Parathyroid: Calcium & phosphate regulation

Question 1

How does Ca2+ exist in the body?

Answer 1

body has to regulate plasma conc of free ionised Ca2+

1. free ionised Ca2+
2. bound to serum proteins (e.g. albumin)
3. complexed (with organic anions) e.g. citrate / oxaloate

Question 2

how is Ca2+ & phosphate homeostasis linked?

Answer 2

1. both major components of hydroxyapatite crystals –> bone mineralisation
2. both regulated by parathyroid hormone (PTH) & calcitriol (some calcitonin) - hormone acting on bone, kidneys, GI tract to control plasma levels of Ca2+ & Pi

Question 3

List the hormones involved in the control of Ca2+ levels in serum

Answer 3

1. PTH: increase PTH increases Ca2+
2. vit D: active form = calcitriol
3. Calcitonin: preserve maternal skeleton during pregnancy

Question 4

Describe the hormonal regulation of serum calcium

Answer 4

high Ca2+ negatively suppresses PTH release (neg feedback)
chief cells of parathyroid gland releases PTH
chief cells have unique G-protein Ca2+ receptors on cell surface

PTH from chief cells induce serum conc. of Ca2+, but at high conc of Ca2+, suppresses PTH release (neg. feedback)

Question 5

Describe the series of events that happens when the serum Ca2+ raises

Answer 5

increase Ca2+ –> binds to G-protein receptors on chief cells of parathyroid –> stimulates PLC –> inhibits adenylate cyclase –> decrease cAMP –> decrease PTH

Question 6

Explain the interaction of parathyroid and vit D

Answer 6

vit D: not regulated, made in skin (sunlight) / absorbed from gut (diet), short 1/2 life
vit D converted to calciferol in liver (longer 1/2 life about 2 weeks)
calciferol converted to calcitriol in kidney (calcitriol regulated by PTH)
when PTH increase/decrease can affect conc. of Ca2+

Question 7

explain the regulation of parathyroid hormone and vit D

Answer 7

PTH regulates calcitriol (activated), Ca2+ regulates PTH (neg feedback)

Question 8

Explain where Vit D2, D3, calciferol & calcitriol & PTH are produced and their action

Answer 8

Vit D2: diet gut, D3: sunlight skin, Calciferol: 1st hydroxylation of vit D
Calcitriol: kidney (2nd hydroxylation of vit D), increases Ca2+ absorption (binds to Ca2+ in the gut)
PTH: parathyroid gland, increase conversion to calcitriol, increase Ca2+ release from bones, increase Ca2+ reabsorption in kidney

Question 9

Explain the significance of renal function on Ca2+ metabolism

Answer 9

PTH: increase Ca2+ reabsorption in distal convoluted tubule (DST) - tubule cells through NCX (3Na+ Ca2+ exchanger)
Pi removed from circulation by inhibiting the proximal tubule (PT) reabsorption - prevents Ca2+ store formation (hydroxyapatite crystals)

Question 10

Describe the disorders of Ca2+ metabolism & metabolic bone disease: hypocalcaemia

Answer 10

Low Ca2+ bind to neuromuscular membrane - Na+ depolarises membrane more readily (more negative)
decrease Ca2+ –> increase PTH –> increase reabsorption in kidney of Ca2+ –> increase calcitriol –> increase Ca2+ from gut absorption
results in hyper-excitability: 1. paraesthesia 2. tetany (muscle spasm) 3. paralysis 4. convulsions

Question 11

What is deficiency of Ca2+ in children called? How does it present itself?

Answer 11

Rickets

1. bowed legs (knees bend out)
2. soft spot on head slow to close
3. bony neckline
4. big, lumpy joints

Question 12

Describe the disorders of Ca2+ metabolism & metabolic bone disease: PTH deficiency. What can cause it? what does it lead to?

Answer 12

surgical removal of PT glands –> cause hypocalcaemia symptoms within 48 hrs

1. hyper-excitability of NMJ & paraesthesia
2. tetanic contraction of skeletal muscle
3. convulsions, if affect respiratory muscles –> death

Question 13

Describe the disorders of Ca2+ metabolism & metabolic bone disease: hypercalcaemia

Answer 13

Moans, Groans, Stones: constipated & dehydration, depression & tiredness, kidney stones (renal calculi) & kidney damage
increase plasma Ca2+ –> decrease PTH secretion –> kidney decrease reabsorption of Ca2+ –> decrease calcitriol –> decrease Ca2+ from gut

Question 14

What is PTHrP? what can it lead to?

Answer 14

parathyroid hormone related peptide: peptide hormone (similar to PTH) produced in tumours can lead to unexplained hypercalcaemia, is secreted by some cancer cells –> humeral hypercalcaemia of malignancy (HHM)
increase Ca2+ release from bones, decrease renal Ca2+ excretion, decrease renal phosphate reabsorption (no Ca2+ stones),
does NOT increase C-1 hydroxylase –> NO increase in calcitriol conc.

Question 15

Explain the significance of maintaining serum Ca2+ levels within set limits

Answer 15

Ca2+ in: hormone secretion
muscle contraction - remove tropomyosin from actin filament binding site
nerve conduction - depolarise membrane
activation of enzyme
exocytosis