Pathophysiology
Most cells in the body normally metabolize glucose to form water and carbon dioxide in a two-step process. First, glucose is broken down to pyruvate through glycolysis. Then, mitochondria oxidize the pyruvate into water and carbon dioxide by means of the Krebs cycle and oxidative phosphorylation. This second step requires oxygen. The net result is ATP, the energy carrier used by the cell to drive useful work, such as muscle contraction. When the energy in ATP is used during cell work (ATP hydrolysis), protons are produced. The mitochondria normally incorporate these protons back into ATP, thus preventing buildup of protons and maintaining neutral pH.
If oxygen supply is inadequate (hypoxia), the mitochondria are unable to continue ATP synthesis at a rate sufficient to supply the cell with the required ATP. In this situation, glycolysis is increased to provide additional ATP, and the excess pyruvate produced is converted into lactate and released from the cell into the bloodstream, where it accumulates over time. While increased glycolysis helps compensate for less ATP from oxidative phosphorylation, it cannot bind the protons resulting from ATP hydrolysis. Therefore, proton concentration rises and causes acidosis.
The excess protons in lactic acidosis are widely believed to actually derive from production of lactic acid. This is incorrect, as cells do not produce lactic acid; pyruvate is converted directly into lactate, the anionic form of lactic acid. When excess intracellular lactate is released into the blood, maintenance of electroneutrality requires a cation (e.g. a proton) to be released, as well. This can reduce blood pH. Glycolysis coupled with lactate production is neutral in the sense that it does not produce excess protons. However, pyruvate production does produce protons. Lactate production is buffered intracellularly, e.g. the lactate-producing enzyme lactate dehydrogenase binds one proton per pyruvate molecule converted. When such buffer systems become saturated, cells will transport lactate into the bloodstream. Hypoxia certainly causes both buildup of lactate and acidification, and lactate is therefore a good "marker" of hypoxia, but lactate itself is not the cause of low pH.
Lactic acidosis sometimes occurs without hypoxia, for example, in rare congenital disorders where mitochondria do not function at full capacity. In such cases, when the body needs more energy than usual, for example during exercise or disease, mitochondria cannot match the cells' demand for ATP, and lactic acidosis results. Also, muscle types that have few mitochondria and preferentially use glycolysis for ATP production (fast-twitch or type II fibers) are naturally prone to lactic acidosis.
The signs of lactic acidosis are deep and rapid breathing, vomiting, and abdominal pain—symptoms that may easily be mistaken for other problems.
Lactic acidosis may be caused by diabetic ketoacidosis or liver or kidney disease, as well as some forms of medication (notably the antidiabetic drugs }. Metformin is, however, unlikely to cause lactic acidosis although the belief remains in clinical practice.
Read more about this topic: Lactic Acidosis