161 infants were included. 1127 daily nutritional records and 795 blood gas data were analyzed. The three groups were different with regard to nutritional intravenous intakes. Group 3 in particular had a higher mean intake of both amino acids (3.3 ± 0.8 g/kg/d and lipids (2.8 ± 1.4 g/kg/d during the first week of life. Metabolic acidosis was more severe in the group with the highest parenteral intake of amino acids and lipids: mean BE = -8.7 ± 3.4 (group 3; -6.4 ± 3.4 (group 2; -5.1 ± 3.0 (group 1]. At the multivariate analysis the significant risk factors for metabolic acidosis were: gestational age, initial base excess, amino acid and lipid intravenous intakes.Acid-base homeostasis was influenced by the nutritional intake. Earlier and higher intravenous amino acid and lipid intakes particularly increased the risk of metabolic acidosis. The nutritional tolerance was different depending on gestational age, and the smaller infants (24-26 week's gestation displayed greater acidotic disequilibrium

Epinephrine-induced lactic acidosis in orthognathic surgery: a report of two cases.

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Son, Hee-Won; Park, Se-Hun; Cho, Hyun-Oh; Shin, Yong-Joon; Son, Jang-Ho

2016-10-01

Submucosal infiltration and the topical application of epinephrine as a vasoconstrictor produce excellent hemostasis during surgery. The hemodynamic effects of epinephrine have been documented in numerous studies. However, its metabolic effects (especially during surgery) have been seldom recognized clinically. We report two cases of significant metabolic effects (including lactic acidosis and hyperglycemia) as well as hemodynamic effects in healthy patients undergoing orthognathic surgery with general anesthesia. Epinephrine can induce glycolysis and pyruvate generation, which result in lactic acidosis, via β2-adrenergic receptors. Therefore, careful perioperative observation for changes in plasma lactate and glucose levels along with intensive monitoring of vital signs should be carried out when epinephrine is excessively used as a vasoconstrictor during surgery.

Grocery store baking soda. A source of sodium bicarbonate in the management of chronic metabolic acidosis.

Science.gov (United States)

Booth, B E; Gates, J; Morris, R C

1984-02-01

Oral sodium bicarbonate is used to treat metabolic acidosis in patients with renal tubular acidosis. Since infants and young children are unable to swallow tablets, those affected must ingest sodium bicarbonate in a powder or liquid form. Pharmacy-weighed sodium bicarbonate is expensive and inconvenient to obtain; some pharmacists are reluctant to provide it. We determined that the sodium bicarbonate contained in 8-oz boxes of Arm and Hammer Baking Soda was sufficiently constant in weight that, dissolved in water to a given volume, it yielded a quantitatively acceptable therapeutic solution of sodium bicarbonate at a cost of approximately 3 percent of that of pharmacy-weighed sodium bicarbonate. Grocery store baking soda can be a safe, economical, and convenient source of sodium bicarbonate for the treatment of chronic metabolic acidosis in infants and young children.

Acidosis slows electrical conduction through the atrio-ventricular node.

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Nisbet, Ashley M; Burton, Francis L; Walker, Nicola L; Craig, Margaret A; Cheng, Hongwei; Hancox, Jules C; Orchard, Clive H; Smith, Godfrey L

2014-01-01

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 ± 7.2 ms (n = 8) at a pacing cycle length (PCL) of 300 ms (37°C). Tact increased at shorter PCL, and the hypercapnic solution prolonged Tact further: at 150 ms PCL, Tact was prolonged from 131.0 ± 5.2 to 174.9 ± 16.3 ms. 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 AVN 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.

Acidosis slows electrical conduction through the atrio-ventricular node

Directory of Open Access Journals (Sweden)

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.

Interarterial course of anomalous right coronary artery: Pathophysiology, diagnosis, and treatment

Directory of Open Access Journals (Sweden)

George Renchao Wu, BS

2017-12-01

A timely diagnosis of an anomalous coronary artery is critical in symptomatic patients because of the risk of sudden cardiac death, especially in patients with arteries with an interarterial course. This case demonstrates the importance of making the correct diagnosis, as appropriate surgical management can drastically improve outcomes.

Changes in Whole-Body Oxygen Consumption and Skeletal Muscle Mitochondria During Linezolid-Induced Lactic Acidosis.

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Protti, Alessandro; Ronchi, Dario; Bassi, Gabriele; Fortunato, Francesco; Bordoni, Andreina; Rizzuti, Tommaso; Fumagalli, Roberto

2016-07-01

To better clarify the pathogenesis of linezolid-induced lactic acidosis. Case report. ICU. A 64-year-old man who died with linezolid-induced lactic acidosis. Skeletal muscle was sampled at autopsy to study mitochondrial function. Lactic acidosis developed during continuous infusion of linezolid while oxygen consumption and oxygen extraction were diminishing from 172 to 52 mL/min/m and from 0.27 to 0.10, respectively. Activities of skeletal muscle respiratory chain complexes I, III, and IV, encoded by nuclear and mitochondrial DNA, were abnormally low, whereas activity of complex II, entirely encoded by nuclear DNA, was not. Protein studies confirmed stoichiometric imbalance between mitochondrial (cytochrome c oxidase subunits 1 and 2) and nuclear (succinate dehydrogenase A) DNA-encoded respiratory chain subunits. These findings were not explained by defects in mitochondrial DNA or transcription. There were no compensatory mitochondrial biogenesis (no induction of nuclear respiratory factor 1 and mitochondrial transcript factor A) or adaptive unfolded protein response (reduced concentration of heat shock proteins 60 and 70). Linezolid-induced lactic acidosis is associated with diminished global oxygen consumption and extraction. These changes reflect selective inhibition of mitochondrial protein synthesis (probably translation) with secondary mitonuclear imbalance. One novel aspect of linezolid toxicity that needs to be confirmed is blunting of reactive mitochondrial biogenesis and unfolded protein response.

Carbonic anhydrase IX inhibition affects viability of cancer cells adapted to extracellular acidosis.

Science.gov (United States)

Andreucci, Elena; Peppicelli, Silvia; Carta, Fabrizio; Brisotto, Giulia; Biscontin, Eva; Ruzzolini, Jessica; Bianchini, Francesca; Biagioni, Alessio; Supuran, Claudiu T; Calorini, Lido

2017-12-01

Among the players of the adaptive response of cancer cells able to promote a resistant and aggressive phenotype, carbonic anhydrase IX (CAIX) recently has emerged as one of the most relevant drug targets. Indeed, CAIX targeting has received a lot of interest, and selective inhibitors are currently under clinical trials. Hypoxia has been identified as the master inductor of CAIX, but, to date, very few is known about the influence that another important characteristic of tumor microenvironment, i.e., extracellular acidosis, exerts on CAIX expression and activity. In the last decades, acidic microenvironment has been associated with aggressive tumor phenotype endowed with epithelial-to-mesenchymal transition (EMT) profile, high invasive and migratory ability, apoptosis, and drug resistance. We demonstrated that melanoma, breast, and colorectal cancer cells transiently and chronically exposed to acidified medium (pH 6.7 ± 0.1) showed a significantly increased CAIX expression compared to those grown in standard conditions (pH 7.4 ± 0.1). Moreover, we observed that the CAIX inhibitor FC16-670A (also named SLC-0111, which just successfully ended phase I clinical trials) not only prevents such increased expression under acidosis but also promotes apoptotic and necrotic programs only in acidified cancer cells. Thus, CAIX could represent a selective target of acidic cancer cells and FC16-670A inhibitor as a useful tool to affect this aggressive subpopulation characterized by conventional therapy escape. Cancer cells overexpress CAIX under transient and chronic extracellular acidosis. Acidosis-induced CAIX overexpression is NF-κB mediated and HIF-1α independent. FC16-670A prevents CAIX overexpression and induces acidified cancer cell death.

[Dysphagia in Parkinson's Disease: Pathophysiology, Diagnosis and Therapy].

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Suttrup, I; Warnecke, T

2016-07-01

Oropharyngeal and esophageal dysphagia are a frequent, but seldom diagnosed symptom of Parkinson's disease (PD). More than 80 % of patients with PD develop dysphagia during the course of their disease leading to a reduced quality of life, complicated medication intake, malnutrition and aspiration pneumonia, which is a major cause of death in PD. The underlying pathophysiology is poorly understood. Impaired dopaminergic and non-dopaminergic mechanisms of the cortical swallowing network as well as peripheral neuromuscular involvement have been suggested to contribute to its multifactorial genesis. Diagnostic screening methods include PD-specific questionnaires and a modified water test. Fiber optic endoscopic evaluation of swallowing (FEES) and videofluoroscopic swallowing study (VFSS), which complement each other, are the gold standard for evaluation of PD-related dysphagia. For evaluation of esophageal dysphagia, the high-resolution manometry (HRM) may be a helpful tool. In addition to dysphagia-specific treatment by speech and language therapists (SLTs), optimized dopaminergic medication is a meaningful therapeutic option. A promising novel method is intensive training of expiratory muscle strength (EMST). Deep brain stimulation does not seem to have a clinically relevant effect on swallowing function in PD. © Georg Thieme Verlag KG Stuttgart · New York.

Left main coronary artery disease: pathophysiology, diagnosis, and treatment.

Science.gov (United States)

Collet, Carlos; Capodanno, Davide; Onuma, Yoshinobu; Banning, Adrian; Stone, Gregg W; Taggart, David P; Sabik, Joseph; Serruys, Patrick W

2018-06-01

The advent of coronary angiography in the 1960s allowed for the risk stratification of patients with stable angina. Patients with unprotected left main coronary artery disease have an increased risk of death related to the large amount of myocardium supplied by this vessel. Although coronary angiography remains the preferred imaging modality for the evaluation of left main coronary artery stenosis, this technique has important limitations. Angiograms of the left main coronary artery segment can be difficult to interpret, and almost one-third of patients can be misclassified when fractional flow reserve is used as the reference. In patients with clinically significant unprotected left main coronary artery disease, surgical revascularization was shown to improve survival compared with medical therapy and has been regarded as the treatment of choice for unprotected left main coronary artery disease. Two large-scale clinical trials published in 2016 support the usefulness of catheter-based revascularization in selected patients with unprotected left main coronary artery disease. In this Review, we describe the pathophysiology of unprotected left main coronary artery disease, discuss diagnostic approaches in light of new noninvasive and invasive imaging techniques, and detail risk stratification models to aid the Heart Team in the decision-making process for determining the best revascularization strategy for these patients.

Lipid myopathy associated with renal tubular acidosis and spastic diplegia in two brothers.

Science.gov (United States)

Tung, Y C; Tsau, Y K; Chu, L W; Young, C; Shen, Y Z

2001-07-01

Lipid myopathy is a group of disorders involving mitochondrial fatty acid oxidation. We describe two brothers, 3 years 8 months old and 2 years 9 months old, respectively, with progressive spastic diplegia, developmental delay, failure to thrive, and chronic metabolic acidosis who had lipid myopathy and renal tubular acidosis. Brain magnetic resonance imaging revealed demyelinating changes in the periventricular white matter, which was compatible with spastic diplegia. These symptoms may be related to errors in fatty acid metabolism. Cerebral palsy had been misdiagnosed in both of these patients at another hospital. Therefore, for patients with late-onset and progressive spastic diplegia, detailed investigations for underlying diseases are warranted.

Common, yet elusive: a case of severe anion gap acidosis.

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Agrawal, Akanksha; Kishlyansky, Marina; Biso, Sylvia; Patnaik, Soumya; Punjabi, Chitra

2017-09-01

Acid-base disturbances are common occurrence in hospitalized patients with life threatening complications. 5-oxoproline has been increasingly recognized as cause of high anion gap metabolic acidosis (AGMA) in association with chronic acetaminophen use. However, laboratory workup for it are not widely available. We report case of 56-year-old female with severe AGMA not attributable to ketoacidosis, lactic acidosis or toxic ingestion. History was significant for chronic acetaminophen use, and laboratory workup negative for all frequent causes of AGMA. Given history and clinical presentation, our suspicion for 5-oxoproline toxicity was high. Our patient required emergent hemodialysis and subsequently improved clinically. With an increasing awareness of the uncommon causes of high AGMA, tests should be more readily available to detect their presence. Physicians should be more vigilant of underdiagnosed causes of AGMA if the presentation and laboratory values do not reflect a common cause, as definitive treatment may vary based on the offending agent.

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

Science.gov (United States)

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.

Ruminal Acidosis in Feedlot: From Aetiology to Prevention

OpenAIRE

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 ...

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

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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.

Effects of induced subacute ruminal acidosis on milk fat content and milk fatty acid profile.

Science.gov (United States)

Enjalbert, F; Videau, Y; Nicot, M C; Troegeler-Meynadier, A

2008-06-01

Two lactating dairy cows fitted with a rumen cannula received successively diets containing 0%, 20%, 34% and again 0% of wheat on a dry matter basis. After 5, 10 and 11 days, ruminal pH was measured between 8:00 and 16:00 hours, and milk was analysed for fat content and fatty acid profile. Diets with 20% and 34% wheat induced a marginal and a severe subacute ruminal acidosis respectively. After 11 days, diets with wheat strongly reduced the milk yield and milk fat content, increased the proportions of C8:0 to C13:0 even- or odd-chain fatty acids, C18:2 n-6 and C18:3 n-3 fatty acids but decreased the proportions of C18:0 and cis-9 C18:1 fatty acids. Wheat also increased the proportions of trans-5 to trans-10 C18:1, the latter exhibiting a 10-fold increase with 34% of wheat compared with value during the initial 0% wheat period. There was also an increase of trans-10, cis-12 C18:2 fatty acid and a decrease of trans-11 to trans-16 C18:1 fatty acids. The evolution during adaptation or after return to a 0% wheat diet was rapid for pH but much slower for the fatty acid profile. The mean ruminal pH was closely related to milk fat content, the proportion of odd-chain fatty acids (linear relationship) and the ratio of trans-10 C18:1/trans-11 C18:1 (nonlinear relationship). Such changes in fatty acid profile suggested a possible use for non-invasive diagnosis of subacute ruminal acidosis.

Renal tubular acidosis secondary to jejunoileal bypass for morbid obesity

DEFF Research Database (Denmark)

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...

MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, Stroke) – a Diagnosis Not to be Missed

LENUS (Irish Health Repository)

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.

Mitochondrial Encephalomyopathy With Lactic Acidosis and Stroke-Like Episodes—MELAS Syndrome

Science.gov (United States)

Henry, Caitlin; Patel, Neema; Shaffer, William; Murphy, Lillian; Park, Joe

2017-01-01

Background: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) syndrome is a rare inherited disorder that results in waxing and waning nervous system and muscle dysfunction. MELAS syndrome may overlap with other neurologic disorders but shows distinctive imaging features. Case Report: We present the case of a 28-year-old female with atypical stroke-like symptoms, a strong family history of stroke-like symptoms, and a relapsing-remitting course for several years. We discuss the imaging features distinctive to the case, the mechanism of the disease, typical presentation, imaging diagnosis, and disease management. Conclusion: This case is a classic example of the relapse-remitting MELAS syndrome progression with episodic clinical flares and fluctuating patterns of stroke-like lesions on imaging. MELAS is an important diagnostic consideration when neuroimaging reveals a pattern of disappearing and relapsing cortical brain lesions that may occur in different areas of the brain and are not necessarily limited to discrete vascular territories. Future studies should investigate disease mechanisms at the cellular level and the value of advanced magnetic resonance imaging techniques for a targeted approach to therapy. PMID:29026367

Ruminal Acidosis in Feedlot: From Aetiology to Prevention

Directory of Open Access Journals (Sweden)

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.

Ruminal acidosis in feedlot: from aetiology to prevention.

Science.gov (United States)

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.

Prevalence and magnitude of acidosis sequelae to rice-based feeding regimen followed in Tamil Nadu, India.

Science.gov (United States)

Murugeswari, Rathinam; Valli, Chinnamani; Karunakaran, Raman; Leela, Venkatasubramanian; Pandian, Amaresan Serma Saravana

2018-04-01

In Tamil Nadu, a southern state of India, rice is readily available at a low cost, hence, is cooked (cooking akin to human consumption) and fed irrationally to cross-bred dairy cattle with poor productivity. Hence, a study was carried out with the objective to examine the prevalence of acidosis sequelae to rice-based feeding regimen and assess its magnitude. A survey was conducted in all the 32 districts of Tamil Nadu, by randomly selecting two blocks per districts and from each block five villages were randomly selected. From each of the selected village, 10 dairy farmers belonging to the unorganized sector, owning one or two cross-bred dairy cows in early and mid-lactation were randomly selected so that a sample size of 100 farmers per district was maintained. The feeding regimen, milk yield was recorded, and occurrence of acidosis and incidence of laminitis were ascertained by the veterinarian with the confirmative test to determine the impact of feeding cooked rice to cows. It is observed that 71.5% of farmers in unorganized sector feed cooked rice to their cattle. The incidence of acidosis progressively increased significantly (p<0.05) from 29.00% in cows fed with 0.5 kg of cooked rice to 69.23% in cows fed with more than 2.5 kg of cooked rice. However, the incidence of acidosis remained significantly (p<0.05) as low as 9.9% in cows fed feeding regimen without cooked rice which is suggestive of a correlation between excessive feeding cooked rice and onset of acidosis. Further, the noticeable difference in the incidence of acidosis observed between feeding cooked rice and those fed without rice and limited intake of oil cake indicates that there is a mismatch between energy and protein supply to these cattle. Among cooked rice-based diet, the incidence of laminitis increased progressively (p<0.05) from 9.2% to 37.9% with the increase in the quantum of cooked rice in the diet. The study points out the importance of protein supplementation in rice-based feeding

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

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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.

Serum proteinogram in sheep with acute ruminal lactic acidosis

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Amanda F. Sabes

2017-06-01

Full Text Available The electrophoretic fractionation represents one of the most reliable methods for the identification of blood proteins in ruminants. The aim of this study was to evaluate the serum proteinogram of sheep with acute ruminal lactic acidosis (ARA using the SDS-PAGE electrophoresis technique. Ten Santa Inês ewes were used and blood was collected to establish the basal values for induction of ARA. Sucrose was administered orally in a single dose of 15 g/kg body mass. After the administration, blood samples were obtained at the following moments: 4, 8, 12, 16, 20, 24, 28, 32, 36, 48, 72, 96, 120 and 144 h. Subsequently, samples were obtained every seven days for three further weeks, until complete one month. The total of 13 proteins were identified: immunoglobulins A and G, ceruloplasmin, transferrin, albumin, α1-antitrypsin, haptoglobin, α1-acid glycoprotein, proteins of molecular weight 95, 46, 36 and 31 kDa. The increase of haptoglobin from 08 h coincides with the ruminal pH decrease, possibly due to the death of Gram negative bacteria and also the inflammatory process on the rumen. Fibrinogen was presented on highest mean at 48 h and returned to normal with 144 h. We can conclude that changes in serum levels of acute phase proteins can assist the clinical evaluation and diagnosis of ARA in sheep.

A Clinical Approach to the Diagnosis of Acid-Base Disorders

OpenAIRE

Bear, Robert A.

1986-01-01

The ability to diagnose and manage acid-base disorders rapidly and effectively is essential to the care of critically ill patients. This article presents an approach to the diagnosis of pure and mixed acid-base disorders, metabolic or respiratory. The approach taken is based on using the law of mass-action equation as it applies to the bicarbonate buffer system (Henderson equation), using sub-classifications for diagnostic purposes of causes of metabolic acidosis and metabolic alkalosis, and ...

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

Science.gov (United States)

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

2016-01-01

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. PMID:27009341

X-ray criteria of the differential diagnosis of hereditary tubulopathies in children

International Nuclear Information System (INIS)

Bosin, V.Yu.; Kondrina, V.V.; Mulyk, T.E.; Verbitskaya, A.I.

1995-01-01

In search for x-ray signs of skeletal involvement specific for each type of hereditary tubulopathies Vitamin D-resistant rickets, Renal tubular acidosis, Toni-Debre-Fanconi disease, the authors analyze the results of clinical and X-ray examinations of 144 children aged 2 to 16. Study demonstrated the possibility and high reliability of X-ray differential diagnosis of various forms of hereditary tubulopathies in children. 5 refs., 8 figs., 2 tabs

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

Directory of Open Access Journals (Sweden)

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.

An unusual cause of high anion gap metabolic acidosis: pyroglutamic acidemia. A case report.

Science.gov (United States)

Romero, Jorge E; Htyte, Nay

2013-01-01

Pyroglutamic acidemia is an uncommon metabolic disorder, which is usually diagnosed at early ages. The mechanism of action is thought to be glutathione depletion, and its clinical manifestations consist of hemolytic anemia, mental retardation, ataxia, and chronic metabolic acidosis. However, an acquired form has been described in adult patients, who usually present with confusion, respiratory distress, and high anion gap metabolic acidosis (HAGMA). It is also associated with many conditions, including chronic acetaminophen consumption. A 68-year-old white male, with chronic acetaminophen use presented to our service on multiple occasions with severe HAGMA. The patient was admitted to the intensive care unit and required mechanical ventilation and aggressive supportive measures. After ruling out the most frequent etiologies for his acid-base disorder and considering the long history of Tylenol ingestion, his 5-oxiproline (pyroglutamic acid) levels were sent to diagnose pyroglutamic acidemia. Clinicians need to be aware of this cause for metabolic acidosis since it might be a more common metabolic disturbance in compromised patients than would be expected. Subjects with HAGMA that cannot be explained by common causes should be tested for the presence of 5-oxoproline. Discontinuation of the offending drug is therapeutic.

Diagnosing the pathophysiologic mechanisms of nocturnal polyuria.

Science.gov (United States)

Goessaert, An-Sofie; Krott, Louise; Hoebeke, Piet; Vande Walle, Johan; Everaert, Karel

2015-02-01

Diagnosis of nocturnal polyuria (NP) is based on a bladder diary. Addition of a renal function profile (RFP) for analysis of concentrating and solute-conserving capacity allows differentiation of NP pathophysiology and could facilitate individualized treatment. To map circadian rhythms of water and solute diuresis by comparing participants with and without NP. This prospective observational study was carried out in Ghent University Hospital between 2011 and 2013. Participants with and without NP completed a 72-h bladder dairy. RFP, free water clearance (FWC), and creatinine, solute, sodium, and urea clearance were measured for all participants. The study participants were divided into those with (n=77) and those without (n=35) NP. The mean age was 57 yr (SD 16 yr) and 41% of the participants were female. Compared to participants without NP, the NP group exhibited a higher diuresis rate throughout the night (p=0.015); higher FWC (p=0.013) and lower osmolality (p=0.030) at the start of the night; and persistently higher sodium clearance during the night (p<0.001). The pathophysiologic mechanism of NP was identified as water diuresis alone in 22%, sodium diuresis alone in 19%, and a combination of water and sodium diuresis in 47% of the NP group. RFP measurement in first-line NP screening to discriminate between water and solute diuresis as pathophysiologic mechanisms complements the bladder diary and could facilitate optimal individualized treatment of patients with NP. We evaluated eight urine samples collected over 24h to detect the underlying problem in NP. We found that NP can be attributed to water or sodium diuresis or a combination of both. This urinalysis can be used to adapt treatment according to the underlying mechanism in patients with bothersome consequences of NP, such as nocturia and urinary incontinence. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Severe hypophosphataemia during recovery from acute respiratory acidosis.

OpenAIRE

Storm, T L

1984-01-01

Three elderly patients with established chronic obstructive airways disease were admitted with a short history of increasing dyspnoea and tiredness and (in two cases) a deterioration in mental state. Acute respiratory acidosis was diagnosed and mechanical ventilation instituted. Two hours after beginning mechanical ventilation the mean arterial pH had risen to 7.40, but all patients showed a dramatic fall in the serum phosphate concentration (lowest value 0.3 mmol/l (0.9 mg/100 ml] accompanie...

Extracellular acidosis and very low [Na+ ] inhibit NBCn1- and NHE1-mediated net acid extrusion from mouse vascular smooth muscle cells.

Science.gov (United States)

Bonde, L; Boedtkjer, E

2017-10-01

The electroneutral Na + , HCO3- cotransporter NBCn1 and Na + /H + exchanger NHE1 regulate acid-base balance in vascular smooth muscle cells (VSMCs) and modify artery function and structure. Pathological conditions - notably ischaemia - can dramatically perturb intracellular (i) and extracellular (o) pH and [Na + ]. We examined effects of low [Na + ] o and pH o on NBCn1 and NHE1 activity in VSMCs of small arteries. We measured pH i by 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein-based fluorescence microscopy of mouse mesenteric arteries and induced intracellular acidification by NH4+ prepulse technique. NBCn1 activity - defined as Na + -dependent, amiloride-insensitive net base uptake with CO 2 /HCO3- present - was inhibited equally when pH o decreased from 7.4 (22 mm HCO3-/5% CO 2 ) by metabolic (pH o 7.1/11 mm HCO3-: 22 ± 8%; pH o 6.8/5.5 mm HCO3-: 61 ± 7%) or respiratory (pH o 7.1/10% CO 2 : 35 ± 11%; pH o 6.8/20% CO 2 : 56 ± 7%) acidosis. Extracellular acidosis more prominently inhibited NHE1 activity - defined as Na + -dependent net acid extrusion without CO 2 /HCO3- present - at both pH o 7.1 (45 ± 9%) and 6.8 (85 ± 5%). Independently of pH o , lowering [Na + ] o from 140 to 70 mm reduced NBCn1 and NHE1 activity respiratory (ΔpH i /ΔpH o  = 71 ± 4%) than metabolic (ΔpH i /ΔpH o  = 30 ± 7%) acidosis. Extracellular acidification inhibits NBCn1 and NHE1 activity in VSMCs. NBCn1 is equivalently inhibited when pCO 2 is raised or [HCO3-] o decreased. Lowering [Na + ] o inhibits NBCn1 and NHE1 markedly only below the typical physiological and pathophysiological range. We propose that inhibition of Na + -dependent net acid extrusion at low pH o protects against cellular Na + overload at the cost of intracellular acidification. © 2017 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Effects of intravenous hyperosmotic sodium bicarbonate on arterial and cerebrospinal fluid acid-base status and cardiovascular function in calves with experimentally induced respiratory and strong ion acidosis.

Science.gov (United States)

Berchtold, Joachim F; Constable, Peter D; Smith, Geoffrey W; Mathur, Sheerin M; Morin, Dawn E; Tranquilli, William J

2005-01-01

The objectives of this study were to determine the effects of hyperosmotic sodium bicarbonate (HSB) administration on arterial and cerebrospinal fluid (CSF) acid-base balance and cardiovascular function in calves with experimentally induced respiratory and strong ion (metabolic) acidosis. Ten healthy male Holstein calves (30-47 kg body weight) were instrumented under halothane anesthesia to permit cardiovascular monitoring and collection of blood samples and CSE Respiratory acidosis was induced by allowing the calves to spontaneously ventilate, and strong ion acidosis was subsequently induced by i.v. administration of L-lactic acid. Calves were then randomly assigned to receive either HSB (8.4% NaHCO3; 5 ml/kg over 5 minutes, i.v.; n=5) or no treatment (controls, n=5) and monitored for 1 hour. Mixed respiratory and strong ion acidosis was accompanied by increased heart rate, cardiac index, mean arterial pressure, cardiac contractility (maximal rate of change of left ventricular pressure), and mean pulmonary artery pressure. Rapid administration of HSB immediately corrected the strong ion acidosis, transiently increased arterial partial pressure of carbon dioxide (P(CO2)), and expanded the plasma volume. The transient increase in arterial P(CO2) did not alter CSF P(CO2) or induce paradoxical CSF acidosis. Compared to untreated control calves, HSB-treated calves had higher cardiac index and contractility and a faster rate of left ventricular relaxation for 1 hour after treatment, indicating that HSB administration improved myocardial systolic function. We conclude that rapid i.v. administration of HSB provided an effective and safe method for treating strong ion acidosis in normovolemic halothane-anesthetized calves with experimentally induced respiratory and strong ion acidosis. Fear of inducing paradoxical CSF acidosis is not a valid reason for withholding HSB administration in calves with mixed respiratory and strong ion acidosis.

Severity of acidosis affects long-term survival in COPD patients with hypoxemia after intensive care unit discharge.

Science.gov (United States)

Gungor, Sinem; Kargin, Feyza; Irmak, Ilim; Ciyiltepe, Fulya; Acartürk Tunçay, Eylem; Atagun Guney, Pinar; Aksoy, Emine; Ocakli, Birsen; Adiguzel, Nalan; Karakurt, Zuhal

2018-01-01

Patients admitted to the intensive care unit (ICU) with acute respiratory failure (ARF) due to COPD have high mortality and morbidity. Acidosis has several harmful effects on hemodynamics and metabolism, and the current knowledge regarding the relationship between respiratory acidosis severity on the short- and long-term survival of COPD patients is limited. We hypothesized that COPD patients with severe acidosis would have a poorer short- and long-term prognosis compared with COPD patients with mild-to-moderate acidosis. This retrospective observational cohort study was conducted in a level III respiratory ICU of a tertiary teaching hospital for chest diseases between December 1, 2013, and December 30, 2014. Subject characteristics, comorbidities, ICU parameters, duration of mechanical ventilation, length of ICU stay, ICU mortality, use of domiciliary noninvasive mechanical ventilation (NIMV) and long-term oxygen therapy (LTOT), and short- and long-term mortality were recorded. Patients were grouped according to their arterial blood gas (ABG) values during ICU admission: severe acidotic (pH≤7.20) and mild-to-moderate acidotic (pH 7.21-7.35). These groups were compared with the recorded data. The mortality predictors were analyzed by logistic regression test in the ICU and the Cox regression test for long-term mortality predictors. During the study period, a total of 312 COPD patients admitted to the ICU with ARF, 69 (72.5% male) in the severe acidosis group and 243 (79% male) in the mild-to-moderate acidosis group, were enrolled. Group demographics, comorbidities, duration of mechanical ventilation, and length of ICU stay were similar in the two groups. The severe acidosis group had a significantly higher rate of NIMV failure (60.7% vs 40%) in the ICU. Mild-to-moderate acidotic COPD patients using LTOT had longer survival after ICU discharge than those without LTOT. On the other hand, severely acidotic COPD patients without LTOT showed shorter survival than

An acidosis-sparing ketogenic (ASK) diet to improve efficacy and reduce adverse effects in the treatment of refractory epilepsy.

Science.gov (United States)

Yuen, Alan W C; Walcutt, Isabel A; Sander, Josemir W

2017-09-01

Diets that increase production of ketone bodies to provide alternative fuel for the brain are evolving from the classic ketogenic diet for epilepsy devised nearly a century ago. The classic ketogenic diet and its more recent variants all appear to have similar efficacy with approximately 50% of users showing a greater than 50% seizure reduction. They all require significant medical and dietetic support, and there are tolerability issues. A review suggests that low-grade chronic metabolic acidosis associated with ketosis is likely to be an important contributor to the short term and long term adverse effects of ketogenic diets. Recent studies, particularly with the characterization of the acid sensing ion channels, suggest that chronic metabolic acidosis may increase the propensity for seizures. It is also known that low-grade chronic metabolic acidosis has a broad range of negative health effects and an increased risk of early mortality in the general population. The modified ketogenic dietary treatment we propose is formulated to limit acidosis by measures that include monitoring protein intake and maximizing consumption of alkaline mineral-rich, low carbohydrate green vegetables. We hypothesize that this acidosis-sparing ketogenic diet is expected to be associated with less adverse effects and improved efficacy. A case history of life-long intractable epilepsy shows this diet to be a successful long-term strategy but, clearly, clinical studies are needed. Copyright © 2017 Elsevier Inc. All rights reserved.

Prevalence and magnitude of acidosis sequelae to rice-based feeding regimen followed in Tamil Nadu, India

Directory of Open Access Journals (Sweden)

Rathinam Murugeswari

2018-04-01

Full Text Available Background and Aim: In Tamil Nadu, a southern state of India, rice is readily available at a low cost, hence, is cooked (cooking akin to human consumption and fed irrationally to cross-bred dairy cattle with poor productivity. Hence, a study was carried out with the objective to examine the prevalence of acidosis sequelae to rice-based feeding regimen and assess its magnitude. Materials and Methods: A survey was conducted in all the 32 districts of Tamil Nadu, by randomly selecting two blocks per districts and from each block five villages were randomly selected. From each of the selected village, 10 dairy farmers belonging to the unorganized sector, owning one or two cross-bred dairy cows in early and mid-lactation were randomly selected so that a sample size of 100 farmers per district was maintained. The feeding regimen, milk yield was recorded, and occurrence of acidosis and incidence of laminitis were ascertained by the veterinarian with the confirmative test to determine the impact of feeding cooked rice to cows. Results: It is observed that 71.5% of farmers in unorganized sector feed cooked rice to their cattle. The incidence of acidosis progressively increased significantly (p<0.05 from 29.00% in cows fed with 0.5 kg of cooked rice to 69.23% in cows fed with more than 2.5 kg of cooked rice. However, the incidence of acidosis remained significantly (p<0.05 as low as 9.9% in cows fed feeding regimen without cooked rice which is suggestive of a correlation between excessive feeding cooked rice and onset of acidosis. Further, the noticeable difference in the incidence of acidosis observed between feeding cooked rice and those fed without rice and limited intake of oil cake indicates that there is a mismatch between energy and protein supply to these cattle. Among cooked rice-based diet, the incidence of laminitis increased progressively (p<0.05 from 9.2% to 37.9% with the increase in the quantum of cooked rice in the diet. Conclusion: The

Autoimmune hepatitis : Pathogenesis, diagnosis and treatment

NARCIS (Netherlands)

van den Berg, AP

Background: Autoimmune hepatitis (AIH) is a chronic necro-inflammatory disease of the liver. Early recognition is important in order to prevent the development of cirrosis. This review discusses recent developments in the fields of diagnosis, pathophysiology and management of AIH. Methods: Relevant

Hypercapnic respiratory acidosis: a protective or harmful strategy for critically ill newborn foals?

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Vengust, Modest

2012-10-01

This paper reviews both the beneficial and adverse effects of permissive hypercapnic respiratory acidosis in critically ill newborn foals. It has been shown that partial carbon dioxide pressure (PCO2) above the traditional safe range (hypercapnia), has beneficial effects on the physiology of the respiratory, cardiovascular, and nervous system in neonates. In human neonatal critical care medicine permissive hypercapnic acidosis is generally well-tolerated by patients and is more beneficial to their wellbeing than normal carbon dioxide (CO2) pressure or normocapnia. Even though adverse effects of hypercapnia have been reported, especially in patients with central nervous system pathology and/or chronic infection, critical care clinicians often artificially increase PCO2 to take advantage of its positive effects on compromised neonate tissues. This is referred to as therapeutic hypercapnia. Hypercapnic respiratory acidosis is common in critically ill newborn foals and has traditionally been considered as not beneficial. A search of online scientific databases was conducted to survey the literature on the effects of hypercapnia in neonates, with emphasis on newborn foals. The dynamic status of safety levels of PCO2 and data on the effectiveness of different carbon dioxide levels are not available for newborn foals and should be scientifically determined. Presently, permissive hypercapnia should be implemented or tolerated cautiously in compromised newborn foals and its use should be based on relevant data from adult horses and other species.

Preeclampsia: from Pathophysiology to Treatment

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Kaculini Enton

2016-12-01

Full Text Available Preeclampsia is a multisystem disorder unique to human pregnancy and is its most common glomerular complication. It occurs in 2% to 8% of pregnancies and is a major contributor to maternal mortality worldwide. Although the pathophysiology of this syndrome is not fully understood, many pathogenetic mechanisms are involved in this disorder. The role of the placenta is crucial in the development of this disorder. Some pathogenetic mechanisms involved in this disease comprise defective deep placentation, autoantibodies to type-1 angiotensin II receptor, endothelial dysfunction, oxidative stress, platelet and thrombin activation, intravascular inflammation, and the imbalance between angiogenic and antiangiogenic factors which is thought to be one of the most crucial mechanisms. Further understanding of the full picture could enhance our current knowledge of the pathogenesis of preeclampsia and improve its treatment. Thus, based on specific biomarkers the diagnosis and subclassification of preeclampsia might be more accurate in identifying patients at risk, monitoring disease progression and providing effective interventions

Sodium bicarbonate on severe metabolic acidosis during prolonged cardiopulmonary resuscitation: a double-blind, randomized, placebo-controlled pilot study.

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Ahn, Shin; Kim, Youn-Jung; Sohn, Chang Hwan; Seo, Dong Woo; Lim, Kyoung Soo; Donnino, Michael W; Kim, Won Young

2018-04-01

Sodium bicarbonate administration during cardiopulmonary resuscitation (CPR) is controversial. Current guidelines recommend sodium bicarbonate injection in patients with existing metabolic acidosis, but clinical trials, particularly, those involving patients with acidosis, are limited. We aimed to evaluate the efficacy of sodium bicarbonate administration in out-of-hospital cardiac arrest (OHCA) patients with severe metabolic acidosis during prolonged CPR. Prospective, double-blind, randomized placebo-controlled pilot trial was conducted between January 2015 and December 2015, at a single center emergency department (ED). After 10 minutes of CPR, patients who failed to achieve return of spontaneous circulation (ROSC) and with severe metabolic acidosis (pH<7.1 or bicarbonate <10 mEq/L) were enrolled. Sodium bicarbonate (n=25) or normal saline (n=25) were administered. The primary end point was sustained ROSC. The secondary end points were the change of acidosis and good neurologic survival. Sodium bicarbonate group had significant effect on pH (6.99 vs. 6.90, P=0.038) and bicarbonate levels (21.0 vs. 8.0 mEq/L, P=0.007). However, no significant differences showed between sodium bicarbonate and placebo groups in sustained ROSC (4.0% vs. 16.0%, P=0.349) or good neurologic survival at 1 month (0.0% vs. 4.0%, P=1.000). The use of sodium bicarbonate improved acid-base status, but did not improve the rate of ROSC and good neurologic survival. We could not draw a conclusion, but our pilot data could be used to design a larger trial to verify the efficacy of sodium bicarbonate. NCT02303548 (http://www.ClinicalTrials.gov).

Hypoglycemia and severe lactic acidosis in a dog following metformin exposure

OpenAIRE

Barrella, Nicole; Eisenberg, Beth; Simpson, Stephanie Nicole

2017-01-01

Key Clinical Message Hypoglycemia and lactic acidosis are rare complications with metformin use in humans. As metformin is not commonly used in veterinary medicine, severe adverse effects secondary to exposure are not known. Awareness of potentially life‐threatening complications with metformin exposure is an important addition to the veterinary literature.

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

DEFF Research Database (Denmark)

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 serum...... parathyroid hormone. As we found RTA in 9% (95% confidence limits 2-21%) of our patients, screening for acidosis is recommended in obesity patients after malabsorptive operations. RTA can be verified through an ammonium loading test. Before deciding on re-establishing bowel continuity due to RTA, we suggest...... and vitamin D supplementation. If RTA can be abolished through correction of calcium homeostasis, reoperation may be avoided. Before deciding on re-establishing bowel continuity in JIB patients with RTA, we therefore suggest that patients be evaluated for secondary hyperparathyroidism and any calcium...

[Irritable bowel syndrome: New pathophysiological hypotheses and practical issues].

Science.gov (United States)

Duboc, H; Dior, M; Coffin, B

2016-08-01

In 2015, besides the fact that it still fills the gastroenterologists' offices and impairs patient's quality of life, the irritable bowel syndrome has considerably evolved on several points. The pathophysiology is now organized around a consensual hypothesis called the "brain-gut axis", which gather all the influences of peripheral factors as gut microbiota or local serotonin secretion, on the central pain perception, contributing to visceral hypersensitivity and transit modifications. About the diagnosis, the key message is "avoid over-prescription" of additional tests, and reminds that a positive clinical diagnosis based on Rome III criteria is possible after the elimination of simple clinical warning signs. Finally, the food component, a neglected and historical claim of patients, finally finds a strong scientific rational, with a diet low in fermentable sugar and polyols, that gives positive and reproducible results. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Metformin-associated lactic acidosis in a peritoneal dialysis patient

OpenAIRE

Najlaa Almaleki; Mohammad Ashraf; Majdi M Hussein; Syed A Mohiuddin

2015-01-01

Metformin is one of the commonly used drugs in type-2 diabetes mellitus. It reduces glucose levels by increasing insulin sensitivity, reducing hepatic glucose release and increasing muscle uptake. One of the serious complications associated with metformin use is lactic acidosis, and it is associated with high morbidity and mortality. This is more likely to happen in patients with renal failure due to reduced clearance. International guidelines recommend discontinuing metformin in advanced ren...

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

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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.

Rhabdomyolysis: Pathogenesis, Diagnosis, and Treatment

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Torres, Patrick A.; Helmstetter, John A.; Kaye, Adam M.; Kaye, Alan David

2015-01-01

Background Rhabdomyolysis is a complex medical condition involving the rapid dissolution of damaged or injured skeletal muscle. Methods This review focuses on the epidemiology, pathophysiology, causes, presentation, diagnosis, complications, management, and anesthetic considerations related to rhabdomyolysis. Results Any form of muscle damage––and by extension any entity that causes muscle damage––can initiate rhabdomyolysis. One of the most important treatment goals when rhabdomyolysis is suspected is avoiding acute kidney injury. Conclusion All clinicians should be aware of common causes, diagnosis, and treatment options. PMID:25829882

Early diagnosis of Alzheimer's disease. Clinical significance and future perspectives

International Nuclear Information System (INIS)

Buerger, K.; Teipel, S.J.; Hampel, H.

2000-01-01

Early diagnosis of Alzheimer's disease describes the recognition and diagnosis in patients with very mild dementia. Internationally accepted diagnostic criteria support the diagnosis based on clinical evaluation. Recent advances in structural and functional neuroimaging as well as studies on specific proteins in the cerebro-spinal fluid that are related to distinct pathophysiological disease processes are most promising approaches to defining biological markers of Alzheimer's disease. (orig.) [de

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

Science.gov (United States)

Maneksh, Delinda; Sidharthan, Anita; Kettimuthu, Kavithapriya; Kanthakumar, Praghalathan; Lourthuraj, Amala A; Ramachandran, Anup; Subramani, Sathya

2010-06-01

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. To demonstrate features of C. collinus toxicity in a rat model and to identify its mechanism(s) of action. 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. 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. 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.

Lactate point-of-care testing for acidosis: Cross-comparison of two devices with routine laboratory results

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Remco van Horssen

2016-04-01

Full Text Available Objectives: Lactate is a major parameter in medical decision making. During labor, it is an indicator for fetal acidosis and immediate intervention. In the Emergency Department (ED, rapid analysis of lactate/blood gas is crucial for optimal patient care. Our objectives were to cross-compare-for the first time-two point-of-care testing (POCT lactate devices with routine laboratory results using novel tight precision targets and evaluate different lactate cut-off concentrations to predict metabolic acidosis. Design and methods: Blood samples from the delivery room (n=66 and from the ED (n=85 were analyzed on two POCT devices, the StatStrip-Lactate (Nova Biomedical and the iSTAT-1 (CG4+ cassettes, Abbott, and compared to the routine laboratory analyzer (ABL-735, Radiometer. Lactate concentrations were cross-compared between these analyzers. Results: The StatStrip correlated well with the ABL-735 (R=0.9737 and with the iSTAT-1 (R=0.9774 for lactate in umbilical cord blood. Lactate concentrations in ED samples measured on the iSTAT-1 and ABL-735 showed a correlation coefficient of R=0.9953. Analytical imprecision was excellent for lactate and pH, while for pO2 and pCO2 the coefficient of variation was relatively high using the iSTAT-1. Conclusion: Both POCT devices showed adequate analytical performance to measure lactate. The StatStrip can indicate metabolic acidosis in 1 μl blood and will be implemented at the delivery room. Keywords: Lactate, Point-of-care testing, Blood gas, Fetal acidosis

Radiopharmaceuticals for diagnosis and treatment of arthritis

International Nuclear Information System (INIS)

Hosain, F.; Haddon, M.J.; Hosain, H.; Drost, J.K.; Spencer, R.P.

1990-01-01

A brief review is given of radiopharmaceuticals for the diagnosis and treatment of arthritis. Topics covered include the pathophysiology of arthritis and the basis for the use of radiotracers, diagnostic procedures and radiotracer applications and therapeutic approaches and radionuclide applications. (UK)

Acidosis-mediated regulation of the NHE1 isoform of the Na⁺/H⁺ exchanger in renal cells.

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Odunewu, Ayodeji; Fliegel, Larry

2013-08-01

The mammalian Na⁺/H⁺ exchanger isoform 1 (NHE1) is a ubiquitous plasma membrane protein that regulates intracellular pH by removing a proton in exchange for extracellular sodium. Renal tissues are subject to metabolic and respiratory acidosis, and acidosis has been shown to acutely activate NHE1 activity in other cell types. We examined if NHE1 is activated by acute acidosis in HEK293 and Madin-Darby canine kidney (MDCK) cells. Acute sustained intracellular acidosis (SIA) activated NHE1 in both cell types. We expressed wild-type and mutant NHE1 cDNAs in MDCK cells. All the cDNAs had a L163F/G174S mutation, which conferred a 100-fold resistance to EMD87580, an NHE1-specific inhibitor. We assayed exogenous NHE1 activity while inhibiting endogenous activity with EMD87580 and while inhibiting the NHE3 isoform of the Na⁺/H⁺ exchanger using the isoform-specific inhibitor S3226. We examined the activation and phosphorylation of the wild-type and mutant NHE1 proteins in response to SIA. In MDCK cells we demonstrated that the amino acids Ser⁷⁷¹, Ser⁷⁷⁶, Thr⁷⁷⁹, and Ser⁷⁸⁵ are important for NHE1 phosphorylation and activation after acute SIA. SIA activated ERK-dependent pathways in MDCK cells, and this was blocked by treatment with the MEK inhibitor U0126. Treatment with U0126 also blocked activation of NHE1 by SIA. These results suggest that acute acidosis activates NHE1 in mammalian kidney cells and that in MDCK cells this activation occurs through an ERK-dependent pathway affecting phosphorylation of a distinct set of amino acids in the cytosolic regulatory tail of NHE1.

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

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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

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

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Forster, Christian; Schriewer, Jens; John, Stefan; Eckardt, Kai-Uwe; Willam, Carsten

2013-07-24

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. 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. 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. 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.

Acidosis y coma en el Diabético

OpenAIRE

Alfredo Jácome Roca

1992-01-01

Definición. La cetoacidosis diabética (CAD)y 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 ...

[A clinical case of lactic acidosis development in a diabetic patient taking metformin].

Science.gov (United States)

Cezur, Mustafa; Celmen, Nedim; Cetinbas, Riza; Badalov, Pavel; Erdemli, Ozcan

2009-01-01

Metformin is a biguanide. Due to its effects in decreasing the hepatic production of glucose and in increasing insulin sensitivity in peripheral tissues, such as adipose tissue and skeletal muscle, the agent is used in metabolic syndrome and type 2 diabetes mellitus and, in which insulin resistance is especially pronounced. Eighty-one-year old male patient was admitted to the emergency unit with sudden vertigo, tiredness, dyspnea, cyanosis, and lethargy. He had had type 2 diabetes mellitus for 10 years and was taking glargin 12 U/kg once daily and metformin (glucophage) 850 mg thrice daily. The patient showed no cooperation and orientation. Metabolic acidosis, hypoxemia, and hypercapnea were detected in arterial blood gases (ABG). The patient was transferred to an intensive care unit of the hospital; endotracheal intubation was applied and mechanic ventilation was started. On the following day, his ABG got better; he was disconnected and weaning was applied. Lung X-ray study revealed no signs of pneumonia or pulmonary edema. On the same day, extubation was ended and O2 was given by mask at a rate of 4 L/min. After the patient's vital signs, blood sugar, and lactate levels were stabilized; his treatment regimen was arranged again and the patient was discharged on day 4 of his admission. Dyspnea, acidosis, and hypoxia seen in the patient were thought to be due to lactic acidosis which may rarely occur when metformin is used.

Renal Tubular Acidosis an Adverse Effect of PD-1 Inhibitor Immunotherapy

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Sandy El Bitar

2018-01-01

Full Text Available Immune checkpoint blockade therapy is gaining popularity among oncologists for treatment of solid and hematologic malignancies. The widespread use of these agents resulted in increasing incidence of renal immune-related adverse events. Reported renal toxicity described so far includes acute interstitial nephritis, minimal change disease, and immune complex glomerulonephritis. We report the case of a 79-year-old female with metastatic non-small cell lung cancer on anti-PD-1 therapy nivolumab. After the 4th administration of nivolumab, the treatment course was complicated with normal anion gap metabolic acidosis. Urine and blood studies were in favor of distal renal tubular acidosis (RTA. Following a negative workup for an underlying etiology, immunotherapy-induced RTA was suspected. Withholding of the offending agent and initiation of steroid therapy resulted in adequate response. The present report provides the first presentation of RTA as a renal immune-related adverse event secondary to nivolumab. Nephrologists and oncologists should be familiar with potentially life-threatening renal side effects induced by immune checkpoint inhibitors.

Respiratory alkalosis and metabolic acidosis in a child treated with sulthiame.

Science.gov (United States)

Weissbach, Avichai; Tirosh, Irit; Scheuerman, Oded; Hoffer, Vered; Garty, Ben Zion

2010-10-01

To report on severe acid-base disturbance in a child with symptomatic epilepsy treated with sulthiame. A 9.5-year-old boy with chronic generalized tonic-clonic seizures was treated with carbamazepine and valproic acid. Because of poor seizure control, sulthiame was added to the treatment. Two months later, he presented at the emergency department with severe weakness, headache, dizziness, dyspnea, anorexia, and confusional state. Arterial blood gas analysis showed mixed respiratory alkalosis with high anion gap metabolic acidosis. Sulthiame-induced acid-base disturbance was suspected. The drug was withheld for the first 24 hours and then restarted at a reduced dosage. The arterial blood gases gradually normalized, the confusion disappeared, and the patient was discharged home.Three months later, 4 weeks after an increase in sulthiame dosage, the patient was once again admitted with the same clinical picture. Improvement was noted after the drug dosage was reduced. This is the first report of mixed respiratory alkalosis and metabolic acidosis in a child treated with sulthiame. Monitoring of the acid-base status should be considered in patients treated with sulthiame.

Transient acidosis while retrieving a fear-related memory enhances its lability

Science.gov (United States)

Du, Jianyang; Price, Margaret P; Taugher, Rebecca J; Grigsby, Daniel; Ash, Jamison J; Stark, Austin C; Hossain Saad, Md Zubayer; Singh, Kritika; Mandal, Juthika; Wemmie, John A; Welsh, Michael J

2017-01-01

Attenuating the strength of fearful memories could benefit people disabled by memories of past trauma. Pavlovian conditioning experiments indicate that a retrieval cue can return a conditioned aversive memory to a labile state. However, means to enhance retrieval and render a memory more labile are unknown. We hypothesized that augmenting synaptic signaling during retrieval would increase memory lability. To enhance synaptic transmission, mice inhaled CO2 to induce an acidosis and activate acid sensing ion channels. Transient acidification increased the retrieval-induced lability of an aversive memory. The labile memory could then be weakened by an extinction protocol or strengthened by reconditioning. Coupling CO2 inhalation to retrieval increased activation of amygdala neurons bearing the memory trace and increased the synaptic exchange from Ca2+-impermeable to Ca2+-permeable AMPA receptors. The results suggest that transient acidosis during retrieval renders the memory of an aversive event more labile and suggest a strategy to modify debilitating memories. DOI: http://dx.doi.org/10.7554/eLife.22564.001 PMID:28650315

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

DEFF Research Database (Denmark)

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...... completely the CBF increase caused by Az-induced extracellular acidosis or by CO2, but it did not influence the CBF increase produced by sodium nitroprusside or papaverine. The results suggest that indomethacin exerts its action on CO2 reactivity by a nonprostaglandin-mediated mechanism that directly......Indomethacin is known to attenuate quite markedly the increase in CBF during hypercapnia. Hypercapnia is, in all likelihood, mediated by the acid shift at the level of the smooth muscle cells of the cerebral arterioles. We therefore investigated the effect of indomethacin on the CBF increase caused...

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

Oxidative response of neutrophils to platelet-activating factor is altered during acute ruminal acidosis induced by oligofructose in heifers

OpenAIRE

Concha, Claudia; Carretta, María Daniella; Alarcón, Pablo; Conejeros, Ivan; Gallardo, Diego; Hidalgo, Alejandra Isabel; Tadich, Nestor; Cáceres, Dante Daniel; Hidalgo, María Angélica; Burgos, Rafael Agustín

2014-01-01

Reactive oxygen species (ROS) production is one of the main mechanisms used to kill microbes during innate immune response. D-lactic acid, which is augmented during acute ruminal acidosis, reduces platelet activating factor (PAF)-induced ROS production and L-selectin shedding in bovine neutrophils in vitro. This study was conducted to investigate whether acute ruminal acidosis induced by acute oligofructose overload in heifers interferes with ROS production and L-selectin shedding in blood ne...

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

Science.gov (United States)

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.

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

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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.

pHj, contractility and Ca-balance under hypercapnic acidosis in the myocardium of different vertebrate species

DEFF Research Database (Denmark)

Gesser, H; Bonefeld-Jørgensen, Eva Cecilie

1982-01-01

The influence of hypercapnic acidosis upon the heart was examined in four vertebrate species. The CO2 in the tissue bath was increased from 2.7 to 15% at 12 degrees C for flounder (Platichthys flesus) and cod (Gadus morhua) and from 3 to 13% at 22 degrees C for turtle (Pseudemys scripta) and rain......The influence of hypercapnic acidosis upon the heart was examined in four vertebrate species. The CO2 in the tissue bath was increased from 2.7 to 15% at 12 degrees C for flounder (Platichthys flesus) and cod (Gadus morhua) and from 3 to 13% at 22 degrees C for turtle (Pseudemys scripta...

Acid-Base and Electrolyte Disorders in Patients with and without Chronic Kidney Disease: An Update.

Science.gov (United States)

Dhondup, Tsering; Qian, Qi

2017-12-01

Kidneys play a pivotal role in the maintenance and regulation of acid-base and electrolyte homeostasis, which is the prerequisite for numerous metabolic processes and organ functions in the human body. Chronic kidney diseases compromise the regulatory functions, resulting in alterations in electrolyte and acid-base balance that can be life-threatening. In this review, we discuss the renal regulations of electrolyte and acid-base balance and several common disorders including metabolic acidosis, alkalosis, dysnatremia, dyskalemia, and dysmagnesemia. Common disorders in chronic kidney disease are also discussed. The most recent and relevant advances on pathophysiology, clinical characteristics, diagnosis, and management of these conditions have been incorporated.

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

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Margarita Irene Rocha-Gómez

2015-08-01

Full Text Available 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 medición del transporte tubular máximo de bicarbonato y con la capacidad de acidificación urinaria (procedimientos de referencia para clasificar el tipo de acidosis tubular renal en pacientes pediátricos. Material y método: el estudio se realizó en niños con diagnóstico de acidosis tubular renal. El primer día se recolectó la muestra sérica y urinaria de dos horas. Al día siguiente se efectuaron los procedimientos de referencia administrando bicarbonato de sodio en 8 horas; las muestras se colectaron cada hora y se determinaron la reabsorción de bicarbonato y la acidificación urinaria.  Resultados: se incluyeron 19 pacientes y en 17 casos la colección urinaria de dos horas confirmó el diagnóstico de los procedimientos de referencia. La recolección urinaria de dos horas tuvo sensibilidad de 0.94 y especificidad de 0.67 para el diagnóstico de acidosis tubular renal distal. Conclusión: la recolección de orina de dos horas se realiza en forma menos invasiva y ofrece resultados semejantes a los procedimientos de referencia.

Renal tubular acidosis complicated with hyponatremia due to cortisol insufficiency

OpenAIRE

Izumi, Yuichiro; Nakayama, Yushi; Onoue, Tomoaki; Inoue, Hideki; Mukoyama, Masashi

2015-01-01

Adrenocortical insufficiency such as occurs in Addison's disease causes hyponatremia and renal tubular acidosis (RTA). Hyponatremia results from both aldosterone and cortisol insufficiency. RTA is due to aldosterone insufficiency. The involvement of cortisol in RTA is unclear. Here, we report a woman in her 70s who was admitted to our hospital with severe hyponatremia (106 mEq/l) and RTA. The patient exhibited low plasma cortisol levels with little response to rapid adrenocorticotropic hormon...

Changes in bone sodium and carbonate in metabolic acidosis and alkalosis in the dog

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Burnell, James M.

1971-01-01

Metabolic acidosis and alkalosis were produced in adult dogs over 5- to 10-day periods. Midtibial cortical bone was analyzed for calcium, sodium, phosphorus, and carbonate. In acidosis bone CO3/Ca decreased 9.5% and bone Na/Ca decreased 6.3%. In alkalosis bone CO3/Ca increased 3.1% and bone Na/Ca increased 3.0%. Previous attempts to account for changes in net acid balance by summation of extra- and intracellular acid-base changes have uniformly resulted in about 40-60% of acid gained or lost being “unaccounted for.” If it is assumed that changes in tibial cortex reflect changes in the entire skeletal system, changes in bone CO3= are sufficiently large to account for the “unaccounted for” acid change without postulating changes in cellular metabolic acid production. PMID:5540172

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

NARCIS (Netherlands)

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

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;

Stroke MRI: pathophysiology, potential and perspectives

International Nuclear Information System (INIS)

Fiehler, J.; Kucinski, T.; Zeumer, H.

2004-01-01

Magnetic resonance imaging (MRT) is increasingly utilized as the primary imaging modality in major stroke centers. The ability to depict several aspects of individual pathophysiology makes the use of MRI in stroke both attractive and complex. Profound knowledge of the pathophysiology of the imaging findings is crucial for a rational diagnostic workup. The pathophysiology of MRI in stroke will be reviewed considering recent experiences in clinical application, and the potential of stroke MRI will be assessed. Further perspectives like application of 'blood oxygen level dependent' (BOLD) and the use of multiparametric prediction maps will be discussed. (orig.) [de

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

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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.

Pathophysiology, Evaluation, and Management of Chronic Watery Diarrhea

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Camilleri, Michael; Sellin, Joseph H.; Barrett, Kim E.

2016-01-01

Chronic watery diarrhea poses a diagnostic and therapeutic challenge and is often a disabling condition for patients. Although acute diarrhea is likely to be caused by infection, the causes of chronic diarrhea (more than 4 weeks in duration) are more elusive. We review on the pathophysiology, diagnosis, and treatment of chronic diarrhea. Drawing on recent insights into the molecular mechanisms of intestinal epithelial transport and barrier function, we discuss how diarrhea can result from a decrease in luminal solute absorption, an increase in secretion, or both, as well as derangements in barrier properties. We also describe the various extra-epithelial factors that activate diarrheal mechanisms. Finally, clinical evaluation and tests used in assessment of patients presenting with chronic diarrhea are reviewed, and an algorithm guiding therapeutic decisions and pharmacotherapy is presented. PMID:27773805

Metabolic acidosis: expected and fatal adverse effects of metformin and empagliflozin: a case series and literature review

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Miriam Čupić

2016-09-01

Full Text Available Metformin, a well-known first-line diabetes therapy, and the recently developed sodium- glucose co-transporter 2 (SGLT2 inhibitor empagliflozin are widely used oral antihyperglycemic drugs in the long-term treatment of type 2 diabetes mellitus (T2DM. Metabolic acidosis is a potentially fatal adverse effect (AE of these drugs with a high mortality rate. However, the reported incidence of metabolic acidosis in clinical practice has been proven to be very low. Nevertheless, it should be considered that the event rates are based on confounded data and spontaneous case reports. Metformin increases plasma lactate levels by inhibiting mitochondrial respiration, which, accompanied by elevated plasma metformin concentrations (in renal impairment and a secondary event that further disrupts lactate production (e.g., hypoperfusion, sepsis, typically leads to metformin-associated lactic acidosis (MALA. At the same time, SGLT2 inhibitors are thought to promote ketogenesis and precipitate ketoacidosis by their extra-pancreatic glucuretic mode of action. The present article describes 3 patients suffering from severe metabolic acidosis caused by metformin or empagliflozin, presents similar cases reported in the literature, and assesses the possible etiopathogenesis of the metabolic derangement. Diabetic patients should be educated about the importance of regular fluid and food intake as well as regular blood and urine glucose and ketone self-checkups, whereas physicians should be more aware that the key to an effective use of all glucose-lowering medication is appropriate patient selection, counseling, and follow-up. It is a good clinical sense which will ensure that physicians are able to translate pharmaceutical advances into clinical benefits for patients with T2DM.

MDD diagnosis based on partial-brain functional connection network

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Yan, Gaoliang; Hu, Hailong; Zhao, Xiang; Zhang, Lin; Qu, Zehui; Li, Yantao

2018-04-01

Artificial intelligence (AI) is a hotspot in computer science research nowadays. To apply AI technology in all industries has been the developing direction for researchers. Major depressive disorder (MDD) is a common disease of serious mental disorders. The World Health Organization (WHO) reports that MDD is projected to become the second most common cause of death and disability by 2020. At present, the way of MDD diagnosis is single. Applying AI technology to MDD diagnosis and pathophysiological research will speed up the MDD research and improve the efficiency of MDD diagnosis. In this study, we select the higher degree of brain network functional connectivity by statistical methods. And our experiments show that the average accuracy of Logistic Regression (LR) classifier using feature filtering reaches 88.48%. Compared with other classification methods, both the efficiency and accuracy of this method are improved, which will greatly improve the process of MDD diagnose. In these experiments, we also define the brain regions associated with MDD, which plays a vital role in MDD pathophysiological research.

Draft Genome Sequence of Lactobacillus delbrueckii Strain #22 Isolated from a Patient with Short Bowel Syndrome and Previous d-Lactic Acidosis and Encephalopathy.

Science.gov (United States)

Domann, Eugen; Fischer, Florence; Glowatzki, Fabian; Fritzenwanker, Moritz; Hain, Torsten; Zechel-Gran, Silke; Giffhorn-Katz, Susanne; Neubauer, Bernd A

2016-07-28

d-Lactic acidosis with associated encephalopathy caused by overgrowth of intestinal lactic acid bacteria is a rarely diagnosed neurological complication of patients with short bowel syndrome. Here, we report the draft genome sequence of Lactobacillus delbrueckii strain #22 isolated from a patient with short bowel syndrome and previous d-lactic acidosis/encephalopathy. Copyright © 2016 Domann et al.

Reevaluation of the Thyroid Scan for the Assessment of Pathophysiologic Status of Thyroid Disease

International Nuclear Information System (INIS)

Woo, In Sook; Nah, Jung Il; Kim, Deog Yoon

1991-01-01

To diagnosis and understand the pathophysiologic status of thyroid disease, not only hormonal measurements but also thyroid scan is believed to have a unique role. Especially in the cases of the change of the thyroid function by thyroiditis, it is emphasized that thyroid scan can be helpful in differential diagnosis, Discordant results of thyroid hormone levels and thyroid scan are found in transient hyperthyroidism, or in transient hypothyroidism. We analysed and reevaluated thyroid scan to look at the importance of thyroid scan. The results are summarised as follows: 1) 80%. of hyperthyroid patients had hyperthyroidism increased RAIU with even density, they are compatible with Graves' disease. 2) 2.1% of hyperthyroid patients had normal or decreased RAIU, which are classified as high iodine turn over genuine hyperthyroidism. 3) 8.5% of hyperthyroid patients had markedly decreased RAIU at both 2 hour and 24 hour, whose pathologic processes are suggested to be heterogenous namely subacute thyroiditis, postpartum thyroiditis, Hashimoto's thyroiditis, and pamless thyroiditis. 4) 45% of hypothyroid patients had increased 24 hr RAIU, 30% of hypothyroid patients were normal, 25%, decreased. In conclusion, thyroid scan should be reevaluated its useful role to asses the pathophysiologic status of thyroid disease. Especially in cases of transient thyrotoxicosis, thyroid scan is essential to diagnose and follow up the disease process.

Reevaluation of the Thyroid Scan for the Assessment of Pathophysiologic Status of Thyroid Disease

Energy Technology Data Exchange (ETDEWEB)

Woo, In Sook; Nah, Jung Il; Kim, Deog Yoon [Kyunghee University College of Medicine, Seoul (Korea, Republic of)

1991-03-15

To diagnosis and understand the pathophysiologic status of thyroid disease, not only hormonal measurements but also thyroid scan is believed to have a unique role. Especially in the cases of the change of the thyroid function by thyroiditis, it is emphasized that thyroid scan can be helpful in differential diagnosis, Discordant results of thyroid hormone levels and thyroid scan are found in transient hyperthyroidism, or in transient hypothyroidism. We analysed and reevaluated thyroid scan to look at the importance of thyroid scan. The results are summarised as follows: 1) 80%. of hyperthyroid patients had hyperthyroidism increased RAIU with even density, they are compatible with Graves' disease. 2) 2.1% of hyperthyroid patients had normal or decreased RAIU, which are classified as high iodine turn over genuine hyperthyroidism. 3) 8.5% of hyperthyroid patients had markedly decreased RAIU at both 2 hour and 24 hour, whose pathologic processes are suggested to be heterogenous namely subacute thyroiditis, postpartum thyroiditis, Hashimoto's thyroiditis, and pamless thyroiditis. 4) 45% of hypothyroid patients had increased 24 hr RAIU, 30% of hypothyroid patients were normal, 25%, decreased. In conclusion, thyroid scan should be reevaluated its useful role to asses the pathophysiologic status of thyroid disease. Especially in cases of transient thyrotoxicosis, thyroid scan is essential to diagnose and follow up the disease process.

Early respiratory acidosis is a new risk factor for pneumonia after lung resection.

Science.gov (United States)

Planquette, Benjamin; Le Pimpec-Barthes, Françoise; Trinquart, Ludovic; Meyer, Guy; Riquet, Marc; Sanchez, Olivier

2012-03-01

Postoperative pneumonia (POP) is a life-threatening complication of lung resection (LR). Its risk factors, bacteriological profile and outcome are not well known. The aims of this study were to describe the outcome and causal bacteria and to identify risk factors for POP. We reviewed all cases admitted to intensive care after LR. Clinical parameters, operative and postoperative data were recorded. POP was suspected on the basis of fever, radiographic infiltrate, and either leucocytosis or purulent sputum. The diagnosis was confirmed by culture of a respiratory sample. Risk factors for POP were identified by univariate and multivariate analysis. We included 159 patients in this study. POP was diagnosed in 23 patients (14.4%) and was associated with a higher hospital mortality rate (30% versus 5%, P = 0.0007) and a longer hospital stay. Members of the Enterobacteriaceae and Pseudomonas species were the most frequently identified pathogens. Early respiratory acidosis (ERA; OR, 2.94; 95% CI, 1.1-8.1), blood transfusion (OR, 3.8; 95% CI, 1.1-13.1), bilobectomy (OR, 7.26; 95% CI, 1.2-43.1) and smoking history (OR, 1.84; 95% CI, 1.1-3) were identified as independent risk factors. ERA may be a risk factor for POP and could serve as a target for therapeutic interventions.

Diet, evolution and aging--the pathophysiologic effects of the post-agricultural inversion of the potassium-to-sodium and base-to-chloride ratios in the human diet.

Science.gov (United States)

Frassetto, L; Morris, R C; Sellmeyer, D E; Todd, K; Sebastian, A

2001-10-01

, reduced bone resorption rates, improved nitrogen balance, and mitigated the normally occurring age-related decline in growth hormone secretion--all without restricting dietary NaCl. Moreover, we found that co-administration of an alkalinizing salt of potassium (potassium citrate) with NaCl prevented NaCl from increasing urinary calcium excretion and bone resorption, as occurred with NaCl administration alone. Earlier studies estimated dietary acid load from the amount of animal protein in the diet, inasmuch as protein metabolism yields sulfuric acid as an end-product. In cross-cultural epidemiologic studies, Abelow found that hip fracture incidence in older women correlated with animal protein intake, and they suggested a causal relation to the acid load from protein. Those studies did not consider the effect of potential sources of base in the diet. We considered that estimating the net acid load of the diet (i. e., acid minus base) would require considering also the intake of plant foods, many of which are rich sources of K-base, or more precisely base precursors, substances like organic anions that the body metabolizes to bicarbonate. In following up the findings of Abelow et al., we found that plant food intake tended to be protective against hip fracture, and that hip fracture incidence among countries correlated inversely with the ratio of plant-to-animal food intake. These findings were confirmed in a more homogeneous population of white elderly women residents of the U.S. These findings support affirmative answers to the questions we asked above. Can we provide dietary guidelines for controlling dietary net acid loads to minimize or eliminate diet-induced and age-amplified chronic low-grade metabolic acidosis and its pathophysiological sequelae. We discuss the use of algorithms to predict the diet net acid and provide nutritionists and clinicians with relatively simple and reliable methods for determining and controlling the net acid load of the diet. A more

Epidemiology, genetics, pathophysiology, and prognostic classifications of cerebral arteriovenous malformations.

Science.gov (United States)

Ozpinar, Alp; Mendez, Gustavo; Abla, Adib A

2017-01-01

Arteriovenous malformations (AVMs) are vascular deformities involving fistula formation of arterial to venous structures without an intervening capillary bed. Such anomalies can prove fatal as the high arterial flow can disrupt the integrity of venous walls, thus leading to dangerous sequelae such as hemorrhage. Diagnosis of these lesions in the central nervous system can often prove challenging as intracranial AVMs represent a heterogeneous vascular pathology with various presentations and symptomatology. The literature suggests that most brain AVMs (bAVMs) are identified following evaluation of the etiology of acute cerebral hemorrhage, or incidentally on imaging associated with seizure or headache workup. Given the low incidence of this disease, most of the data accrued on this pathology comes from single-center experiences. This chapter aims to distill the most important information from these studies as well as examine meta-analyses on bAVMs in order to provide a comprehensive introduction into the natural history, classification, genetic underpinnings of disease, and proposed pathophysiology. While there is yet much to be elucidated about AVMs of the central nervous system, we aim to provide an overview of bAVM etiology, classification, genetics, and pathophysiology inherent to the disease process. © 2017 Elsevier B.V. All rights reserved.

Digestive system-related pathophysiological symptoms of Sasang typology: Systematic review.

Science.gov (United States)

Lee, Mi Suk; Sohn, Kyungwoo; Kim, Yun Hee; Hwang, Min-Woo; Kwon, Young Kyu; Bae, Na Young; Chae, Han

2013-06-01

The purpose of this study was to review clinical studies on digestive system-related pathophysiological symptoms of each Sasang type to obtain the generalizable typespecific clinical features, which are important for the diagnosis of the Sasang type and subsequent disease treatment. Sasang typology and digestive system symptom-related keywords were used to search through eight domestic and foreign databases up to March 2012. The results were organized and analyzed based on four categories [digestive function, appetite, eating pattern, and body mass index (BMI)] to elucidate type-specific symptoms. Sasang type-specific digestive system-related symptoms were identified by reviewing 30 related articles that were gathered by searching through the databases. The Tae-Eum (TE) type had the highest digestive functions and the So-Eum (SE) type had the lowest. The TE type appeared to have larger volume with fast eating speed compared with the SE type and individuals in the TE category preferred fatty or salty food, which is responsible for the high occurrence rates of organic digestive diseases such as gastritis. Moreover, BMI was higher in the TE type and lower in the SE type. We systematically reviewed previously published clinical reports on digestive functions, which can be used to meet the objective of Sasang-type differentiation and pathophysiological pattern identification.

Digestive system-related pathophysiological symptoms of Sasang typology: Systematic review

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Mi Suk Lee

2013-06-01

Full Text Available The purpose of this study was to review clinical studies on digestive system-related pathophysiological symptoms of each Sasang type to obtain the generalizable typespecific clinical features, which are important for the diagnosis of the Sasang type and subsequent disease treatment. Sasang typology and digestive system symptom-related keywords were used to search through eight domestic and foreign databases up to March 2012. The results were organized and analyzed based on four categories [digestive function, appetite, eating pattern, and body mass index (BMI] to elucidate type-specific symptoms. Sasang type-specific digestive system-related symptoms were identified by reviewing 30 related articles that were gathered by searching through the databases. The Tae-Eum (TE type had the highest digestive functions and the So-Eum (SE type had the lowest. The TE type appeared to have larger volume with fast eating speed compared with the SE type and individuals in the TE category preferred fatty or salty food, which is responsible for the high occurrence rates of organic digestive diseases such as gastritis. Moreover, BMI was higher in the TE type and lower in the SE type. We systematically reviewed previously published clinical reports on digestive functions, which can be used to meet the objective of Sasang-type differentiation and pathophysiological pattern identification.

Hypercapnic Acidosis Preserves Gastric Mucosal Microvascular Oxygen Saturation in a Canine Model of Hemorrhage.

NARCIS (Netherlands)

Schwartges, Ingo; Picker, Olaf; Beck, Christopher; Scheeren, Thomas W. L.; Schwarte, Lothar A.

2010-01-01

The authors aimed to clarify the effects of hypercapnic acidosis and its timing on gastric mucosal oxygenation in a canine model of hemorrhage. This was designed as a prospective, controlled, randomized animal study set in a university research laboratory. Five chronically instrumented dogs were

Lactic Acidosis with Chloramphenicol Treatment in a Child with Cystic Fibrosis.

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Goyer, Isabelle; Iseppon, Massimiliano; Thibault, Céline; Abaji, Rachid; Krajinovic, Maja; Autmizguine, Julie

2017-01-30

Children with cystic fibrosis are commonly colonized with multi-resistant bacteria. In such patients, infectious exacerbation may require salvage therapy with uncommonly used antimicrobials, including chloramphenicol. Chloramphenicol is rarely used nowadays because of the associated severe adverse events. We describe the case of a 15-year-old female with terminal cystic fibrosis who required intravenous (IV) chloramphenicol treatment for a Burkholderia cepacia (B. cepacia) exacerbation. The child subsequently developed lactic acidosis and secondary respiratory compensation adding to her baseline respiratory distress. Based on the Naranjo scale, the probability of chloramphenicol being the cause of the hyperlactatemia and associated respiratory distress was rated as probable, as the adverse effects resolved upon discontinuation of the drug. Subsequent genotyping for mitochondrial polymorphism (G3010A) confirmed a possible susceptibility to lactic acidosis from mitochondrial RNA-inhibiting agents such as chloramphenicol. Hyperlactatemia is a rare but life threatening adverse effect that has been previously reported with chloramphenicol exposure, but is not generally thought of. Clinicians should be aware of this potentially life threatening, but reversible adverse event. Lactate should be monitored under chloramphenicol and it should be discontinued as soon as this complication is suspected, especially in patients with low respiratory reserve. © 2017 Journal of Population Therapeutics and Clinical Pharmacology. All rights reserved.

Acidosis, but Not Alkalosis, Affects Anaerobic Metabolism and Performance in a 4-km Time Trial.

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Correia-Oliveira, Carlos Rafaell; Lopes-Silva, João Paulo; Bertuzzi, Romulo; McConell, Glenn K; Bishop, David John; Lima-Silva, Adriano Eduardo; Kiss, Maria Augusta Peduti Dal'molin

2017-09-01

This study aimed to determine the effect of preexercise metabolic acidosis and alkalosis on power output (PO) and aerobic and anaerobic energy expenditure during a 4-km cycling time trial (TT). Eleven recreationally trained cyclists (V˙O2peak 54.1 ± 9.3 mL·kg·min) performed a 4-km TT 100 min after ingesting in a double-blind matter 0.15 g·kg of body mass of ammonium chloride (NH4Cl, acidosis), 0.3 g·kg of sodium bicarbonate (NaHCO3, alkalosis), or 0.15 g·kg of CaCO3 (placebo). A preliminary study (n = 7) was conducted to establish the optimal doses to promote the desirable preexercise blood pH alterations without gastrointestinal distress. Data for PO, aerobic and anaerobic energy expenditure, and blood and respiratory parameters were averaged for each 1 km and compared between conditions using two-way repeated-measures ANOVA (condition and distance factors). Gastrointestinal discomfort was analyzed qualitatively. Compared with placebo (pH 7.37 ± 0.02, [HCO3]: 27.5 ± 2.6 mmol·L), the NaHCO3 ingestion resulted in a preexercise blood alkalosis (pH +0.06 ± 0.04, [HCO3]: +4.4 ± 2.0 mmol·L, P 0.05). Minimal gastrointestinal distress was noted in all conditions. Preexercise acidosis, but not alkalosis, affects anaerobic metabolism and PO during a 4-km cycling TT.

Hyperosmolar metabolic acidosis in burn patients exposed to glycol based topical antimicrobials-A systematic review.

Science.gov (United States)

Leibson, Tom; Davies, Paige; Nickel, Cheri; Koren, Gideon

2018-06-01

The well documented susceptibility of burn patients to acquired infections via damaged skin mandates application of antimicrobial agents. These agents are dissolved in various vehicles that augment skin absorption thus allowing greater efficacy. Polyethylene glycol (PEG) and Propylene glycol (PropG) are among the most commonly used vehicles, and both have been used in numerous medications and cosmetic products over the past few decades. Rarely, burn patients treated with agents containing these glycols present with a life threatening systemic toxidrome of hyperosmolar metabolic acidosis. We present a systematic review of outcomes in burn patients treated with similar agents. Relevant studies were identified through systematic searches conducted in MEDLINE (Ovid), Embase (Ovid), CENTRAL (Ovid), and Web of Science (Thomson Reuters), from database inception to August 4th, 2016. All publications of clinical burn patient studies included at least one arm receiving a glycol based topical therapy. A total of 61 studies involving 10,282 patients and 4 different antimicrobial medications fulfilled the inclusion criteria. Nine burn patients (0.09%) were documented to present with hyperosmolar metabolic acidosis during topical silver sulfadiazine treatment. Propylene glycol isolated from their blood accounted for the high osmole gap. This first systematic review found very few cases of documented hyperosmolar metabolic acidosis, all within one study that had set to specifically explore this toxidrome. High index of suspicion with frequent osmolar gap monitoring may help identify future toxicities in a timely manner. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

The pathophysiology of migraine: implications for clinical management.

Science.gov (United States)

Charles, Andrew

2018-02-01

The understanding of migraine pathophysiology is advancing rapidly. Improved characterisation and diagnosis of its clinical features have led to the view of migraine as a complex, variable disorder of nervous system function rather than simply a vascular headache. Recent studies have provided important new insights into its genetic causes, anatomical and physiological features, and pharmacological mechanisms. The identification of new migraine-associated genes, the visualisation of brain regions that are activated at the earliest stages of a migraine attack, a greater appreciation of the potential role of the cervical nerves, and the recognition of the crucial role for neuropeptides are among the advances that have led to novel targets for migraine therapy. Future management of migraine will have the capacity to tailor treatments based on the distinct mechanisms of migraine that affect individual patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

Changes in the relative population size of selected ruminal bacteria following an induced episode of acidosis in beef heifers receiving viable and non-viable active dried yeast.

Science.gov (United States)

Mohammed, R; Vyas, D; Yang, W Z; Beauchemin, K A

2017-06-01

To characterize the changes in the relative population size (RPS) of select ruminal bacteria and rumen fermentation variables in beef heifers supplemented with a strain of Saccharomyces cerevisiae as viable active dried (ADY) or killed dried (KDY) yeast following an induced episode of ruminal acidosis. Six ruminally cannulated beef heifers fed a diet consisting of 50% forage and 50% grain (dry matter basis) were used in a replicated 3 × 3 Latin square design with three 28-day periods. Treatments were: (i) control (CTRL; no yeast); (ii) ADY (4 g day -1 providing 10 10  CFU per g; AB Vista, UK); and (iii) KDY (4 g day -1 autoclaved ADY). The acidosis challenge was induced on day 22 and rumen samples were collected on day 15 (baseline; BASE), day 22 (challenge day; CHAL), and on day 29 (168th hour post acid challenge or recovery, REC) of each period. Over the study, duration of pH Yeast supplementation, irrespective of its viability, showed beneficial effects on ruminal pH variables in animals more susceptible to acidosis. Rumen microbial population was altered with the induction of severe acidosis. Most of the changes reverted back to baseline values during the recovery phase. Yeast supplementation reduced subacute rumen acidosis in the most susceptible cattle, but failed to attenuate severe acidosis induced by a grain challenge. The study provided valuable insight into the mechanism by which acidosis affects cattle performance. Individual animal variation in ruminal fermentation partly explained the variability in response to yeast supplementation in the study. © 2017 Her Majesty the Queen in Right of Canada. Journal of Applied Microbiology © 2017 The Society for Applied Microbiology.

17β-Estradiol Enhances ASIC Activity in Primary Sensory Neurons to Produce Sex Difference in Acidosis-Induced Nociception.

Science.gov (United States)

Qu, Zu-Wei; Liu, Ting-Ting; Ren, Cuixia; Gan, Xiong; Qiu, Chun-Yu; Ren, Ping; Rao, Zhiguo; Hu, Wang-Ping

2015-12-01

Sex differences have been reported in a number of pain conditions. Women are more sensitive to most types of painful stimuli than men, and estrogen plays a key role in the sex differences in pain perception. However, it is unclear whether there is a sex difference in acidosis-evoked pain. We report here that both male and female rats exhibit nociceptive behaviors in response to acetic acid, with females being more sensitive than males. Local application of exogenous 17β-estradiol (E2) exacerbated acidosis-evoked nociceptive response in male rats. E2 and estrogen receptor (ER)-α agonist 1,3,5-Tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole, but not ERβ agonist 2,3-bis(4-hydroxyphenyl)-propionitrile, replacement also reversed attenuation of the acetic acid-induced nociceptive response in ovariectomized females. Moreover, E2 can exert a rapid potentiating effect on the functional activity of acid-sensing ion channels (ASICs), which mediated the acidosis-induced events. E2 dose dependently increased the amplitude of ASIC currents with a 42.8 ± 1.6 nM of EC50. E2 shifted the concentration-response curve for proton upward with a 50.1% ± 6.2% increase of the maximal current response to proton. E2 potentiated ASIC currents via an ERα and ERK1/2 signaling pathway. E2 also altered acidosis-evoked membrane excitability of dorsal root ganglia neurons and caused a significant increase in the amplitude of the depolarization and the number of spikes induced by acidic stimuli. E2 potentiation of the functional activity of ASICs revealed a peripheral mechanism underlying this sex difference in acetic acid-induced nociception.

Zebrafish as a Model System for Investigating the Compensatory Regulation of Ionic Balance during Metabolic Acidosis

Directory of Open Access Journals (Sweden)

Lletta Lewis

2018-04-01

Full Text Available Zebrafish (Danio rerio have become an important model for integrative physiological research. Zebrafish inhabit a hypo-osmotic environment; to maintain ionic and acid-base homeostasis, they must actively take up ions and secrete acid to the water. The gills in the adult and the skin at larval stage are the primary sites of ionic regulation in zebrafish. The uptake of ions in zebrafish is mediated by specific ion transporting cells termed ionocytes. Similarly, in mammals, ion reabsorption and acid excretion occur in specific cell types in the terminal region of the renal tubules (distal convoluted tubule and collecting duct. Previous studies have suggested that functional regulation of several ion transporters/channels in the zebrafish ionocytes resembles that in the mammalian renal cells. Additionally, several mechanisms involved in regulating the epithelial ion transport during metabolic acidosis are found to be similar between zebrafish and mammals. In this article, we systemically review the similarities and differences in ionic regulation between zebrafish and mammals during metabolic acidosis. We summarize the available information on the regulation of epithelial ion transporters during acidosis, with a focus on epithelial Na+, Cl− and Ca2+ transporters in zebrafish ionocytes and mammalian renal cells. We also discuss the neuroendocrine responses to acid exposure, and their potential role in ionic compensation. Finally, we identify several knowledge gaps that would benefit from further study.

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

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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.

CT diagnosis of congenital anomalies of the central nervous system

International Nuclear Information System (INIS)

Mori, Koreaki

1980-01-01

In the diagnosis of central nervous system congenital anomalies, understanding of embryology of the central nervous system and pathophysiology of each anomaly are essential. It is important for clinical approach to central nervous system congenital anomalies to evaluate the size of the head and tention of the anterior fontanelle. Accurate diagnosis of congenital anomalies depends on a correlation of CT findings to clinical pictures. Clinical diagnosis of congenital anomalies should include prediction of treatability and prognosis, in addition to recognition of a disease. (author)

Successful Management of Refractory Type 1 Renal Tubular Acidosis with Amiloride

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Patrick Oguejiofor

2017-01-01

Full Text Available 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.

Ruminal acidosis and the rapid onset of ruminal parakeratosis in a mature dairy cow: a case report

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Croom Jim

2009-10-01

Full Text Available Abstract A mature dairy cow was transitioned from a high forage (100% forage to a high-grain (79% grain diet over seven days. Continuous ruminal pH recordings were utilized to diagnose the severity of ruminal acidosis. Additionally, blood and rumen papillae biopsies were collected to describe the structural and functional adaptations of the rumen epithelium. On the final day of the grain challenge, the daily mean ruminal pH was 5.41 ± 0.09 with a minimum of 4.89 and a maximum of 6.31. Ruminal pH was under 5.0 for 130 minutes (2.17 hours which is characterized as the acute form of ruminal acidosis in cattle. The grain challenge increased blood beta-hydroxybutyrate by 1.8 times and rumen papillae mRNA expression of 3-hydroxy-3-methylglutaryl-coenzyme A synthase by 1.6 times. Ultrastructural and histological adaptations of the rumen epithelium were imaged by scanning electron and light microscopy. Rumen papillae from the high grain diet displayed extensive sloughing of the stratum corneum and compromised cell adhesion as large gaps were apparent between cells throughout the strata. This case report represents a rare documentation of how the rumen epithelium alters its function and structure during the initial stage of acute acidosis.

LACTIC ACIDOSIS: A RARE MANIFESTATION OF SYNTHETIC MARIJUANA INTOXICATION.

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Antill, T; Jakkoju, A; Dieguez, J; Laskhmiprasad, L

2015-01-01

Synthetic cannabinoids are designer drugs that mimic the effect of cannabis, which has become popular with young drug users. These drugs have a similar chemical structure and pharmacologic effects as marijuana, but seem to be more potent. These substances have been banned by the US Drug Enforcement Agency in 2010. Prior to 2010, these drugs were perceived as "safer" by the general population. Synthetic cannabinoids cause effects similar to marijuana making the subjects euphoric. However, they act as full, rather than partial, agonist at the receptor sites causing more severe side effects such as severe agitation, seizures, acute renal failure, and lactic acidosis.

Screening renal stone formers for distal renal tubular acidosis

DEFF Research Database (Denmark)

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...... RTA in renal stone formers. Regardless of whether the acidification defect is primary or secondary to stone formation, however, all renal stone formers with distal RTA can expect to benefit from prophylactic alkaline therapy and it is recommended that the screening procedure, which is easy to use...

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

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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.

Pathophysiology, Clinical, and Therapeutic Aspects of Narcolepsy

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Pinar Guzel Ozdemir

2014-09-01

Full Text Available Narcolepsy is a lifelong sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucination, and sleep paralysis. The exact cause remains unknown, but there is significant evidence that hypocretin deficiency plays an integral role. There have been advances in the understanding of the pathogenesis of narcolepsy. It has a negative effect on the quality of life and can restrict the patients from certain careers and activities. Diagnosis relies on patient history and objective data gathered from polysomnography and multiple sleep latency testing. Treatment focuses on symptom relief through medication, education, and behavioral modification. Both classic pharmacological treatments as well as newer options have significant problems, especially because of side effects and abuse potential. Some novel modalities are being examined to expand options for treatment. In this review, the pathophysiological, clinical, and pharmacotherapeutic aspects of narcolepsy are discussed. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2014; 6(3.000: 271-283

Fluoxetine treatment abolishes the in vitro respiratory response to acidosis in neonatal mice.

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Voituron, Nicolas; Shvarev, Yuri; Menuet, Clément; Bevengut, Michelle; Fasano, Caroline; Vigneault, Erika; El Mestikawy, Salah; Hilaire, Gérard

2010-10-26

To secure pH homeostasis, the central respiratory network must permanently adapt its rhythmic motor drive to environment and behaviour. In neonates, it is commonly admitted that the retrotrapezoid/parafacial respiratory group of neurons of the ventral medulla plays the primary role in the respiratory response to acidosis, although the serotonergic system may also contribute to this response. Using en bloc medullary preparations from neonatal mice, we have shown for the first time that the respiratory response to acidosis is abolished after pre-treatment with the serotonin-transporter blocker fluoxetine (25-50 µM, 20 min), a commonly used antidepressant. Using mRNA in situ hybridization and immunohistology, we have also shown the expression of the serotonin transporter mRNA and serotonin-containing neurons in the vicinity of the RTN/pFRG of neonatal mice. These results reveal that the serotonergic system plays a pivotal role in pH homeostasis. Although obtained in vitro in neonatal mice, they suggest that drugs targeting the serotonergic system should be used with caution in infants, pregnant women and breastfeeding mothers.

Tuberculosis 2: Pathophysiology and microbiology of pulmonary ...

African Journals Online (AJOL)

2005-08-01

Aug 1, 2005 ... February 2013 Downloaded from www.southsudanmedicaljournal.com. MaIN arTIClES. 10. Tuberculosis 2: Pathophysiology and microbiology of pulmonary tuberculosis. Robert L. Serafino Wania MBBS, MrCP, MSc (Trop Med). Pathophysiology. Inhalation of Mycobacterium tuberculosis leads to one of.

Pathophysiology of cervical myelopathy.

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Baptiste, Darryl C; Fehlings, Michael G

2006-01-01

Cervical myelopathy is a group of closely related disorders usually caused by spondylosis or by ossification of the posterior longitudinal ligament and is characterized by compression of the cervical spinal cord or nerve roots by varying degrees and number of levels. The decrease in diameter of the vertebral canal secondary to disc degeneration and osteophytic spurs compresses the spinal cord and nerve roots at one or several levels, producing direct damage and often secondary ischemic changes. Clinicians who treat cervical myelopathy cord injuries should have a basic understanding of the pathophysiology and the processes that are initiated after the spinal cord has been injured. Literature review. Literature review of human cervical myelopathy and clinically relevant animal models to further our understanding of the pathological mechanisms involved. The pathophysiology of cervical myelopathy involves static factors, which result in acquired or developmental stenosis of the cervical canal and dynamic factors, which involve repetitive injury to the cervical cord. These mechanical factors in turn result in direct injury to neurons and glia as well as a secondary cascade of events including ischemia, excitotoxicity, and apoptosis; a pathobiology similar to that occurring in traumatic spinal cord injury. This review summarizes some of the significant pathophysiological processes involved in cervical myelopathy.

Acute respiratory acidosis and alkalosis – A modern quantitative interpretation

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Andraž Stožer

2014-03-01

Full Text Available Background: Three different approaches for assessing the acid-base status of a patient exist, i.e. the Boston, Copenhagen, and Stewart´s approach, and they employ different parameters to assess a given acid-base disturbance. Students, researchers, and clinicians are getting confused by heated debates about which of these performs best and by the fact that during their curricula, they typically get acquainted with one of the approaches only, which prevents them to understand sources employing other approaches and to critically evaluate the advantages and drawbacks of each approach. In this paper, the authors introduce and define the basic parameters characterizing each of the approaches and point out differences and similarities between them. Special attention is devoted to how the different approaches assess the degree of change in the concentration of plasma bicarbonate that occurs during primary respiratory changes; proper understanding of these is necessary to correctly interpret chronic respiratory and metabolic acid-base changes.Conclusion: During acute respiratory acidosis the concentration of bicarbonate rises and during acute respiratory alkalosis it falls, depending on the buffering strength of non-bicarbonate buffers. During acute respiratory acid-base disturbances, buffer base (employed by the Copenhagen approach, apparent and effective strong ion difference, as well as strong ion gap (employed by the Stewart approach remain unchanged; the anion gap (employed by the Boston and Copenhagen approach falls during acute respiratory acidosis and rises during acute respiratory alkalosis.

Transforming pathophysiology instruction through narrative pedagogy and Socratic questioning.

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Rogge, M M

2001-01-01

Pathophysiology, heavily content driven, has typically been taught through the use of traditional behavioral pedagogy and a reliance on the formal lecture. The author describes the limitations of this approach to teaching pathophysiology and describes the use of narrative pedagogy and Socratic questioning as alternative methods of instruction to augment lecture methods. Specific strategies for transforming traditional classroom teaching by using Socratic questions in a pathophysiology course for nurse practitioners are described. Student and faculty reactions to the initial efforts to transform pathophysiology instruction are also described.

Clinical manifestations and pathophysiology of lissencephaly

International Nuclear Information System (INIS)

Oi, Shizuo; Sasaki, Koji; Yamada, Hiroshi; Ando, Shoko; Tamura, Yasunori; Fukuda, Kuniaki; Furukawa, Seikyo; Matsumoto, Satoshi.

1985-01-01

Four cases of lissencephaly were analyzed in light of clinical manifestations, CT findings and the state of hydrocephalus. Lissencephaly had been diagnosed mainly by autopsy until CT scan was introduced in the early 1970's. Since then, diagnosis of lissencephaly early in life is possible. Presently the major interest in this congenital CNS anomaly, which is caused by a neuronal migration disorder in the relatively late stages of fetal development, is to learn the dynamic pathophysiological state and management. The purpose of this paper is to analyze those points of lissencephaly in diagnosis during life and possible treatment in the hydrocephalic state. The common findings in CT in all four cases are as follows: No. 1. smooth cortical surface (agyria--pachygyria), No. 2. wide sylvian fissure (complete or incomplete lack of opercularization, No. 3. ventricular dilatation (remarkable bilateral enlargement of lateral ventricle and third ventricle--colpocephaly), No. 4. wide subdural or subarachnoid space in supratentorial region, No. 5. periventricular low density, No. 6. midline cavum, No. 7. normal CT findings in posterior fossa structure. Three out of four patients demonstrated full or bulged and tense anterior fontanella. Because of this suggestion of increased intracranial pressure and enlarged ventricles with periventricular lucency in CT findings, one patient underwent CT cisternography for dynamic analysis of the CSF circulation and continuous ICP monitoring for dynamic evaluation of the ICP pattern. The results revealed very much delayed CSF circulation and intermittently increased. ICP, with pressure waves appearing in 35.7 % of all recordings. (J.P.N.)

Feline hyperparathyroidism: pathophysiology, diagnosis and treatment of primary and secondary disease.

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Parker, Valerie J; Gilor, Chen; Chew, Dennis J

2015-05-01

Hyperparathyroidism exists in primary and secondary forms. Primary hyperparathyroidism has typically been considered a disease that uncommonly affects cats, but this condition is more prevalent than previous diagnoses would suggest. Secondary hyperparathyroidism may be caused by either nutritional influences (ie, nutritional secondary hyperparathyroidism) or chronic kidney disease (ie, renal secondary hyperparathyroidism). Tertiary hyperparathyroidism has yet to be documented in veterinary medicine, but it is possible that this condition occurs in some cats following longstanding renal secondary hyperparathyroidism. Diagnosis of this group of calcium metabolic disorders presents a number of challenges for the clinician. For example, clinical signs can be non-specific and, especially in the case of primary hyperparathyroidism, there is often a low index of suspicion for the disease; careful sample handling is required for testing of parathyroid hormone (PTH) and ionized calcium levels; and there is currently no feline-specific assay for PTH, which has implications for test sensitivity and interpretation of results. This article briefly outlines PTH and calcium physiology by way of introduction to a review of PTH measurement and interpretation. Various forms of feline hyperparathyroidism are then described, encompassing diagnosis and treatment options. © ISFM and AAFP 2015.

Is lactic acidosis a cause of exercise induced hyperventilation at the respiratory compensation point?

OpenAIRE

Meyer, T; Faude, O; Scharhag, J; Urhausen, A; Kindermann, W

2004-01-01

Objectives: The respiratory compensation point (RCP) marks the onset of hyperventilation ("respiratory compensation") during incremental exercise. Its physiological meaning has not yet been definitely determined, but the most common explanation is a failure of the body's buffering mechanisms which leads to metabolic (lactic) acidosis. It was intended to test this experimentally.

Narcolepsy and Psychiatric Disorders: Comorbidities or Shared Pathophysiology?

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Anne Marie Morse

2018-02-01

Full Text Available Narcolepsy and psychiatric disorders have a significant but unrecognized relationship, which is an area of evolving interest, but unfortunately, the association is poorly understood. It is not uncommon for the two to occur co-morbidly. However, narcolepsy is frequently misdiagnosed initially as a psychiatric condition, contributing to the protracted time to accurate diagnosis and treatment. Narcolepsy is a disabling neurodegenerative condition that carries a high risk for development of social and occupational dysfunction. Deterioration in function may lead to the secondary development of psychiatric symptoms. Inversely, the development of psychiatric symptoms can lead to the deterioration in function and quality of life. The overlap in pharmaceutical intervention may further enhance the difficulty to distinguish between diagnoses. Comprehensive care for patients with narcolepsy should include surveillance for psychiatric illness and appropriate treatment when necessary. Further research is necessary to better understand the underlying pathophysiology between psychiatric disease and narcolepsy.

Mechanism of potassium depletion during chronic metabolic acidosis in the rat

International Nuclear Information System (INIS)

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

1987-01-01

Pair-fed rats on a normal K diet were given either 1.5% NH 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 4 Cl ingestion than in the control animals. Adrenalectomized rats were treated with either normal (4 μg/day) or high (22 μg/day) aldosterone replacement while ingesting NH 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

Systematic review of type-specific pathophysiological symptoms of Sasang typology

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Yoo Ri Han

2016-06-01

Full Text Available Previous studies on the Sasang typology have focused on the differential diagnosis of each Sasang type with type-specific pathophysiological symptoms (TSPS. The purpose of this study was to elucidate the latent physiological mechanism related to these clinical indicators. We searched six electronic databases for articles published from 1990 to 2015 using the Sasang typology-related keywords, and found and analyzed 35 such articles. The results were summarized into six TSPS categories: perspiration, temperature preference, sleep, defecation, urination, and susceptibility to stress. The Tae-Eum and So-Eum types showed contrasting features with TSPS, and the So-Yang type was in the middle. The Tae-Eum type has good digestive function, regular bowel movement and defecation, high sleep quality, and low susceptibility to stress and cold. The Tae-Eum type has relatively large volumes of sweat and feels fresh after sweating; however, the urine is highly concentrated. These clinical features might be related to the biopsychological traits of the Tae-Eum type, including a low trait anxiety level and high ponderal and body mass indices. This study used the autonomic reactivity hypothesis for explaining the pathophysiological predispositions in the Sasang typology. The Tae-Eum and So-Eum Sasang types have a low threshold in parasympathetic and sympathetic activation, respectively. This study provides a foundation for integrating traditional Korean personalized medicine and Western biomedicine.

[A young child with respiratory acidosis and hypoxia from mechanical ventilation with equipment made for adults].

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Joor, Fleur; Markhorst, Dick G; Kneyber, Martin C J; van Heerde, Marc

2011-01-01

During mechanical ventilation of young children, problems may arise due to the additional dead space of the ventilation circuit. This may lead to respiratory acidosis and even hypoxia in the child. A 3-month-old boy suffered from frequent apnoea. He was mechanically ventilated for this. Shortly after its initiation, he developed severe respiratory acidosis, hypoxemia and circulatory insufficiency. This was due to a large additional dead space caused by the use of equipment components made for adults. After he was switched to a circuit suitable for himself, he recovered rapidly. As a rule of thumb, an additional dead space of 1.5-2 ml/kg body weight is acceptable in young children. Emergency wards for young children should have specific equipment to mechanically ventilate them, and have a protocol paying explicit attention to the dead space.

Diagnosis of propionic acidemia by gas chromatography coupled to mass spectrometry in a case analysis

International Nuclear Information System (INIS)

Camayd Viera, Ivette; Robaina Jimenez, Zoe; Contreras Roura, Jiovanna

2011-01-01

Propionic acidemia is an inherited metabolic disease caused by a deficiency in the propionyl-CoA carboxilase, a biotin-dependent mitochondrial enzyme. The disorder is a clinically heterogeneous disease and one of the most frequently occurring organic acidurias. We report the first Cuban case with a severe form of propionic acidemia followed by acidosis and death. The diagnosis was carried out by gas chromatography coupled to mass spectrometry. Our aim is to highlight the importance of organic acids urine analysis as part of the first laboratory tests in undiagnosed seriously ill children. The definitive diagnosis is important as it serves as a clear guideline to establish a suitable treatment and allows geneticists to provide patients with a proper genetic counseling

Anorexia nervosa and chronic renal insufficiency: a prescription for disaster.

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Luthra, M; Davids, M R; Shafiee, M A; Halperin, M L

2004-03-01

Our imaginary consultant, Professor McCance, is asked to explain the basis for four major acute electrolyte abnormalities in a young woman with long-standing anorexia nervosa. She has a severe degree of hypokalaemia (2.0 mmol/l) with renal potassium wasting, a contracted extracellular fluid volume with renal NaCl wasting, hyponatraemia (118 mmol/l) while excreting hypoosmolar urine, and metabolic acidosis with a normal plasma anion gap (pH 7.20, bicarbonate 9 mmol/l). McCance begins his discussion by considering the basis for hypokalaemia, as this electrolyte disorder is potentially life-threatening. Its pathophysiology is linked to the other major findings, using principles of integrative physiology together with a deductive and quantitative analysis. Nevertheless, to reach his final diagnosis, he requires information about newer molecular discoveries. Not only is he able to suggest a likely diagnosis, but he also devises a novel long-term plan for therapy.

Distal renal tubular acidosis and quadriparaesis in Sjögren′s syndrome: A cunning congregate

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Arundhati G Diwan

2014-01-01

Full Text Available Sjögren′s syndrome (SS is a chronic autoimmune disease, chiefly affecting the exocrine glandular function of salivary glands and lacrimal glands. Rarely, it involves the kidneys, central and peripheral nervous system, muscloskeletal apparatus and lungs. We report a rare constellation of SS with distal renal tubular acidosis and quadriparaesis in a young female. History of quadriparaesis was acute, with rapid progression. Supplementary treatment for severe hypokalemia was instituted at the earliest, lest the patient develop respiratory muscle weakness. Concomitantly, metabolic acidosis with alkaline urine was suspected and subsequently investigated. Eventually, this was attributed to impaired renal acidification of urine in the distal tubules. History of dryness of eyes and mouth since 6 months justified salivary gland biopsy. The results yielded a lymphocytic infiltrative pathology strongly favoring SS. The patient benefited from prompt potassium replacement therapy and had complete resolution over the next week. Supportive treatment for predictable manifestations was continued along with potassium supplements.

Lactate levels and risk of lactic acidosis with metformin in diabetic kidney disease patients

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P K Bipi

2017-01-01

Full Text Available Metformin as an oral antidiabetic drug (OAD is not recommended in renal failure due to the presumed risk of lactic acidosis though it has advantages in cardiovascular protection with a low risk of hypoglycemia. Few studies have measured lactic acid blood levels in patients with diabetic kidney disease on metformin and demonstrated lactic acidosis. The aim of our study is to see if patients with diabetic kidney disease are at risk of elevated lactate blood levels and lactic acidosis. Lactate levels and blood pH were estimated in patients with type 2 diabetes mellitus receiving metformin in different stages of chronic kidney disease (CKD and were compared with a similar group not receiving metformin. Patients with diabetic kidney disease, with estimated glomerular filtration rate <60 mL/min who were previously receiving metformin started in centers elsewhere and referred here were studied and compared with a similar group taking other OADs or insulin. Independent sample t-test or ANOVA were used to compare quantitative variables between groups. Pearson correlation was used to analyze association between quantitative variables and linear regression analysis and was employed to note the relationship between quantitative variables. Of 57 patients who received a mean dose of 1.134 grams of metformin, 33 (55.9% were in stage 3, 16 (28.1% in stage 4, and 8 (14% in stage 5 CKD. Mean serum pH (P = 0.572, bicarbonate (P = 0.978, and plasma lactate (P = 0.449 levels in those taking and not taking metformin were comparable. There was no difference in the plasma lactate levels in different stages of CKD in the metformin group (P = 0.498 although there was significant correlation with metformin dose (P <0.05. Blood lactate levels were not elevated in patients with diabetic kidney disease at a daily dose of metformin <1 g.

Sodium bicarbonate use and the risk of hypernatremia in thoracic aortic surgical patients with metabolic acidosis following deep hypothermic circulatory arrest

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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.

Successful management of drug-induced hypercapnic acidosis with naloxone and noninvasive positive pressure ventilation.

Science.gov (United States)

Agrafiotis, Michalis; Tryfon, Stavros; Siopi, Demetra; Chassapidou, Georgia; Galanou, Artemis; Tsara, Venetia

2015-02-01

A 74-year-old man was referred to our hospital due to deteriorating level of consciousness and desaturation. His Glasgow Coma Scale was 6, and his pupils were constricted but responded to light. Chest radiograph was negative for significant findings. Arterial blood gas evaluation on supplemental oxygen revealed severe acute on chronic respiratory acidosis: pH 7.15; PCO2, 133 mm Hg; PO2,64 mm Hg; and HCO3, 31 mmol/L. He regained full consciousness (Glasgow Coma Scale, 15) after receiving a 0.4 mg dose of naloxone, but because of persistent severe respiratory acidosis (pH 7.21; PCO2, 105 mm Hg), he was immediately commenced on noninvasive positive pressure ventilation (NIV) displaying a remarkable improvement in arterial blood gas values within the next few hours. However, in the days that followed, he remained dependent on NIV, and he was finally discharged on a home mechanical ventilation prescription. In cases of drug-induced respiratory depression, NIV should be regarded as an acceptable treatment, as it can provide ventilatory support without the increased risks associated with invasive mechanical ventilation.

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

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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.

Cardiorenal Syndrome: Diagnosis and Treatment

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O.O. Melnyk

2017-02-01

Full Text Available In the diagnosis of cardiorenal syndrome (CRS, the biological markers are widely used, they can be applied to identify the pathophysiological stages of CRS, to assess the amount of risk, prognosis and outcome, as well as to monitor the effectiveness of treatment. CRS therapy includes diuretics, vasodilators, angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, nitrates and cardiac glycosides. One of the most effective methods of CRS treatment is the use of renal replacement therapy.

Value of point-of-care ketones in assessing dehydration and acidosis in children with gastroenteritis.

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Levy, Jason A; Waltzman, Mark; Monuteaux, Michael C; Bachur, Richard G

2013-11-01

Children with gastroenteritis often develop dehydration with metabolic acidosis. Serum ketones are frequently elevated in this population. The goal was to determine the relationship between initial serum ketone concentration and both the degree of dehydration and the magnitude of acidosis. This was a secondary analysis of a prospective trial of crystalloid administration for rapid rehydration. Children 6 months to 6 years of age with gastroenteritis and dehydration were enrolled. A point-of-care serum ketone (beta-hydroxybutyrate) concentration was obtained at the time of study enrollment. The relationship between initial serum ketone concentration and a prospectively assigned and previously validated clinical dehydration score, and serum bicarbonate concentration, was analyzed. A total of 188 patients were enrolled. The median serum ketone concentration was elevated at 3.1 mmol/L (interquartile range [IQR] = 1.2 to 4.6 mmol/L), and the median dehydration score was consistent with moderate dehydration. A significant positive relationship was found between serum ketone concentration and the clinical dehydration score (Spearman's rho = 0.22, p = 0.003). Patients with moderate dehydration had a higher median serum ketone concentration than those with mild dehydration (3.6 mmol/L vs. 1.4 mmol/L, p = 0.007). Additionally, the serum ketone concentration was inversely correlated with serum bicarbonate concentration (ρ = -0.26, p Children with gastroenteritis and dehydration have elevated serum ketone concentrations that correlate with both degree of dehydration and magnitude of metabolic acidosis. Point-of-care serum ketone measurement may be a useful tool to inform management decisions at the point of triage or in the initial evaluation of children with gastroenteritis and dehydration. © 2013 by the Society for Academic Emergency Medicine.

Variation of bacterial communities and expression of Toll-like receptor genes in the rumen of steers differing in susceptibility to subacute ruminal acidosis.

Science.gov (United States)

Chen, Yanhong; Oba, Masahito; Guan, Le Luo

2012-10-12

In order to determine differences in the ruminal bacterial community and host Toll-like receptor (TLR) gene expression of beef cattle with different susceptibility to acidosis, rumen papillae and content were collected from acidosis-susceptible (AS, n=3) and acidosis-resistant (AR, n=3) steers. The ruminal bacterial community was characterized using PCR-denaturing gradient gel electrophoresis (PCR-DGGE) and quantitative real time PCR (qRT-PCR) analysis. Global R analysis of bacterial profile similarity revealed that bacterial diversity was significantly different between AR and AS groups for both rumen content (P=0.001) and epithelial (P=0.002) communities. The copy number of total bacterial 16S rRNA genes in content of AS steers was 10-fold higher than that of AR steers, and the copy number of total 16S rRNA genes of epimural bacteria in AR steers was positively correlated with ruminal pH (r=0.59, P=0.04), and negatively correlated with total VFA concentration (r=-0.59, P=0.05). The expressions of host TLR2 and 4 genes were significantly higher in AR steers compared to those in AS steers. These findings enhance our understanding about the ruminal microbial ecology and host gene expression changes that may be useful in the prevention of ruminal acidosis. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of lung protective mechanical ventilation associated with permissive respiratory acidosis on regional extra-pulmonary blood flow in experimental ARDS.

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Hering, Rudolf; Kreyer, Stefan; Putensen, Christian

2017-10-27

Lung protective mechanical ventilation with limited peak inspiratory pressure has been shown to affect cardiac output in patients with ARDS. However, little is known about the impact of lung protective mechanical ventilation on regional perfusion, especially when associated with moderate permissive respiratory acidosis. We hypothesized that lung protective mechanical ventilation with limited peak inspiratory pressure and moderate respiratory acidosis results in an increased cardiac output but unequal distribution of blood flow to the different organs of pigs with oleic-acid induced ARDS. Twelve pigs were enrolled, 3 died during instrumentation and induction of lung injury. Thus, 9 animals received pressure controlled mechanical ventilation with a PEEP of 5 cmH 2 O and limited peak inspiratory pressure (17 ± 4 cmH 2 O) versus increased peak inspiratory pressure (23 ± 6 cmH 2 O) in a crossover-randomized design and were analyzed. The sequence of limited versus increased peak inspiratory pressure was randomized using sealed envelopes. Systemic and regional hemodynamics were determined by double indicator dilution technique and colored microspheres, respectively. The paired student t-test and the Wilcoxon test were used to compare normally and not normally distributed data, respectively. Mechanical ventilation with limited inspiratory pressure resulted in moderate hypercapnia and respiratory acidosis (PaCO 2 71 ± 12 vs. 46 ± 9 mmHg, and pH 7.27 ± 0.05 vs. 7.38 ± 0.04, p respiratory acidosis was associated with an increase in cardiac output. However, the better systemic blood flow was not uniformly directed to the different organs. This observation may be of clinical interest in patients, e.g. with cardiac, renal and cerebral pathologies.

Regional anesthesia is safe and effective for lower limb orthopedic surgery in patient with renal tubular acidosis and hypokalemia

Directory of Open Access Journals (Sweden)

Indira Gurajala

2018-01-01

Full Text Available Renal tubular acidosis (RTA with hypokalemia may precipitate acute respiratory failure and potentially fatal arrhythmias like ventricular fibrillation. Though there are random reports of respiratory failure needing mechanical ventilation and sudden death in patients with RTA and hypokalemia, the anesthetic management of these patients has not been clearly elucidated. Acidosis and hypokalemia have significant interactions with both general and local anesthetics and alter their effect substantially. Proper preoperative planning and optimization are required for the safe conduct of anesthesia in this subset of patients. We describe a case of distal RTA, hypokalemia, and metabolic bone disease in whom central neuraxial anesthesia was effectively used for lower limb orthopedic surgery with no complications.

Citrate metabolism and its complications in non-massive blood transfusions: association with decompensated metabolic alkalosis+respiratory acidosis and serum electrolyte levels.

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Bıçakçı, Zafer; Olcay, Lale

2014-06-01

Metabolic alkalosis, which is a non-massive blood transfusion complication, is not reported in the literature although metabolic alkalosis dependent on citrate metabolism is reported to be a massive blood transfusion complication. The aim of this study was to investigate the effect of elevated carbon dioxide production due to citrate metabolism and serum electrolyte imbalance in patients who received frequent non-massive blood transfusions. Fifteen inpatients who were diagnosed with different conditions and who received frequent blood transfusions (10-30 ml/kg/day) were prospectively evaluated. Patients who had initial metabolic alkalosis (bicarbonate>26 mmol/l), who needed at least one intensive blood transfusion in one-to-three days for a period of at least 15 days, and whose total transfusion amount did not fit the massive blood transfusion definition (alkalosis+respiratory acidosis developed as a result of citrate metabolism. There was a positive correlation between cumulative amount of citrate and the use of fresh frozen plasma, venous blood pH, ionized calcium, serum-blood gas sodium and mortality, whereas there was a negative correlation between cumulative amount of citrate and serum calcium levels, serum phosphorus levels and amount of urine chloride. In non-massive, but frequent blood transfusions, elevated carbon dioxide production due to citrate metabolism causes intracellular acidosis. As a result of intracellular acidosis compensation, decompensated metabolic alkalosis+respiratory acidosis and electrolyte imbalance may develop. This situation may contribute to the increase in mortality. In conclusion, it should be noted that non-massive, but frequent blood transfusions may result in certain complications. Copyright © 2014 Elsevier Ltd. All rights reserved.

Correction of metabolic acidosis with potassium citrate in renal transplant patients and its effect on bone quality.

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Starke, Astrid; Corsenca, Alf; Kohler, Thomas; Knubben, Johannes; Kraenzlin, Marius; Uebelhart, Daniel; Wüthrich, Rudolf P; von Rechenberg, Brigitte; Müller, Ralph; Ambühl, Patrice M

2012-09-01

Acidosis and transplantation are associated with increased risk of bone disturbances. This study aimed to assess bone morphology and metabolism in acidotic patients with a renal graft, and to ameliorate bone characteristics by restoration of acid/base homeostasis with potassium citrate. This was a 12-month controlled, randomized, interventional trial that included 30 renal transplant patients with metabolic acidosis (S-[HCO(3)(-)] 24 mmol/L, or potassium chloride (control group). Iliac crest bone biopsies and dual-energy X-ray absorptiometry were performed at baseline and after 12 months of treatment. Bone biopsies were analyzed by in vitro micro-computed tomography and histomorphometry, including tetracycline double labeling. Serum biomarkers of bone turnover were measured at baseline and study end. Twenty-three healthy participants with normal kidney function comprised the reference group. Administration of potassium citrate resulted in persisting normalization of S-[HCO(3)(-)] versus potassium chloride. At 12 months, bone surface, connectivity density, cortical thickness, and cortical porosity were better preserved with potassium citrate than with potassium chloride, respectively. Serological biomarkers and bone tetracycline labeling indicate higher bone turnover with potassium citrate versus potassium chloride. In contrast, no relevant changes in bone mineral density were detected by dual-energy X-ray absorptiometry. Treatment with potassium citrate in renal transplant patients is efficient and well tolerated for correction of metabolic acidosis and may be associated with improvement in bone quality. This study is limited by the heterogeneity of the investigated population with regard to age, sex, and transplant vintage.

Oxidative response of neutrophils to platelet-activating factor is altered during acute ruminal acidosis induced by oligofructose in heifers.

Science.gov (United States)

Concha, Claudia; Carretta, María Daniella; Alarcón, Pablo; Conejeros, Ivan; Gallardo, Diego; Hidalgo, Alejandra Isabel; Tadich, Nestor; Cáceres, Dante Daniel; Hidalgo, María Angélica; Burgos, Rafael Agustín

2014-01-01

Reactive oxygen species (ROS) production is one of the main mechanisms used to kill microbes during innate immune response. D-lactic acid, which is augmented during acute ruminal acidosis, reduces platelet activating factor (PAF)-induced ROS production and L-selectin shedding in bovine neutrophils in vitro. This study was conducted to investigate whether acute ruminal acidosis induced by acute oligofructose overload in heifers interferes with ROS production and L-selectin shedding in blood neutrophils. Blood neutrophils and plasma were obtained by jugular venipuncture, while ruminal samples were collected using rumenocentesis. Lactic acid from plasma and ruminal samples was measured by HPLC. PAF-induced ROS production and L-selectin shedding were measured in vitro in bovine neutrophils by a luminol chemiluminescence assay and flow cytometry, respectively. A significant increase in ruminal and plasma lactic acid was recorded in these animals. Specifically, a decrease in PAF-induced ROS production was observed 8 h after oligofructose overload, and this was sustained until 48 h post oligofructose overload. A reduction in PAF-induced L-selectin shedding was observed at 16 h and 32 h post oligofructose overload. Overall, the results indicated that neutrophil PAF responses were altered in heifers with ruminal acidosis, suggesting a potential dysfunction of the innate immune response.

Epimural Indicator Phylotypes of Transiently-Induced Subacute Ruminal Acidosis in Dairy Cattle

OpenAIRE

Wetzels, Stefanie U.; Mann, Evelyne; Metzler-Zebeli, Barbara U.; Pourazad, Poulad; Qumar, Muhammad; Klevenhusen, Fenja; Pinior, Beate; Wagner, Martin; Zebeli, Qendrim; Schmitz-Esser, Stephan

2016-01-01

The impact of a long-term subacute rumen acidosis (SARA) on the bovine epimural bacterial microbiome (BEBM) and its consequences for rumen health is poorly understood. This study aimed to investigate shifts in the BEBM during a long-term transient SARA model consisting of two concentrate-diet-induced SARA challenges separated by a 1-week challenge break. Eight cows were fed forage and varying concentrate amounts throughout the experiment. In total, 32 rumen papilla biopsies were taken for DNA...

Headache attributed to airplane travel: diagnosis, pathophysiology, and treatment - a systematic review.

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Bui, Sebastian Bao Dinh; Gazerani, Parisa

2017-08-16

Headache attributed to airplane travel, also named "airplane headache" (AH) is a headache that occurs during take-off and landing. Today, there are still uncertainties about the pathophysiology and treatment of AH. This systematic review was performed to facilitate identification of the existing literature on AH in order to discuss the current evidence and areas that remain to be investigated in AH. The systematic literature search was performed in 3 relevant medical databases; PubMed, Scopus, and Embase. The search yielded 220 papers and the papers were sorted based on inclusion and exclusion criteria established for this study. This systematic review included 39 papers. Main findings revealed that AH attacks are clinically stereotyped and appear mostly during landing phases. The headache presents as a severe painful headache that often disappears within 30 min. The pain is unilateral and localized in the fronto-orbital region. Sinus barotrauma has been considered as the main cause of AH. Nonsteroidal anti-inflammatory drugs and triptans have been taken by passengers with AH, to relieve the headache. Based on this systematic review, further studies seem required to investigate underlying mechanisms in AH and also to investigate the biological effects of nonsteroidal anti-inflammatory drugs and triptans for alleviating of AH. These studies would advance our understanding of AH pathogenesis and potential use of treatments that are not yet established.

Biomarkers identified by urinary metabonomics for noninvasive diagnosis of nutritional rickets.

Science.gov (United States)

Wang, Maoqing; Yang, Xue; Ren, Lihong; Li, Songtao; He, Xuan; Wu, Xiaoyan; Liu, Tingting; Lin, Liqun; Li, Ying; Sun, Changhao

2014-09-05

Nutritional rickets is a worldwide public health problem; however, the current diagnostic methods retain shortcomings for accurate diagnosis of nutritional rickets. To identify urinary biomarkers associated with nutritional rickets and establish a noninvasive diagnosis method, urinary metabonomics analysis by ultra-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis were employed to investigate the metabolic alterations associated with nutritional rickets in 200 children with or without nutritional rickets. The pathophysiological changes and pathogenesis of nutritional rickets were illustrated by the identified biomarkers. By urinary metabolic profiling, 31 biomarkers of nutritional rickets were identified and five candidate biomarkers for clinical diagnosis were screened and identified by quantitative analysis and receiver operating curve analysis. Urinary levels of five candidate biomarkers were measured using mass spectrometry or commercial kits. In the validation step, the combination of phosphate and sebacic acid was able to give a noninvasive and accurate diagnostic with high sensitivity (94.0%) and specificity (71.2%). Furthermore, on the basis of the pathway analysis of biomarkers, our urinary metabonomics analysis gives new insight into the pathogenesis and pathophysiology of nutritional rickets.

Severe metabolic alkalosis, hypokalemia, and respiratory acidosis induced by the Chinese herbal medicine yokukansan in an elderly patient with muscle weakness and drowsiness.

Science.gov (United States)

Yamada, Shunsuke; Tokumoto, Masanori; Kansui, Yasuo; Wakisaka, Yoshinobu; Uchizono, Yuji; Tsuruya, Kazuhiko; Ooboshi, Hiroaki

2013-05-01

Yokukansan is a Chinese herbal medicine containing licorice that has been shown to alleviate the behavioral and psychological symptoms of Alzheimer's disease, with few adverse effects. Increasing numbers of patients with Alzheimer's disease in Japan are now being treated with this drug. However, yokukansan should be used with caution because of its potential to induce pseudoaldosteronism through the inhibition of 11-beta-hydroxysteroid dehydrogenase type 2, which metabolizes cortisol into cortisone. We present the case of an 88-year-old woman with a history of Alzheimer's disease who was transferred to our emergency department because of drowsiness, anorexia, and muscle weakness. Her blood pressure was 168/90 mmHg. Laboratory data showed serum potassium of 1.9 mmol/l, metabolic alkalosis (pH 7.54; HCO 3 - , 50.5 mmol/l; chloride, 81 mmol/l; sodium, 140 mmol/l), and respiratory disorders (pCO 2 , 60.5 mmHg; pO 2 , 63.8 mmHg). Plasma renin activity and aldosterone concentration were suppressed, and urinary potassium excretion was 22 mmol/l (calculated transtubular potassium gradient 12.9). An electrocardiogram showed flat T-waves and U-waves with ventricular premature contractions. Echocardiography denied volume depletion. Medical interview disclosed that she had been treated with a Chinese herbal medicine (yokukansan) containing licorice. The final diagnosis was pseudoaldosteronism and respiratory acidosis induced by licorice. Hypokalemia, metabolic alkalosis, and respiratory acidosis all subsided shortly after the discontinuation of yokukansan and initiation of intravenous potassium replacement. This case highlights the need for nephrologists to consider the possible involvement of Chinese herbal medicines, including yokukansan, when they encounter hypokalemia in elderly patients.

Clinical Presentation and Diagnosis of Neuroendocrine Tumors.

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Vinik, Aaron I; Chaya, Celine

2016-02-01

Neuroendocrine tumors (NETs) are slow-growing neoplasms capable of storing and secreting different peptides and neuroamines. Some of these substances cause specific symptom complexes, whereas others are silent. They usually have episodic expression, and the diagnosis is often made at a late stage. Although considered rare, the incidence of NETs is increasing. For these reasons, a high index of suspicion is needed. In this article, the different clinical syndromes and the pathophysiology of each tumor as well as the new and emerging biochemical markers and imaging techniques that should be used to facilitate an early diagnosis, follow-up, and prognosis are reviewed. Copyright © 2016 Elsevier Inc. All rights reserved.

Current concepts in the pathophysiology of glaucoma

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Agarwal Renu

2009-01-01

Full Text Available Glaucoma, the second leading cause of blindness, is characterized by changes in the optic disc and visual field defects. The elevated intraocular pressure was considered the prime factor responsible for the glaucomatous optic neuropathy involving death of retinal ganglion cells and their axons. Extensive investigations into the pathophysiology of glaucoma now reveal the role of multiple factors in the development of retinal ganglion cell death. A better understanding of the pathophysiological mechanisms involved in the onset and progression of glaucomatous optic neuropathy is crucial in the development of better therapeutic options. This review is an effort to summarize the current concepts in the pathophysiology of glaucoma so that newer therapeutic targets can be recognized. The literature available in the National Medical Library and online Pubmed search engine was used for literature review.

[Sleep apnea and heart failure: pathophysiology, diagnosis and therapy].

Science.gov (United States)

Monda, Cinzia; Scala, Oriana; Paolillo, Stefania; Savarese, Gianluigi; Cecere, Milena; D'Amore, Carmen; Parente, Antonio; Musella, Francesca; Mosca, Susanna; Filardi, Pasquale Perrone

2010-11-01

Sleep apnea, defined as a pathologic pause in breathing during sleep >10 s, promotes the progression of chronic heart failure and may be a predictor of poor prognosis. It causes, in fact, several mechanical, hemodynamic, chemical and inflammatory changes that negatively compromise cardiovascular homeostasis of heart failure patients. Sleep apnea is recognized as sleep apnea syndrome when specific symptoms, such as sleepiness and headache during the daytime and snoring, are present and is diagnosed with an overnight test called polysomnography. There are two different forms of sleep apnea, central and obstructive. Breathing is interrupted by the loss of respiratory drive and the lack of respiratory effort in the central form, which affects about 40-60% of heart failure patients. In obstructive sleep apnea, breathing stops when throat muscles relax, despite respiratory effort. This form affects about 3% of the general population, while it is present in at least 30% of heart failure patients. The diagnosis of sleep disorders in heart failure becomes very important to help patients adopting lifestyle changes and starting specific therapies to improve quality of life and retard the progression of chronic heart failure.

The pathophysiology of Peyronie's disease.

Science.gov (United States)

El-Sakka, Ahmed I; Salabas, Emre; Dinçer, Murat; Kadioglu, Ates

2013-09-01

To review the contemporary knowledge of the pathophysiology of Peyronie's disease (PD). Medline was searched for papers published in English from 2000 to March 2013, using the keywords 'Peyronie's disease' and 'pathophysiology'. More than 300 relevant articles were identified for the purpose of this review. Unfortunately only a few studies had a high level of evidence, and the remaining studies were not controlled in their design. Many theories have been proposed to explain the cause of PD, but the true pathogenesis of PD remains an enigma. Identifying particular growth factors and the specific genes responsible for the induction of PD have been the ultimate goal of research over the past several decades. This would provide the means to devise a possible gene therapy for this devastating condition. We discuss present controversies and new discoveries related to the pathophysiology of this condition. PD is one of the most puzzling diseases in urology. The pathogenesis remains uncertain and there is still controversy about the best management. The pathogenesis of PD has been explored in animal models, cell cultures and clinical trials, but the results have led to further questions. New research on the aetiology and pathogenesis of PD is needed, and which will hopefully improve the understanding and management for patients with this frustrating disease.

A vicious circle in chronic lymphoedema pathophysiology?

DEFF Research Database (Denmark)

Cucchi, F; Rossmeislova, L; Simonsen, L

2017-01-01

Chronic lymphoedema is a disease caused by a congenital or acquired damage to the lymphatic system and characterized by complex chains of pathophysiologic events such as lymphatic fluid stasis, chronic inflammation, lymphatic vessels impairment, adipose tissue deposition and fibrosis. These event....... Together, these observations indicate strong reciprocal relationship between lymphatics and adipose tissue and suggest a possible key role of the adipocyte in the pathophysiology of chronic lymphoedema's vicious circle....

Urinary Tract Infections in Pregnancy - Diagnosis, Treatment and Prevention

OpenAIRE

Figueiredo, A; Gomes, G; Campos, A

2012-01-01

Objectives: Literature review of classification, epidemiology, pathophysiology, microbiology, clinical presentation, diagnosis, complications, treatment and prevention of urinary tract infections (UTI) in pregnancy. Data Sources and Review Methods: Bibliographic research in Medline, through PubMed and Medscape, of systematic reviews, observational studies, clinical guidelines, meta-analyses and randomized controlled trials published between January 1992 and December 2010. Results: Asymp...

Whole-exome sequencing as a diagnostic tool for distal renal tubular acidosis

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Paula Cristina Barros Pereira

2015-11-01

Full Text Available Objective: Distal renal tubular acidosis (dRTA is characterized by metabolic acidosis due to impaired renal acid excretion. The aim of this study was to demonstrate the genetic diagnosis of four children with dRTA through use of whole-exome sequencing. Methods: Two unrelated families were selected; a total of four children with dRTA and their parents, in order to perform whole-exome sequencing. Hearing was preserved in both children from the first family, but not in the second, wherein a twin pair had severe deafness. Whole-exome sequencing was performed in two pooled samples and findings were confirmed with Sanger sequencing method. Results: Two mutations were identified in the ATP6V0A4 and ATP6V1B1 genes. In the first family, a novel mutation in the exon 13 of the ATP6V0A4 gene with a single nucleotide change GAC → TAC (c.1232G>T was found, which caused a substitution of aspartic acid to tyrosine in position 411. In the second family, a homozygous recurrent mutation with one base-pair insertion (c.1149_1155insC in exon 12 of the ATP6V1B1 gene was detected. Conclusion: These results confirm the value of whole-exome sequencing for the study of rare and complex genetic nephropathies, allowing the identification of novel and recurrent mutations. Furthermore, for the first time the application of this molecular method in renal tubular diseases has been clearly demonstrated. Resumo: Objetivo: A acidose tubular renal distal (ATRd é caracterizada por acidose metabólica devido a excreção renal de ácido prejudicada. O objetivo deste artigo é apresentar o diagnóstico genético de quatro crianças com ATRd utilizando o sequenciamento total do exoma. Métodos: Selecionamos duas famílias não relacionadas, totalizando quatro crianças com ATRd e seus pais, para realizar o sequenciamento total do exoma. A audição foi preservada em ambas as crianças da família um, porém em nenhuma criança da família dois, na qual um par de gêmeas teve

Respiratory signaling of locus coeruleus neurons during hypercapnic acidosis in the bullfrog, Lithobates catesbeianus.

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Santin, J M; Hartzler, L K

2013-02-01

The locus coeruleus (LC) in the brainstem senses alterations in CO(2)/pH and influences ventilatory adjustments that restore blood gas values to starting levels in bullfrogs (Lithobates catesbeianus). We hypothesized that neurons of the bullfrog LC are sensitive to changes in CO(2)/pH and that chemosensitive responses are intrinsic to individual neurons. In addition, we hypothesized putative respiratory control neurons of the bullfrog LC would be stimulated by hypercapnic acidosis within physiological ranges of P(CO(2))/pH. 84% of LC neurons depolarized and increased firing rates during exposure to hypercapnic acidosis (HA). A pH dose response curve shows LC neurons from bullfrogs increase firing rates during physiologically relevant CO(2)/pH changes. With chemical synapses blocked, half of chemosensitive neurons lost sensitivity to HA; however, gap junction blockade did not alter chemosensitive responses. Intrinsically chemosensitive neurons increased input resistance during HA. These data demonstrate that majority of neurons within the bullfrog LC elicit robust firing responses during physiological ΔCO(2)/pH, likely enabling adjustment of acid-base balance through breathing. Copyright © 2012 Elsevier B.V. All rights reserved.

Chloride content of solutions used for regional citrate anticoagulation might be responsible for blunting correction of metabolic acidosis during continuous veno-venous hemofiltration.

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Jacobs, Rita; Honore, Patrick M; Diltoer, Marc; Spapen, Herbert D

2016-08-26

Citrate, the currently preferred anticoagulant for continuous veno-venous hemofiltration (CVVH), may influence acid-base equilibrium. The effect of 2 different citrate solutions on acid-base status was assessed according to the Stewart-Figge approach in two consecutive cohorts of critically ill adult patients. The first group received Prismocitrate 10/2 (PC10/2; 10 mmol citrate/L). The next group was treated with Prismocitrate 18/0 (PC18; 18 mmol citrate/L). Both groups received bicarbonate-buffered fluids in post-dilution. At similar citrate flow, the metabolic acidosis present at baseline in both groups was significantly attenuated in PC18 patients but persisted in PC10/2 patients after 24 h of treatment (median pH 7,42 vs 7,28; p = 0.0001). Acidosis in the PC10/2 group was associated with a decreased strong ion difference and an increased strong ion gap (respectively 43 vs. 51 mmol/L and 17 vs. 12 mmol/L, PC10/2 vs. PC18; both p = 0.001). Chloride flow was higher in PC10/2 than in PC18 subjects (25.9 vs 14.3 mmol/L blood; p < 0.05). Correction of acidosis was blunted in patients who received 10 mmol citrate/L as regional anticoagulation during CVVH. This could be explained by differences in chloride flow between the applied citrate solutions inducing hyperchloremic acidosis.

Gaucher Disease: The Metabolic Defect, Pathophysiology, Phenotypes And Natural History

Science.gov (United States)

Baris, Hagit N.; Cohen, Ian J.; Mistry, Pramod K.

2015-01-01

Gaucher disease (GD), a prototype lysosomal storage disorder, results from inherited deficiency of lysosomal glucocerebrosidase due to biallelic mutations in GBA. The result is widespread accumulation of macrophages engorged with predominantly lysosomal glucocerebroside. A complex multisystem phenotype arises involving the liver, spleen, bone marrow and occasionally the lungs in type 1 Gaucher disease; in neuronopathic fulminant type 2 and chronic type 3 disease there is in addition progressive neurodegenerative disease. Manifestations of Gaucher disease type 1 (GD1) include hepatosplenomegaly, cytopenia, a complex pattern of bone involvement with avascular osteonecrosis (AVN), osteoporosis, fractures and lytic lesions. Enzyme replacement therapy became the standard of care in 1991, and this has transformed the natural history of GD1. This article reviews the clinical phenotypes of GD, diagnosis, pathophysiology and its natural history. A subsequent chapter discusses the treatment options. PMID:25345088

Obesity: Pathophysiology and Intervention

Directory of Open Access Journals (Sweden)

Yi Zhang

2014-11-01

Full Text Available Obesity presents a major health hazard of the 21st century. It promotes co-morbid diseases such as heart disease, type 2 diabetes, obstructive sleep apnea, certain types of cancer, and osteoarthritis. Excessive energy intake, physical inactivity, and genetic susceptibility are main causal factors for obesity, while gene mutations, endocrine disorders, medication, or psychiatric illnesses may be underlying causes in some cases. The development and maintenance of obesity may involve central pathophysiological mechanisms such as impaired brain circuit regulation and neuroendocrine hormone dysfunction. Dieting and physical exercise offer the mainstays of obesity treatment, and anti-obesity drugs may be taken in conjunction to reduce appetite or fat absorption. Bariatric surgeries may be performed in overtly obese patients to lessen stomach volume and nutrient absorption, and induce faster satiety. This review provides a summary of literature on the pathophysiological studies of obesity and discusses relevant therapeutic strategies for managing obesity.

Atropine use may lead to post-operative respiratory acidosis in neonates receiving ductal ligation: A retrospective cohort study.

Science.gov (United States)

Chang, Szu-Ling; Lin, Wen-Li; Weng, Chien-Hsiang; Wu, Shye-Jao; Tsai, Hsin-Jung; Wang, Shwu-Meei; Peng, Chun-Chih; Chang, Jui-Hsing

2018-04-01

Patent ductus arteriosus (PDA) is one of the most common cardiac conditions in preterm infants. Closure of the PDA in symptomatic patients can be achieved medically or surgically. Atropine is commonly administered in general anesthesia as a premedication in this age group but with limited evidence addressing the effect of its use. Our study examined the association of the use of atropine as a premedication in PDA ligation and the risk of post-operative respiratory complications. This retrospective cohort study included 150 newborns who have failed medical treatment for PDA and received PDA ligation during 2008-2012 in a single tertiary medical center. Ninety-two of them (61.3%) received atropine as premedication for general anesthesia while 58 (38.7%) did not. Post-operative respiratory condition, the need of cardiopulmonary resuscitation and the presence of bradycardia were measured. Patients with atropine use were associated with increased odds of respiratory acidosis in both univariate analysis (22.9% vs 7.3%; OR = 3.785, 95% CI = 1.211-11.826, p = 0.022) and multivariate analysis (OR = 4.030, 95% CI = 1.230-13.202, p = 0.021), with an even higher odds of respiratory acidosis in patients receiving both atropine and ketamine. The use of atropine as premedication in general anesthesia for neonatal PDA ligation is associated with higher risk of respiratory acidosis, which worsens with the combined use of ketamine. Copyright © 2017. Published by Elsevier B.V.

Review article: dyssynergic defaecation and biofeedback therapy in the pathophysiology and management of functional constipation.

Science.gov (United States)

Skardoon, G R; Khera, A J; Emmanuel, A V; Burgell, R E

2017-08-01

Functional constipation is a common clinical presentation in primary care. Functional defaecation disorders are defined as the paradoxical contraction or inadequate relaxation of the pelvic floor muscles during attempted defaecation (dyssynergic defaecation) and/or inadequate propulsive forces during attempted defaecation. Prompt diagnosis and management of dyssynergic defaecation is hindered by uncertainty regarding nomenclature, diagnostic criteria, pathophysiology and efficacy of management options such as biofeedback therapy. To review the evidence pertaining to the pathophysiology of functional defaecation disorders and the efficacy of biofeedback therapy in the management of patients with dyssynergic defaecation and functional constipation. Relevant articles addressing functional defaecation disorders and the efficacy of biofeedback therapy in the management of dyssynergic defaecation and functional constipation were identified from a search of Pubmed, MEDLINE Ovid and the Cochrane Library. The prevalence of dyssynergic defaecation in patients investigated for chronic constipation is as many as 40%. Randomised controlled trials have demonstrated major symptom improvement in 70%-80% of patients undergoing biofeedback therapy for chronic constipation resistant to standard medical therapy and have determined it to be superior to polyethylene glycol laxatives, diazepam or sham therapy. Long-term studies have shown 55%-82% of patients maintain symptom improvement. Dyssynergic defaecation is a common clinical condition in patients with chronic constipation not responding to conservative management. Biofeedback therapy appears to be a safe, successful treatment with sustained results for patients with dyssynergic defaecation. Further studies are required to standardise the diagnosis of dyssynergic defaecation in addition to employing systematic protocols for biofeedback therapy. © 2017 John Wiley & Sons Ltd.

Hydroxychloroquine-induced cardiomyopathy: case report, pathophysiology, diagnosis, and treatment.

Science.gov (United States)

Yogasundaram, Haran; Putko, Brendan N; Tien, Julia; Paterson, D Ian; Cujec, Bibiana; Ringrose, Jennifer; Oudit, Gavin Y

2014-12-01

Drug-induced heart and vascular disease remains an important health burden. Hydroxychloroquine and its predecessor chloroquine are medications commonly used in the treatment of systemic lupus erythematosus, rheumatoid arthritis, and other connective tissue disorders. Hydroxychloroquine interferes with malarial metabolites, confers immunomodulatory effects, and also affects lysosomal function. Clinical monitoring and early recognition of toxicity is an important management strategy in patients who undergo long-term treatment with hydroxychloroquine. Retinal toxicity, neuromyopathy, and cardiac disease are recognized adverse effects of hydroxychloroquine. Immediate withdrawal of hydroxychloroquine is essential if toxicity is suspected because of the early reversibility of cardiomyopathy. In addition to recommended ophthalmological screening, regular screening with 12-lead electrocardiogram and transthoracic echocardiography to detect conduction system disease and/or biventricular morphological or functional changes should be considered in hydroxychloroquine-treated patients. Cardiac magnetic resonance imaging and endomyocardial biopsy are valuable tools to provide prognostic insights and confirm the diagnosis of hydroxychloroquine-induced cardiomyopathy. In conclusion, chronic use of hydroxychloroquine can result in an acquired lysosomal storage disorder, leading to a drug-induced cardiomyopathy characterized by concentric hypertrophy and conduction abnormalities associated with increased adverse clinical outcomes and mortality. Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.

Diagnosis and management of feline hyperthyroidism: current perspectives

OpenAIRE

Grauer, Gregory F; Schermerhorn,Thomas; Armbrust,Laura; Vaske,Heather

2014-01-01

Heather H Vaske, Thomas Schermerhorn, Laura Armbrust, Gregory F Grauer Department of Clinical Sciences, Kansas State University, Manhattan, KS, USA Abstract: Previous and ongoing research has provided insights to the pathophysiology and diagnosis of hyperthyroidism as well as new treatment modalities. This paper reviews the etiology, clinical presentation, and clinicopathologic changes associated with hyperthyroidism, and provides a thorough explanation of confirmatory testing and treatment ...

Pathophysiology, Evaluation, and Treatment of Bloating

Science.gov (United States)

Gabbard, Scott L.; Crowell, Michael D.

2011-01-01

Abdominal bloating is commonly reported by men and women of all ages. Bloating occurs in nearly all patients with irritable bowel syndrome, and it also occurs in patients with other functional and organic disorders. Bloating is frequently disturbing to patients and frustrating to clinicians, as effective treatments are limited and are not universally successful. Although the terms bloating and abdominal distention are often used interchangeably, these symptoms likely involve different pathophysiologic processes, both of which are still not completely understood. The goal of this paper is to review the pathophysiology, evaluation, and treatment of bloating and abdominal distention. PMID:22298969

[The role of lactate acidosis in the development and treatment of various neurologic syndromes in children and adolescents].

Science.gov (United States)

Arveladze, G A; Geladze, N M; Sanikidze, T B; Khachapuridze, N S; Bakhtadze, S Z

2015-02-01

The aim of the study was to detect the role of lactate acidosis, also to find the share of mitochondrial insufficiency in development of various neurologic syndromes in children and adolescents. The detection of cellular energetic metabolism and acid based imbalance is also important for finding the specific method of management. We have studied 200 patients with various degree of neurodevelopment delay with epilepsy and epileptic syndromes, headache, vertigo, early strokes, floppy infant syndrome, atrophy of ophthalmic nerve, cataracta, neurosensory deafness, systemic myopathy, cerebral palsy. In 27% of cases with various ages we have detected lactate acidosis and increase level of pyruvate. Mitochondrial insufficiency was seen in 8% of cases which gives us opportunity to find the specific method of treatment in this group of patients. Each patient with neurological symptoms requires correction of parameters of energetic and oxidative metabolism.

An in vitro analysis of the effect of acidosis on coagulation in chronic disease states - a thromboelastograph study.

Science.gov (United States)

White, Hayden; Bird, Robert; Sosnowski, Kellie; Jones, Mark

2016-06-01

Thrombosis is a complication of many chronic illnesses. Chronic obstructive pulmonary disease (COPD) and diabetes mellitus are common medical conditions frequently associated with a hypercoagulable state. Acidaemia has been shown to reduce coagulation. COPD and diabetes mellitus during acute deterioration can present with a severe acidaemia. The impact of this acidaemia on coagulation is poorly studied. Patients presenting with a diagnosis of diabetic ketoacidosis or type II respiratory failure from COPD and a pH of less than 7.2 were included in our study. A coagulation screen and a thromboelastograph (TEG) were performed on admission and 24 hours later. The mean pH on admission was 7.07 and mean base excess was -16.3. The activated partial thromboplastin time was associated with pH change but remained within the normal range (26-41 s). All other coagulation and TEG parameters failed to show evidence of association (p>0.05). In the two models of non-haemorrhagic acidosis investigated, coagulation was not altered by the changes in pH. More work is needed to understand the complex relationship between factors affecting coagulation in individual disease processes. © 2016 Royal College of Physicians.

Respiratory gas exchange as a new aid to monitor acidosis in endotoxemic rats: relationship to metabolic fuel substrates and thermometabolic responses.

Science.gov (United States)

Steiner, Alexandre A; Flatow, Elizabeth A; Brito, Camila F; Fonseca, Monique T; Komegae, Evilin N

2017-01-01

This study introduces the respiratory exchange ratio (RER; the ratio of whole-body CO 2 production to O 2 consumption) as an aid to monitor metabolic acidosis during the early phase of endotoxic shock in unanesthetized, freely moving rats. Two serotypes of lipopolysaccharide (lipopolysaccharide [LPS] O55:B5 and O127:B8) were tested at shock-inducing doses (0.5-2 mg/kg). Phasic rises in RER were observed consistently across LPS serotypes and doses. The RER rise often exceeded the ceiling of the quotient for oxidative metabolism, and was mirrored by depletion of arterial bicarbonate and decreases in pH It occurred independently of ventilatory adjustments. These data indicate that the rise in RER results from a nonmetabolic CO 2 load produced via an acid-induced equilibrium shift in the bicarbonate buffer. Having validated this new experimental aid, we asked whether acidosis was interconnected with the metabolic and thermal responses that accompany endotoxic shock in unanesthetized rats. Contrary to this hypothesis, however, acidosis persisted regardless of whether the ambient temperature favored or prevented downregulation of mitochondrial oxidation and regulated hypothermia. We then asked whether the substrate that fuels aerobic metabolism could be a relevant factor in LPS-induced acidosis. Food deprivation was employed to divert metabolism away from glucose oxidation and toward fatty acid oxidation. Interestingly, this intervention attenuated the RER response to LPS by 58%, without suppressing other key aspects of systemic inflammation. We conclude that acid production in unanesthetized rats with endotoxic shock results from a phasic activation of glycolysis, which occurs independently of physiological changes in mitochondrial oxidation and body temperature. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Anatomical architecture and responses to acidosis of a novel respiratory neuron group in the high cervical spinal cord (HCRG) of the neonatal rat.

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Okada, Y; Yokota, S; Shinozaki, Y; Aoyama, R; Yasui, Y; Ishiguro, M; Oku, Y

2009-01-01

It has been postulated that there exists a neuronal mechanism that generates respiratory rhythm and modulates respiratory output pattern in the high cervical spinal cord. Recently, we have found a novel respiratory neuron group in the ventral portion of the high cervical spinal cord, and named it the high cervical spinal cord respiratory group (HCRG). In the present study, we analyzed the detailed anatomical architecture of the HCRG region by double immunostaining of the region using a neuron-specific marker (NeuN) and a marker for motoneurons (ChAT) in the neonatal rat. We found a large number of small NeuN-positive cells without ChAT-immunoreactivity, which were considered interneurons. We also found two and three clusters of motoneurons in the ventral portion of the ventral horn at C1 and C2 levels, respectively. Next, we examined responses of HCRG neurons to respiratory and metabolic acidosis in vitro by voltage-imaging together with cross correlation techniques, i.e., by correlation coefficient imaging, in order to understand the functional role of HCRG neurons. Both respiratory and metabolic acidosis caused the same pattern of changes in their spatiotemporal activation profiles, and the respiratory-related area was enlarged in the HCRG region. After acidosis was introduced, preinspiratory phase-dominant activity was recruited in a number of pixels, and more remarkably inspiratory phase-dominant activity was recruited in a large number of pixels. We suggest that the HCRG composes a local respiratory neuronal network consisting of interneurons and motoneurons and plays an important role in respiratory augmentation in response to acidosis.

Impact of membrane lung surface area and blood flow on extracorporeal CO2 removal during severe respiratory acidosis.

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Karagiannidis, Christian; Strassmann, Stephan; Brodie, Daniel; Ritter, Philine; Larsson, Anders; Borchardt, Ralf; Windisch, Wolfram

2017-12-01

Veno-venous extracorporeal CO 2 removal (vv-ECCO 2 R) is increasingly being used in the setting of acute respiratory failure. Blood flow rates through the device range from 200 ml/min to more than 1500 ml/min, and the membrane surface areas range from 0.35 to 1.3 m 2 . The present study in an animal model with similar CO 2 production as an adult patient was aimed at determining the optimal membrane lung surface area and technical requirements for successful vv-ECCO 2 R. Four different membrane lungs, with varying lung surface areas of 0.4, 0.8, 1.0, and 1.3m 2 were used to perform vv-ECCO 2 R in seven anesthetized, mechanically ventilated, pigs with experimentally induced severe respiratory acidosis (pH 7.0-7.1) using a 20Fr double-lumen catheter with a sweep gas flow rate of 8 L/min. During each experiment, the blood flow was increased stepwise from 250 to 1000 ml/min. Amelioration of severe respiratory acidosis was only feasible when blood flow rates from 750 to 1000 ml/min were used with a membrane lung surface area of at least 0.8 m 2 . Maximal CO 2 elimination was 150.8 ml/min, with pH increasing from 7.01 to 7.30 (blood flow 1000 ml/min; membrane lung 1.3 m 2 ). The membrane lung with a surface of 0.4 m 2 allowed a maximum CO 2 elimination rate of 71.7 mL/min, which did not result in the normalization of pH, even with a blood flow rate of 1000 ml/min. Also of note, an increase of the surface area above 1.0 m 2 did not result in substantially higher CO 2 elimination rates. The pressure drop across the oxygenator was considerably lower (respiratory acidosis, irrespective of the surface area of the membrane lung being used. The converse was also true, low surface membrane lungs (0.4 m 2 ) were not capable of completely correcting severe respiratory acidosis across the range of blood flows used in this study.

A Bovine Hemoglobin-Based Oxygen Carrier as Pump Prime for Cardiopulmonary Bypass: Reduced Systemic Lactic Acidosis and Improved Cerebral Oxygen Metabolism During Low-flow in a Porcine Model

Science.gov (United States)

2010-11-10

1 A bovine hemoglobin-based oxygen carrier as pump prime for cardiopulmonary bypass: reduced systemic lactic acidosis and improved cerebral...2010 2. REPORT TYPE Final Report 3. DATES COVERED (From - To) June 2007 - November 2010 4. TITLE AND SUBTITLE A bovine hemoglobin-based oxygen...carrier as pump prime for cardiopulmonary bypass: reduced systemic lactic acidosis and improved cerebral oxygen metabolism during low-flow in a

Pathophysiology of Pulmonary Hypertension in Chronic Parenchymal Lung Disease.

Science.gov (United States)

Singh, Inderjit; Ma, Kevin Cong; Berlin, David Adam

2016-04-01

Pulmonary hypertension commonly complicates chronic obstructive pulmonary disease and interstitial lung disease. The association of chronic lung disease and pulmonary hypertension portends a worse prognosis. The pathophysiology of pulmonary hypertension differs in the presence or absence of lung disease. We describe the physiological determinants of the normal pulmonary circulation to better understand the pathophysiological factors implicated in chronic parenchymal lung disease-associated pulmonary hypertension. This review will focus on the pathophysiology of 3 forms of chronic lung disease-associated pulmonary hypertension: idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, and sarcoidosis. Copyright © 2016 Elsevier Inc. All rights reserved.

An update on oxidative stress-mediated organ pathophysiology.

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Rashid, Kahkashan; Sinha, Krishnendu; Sil, Parames C

2013-12-01

Exposure to environmental pollutants and drugs can result in pathophysiological situations in the body. Research in this area is essential as the knowledge on cellular survival and death would help in designing effective therapeutic strategies that are needed for the maintenance of the normal physiological functions of the body. In this regard, naturally occurring bio-molecules can be considered as potential therapeutic targets as they are normally available in commonly consumed foodstuffs and are thought to have minimum side effects. This review article describes the detailed mechanisms of oxidative stress-mediated organ pathophysiology and the ultimate fate of the cells either to survive or to undergo necrotic or apoptotic death. The mechanisms underlying the beneficial role of a number of naturally occurring bioactive molecules in oxidative stress-mediated organ pathophysiology have also been included in the review. The review provides useful information about the recent progress in understanding the mechanism(s) of various types of organ pathophysiology, the complex cross-talk between these pathways, as well as their modulation in stressed conditions. Additionally, it suggests possible therapeutic applications of a number of naturally occurring bioactive molecules in conditions involving oxidative stress. Copyright © 2013 Elsevier Ltd. All rights reserved.

Proposed guidelines for the diagnosis and management of methylmalonic and propionic acidemia

DEFF Research Database (Denmark)

Baumgartner, Matthias R; Hörster, Friederike; Dionisi-Vici, Carlo

2014-01-01

Methylmalonic and propionic acidemia (MMA/PA) are inborn errors of metabolism characterized by accumulation of propionic acid and/or methylmalonic acid due to deficiency of methylmalonyl-CoA mutase (MUT) or propionyl-CoA carboxylase (PCC). MMA has an estimated incidence of ~ 1: 50,000 and PA of ~...... recognition and delayed diagnosis due to nonspecific clinical presentation and insufficient awareness of health care professionals because of disease rarity.......:100'000 -150,000. Patients present either shortly after birth with acute deterioration, metabolic acidosis and hyperammonemia or later at any age with a more heterogeneous clinical picture, leading to early death or to severe neurological handicap in many survivors. Mental outcome tends to be worse in PA...

Effects of Tight Versus Non Tight Control of Metabolic Acidosis on Early Renal Function After Kidney Transplantation

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Farhad Etezadi

2012-09-01

Full Text Available Background Recently, several studies have been conducted to determine the optimal strategy for intraoperative fluid replacement therapy in renal transplantation surgery. Since infusion of sodium bicarbonate as a buffer seems to be safer than other buffer compounds (lactate, gluconate, acetatethat indirectly convert into it within the liver, We hypothesized tight control of metabolic acidosis by infusion of sodium bicarbonate may improve early post-operative renal function in renal transplant recipients. Methods:120 patients were randomly divided into two equal groups. In group A, bicarbonate was infused intra-operatively according to Base Excess (BE measurements to achieve the normal values of BE (5 to +5 mEq/L. In group B, infusion of bicarbonate was allowed only in case of severe metabolic acidosis (BE [less than or equal to] 15 mEq/L or bicarbonate [less than or equal to] 10 mEq/L or PH [less than or equal to] 7.15. Minute ventilation was adjusted to keep PaCO2 within the normal range. Primary end-point was sampling of serum creatinine level in first, second, third and seventh post-operative days for statistical comparison between groups. Secondary objectives were comparison of cumulative urine volumes in the first 24 h of post-operative period and serum BUN levels which were obtained in first, second, third and seventh post-operative days. Results:In group A, all of consecutive serum creatinine levels were significantly lower in comparison with group B. With regard to secondary outcomes, no significant difference between groups was observed. Conclusion:Intra-operative tight control of metabolic acidosis by infusion of Sodium Bicarbonate in renal transplant recipients may improve early post-operative renal function.

Effects of tight versus non tight control of metabolic acidosis on early renal function after kidney transplantation

Directory of Open Access Journals (Sweden)

Etezadi Farhad

2012-09-01

Full Text Available Abstract Background Recently, several studies have been conducted to determine the optimal strategy for intra-operative fluid replacement therapy in renal transplantation surgery. Since infusion of sodium bicarbonate as a buffer seems to be safer than other buffer compounds (lactate, gluconate, acetatethat indirectly convert into it within the liver, We hypothesized tight control of metabolic acidosis by infusion of sodium bicarbonate may improve early post-operative renal function in renal transplant recipients. Methods 120 patients were randomly divided into two equal groups. In group A, bicarbonate was infused intra-operatively according to Base Excess (BE measurements to achieve the normal values of BE (−5 to +5 mEq/L. In group B, infusion of bicarbonate was allowed only in case of severe metabolic acidosis (BE ≤ −15 mEq/L or bicarbonate ≤ 10 mEq/L or PH ≤ 7.15. Minute ventilation was adjusted to keep PaCO2 within the normal range. Primary end-point was sampling of serum creatinine level in first, second, third and seventh post-operative days for statistical comparison between groups. Secondary objectives were comparison of cumulative urine volumes in the first 24 h of post-operative period and serum BUN levels which were obtained in first, second, third and seventh post-operative days. Results In group A, all of consecutive serum creatinine levels were significantly lower in comparison with group B. With regard to secondary outcomes, no significant difference between groups was observed. Conclusion Intra-operative tight control of metabolic acidosis by infusion of Sodium Bicarbonate in renal transplant recipients may improve early post-operative renal function.

Respiratory acidosis prolongs, while alkalosis shortens, the duration and recovery time of vecuronium in humans.

Science.gov (United States)

Yamauchi, Masanori; Takahashi, Hiromi; Iwasaki, Hiroshi; Namiki, Akiyoshi

2002-03-01

To determine the effects of respiratory acidosis and alkalosis by mechanical ventilation on the onset, duration, and recovery times of vecuronium. Randomized, prospective study. Operating rooms in the Sapporo Medical University Hospital and Kitami Red Cross Hospital. 90 ASA physical status I and II patients undergoing lower abdominal surgery. Patients were randomly allocated to one of three groups by arterial carbon dioxide tension level (PaCO2; mmHg) after induction: hyperventilation group (PaCO2 = 25-35), normoventilation group (PaCO2 = 35-45), and hypoventilation group (PaCO2 = 45-55). Anesthesia was maintained by spinal block with inhalation of 50% to 66% nitrous oxide in oxygen and intermittent intravenous administration of fentanyl and midazolam with tracheal intubation. After vecuronium 0.08 mg/kg was given, onset, duration, and recovery time were measured by mechanomyography (Biometer Myograph 2,000, Odense, Denmark). There were significant differences in the duration and recovery time of vecuronium among the normoventilation group (12.7 +/- 3.3 min and 11.8 +/- 2.8 min, respectively), the hyperventilation group (10.6 +/- 3.5 min and 9.2 +/- 2.7 min, respectively; p respiratory acidosis and shortened in respiratory alkalosis.

Sickle cell disease and complex congenital cardiac surgery: a case report and review of the pathophysiology and perioperative management.

Science.gov (United States)

Sanders, D B; Smith, B P; Sowell, S R; Nguyen, D H; Derby, C; Eshun, F; Nigro, J J

2014-03-01

Sickle cell anemia and thalassemia are hemoglobinopathies rarely encountered in the United States. Compounded with congenital heart disease, patients with sickle cell disease (SCD) requiring cardiopulmonary bypass and open-heart surgery represent the proverbial "needle in the haystack". As such, there is some trepidation on the part of clinicians when these patients present for complex cardiac surgery. SCD is an autosomal, recessive condition that results from a single nucleotide polymorphism in the β-globin gene. Hemoglobin SS molecules (HgbSS) with this point mutation can polymerize under the right conditions, stiffening the erythrocyte membrane and distorting the cellular structure to the characteristic sickle shape. This shape change alters cellular transit through the microvasculature. As a result, circumstances such as hypoxia, hypothermia, acidosis or diminished blood flow can lead to aggregation, vascular occlusion and thrombosis. Chronically, SCD can give rise to multiorgan damage secondary to hemolysis and vascular obstruction. This review and case study details an 11-year-old African-American male with known SCD who presented to the cardiothoracic surgical service with congenital heart disease consisting of an anomalous, intramural right coronary artery arising from the left coronary sinus for surgical consultation and subsequent surgical correction. This case report will include a review of the pathophysiology and current literature regarding preoperative, intraoperative and postoperative management of SCD patients.

MTO1 mutations are associated with hypertrophic cardiomyopathy and lactic acidosis and cause respiratory chain deficiency in humans and yeast.

Science.gov (United States)

Baruffini, Enrico; Dallabona, Cristina; Invernizzi, Federica; Yarham, John W; Melchionda, Laura; Blakely, Emma L; Lamantea, Eleonora; Donnini, Claudia; Santra, Saikat; Vijayaraghavan, Suresh; Roper, Helen P; Burlina, Alberto; Kopajtich, Robert; Walther, Anett; Strom, Tim M; Haack, Tobias B; Prokisch, Holger; Taylor, Robert W; Ferrero, Ileana; Zeviani, Massimo; Ghezzi, Daniele

2013-11-01

We report three families presenting with hypertrophic cardiomyopathy, lactic acidosis, and multiple defects of mitochondrial respiratory chain (MRC) activities. By direct sequencing of the candidate gene MTO1, encoding the mitochondrial-tRNA modifier 1, or whole exome sequencing analysis, we identified novel missense mutations. All MTO1 mutations were predicted to be deleterious on MTO1 function. Their pathogenic role was experimentally validated in a recombinant yeast model, by assessing oxidative growth, respiratory activity, mitochondrial protein synthesis, and complex IV activity. In one case, we also demonstrated that expression of wt MTO1 could rescue the respiratory defect in mutant fibroblasts. The severity of the yeast respiratory phenotypes partly correlated with the different clinical presentations observed in MTO1 mutant patients, although the clinical outcome was highly variable in patients with the same mutation and seemed also to depend on timely start of pharmacological treatment, centered on the control of lactic acidosis by dichloroacetate. Our results indicate that MTO1 mutations are commonly associated with a presentation of hypertrophic cardiomyopathy, lactic acidosis, and MRC deficiency, and that ad hoc recombinant yeast models represent a useful system to test the pathogenic potential of uncommon variants, and provide insight into their effects on the expression of a biochemical phenotype. © 2013 The Authors. *Human Mutation published by Wiley Periodicals, Inc.

A Comparison of Treating Metabolic Acidosis in CKD Stage 4 Hypertensive Kidney Disease with Fruits and Vegetables or Sodium Bicarbonate

Science.gov (United States)

Goraya, Nimrit; Simoni, Jan; Jo, Chan-Hee

2013-01-01

Summary Background and objectives Current guidelines recommend Na+-based alkali for CKD with metabolic acidosis and plasma total CO2 (PTCO2) fruits and vegetables with oral NaHCO3 (HCO3) regarding the primary outcome of follow-up estimated GFR (eGFR) and secondary outcomes of improved metabolic acidosis and reduced urine indices of kidney injury. Design, setting, participants, & measurements Individuals with stage 4 (eGFR, 15–29 ml/min per 1.73 m2) CKD due to hypertensive nephropathy, had a PTCO2 level fruits and vegetables dosed to reduce dietary acid by half (n=36). Results Plasma cystatin C–calculated eGFR did not differ at baseline and 1 year between groups. One-year PTCO2 was higher than baseline in the HCO3 group (21.2±1.3 versus 19.5±1.5 mM; Pfruits and vegetables group (19.9±1.7 versus 19.3±1.9 mM; Pfruits and vegetable group (Pfruits and vegetables or NaHCO3 in individuals with stage 4 CKD yielded eGFR that was not different, was associated with higher-than-baseline PTCO2, and was associated with lower-than-baseline urine indices of kidney injury. The data indicate that fruits and vegetables improve metabolic acidosis and reduce kidney injury in stage 4 CKD without producing hyperkalemia. PMID:23393104

Cortical activity, ionic homeostasis, and acidosis during rat brain repetitive ischemia.

Science.gov (United States)

Matsumoto, T; Obrenovitch, T P; Parkinson, N A; Symon, L

1990-08-01

Recent data strongly suggest that repetitive ischemic episodes have an adverse cumulative effect on development of edema and tissue damage. We wanted to assess further whether special risks such as exacerbation of extracellular acidification reflecting progressive exhaustion of the capacity to buffer H+ in the extracellular space are associated with repeated short ischemic insults. We monitored spontaneous electrical activity, extracellular direct-current potential, extracellular H+ activity, and tissue PCO2 in the cerebral cortex of rats subjected to four cycles of 3-minute ischemia produced by four-vessel occlusion with 27-minute reperfusion after each insult. Except for electrical activity, which failed to recover fully from the first ischemic insult, all parameters returned to a level close to normal after each reperfusion. Changes during ischemia did not evolve with repetition of the insult. Electrical silence occurred within approximately 20 seconds after the onset of each ischemic episode and always preceded the steep drop of direct-current potential, indicating ischemic depolarization. Each four-vessel occlusion immediately initiated a steep rise of tissue PCO2 and extracellular H+ activity, with extracellular H+ activity reaching a maximum within approximately 145 seconds. Changes in extracellular H+ activity during each recirculation period consistently included an additional and short-lasting increase associated with repolarization, a rapid decrease closely related to that of tissue PCO2, and a slow progressive return to normal. These results suggest that short, repetitive ischemic episodes severe enough to produce cell membrane depolarization and maximum acidosis of the neuronal microenvironment do not have a deleterious cumulative effect on the studied parameters, in particular, on interstitial acidosis.

A comparison of treating metabolic acidosis in CKD stage 4 hypertensive kidney disease with fruits and vegetables or sodium bicarbonate.

Science.gov (United States)

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

2013-03-01

Current guidelines recommend Na(+)-based alkali for CKD with metabolic acidosis and plasma total CO2 (PTCO2) < 22 mM. Because diets in industrialized societies are typically acid-producing, we compared base-producing fruits and vegetables with oral NaHCO3 (HCO3) regarding the primary outcome of follow-up estimated GFR (eGFR) and secondary outcomes of improved metabolic acidosis and reduced urine indices of kidney injury. Individuals with stage 4 (eGFR, 15-29 ml/min per 1.73 m(2)) CKD due to hypertensive nephropathy, had a PTCO2 level < 22 mM, and were receiving angiotensin-converting enzyme inhibition were randomly assigned to 1 year of daily oral NaHCO3 at 1.0 mEq/kg per day (n=35) or fruits and vegetables dosed to reduce dietary acid by half (n=36). Plasma cystatin C-calculated eGFR did not differ at baseline and 1 year between groups. One-year PTCO2 was higher than baseline in the HCO3 group (21.2±1.3 versus 19.5±1.5 mM; P<0.01) and the fruits and vegetables group (19.9±1.7 versus 19.3±1.9 mM; P<0.01), consistent with improved metabolic acidosis, and was higher in the HCO3 than the fruits and vegetable group (P<0.001). One-year urine indices of kidney injury were lower than baseline in both groups. Plasma [K(+)] did not increase in either group. One year of fruits and vegetables or NaHCO3 in individuals with stage 4 CKD yielded eGFR that was not different, was associated with higher-than-baseline PTCO2, and was associated with lower-than-baseline urine indices of kidney injury. The data indicate that fruits and vegetables improve metabolic acidosis and reduce kidney injury in stage 4 CKD without producing hyperkalemia.

95th Anniversary of Pathophysiology in Croatia.

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Kovač, Zdenko

2017-12-01

University level of Pathophysiology research and teaching in Croatia had started with the third year of Medical School of Zagreb in academic year 1919./20. Ever since, despite historical changes of the main university stake holder, the state of Croatia, Department of Pathophysiology development progressed and has made visible academic achievements, with a broader effect in medical community. The first 95 years of academic tradition and major achievements are shortly described in this paper. Professor Miroslav Mikuličić envisioned Pathophysiology in close relations with Pharmacology and made the pioneering steps of establishing the "double" department at Šalata. His group was academically very pro-active, with strong international scientific participation and recruitment of professionals. The group published the first voluminous textbook of Pharmacology and Pathophysiology, in Croatian. In fifties, professor Pavao Sokolić established clinical pathophysiology within the Hospital Centre at Rebro. Out of "double" department two new departments were founded, the Pathophysiology one was completed with the clinical ward. That institutional move from Šalata hill to the Rebro hill was a necessary gigantic step and a prerequisite for the proper further development. It was in accordance with the concept of the Mikuličić's program of Pathophysiology from 1917. Pavao Sokolić has been remembered for his visions, deep insights into etiopathogenesis, ability to transfer knowledge and friendly relations to students. Sharp intellectual power, emanating charisma, academic erudition and unique clinical competencies made the legendary image of the "Teacher" - as students used to refer to him with admiration. He was second to no one when complex patient issues were to be resolved. Clinical Hospital Centre Zagreb and his Department at Rebro have become a referral point to whom to go to despair. Students recognized in their Teacher the landmark of Croatian medicine, which made a

Initial Diagnosis and Management of Coma.

Science.gov (United States)

Traub, Stephen J; Wijdicks, Eelco F

2016-11-01

Coma represents a true medical emergency. Drug intoxications are a leading cause of coma; however, other metabolic disturbances and traumatic brain injury are also common causes. The general emergency department approach begins with stabilization of airway, breathing, and circulation, followed by a thorough physical examination to generate a limited differential diagnosis that is then refined by focused testing. Definitive treatment is ultimately disease-specific. This article presents an overview of the pathophysiology, causes, examination, and treatment of coma. Copyright © 2016 Elsevier Inc. All rights reserved.

Review of the relationship between nutrition and lameness in pasture-fed dairy cattle.

Science.gov (United States)

Westwood, C T; Bramley, E; Lean, I J

2003-10-01

Lameness of dairy cattle fed predominantly on pasture is increasingly recognised as one of the most costly disease conditions affecting dairy herds in New Zealand and Australia. Numerous risk factors are involved in the aetiology of claw lameness, including environment and factors associated with the conformation of individual cows. The role of nutrition requires further definition. Australasian pastures are characterised by low levels of fibre and effective fibre, rapid rates of fibre degradation, high water content, and high concentrations of rumen degradable protein during the autumn, winter and spring months. Relationships between high-quality vegetative pastures and ruminal acidosis may increase the risk of laminitis, particularly where pasture is supplemented with grains or other feeds containing significant amounts of starch. This article reviews the incidence, prevalence and pathophysiology of ruminal acidosis and laminitis and considers mechanisms by which acidosis may occur in pasture-fed cows. Techniques for diagnosing ruminal acidosis are reviewed, and practical strategies to avoid it are proposed. Currently, there is little information on the incidence and prevalence of ruminal acidosis and laminitis in pasture-fed cattle. The evidence gathered in this review suggests that ruminal acidosis and laminitis should be considered in the aetiology of lameness in pasture-fed dairy herds.

Pathophysiology of gastroesophageal reflux disease

NARCIS (Netherlands)

Boeckxstaens, Guy E.; Rohof, Wout O.

2014-01-01

Gastroesophageal reflux disease (GERD) is one of the most common digestive diseases in the Western world, with typical symptoms, such as heartburn, regurgitation, or retrosternal pain, reported by 15% to 20% of the general population. The pathophysiology of GERD is multifactorial. Our understanding

Pathophysiological mechanisms of insulin resistance

NARCIS (Netherlands)

Brands, M.

2013-01-01

In this thesis we studied pathophysiological mechanisms of insulin resistance in different conditions in humans, i.e. in obesity, during lipid infusions, after hypercaloric feeding, and glucocorticoid treatment. We focused on 3 important hypotheses that are suggested to be implicated in the

The Challenge in Diagnosis and Current Treatment of Chronic Thromboembolic Pulmonary Hypertension

Directory of Open Access Journals (Sweden)

Anggoro Budi Hartopo

2017-04-01

Full Text Available Chronic thromboembolic pulmonary hypertension (CTEPH is currently underdiagnosis and consequently undertreatment in the clinical practice. A deficient in diagnostic modality and treatment availability especially in developing countries makes the CTEPH diagnosis unlikely to confirm. However, high index of clinical suspicion of CTEPH will lead to proper diagnosis and correct treatment  with significant reduction in morbidity and mortality. Left untreated, the mean survival time is 6.8 years and the three year mortality rate may be as high as 90 %. The pathophysiology, diagnosis and treatment of CTEPH are necessary to be shared among internists and primary care physicians, in order to improve the overall outcome of the patients.

Assessing pathophysiology of cancer anorexia.

Science.gov (United States)

Laviano, Alessandro; Koverech, Angela; Seelaender, Marilia

2017-09-01

Cancer anorexia is a negative prognostic factor and is broadly defined as the loss of the interest in food. However, multiple clinical domains contribute to the phenotype of cancer anorexia. The characterization of the clinical and molecular pathophysiology of cancer anorexia may enhance the efficacy of preventive and therapeutic strategies. Clinical trials showed that cancer anorexia should be considered as an umbrella encompassing different signs and symptoms contributing to appetite disruption in cancer patients. Loss of appetite, early satiety, changes in taste and smell are determinants of cancer anorexia, whose presence should be assessed in cancer patients. Interestingly, neuronal correlates of cancer anorexia-related symptoms have been revealed by brain imaging techniques. The pathophysiology of cancer anorexia is complex and involves different domains influencing eating behavior. Limiting the assessment of cancer anorexia to questions investigating changes in appetite may impede correct identification of the targets to address.

Presentation of an experimental method to induce in vitro ("organ chambers") respiratory acidosis and its effect on vascular reactivity.

Science.gov (United States)

Nadai, Tales Rubens de; Silveira, Ana Paula Cassiano; Monteiro, Ariadne Santana e Neves; Campos, Debora Ribeiro; Carvalho, Marco Tulio Rezende de; Albuquerque, Agnes Afrodite Sumarelli; Celotto, Andrea Carla; Evora, Paulo Roberto Barbosa

2014-11-01

To create in vitro a model to generate acidosis by CO2 bubbling "organ chambers", which would be useful for researchers that aim to study the effects of acid-base disturbs on the endothelium-dependent vascular reactivity. Eighteen male Wistar rats (230-280 g) were housed, before the experiments, under standard laboratory conditions (12h light/dark cycle at 21°C), with free access to food and water. The protocol for promoting in vitro respiratory acidosis was carried out by bubbling increased concentrations of CO2. The target was to achieve an ideal way to decrease the pH gradually to a value of approximately 6.6.It was used, initially, a gas blender varying concentrations of the carbogenic mixture (95% O2 + 5% CO2) and pure CO2. 1) 100% CO2, pH variation very fast, pH minimum 6.0; 2) 90%CO2 pH variation bit slower, pH minimum 6.31; 3) 70%CO2, pH variation slower, pH minimum 6.32; 4) 50% CO2, pH variation slower, pH minimum 6:42; 5) 40 %CO2, Adequate record, pH minimum 6.61, and; 6) 30 %CO2 could not reach values below pH minimum 7.03. Based on these data the gas mixture (O2 60% + CO2 40%) was adopted. This gas mixture (O2 60% + CO2 40%) was effective in inducing respiratory acidosis at a speed that made, possible the recording of isometric force.

Intravenous hypertonic saline solution (7.5%) and oral electrolytes to treat of calves with noninfectious diarrhea and metabolic acidosis.

Science.gov (United States)

Leal, M L R; Fialho, S S; Cyrillo, F C; Bertagnon, H G; Ortolani, E L; Benesi, F J

2012-01-01

The aim of this study was to compare the efficacy of treating osmotic diarrhea and dehydration in calves with hypertonic saline solution (HSS) IV, isotonic electrolyte solution (IES) PO, and a combination of these 2 solutions (HSS + IES). Eighteen male calves 8-30 days of age were used to evaluate the efficacy of 3 methods of fluid therapy after induction of osmotic diarrhea and dehydration. The diarrhea and dehydration were induced by administration of saccharose, spironolactone, and hydrochlorothiazide for 48 hours. The animals were randomly divided into 3 experimental groups: Group 1: 7.2% hypertonic saline solution-HSS (5 mL/kg IV); Group 2: oral isotonic electrolyte solution IES (60 mL/kg PO); or Group 3: HSS+IES. Clinical signs and laboratory finding observed 48 hours post-induction (Time 0) included diarrhea, dehydration, lethargy, and metabolic acidosis. Calves treated with HSS + IES experienced decreases in hematocrit, total protein concentration, albumin concentration, urea nitrogen concentration, and plasma volume as well as increases in blood pH, blood bicarbonate concentration, and central venous pressure between 1 and 3 hours post-treatment. These findings also were observed in animals treated with IES, however, at a slower rate than in the HSS + IES-treated animals. Animals treated with HSS continued to display signs of dehydration, lethargy, and metabolic acidosis 24 hours post-treatment. Treatment with a combination of HSS and IES produced rapid and sustainable correction of hypovolemia and metabolic acidosis in calves with noninfections diarrhea and dehydration. Copyright © 2012 by the American College of Veterinary Internal Medicine.

Gas embolism: pathophysiology and treatment

NARCIS (Netherlands)

van Hulst, Robert A.; Klein, Jan; Lachmann, Burkhard

2003-01-01

Based on a literature search, an overview is presented of the pathophysiology of venous and arterial gas embolism in the experimental and clinical environment, as well as the relevance and aims of diagnostics and treatment of gas embolism. The review starts with a few historical observations and

Lactate Clearance and Vasopressor Seem to Be Predictors for Mortality in Severe Sepsis Patients with Lactic Acidosis Supplementing Sodium Bicarbonate: A Retrospective Analysis.

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Su Mi Lee

Full Text Available Initial lactate level, lactate clearance, C-reactive protein, and procalcitonin in critically ill patients with sepsis are associated with hospital mortality. However, no study has yet discovered which factor is most important for mortality in severe sepsis patients with lactic acidosis. We sought to clarify this issue in patients with lactic acidosis who were supplementing with sodium bicarbonate.Data were collected from a single center between May 2011 and April 2014. One hundred nine patients with severe sepsis and lactic acidosis who were supplementing with sodium bicarbonate were included.The 7-day mortality rate was 71.6%. The survivors had higher albumin levels and lower SOFA, APACHE II scores, vasopressor use, and follow-up lactate levels at an elapsed time after their initial lactate levels were checked. In particular, a decrement in lactate clearance of at least 10% for the first 6 hours, 24 hours, and 48 hours of treatment was more dominant among survivors than non-survivors. Although the patients who were treated with broad-spectrum antibiotics showed higher illness severity than those who received conventional antibiotics, there was no significant mortality difference. 6-hour, 24-hour, and 48-hour lactate clearance (HR: 4.000, 95% CI: 1.309-12.219, P = 0.015 and vasopressor use (HR: 4.156, 95% CI: 1.461-11.824, P = 0.008 were significantly associated with mortality after adjusting for confounding variables.Lactate clearance at a discrete time point seems to be a more reliable prognostic index than initial lactate value in severe sepsis patients with lactic acidosis who were supplementing with sodium bicarbonate. Careful consideration of vasopressor use and the initial application of broad-spectrum antibiotics within the first 48 hours may be helpful for improving survival, and further study is warranted.

Diagnosis of toxic alcohols: limitations of present methods.

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Kraut, Jeffrey A

2015-01-01

Methanol, ethylene glycol, diethylene glycol, and propylene glycol intoxications are associated with cellular dysfunction and an increased risk of death. Adverse effects can develop quickly; thus, there is a need for methods for rapidly detecting their presence. To examine the value and limitations of present methods to diagnose patients with possible toxic alcohol exposure. I searched MEDLINE for articles published between 1969 and 2014 using the terms: toxic alcohols, serum osmolality, serum osmol gap, serum anion gap, metabolic acidosis, methanol, ethylene glycol, diethylene glycol, propylene glycol, and fomepizole. Each article was reviewed for additional references. The diagnosis of toxic alcohol exposure is often made on the basis of this history and physical findings along with an increase in the serum osmol and anion gaps. However, an increase in the osmol and/or anion gaps is not always present. Definitive detection in blood requires gas or liquid chromatography, laborious and expensive procedures which are not always available. Newer methods including a qualitative colorimetric test for detection of all alcohols or enzymatic tests for a specific alcohol might allow for more rapid diagnosis. Exposure to toxic alcohols is associated with cellular dysfunction and increased risk of death. Treatment, if initiated early, can markedly improve outcome, but present methods of diagnosis including changes in serum osmol and anion gap, and use of gas or liquid chromatography have important limitations. Development of more rapid and effective tests for detection of these intoxications is essential for optimal care of patients.

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

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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.

Central lactic acidosis, hyperventilation, and respiratory alkalosis: leading clinical features in a 3-year-old boy with malignant meningeal melanoma.

Science.gov (United States)

Blüher, Susann; Schulz, Manuela; Bierbach, Uta; Meixensberger, Jürgen; Tröbs, Ralf-Bodo; Hirsch, Wolfgang; Schober, Ralf; Kiess, Wieland; Siekmeyer, Werner

2008-04-01

Meningeal tumors are extremely rare in children and are diagnostically as well as therapeutically challenging. Among the least common types of malignancies in childhood is malignant melanoma, counting for less than 1% of pediatric tumors. Due to the rarity and the wide spectrum of appearance, initial clinical features may be misleading. A 3-year-old boy was referred to our hospital with symptoms of hyperventilation, dyspnoea, tachycardia, respiratory alkalosis, inarticulate speech, and fatigue. Measurement of pH in cerebrospinal fluid (CSF) yielded central lactic acidosis despite alkalosis in peripheral blood. Diagnostic imaging procedures as well as histology and immunohistochemistry revealed the diagnosis of a malignant meningeal melanoma. We hypothesize that central lactate production of the tumor nests might have induced central acidification, thus inducing hyperventilation by stimulation of central chemoreceptors. This case is a model example of the key role of central pH as an inducer/suppressor of ventilation in humans and illustrates the critical importance of central pH for regulating both ventilation and acid-base homeostasis. Thus, pH of CSF should be measured whenever a malignant brain tumor is suspected.

Teaching acid/base physiology in the laboratory

DEFF Research Database (Denmark)

Friis, Ulla G; Plovsing, Ronni; Hansen, Klaus

2010-01-01

exercise in acid/base physiology that would provide students with unambiguous and reproducible data that clearly would illustrate the theory in practice. The laboratory exercise was developed to include both metabolic acidosis and respiratory alkalosis. Data were collected from 56 groups of medical...... students that had participated in this laboratory exercise. The acquired data showed very consistent and solid findings after the development of both metabolic acidosis and respiratory alkalosis. All results were consistent with the appropriate diagnosis of the acid/base disorder. Not one single group...... failed to obtain data that were compatible with the diagnosis; it was only the degree of acidosis/alkalosis and compensation that varied....

A Practical Approach to the Diagnosis and Understanding of Chronic Low Back Pain, Based on Its Pathophysiology.

NARCIS (Netherlands)

Groen, Gerbrand; Beese, Ulrich; Van de Kelft, Erik; Groen, Robertus; Van de Kelft, Eric

2016-01-01

As outlined abundantly in this book, chronic low back pain is not a diagnosis, but a symptom. Thorough knowledge of the cause and nature of the pain might help when looking for a correct diagnosis. Often, this clinical knowledge is more important with respect to therapeutic strategies than advanced

Thalassemia: Pathophysiology and management. Part A

International Nuclear Information System (INIS)

Fucharoen, S.; Rowley, P.T.; Paul, N.W.

1988-01-01

This book contains papers divided among the following sections: molecular biology and pathogenesis; pathophysiology - molecular and cellular; clinical manifestations and hematologic changes; cardiopulmonary defects and platelet function; hormones and minerals; and infection and immunology

Amelogenesis Imperfecta with Distal Renal Tubular Acidosis: A Novel Syndrome?

Science.gov (United States)

Misgar, R A; Hassan, Z; Wani, A I; Bashir, M I

2017-01-01

Amelogenesis imperfecta (AI) is a heterogeneous group of inherited dental enamel defects. It has rarely been reported in association with multiorgan syndromes and metabolic disorders. The metabolic disorders that have been reported in association with AI include hypocalciuria, impaired urinary concentrating ability, and Bartter-like syndrome. In literature, only three cases of AI and distal renal tubular acidosis (dRTA) have been described: two cases in adults and a solitary case in the pediatric age group. Here, we report a child with AI presenting with dRTA; to the best of our knowledge, our reported case is the only second such case in pediatric age group. Our case highlights the importance of recognizing the possibility of renal abnormalities in patients with AI as it will affect the long-term prognosis.

Amelogenesis imperfecta with distal renal tubular acidosis: A novel syndrome?

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R A Misgar

2017-01-01

Full Text Available Amelogenesis imperfecta (AI is a heterogeneous group of inherited dental enamel defects. It has rarely been reported in association with multiorgan syndromes and metabolic disorders. The metabolic disorders that have been reported in association with AI include hypocalciuria, impaired urinary concentrating ability, and Bartter-like syndrome. In literature, only three cases of AI and distal renal tubular acidosis (dRTA have been described: two cases in adults and a solitary case in the pediatric age group. Here, we report a child with AI presenting with dRTA; to the best of our knowledge, our reported case is the only second such case in pediatric age group. Our case highlights the importance of recognizing the possibility of renal abnormalities in patients with AI as it will affect the long-term prognosis.

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

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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.

Hypothyroidism After a Cancer Diagnosis: Etiology, Diagnosis, Complications, and Management

Science.gov (United States)

Carter, Yvette; Sippel, Rebecca S.

2014-01-01

Hypothyroidism is a common disease that is easily treated in the majority of cases, when readily diagnosed; however, presentation of an aggregate of its symptoms is often clinically overlooked or attributed to another disease and can potentially be lethal. Already prevalent in older women, its occurrence in younger patients is rising as a result of radiation therapy, radioactive iodine therapy, and newer antineoplastic agents used to manage various malignancies. The presence of nonspecific constitutional symptoms and neuropsychiatric complaints in cancer patients can be attributed to a myriad of other diagnoses and therapies. Thyroid dysfunction can be easily overlooked in cancer patients because of the complexity of cancer’s clinical picture, particularly in the pediatric population. Underdiagnosis can have important consequences for the management of both hypothyroidism and the malignancy. At minimum, quality of life is adversely affected. Untreated hypothyroidism can lead to heart failure, psychosis, and coma and can reduce the effectiveness of potentially life-saving cancer therapies, whereas iatrogenic causes can provoke atrial fibrillation and osteoporosis. Consequently, the diagnosis and treatment of hypothyroidism in cancer patients are pertinent. We summarize the history, epidemiology, pathophysiology, clinical diagnosis, and management of hypothyroidism in cancer patients. PMID:24309982

Hypothyroidism after a cancer diagnosis: etiology, diagnosis, complications, and management.

Science.gov (United States)

Carter, Yvette; Sippel, Rebecca S; Chen, Herbert

2014-01-01

Hypothyroidism is a common disease that is easily treated in the majority of cases, when readily diagnosed; however, presentation of an aggregate of its symptoms is often clinically overlooked or attributed to another disease and can potentially be lethal. Already prevalent in older women, its occurrence in younger patients is rising as a result of radiation therapy, radioactive iodine therapy, and newer antineoplastic agents used to manage various malignancies. The presence of nonspecific constitutional symptoms and neuropsychiatric complaints in cancer patients can be attributed to a myriad of other diagnoses and therapies. Thyroid dysfunction can be easily overlooked in cancer patients because of the complexity of cancer's clinical picture, particularly in the pediatric population. Underdiagnosis can have important consequences for the management of both hypothyroidism and the malignancy. At minimum, quality of life is adversely affected. Untreated hypothyroidism can lead to heart failure, psychosis, and coma and can reduce the effectiveness of potentially life-saving cancer therapies, whereas iatrogenic causes can provoke atrial fibrillation and osteoporosis. Consequently, the diagnosis and treatment of hypothyroidism in cancer patients are pertinent. We summarize the history, epidemiology, pathophysiology, clinical diagnosis, and management of hypothyroidism in cancer patients.

A Unified Pathophysiological Construct of Diabetes and its Complications.

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Schwartz, Stanley S; Epstein, Solomon; Corkey, Barbara E; Grant, Struan F A; Gavin Iii, James R; Aguilar, Richard B; Herman, Mary E

2017-09-01

Advances in understanding diabetes mellitus (DM) through basic and clinical research have helped clarify and reunify a disease state fragmented into numerous etiologies and subtypes. It is now understood that a common pathophysiology drives the diabetic state throughout its natural history and across its varied clinical presentations, a pathophysiology involving metabolic insults, oxidative damage, and vicious cycles that aggravate and intensify organ dysfunction and damage. This new understanding of the disease requires that we revisit existing diagnostics and treatment approaches, which were built upon outmoded assumptions. 'The Common Pathophysiologic Origins of Diabetes Mellitus and its Complications Construct' is presented as a more accurate, foundational, and translatable construct of DM that helps make sense of the hitherto ambiguous findings of long-term outcome studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

Science.gov (United States)

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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Prognostic indicators in patients presenting with acute cardiogenic pulmonary edema treated with CPAP: it's not the acid that matters, it's back to basics

OpenAIRE

Schlosshan, Dominik; Elliott, Mark

2010-01-01

Several prognostic markers have been identified for patients admitted with acute cardiogenic pulmonary edema. Most of the markers are based on clinical risk scores. Unlike hypercapnic respiratory failure, acidosis is not an adverse predictor in these patients. Hemodynamic variables that assess pathophysiological mechanisms may be more helpful to guide appropriate management.

Sodium–glucose cotransporter-2 inhibition and acidosis in patients with type 2 diabetes: a review of US FDA data and possible conclusions

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D'Elia JA

2017-06-01

Full Text Available John A D’Elia,1 Alissa R Segal,1,2 George P Bayliss,3 Larry A Weinrauch1 1Kidney and Hypertension Section, Joslin Diabetes Center, Harvard Medical School, 2Department of Pharmacy Practice, MCPHS University, Boston, MA, 3Division of Kidney Diseases and Hypertension, Rhode Island Hospital, Alpert Medical School, Brown University, Providence, RI, USA Objective: To evaluate whether adverse event reports to the US Food and Drug Administration on incidents of ketoacidosis from use of sodium glucose cotransport inhibitors (SGLT2 inhibitors provide insight into ways this new class of drugs is being prescribed with other antihyperglycemic agents; to examine possible mechanisms to explain ketoacidosis.Design and methods: Reports of adverse events concerned to SGLT2 inhibitors, namely, empagliflozin, dapagliflozin, and canagliflozin were obtained under the Freedom of Information Act for 5 years ending in August 31, 2015. The data were evaluated for incidents of ketoacidosis by looking for keywords such as diabetic ketoacidosis, ketoacidosis, lactic acidosis, acidosis, and metabolic acidosis. Results were tabulated individually for empagliflozin (n=260 adverse event reports, dapagliflozin (n=520, and canagliflozin (n=2159. Adverse events were categorized according to age, gender, and insulin use.Results: There were 46, 144, and 450 reports of ketoacidosis concerned with the use of empagliflozin, dapagliflozin, and canagliflozin, respectively. The use of SGLT2 inhibitors was not strictly limited to patients with type 2 diabetes but was cut across categories of insulin use, including a total of 172 cases of SGLT2-related ketoacidosis in individuals above the age of 40 who were not on insulin.Conclusion: Further studies should focus to detect pleiotropic effects of SGLT2 inhibitors, particularly with other oral antihyperglycemic drugs or insulin. A review of the literature suggests that patients with type 2 diabetes with low C-peptide level may be at

Erectile dysfunction as a manifestation of urogenital autonomic neuropathy in patients with type 1 diabetes: epidemiology, classification, pathophysiology, diagnosis and treatment options

OpenAIRE

Gagik Radikovich Galstyan; yana Grigor'evna Shwarts; Sergey Anatol'evich Dubsky; Aleksandr Evgen'evich Lepetukhin; Roman Viktorovich Rozhivanov; Dmitry Gennadievich Kurbatov

2014-01-01

Sexual dysfunction characterized by a significant decline in the quality of life of patients and leading to infertility and problems in social life is diagnosed in more than 40% of patients with diabetes mellitus (DM).Erectile dysfunction is the most common sexual disorder in DM patients. The article describes epidemiology, classification, pathophysiology, diagnostic and treatment of erectile dysfunction in T1DM patients.

Hypertension in women--pathophysiological and clinical aspects.

Science.gov (United States)

Erdine, Serap; Arslan, Eren; Olszanecka, Agnieszka

2012-01-01

Hypertension is the most important risk factor, responsible for cardiovascular morbidity and mortality worldwide, both in men and women. Cardiovascular disorders in women are still underestimated, due to lower absolute risk calculations and the underdetection of classical risk factors. In recent years the differences in pathophysiology and the clinical presentation and treatment of cardiac diseases in women have become fields of interest and research. Several studies have examined gender-related differences in the pathophysiology of hypertension, its prevalence and control. The influence of menopause, obesity and salt-sensitivity on the pathogenesis of hypertension in women has been widely investigated. This article presents current data on differences in prevalence, control and mechanisms of hypertension in women.

Subacute ruminal acidosis (SARA) in grazing Irish dairy cows.

Science.gov (United States)

O'Grady, Luke; Doherty, Michael L; Mulligan, Finbar J

2008-04-01

Subacute ruminal acidosis (SARA) is a significant production disease of dairy cattle. Previous concerns have been raised over the occurrence of SARA in pasture-fed dairy cattle and the potential consequences of laminitis and lameness. Highly digestible perennial rye grass contains high concentrations of rapidly fermentable carbohydrate and low concentrations of physical effective fibre that may result in SARA. This study conducted a point prevalence survey of rumen health status in grazing Irish dairy cattle fed predominantly perennial rye grass-based pasture. The survey assessed rumen fluid, animal health status, milk production data and pasture composition. A total of 144 cows between 80 and 150 days in milk were sampled on 12 farms. Eleven percent of cows were classified as affected with SARA (pH 5.8). The study showed that low rumen pH is prevalent in grazing Irish dairy cattle consuming perennial rye grass-based pasture and raises concerns regarding effective pasture utilisation and possible consequences for animal health.

Acute Kidney Injury: Definition, Pathophysiology and Clinical Phenotypes.

Science.gov (United States)

Makris, Konstantinos; Spanou, Loukia

2016-05-01

Acute kidney injury (AKI) is a clinical syndrome that complicates the course and worsens the outcome in a significant number of hospitalised patients. Recent advances in clinical and basic research will help with a more accurate definition of this syndrome and in the elucidation of its pathogenesis. With this knowledge we will be able to conduct more accurate epidemiologic studies in an effort to gain a better understanding of the impact of this syndrome. AKI is a syndrome that rarely has a sole and distinct pathophysiology. Recent evidence, in both basic science and clinical research, is beginning to change our view for AKI from a single organ failure syndrome to a syndrome where the kidney plays an active role in the progress of multi-organ dysfunction. Accurate and prompt recognition of AKI and better understanding of the pathophysiologic mechanisms underlying the various clinical phenotypes are of great importance to research for effective therapeutic interventions. In this review we provide the most recent updates in the definition, epidemiology and pathophysiology of AKI.

Pancreatitis in dogs and cats: definitions and pathophysiology.

Science.gov (United States)

Watson, P

2015-01-01

Pancreatitis, or inflammation of the pancreas, is commonly seen in dogs and cats and presents a spectrum of disease severities from acute to chronic and mild to severe. It is usually sterile, but the causes and pathophysiology remain poorly understood. The acute end of the disease spectrum is associated with a high mortality but the potential for complete recovery of organ structure and function if the animal survives. At the other end of the spectrum, chronic pancreatitis in either species can cause refractory pain and reduce quality of life. It may also result in progressive exocrine and endocrine functional impairment. There is confusion in the veterinary literature about definitions of acute and chronic pancreatitis and there are very few studies on the pathophysiology of naturally occurring pancreatitis in dogs and cats. This article reviews histological and clinical definitions and current understanding of the pathophysiology and causes in small animals by comparison with the much more extensive literature in humans, and suggests many areas that need further study in dogs and cats. © 2015 British Small Animal Veterinary Association.

Diagnosis and Management of Gastroenteropathy Asssociated to Non-steroidal Anti-Inflammatory Drugs

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Stella Ilone

2016-09-01

Full Text Available Non-steroidal anti-inflammatory drugs (NSAIDs is a group of drugs used to treat pain, inflammation, and fever. High consumption of NSAIDs associated with high gastrointestinal side effects. Common complaint from patients, which ranging from mild heartburn to the onset of gastrointestinal bleeding, often complicates the adequate administration of NSAIDs. Various methods have been developed to reduce the likelihood of gastroenteropathy complication. Early diagnosis, appropriate prompt treatment, as well as adequate monitoring will reduce morbidity and mortality from complications due to NSAIDs. This paper will discuss the diagnosis and management of gastro-enteropathy NSAID through approaching the underlying pathophysiology.

ETIOLOGY, PATHOGENESIS AND CLINICAL DIAGNOSIS OF PEYRONIE’S DISEASE

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Тарас Валерьевич Шатылко

2017-03-01

Full Text Available Peyronie’s disease remains an understudied progressing disease being  one of the relevant problems of modern urology and andrology. This condition may cause erectile dysfunction in men of fertile age and its negative impact on sexual function adversely affects patients’ quality of life. This article reviews epidemiology, pathophysiology and specifics of recording history and clinical diagnosis of Peyronie’s disease, that includes questionnaires, physical examination, evaluation of erectile function and penile deformity.

Lifetime exercise intolerance with lactic acidosis as key manifestation of novel compound heterozygous ACAD9 mutations causing complex I deficiency.

Science.gov (United States)

Schrank, Bertold; Schoser, Benedikt; Klopstock, Thomas; Schneiderat, Peter; Horvath, Rita; Abicht, Angela; Holinski-Feder, Elke; Augustis, Sarunas

2017-05-01

We report a 36-year-old female having lifetime exercise intolerance and lactic acidosis with nausea associated with novel compound heterozygous Acyl-CoA dehydrogenase 9 gene (ACAD9) mutations (p.Ala390Thr and p.Arg518Cys). ACAD9 is an assembly factor for the mitochondrial respiratory chain complex I. ACAD9 mutations are recognized as frequent causes of complex I deficiency. Our patient presented with exercise intolerance, rapid fatigue, and nausea since early childhood. Mild physical workload provoked the occurrence of nausea and vomiting repeatedly. Her neurological examination, laboratory findings and muscle biopsy demonstrated no abnormalities. A bicycle spiroergometry provoked significant lactic acidosis during and following exercise pointing towards a mitochondrial disorder. Subsequently, the analysis of respiratory chain enzyme activities in muscle revealed severe isolated complex I deficiency. Candidate gene sequencing revealed two novel heterozygous ACAD9 mutations. This patient report expands the mutational and phenotypic spectrum of diseases associated with mutations in ACAD9. Copyright © 2017 Elsevier B.V. All rights reserved.

Erectile dysfunction as a manifestation of urogenital autonomic neuropathy in patients with type 1 diabetes: epidemiology, classification, pathophysiology, diagnosis and treatment options

Directory of Open Access Journals (Sweden)

Gagik Radikovich Galstyan

2014-05-01

Full Text Available Sexual dysfunction characterized by a significant decline in the quality of life of patients and leading to infertility and problems in social life is diagnosed in more than 40% of patients with diabetes mellitus (DM.Erectile dysfunction is the most common sexual disorder in DM patients. The article describes epidemiology, classification, pathophysiology, diagnostic and treatment of erectile dysfunction in T1DM patients.

Dissecting carboxypeptidase E: properties, functions and pathophysiological roles in disease

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Lin Ji

2017-04-01

Full Text Available Since discovery in 1982, carboxypeptidase E (CPE has been shown to be involved in the biosynthesis of a wide range of neuropeptides and peptide hormones in endocrine tissues, and in the nervous system. This protein is produced from pro-CPE and exists in soluble and membrane forms. Membrane CPE mediates the targeting of prohormones to the regulated secretory pathway, while soluble CPE acts as an exopeptidase and cleaves C-terminal basic residues from peptide intermediates to generate bioactive peptides. CPE also participates in protein internalization, vesicle transport and regulation of signaling pathways. Therefore, in two types of CPE mutant mice, Cpefat/Cpefat and Cpe knockout, loss of normal CPE leads to a lot of disorders, including diabetes, hyperproinsulinemia, low bone mineral density and deficits in learning and memory. In addition, the potential roles of CPE and ΔN-CPE, an N-terminal truncated form, in tumorigenesis and diagnosis were also addressed. Herein, we focus on dissecting the pathophysiological roles of CPE in the endocrine and nervous systems, and related diseases.

Prenatal Diagnosis of Dextrotransposition of the Great Arteries

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Jeng-Hsiu Hung

2008-10-01

Full Text Available Dextrotransposition of the great arteries (DTGA is a common cardiac cause of cyanosis in newborn infants that can cause acidosis and death within a short period of time unless there is a large atrial-level shunt or a patent ductus arteriosus. Here, we report a case of prenatal diagnosis of DTGA at 24+1 gestational weeks. In a tilted 4-chamber view, the pulmonary trunk branched to the left and the right pulmonary, with its root connected to the left ventricle outflow tract. In the short-axis view, the pulmonary trunk was shown to be parallel with the ascending aortic root. Cesarean section was performed due to the nonreassuring fetal status at 38+5 gestational weeks. The male neonate appeared to have mild cyanotic symptoms and weighed 3,108 g. Apgar scores were 8 and 9 at 1 and 5 minutes, respectively. Neonatal echocardiography was performed immediately after birth and the findings confirmed DTGA associated with atrial septal defect secundum. Postnatally, angiography confirmed the echocardiographic diagnosis of DTGA with a large atrial septal defect secundum and a large patent ductus arteriosus. Jatene arterial switch operation and atrial septal defect closure with Gore-Tex patch were performed. The neonate withstood the operation well and was discharged 27 days after birth weighing 2,950 g and in a stable condition. Prenatal diagnosis of DTGA can greatly aid to prepare the patient's family and the surgeon and significantly improve the outcome of complex heart disease in the neonatal period.

[Circadian blood pressure variation under several pathophysiological conditions including secondary hypertension].

Science.gov (United States)

Imai, Yutaka; Hosaka, Miki; Satoh, Michihiro

2014-08-01

Abnormality of circadian blood pressure (BP) variation, i.e. non-dipper, riser, nocturnal hypertension etc, is brought by several pathophysiological conditions especially by secondary hypertension. These pathophysiological conditions are classified into several categories, i.e. disturbance of autonomic nervous system, metabolic disorder, endocrine disorder, disorder of Na and water excretion (e.g. sodium sensitivity), severe target organ damage and ischemia, cardiovascular complications and drug induced hypertension. Each pathophysiological condition which brings disturbance of circadian BP variation is included in several categories, e.g. diabetes mellitus is included in metabolic disorder, autonomic imbalance, sodium sensitivity and endocrine disorder. However, it seems that unified principle of the genesis of disturbance of circadian BP variation in many pathophysiological conditions is autonomic imbalance. Thus, it is concluded that disturbance of circadian BP variation is not purposive biological behavior but the result of autonomic imbalance which looks as if compensatory reaction such as exaggerated Na-water excretion during night in patient with Na-water retention who reveals disturbed circadian BP variation.

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

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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.

Velopharyngeal sphincter pathophysiologic aspects in the in cleft palat

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Collares, Marcus Vinicius Martins

2008-09-01

Full Text Available Introduction: Cleft lip and palate are common congenital abnormalities with typical functional disorders on speech, deglutition and middle ear function. Objective: This article reviews functional labiopalatine disorders through a pathophysiological view. Method: We performed a literature search on line, as well as books and periodicals related to velopharyngeal sphincter. Our sources were LILACS, MEDLINE and SciELO databases, and we applied to the research Keywords of interest on the velopharyngeal pathophysiology, for articles published between 1965 and 2007. Conclusion: Velopharyngeal sphincter plays a central role in speech, swallowing and middle ear physiology in patients with labiopalatine cleft. At the end of our bibliographic review, pursuant to the velopharyngeal physiology in individuals with this disorder in the functional speech, deglutition and otologic function, we observed that although there is a great number of published data discussing this issue, further studies are necessary to completely understand the pathophysiology, due to the fact they have been exploited superficially.

The Pathophysiology of Eosinophilic Esophagitis

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Daniel Avi Lemberg

2014-05-01

Full Text Available Eosinophilic Esophagitis (EoE is an emerging disease characterised by esophageal eosinophilia (>15eos/hpf, lack of responsiveness to acid-suppressive medication and is managed by allergen elimination and anti-allergy therapy. Although the pathophysiology of EoE is currently unsubstantiated, evidence implicates food and aeroallergen hypersensitivity in genetically predisposed individuals as contributory factors. Genome-wide expression analyses have isolated a remarkably conserved gene-expression profile irrespective of age and gender, suggesting a genetic contribution. EoE has characteristics of mainly TH2 type immune responses but also some TH1 cytokines, which appear to strongly contribute to tissue fibrosis, with esophageal epithelial cells providing a hospitable environment for this inflammatory process. Eosinophil-degranulation products appear to play a central role in tissue remodeling in EoE. This remodeling and dysregulation predisposes to fibrosis. Mast cell-derived molecules such as histamine may have an effect on enteric nerves and may also act in concert with TGF-β to interfere with esophageal musculature. Additionally, the esophageal epithelium may facilitate the inflammatory process under pathogenic contexts such as in EoE. This article aims to discuss the contributory factors in the pathophysiology of EoE.

Lack of correlation between length variation in the DNA polymerase gamma gene CAG repeat and lactic acidosis or neuropathy during antiretroviral treatment

NARCIS (Netherlands)

Chen, Xianghong; Goudsmit, Jaap; van der Kuyl, Antoinette C.

2002-01-01

Antiretroviral therapy, although successful in reducing HIV load and accordingly decreasing the incidence of HIV infection-related symptoms, has its drawbacks in the form of severe side effects. Recognized drug-related side effects are, for example, nausea, fatigue, lactic acidosis, neuropathy,

A Proteomic Approach for the Diagnosis of ‘Oketsu’ (blood stasis, a Pathophysiologic Concept of Japanese Traditional (Kampo Medicine

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Chinami Matsumoto

2008-01-01

Full Text Available ‘Oketsu’ is a pathophysiologic concept in Japanese traditional (Kampo medicine, primarily denoting blood stasis/stagnant syndrome. Here we have explored plasma protein biomarkers and/or diagnostic algorithms for ‘Oketsu’. Sixteen rheumatoid arthritis (RA patients were treated with keishibukuryogan (KBG, a representative Kampo medicine for improving ‘Oketsu’. Plasma samples were diagnosed as either having an ‘Oketsu’ (n = 19 or ‘non-Oketsu’ (n = 29 state according to Terasawa's ‘Oketsu’ scoring system. Protein profiles were obtained by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS and hierarchical clustering and decision tree analyses were performed. KBG treatment for 4 or 12 weeks decreased the ‘Oketsu’ scores significantly. SELDI protein profiles gave 266 protein peaks, whose expression was significantly different between the ‘Oketsu’ and ‘non-Oketsu’ states. Hierarchical clustering gave three major clusters (I, II, III. The majority (68.4% of ‘Oketsu’ samples were clustered into one cluster as the principal component of cluster I. The remaining ‘Oketsu’ profiles constituted a minor component of cluster II and were all derived from patients cured of the ‘Oketsu’ state at 12 weeks. Construction of the decision tree addressed the possibility of developing a diagnostic algorithm for ‘Oketsu’. A reduction in measurement/pre-processing conditions (from 55 to 16 gave a similar outcome in the clustering and decision tree analyses. The present study suggests that the pathophysiologic concept of Kampo medicine ‘Oketsu’ has a physical basis in terms of the profile of blood proteins. It may be possible to establish a set of objective criteria for diagnosing ‘Oketsu’ using a combination of proteomic and bioinformatics-based classification methods.

[MELAS syndrome as a differential diagnosis of ischemic stroke].

Science.gov (United States)

Finsterer, J

2009-01-01

Mitochondrial encephalomyopathy, lactacidosis and stroke-like episode (MELAS) syndrome is a phenotypically and genetically heterogeneous mitochondrial disorder with a clinical onset between the first and third decade. The clinical hallmark is the stroke-like-episode, which mimicks ischemic stroke but is usually transient and non-disabling in nature. The morphological equivalent on MRI is a T2-hyperintensity, predominantly over the temporo-parieto-occipital region, not confined to a vascular territory, which is also hyperintense on diffusion weighted imaging and on apparent diffusion coefficient sequences (vasogenic edema, stroke-like lesion). Additional features include seizures, cognitive decline, psychosis, lactic acidosis, migraine, visual impairment, hearing loss, short stature, diabetes, or myopathy. Muscle biopsy typically shows ragged-red fibers, COX-negative fibers, SDH hyperreactivity, and abnormally shaped mitochondria with paracristalline inclusions. The diagnosis is confirmed by demonstration of a biochemical respiratory chain defect or one of the disease-causing mutations, of which 80 % affect the mitochondrial tRNALeu gene.

Postnatal and antenatal laboratory diagnosis of glutaric aciduria II in a South African family

International Nuclear Information System (INIS)

Henderson, H.E.; Balla, R.; De Jong, G.; Piek, C.J.; Mienie, L.J.; Erasmus, E.

1987-01-01

Glutaric aciduria type II (Ga II) was proved in a neonate who presented shortly after birth with respiratory distress, metabolic acidosis, non-ketotic hypoglycaemia and a sweaty-feet-like odour. The diagnosis was based on elevated levels of glutaric and other acids in the urine and on studies on cultured skin fibroblasts where defective metabolism of fatty acids of varying chain length was demonstrated. Antenatal diagnosis was performed on a subsequent pregnancy in this family where an abnormal amniotic fluid organic acid profile together with defective fatty acid oxidation in cultured amnion cells was indicative of GA II in the fetus. A measure of efficency of butyrate oxidation was obtained by analysis of the amount of 14 C label incorporated into trichloro-acetic acid precipitable macromolecules. The incorporation of ( 3 H) leucine was taken as a general indicator of metabolism in the cell population. This is the first report of this genetic disorder in a South African family and it should be considered in suspected organic acidaemia in the neonatal period

[AV-reentrant tachycardia and Wolff-Parkinson-White syndrome : Diagnosis and treatment].

Science.gov (United States)

Voss, Frederik; Eckardt, Lars; Busch, Sonia; Estner, Heidi L; Steven, Daniel; Sommer, Philipp; von Bary, Christian; Neuberger, Hans-Ruprecht

2016-12-01

The AV-reentrant tachycardia (AVRT) is a supraventricular tachycardia with an incidence of 1-3/1000. The pathophysiological basis is an accessory atrioventricular pathway (AP). Patients with AVRT typically present with palpitations, an on-off characteristic, anxiety, dyspnea, and polyuria. This type of tachycardia may often be terminated by vagal maneuvers. Although the clinical presentation of AVRT is quite similar to AV-nodal reentrant tachycardias, the correct diagnosis is often facilitated by analyzing a standard 12-lead ECG at normal heart rate showing ventricular preexcitation. Curative catheter ablation of the AP represents the therapy of choice in symptomatic patients. This article is the fourth part of a series written to improve the professional education of young electrophysiologists. It explains pathophysiology, symptoms, and electrophysiological findings of an invasive EP study. It focusses on mapping and ablation of accessory pathways.

DMPD: Pathophysiological roles of interleukin-18 in inflammatory liver diseases. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 10807517 Pathophysiological roles of interleukin-18 in inflammatory liver diseases....l) Show Pathophysiological roles of interleukin-18 in inflammatory liver diseases. PubmedID 10807517 Title P...athophysiological roles of interleukin-18 in inflammatory liver diseases. Authors

The pathophysiology of bronchiectasis

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Paul T King

2009-10-01

Full Text Available Paul T KingDepartment of Medicine, Department of Respiratory and Sleep Medicine, Monash University, Monash Medical Centre, Melbourne, Victoria, AustraliaAbstract: Bronchiectasis is defined by permanent and abnormal widening of the bronchi. This process occurs in the context of chronic airway infection and inflammation. It is usually diagnosed using computed tomography scanning to visualize the larger bronchi. Bronchiectasis is also characterized by mild to moderate airflow obstruction. This review will describe the pathophysiology of noncystic fibrosis bronchiectasis. Studies have demonstrated that the small airways in bronchiectasis are obstructed from an inflammatory infiltrate in the wall. As most of the bronchial tree is composed of small airways, the net effect is obstruction. The bronchial wall is typically thickened by an inflammatory infiltrate of lymphocytes and macrophages which may form lymphoid follicles. It has recently been demonstrated that patients with bronchiectasis have a progressive decline in lung function. There are a large number of etiologic risk factors associated with bronchiectasis. As there is generally a long-term retrospective history, it may be difficult to determine the exact role of such factors in the pathogenesis. Extremes of age and smoking/chronic obstructive pulmonary disease may be important considerations. There are a variety of different pathogens involved in bronchiectasis, but a common finding despite the presence of purulent sputum is failure to identify any pathogenic microorganisms. The bacterial flora appears to change with progression of disease. Keywords: bronchiectasis, inflammation, obstructive lung disease, pathophysiology, pathology

The effect of CO2 and non-CO2-generating buffers on cerebral acidosis after cardiac arrest: A 31P NMR study.

Science.gov (United States)

Rosenberg, J M; Martin, G B; Paradis, N A; Nowak, R M; Walton, D; Appleton, T J; Welch, K M

1989-04-01

There is controversy regarding the use of alkalinizing agents during reperfusion after cardiac arrest. The potential deleterious effects of sodium bicarbonate (bicarb) administration, including paradoxic cerebral acidosis, have led to the search for alternative agents. Tromethamine (tris) is a non-CO2-generating buffer that has been proposed for use during cardiopulmonary resuscitation. The purpose of this experiment was to compare the ability of tris with bicarb to correct brain pH (pH B) during reperfusion after a 12-minute cardiac arrest. Adult mongrel dogs were instrumented and placed in the bore of a Bruker Biospec 1.89 tesla superconducting magnet system. Ventricular fibrillation was induced; after 12 minutes, cardiopulmonary bypass was initiated and maintained for two hours with minimum flows of 80 mL/kg/min. Bicarb (n = 5) or tris (n = 5) were administered to correct arterial pH as rapidly as possible. 31P NMR spectra were obtained at baseline and throughout ischemia and reperfusion. The pH B was determined with the inorganic phosphate relative to the phosphocreatine resonance signal shift. Profile analysis indicates a difference between groups (P less than .02) related to an initial delay in pH B correction in the tris group. By 48 minutes of reperfusion, pH B did not differ between the groups. Moreover, there was no evidence of paradoxic cerebral acidosis in the bicarb group. Although tris corrects blood pH as quickly as bicarb, it is less effective in correcting pH B. Absence of paradoxic acidosis may be caused by efficient elimination of CO2 by cardiopulmonary bypass.

Regulation of intracellular pH in cnidarians: response to acidosis in Anemonia viridis.

Science.gov (United States)

Laurent, Julien; Venn, Alexander; Tambutté, Éric; Ganot, Philippe; Allemand, Denis; Tambutté, Sylvie

2014-02-01

The regulation of intracellular pH (pHi) is a fundamental aspect of cell physiology that has received little attention in studies of the phylum Cnidaria, which includes ecologically important sea anemones and reef-building corals. Like all organisms, cnidarians must maintain pH homeostasis to counterbalance reductions in pHi, which can arise because of changes in either intrinsic or extrinsic parameters. Corals and sea anemones face natural daily changes in internal fluids, where the extracellular pH can range from 8.9 during the day to 7.4 at night. Furthermore, cnidarians are likely to experience future CO₂-driven declines in seawater pH, a process known as ocean acidification. Here, we carried out the first mechanistic investigation to determine how cnidarian pHi regulation responds to decreases in extracellular and intracellular pH. Using the anemone Anemonia viridis, we employed confocal live cell imaging and a pH-sensitive dye to track the dynamics of pHi after intracellular acidosis induced by acute exposure to decreases in seawater pH and NH₄Cl prepulses. The investigation was conducted on cells that contained intracellular symbiotic algae (Symbiodinium sp.) and on symbiont-free endoderm cells. Experiments using inhibitors and Na⁺-free seawater indicate a potential role of Na⁺/H⁺ plasma membrane exchangers (NHEs) in mediating pHi recovery following intracellular acidosis in both cell types. We also measured the buffering capacity of cells, and obtained values between 20.8 and 43.8 mM per pH unit, which are comparable to those in other invertebrates. Our findings provide the first steps towards a better understanding of acid-base regulation in these basal metazoans, for which information on cell physiology is extremely limited. © 2013 FEBS.

Pathophysiology and management of pediatric ascites.

Science.gov (United States)

Sabri, Mahmoud; Saps, Miguel; Peters, John M

2003-06-01

Ascites accumulation is the product of a complex process involving hepatic, renal, systemic, hemodynamic, and neurohormonal factors. The main pathophysiologic theories of ascites formation include the "underfill," "overflow," and peripheral arterial vasodilation hypotheses. These theories are not necessarily mutually exclusive and are linked at some level by a common pathophysiologic thread: The body senses a decreased effective arterial blood volume, leading to stimulation of the sympathetic nervous system, arginine-vasopressin feedback loops, and the renin-angiotensin-aldosterone system. Cornerstones of ascites management include dietary sodium restriction and diuretics. Spironolactone is generally tried initially, with furosemide added if clinical response is suboptimal. More refractory patients require large-volume paracentesis (LVP) accompanied by volume expansion with albumin. Placement of a transjugular intrahepatic portosystemic shunt is reserved for individuals with compensated liver function who require very frequent sessions of LVP. Peritoneovenous shunts are not used in contemporary ascites management. Liver transplantation remains the definitive therapy for refractory ascites. Although treatment of ascites fails to improve survival, it benefits quality of life and limits the development of such complications as spontaneous bacterial peritonitis.

Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy

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Hana Starobova

2017-05-01

Full Text Available Chemotherapy-induced neuropathy is a common, dose-dependent adverse effect of several antineoplastics. It can lead to detrimental dose reductions and discontinuation of treatment, and severely affects the quality of life of cancer survivors. Clinically, chemotherapy-induced peripheral neuropathy presents as deficits in sensory, motor, and autonomic function which develop in a glove and stocking distribution due to preferential effects on longer axons. The pathophysiological processes are multi-factorial and involve oxidative stress, apoptotic mechanisms, altered calcium homeostasis, axon degeneration and membrane remodeling as well as immune processes and neuroinflammation. This review focusses on the commonly used antineoplastic substances oxaliplatin, cisplatin, vincristine, docetaxel, and paclitaxel which interfere with the cancer cell cycle—leading to cell death and tumor degradation—and cause severe acute and chronic peripheral neuropathies. We discuss drug mechanism of action and pharmacokinetic disposition relevant to the development of peripheral neuropathy, the epidemiology and clinical presentation of chemotherapy-induced neuropathy, emerging insight into genetic susceptibilities as well as current understanding of the pathophysiology and treatment approaches.

Pathogenesis and Pathophysiology of Pneumococcal Meningitis

Science.gov (United States)

Mook-Kanamori, Barry B.; Geldhoff, Madelijn; van der Poll, Tom; van de Beek, Diederik

2011-01-01

Summary: Pneumococcal meningitis continues to be associated with high rates of mortality and long-term neurological sequelae. The most common route of infection starts by nasopharyngeal colonization by Streptococcus pneumoniae, which must avoid mucosal entrapment and evade the host immune system after local activation. During invasive disease, pneumococcal epithelial adhesion is followed by bloodstream invasion and activation of the complement and coagulation systems. The release of inflammatory mediators facilitates pneumococcal crossing of the blood-brain barrier into the brain, where the bacteria multiply freely and trigger activation of circulating antigen-presenting cells and resident microglial cells. The resulting massive inflammation leads to further neutrophil recruitment and inflammation, resulting in the well-known features of bacterial meningitis, including cerebrospinal fluid pleocytosis, cochlear damage, cerebral edema, hydrocephalus, and cerebrovascular complications. Experimental animal models continue to further our understanding of the pathophysiology of pneumococcal meningitis and provide the platform for the development of new adjuvant treatments and antimicrobial therapy. This review discusses the most recent views on the pathophysiology of pneumococcal meningitis, as well as potential targets for (adjunctive) therapy. PMID:21734248

Adult-onset of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome presenting as acute meningoencephalitis: a case report.

Science.gov (United States)

Hsu, Yu-Chuan; Yang, Fu-Chi; Perng, Cherng-Lih; Tso, An-Chen; Wong, Lee-Jun C; Hsu, Chang-Hung

2012-09-01

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a rare mitochondrial disorder with a wide range of multisystemic symptoms. Epileptic seizures are common features of both MELAS and meningoencephalitis and are typically treated with anticonvulsants. To provide the reader with a better understanding of MELAS and the adverse effects of valproic acid. A 47-year-old man with a history of diabetes, hearing loss, sinusitis, and otitis media was brought to our emergency department due to acute onset of fever, headache, generalized seizure, and agitation. Because acute meningoencephalitis was suspected, the patient was treated with antibiotics on an empirical basis. The seizure activity was aggravated by valproic acid and abated after its discontinuation. MELAS was suspected and the diagnosis was confirmed by the presence of a nucleotide 3243 A→G mutation in the mitochondrial DNA. Detailed history-taking and systematic review help emergency physicians differentiate MELAS from meningoencephalitis in patients with the common presentation of epileptic seizures. Use of valproic acid to treat epilepsy in patients suspected of having mitochondrial disease should be avoided. Underlying mitochondrial disease should be suspected if seizure activity worsens with valproic acid therapy. Copyright © 2012 Elsevier Inc. All rights reserved.

Current challenges and problems in teaching pathophysiology in Ukraine - another reaction to Churilov's paper.

Science.gov (United States)

Ataman, Oleksandr V

2017-12-01

Pathophysiology in Ukraine has rich traditions and achievements in the scientific areas, as well as in teaching academic discipline. Its history, the main Ukrainian scientific schools and their famous representatives are briefly described. The content of existing study program, the main approaches to teaching, and some methodological and organizational problems needed to be solved are characterized. The necessity and usefulness of developing and implementing the three separate courses of discipline (Essential, Clinical and Advanced Pathophysiology) are substantiated. The place of Pathophysiology in the training of physicians with different kinds of their future activity is discussed. Relation of teaching Pathophysiology to Translational and Personalized Medicine is tried to be shown.

[PRIMARY HEADACHE IN CHILDREN AND ADOLESCENTS--DIAGNOSIS AND TREATMENT].

Science.gov (United States)

Matar, Amal Khourieh; Kerem, Nogah C; Srugo, Isaac; Genizi, Jacob

2015-12-01

Primary headaches are one of the most common disorders of childhood, with migraine and tension type headaches (TTHs) being the most frequent ones. In spite of their prevalence, there is paucity of knowledge regarding the underlying pathophysiological mechanisms that cause headaches and regarding the unique aspects of headaches in children and adolescents. To review the literature and summarize the knowledge regarding clinical features, diagnosis and management of primary headache in children and adolescents, mainly migraine and TTH. Most of our current knowledge regarding primary headaches in children and adolescents is driven from extrapolations from studies that were conducted with adult patients. Therefore, it needs to be validated for the different age groups. Migraines may be diagnosed effectively based on the 2nd edition of the International Classification of Headache Disorders (ICHD-II), however, TTH is diagnosed mainly by the absence of features found in other headache types. Treatment strategies for primary headaches vary according to patient's age, family structure, culture and beliefs, headache diagnosis, and based on the disability the headache imposes on the patient's daily living. It was shown that a multidisciplinary approach, that includes continuing counseling, education, and reassurance, in combination with pharmacological and non-pharmacological treatment, is an effective strategy for children and adolescents suffering from primary headaches. Further studies are needed to enrich our knowledge about the pathophysiological mechanisms that cause headaches in children and adolescents and to develop efficient strategies to alleviate their burden.

Pathophysiology of diurnal drooling in Parkinson's disease

NARCIS (Netherlands)

Kalf, J.G.; Munneke, M.; Engel-Hoek, L. van den; Swart, B.J.M. de; Borm, G.F.; Bloem, B.R.; Zwarts, M.J.

2011-01-01

Drooling is an incapacitating feature of Parkinson's disease. Better pathophysiological insights are needed to improve treatment. In this study, we tested the hypothesis that the cause of drooling is multifactorial. We examined 15 patients with Parkinson's disease with distinct diurnal saliva loss

Diagnosis and Surgical Management of Male Pelvic, Inguinal, and Testicular Pain.

Science.gov (United States)

Belanger, Gabriel V; VerLee, Graham T

2016-06-01

Pain occurs in the male genitourinary organs as for any organ system in response to traumatic, infectious, or irritative stimuli. A knowledge and understanding of chronic genitourinary pain can be of great utility to practicing nonurologists. This article provides insight into the medical and surgical management of subacute and chronic pelvic, inguinal, and scrotal pain. The pathophysiology, diagnosis, and medical and surgical treatment options of each are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

Pathophysiology of shunt dysfunction in shunt treated hydrocephalus

DEFF Research Database (Denmark)

Blegvad, C.; Skjolding, A D; Broholm, H

2013-01-01

We hypothesized that shunt dysfunction in the ventricular catheter and the shunt valve is caused by different cellular responses. We also hypothesized that the cellular responses depend on different pathophysiological mechanisms....

Effect of lung-protective ventilation-induced respiratory acidosis on the duration of neuromuscular blockade by rocuronium.

Science.gov (United States)

Taguchi, Shinya; Ono, Kazumi; Hidaka, Hidekuni; Koyama, Yusuke

2016-12-01

The purpose of this study was to elucidate whether lung-protective ventilation-induced respiratory acidosis increased the duration of neuromuscular blockade by rocuronium. A total of 72 patients were enrolled. After the induction of general anesthesia, rocuronium 0.6 mg/kg real body weight was administered. Tidal volume and positive end-expiratory pressure were randomly assigned as either 10 ml/kg predicted body weight and 0 cmH 2 O (group S) or 6 ml/kg and 5 cmH 2 O (group L), respectively. Respiratory rate was started at 10/min. Neuromuscular blockade was monitored by acceleromyography at the adductor pollicis with train-of-four stimulation. The time from the initial bolus injection of rocuronium to first recovery of the first twitch was defined as DUR1. Immediately, rocuronium 0.15 mg/kg was administered. The time from first recovery of the first twitch to second recovery of the first twitch was defined as DUR2. We also measured arterial pH (pH1 and pH2, respectively). Data from 66 patients (33 each in groups L and S) were eventually available. pH1 and pH2 were significantly lower in group L compared with group S [pH1: 7.308 (7.288-7.334) vs. 7.439 (7.423-7.466); p respiratory acidosis increased the duration of neuromuscular blockade by rocuronium.

Blended Learning Versus Traditional Lecture in Introductory Nursing Pathophysiology Courses.

Science.gov (United States)

Blissitt, Andrea Marie

2016-04-01

Currently, many undergraduate nursing courses use blended-learning course formats with success; however, little evidence exists that supports the use of blended formats in introductory pathophysiology courses. The purpose of this study was to compare the scores on pre- and posttests and course satisfaction between traditional and blended course formats in an introductory nursing pathophysiology course. This study used a quantitative, quasi-experimental, nonrandomized control group, pretest-posttest design. Analysis of covariance compared pre- and posttest scores, and a t test for independent samples compared students' reported course satisfaction of the traditional and blended course formats. Results indicated that the differences in posttest scores were not statistically significant between groups. Students in the traditional group reported statistically significantly higher satisfaction ratings than students in the blended group. The results of this study support the need for further research of using blended learning in introductory pathophysiology courses in undergraduate baccalaureate nursing programs. Further investigation into how satisfaction is affected by course formats is needed. Copyright 2016, SLACK Incorporated.

Does high-dose metformin cause lactic acidosis in type 2 diabetic patients after CABG surgery? A double blind randomized clinical trial

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Rahman Ghafari

2011-06-01

Full Text Available Metformin is a dimethyl biguanide oral anti-hyperglycemic agent. Lactic acidosis due to metformin is a fatal metabolic condition that limits its use in patients in poor clinical condition, consequently reducing the number of patients who benefit from this medication. In a double blind randomized clinical trial, we investigated 200 type 2 diabetic patients after coronary artery bypass surgery in the open heart ICU of the Mazandaran Heart Center, and randomly assigned them to equal intervention and control groups. The intervention group received regular insulin infusion along with 2 metformin 500 mg tablets every twelve hours, while the control group received only intravenous insulin with 2 placebo tablets every twelve hours. Lactate level, pH, base excess, blood glucose and serum creatinine were measured over five 12 h periods, with data averaged for each period. The primary outcome in this study was high lactate levels. Comparison between the 2 groups was made by independent Student’s t-test. To compare changes in multiple measures in each group and analysis of group interaction, a repeated measurement ANOVA test was used. There was no significant difference between the 2 groups regarding pH, base excess, or bicarbonate intake (P>0.05. No patient showed lactic acidosis in either group. Lactate levels were 23.0 vs 23.4 in the insulin-metformin and insulin only groups when the study was started, respectively. At the end of the study, those levels were 18.7 vs 18.9, respectively. In addition, the ANOVA repeated measurement test did not show a significant difference in terms of changes in the amount of lactate level between the 2 groups during the five measurement tests of the study period (P>0.05. High-dose metformin (1,000 mg twice daily with insulin does not cause lactic acidosis in type 2 diabetic patients after coronary artery

Acid-base profile and predictors of metabolic acidosis in patients undergoing peritoneal dialysis with lactate- and bicarbonate-buffered peritoneal dialysis solutions.

Science.gov (United States)

Fourtounas, Costas; Savidaki, Eirini; Roumelioti, Marilena; Dousdampanis, Periklis; Hardalias, Andreas; Kalliakmani, Pantelitsa; Papachristou, Evangelos; Drakopoulos, Anastasios; Goumenos, Dimitrios S; Vlachojannis, Jannis G

2006-01-01

Metabolic acidosis correction is one of the goals of renal replacement therapy. Correction of acidosis in peritoneal dialysis (PD) may be affected by PD modalities such as automated PD (APD) or by new solutions containing a combination of bicarbonate and lactate as a buffer [bicarbonate continuous ambulatory PD (CAPD)]. The aim of the present study was to examine the acid-base status of our PD population and to compare the effects of APD, lactate CAPD, and bicarbonate CAPD on serum bicarbonate levels. We studied 35 stable patients undergoing APD (n = 15), lactate-buffered (35 mEq/L) CAPD (n = 14), and bicarbonate/lactate-buffered CAPD (n = 6) for 48.5 +/- 38.1 months. Most of our patients had serum bicarbonate levels in the normal range. In 3 patients (8%), HCO3 was below 22 mEq/L, and in 8 patients (22%; APD = 2, lactate CAPD = 2, bicarbonate CAPD = 4), HCO3 was above 28 mEq/L. We found no statistically significant correlations between HCO3 serum levels and PD prescription, peritoneal membrane characteristics, or intake of calcium carbonate and sevelamer hydrochloride. Patients on bicarbonate CAPD had higher HCO3 serum levels, but this difference disappeared when corrections for duration of dialysis, residual urine volume, and PD adequacy indices were applied. In the studied PD population, adequate correction of metabolic acidosis was achieved, as reflected in serum bicarbonate levels. We observed no difference in serum bicarbonate levels between APD and lactate CAPD patients. The new bicarbonate-buffered PD solutions are more biocompatible and can result in higher serum bicarbonate levels. However, a significant number of PD patients on bicarbonate-buffered solutions may become alkalotic. The clinical significance of these results needs further examination in prospective studies.

Pathophysiological analyses of periventricular nodular heterotopia using gyrencephalic mammals.

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Matsumoto, Naoyuki; Hoshiba, Yoshio; Morita, Kazuya; Uda, Natsu; Hirota, Miwako; Minamikawa, Maki; Ebisu, Haruka; Shinmyo, Yohei; Kawasaki, Hiroshi

2017-03-15

Although periventricular nodular heterotopia (PNH) is often found in the cerebral cortex of people with thanatophoric dysplasia (TD), the pathophysiology of PNH in TD is largely unknown. This is mainly because of difficulties in obtaining brain samples of TD patients and a lack of appropriate animal models for analyzing the pathophysiology of PNH in TD. Here we investigate the pathophysiological mechanisms of PNH in the cerebral cortex of TD by utilizing a ferret TD model which we recently developed. To make TD ferrets, we electroporated fibroblast growth factor 8 (FGF8) into the cerebral cortex of ferrets. Our immunohistochemical analyses showed that PNH nodules in the cerebral cortex of TD ferrets were mostly composed of cortical neurons, including upper layer neurons and GABAergic neurons. We also found disorganizations of radial glial fibers and of the ventricular lining in the TD ferret cortex, indicating that PNH may result from defects in radial migration of cortical neurons along radial glial fibers during development. Our findings provide novel mechanistic insights into the pathogenesis of PNH in TD. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Tics and Tourette's: update on pathophysiology and tic control.

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Ganos, Christos

2016-08-01

To describe recent advances in the pathophysiology of tics and Tourette syndrome, and novel insights on tic control. The cortico-basal ganglia-thalamo-cortical loops are implicated in generation of tics. Disruption of GABAergic inhibition lies at the core of tic pathophysiology, but novel animal models also implicate cholinergic and histaminergic neurotransmission. Tourette syndrome patients have altered awareness of volition and enhanced formation of habits. Premonitory urges are not the driving force behind all tics. The intensity of premonitory urges depends on patients' capacity to perceive interoceptive signals. The insular cortex is a key structure in this process. The trait intensity of premonitory urges is not a prerequisite of voluntary tic inhibition, a distinct form of motor control. Voluntary tic inhibition is most efficient in the body parts that tic the least. The prefrontal cortex is associated with the capacity to inhibit tics. The management of tics includes behavioral, pharmacological and surgical interventions. Treatment recommendations differ based on patients' age. The study of Tourette syndrome pathophysiology involves different neural disciplines and provides novel, exciting insights of brain function in health and disease. These in turn provide the basis for innovative treatment approaches of tics and their associations.

Pathophysiology of obstructive sleep apnea-hypopnea syndrome (OSAHS

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Marco Venegas-Mariño

2017-08-01

Full Text Available Obstructive sleep apnea-hypopnea syndrome (OSAHS is a disease characterized by recurrent upper airway obstruction (UAO, with decreased airflow, intermittent hypoxemia, and awakening during sleep. Two essential factors are related to the pathophysiology of OSAHS: anatomical alterations and reduction or absence of neural control. While studying OSAHS, the site or sites of obstruction of the UA should be identified; they may extend from the nasal wings to the hypopharynx. Another important factor in this syndrome is the nervous influence on muscle tone of the hypopharynx, as well as the changes in blood pH, which are secondary to micro-arousals. Body position and sleep stage determine the severity. The pathophysiology of OSAHS should be understood to properly study a patient and provide the best treatment option.

Four siblings with distal renal tubular acidosis and nephrocalcinosis, neurobehavioral impairment, short stature, and distinctive facial appearance: a possible new autosomal recessive syndrome.

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Faqeih, Eissa; Al-Akash, Samhar I; Sakati, Nadia; Teebi, Prof Ahmad S

2007-09-01

We report on four siblings (three males, one female) born to first cousin Arab parents with the constellation of distal renal tubular acidosis (RTA), small kidneys, nephrocalcinosis, neurobehavioral impairment, short stature, and distinctive facial features. They presented with early developmental delay with subsequent severe mental, behavioral and social impairment and autistic-like features. Their facial features are unique with prominent cheeks, well-defined philtrum, large bulbous nose, V-shaped upper lip border, full lower lip, open mouth with protruded tongue, and pits on the ear lobule. All had proteinuria, hypercalciuria, hypercalcemia, and normal anion-gap metabolic acidosis. Renal ultrasound examinations revealed small kidneys, with varying degrees of hyperechogenicity and nephrocalcinosis. Additional findings included dilated ventricles and cerebral demyelination on brain imaging studies. Other than distal RTA, common causes of nephrocalcinosis were excluded. The constellation of features in this family currently likely represents a possibly new autosomal recessive syndrome providing further evidence of heterogeneity of nephrocalcinosis syndromes. Copyright 2007 Wiley-Liss, Inc.

Inflammatory and Other Biomarkers: Role in Pathophysiology and Prediction of Gestational Diabetes Mellitus

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Abell, Sally K.; De Courten, Barbora; Boyle, Jacqueline A.; Teede, Helena J.

2015-01-01

Understanding pathophysiology and identifying mothers at risk of major pregnancy complications is vital to effective prevention and optimal management. However, in current antenatal care, understanding of pathophysiology of complications is limited. In gestational diabetes mellitus (GDM), risk prediction is mostly based on maternal history and clinical risk factors and may not optimally identify high risk pregnancies. Hence, universal screening is widely recommended. Here, we will explore the literature on GDM and biomarkers including inflammatory markers, adipokines, endothelial function and lipids to advance understanding of pathophysiology and explore risk prediction, with a goal to guide prevention and treatment of GDM. PMID:26110385

Pathophysiology of spontaneous venous gas embolism

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Lambertsen, C. J.; Albertine, K. H.; Pisarello, J. B.; Flores, N. D.

1991-01-01

The use of controllable degrees and durations of continuous isobaric counterdiffusion venous gas embolism to investigate effects of venous gas embolism upon blood, cardiovascular, and respiratory gas exchange function, as well as pathological effects upon the lung and its microcirculation is discussed. Use of N2O/He counterdiffusion permitted performance of the pathophysiologic and pulmonary microstructural effects at one ATA without hyperbaric or hypobaric exposures.

Quantitative Phase Imaging Techniques for the Study of Cell Pathophysiology: From Principles to Applications

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Hyunjoo Park

2013-03-01

Full Text Available A cellular-level study of the pathophysiology is crucial for understanding the mechanisms behind human diseases. Recent advances in quantitative phase imaging (QPI techniques show promises for the cellular-level understanding of the pathophysiology of diseases. To provide important insight on how the QPI techniques potentially improve the study of cell pathophysiology, here we present the principles of QPI and highlight some of the recent applications of QPI ranging from cell homeostasis to infectious diseases and cancer.

The pathophysiology of lifelong premature ejaculation

Science.gov (United States)

2016-01-01

For many decades it has been thought that lifelong premature ejaculation (PE) is only characterized by persistent early ejaculations. Despite enormous progress of in vivo animal research, and neurobiological, genetic and pharmacological research in men with lifelong PE, our current understanding of the mechanisms behind early ejaculations is far from complete. The new classification of PE into four PE subtypes has shown that the symptomatology of lifelong PE strongly differs from acquired PE, subjective PE and variable PE. The phenotype of lifelong PE and therefore also the pathophysiology of lifelong PE is much more complex. A substantial number of men with lifelong PE not only have PE, but also premature erection and premature penile detumescence as part of an acute hypertonic or hypererotic state when engaged in an erotic situation or when making love. As both erectio praecox, ejaculatio praecox, detumescentia praecox, and the hypererotic state are part of the phenotype lifelong PE, it is argued that lifelong PE is not only a disturbance of the timing of ejaculation but also a disturbance of the timing of erection, detumescence and arousal. Since 1998, the pathophysiology of lifelong PE was thought to be mainly mediated by the central serotonergic system in line with genetic polymorphisms of specific serotonergic genes. However, by accepting that lifelong PE is characterized by the reversible hypertonic state the hypothesis of mainly serotonergic dysfunction is no longer tenable. Instead, it has been postulated that the pathophysiology of lifelong PE is mediated by a very complex interplay of central and peripheral serotonergic, dopaminergic, oxytocinergic, endocrinological, genetic and probably also epigenetic factors. Progress in research of lifelong PE can only be accomplished when a stopwatch is used to measure the IELT and the cut-off point of 1 minute for the definition of lifelong PE is maintained. Current use of validated questionnaires, neglect of

CHRONIC OBSTRUCTIVE PULMONARY DISEASE: DEFINITION, EPIDEMIOLOGY, PATHOPHYSIOLOGY, CLINICAL PICTURE AND TREATMENT (GOLD 2013

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M. T. Vatutin

2015-01-01

Full Text Available Chronic obstructive pulmonary disease: definition, epidemiology, pathophysiology, clinical picture (GOLD 2013. Vatutin M.T., Smyrnova G.S., Taradin G.G. The represented translation of the new international guidelines (GOLD 2013 reflected the epidemiology, pathophysiology, clinical picture and treatment of chronic obstructive pulmonary disease.

Atrioventricular conduction abnormality and hyperchloremic metabolic acidosis in toluene sniffing

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Jian-Hsiung Tsao

2011-10-01

Full Text Available Toluene is an aromatic hydrocarbon with widespread industrial use as an organic solvent. As a result of the euphoric effect and availability of these substances, inhalation of toluene-based products is popular among young adults and children. Chronic or acute exposure is known to cause acid–base and electrolyte disorders, and to be toxic to the nervous and hematopoietic systems. We report a 38-year-old man who suffered from general muscular weakness of all extremities after toluene sniffing, which was complicated with hypokalemic paralysis, atrioventricular conduction abnormality, and normal anion gap hyperchloremic metabolic acidosis. Renal function, serum potassium and acid–base status normalized within 3 days after aggressive potassium chloride and intravenous fluid replacement. Electrocardiography showed regression of first-degree atrioventricular block. Exposure to toluene can lead to cardiac arrhythmias and sudden sniffing death syndrome. Tachyarrhythmia is the classical manifestation of toluene cardiotoxicity. Atrioventricular conduction abnormalities have been rarely mentioned in the literature. Knowledge of the toxicology and medical complications associated with toluene sniffing is essential for clinical management of these patients.

Pathophysiological basis of pharmacotherapy in the hepatorenal syndrome

DEFF Research Database (Denmark)

Møller, Søren; Bendtsen, Flemming; Henriksen, Jens H

2005-01-01

Hepatorenal syndrome (HRS) is a functional and reversible impairment of renal function in patients with severe cirrhosis. Major pathophysiological elements include liver dysfunction, a circulatory derangement with central hypovolaemia and neurohumoral activation of potent vasoactive systems leading...

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

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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. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

Pink Masks: Obstructive Sleep Apnoea and the Sociology of Diagnosis

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SHARON HANCOCK

2013-01-01

Full Text Available The sociology of diagnosis takes a new look at diagnostic categories, the means by which they are delivered, and the social consequences of diagnosis for patient and professional alike. Considering the social elements which contribute to the recognition of disease categories and their consequences highlights important phenomena which can enrich the thinking of nurses regardless of whether or not they diagnose as part of their practice. However, the principles of the sociology of diagnosis, while widely debated in academe, have yet to penetrate nursing literature. In this discussion article, we use obstructive sleep apnoea in women as an exemplar to illustrate how a clearly material, pathophysiological disorder has, nonetheless, significant social “content.” We demonstrate the social structures and interests which shape obstructive sleep apnoea as a male disease, and the risks, paradoxically, of both under- and over-diagnosis that arise from this social construction. We use this example to exhort nurses to consider how the social and the biological intermesh and shape how we perceive disease and its impact. This should open the door for more responsive and responsible health care.

Heteromeric ASIC channels composed of ASIC2b and ASIC1a display novel channel properties and contribute to acidosis-induced neuronal death

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Sherwood, Thomas W.; Lee, Kirsten G.; Gormley, Matthew G.; Askwith, Candice C.

2011-01-01

Acid-sensing ion channel (ASIC) subunits associate to form homomeric or heteromeric proton-gated ion channels in neurons throughout the nervous system. The ASIC1a subunit plays an important role in establishing the kinetics of proton-gated currents in the central nervous system and activation of ASIC1a homomeric channels induces neuronal death following local acidosis that accompanies cerebral ischemia. The ASIC2b subunit is expressed in the brain in a pattern that overlaps ASIC1a, yet the contribution of ASIC2b has remained elusive. We find that co-expression of ASIC2b with ASIC1a in Xenopus oocytes results in novel proton-gated currents with properties distinct from ASIC1a homomeric channels. In particular, ASIC2b/1a heteromeric channels are inhibited by the non-selective potassium channel blockers tetraethylammonium (TEA) and barium. In addition, steady-state desensitization is induced at more basic pH values and Big Dynorphin sensitivity is enhanced in these unique heteromeric channels. Cultured hippocampal neurons show proton-gated currents consistent with ASIC2b contribution and these currents are lacking in neurons from mice with an ACCN1 (ASIC2) gene disruption. Finally, we find that these ASIC2b/1a heteromeric channels contribute to acidosis-induced neuronal death. Together, our results show that ASIC2b confers unique properties to heteromeric channels in central neurons. Further, these data indicate that ASIC2, like ASIC1, plays a role in acidosis-induced neuronal death and implicate the ASIC2b/1a subtype as a novel pharmacological target to prevent neuronal injury following stroke. PMID:21715637

Central voice production and pathophysiology of spasmodic dysphonia.

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Mor, Niv; Simonyan, Kristina; Blitzer, Andrew

2018-01-01

Our ability to speak is complex, and the role of the central nervous system in controlling speech production is often overlooked in the field of otolaryngology. In this brief review, we present an integrated overview of speech production with a focus on the role of central nervous system. The role of central control of voice production is then further discussed in relation to the potential pathophysiology of spasmodic dysphonia (SD). Peer-review articles on central laryngeal control and SD were identified from PUBMED search. Selected articles were augmented with designated relevant publications. Publications that discussed central and peripheral nervous system control of voice production and the central pathophysiology of laryngeal dystonia were chosen. Our ability to speak is regulated by specialized complex mechanisms coordinated by high-level cortical signaling, brainstem reflexes, peripheral nerves, muscles, and mucosal actions. Recent studies suggest that SD results from a primary central disturbance associated with dysfunction at our highest levels of central voice control. The efficacy of botulinum toxin in treating SD may not be limited solely to its local effect on laryngeal muscles and also may modulate the disorder at the level of the central nervous system. Future therapeutic options that target the central nervous system may help modulate the underlying disorder in SD and allow clinicians to better understand the principal pathophysiology. NA.Laryngoscope, 128:177-183, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Bovine pododermatitis aseptica diffusa (laminitis) aetiology, pathogenesis, treatment and control.

Science.gov (United States)

Mgasa, M N

1987-01-01

Pododermatitis aseptica diffusa (laminitis) is a major cause of lameness and discomfort to cattle with resultant economic losses. The disease is a result of multifactorial aetiology most of which is not clearly understood. Feeding readily fermentable carbohydrates to unaccustomed cattle predisposes to the disease. Histamine, lactic acid and endotoxins are believed to be involved. Systemic acidosis, histaminosis and endotoxaemia are thought to produce the pathophysiological characteristics of laminitis. The diagnosis is primarily based on the observation of symmetrical and bilateral lesions in hooves and characteristic lameness affecting all feet. Gross lesions include concavity of the dorsal wall, discolorations in the sole and rotation of the pedal bone. Degenerative changes and arteriosclerosis are constant histological findings in the corium, with chronic thrombi and chronic granulation tissue. The disease may be treated conservatively and by application of cyclo-oxygenase inhibiting non-steroidal anti-inflammatory drugs and prevented or controlled by proper feeding and management practices.

Adrenal Disorders and the Paediatric Brain: Pathophysiological Considerations and Clinical Implications

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Vincenzo Salpietro

2014-01-01

Full Text Available Various neurological and psychiatric manifestations have been recorded in children with adrenal disorders. Based on literature review and on personal case-studies and case-series we focused on the pathophysiological and clinical implications of glucocorticoid-related, mineralcorticoid-related, and catecholamine-related paediatric nervous system involvement. Childhood Cushing syndrome can be associated with long-lasting cognitive deficits and abnormal behaviour, even after resolution of the hypercortisolism. Exposure to excessive replacement of exogenous glucocorticoids in the paediatric age group (e.g., during treatments for adrenal insufficiency has been reported with neurological and magnetic resonance imaging (MRI abnormalities (e.g., delayed myelination and brain atrophy due to potential corticosteroid-related myelin damage in the developing brain and the possible impairment of limbic system ontogenesis. Idiopathic intracranial hypertension (IIH, a disorder of unclear pathophysiology characterised by increased cerebrospinal fluid (CSF pressure, has been described in children with hypercortisolism, adrenal insufficiency, and hyperaldosteronism, reflecting the potential underlying involvement of the adrenal-brain axis in the regulation of CSF pressure homeostasis. Arterial hypertension caused by paediatric adenomas or tumours of the adrenal cortex or medulla has been associated with various hypertension-related neurological manifestations. The development and maturation of the central nervous system (CNS through childhood is tightly regulated by intrinsic, paracrine, endocrine, and external modulators, and perturbations in any of these factors, including those related to adrenal hormone imbalance, could result in consequences that affect the structure and function of the paediatric brain. Animal experiments and clinical studies demonstrated that the developing (i.e., paediatric CNS seems to be particularly vulnerable to alterations induced by

Diagnosis of Swimming Induced Pulmonary Edema—A Review

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Grünig, Hannes; Nikolaidis, Pantelis T.; Moon, Richard E.; Knechtle, Beat

2017-01-01

Swimming induced pulmonary edema (SIPE) is a complication that can occur during exercise with the possibility of misdiagnosis and can quickly become life threatening; however, medical literature infrequently describes SIPE. Therefore, the aim of this review was to analyse all individual cases diagnosed with SIPE as reported in scientific sources, with an emphasis on the diagnostic pathways and the key facts resulting in its diagnosis. Due to a multifactorial and complicated pathophysiology, the diagnosis could be difficult. Based on the actual literature, we try to point out important findings regarding history, conditions, clinical findings, and diagnostic testing helping to confirm the diagnosis of SIPE. Thirty-eight cases from seventeen articles reporting the diagnosis of SIPE were selected. We found remarkable differences in the individual described diagnostic pathways. A total of 100% of the cases suffered from an acute onset of breathing problems, occasionally accompanied by hemoptysis. A total of 73% showed initial hypoxemia. In most of the cases (89%), an initial chest X-Ray or chest CT was available, of which one-third (71%) showed radiological signs of pulmonary edema. The majority of the cases (82%) experienced a rapid resolution of symptoms within 48 h, the diagnostic hallmark of SIPE. Due to a foreseeable increase in participation in swimming competitions and endurance competitions with a swimming component, diagnosis of SIPE will be important, especially for medical teams caring for these athletes. PMID:28912730

Visceral hypersensitivity in Irritable Bowel Syndrome:pathophysiological mechanisms

NARCIS (Netherlands)

Kerckhoffs, A.P.M.

2009-01-01

Irritable Bowel Syndrome (IBS) is a functional bowel disease characterized by abdominal pain or discomfort associated with a disordered defecation. No unique pathophysiological mechanism has been identified. It is most likely a multifactorial disease involving alterations in intestinal microbiota

Citrate metabolism in blood transfusions and its relationship due to metabolic alkalosis and respiratory acidosis.

Science.gov (United States)

Li, Kai; Xu, Yuan

2015-01-01

Metabolic alkalosis commonly results from excessive hydrochloric acid (HCl), potassium (K(+)) and water (H2O) loss from the stomach or through the urine. The plasma anion gap increases in non-hypoproteinemic metabolic alkalosis due to an increased negative charge equivalent on albumin and the free ionized calcium (Ca(++)) content of plasma decreases. The mean citrate load in all patients was 8740±7027 mg from 6937±6603 mL of transfused blood products. The citrate load was significantly higher in patients with alkalosis (9164±4870 vs. 7809±3967, P alkalosis + respiratory acidosis and electrolyte imbalance may develop, blood transfusions may result in certain complications.

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

International Nuclear Information System (INIS)

Inamura, K.; Smith, M.L.; Hansen, A.J.; Siesjoe, B.K.

1989-01-01

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)

Interpretation of metabolic acidosis in critically ill patients according to the Stewart theory, ICU Case report

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Adolfo León Tróchez

2010-03-01

Full Text Available The present case is about a 79 years old patient with a history of hypertension, cerebral stroke and untreated inguinal hernia diagnosed 30 years ago, who underwent an emergent umbilical and right crural herniorrhaphy, the surgical procedure was complicated by a regurgitation and aspiration of gastric content. Postoperatively the patient suffered from progressive shortness of breath, requiring ICU admission. She soon developed septic shock of pulmonary origin and with severe decompensated metabolic acidosis associated with lactic acidosis. The patient died after a short time in intensive care. We propose to analyse and illustrate the acid-base aspects of the case according to the Stewart approach, exposing the factors that determine the acid-base factors and their therapeutic implications.

The possible role of gastrointestinal endocrine cells in the pathophysiology of irritable bowel syndrome.

Science.gov (United States)

El-Salhy, Magdy; Hausken, Trygve; Gilja, Odd Helge; Hatlebakk, Jan Gunnar

2017-02-01

The etiology of irritable bowel syndrome (IBS) is unknown, but several factors appear to play a role in its pathophysiology, including abnormalities of the gastrointestinal endocrine cells. The present review illuminates the possible role of gastrointestinal hormones in the pathophysiology of IBS and the possibility of utilizing the current knowledge in treating the disease. Areas covered: Research into the intestinal endocrine cells and their possible role in the pathophysiology of IBS is discussed. Furthermore, the mechanisms underlying the abnormalities in the gastrointestinal endocrine cells in IBS patients are revealed. Expert commentary: The abnormalities observed in the gastrointestinal endocrine cells in IBS patients explains their visceral hypersensitivity, gastrointestinal dysmotility, and abnormal intestinal secretion, as well as the interchangeability of symptoms over time. Clarifying the role of the intestinal stem cells in the pathophysiology of IBS may lead to new treatment methods for IBS.

Diagnosis and Management of Budd Chiari Syndrome: An Update

International Nuclear Information System (INIS)

Copelan, Alexander; Remer, Erick M.; Sands, Mark; Nghiem, Hanh; Kapoor, Baljendra

2015-01-01

Imaging plays a crucial role in the early detection and assessment of the extent of disease in Budd Chiari syndrome (BCS). Early diagnosis and intervention to mitigate hepatic congestion is vital to restoring hepatic function and alleviating portal hypertension. Interventional radiology serves a key role in the management of these patients. The interventionist should be knowledgeable of the clinical presentation as well as key imaging findings, which often dictate the approach to treatment. This article concisely reviews the etiology, pathophysiology, and clinical presentation of BCS and provides a detailed description of imaging and treatment options, particularly interventional management

Diagnosis and Management of Budd Chiari Syndrome: An Update

Energy Technology Data Exchange (ETDEWEB)

Copelan, Alexander, E-mail: alexander.copelan@beaumont.edu [William Beaumont Hospital, Diagnostic Radiology Department (United States); Remer, Erick M., E-mail: remere1@ccf.org; Sands, Mark, E-mail: sandsm@ccf.org [Cleveland Clinic, Imaging Institute (United States); Nghiem, Hanh, E-mail: HNghiem@beaumont.edu [William Beaumont Hospital, Diagnostic Radiology Department (United States); Kapoor, Baljendra, E-mail: kapoorb@ccf.org [Cleveland Clinic, Imaging Institute (United States)

2015-02-15

Imaging plays a crucial role in the early detection and assessment of the extent of disease in Budd Chiari syndrome (BCS). Early diagnosis and intervention to mitigate hepatic congestion is vital to restoring hepatic function and alleviating portal hypertension. Interventional radiology serves a key role in the management of these patients. The interventionist should be knowledgeable of the clinical presentation as well as key imaging findings, which often dictate the approach to treatment. This article concisely reviews the etiology, pathophysiology, and clinical presentation of BCS and provides a detailed description of imaging and treatment options, particularly interventional management.

Unravelling narcolepsy : from pathophysiology to measuring treatment effects

NARCIS (Netherlands)

Heide, van der A.

2017-01-01

Narcolepsy is a disorder of the regulation of sleep and wakefulness, with as its major features excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, sleep paralysis and disturbed nocturnal sleep. The first part of this thesis concernes an overview of the pathophysiology,

Narcolepsy: Pathophysiology and Neuropsychological Changes

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Angela Naumann

2003-01-01

Full Text Available Narcolepsy is now recognized as a distinctive disorder with specific pathophysiology and neurochemical abnormalities. Findings on the role of the neuropeptide hypocretin are opening new avenues of research and new strategies for therapy. Recently, neuropsychological and electrophysiological studies have provided evidence for reduced memory performance on standard memory tests in addition to subjective complaints of forgetfulness which may be related to changes in attentional processing. Further studies are, however, necessary to clarify the neuropsychological profile in narcolepsy. This review focuses on the recent advances in understanding narcolepsy.

Ruminal acidosis and the rapid onset of ruminal parakeratosis in a mature dairy cow: a case report

OpenAIRE

Croom Jim; Hook Sarah E; AlZahal Ousama; Steele Michael A; McBride Brian W

2009-01-01

Abstract A mature dairy cow was transitioned from a high forage (100% forage) to a high-grain (79% grain) diet over seven days. Continuous ruminal pH recordings were utilized to diagnose the severity of ruminal acidosis. Additionally, blood and rumen papillae biopsies were collected to describe the structural and functional adaptations of the rumen epithelium. On the final day of the grain challenge, the daily mean ruminal pH was 5.41 ± 0.09 with a minimum of 4.89 and a maximum of 6.31. Rumin...

Retinal vein occlusion: pathophysiology and treatment options

OpenAIRE

Karia, Niral

2010-01-01

Niral KariaDepartment of Ophthalmology, Southend Hospital, Prittlewell Chase, Westcliff on Sea, Essex, United KingdomAbstract: This paper reviews the current thinking about retinal vein occlusion. It gives an overview of its pathophysiology and discusses the evidence behind the various established and emerging treatment paradigms.Keywords: central, hemispheric, branch, retinal vein occlusion, visual loss

Predisposition to metabolic acidosis induced by topiramate Predisposição a acidose metabólica induzida por topiramato

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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

Pathophysiology of glucagon secretion

International Nuclear Information System (INIS)

Boettger, J.; Pabst, H.W.

1980-01-01

Pathophysiology of glucagon secretion is reviewed in brief separating hyperglucagonemic from hypoclucagonemic states. Many questions concerning the role of glucagon in diabetes mellitus and in other diseases are still unresolved. The clucagon RIA is of clinical significance in a few diseases like glucagonoma, which may present without symptoms of the 'glucagonoma syndrome', the probably very rare hyperglucagonemia and some of the spontaneous hypoglycemias. Glucagon secretion may be evaluated by the determination of fasting immunoreactive glucagon (IRG) and by appropriate function tests as stimulation with i.v. arginine and suppression with oral glucose. However, the glucagon RIA at present is not a routine method, although commercial kits are available. Many pitfalls of radioimmunological glucagon determination still exist. (orig.) [de

Acidose metabólica na infância: por que, quando e como tratá-la? Metabolic acidosis in childhood: why, when and how to treat

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Olberes V. B. Andrade

2007-05-01

controvérsia, o único ponto concordante refere-se à abordagem mais precoce da doença de base e dos mecanismos geradores da acidemia metabólica. Outras alternativas terapêuticas são promissoras; entretanto, os efeitos adversos e a falta de trabalhos controlados em pediatria não determinam evidências suficientes que recomendem sua utilização de rotina.OBJECTIVES: To critically discuss the treatment of metabolic acidosis and the main mechanisms of disease associated with this disorder; and to describe controversial aspects related to the risks and benefits of using sodium bicarbonate and other therapies. SOURCES: Review of PubMed/MEDLINE, LILACS and Cochrane Library databases for articles published between 1996 and 2006 using the following keywords: metabolic acidosis, lactic acidosis, ketoacidosis, diabetic ketoacidosis, cardiopulmonary resuscitation, sodium bicarbonate, treatment. Classical publications concerning the topic were also reviewed. The most recent and representative were selected, with emphasis on consensus statements and guidelines. SUMMARY OF THE FINDINGS: There is no evidence of benefits resulting from the use of sodium bicarbonate for the hemodynamic status, clinical outcome, morbidity and mortality in high anion gap metabolic acidosis associated with lactic acidosis, diabetic ketoacidosis and cardiopulmonary resuscitation. Therefore, the routine use of sodium bicarbonate is not indicated. Potential side effects must be taken into consideration. Treating the underlying disease is essential to reverse the process. The efficacy of other alternative therapies has not been demonstrated in large-scale studies. CONCLUSIONS: Despite the known effects of acidemia on the organism in critical situations, a protective role of acidemia in hypoxic cells and the risk of alkalemia secondary to drug interventions are being considered. There is consensus regarding the advantages of alkali and sodium bicarbonate therapy in cases with normal anion gap; however, in

Pathophysiology of diurnal drooling in Parkinson’s disease

NARCIS (Netherlands)

Lenie van den Engel-Hoek; Johanna Kalf; Bastiaan Bloem; George Borm; Machiel Zwarts; Bert de Swart; Marten Munneke

2011-01-01

Drooling is an incapacitating feature of Parkinson's disease. Better pathophysiological insights are needed to improve treatment. In this study, we tested the hypothesis that the cause of drooling is multifactorial. We examined 15 patients with Parkinson's disease with distinct diurnal saliva loss

Post-traumatic shoulder movement disorders: A challenging differential diagnosis between organic and functional

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Pandey, Sanjay; Nahab, Fatta; Aldred, Jason; Nutt, John; Hallett, Mark

2014-01-01

Peripheral trauma may be a trigger for the development of various movement disorders though the pathophysiology remains controversial and some of these patients have a functional (psychogenic) disorder. We report 3 cases of shoulder movement disorders following trauma to the shoulder region. Physiology was done in all the patients to extend the physical examination. Two patients had history of recurrent shoulder dislocation and were diagnosed with Ehlers-Danlos syndrome. One patient had shoulder injury following repeated falls while performing as a cheerleader. In two patients there were some clinical features suggesting a functional etiology, but physiological studies in all three failed to produce objective evidence of a functional nature. Shoulder movement following trauma is uncommon. Diagnosis in such cases is challenging considering the complex pathophysiology. The movements can be associated with prolonged pain and handicap, and once established they appear resistant to treatment. PMID:25197686

Laryngopharyngeal Reflux: Diagnosis, Treatment, and Latest Research

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Campagnolo, Andrea Maria

2014-01-01

Full Text Available Introduction Laryngopharyngeal reflux (LPR is a highly prevalent disease and commonly encountered in the otolaryngologist's office. Objective To review the literature on the diagnosis and treatment of LPR. Data Synthesis LPR is associated with symptoms of laryngeal irritation such as throat clearing, coughing, and hoarseness. The main diagnostic methods currently used are laryngoscopy and pH monitoring. The most common laryngoscopic signs are redness and swelling of the throat. However, these findings are not specific of LPR and may be related to other causes or can even be found in healthy individuals. Furthermore, the role of pH monitoring in the diagnosis of LPR is controversial. A therapeutic trial with proton pump inhibitors (PPIs has been suggested to be cost-effective and useful for the diagnosis of LPR. However, the recommendations of PPI therapy for patients with a suspicion of LPR are based on the results of uncontrolled studies, and high placebo response rates suggest a much more complex and multifactorial pathophysiology of LPR than simple acid reflux. Molecular studies have tried to identify biomarkers of reflux such as interleukins, carbonic anhydrase, E-cadherin, and mucin. Conclusion Laryngoscopy and pH monitoring have failed as reliable tests for the diagnosis of LPR. Empirical therapy with PPIs is widely accepted as a diagnostic test and for the treatment of LPR. However, further research is needed to develop a definitive diagnostic test for LPR.

Osmolality and respiratory regulation in humans: respiratory compensation for hyperchloremic metabolic acidosis is absent after infusion of hypertonic saline in healthy volunteers.

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Moen, Vibeke; Brudin, Lars; Rundgren, Mats; Irestedt, Lars

2014-10-01

Several animal studies show that changes in plasma osmolality may influence ventilation. Respiratory depression caused by increased plasma osmolality is interpreted as inhibition of water-dependent thermoregulation because conservation of body fluid predominates at the cost of increased core temperature. Respiratory alkalosis, on the other hand, is associated with a decrease in plasma osmolality and strong ion difference (SID) during human pregnancy. We investigated the hypothesis that osmolality would influence ventilation, so that increased osmolality will decrease ventilation and decreased osmolality will stimulate ventilation in both men and women. Our study participants were healthy volunteers of both sexes (ASA physical status I). Ten men (mean 28 years; range 20-40) and 9 women (mean 33 years; range 22-43) were included. All women participated in both the follicular and luteal phases of the menstrual cycle. Hyperosmolality was induced by IV infusion of hypertonic saline 3%, and hypoosmolality by drinking tap water. Arterial blood samples were collected for analysis of electrolytes, osmolality, and blood gases. Sensitivity to CO2 was determined by rebreathing tests performed before and after the fluid-loading procedures. Infusion of hypertonic saline caused hyperchloremic metabolic acidosis with decreased SID in all subjects. Analysis of pooled data showed absence of respiratory compensation. Baseline arterial PCO2 (PaCO2) mean (SD) 37.8 (2.9) mm Hg remained unaltered, with lowest PaCO2 37.8 (2.9) mm Hg after 100 minutes, P = 0.70, causing a decrease in pH from mean (SD) 7.42 (0.02) to 7.38 (0.02), P acidosis was also observed during water loading. Pooled results show that PaCO2 decreased from 38.2 (3.3) mm Hg at baseline to 35.7 (2.8) mm Hg after 80 minutes of drinking water, P = 0.002, and pH remained unaltered: pH 7.43 (0.02) at baseline to pH 7.42 (0.02), P = 0.14, mean difference (confidence interval) = pH -0.007 (-0.017 to 0.003). Our results indicate

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

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Sanchez, Jully M.; Tan, Judy Ann; Farmakiotis, Dimitrios; Aggarwal, Vikas

2011-01-01

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. PMID:21789268

Parkinson's disease : The syndrome, the pathogenesis and pathophysiology

NARCIS (Netherlands)

Bartels, Anna L.; Leenders, Klaus L.

Parkinson's disease (PD) is characterised by a slowly expanding degeneration of neurons particularly in the mesencephalon. The causes are unknown although risk factors in the genetic and toxic domain are being discovered. An important pathophysiological feature in PD is the loss of part of the

Elucidation of pathophysiology and treatment of neuropathic pain

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Vranken, Jan H.

2012-01-01

Neuropathic pain, pain arising as a direct consequence of a lesion or disease affecting the somatosensory system, is relatively common, occurring in about 1% of the population. Studies in animal models describe a number of peripheral and central pathophysiological processes after nerve injury that

[Pubalgia: from diagnosis to return to the sports field].

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Puig, P L; Trouve, P; Savalli, L

2004-08-01

To review reports of the diagnosis and treatment of groin pain (pubalgia) on the basis of anatomical considerations, epidemiology and pathogenicity. We searched the Medline database using the key words groin injury, groin pain, and symphisis syndrome for information on groin pain. Despite the limitations of this study, athletic pubalgia appears to be a real diagnosis, with a long duration of symptoms and a therapeutic challenge. The pathophysiologic processes of this lower abdominal pain resulting from over use is unclear, but muscular imbalance might be involved in the pathogenicity. There is no consensus on the diagnostic criteria and the role of imaging (magnetic resonance imaging). Physicians should eliminate the diagnosis of hip and groin injuries in athletes. Specific rehabilitation should include eliminating the pain-triggering factors, increasing the limited flexibility, and strengthening the abdominal muscles and adductor muscles. The multidisciplinary team's goal is to restore function and prevent recurrence. Successful surgical repair is predictable in well-selected patients. Further studies are required for better assessment of incidence, the natural course of groin pain, and optimal clinical evaluation in screening patients. Overall, a large prospective randomized study of athletes with groin pain would help determine optimal treatment.

Pathophysiological analyses of leptomeningeal heterotopia using gyrencephalic mammals.

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Matsumoto, Naoyuki; Kobayashi, Naoki; Uda, Natsu; Hirota, Miwako; Kawasaki, Hiroshi

2018-03-15

Leptomeningeal glioneuronal heterotopia (LGH) is a focal malformation of the cerebral cortex and frequently found in patients with thanatophoric dysplasia (TD). The pathophysiological mechanisms underlying LGH formation are still largely unclear because of difficulties in obtaining brain samples from human TD patients. Recently, we established a new animal model for analysing cortical malformations of human TD by utilizing our genetic manipulation technique for gyrencephalic carnivore ferrets. Here we investigated the pathophysiological mechanisms underlying the formation of LGH using our TD ferrets. We found that LGH was formed during corticogenesis in TD ferrets. Interestingly, we rarely found Ki-67-positive and phospho-histone H3-positive cells in LGH, suggesting that LGH formation does not involve cell proliferation. We uncovered that vimentin-positive radial glial fibers and doublecortin-positive migrating neurons were accumulated in LGH. This result may indicate that preferential cell migration into LGH underlies LGH formation. Our findings provide novel mechanistic insights into the pathogenesis of LGH in TD.

Modern iron replacement therapy: clinical and pathophysiological insights.

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Girelli, Domenico; Ugolini, Sara; Busti, Fabiana; Marchi, Giacomo; Castagna, Annalisa

2018-01-01

Iron deficiency, with or without anemia, is extremely frequent worldwide, representing a major public health problem. Iron replacement therapy dates back to the seventeenth century, and has progressed relatively slowly until recently. Both oral and intravenous traditional iron formulations are known to be far from ideal, mainly because of tolerability and safety issues, respectively. At the beginning of this century, the discovery of hepcidin/ferroportin axis has represented a turning point in the knowledge of the pathophysiology of iron metabolism disorders, ushering a new era. In the meantime, advances in the pharmaceutical technologies are producing newer iron formulations aimed at minimizing the problems inherent with traditional approaches. The pharmacokinetic of oral and parenteral iron is substantially different, and diversities have become even clearer in light of the hepcidin master role in regulating systemic iron homeostasis. Here we review how iron therapy is changing because of such important advances in both pathophysiology and pharmacology.

Fisiopatologia da enxaqueca Migraine pathophysiology

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MAURICE B. VINCENT

1998-12-01

Full Text Available A fisiopatologia da enxaqueca ainda não foi completamente elucidada. As principais estruturas envolvidas parecem ser o sistema nervoso central (córtex e tronco cerebral, o sistema trigeminovascular e os vasos correspondentes, outras fibras autonômicas que inervam estes vasos, e os vários agentes vasoativos locais, como a SP, CGRP, NO, VIP, NPY, ACh, NA, NKA, entre outros. A depressão alastrante é o fenômeno neurológico que provavelmente justifica achados experimenais e clínicos na enxaqueca. Ela tem velocidade de propagação semelhante à aura, ativa o núcleo espinhal do trigêmeo e está relacionada à liberação de CGRP e NO. Alterações circulatórias detectadas por métodos complementares reforçam o papel da depressão alastrante. A identificação de anormalidades em pelo menos três loci (cromossomas 19 e 1 na enxaqueca hemiplégica familiar ocorreu recentemente. Elas estão relacionadas a anormalidades nos canais de cálcio voltagem dependentes tipo P/Q, específicos do sistema nervoso central, que regulam a liberação de vários neurotransmissores, incluindo possivelmente a serotonina. A exemplo de outras anormalidades neurológicas paroxísticas que resultam da hiperexcitabilidade da membrana plasmática, é possível que a enxaqueca ocorra devido a uma desordem de canais iônicos.The pathophysiology of migraine is not yet fully understood. The most important structures involved seem to be the central nervous system (cortex and brain stem, the trigeminovascular system and related cranial arteries, other autonomic fibres innervating such vessels, and various local vasoactive agents, including SP, CGRP, NO, VIP, NPY, ACh, NA, NKA, among others. The spreading depression phenomenon may explain clinical as well experimental findings in migraine. Its propagation velocity mirrors what is found in clinical aura, it may activate the spinal trigeminal nucleus and may induce CGRP and NO release. Circulatory changes detected with

Pathophysiology of Manganese-Associated Neurotoxicity

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Racette, Brad A.; Aschner, Michael; Guilarte, Tomas R.; Dydak, Ulrike; Criswell, Susan R.; Zheng, Wei

2012-01-01

Conference Summary Manganese (Mn) is a well established neurotoxin associated with specific damage to the basal ganglia in humans. The phenotype associated with Mn neurotoxicity was first described in two workers with occupational exposure to Mn oxide.(Couper, 1837) Although the description did not use modern clinical terminology, a parkinsonian illness characterized by slowness of movement (bradykinesia), masked facies, and gait impairment (postural instability) appears to have predominated. Nearly 100 years later an outbreak of an atypical parkinsonian illness in a Chilean Mn mine provided a phenotypic description of a fulminant neurologic disorder with parkinsonism, dystonia, and neuropsychiatric symptoms.(Rodier J, 1955) Exposures associated with this syndrome were massive and an order of magnitude greater than modern exposures.(Rodier J, 1955; Hobson et al., 2011) The clinical syndrome associated with Mn neurotoxicity has been called manganism. Modern exposures to Mn occur primarily through occupations in the steel industry and welding. These exposures are often chronic and varied, occurring over decades in the healthy workforce. Although the severe neurologic disorder described by Rodier and Couper are no longer seen, several reports have suggested a possible increased risk of neurotoxicity in these workers.(Racette et al., 2005b; Bowler et al., 2007; Harris et al., 2011) Based upon limited prior imaging and pathologic investigations into the pathophysiology of neurotoxicity in Mn exposed workers,(Huang et al., 2003) many investigators have concluded that the syndrome spares the dopamine system distinguishing manganism from Parkinson disease (PD), the most common cause of parkinsonism in the general population, and a disease with characteristic degenerative changes in the dopaminergic system.(Jankovic, 2005) The purpose of this symposium was to highlight recent advances in the understanding of the pathophysiology of Mn associated neurotoxicity from C. elegans

Inflammatory fatigue and sickness behaviour - lessons for the diagnosis and management of chronic fatigue syndrome.

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Arnett, S V; Clark, I A

2012-12-10

Persistent and severe fatigue is a common part of the presentation of a diverse range of disease processes. There is a growing body of evidence indicating a common inflammatory pathophysiology underlying many conditions where fatigue is a primary patient concern, including chronic fatigue syndrome. This review explores current models of how inflammatory mediators act on the central nervous system to produce fatigue and sickness behaviour, and the commonality of these processes in conditions as diverse as surgical trauma, infection, various cancers, inflammatory bowel disease, connective tissue diseases and autoimmune diseases. We also discuss evidence indicating chronic fatigue syndrome may have important pathophysiological similarities with cytokine mediated sickness behaviour, and what lessons can be applied from sickness behaviour to chronic fatigue syndrome with regards to the diagnosis and management. Copyright © 2012 Elsevier B.V. All rights reserved.

Effect of mechanical ventilation on systemic oxygen extraction and lactic acidosis during early septic shock in rats.

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Griffel, M I; Astiz, M E; Rackow, E C; Weil, M H

1990-01-01

We studied the effect of mechanical ventilation on systemic oxygen extraction and lactic acidosis in peritonitis and shock in rats. Sepsis was induced by cecal ligation and perforation. After tracheostomy, rats were randomized to spontaneous breathing (S) or mechanical ventilation with paralysis (V). Five animals were studied in each group. The V animals were paralyzed with pancuronium bromide to eliminate respiratory effort. Mechanical ventilation consisted of controlled ventilation using a rodent respirator with periodic adjustment of minute ventilation to maintain PaCO2 and pH within normal range. Arterial and central venous blood gases and thermodilution cardiac output were measured at baseline before abdominal surgery, and sequentially at 0.5, 3.5, and 6 h after surgery. At 6 h, cardiac output was 193 +/- 30 ml/kg.min in S animals and 199 +/- 32 ml/kg.min in V animals (NS). The central venous oxygen saturation was 27.4 +/- 4.7% in S animals and 30.0 +/- 6.4% in V animals (NS). Systemic oxygen extraction was 70 +/- 5% in S animals and 67 +/- 6% in V animals (NS). Arterial lactate was 2.4 +/- 0.4 mmol/L in S animals and 2.2 +/- 0.5 mmol/L in V animals (NS). The S animals developed lethal hypotension at 6.6 +/- 0.4 h compared to 6.8 +/- 0.4 h in V animals (NS). These data suggest that mechanical ventilation does not decrease systemic oxygen extraction or ameliorate the development of lactic acidosis during septic shock.

Hepatorenal Syndrome: Aetiology, Diagnosis, and Treatment

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G. Low

2015-01-01

Full Text Available Acute renal impairment is common in patients with chronic liver disease, occurring in approximately 19% of hospitalised patients with cirrhosis. A variety of types of renal impairment are recognised. The most important of these is the hepatorenal syndrome, a functional renal impairment due to circulatory and neurohormonal abnormalities that underpin cirrhosis. It is one of the most severe complications of cirrhosis with survival often measured in weeks to months. A variety of treatment options exist with early diagnosis and appropriate treatment providing the best hope for cure. This paper provides a comprehensive and up-to-date review of hepatorenal syndrome and lays out the topic according to the following sections: pathophysiology, historical developments, diagnostic criteria and limitations, epidemiology, precipitating factors, predictors, clinical and laboratory findings, prognosis, treatment options, prophylaxis, and conclusion.

The single photon diagnosis and the therapy applications in nuclear oncology: past, present and future

International Nuclear Information System (INIS)

Giammarile, F.

2005-01-01

The principal applications of the nuclear medicine concern the diagnosis. It can be added the information in the evaluation of the therapy response and in the evaluation of a future risk. The potential of development in nuclear medicine is in new radiopharmaceuticals, especially new pathophysiologic information can be gotten every time a new molecule is discovered and one of the principal aims of diagnostic imaging is the in vivo tissue characterization. (N.C.)

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

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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

Prenatal Diagnosis of Transposition of the Great Arteries over a 20-Year Period: Improved but Imperfect

Science.gov (United States)

Escobar-Diaz, Maria C; Freud, Lindsay R; Bueno, Alejandra; Brown, David W; Friedman, Kevin; Schidlow, David; Emani, Sitaram; del Nido, Pedro; Tworetzky, Wayne

2015-01-01

Objective To evaluate temporal trends in prenatal diagnosis of transposition of the great arteries with intact ventricular septum (TGA/IVS) and its impact on neonatal morbidity and mortality. Methods Newborns with TGA/IVS referred for surgical management to our center over a 20-year period (1992 – 2011) were included. The study time was divided into 5 four-year periods, and the primary outcome was rate of prenatal diagnosis. Secondary outcomes included neonatal pre-operative status and perioperative survival. Results Of the 340 patients, 81 (24%) had a prenatal diagnosis. Prenatal diagnosis increased over the study period from 6% to 41% (p<0.001). Prenatally diagnosed patients underwent a balloon atrial septostomy (BAS) earlier than postnatally diagnosed patients (0 vs. 1 day, p<0.001) and fewer required mechanical ventilation (56% vs. 69%, p=0.03). There were no statistically significant differences in pre-operative acidosis (16% vs. 26%, p=0.1) and need for preoperative ECMO (2% vs. 3%, p=1.0). There was also no significant mortality difference (1 pre-operative and no post-operative deaths among prenatally diagnosed patients, as compared to 4 pre-operative and 6 post-operative deaths among postnatally diagnosed patients). Conclusion The prenatal detection rate of TGA/IVS has improved but still remains below 50%, suggesting the need for strategies to increase detection rates. The mortality rate was not statistically different between pre- and postnatally diagnosed patients; however, there were significant pre-operative differences with regard to earlier BAS and less mechanical ventilation. Ongoing study is required to elucidate whether prenatal diagnosis confers long-term benefit. PMID:25484180

Advanced MR diagnostic imaging in pediatric glial cell tumors: from morphological to pathophysiological evaluation

International Nuclear Information System (INIS)

Balev, B.; Georgiev, R.; Novakova, M.

2013-01-01

Full text: Introduction: The conventional MR imaging is important, and in most cases necessary imaging tool for studying the macroscopic structure, for localization and distribution of a glial brain tumor. It is an integral part of the optimal MR protocol, which further comprises a diffusion, perfusion techniques, techniques for the permeability and oxygenation assessment, as well as MR spectroscopy to the metabolism assessment. What you will learn: Glial brain tumors in children - incidence, histology, classification, diagnosis; Nature and principles of MR diffusion, perfusion, techniques for permeability and oxygenation assessment, MR spectroscopy; Contemporary techniques allowing to obtain not only MR morphological information but also to evaluate the tumor the pathophysiology: the cellular atypia, cellularity, tumor neovascularization, oxygen consumption, metabolism, status of the blood-brain barrier. This assessment determines the biological potential of the tumor, treatment options and prognosis. Discussion: The findings from conventional MR examinations, incl. administration of gadolinium contrast agents are associated with the degree of glioma and can be useful for their classification. Taking into account that from 20% to 45 % of the unenhanced supratentorial gliomas are malignant, some low-grade gliomas enhance (ganglioglioma, pilocytic astrocytoma, oligodendroglioma), 9% of malignant gliomas have no contrast enhancement, and in general, the contrast enhancement is not seen as a reliable indicator for the infiltration extent. The contemporary MR techniques improve the assessment of the pathophysiology of the tumor which is relevant to its histology and biological potential. Conclusion: Modern MR techniques besides purely diagnostic advantages (determine the extent and distribution of glioma), enable: differentiation of tumor recurrence from radiation necrosis; identification of optimal locations for biopsy or operative resection; prognosis, planning and

Pathophysiology of nocturnal enuresis

DEFF Research Database (Denmark)

Rittig, Søren; Kamperis, Konstantinos

2015-01-01

The perception of the pathogenesis of enuresis has undergone marked changes over the past 30 years from a psychiatric/psychological background to a more somatic model where nighttime urine production and bladder capacity are main components together with an arousal dysfunction that prevents...... that dysfunction of the intrinsic circadian regulation located in the suprachiasmatic nucleus results in dysfunction of one or more of the brainstem centers involved in AVP secretion, arousal function, bladder control, and blood pressure regulation. Furthermore, nocturnal enuresis has a strong genetic influence...... that in some families present as autosomal dominant inheritance with high degree of penetrance. Linkage to several chromosomal areas have been confirmed in such families although a specific causative enuresis gene has not yet been identified. In conclusion, our understanding of enuresis pathophysiology has...

[Exercise-induced inspiratory stridor. An important differential diagnosis of exercise-induced asthma].

Science.gov (United States)

Christensen, Pernille; Thomsen, Simon Francis; Rasmussen, Niels; Backer, Vibeke

2007-11-19

Recent studies suggest that exercise-induced inspiratory stridor (EIIS) is an important and often overlooked differential diagnosis of exercise-induced asthma. EIIS is characterised by astma-like symptoms, but differs by inspiratory limitation, fast recovery, and a lack of effect of inhaled bronchodilators. The prevalence of EIIS is reported to be 5-27%, and affects both children and adults. The pathophysiology, the pathogenesis, and the treatment of the condition are not yet clarified. At present, a population-based study is being conducted in order to address these points.

Molecular pathophysiology of cerebral edema

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Gerzanich, Volodymyr; Simard, J Marc

2015-01-01

Advancements in molecular biology have led to a greater understanding of the individual proteins responsible for generating cerebral edema. In large part, the study of cerebral edema is the study of maladaptive ion transport. Following acute CNS injury, cells of the neurovascular unit, particularly brain endothelial cells and astrocytes, undergo a program of pre- and post-transcriptional changes in the activity of ion channels and transporters. These changes can result in maladaptive ion transport and the generation of abnormal osmotic forces that, ultimately, manifest as cerebral edema. This review discusses past models and current knowledge regarding the molecular and cellular pathophysiology of cerebral edema. PMID:26661240

Pathophysiology and Contributing Factors in Postprostatectomy Incontinence: A Review

NARCIS (Netherlands)

Heesakkers, J.P.F.A.; Farag, F.; Bauer, R.M.M.J.; Sandhu, J.; Ridder, D. de; Stenzl, A.

2017-01-01

CONTEXT: The incidence and awareness of postprostatectomy incontinence (PPI) has increased during the past few years, probably because of an increase in prostate cancer surgery. Many theories have been postulated to explain the pathophysiology of PPI. OBJECTIVE: The current review scrutinizes

18F-fluorodeoxyglucose positron emission tomography might be useful for diagnosis of hepatic amyloidosis

Directory of Open Access Journals (Sweden)

Tawada A

2014-06-01

Full Text Available Akinobu Tawada,1 Tatsuo Kanda,1 Takashi Oide,2 Toshio Tsuyuguchi,1 Fumio Imazeki,1,3 Yukio Nakatani,2 Osamu Yokosuka11Department of Gastroenterology, 2Department of Diagnostic Pathology, Chiba University Hospital, Chuo-ku, Chiba, Japan; 3Safety and Health Organization, Chiba University, Inage-ku, Chiba, JapanAbstract: We report on a woman with hepatic involvement of primary systemic (immunoglobulin light chain, AL amyloidosis. Her diagnosis was confirmed by liver biopsy. Clinical symptoms of hepatic amyloidosis are generally mild at its first stage, with most frequent findings being hepatomegaly and alkaline phosphatase elevation. Recent advances in the understanding of the pathophysiology of systemic amyloidosis have made several treatments available. However, its prognosis is occasionally poor. Because liver biopsy is not always safe, other modalities for the diagnosis are needed. Of interest was that fluorodeoxyglucose (FDG uptake into the liver was observed, compared with that into the spleen, in this patient, indicating that FDG positron emission tomography and computed tomography might be useful for the diagnosis of hepatic amyloidosis with mild liver dysfunction.Keywords: amyloidosis, diagnosis, hepatic involvement, FDG PET

The pathophysiology of arterial vasodilatation and hyperdynamic circulation in cirrhosis

DEFF Research Database (Denmark)

Møller, Søren; Bendtsen, Flemming

2018-01-01

transplantation and point to the pathophysiological significance of portal hypertension. In this paper we aimed to review current knowledge on the pathophysiology of arterial vasodilatation and the hyperdynamic circulation in cirrhosis. This article is protected by copyright. All rights reserved.......Patients with cirrhosis and portal hypertension often develop complications from a variety of organ systems leading to a multiple organ failure. The combination of liver failure and portal hypertension result in a hyperdynamic circulatory state partly owing to simultaneous splanchnic and peripheral...... arterial vasodilatation. Increases in circulatory vasodilators are believed to be due to portosystemic shunting and bacterial translocation leading to redistribution of the blood volume with central hypovolemia. Portal hypertension per se and increased splanchnic blood flow are mainly responsible...

[Tardive dyskinesia--diagnosis and treatment].

Science.gov (United States)

Kazamatsuri, H

1993-11-01

Tardive dyskinesia is defined as a syndrome consisting of abnormal, stereotypical involuntary movements usually of choreoathetoid type, principally affected the mouth, face, limbs and trunk, which occurs relatively late in the course of neuroleptic drug treatment and in the etiology of which the drug treatment is a necessary factor. Presently, the prevalence of tardive dyskinesia in the hospitalized patients in psychiatric hospitals in Japan is estimated to be 20-30%. Epidemiology, possible pathophysiology and symptomatology of tardive dyskinesia are briefly described. Differential diagnosis between this syndrome and other involuntary movements such as psychotic mannerism, senile orofacial dyskinesia, rabbit's syndrome, Pisa syndrome or Meige's syndrome is discussed. Several drugs to suppress involuntary movements of tardive dyskinesia are described. However, there appears to be no consistently reliable therapies for patients who develop the tardive dyskinesia. Treatment for this syndrome, other than neuroleptic withdrawal, are still uncertain.

The rise of pathophysiologic research in the United States: the role of two Harvard hospitals.

Science.gov (United States)

Tishler, Peter V

2013-01-01

Pathophysiologic research, the major approach to understanding and treating disease, was created in the 20th century, and two Harvard-affiliated hospitals, the Peter Bent Brigham Hospital and Boston City Hospital, played a key role in its development. After the Flexner Report of 1910, medical students were assigned clinical clerkships in teaching hospitals. Rockefeller-trained Francis Weld Peabody, who was committed to investigative, pathophysiologic research, was a critical leader in these efforts. At the Brigham, Harvard medical students observed patients closely and asked provocative questions about their diseases. Additionally, physicians returned from World War I with questions concerning the pathophysiology of wartime injuries. At the Boston City Hospital's new Thorndike Memorial Laboratory, Peabody fostered investigative question-based research by physicians. These physicians expanded pathophysiologic investigation from the 1920s. Post-war, Watson and Crick's formulation of the structure of DNA led shortly to modern molecular biology and new research approaches that are being furthered at the Boston Hospitals.