Approximately 1500 mmol of lactate are produced daily by various organs in the body. Lactate is the end product of anaerobic glycolysis. Serum lactate levels reflect the balance between production and elimination of lactate. The liver and kidneys are responsible for metabolizing and eliminating lactate (Moyle, 2002); about 70% to 90% of the body’s lactate is metabolized by the liver, and 10% to 20% is eliminated by the kidneys.

The Cori cycle is the process by which lactic acid or lactate is recycled during anaerobic metabolism. When the energy needs of the body are greater than the oxygen supply, muscle cells and red blood cells produce adenosine triphosphate (ATP) through lactic acid fermentation. During anaerobic glycolysis, pyruvic acid is converted through gluconeogenesis into lactate, which is then converted into glucose for energy (Sharma, 2006). Some lactate is metabolized into CO₂ and water through the citric acid cycle and ultimately eliminated from the body. In normal circumstances, the Cori cycle allows the body to focus on the production of ATP while the liver handles lactate, thereby preventing lactic acidosis through the removal of lactate in the blood. Lactate is produced from pyruvic acid through a chemical reaction with the enzyme lactate dehydrogenase (LDH).

Type A lactic acidosis occurs when the production of anaerobic lactic acid results in hypoxemia, or poor tissue perfusion. This deficit in oxygenation leads to difficulty generating ATP in the absence of oxygen (Moyle, 2002). Lactic acidosis induced by hypoxia is far more common than type B lactic acidosis. Etiologies of type A lactic acidosis include hypovolemic shock, sepsis, congestive heart failure, carbon monoxide poisoning, pheochromocytoma, and catecholamines (Sharma, 2006; Pignanelli & Budzinski-Braunscheidel, 1998). These etiologies can be subdivided into three primary causes: low PO₂ (pulmonary), poor delivery of oxygen (circulatory), or decreased oxygen-carrying capacity (as seen with hemoglobin disorders) (Luft, 2001).

Type B lactic acidosis occurs without hypoxia. It is considered to be the result of impaired lactate metabolism secondary to drugs, toxins, and/or disease processes. Type B lactic acidosis is characterized by a pH less than 7.35 and an arterial serum lactate level greater than 5 mEq/L (5 mmol/L in SI units) (Sharma, 2006). Arterial blood gas values in patients with type B lactic acidosis typically reflect a metabolic acidosis. The hallmark signs and symptoms of this rare oncologic emergency are changes in mental status and hyperventilation (Table 33-2).

Several theories have attempted to explain the etiology of type B lactic acidosis secondary to malignancy. Some propose that in patients with a large tumor burden, anaerobic glycolysis occurs as a result of decreased oxygenation in lactate-producing areas. Intrinsically, tumor cells have a higher rate of glycolysis than normal cells (DeKeulenaer et al., 2003). According to another theory, local tissue hypoxia and anaerobic metabolism occur as a result of microvascular aggregation of leukocytes and leukostasis, which result in the production of lactate. A third theory is that in patients with liver metastasis, lactate accumulates because the liver is unable to eliminate it. Finally, still others theorize that cancer cells themselves can produce lactate.