hyper and hypocalcium Flashcards

1
Q

which one is intracellular and which one is extracellular out of calcium and potassium

A

intracellular=potassium

extracellular=calcium

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2
Q

measurement of extracellular calcium

A

2.1-2.6 mmol/l

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3
Q

what are the 2 extracellular compartments of calcium

A
  • ionised ca that is physically active and stays constant

- calcium that is bound to albumin that is not physiologically active

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4
Q

what is mineral component of bone matrix mineralisation

A

calcium phosphate hydroxyapatite

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5
Q

what does Alk phos do for bones

A

promotes mineralisation
by
-increasing phosphate ion concentration
-hydrolysing pyrophosphate an inhibitor

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6
Q

what is osteopetrosis

A

dysfunctional osteoclasts get increased bone mass

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7
Q

bone remodelling cycle

A
quiescence
resorption
reversal
formation-mineralisation osteocytes 3months
takes 4-6 month total
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8
Q

2 hormones that regulate ionised calcium

A
  • parathyroid hormone=minute by minute regulation

- calcitriol=longer term

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9
Q

how does PTH respond to calcium levels 4

A
  • stimulates efflux of calcium from bone
  • stimulates renal tubular reabsorption of calcium
  • stimulates formation of calcitriol
  • promotes phosphate and bicarb loss from kidney
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10
Q

what does calcitonin do

A

responds to rising calcium in the paracollicular cells of thryoid gland
-reduces osteoclast activity

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11
Q

what is calcitriol

A

activated vit D 1,25 dihydroxy cholecalciferol

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12
Q

formation of calcitriol physiology

A
  1. diet or sun on 7 dehydrocholesterol-> vit D3
  2. vit D3-> liver 25-hydroxylase-> 25-hydroxy-vitD3
  3. 25-hydroxy vit d3-> renal 1-a hydroxylase-> 1,25 dihydroxy vit D which is calcitriol
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13
Q

what regulates 1 alpha hydroxylase in the kidney

A

PTH increases it

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14
Q

action of calcitriol

A
  • increase calcium and phosphate absorption from gut and renal
  • increase reabsorption of bone calcium
  • also need it to reduce PTH levels via swtiching off PTH gene transcription in Parathyroid cells allowing bones to mineralise
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15
Q

mechanism of calcitriol action

A
  • binds to vit d receptor VDR

- VDR calcitriol complex acts through a protein synthesis

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16
Q

difference in calcitriol vs PTH

A
calcitriol
-maintains ionised ca
-long term
-raises phosphate
PTH
-maintains ionised ca
-minute regulation
-decreases phosphate
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17
Q

causes of hypercalcaemia

A
  • primary hyperparat
  • secondary hyperpara
  • tertiary hyperpara
  • hypercalcaemia of malignancy
  • drugs
  • granulomatous disease
  • exogenous vit d excess
  • familial hypocalciuric hypercalcaemia
  • some endocrine diseases
  • immobilisation
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18
Q

causes of hypocalcaemia

A
  • hypoparat autoimmune
  • vit d related disorders
  • hypoparat post surgical
  • chronic kidney disease
  • malabsorption of ca
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19
Q

clinical signs of hypercalcaemia

A
moans
groans
stones
bones 
muscle weakness
anorexia 
nausea
renal(imapir water concen)
abdo pain 
ECG changes (qt shorten)
bones easier fracture
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20
Q

what is factitious hypercalcaemia

A
raised calcium due to high plasma albumin
-venous stasis
-dehydration
-iv albumin 
ie rise in bound but not ionised
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21
Q

age
prevalence
f:m ratio of primary hyperparat

A

6th decade
1 in 500
3:2

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22
Q

what causes primary hyperparat

A

solitary adenoma, hyperplasia and carcinoma

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23
Q

what is primary hyperparathyroidsim

A

autonomous and inappropriate overproduction of PTH leading to hyperca

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24
Q

markers for primary hyperparat

A

elevated PTH
elevated ca
low phosphate

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25
Q

what is secondary hyperparat

A

an appropriate release of PTH in response to hypocalcaemia

26
Q

markers for secondary hyperparat

A

elevated PTH
low calcium
elevated phosphate

27
Q

what is tertiary hyperparat

A

where a secondary overactive gland becomes overactive ie ongoing

28
Q

markers for tertiary hyperparat

A
elevated PTH
elevated calcium
low phosphate
elevated alk phos
vit d normal or decreased
29
Q

diagnosis of primary hyperparat

A
  • raised calcium with inappropriate increased PTH
  • phosphate and bicarb are low
  • alk phos normal to mod increase
  • pth imaging scan (sestamibi)
30
Q

treatment of primary hyperparat

A
  • high ionised calcium
  • rehydrate
  • drugs
  • removal of adenoma
31
Q

drugs for hypercalcaemia 5

A
  • bisphosponates
  • furosemide (loop diuretic)
  • calcitonin
  • glucocorticoids
  • calcmimetic drugs
32
Q

how does bisphosponate work

A

inhibits osteoclast action and bone resorption

33
Q

how does furosemide work

A

inhibits distal calcium reabsorption

34
Q

how does calcitonin work

A

inhibits osteoclast activation

35
Q

how does glucocorticoids affect calcium

A

inhibits vitamin d conversion to calcitriol can prolong calcitonin action `

36
Q

how do calcimimetic drugs work

A

bind to calcium sensors and inhibit PTH release (parathyroid carcinomas)

37
Q

most common malignancies causing hypercalcaemia

A

breast and lung cancers

38
Q

2 ways malignancy causes hypercalcaemia

A
  • endocrine factors secreted by malignant cells acting on bone
  • metastatic tumour deposits in bone locally stimulating bone resorption via osteoclast activation
39
Q

what endocrine factors are secreted by cancers

A

PTH related peptide

hodgkin lymphoma possess 1 OHase activity and synthesise calcitriol

40
Q

malignant hypercalcaemia assoc. to bony metastases mechanism

A

20% cases

  • most commonly assoc. to breast and lung
  • secrete osteoclast activating cytokines
  • myeloma produce cytokines that activate osteoclasts RANK IL3 and IL6
41
Q

Investigations for malignancy hypercalcaemia

A
-bone marrow biopsy for multiple myeloma
x-ray skull get pepper pot skull
-raised calcium with suppressed PTH 
-phosphate depends to be high 
-ALK P may be very high (liver or bone metastases)
-phx malignant disease
42
Q

what 2 drugs cause hypercalcaemia

A

lithium

thiazide diuretics

43
Q

what granulomatous disease causes hypercalcaemia

A

sarcoidosis

44
Q

where does sarcoidosis predmoninatly affect
what are the markers for it
mechanism behind

A

90% lungs and 10% skin

  • increase calcium with normal PTH
  • hydroxylation of vit D in granulomas
45
Q

what is FHH and markers

A
  • calcium sensors on parathyroid gland are less sensitive to calcium suppression of PTH
  • altered set point
  • PTH tends to be slightly raised
  • calcium increased
  • urine calcium excretion low
46
Q

what 2 endocrine diseases can cause hypercalcaemia

A

thyrotoxicosis and addison’s disease

47
Q

clinical features of hypocalcaemia

A

-increase in neuromuscular excitability (increase inward na movement)
-neuromuscular
numbness and paraesthesia
-anxiety and fatigue
-muscle cramps, carpo-pedal spasms, bronchial or laryngeal spasm
-seizure

mental

  • personality change
  • confusion

ecg changes, eye problems

48
Q

2 signs for hypocalcamia

A
  1. chvostek: flick facial nerve ie cheek and twitch

2. Trosseau sign: inflate BP cuff and wait a few minutes then hand starts to curl in

49
Q

what is factitious hypocalcaemia

A
  • due to low plasma albumin
  • acute phase response
  • malnutrition or malabsorption
  • liver disease
  • nephrotic syndrome (albumin lost in urine_
50
Q

markers of vitamin d deficiency

A
  • low calcium
  • high PTH
  • phosphate low
  • often raise ALP
51
Q

what is osteomalacia/ rickets

A
  • pathological bone problem with vit d deficient
  • osteoid laid down but not calcified so bone increases at expense of normal calcified bone
  • weak soft bones
52
Q

signs of osteomalacia/rickets

A
  • bone weakness
  • pain
  • bone deformities bow leggged and widening of cartilage at growth plates
53
Q

inherited cause of rickets/osteomalacia 4

A
  • vit d type 1 hydroxylase-renal enzyme (autosomal recessive)
  • defective receptor for calcitriol-type II vit d
  • hypophosphataemic rickets-low phosphate, excessive urine phosphate loss
  • hypophosphatasia (low ALK PHOS)
54
Q

mutation for hypophosphataemic rickets

A

-phosphaturic hormone FGF23/PHEX mutation
for autosomal dominant rickets causes resistance to degrade fgf23
-autosomal recessive is mutation in DMP1 increasing FGF23

55
Q

causes of hypoparathyroid

A
  1. post-surgical removal of thyroid causes damage to parathyroids
  2. suppressed secretion
  3. inherited
56
Q

causes of suppressed secretion of PTH

A
  1. low magnesium

2, maternal hypercalcaemia

57
Q

inherited causes of hypoparat

A

-developmental parathyroid problems

genetic eg DiGeorge

58
Q

marker of hypoparathyroid

A

low calcium
low PTH
phosphate may increase

59
Q

treatment of hypocalcaemia

A
  1. IV calcium
  2. or oral ca, vit d and mg
  3. injection calcium
60
Q

what is osteoporosis

A

reduced bone mineral density
hypercalcaemia
loss of calcifed matrix
-less bone but histologically normal

61
Q

what is osteomalacia

A

reduced bone mineral density
hypocalcaemia
loss of calcified matrix
abnormal histology with wide seams of uncalcifed osteoid