The mechanism of how<unk>  develops from ingesting too much of calcium and absorbable<unk>  is still unclear. However, it is well known that MAS is usually associated with a triad of symptoms that include hypercalcemia,<unk> sis, and acute kidney injury. In general,<unk>  starts with excess calcium levels in the body (hypercalcemia), which causes the body's pH to increase (become more<unk> ne) resulting in metabolic<unk> sis 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 bone's 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. Additionally, hypercalcemia can decrease the reabsorption of water in the kidney's collecting ducts by suppressing antidiuretic hormone (ADH) receptors, contributing to more hypovolemia. Hypercalcemia also results in lower parathyroid hormone (PTH) levels via a negative feedback loop, in which calcium-sensing receptors in the PTH gland are activated by the elevated calcium levels to inhibit PTH production, thus decreasing renal reabsorption of calcium. Hypovolemia then leads to metabolic<unk> sis (increase in blood pH) by stimulating bicarbonate reabsorption in order to maintain extracellular volume. In summary, the symptoms of<unk> sis is the net result of over-consumption of absorbable<unk> , hypercalcemia-induced hypovolemia, and impaired glomerular filtration rate.<unk> sis, in turn, increases calcium-reabsorption from the distal tubules of the nephron, thus exacerbating the hypercalcemia and hypovolemia. Altogether, these result in a cycle of hypercalcemia,<unk> sis, and renal injury characteristic of MAS.
Milk-alkali syndrome
Hyperthyroidism
Hyperinsulinism-hyperammonemia syndrome
Sarcoidosis
Jones syndrome
Refeeding syndrome
Leucine-sensitive hypoglycemia of infancy
Johanson–Blizzard syndrome