Endo 12: Calcium + Phosphate regulation

Question 1

How is secretion of PTH linked to [Ca2+] ?

Answer 1

HIGH [Ca2+] ECF:

• Ca2+ binds to receptor of parathyroid cells
• receptor activation causes inhibition of PTH secretion.

LOW [Ca2+] ECF:

• Ca2+ doesn’t bind to receptor on parathyroid cells
• no inhibition
• so PTH is secreted
• -> leads to increased [Ca2+] in ECF

Question 2

What are 5 causes of Vit D deficiency?

Answer 2

1. malabsorption / dietary insufficiency (e.g coeliac disease/IBD)
2. lack of UVB light
3. liver disease
4. renal disease
5. receptor defects (vitamin D receptor defects)

Question 3

How do changes in EC Ca2+ affect nerve + skeletal muscle excitability ?

Answer 3

• generation of AP in nerve + skeletal muscle requires Na+ influx

if there is HIGH ec Ca2+ :

• -> Ca2+ blocks Na+ influx
• -> so there is LESS memb excitability

if there is LOW ec Ca2+:

• -> there is greater Na+ influx
• -> which increases memb excitability

Question 4

What is the normal range for serum Ca2+ ?

Answer 4

2.2-2.6 mmol/L

Question 5

What are some signs + symptoms of HYPOcalcaemia?

Answer 5

• parasthesia
• convulsion
• arrhythmias
• tetany

PCAT
(cats goes numb)

Question 6

What is Chvostek’s sign?

Answer 6

• if you tap facial nerve just below zygomatic arch
• and there is twitching of facial muscles
• -> this indicates neuromuscular irritability due to hypocalcemia.

Question 7

What is Trousseau’s sign?

Answer 7

• inflation of BP cuff for several minutes
• -> causes CARPOPEDAL spasm
• -> where there is neuromuscular irritability due to hypocalcemia

Question 8

What are some causes of HYPO calcaemia?

Answer 8

• vit D deficiency
• Low PTH levels (hypothyroidism)
• -> could be due to surgery, autoimmune, mg deficiency
• PTH resistance (pseudohypoparathyroidism)
• renal failure
• -> impaired 1a hydroxylation causes decrease production of calcitriol

Question 9

What are some signs and symptoms of hypercalcaemia?

Answer 9

(stones) renal effects:
- polyuria + thirst
- chronic renal failure

(abdominal moans) GI effects:

• anorexia
• nausea
• dyspepsia
• constipation
• pancreatitis

(Psychic groans) CNS effects:

• fatigue
• depression
• coma

Stones, abdominal moans, and psychic groans

Question 10

What are the 4 major causes of hypercalcaemia?

Answer 10

1. primary hyperparathyroidism
2. malignancy e.g tumors
   - -> often secretes PTH like peptide
3. conditions with high bone turnover
   - -> e.g paget’s disease of bone
4. vit D excess

Question 11

What are characteristics of primary hyperparathyroidism

Answer 11

• raised Ca2+ (due to no negative feedback)
• low Phosphate
• raised PTH (unsuppressed)

Question 12

What are characteristics of hypercalacaemia of malignancy?

Answer 12

• raised Ca2+

- suppressed PTH

Question 13

What is meant by Vit D deficiency state?

Answer 13

• lack of mineralization in bone.

–> which causes softening of bone, and bone deformities / pain, proximal myopathy

Question 14

vit D deficiency in children leads to :

vit D deficiency in adults leads to :

Answer 14

vit D deficiency in children leads to : RICKETS

vit D deficiency in adults leads to : OSTEOMALACIA

Question 15

What is the difference between primary + secondary hyperparathyroidism ?

Answer 15

PRIMARY: there is no negative feedback
and there is autonomous secretion of PTH despite hypercalcaemia

SECONDARY: there is Vit D deficiency
- so PTH increases to try and normalise serum Ca2+

Question 16

how would you treat primary hyperparathyroidism?

Answer 16

• parathyroidectomy

Question 17

What biochemical finding would you notice in patients with Vit D deficiency?

Answer 17

• Plasma [25(OH)D3] usually low
• Plasma [Ca2+] low
• Plasma [PO43-] low
• [PTH] high

Question 18

how would you treat Vid D deficiency?

a) in patients with normal renal function
b) inpatients with renal failure

Answer 18

how would you treat Vid D deficiency?

a) in patients with normal renal function
- give 25 hydroxy vit D
e. g ergocalciferol / cholecalciferol
- and patients will convert this to calcitriol via 1a hydroxylase

b) in patients with renal failure
- give alfacalcidol

Question 19

What might happen if there was excess vit D?

Answer 19

• may lead to hypercalcaemia
• may lead to hypercalciurea
• -> due to increased absorption of Ca2+

Question 20

what might cause Vit D excess?

Answer 20

• excessive treatment with active metabolites of Vit D

- granulomatous diseases

Question 21

How does the PTH act on the Kidney?

Answer 21

Increases retention of Ca2+

Question 22

How does the PTH act on the bone ?

Answer 22

tells bones to release store of calcium

Question 23

How does the PTH activate Vit D?

Answer 23

the activation of inactive VIT D relies on enzyme which is regulated by PTH

Question 24

What is the role of FGF23 in phosphate regulation

Answer 24

FGF 23 –> from osteocytes
also inhibits reabsorption of phosphate from the urine
increases excretion of phosphate in the urine

and also inhibits calcitriol –> also causes less reabsorption of phosphate

Question 25

What is the role of PTH in phosphate regulation

Answer 25

PTH promotes loss/excretion of phosphates in the urine

Question 26

How is Vit D produced?

Answer 26

VitD precursor = synthesized in skin
and in response to UVB light, Vitamin D3 (inactive) is produced in the liver.
inactive form is converted to activated form in the kidneys
by 1- alpha hydroxylase. (stimulated by PTH)

VitD can also come from diet.