Ca homeostasis: Role of PTH & vit. D3

Nermeen BastawyPhysiology Department

Faculty of MedicineCairo University

Calcium• Functions?•Distribution: 1 kg•Bony skeleton: 99%• IC/ EC (plasma): 1%

Bony skeleton

• Large stable pool (99%): calcium phosphate• Small labile pool (1%): rapidly exchange with ECF

Non exchangeable Calcium

Exch

ange

able

Cal

cium

ECF

Ca ++

• Functions?•Distribution: 1000 g•Bony skeleton: 99%• IC/ EC (plasma): 1%

Plasma Calcium

• Total : 9.4 -11 mg %:• Diffusible (mostly ionized as Ca++)• Non diffusible (plasma ptn-bound)• Ionised Ca is necessary for:

Coagulation Muscles contraction Nerve function

ABSORPTION OF CALCIUM

Upper small intestinePassive diffusion & active transport.AFFECTED BY:Active vit. D3Local GIT factors:Acidity of food products & GIT secretion.Amino acids (Protein meals)Phosphates & oxalates.

PHOSPHOROUS

500 - 800 g (90% in the skeleton). 12 mg/dl ATP, cAMP, 2,3DPG, Phosphoproteins, Phospholipid

Solubility productIf electrolytes concentration in a

solution below a certain value (the solubility product) not ppt.

Calcium and phosphorous in ECF > solubility product, but will not precipitate due to presence of Pyrophosphate (inhibitor).

Ca X P = 10 Ca X P > 10

BONE HISTOLOGY ECM: Ptn: type I collagen Crystals: hydroxyapatite Cells: Osteocytes Osteoblasts Osteoclasts(Remodling unit)

RANK

Regulation of Ca Homeostasis

•PTH•Vit D•Calcitonin

1st line 2nd line

Liver, intestine mitochondria

Parathyroid glandMg++ is necessary for optimal function

ACTIONS OF PTH ON BONE

Rapid Phase: (min-hrs.)

Slow phase: (days- weeks).

PTH

Slow action of PTH

Osteoprotegrin & Denosumab

• OPG Prevent bone resorption & osteoprosis by prevent excess stimulation of osteoclast

DCT

PCT

Calbindin

H+, Mg++

Growth factor

NNC

CPTH-R

Mechanism of PTH action

Low Ca or high Pi

DISTURBANCES OF PARATHYROID GLAND

• Hypoparathyroidism• Primary hyperparathyroidism: due to a tumor of the parathyroid.

• Secondary hyperparathyroidism: CRF phosphate retention

TETANY

Ca++

Excitability Ca++

Excitability

Conditions producing tetany

TYPES OF TETANY• Latent (hidden) tetany: plasma calcium below 9.4 but above 7 mg/dl. Its manifestations don’t appear during rest.

It can be provoked to appear by the following testsTapping the area over the facial nerve:

-Normal: there is only feeling of tap. -hyperexcitable facial nerve: chovestek sign.

Ischemia of the muscles of the upper limb: -normally : feeling of ischemia pain in the upper limb. -hyperexciatble upper limb nerves: carpal spasm or accoucheur hand or trousseau

sign.Galvanic stimulation of the upper limb nerves.

• Manifest tetany: it occur when the plasma calcium drops below 7 mg/dl, the patient is presented with carpal spasm or spasm of laryngeal or spasm of respiratory muscles.