Calcium Dysregulation

Question 1

What can increase Calcium in the body?

Answer 1

Vitamin D

Parathyroid hormone

Question 2

What can decrease Calcium in the body?

Answer 2

Calcitonin

Not sure of physiological role

Question 3

What is Calcitonin secreted by?

Answer 3

Thyroid parafollicular cells

Question 4

What are the main steps of Vitamin D metabolism

Answer 4

UVB shines on the skin
Converts 7-dehydrocholesterol to Pre-Vitamin D3
Converts to Vitamin D3

In the liver 25-hydroxylase converts it to 25(OH)cholecalciferol

In the Kidney 1-alpha-hydroxylase converts to 1,25(OH)2 cholecalciferol

Question 5

What is the active form of Vitamin D?

Answer 5

1,25(OH)2 cholecalciferol

aka Calcitriol

Cannot be measured

Question 6

What do you measure for Vitamin D?

Answer 6

Good marker for how much Vitamin D someone has

25(OH)cholecalciferol

Question 7

What does effect does Calcitriol have on 1-alpha hydroxylase?

Answer 7

Negative feedback

Question 8

What are the effects of Calcitriol?

Answer 8

Absorb phosphates and calcium in the gut

Increased osteoblast activity

Question 9

What are the effects of PTH?

Answer 9

Increased calcium and phosphate reabsorption in the gut by increasing the synthesis of Calcitriol
(Increases 1-alpha hydroxylase activity)

Increases reabsorption of calcium and excretion of phosphate in kidney

PTH stimulates osteoclasts to reabsorb calcium from bone

Question 10

What is the net effect of PTH?

Answer 10

Increases synthesis of Calcitriol

Increase Ca mobilisation from bone

Increases plasma Calcium

Question 11

How does PTH and FGF23 regulate serum phosphate?

Answer 11

Via sodium/phosphate co-transporter

PTH inhibits this channel

Stops phosphate from being reabsorbed increasing excretion

FGF23 inhibits calcitriol

Question 12

What is FGF23?

Answer 12

Factor that is important in the regulation in phosphate

Role is to reduce serum phopsphate

• inhibits calcitriol
• inhibits sodium/phosphate co-transporter

Question 13

What are the signs of Hypocalcaemia?

Answer 13

Paraesthesia
Convulsions
Arrhythmias
Tetany

CATS go numb

Question 14

What are the two signs that are present with hypocalcaemia?

Answer 14

Chvosteks’ sign

Trousseau’s sign

Question 15

What causes low PTH levels?

Answer 15

Surgical - neck surgery
Auto-immune
Magnesium deficiency
Congenital (agenesis, rare)

Question 16

What causes low Vitamin D?

Answer 16

Deficiency - diet, UV light, malabsorption, impaired production (renal failure)

Question 17

What are the signs of hypercalcaemia?

Answer 17

Stones
Abdominal moans
Psychic groans

Question 18

What are stones?

Answer 18

Renal effects

Nephrocalcinosis- kidney stones, renal colic

Question 19

What are abdominal moans?

Answer 19

Anorexia
Nausea
Dyspepsia
Constipation
Pancreatitis

Question 20

What are psychic groans?

Answer 20

CNS effects

Fatigue, depression, impaired concentration, altered mentation, coma (usually >3mmol/L)

Question 21

What is the cause of hyper calcaemia?

Answer 21

Primary hyperparathyroidism

Malignancy

Vitamin D excess (rare)

Question 22

What are the features of primary hyperparathyroidism?

Answer 22

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

Question 23

What are the features of malignancy causing hypercalcaemia?

Answer 23

Bony metastases produce local factors to activate osteoclasts
Certain cancers (eg squamous cell carcinomas) secrete PTH-related peptide that acts at PTH receptors

Question 24

What happens when serum calcium falls?

Answer 24

Feedback to parathyroid gland

Calcium sensor receptor senses this and stimulates PTH production

Question 25

What happens when serum calcium is high?

Answer 25

Feedback to parathyroid gland | Calcium sensor receptor senses this and inhibits PTH production

Question 26

What is an adenoma?

Answer 26

benign tumour of a endocrine gland

Question 27

What would a parathyroid adenoma result in?

Answer 27

Over production of PTH Increases serum calcium Tumour does not respond to negative feedback Primary hyperparathyroidism

Question 28

What is the biochemistry of primary hyperparathyroidism?

Answer 28

High calcium Low phosphate - increased renal phosphate excretion (inhibition of Na/Phosphate transporter in kidney) High PTH

Question 29

What is the treatment of primary hyperparathyroidism?

Answer 29

Parathyroidectomy is treatment of choice for primary hyperparathyroidism

Question 30

What are the risks of untreated hyperparathyroidism?

Answer 30

``` Osteoporosis Renal calculi (stones) Psychological impact of hypercalcaemia – mental function, mood ```

Question 31

How does secondary hyperparathyroidism occur?

Answer 31

Calcium is low | Sensed and PTH is stimulated

Question 32

How are 1ry and 2ry hyperparathyroidism different?

Answer 32

In 1ry calcium is high

Question 33

What is the most common form of secondary hyperparathyroidism?

Answer 33

Vitamin D deficiency

Question 34

What causes Vitamin D deficiency?

Answer 34

Commonly- diet, reduced sunlight Less common cause is renal failure (can't make 1-alpha hydroxylase)

Question 35

How do you treat secondary hyperparathyroidism?

Answer 35

Vitamin D replacement Give 25 hydroxy vitamin D Patient converts this to 1,25 dihydroxy vitamin D via 1a hydroxylase Ergocalciferol 25 hydroxy vitamin D2 Cholecalciferol 25 hydroxy vitamin D3

Question 36

How do you treat secondary hyperparathyroidism in those with renal failure?

Answer 36

inadequate 1a hydroxylation, so can’t activate 25 hydroxy vitamin D preparations Give Alfacalcidol - 1a hydroxycholecalciferol

Question 37

What causes tertiary hyperparathyroidism?

Answer 37

Chronic kidney disease Chronic Vitamin D deficiency Chronic low calcium Increase in PTH to try and restore Ca to normal Parathyroid glad become autonomous and overactive Eventual excess of calcium

Question 38

How do you treat tertiary hyperparathyroidism?

Answer 38

Parathyroidectomy

Question 39

Summarise primary hyperparathyroidism?

Answer 39

Parathyroid adenoma, makes too much PTH | Calcium increases, but PTH stays high (no negative feedback)

Question 40

Summarise secondary hyperparathyroidism?

Answer 40

Normal physiological response to low calcium (commonly caused by low vitamin D) Calcium low/low-normal, PTH high

Question 41

Summarise tertiary hyperparathyroidism?

Answer 41

Complication of chronic renal failure and prolonged calcitriol deficiency Initially calcium falls and PTH rises (secondary hyperparathyroidism), but over a long period high PTH drive by enlarged parathyroid glands increases calcium

Question 42

How do you diagnose hypercalcaemia?

Answer 42

Always look at the PTH

Question 43

How will hypercalcaemia caused by malignancy present?

Answer 43

Normal PTH response to hypercalcaemia is for PTH to fall Hypercalcaemia due to malignancy High calcium (hypercalcaemia) Low/suppressed PTH

Question 44

If PTH is high how do decide which form of hyperparathyroidism it is?

Answer 44

Primary hyperparathyroidism if renal function is normal (eg parathyroid adenoma) Tertiary hyperparathyroidism (all 4 glands enlarged – hyperplastic) if chronic renal failure

Question 45

How do you diagnose Vitamin D deficiency?

Answer 45

Calcium will be low or low/normal PTH will be high (hyperparathyroidism) secondary to the low calcium Vitamin D is measured as 25 (OH) vitamin D Calcitriol (1,25 dihydroxy vitamin D) is very difficult to measure