Endo 13: Calcium and phosphate regulation

Question 1

Relevance of vit D to calcium homeostasis

Answer 1

Vit D–> liver hydroxylated to 25-OH vit. D –> kidney to 1,25-OH vit. D

This hydroxlated from of vit D increases calcium and phosphate absorption from the gut

AND

maintains calcium in bone (difference to PTH!!)

AND

increases reabsorption of Ca2+ in kidney

NEGATIVE FEEDBACK ON PTH

Question 2

How does parathyroid hormone work in calcium homeostasis

Answer 2

Kidneys increase retention of calcium

Bones to release calcium

The enzyme performing the second hydroxylation of vit D (1 alpha hydroxylase) in the kidney is regulated by PTH so you cna get more calcitriol

Question 3

Outline regulation of phosphate levels

Answer 3

PO43- absorbed back into the blood from filtrate in the kidneys by Na+/PO43- symporter in PCT

PTH inhibits this transporter, increasing phosphate excretion and sodium excretion

FGF23 (derived from osteocytes) also inhibits this transporter, and also inhibits calcitriol, thus reducing phosphate absorption in the gut

Question 4

Role of FGF23 in phosphate regulation

Answer 4

FGF23 from osteocytes inhibits reabsorption of phosphate from urine…..

FGF 23 inhibits calcitriol (which is involved in reabsorption in the gut!)

Question 5

T/F FGF 23 reduced PO43- absorption from the kidney

Answer 5

T and also from the gut via reduced calcitriol

Question 6

Outline regulatin of PTH secretion

Answer 6

Ca2+ binding to the calcium sensing receptor on parathyroid cell, inhibiting PTH release

Low Ca2+ will mean that the calcium sensing receptor isnt activated so you get more PTH

Question 7

How is vit D produced

Answer 7

7-dehydrocholesterol (in skin) –> (with UV light cholecalciferol

cholecalciferol is then converted to calcitriol via liver and kidney

(other source of cholecalcferol is from the diet)

Question 8

t/f 25 OH-D3 is biologically active

Answer 8

No… only the 1, 25 OH D3 is active…… converted from 25 OH D3 to 1 25 OHD3 by 1 alpha hydroxylase in the kidneys… REGULATED BY PTH!!!!!

Question 9

Action of calcitriol

Answer 9

Ca++ absorption
in gut

Ca++ maintenance
in bone

Increased renal Ca++ reabsorption

Question 10

Why doesnt Ca2+ just keep on increases

Answer 10

Becase calcitriol has negarive feedback on the PTH (as does high Ca2+, inhibiting PTH release)

Question 11

Cause of vit D deficiency

Answer 11

Diet

Lack of sunlight

GI malabsorption
eg coeliac disease, inflam bowel disease,

Renal failure, Liver failure (due to hydroxylation)

Vitamin D receptor defects (autosomal recessive, rare, resistant to vitamin D treatment)

Question 12

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

Answer 12

AP in nerves and skel muscle needs high Na+ influx across cell membrane…..

High calcium (hypercalc.), ca2+ blocks Na+ influx, so LESS membrane excitability

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

Question 13

Normal serum ca2+

Answer 13

2.2–2.6mmol/L

Question 14

Signs and symptoms of hypocalcaemia

Answer 14

Parasthesia (hands, mouth, feet , lips)

Convulsions

Arrhythmias

Tetany

[CATs go numb]

it sensitises excitable tissues (less Ca2+ competing with Na+) –? muscle cramps/tetany/tinglng

Question 15

What is CHVOSTEK’S SIGN

Answer 15

Tap facial nerve just below zygomatic arch
Positive response = twitching of facial muscles
Indicates neuromuscular irritability due to hypocalcaemia

Question 16

TROUSSEAU’S SIGN

Answer 16

Inflation of BP cuff for several minutes induces carpopedal spasm = neuromuscular irritability due to hypocalcaemia

Question 17

Casues of hypocalcaemia

Answer 17

Vit. D defic.

Low PTH (surigcal,autoimmune or Mg defic. remember it’s Mg dependent!!)

PTH resistance (pseudohypoparathyroidism)

Renal failure
Impaired 1a hydroxylation
decreased production of 1,25(OH)2D3

Question 18

Hypercalcaemia signs and symptoms

Answer 18

Stones, abdominal moans and
psychic groans

reduced neuronal excitability so atonal muscles

STONES (renal effect) –> Polyuria & thirst
Nephrocalcinosis, renal colic, chronic renal failure

Abdominal moans: GI effects (anorexia, nausea, dyspepsia, constipation, pancreatitis)

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

Question 19

Hypercalcaemia causes

Answer 19

Primary hyperparathyroidism

Malignancy – tumours/metastases often secrete a PTH-like peptide (paraneoplastic)

Conditions with high bone turnover (hyperthyroidism, Paget’s disease of bone – immobilised patient)

Vitamin D excess (rare)

Question 20

Primary hyperparathyroidism diagnosis

Answer 20

Due to a busy parathyroid gland

HYPERCALCAEMIA
Low phosphate
Raised (unsuppressed- negative feedback doesn’t work) PTH

Question 21

Hypercalcaemia of malignancy

Answer 21

Raised calcium
Suppressed PTH (PTH like peptide instead!)

Question 22

Define vit D defic.

Answer 22

lack of mineralisation in bone

ricets in kids and osteomalacia in adults

Softening of bone, bone deformity, proximal myopathy, pain

Question 23

Treatment of primary hyperparathyroidism

Answer 23

PARATHYROIDECTOMY

Question 24

Secondary hyperparathyroidism

Answer 24

Vitamin D deficiency –> low calcium (HYPOCALCAEMIA)

and
PTH INCREASES TO TRY TO NORMALISE SERUM CALCIUM

i.e. this is a NORMAL PHYSIOLOGICAL RESPONSE

Question 25

Biochemical findings in vit D deficiency

Answer 25

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….bcause it’s hard to measure, 25 cholecalciferol is measured instead )

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

Plasma [PO43-] low (reduced gut absorption)

[PTH] high (2o hyperparathyroidism)

Question 26

Treatment of vit D def.

Answer 26

In patients with normal renal function
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
Cholecalciferol 25 hydroxy vitamin D3

In patients with renal failure - inadequate 1a hydroxylation, so can’t activate 25 hydroxyl vitamin D preparations
Give Alfacalcidol - 1a hydroxycholecalciferol… which is active vitamin D (very potent)

Question 27

Cause and consequence of vitamin D excess

Answer 27

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

Can occur as a result of:

1. excessive treatment with active metabolites of vitamin D eg Alfacalcidol
2. 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