Ca ++ and P i Homeostasis

Ca++ and Pi Homeostasis

Ca++ in the plasma

• [Ca++ ] in plasma: 2.5 mM, of which about ½ is bound and thus physiologically inactive.

• Ratio of free/bound is sensitive to [H+] and [HPO4

2-] according to the solubility product constant

Effector Sites

– Bone (contains 99% of total body Ca++ as

phosphate salt)

– GI tract (mediates uptake from diet, but also carries out some secretion)

– Kidney (loss/conservation of plasma Ca++ and phosphate)

Regulatory hormones

• Parathormone from parathyroids – 4 (usually) located (usually) on ventral surface of thyroid

• 1,25 diOH cholecalciferol (1,25 diOH D)

• Calcitonin from thyroid

Parathormone (PTH)

• secretion stimulated by drop in plasma free Ca++ activity – not total plasma Ca++ - protects plasma free Ca++

• Effects: – increased bone breakdown (osteoclasts)– Increased activation of “Vitamin” D– Increased renal Ca++ recovery (connecting

tubule segment of DT)– Decreased renal phosphate reabsorption

“Vitamin” D (1,25 diOH Cholecalciferol)

Synthesis:

(Diet, liver synthesis)

7-dehydrocholesterol(Skin) Vit D3

(Liver - 25-hydroxylase)

12-OH CC

Kidney – 1-hydroxylase

Kidney - 24-hydroxylase

24,25-diOH CC (inactive)

1,25 diOH CC (active)

PO4PTH

PTHPO4

UV light

1,25-diOH CC effects

• Increased Ca++ uptake in intestine (direct)• Increased bone mineralization (indirect – the

result of uptake stimulation)• Increased bone breakdown (direct, like PTH)• Estrogen and testosterone have similar effects;

corticosteroids have antagonistic effects• Vit. D is necessary for bone growth, but can

channel dietary Ca++ into plasma or bone depending on the levels of PTH.

Calcitonin

• Secreted by thyroid

• Inhibits bone breakdown

• Role in Ca++ homeostasis in humans is apparently minor, but it is used as a drug against osteoporosis – must be injected or applied as a nasal mist.

Fate Map of Ca++ in the bodyBONE (1 kg)

PLASMA

INTESTINE KIDNEY

FECES

825 mg/d

URINE

PTH, corticosteroid

1,25 diOH CCcalcitonin

Diet

1,000mg/dPTH

1,25 diOH CC

500 mg/d

10,000 mg/d

9,825 mg/d

175 mg/d

280 mg/d

325 mg/d

Coordinated responses in calcium homeostasis

How about phosphate regulation?

Remember that decreasing plasma phosphate will increase plasma free calcium

Short-term effects of disorders of Ca++ regulation

• Hypocalcemia: increased excitability of nerve and muscle with characteristic muscle spasms and contractures and cardiac arrhythmias – CNS agitation- – “grass tetany” in grazing animals that feed on

low Ca++/high Mg++ diet

• Hypercalcemia: depressed excitability of excitable cells – lethargy, memory loss– PTH-secreting parathyroid tumors

Long-term effects of homeostatic failure

• Vit. D deficiency or dietary Ca++ deficiency– Rickets – malformed bone in children– Osteomalacia – adult rickets

• Lack of sex steroids after puberty, or treatment with corticosteroids– osteoporosis – loss of bone mass, without

morphological abnormality

What you need to know about K+ regulation

• Plasma [K+] = 4 mEq/l• Dietary K+ partitioned mainly into intracellular

compartment• Kidney filters K+, essentially all of the filtered load is

reabsorbed in the PCT• But then, some K+ is secreted in the DCT at rates

determined by 2 factors:– Aldosterone levels, which are responsive to plasma [K+]– Plasma [H+ ], because the DCT secretes a mix of H+ and K+ to

maintain charge balance against Na+ absorption, and the secreted ions compete with one another