Calcium Dysregulation

Question 1

What hormones increase calcium?

Answer 1

Vitamin D:
Synthesised in skin or dietary intake
Aka calcitriol/ 1,25-dihydroxy cholecalciferol

Parathyroid hormone:
Secreted by parathyroid glands

These are the main regulators of calcium and phosphate and act through Kidney, Bone, Gut

Question 2

Which hormones decrease calcium?

Answer 2

Calcitonin:
Secreted by thyroid parafollicular cells
Can reduce calcium acutely but no pathology if removed

Question 3

What happens in vitamin D metabolism?

Answer 3

Skin:
UVB sun rays hit skin -
7-dehydrocholesterol -> previtamin D3 -> vitamin D3

Diet:
Ingested vitamin D2 (turned to D3)

Both go into blood

Liver:
25-hydroxylase turns vitamin D3 -> 25-hydroxy cholecalciferol

Kidney:
1 alpha-hydroxylase turns 25(OH)cholecalciferol -> 1,25-dihydroxy cholecalciferol

Basically:
25 hydroxylase in liver
1 alpha hydroxylase in kidney

1,25(OH)2 vitamin D is the active form = calcitriol

Question 4

How are vitamin D levels in the body measured?

Answer 4

Serum 25 hydroxy cholecalciferol

Question 5

How is vitamin D synthesis regulated?

Answer 5

1,25 dihydroxy cholecalciferol (calcitriol) regulates its own synthesis

It decreases transcription of 1 alpha hydroxylase

Question 6

What are the effects of vitamin D on the body?

Answer 6

Bone:
Increased osteoblasts (makes bone) activity 

Gut:
Increases calcium absorption
Increases phosphate absorption

Kidney:
Increases calcium reabsorption
Increases phosphate reabsorption

So In all increases serum calcium

Question 7

What are the effects of parathyroid hormone on the body?

Answer 7

Bone:
Increases calcium resorption (calcium taken from bone into blood) (osteoclasts?)

Kidney:
Increases calcium reabsorbtion 
Increases phosphate excretion 
Increases 1-alpha hydroxylase activity 
-> 
This increases vitamin D synthesis

Gut:
Through vitamin D
Increases calcium absorption
Increases phosphate absorption

All increases plasma calcium

The net effect on phosphate is pretty much neutral, equal uptake and excretion

Question 8

How is serum phosphate regulated?

Answer 8

There is a Na*/PO4 3- cotta spotter in the proximal convoluted tubule of the kidneys
It allows for reabsorbtion of potassium back into the blood

It is inhibited by PTH and FGF23

So these decrease serum phosphate

Question 9

What is FGF23?

Answer 9

Regulates serum phosphate

Inhibits sodium phosphate co transporter in PCT.

Leads to more phosphate excretion

It also has an inhibitory effect on vitamin D (which itself causes increases phosphate and calcium absorption) so less phosphate is absorbed from gut

Lowers phosphate

Question 10

What are the symptoms of hypocalcaemia?

Answer 10

Sensitises excitable tissues:

Paraesthesia
Convulsions
Arrhythmias
Tetany (can contract but not relax)

CATs go numb

Chvosteks sign - when facial nerve over zygomatic arch is tapped, eye twiches only in high calcium

Trousseaus sign - inflate blood pressure cuff, hand contracts but cat relax and spasms instead (only in high calcium)

Question 11

What are the causes of hypocalcaemia?

Answer 11

Low PTH (hypoparathyroidism) :
Neck surgery 
Auto immune
Magnesium deficiency (needed for hormone synthesis)
Congenital (agenesis, rare)

Low vitamin D:
Deficiency - diet, low UV, malabsorption, impaired production (renal failure)

Question 12

What are the symptoms of hypercalcaemia?

Answer 12

Renal:
Nephrocalcinosis- kidney stones (made of calcium), cause renal colic

GI effects - anorexia, nausea, constipation, pancreatitis

CNS effects - fatigue, depression, impaired concentration, altered mentation, coma

Stones, abdominal moans, psychic groans

Question 13

What are the causes of hypercalcaemia?

Answer 13

Primary hyperparathyroidism:
Too much PTH
Usually due to a parathyroid gland adenoma
No negative feedback - high PTH but high calcium

Malignancy:
Bony metastases produce local factors that activate osteoclasts
Certain cancers (eg. Squamous cell carcinoma) secrete PTH-related peptide that acts on PTH receptors

Vitamin D excesss
Rare

Question 14

What is the relationship between parathyroid hormone and calcium levels?

Answer 14

Negative feedback

High calcium, low PTH

Low Calcium, high PTH

Inversely proportional

Question 15

How does a parathyroid adenoma cause hypercalcaemia?

Answer 15

Primary hyperparathyroidism

Cancer to at least 1/4 parathyroid glands. Produces too much PTH

Calcium increases

Lack of negative feedback (high calcium, PTH should be low). Due to autonomous secretion of PTH from adenoma

Also low phosphate, increased renal excretion

Question 16

How is primary hyperthyroidism treated?

Answer 16

Caused by a parathyroid adenoma

So surgery - parathyroidectomy

If left untreated:
Osteoporosis
Renal calculi(stones)
Psychological impact

Question 17

What is secondary hyperparathyroidism?

Answer 17

Can Just be the normal physiological response to hypocalcaemia

PTH is high secondary to low calcium

Also vitamin D deficiency (so PTH does more of the work)

Lack in diet, or UV light. May also be renal failure (can’t make calcitriol)

Question 18

How is secondary hyperparathyroidism treated?

Answer 18

Vitamin D replacement

(in patients with normal renal function) You give 25 hydroxy vitamin D

Patient coverts it into 1,25 dihydroxy vitamin D via 1 alpha hydroxylase

Ergocalcoferol - 25 hydroxy vitamin D3
Cholecalciferol - 25 hydroxy vitamin D2

In patients with renal failure:
Give alfacalcidol - 1 alpha hydroxycholecalciferol

People with renal failure have inadequate 1 alpha hydroxylation, so can’t activate the other replacements

Question 19

What is tertiary hyperparathyroidism?

Answer 19

Rare

Chronic renal failure, so chronic vitamin D deficiency

So really low calcium

So much higher PTH to account for this. Parathyroid gland hyperplasia (get much bigger)

This causes hypercalcaemia eventually

Treatment is parathyroidectomy

Question 20

How is hypercalcaemia diagnosed?

Answer 20

When presented with hypercalcaemia, always look at PTH

If they have raised PTH: hyperparathyroidism (1°/2°/3°)

If renal function is normal - primary hyperparathyroidism (eg. Adenoma)

Tertiary - all 4 glands are enlarged, chronic renal failure

Question 21

How is vitamin D deficiency diagnosed?

Answer 21

Calcium will be low or low/normal

PTH will be high (secondary hyperparathyroidism) due to low calcium

25(OH) vitamin D is measured (calcitriol is very difficult to measure)