Chapter 18 Anemia Hematology PPT

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CHAPTER 18

ANEMIAS:

Red Blood Cell Morphology

and Approach to Diagnosis TESHAUNA ESCOBAR



Background

Red blood cells (RBCs) peror! the "ital physiologic unction o oxygen delivey !o !"e !iss#es#

The ter! anemia is deri"ed ro! the $reek %ord anaimia

, !eaning&%ithout 'lood#(

A decrease in the nu!'er o RBCs) or the a!ount o he!oglo'in in theRBCs) results in*

decreased o+ygen deli"ery and,

su'se-uent tissue hypo+ia#

.t is a co!!only encountered condition a/ecting an esti!ated 0#12 'illionpeople %orld%ide#



$E%INITI&N &% ANEMIA

%#nc!ion'l deni!ion:

a decrease in the o+ygen carrying capacity o the 'lood#

can arise i there is ins#cien! "e*oglobin or the "e*oglobin isnon+#nc!ion'l#

&,e'!ion'l deni!ion:

a reduction) ro! the 'aseline "alue) in the total nu!'er o RBCs) a!ount o

circulating he!oglo'in) and RBC !ass or a particular patient#

Conven!ion'l deni!ion:

a decrease in RBCs) he!oglo'in) and he!atocrit 'elo% the reerence range orhealthy indi"iduals o the sa!e age) se+) and race) under si!ilar en"iron!entalconditions#



C-INICA- %IN$IN.S

The classic sy!pto!s* atigue and shortness o 'reath#

iron de3ciency %hich can lead to an interesting sy!pto! called pica

Certain eatures to 'e e"aluated closely during the physicale+a!ination to pro"ide clues to he!atologic disorders*

skin 4or pallor) 5aundice) petechiae6) eyes 4or he!orrhage6) and !outh 4or !ucosal'leeding6#

sternal tenderness) ly!phadenopathy) cardiac !ur!urs) spleno!egaly) and

hepato!egaly#

7aundice 'ecause it !ay 'e due to increased RBC destruction) %hich suggests a

he!olytic co!ponent to the ane!ia#

"ital signs

rapid all in he!oglo'in concentration, tachycardia 4ast heart rate6



PH/SI&-&.IC A$APTATI&NS

Reduced deli"ery o o+ygen to tissues caused 'y reduced he!oglo'in causes an increase erythropoietin secretion 'y the kidneys#

Erythropoietin sti!ulates the RBC precursors in the 'one !arro%) %hich leads to the relea!ore RBCs into the circulation#

8ith persistent ane!ia) !"e body i*,le*en!s ,"ysiologic 'd',!'!ions !o ince'se !oxygen0c'ying c','ci!y o+ ' ed#ced '*o#n! o+ "e*oglobin#

Heart rate) respiratory rate) and cardiac output are increased#

The tissue hypo+ia triggers an increase in RBC 'isphosphoglycerate that results in increasdeli"ery o o+ygen to tissues#



MECHANISMS &% ANEMIA

The lie span o the RBC in the circulation is a'out 12 d'ys3

.n a healthy indi"idual %ith no ane!ia) each day appro+i!ately 09 o the RBCs are re!o"ed ro! circulation due tosenescence) 'ut the 'one !arro% continuously produces RBC to replace those lost#

He*'!o,oie!ic s!e* cells de"elop into erythroid precursor cells) and the 'one !arro%appropriately releases reticulocytes that !ature into RBCs in the peripheral circulation#

Ade4#'!e RBC ,od#c!ion e4#ies se"eral nutritional actors*

such as iron) "ita!in B02) and olate#

$lo'in synthesis also !ust unction nor!ally#

.n conditions %ith excessive bleeding o "e*olysis*

the 'one !arro% !ust increase RBC production to co!pensate or the increased RBC loss#

The !aintenance o a sta'le he!oglo'in concentration re-uires the production o unctionally nor!al#

RBCs in su:cient nu!'ers to replace the a!ount lost#



Ine5ec!ive 'nd Ins#cien!Ey!"o,oies

Ey!"o,oiesis ; the ter! used or !arro% erythroid prolierati"e acti"ity#

Nor!al erythropoiesis occurs in the 'one !arro%#

E5ec!ive ey!"o,oiesis 0 the 'one !arro% is a'le to produce unctional RBCs thatlea"e the !arro% and supply the peripheral circulation %ith ade-uate nu!'ers o cells#

Ine5ec!ive ey!"o,oiesis 0 production o erythroid progenitor cells that are deecti"e

Deecti"e progenitors <

oten destroyed in the 'one !arro% 'eore !aturation and released into the peripheralcirculation#

Characteristics o ine5ec!ive ey!"o,oiesis*

Meg'lobl's!ic 'ne*i'

T"'l'sse*i'

Sideobl's!ic 'ne*i'



Ine5ec!ive 'nd Ins#cien!Ey!"o,oies

Ins#cien! ey!"o,oiesis

a dece'se in the nu!'er o erythroid precursors in the 'one !arro%#

Se"eral actors can lead to*

dece'sed RBC ,od#c!ion) including a de3ciency o iron 4inade-uateintake) !ala'sorption)

e+cessi"e loss ro! chronic 'leeding6,

deciency o+ ey!"o,oie!in) the hor!one thatsti!ulates erythroid precursor prolieration and

!aturation 4renal disease6,

loss o+ !"e ey!"oid ,ec#sos due to an autoi!!une reaction 4aplastic ane!ia)

ac-uired pure red cellaplasia6 or inection 4par"o"irus B0=6,

s#,,ession o+ !"e ey!"oid ,ec#sos due to in3ltration o the 'one !arro% %ith

granulo!as 4sarcoidosis6 or !alignant cells 4acute leuke!ia6#%) resulting in decreased RBCproduction and ane!ia#



Ac#!e Blood -oss 'nd He*olysis

Ane*i' can also de"elop 's ' es#l! o+ 'c#!e blood loss 4such astrau!atic in5ury6 or ,e*'!#e "e*olysis resulting in a shortenedRBC lie span#

8ith acute 'lood loss and e+cessi"e he!olysis) the 'one !arro% is a'le to increase

production o RBCs) 'ut the le"el o response is inade-uate to co!pensate or the

e+cessi"e RBC loss#

N#*eo#s c'#ses o+ "e*olysis:

in!insic de+ec!s in the RBC *e*b'ne) en6y*e sys!e*s) or"e*oglobin

ex!insic c'#ses such as 'n!ibody0*edi'!ed ,ocesses) *ec"'nic'l+'g*en!'!ion) or in+ec!ion0el'!ed des!#c!ion i the le"el o responseis inade-uate to co!pensate or the e+cessi"e RBC loss#



-AB&RAT&R/ $IA.N&SIS &%ANEMIA

Co!plete Blood Cell Count %ith Red Blood Cell .ndices*

To detect the presence o ane!ia)

the !edical la'oratory proessional peror!s a co!plete 'lood count using an auto!ated he!atology analy>er !ode!e*ine !"e RBC co#n!7 "e*oglobin concen!'!ion7 "e*'!oci!7 RBC indices7 "i!eblood cell (9BC) co'nd ,l'!ele! co#n!#

The RBC indices include the !ean cell "olu!e 4MC?6) !ean cell he!oglo'in 4MCH6) and !ean cell he!oglo'in concentration

MC (Me'n Cell ol#*e)

Most i!portant o these indices

a !easure o the a"erage RBC "olu!e in e!toliters 4@6#

Auto!ated he!atology analy>ers also pro"ide an RBC histogra! and the red 'lood cell distri'ution %idth 4RD86#

Rel'!ive 'nd 'bsol#!e e!ic#locy!e co#n! s"o#ld be:

peror!ed or e"ery patient %hen ane!ia is ound#

A#!o*'!ed 'n'ly6es peror! reticulocyte counts %ith greater accuracy and precision than !anual counting !et

RBC "is!og'*

RBC vol#*e +e4#ency dis!ib#!ion c#ve %ith the relati"e nu!'er o cells plotted on the ordinate and RBC "ole!toliters on the a'scissa#



-AB&RAT&R/ $IA.N&SIS &%ANEMIA

Co*,le!e Blood Cell Co#n! i!" Red Blood Cell Indices*

Abno*'li!ies include*

s"i+! in !"e c#ve to the le+! (*icocy!osis) or to the ig"! (*'cocy!osis)

idening o+ !"e c#ve caused 'y a greater "ariation o RBC "olu!e a'out the !ean or 'y the preo t%o populations o RBCs %ith di5een! vol#*es ('nisocy!osis)

The histogra! co!ple!ents the peripheral 'lood 3l! e+a!ination in identiying "ariant RBC popul

The RD8 is the coe:cient o "ariation o RBC "olu!e e+pressed as a percentage

Indic'!es v'i'!ion in RBC vol#*e %ithin the population !easured and correlates %ith anisocyt

the peripheral 'lood 3l!#

A#!o*'!ed 'n'ly6es calculate the RD8 'y di"iding the standard de"iation o the RBC "olu!e 'yMC? and then !ultiplying 'y 0 to con"ert to a percentage#



Re!ic#locy!e Co#n!

The e!ic#locy!e co#n! is an i!portant tool to 'ssess !"e bone *'o;s'bili!y !o ince'se RBC ,od#c!ion in es,onse !o 'n 'ne*i'3

Reticulocytes ; young RBCs that lack a nucleus 'ut still contain residual ri'onucleic4RNA6#

Circulate peripherally or only 0 day %hile co!pleting their de"elop!ent#

The adult reerence range is #9 to 0#9 e+pressed as a percentage o the total no RBCs#

The ne%'orn reerence range is 0#9 to #9) 'ut these "alues change to appro+i!those o an adult %ithin a e% %eeks ater 'irth#

An 'bsol#!e e!ic#locy!e co#n! ; deter!ined 'y *#l!i,lying !"e ,ecene!ic#locy!es by !"e RBC co#n!3



Re!ic#locy!e Co#n!



Pei,"e'l Blood %il*Ex'*in'!ion

An i*,o!'n! co*,onen! in !"e ev'l#'!ion o+ 'n 'ne*i' ; ex'*in'!ion o+ !"e ,ei,"blood l*7 i!" ,'!ic#l' '!!en!ion !o RBC di'*e!e7 s"',e7 colo7 'nd inc

The peripheral 'lood 3l! also ser"es as a -uality control to "eriy the results produced 'y auto!ated ana

No*'l RBCs on ' 9ig"!0s!'ined blood l* are nearly unior!) ranging ro! 1 to ! in dia!eter#

S!all or !icrocytic cells are less than 1 ! in dia!eter) and large or !acrocytic RBCs are greater than dia!eter#

E+a!ples*

sic<le cells

S,"eocy!es

Sc"is!ocy!es

ov'l *'cocy!es

RBC inclusions*

E+* *'l'i'l ,''si!es7 b'so,"ilic s!i,,ling7 'nd Hoell0=olly bodies

detected only 'y studying the RBCs on a peripheral 'lood 3l!



Bone M'o Ex'*in'!ion

The cause o !any ane!ias can 'e deter!ined ro! the history) physical e+a!ination) andresults o la'oratory tests on peripheral 'lood#

'one !arro% aspiration and 'iopsy !ay "el, in es!'blis"ing !"e c'#se o+ 'ne*i'

'one !arro% e+a!inations is indic'!ed +o ' ,'!ien! i!" 'n #nex,l'ined 'ne*i' associated%ith or %ithout other cytopenias) e"er o unkno%n origin) or suspected he!atologic !alignancy#

'one !arro% e+a!inations ev'l#'!e "e*'!o,oiesis

de!e*ine i+ !"ee is 'bno*'l inl!'!ion o+ !"e *'o#

.!portant 3ndings in the !arro% that point to the underlying cause o the ane!ia includea'nor!al cellularity o the !arro%

E+a!ple* hypocellularity in aplastic ane!ia

E"idence o ine/ecti"e erythropoiesis and !egalo'lastic chages

E+* "ita!in B02 de3ciency or (*yelodys,l's!ic syndo*e6 lack o iron on iron stains o the 'one!arro% 4!"e gold s!'nd'd +o di'gnosis o+ ion deciency6

resence o granulo!a) 3'rosis) inectious agents) and tu!or cells that !ay 'e inhi'iting nor!al

erythropoiesis#







&!"e -'bo'!oy Tes!s

Ro#!ine #in'lysis

4to detect he!oglo'inuriaor an increase in uro'ilinogen6

To detect he!aturia or he!osiderin an

An'lysis o+ s!ool

To detect occult 'lood or intestinal parasites6# Also) certin

&!"e C"e*is!y s!#dies #se+#l:

Renal and hepatic unction tests

Ater the co!pletion o he!atologic la'oratory studies the ane!ia !ay 'e classi3ed 'ased on reticulocyte countMC?) and peripheral 'lood 3l! 3ndings#

Ion s!#dies (incl#ding se#* ion7 !o!'l ion0binding c','ci!y7 !'ns+ein s'!#'!ion7se#* +ei!in) are "alua'le i an inappropriately lo% reticulocyte count and a !icrocytic ane!ia are present

Se#* vi!'*in B1 'nd se#* +ol'!e 'ss'ys are helpul in in"estigating a !acrocytic ane!ia %ith a lo%reticulocyte count

$iec! 'n!iglob#lin !es! can di/erentiate autoi!!une he!olytic ane!ias ro! he!olytic ane!ias %ith othercauses#

Because o the nu!erous potential etiologies o ane!ia) the cause needs to 'e deter!ined 'eore initiation o th



APPR&ACH T& EA->ATIN.ANEMIAS

The approach to the patient %ith ane!ia 'egins %ith taking a co!pletehistory and peror!ing a physical e+a!ination#

Ne0onse! +'!ig#e 'nd s"o!ness o+ be'!" suggest an acute drop inthe he!oglo'in concentration) %hereas a lack o sy!pto!s suggests a long

standing or congenital condition#

RBC count and co!parison o these "alues %ith the reerence range or healthyindi"iduals o the sa!e age) se+) race) and en"iron!ent#





Re!ic#locy!e Co#n! 'nd Ane*i'Cl'ssic'!ion

The 'bsol#!e e!ic#locy!e co#n! is useul in initially classiyingane!ias into the categories o decreased RBC production 4decreasedreticulocyte count6 and shortened RBC sur"i"al 4increased reticulocytecount6#

8hen the reticulocyte count is decreased) the MC? can urther classiy

the ane!ia into three su'groups* (1) no*ocy!ic 'ne*i's

() *icocy!ic 'ne*i's

(?) *'cocy!ic 'ne*i's



Re!ic#locy!e Co#n! 'nd Ane*i'Cl'ssic'!ion



Me'n Cell ol#*e 'nd Ane*i'Cl'ssic'!ion

Micocy!ic 'ne*i' is characteri>ed 'y an MC? o less than @ %ith s!all RBCs 4less tha! in dia!eter6

Hy,oc"o*i') characteri>ed 'y an MCHC o less than F2 gGd@ and increased central pallor the RBCs) !ay acco!pany the !icrocytosis#

Micocy!ic 'ne*i's are caused 'y conditions that result in reduced he!oglo'in synthesis

iron de3ciency) ina'ility to utili>e iron 4chronic ina!!atory states6) glo'in synthesis deect

4thalasse!ia6) and he!e synthesis deect 4sidero'lastic ane!ia) lead poisoning6

The *os! co**on *icocy!ic 'ne*i' es#l!s +o* 'n ion level !"'! is ins#cien! +*'in!'ining no*'l ey!"o,oiesis

it is characteri>ed 'y a'nor!al results on iron studies#

M'cocy!ic 'ne*i' is characteri>ed 'y an MC? greater than 0 @ %ith large RBCs 4greatthan ! in dia!eter6#

Macrocytic ane!ias !ay 'e *eg'lobl's!ic o non*eg'lobl's!ic#

Meg'lobl's!ic 'ne*i's are caused 'y conditions that i!pair synthesis o deo+yri'onucleacid 4DNA6) such as "ita!in B02 and olate de3ciency or !yelodysplasia#



Me'n Cell ol#*e 'nd Ane*i'Cl'ssic'!ion

N#cle' M'!#'!ion lags 'ehind cytoplas!ic de"elop!ent as a result o i!paired DNA synthesis

Penicio#s 'ne*i' is one cause o "ita!in B02 de3ciency) %hereas !ala'sorption secondary toina!!atory 'o%el disease is one cause o olate de3ciency

A *eg'lobl's!ic 'ne*i' characteri>ed 'y*

o"al !acrocytes and hyperseg!ented neutrophils in the peripheral 'lood and 'y !egalo'lasts or largenucleated RBC precursors in the 'one !arro%#

The MC? in !egalo'lastic ane!ia can 'e !arkedly increased 4up to 0 @6) 'ut !odest increases 40 to 0

@6 occur as %ell#

Non0*eg'lobl's!ic +o*s o+ 'ne*i' are also characteri>ed 'y large RBCs) 'ut in contrast to!egalo'lastic ane!ias)

Typically related to !e!'rane changes o%ing to disruption o the cholesterol;to;phospholipid ratio#

These !acrocytic cells are !ostly round) and the !arro% nucleated RBCs do not display theegalo'lastic !aturation changes#

M'cocy!ic 'ne*i's are oten seen in patients %ith chronic li"er disease and 'one !arro% ailuris rare or the MC? to 'e greater than 00 @ in these non!egalo'lastic ane!ias#

No*ocy!ic 'ne*i' is characteri>ed 'y an MC? in the range o to 0 @#



Red Blood Cell $is!ib#!ion9id!"

To deter!ine the cause o an ane!ia %hen used in con5unction %iththe MC?#

Each o the three MC? categories !entioned pre"iously (no*ocy!ic7*icocy!ic7 *'cocy!ic) can also 'e su'classi3ed 'y the RD8 as

"o*ogeneo#s (no*'l R$9)

"e!eogeneo#s (ince'sed o "ig" R$9)












He*oly!ic Ane*i's

Ele"ated reticulocyte count caused 'y shortened sur"i"al o RBCs) an

inves!ig'!ion +o ' "e*oly!ic 'ne*i' is re-uired#

Nu!erous in!insic 'nd ex!insic c'#ses o+ "e*olysis e+ist#

A direct ant glo'ulin test helps di/erentiate i!!une;!ediated destruction ro! thother causes#

.n the other he!olytic ane!ias) re"ie%ing the peripheral 'lood 3l! is "ital ordeter!ining the cause o the he!olysis#

P'!"o,"ysiologic Cl'ssic'!ion

$rouped 'y the !echanis! causing the ane!ia

The ane!ias caused 'y decreased RBC production 4e#g#) disorders o DNA synthesdistinguished ro! the ane!ias caused 'y increased RBC destruction or loss 4intriand e+trinsic a'nor!alities o RBCs#



EN$

Chapter 18 Anemia Hematology PPT

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