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
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