diabetestalk.net

How Does Lactic Acidosis Happen?

Etiology And Therapeutic Approach To Elevated Lactate

Etiology And Therapeutic Approach To Elevated Lactate

Etiology and therapeutic approach to elevated lactate aResearch Center for Emergency Medicine, Aarhus University Hospital, Denmark bDepartment of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States cDepartment of Medicine, Division of Pulmonary Critical Care Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States bDepartment of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States dDepartment of Anesthesia Critical Care, Beth Israel Deaconess Medical Center, Boston, MA, United States bDepartment of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States cDepartment of Medicine, Division of Pulmonary Critical Care Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States aResearch Center for Emergency Medicine, Aarhus University Hospital, Denmark bDepartment of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States cDepartment of Medicine, Division of Pulmonary Critical Care Medicine, Beth Israel Deaconess Medical Center, Boston, MA, United States dDepartment of Anesthesia Critical Care, Beth Israel Deaconess Medical Center, Boston, MA, United States Corresponding author: Michael W. Donnino Beth Israel Deaconess Medical Center One Deaconess Road, W/CC 2 Boston, Boston, MA 02215 Phone: 617-754-2450 Fax: 617-754-2350 [email protected] The publisher's final edited version of this article is available at Mayo Clin Proc See other articles in PMC that cite the published article. Lactate levels are commonly evaluated in acutely ill patients. Although most commonly used in the context of evaluating shock, lactate can be elevated for many reasons. While tissue hypoperfusion is probably the most common cause of elevation Continue reading >>

Lactic Acidosis: What You Need To Know

Lactic Acidosis: What You Need To Know

Lactic acidosis is a form of metabolic acidosis that begins in the kidneys. People with lactic acidosis have kidneys that are unable to remove excess acid from their body. If lactic acid builds up in the body more quickly than it can be removed, acidity levels in bodily fluids — such as blood — spike. This buildup of acid causes an imbalance in the body’s pH level, which should always be slightly alkaline instead of acidic. There are a few different types of acidosis. Lactic acid buildup occurs when there’s not enough oxygen in the muscles to break down glucose and glycogen. This is called anaerobic metabolism. There are two types of lactic acid: L-lactate and D-lactate. Most forms of lactic acidosis are caused by too much L-lactate. Lactic acidosis has many causes and can often be treated. But if left untreated, it may be life-threatening. The symptoms of lactic acidosis are typical of many health issues. If you experience any of these symptoms, you should contact your doctor immediately. Your doctor can help determine the root cause. Several symptoms of lactic acidosis represent a medical emergency: fruity-smelling breath (a possible indication of a serious complication of diabetes, called ketoacidosis) confusion jaundice (yellowing of the skin or the whites of the eyes) trouble breathing or shallow, rapid breathing If you know or suspect that you have lactic acidosis and have any of these symptoms, call 911 or go to an emergency room right away. Other lactic acidosis symptoms include: exhaustion or extreme fatigue muscle cramps or pain body weakness overall feelings of physical discomfort abdominal pain or discomfort diarrhea decrease in appetite headache rapid heart rate Lactic acidosis has a wide range of underlying causes, including carbon monoxide poisoni Continue reading >>

Mala: Metformin-associated Lactic Acidosis

Mala: Metformin-associated Lactic Acidosis

By Charles W. O’Connell, MD Introduction Metformin is a first-line agent for type 2 diabetes mellitus often used as monotherapy or in combination with oral diabetic medications. It is a member of the biguanide class and its main intended effect is expressed by the inhibition of hepatic gluconeogenesis. In addition, metformin increases insulin sensitivity, enhances peripheral glucose utilization and decreases glucose uptake in the gastrointestinal tract. Phenformin, a previously used biguanide, as withdrawn from the market in the 1970’s due its association with numerous cases of lactic acidosis. Metformin is currently used extensively in the management of diabetes and is the most commonly prescribed biguanide worldwide. The therapeutic dosage of metformin ranges from 850 mg to a maximum of 3000 mg daily and is typically divided into twice daily dosing. It is primarily used in the treatment of diabetes but has been used in other conditions associated with insulin resistance such as polycystic ovarian syndrome. MALA is a rare but well reported event that occurs with both therapeutic use and overdose states. Case presentation A 22-year-old female presents to the Emergency Department after being found alongside a suicide note by her family. She was thought to have taken an unknown, but large amount of her husband’s metformin. She arrives at the ED nearly 10 hours after ingestion. She was agitated, but conversant. She reports having nausea and vague feelings of being unwell and is very distraught over the state of her critically ill husband. She has some self-inflicted superficial lacerations over her left anterior forearm. Her vital assigns upon arrival were: T 98.9 degrees Fahrenheit, HR initially 140 bpm which improved to 110 bpm soon after arrival, BP 100/50, RR 22, Continue reading >>

Lactate And Lactic Acidosis

Lactate And Lactic Acidosis

The integrity and function of all cells depend on an adequate supply of oxygen. Severe acute illness is frequently associated with inadequate tissue perfusion and/or reduced amount of oxygen in blood (hypoxemia) leading to tissue hypoxia. If not reversed, tissue hypoxia can rapidly progress to multiorgan failure and death. For this reason a major imperative of critical care is to monitor tissue oxygenation so that timely intervention directed at restoring an adequate supply of oxygen can be implemented. Measurement of blood lactate concentration has traditionally been used to monitor tissue oxygenation, a utility based on the wisdom gleaned over 50 years ago that cells deprived of adequate oxygen produce excessive quantities of lactate. The real-time monitoring of blood lactate concentration necessary in a critical care setting was only made possible by the development of electrode-based lactate biosensors around a decade ago. These biosensors are now incorporated into modern blood gas analyzers and other point-of-care analytical instruments, allowing lactate measurement by non-laboratory staff on a drop (100 L) of blood within a minute or two. Whilst blood lactate concentration is invariably raised in those with significant tissue hypoxia, it can also be raised in a number of conditions not associated with tissue hypoxia. Very often patients with raised blood lactate concentration (hyperlactatemia) also have a reduced blood pH (acidosis). The combination of hyperlactatemia and acidosis is called lactic acidosis. This is the most common cause of metabolic acidosis. The focus of this article is the causes and clinical significance of hyperlactatemia and lactic acidosis. The article begins with a brief overview of normal lactate metabolism. Normal lactate production and Continue reading >>

Metformin And Fatal Lactic Acidosis

Metformin And Fatal Lactic Acidosis

Publications Published: July 1998 Information on this subject has been updated. Read the most recent information. Dr P Pillans,former Medical Assessor, Centre for Adverse Reactions Monitoring (CARM), Dunedin Metformin is a useful anti-hyperglycaemic agent but significant mortality is associated with drug-induced lactic acidosis. Significant renal and hepatic disease, alcoholism and conditions associated with hypoxia (eg. cardiac and pulmonary disease, surgery) are contraindications to the use of metformin. Other risk factors for metformin-induced lactic acidosis are sepsis, dehydration, high dosages and increasing age. Metformin remains a major reported cause of drug-associated mortality in New Zealand. Of the 12 cases of lactic acidosis associated with metformin reported to CARM since 1977, 2 occurred in the last year and 8 cases had a fatal outcome. Metformin useful but small risk of potentially fatal lactic acidosis Metformin is a useful therapeutic agent for obese non-insulin dependent diabetics and those whose glycaemia cannot be controlled by sulphonylurea monotherapy. Lactic acidosis is an uncommon but potentially fatal adverse effect. The reported frequency of lactic acidosis is 0.06 per 1000 patient-years, mostly in patients with predisposing factors.1 Examples of metformin-induced lactic acidosis cases reported to CARM include: A 69-year-old man, with renal and cardiac disease, was prescribed metformin due to failing glycaemic control on glibenclamide monotherapy. He was well for six weeks, then developed lactic acidosis and died within 3 days. Post-surgical lactic acidosis caused the death of a 70-year-old man whose metformin was not withdrawn at the time of surgery. A 56-year-old woman, with no predisposing disease, died from lactic acidosis following major 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 >>

Lactic Acidosis And Exercise: What You Need To Know

Lactic Acidosis And Exercise: What You Need To Know

Muscle ache, burning, rapid breathing, nausea, stomach pain: If you've experienced the unpleasant feeling of lactic acidosis, you likely remember it. It's temporary. It happens when too much acid builds up in your bloodstream. The most common reason it happens is intense exercise. Symptoms The symptoms may include a burning feeling in your muscles, cramps, nausea, weakness, and feeling exhausted. It's your body's way to tell you to stop what you're doing The symptoms happen in the moment. The soreness you sometimes feel in your muscles a day or two after an intense workout isn't from lactic acidosis. It's your muscles recovering from the workout you gave them. Intense Exercise. When you exercise, your body uses oxygen to break down glucose for energy. During intense exercise, there may not be enough oxygen available to complete the process, so a substance called lactate is made. Your body can convert this lactate to energy without using oxygen. But this lactate or lactic acid can build up in your bloodstream faster than you can burn it off. The point when lactic acid starts to build up is called the "lactate threshold." Some medical conditions can also bring on lactic acidosis, including: Vitamin B deficiency Shock Some drugs, including metformin, a drug used to treat diabetes, and all nucleoside reverse transcriptase inhibitor (NRTI) drugs used to treat HIV/AIDS can cause lactic acidosis. If you are on any of these medications and have any symptoms of lactic acidosis, get medical help immediately. Preventing Lactic Acidosis Begin any exercise routine gradually. Pace yourself. Don't go from being a couch potato to trying to run a marathon in a week. Start with an aerobic exercise like running or fast walking. You can build up your pace and distance slowly. Increase the Continue reading >>

Lactic Acidosis

Lactic Acidosis

Background In basic terms, lactic acid is the normal endpoint of the anaerobic breakdown of glucose in the tissues. The lactate exits the cells and is transported to the liver, where it is oxidized back to pyruvate and ultimately converted to glucose via the Cori cycle. In the setting of decreased tissue oxygenation, lactic acid is produced as the anaerobic cycle is utilized for energy production. With a persistent oxygen debt and overwhelming of the body's buffering abilities (whether from chronic dysfunction or excessive production), lactic acidosis ensues. [1, 2] (See Etiology.) Lactic acid exists in 2 optical isomeric forms, L-lactate and D-lactate. L-lactate is the most commonly measured level, as it is the only form produced in human metabolism. Its excess represents increased anaerobic metabolism due to tissue hypoperfusion. (See Workup.) D-lactate is a byproduct of bacterial metabolism and may accumulate in patients with short-gut syndrome or in those with a history of gastric bypass or small-bowel resection. [3] By the turn of the 20th century, many physicians recognized that patients who are critically ill could exhibit metabolic acidosis unaccompanied by elevation of ketones or other measurable anions. In 1925, Clausen identified the accumulation of lactic acid in blood as a cause of acid-base disorder. Several decades later, Huckabee's seminal work firmly established that lactic acidosis frequently accompanies severe illnesses and that tissue hypoperfusion underlies the pathogenesis. In their classic 1976 monograph, Cohen and Woods classified the causes of lactic acidosis according to the presence or absence of adequate tissue oxygenation. (See Presentation and Differentials.) The causes of lactic acidosis are listed in the chart below. Go to Acute Lactic Ac Continue reading >>

Lactic Acidosis: Symptoms, Causes, And Treatment

Lactic Acidosis: Symptoms, Causes, And Treatment

Lactic acidosis occurs when the body produces too much lactic acid and cannot metabolize it quickly enough. The condition can be a medical emergency. The onset of lactic acidosis might be rapid and occur within minutes or hours, or gradual, happening over a period of days. The best way to treat lactic acidosis is to find out what has caused it. Untreated lactic acidosis can result in severe and life-threatening complications. In some instances, these can escalate rapidly. It is not necessarily a medical emergency when caused by over-exercising. The prognosis for lactic acidosis will depend on its underlying cause. A blood test is used to diagnose the condition. Lactic acidosis symptoms that may indicate a medical emergency include a rapid heart rate and disorientaiton. Typically, symptoms of lactic acidosis do not stand out as distinct on their own but can be indicative of a variety of health issues. However, some symptoms known to occur in lactic acidosis indicate a medical emergency. Lactic acidosis can occur in people whose kidneys are unable to get rid of excess acid. Even when not related to just a kidney condition, some people's bodies make too much lactic acid and are unable to balance it out. Diabetes increases the risk of developing lactic acidosis. Lactic acidosis may develop in people with type 1 and 2 diabetes mellitus , especially if their diabetes is not well controlled. There have been reports of lactic acidosis in people who take metformin, which is a standard non-insulin medication for treating type 2 diabetes mellitus. However, the incidence is low, with equal to or less than 10 cases per 100,000 patient-years of using the drug, according to a 2014 report in the journal Metabolism. The incidence of lactic acidosis is higher in people with diabetes who Continue reading >>

Lactic Acidosis

Lactic Acidosis

Patient professional reference Professional Reference articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use. You may find one of our health articles more useful. Description Lactic acidosis is a form of metabolic acidosis due to the inadequate clearance of lactic acid from the blood. Lactate is a byproduct of anaerobic respiration and is normally cleared from the blood by the liver, kidney and skeletal muscle. Lactic acidosis occurs when the body's buffering systems are overloaded and tends to cause a pH of ≤7.25 with plasma lactate ≥5 mmol/L. It is usually caused by a state of tissue hypoperfusion and/or hypoxia. This causes pyruvic acid to be preferentially converted to lactate during anaerobic respiration. Hyperlactataemia is defined as plasma lactate >2 mmol/L. Classification Cohen and Woods devised the following system in 1976 and it is still widely used:[1] Type A: lactic acidosis occurs with clinical evidence of tissue hypoperfusion or hypoxia. Type B: lactic acidosis occurs without clinical evidence of tissue hypoperfusion or hypoxia. It is further subdivided into: Type B1: due to underlying disease. Type B2: due to effects of drugs or toxins. Type B3: due to inborn or acquired errors of metabolism. Epidemiology The prevalence is very difficult to estimate, as it occurs in critically ill patients, who are not often suitable subjects for research. It is certainly a common occurrence in patients in high-dependency areas of hospitals.[2] The incidence of symptomatic hyperlactataemia appears to be rising as a consequence of the use of antiretroviral therapy to treat HIV infection. It appears to increase in those taking stavudine (d4T) regimens.[3] Causes of lactic acid Continue reading >>

Lactic Acidosis: Background, Etiology, Epidemiology

Lactic Acidosis: Background, Etiology, Epidemiology

Author: Kyle J Gunnerson, MD; Chief Editor: Michael R Pinsky, MD, CM, Dr(HC), FCCP, MCCM more... In basic terms, lactic acid is the normal endpoint of the anaerobic breakdown of glucose in the tissues. The lactate exits the cells and is transported to the liver, where it is oxidized back to pyruvate and ultimately converted to glucose via the Cori cycle. In the setting of decreased tissue oxygenation, lactic acid is produced as the anaerobic cycle is utilized for energy production. With a persistent oxygen debt and overwhelming of the body's buffering abilities (whether from chronic dysfunction or excessive production), lactic acidosis ensues. [ 1 , 2 ] (See Etiology.) Lactic acid exists in 2 optical isomeric forms, L-lactate and D-lactate. L-lactate is the most commonly measured level, as it is the only form produced in human metabolism. Its excess represents increased anaerobic metabolism due to tissue hypoperfusion. (See Workup.) D-lactate is a byproduct of bacterial metabolism and may accumulate in patients with short-gut syndrome or in those with a history of gastric bypass or small-bowel resection. [ 3 ] By the turn of the 20th century, many physicians recognized that patients who are critically ill could exhibit metabolic acidosis unaccompanied by elevation of ketones or other measurable anions. In 1925, Clausen identified the accumulation of lactic acid in blood as a cause of acid-base disorder. Several decades later, Huckabee's seminal work firmly established that lactic acidosis frequently accompanies severe illnesses and that tissue hypoperfusion underlies the pathogenesis. In their classic 1976 monograph, Cohen and Woods classified the causes of lactic acidosis according to the presence or absence of adequate tissue oxygenation. (See Presentationand Differe Continue reading >>

What Happens When Lactate Levels Are High?

What Happens When Lactate Levels Are High?

What Happens When Lactate Levels Are High? Joseph Pritchard graduated from Our Lady of Fatima Medical School with a medical degree. He has spent almost a decade studying humanity. Dr. Pritchard writes as a San Francisco biology expert for a prominent website and thoroughly enjoys sharing the knowledge he has accumulated. Elevated lactate levels can affect your heart rhythm. Lactic acid is a by-product of the process cells use to produce energy. As cells convert glucose to energy, they use oxygen. If there is not enough oxygen within the cell, the cell is still able to produce energy, but also produces lactic acid. The cells releases lactic acid into the blood, where it is converted to a similar molecule called lactate. High lactate levels within the blood can harm your cells, the University of New Mexico warns. There are certain conditions that cause a decrease in oxygen levels and thus lactic acidosis. Severe hypoxia, such as in patients in shock, congestive heart failure, liver disease and lung disease are all possible causes of elevated lactate levels, according to MedlinePlus, a service of the National Institutes of Health. These diseases force the body to make energy without having enough oxygen. Elevated lactate levels can lead to severe complications. Lactic acidosis is a disorder that occurs when lactate levels in your bloodstream rise above the normal limits. Symptoms of this condition include an abnormal heartbeat, difficulty breathing, nausea, vomiting, muscle weakness, inflammation of the pancreas, fatigue, weight loss and enlargement of the liver, AidsHealth.org explains. If you experience these symptoms, immediately consult your doctor, as lactic acidosis is a potentially life-threatening condition. Measuring lactate levels requires a blood test called a Continue reading >>

Lactic Acidosis

Lactic Acidosis

The buildup of lactic acid in the bloodstream. This medical emergency most commonly results from oxygen deprivation in the body’s tissues, impaired liver function, respiratory failure, or cardiovascular disease. It can also be caused by a class of oral diabetes drugs called biguanides, which includes metformin (brand name Glucophage). Another biguanide called phenformin was pulled from the market in the United States in 1977 because of an unacceptably high rate of lactic acidosis associated with its use. Concerns about lactic acidosis also delayed the introduction of metformin to the U.S. market until 1995, despite the fact that it had been widely used for years in other countries. There have been reports of lactic acidosis occurring in people taking metformin, and the U.S. Food and Drug Administration estimates that lactic acidosis occurs in 5 out of every 100,000 people who use metformin for any length of time. However, this risk is much lower than it was in people taking phenformin, and it is not clear whether the episodes of lactic acidosis associated with metformin have actually been due to metformin use. In fact, the lactic acidosis could have been explained by the person’s diabetes and related medical conditions. Nonetheless, diabetes experts recommend that metformin not be used in people with congestive heart failure, kidney disease, or liver disease. They also recommend that it be discontinued (at least temporarily) in people undergoing certain medical imaging tests called contrast studies. Symptoms of lactic acidosis include feeling very weak or tired or having unusual muscle pain or unusual stomach discomfort. Continue reading >>

Lactic Acidosis

Lactic Acidosis

Type B Lactic acidosis type B is associated with certain diseases (e.g., diabetes mellitus), some drugs—notably biguanides, certain toxins, and some inborn errors of metabolism (Table I). Tissue hypoxia and hypotension are not obvious features of type B lactic acidosis but may supervene as a consequence of the acidemia. The incidence of lactic acidosis among patients with diabetes has declined since the biguanide phenformin (phenylethybiguanide) was withdrawn in many countries during the 1970s. Lactic acidosis occurred approximately 10–15 times more frequently during phenformin therapy than with metformin. An inherited inability to hydroxylate phenformin may explain the higher risk of lactic acidosis than with metformin. Lactic acidosis complicating metformin (dimethylbiguanide) occurs much less commonly, with most cases being reported among patients in whom biguanide therapy is contraindicated (e.g., renal impairment or hypoxic states). LACTIC ACIDOSIS Lactic acidosis occurs whenever lactate production exceeds its utilization. This can occur with tissue hypoxia or in nonhypoxemic conditions when cellular metabolism is impaired. Type A lactic acidosis is the hypoxic form. It can occur with true hypoxemia, severe anemia, reduced oxygen delivery from poor perfusion, or from dramatically increased tissue demand from exercise, convulsions, or heat stroke.1,3,4,7 Type B lactic acidosis is the nonhypoxic form. It occurs in the face of adequate oxygen delivery when mitochondrial oxidative function is abnormal. This can occur with drugs or toxins, hypoglycemia, diabetes mellitus, liver failure, renal failure, lymphosarcoma, sepsis, and inborn errors of metabolism (Box 60-1).1,2,4 PROGNOSIS AND FUTURE PERSPECTIVES Primary lactic acidosis of the neonate usually ends in death Continue reading >>

Lactic Acidosis

Lactic Acidosis

Fast facts Lactic acidosis is a build-up of lactic acid in your blood. It can be the result of intense exercise, severe dehydration, an underlying medical condition, or as a reaction to some substances and medications. Symptoms of lactic acidosis can initially include weakness and nausea. More severe symptoms, such as chest pain, a fast heartbeat or breathing difficulties, require immediate medical attention. You can reduce your risk of lactic acidosis by not abusing alcohol and by properly managing diabetes if you have it. What is lactic acidosis? Lactic acidosis is a build-up of lactic acid in your blood. It makes the blood too acidic. Inside the cells of your body, there are structures called mitochondria. Their role is to supply energy to the cells. Mitochondria break down glucose for energy using oxygen, a process known as aerobic respiration. In situations when your body is starved for oxygen, or needs a lot of energy very quickly (such as during intense exercise), your mitochondria can switch to an alternative process known as anaerobic respiration. It is much less efficient, but it does not require oxygen and can, for a brief period, produce energy more quickly. Anaerobic respiration produces lactic acid (also known as lactate), making the blood more acidic. In most cases this is not a problem, because your liver and kidneys handle the excess lactic acid once your body starts to recover from oxygen starvation and returns to normal. However, when your body produces lactic acid faster than it can be removed, lactic acid builds up in your blood. Causes and risk factors Causes and risk factors of lactic acidosis include: Intense exercise; Low blood sugar, and; Some substances and medications - such as alcohol, cocaine, epinephrine, isoniazid, salicylates, and the di Continue reading >>

More in ketosis