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YR5 Chemical Pathology > Calcium metabolism > Flashcards

Calcium metabolism Flashcards

1
Q

Calcium in serum exists in 3 forms - what are they and % of each?

A
  1. Free: ionised, active (50%)
  2. Albumin bound (40%)
  3. Complexed (10%) to citrate/ phosphate
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2
Q

Normal Ca range?
Corrected Ca2+ calculation?

A

2.2 - 2.6 mM/L
Serum Ca + 0.02(40-serum albumin g/l)

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3
Q

What is total calcium confounded by? Give causes of this. What do we use in these cases?

A

Albumin

Low: Sepsis, burns, low protein, liver/ kidney dysfunction
Gives low total calcium, corrected Ca will be higher

High: dehydration, high protein
Gives high total calcium, corrected Ca will be lower

Use Corrected calcium

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4
Q

PTH - it is released in response to…?
4 roles of PTH?

A

Low free Ca in serum
1. GUT: Ca absorption
2. KIDNEY: Ca resorption + Pi excretion + stimulates 1-alpha-hydroxylase
4. BONE: activates osteoclast for Ca resorption

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5
Q

What is the role of 1-alpha hydroxylase?

A

Converts 25(OH)D3 to 1,25(OH)2D3 = ACTIVE CALCITRIOL

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6
Q

Name the organ and condition in which 1-alpha-hydroxylase is expressed ectopically

A

Sarcoid tissue in lung
Causes hypercalcemia in summer (more vitamin D activation in sun)

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7
Q

4 Causes of Vit D deficiency

A

Renal failure (low 1-a-hydroxylase)
Anticonvulsants e.g. Phenytoin in kids
No sun exposure
Chappatis

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8
Q

5 Features of Rickets

A

Bowed legs
Costochondral swelling
Widened epiphyses at wrist
Myopathy
Low Ca, Low Pi

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9
Q

5 features of osteomalacia

A

Looser’s zones (psuedofractures)
Increased fracture risk
Bone + muscle pain
Low Ca, Low Pi (neither absorbed from gut)
High ALP (osteoblasts trying to make new bone)

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10
Q

phosphate levels in:

2ndary HyperPTH from CKD
2ndary hyperPTH from vit D deficiency

A

PO4 levels are:
high in CKD (inability to excrete)

low in vit D deficiency (due to PTH being so high)

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11
Q

Familial benign hypercalcemia

-Level of urine Ca
- Level of plasma Ca
- Level of PTH

A

defect in Ca sensing receptor in parathyroid gland + kidneys

urine Ca low
plasma Ca high
PTH high

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12
Q

pseudohypoparathyroidism
- PTH, Ca and PO4 levels?

A

PTH resistance

i.e. high levels of PTH, low Ca, high Phosphate

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13
Q

What pathology is caused by hypercalcaemia?

A

Failure of depolarisation
Stones: polyuria
Bones
Groans: constipation
Moans: confusion, seizures

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14
Q

What pathology is caused by hypocalcaemia?

A

“Trigger happy CNS”
Epilepsy (aberrant firing of nerves + muscles)
CATs go numb
Convulsions
Arrythmias
Tetany
Numbness in hands, feet + perineal

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15
Q

Describe the importance of maintaining circulating calcium levels

A

Needed for normal nerve + muscle function
Sacrifice Ca from bone if circulating Ca is low to maintain level
Increases risk of fracture

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16
Q

Describe the 2 hydroxylation reactions in vitamin D metabolism.

A

Liver: Cholecalciferol hydroxylated to 25-hydroxycholecalciferol
Kidneys: undergoes 2nd hydroxylation (by 1-alpha-hydroxylase) to 1,25-dihydroxycholecalciferol (calcitriol)

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17
Q

What is the principle effect of calcitriol?

A

Increase Ca, Mg + phosphate absorption in the small intestines

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18
Q

What are the secondary effects of calcitriol?

A

Increased reabsorption of Ca + decreased reabsorption of phosphate in kidneys (via FGF23)
Stimulates bone formation

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19
Q

What are the 2 forms of vitamin D?

A

D3: animals in diet/ synth in skin - cholecalciferol
D2: plants - ergocalciferol

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20
Q

Describe the action of calcitriol

A

Enters enterocytes in small intestine to increase activity of calcium channels to absorb more

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21
Q

What is usually measured to gauge the level of calcitriol? What condition must be fulfilled for this to be a good measure of calcitriol?

A

25-hydroxycholecalciferol (stored in liver)
Only good in the case of normal renal function

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22
Q

Describe the diagnostic characteristics of vitamin D deficiency.

A

Plasma Calcium = LOW
Plasma 25-hydroxycholecalciferol = LOW
Plasma PTH = HIGH (2 to hyperparathyroidism stimulated by the hypocalcaemia)
Plasma Phosphate = LOW
Radiological findings e.g. widened osteoid seams

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23
Q

Why does ALP rise in fractures or other conditions with high bone turnover?

A

Osteoblasts release ALP in bone formation

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24
Q

What would you expect the plasma phosphate level to be in someone with renal failure and why?

A

HIGH
GFR is low + there is a decrease in plasma excretion via the kidneys

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25
Q

What would you expect the plasma calcium level to be in someone with renal failure and why?

A

LOW
Not producing as much calcitriol (due to renal failure interfering with 1-alpha hydroxylase) so there is less Ca2+ absorption in the small intestines

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26
Q

What regulates phosphate metabolism?

A

Fibroblast growth factor 23 (FGF 23)

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27
Q

What happens when phosphate levels rise too high?

A

FGF 23 is stimulated to reduce circulating phosphate levels
Major effect in kidney

28
Q

What is the difference between Vitamin D and PTH in terms of phosphate absorption?

A

Vitamin D: increases calcium + phosphate absorption

PTH: increases calcium only (phosphate trashing hormone)

29
Q

Give 3 conditions associated with Vitamin D deficiency

A

Cancer
AI disease
Metabolic syndrome

30
Q

What is the difference between osteoporosis and osteomalacia?

A

Osteomalacia: defective bone mineralisation. LOW Calcium
Osteoporosis: normal bone structure, but weak, less total bone. NORMAL Calcium

31
Q

How do anticonvulsants cause vitamin D deficiency?

A

Potent first pass metabolites induce liver enzymes resulting in increased Vitamin D metabolism

32
Q

How does osteoporosis present?

A

Asymptomatic until 1st fracture
Commonly NOF, Vertebral or Wrist (Colle’s)

33
Q

How can osteoporosis be scored from a DEXA scan?

A

T: SD from young healthy population of same gender. Fracture risk.
Z: SD from mean age-matched control. Identifies in young.

34
Q

What categories arise from the T score?

A

< -2.5: OsteoPOROSIS, need tx to prevent fracture
-1 to -2.5: OsteoPENIA, at risk

35
Q

3 Lifestyle changes to reduce fracture risk in osteoporosis

A

Weight bearing exercise
Stop smoking
Reduce EtOH

36
Q

6 Rx for osteoporosis

A

Vitamin D
Bisphosphonates: reduce bone resorption e.g. Alendronate
Teriparatide
HRT: E2
SERMs: selective estrogen receptor modulator e.g. Tamoxifen
Denosumab

37
Q

How is Alendronate taken? Why is there reluctance to compliance?

A

PO once per week with plenty of water on an empty stomach
Wait 30m before breakfast
Stay upright
Can irritate stomach
SE: Osteonecrosis of jaw

38
Q

Give an alternative bisphosphonate to alendronate

A

Zolendronate IV
Once per year

39
Q

Give 4 categories of risk factors for early osteoporosis

A

Lifestyle: sedentary, EtOH, smoking, low BMI, nutrition
Endo: hyperprolactinaemia, thyrotoxicosis, Cushing’s
Drugs: steroids
Other: genetic

40
Q

How do you determine hypercalcaemia aetiology?

A
  1. Repeat test
  2. What is the PTH?
    If suppressed: cause outside parathyroid
    If normal/ high: parathyroid gland problem
41
Q

Give the most common, and 3 rarer causes of hypercalcaemia with low PTH

A

Metastatic CANCER
Sarcoid
Vit D excess
Thyrotoxicosis

42
Q

Give the most common, and a rarer causes of hypercalcaemia with normal/ high PTH

A

Primary Hyperparathyroidism
Familial hypocalciuric hypercalcaemia

43
Q

3 facts about primary hyperparathyroidism

A

F > M
Parathyroid adenoma 80% (mostly single) or hyperplasia/ carcinoma
Tx: Remove parathyroid

44
Q

Parathyroid hyperplasia is associated to which condition

A

MEN1

45
Q

What lab findings would be seen in primary hyperparathyroidism?

A

Serum Ca HIGH
Serum Phos LOW
PTH N or HIGH
Urine Ca HIGH

46
Q

4 Sx someone with primary hyperparathyroidism may present with

A

Stones: Renal calculi
Bones: Fracture e.g. Colle’s
Moans: Constipation
Groans: Confusion

47
Q

Pathophysiology of familial hypocalciuric hypercalcaemia

A

Calcium sensing receptor mutation
Reduced sensitivity to calcium
Tissue can’t “see” high calcium
Reduced urine calcium

48
Q

3 types of hypercalcaemia in malignancy

A
  1. Humoral: SCLC, kidney, breast. PTHrP produced
  2. Bone mets: local bone osteolysis (invasion)
  3. Haematological e.g. Myeloma
49
Q

When is production of PTHrP not pathological?

A

Prior to birth, placenta makes PTHrP to allow foetus to get calcium

50
Q

5 non-PTH causes of hypercalcaemia

A

Sarcoidosis: Non renal 1 alpha hydroxylation
Thyrotoxicosis: Thyroxine leads to bone resorption
Hypoadrenalism: decreased renal excretion
Thiazide diuretics: increase reabsorption
Excess vit D: Sunbeds

51
Q

Acute management of hypercalcaemia

A

FLUIDS: 0.9% Saline 1L/hr
4L daily if no HF
IV 1st day at least

52
Q

When are bisphosphonates given for hypercalcaemia?

A

if cause KNOWN to be CANCER
Alendronate: creates barrier of indestructible bone, can’t be invaded by cancer cells

53
Q

Why would giving bisphosphonates to a patient with primary hyperparathyroidism be problematic?

A

Bone becomes indestructable
Leads to hypocalcaemia post-parathyroidectomy

54
Q

What is Chvostek’s sign?

A

Twitch of facial muscles on tapping cheek in front of ear

55
Q

What is Trousseau’s sign?

A

Carpal spasm
BP cuff pumped to high pressure, causes albumin to rise, more will bind to ionised calcium, further reducing calcium.
Can’t open hand

56
Q

4 signs of hypocalacemia

A

Chvosteks
Trousseau’s
Hyperreflexia
Convulsions/ laryngeal spasm (stridor)

57
Q

Tx for hypocalcaemia

A

IV calcium
Vitamin D

58
Q

3 causes of hypocalcaemia that is non PTH driven (secondary hyperparathyroidism- PTH will be high)

A

Vit D deficiency
CKD: lack 1 alpha hydroxylation
Pseudohypoparathyroidism

59
Q

4 causes of hypocalcaemia due to low PTH

A

Surgical (post thyroidectomy / parathyroidectomy)
AI hypoparathyroidism
Congenital absence e.g. Di George syndrome
Mg deficiency (needed to make PTH)

60
Q

What characterises Paget’s disease?

A

increased but uncontrolled bone turnover.
Primarily a disorder of osteoclasts, with excessive osteoclastic resorption followed by increased osteoblastic activity.

61
Q

3 bone signs/ sx in Pagets

A

Focal bone pain
Bone warmth
Deformity/ fracture

62
Q

Why do those with Paget’s disease develop heart failure?

A

Bone shunts blood through it
Have high throughput of blood through bone
Makes heart work harder

63
Q

3 complications arising from bone causing compression in Pagets

A

Spinal cord compression
Blindness
Deafness

64
Q

What biochemistry is found in Paget’s?

A

HIGH ALP
EVERYTHING else is NORMAL
Ca + phos normal as osteoclasts + blasts are both active

65
Q

From lowest to highest calcium level, rank the following conditions:
(Breast) Cancer
Pagets
2nd HPT
Osteoporosis
1st HPT

A
  1. (Breast) Cancer patients
  2. 1st HPT
  3. Osteoporosis + Pagets have normal so would need distinguishing feature
  4. 2nd HPT

YR5 Chemical Pathology (16 decks)

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