From the Guidelines
Hypocalcemia and metabolic alkalosis are often caused by underlying conditions such as Bartter syndrome, 22q11.2 deletion syndrome, and chronic kidney disease.
Causes of Hypocalcemia and Metabolic Alkalosis
- Bartter syndrome: a rare genetic disorder characterized by hypokalemic metabolic alkalosis, hypocalcemia, and hypercalciuria 1
- 22q11.2 deletion syndrome: a genetic disorder that can cause hypoparathyroidism, leading to hypocalcemia, and may also be associated with hypomagnesemia and hypothyroidism 1
- Chronic kidney disease (CKD): can cause hypocalcemia due to impaired vitamin D metabolism, phosphate retention, and skeletal resistance to parathyroid hormone (PTH) 1
Pathophysiology
- Hypocalcemia: can be caused by decreased intestinal calcium absorption, increased urinary calcium excretion, or impaired parathyroid hormone (PTH) secretion or action
- Metabolic alkalosis: can be caused by excessive bicarbonate intake, vomiting, or certain medications, and is often associated with hypokalemia and hypochloremia
Diagnosis and Treatment
- Bartter syndrome: diagnosis is based on clinical presentation, laboratory findings, and genetic testing; treatment involves management of electrolyte imbalances and renal function 1
- 22q11.2 deletion syndrome: diagnosis is based on clinical presentation, laboratory findings, and genetic testing; treatment involves management of hypocalcemia, hypomagnesemia, and hypothyroidism, as well as monitoring for other associated conditions 1
- Chronic kidney disease: diagnosis is based on clinical presentation, laboratory findings, and imaging studies; treatment involves management of electrolyte imbalances, acid-base disorders, and bone mineral metabolism, as well as slowing progression of kidney disease 1
From the Research
Causes of Hypocalcemia and Metabolic Alkalosis
- Hypocalcemia can be caused by various factors, including hypoalbuminemia, sepsis, red cell transfusions, and renal failure 2
- Metabolic alkalosis can be caused by hypercalcemia, which activates the calcium-sensing receptor in the thick ascending limb of Henle and inactivates the 2 chloride sodium potassium co-transporter, inducing a hypokalemic metabolic alkalosis 3
- Hypomagnesemia can also lead to hypokalemia and hypocalcemia, with clinical characteristics including renal potassium and calcium wasting, and acid-base and electrolyte abnormalities such as respiratory and metabolic alkalosis 4
- Low parathyroid hormone levels can also contribute to hypocalcemia, with clinical manifestations ranging from mild to life-threatening 5
- Autosomal dominant hypocalcemia type 1 (ADH1) can also lead to hypokalemia and metabolic alkalosis, due to activating mutations in the calcium-sensing receptor (CaSR) gene, which affects calcium and magnesium homeostasis in the kidney 6
Underlying Mechanisms
- The calcium-sensing receptor (CaSR) plays a crucial role in calcium and magnesium homeostasis in the kidney, and activating mutations in the CaSR gene can lead to hypokalemia and metabolic alkalosis 6
- The Na(+)-Cl(-) cotransporter (NCCT) in the distal convoluted tubule can be secondarily affected in ADH1, leading to hypokalemia 6
- Hypocalcemia can lead to increased calcium binding to protein, which can increase with alkalosis, leading to low ionized calcium levels 2
Patient Characteristics
- Critically ill patients are at risk of hypocalcemia, with 64% of patients in one study having serum calcium levels less than 8.5 mg/dl 2
- Patients with hypomagnesemic hypokalemia and hypocalcemia exhibit multiple interrelated acid-base and electrolyte abnormalities, including hypokalemia, hypophosphatemia, and respiratory and metabolic alkalosis 4
- Patients with ADH1 may present with hypokalemia and metabolic alkalosis, as well as hypocalcemia and inadequate parathyroid hormone secretion 6