This is a page discussing the fundamental science behind the production of lactate, as an introduction to the various types of lactic acidosis.
It is a tribute to Dr Kerry Brandis, whose online resource remains a definitive source for the acid-base enthusiast. Other than his works, I have referenced Chapter 15 of Ohs Manual, by Alistair Nichol and D J Cooper.
The Cori cycle
This brief digression into the Cori cycle (named after Carl and Gerty Cori) is to remind us that the body is a constant source of massive amounts of lactate. There is a daily production of roughly 0.8 mmol per kg per hour of lactate each day, about 1500 mmol per day. almost none of which is ever found in one’s bloodstream because of the massive hepatic capacity to complete the metabolic conversion of lactate to glucose.
Lactate dehydrogenase is the chief enzyme responsible for the conversion of lactate to pyruvate, and pyruvate to lactate. The reaction is very rapid and much of the time it is convenient to view this as an equilibrium.
Intracellularly, the ratio of lactate to pyruvate is maintained at 10 : 1. There is way more lactate than pyruvate.
The lactate has a pKa of 4.0, and so at a physiological pH it is fully dissociated into the lactate conjugate base and a H+ ion. Thus, for every 1 mmol of lactate in the extracellular fluid, one may expect the bicarbonate to decrease by 1 mmol.
There are many origins of lactate. The tissues all seem to share the responsibility for its production while the patient is at rest. Kerry Brandis and Life in the Fast Lane give the following table, as a breakdown of tissues and their relative contribution to the total body lactate production.
- skin - 25%
- red cells - 20%
- brain - 20%
- muscle - 25%; at rest muscle seems to metabolise glucose at 22mg per kg per hr, or 1.2mmol/kg/hr, of which about 50% is returned to the blood as lactate.
- gut - 10%
Lactate is produced from pyruvate, and pyruvate is produced by glycolysis (85% of it).
The rate of glycolysis depends on intracellular pH.
Acidosis decreases glycolysis and alkalosis increases it. Thus, in the state of intracellular alkalosis, more pyruvate is produced, which in an oxygen poor environment will be metabolized into lactate instead of being oxidized in the Krebs cycle. This has been demonstrated in studies of the effect of bicarbonate therapy on hypoxic lactic acidosis (turns out, the lactate increases)
Additional notes on the metabolism of lactate and the other "bicarbonate precursors" can be seen here.