Calcium and Phosphate regulation

Question 1

Describe the process of phosphate reabsorption

Answer 1

Phosphate is reabsorbed via sodium phosphate transporter into the proximal convoluted tubule cells

Question 2

How dos PTH regulate phosphate reabsorption

Answer 2

Inhibits renal phosphate reabsorption by inhibiting the sodium phosphate co-transport

Question 3

How dos FGF23 regulate phosphate reabsorption

Answer 3

Inhibits the sodium phosphate co-transporters and inhibits calcitriol synthesis, reducing phosphate reabsorption from the gut

Question 4

Explain how the parathyroid gland responds to calcium levels in the blood

Answer 4

Calcium binds to a receptor in high calcium conc.
Receptor activates
Inhibition of PTH secretion

Question 5

How is calcitriol synthesised

Answer 5

1. UV light converts 7-dehydrocholesterol into cholecalciferol/vit D3 (obtained from the diet via ergocalciferol)
2. Synthesis of 2,5-hydroxy-cholecalciferol in the liver (+2 OH groups)
3. PTH stimulates 1𝛼 hydroxylase
4. synthesis of 1,25-di-hydroxycholecalciferol in the kidney

Question 6

What does calcitriol / 1,25(OH)2D3 stimulate

Answer 6

Ca2+ absorption in the gut
Ca2+ maintenance in the bone
Increased renal Ca2+ reabsorption
-ve feedback on the PTH

Question 7

What are the causes of vitamin D deficiency

Answer 7

Diet 
Lack of sunlight (UVB)
GI malabsorption (coeliac, IBS)
Renal failure
Liver failure 
Vit D receptor defects

Question 8

Describe vitamin D receptor defects

Answer 8

Autosomal recessive
Rare
Resistant to vit D treatment

Question 9

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

Answer 9

Hypercalcaemia = calcium blocks Na+ influx -> less membrane excitability

Hypocalcaemia = enables greater sodium influx -> more membrane excitability

Question 10

What are the signs symptoms of hypocalcaemia

Answer 10

Parasthesia (hands, mouth, feet , lips)
Convulsions
Arrhythmias
Tetany
Muscle cramps/tingling

Question 11

What is chvostek’s sign

Answer 11

Tap facial nerve just below the zygomatic arch
+ve response = twitching of facial muscles
Indicates neuromuscular irritability due to hypocalcaemia

Question 12

What is trousseau’s sign

Answer 12

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

Question 13

What are the causes of hypocalcaemia

Answer 13

Vitamin D deficiency
Low PTH levels (hypoparathyroidism)
PTH resistance (pseudohypoparathyroidism)
Renal failure

Question 14

What causes hypoparathyroidism

Answer 14

Surgical – neck surgery
Auto-immune
Magnesium deficiency

Question 15

How does renal failure cause hypocalcaemia

Answer 15

Impaired 1a hydroxylation ->decreased production of 1,25(OH)2D3

Question 16

What is the normal range of calcaemia

Answer 16

2.2-2.6 mmol/L

Question 17

What are the renal effects of hypercalcaemia (signs and symptoms)

Answer 17

Renal stones
polyuria
polydipsia

Question 18

What are the causes of hypercalcaemia

Answer 18

Primary hyperparathyroidism
Malignancy - tumours/metastases often secrete a PTH-like peptide
Conditions with high bone turnover (hyperthyroidism, Paget’s disease of bone – immobilised patient)
Vitamin D excess (rare)

Question 19

How is primary hyperparathyroidism diagnosed

Answer 19

Raised calcium
Raised PTH
Low phosphate

Question 20

How is hypercalcaemia of malignancy diagnosed

Answer 20

Raised calcium

Suppressed PTH

Question 21

What is the definition of vitamin D deficiency and what are the states in children and adults

Answer 21

Lack of mineralisation in bone

children - rickets
Adults - osteomalaxcia

Question 22

What does vitamin D deficiency result

Answer 22

Results in softening of bone
Bone deformities
Bone pain
Severe proximal myopathy.

Question 23

What is the treatment of primary hyperparathyroidism

Answer 23

parathyroidectomy

Question 24

How is secondary hyperparathyroidism diagnosed

Answer 24

Low calcium

Increased PTH

Question 25

What are the biochemical findings in vitamin D deficiency

Answer 25

Plasma [25(OH)D3] is low Plasma Ca2+ is low Plasma phosphate low PTH high

Question 26

How is vitamin D deficiency treated when the patient has normal renal function

Answer 26

Give 25 hydroxy vitamin D (25 (OH) D) Patient converts this to 1,25 dihydroxy vitamin D (1,25 (OH)2 D) via 1a hydroxylase Ergocalciferol 25 hydroxy vitamin D2 Cholecalciferol 25 hydroxy vitamin D3

Question 27

How is vitamin D deficiency treated when the patient is in renal failure

Answer 27

Give Alfacalcidol - 1a hydroxycholecalciferol

Question 28

What can vitamin D excess lead to

Answer 28

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

Question 29

What can vitamin D excess (intoxication) occur as a result of

Answer 29

excessive treatment with active metabolites of vitamin D eg Alfacalcidol granulomatous diseases such as sarcoidosis, leprosy and tuberculosis (macrophages in the granuloma produce 1a hydroxylase to convert 25(OH) D to the active metabolite 1,25 (OH)2 D

Question 30

What are the actions of PTH on the kidney

Answer 30

Increased calcium reabsorption Increased phosphate excretion Stimulates 1alpha-hydrolxylase activity -> calcitriol synthesis

Question 31

What are the actions of PTH at the small intestine

Answer 31

Increased Ca2+ absorption | Increased phosphate absorption

Question 32

What are the actions of PTH in the bone

Answer 32

Stimulation of osteoclasts and inhibition of osteoblasts | Increased bone resorption (decreased bone mass)

Question 33

What are the GI effects of hypercalcaemia (signs and symptoms)

Answer 33

``` Abdominal moans Anorexia Nausea Dyspepsia Constipation Pancreatitis ```

Question 34

What are the CNS effects of hypercalcaemia (signs and symptoms)

Answer 34

``` Psychic groans Fatigue Depression Impaired concentration Altered mentation Coma ```