CALCITROPIC HORMONES

DR NILESH KATE
MBBS,MD
ASSOCIATE PROF
ESIC MEDICAL COLLEGE, GULBARGA.
DEPT. OF PHYSIOLOGY
CALCITROPIC
HORMONES

OBJECTIVES.
 PARATHYROID HORMONES
 VITAMIN D
 CALCITONIN
 PTH- related protein and other hormones
 APPLIED ASPECTS
 Hyper parathyroidism & Hypercalcemia
 Hypoparathyroidism & Hypocalcemia
 Metabolic bone diseases.

FUNCTIONAL ANATOMY OF
PARATHYROID GLAND
 2 pairs of small glands
on back side of
thyroid.
 Size – 6×4×2
 Weight – 140 mg.
Saturday, May 12, 2018

HISTOLOGICAL STRUCTURE
 Chief cells – also called
Principal cells
 More numerous, secrete
PTH
 Oxyphil cells
 Larger than chief cells
 First appear at puberty.

STRUCTURE, SYNTHESIS AND
SECRETIONS OF PTH
 Structure – single chain
polypeptide chain,
containing 84 amino acids,
 Mol wt - 9500
 Synthesis – from
PreproPTH.
 Secretions – By amount of
Ca sensed by receptors in
parathyroid & secreted by
chief cells by exocytosis.

REGULATION OF PTH
SECRETIONS
 Role of plasma
ionized calcium.
 Max secretion occurs at
plasma Ca level –
3.5mg/dl
 Low basal rate at Ca
level 5.5mg/dl.

REGULATION OF PTH
SECRETIONS
 Role of serum Magnesium conc.-
 Mild decrease – stimulate PTH
 Severe decrease – Inhibit PTH secretion
 Role of plasma phosphate conc. – rise in P Causes
fall in Ca & rise in PTH
 Role of vit 1,25(OH)2D3- decreases PTH

PLASMA LEVEL, HALF LIFE &
DEGRADATION.
 Plasma level – 130pg/ml
 Half life – 5-8 min.
 Degradation –
 In Peripheral Tissue
 Predominantly splits in Liver

ACTIONS OF PTH
Plasma Ca Plasma P
 Actions on bone –
 Actions on kidney
 Actions on intestine

ACTIONS ON BONE
 Stimulate Ca & P reabsorpetion by
 Rapid phase of Demineralization – By Osteocytic
Osteolysis.
 Ca transferred from Bone canalicular fluid to Osteocytes
to ECF
 Slow phase of Demineralization – PTH stimulate
formation of new osteoclasts & initiate bone resorption.

ACTIONS ON KIDNEY
 Increase Ca
reabsorption
 Inhibition of P
reabsorption in PCT
 Stimulate
reabsorption of Mg
 Stimulate synthesis of
1,25(OH)2

ACTIONS ON INTESTINE
 Enhances Ca & P
reabsorption from
intestines by
increasing syntheis of
1,25(OH)2

VITAMIN D
 Closely related steroid
produced by action of
ultraviolet light on
certain provitamins
 1,25(OH)2 – active
form
 Also called as
“Calcitriol.”

FORMATION OF CALCITRIOL
 Sources of Vit D3
 Dietary sources –
fish, liver oil, egg yolk
 Daily need – 400IU

SYNTHESIS OF VITAMIN D3
 Cutaneous – Mainly
Keratinocytes.

REGULATION OF SECRETION
OF D3
 Plasma Ca
 Ca - PTH - 1,25(OH)2D3
 Plasma phosphate level
 P - 1,α-hydroxylase --
1,25(OH)2D3
 1,25(OH)2D3– by negative
feedback effect.

MECHANISM OF ACTION OF
CALCITRIOL
 By Gene expression.

ACTIONS OF CALCITRIOL
 Regulation of plasma level of calcium and phosphate
 Action on intestine – by increasing Ca absorption
 Action on Bone – by Bone resorption, Osteocytic Osteolysis, Bone
Mineralization.
 Action on Kidney- by increasing Ca & P absorption.
 Other actions of calcitriol.
 Calcium transport into skeletal & cardiac muscle
 Stimulation of differentiation of keratinocytes and inhibition of their
proliferation
 Stimulation of differentiation of immune cells.
 Regulation of growth & production of growth factors.

CALCITONIN
 Synthesis
 In C cells or
Parafollicular cells of
thyroid gland.
 Structure –
 Straight chain
polypeptide with 32
amino acids
 Mol wt -3200

REGULATION OF SECRETION
 Increase in plasma
calcium conc – only if
serum Ca < 9.5mg/dl
 Gastrointestinal
hormones – Gastrin,
CCK, Glucagon, Secretin
 Other factors – β
adreneric agonists,
Dopamine & oestrogen.

PLASMA LEVEL, HALF LIFE &
DEGRADATION.
 Plasma level – 10-20pg/ml
 Half life – less than 10 min.
 Degradation – and cleared by kidney.

ACTIONS OF CALCITONIN
 Action on bone
 Action on kidney.

PHYSIOLOGICAL SIGNIFICANCE
OF CALCITONIN
 In Kids it plays a major role in skeletal
development by promoting Ca storage in bones
 Prevents post prandial hypercalcemia.
 Protects maternal bones from excess Ca loss
during pregnancy.
 Participate in fetal skeletal development.
 Functional role in bone loss after menopause.
 Role in acute treatment of hypercalcemia & bone
diseases.

PHYSIOLOGICAL ROLE OF
PTHrP
 Regulation of
endochondral bone
formation
 Role in breast
development
 Role in tooth development
 Role in skin development.
 Protective role in CNS.

OTHER HORMONES AND HUMORAL
FACTORS AFFECTING CALCIUM
 Growth hormome
 Glucocorticoids
 Thyroid hormones
 Insulin
 Ostrogen.

APPLIED ASPECTS
Hyper parathyroidism & Hypercalcemia
Hypoparathyroidism & Hypocalcemia
Metabolic bone diseases.

HYPER PARATHYROIDISM

HYPERCALCEMIA
 Causes
 Hypercalcemia of malignancy
 Familial hypercalcemia.

HYPOPARATHYROIDISM

TRUE HYPOPARATHYROIDISM

PSEUDO
HYPOPARATHYROIDISM

TETANY
 Cause
 Hypocalcemia
 Hypomagnesemia.
 Alkalosis.
 Clinical features.
 Capopedal spasm
 Laryngeal stridor
 Parasthesias – Tingling sensation in peripheral part of limb or around
mouth.
 Trousseau’s sign- Occlusion of limb for 3 min causes carpal spasm.
 Chvostek’s sign – Tapping Fascial nerve at angle of Jaw causes
twitching of facial muscles.

METABOLIC BONE DISEASE
 Rickets – Defective bone
mineralization in children.
 Causes and types
 Vitamin D deficiency
 Vit D resistant rickets
 Clinical features
 Treatment – Vit D- 25-125
mg/day for 6-8 weeks
followed by 200-400 IU
daily.

 Osteomalacia- Adult
counterpart of Rickets
 Skeletal abnormality
 Tetany.
 Treatment- Vit D- 25-
125 mg/day for 6-8
weeks followed by 200-
400 IU daily.

 Osteoporosis – Reduction
of bone mass per unit
volume with normal ratio of
bone matrix & mineral
component.
 Bone density -
 Incidence of fractures.
 Treatments – Ca intake,
Moderate exercise &
Oestrogen treatment.

 Osteopetrosis
 Bone density increases due to
defective bone resorption.
 Osteoclast activity defective
 Features
 Neurological defects –
Narrowing of foramina of
bone through which nerve
passes.
 Haematological defects –
narrowing of bone marrow
activity.

CALCITROPIC HORMONES

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