12 - Calcium and Phosphate Regulation Flashcards by Anisha Malli

Explain the mechanism of calcium homeostasis

Parathyroid Glands make PTH (Parathryroid Hormone)

PTH:

turn kidneys to increase retention of calcium
tells bones to release calcium
regulates enzyme (1α-hydroxylase) that activates vitamin D in the kidneys

Liver makes and stores 25-hydroxy-vitamin D (inactive vitamin D) = CALCIDIOL

Kidneys convert calcidiol to 1,25-dihydroxy-vitamin D = CALCITRIOL

Calcitriol causes increased absorption of phosphate from the small intestine and increased reabsorption of calcium from the gut

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What hormone, other than PTH, regulates phosphate?

Fibroblast Growth Factor 23 (FGF23)

Comes from osteocytes

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How does the hormone FGF23 regulate phosphate?

Inhibits reabsorption of phosphate from the urine and promotes phosphate excretion in the urine

It also inhibits calcitriol

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Which hormones regulate phosphate?

PTH

FGF23

[However, Calcitriol increases absorption of phosphate from the small intestine and has a counter-effect to these two hormones]

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How does the hormone PTH regulate phosphate?

Inhibits reabsorption of phosphate from the urine

Promotes phosphate excretion in the urine

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What is the interaction between calcitriol and FGF23?

FGF23 inhibits calcitriol

This is important because calicitriol helps reabsorption of phosphate from the gut whereas FGF23 wants the body to excrete phosphate

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What is PO4^-3?

Phosphate

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What happens when there is high calcium in the blood, with regards to parathyroid cells?

Calcium binds to calcium sensor receptor on surface of parathyroid cell

This inhibits PTH secretion

This is because PTH increases serum calcium, so if PTH is high then it will increase serum calcium even more

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What does PTH do to serum calcium?

PTH increases serum calcium

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What happens when there is low calcium in the blood, with regards to parathyroid cells?

Calcium doesn’t bind to calcium sensor receptor on surface of parathyroid cell

No inhibition of PTH

More PTH is secreted

Serum calcium increases

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How is vitamin D synthesised?

SKIN
- 7-dehydrocholesterol (precursor)

—> UVB light

LIVER

vitamin D3 (cholecalciferol)
vitamin D2 from diet (ergocalciferol)
both of the above become 25-OH-D3 which is inactive vitamin D and this occurs in the liver

KIDNEYS

25-OH-D3 becomes 1,25(OH)2-D3 which is active vitamin D
carried out by renal 1α-hydroxylase
stimulated by PTH

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What is the biologically active form of vitamin D?

1,25-dihydroxy-D3

Calcitriol

Converted in the kidneys

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How is calcitriol production regulated?

Exerts negative feedback on PTH to prevent hypercalcaemia

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What are some causes of vitamin D deficiency?

GI Malabsorption

inflammatory bowel disease
coeliac disease

Dietary insufficiency

Lack of sunshine

ethnicity
covered clothing

Liver Disease

Renal Disease

Vitamin D Receptor Defects

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Why do Vitamin D receptor defects occur?

Autosomal recessive

Rare

These people are resistant to vitamin D treatment

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

Generation of an AP in nerves/skeletal muscle requires Na+ influx across a cell membrane

High EC calcium (hypercalcaemia) blocks Na+ influx
Therefore, less membrane excitability

Low EC calcium (hypocalcaemia) enables greater Na+ influx. Therefore, more membrane excitability

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What is the normal range of serum calcium?

2.2-2.6 mmmol/L

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What are the signs and symptoms of hypocalcaemia?

MORE SODIUM GOING INTO CELLS
SENSITISES EXCITABLE TISSUES;
MUSCLE CRAMPS/TETANY/TINGLING

Parasthesia (hands, mouth, feet, lips)

Convulsions

Arrhythmias

Tetany

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What is Parasthesia?

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An abnormal sensation, typically tingling or pricking (‘pins and needles’)

Numbness

What is Chvostek’s Sign?

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Tap facial nerve below zygomatic arch

Positive Response = twitching of facial muscles

Indicates neuromuscular irritability due to hypocalcaemia

What is Trosseau’s Sign?

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Inflation of BP cuff for several minutes

Positive Response = induces carpopedal spasm

Indicates neuromuscular irritability due to hypocalcaemia

What signs can be demonstrated in a person with neuromuscular irritability due to hypocalcaemia?

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Chvostek’s Sign

Trosseau’s Sign

What is a carpopedal spasm?

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Involuntary contraction of the feet or the hands

What are some causes of hypocalcaemia?

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Vitamin D Deficiency

Low PTH Levels [hypoparathyrodism]

surgical
auto-immune
magnesium deficiency

PTH Resistance

e.g. pseudohypoparathryoidism
receptor doesn’t allow PTH to work
you would think PTH would be low because calcium is low, but it is high

Renal Failure

impaired 1α-hydroxylation
decreased 1,25-dihydroxy-D3 (active vitamin D, calcitriol)

What 3 factors can cause hypoparathyroidism?

Surgical reasons - e.g. neck surgery Auto-Immune reasons - destruction of parathyroid glands Magnesium Deficiency - needed for PTH to work

What are the signs and symptoms of hypercalcaemia?

LESS SODIUM GOING INTO CELLS REDUCED NEURONAL EXCITABILITY; ATONAL MUSCLES Stones [RENAL EFFECTS] - polyuria - thirst - nephrocalcinosis - renal stones - 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 (>3mmol/L)

What is mentation?

Mental activity

What is dyspepsia?

Indigestion

What is nephrocalcinosis?

A term used to describe deposition of calcium salts in the renal parenchyma.

What is renal colic?

The type of pain you get when urinary stones block part of your urinary tract

What are the causes of hypercalcaemia?

Primary Hyperparathyroidism - too much PTH Malignancy [tumours/metastases] - often secrete a PTH-like peptide Conditions with High Bone Turnover - increased calcium reabsorption - hyperthyroidism - Paget's disease of bone - immobilised patient Vitamin D Excess [rare]

What is a diagnostic approach to hypercalcaemia?

PRIMARY HYPERPARATHYROIDISM - Parathyroid adenoma Raised calcium Raised (unsuppressed) PTH PTH increases serum calcium HYPERCALCAEMIA OF MALIGNANCY - squamous cells metastases in bone Raised calcium Low PTH due to negative feedback

Define Vitamin D Deficiency States

Lack of mineralisation in bone Results in - 'softening' of bone - bone deformities - bone pain - severe proximal myopathy

What are the severe diseases cause by vitamin D deficiency?

CHILDREN = rickets ADULTS = osteomalacia

What is the treatment for primary hyperparathyroidism?

Parathyroidectomy | - take out the parathyroid adenoma

What is secondary hyperparathyroidism?

Low in calcium - e.g. maybe due to vitamin D deficiency PTH increases to try and normalise serum calcium

What are the biochemical findings in vitamin D deficiency?

Plasma 1,25-dihydroxy-D3 usually low Plasma calcium low - may be normal if secondary hyperparathyrodism has developed and been corrected Plasma phosphate low - reduced gut absorption Plasma PTH high - secondary hyperparathyroidism EACH MAY DIFFER DEPENDING ON CAUSE OF VIT D DEFICIENCY

What is primary hyperparathyroidism?

No negative feedback of calcium on the parathyroid glands Autonomous PTH secretion despite hypercalcaemia

What is the biochemical difference between primary and secondary hyperparathyroidism?

Both have high PTH Primary = high calcium Secondary = low calcium

Why isn't 1,25-dihydroxy- vitamin D measured to assess the body's vitamin D stores?

The assay to do so is very difficult and time-consuming

What is measured to assess the body's vitamin D stores?

Plasma 25-hydroxy-D3 This is inactive vitamin D

How is vitamin D deficiency treated?

IN PATIENTS WITH NORMAL RENAL FUNCTION - give 25-hydroxy-vitamin D (Ergocalciferol or Cholecalciferol) - patients covert this to 1,25-dihydroxy-vitamin D - via 1α-hydroxylase IN PATIENTS WITH RENAL FUNCTION - inadequate 1α-hydroxylation - can't activate 25-hydroxy-vitamin D preparations - give 1α-hydroxycholecalciferol (Alfacalcidol) - this is active vitamin D and is not available over the counter

What is Ergocalciferol?

25-hydroxy-vitamin D2

What is Cholecalciferol?

25-hydroxy-vitamin D3 - meant to be slightly better absorbed than Ergocalciferol

What occurs in patients with vitamin D excess (intoxication)?

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

What is hypercalciuria?

The condition of elevated calcium in the urine

What can cause vitamin D excess (intoxication)?

Can occur as a result of: Excessive treatment with active metabolites of vitamin - e.g. Alfacacidol Granulomatous Diseases - e.g. sarcoidosis, leprosy, tuberculosis - macrophages in the granuloma produce 1α-hydroxylase - this means more inactive 25-hydroxy-vitamin D is converted to the active 1,25-dihydroxy-vitamin D

12 - Calcium and Phosphate Regulation Flashcards

(47 cards)