Got Calcium?

Ca2+

 Calcium

body distribution Plasma calcium regulation Action control of calcium Synthesis and actions of hormones regulating calcium ions Diseases Laboratory methods and interpretations

 Plasma

calcium totals 2.4 mM (9.4 mg/dl) o Free calcium is 1.2 mM

calcium is tightly regulated (5%) o Too low = neuronal hyper-excitability o Too high = neuronal depression Control points for calcium
Free

Vitamin

D3 Parathyroid Hormone Calcitonin Skeletal Loading

Vitamin

D3 (Cholecalciferol) o 25-Hydroxycholecalciferol
o 1,25-Dihydroxycholecalciferol

Synthesis of Vitamin D

Humans

acquire vitamin D from two sources

Vitamin

D is not a classic hormone because it is not produce and secreted by an endocrine gland. Nor is it a true vitamin since it can be synthesized de novo.

Vitamin

D is a true hormone that acts on distant target cells to evoke responses after binding to high affinity receptors

A lipid

soluble hormone that binds to a typical nuclear receptor, analogous to steroid hormones.

Promotes

intestinal absorption

of calcium Causes synthesis of calciumbinding protein and related facilitated transport Takes a couple of days to fully develop response

Works

with PTH to cause calcium absorption from bone

Osteoblasts,

but not osteoclasts have vitamin D receptors. 1,25-(OH)2-D acts on osteoblasts which produce a paracrine signal that activates osteoclasts to resorb Ca++ from the bone matrix. 1,25-(OH)2-D also stimulates osteocytic osteolysis.

 Secreted

by parathyroid glands Polypeptide Peptide fragments can be active for periods measured in hours Operates in tissues via cAMP second messenger

Parathyroid Hormone

Calcium Signal Transduction in Parathyroid Gland

G-Protein
600 AA external domain

Coupled Receptor Activates Phospholipase C

o Leads to increased

Phosphorylation sites 200 AA internal domain

Diacylglycerol (DG) and Inositol trisphosphate (IP3) as secondary messengers o Inhibits adenylate cyclase to reduce cAMP

Present in C cells of Thyroid Gland

o Regulates calcitonin secretion

Hyperparathyroidism

Calcitonin

acts to decrease plasma Ca++ levels.

The

major stimulus of calcitonin secretion is a rise in plasma Ca++ levels Calcitonin is a physiological antagonist to PTH with regard to Ca++ homeostasis

The

target cell for calcitonin is the osteoclast.

Serum

Calcitonin

Pentagastrin

(Pg) Stimulation Test

Calcium

Stimulation Test

Rickets

o Abnormal mineralization of bone

resulting from vitamin D deficiency (growing bone in children)

Osteomalacia

o Adults

Osteoporosis

o Porous bones o Dual Energy X-ray Absorptiometry

(DXA) o Bone Mineral Densitometry

o CT or MRI