B AB8


. LACTIC ACIDOSIS

Lactic acidosis is a common cause of metabolic acidosis.



1,2,3 8.1.1 DAILY PRODUCTION OF LACTATE Each day the body has an excess production the blood stream and is subsequently metabolised mostly in the liver. This internal cycling with production by the tissues and transport to and metabolism by the liver and kidney is known as the Cori cycle. This normal process does not represent any net fixed acid production which requires excretion from the body. All tissues can produce lactate under anaerobic conditions but tissues with active glycolysis produce excess lactate from glucose under normal conditions and this lactate tends to spill over into the blood.


Lactate is produced from pyruvate in a reaction catalysed by lactate dehydrogenase:

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. MECHANISMS INVOLVED IN LACTIC ACIDOSIS



Lactic acidosis can occur due to: * excessive tissue lactate production * impaired hepatic metabolism of lactate In most clinical cases it is probable that both processes are contributing to the development of the acidosis. The liver has a large capacity to metabolise lactate so increased peripheral production alone is unlikely to lead to other than transient acidosis. The situation is analogous to a respiratory acidosis where increased CO2 production alone is rarely responsible because of the efficient respiratory acidosis. In situations where lactic acidosis is clearly due to excessive hour once the precipitating disorder is no longer present. In severe exercise, lactate levels can rise to very high levels eg up to 30 mmol/l.


Respiratory compensation for the acidosis may not be significant because of the short time involved. However, there are other causes of hyperventilation present and arterial pCO2 is typically reduced providing partial compensation. For example, exercise results in markedly increased ventilation and the cause of this is largely unknown. The arterial pCO2 usually falls with exercise and this is not considered to be due to the lactic acidosis as it occurs even in less severe exercise where there is little excess lactate produced. A continuing lactic acidosis means that there is continuing production a normal liver at one extreme, or to increased production in due to cirrhosis, sepsis, hypoperfusion due hypovolaemia or the other extreme.

PYRUVATE + NADH + H+ LACTATE + NAD+



This reaction is so rapid that pyruvate and lactate can be considered to be always in an equilibrium situation.







Normally the ratio of the Law of Mass Action determines the balance between lactate and pyruvate.


This ratio is also used to denote the redox state within the cytoplasm. Lactic acid has a pK value of about 4 so it is fully dissociated into lactate and H+ at body pH. In the extracellular fluid, the H+ titrates bicarbonate on a one for one basis.

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