Ca 2+ homeostasis

Definition :

A maintainance/adjustment of constant free plasma [ca 2+ ] in our body.

Proportion of ca 2+

100% 1 %

0.9%

cell

0.1% ECF99%

bone 41% -plasma

protein

50% - free ions

9 % - anion

Functions of ca 2+

Blood clotting

Neuromuscular activity

Excitation-

contraction

coupling

Maintenance of tight junction btw cell

What is the effect if no ca

homeostasis??????

For example

↓ [ca 2+ ] in ECF

↓

↑ Na channel permeability

↓

More Na influx

↓

Easy reach threshold (even more negative value)

↓

Fire AP easily

↓

Spontaneous discharge of AP

Muscle cramp

For example

↑ [ca 2+ ] in ECF

↓

↓ Na channel permeability

↓

Less Na influx

↓

Difficult to reach threshold (even more negative value)

↓

Less AP

↓Muscle weakne

s

What are the factors can

alter [ ca 2+] in

ECF??

Alteration of the forms of Ca2+ in plasma

Changes in plasma protein

concentration-total

[ca]=[protein]-not cause parallel

change of ionized ca

↑[plasma protein]→↑total [ca]

↑[plasma protein]→↑t

otal [ca]

Changes in anion

concentration

alter the ionized Ca2+ concentration

↑[anion]→↑ ca complexed with anion→↓free ca

↑[anion]→↑ ca complexed with

anion→↓free ca

Acid-base abnormalities

alter the ionized Ca2+ concentration

Acidemia:↑H →↓ ca bind to

anion→↑ free ca

Alkalemia ; ↓ H→↑ca bind to anion→↓free ca

Regulatory mechanism

Calcium homeostasis involve 3 organs and 3 hormones

Kidney vitamin D

Intestine PTH [parathyroid hormone]

Bone calcitonin

To illustrate :

GIT- stimulated via vitamin D

we ingest 1000mg/dl

350mg/dl is absorbed from GIT

150mg/dl is secreted into GIT

Net absorption → 200mg/dl→ ca 2+ pool in ECF

Remaining 800mg/dl excreted into feces

Bone –stimulated by PTH + vit D and inhibit by calcitonin

Bone remodelling= bone resorption

No net gain or loss of ca

Kidney – stimulated by PTH

Approximately

10 %→excreted in urine

41% →ca bound to plasma protein

9 %→ combine with anion*

50 %→ ionized*

* filtered in the glomerulus

In renal tubules, 99 % is filtered

90 % - reabsorbed in proximal tubule,LOH,early distal tubule

9 % - is selective depending on ca 2+ concentration in blood

When [ca] ↓→reabsorption is great→almost no ca is lost in urine

When [ca] ↑→reabsorption is less→ ca is lost in urine

# the most important factor controlling this reabsorption in distal portion is PTH

calcitonin

Straight chain pepetide of 32

amino acid

Synthesize in parafollicular cell in thyroid

gland

Calcitonin receptor-

serpentine

Calcitonin have opposite effect to PTH.

Human bone

Not participate in minute-minute regulation of plasma ca in human

Main respond →inhibit osteolytic bone resorption

↓

↓ plasma ca

 

Calcitonin has weak effect on plasma ca in adult human

Why weak ?•Reduction ca by calcitonin lead to powerful stimulation of PTH which override calcitonin effect•In adult ,daily rate of reabsorbtion and deposition of ca are smaal compared to child or Paget disease (osteolytic activity is great and calcitonin effect is potent)

Immediate effect Prolonged effect

↑[ ca ] in plasma↓

Calcitonin stimulated to secrete

↓Calcitonin bind receptor

(coupled to G –protein )on osteoclast

↓Adenylyl

cyclase/phospholipase↓

• Inhibit resorption activity on osteoclast

↓↓ [ca] is released to ECF from

bone

Secondarily to ↓osteoclastic activity

↓formation of new osteoclast followed by decrease of osteoblast

↓activity of osteoclastic and osteoblastic activity

Pronounced effect of calcitonin on

• Paget disease

Increase osteoclastic activity→ calcitonin stimulation to inhibit resorption of bone→↓ [ca] in plasma

• pregnancy mother

Ca is needed for the formation of bone in infants and lactation process→ ca from mother’s bone→to prevent from excess resorption activity on bene→calcitonin action play its role