1b Calcium Dysregulation

Question 1

What are the two hormones which control serum calcium?

Answer 1

Vitamind D and Parathyroid hormone

Question 2

What are the three places in which the regulators of serum calcium act?

Answer 2

Kidney, bone and the gut

Question 3

What hormone acts to decrease serum calcium?

Answer 3

Calcitonin

Question 4

Where is calcitonin secreted from?

Answer 4

The thyroid parafollicular cells

Question 5

What effect does calcitonin have on serum calcium?

Answer 5

Reduces calcium acutely - however no negative effect if the parafollicular cells are removed eg thyroidectomy

Question 6

What is tested for when a patients vitamin D levels are measured?

Answer 6

Serum 25-OH Vitamin D NOT CALCITRIOL

Question 7

How does calcitriol regulate its own synthesis?

Answer 7

it decreases transcription of 1-alpha hydroxylase

Question 8

Describe how calcitriol is produced?

Answer 8

UVB from sun
7 dehydrocholesterol
Pre-vitamin D3 to Vitamin D3
D3 converted to 25 (OH) Cholecalciferol
Then to 1,25 (OH)2 cholecalciferol

Question 9

Where is 25 hydroxylase found?

Answer 9

Liver

Question 10

Where is 1-alpha hydroxylase found?

Answer 10

In the kidney

Question 11

Which form of vitamin D is found in the diet?

Answer 11

D2- ERGOCALCITRIOL

Question 12

What are the effects of calcitriol on the kidneys?

Answer 12

Increased calcium and Phosphate reabsorption

Question 13

What are the effects of calcitriol on the gut?

Answer 13

Increased phosphate and calcium absorption

Question 14

What are the effects of calcitriol on the bone?!!!!!!

Answer 14

Increased osteoblast activity - bone building

Question 15

What are the effects of PTH on the kidney?Are they direct or indirect? (3)

Answer 15

DIRECT,Increased Calcium reabsorption and phosphate excretion and 1-alpha hydroxylase activity

Question 16

What impact does PTH have on the gut?Are they direct or indirect?

Answer 16

INDIRECT, The increased 1-alpha hydroxylase activity leads to more vitamin D, therefore more calcium and phosphate absorption

Question 17

What is the effect of PTH on the bone?

Answer 17

Increased Calcium resorption from the bone OSTEOBLAST -> rankl -> OSTEOCLAST ACTIVITY ^

Question 18

Why is the net effect on phosphate 0?

Answer 18

PTH = Excretion
Vitamin D = Reabsorption therefore overall effect is zero

Question 19

What is the effect of FGF23?

Answer 19

Increases phosphate excretion by blocking Sodium/phosphate cotransporter

Question 20

How does FGF23 work?

Answer 20

It inhibits the Na+/PO4 3- co transporter in the apical membrane of the proximal tubule, therefore more phosphate in the filtrate being excreted

Question 21

What is the effect on FGF23 on calcitriol?

Answer 21

It inhibits the effects of calcitriol, leading to less phosphate reabsorption from the gut

Question 22

What is chvosteks sign?

Answer 22

Facial paraesthesia - when tapping the zygomatic arch

Question 23

What is trousseau’s sign?

Answer 23

When inflating a blood pressure cuff, the wrist = tetany = unable to relax a contracted wrist

Question 24

What are the signs and symptoms of hypocalcaemia? Think inversely to sodium

Answer 24

Convulsions
Arrhythmias
Tetany
Paraethesia

Question 25

What are the causes of hypocalcaemia?

Answer 25

Low PTH - neck surgery - autoimmune - magnesium deficiency - congenital Low Vitamin D - deficiency - poor metabolism - lack of sunshine - renal failure

Question 26

What are the signs and symptoms of hypercalcaemia?

Answer 26

Stones, abdominal moans and psychic groans and reduced neuronal excitability - kidney stones - constipation, pancreatitis, nausea - Fatigue, depression, impaired concentration, low mood

Question 27

What are the causes of hypercalcaemia?

Answer 27

Primary hyperparathyroidism Malignancy Vitamin D excess

Question 28

What is primary pyerparathyroidism?

Answer 28

When the patient has too much PTH, usually due to a Malignancy (parathyroid gland adenoma)

Question 29

What happens to levels of PTH and Ca2+ in primary hyperparathyroidism?

Answer 29

they both increase

Question 30

How do malignancies cause hyperparathyroidism?

Answer 30

Bony metastases produce local factors to activate osteoclasts = more bone breaking Some cancers also secrete PTH related peptide which acts as PTH therefore higher Ca2+ (PTHpn)

Question 31

What is the normal relationship between PTH and Calcium?

Answer 31

High PTH = Lower Ca2+

Question 32

High PTH, and high Ca2+, what has happened?

Answer 32

Primary hyperparathyroidism - Parathyroid adenoma which produced too much PTH - Ca2+ also increases, but no negative feedback to reduce the Ca2+ therefore both are high

Question 33

What happens to phosphate in primary hyperparathyroidism?

Answer 33

Low phosphate - increased renal phosphate excretion

Question 34

What is the treatment of choice of primary hyperparathyroidism?

Answer 34

Parathyroidectomy - cut out the gland

Question 35

What are the risks of untreated primary hyperparathyroidism?

Answer 35

osteoporosis Renal calculi Mental function reduced, mood

Question 36

What is secondary hyperparathyroidism?

Answer 36

The normal physiological response to high PTH, so low Ca2+

Question 37

What is the most common cause of hyperparathyroidism?

Answer 37

Vitamin D deficiency, as lack of vitamin D = lower Ca2+, therefore PTH will rise to try increase Ca2+

Question 38

Why can calcitriol not be made in renal failure?

Answer 38

renal 1-alpha-hydroxylase is not made, therefore no vitamin D

Question 39

What is the treatment of choice in secondary hyperparathyroidism with patients with normal renal function?

Answer 39

Vitamin D replacement - give 25 hydroxy Vitamin D (inactive forms as the body can convert them itself)

Question 40

What are the two forms of vitamin D?

Answer 40

Ergocalciferol - D2 Cholecalciferol - D3

Question 41

What is the treatment of choice

Answer 41

cholecalciferol

Question 42

What is the treatment of choice in secondary hyperparathyroidism with patients with impaired renal function?

Answer 42

Alfacalcidol - already hydroxylaed vitamin D

Question 43

What is tertiary hyperparathyroidism?

Answer 43

a complication of chronic renal failure, leading to chronic vit d deficiency - this leads to the parathyroid gland working extra hard to produce PTH that eventually hypertrophy of the gland occurs, which can lead to autonomous secretions of PTH

Question 44

What is seen in tertiary hyperparathyroidism?

Answer 44

Initially, High PTH and low Ca2+, but overtime = Ca2+ rises

Question 45

What is the treatment for tertiary hyperparathyroidism?

Answer 45

Parathyroidectomy

Question 46

What is the normal PTH response to hypercalcaemia?

Answer 46

PTH to fall

Question 47

What happens to PTH and calcium when you have hypercalcaemia due to malignancy?

Answer 47

High Calcium Low / suppressed PTH

Question 48

what are the differentials for hypercalcaemia with raised PTH?

Answer 48

If normal renal function - primary hyperparathyroidism If chronic renal failure - tertiary hyperparathyroidism

Question 49

What condition does a patient have if they have low Ca2+ and high PTH?

Answer 49

Secondary hyperparathyroidism = due to vitamin d deficiency

Question 50

Does anything work directly on osteoclasts?

Answer 50

NO, receptor on osteoblast gives RANKL signals to osteoclast