hyper and hypocalcium Flashcards
which one is intracellular and which one is extracellular out of calcium and potassium
intracellular=potassium
extracellular=calcium
measurement of extracellular calcium
2.1-2.6 mmol/l
what are the 2 extracellular compartments of calcium
- ionised ca that is physically active and stays constant
- calcium that is bound to albumin that is not physiologically active
what is mineral component of bone matrix mineralisation
calcium phosphate hydroxyapatite
what does Alk phos do for bones
promotes mineralisation
by
-increasing phosphate ion concentration
-hydrolysing pyrophosphate an inhibitor
what is osteopetrosis
dysfunctional osteoclasts get increased bone mass
bone remodelling cycle
quiescence resorption reversal formation-mineralisation osteocytes 3months takes 4-6 month total
2 hormones that regulate ionised calcium
- parathyroid hormone=minute by minute regulation
- calcitriol=longer term
how does PTH respond to calcium levels 4
- stimulates efflux of calcium from bone
- stimulates renal tubular reabsorption of calcium
- stimulates formation of calcitriol
- promotes phosphate and bicarb loss from kidney
what does calcitonin do
responds to rising calcium in the paracollicular cells of thryoid gland
-reduces osteoclast activity
what is calcitriol
activated vit D 1,25 dihydroxy cholecalciferol
formation of calcitriol physiology
- diet or sun on 7 dehydrocholesterol-> vit D3
- vit D3-> liver 25-hydroxylase-> 25-hydroxy-vitD3
- 25-hydroxy vit d3-> renal 1-a hydroxylase-> 1,25 dihydroxy vit D which is calcitriol
what regulates 1 alpha hydroxylase in the kidney
PTH increases it
action of calcitriol
- 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
mechanism of calcitriol action
- binds to vit d receptor VDR
- VDR calcitriol complex acts through a protein synthesis
difference in calcitriol vs PTH
calcitriol -maintains ionised ca -long term -raises phosphate PTH -maintains ionised ca -minute regulation -decreases phosphate
causes of hypercalcaemia
- primary hyperparat
- secondary hyperpara
- tertiary hyperpara
- hypercalcaemia of malignancy
- drugs
- granulomatous disease
- exogenous vit d excess
- familial hypocalciuric hypercalcaemia
- some endocrine diseases
- immobilisation
causes of hypocalcaemia
- hypoparat autoimmune
- vit d related disorders
- hypoparat post surgical
- chronic kidney disease
- malabsorption of ca
clinical signs of hypercalcaemia
moans groans stones bones muscle weakness anorexia nausea renal(imapir water concen) abdo pain ECG changes (qt shorten) bones easier fracture
what is factitious hypercalcaemia
raised calcium due to high plasma albumin -venous stasis -dehydration -iv albumin ie rise in bound but not ionised
age
prevalence
f:m ratio of primary hyperparat
6th decade
1 in 500
3:2
what causes primary hyperparat
solitary adenoma, hyperplasia and carcinoma
what is primary hyperparathyroidsim
autonomous and inappropriate overproduction of PTH leading to hyperca
markers for primary hyperparat
elevated PTH
elevated ca
low phosphate
what is secondary hyperparat
an appropriate release of PTH in response to hypocalcaemia
markers for secondary hyperparat
elevated PTH
low calcium
elevated phosphate
what is tertiary hyperparat
where a secondary overactive gland becomes overactive ie ongoing
markers for tertiary hyperparat
elevated PTH elevated calcium low phosphate elevated alk phos vit d normal or decreased
diagnosis of primary hyperparat
- raised calcium with inappropriate increased PTH
- phosphate and bicarb are low
- alk phos normal to mod increase
- pth imaging scan (sestamibi)
treatment of primary hyperparat
- high ionised calcium
- rehydrate
- drugs
- removal of adenoma
drugs for hypercalcaemia 5
- bisphosponates
- furosemide (loop diuretic)
- calcitonin
- glucocorticoids
- calcmimetic drugs
how does bisphosponate work
inhibits osteoclast action and bone resorption
how does furosemide work
inhibits distal calcium reabsorption
how does calcitonin work
inhibits osteoclast activation
how does glucocorticoids affect calcium
inhibits vitamin d conversion to calcitriol can prolong calcitonin action `
how do calcimimetic drugs work
bind to calcium sensors and inhibit PTH release (parathyroid carcinomas)
most common malignancies causing hypercalcaemia
breast and lung cancers
2 ways malignancy causes hypercalcaemia
- endocrine factors secreted by malignant cells acting on bone
- metastatic tumour deposits in bone locally stimulating bone resorption via osteoclast activation
what endocrine factors are secreted by cancers
PTH related peptide
hodgkin lymphoma possess 1 OHase activity and synthesise calcitriol
malignant hypercalcaemia assoc. to bony metastases mechanism
20% cases
- most commonly assoc. to breast and lung
- secrete osteoclast activating cytokines
- myeloma produce cytokines that activate osteoclasts RANK IL3 and IL6
Investigations for malignancy hypercalcaemia
-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
what 2 drugs cause hypercalcaemia
lithium
thiazide diuretics
what granulomatous disease causes hypercalcaemia
sarcoidosis
where does sarcoidosis predmoninatly affect
what are the markers for it
mechanism behind
90% lungs and 10% skin
- increase calcium with normal PTH
- hydroxylation of vit D in granulomas
what is FHH and markers
- 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
what 2 endocrine diseases can cause hypercalcaemia
thyrotoxicosis and addison’s disease
clinical features of hypocalcaemia
-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
2 signs for hypocalcamia
- 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
what is factitious hypocalcaemia
- due to low plasma albumin
- acute phase response
- malnutrition or malabsorption
- liver disease
- nephrotic syndrome (albumin lost in urine_
markers of vitamin d deficiency
- low calcium
- high PTH
- phosphate low
- often raise ALP
what is osteomalacia/ rickets
- 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
signs of osteomalacia/rickets
- bone weakness
- pain
- bone deformities bow leggged and widening of cartilage at growth plates
inherited cause of rickets/osteomalacia 4
- 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)
mutation for hypophosphataemic rickets
-phosphaturic hormone FGF23/PHEX mutation
for autosomal dominant rickets causes resistance to degrade fgf23
-autosomal recessive is mutation in DMP1 increasing FGF23
causes of hypoparathyroid
- post-surgical removal of thyroid causes damage to parathyroids
- suppressed secretion
- inherited
causes of suppressed secretion of PTH
- low magnesium
2, maternal hypercalcaemia
inherited causes of hypoparat
-developmental parathyroid problems
genetic eg DiGeorge
marker of hypoparathyroid
low calcium
low PTH
phosphate may increase
treatment of hypocalcaemia
- IV calcium
- or oral ca, vit d and mg
- injection calcium
what is osteoporosis
reduced bone mineral density
hypercalcaemia
loss of calcifed matrix
-less bone but histologically normal
what is osteomalacia
reduced bone mineral density
hypocalcaemia
loss of calcified matrix
abnormal histology with wide seams of uncalcifed osteoid
