PARATHYROID HORMONE (PTH)

SOURCE

SYNTHESIS 1. Preprohormone=110 A.A. 2. Prohormone= 90 A.A. 3. Hormone= 84 A.A.( Mol.wt.=9500)

NORMAL PLASMA VALUE Normal plasma value is 10 – 55 pg/ml. Plasma half-life is 10 minutes.

MECHANISM OF ACTION They increase intracellular cAMP in the osteoblasts and osteocytes.

ACTIONS 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 FROM BONE CALCIUM & PO4 REMOVAL FROM BONE 1. This is done in two phases : a. A rapid phase. b. A slow phase.

RAPID 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 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 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 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 SECRETION 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.

HYPOPARATHYROIDISM 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 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 Tetany Ca. conc. Between 10 to 6ng/dL 1. 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 PARATHYROIDISM(MILD) PRIMARY HYPER 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 PARATHYROID(SEVERE) PRIM. HYPER 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 Hyperparathyroidism 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.

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

CALCITRIOL

SYNTHESIS 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 CALCITRIOL 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 SECRETION 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.

RICKETS 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.

OSTEOMALACIA 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.

CALCITONIN

SOURCE 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 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.

IMPORTANCE 1. Much less important than PTH. 2. Important in children. 3. Not important in adults.

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