Endocrine Control of Calcium Metabolism

Question 1

What is the calcium distribution in the body?

Answer 1

99% in bones and teeth

0. 9% in ICF
1. 1% in ECF

Question 2

Does calcium blood level need to be precisely regulated?

Answer 2

yes

Question 3

Of the 0.1% of calcium in ECF, how much is actually available?

Answer 3

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

Question 4

What is ECF?

Answer 4

interstitial fluid + plasma

Question 5

What is the tiny fraction of free Ca2+ in ECF critically important for?

Answer 5

maintaining several essential physiological functions including:

• neuromuscular excitability and synaptic transmission
• excitation-contraction coupling in cardiac and skeletal muscles
• blood clotting

Question 6

Where does calcium go after being obtained in diet?

Answer 6

absorbed in small intestine → deposited in bones and teeth

Question 7

What do bones serve as reservoir for?

Answer 7

to provide adequate plasma calcium for minute-to-minute regulation of body needs

Question 8

What does the control of calcium metabolism involve? (2)

Answer 8

• regulation of calcium homeostasis

- regulation of calcium balance

Question 9

What does the regulation of calcium homeostasis involve?

Answer 9

minute-to-minute adjustments to maintain relatively constant free plasma calcium

Question 10

What does the regulation of calcium balance involve?

Answer 10

long-term weeks to months adjustments to maintain relatively constant body calcium

Question 11

What are the 3 hormones that maintain calcium metabolism?

Answer 11

• parathyroid hormone (PTH)
• 1,25-dihydroxycholecalciferol (1,25-DHC)
• calcitonin

Question 12

Where does parathyroid hormone (PTH) come from?

Answer 12

parathyroid gland

Question 13

What is 1,25-dihydroxycholecalciferol (1,25-DHC)?

Answer 13

biologically active derivative of vitamin D or calcitriol

Question 14

What is calcitonin produced by?

Answer 14

C cells of thyroid gland

Question 15

What is parathyroid hormone (PTH) produced by?

Answer 15

4 small parathyroid glands located on posterior surface of the thyroid gland

Question 16

What is parathyroid hormone (PTH) release triggered by?

Answer 16

hypocalcemia (low blood calcium levels)

Question 17

What is parathyroid hormone (PTH) release inhibited by?

Answer 17

hypercalcemia (high blood calcium levels)

Question 18

What are the main targets of parathyroid hormone (PTH)? (3)

Answer 18

• bone
• kidney
• intestine (indirectly)

Question 19

PTH Effects on Skeleton

How can parathyroid hormone (PTH) increase plasma calcium concentration?

Answer 19

• inducing fast movement of small amounts of calcium present in bone fluid (“labile pool’’) into plasma
• stimulating bone resorption through indirect mechanism:

Question 20

PTH Effects on Skeleton

What is the indirect mechanism by which bone resorption is stimulated (to increase plasma calcium concentration)?

Answer 20

• 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

Question 21

PTH Effects on Skeleton

What happens when there is an increase in parathyroid hormone (PTH)?

Answer 21

increase movement of labile of Ca2+ in bone fluid to plasma + increase bone resorption → increase plasma Ca2+

Question 22

PTH Effects on Skeleton

What are osteoblasts?

Answer 22

multi-nucleated cells that are involved in bone resorption

carry PTH receptors

Question 23

PTH Effects on Skeleton

How are osteoblasts formed?

Answer 23

PTH binds to osteoblast → RANK ligand → osteoclast

Question 24

PTH Effects on Kidney

What does parathyroid hormone (PTH) stimulate kidneys to do?

Answer 24

reabsorb calcium → decrease loss of Ca2+ in urine

Question 25

PTH Effects on Kidney

What does parathyroid hormone (PTH) promote?

Answer 25

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+

Question 26

PTH Effects on Kidney

Parathyroid hormone also enhances activation of what?

Answer 26

vitamin D by kidney

Question 27

Vitamine D – Diagram

Answer 27

–

Question 28

How much calcium is absorbed in small intestine?

Answer 28

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

Question 29

Where is vitamin D absorbed, and by what mechanism?

Answer 29

15% in small intestine by passive absorption

75% in small intestine by active transport system

Question 30

Is steroid-like vitamin D biologically active or inactive?

Answer 30

inactive – both liver and kidneys must participate in its conversion to active 1,25- dihydroxycholecalciferol

Question 31

What happens to vitamin D when parathyroid hormone (PTH) increases?

Answer 31

increase active vitamin D3 → increase Ca2+ reabsorption in gut → increase blood Ca2+

Question 32

Why is vitamin D important for bone formation?

Answer 32

stimulates uptake of phosphate ions, which is important for bone functions

Question 33

What is calcitonin (CT)?

Answer 33

hypocalcemic (calcium-lowering) factor synthesized by C cells of thyroid gland

Question 34

What is the release of calcitonin regulated by?

Answer 34

regulated by plasma Ca2+

increase Ca2+ → increase CT

Question 35

What role does calcitonin have?

Answer 35

• distinct effects on bone function

- limited role in normal calcium homeostasis

Question 36

How do we know that calcitonin (CT) has limited role in normal calcium homeostasis?

Answer 36

patients with significant abnormalities of secretion of calcitonin have normal calcium levels

Question 37

What does recent evidence suggest as a possible role of calcitonin?

Answer 37

possible role in protecting bone integrity when there is high calcium demand, such as during pregnancy or breastfeeding