Calcium & Phosphate Regulation Flashcards by Rama Jha

Main parts of the body involved in the reabsorption of Ca2+?

Bone

Kidney

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Calcidiol & Calcitriol?

Calcidiol - made in LIVER (first hydroxylation step)

Calcitriol - made in the KIDNEYS (second hydroxylation step)

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Effects of VitD, PTH and calcitriol on Ca2+ homeostatis?

VitD - goes on to make calcidiol/calcitriol

PTH
o causes bone to release Ca2+
o causes kidney to INCREASE calcitriol synthesis
o causes kidney to DECREASE Ca2+ excretion

Calcitriol
o causes Ca2+ RELEASE in BONE
o causes Ca2+ reabsorption in GUT

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The 2 ways that PO4 is regulated?

Kidneys
o Na+/PO4(3-) co-transporter increases PO4 reabsorption from the urine to the PCT and to the blood
PTH
o INHIBITS the co-transporter so MORE PO4 loss in urine

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Another factor that regulated phosphate?

FGF23

-ve feedback on the co-transporter

IT ALSO -ve feedback on CALCITRIOL so:
o LESS PO4 reabsorption in the GUT

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How is PTH regulated?

via. Parathyroid cells

HIGH [Ca2+]:
o Ca2+ binds to receptors
o receptor activation leads to INHIBITION of PTH secretion

LOW [Ca2+]:
 o Ca2+ NOT binds to receptor
 o NO INHIBITION
 o PTH is secreted
 o PTH action in body leads to INCREASED [Ca2+]

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2 ways to get VitD in the body?

DIET

2. SUNSHINE (UVB light)

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Precursor of VitD, VitD3 and VitD2?

Precursor - 7-dehydrocholesterol

VitD3 - Cholecalciferol

VitD2 - Ergocalciferol

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What causes the inactive VitD to become activated?

RENAL 1alpha-hydroxylase

o Stimulated by PTH
o Changes calciferol TO calcitriol

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5 principal causes of VitD deficiency?

Block in UVB light catalysation
Malabsorption OR Diet insufficiency
o e.g. Chron’s OR coeliac disease OR inflam BD
Liver disease
o NO 1st hydroxylation
Renal disease
o NO 2nd hydroxylation
Receptor defects
o autosomal recessive - RARE!!

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HIGH EC Ca2+?

HYPERcalcaemia

Ca2+ BLOCKS Na+ influx
SO
LESS membrane excitability

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LOW EC Ca2+?

HYPOcalcaemia

Allows for GREATER Na+ influx
SO
MORE membrane excitability

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Normal serum range of Ca2+?

2.2 - 2.6 mmol/L

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Symptoms of HYPOcalcaemia?

TOO MUCH excitability
o muscle cramps/tetany
o tingling

PCAT

P - parasthesia (hands, mouth, feet, lips)
C - convulsions
A - arrhythmias (Ca2+ has effect on heart)
T - tetany

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Signs of HYPOcalcaemia?

Chvostek’s Sign
- indicates neuromuscular irritability due to hypocalcaemia

o Tap FACIAL NERVE just BELOW zygomatic arch
o Positive response = twitching of facial muscles

Trousseau’s Sign
- carpopendal spasm, neuromuscular irritability due to hypocalcaemia

o Inflate BP cuff for several minutes
o Positive response = carpopedal spasm

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Causes of HYPOcalcaemia?

VitD deficiency
- LOW calcitriol
LOW PTH levels - HYPOparathyroidism
- due to surgical (neck surgery), auto-immune, Mg2+ deficiency
PTH resistance
- pseudohypoparathyroidism
Renal failure
- Impaired 1alpha-hydroxylation SO decreased production of calcitriol

Symptoms of HYPERcalcaemia?

’ Stones, abdominal moans and psychic groans’
i.e. everything SLOWS DOWN (atonal muscles)

Stones = RENAL effects
 o Polyuria &amp; thirst
 o Nephrocalcinosis (deposits of Ca2+ accumulate), renal colic, chronic renal failure

Abdominal moans = GI effects
 o Anorexia
 o Nausea
 o Dyspepsia
 o Constipation
 o Pancreatitis

Psychic groans = CNS effects
 o Fatigue
 o Depression
 o Impaired concentration
 o Altered mentation
 o Coma

Causes of HYPERcalcaemia?

PRIMARY hyperparathyroidism
o benign adenoma of parathyroid
o HIGH PTH = HIGH Ca2+ (NO -ve feedback as autonomous)
Malignancy
o tumours/metastases
o often secrete a PTH-like peptide
Condition with a HIGH BONE TURNOVER
o e.g. hyperthyroidism, Paget’s disease of bone
VitD Toxicosis
o RARE!!

Diagnostic approach to HYPERcalcaemia when 1o HYPERPARATHYROIDISM?

1o HYPERPARATHYROIDISM

HIGH Ca2+ & HIGH PTH

o RAISED Ca2+
o LOW PO4
o RAISED (unsuppressed) PTH

Diagnostic approach to HYPERcalcaemia when MALIGNANCY?

HIGH Ca2+
BUT
LOW PTH

-ve feedback still works!!! (compared to 1o hyperparathyroisim)

Principal effects of VitD on intestine & kidney?

Intestinal:
o ABSORPTION of Ca2+, Mg2+ & PO4

Kidneys:
o REABSORPTION of Ca2+
o DECREASED PO4 reabsorption (via. FGF23)

Definition of VitD deficiency?

Lack of MINERALISATION in bone

What does VitD deficiency lead to?

‘Softening’ of bone
Bone deformities
Bone pain
Severe proximal myopathy

Children = RICKETS
Adults = OSTEOMALACIA (NOT osteoporosis!!!)

Treatment of 1o hyperparathyroidism?

Parathyroidectomy

2o hyperparathyroidism?

NO Calcitriol (VitD deficiency!) SO LOWER Ca2+ (can be normal if PTH normalises it!) BUT HIGH PTH to try to normalise serum Ca2+

Biochemical findings in VitD deficiency?

1. Plasma calciferol is usually LOW (do NOT measure calcitriol to assess body VitD dtores normally!) 2. Plasma Ca2+ is LOW (may be normal if 2o hyperparathyroidism develops) 3. Plasma PO4 is LOW (reduced gut absorption) 4. PTH is high (2o hyperparathyroidism)

Radiological findings of VitD deficiency?

Widened osteoid seams i.e. 'Brown Tumours' | bone lesions showing excessive osteoclastic bone resorption

What does treatment of VitD deficiency depend on?

Renal function

Treatment of VitD deficiency in patients with NORMAL renal function?

Give synthetic Calciferol - hydroxylases further via. kidney Ergocalciferol - VitD2 Cholecalciferol - VitD3

Treatment of VitD deficiency in patients with IMPAIRED renal function?

Inadequate 1alpha-hydroxylase SO give ready-hydroxylated VitD Alfacalcidol - 1alpha-hydroxycholecalciferol

What can VitD toxicosis lead to?

HYPERcalcaemia & HYPERcalciuria! as INCREASED intestinal absorption of Ca2+!

VitD toxicosis can occur as a result of?

1. Excessive treatment w. active metabolites of VitD e. g. alfacalcidol 2. Granulomatous diseases e.g. sarcoidosis, leprosy and TB o macrophages in the granuloma produce 1alpha-hydoxylase, which overproduced VitD