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Year 5 Pathology Lectures > 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

Recall the 3 forms of serum calcium?

A

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

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3
Q

What is “corrected calcium”?

What is the equation for calculating it?

A

Calcium corrected for albumin level

Serum calcium + 0.02(40 - serum albumin)

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4
Q

How can ionised calcium be measured?

A

Blood gas

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5
Q

What is the key role of circulating calcium?

A

Nerve and muscle function

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6
Q

What are the actions of PTH?

A
  1. Increase bone Ca and phosphate resorption
  2. Increase renal Ca reabsorption and phosphate wasting
  3. Increase 1-alpha hydroxylase action in kidneys - this increases vit D activation, and vit D increases gut absorption of vit D
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7
Q

What type of hormone is PTH?

A

Peptide hormone

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8
Q

What type of hormone is vitamin D?

A

Steroid hormone (derived from cholesterol)

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9
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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10
Q

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

A

Sarcoidosis - in sarcoid lung tissue. This is why sarcoidosis causes hypercalcaemia.

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11
Q

Where is 25 hydroxylase found?

A

Liver

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12
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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13
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 ALP is leaked into blood

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

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14
Q

Which electrolyte is necessary for PTH synthesis?

A

Magnesium

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15
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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16
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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17
Q

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

A

Children: Rickets
Adults: osteomalacia

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18
Q

Recall 5 risk factors for vit D deficiency

A 
Lack of sunlight exposure + dark skin
Renal disease or failure
Anti-convulsants -> cause Vit D breakdown
Dietary (chapatis)
Malabsorption (eg coeliac)
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19
Q

Recall 4 clinical features of osteomalacia, including the biochemistry

A

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

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20
Q

Recall 4 clinical features of Rickets

A

Bowed legs
Costochondral swelling
Widened epiphyses at the wrists
Myopathy

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21
Q

Why does chappati consumption increase vit D deficiency?

A 
Phytic acid
(This chelates vit D in gut, adding to the vit D deficiency)
22
Q

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

A

Vit D deficiency

23
Q

What is the expected calcium and phosphate level in osteoporosis?

A

Normal

24
Q

Recall 3 endocrine causes of osteoporosis

A

Cushings’s
Hyperthyroidism
Acidosis (less common)

25
Q

What are the 3 typical fragility fractures seen in osteoporosis

A

NOF

Colle’s (wrist)
Vertebral

26
Q

Recall the symptoms of Paget’s disease

A

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

27
Q

Which bones are most commonly affected by Paget’s?

A

Pelvis, femur, skull and tibia

28
Q

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

A

IV radiolabelled bisphosphonates

29
Q

How is pain treated in Paget’s disease?

A

Bisphosphonates

30
Q

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

A

High

31
Q

What are the symptoms of hypercalcaemia?

A

Bones, stones, abdominal moans, psychic groans

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)

32
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 = inappropriate response to hypercalcaemia therefore = a problem with PTH regulation (mostly primary hyperparathyroidism, rarely, familial hypocalcuric hypercalcaemia)
33
Q

Which 3 types of malignancy might cause hypercalcaemia?

A
  1. Lung Cancer (squamous cell can produce PTHrP)
  2. Bony metastases - causes local osteolysis
  3. Haematological malignancy (eg myeloma and CRAB)
34
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 Men-1)
35
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)

36
Q

How does thyrotoxicosis affect calcium?

A

Causes hypercalcaemia via increased bone resorption

37
Q

How do thiazide diuretics affect calcium?

A

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

38
Q

How should hypercalcaemia be treated?

A

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

Treat underlying cause

39
Q

When can bisphosphonates be used to treat hypercalcaemia?

A

Only if the cause is known to be malignant

40
Q

Recall 2 signs of hypocalcaemia

A

Chovstek’s (C = cheek)

Trousseau’s (T = Tighten BP cuff)

41
Q

Which calcium imbalance may cause stridor, and why?

A

Hypocalcaemia - due to laryngeal spasm

42
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

43
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
44
Q

Recall some differentials for hypocalcaemia when the PTH is high

A

This is an appropriate response to low calcium - SECONDARY HYPERPARATHYROIDISM

Could be due to:

  1. Vit D deficiency (most common cause)
  2. CKD (as low renal alpha-1-hydroxylase)
  3. Pseudohypoparathyroidism (gene deficit –> PTH resistance)
45
Q

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

A

Z score = compared to someone of same age and gender

T score = compared to healthy, young adult

46
Q

Recall 3 lifestyle modifications that can treat osteoporosis

A

Weight-bearing exercise
Stop smoking
Reduce EtOH

47
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

48
Q

How does hypoadrenalism (Addisson’s) affect calcium?

A

Hypercalcaemia

Renal calcium transport decreased

49
Q

Is neuromuscular excitability a sign of hypocalcaemia or hypercalcaemia?

A

Hypocalcaemia

50
Q

What is the calcium level in Paget’s disease?

A

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

51
Q

How does Paget’s disease affect the heart?

A

Causes high output cardiac failure

Year 5 Pathology Lectures (87 decks)

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