2. Parathyroid Gland
ο Human beings have four parathyroid glands, which
are situated on the posterior surface of upper and
lower poles of thyroid gland.
ο Develop at about 10 th week of pregnancy from 3 and
4 branchial pouches
ο Parathyroid glands are very small in size, measuring
about 6 mm long, 3 mm wide and 2 mm thick, with
dark brown color.
ο Major regulator of calcium and phosphate metabolism
3.
4.
5. Histology
ο Made up of chief cells and oxyphil cells.
1.Chief cells:
2.predominant
ο Secrete parathormone.
3.Oxyphil cells
ο Degenerated chief cells and their function is
unknown.
ο May secrete parathormone during pathological
condition called parathyroid adenoma.
6.
7. Parathormone
ο Secreted by parathyroid gland
ο Essential for the maintenance of blood calcium
level within a very narrow critical level.
ο Maintenance of blood calcium level is necessary
because calcium is an important inorganic ion for
many physiological functions.
8. ο Calcium is very essential for many activities in the
body such as:
1. Bone and teeth formation
2. Neuronal activity
3. Skeletal muscle activity
4. Cardiac activity
5. Smooth muscle activity
6. Secretory activity of the glands
7. Cell division and growth
8. Coagulation of blood
9. ο Source of Secretion
ο Secreted by the chief cells of the parathyroid
glands.
11. ο Half-life and Plasma Level
ο Parathormone has a half-life of 10 minutes.
ο Normal plasma level of PTH is about 1.5 to 5.5
ng/dL.
12. ο Synthesis
ο Synthesized from the precursor called pre-pro-PTH
containing 115 amino acids.
ο First, the pre-pro-PTH enters the endoplasmic
reticulum of chief cells of parathyroid glands.
ο There it is converted into a prohormone called pro-
PTH, which contains 96 amino acids.
ο Pro-PTH enters the Golgi apparatus, where it is
converted into PTH.
13. ο Metabolism
ο 60 β 70 % of PTH is degraded by Kupffer cells of
liver, by means of proteolysis.
ο Degradation of about 20% to 30% PTH occurs in
kidneys and to a lesser extent in other organs.
14. ο Actions Of Parathormone On Blood Calcium
Level
ο Primary action of PTH is to maintain the blood
calcium level within the critical range of 9 to 11
mg/dL.
ο PTH maintains blood calcium level by:
1. Resorption of Ca from Bones
2. Reabsorption Ca from the renal tubules (Kidney)
3. Absorption of Ca from Gastrointestinal tract.
15. ο On Bones
ο Parathormone enhances the resorption of calcium
from the bones by acting on osteoblasts and
osteoclasts of the bone.
ο Resorption of calcium from bones occurs in two
phases:
1. Rapid phase
2. Slow phase.
16. ο Rapid phase
ο Rapid phase occurs within minutes after the release
of PTH from parathyroid glands.
ο Immediately after reaching the bone, PTH gets
attached with the receptors on the cell membrane of
osteoblasts and osteocytes.
ο The hormone-receptor complex increases the
permeability of membranes of these cells for
calcium ions.
17. ο It accelerates the calcium pump mechanism, so
that calcium ions move out of these bone cells and
enter the blood at a faster rate.
18. ο Slow phase
ο Slow phase of calcium resorption from bone is due
to the activation of osteoclasts by PTH.
ο When osteoclasts are activated, some substances
such as proteolytic enzymes, citric acid and lactic
acid are released from lysosomes of these cells.
ο All these substances digest or dissolve the organic
matrix of the bone, releasing the calcium ions.
ο The calcium ions slowly enter the blood.
19. ο On Kidney
ο PTH increases the reabsorption of calcium from the
renal tubules along with magnesium ions an
hydrogen ions.
ο It increases calcium reabsorption mainly from distal
convoluted tubule and proximal part of collecting
duct.
ο PTH also increases the formation of 1,25- di-
hydroxycholecalciferol (activated form of
vitamin D) from 25-hydroxycholecalciferol in
20. ο On Gastrointestinal Tract
ο PTH increases the absorption of calcium ions from the
GI tract indirectly.
ο It increases the formation of 1,25-
dihydroxycholecalciferol in the kidneys.
ο This vitamin, in turn increases the absorption of calcium
from GI tract.
ο Thus, the activated vitamin D is very essential for the
absorption of calcium from the GI tract & PTH is
essential for the formation of activated vitamin D.
21. ο Role of PTH in the activation of vitamin D
ο Vitamin D is very essential for calcium absorption
from the GI tract.
ο But vitamin D itself is not an active substance.
ο Instead, vitamin D has to be converted into 1, 25-
dihydroxycholecalciferol in the liver and kidney in
the presence of PTH.
ο The 1,25-dihydroxycholecalciferol is the active
product
22.
23. ο Activation of vitamin D
ο There are various forms of vitamin D.
ο But, the most important one is vitamin D3.
ο It is also known as cholecalciferol.
ο Vitamin D3 is synthesized in the skin from 7-
dehydrocholesterol, by the action of ultraviolet rays
from the sunlight.
ο It is also obtained from dietary sources.
24. ο The activation of vitamin D3 occurs in two steps:
ο First step
ο Cholecalciferol (vitamin D3) is converted into 25-
hydroxycholecalciferol in the liver
ο This process is limited and is inhibited by 25-
hydroxycholecalciferol itself by feedback
mechanism
25. ο Second step
ο 25-hydroxycholecalciferol is converted into 1,25-
dihydroxycholecalciferol (calcitriol) in kidney.
ο It is the active form of vitamin D3.
ο This step needs the presence of PTH
26.
27. ο Role of Calcium Ion in Regulating 1, 25-Dihydroxycholecalciferol
ο When blood calcium level increases, it inhibits the
formation of 1,25-dihydroxycholecalciferol. The
mechanism involved in the inhibition of the
formation of 1,25-dihydroxycholecalciferol is as
follows:
28. 1. Increase in calcium ion concentration directly
suppresses the conversion of 25-
hydroxycholecalciferol into 1,25-dihydroxy
cholecalciferol.
2. Increase in calcium ion concentration decreases
the PTH secretion, which in turn suppresses the
conversion of 25-hydroxycholecalciferol into 1,25-
dihydroxycholecalciferol
29. ο Actions of 1, 25-Dihydroxycholecalciferol
ο It increases the absorption of calcium from the
intestine, by increasing the formation of calcium
binding proteins in the intestinal epithelial cells.
ο These proteins act as carrier proteins for facilitated
diffusion, by which the calcium ions are transported.
ο The proteins remain in the cells for several weeks
after 1,25-dihydroxycholecalciferol has been
removed from the body, thus causing a prolonged
effect on calcium absorption
30. ο It increases the synthesis of calcium-induced
ATPase in the intestinal epithelium
ο It increases the synthesis of alkaline phosphatase in
the intestinal epithelium
ο It increases the absorption of phosphate from
intestine along with calcium
31. Regulation Of Parathormone Secretion
ο Blood level of calcium is the main factor
regulating the secretion of PTH.
ο Blood phosphate level also regulates PTH
secretion.
32. ο Blood Level of Calcium
ο Parathormone secretion is inversely proportional to
blood calcium level.
ο Increase in blood calcium level decreases PTH
secretion.
ο Conditions when PTH secretion decreases are:
1. Excess quantities of calcium in the diet
2. Increased vitamin D in the diet
3. Increased resorption of calcium from the bones,
caused by some other factors such as bone
diseases.
33.
34. ο On the other hand, decrease in calcium ion
concentration of blood increases PTH secretion, as in
the case of rickets, pregnancy and in lactation
35.
36. ο Blood Level of Phosphate
ο PTH secretion is directly proportional to blood
phosphate level.
ο Whenever the blood level of phosphate increases it
combines with ionized calcium to form calcium
hydrogen phosphate.
ο This decreases ionized calcium level in blood which
stimulates PTH secretion