24 Parathyroid Gland and Calcium for Students

7/30/2019 24 Parathyroid Gland and Calcium for Students

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Got Calcium? Ca2+


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Calcium body distribution

Plasma calcium regulation

Action control of calciumSynthesis and actions of hormones

regulating calcium ions

DiseasesLaboratory methods and interpretations


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Plasma calcium totals 2.4 mM (9.4 mg/dl)

o Free calcium is 1.2 mM


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Free calcium is tightly regulated (5%)

o Too low = neuronal hyper-excitability

o Too high = neuronal depressionControl points for calcium


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Vitamin D3

Parathyroid Hormone

CalcitoninSkeletal Loading


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Vitamin D3 (Cholecalciferol)

o25-Hydroxycholecalciferol

o1,25-Dihydroxycholecalciferol
http://en.wikipedia.org/wiki/Image:Cholecalciferol.png


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Synthesis of

Vitamin D


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Humans acquire vitamin Dfrom two sources


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Vitamin D is not a classichormone because it is not

produce and secreted by anendocrine gland.

Nor is it a true vitaminsince it can be synthesizedde novo.


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Vitamin D is a true hormonethat acts on distant target cells

to evoke responses afterbinding to high affinityreceptors


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A lipid soluble hormonethat binds

to a typical nuclear receptor,

analogous to steroid hormones.


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Promotes intestinal absorption

of calcium

Causes synthesis of calcium-binding protein and related

facilitated transport

Takes a couple of days to fully

develop response


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Works with PTHto cause

calcium absorption from

bone


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Osteoblasts, but not osteoclasts havevitamin D receptors.

1,25-(OH)2-D acts on osteoblasts

which produce a paracrine signal thatactivates osteoclasts to resorb Ca++from the bone matrix.

1,25-(OH)2-D also stimulatesosteocytic osteolysis.


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Secreted by parathyroid glands

Polypeptide

Peptide fragments can be active for periods

measured in hours

Operates in tissues via cAMP second

messenger


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Parathyroid Hormone


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G-ProteinCoupled Receptor

ActivatesPhospholipase Co Leads to increased

Diacylglycerol (DG) and Inositoltrisphosphate (IP3) as

secondary messengerso Inhibits adenylate cyclase to

reduce cAMP

Present in C cells of ThyroidGlando Regulates calcitonin secretion

Calcium Signal Transduction in Parathyroid Gland

600 AA external

domain

200 AA internal

domain

Phosphorylation

sites


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Hyperparathyroidism


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Calcitonin acts to decrease plasmaCa++ levels.


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The major stimulus of calcitonin

secretion is a rise in plasma Ca++

levelsCalcitonin is a physiological

antagonist to PTH with regard to

Ca++ homeostasis


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The target cell for calcitonin is theosteoclast.


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Serum Calcitonin


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Pentagastrin (Pg) Stimulation Test


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Calcium Stimulation Test


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Rickets

oAbnormal mineralization of boneresulting from vitamin D deficiency

(growing bone in children)

Osteomalacia

oAdults


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Osteoporosis

oPorous bones

oDual Energy X-ray Absorptiometry(DXA)

oBone Mineral Densitometry

oCT or MRI


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24 Parathyroid Gland and Calcium for Students