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|Acids and bases|
Acid–base homeostasis is that part of biologic homeostasis which is concerned with the proper balance between acids and bases in the extracellular fluids, and therefore determines the body's extracellular fluids' pH. Many of the body's extracellular components (including the proteins on the exterior surfaces of its cells) are very sensitive for their 3D configurations (or "tertiary structures") on the extracellular pH. Sringent mechanisms therefore exist to maintain the pH within very narrow limits. Outside the acceptable range of pH, proteins are denatured, causing enzymes and cellular transmembrane ion channels (among others) to malfunction. In the worst cases death may occur if the situation remains unremedied.
In various animals, including humans, acid–base homeostasis is maintained by means of three interconnected systems. The first are the various chemical buffers which minimize pH changes that would otherwise occur in their absence. They do not correct pH deviations, but only serve to limit the extent of the change that would otherwise occur. These buffers include the bicarbonate buffer system, the phosphate buffer system, and the protein buffer system. Physiological corrective measures make use of, primarily, the bicarbonate buffer system. This is because abnormalities in the carbonic acid (H2CO3, or dissolved carbon dioxide) concentration in the blood plasma can rapidly be corrected by variations in the rate and depth of breathing (i.e. by hyperventilation or hypoventilation). Abnormally low or high plasma bicarbonate (HCO−
3) ion concentrations can be corrected by the excretion of H+ or HCO−
3 ions in the urine, in instances where the plasma pH is abnormal. Plasma pH abnormalities are known as acidosis or alkalosis depending on which way the pH has deviated from normal.
The body's acid–base balance is normally tightly regulated by buffering agents, the respiratory system, and the renal system, keeping the arterial blood pH between 7.36 and 7.42. Several buffering agents that reversibly bind hydrogen ions and impede any change in pH exist. Extracellular buffers include bicarbonate and ammonia, whereas proteins and phosphate act as intracellular buffers; the relationship between multiple buffers in the same solution is described by the isohydric principle. The bicarbonate buffering system is especially key, as carbon dioxide (CO2) can be shifted through carbonic acid (H
3) to hydrogen ions and bicarbonate (HCO−
3) as shown below.
Acid–base imbalances that overcome the buffer system can be compensated in the short term by changing the rate of ventilation. This alters the concentration of carbon dioxide in the blood, shifting the above reaction according to Le Chatelier's principle, which in turn alters the pH. For instance, if the blood pH drops too low (acidemia), the body will compensate by increasing breathing thereby expelling CO2, and shifting the above reaction to the left such that fewer hydrogen ions are free; thus the pH will rise back to normal. For alkalemia, the opposite occurs.
The kidneys are slower to compensate, but renal physiology has several powerful mechanisms to control pH by the excretion of excess acid or base. In response to acidosis, tubular cells reabsorb more bicarbonate from the tubular fluid, collecting duct cells secrete more hydrogen and generate more bicarbonate, and ammonia genesis leads to increased formation of the NH
3 buffer. In responses to alkalosis, the kidney may excrete more bicarbonate by decreasing hydrogen ion secretion from the tubular epithelial cells, and lowering rates of glutamine metabolism and ammonium excretion.
Acid–base imbalance occurs when a significant insult causes the blood pH to shift out of the normal range (7.35 to 7.45). In the fetus, the normal range differs based on which umbilical vessel is sampled (umbilical vein pH is normally 7.25 to 7.45; umbilical artery pH is normally 7.18 to 7.38). An excess of acid in the blood is called acidemia and an excess of base is called alkalemia. The process that causes the imbalance is classified based on the etiology of the disturbance (respiratory or metabolic) and the direction of change in pH (acidosis or alkalosis). There are four basic processes: metabolic acidosis, respiratory acidosis, metabolic alkalosis, and respiratory alkalosis. One or a combination may occur at any given time.
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