Calcium

Question 1

What changes occur when serum calcium is low?

Answer 1

• PTH is released by chief cells in the parathyroid gland
• reduces the reabsorption/increases excretion of phosphate in the kidney while decreasing calcium excretion
• increases calcium and phosphate excretion in the bone
• increases the absorption of calcium and phosphate in the intestines
• causes vitamin D activation int he kidneys
• inhibits sodium/water/bicarbonate reabsorption via effects on Na/H exchanger and Na/K ATPase

Question 2

Where did the superior and inferior parathyroid glands originate from?

Answer 2

Develop from endodermal outpouchings
Inferior parathyroid: III out pouching
Superior parathyroid: IV out pouching

Question 3

What type of receptor is the calcium sensing receptor?

Answer 3

GPCR

Question 4

What is the effect of calcium binding to the calcium sensing receptor?

Answer 4

• Reduces PTH secretion
• Increases breakdown of stored PTH
• Suppresses transcription of PTH gene

Question 5

What is the result of inactivating mutations to the calcium sensing receptor?

Answer 5

Familial hypocalciuric hypercalcaemia (autosomal dominant)

- CaSR can’t sense high calcium –> PTH not suppressed by high calcium –> Ca2+ reabsorption not stopped

Question 6

What is the effect of activated vitamin/calcitriol on PTH?

Answer 6

Suppresses PTH gene transcription

Question 7

What is the effect of activated phosphate on PTH?

Answer 7

Stimulates PTH gene transcription

Question 8

Where is most Ca2+ reabsorbed in the renal system?

Answer 8

Proximal tubule

Question 9

How is Ca2+ reabsorbed at the:

• Proximal tubule
• Loop of henle
• Distal tubule

Answer 9

• Proximal tubule: paracellularly
• Loop of henle: para/transcellularly
• Distal tubule: via TRPV Ca2+ channels

Question 10

What is the effect of PTH and calcitriol on RANKL and OPG?

Answer 10

• stimulate RANKL

- downregulate OPG

Question 11

What is the role of RANKL?

Answer 11

RANKL is released by osteoblasts

• RANKL is a receptor activator for nuclear factor kB ligand and colony stimulating factor 1
• promotes osteoclastogenesis and osteoclast function

Question 12

What is the role of OPG?

Answer 12

OPG = osteoprotegerin

- inhibits osteoclastogenesis

Question 13

What is the effect of PTH on IGF1 and IL1?

Answer 13

Increases both

Question 14

What can primary hyperparathyroidism result in?

Answer 14

• terminal tuft erosion
• rugger jersey spine
• subperiosteal erosion
• brown tumour

Question 15

What type of receptor is vitamin D receptor?

Answer 15

nuclear and membrane bound

Question 16

What occurs when vitamin D receptor is activated?

Answer 16

• inhibits action 1-alpha hydroxylase
• this reduces the amount of 1,25-vitamin D able to bind to VDR

*function of the VDR is to increase calcium and phosphate absorption from the gut and kidneys

Question 17

Apart from inside the kidney, where else is calcitriol produced and why? In what situations doe this occur?

Answer 17

Macrophages

• inside a macrophage calcitriol acts as a cytokines
• modulates body defences against microbial invaders stimulating the innate immune response

Occurs when macrophages are activated (such as in TB and sarcoid granulomata) –> can lead to hypercalcaemia

Question 18

Explain how calcium is absorbed from the gut.

Answer 18

• calcium in the lumen can travel to interstitial space in the gut para/transcellularly
• calbindin is produced in the gut cells (enterocytes) –> it grabs Ca2+ inside the cell and releases it into the interstitium
• Ca2+ in the interstitium can enter the blood

Question 19

What are the effects of vitamin D on parathyroid glands?

Answer 19

• modest reduction in PTH transcription

Question 20

What are the effects of vitamin D on bones?

Answer 20

• reduces expression of type 1 collagen
• increases level of osteocalcin + RANKL
• facilitates osteoclast differentiation

Question 21

What are the effects of vitamin D on phosphate?

Answer 21

• increases phosphate absorption from the gut

- increases levels of FGF23 to remove it via renal excretion

Question 22

What are the effects of vitamin D on amino acids?

Answer 22

increases amino acid uptake

*deficiency in vitamin D results in myopathy

Question 23

What can vitamin D deficiency lead to?

Answer 23

• rickets
• osteomalacia
• osteoporosis

Question 24

What is FGF23?

Answer 24

phosphatonin - hormones that reduces serum phosphate

• it is secreted by osteocytes
• actives inhibition of vitamin D

Question 25

What is the result of an activating mutation in FGF23?

Answer 25

Autosomal dominant hypophosphataemic rickets

Question 26

What is the result of a benign neoplasm that inappropriately produces fibroblast growth factor 23?

Answer 26

tumour-induced osteomalacia

Question 27

What effect does familial tumoral calcinosis have on FGF23 levels?

Answer 27

FGF23 levels are low

Question 28

Where is calcitonin produced? What is its role?

Answer 28

Produced by thyroid C cells | Lowers calcium levels

Question 29

What are potential causes of primary HPT?

Answer 29

- parathyroid adenoma - carcinoma - hyperplasia

Question 30

What are potential causes of secondary HPT?

Answer 30

- physiological compensation for hypocalcaemia | - vitamin D deficiency

Question 31

What are potential causes of tertiary HPT?

Answer 31

- autonomous PTH production following chronic secondary PHPT

Question 32

What are the S+S/is the result of HPT?

Answer 32

- hypercalcaemia - polyuria and polydipsia - kidney stones - osteoporosis - mood disorder

Question 33

How is primary HPT diagnosed?

Answer 33

1. serum calcium and PTH 2. 24h urine calcium 3. urine calcium creatinine excretion index 4. renal ultrasound 5. DEXA scan

Question 34

What are the S+S of hypocalcaemia?

Answer 34

- convulsions - confusion - tetany - tachyarrhythmia

Question 35

What are the causes of hypocalcaemia?

Answer 35

- hypoparathyroidism: iatrogenic, autoimmune, genetic - vitamin D deficiency - chronic kidney disease - PTH resistance

Question 36

How would you treat acute and chronic hypoparathyroidism?

Answer 36

1. acute: IV/oral calcium replacement 2. chronic: alfacalcidol orally - increases gut absorption of calcium - however there will still be hypercalciuria = increased risk of kidney stones