Endocrine Control of Calcium Metabolism Flashcards
What is the calcium distribution in the body?
99% in bones and teeth
- 9% in ICF
- 1% in ECF
Does calcium blood level need to be precisely regulated?
yes
Of the 0.1% of calcium in ECF, how much is actually available?
ultimately, only about 0.05% of available Ca2+ is present in ECF and is free, making it biologically active and subject to regulation
0.05% bound to albumin
What is ECF?
interstitial fluid + plasma
What is the tiny fraction of free Ca2+ in ECF critically important for?
maintaining several essential physiological functions including:
- neuromuscular excitability and synaptic transmission
- excitation-contraction coupling in cardiac and skeletal muscles
- blood clotting
Where does calcium go after being obtained in diet?
absorbed in small intestine → deposited in bones and teeth
What do bones serve as reservoir for?
to provide adequate plasma calcium for minute-to-minute regulation of body needs
What does the control of calcium metabolism involve? (2)
- regulation of calcium homeostasis
- regulation of calcium balance
What does the regulation of calcium homeostasis involve?
minute-to-minute adjustments to maintain relatively constant free plasma calcium
What does the regulation of calcium balance involve?
long-term weeks to months adjustments to maintain relatively constant body calcium
What are the 3 hormones that maintain calcium metabolism?
- parathyroid hormone (PTH)
- 1,25-dihydroxycholecalciferol (1,25-DHC)
- calcitonin
Where does parathyroid hormone (PTH) come from?
parathyroid gland
What is 1,25-dihydroxycholecalciferol (1,25-DHC)?
biologically active derivative of vitamin D or calcitriol
What is calcitonin produced by?
C cells of thyroid gland
What is parathyroid hormone (PTH) produced by?
4 small parathyroid glands located on posterior surface of the thyroid gland
What is parathyroid hormone (PTH) release triggered by?
hypocalcemia (low blood calcium levels)
What is parathyroid hormone (PTH) release inhibited by?
hypercalcemia (high blood calcium levels)
What are the main targets of parathyroid hormone (PTH)? (3)
- bone
- kidney
- intestine (indirectly)
PTH Effects on Skeleton
How can parathyroid hormone (PTH) increase plasma calcium concentration?
- inducing fast movement of small amounts of calcium present in bone fluid (“labile pool’’) into plasma
- stimulating bone resorption through indirect mechanism:
PTH Effects on Skeleton
What is the indirect mechanism by which bone resorption is stimulated (to increase plasma calcium concentration)?
- PTH binds to receptors expressed by bone-depositing osteoblasts, causing them to release cytokines – including RANK ligand
- cytokines activate receptors on preosteoclasts, causing them to mature into large, multinucleated bone-absorbing osteoclast
PTH Effects on Skeleton
What happens when there is an increase in parathyroid hormone (PTH)?
increase movement of labile of Ca2+ in bone fluid to plasma + increase bone resorption → increase plasma Ca2+
PTH Effects on Skeleton
What are osteoblasts?
multi-nucleated cells that are involved in bone resorption
carry PTH receptors
PTH Effects on Skeleton
How are osteoblasts formed?
PTH binds to osteoblast → RANK ligand → osteoclast
PTH Effects on Kidney
What does parathyroid hormone (PTH) stimulate kidneys to do?
reabsorb calcium → decrease loss of Ca2+ in urine
PTH Effects on Kidney
What does parathyroid hormone (PTH) promote?
elimination of phosphate ions (PO43-) in urine → important to prevent redepositing of Ca2+ in bone
increase PTH → increase Ca2+ reabsorption and increase PO43- excretion in kidney → increase plasma Ca2+
PTH Effects on Kidney
Parathyroid hormone also enhances activation of what?
vitamin D by kidney
Vitamine D – Diagram
–
How much calcium is absorbed in small intestine?
typical daily intake of Ca2+ is ~1000 mg – about 15% of it is absorbed in small intestine by passive absorption, which is not sufficient to sustain calcium balance
Where is vitamin D absorbed, and by what mechanism?
15% in small intestine by passive absorption
75% in small intestine by active transport system
Is steroid-like vitamin D biologically active or inactive?
inactive – both liver and kidneys must participate in its conversion to active 1,25- dihydroxycholecalciferol
What happens to vitamin D when parathyroid hormone (PTH) increases?
increase active vitamin D3 → increase Ca2+ reabsorption in gut → increase blood Ca2+
Why is vitamin D important for bone formation?
stimulates uptake of phosphate ions, which is important for bone functions
What is calcitonin (CT)?
hypocalcemic (calcium-lowering) factor synthesized by C cells of thyroid gland
What is the release of calcitonin regulated by?
regulated by plasma Ca2+
increase Ca2+ → increase CT
What role does calcitonin have?
- distinct effects on bone function
- limited role in normal calcium homeostasis
How do we know that calcitonin (CT) has limited role in normal calcium homeostasis?
patients with significant abnormalities of secretion of calcitonin have normal calcium levels
What does recent evidence suggest as a possible role of calcitonin?
possible role in protecting bone integrity when there is high calcium demand, such as during pregnancy or breastfeeding
