Pharmacology: Calcium Homeostasis & Parathyroid Hormones

Study Notes

Ca2+ is the most abundant mineral in the human body
Approximately 1 kg of Ca2+ is stored in bones in the form of phosphate and hydroxide salts, predominantly as hydroxyapatite
Ca2+ exists in three forms in plasma: 50% ionized or biologically active, 45% bound to plasma proteins (mainly albumin), and 5% complexed to phosphate and citrate

The movement and regulation of Ca2+ in and out of the body, and between body compartments (fluids, bones)
Maintained by two polypeptide hormones (parathyroid hormone, calcitonin) and a steroid hormone (calcitriol) as well as serum calcium and phosphate levels

Secreted by the parathyroid gland in response to low calcium levels in the blood
Regulates calcium and phosphate levels in blood circulation in conjunction with calcitriol
Increases calcium levels and decreases phosphate levels
Antagonistic to calcitonin
Effects are present in bones, kidneys, and small intestines

Stimulates the release of calcium indirectly via osteoclasts, causing resorption/destruction of bones
Directly stimulates osteoblasts, which differentiate into osteoclasts, stimulating bone formation
Osteoclasts activity exceeds osteoblasts activity, leading to bone resorption and release of calcium into the blood

Targets the distal convoluted tubule and collecting duct, directly increasing calcium reabsorption
Decreases phosphate reabsorption at the proximal tubule, leading to increased excretion of phosphates and decreased serum phosphate levels
Decreased serum phosphate levels lead to decreased serum calcium-phosphate formation, increasing levels of serum ionized calcium

Stimulates the production of 1-alpha-hydroxylase in the proximal convoluted tubule of the kidney, required for the synthesis of active vitamin D (calcitriol)
Calcitriol increases intestinal absorption of calcium, increasing serum calcium levels

Total serum [Ca2+] < 8.8 mg/dL (< 2.2 mmol/L) in the presence of normal plasma protein (albumin) concentrations
Serum ionized [Ca2+] < 4.7 mg/dL (< 1.17 mmol/L)
May be hereditary or acquired (liver disease, kidney disease, diet, medication, surgery, hypoparathyroidism)
Treatment depends on the cause, severity, presence of symptoms, and how rapidly the hypocalcemia developed

Total serum [Ca2+] > 10.4 mg/dL (> 2.6 mmol/L)
Serum ionized [Ca2+] > 5.2 mg/dL (> 1.3 mmol/L)
Can result from excess calcium entering the ECF or insufficient calcium excretion from the kidneys
Approximately 90% of cases are caused by hyperparathyroidism (usually mild, asymptomatic, and sustained for years) or malignancy (usually rapidly progressive)

Characterized by excessive production of PTH
Primary hyperparathyroidism: unregulated levels of PTH usually from a hormone-secreting parathyroid adenoma or parathyroid hyperplasia or rarely parathyroid carcinoma
Secondary hyperparathyroidism: ↑ production of PTH secondary to hypocalcemia or hyperphosphatemia, typically as a result of vitamin D deficiency and/or chronic kidney disease (CKD)
Tertiary hyperparathyroidism: excessive secretion of PTH due to chronic secondary hyperparathyroidism (autonomous hypersecretion of PTH)