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METABOLISM 2 > Calcium > Flashcards

Flashcards in Calcium Deck (41):
1

What are the three types of protein?

Peptide, steroid and amine

2

In what forms may calcium be found in the blood plasma?

50% is bound to protein such as albumin (but can be globulin), 40% is ionised and 10% is in a complex with phosphate or citrate

3

Where is most of the body calcium found?

Within cells

4

What happens to ionised calcium levels in response to acidosis?

They increase;
Albumin will bind to more H+ ions in order to buffer the decrease in pH and therefore there are less sites available for calcium to bind, and therefore the calcium is released as a non-bound ionic form (Ca2+)

5

What happens to ionised calcium levels in response to alkalosis?

They decrease;
Albumin will bind to less H+ ions in order to buffer the increased pH by allowing the circulation of more H+ and therefore there are more sites available on the albumin molecule for the binding of calcium, and therefore less is circulating in the ionised form

6

Where does most renal calcium reabsorption occur?

In the proximal tubule via paracellular routes

7

Describe the role of the proximal tubule in the reabsorption of calcium

This is where most of the calcium is reabsorbed, and this is by paracellular routes (between the cells) that is driven by the voltage gradient and is independent of PTH

8

Describe the role of the Loop of Henle in the reabsorption of calcium

About 20% of calcium reabsorption occurs here by paracellular and transcellular transport that is voltage-dependent

9

Describe the role of the distal tubule in the reabsorption of calcium

About 10% of calcium reabsorption occurs here via transcellular routes and this is PTH-dependent as it upregulates the TRPV calcium channels (apical surface), calcium ATPase and 3Na+/Ca2+ exchanger (basolateral membrane)

10

What happens when the calcium sensing receptor (CaSR) in the thick Loop of Henle is activated?

It causes the down regulation of the Na+/K+/2Cl- receptor on the apical surface

11

What drugs would inhibit the reabsorption of calcium in the Loop of Henle?

Loop diuretics

12

How does PTH affect the function of the proximal convoluted tubule?

Down-regulates sodium-phosphate transporters which reduces phosphate reabsorption, and increases gluconeogenesis in the PCT

13

How is PTH involved in the metabolism of vitamin D?

Allows conversion of calcidiol to calcitriol

14

How does PTH affect reabsorption of water, sodium and bicarbonate?

It inhibits their reabsorption via effects on the Na/H+ exchanger and the Na+/K+ ATPase

15

Describe how PTH is produced

There is translation to form pre-proPTH which migrates to the RER and is cleaved to form proPTH . The proPTH is then transported to the golgi apparatus where it is cleaved to form PTH and enters vesicles which are then stores or leave by exocytosis

16

What is the action of PTH on the kidney?

in the kidney PTH leads to decreased calcium excretion and increased phosphate excretion (to compensate for the increased phosphate levels derived from osteoclastic function).

Therefore there is more calcium reabsorbed and less phosphate reabsorbed

17

What is the action of PTH on bone?

To increase calcium and phosphate reabsorption

18

What is the action of PTH on the intestines?

Increased absorption of calcium and phosphate in the gut, mainly by indirect action of activating vitamin D

19

Where is the calcium sensing receptor found?

Everywhere, but most importantly the parathyroid gland and the kidney

20

What happens when calcium binds to the calcium sensing receptor?

Causes reduced PTH secretion, increased breakdown of stored PTH and suppressed transcription of the PTH gene

21

What is bone itself primarily made up of?

Collagen and hydroxyapatite

22

What causes mineralisation of bone?

Calcium, phosphate and alkaline phosphatase (ALP)

23

What is the mechanism of action of PTH on bone?

increases RANKL, decreased OPG, increases IGF1 and IL-1 which work to increase osteoclast activity (increased bone resorption)

24

What is the mechanism of action of calcitriol on bone?

Increases RANKL levels, decreased OPG (osteoprotegerin) and increases gut calcium absorption. Therefore increases serum calcium levels

25

What is the mechanism of action of glucocorticoid/cortisol on bone?

this reduces osteoblast numbers (reduced bone deposition) and mineral production as well as increasing RANKL

26

What is the mechanism of action of oestrogen on bone?

oestrogen contributes to epiphyseal closure, reduced cytokine sensitivity and inhibits bone remodelling

27

What molecule forms cholecalciferol on exposure to UVB light in the skin?

7-dehydrocholesterol is cleaved on exposure to UVB light and produces cholecalciferol

28

Which enzyme regulates the conversion of calcidiol to calcitriol in the kidneys?

1-alpha hydroxylase

29

What molecules promote conversion of calcidiol to calcitriol in the kidneys?

1-alpha hydroxylase is promoted/activated by increased PTH, decreased calcium or decreased phosphate levels

30

What molecules inhibit conversion of calcidiol to calcitriol in the kidneys?

1-alpha hydroxylase is inhibited by increased calcium, phosphate or increased calcitriol levels

31

What is the major role of calcitriol (activated vitamin D)?

To increase calcium and phosphate absorption the gut

OTHER ROLES:
- reduction in PTH transcription in the PTG
- Increased FGF23 levels to remove excess phosphate in the urine
- increase AA uptake

32

Where is the vitamin D receptor found?

The vitamin D receptor is found predominantly bound to the nucleus, but there are also some receptors present on the plasma membrane

33

What is the role of FGF23?

This is a phosphotonin molecule that is released due to activation from phosphate and calcidiol levels; FGF23 is involved in increasing renal excretion of phosphate and inhibit 1-alpha hydroxylase to prevent calcidiol conversion to calciltriol.

34

What is primary hyperparathyroidism?

This can occur when there is an absence of hypocalcaemia, parathyroid adenoma, carcinoma or hyperplasia all of these factors lead to hypercalcaemia development which can cause polyuria, polydipsia, kidney stones, osteoporosis and mood disorder

35

What is secondary hyperparathyroidism?

This occurs when the body begins to compensate for hypocalcaemia by secreting excess amounts of PTH

36

What is tertiary hyperparathyroidism?

This is where the body’s PTH production becomes independent of calcium levels and this is due to chronic secondary hyperparathyroidism

37

What is hypoparathyroidism?

This is usually caused by treatment given for hyperparathyroidism (iatrogenic) or as a result of chronic kidney disease or vitamin d deficiency, and therefore causes hypocalcaemia which can lead to convulsions, arrhythmia, tetany and paraesthesia

38

How do you treat acute hypoparathyroidism?

Calcium replacement therapy

39

How do you treat chronic hypoparathyroidism?

Calcitriol supplementation to increase gut absorption of calcium

40

How may calcitriol supplementation lead to the development of kidney stones?

The use of calcitriol supplements will increase the absorption of calcium, but because PTH will not be produced by the body, there won’t be a reduction in calcium reabsorption in the kidney, so it will continue to be excreted at a high rate. This excess calcium presence in the renal fluid leads to hypercalciuria which increases the risk of developing kidney stones, even if the plasma calcium is low.

41

What is familial hypocacliuric hypercalcaemia (FHH)?

This involves inactivating mutations of the calcium sensing receptor and therefore the parathyroid gland can't detect high calcium levels effectively, so PTH secretion isn't suppressed by elevated calcium levels. In addition, the calcium sensing receptor in the kidney is not activated and therefore there is no increase in calcium excretion when serum levels are raised, and this leads to the development of high serum calcium and low urinary calcium