Acidosis lactic

As discussed earlier, some tissues produce lactate as an end product of metabolism. The lactate produced is L-lactate and is commonly referred to simply as lactate. As we will see in the following discussion, D-lactate is also produced under certain pathological conditions, which presents a unique clinical problem. 

Under normal conditions, lactate is metabolized in the liver and the blood lactate level is between 1 and 2 mM. Lactate accumulation in body fluids can be due to increased production and/or decreased utilization. Blood lactate-to-pyruvate ratio below 25 suggests defects in a gluconeogenic enzyme (Chapter 15) or pyruvate dehydrogenase (discussed later). A common cause of lactic acidosis is tissue hypoxia caused by shock, cardiopulmonary arrest, and hypoperfusion. Inadequate blood flow leads to deprivation of oxygen and other nutrients to the tissue cells as well as to the removal of waste products. Oxygen deprivation leads to decreased ATP production and accumulation of NADH, which promotes conversion of pyruvate to lactate. 

A major cause of acidosis that occurs during inadequate cellular oxygen delivery is continual hydrolysis of the available supply of ATP that releases protons  

Laboratory assessment includes measurements of blood lactate, pyruvate, j8-hydroxybutyrate, and acetoacetate (Chapter 39). The primary treatment of lactic acidosis involves correcting the underlying cause such as reversal of circulatory failure. 

This unusual form of lactic acidosis is due to increased production and accumulation of D-lactate in circulation. The normal isomer synthesized in the human body is L-lactate but the D-lactate isomer can occur in patients with jejunoileal bypass, small bowel resection, or other types of short bowel syndrome. In these patients, ingested starch and glucose bypass the normal metabolism in the small intestine and lead to increased delivery of nutrients to the colon where gram-positive, anaerobic bacteria (e.g., Lactobacilli) ferment glucose to D-lactate. The D-lactate is absorbed via the portal circulation. 

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Metformin Renal or liver disease any predisposition to hypoxia Gastro intestinal upsets risk of lactic acidosis if wrongly prescribed Creatinine, Hb or Vit B12b... 

A class of drug derived from guanidine, including metformin and phenformin. Metformin is currently widely used in humans for the treatment of type 2 diabetes. Phenformin was formerly also widely used but was withdrawn because of problems with lactic acidosis. 

Under certain circumstances, and very rarely, the inhibition of gluconeogenesis by metformin may suppress lactic acid metabolism and precipitate a potentially fatal lactic acidosis. Impairment of renal function, liver disease, alcoholism, conditions that give rise to increased lactate production (e.g. congestive heart failure, infections) are therefore contraindications for the application of metformin. 

Lactic acidosis (buildup of lactic acid in the blood) may also occur with die administration of metformin. Although lactic acidosis is a rare adverse reaction, its occurrence is serious and can be fatal. Lactic acidosis occurs mainly in patients with kidney dysfunction. Symptoms of lactic acidosis include malaise (vague feeling of bodily discomfort), abdominal pain, rapid respirations, shortness of breath, and muscular pain. In some patients vitamin B12 levels are decreased. This can be reversed with vitamin B12 supplements or with discontinuation of the drug therapy. Because... 

There is a risk of acute renal failure when iodi-nated contrast material that is used for radiological studies is administered with metformin. Metformin therapy is stopped for 48 hours before and after radiological studies using iodinated material. Alcohol, amiloride, digoxin, morphine, procainamide, quini-dine, quinine ranitidine, triamterene, trimethoprim, vancomycin, cimetidine, and furosemide all increase the risk of hypoglycemia. There is an increased risk of lactic acidosis when metformin is administered with the glucocorticoids. 

MANAGING LACTIC ACIDOSIS. When taking metformin, the patient is at risk for lactic acidosis. The nurse monitors die patient for symptoms of lactic acidosis, which include unexplained hyperventilation, myalgia, malaise, gastrointestinal symptoms, or unusual somnolence If the patient experiences these symptoms, the nurse should contact the primary care provider at once. Elevated blood lactate levels of greater than 5 mmol/L are associated with lactic acidosis and should be reported immediately. Once a patient s diabetes is stabilized on metformin therapy, the adverse GI reactions that often occur at the beginning of such therapy are unlikely to be related to the drug therapy. A later occurrence of GI symptoms is more likely to be related to lactic acidosis or other serious disease. 

Metformin—there is a risk of lactic acidosis when using this drug. Discontinue die drug therapy and notify the health care provider immediately if any of the following should occur respiratory distress, muscular aches, unusual somnolence, unexplained malaise, or nonspecific abdominal distress. 

Patients with complex I deficiency may also present with severe congenital lactic acidosis, hypotonia, weakness, cardiomyopathy, and cardiorespiratory failure caus-... 

This complex contains 11 polypeptide subunits of which only one is encoded by mtDNA. Defects of complex III are relatively uncommon and clinical presentations vary. Fatal infantile encephalomyopathies have been described in which severe neonatal lactic acidosis and hypotonia are present along with generalized amino aciduria, a Fanconi syndrome of renal insufficiency and eventual coma and death. Muscle biopsy findings may be uninformative since abnormal mitochondrial distribution is not seen, i.e., there are no ragged-red fibers. Other patients present with pure myopathy in later life and the existence of tissue-specific subunits in complex III has been suggested since one of these patients was shown to have normal complex 111 activity in lymphocytes and fibroblasts. 

Before an antiviral agent becomes a drug, advanced toxicity testing, pharmacological combination, and drug-interaction studies are needed. The use of new cell-based assays that can predict mitochondrial toxicity, lactic acidosis, peripheral neuropathy, anemia, hypersensitivity, lipodystrophy, and other potential side effects can alleviate these issues (Stuyver et al. 2002). 

The condition known as fatal infantile mitochondrial myopathy and renal dysfunction involves severe diminution or absence of most oxidoreductases of the respiratory chain. MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke) is an inherited condition due to NADHiubiquinone oxidoreductase (complex I) or cytochrome oxidase deficiency. It is caused by a muta-... 

Inhibition of Pyruvate Metabolism Leads to Lactic Acidosis... 

Gonditions that involve an inability to metabofize pyruvate frequently lead to lactic acidosis. 

Antiretroviral toxic neuropathy Any stage Subacute rarely acute with lactic acidosis Distal sensory loss and neuropathic pain Toxic neuropathy mitochondrial damage... 

NRTls are structural analogues of the natural nucleotides that form the building blocks of RNA and DNA in human cells. Their use as part of HAART has dramatically modified the natural history of HIV infection. They, however, cause a range of drag- or tissue-specific toxicides zidovudine (AZT) causes myopathy zalcitabine (ddC), didanosine (ddl), and lamivudine (3TC) cause neuropathy stavudine (d4T) causes neuropathy or myopathy and lactic acidosis (Dalakas 2001). During phase 1 and 11 trials, the dose-limiting toxicity of didanosine, zalcitabine, and stavudine was identified as peripheral neuropathy (Dalakas 2001). 

Convincing data in lactic acidosis is lacking D Manage underlying etiology... 

Lactic acidosis, which typically accompanies hypovolemic shock as a consequence of tissue hypoxia, is best treated by reversal of the underlying cause. Administration of alkalizing agents such as sodium bicarbonate has not been demonstrated to have any... 

Adverse effects are minimal and include fatigue, diarrhea, nausea, vomiting, and headaches. In rare cases, pancreatitis, hepatomegaly, and potentially fatal lactic acidosis have been reported. ALT levels should be monitored carefully, especially when lamivudine has been discontinued, as an elevation may indicate a flare in disease activity that may lead to liver failure. 

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