Lactic acidosis

Lactic acidosis
Classification and external resources
Lactic acid
ICD-10	E87.2
ICD-9	276.2
DiseasesDB	29145
MedlinePlus	000391
eMedicine	article/768159
MeSH	D000140

Lactic acidosis is a condition caused by the buildup of lactic acid in the body. It leads to acidification of the blood (acidosis), and is considered a distinct form of metabolic acidosis.^[1] Tissue hypoxia and hypoperfusion force cells to breakdown glucose anaerobically. The result is lactic acid formation. Therefore elevated lactic acid with clinical signs and symptoms is indicative of tissue hypoxia, hypoperfusion and possible damage. Lactic acidosis is characterized by lactate levels >5 mmol/L and serum pH <7.35.^[2]

Pathophysiology

Many cells in the body normally burn glucose to form water and carbon dioxide. This is a two-step process. First, glucose is broken down into pyruvate by mean of glycolysis. Then the mitochondria, by means of the Krebs cycle, oxidize pyruvate into water and carbon dioxide, using oxygen. When there is a lack of oxygen in the blood, then the mitochondria cannot burn all the pyruvate produced by glycolysis, and pyruvate accumulates in the cell. This accumulation cannot be tolerated by the cell which converts pyruvate to lactate and evacuates it into the blood, hence causing lactic acidosis.

As a rare congenital disease, some children have a propensity for lactic acidosis because their mitochondria do not work properly. When their body needs more energy than usual, for example when they exercise or when they are diseased, they burn more glucose and produce more pyruvate. But because their mitochondria are slow, pyruvate cannot be converted to water and carbon dioxide fast enough. This causes pyruvate to accumulate. The cell transforms this excess into lactate which diffuses into the blood and causes lactic acidosis.

The signs of lactic acidosis are deep and rapid breathing, vomiting, and abdominal pain—symptoms that may easily be mistaken for other problems.

Lactic acidosis may be caused by diabetic ketoacidosis or liver or kidney disease, as well as some forms of medication (most notably the anti-diabetic drug phenformin). Some anti-HIV drugs (antiretrovirals) warn doctors in their prescribing information to regularly watch for symptoms of lactic acidosis caused by mitochondrial toxicity. Heavy metal toxicity, including poisoning with arsenic, can raise lactate levels and lead to generalized metabolic acidosis as well.

There is some doubt as to whether lactic acid truly produces 'acidosis', rather it is thought to be from ATP conversion to ADP.

Classification

The Cohen-Woods classification categorizes causes of lactic acidosis as follows:^[3]

• Type A: Decreased perfusion or oxygenation
• Type B:
  • B1: Underlying diseases (sometimes causing type A)
  • B2: Medication or intoxication
  • B3: Inborn error of metabolism

Causes

There several different causes of lactic acidosis.^[4]

These causes include:

• Genetic conditions
  • MELAS, or Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes
  • Glycogen storage disease
  • Fructose 1,6-diphosphatase deficiency
  • Pyruvate dehydrogenase deficiency

• Drugs
  • phenformin^[5]
  • metformin^[6]
  • isoniazid toxicity
  • nucleoside reverse transcriptase inhibitors
  • potassium cyanide (Cyanide poisoning)

• Other
  • Hypoxia and hypoperfusion
  • Hemorrhage
  • Ethanol toxicity
  • Sepsis
  • Shock
  • Hepatic disease
  • Diabetic ketoacidosis
  • Muscular exercise
  • Regional hypoperfusion (bowel ischemia, marked cellulitis...)
  • Non-Hodgkin's and Burkitt lymphoma

Associated conditions

Lactic acidosis is an underlying process of rigor mortis. Tissue in the muscles of the deceased resort to anaerobic metabolism in the absence of oxygen and significant amounts of lactic acid are released into the muscle tissue. This along with the loss of ATP causes the muscles to grow stiff.^{[citation needed]}

Lactic acidosis may also result from Vitamin B1 (thiamine) deficiency.

In Animals

Reptiles, which rely primarily on anaerobic power for intense movements, can be particularly susceptible to lactic acidosis. In particular, during the capture of large crocodiles, the animals frequently build up enough blood lactate to significantly alter the blood's pH, often rendering them unable to respond to stimuli or move.^[7] There are recorded cases in which particularly large crocodiles who put up extreme resistance to capture later died of the resulting pH imbalance.^[8]

See also

• Metabolic acidosis

References