12 - calcium and phosphate regulation

Question 1

Where are the parathyroid glands and what do they produce?

Answer 1

4 of them , located behind the thyroid gland

produce parathyroid hormone (PTH)

Question 2

What ion does PTH regulate?

Answer 2

calcium

PTH increases serum calcium

Question 3

State the 3 functions of PTH

Answer 3

• interacts the kidney to absorb calcium (excrete less calcium)
• promotes calcium release from the bones
• regulates the conversion of inactive vitamin D (25-hydroxy-vitamin-D) -> active vitamin D (calcitriol)

Question 4

What is the action of active vitamin D (calcitriol)?

Answer 4

it promotes calcium reabsorption from the gut and bones -> increases serum Ca

(and increases absorption of phosphate from the gut)

Question 5

How is phosphate reabsorbed in the kidney?

Answer 5

in the proximal convoluted tubule, phosphate is reabsorbed using sodium-transport co-transporters - phosphate leaves the nephron tubules indenters the cells

Question 6

Describe the mechanism by which PTH affects the mechanism of phosphate reabsorption in the kidney nephron

Answer 6

inhibits the sodium-transport co-transporters

Question 7

Describe the excretion and serum levels of phosphate in a person with primary hyperparathyroidism

Answer 7

increased phosphate excretion.

low serum phosphate due to inhibition of phosphate reuptake at the proximal convoluted tubule.

Question 8

What is FGF 23? Where does it come from?

Answer 8

Fibroblast growth factor 23 from osteocytes

Question 9

In which 2 ways does FGF 23 inhibit the reabsorption of phosphate?

Answer 9

1- via the sodium-phosphate cotransporter

2- inhibits calcitriol (calcitriol assists phosphate reabsorption from gut).

Question 10

Describe the mechanism of regulation of PTH secretion

Answer 10

Parathyroid cells have calcium-sensing receptors on their surface.

When you have high calcium in the ECF, calcium binds to these receptors.
THIS INHIBITS PTH SECRETION - when your Ca is high, PTH is inhibited.

When you have a low serum calcium in the ECF, less calcium binds to these receptiors -> less PTH inhibition -> more PTH release -> mechanisms to increase serum Ca.

Question 11

What are 2 ways in which the body can get vitamin D?

Answer 11

• from the diet (ergocalciferol)

- via UVB light

Question 12

Describe the mechanism by which we can get vitamin D via UVB light and the role of PTH in this process

Answer 12

• UVB light converts 7-dehydrocholesterol -> cholecalciferol
• In the liver, cholecalciferol is converted to 25-OH-D3 (BIOLOGICALLY INACTIVE)
• 1α-hydroxylase in the KIDNEY converts 25-OH-D3 -> 1,25-(OH)2-D3 (BIOLOGICALLY ACTIVE)
  NOTE: ^this conversion is stimulated by PTH.

Question 13

What is the role of vitamin D in calcium (and phosphate) homeostasis (4)

Answer 13

Active vitamin D:

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

(calcitriol and vitamin D work together to increase Ca2+)

Question 14

State the causes of vitamin D deficiency (5)

Answer 14

• A poor diet and malabsorption
• not enough sunlight exposure/too much sun cream
• Liver and renal diseases of ANY CAUSE - because both organs are critical for vitamin D production
• vitamin D resistant rickets – vitamin D production is normal, but there are receptor defects (rare)

Question 15

HOW DO CHANGES IN EXTRACELLULAR CALCIUM AFFECT NERVE AND SKELETAL MUSCLE EXCITABILITY?
(remember generation of an AP in nerves/skeletal muscle requires Na+ influx across cell membrane)

Answer 15

• HIGH EC calcium (HYPERcalcaemia) = Ca2+ blocks Na+ influx, so LESS membrane excitability
• LOW EC calcium (HYPOcalcaemia) = enables GREATER Na+ influx, so MORE membrane excitability

(i.e. Na+ and Ca2+ compete)

Question 16

State the normal range for serum calcium

Answer 16

2.2–2.6 mmol/L

Question 17

How can we assess for hypocalcaemia in a patient?

Answer 17

using Chvostek’s sign and Trousseau’s sign

assess for neuromuscular irritability

Question 18

What are the general signs and symptoms for hypocalcaemia?

Answer 18

• involve sensitisation of excitable tissues (muscle cramps/tetany, tingling) - nerve hyperexcitability
• Paraesthesia (hands, mouth, feet lips), convulsions (EXTREME), arrhythmias and tetany may occur
  (PCAT)

Question 19

How do you test a patient for Chvostek’s sign?
What is a positive indicator response?
What does it indicate?

Answer 19

• Tap the facial nerve just below the zygomatic arch (cheek bone)
• A positive response will involve twitching of the facial muscles
• This indicates neuromuscular irritability due to hypocalcaemia

Question 20

How do you test a patient for Trosseau’s sign?
What is a positive indicator response?
What does it indicate?

Answer 20

• You inflate a BP cuff and leave it like that for several minutes
• This induces carpopedal spasm = neuromuscular irritability (hand contracts and can’t be relaxed)

Question 21

State the causes of hypocalcaemia

Answer 21

• Vitamin D deficiency
• hypoparathyroidism
—–> surgical causes (neck surgery)
—–> auto-immune
—–> magnesium deficiency (needed for PTH)
• PTH resistance e.g. pseudohypoparathyroidism (receptor defects)
• Renal failure: Impaired 1a hydroxylation -> decreased production of 1,25(OH)2D3

Question 22

Describe the effect of hypercalcaemia on neuronal excitability.

Answer 22

It reduces neuronal excitability and you get atonal muscles

Question 23

What are the main signs and symptoms of hypercalcaemia?

Answer 23

Stones, abdominal moans and psychic groans

Stones – renal effects
• Polyuria + polydipsia
• Nephrocalcinosis = deposition of calcium in the kidneys (can cause renal colic)
Abdominal moans – GI effects
• Anorexia, nausea, constipation, pancreatitis, dyspepsia
Psychic groans – CNS effects
• Fatigue, depression, impaired concentration, altered mentation, coma

Question 24

State the causes of hypercalcaemia (4)

Answer 24

• 1° hyperparathyroidism
• Malignancy – tumours/metastases often secrete a PTH-like peptide
• Conditions with high bone turnover (hyperthyroidism, Paget’s disease of bone – immobilised patient)
• Vitamin D excess (rare)

Question 25

Give the normal physiological response that would occur when serum Ca2+ falls

Answer 25

PTH increases -> Increased calcium reabsorption from the kidney -> Increased production of calcitriol -> Increased calcium reabsorption from bones PTH exerts negative feedback, to stop production of PTH and maintain normal serum calcium

Question 26

Describe how you would differentiate between primary hyperparathyroidism and malignancy causing hypercalcaemia.

Answer 26

(look at PTH levels) In 1° hyperparathyroidism there is no negative feedback because the parathyroid adenoma will be producing PTH autonomously • PTH = HIGH • Plasma Calcium = HIGH In malignancy, the negative feedback will be intact as it is due to increased bone turnover due to bony metastases • PTH = LOW • Plasma Calcium = HIGH

Question 27

What is the treatment if primary hyperparathyroidism?

Answer 27

parathyroidectomy

Question 28

Define Vitamin D Deficiency

Answer 28

lack of mineralisation in bone

Question 29

What does vitamin D deficiency cause? State some symptoms.

Answer 29

``` Lack of bone mineralisation Softening of bone (can lead to bowing of the legs) Bone deformities Bone pain Severe proximal myopathy ```

Question 30

What are the different names for vitamin D deficiency in children and adults?

Answer 30

Children – Rickets | Adults – Osteomalacia

Question 31

What are the serum levels in secondary hyperparathyroidism? What is the usual cause?

Answer 31

PTH is high, secondary to low Ca2+ | usually due to vitamin D deficiency

Question 32

Describe what happens in tertiary hyperparathyroidism

Answer 32

- Initial chronic low plasma calcium ion concentration - The parathyroid gland is being massively stimulated for a long time - Eventually, the PTH becomes autonomous and stops responding to negative feedback (causes an increased plasma calcium ion level - similar to 1° hyperparathyroidism)

Question 33

PRIMARY and TERTIARY hyperparathyroidism are associated with _________

Answer 33

HYPERCALCAEMIA

Question 34

Describe the biochemical finding in vitamin D deficiency

Answer 34

``` (very difficult to measure calcitriol) Plasma 25-hydroxycholecalciferol = LOW Plasma Calcium = LOW Plasma Phosphate = LOW Plasma PTH = HIGH (2° hyperparathyroidism stimulated by the hypocalcaemia) ```

Question 35

Describe the treatment of vitamin D deficiency in the case of normal renal function.

Answer 35

Give 25-hydroxy vitamin D This can be in the form of: • Ergocalciferol = 25-hydroxy vitamin D2) • Cholecalciferol = 25-hydroxy vitamin D3

Question 36

Describe the treatment of vitamin D deficiency in the case of renal failure.

Answer 36

Alfacalcidol = 1-hydroxycholecalciferol (active vitamin D)

Question 37

What can vitamin D excess lead to?

Answer 37

Hypercalcaemia and hypercalciuria (due to increased intestinal absorption of calcium)

Question 38

What can vitamin D excess result from?

Answer 38

- Excessive treatment with active metabolites of vitamin D, as in patients with chronic renal failure (wrong dose) - Granulomatous disease – granulomatous tissue has 1-hydroxylase so it can be a source of ectopic calcitriol