What is the pathophysiology of milk alkaline syndrome?

From the Guidelines

Milk-alkali syndrome is a condition characterized by hypercalcemia, metabolic alkalosis, and kidney injury, resulting from excessive calcium intake, typically from calcium-containing antacids or supplements combined with milk. The pathophysiology of milk-alkali syndrome involves a complex interplay of factors, including high calcium intake, reduced kidney function, and impaired calcium excretion. Although the provided evidence does not directly address milk-alkali syndrome, it discusses the effects of diuretics on electrolyte balance and acid-base status, which can be relevant to understanding the syndrome's pathophysiology 1.

Key Factors

• High calcium intake raises blood calcium levels, which can reduce kidney function and impair calcium excretion
• Alkaline substances, like calcium carbonate, increase blood pH, creating metabolic alkalosis
• Metabolic alkalosis further decreases calcium excretion by enhancing renal calcium reabsorption
• Kidney function worsens, bicarbonate excretion decreases, worsening the alkalosis
• Elevated calcium can cause nephrocalcinosis and further kidney damage

Clinical Considerations

• Risk factors include decreased kidney function, older age, and medications affecting calcium metabolism
• The syndrome is reversible if caught early by discontinuing the offending agents, but prolonged exposure can lead to permanent kidney damage and calcification of soft tissues
• It is essential to monitor serum electrolytes and kidney function in patients at risk of developing milk-alkali syndrome, especially those with a history of excessive calcium intake or kidney disease.

From the Research

Pathophysiology of Milk Alkaline Syndrome

The pathophysiology of milk alkaline syndrome is characterized by:

• Hypercalcemia: elevated levels of calcium in the blood 2, 3, 4, 5, 6
• Metabolic alkalosis: a condition in which the blood becomes too alkaline 2, 3, 4, 5, 6
• Renal insufficiency: a decrease in kidney function 2, 3, 4, 5, 6

Mechanisms

The exact mechanisms of milk alkaline syndrome are not fully understood, but it is thought to involve:

• An interplay between hypercalcemia and alkalosis in the kidneys, leading to a self-reinforcing cycle 3
• Increased renal tubular reabsorption of calcium and decreased ionized calcium, leading to increased secretion of parathyroid hormone and activation of vitamin D3 2
• Sustained metabolic alkalosis, which can cause an increase in renal tubular reabsorption of calcium and a decrease in ionized calcium 2

Causes

Milk alkaline syndrome can be caused by:

• Ingestion of large amounts of calcium and absorbable alkali, such as calcium carbonate 3, 6
• Loop-diuretic-induced alkaline load and polypharmacy 5
• Overconsumption of calcium-containing products, such as milk, calcium carbonate antacid, and calcium-containing prenatal vitamins 6

Clinical Presentation

The clinical presentation of milk alkaline syndrome can include:

• Hypercalcemia, metabolic alkalosis, and renal insufficiency 2, 3, 4, 5, 6
• Symptoms such as flank pain, nausea, vomiting, anorexia, headache, and lightheadedness 6
• Electrocardiogram abnormalities, renal dysfunction, and chloride-resistant metabolic alkalosis 5