Liver lactic acidosis

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

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. 

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. 

This isotonic volume expander contains sodium, potassium, chloride, and lactate that approximates the fluid and electrolyte composition of the blood. Ringer s lactate (also known as lactated Ringer s or LR) provides ECF replacement and is most often used in the perioperative setting, and for patients with lower GI fluid losses, burns, or dehydration. The lactate component of LR works as a buffer to increase the pH. Large volumes of LR may cause metabolic alkalosis. Because patients with significant liver disease are unable to metabolize lactate sufficiently, Ringer s lactate administration in this population may lead to accumulation of lactate with iatrogenic lactic acidosis. The lactate is not metabolized to bicarbonate in the presence of liver disease and lactic acid can result. 

Biguanides such as metformin are thought to inhibit mitochondrial oxidation of lactic acid, thereby increasing the chance of lactic acidosis occurring. Fortunately, the incidence of lactic acidosis in clinical practice is rare. Patients at greatest risk for developing lactic acidosis include those with liver disease or heavy alcohol use, severe infection, heart failure, and shock. Thus, it is common practice to evaluate liver function prior to initiation of metformin. 

Defects of complex IV. These disorders, also termed COX deficiency, have clinical phenotypes that fall into two main groups one in which myopathy is the predominant or exclusive manifestation and another in which brain dysfunction predominates (Fig. 42-3). In the first group, the most common disorder is fatal infantile myopathy, causing generalized weakness, respiratory insufficiency and death before age 1 year. There is lactic acidosis and renal dysfunction, with glycosuria, phosphaturia and aminoaciduria, also termed DeToni-Fanconi-Debre syndrome. The association of myopathy and cardiopathy in the same patient and myopathy and liver disease in the same family has also been described [14]. 

Mutations in one nuclear gene (ATP12), encoding an ATPase assembly protein, have been associated with complex V deficiency in an infant with congenital lactic acidosis and a rapidly fatal disorder affecting brain, liver, heart, and muscle [19]. 

Benign Not evident while sole nutrition is breast milk Severe hypoglycemia and lactic acidosis after fructose ingestion Vomiting, apathy, diarrhea Liver damage and jaundice Proximal renal tubule disorder resembling Fanconi syndrome Treatment eliminate sources of fructose from diet... 

This is, quantitatively, extremely important. One condition in which the liver fails to take up protons and lactate is when a considerable amount of blood has been lost (e.g. during or after an accident). To compensate for this, blood flow to the splanchnic area, including the liver, is severely reduced so that the liver becomes hypoxic, and not enough ATP can be generated to maintain gluconeogenesis. Consequently, lactate and protons accumulate in the blood and the pH falls a condition known as lactic acidosis. It is important, therefore, to maintain blood volume after an accident, which is usually done by infusion of fluid. 

A well-established inhibitor of gluconeogenesis is ethyl alcohol. This can cause problems in at least two situations. When alcoholic patients enter an alcoholic binge , they do not eat, so that liver glycogen is soon depleted. Since gluconeogenesis is inhibited, both hypoglycaemia and, as indicated below, lactic acidosis can develop. Indeed they may be the two most important factors that precipitate coma and collapse in the alcoholic patient. 

Lactic acidosis/severe hepatomegaly with steatosis Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs alone or in combination with other antiretrovirals. Exercise particular caution when administering nucleoside analogs to any patient with known risk factors for liver disease. 

T Pancreatic insulin release Metformin Peripheral insulin sensitivity hepatic glucose output/production i intestinal glucose absorption Dose Ist-line (naive pts), 1.25/250 mg PO daily-bid 2nd-line, 2.5/500 mg or 5/500 mg bid (max 20/2000 mg) take w/ meals, slowly T dose hold before 48 h after ionic contrast media Caution [C, -] Contra SCr >1.4 mg/dL in females or >1.5 mg/dL in males hypoxemic conditions (sepsis, recent MI) alcoholism metabolic acidosis liver Dz Disp Tabs SE HA, hypoglycemia, lactic acidosis, anorexia, N/V, rash Additional Interactions T Effects W/ amiloride, ciprofloxacin cimetidine, digoxin, miconazole, morphine, nifedipine, procainamide, quinidine, quinine, ranitidine, triamterene,... 

Chariot, P. et al. (1999) Zidovudine-induced mitochondrial disorder with massive liver steatosis, myopathy, lactic acidosis, and mitochondrial DNA depletion. Journal of Hepatology, 30 (1), 156-160. 

Adverse gastrointestinal symptoms (nausea, vomiting, anorexia, metallic taste, abdominal discomfort, and diarrhea) occur in up to 20% of individuals taking metformin this can be minimized by starting at a low dose and slowly titrating the dose upward with food. Like phenformin, metformin can cause lactic acidosis, but its occurrence is rare except when renal failure, hypoxemia, or severe congestive heart failure is present or when coadministered with alcohol. Metformin is also contraindicated in persons with hepatic dysfunction, but it appears to be safe for use in the hepatic steatosis that often occurs with fatty infiltration of the liver in poorly controlled type II diabetics. 

L A. Metformin causes lactic acidosis in patients with renal failure and severe congestive heart failure. It does not increase the risk of ketoacidosis and showed a reduction in cardiovascular comorbidities in a large study. It is contraindicated in patients with severe liver disease but does not cause hepatic necrosis. When used as monotherapy, metformin rarely causes hypoglycemia. 

Accumulation of metformin can occur in patients with renal insufficiency, and interference with pyruvate metabolism can lead to severe lactic acidosis. Lactic acidosis is more likely in situations associated with anaerobic metabolism, and metformin should not be given to patients with renal disease, liver disease, or severe pulmonary or cardiac disease predisposing to hypoxia. It is recommended to switch patients taking metformin to another oral hypoglycaemic prior to cardiac or other major surgery. 

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