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Parathyroid Gland
DANISH HASSAN
LECTURER, UNIVERSITY OF SARGODHA
Parathyroid Gland
 Human beings have four parathyroid glands,
which are situated on the posterior surface of
upper and lower poles of thyroid gland.
 Parathyroid glands are very small in size,
measuring about 6 mm long, 3 mm wide and 2
mm thick, with dark brown color.
Histology
 Made up of chief cells and oxyphil cells.
1. Chief cells:
 Secrete parathormone.
2. Oxyphil cells
 Degenerated chief cells and their function is
unknown.
 May secrete parathormone during pathological
condition called parathyroid adenoma.
Parathormone
 Secreted by parathyroid gland
 Essential for the maintenance of blood calcium
level within a very narrow critical level.
 Maintenance of blood calcium level is necessary
because calcium is an important inorganic ion for
many physiological functions.
 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
 Source of Secretion
 Secreted by the chief cells of the parathyroid
glands.
 Chemistry
 Parathormone is protein in nature, having 84 amino
acids.
 Its molecular weight is 9,500
 Half-life and Plasma Level
 Parathormone has a half-life of 10 minutes.
 Normal plasma level of PTH is about 1.5 to 5.5 ng/dL.
 Synthesis
 Synthesized from the precursor called pre-pro-PTH
containing 115 amino acids.
 First, the pre-pro-PTH enters the endoplasmic
reticulum of chief cells of parathyroid glands.
 There it is converted into a prohormone called pro-
PTH, which contains 96 amino acids.
 Pro-PTH enters the Golgi apparatus, where it is
converted into PTH.
 Metabolism
 60 – 70 % of PTH is degraded by Kupffer cells of liver,
by means of proteolysis.
 Degradation of about 20% to 30% PTH occurs in
kidneys and to a lesser extent in other organs.
 Actions Of Parathormone On Blood Calcium Level
 Primary action of PTH is to maintain the blood
calcium level within the critical range of 9 to 11
mg/dL.
 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.
 On Bones
 Parathormone enhances the resorption of calcium
from the bones by acting on osteoblasts and
osteoclasts of the bone.
 Resorption of calcium from bones occurs in two
phases:
1. Rapid phase
2. Slow phase.
 Rapid phase
 Rapid phase occurs within minutes after the release
of PTH from parathyroid glands.
 Immediately after reaching the bone, PTH gets
attached with the receptors on the cell membrane
of osteoblasts and osteocytes.
 The hormone-receptor complex increases the
permeability of membranes of these cells for
calcium ions.
 It accelerates the calcium pump mechanism, so
that calcium ions move out of these bone cells and
enter the blood at a faster rate.
 Slow phase
 Slow phase of calcium resorption from bone is due
to the activation of osteoclasts by PTH.
 When osteoclasts are activated, some substances
such as proteolytic enzymes, citric acid and lactic
acid are released from lysosomes of these cells.
 All these substances digest or dissolve the organic
matrix of the bone, releasing the calcium ions.
 The calcium ions slowly enter the blood.
 PTH increases calcium resorption from bone by
stimulating the proliferation of osteoclasts also.
 On Kidney
 PTH increases the reabsorption of calcium from the
renal tubules along with magnesium ions an
hydrogen ions.
 It increases calcium reabsorption mainly from distal
convoluted tubule and proximal part of collecting
duct.
 PTH also increases the formation of 1,25- di-
hydroxycholecalciferol (activated form of vitamin
D) from 25-hydroxycholecalciferol in kidneys.
 On Gastrointestinal Tract
 PTH increases the absorption of calcium ions from
the GI tract indirectly.
 It increases the formation of 1,25-
dihydroxycholecalciferol in the kidneys.
 This vitamin, in turn increases the absorption of
calcium from GI tract.
 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.
 Role of PTH in the activation of vitamin D
 Vitamin D is very essential for calcium absorption
from the GI tract.
 But vitamin D itself is not an active substance.
 Instead, vitamin D has to be converted into 1, 25-
dihydroxycholecalciferol in the liver and kidney in
the presence of PTH.
 The 1,25-dihydroxycholecalciferol is the active
product
 Activation of vitamin D
 There are various forms of vitamin D.
 But, the most important one is vitamin D3.
 It is also known as cholecalciferol.
 Vitamin D3 is synthesized in the skin from 7-
dehydrocholesterol, by the action of ultraviolet rays
from the sunlight.
 It is also obtained from dietary sources.
 The activation of vitamin D3 occurs in two steps:
 First step
 Cholecalciferol (vitamin D3) is converted into 25-
hydroxycholecalciferol in the liver
 This process is limited and is inhibited by 25-
hydroxycholecalciferol itself by feedback
mechanism
 Second step
 25-hydroxycholecalciferol is converted into 1,25-
dihydroxycholecalciferol (calcitriol) in kidney.
 It is the active form of vitamin D3.
 This step needs the presence of PTH
 Role of Calcium Ion in Regulating 1, 25-
Dihydroxycholecalciferol
 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:
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
 Actions of 1, 25-Dihydroxycholecalciferol
 It increases the absorption of calcium from the
intestine, by increasing the formation of calcium
binding proteins in the intestinal epithelial cells.
 These proteins act as carrier proteins for facilitated
diffusion, by which the calcium ions are transported.
 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
 It increases the synthesis of calcium-induced ATPase
in the intestinal epithelium
 It increases the synthesis of alkaline phosphatase in
the intestinal epithelium
 It increases the absorption of phosphate from
intestine along with calcium
Regulation Of Parathormone
Secretion
 Blood level of calcium is the main factor
regulating the secretion of PTH.
 Blood phosphate level also regulates PTH
secretion.
 Blood Level of Calcium
 Parathormone secretion is inversely proportional to
blood calcium level.
 Increase in blood calcium level decreases PTH
secretion.
 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.
 On the other hand, decrease in calcium ion
concentration of blood increases PTH secretion, as in
the case of rickets, pregnancy and in lactation
 Blood Level of Phosphate
 PTH secretion is directly proportional to blood
phosphate level.
 Whenever the blood level of phosphate increases it
combines with ionized calcium to form calcium
hydrogen phosphate.
 This decreases ionized calcium level in blood which
stimulates PTH secretion
Parathyroid gland

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Parathyroid gland

  • 2. Parathyroid Gland  Human beings have four parathyroid glands, which are situated on the posterior surface of upper and lower poles of thyroid gland.  Parathyroid glands are very small in size, measuring about 6 mm long, 3 mm wide and 2 mm thick, with dark brown color.
  • 3.
  • 4.
  • 5. Histology  Made up of chief cells and oxyphil cells. 1. Chief cells:  Secrete parathormone. 2. Oxyphil cells  Degenerated chief cells and their function is unknown.  May secrete parathormone during pathological condition called parathyroid adenoma.
  • 6.
  • 7. Parathormone  Secreted by parathyroid gland  Essential for the maintenance of blood calcium level within a very narrow critical level.  Maintenance of blood calcium level is necessary because calcium is an important inorganic ion for many physiological functions.
  • 8.  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.  Source of Secretion  Secreted by the chief cells of the parathyroid glands.
  • 10.  Chemistry  Parathormone is protein in nature, having 84 amino acids.  Its molecular weight is 9,500
  • 11.  Half-life and Plasma Level  Parathormone has a half-life of 10 minutes.  Normal plasma level of PTH is about 1.5 to 5.5 ng/dL.
  • 12.  Synthesis  Synthesized from the precursor called pre-pro-PTH containing 115 amino acids.  First, the pre-pro-PTH enters the endoplasmic reticulum of chief cells of parathyroid glands.  There it is converted into a prohormone called pro- PTH, which contains 96 amino acids.  Pro-PTH enters the Golgi apparatus, where it is converted into PTH.
  • 13.  Metabolism  60 – 70 % of PTH is degraded by Kupffer cells of liver, by means of proteolysis.  Degradation of about 20% to 30% PTH occurs in kidneys and to a lesser extent in other organs.
  • 14.  Actions Of Parathormone On Blood Calcium Level  Primary action of PTH is to maintain the blood calcium level within the critical range of 9 to 11 mg/dL.  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.  On Bones  Parathormone enhances the resorption of calcium from the bones by acting on osteoblasts and osteoclasts of the bone.  Resorption of calcium from bones occurs in two phases: 1. Rapid phase 2. Slow phase.
  • 16.  Rapid phase  Rapid phase occurs within minutes after the release of PTH from parathyroid glands.  Immediately after reaching the bone, PTH gets attached with the receptors on the cell membrane of osteoblasts and osteocytes.  The hormone-receptor complex increases the permeability of membranes of these cells for calcium ions.
  • 17.  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.  Slow phase  Slow phase of calcium resorption from bone is due to the activation of osteoclasts by PTH.  When osteoclasts are activated, some substances such as proteolytic enzymes, citric acid and lactic acid are released from lysosomes of these cells.  All these substances digest or dissolve the organic matrix of the bone, releasing the calcium ions.  The calcium ions slowly enter the blood.
  • 19.  PTH increases calcium resorption from bone by stimulating the proliferation of osteoclasts also.
  • 20.  On Kidney  PTH increases the reabsorption of calcium from the renal tubules along with magnesium ions an hydrogen ions.  It increases calcium reabsorption mainly from distal convoluted tubule and proximal part of collecting duct.  PTH also increases the formation of 1,25- di- hydroxycholecalciferol (activated form of vitamin D) from 25-hydroxycholecalciferol in kidneys.
  • 21.
  • 22.  On Gastrointestinal Tract  PTH increases the absorption of calcium ions from the GI tract indirectly.  It increases the formation of 1,25- dihydroxycholecalciferol in the kidneys.  This vitamin, in turn increases the absorption of calcium from GI tract.  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.
  • 23.  Role of PTH in the activation of vitamin D  Vitamin D is very essential for calcium absorption from the GI tract.  But vitamin D itself is not an active substance.  Instead, vitamin D has to be converted into 1, 25- dihydroxycholecalciferol in the liver and kidney in the presence of PTH.  The 1,25-dihydroxycholecalciferol is the active product
  • 24.
  • 25.  Activation of vitamin D  There are various forms of vitamin D.  But, the most important one is vitamin D3.  It is also known as cholecalciferol.  Vitamin D3 is synthesized in the skin from 7- dehydrocholesterol, by the action of ultraviolet rays from the sunlight.  It is also obtained from dietary sources.
  • 26.  The activation of vitamin D3 occurs in two steps:  First step  Cholecalciferol (vitamin D3) is converted into 25- hydroxycholecalciferol in the liver  This process is limited and is inhibited by 25- hydroxycholecalciferol itself by feedback mechanism
  • 27.  Second step  25-hydroxycholecalciferol is converted into 1,25- dihydroxycholecalciferol (calcitriol) in kidney.  It is the active form of vitamin D3.  This step needs the presence of PTH
  • 28.
  • 29.  Role of Calcium Ion in Regulating 1, 25- Dihydroxycholecalciferol  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:
  • 30. 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
  • 31.  Actions of 1, 25-Dihydroxycholecalciferol  It increases the absorption of calcium from the intestine, by increasing the formation of calcium binding proteins in the intestinal epithelial cells.  These proteins act as carrier proteins for facilitated diffusion, by which the calcium ions are transported.  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
  • 32.  It increases the synthesis of calcium-induced ATPase in the intestinal epithelium  It increases the synthesis of alkaline phosphatase in the intestinal epithelium  It increases the absorption of phosphate from intestine along with calcium
  • 33.
  • 34. Regulation Of Parathormone Secretion  Blood level of calcium is the main factor regulating the secretion of PTH.  Blood phosphate level also regulates PTH secretion.
  • 35.  Blood Level of Calcium  Parathormone secretion is inversely proportional to blood calcium level.  Increase in blood calcium level decreases PTH secretion.  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.
  • 36.  On the other hand, decrease in calcium ion concentration of blood increases PTH secretion, as in the case of rickets, pregnancy and in lactation
  • 37.
  • 38.  Blood Level of Phosphate  PTH secretion is directly proportional to blood phosphate level.  Whenever the blood level of phosphate increases it combines with ionized calcium to form calcium hydrogen phosphate.  This decreases ionized calcium level in blood which stimulates PTH secretion