12. Calcium and Phosphate Regulation

Question 1

Effect on PTH of fall in serum calcium

Answer 1

Increased production

Question 2

PTH THREE main mechanisms of action

Answer 2

1. Mobalises calcium from bone to increase [plasma calcium]
2. Direct effect on the kidneys to increase calcium reabsorption
3. Indirectly via the activation of vitamin D- stimulates the kidneys to produce 1a-hydroxylase which converts the precursor 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol (calcitrol)

Question 3

TWO effects of calcitrol on serum calcium

Answer 3

1. Increases calcium absorption in the intestines
2. Increases calcium mobalisation in bone- activate osteoblasts which relesase RANKL

Question 4

Main aspects of phosphate regulation

Answer 4

Occurs via the gut and the kidneys

• Phosphate is reabsorbed via sodium phosphate transporter cells
• PTH inhibits renal phosphate reabsorption by inhibiting these transporters
• SO in primary hyperparathyroidism serum phosphate is LOW
• FGF23- derivied from bone- also inhibits phosphate reabsorption by blocking the transporters as well as calcitrol

Question 5

Regulation of PTH Secretion

Answer 5

Via:

• Calcium sensor receptor- when calcium conc. is high it will bind to this on the surface of the parathyroid cell- causes PTH inhibition

Question 6

Sources and effects of calcitriol (vitamin D)

Answer 6

Sources of vitamin D:

• UV acts on 7-dehydrocholesterol in the skin to form cholecalciferol (D3)
• Our diet contains ergocalciferol (D2)

Colecalciferol is converted to 25-hydroxycholecalciferol in the liver- inactive vitamin D

Then it is activated in into 1,25 dihydroxycholecalciferol (calcitriol) in the kidneys via 1a-hydroxylase

Effects of calcitriol:

• Increased calcium absorption in the intestines
• increased calcium maintainence in bone
• increased renal reabsorption of calcium
• negative feedback on PTH

Question 7

Causes of Vitamin D deficiency

Answer 7

• Diet (lack of ergocalcitrol)
• Lack of sulight
• Gastrointestinal malabsorption (due to coeliac disease IBS etc.)
• Renal failure, liver failure (cannot produce or store calcitriol)
• Lack of receptors for calcitriol (autosomal recessive- RARE)

Question 8

How does increasing calcium EC conc. affect nerve and skeletal muscle excitability?

Answer 8

Requires Na⁺ influx accross cell membrane

HYPERcalcaemia= Ca²⁺ blcoks Na⁺ influx, so LESS membrane excitability

Question 9

Normal range for serum calcium

Answer 9

2.2-2.6 mmol/l

Question 10

Signs and symptoms of hypocalcaemia

Answer 10

• Parasthesia (numbness in hands, mouth feet and lips)
• Arrhythmias
• Convulsions
• Tetany

CATs GO NUMB

Hypocalcaemia sensitises excitable tissue

Question 11

Chvostek’s sign for hypocalcaemia

Answer 11

• Tap the fascial nerve just below the zygomatic arch
• POSITIVE response= twitching of fascial muscles
• Indicates neuromuscular irrritability

Question 12

Trosseau’s Sign for hypocalcaemia

Answer 12

Inflation of the blood pressure cuff induces carpopedal spasm

again due to neuromuscular irritability

Question 13

Causes of hypocalcaemia

Answer 13

• Vitamin D deficiency
• Low PTH levels= hypoparathyroidism
  
  • ​Surgical- parathyroidectomy
  • Auto-immune
  • Magnesium deficiency (needed for it to function)
• PTH resistence
• Renal failure- impaired 1a-hydroxylase, lack of calcitriol

Question 14

Signs and symptoms of hypercalcaemia

Answer 14

• Stones- renal effects
  
  • Polyuria + Thirst
  • Nephrocalcinosis (deposition of calcium in the kidneys)
• Abdominal moans- GI effects
  
  • Anorexia, nausea, dyspepsia, constipation, pancreatitis
• Phychic groans- CNS effects
  
  • Fatigue, depression, imparied concentration, altered mentation, coma

Question 15

Causes of Hypercalcaemia

Answer 15

Mostly:

1. PRIMARY HYPERPARATHYROIDISM- due to a parathyroid adenoma which produces excessive amounts of PTH

2. MALIGNANCY- tumours/ metastases- can be due to a bone metastasis which increases turnover or a rumour producing PTH like peptides

Some:

3. Conditions with high bone turnover- Hyperthyroidism, Padget’s disease of bone

4. Vitamin D excess

Question 16

Diagnosing Primary Hyperparathyroidism

Answer 16

Looking at serum concentrations:

• Calcium- HIGH
• Phosphate- LOW
• PTH- HIGH

Question 17

Diagnosing hypercalcaemia of malignancy (bone metastases)

Answer 17

Calcium rises but negative feedback is still intact so:

• Calcium- HIGH
• PTH- LOW

Question 18

Vitamin D Deficiency state definition and result

Answer 18

Lack of mineralisation in bone

results in:

• Softening of bone- characteristic bowing of the legs
• Bone deformities
• Bone pain
• Severe proximal myopathy

Deficiency is: Rickets in children, Osteomalacia in adults

Question 19

Diagnosing secondary hyperparathyroidism

Answer 19

Vitamin D deficiency leads to decreased calcium

PTH increases to normalise serum calcium

Generally 25-hydroxycholecalciferol is measured as a gage of the amount of calcitriol

Question 20

Treatment of vitamin D deficiency

Answer 20

• In patients with NORMAL RENAL FUNCTION
  
  • Give 25-hydroxy vitamin D
  • Patients can convert this to calcitriol via 1a- hydroxylase
  • can be ergocalciferol or cholecalciferol
• In patients with RENAL FAILURE
  
  • ​Dont have their own 1a- hydroxylase
  • So they cant activate 25-hydroxy vitamin D preparations
  • Give ALFACALCIDOL- 1-hydroxycholecaliferol

Question 21

Vitamin D Excess (intoxication)

Answer 21

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

Vitamin D excess can occur as a result of:

• Excessive treatment with active metabolites of vitamin D, as in patients with chronic renal failure
• Granulomatous Disease - e.g. sarcoidosis, leprosy and tuberculosis

Granulomatous tissue can convert 25-hydroxycholecalciferol to the active metabolite 1,25-dihydroxycholecalciferol

This is because granulomatous tissues have 1a hydroxylase