Transcript 4-En-Parathyroid

Parathyroid Gland and
Related Hormones
Vitamin D and Calcitonin
Prof. K. Sivapalan
Structure of Bone
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Cells in Bone
• Osteocytes- resting cells.
• Osteoblasts are active in bone formation
• Calcification occurs only in bone and not usually
in tissues.
• Osteoclasts are responsible for removal of bone
• Remodeling- continuous removal and formation.
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Bone structure .
• Collagen fiber laid down by fibroblasts is the
basic inter cellular substance.
• Hydroxyappetite [Ca10(PO4)6(OH)2] crystals +
other surface crystals, CaHPO4 are deposited
on collagen by osteoblasts.
• Osteocytes are arranged in Havesian system.
• Stimuli of bone formation– stress and strain.
– growth factors and hormones.
– (calcium and protein)
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Plasma Calcium.
• Calcium phosphate readily ionizes and
equilibrates with plasma.
• Plasma calcium– 50% bound to protein,
– 5% complex with anions of plasma,
– 45% ionized (active).
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Calcium Balance
• Gain during growth.
• Plateau- middle age.
• Loss in old age osteoporosis.
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Phosphorous
• Total body phosphorus is 500 to 800 g (16.1–
25.8 mol), 85–90% of which is in the skeleton.
• Total plasma phosphorus is about 12 mg/dL,
with two-thirds of this total in organic compounds
and the remaining inorganic phosphorus (Pi)
mostly in PO43–, HPO42–, and H2PO4–.
• The amount of phosphorus normally entering
bone is about 3 mg (97 µmol)/kg/d, with an
equal amount leaving via reabsorption
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Vitamin D.
• Control of synthesis:
• Feed back in kidney- higher plasma calcium
inhibiting [production of inactive 24,25
dihydroxycholycalciferol]
• Parathormaone stimulation production in
kidney
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Actions of Vitamin D.
• Increases absorption of Calcium in intestine and
kidney [Calbindins in intestine, kidney etc].
• Increases osteoclasts in bone.
• Increase plasma calcium.
• Bone formation ? Indirect through plasma
calcium levels.
• Differentiation of immune cells and keratinocytes
of skin.
• Rickets is the result of deficiency in children.
Low plasma calcium leads to non calcification of
epyphysis with excess growth of cartilage and
week bone. Adults- osteomalasia.
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“Anti-aging" protein
• An "anti-aging" protein called -Klotho (named after Klotho, a
daughter of Zeus in Greek mythology who spins the thread of life)
has also recently been discovered to play important roles in calcium
and phosphate homeostasis, in part by reciprocal effects on 1,25dihydroxycholecalciferol levels.
• Mice deficient in -Klotho displayed accelerated aging, decreased
bone mineral density, calcifications, and hypercalcemia and
hyperphosphatemia. -Klotho plays an important role in stabilizing the
membrane localization of proteins important in calcium and
phosphate (re)absorption, such as TRPV5 and Na, K ATPase.
• Likewise, it enhances the activity of another factor, fibroblast growth
factor 23 (FGF23), at its receptor. FGF23 thereby decreases renal
NaPi-IIa and NaPi-IIc expression and inhibits the production of 1 hydroxylase, reducing levels of 1,25-dihydroxycholecalciferol
(Clinical Box 23–1).
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CALCITONIN.
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From para follicular cells of thyroid.
32 amino acids, 3000 mw.
EffectsReduce osteiclastic activity
Increase osteoblastic activity.
Reduce formation of osteoblasts.
Control- calcium feedback.
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PARATHYROID HORMONE
• gland- 4 lobs, behind
thyroid.
• 84AA, mw- 9500.
• Half life- 20 min.
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Actions of Parathyroid Hormone
• Maintenance of plasma calcium.
• Bone– increase osteoclastic activity.
– reduces osteoblastic activity.
• Kidney– increase conversion of Vitamin D.
– increase reabsorption of calcium
– decrease re-absorption of phosphates.
• Intestine– increase calcium absorption- direct action is mild.
Main action is through increased Vitamin D.
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Control of Secretion of Parathyroid
Hormone.
• Calcium negative feedback.
• β adrenergic stimulation increases
secretion.
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Hyper Parathyroidism
• Causes- tumors. (in pregnancy and
lactation hypertrophy is normal).
• Effect- increased plasma calcium.
• Bone– increased osteoclastic activity.
– easily broken bones, multiple fractures with
mild trauma.
– X ray- eaten up bone appearence.
– increased alkaline phosphatase
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Other effects of Hypercalcaemia.
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depression of nerves.
muscular weakness.
constipation
abdominal pain
peptic ulcer
loss of appetite
reduced diastole of the
heart.
• unconsciousness.
• confusion
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mental retardation
delusions
hallucinations.
metastatic calcification in
lungs, kidneys, thyroid,
arteries, etc.
• Renal calculi.
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Hypoparathyroidism
• Reduced plasma Calcium
• Tetany.
• Carpo-pedal spasm
(Trousseau's sign)
• Facial muscle twitch on
tapping.- (Chvostek's sign)
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Other effects of
Hypoparathyroidism.
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muscular weakness
irritability
cataracts
calcified basal ganglia.
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In children,
• defective tooth
development
• metal retardation
• emotional labiality.
• irritability
• anxiety
• depression
• delirium
• Delusions and psychosis
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