12. Calcium and phosphate regulation

Question 1

where is parathyroid hormone (PTH) made and where is this situated?

Answer 1

made by the parathyroid glands

the 4 glands are behind the thyroid gland

Question 2

what are the 3 functions of PTH?

Answer 2

• instructs the small intestines and kidneys to absorb calcium (to excrete less calcium)
• promotes calcium release from the bones
• regulates the conversion of inactive vitamin D (25-hydroxy-vitamin-D) to active vitamin D (calcitriol)

Question 3

what does active vitamin D promote?

Answer 3

calcium reabsorption from the gut and bones leading to increased serum calcium

Question 4

where and how does phosphate reabsorption occur?

Answer 4

in the nephron (proximal convoluted tubule)

phosphate is reabsorbed using sodium-phosphate co-transporters. phosphate leaves the nephron lumen and enters the cells

Question 5

what does primary hyperparathyroidism cause?

Answer 5

PTH inhibits the reabsorption of phosphates, therefore primary hyperparathyroidism increases phosphate excretion and less it taken up at the proximal convoluted tubule

Question 6

what is FGF23 and what does it do?

Answer 6

fibroblast growth factor 23

it inhibits the reabsorption of phosphate

1. via the sodium-phosphate cotransporter
2. via the inhibition of calcitriol (which assists phosphate absorption from the gut)

Question 7

how is PTH secretion regulated?

Answer 7

parathyroid cells have calcium-sensing receptors on their surface

when there is high ECF calcium, calcium binds to these receptors and PTH secretion is inhibited

when there is low ECF calcium the reduced binding of calcium means PTH is inhibited less and more is released

Question 8

how can we get vitamin D?

Answer 8

• from diet (ergocalciferol)

- via UV light (converts 7-dehydrocholesterol to cholecalciferol)

Question 9

what happens to cholecalciferol in the liver?

Answer 9

it is converted to 25-OH-D3 (which is biologically inactive)

Question 10

what is the role of renal 1a-hydroxylase?

Answer 10

1a-hydroxylase in the kidney converts 25-OH-D3 to 1,25-(OH)2-D3 (calcitriol), which is biologically active

the conversion is stimulated by PTH

Question 11

what does active vitamin D do?

Answer 11

• promotes Ca and phosphate reabsorption in the gut
• promotes calcium maintenance in bones
• increases renal calcium reabsorption
• produces negative feedback on PTH (calcitriol receptors on PT cells)

Question 12

what can cause vitamin D deficiency?

Answer 12

• poor diet or malabsorption (due to coeliac disease, IBD)
• lack of sunlight
• liver disease
• renal disease
• vitamin D resistant rickets (where vitamin D production is normal but there are receptor defects)

Question 13

how do changes in extracellular calcium affect nerve and skeletal muscle excitability?

Answer 13

to generate an AP in nerves/skeletal muscle requires Na+ influx across the cell membrane

• high EC calcium (hypercalcaemia) = Ca2+ blocks Na+ influx, so less membrane excitability
• low EC calcium (hypocalcaemia) =greater Na+ influx so more membrane excitability

Question 14

state the normal calcium range and describe the signs and symptoms of hypocalcaemia

Answer 14

normal range for serum Ca2+ = 2.2-2.6mmol/L

SIGNS AND SYMPTOMS OF HYPOCALCAEMIA

• sensitisation of excitable tissues (muscle cramps/tetany, tingling)
• paraesthesia (tingling of the hands, mouth, feet, lips),
• convulsions
• arrhythmias

Question 15

how can hypocalcaemia be assessed?

Answer 15

• Chvostek’s sign

- Trousseau’s sign

Question 16

describe how Chvostek’s sign can be used to assess hypocalcaemia

Answer 16

• tap the facial nerve just below the zygomatic arch (cheek bone)
• positive response = twitching of the facial muscles
• this indicates neuromuscular irritability due to hypocalcaemia

Question 17

describe how Trousseau’s sign can be used to assess hypocalcaemia

Answer 17

• inflate a BP cuff and leave it for several minutes

- this induces carpopedal spasm indicating neuromuscular irritability (hand contracts and cant be relaxed)

Question 18

what are the causes of hypocalcaemia?

Answer 18

• vitamin D deficiency (required for calcium homeostasis)
• low PTH levels (hypoparathyroidism)
• surgical causes (neck surgery)
• auto-immune
• magnesium deficiency (needed for PTH)
• PTH resistance (pseudohypoparathyroidism) due to receptor defects
• renal failure

Question 19

what does hypercalcaemia result in?

Answer 19

reduced neuronal excitability

“stones, abdominal moans and psychic groans”:

Question 20

what does “stones” mean in relation to hypercalcaemia?

Answer 20

STONES = renal effects of hypercalcaemia

• polyuria & thirst
• nephrocalcinosis
• renal colic
• chronic renal failure

Question 21

what does “abdominal moans” mean in relation to hypercalcaemia?

Answer 21

ABDOMINAL MOANS = GI effects of hypercalcaemia

• anorexia
• nausea
• dyspepsia
• constipation
• pancreatitis

Question 22

what does “psychic groans” mean in relation to hypercalcaemia?

Answer 22

PSYCHIC GROANS = CNS effects of hypercalcaemia

• fatigue
• depression
• impaired concentration
• altered mental activity
• coma

Question 23

what are the causes of hypercalcaemia?

Answer 23

• primary hyperparathyroidism
• malignancy (tumours/metastases often secrete a PTH-like peptide)
• conditions with high bone turnover (hyperparathyroidism, Paget’s disease of bone)
• vitamin D excess (rare)

Question 24

serum Ca fall –> PTH increase

what does this result in and why?

Answer 24

• increased calcium reabsorption from the kidneys
• increased production of calcitriol
• increased calcium reabsorption from bones

PTH exerts -ve feedback to stop production of PTH and maintain normal serum Ca

Question 25

what is primary hyperparathyroidism?

Answer 25

tumour in the parathyroid which causes a large increase in PTH secretion - there is limited -ve feedback and continued production of PTH despite hypercalcaemia

Question 26

how is hypercalcaemia with malignancy different from primary hyperparathyroidism?

Answer 26

patients present with high calcium but there is -ve feedback so as serum Ca rises, PTH falls

Question 27

what is the treatment of primary hyperparathyroidism?

Answer 27

parathyroidectomy

Question 28

what is vitamin d deficiency?

Answer 28

lack of mineralisation in bone

results in “softening” of bone, bone deformities, bone pain, severe proximal myopathy

in children = rickets, in adults = osteomalacia

Question 29

what is secondary hyperparathyroidism?

Answer 29

usually due to vitamin D deficiency leading to low calcium

renal failure leads to loss of calcium in the urine which will stimulate the parathyroid to release PTH in an attempt to normalise serum calcium

Question 30

what is tertiary hyperparathyroidism?

Answer 30

initial chronic low plasma calcium ion concentration followed by massive stimulation of the parathyroid gland for a long time, resulting in desensitisation of the -ve feedback mechanism to PTH so plasma calcium increases

Question 31

which types of hyperparathyroidism are associated with hypercalcaemia?

Answer 31

primary and tertiary

Question 32

what are the biochemical findings in vitamin D deficiency?

Answer 32

• plasma [25(OH)D4] usually low
• plasma [Ca2+] low
• plasma [(PO4)3-] low (due to reduced gut absorption)
• [PTH] high

Question 33

what is the treatment of vitamin D deficiency in patients with normal renal function?

Answer 33

• give 25 hydroxy-vitamin D (which patient will convert to the active form 1,25 dihydroxy-vitamin D via 1a hydroxylase)
• can alternatively give ergocalciferol or cholecalciferol

Question 34

what is the treatment of vitamin D deficiency in patients with renal failure?

Answer 34

give alfacalcidol (active vitamin D) because they have inadequate 1a hydroxylation

Question 35

what does vitamin D excess result in?

Answer 35

INTOXICATION

- can lead to hypercalcaemia and hypercalciuria due to increased intestinal absorption of calcium

Question 36

what can vitamin D excess be caused by?

Answer 36

• excessive treatment with active metabolites of vitamin D (e.g. wrong dose of alfacalcidol)
• granulomatous diseases such as sarcoidosis, leprosy and TB: macrophages in the granuloma produce 1a-hydroxylase to convert 25(OH)D to the active metabolite (very rare)