Major electrolytes such as sodium, potassium, calcium, magnesium, chloride, bicarbonate, and phosphate are distributed differently between the extracellular fluid (ECF) and intracellular fluid (ICF) compartments. Calcium homeostasis is tightly regulated by parathyroid hormone (PTH), vitamin D, and calcitonin which act to increase or decrease calcium resorption in bones and reabsorption in kidneys. Hypocalcemia and hypercalcemia can result from disorders of the parathyroid glands or kidneys. Similarly, phosphate levels are regulated by PTH, vitamin D, and calcitonin to affect bone levels, and disorders can cause hypo- or hyperphosphatemia. Magnesium is also regulated and

1. DR FARHANA ATIA
ASSOCIATE PROFESSOR, BIOCHEMISTRY
NILPHAMARI MEDICAL COLLEGE, NILPHAMARI
Major Electrolytes &
Their Homeostasis

2. ELECTROLYTE DISTRIBUTION
ELECTROLYTES ECF ICF
Na⁺ 140 mmol/L 10 mmol/L
K⁺ 4 mmol/L 140 mmol/L
Ca⁺⁺ 2.5 mmol/L 0.1 μmol/L
Mg⁺⁺ 1.5 mmol/L 30 mmol/L
Cl⁻ 100 mmol/L 4 mmol/L
HCO₃⁻ 27 mmol/L 10 mmol/L
PO₄⁻⁻ 2 mmol/L 60 mmol/L
Glucose 5.5 mmol/L 0-1 mmol/L
Protein 2 gm/dL 16 gm/dL
Harper’s Illustrated Biochemistry 31st edition p-460

3. Calcium
Calcium is the most abundant mineral in our body
Body calcium content: 1-1.5 kg
In skeletal system (bones & teeth): >99% as hydroxyapatite
crystal
In soft tissue cell: 0.5%
In ECF: 0.1-0.2%
Hydroxyapatite crystal:
Ca₉(PO₄)₆ + Ca⁺⁺ + 2H₂O Ca₁₀(PO₄)₆ (OH)₂ + 2H⁺

4. Distribution of plasma Calcium
Total plasma Ca : 2.5 mmol/L
Diffusible: 1.34 mmol/L 60%
• 50% of total is ionized Ca: 1.18 mmol/L (active form/ free form)
• 10% of total as complex with HCO₃⁻, PO₄⁼, citrate: 0.16 mmol/L
Non diffusible (Protein-bound): 1.16 mmol/L 40%
• 80% (32% of total) bound to albumin: 0.92 mmol/L
• 20% (8% of total) bound to globulin: 0.24 mmol/L

5. Free Calcium is Physiologically Important
It is the biologically active form of calcium
This free calcium (not total calcium) is under hormonal
control
The free calcium concentration determine the body calcium
status
Normocalcemia
Hypocalcemia
Hypercalcemia

6. Assessment of Calcium Status
Direct method: Measure free Ca⁺⁺
conc.
Indirect method: Measure total
calcium conc. & albumin conc.
T [Ca] ↑↑
[Alb] ↑↑
Free Ca normal
No symptom
T [Ca] normal
[Alb] ↓
Free Ca ↑
Hypercalcaemia
T [Ca] normal
[Alb] ↑
Free Ca ↓
Hypocalcaemia
Adjusted Calcium level: In
abnormal serum albumin
concentration
Total [Ca] + 0.02X(47-A) gm/L
[Total body albumin= 47 gm
1 gm albumin binds with 0.02
mmol/L of Ca]

7. Calcium Balance
Intake: 800 mg/day (orally)
Output: 800 mg/day (Urine- 200 mg/day, Stool- 600 mg/day)
Renal Handling of Ca⁺⁺
Tubular Load: 250 mmol/day
Reabsorption: about 98%
PCT: 60-70%
ALLH: 20%
DCT & CD: 5-10% (Major site for regulation of Ca excretion)
 Excretion: 15-20 mmol/day; < 5% of TL

8. Regulation of Plasma Ca Homeostasis
Parathyroid Hormone (PTH): ↑Ca⁺⁺
Vitamin D/ Calcitriol [1,25(OH)₂D₃]: ↑Ca⁺⁺
Calcitonin: ↓Ca⁺⁺
Magnesium: ↓Mg⁺⁺ prevents PTH release & cause ↓Ca⁺⁺
Plasma binding: Approximately 40% of plasma Ca is
bound to plasma protein & remaining free Ca is
biologically active. Labs usually measure total plasma Ca.
So total Ca for albumin needs to be corrected.

9. Parathyroid Hormone (PTH)
Secretion: By four parathyroid gland
Stimulation: By ↓serum Ca⁺⁺
Overall effect: ↑Ca⁺⁺ & ↓PO₄³⁻
Actions:
↑ Osteoclast activity by releasing Ca⁺⁺ &
PO₄³⁻ from bones
↑Ca⁺⁺ & ↓PO₄³⁻ reabsorption in the
kidney
↑ Renal production of active vitamin D

10. Calcitriol
Biologically active form of vitamin D
Stimulation by ↓Ca⁺⁺, ↓PO₄³⁻ & ↑PTH
 Actions are:
↑Ca⁺⁺ & ↑PO₄³⁻ absorption from the
gut
Inhibition of PTH release
Enhance bone turnover
↑Ca⁺⁺ & ↑PO₄³⁻ reabsorption in the
kidney
Calcitriol

11. Calcitonin
Made in C cells of thyroid
Overall effect: ↓Ca⁺⁺ & ↓PO₄³⁻
Actions:
◦Opposite effect of Vit-D &
PTH
↓Ca mobilization from bone
↑ Ca excretion in kidney

12. Hypocalcemia
Causes of hypocalcemia (<2 mmol/L)
With ↑PO₄³⁻ With ↔ or ↓PO₄³⁻
Chronic kidney disease
Hypoparathyroidism
Pseudohypoparathyroidism
Acute rhabdomyolysis
Hypomagnesemia
Vitamin D deficiency
Osteomalacia
Acute pancreatitis
Overhydration
Respiratory alkalosis

13. Features of Hypocalcemia
Spasm (carpopedal spasm: Trousseau’s sign)
Perioral paresthesia
Seizure
Laryngospasm
Neuromuscular excitability
(Chvostek’s sign)
Cataract
Cardiomyopathy

14. Hypercalcemia (>2.5 mmol/L)
Dehydration
Hyperparathyroidism
(1⁰ or 3⁰)
Myeloma
Vitamin D excess
Sarcoidosis
Milk-alkali-syndrome
Bone metastases from
◦ Breast
◦ Lung
◦ Prostate
◦ Kidney
◦ Thyroid
Thyrotoxicosis
Lithium

15. Phosphate
Second most abundant mineral in the body (1% of total
body weight)
Body phosphate content
In skeletal system: 85% ; 500-700 gm; as hydroxyapatite
crystal
In soft tissue: as nucleic acid, cell membrane
phospholipid
In plasma: 0.81 to 1.45 mmol/L

16. Importance of Phosphate
Build and repair bones and teeth
 Integral component of several organic compounds, including
nucleic acids and cell membrane phospholipids
 Involved in aerobic and anaerobic energy metabolism (2,3-
DPG, ADP, ATP)
Major intracellular anion but is also present in plasma
Help nerves function, make muscles contract
Also help with the kidney function & Normal heartbeat

17. Renal Handling of Phosphate
Tubular load: 150-200 mmol/day
Reabsorption: About 90%
In PCT: 70-80% reabsorption
Mechanism: Na⁺-PO₄³⁻ symport
mechanism which is inhibited by
PTH hormone
Excretion: About 10%; 20 mmol/day

18. Regulation of Phosphate
The amount of phosphate in the blood affects the
level of calcium in the blood
Calcium and phosphate in the body react in opposite
ways: as blood calcium levels rise, phosphate levels fall
Parathyroid Hormone (PTH): ↓PO₄³⁻
Vitamin D/ Calcitriol [1,25(OH)₂D₃]: ↑PO₄³⁻
Calcitonin: ↓PO₄³⁻

19. Hypophosphatemia
Common & little significance unless severe (<0.4 mmol/L)
Causes:
Vitamin D deficiency
Inadequate oral intake
Severe diabetic ketoacidosis
Renal tubular dysfunction
Primary hyperparathyroidism

20. Hyperphosphatemia
Rare
Usually due to chronic kidney disease
Hypoparathyroidism
Metabolic acidosis
Respiratory acidosis

21. Magnesium
Distribution in body
In bone: 65%
In cells: 35%
Plasma concentration (0.85 to 1.10 mmol/L) tends to follow
that of Ca⁺⁺ & K⁺
Mg2+ homeostasis depends on three organs:
Intestine: facilitating Mg2+ uptake
Bone: main Mg2+ storage system of the body
Kidney: responsible for Mg2+ excretion

22. Disorder of Magnesium Homeostasis
Hypomagnesemia
Diuretics
Severe diarrhea
Ketoacidosis
Alcohol abuse
With ↓Ca⁺⁺, ↓K⁺, ↓PO₄³⁻
Hypermagnesemia
Little significance unless
severe (>7.5 mmol/L)
Renal failure
Iatrogenic (excessive
antacids)

23. Thank You