Year 2: Calcium and Phosphate regulation

Question 1

Explain the role of PTH in calcium homeostasis

Answer 1

PTH is secreted when Ca2+ is low leading to

1. Kidney
   
   • promotes reabsorbtion of Calcium
   • Activation of active Vit D
2. Bone
   
   • release of Calcium and phosphate

Question 2

Explain the role of Vitamine D in calcium homeostasis

Answer 2

Gets activated by Renal 1a-hydroxylase (stimmulated by PTH) to Calcitriol causes and increase in

1. Calcium absorbtion in the small intestine
2. Bone mineralisation
3. negative feedback on PTH

Question 3

Explain the regulation of release of PTH

Answer 3

1. Regulated by plasma Calcium levels
   
   1. at high concentrations: calcium binds to receptor and inhibits release
2. -ve feedback of Calcitriol

Question 4

What are the sources of Vitamin D?

Answer 4

1. Sunlight
   
   • activation of precursor in skin by UV light
2. Diet (limited)

Question 5

What is the site of storage of Vit D?

In which form is it stored?

Answer 5

It is stored as 25 OH D₃ in the liver (until activated by the kidney)

Question 6

Explain the activation of Vit D

Answer 6

Activated by renal 1alpha- hydroxylase in the kidney

stimmlated by PTH

Causing hydoxilisation of 25 OH D₃ to 1,25(OH)₂ D₃ (Calcitriol)

Question 7

What is the role and effect of Calcitriol?

Answer 7

1. Increase Ca2+ and calcium absorbtion in gut
2. Increase renal calcium reabsorbtion
3. Increase bone mineralisation
4. -ve feedback on PTH

Question 8

What are the causes of Vit D deficiency?

Answer 8

Can go wron every step of the way:

1. Lack of sunlight
2. Malnutrition/Malabsorbtion (very common in uk in combination with low sunlight)
3. Liver disease –> Lack of storage site
4. Renal disease –> Lack of 1alpha-hydroxylase
5. Defects in Vit D receptor (rare, autosomal recessive)

Question 9

What are the possible causes for hypocalcaemia?

Answer 9

1. Vit D deficiency
2. Renal failure –> no hydroxylation + activation of VIt D
3. Hypoparathyroidism
   
   • Durgical damage to PT- glands
   • Auto-immune
   • magnesium deficiency
4. Pseudo-hypoparathyroidism (PTH resistance)

Question 10

What are the possible causes for hypercalcaemia?

Answer 10

1. Primary hyperparathyroidism (e.g. autoimmune)
2. Malignancy
   
   • metastisis release Ca2+ from bone
   • ectopic –> release of PTH like hormone
3. Conditions with high bone turnover
   
   • hyperthyroidism
   • Paget’s disease

• Vitamine D excess (rare)

Question 11

What are the clinical signs and symptoms of Hypercalcaemia?

Answer 11

High Ca2+ blocks Na+ influx into cells –> less excitability causing

• Stones, abdominal moans and psychic groans
  
  • Stones= renal effects
    
    • polyuria + thirst –> attemt to excrete
    • Nephrocalcinosis –> colic + renal failure
  • Abdominal moans
    
    • reduced muscle activity leading to
    • anorexia, constipation, nausea
  • Psychic effects
    
    • depression, low mood, fatigue, altered mentation
    • Coma (>3mmol/l)

Question 12

What are the clinical signs and symptoms of hypocalcaemia?

Answer 12

Causes more Na+ influx into cell –> easier exitable

• Parasthesia (tingeling) in mouth, fingers, toes
• Convulsions (Krampf)
• Arrythmias
• Tetany

Can be tested by

1. Chvostek’s sign
   
   • tapping of facial nerve on zygomatic arch causes twitching of muscle
2. Trousseau’s sign
   
   • inflation of BP cuff causes carpopendal spasm

Question 13

What is the Chvostek’s sign?

Answer 13

Sign of Hypocalcaemia

• taping on facial nerve near zygomatic arch induces twitching of facial muscle

Question 14

What is the Trousseau’s sign?

Answer 14

Sign of Hypocalcaemia

• Inflation of BP cuff causes carpopendal spasm in hand

Question 15

What is primary hyperparathyroidism?

How would the laboratory findings look like?

Answer 15

Primary= too much production of PTH due to loss of -ve feedback (e.g. autoimmune)

• High PTH
• HIgh Ca2+
• (low Po₄³-)

Question 16

What is secondary hyperparathyroidism?

How would the laboratroy findings look like?

Answer 16

High PTH levels in response to low Ca2+ levels (due to Vit D deficiency)

• Low Ca2+
• Try to increase by high PTH
• but not possible because problem is: Vit D deficiency

Question 17

Explain Hypercalcaemia of malignancy

How would the laboratory findings look like?

Answer 17

1. Release of Ca2+ or ectopic PTH (like peptide release
   
   • low PTH (feedback works)
   • high Ca2+ (not regulated by PTH anymore)

Question 18

How would the laboratory findings in someone with Vit D deficiency look like?

Answer 18

Normally

• Vit D low (25 OH D₃ meausured)
• Ca2+ low (might be normal if 2nd hyperparathyroidism activated –> bone degradation)
• PO_4^3- low (low gut absorbtion)
• PTH high (secondary hyperparathyroidism)

Question 19

What are the effects of Vit D deficiency?

Answer 19

Low Ca2+ and

1. Rickets in children
2. Osteomalacia in adults

–> Softening of bone due to use of Ca2+ from bone + lack of mineralisation of bone

Question 20

How do you treat Vit D deficiency?

Answer 20

1. Patients with normal renal function
   
   • replacement of inactive Vit D
     
     • Cholecicalciferol (25OHD₃)
     • Ergocalciferol (25OH D₂)
   • gets activated by 1alpha-hydroxylase
2. Patients with renal failure
   
   • replacement with active form
     
     • Alfacalcidol - 1a hydroxycholecalciferol

Question 21

What are the signs of a Vit D intoxication?

Answer 21

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

Question 22

What are the possible reasons for a Vit D intoxication?

Answer 22

1. Too much treatment with active compound of Vit D –> Alfacalcidiol
2. Granulomatous disease (e.g. TB, leprosy)
   
   • macrophages release 1alpha-hydroxlase (activates Vit D)