Figure 639

Pathophysiology of the milk-alkali syndrome. The milk-alkali syndrome comprises the triad of hypercalcemia, renal insufficiency, and metabolic alkalosis and is caused by the ingestion of large amounts of calcium and absorbable alkali. Although large amounts of milk and absorbable alkali were the culprits in the classic form of the syndrome, its modern version is usually the result of large doses of calcium carbonate alone. Because of recent emphasis on prevention and treatment of osteoporosis with calcium carbonate and the availability of this preparation over the counter, milk-alkali syndrome is currently the third leading cause of hypercalcemia after primary hyper-parathyroidism and malignancy. Another common presentation of the syndrome originates from the current use of calcium carbonate in preference to aluminum as a phosphate binder in patients with chronic renal insufficiency. The critical element in the pathogenesis of the syndrome is the development of hypercalcemia that, in turn, results in renal dysfunction. Generation and maintenance of metabolic alkalosis reflect the combined effects of the large bicarbonate load, renal insufficiency, and hypercal-cemia. Metabolic alkalosis contributes to the maintenance of hypercalcemia by increasing tubular calcium reabsorption. Superimposition of an element of volume contraction caused by vomiting, diuretics, or hypercalcemia-induced natriuresis can worsen each one of the three main components of the syndrome. Discontinuation of calcium carbonate coupled with a diet high in sodium chloride or the use of normal saline and furosemide therapy (depending on the severity of the syndrome) results in rapid resolution of hypercalcemia and metabolic alkalo-sis. Although renal function also improves, in a considerable fraction of patients with the chronic form of the syndrome serum creatinine fails to return to baseline as a result of irreversible structural changes in the kidneys [27].

Clinical syndrome Affected gene Affected chromosome Localization of tubular defect

Bartter's syndrome

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