Abstract

Of the two types of lactic acidosis, Type B is the most difficult to explain in terms of mechanisms of lactic acid accumulation because the tissue hypoxia that accompanies Type A is not present except as a terminal event. The methods of pharmacokinetics show that for lactate to accumulate to an extent that would disturb acid-base balance, either lactate synthesis or lactate removal would have to be increased or decreased, respectively, by about 7-10-fold. To produce lactic acidosis within a few hours, synthesis would have to increase at the same time as clearance decreased. At normal contribution of the liver to the total lactate clearance (30%-40%), a total cessation of hepatic lactate clearance would not result in lactic acidosis without a concomitant rise in the rate of lactate synthesis. Again, to produce an acidosis this increase would have to be about 8-fold at a normal fractional hepatic clearance. The control of hepatic lactate uptake is discussed in the light of the relatively low hepatic extraction of lactate and in relation to to two main models of hepatic drug (lactate) clearance; the 'well-stirred' and 'parallel-tube' models.