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Chemical Pathology > Y Lectures 1&2: Calcium Metabolism > Flashcards

Y Lectures 1&2: 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/ionisedBound to albuminComplexed with citrate/phosphate

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5
Q

What is “corrected calcium”?

A

Calcium corrected for albumin level

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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 resorption2. Increase renal Ca resorption3. 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 kidney2. Renal phosphate wasting3. 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

HypercalcaemiaSacroid 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 boneWhen it does this, some Alk phos is leaked into bloodTherefore, 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 structureOstemalacia = 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 bone2. 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: RickettsAdults: osteomalacia

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27
Q

Recall 4 risk factors for vit D deficiency

A

Lack of sunlight exposureDark skinDietaryMalabsorption (eg coeliac)

28
Q

Recall 4 clinical features of osteomalacia, including the biochemistry

A

Bone and muscle painIncreased fracture riskLooser’s zone fracturesBiochem: low Ca and Pi, raised ALP

29
Q

Recall 4 clinical features of Rickets

A

Bowed legsCostochondral swellingWidened epiphyses at the wristsMyopathy

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’sHyperthyroidismAcidosis (less common)

34
Q

What are the 3 typical fragility fractures seen in osteoporosis

A

NOFColle’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 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 lab2. 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 mutatedPTH glands can’t detect Ca so wellCauses 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 hourTreat 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 DNb: 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 thyroidectomy2. 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 HYERPARATHYROIDISMCould 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 ageT score = copared to healthy, young female

56
Q

Recall 3 lifestyle modifications that can treat osteoporosis

A

Weight-bearing exerciseStop smokingReduce 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/LIt 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

BonesStonesPsychic roansAbdominal moans

62
Q

How does hypoadrenalism (Addisson’s) affect calcium?

A

HypercalcaemiaRenal 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

Chemical Pathology (10 decks)

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