Lactic acidosis ethanol

Schwab RA, Bachhuber BH. Delirium and lactic acidosis caused by ethanol and niacin coingestion. Am J Emerg Med 1991 9(4) 363-5. 

Infusions of fructose or sorbitol can cause lactic acidosis (425,426), particularly in combination with ethanol. 

Batstone GF, Alberti KG, Dewar AK. Reversible lactic acidosis associated with repeated intravenous infusions of sorbitol and ethanol. Postgrad Med J 1977 53(623) 567-9. 

Note that ethanol consumption leads to an accumulation ofNADH. This high concentration of NADH inhibits gluconeogenesis by preventing the oxidation of lactate to pyruvate. In fact, the high concentration ofNADH will cause the reverse reaction to predominate, and lactate will accumulate. The consequences may be hypoglycemia and lactic acidosis. 

Methanol is widely available as a solvent and in paints and antifreezes, and may be consumed as a cheap substitute for ethanol. As little as 10 ml may cause permanent blindness and 30 ml may kill, through its toxic metabolites. Methanol, like ethanol, is metabolised by zero-order processes that involve the hepatic alcohol and aldehyde dehydrogenases, but whereas ethanol forms acetaldehyde and acetic acid which are partly responsible for the unpleasant effects of hangover, methanol forms formaldehyde and formic acid. Blindness may occur because aldehyde dehydrogenase present in the retina (for the interconversion of retinol and retinene) allows the local formation of formaldehyde. Acidosis is due to the formic acid, which itself enhances pH-dependent hepatic lactate production, so that lactic acidosis is added. 

Phenformin is the only biguanide to have been marketed in the United States and removed from the market by the US Food and Drug Administration (FDA) in 1977 because of its association with the development of lactic acidosis, a metabolic aberration that results in mortality in 50-75% of cases. Ethanol intake before the administration of phenformin therapeutic doses or excessive dose appears to predispose the patient to the development of lactic acidosis with a serious outcome. Phenformin and its other relative biguanides are still sold in European and other countries worldwide. 

Lactic acidosis occurs in two clinical settings (1) type A (hypoxic), associated with decreased tissue oxygenation, such as shock, hypovolemia, and left ventricular failure and (2) type B (metabolic), associated with disease (e.g., diabetes melUtus, neoplasia, liver disease), drugs and/or toxins (e.g., ethanol, methanol, and salicylates), or inborn errors of metabolism (e.g., methylmalonic aciduria, propionic acidemia, and fatty acid oxidation defects). Lactic acidosis is not uncommon and occurs in approximately 1% of hospital admissions. It has a mortality rate greater than 60%, which approaches 100% if hypotension is also present. Type A is much more common. 

Lactic acidosis is also caused by (1) drugs and toxins, such as ethanol, methanol, biguanides, isoniazid (see previous discussion), and streptozotocin (2) acquired and hereditary defects in enzymes involved in gluconeogenesis (3) disorders such as severe acidosis, uremia, liver failure, tumors, and seizures (4) anesthesia and (5) abnormal intestinal bacteria producing n-lactate (described in Chapter 25). 

Alcohol taken in excess tends to prevent gluconeogenesis from lactate in the liver, because oxidation of ethanol to acetaldehyde competes for the NAD" that is necessary for the conversion of lactate to pyruvate. Severe acidosis, such as diabetic ketoacidosis, may suppress lactate conversion and cause a shift in the lactate-pyruvate equilibrium with the accumulation of H. This shift may, in part, be responsible for the lactic acidosis seen in diabetics. 

However, ethanol ingestion also has acute effects on liver metabolism, including inhibition of fatty acid oxidation and stimulation of triacylglycerol synthesis, leading to a fatty liver. It also can result in ketoacidosis or lactic acidosis and cause hypoglycemia or hyperglycemia, depending on the dietary state. These effects are considered reversible. 

Taboulet P, Clemessy J-L, Freminet A, Baud FJ. A case of life-threatening lactic acidosis after smoke inhalation - interference between B-adrenergic agents and ethanol Intensive Care Med (1995)21,1039-42. 

The oxidation of ethanol results in an unregulated overproduction of NADH, which has several consequences. A rise in the blood levels of lactic acid and ketone bodies causes a fall in blood pH, or acidosis. The liver is damaged because the excess NADH causes excessive fat formation as well as the generation of acetaldehyde, a reactive molecule. Severe liver damage can result. 

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