Alkalosis may also be divided into metabolic and respiratory types. In metabolic alkalosis, three relatively common situations should be discussed.

Alkali administration. Alkali administration most commonly occurs when sodium bicarbonate is taken in large quantities for the treatment of peptic ulcer symptoms. If this happens, excess HCO–3 is absorbed above the amount needed to neutralize stomach hydrochloric acid (HCl). The numerator of the Henderson-Hasselbalch equation is increased, the normal 20:1 ratio is increased, and the pH therefore rises. The CO2 content also rises because of the additional HCO–3. Lactate, citrate, or acetate in sufficient quantities may also produce alkalosis, since they are metabolized to HCO–3.

Acid-losing alkalosis. Acid-losing alkalosis most frequently results from severe or protracted vomiting, as may occur with pyloric stenosis. Gastric HCl is lost in vomiting. Gastric HCl was originally produced by conversion of H2CO3 to HCO–3 and H+, mediated by carbonic anhydrase of the gastric mucosa. The HCO–3 is kept in the bloodstream, but the H+ is secreted into the gastric lumen as HCl. When HCl is lost through vomiting, the H+ component of HCl is also continually being lost. The CO2 content becomes increased, because the HCO–3 that is released when HCl is produced remains in the bloodstream and increases when additional HCl is formed to replace that which is being lost. Therefore, the 20:1 ratio is increased and the pH is increased. Since H2CO3 is decreased, as it is being continually used to produce more HCl, the lungs tend to retain CO2 to compensate. Therefore, PCO2 may actually increase, although not enough to prevent increase of the 20:1 ratio.

Hypokalemic alkalosis. Hypokalemic alkalosis is most commonly due to excess potassium ion (K+) loss by the kidney, as might happen with overuse of certain diuretics that cause K+ as well as sodium ion (Na+) loss. Normally, most body K+ is intracellular, whereas most Na+ and H+ is extra-cellular. When excess K+ is lost in the urine, intracellular K+ diffuses out of the cells to replace some of that being lost from plasma; Na+ and H+ move into the cells to replace the K+ that has moved out. Thus, H+ is lost from extracellular fluid and plasma. A second mechanism depends on the fact that sodium is reabsorbed from the urine into the renal distal tubule cells by an active transport mechanism. This transport mechanism involves excretion of H+ and K+ into the urine to replace the reabsorbed Na+. In this exchange (or transport) system, H+ and K+ compete with each other. Therefore, if an intracellular deficit of K+ exists (in the tubule cells), more H+ is excreted into the urine to allow the reabsorption of the same quantity of sodium without losing as much K+. The result of renal H+ loss and extracellular H+ loss is an acid-losing type of alkalosis. Therefore, more H+ is manufactured by the kidney from H 2CO3 to replace lost extracellular fluid H+: more HCO–3 ions are thereby formed, and the numerator of the Henderson-Hasselbalch equation is increased. The denominator is eventually increased if the lungs attempt to compensate by increasing CO2 retention by slower breathing. However, respiratory compensation is frequently minimal or insignificant in hypokalemic alkalosis, so that the PCO2 frequently remains normal. Also, the urine pH is decreased because of the excess H+ being excreted in the urine. This is the opposite of what one would ordinarily expect, because in acidosis, the kidney usually attempts to compensate by excreting more H+(acid urine), whereas in alkalosis it normally tries to conserve H+ and thus produces a urine of higher pH (alkaline urine).