Disregulation of calcium

Question 1

Which hormones increase serum calcium?

Answer 1

Vitamin D and PTH

Question 2

Which hormones decrease serum calcium?

Answer 2

Calcitonin - but no negative effects if removed

Question 3

How does Vitamin D3 get activated?

Answer 3

Vitamin D3 goes to liver (25-hydroxylase) to kidney (1-alpha-hydroxylase) to become 1,25(OH)2 cholecalciferol (aka calcitriol)

Question 4

What are the three effects of calcitriol?

Answer 4

Ca2+ & PO43- absorbed from the kidney and gut, and osteoclast increased (to reabsorb calcium from bone)

Question 5

What are the four effects of PTH? (stimulates calcitriol)

Answer 5

CA2+ & PO43- absorbed from gut,
renal secretion of phosphate in kidney,
osteoblast and 1-alpha-hydroxylase activity

Question 6

How does PTH affect renal excretion of phosphate and why?

Answer 6

Increased renal excretion, inhibits Na+/PO43- cotransporter, more released in urine (acts as homeostasis - PO43- stimulates PTH release, so need to remove to prevent overproduction of PTH)

Question 7

Why does PTH lead to proximal myopathy?

Answer 7

Bone Ca2+ absorption leads to osteomalacia which causes weakness in limbs (proximal myopathy)

Question 8

What demographic of patients are more at risk of proximal myopathy?

Answer 8

Lactovegetarian Asian patients

Question 9

What other molecule regulates phosphate levels and where is it released?

Answer 9

FGF23 // in the bones

Question 10

What are the two effects of FGF23?

Answer 10

Inhibits Na+/PO43- cotransporter (more phosphate release in urine), inhibits synthesis of calcitriol
decreases serum phosphate

Question 11

What are the four signs of hypocalcaemia?
(excitation)

Answer 11

CATs go numb - convulsions, arrhythmias, tetany, parasthesia

Question 12

What are two signs in the presentation of hypocalcaemia?

Answer 12

Trosseau’s Sign (carpopedal spasm), inflating bp cuff, cannot relax the hand
Chvostek’s sign (facial parasthesia)

Question 13

What are the two hormone deficiencies that may cause hypocalcaemia and what causes them?

Answer 13

Hypoparathyroidism - autoimmune, magnesium deficiency, congenital and surgical (neck surgery) //
Vitamin D deficiency - poor diet, renal failure, lack of UV

Question 14

What are the 3 signs of Hypercalcaemia (aka the rhyme - flattened)

Answer 14

Kidney stones (nephrocalcaemia causes renal colic), due to filtration issue
Abdominal moans (anorexia, nausea, dyspepsia, pancreatitis and constipation), atonal gut - no peristalsis
Psychic groans (fatigue, depression, low concentration) and atonal muscles

Question 15

What are the three causes of Hypercalcaemia and the relative proportions?

Answer 15

Primary hyperparathyroidism (90%),
Malignancy - bony metastases, certain cancers secrete PTH related peptide
Vitamin D excess (rare)

Question 16

How does primary hyperparathyroidism work?

Answer 16

Parathyroid adenoma - continual increase of PTH regardless of calcium levels (no negative feedback)

Question 17

Normal relationship between calcium and PTH

Answer 17

Inverse relationship
High calcium = low PTH
High PTH = low calcium

Question 18

Biochemistry of primary hyperparathyroidism

Answer 18

High calcium
Low phosphate, increased renal phosphate excretion
High PTH

Question 19

How would you treat kidney stones and depression in hospital?

Answer 19

IV Saline Hydration

Question 20

How do you treat primary hyperparathyroidism?

Answer 20

Parathyroidectomy

Question 21

What are two conditions formed from not treating primary hyperparathyroidism?

Answer 21

Osteoporosis (low phosphate, calcium extracted), Hypercalcaemia

Question 22

How does secondary hyperparathyroidism work?

Answer 22

Low vitamin D means low calcium, PTH will increase as a result // can be due to renal failure as they cannot make calcitriol

Question 23

Secondary hyperparathyroidism

Answer 23

Normal physiological response to hypocalcemia
usually due to vit D deficiency

Question 24

What are the two drugs you’d give for secondary hyperparathyroidism?

Answer 24

Vitamin D3,
Alfacalcidol (kidney failure) - have faulty 1-alphahydroxylase .: give them active vit D

Question 25

How does tertiary hyperparathyroidism work?
Chronic vit D deficiency .: no calcitriol

Answer 25

Chronic renal failures (as a progression from secondary) - low calcium, PTH increases too much (hyperplasia of parathyroid gland), Hypercalcaemia due to autonomous PTH secretion

Question 26

How would you treat tertiary hyperparathyroidism?

Answer 26

Parathyroidectomy

Question 27

Mechanism of malignancy hypercalcaemia?

Answer 27

Suppressed PTH (aka physiological response - has nothing to do with parathyroid gland) - negative feedback is normal
high calcium in the bloodstream

Bone mets make PTH related peptides which stim osteoclasts

Question 28

Impact of Primary hyperparathyroidism on PTH and renal fct?

Answer 28

High PTH but normal renal function

Question 29

What is the diagnostic approach for tertiary hyperparathyroidism?

Answer 29

High PTH and hyperplasia of organs and abnormal renal function

Question 30

What is the diagnostic approach for secondary hyperparathyroidism?

Answer 30

High PTH, low vitamin D and calcium

Question 31

How to measure calcium levels

Answer 31

Not calcitriol
measure 25-cholecalciferol in the blood
Not useful with patients with chronic renal failure

Question 32

Hypercalcaemia treatment

Answer 32

Hydration, via IV saline solution
Bisphosphonate, inhibit osteoclasts to stop bone reabsorption and decrease calcium (zoledronate)