METABOLIC ALKALOSIS (PRIMARY BICARBONATE EXCESS):

Alkalosis occurs when excess base is added, elimination of base is impaired or loss of acid. Any of these can lead to primary bicarbonate excess, such that the ratio of bicarbonate/carbonic acid becomes >20:1. If severe alkalosis occurs there is tetany even calcium is normal. The cause of tetany is due to loss of ionized calcium due to increased binding of calcium ion by proteins (mainly albumin) and other anions. Measurement of Cl^- status is helpful, as cause of metabolic alkalosis fall into Cl^- responsive, Cl^- resistant, and exogenous base categories.

Chloride responsive metabolic alkalosis:

The cause of this condition is due to hypovolemia. When ECF is severely depleted, the resulting acid-base disorder is referred to as contraction alkalosis. Renal bicarbonate retention will occur in response to hypovolemia under the action of increased aldosterone. This will also result in increased reabsorption of sodium together with bicarbonate and excretion of K and H. The resulting hypokalemia contributes to alkalosis. Urine Cl^- will be <10 mmol/L as both available Cl and HCO₃ are reabsorbed with Na. Common cause of contraction alkalosis include prolonged vomiting, duodenal obstruction, villous adenoma (unregulated secretion of HCl) and use of diuretics.

Gastrointestinal loss of HCl: 

There is excessive loss of HCl from stomach and hypovolemia. In this hypochloremic, hypovolemic setting the kidney reabsorb Na to store volume and excess bicarbonate is reabsorbed in the absence of sufficient Cl^- to maintain electrical neutrality. In addition H⁺ and K⁺ are secreted in exchange for Na⁺. Urine Cl^- will be <10 mmol/L.

Diuretic therapy: 

Use of diuretics like Lasix, bumex blocks sodium, potassium and chloride reabsorption. These acts of ascending limb of loop of henle. The resulting increase in sodium concentration reaching the DCT, when combined with activation of renin-angiotensin-aldosterone axis, leads to increased urinary excretion of K⁺ and H⁺. This is commonly seen among patients abusing diuretics for the purpose of weight loss.

Chloride resistant metabolic alkalosis:

This is almost always associated with either an underlying disease (primary hyperaldosteronism, Cushing’s syndrome or Bartter’s syndrome) or with excess addition of exogenous base. In these conditions urine Cl will be >20 mmol/L.

During excess adrenocortical excess K and H are wasted by kidney due to increased Na reabsorption stimulated by elevated aldosterone or cortisol. The hypokalemia often contributes to alkalosis. The resulting decreased tubular K concentration stimulates ammonia production and thus renal H excretion and ammonium. This is accompanied by enhanced bicarbonate reabsorption. During primary and secondary hypoeraldosteronism, ACTH producing adenoma (Cushing’s disease), and primary adrenal adenomas producing glucocorticoid (Cushing’s syndrome) or aldosterone in these conditions there is increased mineralocorticoid, glucocorticoid, or both. The excess cortisol exerts a mineralocorticoid effect on the distal tubule aldosterone receptors.

Finally a rare etiology of Cl resistant alkalosis is a genetic (autosomal recessive) defect in Cl^- reabsorption within the thick ascending limb of loop of Henle, a condition known as Bartter’s syndrome.

Exogenous base:

It includes citrate toxicity following massive blood transfusion, iv therapy of bicarbonate solutions, ingestion of large quantity of milk and antacids in treatment of gastritis and peptic ulcers (milk-alkali syndrome).

Compensatory mechanism:

Respiratory mechanism:

The increase in pH depress respiratory center, causing hypercapnia, which in turn cause increase in cH₂CO₃ and cdCO₂. Thus the ratio of cHCO₃/cdCO₂ approaches normal value.

Renal compensatory mechanism:

The kidney respond to alkalosis by decrease in Na-H exchange, decreased formation of ammonia, and decrease reclamation of bicarbonate.

Laboratory findings:

Blood plasma value for cHCO₃^-, cdCO₂ and plasma total CO₂ concentration are increased and the ratio is high. A higher than expected pCO₂ indicates superimposed respiratory acidosis. In prolonged vomiting Cl^- (sometimes K⁺) are low due to loss in vomitus. Proteins may be falsely increased due to dehydration, and if food intake is inadequate ketone bodies are formed increasing the organic acid fraction.