**3. Causes for hyperlactatemia**

Hyperlactatemia is usually defined as more than >4 mmol/liter or 40 mg/dL, a result of conditions in which production exceeds utilization. Hyperlactatemia can be associated with acidosis, alkalosis and normal blood pH, and can also be found in conditions of normoxia, hypoxia and anoxia (Handy, 2006).

Since lactate is a byproduct of anaerobic metabolism, it becomes elevated in hypoperfusion states when pyruvate cannot enter the Krebs cycle due to insufficient oxygen supply and is converted to lactate. Lactate-producing tissues include the skin, erythrocytes, brain, skeletal muscles, leukocytes and the renal medulla. Lactate-consuming tissues include the liver, renal cortex and heart. Overproduction and under-consumption result in hyperlactatemia, which can be *physiologic* or *pathologic*. Specifically, increased lactate production can be physiologic as a result of postprandial rest, postabsorptive rest, sustained submaximal exercise or catecholamine-stimulated glycolysis (Mizock, 1989). The primary role of lactate overproduction is clear in certain disorders: for example, plasma lactate levels may transiently be as high as 15 mmol/L during a grand mal seizure, and 20-25 mmol/L during maximally intense exercise, with the systemic pH falling to as low as 6.80. Studies on these subjects have demonstrated rapid recovery of acid-base balance with a maximum rate of lactate utilization that can reach as high as 320 mmol/h.

Impairment of oxidative pathways during lactate production results in a net gain of H**<sup>+</sup>** whereupon acidosis occurs. The pathologic causes of hyperlactatemia were historically divided between those with evidence of one or another of the well-known causes of hypoxia; and those with no detectable disturbance in oxygen transport in the usual sense (Huckabee, 1961). As a result, hyperlactatemia may occur without (primary) or with (secondary) tissue hypoperfusion, a distinction proposed by Cohen and Woods in 1976 (as cited in Mizock, 1989). However, many critically ill patients can have hyperlactatemia as a result from both of those mechanisms (Phypers, 2006).
