Milk Alkali Syndrome

Today we discussed a case of altered mental status in a patient who was found to have hypercalcemia secondary to milk alkali syndrome. A few learning points: 

1) This syndrome (defined as a triad of: hypercalcemia, renal insufficiency, and metabolic alkalosis) was first discovered in the early 1900s when the treatment for peptic ulcer disease included drinking copious milk and taking sodium bicarbonate tablets/powders (called "Sippy Powders" after Bertram Sippy) . The frequency of this syndrome declined sharply with the advent of H2 blockers and now PPIs.

Although, there has been a recent resurgence (in the setting of readily available calcium carbonate OTC and the use of calcium supplements for osteoporosis prevention)--now about 1 in 10 cases of hypercalcemia, the third leading cause behind primary hyperparathyroidism and malignancy. 

2) Hypercalcemia affects the kidney in several ways including increasing vasoconstriction (which decreases GFR), inhibiting the Na-K-CL cotransporter leading to natriuresis and blocking the ADH-dependent water reabsorption leading to volume depletion and absorption of bicarbonate (contraction alkalosis). Alkalosis contributes to the maintenance of volume depletion and hypercalcemia (see below). Also, vomiting due to hypercalcemia can worsen the alkalemia and hypercalcemia.

Schematic of how hypercalcemia and metabolic alkalosis are generated and maintained in the milk alkali syndrome. GI, gastrointestinal; HCO3, bicarbonate; CTR, calcitriol; ADH, antidiuretic hormone; A2, angiotensin 2; K+, potassium. An “s” preceding the name indicates serum. Clinical Journal of the American Society of Nephrology

Schematic of how hypercalcemia and metabolic alkalosis are generated and maintained in the milk alkali syndrome. GI, gastrointestinal; HCO3, bicarbonate; CTR, calcitriol; ADH, antidiuretic hormone; A2, angiotensin 2; K+, potassium. An “s” preceding the name indicates serum.

Clinical Journal of the American Society of Nephrology