Hypophosphatemia Causes and Effects

Phosphate Homeostasis

• 85% of phosphate is present in bones, and the remainder is present in intracellular and extracellular matrices.
• Extracellular phosphate is present as organic forms in mixture with HPO4.
• Intracellular phosphate has various functions, including cellular energy (ATP), intracellular buffering, components of cell membranes, nucleic acids, cell signaling, and enzyme activation.

Hypophosphatemia

• Defined as a decrease in plasma phosphate levels.
• Associated with widespread cellular dysfunction, which can lead to death.
• Causes include:
  • Decreased intake (vitamin D deficiency)
  • Decreased absorption (malabsorption and antacid medication)
  • Increased excretion (primary and secondary hyperparathyroidism)
  • Phosphate redistribution (insulin-induced cellular uptake, acidosis shifting phosphate out of cells)
• Symptoms include muscle pain and weakness (including respiratory muscle weakness), osteomalacia, and rickets.

Hyperphosphatemia

• Defined as an increase in plasma phosphate levels.
• Combines with calcium to form calcium-phosphate, leading to hypocalcemia and tetany, and metastatic calcification.
• Causes include:
  • Intravenous phosphate therapy
  • Parathyroid hormone (PTH)
  • Vitamin D
  • Other factors (e.g., kidney disease, cancer)

Calcium Homeostasis Disorders

Hypercalcemia

• Defined as an increase in plasma calcium levels.
• Causes include:
  • Hyperparathyroidism
  • Multiple myeloma (bone destruction)
  • Ectopic PTH-related peptide
  • Vitamin D excess, drugs, and other endocrine disorders
• Serum PTH level is a differential test to diagnose the cause of hypercalcemia.

Hypocalcemia

• Defined as a decrease in plasma calcium levels.
• Causes include:
  • Vitamin D deficiency
  • Hypoparathyroidism
  • Hypoproteinemia (hypoalbuminemia)
  • Chronic renal failure
  • Acute pancreatitis
  • Magnesium deficiency

Osteomalacia and Rickets

• Describe a single disease, with osteomalacia occurring in adults and rickets in children.
• Characterized by softening of bones due to deficient mineralization in normal organic matrix.
• Causes include:
  • Vitamin D deficiency (dietary or sunlight-related)
  • Secondary causes (liver or kidney disease, cancer)
• Symptoms include bone pain, weakness, and deformity.

Osteoporosis

• Defined as a bone disorder characterized by significant low bone mineralization leading to weakened bone matrix and increased fracture risk.
• Causes include:
  • Vitamin D and calcium deficiency
  • Low estrogen levels
  • Medication (e.g., long-term glucocorticoid therapy)
  • Lifestyle factors (e.g., heavy alcohol consumption, smoking)
  • Hyperparathyroidism
  • Excessive caffeine
• Diagnosis involves measurement of bone mineral density (BMD) by Dual X-ray Absorptiometry (DXA scan).

Paget's Disease (Osteitis Deformans)

• Defined as a disorder of bone architecture resulting from an increased rate of bone remodeling, mainly affecting the skull and long bones.
• Characterized by increased bone resorption, followed by increased bone formation, leading to bone deformity, pain, and fracture.
• Diagnosis involves X-ray examination (cotton wool spot in the skull).

Precautions in Sample Collection

• Serum is preferred, but heparin-containing tubes are acceptable.
• Tubes containing citrate or EDTA should be avoided, as they complex with calcium and give false low results.
• Samples should be separated immediately, or stored at 4°C, or frozen for months.
• Hemolyzed samples should be rejected, as RBCs contain calcium and can give falsely elevated results.
• Lipemic samples should be rejected or diluted.

Plasma Calcium and Phosphate Levels

• Plasma calcium levels have diurnal variations, and first-morning samples are preferred.
• Diet has a high content of phosphate, and fasting samples are required.
• Hemolyzed samples should be rejected, as RBCs contain calcium and can give falsely elevated results.
• Lipemic samples should be rejected or diluted.