calcium homeostasis

1. Calcium
Homeostasis
PRAKASH POKHREL

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

3. Introduction
▶ Total plasma [Ca++] = 2.5mmol/L
▶ Range is 2.1 to 2.6 mmol/L
▶ Very tightly controlled
Body
content
Bone intracellular extracellular
Calcium 1300 gm 99% 1% 0.1%

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 and numbness (sensory) and
spontaneous muscle twitches (motor neurons and
muscles)

8. Functions of Calcium
▶ 2. Homeostasis
-activation of clotting enzyme is the plasma

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

10. 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

11. 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.

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

13. Calcium Homeostasis

14. 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.

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

16. Parathyroid Hormone (PTH)
▶ Regulation of PTH by plasma calcium concentration

17. Parathyroid Hormone (PTH)
▶ Mechanism
Increase in extracellular calcium concentration  Ca2+
binds to the receptor and activates phospholipase C 
increased levels of IP04/Ca2+  which inhibits PTH
secretion.
When extracellular Ca2+ is decreased, there is decreased
Ca2+ binding to the receptor, which stimulates PTH
secretion.

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

19. 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

20. 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

21. Parathyroid Hormone (PTH)

22. Vitamin D

23. Vitamin D
▶ Actions of vitamin D

24. 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

25. 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 o
2+
steoclastic bone
resorption, which decreases the plasma Ca concentration.
▶ calcitonin does
2+
not participate in the minute-to-minute regulation of
the plasma Ca concentration in humans.
▶ a physiologic role for calcitonin in humans is uncertain because
neither thyroidectomy (with decreased calcitonin levels) nor thyroid
tum
2+
ors (with increased calcitonin levels) cause a derangement of
Ca metabolism, as would be expected if calcitonin had important
regulatory functions.

26. Calcium handling in the nephron

27. 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

28. 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.

29. 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.

30. Hypocalcaemia
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

31. Hypercalcemia
▶ Causes

32. 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)

33. 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)

34. Summary
▶ A decrease in calcium level – stimulate PTH release –
increase bone reabsorption, increase Ca2+ reabsorption
from kidney (DCT), decrease PO4 reabsorption 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.

35. Reference
▶ Physiology by Linda S. Costanzo 3rd edition