Calcium and Phosphate Regulation

Question 1

What is the role of calcium in the body? (5)

Answer 1

1. Bones and teeth
2. Nervous system
3. Muscle contraction
4. Blood circulation
5. Endocrine homeostasis
   - most abundant metal in body
   - all requirements should be met via diet

Question 2

Which 3 hormones regulate serum calcium levels?

Answer 2

1. PTH (parathyroid hormone) —> inc
2. Vitamin D —> inc
   - both via kidneys, bones, gut actions
3. Calcitonin —> dec

Question 3

Which 3 hormones regulate serum phosphate levels?

Answer 3

1. PTH (parathyroid hormone) —> inc
2. Vitamin D —> inc
3. FGF23 (fibroblast growth factor 23) —> dec

Question 4

How is calcium distributed in the body? (3)

Answer 4

1. Skeleton and teeth —> 99%
2. Intracellular —> 1%
3. Extracellular —> 0.1% (tightly regulated)

Question 5

What are the 2 types of vitamin D?

Answer 5

1. Ergocalciferol = Vitamin D2
   
   • plant foods
2. Cholecalciferol = Vitamin D3
   
   • fatty animal foods (oily fish, egg yolks)
   • produced in body via sun exposure

Question 6

How is vitamin D metabolised in the body?

Answer 6

1. UVB rays absorbed by skin
2. 7-dehydrocholesterol —> pre-vitamin D3
   
   • skin
3. Pre-vitamin D3 —> vitamin D3
   
   • skin
4. Vitamin D3 —> 25(OH)cholecalciferol
   Vitamin D2 (from diet) —> 25-(OH)cholecalciferol
   
   • liver
   • 25-hydroxylase enzyme
   • biologically inactive —> indicator of vitD levels
5. 25(OH)cholecalciferol —> 1,25-(OH)2cholecalciferol
   = calcitriol
   
   • kidney
   • 1-alpha-hydroxylase enzyme (transcription dec
     with calcitriol production —> -ve feedabck)

Question 7

How does calcitriol regulate its own synthesis?

Answer 7

Calcitriol —> decreases transcription of 1-alpha-hydroxylase —> decreases hydroxylation of 25(OH)cholecalciferol —> dec calcitriol production

Question 8

What is the role of calcitriol in the body?

Answer 8

Increase Ca 2+ and PO4 3- absorption from gut
+ Ca 2+ reabsorption in bones
+ Ca 2+ and PO4 3- reabsorption by kidneys

Question 9

What is PTH and when is it released?

Answer 9

Parathyroid hormone
- Low serum Ca —> chief cells in parathyroid glands
detect via G-protein couples Ca receptors —> secrete
pre-pro-PTH —> cleaved —> PTH

Question 10

What is the role of PTH in the body?

Answer 10

Inc serum calcium levels:

Bones
- inc calcium release

Kidney
- inc calcitriol production
- inc calcium reabsorption
- inc phosphate release

Gut (effected by inc calcitriol)
- inc calcium absorption
- inc phosphate absorption

Question 11

How do hormones regulate calcium release from bones?

Answer 11

More hormone —> more binds to hormone-specific receptor on osteoblasts —> releases more OAFs (Osteoclast Activating Factors eg. RANKL) —> osteoclast breakdown more bone —> more calcium released

Low calcium —> more osteoclast activity
Normal —> more osteoblast activity

Question 12

What is calcitonin?

Answer 12

Hormone that decreases serum calcium levels
- via dec osteoclast activity and dec kidney
reabsorption
- secreted from parafollicular cells in thyroid gland
- not needed —> thyroid removal doesn’t lead to
hypercalcaemia

Question 13

What is the role of FGF23?

Answer 13

dec serum phosphate levels
- binds to Na/PO4 co-transporters in proximal tubule
—> dec PO4 reabsorption into peritubular capillary

Question 14

What is hypercalcaemia?

Answer 14

High serum calcium
—> blocks Na+ influx —> dec membrane excitability

Question 15

What is hypocalcaemia?

Answer 15

Low serum calcium
—> inc Na+ influx —> dec membrane excitability

Question 16

What are the 4 symptoms of hypocalcaemia?

Answer 16

1. Paraesthesia (hands, mouth, feet, lips)
2. Convulsions
3. Arrhythmias
4. Tetany

Question 17

What are the 2 causes of hypocalcaemia?

Answer 17

1. Hypoparathyroidism (low PTH)
   
   • surgeries eg. neck
   • auto-immune
   • Mg deficiency
   • congenital eg. agenesis of parathyroid glands
2. Vitamin D deficiency
   
   • Malabsorption
   • Dietary
   • Low sun exposure
   • Liver disease
   • Renal disease
   • Vit D receptor fault

Question 18

What are the 4 causes of hypoparathyroidism?

Answer 18

1. Surgeries eg. neck
2. Auto-immune
3. Mg deficiency
4. Congenital eg. agenesis of parathyroid glands

Question 19

What are the 6 causes of vitamin D deficiency?

Answer 19

1. Malabsorption
2. Dietary insufficiency
3. Low sun exposure (skin)
   
   • dec 7-dehydrocholesterol —> vit D3
4. Liver disease
   
   • dec vit D2/3 —> 25-OH D3
5. Renal disease
   
   • dec 25-OH vitD3 —> 1,25-(OH)2 D3
6. Vit D receptor fault
   
   • rare

Question 20

What does vitamin D deficiency lead to? (2)

Answer 20

Lack of bone mineralisation
- Children —> rickets
- bowing of bones
- Adults —> osteomalacia
- fractures, proximal myopathy

Question 21

What are the 2 tests for hypocalcaemia?

Answer 21

1. Chvostek’s sign
   
   • tap facial nerve below zygomatic arch —> face
     twitch
2. Trousseau’s sign
   
   • inflate BP cuff round arm for minutes —>
     carpopedal spasm

Question 22

What are the symptoms of hypercalcaemia? (3)

Answer 22

1. Stones (renal)
   
   • nephrocalcinosis —> kidney stones + renal colic
2. Moans (GI)
   
   • anorexia
   • nausea
   • dyspepsia (indigestion)
   • constipation
   • pancreatitis
3. Groans (CNS)
   
   • fatigue
   • depression
   • impaired concentration
   • altered mentation
   • coma —> >3mmol/L

Question 23

What are the 3 causes of hypercalcaemia?

Answer 23

1. Primary hyperparathyroidism —> high PTH
   
   • usually parathyroid gland adenoma
2. Malignancy
   
   • bony metastases —> inc OAFs production
3. Vitamin D excess
   
   • rare