ca haemostasis Flashcards
what are the roles of ca
skeleton and muscle function
metabolic - action potentials, intracellular signalling
molecular levels in
* osteoporosis
* osteomalacia/rickets
* paget’s
* parathyroid bone disease
* renal bone disease
forms of ca in serum
Free (ionised) = 50% = biologically active
Protein bound = 40% = bound to albumin
Complexed = 10% = citrate/phosphate
1% of all ca is in plasma
what is normal total ca and what is corrected ca
2.2-2.6 mmol/L = normal ca
corrected = serum ca + 0.02 x (40-serum albumin in g/L)
why do we use corrected ca
if albumin was normal what would the ca be - would hope is the same as total ca. if low albumin = less bound ca = higher proportion as free
Corrected ca = serum ca + 0.02*(40-serum albumin)
Normal albumin is 40 - so if had normal albumin corrected ca = total ca
Low albumin = low bound ca and normal free ca
Therefore corrected ca tells you if problem is with the calcium or the albumin
note - can measure ionised ca too
summarise response to low Ca
detected by parathyroid gland
Releases PTH
Gets Ca from bone, gut absorption and resorption from kidney and renal 1 a hydroxylase (regulatory step - only works when PTH turns it on)
1 a OH - activates Vit D - increased intestinal ca absorption
Result in rise in plasma ca
what type of hormone is vit D
steroid
summarise PTH
- 84aa protein
- Only released from parathyroids
- Bone and renal ca resorpyion
- Stimulates 1 a OH vit D sythn to make 1,25 (OH)2 vit D synthesis
- Also stimulates renal phosphate wasting
- Maintain normal Ca-phos product
- If Ca too high - crystalises so don’t want this to happen = stones
summarise vit D synthesis
Sun - then make some vit D
In liver - first pass metabolism -> 25-OH-Vit D (what measure when do assay - but inactive, stored vit D)
PTH turn on kidney - add OH to vit D (enzyme is 1a hydroxylase) = active vit D
types of vit D
Vit D3 is synth is skin - cholecalciferon
Vit D2 plant vitamin - ergocalciferol
Both are active - both do the same thing
why is vit D activated in sarcoid
lung condition with granulomata in lung - ectopic 1 a OH and not regulated - might become hyperca
what is calcitriol
Calcitriol same thing as 1,25 OH vit D
Active form - give when have no kidneys
roles of 1,25 OH Vit D
Increases intestinal ca absorption and intestinal phos absorption
Critical for bone formation
Vit D receptor controls many genes for cell proliferation, immune system
Vit D deficiency associated with ca, autoimmune disease, metabolic syndrome
Vit D levels are linked to poverty - which is what causes the conditions
Vit D will prevent fractures in much later life - prevent osteomalacia
role of PTH
stim osteoclasts - rise in ca and phos from bone
Phos lost from bone
use of bone alkaline phosphtase
can see if normal PTH activity because bone releases alk phos
Can see if have normal bone degrading too fast - see if have osteoporisis - see if increased bone transfer
role of skeleton
Structural framework
Strong
Lightwht
Mobile
Protects vital organs
Capable of orderly growth and remodelling
Metabolic role in ca homeostasis
Main resevoir of ca and phos
what are the metabolic bone diseases
osteoporosis - bone is normal but weak - less bone per unit volume
osteomalacia - bones decalcified, more protein and less ca than normal
paget’s - thought to have been caused by virus but never found
parathyroid bone disease - tumour of the parathyroid
renal osteodystrophy - no 1a hydroxylase
summarise vitamin D deficiency
Defective bone mineralisation
In childhood = rickets, in adulthood = osteomalacia
Rickets - end of bone gets wider
Osteomalacia - fracture when young
RF: lack of sun, dark skin, dietary, malabsorption
clinical features of osteomalacia
Looser zones - pseudofractures - part way through bone, don’t break until trauma. Increased fracture risk
Sx - bone and muscle pain
Low Ca and phos and raised ALP - both not absorbed from the gut
clinical features of rickets
bowed legs, costochondral swelling, widened epiphyses at the wrists, myopathy - waddling gate and nerve->muscle function doenst work
Risk - after childbirth and in lactation because baby take ca
causes of osteomalacia
renal fauilure=don’t activate Vit D,
anticonvulsants induce breakdown of vit D (phenytoin),
lack of sunlight,
chappatis (contain phytic acid = chelate vit D)
Anticonvulsant rickets - counteract by giving vit D when give anticonvulsants. anticonvulsant - induce enzyme that makes inactive vit D
biochemistry for osteomalacia
low ca
low phos
high ALP
summarise osteoporosis
Losing bone mass
Cause of pathological fracture
Occuring more often as people live longer
Lack of use of bone: immobilisation, caused by progressive slow loss - excess steroid and thyroxine and lack of oestrogen all contribute
Post-menopausal
Biochem - completely normal - ca, phos and PTH are all completely normal
Reduced bone mineraldensity, asymptomatic until fracture (1st sx!)
Typical fracture - neck of femur fracture, vertebral, wrist (colles)
dx of osteoporosis
Bone density scan - DEXA - hip, spine, wrist
Compare with normal healthy young person of same gender - T score
We know as everyone gets older they will get fracture
Z score is age matched - show much worse than everyone else. Useful to show accelarated bone mass in younger population
T <-2.5 SD from mean - then by definition have osteoporosis
T -1 - -2.5 = osteopenia
