L20 Haematology Flashcards
LO2: outl haemopoiesis, expl how cellul compons of blood der from SCs.
-BM to periph RBCs to rem by reticulo endoth sys eg Mac etc, predom spleen, also liver.
BM=RBC, platelet and most WBC prod. Extens through skel in infant. Lim haematopoietic tiss in ad: predom pelvis, sternum, skull, ribs, verteb. CA of BM= probs here.
-histol- take core marrow us from iliac crest. Trephine biop. Stain. Should be 50% fat, megakeryocs prod platelets, cells that prod W+RBC precurs.
BM lattice, trabec and fat spaces. BM cells btw trabec, early cells from bone edges, move to marrow as mat. Calls att to stroma of BM for nutr and GH. Dis=stroma fibrotic=cells not grow here they go to spleen/liv= organomegaly. Eg myelofibrosis. Cells prod in spleen instead.
-haemopoiesis- der from progenitor SC. daught diff. Dev driven by cytok horms:
Erythropoietin- RBC dev, tx in anaem. Thrombopoietin- platelet dev. G-CSF (tx in chemo), GMCSF, IL-6 etc all for WBC dev.
Horms somet prod in interstit cells of BM. (See diag).
GMCSF and IL3 form comm myel progenitor. Lymphoc TNF, TGF, IL2/7/12.
Lymphoc leave BM, some pass through thymus=T. Others B. Furth div and diff in LN and L aggregs.
-in fetus BC 1st prod by mesod of YS, then liv, then spleen, then BM. Early BC held in BM by adhesion molecs (Coll and fibronectin). As BC mat adhesions molec Rs down reg= red mat cells to circ. Cytok GFs regul div and diff.
-perpih counts- Hb 130-160g/l. RBC 4.4-5.5x10^12/l. WBC 7-11x10^9/l. Platelet 150-400x10^9/l.
LO3: desc struc and func of: eryhtrodermic and reticulo can, lymphoc, monoc, granulocs or PM leucocytes (neut, basophil, eosinophil). Platelets.
LO4: recog those cells in photo of blood smear and disc their poten locat and histol feats rel to func.
-blood corpuscles make RBC erythrocytes or WBC leucocytes which form PMN granulocs or agranuloc. Also platelets.
LO5: how and where platelets prod and their lifesp and func.
-big megakeryocs only in BM prod platelets. Cells incr size and replic DNA. Platelets bud off cytop, no nuc, are cell frags. Prod contr by thrombopoietin (TPO). 2-3um. Most stored in spleen.
-func- adhesion to CT, aggreg, Plip mem to facil clott. Platelet plug in dam BV immed. Trop other cells. Send sigs and have Rs to bind other platelets after bind Coll on brok endoth. Also start clott casc= lot pre prots in blood activ=fibrin clot arnd plug.
-struc-
Mem- Plip surf BS for CF and platelet adhesion via GP Rs. Bind tiss and platelets.
Cytop conts: alpha grans- GP’s rel when activ facil clot format, cont fibrinogen, vWF etc. Also dense bods- serotonin, ADP, catecholamines and Ca for platelet aggreg.
-adhesion- dam vess wall expos underly tiss. Platelets adhere via vWB fac Rs and form platelet plug.
-aggreg- rel ADP from alpha and dense granules.
GP IIb/IIIa Rs exposed- bind other platelets and tiss faces. Prim and sec aggreg.
-platelet cent purp in blood smear. 5HT=constric BV, lot Plip FIII activs prothrombin to thrombin =sol fibrinogen to insol fibrin.
-platelets and CFs- prim plug not strng enough. Inv in activ clott casc. Interac with CFs eg VII, IX, X. Fibrin mesh traps platelets and RBCs. Tiny vess dam all time.
LO1: RBC lifespan and struc rel to func. And catab and destr.
-2.5bn RBC/kg/d. 2.5bn platelets/kg/d. 1bn granulocs/kg/d.
RBC surv 120d. Incr destr if eg mem abn, autoimm, can=anaem. Platelet 10d. Neur 2-4d. Lymphoc 1d (active eg infec) to years (mem).
-maint Hb in reduced ferrous state so can bind O. Maint osmot eq. Gen ATP. As mat lose nuc, can’t make more prot so restric life, need make energ to maint mem.
-struc- biconc flexib disc 8um. High SA:vol. flex through capills. Mem imp eg hered spherocytosis. Min diam 3.5um.
Mem- gp’s and glycophorins etc. Mut in genes encod can decr flex. Congenital/acq alt mem compons change shape RBC eg spheroc, spicules.
2 configs- oxyHb relaxed bind struc eg high O, CO. Deoxy tight eg high H+, 23BPG, low O.
-func- carry O and CO2 reversible. Tightn deps on types chains.
Globin chains- protec haem molec from oxid, confer sol, permit var in O affin (shape change).
S chains instead beta= sickle, lower affin.
-1% circ RBCs are reticulocs- just left BM.
-Hb synth- globin gene crusts on chrom 11 and 16-exp diff stages. Chains synth indep and comb to=diff Hb. Switch feral to ad at 3-6mth. (Graph).
-RBC metab- 2 main paths-
Embden Meyerhof- gluc to lactate. ATP gen.
Hexose monoP path- G6P metab. Gen NADPH.
-contr erythropoiesis- decr pO2 blood detec in interstit peri tubular cells kidn= prod EPO horm= stim mat and rel RC from BM= incr Hb=incr pO2= neg feedb on EPO prod. (Diag).
-Hb catab- RBC breakd in liv and spleen. Iron recyc and protoporphyrin of haem metab to bili. RBC to Hb to haem to bili.
Globin chains brok to AA in retic endoth sys, haem remains. Brok in liv conv to bili. If excess bili eg Ab breakd haem in circ = urobilinogen. But most haem brok in liv cells, excret through bile duct to int, out as stercobilin an some uro.
WBCs- leucocytes. Leishmania stain blood smear.
- PMN granulocs- round 10-12um. Nuc 2-5 lobes. Classif acc to staining.
- agranulocs- mononuc.
Neutroph-
-granuloc from myel progenitor. Multilob nuc. Pale cytop, faint grans. AV surv 10hr. Form pus. Most numerous granuloc.
-mat- myeloblast to promyelocyte to myelocyte to metamyelocyte to band to neut. block 1st step= build up myeloblast=leuk.
Contr by G-CSF or GM CSF (given in chemo). Mainly horm contr. G-CSF=prod incr neut. decr time to rel of mat cells from BM. Incr chemotxis. Incr phagoc and kill.
-func- eng org, enzs in grans kill. Specif grans- lactoferrin, hCAP18, lysoz. Azurophil grans- alpha defensin, lysoz. Cytok sig to exit blood, chemotxis to infec, eng and kill.
Eosinophil
-bi lobed nuc. Us few in periph blood. 3-8hr in circ. Live 8-12d. Mig to epith surfs where Ag stim eg drug reac, asthma, eczema. Big red grans cont arginine Plip, enzs. Phagoc of Ag-Ab complexes. Gran enz destr. Grans more dense, large, and orange than neut. med hypersensit reads eg skin inflamm.
Can rel cytotox enzs to dam larger parties, numbers incr in assoc with allerg reacts and atopy. Hay fever.
Lot grans. V mob cells, weakly phagoc.
Basophil
-rare. 0.2-1% circ leucocytes. Often bi lobed nuc. Half life 2.5d. Dense grans cont his tine, heparin, hyaluronic ac, serotonin. Grans often cov nuc. Active in allerg. Incr in myeloprolif disords.
Many large dark purp grans and med acute inflamm reacts. After loc tiss dam, rel Basoph to tiss at site. Histamine= vasodilat and leak fluid to tiss=odema. Heparin prev clott.
Monocyte
-mig to tis=Mac. Resp to inflamm and Ag stim. Diapers is into tiss. Lysoz cont lysoz, complem, ILs, arachidonic ac, CSF.
Phago and pinocytosis. Large with folded nuc, grey/blue cytop and occas vacuoles. Out circ after20-40d and mig to Mac in organs eg Kupffer, glial. Can chemotax tow infec, inflamm, neoplasm. Can phagoc and interac T.
-2x size neut. nuc may app lobed but just indented. LOT cytop, can’t see lysos in cytop us. Motile and phagoc. Readily pass walls tiny capills. May return to circ when imm resp.
Lymphoc
-smaller than other WBCs, sim to RBC. Orig in BM.
B cell humoral imm-Ab form.
T cellul imm. CD4 Th and CD8 CTL suppressor.
NK cell me cytotox.
-func- surf Rs for non self Ag and self Ag (histocompatability Ag). B have surf Ig, complem compon. T carry Rs for Ig. NK carry Rs for Fc.
-B exp Ag specif Ig. A rearr Ig genes due dev. Diff light chains. See Ag, prod daught to prod specif Ig. May re circ. Interac with T, transf to plasmablast or mem cells in LN. Plasmablast mig to marrow and form plasma cells=Ig prod. Mem activ fast on 2nd expos.
B prod in BM to circ mat B with diff AGRs in PM. See Ag=mem or interac with T=cytok resp.
-T- mig to thymus early in dev and undergo TCR gene rearr. Allow I’d all Ag, lot mut. Bind best then more mut by rearr and prod specif daught=mem and plasma. Diff to CD4+Th and CD8+ CTL on activ. CD4 induce prolif and diff of T and B, activ Mac. CD8 cytotox, incl apop. (Diag).
-NK- recog self. Kill non self. Kill by lysis, same mech as T.
-Lymphoc are small cells rnd nuc. Norm pale cytop. Over 5% are T. Only cells which can recog HLA hum lleucocyte Ag but not reac Ag them. CD4 recog Ag att to HLAII. They stim CTL recog and kill vir infec host cell. CD4 also transf B to plasma. B stim by Ag to immunoblast then plasma cells.
-with neut lymphoc are most comm WBC in blood. V high nucleo cytop ratio. In EM see small cytop projecs. In larger lymphocs cytop more. Nuc chromatin stains dark, clumped. Need mAbs to ID diff lymphoc subsets.
Small ymphocs are actively mob cells, can pass btw endoth cells to tiss. Accum in tiss eg in chronic inflamm states and arnd skin grafts. Ret to blood via lymphat sys. Fundamental in adap resp.
Reticulo-endothelial sys (RES). Destr cells at end life eg run out prot.
-part of imm sys cont phagoc cells- monoc, Mac, Kupffer, tiss histiocytes, microglia.
Eng dying cells, destr and recyc aa’s, haem etc.
Cells of RES Id and mount approp imm resp for Ag. Main organs are spleen, liv, LN (kill dying lymphoc). All blood passes through spleen and liv. EC fluid travels via lymphatics to LN. Recyc nutr and AA. Fe from have retained in Mac to BM to RBC.
-integ appr to diag- diffic to diff imm cells microsc. Look at mem prot eg Ig. Genet- cytogenetic or molec appr see if mut, eg in pt with haematolog malig.
Plasma-liq phase.
-structure less, homog under LM. 55% of 6L blood. Tot blood= 7% bod weight.
Plasma cont lot prot (alb, globulins, fibrinogen) and traces min ions. Al diss in water (90% plasma). Plasma alos cont tiny fat globules and small partics of brok down BCs.
LO6: contrast poten of WBCs to Mobil, div and transf with that of cells der from other organs.
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