Transcript 4c990df2d120a89

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
• 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)
• 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)
• 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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