Download MBBS Parathyroid Hormone Lecture PPT

Parathyroid hormone from parathyroid glands
Anatomy

Humans have 4 parathyroid glands.

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? 2 in superior pole of thyroid and 2 in its inferior pole.
? Contain 2 distinct cells

chief cells: contains golgi apparatus +ER + secretory

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granules.

? Secreates PTH.

Oxyphil cells : contains numerous mitochondria +oxyphil

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granules.

? Seen before puberty and no. es with age.
? Function unknown

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Parathyroid hormone
?Polypeptide hormone
?Secreted by parathyroid glands

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Preprohormone (110 A.As)ER

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prohormone (90 A.As)Golgi apparatus

hormone (84 A.As - ---->packed in secretory

granules)

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?Normal level of PTH in plasma 10-55pg/ml.

Half life approx. 10 min , removed by liver.
Physiological actions

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plasma calcium level (by its effect on bone, kidney,

intestine)On bone :-

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?Stimulates osteoclastic activity (indirect action)

bone resorption.
?PTH stimulates precursor

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cells(monocyte,macrophages,etc;)into osteoclast.
?Hydroxyproline excretion in urine is an index of

osteoclastic activity
?fast Ca2+ efflux into the plasma from the small

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labile pool
Contd.

? Stimulation of osteolysis: PTH activate the

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process of osteocytic osteolysis.

Ca from bone fluid Osteocyte

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ECF Osteoblasts
? PTH also inhibits the synthesis of collagen by

osteoblasts.

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?Net effect is in bone mass in low conc. And
in bone mass in high conc.

On kidney

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?es Ca2+ reabsorption (late DCT, collecting tubule,

ascending limb of Henle's loop) by regulating the

expression of TRPV5 channels)

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?esPO 3-

4 excretion (PCT)---> phosphaturia by

inhibiting Na-Pi II a

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enhances the activation of vitamin D by kidney

On intestine

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?Indirectly increases both Calcium and Phosphate

absorption from the small intestine by activating

vitamin D.

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Final effect :ed plasma calcium;

ed phosphate
Regulation of PTH secretion

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Plasma concentration of ionized Calcium .

?Inverse relationship
?parathyroid glands hypertrophy :-rickets,pregnancy,

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lactation
?Recently,calcium sensing receptors(CaSR) has been

identified on chief cells.

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?CaSR is a G- protein coupled receptor attached to

phospholipase C and on binding to Ca generates IP3

&DAG.

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?IP3 & DAG release Ca from cytosolic store and activate

protein kinase C that inhibits PTH secretion.
?Vitamin D : es formation of preproPTH
?Plasma phosphate

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Rise in plasma phosphate : stimulates PTH

?Other factors :

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cAMP, agonists, dopamine, histamine - level

agonists, prostaglandins - level
Mechanism of action:-

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3 receptors:-

1. hPTH/PTHrP receptor. :binds to PTH

&PTHrP,main receptor to regulate plasma

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calcium.

2. PTH2 (hPTH2-R) : binds to PTH, but not to

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PTHrP . Found in brain, placenta & pancreas

3. CPTH which reacts with the carboxyl

terminal rather than the amino terminal of

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PTH.

PTH binds to its receptors and activates both

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adenylyl cyclase and phospholipase C pathway

PTHrP

? Another protein with PTH activity..

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? Has 140 amino acid, encoded by gene on ch.12

whereas PTH by ch.11.

? Although both bind on same receptor

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hPTH/PTrP, yet their physiological actions are

different.

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? PTHrP acts close to where it is formed (paracrine

factor).

? Has effect on cartilage ,brain,placenta ,smooth

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muscle in utero.

? It is also present in enamel epithelium of teeth.
Applied physiology

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Hyperparathyroidism

Hypoparathyroidism

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primary

Hyperparathyroidism

secondary

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Primary hyperparathyroidism

Tumor of parathyroid gland

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Features :-

hypercalcemia, hypophosphatemia, demineralisation of

bone, hypercalciuria, renal stones

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Extreme PTH : parathyroid poisoning, metastatic

calcification

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?high level of plasma alkaline phosphatase --- an

important diagnostic finding
?Secondary hyperparathyroidism

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?Seen in chronic renal disease, rickets.
?In these diseases ,the chronic hypocalcemia causes

PTH secretion.
Hypoparathyroidism

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True hypoparathyroidism

- m/c : damage to glands/their blood

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supply/inadvertent removal e.g;.during thyroidectomy.

Pseudo-hypoparathyroidism

?PTH level normal/elevated

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Defect : receptors/ post-receptor

Features :-

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?hypocalcemia (6-7mg/dL)
?Hyperphosphatemia (6-16mg/dL)
Tetany

? Carpopedal spasm

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?Laryngeal spasm leading to asphyxia
?Convulsions & seizures

?Paraesthesia

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CVS :-

?dilatation of heart
?arrhythmias
?prolonged ST &QT intervals

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? hypotension
? heart failure
Latent tetany : subclinical tetany

?Neuromuscular hyperexcitability d/t

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hypocalcemia
?Provocative tests:-

Chvostek's sign

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Trousseau's sign

Management of hypoparathyroidism

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? PTH
?Vitamin D (100,000units/day) along

with calcium (1-2gms/day)
?Injections of calcium salts

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?

? Is parathyroid gland essential for life?
? Why hypoparathyroidism is common after

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thyroid surgery and its effects ?

? What is the role of plasma calcium & vit D in the

regulation of PTH secretion?

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? Difference between primary and secondary

hyperparathyroidism ?

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? In hypocalcemic tetany ,hyperexitibility is due to

.......

? List physiological actions of PTH.

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?Hypercalcemia of malignancy?
?Local osteolytic hypercalcemia?