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Year 5 - Pathology ICSM1 > Chemical Pathology 10 - Calcium metabolism > Flashcards

Chemical Pathology 10 - Calcium metabolism Flashcards

1
Q

Around what percentage of the body’s calcium is in the skeleton?

A

99%

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2
Q

What % of serum calcium is free/ionised?

A

50%

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3
Q

Which form of serum calcium is biologically active?

A

Ionised

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4
Q

Recall the 3 forms of serum calcium?

A

Free/ionised 50%
Bound to albumin 40%
Complexed with citrate/phosphate 10%

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5
Q

What is “corrected calcium”?

A

Calcium corrected for albumin level Ca + 0.02 x (40- albumin)

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6
Q

How can ionised calcium be measured?

A

Blood gas

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7
Q

What is the key role of circulating calcium?

A

Nerve and muscle function

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8
Q

Where in the body is calcium level detected for calcium homeostasis?

A

Parathyroid gland

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9
Q

Which cells are involved in releasing calcium from bone?

A

Osteoclasts

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10
Q

Recall the 3 ways in which PTH can act to increase serum calcium

A
  1. Increase bone Ca resorption
  2. Increase renal Ca resorption
  3. Indirectly: increase 1-alpha hydroxylase action in kidneys - this increased vit D activation, and vit D increases gut absorption of vit D
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11
Q

What type of hormone is PTH?

A

Peptide hormone

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12
Q

What type of hormone is vitamin D?

A

Steroid hormone (derived from cholesterol)

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13
Q

What are the actions of PTH?

A
  1. Increased resorption of calcium from bone and kidney
  2. Renal phosphate wasting
  3. Increase renal 1 alpha hydroxylase, which activates vit D
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14
Q

Recall the pathway of vit D synthesis

A
  1. Cholecalciferol obtained from diet or converted by sunlight exposure from 7-dehydrocholesterol
  2. 100% of absorbed cholecalciferol is converted to storage form (vit D3) in liver conversion by 25 hydroxylase
  3. Activated by renal 1-alpha-hydroxylase - an enzyme under control of PTH - to the active form (1,25-(OH)2 D3)
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15
Q

Which hormone stimulates 1-alpha-hydroxylase production by the kidney?

A

PTH

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16
Q

In which disease can 1 alpha hydroxylase be produced outside the kidney, and where?

A

Sarcoidosis - in sarcoid lung tissue

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17
Q

Does sarcoidosis cause hypo or hypercalcaemia?

A

Hypercalcaemia

Sacroid tissue releases 1 alpha hydroxylase –>
Vit D activated outside the kidney –> calcium increased

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18
Q

Where is 1-alpha-hydroxylase produced in sarcoidosis?

A

Lung sarcoid tissue

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19
Q

What is calcitriol another name for?

A

1,25-dihydroxycholecalciferol

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20
Q

Where is 25 hydroxylase found?

A

Liver

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21
Q

What effect does 1,25(OH)2 vit D (active form) have on calcium and phosphate?

A

Increases calcium and phosphate absorption from intestines

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22
Q

Why is bone-specific ALP high when there is increased bone turnover?

A

Alkaline phosphatase pushes calcium and phosphate into bone

When it does this, some Alk phos is leaked into blood

Therefore, when you have increased bone turnover, you can measure the bone-specific AlkPhos in the blood and it will be high

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23
Q

Which electrolyte is necessary for PTH synthesis?

A

Magnesium

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24
Q

What is the difference between osteoporosis and osteomalacia in terms of bone structure and mass?

A 
Osteoporosis = less bone of normal structure
Ostemalacia = normal amount of bone of wacky structure
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25
Q

What type of bone disease is caused by renal failure?

A

Renal osteodystrophy

  1. Can’t make 1 alpha hydroxylase –> lack of calcium absorption into bone
  2. Can’t excrete phosphate in kidney failure
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26
Q

Which conditions are caused by vit D deficiency in children and adults?

A

Children: Ricketts
Adults: osteomalacia

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27
Q

Recall 4 risk factors for vit D deficiency

A

Lack of sunlight exposure
Dark skin
Dietary
Malabsorption (eg coeliac)

28
Q

Recall 4 clinical features of osteomalacia, including the biochemistry

A

Bone and muscle pain
Increased fracture risk
Looser’s zone fractures (AKA insufficiency fractures)
Biochem: low Ca and Pi, raised ALP

29
Q

Recall 4 clinical features of Rickets

A

Bowed legs
Costochondral swelling
Widened epiphyses at the wrists
Myopathy

30
Q

Why does chappati consumption increase vit D deficiency?

A 
Phytic acid
(This chelates vit D in gut, adding to the vit D deficiency)
31
Q

What is the biochemsistry of low calcium, low phosphate and high Alk Phos indicative of?

A

Vit D deficiency

32
Q

What is the expected calcium and phosphate level in osteoporosis?

A

Normal

33
Q

Recall 3 endocrine causes of osteoporosis

A

Cushings’s
Hyperthyroidism
Acidosis (less common)

34
Q

What are the 3 typical fragility fractures seen in osteoporosis

A

NOF

Colle’s (wrist)
Vertebral

35
Q

What scan is used to diagnose osteoporosis?

A

DEXA scan

36
Q

Recall the symptoms of Paget’s disease

A

PAIN, warmth, deformity, fracture, increased risk of high output cardiac failure

37
Q

Which bones are most commonly affected by Paget’s?

A

Pelvis, femur, skull and tibia

38
Q

What is the gold standard investigation for diagnosing Paget’s disease?

A

IV radiolabelled bisphosphonates

39
Q

How is pain treated in Paget’s disease?

A

Bisphosphonates

40
Q

What is the expected ALP level in Paget’s disease?

A

High

41
Q

What are the symptoms of hypercalcaemia?

A

Polyuria and polydipsia (increased solute –> increased urine volume)

Constipation (calcium causes muscle movement to slow down)

Neurological - seizures, confusion, coma (but only if Ca >3.0)

42
Q

Recall how hypercalcaemia should be investigated to determine a cause - and some differentials for your diagnostic approach

A
  1. Question whether it is a genuine result - send back to lab
  2. What is the PTH?
    3a. If PTH is LOW this is an appropriate response so could be due to malignancy, or more rarely - sarcoid/ thyrotoxicosis
    3b. If PTH is HIGH (suppressed) = inappropriate response to hypercalcaemia therefore = a problem with PTH regulation (mostly primary hyperparathyroidism, rarely, familial hypocalcuric hypercalcaemia)
43
Q

Which 3 types of malignancy might cause hypercalcaemia?

A
  1. Small Cell Lung Cancer (produces PTHrP)
  2. Bony metastases - causes local osetolysis
  3. Haematological malignancy (eg myeloma and CRAB)
44
Q

Recall some causes of primary hyperparathyroidism, and which of these is most common

A 
Parathyroid adenoma (most common) 
Parathyroid hyperplasia (rare) 
Parathyroid carcinoma (eg in Men1)
45
Q

What is the pathophysiology of familial hypocalcuric hypercalcaemia?

A

Calcium Sensing Receptor (CaSR) is mutated

PTH glands can’t detect Ca so well

Causes a MILD hypercalcaemia which is asymptomatic

There will be low urinary calcium (in name)

46
Q

How does thyrotoxicosis affect calcium?

A

Causes hypercalcaemia via increased bone resorption

47
Q

How do thiazide diuretics affect calcium?

A

Cause hypercalcaemia - due to reduced calcium transport in the renal tubules

48
Q

How should hypercalcaemia be treated?

A

FLUIDS, fluids, fluids!
0.9% saline - 1L over 1 hour

Treat underlying cause

49
Q

When can bisphosphonates be used to treat hypercalcaemia?

A

Only if the cause is known to be malignant

50
Q

Recall 2 signs of hypocalcaemia

A

Chovstek’s (C = cheek)

Trousseau’s (T = Tighten BP cuff)

51
Q

Which calcium imbalance may cause stridor, and why?

A

Hypocalcaemia - due to laryngeal spasm

52
Q

How should hypocalcaemia be treated?

A

Calcium + activated vit D

Nb: If cause is vit D deficiency (rare in UK) then give regular (not activated) vit D

53
Q

Recall some differentials for hypocalcaemia when the PTH is low

A

This is an inappropriate response (low calcium should cause high PTH)

Could be due to:

  1. Surgical mishap during thyroidectomy
  2. Autoimmune hypoparathyroidism (rare)
  3. Di George syndrome (even rarer! Agenesis of parathyroids)
  4. Magnesium deficiency - can be caused by OMEPRAZOLE
54
Q

Recall some differentials for hypocalcaemia when the PTH is high

A

This is an appropriate response to low calcium - SECONDARY HYERPARATHYROIDISM

Could be due to:

  1. Vit D deficiency (common)
  2. CKD (as low renal alpha-1-hydroxylase)
  3. Pseudohypoparathyroidism (gene deficit –> PTH resistance)
55
Q

What is the difference between the Z score and the T score in osteoporosis?

A

Z score = compared to someone of same age

T score = copared to healthy, young female

56
Q

Recall 3 lifestyle modifications that can treat osteoporosis

A

Weight-bearing exercise
Stop smoking
Reduce EtOH

57
Q

Give an example of a bisphosphonate drug

A

Alendronate

58
Q

How do SERM drugs work in osteoporosis treatment?

A

Antagonist of oestrogen at the breast but an agonist in the bone - so it reduces risk of breast Ca but increases bone density

59
Q

What plasma Ca level will you get in a patient with osteoporosis?

A

2.40 mmol/L

It will be normal because in osteoporosis, Ca is normal

60
Q

What is the first thing to measure in a hypercalcaemic patient?

A

PTH

61
Q

What are the 4 main symptoms of primary hyperPTH?

A

Bones
Stones
Psychic roans
Abdominal moans

62
Q

How does hypoadrenalism (Addisson’s) affect calcium?

A

Slight Hypercalcaemia

Renal calcium transport decreased

63
Q

Is neuromuscular excitability a sign of hypocalcaemia or hypercalcaemia?

A

Hypocalcaemia

64
Q

What is the most common cause of secondary hyperPTH?

A

Vit D deficiency

65
Q

What is the calcium level in Paget’s disease?

A

Normal because even though turnover is high the balance of calcium is normal

66
Q

How does Paget’s disease affect the heart?

A

Causes high output cardiac failure

Year 5 - Pathology ICSM1 (85 decks)

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