However, it is well known that MAS is usually associated with a triad of symptoms that include hypercalcemia, alkalosis, and acute kidney injury. In general, milk-alkali syndrome starts with excess calcium levels in the body (hypercalcemia), which causes the bodys pH to increase (become more alkaline) resulting in metabolic alkalosis and ultimately contributes to a decrease in renal function.Factors involved in the development of hypercalcemia include excess intestinal absorption of calcium, saturation of the bones buffering capacity for calcium, decreased renal excretion, and abnormal vitamin D metabolism. Underlying kidney disease is a risk factor for MAS, but even people with healthy kidneys can develop the syndrome.For a healthy individual, if calcium levels are high, the kidneys will decrease its production of calcitriol (active vitamin D) by reducing the hydroxylation of calcidiol (inactive vitamin D); lower calcitriol levels means a lower rate of calcium absorption in the small intestine, which eventually offsets the elevated calcium levels. However, excessive ingestion of calcium of more than 10-15 g per day has been reported to cause calcium levels too high for renal calcitriol suppression to control, resulting in net calcium absorption that ultimately causes hypercalcemia.Hypercalcemia affects the kidneys in multiple ways that altogether contributes to hypovolemia. Prolonged hypercalcemia can decrease glomerular filtration rate (GFR) via vasoconstriction, reduce creatinine clearance, and eventually cause renal insufficiency. Hypercalcemia also causes natriuresis by blocking the Na-K-Cl cotransporter (NKCC) in the medullary thick ascending limb of the loop of Henle, leading increased sodium excretion followed by water excretion that leads to hypovolemia.
These abnormal calcium deposits often collect metastatically in the body, including throughout the periarticular tissue, subcutaneous tissue, central nervous system, liver, kidneys, adrenal, bones, and lungs. If ingestion of calcium and alkali is continued, neurologic symptoms such as memory loss, personality changes, lethargy, stupor, and coma will persistently develop over time, as a result of the extreme hypercalcemia and electrolyte imbalances.People with milk-alkali syndrome commonly show signs of renal dysfunction, a hallmark symptom of milk-alkali syndrome, at early stages of disease progression. Several lab test results, such as elevated blood urea nitrogen (BUN) and elevated creatinine, are illustrative of azotemia and kidney impairment. Histologically, the kidneys of individuals with milk-alkali syndrome have been shown to have "complete glomerulus hyalinization, thickening of the Bowmans capsule, tubular atrophy, vascular changes, and diffuse lymphocytic infiltration. "Other laboratory tests, such as measuring serum bicarbonate, pH, 1,25-OH vitamin D, and parathyroid hormone (PTH) can show signs of milk-alkali syndrome. Specifically, bicarbonate and pH would be elevated while 1,25-OH vitamin D and PTH would be suppressed. Causes
Milk-alkali syndrome is caused by ingesting excessive amounts of both calcium (usually in the form of dietary supplements such as calcium carbonate, which is commonly taken to prevent or treat osteoporosis) and absorbable alkali (as are found in antacid drugs).Presently, consumption of extensively large amounts of calcium carbonate has replaced the over-ingestion of milk products, or milk and bicarbonate, as the most prominent cause of MAS. Excessive consumption of calcium generally means taking in more than 4 to 5 g of calcium carbonate every day.