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Pathology > Chemical Pathology - Calcium Metabolism > Flashcards

Chemical Pathology - Calcium Metabolism Flashcards

1
Q

why does the blood calcium level need to be fixed

A

nerves and muscles rely on it for depolarisation

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2
Q

symptoms of hypercalcaemia

A 
stones
bones
groans
moans
nephrogenic DI
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3
Q

symptoms of hypocalcaemia

A

epilepsy (aberrant firing of nerves/muscles)

CATS go numb (convulsions, arrhythmias, tetany and numbness)

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4
Q

normal Ca level

A

2.2-2.6mmol/l

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5
Q

3 forms Ca is found in the serum

A
  1. free and ionised (50%) –> can be measured on blood gas machine
  2. protein bound to albumin (40%)
  3. complexed with citrate/phosphate (10%)
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6
Q

why is it important to check the albumin level?

A

abnormal Ca affects free Ca (e.g. sepsis)
Corrected Ca compensated for albumin
corrected Ca shows if the problem is albumin and ionised Ca will be normal

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7
Q

when is PTH released

A

hypocalcaemia

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8
Q

what are the actions of PTH

A
  • 1 alpha hydroxylase activation = calcidol to calcitriol = gut effects
  • osteoclast activation = Ca liberation
  • direct renal Ca resorption
  • direct renal phosphate excretion
    RESULT IN RISE IN PLASMA CA
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9
Q

what are the 2 steroid hormones involved in Ca homeostasis

A

PTH

Vit D

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10
Q

what are the 2 forms of Vit D and what are they activated by?

A

both are forms of alfacalcidol and are both activated by 1 alpha hydroxylase
D3 = CHOLECALCIFEROL (animal product synthesised in skin from sunlight)
D2 = ERGOCALCIFEROL (plant vitamin)

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11
Q

what happens next to cholecalciferol (Vit D3) and where does it happen?

A

Vit D3 from skin/food intake is hydroxylated at 25 position by 25 hydroxylase
IN LIVER
25 hydroxy vit D is inactive. Stored and measured form of Vit D

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12
Q

Where does the Vit D become activated? By which enzyme?

A

Activation of Vit D in kidney by 1 alpha hydroxylase

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13
Q

where can 1 alpha hydroxylase also be expressed?

A

in lungs of sarcoid tissue

sarcoid = hypercalcaemia especially in summer when sunlight and Ca go up (more Vit D activation)

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14
Q

summarise the activation pathway of Vit D

A
  1. Vit D3 (Cholecalciferol)
  2. 25 hydroxy Vit D3 (by 25 hydroxylase in liver)
  3. 1, 25 dihydroxy Vit D3 (Calcitriol) (by 1 alpha hydroxylase under action of PTH)
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15
Q

what is the role of Calcitriol?

A
  • intestinal Ca and phosphate absorption

- bone formation (with osteoblasts)

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16
Q

what happens when you have a Vit D deficiency in children and adults?

A

Defective bone mineralisation

  1. childhood = rickets
  2. adults = osteomalacia
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17
Q

what are the risk factors for Vit D deficiency?

A
  • lack of sunlight exposure
  • dark skin
  • dietary
  • malabsorption
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18
Q

what are the clinical features of osteomalacia?

A
  • bone and muscle pain
  • inc fracture risk
  • looser’s zones (pseudo fractures)
  • bio chem: low Ca and P, raised ALP
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19
Q

what are the clinical features of rickets?

A
  • bowed legs
  • costochondral swelling
  • widened epiphyses at the wrists
  • myopathy
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20
Q

what are the causes of osteomalacia?

A

LACK OF CA

  • renal failure
  • lack of sunlight
  • Vit D def
  • anticonvulsants that induce breakdown of Vit D (phenytoin)
  • Chappatis (phytic acid chelates Vit D, prevents absorption)
21
Q

what is the most common cause of osteoporosis

A

lack of oestrogen

22
Q

what happens in osteoporosis

A
  • loss of bone mass
  • residual bone is normal structure
  • normal Ca
  • normal mineralisation
  • NORMAL biochemistry
23
Q

what fractures does osteoporosis present with?

A
  • NOF
  • Vertebral
  • Colle’s
24
Q

how do you diagnose osteoporosis

A 
DEXA scan
T score (from young healthy population)
Z score (age matched control)
25
Q

T score for osteoporosis and osteopenia

A

Osteoporosis: T score < -2.5
Osteopenia: T score -1 and -2.5

26
Q

what are the lifestyle treatments for osteoporosis

A
  • weight bearing exercise
  • stop smoking
  • reduce alcohol
27
Q

what are the drug treatments for osteoporosis

A
  • Vit D/Ca
  • bisphosphonates (dec bone resoprtion)
  • teriparatide (PTH derivative)
  • strontium (anti-resoptive)
  • oestrogens (HRT)
  • SERMS (oestrogen like drug e.g. Tamoxifen)
  • Denosumab (biological anti-RANK-L antibody)
28
Q

when a patient has hypercalcaemia what should you first think?

A
  1. is it a genuine result? (repeat)

2. what is the PTH

29
Q

what is the commonest cause of hypercalcaemia?

A

primary hyperparathyroidism

30
Q

what are the causes of primary hyperparathyroidism?

A

parathyroid adenoma (80%)
hyperplasia associated with MEN1, 2a
malignancy

31
Q

biochemical results of primary hyperparathyroidism

A
  • inc serum Ca
  • inc PTH
  • dec serum P
  • inc urine Ca due to hypercalcaemia
  • inc/normal Alk phos
32
Q

what happens in Familial Hypocalciuric Hypercalcaemia (FHH)?

A

mutation in Calcium sensing receptor
reduced sensitivity to Ca
higher set point for PTH release
= mild hypercalcaemia and reduced urine Ca

33
Q

what is the primary defect in secondary hyperparathyroidism?

A

renal failure

Vit D deficiency

34
Q

biochemical results in secondary hyperparathyroidism

A
  • low Ca
  • high P
  • high alk phos
  • dec Vit D
35
Q

what is the primary defect in tertiary hyperparathyroidism?

A

autonomous PTH secretion

36
Q

biochemical results in tertiary hyperparathyroidism

A
  • high Ca
  • low P
  • high PTH
  • high Alk phos
  • normal Vit D
37
Q

what are the 3 types of hypercalcaemia in malignancy

A
  1. humoral hypercalcaemia of malignancy (PTHrP)
  2. bone mets (breast Ca)
  3. haematological malignancy (myeloma
38
Q

what are some other causes of non-PTH driven hypercalcaemia

A
  • sarcoidosis
  • thyrotoxicosis (thyroxine = bone resorption)
  • hypoadrenalism (renal Ca transport)
  • thiazide diuretics (renal Ca transport)
  • excess Vit D (sunbeds)
39
Q

what is the tx of hypercalcaemia?

A

FLUIDS (0.9% saline, 1L/hour)

treat underlying cause

40
Q

when should you give bisphosphonates?

A

if hypercalcaemia caused by malignancy

41
Q

what are the signs of hypocalcaemia?

A
  • NM excitability: Chvostek’s sign (face), Trousseau’s sign, hyperreflexia
  • convulsions
42
Q

what are the causes of hypocalcaemia when there is a high PTH

A

secondary hyperparathyroidism

  • Vit D def
  • CKD (lack of 1 alpha hydroxylase)
  • PTH resistance
43
Q

what are the causes of hypocalcaemia when there is a low PTH

A
  • surgical (e.g. post-thyroidectomy)
  • AI hypoparathyroidism
  • congenital absence of parathyroids (e.g. DiGeorge)
  • Mg def (PTH regulation)
44
Q

What is Paget’s disease?

A

focal disorder of bone remodelling

45
Q

what are the signs and symptoms of Paget’s?

A
  • bone pain
  • deformity
  • warmth
  • fracture
  • cardiac failure
  • malignancy
  • compression (blindness, deafness)
46
Q

which bones does Paget’s affect the most?

A

pelvis
femur
skull
tibia

47
Q

biochemistry of Pagets

A
  • high Alk phos

- Ca and P are normal

48
Q

what is the tx of Pagets

A

bisphosphonates for pain

Pathology (21 decks)

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