Calcium Homeostasis & Vitamin D

Question 1

Where is calcium found in the diet?

Answer 1

Cereals

Milk

Question 2

How much calcium do we need per day?

Answer 2

807mg/day

Question 3

Where is phosphorus found in the diet?

Answer 3

Cereals

Milk

Meat

Question 4

What food/ingredient is fortified with calcium by law?

Answer 4

White flour

Question 5

How much calcium is absorbed in the diet and from supplements?

Answer 5

Diet - 25-35%

Supplements - 35-40%

Question 6

What can increase calcium bioavailability?

Answer 6

Casein and lactose in dairy products

Question 7

What substances inhibit calcium absorption in the gut?

Answer 7

Oxalate

Phytate

Question 8

What is the most important inhibitor of calcium absorption in the gut?

Answer 8

Phytate

Question 9

What is the most potent inhibitor of calcium absorption in the gut?

Answer 9

Oxalate

Question 10

When do calcium requirements increase?

Answer 10

During growth spurts

Lactation (+550mg/day)

Question 11

What are normal plasma calcium levels?

Answer 11

2.25-2.6mM (~2mM)

Question 12

Where in the GI tract is calcium absorbed?

Answer 12

Duodenum

Question 13

How is calcium absorbed in the GI tract? (3)

Answer 13

Taken up in ion form through ECaC/CaT1 down concentration gradient

Binds to calcium-binding protein/calbindin which translocates calcium to the BL membrane

Ca-ATPase or Na/Ca exchanger used to export calcium

Question 14

What is the ratio of ions transported by the Na/Ca exchanger?

Answer 14

3Na to 1Ca

Question 15

What is upregulated in the duodenum by vitamin D?

Answer 15

ECaC and CaBP expression

Question 16

Which calcium-binding protein is larger: duodenal or renal?

Answer 16

Renal

Question 17

What percentage of circulating calcium is free/ionised?

Answer 17

~50%

Question 18

What form of calcium is freely filtered at the renal corpuscle?

Answer 18

Ionised calcium

Question 19

Where is calcium freely and passively reabsorbed from the nephron?

Answer 19

PCT and thick ascending limb ~95%

Question 20

Where does controlled reabsorption of calcium occur in the nephron?

Answer 20

DCT and upper part of collecting duct

Question 21

What is NCX1?

Answer 21

Na/Ca exchanger on BL membrane of duodenal enterocytes and cells of DCT

Question 22

What does PMCA1b stand for?

Answer 22

Plasma membrane Ca-ATPase 1b

Question 23

What stimulates reabsorption of calcium from the nephron?

Answer 23

Vitamin D and parathyroid hormone

Question 24

What inhibits reabsorption of calcium from the nephron?

Answer 24

Calcitonin

Question 25

What type of hormone is calcitonin?

Answer 25

Peptide

Question 26

Where are calcium-sensing receptors found? (4)

Answer 26

Parathyroid gland Thyroid Bone Renal tubules

Question 27

What is stimulated by low plasma calcium (hormonal)?

Answer 27

Increased PTH and inhibition of calcitonin secretion

Question 28

What is stimulated by high plasma calcium (hormonal)?

Answer 28

Increased calcitonin and inhibition of PTH secretion

Question 29

Describe what happens when plasma calcium decreases below normal.

Answer 29

Detection by calcium-sensing receptors Increased PTH and inhibition of calcitonin secretion PTH activates vitamin D Increased: - Renal calcium reabsorption - Intestinal calcium absorption - Bone resorption

Question 30

Describe what happens when plasma calcium increases above normal.

Answer 30

Detection by calcium-sensing receptors Increased calcitonin and inhibition of PTH secretion Decreased renal reabsorption/increased renal excretion

Question 31

What are the two precursors of vitamin D?

Answer 31

Cholecalciferol (D3) Ergocalciferol (D2)

Question 32

Where does the majority of vitamin D come from in humans?

Answer 32

Action of UV B-radiation on skin to convert 7-dehydrocholesterol into cholecalciferol (photoconversion)

Question 33

What takes up pre-vitamin D for storage?

Answer 33

Liver

Question 34

What is the first metabolite of vitamin D and how does it circulate?

Answer 34

25 hydroxy vitamin D (25-OH-D) Bound to vitamin D-binding protein

Question 35

Where is 25-OH-D activated?

Answer 35

Kidneys

Question 36

What causes activation of 25-OH-D and how?

Answer 36

Decreased plasma levels of vitamin D, calcium or phosphate; parathyroid hormone Stimulates an α-hydroxylase in kidney to cause a second hydroxylation to form 1, 25 dihydroxy vitamin D

Question 37

What is the active form of vitamin D?

Answer 37

1, 25 dihydroxy vitamin D

Question 38

What is the "off switch" in vitamin D activation?

Answer 38

If vitamin D, calcium or phosphate levels rise too quickly then a second hydroxylation forms 24, 25 dihydroxy vitamin D (inactive) instead

Question 39

In the UK, when is vitamin D formed by photoconversion?

Answer 39

April to September

Question 40

How much vitamin D is recommended per day?

Answer 40

10ug/day (above 4yo)

Question 41

What foods contain more vitamin D than others? (4)

Answer 41

Egg yolk (5ug/100g) Margarines Cod liver oil (210ug/100g) Dairy in USA

Question 42

What food is fortified with vitamin D by law in the UK?

Answer 42

Margarines

Question 43

How does phytate affect vitamin D stores?

Answer 43

Decreases stores Blocks calcium absorption so less plasma calcium which stimulates activation of vitamin D to maintain homeostasis

Question 44

How do anticonvulsants affect vitamin D activation?

Answer 44

Inhibit activation Inhibit the cytochrome-based enzymes involved in activation

Question 45

What are some renal risk factors for vitamin D deficiency? (6)

Answer 45

Low PTH High phosphate Rickets Some tumours Renal failure Nephrectomy

Question 46

What role does vitamin D have on growing bones?

Answer 46

Controls growth and turnover Acts on growth plates in proliferative zone - main trigger in differentiation of chondrocytes from proliferative to hypertrophic cells

Question 47

How does a vitamin D deficiency cause rickets?

Answer 47

Cells in growth plates remain proliferative More matrix and plate expands and becomes too flimsy to support weight

Question 48

What are the clinical features of rickets? (3)

Answer 48

Knock-knees/bow-legs (femur) Enlarged wrists Rachitic rosary (ribcage)

Question 49

What effect does vitamin D deficiency have on adults? (3)

Answer 49

Osteomalacia Increased PTH levels so more bone resorption but insufficient mineral to complete remodelling Unmineralised, collagen-rich matrix appears as looser zones/pseudofractures on x-rays