Lactic acidosis

Lactic acidosis is a medical condition characterized by the buildup of lactate (especially L-lactate) in the body, with formation of an excessively low pH in the bloodstream. It is a form of metabolic acidosis, in which excessive acid accumulates due to a problem with the body's oxidative metabolism. Lactic acidosis is a medical condition characterized by the buildup of lactate (especially L-lactate) in the body, with formation of an excessively low pH in the bloodstream. It is a form of metabolic acidosis, in which excessive acid accumulates due to a problem with the body's oxidative metabolism. Lactic acidosis is typically the result of an underlying acute or chronic medical condition, medication, or poisoning. The symptoms are generally attributable to these underlying causes, but may include nausea, vomiting, Kussmaul breathing (laboured and deep), and generalised weakness. The diagnosis is made on biochemical analysis of blood (often initially on arterial blood gas samples), and once confirmed, generally prompts an investigation to establish the underlying cause to treat the acidosis. In some situations, hemofiltration (purification of the blood) is temporarily required. In rare chronic forms of lactic acidosis caused by mitochondrial disease, a specific diet or dichloroacetate may be used. The prognosis of lactic acidosis depends largely on the underlying cause; in some situations (such as severe infections), it indicates an increased risk of death. The Cohen-Woods classification categorizes causes of lactic acidosis as: Lactic acidosis is commonly found in people who are unwell, such as those with severe heart and/or lung disease, a severe infection with sepsis, the systemic inflammatory response syndrome due to another cause, severe physical trauma, or severe depletion of body fluids. Symptoms in humans include all those of typical metabolic acidosis (nausea, vomiting, generalized muscle weakness, and laboured and deep breathing). The several different causes of lactic acidosis include: 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 for metabolic activities and to perform work, such as muscle contraction. When the energy in ATP is used during cell work via ATP hydrolysis, hydrogen ions, (positively charged protons) are released. The mitochondria normally incorporate these free hydrogen nuclei back into ATP, thus preventing buildup of unbound hydrogen cations, and maintaining neutral pH. If oxygen supply is inadequate (hypoxia), the mitochondria are unable to continue creating ATP at a rate sufficient to meet the cell's energy needs. 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 hydrogen cations that result from ATP hydrolysis. Therefore, hydrogen cation concentration rises and causes acidosis. The excess hydrogen cations produced during 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 of the blood requires that a cation be released into the blood, as well. This can reduce blood pH. Glycolysis coupled with lactate production is neutral in the sense that it does not produce excess hydrogen cations; however, pyruvate production does produce them. Lactate production is buffered intracellularly, e.g. the lactate-producing enzyme, lactate dehydrogenase, binds one hydrogen cation per pyruvate molecule converted. When such buffer systems become saturated, cells will transport lactate into the bloodstream. Hypoxia certainly causes both a buildup of lactate and acidification, and lactate is therefore a good 'marker' of hypoxia, but lactate itself is not the cause of low pH. During exercise and some illnesses, lactate production is not generated by lack of oxygen, per se, but by the catecholamine-driven metabolism of glucose (glycolysis) that cells use when they cannot get enough energy from oxygen-based reactions.