Calcium and Phosphorus Metabolism

Calcium and Phosphorus Metabolism

• Calcium is the most common mineral in the human body and essential for many metabolic processes

Biological Roles of Calcium

• Calcium is the most abundant mineral in the human body
• Contributes to mineralized tissue as Hydroxyapatite [Ca10(PO4)6(OH)2] in bone, dentin, cementum & enamel
• Plays a role in neuromuscular excitability via neurotransmitter release
• Important for clot formation
• Involved in cell-cell adhesion
• Acts as an intracellular 2nd messenger for hormone and enzyme activities

Biological Roles of Phosphorus

• Contributes to mineralized tissue: Hydroxyapatite
• Important for phosphorylated metabolites like ATP, UDP-glucose, and glucose 6-phosphate creatine phosphate
• Is a component of DNA and RNA
• Contributes to Phospholipids
• Exists as free ortho- & pyro- phosphates
• Important for Phosphoenzymes during phosphorylation and dephosphorylation of enzymes to regulate metabolic activity

Distribution of Calcium

• The total calcium content in the body is 1.2 kg
• 99% of calcium is in the skeletal system and teeth; the remainder is in extracellular fluid
• Normal serum calcium levels range from 8.5-10.5 mg/dl

Calcium Distribution in ECF-Plasma

• About 45% is bound to proteins, mostly albumin
• Around 55% is diffusible
  • 45% of calcium is ionized in a physiologically active form
  • 10% is complexed with anions like citrate, sulphate, and phosphate

Impact of Albumin on Calcium Levels

• A decrease in serum albumin of 1 gram/dl leads to a 0.8 mg/dl decrease in total blood calcium level
• Measured calcium levels should be adjusted in hypoalbuminemia because patients with low albumin have lower total serum calcium than reference values but normal unbound calcium

Calcium Level Adjustment Equation

• Adjusted calcium (mg/dl) = Measured total calcium (mg/dl) + [0.8 × (4 – serum albumin-g/dl)]
• 4 in the equation represents the average serum albumin level

Example Calculation:

• Serum albumin: 2.5 gram/dl
• Measured serum calcium: 8 mg/dl
• Correction: (4-2.5) x (0.8) =1.2
• Adjusted/corrected total calcium: 8 + 1.2 = 9.2 mg/dl

Distribution of Phosphorus

• 80% of P₁ is present in mineralized tissue [Ca10(PO4)6(OH)2]
• The remainder is mostly intracellular, bound to lipids and proteins or in membrane or in nucleotide/nucleic acid structures
• Only 1% is in soft tissues and extracellular fluid
• Kidneys regulate extracellular phosphate levels with PTH decreasing renal tubular reabsorption

Regulation of Calcium Metabolism

• Regulatory hormones: Parathyroid hormone (PTH), Vitamin D and metabolites, and Calcitonin
• Regulatory tissues/mechanisms: GI reabsorption, Renal excretion, and Bone

Parathyroid Hormone (PTH)

• Parathyroid glands secrete it in response to low serum [Ca2+] levels
• Increases serum calcium levels
• Stimulates renal reabsorption of calcium
• Stimulates GI absorption of calcium
• Stimulates bone resorption
• Inhibits bone formation and mineralization
• Stimulates the synthesis of calcitriol

Calcitriol (Active Vitamin D3)

• Increases serum ionized calcium
• Stimulates GI absorption of both Ca & P
• Stimulates renal reabsorption of both Ca & P
• Stimulates bone resorption

Calcitonin

• Secreted from parafollicular C cells of the thyroid gland, a peptide hormone
• Reduces plasma [Ca2+] by inhibiting bone resorption
• Inhibits reabsorption of Ca2+ from renal tubules

Hypocalcemia Mechanisms

• Decreased GI absorption
• Decreased bone resorption
• Increased urinary excretion

Causes of Decreased GI Absorption

• Poor dietary intake of calcium
• Impaired absorption of calcium (Vitamin D deficiency, decreased conversion of vit. D to calcitriol, liver failure, renal failure, low PTH, hyperphosphatemia)

Other Causes of Hypocalcemia

• Low PTH
• Vitamin D deficiency / low calcitriol
• Magnesium (Mg) deficiency is the most frequent cause of hypocalcemia in hospitalized patients

Hypercalcemia Causes

• Increased GI absorption (Milk-alkali syndrome, elevated calcitriol)
• Increased loss from bone, resulting in increased resorption (Elevated PTH-hyperparathyroidism and Malignancy-osteolytic metastases)
• Increased bone turnover resulting in (Paget's disease of bone, hyperthyroidism)
• Decreased bone mineralization (Elevated PTH)
• Decreased urinary excretion (Elevated calcitriol and PTH)

Milk-Alkali Syndrome

• Characterized by hypercalcemia, metabolic alkalosis, and acute kidney injury
• Associated with the ingestion of large amounts of calcium and absorbable alkali
• Common sources are dietary supplements taken to prevent osteoporosis and antacids
• May lead to kidney failure if untreated

Top Three Leading Causes of Hypercalcemia

• Hyperparathyroidism
• Malignancy-osteolytic metastases
• Milk-alkali syndrome

Bone Diseases

• Bone metastases can be caused by cancers of the breast, lung, renal, and prostate leading to pain, pathologic fractures, hypercalcemia, and increased alkaline phosphatase
• Hyperparathyroidism
• Osteomalacia / Rickets
• Osteoporosis
• Paget Disease

Osteomalacia

• Results from a deficiency or impaired metabolism of Vitamin D (or calcium)
• Adulthood: Enlarged / non-mineralized osteoid tissue (organic matrix not involved)
• Childhood: Occurs as classical rickets with defective mineralization or calcification of bones before epiphyseal closure
• Results in Hypocalcemia and hypophosphatemia
• Increased alkaline phosphatase is observed, with increased PTH

Osteoporosis

• A bone remodeling disease common among post-menopausal women (25% in women, 5% in men of > 60 years)
• Leads to reduced bone volume, density, and strength
• Results in increased susceptibility to bone fractures
• Decreased osteoblastic & increased osteoclastic activity

Calcium RDA (Recommended Daily Allowance)

• Children (0-3 years): 500 mg/day
• Children (4-8 years): 800 mg/day
• Children (9-18 years): 1300 mg/day
• Adults (19-50 years): 1000 mg/day
• Adults (>50 years): 1200 mg/day
• Pregnant or lactating (<19 years): 1300 mg/day
• Pregnant or lactating (19-50 years): 1000 mg/day