**_🧪Endocrinology🧪 - Calcium Dysregulation Flashcards

1
Q

What are the main regulatory hormones of calcium homeostasis?

A

Vitamin D and parathyroid hormone (PTH)

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2
Q

What acts to increase calcium levels?

A

Vitamin D and PTH

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3
Q

What acts to decrease calcium levels?

A

Calcitonin

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4
Q

Outline calcitonin

A

Secreted by thyroid parafollicular cells (note not parathyroid cells)
Can reduce calcium acutely, not physiologically important as thyroidectomy shows no negative impact on calcium levels

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5
Q

Outline Vitamin D3 production

A

Occurs in skin - 7-dehydrocholesterol interacts with UVB light to make pre-vitamin D3, which is then converted into vitamin D3

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6
Q

Outline vitamin D production

A

Vitamin D3 from skin and D2 from diet enters the liver through the bloodstream
25-hydroxylase catalyses conversion into 25(OH)cholecalciferol in the liver
25(OH)cholecalciferol converted to 1,25(OH)2cholecalciferol (calcitriol) in the kidney, catalysed by 1 alpha-hydroxylase

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7
Q

How is serum vitamin D measured?

A

Calcitriol never measured itself
25-OH much more stable in blood and easy to measure - gives good indicator of vitamin D status

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8
Q

What are the actions of calcitriol?

A

Overall effect is increase in serum calcium and phosphate
Increases calcium and phosphate reabsorption in kidney
Increases calcium and phosphate absorption in the gut

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9
Q

What are the actions of PTH?

A

Net effects is increased calcium and decreased phosphate
Increases calcium resorption from bone(increases osteoclast activity)
Increases calcium reabsorption in the kidney
Increases phosphate excretion/decreases phosphate reabsorption
Increase 1 alpha-hydroxylase activity (therefore increases calcitriol synthesis)
Indirectly increases gut absorption of calcium and phosphate (overall net decrease in phosphate due to increased excretion)

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10
Q

How does PTH increase renal phosphate excretion?

A

Inhibits sodium phosphate co-transporter in the kidney - responsible for reabsorption of phosphate
Inhibits this transporter along with FGF23

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11
Q

What is the overall role of FGF23?

A

Increases phosphate excretion by preventing phosphate reabsorption, and also decreases phosphate absorption in the gut

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12
Q

What is the mechanism of FGF23?

A

FGF23 prevents renal phosphate reabsorption by inhibiting the sodium/phosphate co-transporter from transporting sodium and phosphate out of the renal filtrate (note sodium is affected here, not calcium)
FGF23 also reduces 1 alpha-hydroxylase activity and promotes calcitriol degradation, lowering calcitriol levels and reduces phosphate absorption in the gut

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13
Q

What are the signs and symptoms of hypocalcaemia?

A

Sensitises excitable tissue; muscles, neurons etc…
Paresthesia (hands, mouth, feet, lips)
Convulsions
Arrythmias
Tetany (muscle contracts and cannot relax)
Chvostek’s sign - tapping of zygomatic arch causes facial twitch
Trousseau’s sign - carpopedal spasm induced by inflating of blood pressure cuff

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14
Q

What are the 2 main causes of hypocalcaemia?

A

Low PTH levels - hypoparathyroidism
Low vitamin D levels - vitamin D deficiency
(can have low calcium in diet, but generally looking at the 2 above causes)

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15
Q

How can hypoparathyroidism arise?

A

Surgery - neck surgery, classic example is a thyroidectomy
Autoimmune damage
Congenital (agenesis, rare, would present as a neonate)

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16
Q

How can vitamin D deficiency arise?

A

Poor diet/malabsorption
Lack of UV light, sunlight exposure
Impaired production (renal failure)

17
Q

What are the signs and symptoms of hypercalcaemia?

A

“Stones, abdominal moans, psychic groans”
Reduced excitability of tissue - lack of neuronal excitability, atonal muscles
Stones - renal effects - nephrocalcinosis (kidney stones, renal colic)
Abdominal moans - GI effects - anorexia, nausea, dyspepsia, constipation, pancreatitis
Psychic groans - CNS effects - fatigue, depression, impaired concentration, altered mentation, coma (usually >3mmol/L)
Overall: kidney stones, slowing of GI tract, slowing of CNS

18
Q

What are the causes of hypercalcaemia?

A

(Primary/secondary/tertiary) hyperparathyroidism
Malignancy - certain cancers secrete PTH-related peptide that acts at PTH receptors
Vitamin D excess (rare)

19
Q

What is primary hyperparathyroidism?

A

Parathyroid adenoma - produces too much PTH
Calcium increases - no negative feedback due to autonomous secretion of PTH from adenoma

20
Q

What is the biochemistry of primary hyperparathyroidism?

A

High calcium
Low phosphate - increased renal phosphate excretion
High PTH (not suppressed by hypercalcaemia)

21
Q

What is the normal treatment for primary hyperparathyroidism?

A

Parathyroidectomy

22
Q

What are the risks of untreated hyperparathyroidism?

A

Osteoporosis
Renal calculi (stones)
Psychological impact - mental function, mood

23
Q

What is secondary hyperparathyroidism?

A

Increased PTH due to hypocalcaemia, normal physiological response
Problem lies with root cause of hypocalcaemia, not PTH
PTH Is unable to raise calcium levels for whatever reason

24
Q

What is the main difference between primary and secondary hyperparathyroidism?

A

Primary has abnormal parathyroid gland, secondary is normal
Primary has hypercalcaemia, secondary has hypocalcaemia

25
Q

What are the causes of secondary hyperparathyroidism?

A

Most common is vitamin D deficiency
common - diet, reduced sunlight
less common, but important - renal failure, inability to make calcitriol
Absence of calcitriol makes elevating calcium almost impossible

26
Q

What is the treatment of secondary hyperparathyroidism?

A

Vitamin D replacement
Normal renal function - 25(OH) vitamin D - patient’s kidneys will convert to calcitriol
Impaired renal function/renal failure - give alfacalcidol (active vitamin D replacement)

27
Q

What can untreated secondary hyperparathyroidism lead to?

A

Tertiary hyperparathyroidism

28
Q

What is tertiary hyperparathyroidism?

A

Chronic hypocalcaemia (chronic vit-D deficiency or chronic renal failure)
Chronic elevated PTH production - leads to eventual hyperplasia of parathyroid glands
Parathyroid glands start to autonomously secrete PTH

29
Q

Outline tertiary hyperparathyroidism

A

Tertiary hyperparathyroidism is rare
Occurs usually in chronic renal failure - inability to make calcitriol
PTH increases (hyperparathyroidism)
Parathyroid glands enlarge (hyperplasia)
Autonomous PTH secretion eventually leads to hypercalcaemia
Notice secondary hyperparathyroidism features hypocalcaemia, leading to tertiary which is hypercalcaemic

30
Q

What is the treatment for tertiary hyperparathyroidism?

A

Parathyroidectomy
Can also give bisphosphonates, prevents osteoclast activation

31
Q

What is the diagnostic approach with hypercalcaemia?

A

First thing to look at should be the PTH

32
Q

What might cause high calcium with low PTH?

A

Malignancies (secretion of PTH-related peptide)
Malignancy always needs to be ruled out first

33
Q

What is the diagnosis for raised calcium and PTH?

A

Hyperparathyroidism
Primary if renal function is normal
Tertiary if abnormal renal function

34
Q

What can you expect to see with Vitamin D deficiency?

A

Calcium will be low (also can be lower end of normal), PTH will be high
Vitamin D is measured as 25(OH) vitamin D, calcitriol itself very difficult to measure

35
Q

How does PTH cause bone resorption?

A

Binds to PTH receptor on osteoblast, which combined with osteoclast binding factors produces an osteoclast, which resorbs bone

36
Q

What can be used to counteract chronically raised PTH levels?

A

Bisphosphonates

37
Q

What is the mechanism of action for bisphosphonates?

A

Inhibits osteoclast activation and activity

38
Q

What are some risk factors for vitamin D deficiency?

A

Pigmented skin (South asian, african, carribean, south american ancestry etc…)
Living in low sunlight country (e.g. the UK)
Low calcium in diet (poor diet, vegan diets - no dairy and so potentially low calcium)