Week 2 - Calcium, Phosphate, and Magnesium Metabolism

Calcium Metabolism

• Storage of Calcium:

  • 99% in bone/skeleton

  • 1% intracellular

  • 0.1% extracellular (predominantly bound to plasma proteins, mainly albumin)

• Functions of Calcium:

  • Essential for blood clotting

  • Muscle contraction process

  • Bone growth and remodeling

  • Cell signaling, including neurotransmitter release (exocytosis)

• Laboratory Measurement:

  • Methods include:

    • Spectrophotometric: e.g., metallochromic indicators (5-nitro-5'-methyl-BAPTA, o-cresolphthalein)

    • Ion-selective electrodes: for ionized calcium (blood gas instruments)

  • Reference range for adjusted calcium: 2.20-2.60 mmol/L

    • <2.20 mmol/L = hypocalcaemia

    • 2.60 mmol/L = hypercalcaemia

  • Adjusted Calcium Calculation:

    • Formula: adjusted calcium = measured calcium + ((40 - albumin) x 0.02)

Phosphate Metabolism

• Distribution:

  • 85% in bone, 14% in cells, 1% in blood

• Functions of Phosphate:

  • Bone mineralization

  • Energy metabolism (ATP formation)

  • Nucleic acids synthesis

  • Acts as a buffer in urine

  • Signaling and enzyme cofactor

• Laboratory Measurement:

  • Methods: Generally spectrophotometrically with ammonium molybdate indicator

  • Reference range: 0.8-1.5 mmol/L

Magnesium Metabolism

• Functions of Magnesium:

  • Enzyme cofactor for numerous reactions

  • Energy metabolism and ATP utilization

  • Membrane stabilization and neuromuscular excitability

• Laboratory Measurement:

  • Spectrophotometric methods using indicators like Xylidyl blue

  • Reference range: 0.7-1.0 mmol/L

Regulation of Calcium, Phosphate and Magnesium

• Major Regulators:

  • Parathyroid Hormone (PTH)

  • Vitamin D

  • Additional hormones:

    • PTH-related peptide (PTHrp)

    • Calcitonin

    • Fibroblast Growth Factor 23 (FGF23) affecting phosphate

• Actions of PTH:

  • Increases calcium reabsorption in kidneys

  • Promotes bone resorption and release of calcium and phosphate

  • Activates vitamin D

  • Dependent on magnesium levels for secretion

Disorders Related to Calcium, Phosphate and Magnesium

• Hypercalcemia:

  • Symptoms: bone pain, kidney stones, abdominal pain, psychological effects ("moans and groans")

  • Mechanisms: increased intestinal absorption, renal retention, and skeletal resorption

• Hypocalcemia:

  • Symptoms: neuromuscular excitability, tetany, cardiac changes

  • Causes: vitamin D deficiency, hypoparathyroidism, renal failure

• Hyperphosphatemia:

  • Linked to low calcium levels; chronic leads to tissue calcification

  • Diabetes ketoacidosis can cause acute effects due to acid-base disturbances

• Hypophosphatemia:

  • Can be asymptomatic or lead to muscle weakness and respiratory failure

  • Commonly caused by redistribution into cells or bone, or renal/GI loss

• Hypermagnesemia:

  • Very rare; results in ECG changes, respiratory issues

• Hypomagnesemia:

  • Leads to arrhythmias, confusion, muscle weakness; commonly due to malnourishment or medications

Metabolic Bone Diseases

• Osteoporosis: Low bone mass and density

• Rickets/Osteomalacia: Due to vitamin D or phosphate deficiency; diagnosed with DEXA scan

• Paget’s Disease: Affects the bone remodeling process leading to weakness

• Chronic Kidney Disease Mineral and Bone Disorders (CKD-MBD): Result from vitamin D activation issues, leading to complications in bone health

Bone Turnover Markers

• Indicative of bone health and metabolic activity

  • Formation markers: P1NP, ALP

  • Resorption markers: CTX

• Useful for monitoring treatment but subject to variability

• Further Reading: Clinical Utility of Bone Marker Measurements and other relevant literature for understanding the diagnostic implications of bone turnover markers.

Case Studies

• Case 1: 52-year-old male with low adjusted calcium, high ALP (indicating primary hyperparathyroidism possibly due to vitamin D deficiency)

• Case 2: 80-year-old male with signs pointing towards acute kidney injury related to electrolyte imbalance and metabolic derangements.