16. Disturbances in mineral metabolism (Ca, P, Mg). Pathophysiology of osteoporosis and osteomalacia.

DISTURBANCES IN MINERAL METABOLISM (Ca, P, Mg). OSTEOPOROSIS AND OSTEOMALACIA

Calcium

• 99% of calcium is located in the bone, and the remainder inside cells and ECF
• Normal calcium levels = 2.12 - 2.62 mmol/L
• Serum calcium exists in three forms:

1. Ionized - 50%

• Free to leave the vascular compartment and participate in cellular functions

2. Protein bound - 40%

• Bound mostly to albumin and cannot diffuse or pass through the capillary wall to leave the vascular compartment

3. Complexed - 10%

• Chelated with citrate, phosphate, and sulfate
• Major functions of calcium:
• Calcification of bone and teeth
• Muscle contraction
• Role in neuromuscular transmission
• Role in blood coagulation
• Maintenance of cell membrane
• The extracellular concentrations of calcium and phosphate are reciprocally regulated such that calcium levels fall when phosphate levels are high and vice versa

Hormonal regulation of serum calcium

1. Parathyroid hormone

• Secreted by the parathyroid glands
• Released when there is a decrease in serum calcium
• The main function is to increase serum calcium levels by:
• Promoting the release of calcium from bone (resorption)
• Increasing the activation of vitamin D as a means of enhancing intestinal absorption of calcium
• Stimulating calcium conservation by the kidney while increasing phosphate excretion

2. Vitamin D

• Vitamin D3 = precursor of the active form of vitamin D
• It is synthesised in the skin or obtained from foods in the diet → hydroxylated in the liver → transformed to its active form in the kidney (calcitriol)
• Acts to increase serum calcium levels:
• Increases the absorption of calcium from the intestine
• However inhibits the release of Ca2+ from bones (resorption)

3. Calcitonin

• Produced by C cells in the thyroid
• Acts to reduce serum calcium levels:
• Inhibits the release of calcium from bones (resorption)

Organ regulation of serum calcium

1. Intestine

• Low plasma Ca2+ → increased vitamin D3 → increased absorption
• High plasma Ca2+ → decreased vitamin D3 → decreased absorption

2. Bone

• Low plasma Ca2+ → increased PTH → increased bone resorption → increased plasma Ca2+
• High plasma Ca2+ → increased calcitonin → decreased bone resorption → decreased plasma Ca2+

3. Kidneys

• Low plasma Ca2+ → decreased renal Ca2+ excretion → increased plasma Ca2+
• High plasma Ca2+ → increased renal Ca2+ excretion → decreased plasma Ca2+

Hypercalcemia

• > 2.62 mmol/L

Causes of hypercalcemia

• Hyperparathyroidism (due to adenoma, hyperplasia, carcinoma)
• Increased intestinal absorption
• Thyrotoxicosis → ↑ Thyroid hormone → ↑ osteoclastic activity → ↑ bone resorption
• Prolonged immobilization → lack of weight-bearing activities → osteoclast activation → bone demineralization → hypercalcemia
• Adrenal insu ciency