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Normally pH remains relatively constant both outside and inside the cells. Alterations in the acid-base balance are resisted by extracellular and intracellular chemical buffers and by respiratory and renal regulation. In the first place, kidneys and blood buffers attempt to correct metabolic disorders and lungs attempt to correct respiratory disorders. (Brewer 1990) Buffering in blood and extracellular fluid occurs in minutes. Acid or base added to the body enter cells and bone slowly, over hours (Rhoades & Tanner 1995). In human body, respiratory compensation for a metabolic disorder begins within minutes and is complete in 12-24 hours. Metabolic compensation for respiratory disorder (increase of bicarbonate in respiratory acidosis and decrease of bicarbonate in respiratory alkalosis) occurs more slowly: it begins in hours and requires 2-5 days for completion (Brewer 1990). After the compensations, the state of acid-base disturbance can be considered as chronic. The change in pH in blood (produced when acid or base is added) is minimized by chemical buffers, but they do not entirely prevent the pH change (Rhoades & Tanner 1995). In fact, in a disturbance of the acid-base balance, neither buffers nor the respiratory or renal systems are completely successful in correcting pH until the underlying reason for the disorder has been removed (Brewer 1990). A normal adult produces about 300 liters of CO2 daily from the metabolism of foodstuffs. In the blood, CO2 reacts with water to form carbonic acid, which dissociates to H+ and HCO3-. In the lung capillaries they are converted back to CO2 and water and the CO2 is expired. (Rhoades & Tanner 1995). As a secondary respiratory compensation, the lungs react to metabolic acidosis and alkalosis. Metabolic acidosis stimulates breathing causing hyperventilation while metabolic alkalosis suppresses it. These are attempts to correct pH by changing the concentration of carbon dioxide and carbonic acid in the blood. (Rhoades & Tanner 1995)

Oxidation of proteins and amino acids produces strong acids, like sulfuric, hydrochloric, and phosphoric acids, in the normal metabolism. These and other non-carbonic (non-volatile) acids are buffered in the body and must then be excreted by the kidneys (Rhoades & Tanner 1995). The most important extracellular buffer is bicarbonate, which usually buffers these non-volatile acids. The kidneys regenerate the bicarbonate used in buffering by excreting hydrogen ions in the urine as ammonium and titratable acids (Brewer 1990). Other major chemical pH buffers in the body are inorganic phosphate and plasma proteins in the extracellular fluid, cell proteins, organic phosphates and bicarbonate in the intracellular fluid, and mineral phosphates and mineral carbonates in bone (Rhoades & Tanner 1995).

The kidneys have two important roles in the maintaining of the acid-base balance: to reabsorb bicarbonate from and to excrete hydrogen ions into urine. 4500 mmol of bicarbonate are filtered into the primary filtrate of urine daily, but only 2 mmol of it are finally excreted. 70-80% of bicarbonate is reabsorbed in the first part of proximal tubule, 10-20% in the loop of Henle and 5-10% in the distal tubule and collecting ducts. (Jalanko & Holmberg 1998) Carbonic anhydrase plays an important role in the reabsorption in the proximal tubule. Disturbance in the reabsorption of bicarbonate in the proximal tubule leads to metabolic acidosis, hyperchloremia and alkalotic urine. This disease is named as "type II renal tubular acidosis" (N25.8). (Jalanko & Holmberg 1998) Renal tubules actively secrete hydrogen ions. Most of this takes place in the distal part of the nephron, but active transport of hydrogen ions occurs in the proximal tubule, too. The H-ATPase of the apical cell membrane secretes hydrogen ions into urine. For each hydrogen ion secreted, one bicarbonate molecule is transported to the interstitial fluid, from there it diffuses into the bloodstream. Fifty mmol of hydrogen ions are normally excreted daily. (Jalanko & Holmberg 1998) If the hydrogen ions are not properly secreted into the collecting ducts, the result is metabolic acidosis, hypokalemia, hypocalcemia, nephrocalcinosis and an alkalotic urine. This disease is called "type I renal tubular acidosis" (N25.8). (Jalanko & Holmberg 1998) The maximal hydrogen ion gradient, against which the transport mechanism can secrete H+ ions, corresponds to a urine pH of 4.5 in humans. However, three important molecules remove free hydrogen ions from the tubular fluid permitting more acid to be secreted: H+ is bound to ammonia, phosphate and bicarbonate to form NH4+, H2PO4-, CO2 and H2O. (Ganong 1991) The source of the hydrogen ions secreted by the tubular cells is not completely certain. It is probably produced by dissociation of H2CO3. The acid-secreting cells contain carbonic anhydrase, which facilitates the rapid formation of H2CO3 from CO2 and water. The renal acid secretion is mainly regulated by the changes in the intracellular pCO2, potassium concentration, carbonic anhydrase activity and adrenocortical hormone concentration. (Ganong 1991)

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Q: How will the body respond to maintain acid- base balance If a strong acid is added to the extracellular fluid?
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