Lactate accumulation in hepatic or renal failure

It requires no enormous effort of the intellect to expect a substance to build up in the body fluids when you have disabled that organ which is responsible for its clearance. So with lactate, the loss of enough liver cells will give rise to a lactic acidosis. To a lesser extent, renal failure will diminish the kidney's meager contribution to the task of lactate clearance.

Normal clearance of lactate

Normally, the rate of hepatic clearance increases linearly with increasing lactate levels; it can increase seven-fold in the context of strenuous exercise, for example. It takes a lot to saturate these mechanisms; however obviously there must be a limit. Consider that if these were perfectly responsive, there would never be any lactic acidosis in a person with a normal liver. Severe lactic acidosis without hepatic dysfunction is actually a rather frequent occurrence, which means that in these situations hepatic and renal clearance mechanisms (though working at a greatly increased capacity) are not coping with the increased rate of lactate production.

Impairment of hepatic blood flow and oxygenation

Authoritative sources report that the liver received 25% of  cardiac output. Of that blood, 75% is supplied by the portal vein.

The portal vein also supplies a large portion of the hepatic oxygen demands, 50-60%. If hepatic blood flow is decreased to 25% of the normal, the rate of lactate clearance begins to suffer- predominantly because the lactate is not being delivered to the periportal hepatocytes.

Then, if you also decrease hepatic oxygenation, the liver is forced to survive on anaerobic glycolysis. This creates the unusual problem where it becomes a major source of lactate, rather than the method of its clearance.

Impairment of renal function

Yes, this is a page about lactic acidosis as a result of hepatic insufficiency, but the kidneys merit a mention. There is a “lactate threshold” for proximal tubular resorption of lactate. One must remember that lactate is normally a useful participant in the Cori cycle. If it were allowed to constantly leak out via the nephron, it would result in a constant loss of fuel, and so (like glucose) at normal concentrations the proximal tubule is very efficient at retrieving it from the tubular lumen.

At concentrations above 5-6mmol/L, the kidney begins to leak lactate into the urine, and so only in situations of severe lactic acidosis does this clearance mechanism begin to play a significant role.

However, under normal conditions the  kidney is also responsible for some proportion of lactate clearance by metabolism (back into glucose) – approximately 15% of it, if dog kidneys are anything to go by. The renal cortex is responsible for this; the medulla on the other hand is a lactate-producing organ which relies on the Cori cycle.