Calcium Dysregulation

Question 1

what causes an increase in serum calcium?

Answer 1

vitamin d and parathyroid hormone

Question 2

which hormone causes a decrease in serum calcium?

Answer 2

Calcitonin released by thyroid parafolliculae cells

Question 3

what are the body’s sources of each of these?

Answer 3

• vitamin dsynthesised in skin or absorbed from diet
• parathyroid hormoneparathyroid glands
• calcitoninthyroid parafollicular cells

Question 4

vit D3 skin metabolism pathway?

Answer 4

7-dehydrocholesterol + UVB → pre-vitamin D3 → vit D3 (inactive form)

Question 5

what form of vitamin D is absorbed from the gut?

Answer 5

Vitamin d2

Question 6

how are these inactive forms converted to active forms?

Answer 6

vit D3 → 25(OH)cholecalciferol → 1, 25(OH)2-cholecalciferol

Question 7

Which enzymes convert vitamin D

Answer 7

25-hydroxylase in liver and 1-alpha-hydroxylase in kidney

Question 8

what is the active form of vit D?

Answer 8

Calcitriol

Question 9

how is its production from vit D3 regulated?

Answer 9

calcitriol decreases transcription of 1-alpha-hydroxylase

Question 10

effects of calcitriol?

Answer 10

increased osteoblast activity

more gut Ca2+ and phosphate absorption

more kidney Ca2+ and PO34- reabsorption

Question 11

effects of parathyroid hormone?

Answer 11

more Ca2+ resorption from bones (osteoclast)

more 1-alpha-hydroxylase activity → more Ca2+ and phosphate absorption from gut

more Ca2+ reabsorption from kidney, more phosphate excretion

Question 12

how is serum phosphate regulated?

Answer 12

by FGF23 → downregulates calcitriol so less phosphate reabsorption through sodium phosphate co transporter

PTH a,so inhibits via fgf23

Question 13

symptoms of hypocalcaemia?

Answer 13

paraesthesia, convulsions, arrhythmias, tetany

• chvostek’s signtwitch in facial muscle when gently tapping patient’s cheek
• trousseau’s signcarpopedal spasm on ischaemia (blood pressure cuff)

Question 14

Causes of hypocalcaemia

Answer 14

• low PTH level → hypoparathyroidismsurgicalautoimmunemagnesium deficiencycongenital (rare)
• low vit D leveldeficiency (poor diet, UV light exposure, renal failure → impaired production)

Question 15

symptoms of hypercalcaemia?

Answer 15

atonal muscles (reduced excitability)

stones, moans and abdomen groans

→ kidney stones

fatigue, depression, impaired concentration, coma at extreme high (above 3 mmol/L)

anorexia, nausea, dyspepsia, constipation, pancreatitis

Question 16

Causes of hypercalcaemia

Answer 16

• primary hyperparathyroidismusually parathyroid gland adenoma
• malignancybony metastases produce local factors overactivating osteoclastssome cancers secrete PTH-related peptide
• vit D excess (rare)diet

Question 17

primary vs secondary hyperparathyroidism (Ca2+ level)?

Answer 17

primary has high Ca2+ and high PTH

secondary has low Ca2+ and high PTH

Question 18

primary vs secondary hyperparathyroidism (cause)?

Answer 18

primary = parathyroid adenoma independently producing too much PTH. Calcium increases but no negative feedback to suppress autonomous PTH

secondary = normal response to low serum Ca2+ e.g. vit D deficiency (diet, UV, renal failure)

Question 19

treatment for primary hyperparathyroidism?

Answer 19

parathyroidectomy

Question 20

treatment for secondary hyperparathyroidism?

Answer 20

Vitamin D replacement
Patients with normal Rena, function give 25 hydroxy vitamin D so pt makes calcitriol
(Vitamin D 2 is ergocalciferol and D3 is cholecalciferol)

In renal failure there isn’t enough 1 alpha hydroxylase so give alfacalcidol

Question 21

cause of tertiary hyperparathyroidism?

Answer 21

chronic renal failure → chronic vit D deficiency → low Ca2+ thus high PTH

Question 22

Pathology of tertiary hyperparathyroidism

Answer 22

long time overactive parathyroid gland → PTH up and Ca2+ up

involves hyperplasia

Occurs in chronic renal failure
Treat with parathyroidectimy

Question 23

Normal PTH response to hypercalcaemia

Answer 23

pth falls

Question 24

management of hypercalcaemia of malignancy?

Answer 24

bisphosphonates → osteoclast activity inhibitors
PTH wouldn’t be raised but calcium would