Calcium and phosphate regulation

Question 1

what does PTH do to the bone and kidney?

Answer 1

bone: releases calcium and phosphorus
kidney: increases calcitriol formation and decreases excretion of calcium (+too much decreases serum phosphate)

Question 2

where is PTH released from?

Answer 2

parathyroid glands sense low serum calcium

Question 3

explain how phosphate regulation works

Answer 3

Phosphate reabsorption occurs via the gut and the kidneys. Phosphate is reabsorbed via sodium phosphate transporter cells. In the kidney, shown here, reabsorption of phosphate via these transporters results in less sodium excretion in the urine. Increased phosphate loss in the urine would lower serum phosphate levels.

Question 4

what affects phosphate regulation?

Answer 4

PTH inhibits renal phosphate reabsorption by inhibiting these transporters (NA/PO4) – so in primary hyperparathyroidism, serum phosphate is low due to increased urine phoshate excretion.
FGF23 – derived from osteocytes – also inhibits phosphate reabsorption in the kidneys by inhibiting these transporters and also inhibits synthesis of calcitriol, causing less phosphate absorption from the gut.

Question 5

Parathyroid cells:
what events occur in

• high calcium conc
• low calcium conc

Answer 5

calcium binds to receptor and the receptor activation leads to inhibition of PTH secretion

calcium not bound to receptor so no inhibition and PTH is secreted.

Question 6

how is calcitriol formed?

Answer 6

skin: 7-dehydrocholesterol goes to cholecalciferl with UVB 
Vit D (ergocalciferol can also be obtained from the diet) 

In liver: cholecalciferol turns to 25 OH-D3 via 25 hydroxylase (measure his for vit D deficiency)

Kidney: 25 OH-D3 turns to 1,25 (OH)2 D3 (calcitriol) using renal 1-alpha-hydroxylase (stimulated by PTH)

Question 7

what does calcitriol do?

Answer 7

Calcitriol is the active form of Vit D and needs to be synthesised in the kidney- KEY, using the enzyme 1-alpha-hydroxylase 
Ca absorption in gut 
Ca maintenance n bone 
Increases renal Ca reabsorption 
Neg feedback on PTH

Question 8

causes of vit D deficiency

Answer 8

Diet
Lack of sunlight
GI malabsorption,eg coeliac disease, inflam bowel disease,
Renal failure, Liver failure
Vitamin D receptor defects (autosomal recessive, rare, resistant to vitamin D treatment)

Question 9

HOW DO CHANGES IN EC CALCIUM AFFECT NERVE AND SKELETAL MUSCLE EXCITABILITY?

• high ec cal
• low ec cal

Answer 9

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

HIGH ec calcium (HYPERcalcaemia) = Ca2+ blocks Na+ influx, so LESS membrane excitability

LOW ec calcium (HYPOcalcaemia) = enables GREATER Na+ influx, so MORE membrane excitability

Question 10

what is normal Ca range?

Answer 10

normal range serum Ca2+ ~ 2.2–2.6mmol/L

Question 11

signs and symptoms of hypocalcaemia:

Answer 11

muscle cramps/tetany,
tingling

Parasthesia (hands, mouth, feet , lips)
Convulsions
Arrhythmias
Tetany

[CATs go numb]

Question 12

2 clinical signs/tests that indicate hypocalcaemia

Answer 12

-Chvostek’s sign
Tap facial nerve just below zygomatic arch
Positive response = twitching of facial muscles
Indicates neuromuscular irritability due to hypocalcaemia

-Trousseau’s sign
Inflation of BP cuff for several minutes induces carpopedal spasm = neuromuscular irritability due to hypocalcaemia

Question 13

causes of hypocalcaemia

Answer 13

Vitamin D deficiency
Low PTH levels = hypoparathyroidism
(Surgical –0 neck surgery, Auto-immune, Magnesium deficiency)
PTH resistance eg pseudohypoparathyroidism
Renal failure: Impaired 1a hydroxylation
leads to decreased production of 1,25(OH)2D3

Question 14

signs and symptoms of hypercalcaemia

Answer 14

‘Stones, abdominal moans and
psychic groans’

Stones – renal effects
Polyuria & thirst
Nephrocalcinosis, renal colic, chronic renal failure

Abdominal moans - GI effects
Anorexia, nausea, dyspepsia, constipation, pancreatitis

Psychic groans - CNS effects
Fatigue, depression, impaired concentration, altered mentation, coma (usually >3mmol/L)

Question 15

causes of hypercalcaemia

Answer 15

Primary 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 16

what are the Ca, phosphate and PTH levels like in primary hyperparathyroidism and why?

Answer 16

Raised calcium
Low phosphate
Raised (unsuppressed) PTH

NO negative feedback
Autonomous PTH secretion DESPITE hypercalcaemia. Abnormal functioning parathyroid gland keeps making PTH despite the raised Cal - does it’s own thing

Question 17

what are the Ca, phosphate and PTH levels like in hypercalcaemia of malignancy?

Answer 17

Raised calcium
Suppressed PTH
-no issue with parathyroid hormone it’s to do with cancer deposits in the bones, so there is still negative feedback occurring

Question 18

define vit D deficiency and what it can result in

• children

- adults

Answer 18

Definition: lack of mineralisation in bone
Results in “softening” of bone (leading to bowing of legs), bone deformities, bone pain; severe proximal myopathy.

In children - RICKETS
In adults - OSTEOMALACIA

Question 19

treatment of primary hyperparathyroidism

Answer 19

parathyroidectomy

Question 20

what happens in secondary hyperparathyroidism?

Answer 20

there is a vit D deficiency so Cal is low

PTH INCREASES TO TRY TO NORMALISE SERUM CALCIUM
= SECONDARY HYPERPARATHYROIDISM

So the PTH is high

Question 21

what are the biochemical findings in vit D deficiency?

Answer 21

Plasma [25(OH)D3] usually low (NB we don’t measure 1,25 dihydroxy vitamin D (1,25 (OH)2 D) to assess body vitamin D stores)

Plasma [Ca2+] low (may be normal if 2o hyperparathyroidism has developed)

Plasma [PO43-] low (reduced gut absorption)

[PTH] high (2o hyperparathyroidism)

Question 22

treatment of vit D deficiency in patients with normal renal functions

Answer 22

Give 25 hydroxy vitamin D (25 (OH) D)
Patient converts this to 1,25 dihydroxy vitamin D (1,25 (OH)2 D) via 1a hydroxylase

Ergocalciferol 25 hydroxy vitamin D2 (type found in food)
Cholecalciferol 25 hydroxy vitamin D3

Question 23

treatment of vit D deficiency in patients with renal failure

Answer 23

inadequate 1a hydroxylation, so can’t activate 25 hydroxyl vitamin D preparations
Give Alfacalcidol - 1a hydroxycholecalciferol (active form)

Question 24

what can vit D excess lead to?

Answer 24

Can lead to hypercalcaemia and hypercalciuria due to increased intestinal absorption of calcium

Question 25

what can vit D excess occur as a result of?

Answer 25

excessive treatment with active metabolites of vitamin D eg Alfacalcidol

granulomatous diseases such as sarcoidosis, leprosy and tuberculosis (macrophages in the granuloma produce 1a hydroxylase to convert 25(OH) D to the active metabolite 1,25 (OH)2 D