Lactic acid in blood

Savory J, Kaplan A. A gas chromatographic method for the determination of lactic acid in blood, Clin Chem 1966 12 559-69. 

Most investigations have employed the technique of Barker and Sum-merson (Bl) (transformation into acetaldehyde, which is estimated colorimetrically by its reaction with p-hydroxydiphenyl) or a modification of the original technique (B20, H30, M6, T25). More recent studies have been made with specific enzymatic methods using lactic dehydrogenase (H27). The stabilization of lactic acid in blood samples has been studied by Long (L16). 

The normal concentration of lactic acid in blood plasma found by most authors lies between 8 and 17 mg% in resting subjects (K14). 

We shall not consider the factors which influence lactic acid in blood and urine, as such factors have been previously reviewed (F2, K5, P4). 

L16. Long, C., The stabilization and estimation of lactic acid in blood samples. Biochem. J. 40, 27 (1946). 

The accumulation of pyruvic acid and a-ketoglutar-ate in vitamin C deficiency may be explained by the reduced concentration of CoA in ascorbic acid-deficient animals. The coenzyme is involved in the decarboxylation of both metabolites, but again, it has been suggested that the effect of ascorbic acid is secondary. The increased levels of pyruvic and lactic acids in blood could be caused by the insulin deficiency that develops in scorbutic animals. This conclusion finds support in the observation that fructose administration normalizes pyruvic and lactic acid levels. Whether the increased levels of a-ketoglutarate in scorbutic animals could result from decreased use in protein hydroxyla-tion remains to be seen. 

Gas Chromatographic Method for the Determination of Lactic Acid in Blood... 

The combination of HPICE/HPIC was successftiUy applied by Rich et aL [22] to the separation of pyruvic acid and lactic acid in blood sera. At that time, a separation of organic acids in biological hquids could not be accomplished solely by ion-... 

Lactic acidosis (buildup of lactic acid in the blood) may also occur with die administration of metformin. Although lactic acidosis is a rare adverse reaction, its occurrence is serious and can be fatal. Lactic acidosis occurs mainly in patients with kidney dysfunction. Symptoms of lactic acidosis include malaise (vague feeling of bodily discomfort), abdominal pain, rapid respirations, shortness of breath, and muscular pain. In some patients vitamin B12 levels are decreased. This can be reversed with vitamin B12 supplements or with discontinuation of the drug therapy. Because... 

Lactic acidosis A condition caused by build-up of lactic acid in the body. It leads to acidification of the blood (acidosis), and is a form of metabolic acidosis. 

Straightforward thiamine deficiency in man, beri-beri, is characterized by accumulation of pyruvic and lactic acids in the blood and brain, and impairment of cardiovascular, nervous, and gastrointestinal function (DIO, G17, P4, Yl). Neurological lesions characterize thiamine deficiency in growing rats (B40), guinea pigs (M6), mice (M13), chicks, and pigeons (B30). The effects of thiamine deficiency on the central nervous system of animals have been reviewed (DIO). 

The lactate formed by active skeletal muscles (or by erythrocytes) can be recycled it is carried in the blood to the liver, where it is converted to glucose during the recovery from strenuous muscular activity. When lactate is produced in large quantities during vigorous muscle contraction (during a sprint, for example), the acidification that results from ionization of lactic acid in muscle and blood limits the period of vigorous activity. The best-conditioned athletes can sprint at top speed for no more than a minute (Box 14-1). 

Lactic acid is the cause of one of many possible disorders in human acid-base metabolism. Lactic acidosis represents an accumulation of lactic acid in the blood and tissues. This condition gradually depletes the natural buffers in the body and there is a consequent lowering of pH. As described in the entry on Glycolysis, lactic acid is the end product til (hat pmcess. Lactic acid blood levels are determined by at least Tour factors. The rate of generation of lactic acid the rate of transport from tissues to plasma and from plasma to the liver (point of utilization of lactic acid) the rate uf utilization and excretion of lactic acid by the kidneys. Normally, all of these funclions are maintained in balance to give a normal blood lactate concentration of about I niFq/l. 

Additional experiments have been conducted in severely head-injured cats to assess the effects of U-74006F on brain energy metabolites [61]. A 1 mg/kg i.v. dose administered at 30 minutes post-injury, plus a second 0.5 mg/kg dose 2 hours later, resulted in an improved metabolic profile within the injured hemisphere measured at 4 hours. Most notably, U-74006F significantly reduced post-traumatic accumulation of lactic acid in both the cerebral cortex and the sub-cortical white matter. This biochemical effect suggests an improved maintenance of cerebral blood flow in the injured brain. As noted above, U-74006F does very effectively reduce progressive development of post-traumatic ischemia in experimental cat spinal-cord injury [24,27] which may also provide the explanation for the reduction of post-traumatic lactate levels in the injured brain. 

Buffers in Blood Your blood is a slightly alkaline solution with a pH of approximately 7.4. To be healthy, that pH must be maintained within narrow limits. A condition called acidosis occurs if the pH falls more than 0.3 units below 7.4. An equally serious condition called alkalosis exists if the pH rises 0.3 units. You may have experienced a mild case of acidosis if you have overexerted and developed a cramp in your leg. Cramping results from the formation of lactic acid in muscle tissue. 

In people with a phosphatase deficiency, pyruvate dehydrogenase is always phosphorylated and thus inactive. Consequently, glucose is processed to lactate rather than acetyl CoA. This condition results in unremitting lactic acidosis—high blood levels of lactic acid. In such an acidic environment, many tissues malfunction, most notably the central nervous... 

Salicylate, which is a degradation product of aspirin in the human, is lipid soluble and has a dissociable proton. In high concentrations, as in salicylate poisoning, salicylate is able to partially uncouple mitochondria. The decline of ATP concentration in the cell and consequent increase of AMP in the cytosol stimulates glycolysis. The overstimulation of the glycolytic pathway (see Chapter 22) results in increased levels of lactic acid in the blood and a metabolic acidosis. Fortunately, Dennis Veere did not develop this consequence of aspirin poisoning (see Chapter 4). 

Reaction 15.4 is a net ionic reaction for the buffering process. When a total reaction is written, we see that the effect of the buffering is to replace lactic acid in the blood by carbonic acid, which is a weaker acid and so releases fewer H" ions to the blood than does lactic acid ... 

In the body, conjugate acid-base pairs are more common. In the blood, for example, the carbonic acid/bicarbonate pair helps to control the pH. This buffer can be overcome, though, and some potentially dangerous situations can arise. If a person exercises strenuously, lactic acid from the muscles is released into the bloodstream. If there s not enough bicarbonate ion to neutralize the lactic acid, the blood pH drops, and the person is said to be in acidosis. Diabetes may also cause acidosis. On the other hand, if a person hyperventilates (breathes too fast), she breathes out too much carbon dioxide. The carbonic acid level in the blood is reduced, causing the blood to become too basic. This condition, called alkalosis, can be very serious. 

Write a balanced equation for the conversion of glucose to lactic acid, and then consider the degree of ionization of lactic acid in a solution of pH 7.4, the normal pH of blood plasma. 

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