Calcium and Phosphate Regulation

Question 1

How do PTH and vitamin D interact?

Answer 1

PTH produced in parathyroid gland - makes kidneys retain more calcium, makes bones release calcium, regulate activation of vitamin D in kidneys leading to increased reabsorbtion of calcium in gut

Question 2

Outline the process of phosphate regulation

Answer 2

Phosphate into proximal convoluted tube from urine via Na+/PO4 3- co-transporter ( PTH and FGF23 promote excretion into urine)

*FGF23 inhibit calcitriol leading to less phosphate absorption in gut

Question 3

How is PTH secretion regulated?

Answer 3

High extracellular [Ca2+]
Ca2+ binds to receptor -> recptor activation -> inhibition of PTH secretion

Low extracellular [Ca2+]
Ca2= not bound to receptor -> no inhibition -> PTH secreted -> increased extracellular [Ca2+]

Question 4

How is vitamin D produced?

Answer 4

7-dehyrocholesterol (skin) -> cholecalciferol (vitamin d3) via UVB light

Cholecalciferol + ergocalciferol (vit D3 from diet) -> 25-OH- D3 (in liver)

25-OH-D3 -> 1,25(OH)2D3 (calciferol) via renal 1 alpha- hyroxylase

• calciferol -> calcium absorption in gut, calcium mainatenance in bone and increased renal calcium reabsorption

Also has negative feedback on pth

Question 5

What are some causes of vitamin D deficiency?

Answer 5

1. Malabsorption (e.g coeliac disease) or dietary insufficiency
2. Lack of sunshine (UVB light) - light has to shine for longer on darker skin to activate the same amount of vit D
3. Liver disease (first conversion)
4. Renal disease (second conversion)
5. Receptor defects

Question 6

How do changes in extracellular calcium affect nerve and skeletal muscle excitability?

Answer 6

Na+influx Across cell membrane required to generate AP

High EC calcium -> Na+ influx blocked -> less embrace excitability

Low EC calcium -> greater Na+ Influx -> more membrane excitability

Question 7

What is the normal range for serum calcium?

Answer 7

2.2-2.6 mmol/L

Question 8

How would someone present with hypocalcaemia?

Answer 8

Sensitises excitable tissue - muscle cramps/tetany, tingling

PCAT
Parasthesia (hands, mouth, lips, feet)
Convulsions
Arrythmias
Tetany

Question 9

What is Chvostek’s sign?

Answer 9

Tap facial nerve just below zygomatic arch

Positive response = twitching of facial muscles

*indicates neuromscular excitability due to hypocalcaemia

Question 10

What is Trousseau’s sign?

Answer 10

Inflation of BP cuff for several minutes induces carpopedal spasm ( neuromuscular irritability due to hypocalcaemia)

Question 11

What are some causes of hypocalcaemia?

Answer 11

Vit D deficiency

Low PTH (hypoparathyroidism)

• neck surgery
• auto-immune
• magnesium deficiency

PTH resistance e.g pseudohypoparathyroidism

Renalfailure
- I aired 1 alpha-hydroxylation -> decreased production of 1,25(OH)2D3

Question 12

How would someone present with hypercalcaemia?

Answer 12

Reduced neuronal excitability -> atonal muscles

‘Stones, abdominal moans, psychic groans’

Stones (renal effect)

• polyurethaning and thirst
• nephrocalcciosis, renal colic, chronic renal failure

Abdomianlmoans (GI effect)
- anorexia nausea, dyspnoea, constipation pancreatitis

Psychi groans (CNS effects)
Fatigue, depression, impaired concentration, littered mentation, coma (usually >3mmol/L)

Question 13

What are some causes of hypercalcaemia?

Answer 13

Primary hyperparathyroidism

Malignancy 90%(tumours/metastises)
- often secrete PTH-like peptide

Conditions with high bone turnover- hyperthyroidism, Paget’s disease)

Vit D excess (rare)

Question 14

What happens in primary hyperparathyroidism?

Answer 14

E.g adenoma

Increased PTH -> Raised calcium and low phosphate due to no negative feedback

Question 15

What happens in hypercalcaemia of magnancy?

Answer 15

Increased calcium but low PTH due to boney metastises

Question 16

What happens in secondary hyperparathyroidism?

Answer 16

Vitamin D deficiency -> Low calcium and low phosphate

Increased PTH to try to normalise serum calcium

Question 17

What are the treatments for vitamin D deficiency?

Answer 17

Normal renal function
- give 25-OH-D3
- patient converts it to 1,25 dihyroxy vit D (1,25(OH)2D3 via 1 alpha-hydroxylase
>ergocalciferol (25(oh)D2) or cholicalciferol

Renal failure

• inadequate 1 alpha-hydroxylation so can’t activate 25 hydroxyl vit D preparations
• give alfacalidol (1 alpha hydroxycholecalciferol)

*very potent so not available over the counter

Question 18

What are the causes and effects of excess vitamin d?

Answer 18

Causes:

• excessive treatment wth active metabolites of vit D .g alfacalcidol
• granulomatous disease (e.g sarcaoidosis, leprosy, and TB) - macrophages in granuloma produce 1 alpha hydroxylase to convert 25(OH)D3 to active metabolite 1,25(OH)2D3

Can lead to hypercalcaemia and hypercalcaemia due to increased intestinal absorption of calcium