PARATHYROID HORMONE PARATHYROID HORMONE (PTH)(PTH)

SOURCESOURCE

SYNTHESIS SYNTHESIS

• 1. Preprohormone=110 A.A.

• 2. Prohormone= 90 A.A.

• 3. Hormone= 84 A.A.( Mol.wt.=9500)

NORMAL PLASMA VALUENORMAL PLASMA VALUE

Normal plasma value is 10 – 55 pg/ml.

Plasma half-life is 10 minutes.

MECHANISM OF ACTIONMECHANISM OF ACTION

They increase intracellular cAMP in the osteoblasts and osteocytes.

ACTIONS 0F PTHACTIONS 0F PTH

1.It increases plasma calcium level due to, increased :

a. Removal from bones.

b. Reabsorption in kidneys.

c. Absorption from G.I.T.

CALCIUM & PO4 REMOVAL CALCIUM & PO4 REMOVAL FROM BONEFROM BONE

• 1. This is done in two phases :• a. A rapid phase.

• b. A slow phase.

RAPID PHASERAPID PHASE

• 1. Begins in few minutes.

• 2. Increses for hours.

• 3. Occurs mainly due to, increasing• the membrane permeability of osteocytes, and osteoblasts, for Ca. & PO4 on the B.F.side.

• 4. This increases Ca++ entry into these cells.

5. This stimulates the Ca++ pump which pumps more Ca.++ to E.C.F. 6. This Ca.& PO4 comes from

amorphous CaPO4,& the process is called osteolysis.

SLOW PHASESLOW PHASE

• 1. Takes several days or even weeks to become • fully active.

2. Occurs due to release of factors from • osteoblasts or osteocytes.

• 3. Occurs in two stages :

• a. Activation of existing osteoclasts.• • b. Formation of new osteoclasts

ACTIONS ON KIDNEYSACTIONS ON KIDNEYS

• 1. P.T.H. increases the reabsorption of calcium in the D.T.and C.T.

• 2. It increases phosphate excretion in the urine by strongly inhibiting phosphate reabsorption in the proximal tubules.

Called Phosphaturic action.

ACTIONS ON INTESTINESACTIONS ON INTESTINES

1. Parathormone increases the activation of vitamin D3 in kidneys.

2.Calcium is absorbed from GIT under

the influence of activated vitamin D3 (1-25-dihydroxy cholecalciferol or 1,25, DHCC)

3. It enhances phosphate absorption from the intestines similarly.

REGULATION OF REGULATION OF SECRETIONSECRETION

• PTH secretion is regulated in negative feedback mechanism by action of ionized calcium on parathyroid glands.

• • When plasma calcium is high PTH secretion

is inhibited. When plasma calcium becomes low, it increases PTH

secretion.

HYPOPARATHYROIDISMHYPOPARATHYROIDISM

1. Deficiency of PTH can occur due to accidental removal of parathyroid glands during thyroid surgery.

2. Symptoms develop in 2–3 days. 3. Decreased PTH causes decreased

plasma Ca ++ and increased plasma phosphate.

4. This causes hypocalcemic tetany.

HYPOCALCEMIC TETANYHYPOCALCEMIC TETANY

• SYMPTOMS : A: At about 6ng/ dL. Increased neuromuscular excitability, causes spontaneous spasm of muscles of upper limb leading to flexion of the wrist and thumb, with extension of fingers(Carpopedal spasm.)

• B: At about 4ng/dL: Involvement of laryngeal muscles can cause noisy breathing or even airway obstruction, & death.

Tests for Latent TetanyTests for Latent Tetany

Ca. conc. Between 10 to 6ng/dL1. Chvostek’s sign :

• Tapping facial nerve causes contraction of facial muscles.

2. Trousseau’s sign :Occlusion of blood supply to upper limb

causes carpopedal spasm.

PRIMARY HYPER PRIMARY HYPER PARATHYROIDISM(MILD)PARATHYROIDISM(MILD)

• 1.This condition is due to tumour or hyperplasia of parathyroid gland.

• 2.This leads to hypercalcemia, hypophosphatemia, demineralization of the bones, hypercalciuria and formation of renal stones.

• 3.It diminishes neuronal excitability, muscle weakness & constipation.

PRIM. HYPER PRIM. HYPER PARATHYROID(SEVERE)PARATHYROID(SEVERE)

• 1. Bone reabsorption >> Deposition.

• 2. Easily fractured.

• 3. X rays show extensive decalcification, large cysts. so called Osteitis fibrosa cystica,

or Paget’s disease.

Secondary Secondary HyperparathyroidismHyperparathyroidism

1.This occurs in conditions of chronic renal disease and rickets.

2.The serum calcium is chronically low.3. Low calcium stimulates parathyroid

glands causing compensatory hypertrophy of parathyroid and secondary hyperparathyroidism.

INVESTIGATIONSINVESTIGATIONS

• 1. Serum Ca++ and PO4 .• 2. Serum Alkaline phosphatase.• 3. X ray bones, and abdomen.

CALCITRIOLCALCITRIOL

SYNTHESISSYNTHESIS

• 1. It is chemically ,1,25 dihydroxy • cholecalciferol (DHCC)

2. It is an active form of vitamin D3.

3. It is formed by the action of UV radiation on 7-dehydrocholesterol present in the skin.

FUNCTIONS OF FUNCTIONS OF CALCITRIOLCALCITRIOL

• 1. On GIT :a. Stimulates the absorption of calcium from intestines by increasing the production of Calbindin a carrier protein for calcium, Ca,H,ATPase and Alkaline phosphatase.

b. Increases the intestinal absorption of phosphates as well as magnesium.

• 2. On kidneys :• It increases Ca. & PO4 absorption from renal tubules. 3. On bones: a. Smaller quantities are necessary for normal

mineralization of bone. b. In higher quantities it causes

demineralization of bone.

REGULATION OF REGULATION OF SECRETIONSECRETION

Reduced levels of calcium lead to an increase in formation of 1,25,DHCC, through increased release of PTH.

Increased level of calcium leads to formation of inactive form,24,25,

DHCC.

RICKETSRICKETS

• Vit-D def.• A. Bone deformities in children (bowed

legs, & other weight bearing bones) B. Thickening of wrists( Increased osteoid

formation)• C. Short stature,delayed dentition.• D. Widening of epiphyseal cartilagenous

plate( seen in X rays)• E. Hypocalcemia in severe conditions.• TREATMENT: 1. Vit.D . 2. Ca.& PO4.

3.Regular exposure to sunlight.

OSTEOMALACIAOSTEOMALACIA

• 1. Occurs due to vit.D deficiency,• in adults.• 2. Causes :• a. Steatorrhea,causing loss of Ca.• and vit.D.• b. Renal rickets due to failure of• kidneys to form 1,25 DHCC.• c. Congenital hypophosphatemia.

CALCITONINCALCITONIN

SOURCESOURCE

• Secreted by type C cells or para follicular cells of thyroid gland.

• • It is a polypeptide with 32 amino acids.

• Molecular weight is about 3400.

FUNCTIONS FUNCTIONS

Decreases plasma Ca. levels : A : Major cause : a. Inhibits Ca++ and PO4 removal

from bones through osteocytes & osteoblasts.

- b.Inhibits osteoclastic activity.- c. Inhibits formation of new

osteoclasts.

• B: Minor causes :• a. Increased loss in urine.• b. ? Decreased absorption from

G.I.T.

• Actions are feeble in adults.

• MECHANISM OF ACTION It acts by increasing cyclic AMP.

• REGULATION High serum calcium levels stimulate

calcitonin secretion. Also by :Oestrogens,Gastrin.

IMPORTANCEIMPORTANCE

• 1. Much less important than PTH.

• 2. Important in children.

• 3. Not important in adults.

THANK YOUTHANK YOU