Calcium Metabolism

Question 1

where does calcium come from?

Answer 1

diet

Question 2

why is calcium needed?

Answer 2

• neuromuscular functions
• strength in bones
• intracellular secondary messenger
• co enzyme
• blood clotting (F IV)
• exocytosis

Question 3

where is most of the calcium found in the body?

Answer 3

as salts and minerals in bone (hydroxyapatite)

Question 4

how is calcium found in the blood?

Answer 4

mostly Ca2+ unbound which is free and bioactive,
some bound to proteins
very little as diffusible salts like calcium citrate/lactate

Question 5

from where can calcium be increased in blood?

Answer 5

• absorbtion from gut
• from bone minerals
• absorbed from kidney

Question 6

from where can calcium be decreased in the blood?

Answer 6

• lost cells eg nails
• bone formation
• excreted from kidneys
• less absorbed from gut

Question 7

which hormones control calcium metabolism?

Answer 7

• [Ca2+] increases using PTH and vitamin D3

- [Ca2+] decreases using Calcitonin, this is less well defined

Question 8

where are the parathyroid glands located?

Answer 8

located posterior of the thyroid, 4 glands embedded within the thyroid gland.

Question 9

where is Parathyroid Hormone (PTH) synthesised?

Answer 9

Parathyroid glands

Question 10

where is Calcitonin produced?

Answer 10

parafollicular cells of the thyroid

Question 11

how does the calcium receptor on parathyroid cells work?

Answer 11

GPCR: high calcium concentration acts as an antagonist meaning it surpasses PTH release.

Low calcium levels mean more PTH is released

Question 12

What type of hormone is PTH?

Answer 12

Polypeptide, 84 aas, synthesised from pre-pro PTH.

Question 13

in calcium metabolism why is phosphate co regulated?

Answer 13

as phosphate is associated with calcium mainly in bones which is the biggest store of calcium

Question 14

what is 1,25(OH)2D3?

Answer 14

Active Vitamin D3 or Calcitriol, leading to increased absorption of calcium and phosphate from the small intestines

Question 15

How does PTH cause and increase in calcium concentration?

Answer 15

• stimulates 1 alpha hydroxylase activity in kidney which causes increased vitamin D synthesis
• increased calcium reabsorption in kidneys and therefore increased phosphate excretion
• Bone resorption by stimulation of osteoclasts and inhibition of osteoblasts

Question 16

how does PTH stimulate osteoclast activation?

Answer 16

PTH binds to osteoblasts receptors and cause osteoclast activating factors like RANKL which activate osteoclasts.

Question 17

describe the PTH axis

Answer 17

decreased blood calcium and action of catecholamines cause PTH secretion which leads to the synthesis of Calcitriol and increase in calcium concentration which then negatively feedback on the parathyroid glands

Question 18

why does liver and kidney function effect calcium metabolism?

Answer 18

UV light is needed for the conversion of 7-dehydrocholesterol to cholecalciferol which is vitamin D3 which can also be obtained from diet

cholecalciferol is then hydroxylated to 25(OH)D3 and stored in liver

This is then converted to 1,25(OH)2D3 by 1a-hydroxylase which is stimulated by PTH in the kidney

Question 19

Actions of Calcitriol

Answer 19

increases calcium and phosphate absorption from gut and reabsorption from kidneys to increase calcium levels and replace resorbed bone.

it also increases osteoblast activity

Question 20

how are phosphate levels regulated?

Answer 20

using Fibroblast Growth Factor 23 from osteocytes, if there is too much phosphate, FGF23 inhibits hydroxylases and therefore reduced phosphate and calcium reabsorption. also stimulates excretion of phosphate.

Question 21

how does FGF23 work?

Answer 21

in presence of high phosphate and calcitriol stimulates FGF23 to inhibit Na/PO4 cotransporter meaning phosphate is not reabsorbed and therefore excreted.

Question 22

what type of hormone is calcitonin?

Answer 22

polypeptide, 32aa, synthesised as pre-procalcitonin

Question 23

describe the calcitonin axis

Answer 23

increased calcium and gastrin causes parafollicular cells to release calcitonin. This inhibits osteoclast activity and stimulates calcium excretion from kidneys which decreases the calcium concentration.

Question 24

Causes of HYPOcalcaemia

Answer 24

Vitamin D deficiency
Hypoparathyroidism
Pseudohypoparathyroidism

Question 25

common effects oh hypocalcaemia

Answer 25

neuromuscular spasms: eg Tetany

this is because low calcium makes cells more depolarised hence easier to fire APs.

Question 26

Causes of HypoParathyroidism

Answer 26

• IDIOPATHIC
• hypomagnesaemia
• suppression by raised calcium levels

Question 27

what is pseudohypoparathyroidism?

Answer 27

Genetic disorder known as:
Allbright hereditary Osteodystrophy
fault in GPCR of PTH on target cells hence resistance to PTH.

Question 28

features of all bright hereditary osteodystrophy

Answer 28

• low IQ
• short stature
• bone deformities
• associated endocrine disorders eg hypogonadism

Question 29

clinical features of vitamin D deficiency

Answer 29

• Rickets in children
• Osteomalacia in adults

leading to bowing and fracturing as bones weaker

Question 30

diagnosis of hypoparathyroidism

Answer 30

low calcium, high phosphate as not excreted, low PTH

Question 31

diagnosis of pseudohypoparathyroidism

Answer 31

low calcium, high poshphate, high PTH due to feedback

Question 32

diagnosis of vitamin D deficiency

Answer 32

low calcium, low phosphate as not absorbed by gut, high PTH

Question 33

causes of HYPERcalcaemia

Answer 33

Hyperparathyroidism (primary and tertiary only)

Vitamin D toxicosis

Question 34

what is primary hyperparathyroidism?

Answer 34

adenoma of Parathyroid gland causes excess secretion of PTH leading to high calcium in blood. negative feedback systems are present

Question 35

what is secondary hyperparathyroidism?

Answer 35

renal failure means most calcium is excreted hence low concentrations mean continual PTH secretion.

Question 36

what is tertiary hyperparathyroidism?

Answer 36

as a result of secondary, initial chronic low calcium causes overstimulation of parathyroid glands hence grows and becomes autonomous (no feedback) releasing lots of pTH meaning Calcium levels rise.

Question 37

hypercalcaemia effects

Answer 37

polyuria
renal stones
Gastrin release

Question 38

hyperparathyroidism effect

Answer 38

increased vitamin D synthesis
bone lesions
clubbing
duodenal ulcers

Question 39

Are the Parathyroid Glands on the front or back of the thyroid?

Answer 39

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