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Alcohol Lactic Acidosis Mechanism

Metabolic Acidosis In The Alcoholic: A Pathophysiologic Approach.

Metabolic Acidosis In The Alcoholic: A Pathophysiologic Approach.

Metabolic acidosis in the alcoholic: a pathophysiologic approach. Halperin ML , Hammeke M , Josse RG , Jungas RL . The purpose of this paper is to review the acid-base abnormalities in patients presenting with metabolic acidosis due to acute ethanol ingestion and to review the theoretical constraints on ethanol metabolism in the liver. Alcohol-induced acidosis is a mixed acid-base disturbance. Metabolic acidosis is due to lactic acidosis, ketoacidosis and acetic acidosis but the degree of each varies from patient to patient. Metabolic alkalosis is frequently present due to ethanol-induced vomiting. However, it could be overlooked because of an indirect loss of sodium bicarbonate (as sodium B-hydroxybutyrate in the urine). Nevertheless, the accompanying reduction in ECF volume may play an important role in the pathogenesis of alcoholic acidosis because it could lead to a relative insulin deficiency. Treatment of alcohol acidosis should include sodium, chloride, potassium, phosphorus, magnesium and thiamine replacements along with attention to concomitant clinical problems. Unless hypoglycemia is present, glucose need not be given immediately. We feel that insulin should be withheld unless life-threatening acidemia is present or expected. Lastly, alcohol need not be detected on admission to make the diagnosis of this metabolic disturbance. However, when present, it could contribute directly to the lactic, acetic and B-hydroxybutyric acidoses. With respect to the theoretical constraints on ethanol metabolism, it appears that "overproduction" of NADH in the liver is best averted by converting ethanol to B-hydroxybutyric acid. Continue reading >>

Lactic Acidosis

Lactic Acidosis

Lactic acidosis is a medical condition characterized by the buildup of lactate (especially L-lactate) in the body, which results in an excessively low pH in the bloodstream. It is a form of metabolic acidosis, in which excessive acid accumulates due to a problem with the body's metabolism of lactic acid. Lactic acidosis is typically the result of an underlying acute or chronic medical condition, medication, or poisoning. The symptoms are generally attributable to these underlying causes, but may include nausea, vomiting, rapid deep breathing, and generalised weakness. The diagnosis is made on biochemical analysis of blood (often initially on arterial blood gas samples), and once confirmed, generally prompts an investigation to establish the underlying cause to treat the acidosis. In some situations, hemofiltration (purification of the blood) is temporarily required. In rare chronic forms of lactic acidosis caused by mitochondrial disease, a specific diet or dichloroacetate may be used. The prognosis of lactic acidosis depends largely on the underlying cause; in some situations (such as severe infections), it indicates an increased risk of death. Classification[edit] The Cohen-Woods classification categorizes causes of lactic acidosis as:[1] Type A: Decreased tissue oxygenation (e.g., from decreased blood flow) Type B B1: Underlying diseases (sometimes causing type A) B2: Medication or intoxication B3: Inborn error of metabolism Signs and symptoms[edit] Lactic acidosis is commonly found in people who are unwell, such as those with severe heart and/or lung disease, a severe infection with sepsis, the systemic inflammatory response syndrome due to another cause, severe physical trauma, or severe depletion of body fluids.[2] Symptoms in humans include all those of typical m Continue reading >>

Causes Of Lactic Acidosis

Causes Of Lactic Acidosis

INTRODUCTION AND DEFINITION Lactate levels greater than 2 mmol/L represent hyperlactatemia, whereas lactic acidosis is generally defined as a serum lactate concentration above 4 mmol/L. Lactic acidosis is the most common cause of metabolic acidosis in hospitalized patients. Although the acidosis is usually associated with an elevated anion gap, moderately increased lactate levels can be observed with a normal anion gap (especially if hypoalbuminemia exists and the anion gap is not appropriately corrected). When lactic acidosis exists as an isolated acid-base disturbance, the arterial pH is reduced. However, other coexisting disorders can raise the pH into the normal range or even generate an elevated pH. (See "Approach to the adult with metabolic acidosis", section on 'Assessment of the serum anion gap' and "Simple and mixed acid-base disorders".) Lactic acidosis occurs when lactic acid production exceeds lactic acid clearance. The increase in lactate production is usually caused by impaired tissue oxygenation, either from decreased oxygen delivery or a defect in mitochondrial oxygen utilization. (See "Approach to the adult with metabolic acidosis".) The pathophysiology and causes of lactic acidosis will be reviewed here. The possible role of bicarbonate therapy in such patients is discussed separately. (See "Bicarbonate therapy in lactic acidosis".) PATHOPHYSIOLOGY A review of the biochemistry of lactate generation and metabolism is important in understanding the pathogenesis of lactic acidosis [1]. Both overproduction and reduced metabolism of lactate appear to be operative in most patients. Cellular lactate generation is influenced by the "redox state" of the cell. The redox state in the cellular cytoplasm is reflected by the ratio of oxidized and reduced nicotine ad Continue reading >>

Alcoholic Ketoacidosis: A Case Report And Review Of The Literature

Alcoholic Ketoacidosis: A Case Report And Review Of The Literature

Alcoholic ketoacidosis (AKA) is a condition that presents with a significant metabolic acidosis in patients with a history of alcohol excess. The diagnosis is often delayed or missed, and this can have potentially fatal consequences. There are a variety of non-specific clinical manifestations that contribute to these diagnostic difficulties. In particular, cases of AKA can be misdiagnosed as diabetic ketoacidosis (DKA). Subsequent mismanagement can lead to increasing morbidity and mortality for patients. AKA typically presents with a severe metabolic acidosis with a raised anion gap and electrolyte abnormalities, which are treatable if recognized early and appropriate management instituted. Given the increasing epidemic of alcohol-related healthcare admissions, this is an important condition to recognize and we aim to offer guidance on how to approach similar cases for the practising clinician. We present a 64-year-old female who presented with generalized abdominal pain, nausea, vomiting and shortness of breath. Arterial blood gas analysis showed significant acidaemia with a pH of 7.10, bicarbonate of 2.9 mmol/l and lactate of 11.7 mmol/l. Serum ketones were raised at 5.5 mmol/l. Capillary blood glucose was noted to 5.8 mmol/l. The anion gap was calculated and was elevated at 25 mmol/l. The diagnosis of DKA was queried after initial triage. However, following senior medical review, given a recent history of drinking alcohol to excess, the diagnosis of AKA was felt more likely. Whilst a decreased conscious level may have been expected, our patient was lucid enough to report drinking one to two bottles of wine per day for the past 30 years, with a recent binge the day prior to admission. Subsequent fluid resuscitation and monitoring were instituted. Further biochemical i Continue reading >>

Alcoholic Ketoacidosis

Alcoholic Ketoacidosis

What is alcoholic ketoacidosis? Cells need glucose (sugar) and insulin to function properly. Glucose comes from the food you eat, and insulin is produced by the pancreas. When you drink alcohol, your pancreas may stop producing insulin for a short time. Without insulin, your cells won’t be able to use the glucose you consume for energy. To get the energy you need, your body will start to burn fat. When your body burns fat for energy, byproducts known as ketone bodies are produced. If your body is not producing insulin, ketone bodies will begin to build up in your bloodstream. This buildup of ketones can produce a life-threatening condition known as ketoacidosis. Ketoacidosis, or metabolic acidosis, occurs when you ingest something that is metabolized or turned into an acid. This condition has a number of causes, including: shock kidney disease abnormal metabolism In addition to general ketoacidosis, there are several specific types. These types include: alcoholic ketoacidosis, which is caused by excessive consumption of alcohol diabetic ketoacidosis (DKA), which mostly develops in people with type 1 diabetes starvation ketoacidosis, which occurs most often in women who are pregnant, in their third trimester, and experiencing excessive vomiting Each of these situations increases the amount of acid in the system. They can also reduce the amount of insulin your body produces, leading to the breakdown of fat cells and the production of ketones. Alcoholic ketoacidosis can develop when you drink excessive amounts of alcohol for a long period of time. Excessive alcohol consumption often causes malnourishment (not enough nutrients for the body to function well). People who drink large quantities of alcohol may not eat regularly. They may also vomit as a result of drinking too Continue reading >>

Alcoholic Ketoacidosis

Alcoholic Ketoacidosis

Go to: CHARACTERISATION In 1940, Dillon et al1 described a series of nine patients who had episodes of severe ketoacidosis in the absence of diabetes mellitus, all of whom had evidence of prolonged excessive alcohol consumption. It was not until 1970 that Jenkins et al2 described a further three non‐diabetic patients with a history of chronic heavy alcohol misuse and recurrent episodes of ketoacidosis. This group also proposed a possible underlying mechanism for this metabolic disturbance, naming it alcoholic ketoacidosis. Further case series by Levy et al, Cooperman et al, and Fulop et al were subsequently reported, with remarkably consistent features.3,4,5 All patients presented with a history of prolonged heavy alcohol misuse, preceding a bout of particularly excessive intake, which had been terminated several days earlier by nausea, severe vomiting, and abdominal pain. Clinical signs included tachypnoea, tachycardia, and hypotension. In 1974, Cooperman's series of seven ketoacidotic alcoholic patients all displayed diffuse epigastric tenderness on palpation.4 In contrast to patients with diabetic ketoacidosis, the patients were usually alert and lucid despite the severity of the acidosis and marked ketonaemia. When altered mental status occurred, this was clearly attributable to other causes. Laboratory results included absent blood alcohol with normal or low blood glucose level, no glycosuria, and a variably severe metabolic acidosis with a raised anion gap. This acidosis appeared to result from the accumulation in plasma of lactate and ketone bodies including beta‐hydroxybutyrate (BOHB) and acetoacetate (AcAc).3 Cooperman et al found that near patient testing for ketone bodies using nitroprusside test (Acetest, Ketostix) produced a low to moderate result in th Continue reading >>

Metabolic Abnormalities In Alcoholic Patients: Focus On Acid Base Andelectrolyte Disorders

Metabolic Abnormalities In Alcoholic Patients: Focus On Acid Base Andelectrolyte Disorders

E-mail: [emailprotected] , [emailprotected] Received Date: December 20, 2014; Accepted Date: January 24, 2015; Published Date: January 27, 2015 Citation: Moses Elisaf MD, Rigas Kalaitzidis MD (2015) Metabolic Abnormalities in Alcoholic Patients: Focus on Acid Base and Electrolyte Disorders. J Alcohol Drug Depend 3:185. doi:10.4172/2329-6488.1000185 Copyright: 2015 Moses Elisaf MD, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Alcoholic patients commonly develop a variety of acid-base and electrolyte disturbances. The aim of this review is to describe the most commonly encountered abnormalities and their significant role in the patients morbidity and mortality. Physicians should be aware of these clinically important disturbances caused by alcohol abuse and their underlying pathophysiological mechanisms involved for their appropriate management. Alcoholic Keto Acidosis (AKA) is a medical emergency is more common than previously thought and is characterized by an increased anion gap metabolic acidosis . However, in AKA mixed acid-base disorders are commonly observed. Alcoholic patients also exhibit severe electrolyte derangements. Multifactorial origin hypomagnesaemia is the most common electrolyte abnormality observed. Hypocalcaemia is also a frequent electrolyte disturbance and is commonly associated with hypomagnesaemia. Hypokalemia is occasionally encountered in these patients, while multifactorial origin hypophosphatemia is the second common electrolyte abnormality found. Hyponatremia is also a common electrolyte derangement and may occur subsequent to several mechanisms m Continue reading >>

Chapter 221. Alcoholic Ketoacidosis

Chapter 221. Alcoholic Ketoacidosis

Woods WA, Perina DG. Woods W.A., Perina D.G. Woods, William A., and Debra G. Perina.Chapter 221. Alcoholic Ketoacidosis. In: Tintinalli JE, Stapczynski J, Ma O, Cline DM, Cydulka RK, Meckler GD, T. Tintinalli J.E., Stapczynski J, Ma O, Cline D.M., Cydulka R.K., Meckler G.D., T Eds. Judith E. Tintinalli, et al.eds. Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 7e New York, NY: McGraw-Hill; 2011. Accessed March 27, 2018. Woods WA, Perina DG. Woods W.A., Perina D.G. Woods, William A., and Debra G. Perina.. "Chapter 221. Alcoholic Ketoacidosis." Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 7e Tintinalli JE, Stapczynski J, Ma O, Cline DM, Cydulka RK, Meckler GD, T. Tintinalli J.E., Stapczynski J, Ma O, Cline D.M., Cydulka R.K., Meckler G.D., T Eds. Judith E. Tintinalli, et al. New York, NY: McGraw-Hill, 2011, Alcoholic ketoacidosis is a wide anion gap metabolic acidosis most often associated with acute cessation of alcohol consumption after chronic alcohol abuse and is typically associated with nausea, vomiting, and vague GI complaints. 1 Alcohol metabolism combined with little or no glycogen reserves results in elevated ketoacid levels. Although alcoholic ketoacidosis is usually seen in chronic alcoholics, it has been described in first-time binge drinkers. Repeated episodes can occur. 2 Although with proper treatment this illness is self limited, death has been reported from presumed excessive ketonemia. 24 Ethanol metabolism requires nicotinamide adenine dinucleotide (NAD) and the enzymes alcohol dehydrogenase and aldehyde dehydrogenase to convert ethanol to acetyl coenzyme A. Acetyl coenzyme A may be metabolized directly, resulting in ketoacid production, used as substrate for the Krebs cycle, or used for free fatty acid synthesis ( Figu Continue reading >>

Alcoholism And Lactic Acidosis

Alcoholism And Lactic Acidosis

Learn more about the SDN Exhibition Forums for exclusive discounts and contests. So the way I understood this is that both alcohol metabolism and latcate to pyrvuate conversion require NAD, and with too much alcohol consumption the body uses up all the NAD for alcohol metabolism right? The part that I'm a bit troubled with this mechanism is that unless we are doing extreme exercise, we don't really generate lactic acid. In most cases, the body uses oxidative phosphorylation, right? So lactic acidosis will most likely occur when you drink alcohol and then do extreme exercise, correct? SDN Members don't see this ad. About the ads. My understanding is that high NADH levels from EtOH metab drives the pyruvate -> lactate conversion. So you don't need to be exercising +drinking, either will do it on their own. I actually enjoy your questions, though some things are really easily looked up. The several different causes of lactic acidosis: I actually enjoy your questions, though some things are really easily looked up. The several different causes of lactic acidosis: But the reasons behind why lactic acidosis occurs for these is significantly different.... For example, in exercise- lactic acidosis- due to depletion of ATP such that the ability to generate ATP via oxidation is overwhelmed. This leads to high levels of ADP> than the O2 intake from respiration. When the ADP/ATP ratio are elevated but O2 is no longer sufficient the body switches to anaerobic metabolism to quickly generate ATP= leading to lactic acidosis. In alcoholism, the NADH levels are elevated. Why does this take place? because degeneration of alcohol to acetic acid (the final state) is via transferring electrons from ETOH to aldehyde DEHYDROGENASE and alcohol DEHYDROGENASE to NAD- the elevation to NADH forces Continue reading >>

Toxic Alcohol Ingestions: Clinical Features, Diagnosis, And Management

Toxic Alcohol Ingestions: Clinical Features, Diagnosis, And Management

Abstract Alcohol-related intoxications, including methanol, ethylene glycol, diethylene glycol, and propylene glycol, and alcoholic ketoacidosis can present with a high anion gap metabolic acidosis and increased serum osmolal gap, whereas isopropanol intoxication presents with hyperosmolality alone. The effects of these substances, except for isopropanol and possibly alcoholic ketoacidosis, are due to their metabolites, which can cause metabolic acidosis and cellular dysfunction. Accumulation of the alcohols in the blood can cause an increment in the osmolality, and accumulation of their metabolites can cause an increase in the anion gap and a decrease in serum bicarbonate concentration. The presence of both laboratory abnormalities concurrently is an important diagnostic clue, although either can be absent, depending on the time after exposure when blood is sampled. In addition to metabolic acidosis, acute renal failure and neurologic disease can occur in some of the intoxications. Dialysis to remove the unmetabolized alcohol and possibly the organic acid anion can be helpful in treatment of several of the alcohol-related intoxications. Administration of fomepizole or ethanol to inhibit alcohol dehydrogenase, a critical enzyme in metabolism of the alcohols, is beneficial in treatment of ethylene glycol and methanol intoxication and possibly diethylene glycol and propylene glycol intoxication. Given the potentially high morbidity and mortality of these intoxications, it is important for the clinician to have a high degree of suspicion for these disorders in cases of high anion gap metabolic acidosis, acute renal failure, or unexplained neurologic disease so that treatment can be initiated early. Effect of Alcohols on Serum Osmolality and the Osmolal Gap The normal serum Continue reading >>

Severe Metabolic Acidosis In The Alcoholic: Differential Diagnosis And Management

Severe Metabolic Acidosis In The Alcoholic: Differential Diagnosis And Management

1 A chronic alcoholic with severe metabolic acidosis presents a difficult diagnostic problem. The most common cause is alcoholic ketoacidosis, a syndrome with a typical history but often misleading laboratory findings. This paper will focus on this important and probably underdiagnosed syndrome. 2 The disorder occurs in alcoholics who have had a heavy drinking-bout culminating in severe vomiting, with resulting dehydration, starvation, and then a β- hydroxybutyrate dominated ketoacidosis. 3 Awareness of this syndrome, thorough history-taking, physical examination and routine laboratory analyses will usually lead to a correct diagnosis. 4 The treatment is simply replacement of fluid, glucose, electrolytes and thiamine. Insulin or alkali should be avoided. 5 The most important differential diagnoses are diabetic ketoacidosis, lactic acidosis and salicylate, methanol or ethylene glycol poisoning, conditions which require quite different treatment. 6 The diagnostic management of unclear cases should always include toxicological tests, urine microscopy for calcium oxalate crystals and calculation of the serum anion and osmolal gaps. 7 It is suggested here, however, that the value of the osmolal gap should be considered against a higher reference limit than has previously been recom mended. An osmolal gap above 25 mosm/kg, in a patient with an increased anion gap acidosis, is a strong indicator of methanol or ethylene glycol intoxication. Continue reading >>

Alcoholic Ketoacidosis

Alcoholic Ketoacidosis

Background In 1940, Dillon and colleagues first described alcoholic ketoacidosis (AKA) as a distinct syndrome. AKA is characterized by metabolic acidosis with an elevated anion gap, elevated serum ketone levels, and a normal or low glucose concentration. [1, 2] Although AKA most commonly occurs in adults with alcoholism, it has been reported in less-experienced drinkers of all ages. Patients typically have a recent history of binge drinking, little or no food intake, and persistent vomiting. [3, 4, 5] A concomitant metabolic alkalosis is common, secondary to vomiting and volume depletion (see Workup). [6] Treatment of AKA is directed toward reversing the 3 major pathophysiologic causes of the syndrome, which are: This goal can usually be achieved through the administration of dextrose and saline solutions (see Treatment). Continue reading >>

Glyburide And Metformin (oral Route)

Glyburide And Metformin (oral Route)

Precautions Drug information provided by: Micromedex It is very important that your doctor check your progress at regular visits to make sure this medicine is working properly. Blood tests may be needed to check for unwanted effects. Under certain conditions, too much metformin can cause lactic acidosis. The symptoms of lactic acidosis are severe and quick to appear. They usually occur when other health problems not related to the medicine are present and very severe, such as a heart attack or kidney failure. The symptoms of lactic acidosis include abdominal or stomach discomfort; decreased appetite; diarrhea; fast, shallow breathing; a general feeling of discomfort; muscle pain or cramping; and unusual sleepiness, tiredness, or weakness. If you have any symptoms of lactic acidosis, get emergency medical help right away. It is very important to carefully follow any instructions from your health care team about: Alcohol—Drinking alcohol may cause severe low blood sugar. Discuss this with your health care team. Other medicines—Do not take other medicines unless they have been discussed with your doctor. This especially includes nonprescription medicines such as aspirin, and medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems. Counseling—Other family members need to learn how to prevent side effects or help with side effects if they occur. Also, patients with diabetes may need special counseling about diabetes medicine dosing changes that might occur because of lifestyle changes, such as changes in exercise and diet. Furthermore, counseling on contraception and pregnancy may be needed because of the problems that can occur in patients with diabetes during pregnancy. Travel—Keep your recent prescription and your medical history with yo Continue reading >>

Ketoacidosis

Ketoacidosis

GENERAL ketoacidosis is a high anion gap metabolic acidosis due to an excessive blood concentration of ketone bodies (keto-anions). ketone bodies (acetoacetate, beta-hydroxybutyrate, acetone) are released into the blood from the liver when hepatic lipid metabolism has changed to a state of increased ketogenesis. a relative or absolute insulin deficiency is present in all cases. CAUSES The three major types of ketosis are: (i) Starvation ketosis (ii) Alcoholic ketoacidosis (iii) Diabetic ketoacidosis STARVATION KETOSIS when hepatic glycogen stores are exhausted (eg after 12-24 hours of total fasting), the liver produces ketones to provide an energy substrate for peripheral tissues. ketoacidosis can appear after an overnight fast but it typically requires 3 to 14 days of starvation to reach maximal severity. typical keto-anion levels are only 1 to 2 mmol/l and this will usually not alter the anion gap. the acidosis even with quite prolonged fasting is only ever of mild to moderate severity with keto-anion levels up to a maximum of 3 to 5 mmol/l and plasma pH down to 7.3. ketone bodies also stimulate some insulin release from the islets. patients are usually not diabetic. ALCOHOLIC KETOSIS Presentation a chronic alcoholic who has a binge, then stops drinking and has little or no oral food intake for a few days (ethanol and fasting) volume depletion is common and this can result in increased levels of counter regulatory hormones (eg glucagon) levels of free fatty acids (FFA) can be high (eg up to 3.5mM) providing plenty of substrate for the altered hepatic lipid metabolism to produce plenty of ketoanions GI symptoms are common (eg nausea, vomiting, abdominal pain, haematemesis, melaena) acidaemia may be severe (eg pH down to 7.0) plasma glucose may be depressed or normal or Continue reading >>

Alcoholic Ketoacidosis

Alcoholic Ketoacidosis

Alcoholic ketoacidosis is a metabolic complication of alcohol use and starvation characterized by hyperketonemia and anion gap metabolic acidosis without significant hyperglycemia. Alcoholic ketoacidosis causes nausea, vomiting, and abdominal pain. Diagnosis is by history and findings of ketoacidosis without hyperglycemia. Treatment is IV saline solution and dextrose infusion. Alcoholic ketoacidosis is attributed to the combined effects of alcohol and starvation on glucose metabolism. Alcohol diminishes hepatic gluconeogenesis and leads to decreased insulin secretion, increased lipolysis, impaired fatty acid oxidation, and subsequent ketogenesis, causing an elevated anion gap metabolic acidosis. Counter-regulatory hormones are increased and may further inhibit insulin secretion. Plasma glucose levels are usually low or normal, but mild hyperglycemia sometimes occurs. Diagnosis requires a high index of suspicion; similar symptoms in an alcoholic patient may result from acute pancreatitis, methanol or ethylene glycol poisoning, or diabetic ketoacidosis (DKA). In patients suspected of having alcoholic ketoacidosis, serum electrolytes (including magnesium), BUN and creatinine, glucose, ketones, amylase, lipase, and plasma osmolality should be measured. Urine should be tested for ketones. Patients who appear significantly ill and those with positive ketones should have arterial blood gas and serum lactate measurement. The absence of hyperglycemia makes DKA improbable. Those with mild hyperglycemia may have underlying diabetes mellitus, which may be recognized by elevated levels of glycosylated Hb (HbA1c). Typical laboratory findings include a high anion gap metabolic acidosis, ketonemia, and low levels of potassium, magnesium, and phosphorus. Detection of acidosis may be com Continue reading >>

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