Endo 12 - Ca and Phosphate regulation

Question 1

How many parathyroid glands are there

Answer 1

4

Question 2

Vit D is stored in the liver as?

Answer 2

Calcidiol (25, OH-D)

Question 3

Name 3 action of PTH

Answer 3

1. Reduces Ca excretion in the kidneys
2. Promotes bone resorption
3. Stimulates 1a-hydroxylase in kidneys –> converts inactive Vit D —> active calcitriol

Question 4

Describe phosphate regulation

Answer 4

Phosphate is regulated by the gut and kidneys.

1. Phosphate is reabsorbed with Na+, via a cotransporter (from urine to PCT cell).
2. FGF23 (made by osteocytes) and PTH inhibit the cotransporter —> meaning more phosphate lost in urine.

(Therefore in primary HPT, serum phosphate low due to increased excretion).

3. FGF23 also inhibits calcitriol - which means less phosphate absorption from the gut.

Question 5

Explain how PTH secretion is regulated.

Answer 5

Regulation occurs in parathyroid cells

High Ca conc in ECF/serum binds to PTH receptor —> receptor activation causes inhibition of PTH secretion

Low Ca conc in ECF/serum = less binding / receptor activation = less inhibition = more PTH secretion

Question 6

Explain how calcitriol is synthesised

Answer 6

1. Skin (7-dehydrocholesterol) —> Vitamin D3 - cholecalciferol (via UVB light and dietary Vitamin D)
2. In liver, stores as 25-OH-D3 (inactive).
3. In kidney, activated via renal 1a-hydroxylase to become 1, 25 (OH)2D3 (calcitriol - biologically active)

Question 7

What are the main roles of calcitriol?(active vit d)

Answer 7

1. Ca absorption in gut
2. Ca maintenance in bone
3. Increased renal Ca absorption
4. Negative feedback on PTH (to prevent hypercalcaemia)

Question 8

What are the causes of vitamin D deficiency

Answer 8

1. Diet
2. Lack of sunlight
3. GI malabsorption (coeliac disease, IBD)
4. Renal failure, liver failure
5. Vit D receptor defects (autosomal recessive, rare, resistant to Vit D treatment)

Question 9

How do changes in EC Ca affect nerve and skeletal muscle excitability?

Answer 9

1. High EC Ca = hypercalcaemia = Ca blocks Na influx, so less membrane excitability
2. Low EC Ca = hypocalcaemia = enables greater Na influx, more membrane excitability

Question 10

What are the signs and symptoms of hypocalcaemia

Answer 10

1. Parasthesia (numbness - hands, mouth, feet, lips)
2. Convulsions
3. Arrhythmias
4. Tetany

CATs go numb

Question 11

Name 2 signs of hypocalcaemia that we can use

Answer 11

1. Chvosteks sign - tap facial nerve just below zygomatic arch - positive response = twitching of facial muscles
   (Indicates neuromuscular irritability due to hypocalcaemia)
2. Trousseaus sign - Inflation of BP cuff for several minutes - induces carpopedal spasm - state of tetany as a result of neuromuscular irritability due to hypocalcaemia

Question 12

What are the causes of hypocalcaemia

Answer 12

1. Vit D deficiency
2. HypoPT (due to surgery, auto-immune or Mg deficiency)
3. PTH resistance - i.e. pseudoHypoPT
4. Renal failure (causing impaired 1a-hydroxylation so less calcitriol production)

Question 13

What are the signs and symptoms of hypercalcaemia

Answer 13

Stones, abdominal moans and psychic groans

1. Stones - renal effects (polyuria and thirst, nephrocalcinosis, renal colic, chronic renal failure
2. Abdominal moans - anorexia, nausea, dyspepsia, constipation, pancreatitis
3. Psychic groans - fatigue, depression, impaired concentration, altered mentation, coma

Question 14

What are the causes of hypercalcaemia

Answer 14

1. Primary HPT
2. Malignancy - tumours, metastases (often secrete PTH like peptide)
3. Conditions with high bone turnover (hyperthyroidism, Paget’s, immobilised patient)
4. Vit D excess (rare)

Question 15

What are the features of primary HPT

Answer 15

1. Raised Ca
2. Low phosphate (less renal absorption)
3. Raised (unsuppressed PTH due to no negative feedback)

Question 16

What are the features of hypercalcaemia of malignancy

Answer 16

1. Raised Ca

2. Suppressed PTH (due to negative feedback)

Question 17

What is a vitamin D deficiency state

Answer 17

Lack of mineralisation in bone

Results in softening of bone, bone deformities, bone pain, severe proximal myopathy

Rickets in children
Osteomalacia in adults

Question 18

Differentiate primary and secondary HPT

Answer 18

Primary HPT = no negative feedback, autonomous PTH secretion despite hypercalcaemia. Treated with parathyroidectomy

Secondary HPT = high PTH levels is the RESPONSE to low serum Ca (trying to normalise) e.g. due to Vit D deficiency

Question 19

What are the biochemical findings in Vit D deficiency

Answer 19

1. Plasma 25-OH-D3 (inactive Vit D) low
2. Low plasma Ca (but may be normal if secondary HPT has developed)
3. Low plasma phosphate
4. PTH high (secondary HPT)

Question 20

How is Vit D deficiency treated in patients without renal failure?

Answer 20

If patient has normal renal function - give 25,OH,D3. Patient converts it into calcitriol (1, 25-OH-D3). Can be ergocalciferol based (25, OH D2) or cholecalciferol based (25, OH, D3)

Question 21

How is Vit D deficiency treated in patient with renal failure?

Answer 21

Renal failure = they cannot 1a hydroxylate and activate Vit D into Calcitriol

Give alfacalcidol - 1ahydroxycholecalciferol = acts as calcitriol substitute

Question 22

What can Vit D excess cause

Answer 22

Hypercalcaemia and hypercalcuria due to excess intestinal Ca absorption

Question 23

Name 2 causes of Vit D excess

Answer 23

1. Excessive treatment with active metabolites of Vit D (e.g. alfacalcidol)
2. Granulomatous diseases (rare) - sarcoidosis, leprosy and TB (macrophages in granuloma produce 1a hydroxylase - converts 25(OH)D into calcitriol)