Calcium homeostasis is tightly regulated by the interaction of the parathyroid gland, kidneys, bone, intestine, and hormones. Parathyroid hormone (PTH) increases blood calcium levels by promoting bone resorption and renal calcium reabsorption. Vitamin D assists PTH by increasing intestinal calcium absorption. Disorders occur when calcium levels decrease or increase outside the normal range, which can cause symptoms like numbness, seizures, or kidney stones. Maintaining balanced calcium levels requires the coordinated functions of multiple organ systems and hormones.

1. Calcium Homeostasis
Faez Baherin MBBS
MMed (Emergency) Training Programme USM
Supervised by Dr Hashairi

2. Outline
• Introduction
• Calcium metabolism
- PTH, Calcitonin, Vitamin d
• Functions of calcium
• Disorders of calcium
• Summary

3. Introduction
Body Bone intracellular extracellular
content
Calcium 1300 gms 99% 1% 0.1%
• Total plasma [Ca++] = 2.5mmol/L
• Range is 2.0 to 2.5 mmol/L
• Very tightly controlled

4. Introduction

5. Factors affecting calcium
concentration
1) Changes in plasma protein concentration
- Increased [protein] – increased total [Ca2+]
2) Changes in anion concentration
- Increased [anion] – increased fraction of Ca2+
that is complexed – decrease ionized [Ca2+]
3)Acid base abnormality

6. Acid Base Abnormality

7. Functions of Calcium
• 1. Nerve and muscle functions
- Decreased extracellular calcium – increase
excitability of excitable cells and lowers the
threshold potential – less inward current is
required to depolarize the threshold potential
– less inward current is required to fire AP
- Hence causing tingling ad numbness (sensory)
and spontaneous muscle twitches (motor
neurons and muscles)

8. Functions of Calcium
Cross
bridge
cycling

9. • Increase in intracellular Ca2+ concentration
 Ca2+ binds to troponin C  conformational
change in the troponin complex  moves
tropomyosin out of the way  permitting the
binding of actin to the myosin heads leading
cross-bridge formation and the muscle
contracts as a whole

10. Functions of Calcium
• 2. Homeostasis
-activation of clotting enzyme is the plasma

11. Functions of Calcium
• 3. Preserving bone density
- construction, formation and maintenance of
bone and teeth. This function helps reduce
the occurrence of osteoporosis

12. Functions of Calcium
• 4. Neurotransmitter release
- Directly proportional to the calcium level
- Arrival of action potential to axonal terminal
opening of voltage gated calcium channels
calcium influx into the terminal  transmitter
vesicle fuse with the release sites 
exocytosis-release of transmitters into the
cleft

13. Functions of Calcium
• 5. Calcium assists in maintaining all cells and
connective tissues in the body and regulating
mitotic transition and cell division.
• 6. Essential component in the production of
enzyme and hormones that regulate
digestion, energy, and fat metabolism.

14. Calcium Homeostasis
• Blood calcium is tightly regulated by:
1) Principle organ systems:
Intestine
Bone
Kidney
2) Hormones:
Parathyroid hormone (PTH)
Vitamin D
Calcitonin

15. Calcium Homeostasis

16. Parathyroid Hormone (PTH)
• There are 4 parathyroids glands, located on
the dorsal side of the thyroid
• The blood supply to the parathyroid glands is
from the thyroid arteries.

17. Parathyroid Hormone (PTH)
• Chief cells secrete PTH
• Oxyphil cells – function unknown. Probably
degenerated chief cells

18. Parathyroid Hormone (PTH)
• Regulation of PTH by plasma calcium
concentration

19. Parathyroid Hormone (PTH)
• Mechanism
Increase in extracellular calcium concentration
 Ca2+ binds to the receptor and activates
phospholipase C  increased levels of
IP3/Ca2+  which inhibits PTH secretion.
When extracellular Ca2+ is decreased, there is
decreased Ca2+ binding to the receptor, which
stimulates PTH secretion.

20. Parathyroid Hormone (PTH)
• Actions of PTH on bone, kidney and small intestine
• Direct vs indirect
1) Actions on bone
- PTH receptors on osteoblasts – initial bone formation
(direct action)
- Later on – bone resorption (indirect action) via
cytokines from osteoblast
- Overall effect : promote bone resorption and increase
calcium concentration

21. Parathyroid Hormone (PTH)
• 2. Actions on kidneys

22. Parathyroid Hormone (PTH)
a) Inhibits PO4 reabsorption (inhibits Na-PO4
cotransport in PCT) – phosphaturia – less
complexed Ca-PO4 – increase plasma calcium
b) Stimulates calcium reabsorption (on DCT)
Phosphaturia + Ca2+ reabsorption = increase in
Ca2+ concentration

23. Parathyroid Hormone (PTH)
• 3. Actions on small intestine (indirect)
- Stimulates Ca2+ reabsorption via activation of
vitamin D.
- PTH stimulates renal 1 alpha hydroxylase 
converts 25-hydroxycholecalciferol to 1.25
dihydroxycholecalciferol  stimulates intestinal
Ca2+ absorption

24. Parathyroid Hormone (PTH)

25. PTH Active Bone Urine Serum Serum
Disorder Vit.D Calcium Phosphate
Primary ↑* ↑ ↑ Resorption ↑phosphate ↑ ↓
Hyperparathyroidism ↑ Ca2
↑ cAMP
Surgical ↓* ↓ ↓ Resorption ↓phosphate ↓ ↑
Hypoparathyroidism ↓ cAMP
Pseudohypo- ↑ ↓ ↓ Resorption ↓phosphate ↓ ↑
parathyroidism ↓ cAMP
defective Gs
Humoral ↓ ↑ ↑ Resorption ↑phosphate ↑ ↓
Hypercalcemia of ↑ Ca2
Malignancy ↑ cAMP
(↑ PTH-rp*)
Chronic Renal Failure ↑ ↓* Osteomalacia ↓ Urine ↓ ↑ (due to
↑ Resorption phosphate ↓1,25- ↓ urine
(due to ↓ dihydroxych phosphate)
GFR)* olecalciferol

26. Vitamin D

27. Vitamin D
• Actions of vitamin D

28. Vitamin D
• Common diseases related to vitamin D
1) Rickets - insufficient amounts of calcium and
phosphate to mineralize the growing bones
 growth failure and skeletal deformities
2) Osteomalacia – new bone fails to mineralize
 bending and softening of weight bearing
bones

29. Calcitonin
• a straight-chain peptide with 32 amino acids.
• synthesized and secreted by the parafollicular cells of the thyroid
gland.
• major stimulus for calcitonin secretion is increased plasma Ca2+
concentration
• The major action of calcitonin is to inhibit osteoclastic bone
resorption, which decreases the plasma Ca2+ concentration.
• calcitonin does not participate in the minute-to-minute regulation
of the plasma Ca2+ concentration in humans.
• a physiologic role for calcitonin in humans is uncertain because
neither thyroidectomy (with decreased calcitonin levels) nor thyroid
tumors (with increased calcitonin levels) cause a derangement of
Ca2+ metabolism, as would be expected if calcitonin had important
regulatory functions.

30. Calcium handling in the nephron

31. Calcium handling in the nephron
- 67% of the filtered load is reabsorbed @ PCT
- Ca2+ reabsorption is tightly coupled to Na+
reabsorption in the proximal tubule

32. Calcium handling in the nephron
- @ ALH , 25% of the filtered load of Ca2+ is reabsorbed
- The mechanism of coupling in the thick ascending limb
depends on the lumen-positive potential difference,
which is generated by the Na+-K+-2Cl- cotransporter.
- Loop diuretics such as furosemide inhibit Ca2+
reabsorption to the same extent that they inhibit Na+
reabsorption.

33. Calcium handling in the nephron
• @ DT 8% of the filtered load of Ca2
• the site of regulation of Ca2+ reabsorption.
• the distal tubule is the only nephron segment in which Ca2+
reabsorption is not coupled directly to Na+ reabsorption.
• it has its own regulatory hormone, PTH.
• Thiazide diuretics increase Ca2+ reabsorption, while the other
classes of diuretics decrease it.

34. Hypocalcemia
• Causes

35. Hypocalcemia
Symptoms and signs
• "CATS go numb"- Convulsions, Arrythmias,
Tetany and numbness/parasthesias in hands,
feet, around mouth and lips.
• Trousseau sign of latent tetany (eliciting carpal
spasm by inflating the blood pressure cuff and
maintaining the cuff pressure above systolic)
• Chvostek's sign (tapping of the inferior portion
of the zygoma will produce facial spasms

36. Hypercalcemia
• Causes

37. Hypercalcemia
"Stones, Bones, Groans, Thrones and Psychiatric Overtones“
-Stones (renal or biliary)
-Bones (bone pain)
-Groans (abdominal pain, nausea and vomiting)
-Thrones (sit on throne - polyuria)
-Psychiatric overtones (Depression 30-40%, anxiety, cognitive dysfunction, insomnia,
coma)

38. Calcium Imbalance

39. Summary
• Calcium is crucial for body physiological
function
• It must be tightly regulated to maintain
physiological stability, by the interaction
between the major organs (Intestine, kidney,
bone) and hormones ( PTH, Calcitonin,
Vitamin D)

40. Summary
• A decrease in calcium level – stimulate PTH
release – increase bone resorption, increase Ca2+
reabsorption from kidney (DCT), decrease PO4
reasbsorption from kidney (PCT), and increase
calcium uptake from GI (indirect)
• Vitamin D – same action but increase PO4
reabsorption from kidney
• Calcium imbalance must be recognized and
treated early to prevent any catastrophe.

41. Reference
• Physiology by Linda S. Costanzo 3rd edition