FUNCTIONAL ANATOMY OF PARATHYROID GLANDS Histological structure STRUCTURE, SYNTHESIS AND SECRETION OF PTH REGULATION OF PTH SECRETION MECHANISM OF ACTION AND ACTIONS OF PTH Applied physiology

1. Parathyroid hormone
Dr. Amruta Nitin Kumbhar
Asst. Professor
Dept. of Physiology

2. SLO
 FUNCTIONAL ANATOMY OF PARATHYROID GLANDS
 Histological structure
 STRUCTURE, SYNTHESIS AND SECRETION OF PTH
 REGULATION OF PTH SECRETION
 MECHANISM OF ACTION AND ACTIONS OF PTH
 Applied physiology

3. FUNCTIONAL ANATOMY OF PARATHYROID
GLANDS
 The parathyroid glands are two pairs of small endocrine glands closely ap
plied to the back of the thyroid gland
 gland is about the size of a split pea, measuring 6 × 4 × 2 mm. The total weight of
four normal glands is about 140 mg

4. Histological structure
 The parenchyma of the parathyroid gland is made up of cells that are arranged in
cords.
 The cells of the parathyroid glands are of two main types:
 chief cells and
 oxyphil cells.
 Chief cells, also called as principal cells, are much more numerous. Chief cells
secrete the PTH or parathormone.
 Oxyphil cells. These cells are much larger than the chief cells and first appear at
puberty and their function is still not clear.

5. STRUCTURE, SYNTHESIS AND SECRETION OF
PTH
 Structure- PTH is a single chain polypeptide, containing 84 amino acids and
having molecular weight 9500.
 Synthesis- PTH is synthesized from a precursor molecule called prepro-PTH, which
contains 115 amino acids.
 Secretion- PTH is released from the chief cells by exocytosis in response to
decrease in plasma-ionized calcium concentration that is sensed by the calcium
receptors in the parathyroid cells.

6. REGULATION OF PTH SECRETION
 1. Role of plasma-ionized calcium.
 2. Role of serum magnesium concentration
 3. Role of plasma phosphate concentration
 4. Role of vitamin 1,25(OH)2D3.

7. REGULATION OF PTH SECRETION
 1. Role of plasma-ionized calcium.

8. 2. Role of serum magnesium
concentration
 Mild decrease in serum Mg2+ concentration stimulates PTH secretion, while
 Severe decrease in serum Mg2+ concentration inhibits PTH secretion and
produces symptoms of hypoparathyroidism (e.g. hypocalcaemia).
3. Role of plasma phosphate concentration- A rise in plasma
concentration of phosphate causes an immediate fall in ionized calcium
concentration, which in turn stimulates PTH secretion.
4. Role of vitamin 1,25(OH)2D3- It inhibits transcription of the PTH gene
and decreases PTH secretion

9. PLASMA LEVELS, HALF-LIFE AND
DEGRADATION OF PTH
 Plasma level of PTH is about l30 pg/mL
(approximately 3 × 10−12 M).
 Half-life of PTH in plasma is 5–8 min.
 Degradation of PTH occurs rapidly in the peripheral tissues.
 PTH is predominantly split in the liver.

10. MECHANISM OF ACTION AND ACTIONS OF
PTH
 Mechanism of action of PTH :
 PTH binds to a membrane receptor proteins on the target
cells (in bones, kidney and intestine)
 activates adenylyl cyclase to liberate cAMP.
 The cAMP, increases intracellular calcium that promotes the
phosphorylation of proteins (by kinases).

11. Actions of PTH
1. Actions on the bone

12. 1. Actions on the bone
It stimulates calcium and phosphate resorption from the bones, i.e.
causes decalcification or demineralization of bone
(i) Rapid phase of demineralization: osteocytic osteolysis
In this process, the calcium is transferred from the bone canalicular
fluid into the osteocytes and then into the ECF.
In this process, phosphate is not mobilized along with calcium.

13. (ii) Slow phase of demineralization. This effect requires several
days of exposure to PTH.
stimulates the formation of new osteoclasts from the
osteoprogenitor initiate process of bone resorption in which
calcium and phosphate are released from bone and are
transferred to the ECF.

14. 2. Actions on kidney
(i) Increase in calcium reabsorption. PTH increases the
reabsorption of calcium from the ascending limb of loop of
Henle and the distal tubules of kidney and helps to prevent
hypocalcaemia.
(ii) Inhibition of phosphate reabsorption in the proximal tubule
is the most dramatic effect of PTH on the kidney. This effect
produces phosphaturia and hypophosphataemia.

15. 2. Actions on kidney
(iii) Stimulation of reabsorption of Mg2+ by the renal
tubules.
(iv) Stimulation of synthesis of 1,25-
dihydroxycholecalciferol is a very important action of
PTH in the kidney.

16. 3. Actions on intestines
Parathormone greatly enhances both calcium and
phosphate absorption from intestine indirectly by
increasing synthesis of 1,25-dihydroxycholecalciferol
in the kidney

17. APPLIED ASPECTS
Hyperparathyroidism and hypercalcaemia,
Hypoparathyroidism and hypocalcaemia
 Metabolic bone diseases

18. HYPERPARATHYROIDISM
1. Primary hyperparathyroidism
Aetiology: Primary hyperparathyroidism occurs due to excessive secretion
of PTH by single autonomous parathyroid adenoma (most common).
Clinicobiochemical features - Typical manifestations are
 hypercalcaemia, hypophosphataemia, hypercalciuria and renal calculi
(kidney stones)
 Hypercalcaemia may produce muscle weakness, lethargy and
constipation.
 Since calcium can stimulate release of gastrin there may occur
hyperchlorhydria and peptic ulceration.
 Hypercalcaemia may also cause hypertension, cardiac arrhythmias and
ECG changes

19. Secondary hyperparathyroidism
Excessive PTH secretion occur secondary to persistent
hypocalcaemia, which causes continued stimulation of
parathyroid gland.
Aetiology: typically seen in slowly developing renal failure.
Clinicobiochemical features:
involvement of bones.
Bone pains, fractures and deformity may result.
Alkaline phosphatase and osteocalcin levels are elevated.

20. HYPERCALCAEMIA
Causes
 depending on the levels of PTH can be divided into two
groups:
1. Conditions associated with hypercalcaemia and raised PTH
levels
2. Conditions associated with hypercalcaemia and low or
undetectable PTH levels are:
 Hypercalcaemia of malignancy,
 Multiple myeloma,
Familial hypercalcaemia,
 Hyperthyroidism,

21. Local osteolytic hypercalcaemia is seen in 20% of
the patients which have bone metastasis.
Humoral hypercalcaemia of malignancy is seen in
80% of the patients who do not have bone
metastasis.
Familial hypercalcaemia occurs due to mutations in
the gene for Ca2+ receptor.

22. HYPOPARATHYROIDISM AND
HYPOCALCAEMIA
Hypoparathyroidism refers to a clinical condition characterized
by low level of plasma calcium either due to deficient
production of PTH or its unresponsiveness.
Hypoparathyroidism can be classified into two main groups:
 True hypoparathyroidism and
Pseudohypoparathyroidism.

23. A. True hypoparathyroidism
In true hypoparathyroidism there is deficient production of
PTH due to heritable or acquired causes.
Post-ablative or post-operative hypoparathyroidism. most
common cause of hypoparathyroidism is either
damage to glands or their blood supply or
 their inadvertent removal during thyroidectomy operation.
The incidence is 1% of all the thyroidectomies.

24. B. Pseudohypoparathyroidism
This is a congenital condition, in which PTH production is
normal but the target tissues are resistant to its effects.
 The defect may lie in parathyroid receptors or there may be
post-receptor defect.
The clinical and biochemical features are similar to
hypoparathyroidism, but PTH levels are elevated (since
hypocalcaemia produces more production of PTH).

25. Characteristic features of hypoparathyroidism
Hypocalcaemia.
Total serum calcium may be decreased to 4–8 mg/dL and the
ionized calcium to 3 mg/dL.
A 50% fall in the levels of ionized calcium leads to a clinical
condition called tetany (described below).
Hyperphosphataemia, i.e. an increase in serum inorganic
phosphate levels to 6–16 mg/dL.

26. TETANY
Tetany refers to a clinical condition resulting from increased
neuromuscular excitability.
Causes of tetany include:
1. Hypocalcaemia. Extracellular calcium plays an important role in
membrane integrity and excitability. Thus when concentration of
ionic calcium is reduced to < 50% of normal in ECF, cell membrane
of neurons becomes more permeable resulting in a series of action
potentials. Thus hypocalcaemia is the most common cause of
increased neuromuscular irritability leading to tetany.
2. Hypomagnesaemia also causes tetany, because magnesium ions
are also associated with neuromuscular irritability.
3. Alkalosis, which reduces ionic calcium, can also produce tetany.

27. Clinical features
 Carpopedal spasm: The hands in carpopedal spasm adapt a peculiar
posture in which there occurs flexion at metacarpophalangeal joints,
extension at interphalangeal and there is apposition of thumb (This
peculiar posture of hand is called obstetric hand. Pedal spasm is less
frequent. In it the toes are plantarflexed and feet are drawn up.

28.  Laryngeal stridor (loud sound) results from spasm of laryngeal
muscles. It may produce asphyxia.
 Paraesthesias, i.e. tingling sensations in the peripheral parts of
limbs or around the mouth is common feature.
Trousseau’s sign :(pronounced as ‘Troosoz’s sign’). Occluding the
blood supply to a limb for about 3 min by inflation of a
sphygmomanometer cuff (above the systolic blood pressure
produces characteristic carpal spasm.
Chvostek’s sign : the twitching of facial muscles produced by
tapping the facial nerve at the angle of jaw. This occurs due to
increased excitability of nerves to mechanical stimulation.

29. Latent tetany: In latent or subclinical tetany, the
typical symptoms and signs of tetany are absent,
can be unmasked by following provocative tests:
 Trousseau’s sign and
Chvostek’s sign

30. Management
an intravenous injection of 20 mL of 10% calcium
gluconate is given to correct hypocalcaemia and
relieve tetany.

31. References
1. Text book of medical physiology Indu Khurana
2. Text book of Physiology, Gyuton 2nd south Asian Edition
3. Text book of Physiology, Ganong
4. Comprehensive Text book of Physiology, G.K.Pal vol.I
5. Internet source