The parathyroid glands and vitamin D

Question 1

where is the majority of calcium found?

Answer 1

in bone , largely as precipaited calcium phosphate

Question 2

what are the roles of calcium?

Answer 2

• Muscle contraction
• Membrane stability (promotes electrical stability of nerves & muscles – later slide)
• Neurotransmitter release (e.g. ACh release at n.m.j.)
• Secretory processes (e.g. ADH release from post.pit.)
• Blood clotting
• Intracellular 2nd messenger
• Enzyme Regulation

Question 3

what is the role of calcium in membrane stability?

Answer 3

• Decrease in free ECF Ca2+ increases Na+ permeability
• Depolarizes Em, moving Em closer to threshold
• Consequence: during hypocalcemia, excitable cells reach threshold in response to normally ineffective stimuli.
• Results in muscle spasm (spontaneous contraction of respiratory muscles can lead to death by asphyxiation)

Question 4

what is the role of calcium in excitation-contraction coupling of cardiac and smooth muscle cells?

Answer 4

• Action Potential increases Ca2+ permeability. Entry of ECF Ca2+ into cardiac and smooth muscle cells triggers contractile mechanism.
• (In sk. muscle Ca2+ is released from i/c stores in response to an AP)

Question 5

what are the effect of increase in cytosolic calcium and free ECF calcium?

Answer 5

↑ cytosolic Ca2+ causes contraction, whereas an ↑ in free ECF Ca2+ decreases neuromuscular excitability (& ↓ likelihood of contraction).

Question 6

what is the narrow range of plasma calcium?

Answer 6

2.2 to 2.6 mmol/l

Question 7

what is the intracellular calcium level?

Answer 7

0.1micromol/l

Question 8

Describe the roles of phosphate balance.

Answer 8

• Component of ATP so plays an important part in cellular energy metabolism
• Crucial in activation and deactivation of enzymes (kinases and phosphatases)
• Unlike calcium the plasma phosphate concentration is not strictly regulated (levels fluctuate throughout the day, especially after meals)

Question 9

how are calcium and phosphate balance linked?

Answer 9

1. Both are the principal components of hydroxyapatite crystals in bone
2. Both are regulated by the same hormones: primarily parathyroid hormone (PTH) and calcitriol (and, to a much lesser extent, calcitonin)

Question 10

what 3 systems do PTH, calcitriol and calcitonin act on?

Answer 10

• bone
• kidneys
• GI tract

Question 11

where are the 4 parathyroid glands located?

Answer 11

2 located on the posterior surface of the left lobe of the thyroid gland and 2 more on the right

Question 12

what is the parathyroid gland composed of and what does it synthesise?

Answer 12

-composed of Chief cells, which synthesise and secrete PTH

Question 13

what is the main regulatory of parathyroid hormone?

Answer 13

plasma calcium concentration

Question 14

what does a decrease in plasma calcium conc (hypocalcemia stimulate?

Answer 14

PTH secretion (as does an increase in plasma [phosphorus])

Question 15

Describe the PTH.

Answer 15

• a peptide hormones stored in secretory granules

- circulates freely in plasma and is rapidly metabolised

Question 16

what do chief cells express?

Answer 16

a plasma membrane Ca2+ sensing receptor

Question 17

what does activation of PLC result in?

Answer 17

• results in the release of Ca2+ from intracellular stores and activation of PKC
• Unlike other endocrine cells, the rise in [Ca2+]i and activation of PKC inhibit hormone secretion

Question 18

what are the net effects of PTH on kidney and bone?

Answer 18

to increase plasma [Ca2+] and to lower plasma [phosphate]

Question 19

what do PTH modify transepithelial transport to do?

Answer 19

1. Stimulate renal Ca2+ reabsorption (TAL & DCT), and
2. Inhibit renal phosphate reabsorption (PCT) – PTH-induced phosphaturia prevents precipitation when Ca2+ mobilisation is needed

Question 20

what are the actions of 1,25-dihydroxyvitamin (calcitriol)?

Answer 20

1. Enhance renal Ca2+ reabsorption
2. Enhance Ca2+ absorption by the small intestine
3. Modulate movement of Ca2+ and phosphate in and out of bone

Question 21

In bone, what can PTH promote?

Answer 21

net resorption or net deposition

Question 22

what does persistent increases of PTH on bone favour?

Answer 22

indirectly increases both the number and activity of bone-resorbing osteoclasts

Question 23

what do intermittent increases in plasma (PTH) favour?

Answer 23

bone deposition (synthesis):

• -Net transfer of Ca2+ from bone fluid to osteoblasts via activation of Ca2+ channels on osteocytes
• Promotes osteoblast differentiation and inhibition of osteoblast apoptosis

Question 24

what are the two forms of vitamin D and how are they synthesised?

Answer 24

D3- can be synthesised by the skin if sufficient UV light is absorbed, also found in eggs
D2-only obtained from the diet, largely from vegetables

Question 25

what is the action of vitamin D and how does it do this?

Answer 25

• to raise the plasma concentrations of both Ca2+ and phosphate by:
• Enhancing absorption of Ca2+ and phosphate from the intestine, and
• Enhancing reabsorption of Ca2+ and phosphate from the renal tubules

Question 26

what are the biological actions of 1,25-dihydroxyvitamin (calcitriol)?

Answer 26

Acts on the small intestine and kidney to raise plasma [Ca2+] (effects on bone are complex)

Question 27

what effect does calcitriol have on the small intestine (duodenum)?

Answer 27

• Up-regulates transcellular reabsorption of Ca2+ by increasing expression of epithelial Ca2+ channels, pumps and binding proteins
• Also stimulates the synthesis of a NaPi cotransporter to increase phosphate absorption

Question 28

what effect does calcitriol have on the kidney?

Answer 28

• Acts synergistically with PTH to enhance Ca2+ reabsorption in the DCT and promotes phosphate reabsorption
• Effects are less dramatic than PTH

Question 29

what effect does calcitriol have on bone?

Answer 29

Actions are complex (as a result of direct and indirect actions) and depends on levels of vitamin D

Question 30

what does vitamin D deficiency lead to?

Answer 30

• Leads to impaired intestinal absorption of Ca2+ and hypocalcemia.
• Hypocalcemia in turn leads to an increase in PTH secretion
• PTH leads to increased bone resorption, so bones soften and deform

Question 31

what diseases does vitamin D deficiency cause in children and adults?

Answer 31

children- rickets

adults- osteomalacia

Question 32

what is produced by C cells of the thyroid gland?

Answer 32

calcitonin

Question 33

what triggers the release of calcitonin?

Answer 33

rise in the extracellular [Ca2+] above normal

Question 34

what is the action of calcitonin?

Answer 34

lower plasma [Ca2+]

Question 35

what do osteoclasts express?

Answer 35

calcitonin receptors

Question 36

what effect does calcitonin have on the activity of osteoclasts ?

Answer 36

• Calcitonin inhibits the resorptive activity of osteoclasts, slowing the rate of bone turnover
• Action of calcitonin is hypocalcemic

Question 37

how does calcitonin resultt in a mild phosphaturia in the kidney?

Answer 37

inhibiting phosphate transport in the Proximal transport