7. Blood + Immunology Flashcards
How long can blood be stored before expiry
depends soln CPDA1 -35 days
What determines length time
Survival rate tfused RCC after 24 tfusion
Crite min accept surval 70%
Preserve?
Preservative
Storage cond - low temp
- inhib red cell metab
1/30 gylcoysis
inhib bact
ASeptic tech - streilise equp - min bact contam
CPDA1
is this used in Ireland?
Citrate - anticoag - bind Ca
Phos - buffer - phos 4 metab
Dextrose - ocntin glycoysis + energy
Adnin - sub atp synth
Maint 2 3 dpg better
Storage lesion
Loss plt granulo
loss coag fact
decrease 2 3 dpg odc left
haemolysis
FOrmat microagreg
biochem change K, Na Fall Ph
What happens coag factors
V VIII - labile factors decrease quick
Normal haemostasis - VOOO 35% normal
acute phase protein - endog prod increase - decrease risk inadeq post tufsion
Other levels not signif until 21 days after stor
Packed cells - not plasma - diliton all coag factors
when just RCC + Crystalloid
Plt fuc lost stog 4’C
24-36h - most non functional
mass tfisoon - coag diln tycopenia b4 coag def
Why hyperkalaemia not commoner following tfusion
blood bank blood has a high [K] 12mmol/l @ 7d
despite hyperK not comon cause
Restoration RCC metab act = K reuptake by RCC
Na K Atpse
Elevated catehcol - cell uptake K
Dilutional effect distrib Excell space
Slow tfusion min risk
Compatability testing blood
Why need x match blood
b4 tufsion donor test recp blood - avoid tfusion rxn
blood group imcompat
reacting anbtiobdy
Main point = haemolysis prevention
3 diff procedures
1 Blood typing ABO + Rh
2 Abody screen
3 X match
Two comp - x match
Saline test check abo group
Indir Coombs test - det haemolytic IgG abod
What is indir coombs
presence IgG abod dir against rcc membrane antigens - cause haemolysis
Abod not cause aggult - during other test
Det incomplete abod - margin safet
Incubation
washing
Testing coomb reagent
Coombs control test
What is risk reaction ABO rh Compat donor tfused w/out abod / xmatch
How much reduced
Admin aboRh compat safe addit proced add addit maragin
Abo 99.4
Abo Rh 99.8
Abi rh + neg abod screen 99.94
Abdo Rh compat
neg abod
coombs 99.95
Coombs adds so little - removed routine testing
Plasma proteins
Ablumin
globulin
fibrogen
Glob a1 a2 b g glob
Gama - almost completely composed Ig
What normal conc plasma prot
50-80g L
Alb 45
Glo 25
Fib 3 (acute phase_
IG - 10-15
List fxn plasma protein
Oncotic pressure
transport / carrier fxn
Role a-b balance
Protelyti csystem - complement kinin coag fibrinolytic
Immune resp
Enzyme act
Metab
Albumin
highest concentration 35-55g l
Liver -> circ
12-15g day
25 total proti
Only pl prote not glyco
SStruct
Single polpept chain 585 AA
mol wt 69000
IV half life - circ 20d
5% exchange into ISF /hr
- retunr circ via lymph
Some taken tissue cell - metab aa for intracell use
Present blood 50% and rest 50% exvasc
Main fxn
Oncotic pressure
tport /carrier
Taken up tissue brogken to AA
syhtn protein / energy
Co2 tpor - carbimno n term (hb more)
High conc and Low mol wt 65-80% plasma oncotic pressure
capillary fluid dynamic
main IV volume
Lig bind ffa bili calcium hormone cu drugs
Is alb essential life
no
rar e- no albumin other healthy
other protein increase
Which plasma protein major inbolved bind basic drugs
A1 acid glycoprotein
Alb - binds acidic
retinol bind prot - 1/2 at 10-12h
acute starvation
Immune system
What are the major components
Host defence
Recog
Effector activity
1 Natural / inate
not dep prior exposure
primitive part
a barrier function
b Macrophage
c NK cell
d Complement
e other antibact protein
2 Acquire immunity
Lympohcytes
Powerul spec system
delayed onset - esp new antigen
a Humoral
B lympho - prod spec abod v antigen (can recog more than 2 epitope on invading)
prev exposed
each b can diff plasma - prod 1 type abod
Ig G A M E D
class type heavy chain
some stim b cell - memory cell - faster / larger response
b Cell immunity
T lymph - cell med immunity
T - kill ifncet / for cell
prod Lymphkine
amplify response immune cell
memory T prod
Essential role interaction
What type T lymph present
Cytotoxic
Helper
Suppresor
Memory
TCR - recog spec pep antigen bound to MHC in membrane - prlof activated cytotox T + Memory
Memory persist - futue exposure same antigen
- rapidly prolif
Cytotoxic Have CD8 membrane protein
Helper T cell - dont attack / destroy
regulation other aspect
CD4 on membrane
TCR of cells - recog spec pep antigen when bound to MHC II - knwon as Antigen preseting cell (maco / dendritic)
T cell stim - prolif prod mature help T + Memory helper T
T chemical factor - large amt lymphokines IL2,6 y interfon gran monocyte col stim
lymphokine cause cause
Stim phagocytic activity macropahe
Stim prolif cytotocix T lympho
Stim b lymp - prolif + diffnt into plassma cell
pos feedback - further activation helper T
Helper - Amplification - response
Suppresor - neg feedback control act cyototox t and helper
CD4 - recetpr used HIV virus into help celler
What is a killer cell
Activated cytotox T lympho
Nat killer cell - plasma
Cytotox T lmyph - maut cyto t TCR- membrane cell - bind spec shoty pept antigen MHC1 prot membrane infected cell have spec pept how they are ID perforin inserted membrane attack cell cytotox sub injejct swell and die - killer search new target
NK cel
Lymphocytic lineage Nk Not b - not T Lack antigen recgo mol 10% mononeculear cell - lymphoctes in blood NK attack ill invading body cell mailg ciruses coat abod
not req sensitatisation
no mem or amplif with repeat exposure
innate
What is role MHC In immune rxn
MHC1 v MHC 2
Cell membrane protein
bind short pept antigen
present cells immune sys
2 gene MHC - loc chromo 6
1- two prote
b2 microglob three class a b c
indidiv six mhc 1
all cell mhc 1 on surface
pept bound to MHC class 1 molecule cell display membrane - MHC complex recog - spec abd displayed B or by TCR rec on cytoi - lymp prolif
Class 2 Two membrane span prot II - prd cetrain cell body macro dendrit b cell
Antigen presenting cell
Prtein degraed - external source TCR helper T Cell - bind class II pept complex on APC Act helper T cell prolif prod lymphkine stim rest cells
What are cytokine and lymphokines
Cells immune system secrete various polpetide chemical mediatior
Ig
Cytokine - ptent polypetitde act other cell
cell membrane receports
prod diff body cell
each cytokin
fel cell type predom precuros
production response to spec stimuli
Lymhpokine are cytokine prod lymphocytes
What are groups of cytokines
IL Interferon Chemokin heamatopeitc colony stim facto TNF
What are Chemokines
Chemtatct cytokine attarct chem variy immun reaction
each - prod certain cell attract sepc cell
How are cytokine diff hormones
Not prod sepcial gland
most paracrine / autocrinme action
conc - small =bt extremely potent
Haemostasis
Coag system
Intrinsic + Extrinsic path - join final common fath firbrin clot
Intrinsic activate contact cert surfaces Act factor Xii-> Act XI XIa act IC Ca +Factor VII - Ixa convert X->Xa
Extrinsic pathway
Tissue injury expose thromboplastin
Combin + act VII
Complex act X
Final common path
Xa - Prothrombin-> thrombin (Ca, FV, Plt F 3)
Xa extemly important
Insol fibrin end reslt of 3 steps
Prrteolsyis
Pomyersaion 1
Polmresastion 2
Contract clot - decrease defect vessel wall
plt req cotnract
Role platelets in haemostasis
3 mains tage haemo stasis
vascon damage
form plt plu
blood clot
plt - partic all 3 satge
local vasocon - involved activation coag
sertonin + vasoctive txa2 adp rel act plt - vcon at site
plt adhesion
vWF bind - expos mult bind site on vWF mol
plt glycoprot mech plt adhere site inj
Plt activate
med - activate
Plt aggreg
Fibronge gpIIbIIIa complex plt - plt choesion
txa2 stim plt agreggotion vasocn
opposite prstacyclin
Preventing coagulation
1 Thromboresistant endothel Abense damge - prevent collagin gloycclayx repep plt coag pgi2 - inhib plt agreg no - inhib plt - thrombomodulin - act pro c endothel - heparan sulp = act circ at III smooth - prvent activation
2 Blood washes away mediator
Plasma prot - inhib / lim spread coag
ATIII (inc heparin)
Pro C Pro S thrombodulin
Extrenisc path inhb
fribonoyltic syst
vWF role haemostasis
Role plt adhesion to damage subendothkium
Role plt to plt bind
Bind Factor VIIIplasma - prevent degradation
ppl def vWF - prolong bleeding normal plt count
Citrate toxicity
Adverse effx hypoCa - massive tufsion
normal metab rapidly liver - imparid hypothermia decrease flow
myocardial depression
Ca cant get low enough to cause coag probs before it would cause arrest
Iron
what are major forms dietary iron
Bound haem - myoglob /red cells red meats
organic lgiands most ferric form
some food high iron
oxalate spinach prevent abosiprtion
Absorption Iron
Entercyte duodenum + upper jej
Firstly - Iron ferrous and ferric
Ferric convert to ferrous in stomach
promoted H+ andascrob avid
advant conersion
easily release ligand bound - soluble
Ferric precip >3
not avail abs
Ferrous sol up pH 7.5
avail absorption
Addit low gastric ph some sub - AA
bind ferric form sol chelate form - absorb in duo
Ideallly
1 Reduction of Ferric iron to ferrous - remain solbue at phys ph in do
Formation so chelate ferric release apical membrane
BOth facil low gastric pH
Ferriductase
DMT1
Haem abosorption Diet Hb and my - degrad rel haem haem soluble - alkaline duo contn insol<6 Read abs intact - haem receptor
Indepp dmt1
Haem broken down rel ferrous
Transferrin bind Fe3 on 1 site
normal don tferrin 1/3 saturated
How much iron absorbed day
Balance in = out
Typically .6-1mg dat male
2.1 mg female
Femal - menstrul loss
only 5-10% of whats in diet
Can increase during preg -
How much iron is in the body
Tot body store70kg 3500-3700mg
NEarl all bound protein
Functional pool
Hb 65-70% 2500
Myo 5% 130
other prot 0.2% 8
Tport pool
Tferrin .1% 4mg
Storage pool
Ferritin (liver mostly) 25% 1000mg
Why is always present bound
Chem active
potentially toxic sub
Bind non spec - many prot and impair func
Catalyst many ox reaction - lipid prex cell membrane
AVoid - always bound
No phys control mech - excretion
Control solely - regulation absorption
mense loss - other losses cell slouhgly
amt small
proess uncontrol
Mucosal block
COntrol store - small bowel mucosal cell control absorption - prevent excess entering enterocytes overload - mech malfxn - haemochroma cant excrete excess
If iron low plasma level tferrin high
iron sat low
more iron passes ferritin to mucosal cell to tferrin blood
Iron adequate - sat tferrin higher - iron remin entercote
turonver freq - iron loss cell shed
Mucosal block can be overwhelmed
What is absorbed iron used for
How iron enter cell
Haem bound prot
Hb most imp prot
myoglob cycto catalases oxidase
25mg haem used in hb syhtn
recycle store
All cell req Iron cytochromes for ox phosp w mitochond
tferrin tport iron to membrane
tferrin rec - endocyosis
Release returned intact to ISF
Ferritin
storage iron
entercyte and liver prod apoferr which bind iron
apoferr and iron - ferritn
1 ferritin can have 4000 molecules of Fe3
Cell iron increase bind mRNA - increase tranlsation prot
Increased storage
Liver - stored major
many cell spleen b,m contrain
REtendomacrophage stoarge
Demand = tferr sat fall and increase tferrin sythn
Iron release and conv to Fe++
Ferrous form bind tport - cross membrane
Caerolupasmin convert ferric form can bind tferrin in blood
if irons tore high cell accum hemosiderin- insol cell iron
How is Iron carried blood
Fe++ cnc to Fe+++ carry transferrin
b2 glob
How haem sythn
Iron contain tetraoyike 4 ring join methenyl bridges
Sythn series reaction
first step - condens sucily coa and glyine
How much iron reqd preg
Adult femal store 2-2.5g
Iron req increase 1g
20 weeks takes up 6-mg iron day
Late trimester
foetus taking up 4mg da
Sythn foetal hb
necc other essent haem prot
How iron cross plaental
Against conc grad
tferrin rec trophblast
rel umbil cap
com foetal tferring
effecient
Reduced hb
generally deoxy hb
fe in both form
Oxidation - loss é Fe2 fe3
Methaem prod haem iron hb ox to ferric
Blood groups
What are the major blood groups
Various group genet determine antigen present membrane
Divided based presence / absence
Importane - antigenicity
Most antigenic - ABO
Next Rh
Tell me about ABO - what antigens involved
A
B
H
Gene H - tferase enz - gene involveddoes not directly code antigen - enzyme places fucose reside on end membrane
A - tfrease - NAcetlyglacatosamine end fucose reside - alter A Antigen
B - tfrese - galacctose reside end near fucose - does not code direct
Indi only have H - no A / B - in rCC call O
Have circulating Anti A + B abody
present w/out previous exposure
Also found salivar, kidney, liverlung
Rh only RCC
What Ig class Anti A and Anti B -
Nat occuring - ant a + b - IgM
Some people devlop - igG
Rhesus
Two close releated located on chr 1
each person up to 4 Rh gene
D + CcEe - D or Dand C or C&E or E or e
D antigen - means absence of d antigen
Rh status test
Rh antigen
Rh+ or Rh - based on D antigen sat
Have D - Rh +
85% Cascausian
No naturally occuring abod to Rh (req exposure)
Rh + foetus - Rh - mother affect 1 st preg
Moth not have Rh abod (anti D)
Unless prev exposed Rh +
Previous preg Rh + foetus
Use anti D passive immunisation + Avoid RH+ child bearing age
RH sens during deliver - rare
Other that can cause rxn
Kell Duffy Kidd - also cause haemolytic rxn
Complement
Proteolytic system - present in plasma
aPart innate non spec
> 25 pl prot
Classical / alternative
Come together coomon final pathy
Combine C3
Classical - activated antigen-abod complex
alternative - can be active in absense abod
Classical pathway
11 enzymes - circ inact preuros
11 enz C1 to C9
init - antig-abod complex iMg or igG
end formaing lytic complex
insert cell membrane - pores - cell lysis
C3B - opsonin
coats targets - site phagocyte bind
c3a c5a - anaphylatoxin
mast and baso bind- degran w. rel His
Can be comenced by alternate pathyway also
Reaction known complement activation
What does lead to
Cell lysis Rel mediate - his mast (c3a c5a) Local vdiln Neutrophil aggregation chemotaxis attract pahgo leuco - c5a opsonisation c3b
What antigen abod complex- can activate complement via classical pathway
Single Mol IgM - bound antigen bind act c1 + start complement cascade
some IgG can also activate
Nat AntiA + B abod - IgM - potent activators complmen - causes haemolysis
Signif 1 esterase inhibitor defic to anaes practice
Reg several plasma protease systems
Inher Ad
Hered angioedma
Episodic attcak s- airway
may precip minor trauma
Danazol - induce sytn c1 esterase inhib from normal gene - usual effective preventing attacks
Vitamin K what is diff hormone and vit
Vita org sub
Not prod body
must obt exog sub
req small amt
essential to survial
affects spec biochem rxn
not use caloric source
Vs Hormone
secrete ductless gland
combine sepc rec change metab distant cell
Is vitk essential - where absorbed
Diet Vit K - ecc
some terminal ileum - bile salt fat sol -req bile sol micelle poor - obstructive jaund - absence bile salts cylmicron to lymph
MOA vit K
Vit K - post tranlastion modif - clotting
II VII IX X Pro C+S
Some bone proteins osteocalcin
Modif secon carbox - glut reside
two neg charge - chleation w/ Ca
carboxyase - catalyses rxn vit K cofactor - oxidised during reaction requires reduced active cofacor
1 ezyme inhb coumarin type anticoag - warfarin
Vit K + newborn
Haemoorhage dis nebowrn
prev rout vit K - all infants
Defic - not x placenta clot facto low bact prod vit k colonc not occur - bowel sterile diet intake poor
Some maternal drugs exacerb
pehyntoin - conc liver - inhib vi K
Spec conc Vit K injections
Care - avoid unnec large dose
1-2mg ncc - anticoag required post op
not desired
10mg dose given - large diffic reest anticoag post op
Crempophol EL - solub agent - can cause anaphylactoid
not immed
req snth new cloth fctor
FFP required if immed
Erhythropoetin
what is it
Where is it produced
Glycoprotein - principle factor controll RCC prod
arg term AA removed = 165 aa active hormoe
reg prod control RCC mass - blood oxy carry capactiy
Kidney Liver foetus (10% adult)
Hw controled
Hypoxia - intracel - act tcript factors - bind dna mRNA - epo chr 7
Prod by interstitial fibroblasts peritubular capillary -
What are its actions
EPO - rel kidney circulates BStream - act immature erhytoid cell in BM -
Action solely bind and activate spec cell mbrane EPO rec
=> Differentiation and proliferation to mature Red cell
Interaction - membrane rec - activation knases -
activate cytoplasmic tcription factor
move nucles - act new mrna sytn
How commerc - majr clin use
mamm cell culture
ESRF + Anaemia
What happens to EPO levels bab post birth
day 1 - undet
not found up 12weeks after
phys anaemi newborn
Platelets
small 2-4um cell grafm - budding megakaryocte in BM
CIrc stream life span 8-12 dys
old - remoced macrophage in spleen
priamry hameostats - firstpahses - plt adhes to subend = plt plug
release vcon txa2 + serotonin
essential contraction final clot
normal count
Count 150-300
50 min abnormal bleed surg
spont haem @5
assumin fuction
Produ controlled
Thrombopoeitn
-term diff megakary -
act bind spec rec mega
expected feedback control
How plt conc stored
1 temp 20-24
2agigation-contin platform agitator
-assists gas exhange - min diff dist
3 ph balc 6.2-7.8
special plastic - allow gas exchange
Major disadv store room temp
spesis trsnfion - bacteria multy rapidly
lmits storage durn 5 days
What is the plt count incremenet per bag
5000 to 10000 - lower in conumpstion
TXA2
produciton increase in plt act
decrease camp level
prom rel sub - adp - promote adhesion
Death of a red cell
Life span rbc
how muhc hb breakdown / day
120 days
Hb 150 g /l blood vol 5l
tot hb body 750 g
pred daily braeakd 750/120
~~ 6g day .08%
How are old RCC removed
Spleen bone marrow
abrnomral - recog macophage and removed
10% occurs in blood
hb diss ab dimer - bind haptoglob
haemopexi bind haem
prevention excretio - red loss iron
What happens to hb in macrophage
What components can be recyle
Msot Hb broken macrophage of RES
Globin metab - aa reutilised
haem not reutil - degrded rel iron
iorn back to pool
- Macrophage - haem oxygenase
biliverdin
fe++
CO
Biliverdin to bili (bilv red)
3 BIli -> plasma (alb bound)
4 hepatocyte take bili (fac diff)
5 bili udp gluc - bili mono gluc bili dig
6 conj bili secre bile
Direct v indirect bili
conj bili - direct react directly van de burg rx used to assay
unconj lip sol - req tx mentahol b4 van de rxn - indir bili
Obstructive jaundice - predom form bili blood
Prevent excretion conj bili - spill blood causing conjugate or direct hyperbili (jaund)
