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%
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)
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
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.
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
- 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
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
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 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.
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
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.
