disease chart i3-1 (emmeline).docx
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7/21/2019 Disease Chart I3-1 (Emmeline).docx
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DISEASES – I3 Block, Test 1
ANEMIAS/RBC/Hb DISORDERS Also see attached for Lab Test criteria for anemia disorders
Condition Name Associated Issue/Pathogenesis Patient Sm!toms/T"eatment
#egalo$lastic anemia %egulation o& 'emato!oiesis $ (olate
Aragon-Ching
Defciency in olate causes erythroblasts to synthesize Hb but cannot replicate DNA
eciently → division incomplete and macrocytic cells are released into blood.
Homocysteine levels elevated.
Smear has macroc!tic cells "filled #ith Hb$ and ne%tro&hils #ith '( lobes)ati*%e+ &aleness "&allor$+ li*htheadedness+ and &anc!to&enia
Treat ,ia hi*h dose of folic acid or N-.meth!l TH) "if &ost. chemo$
Pernicious megaloblastic anemia Regulation of Hematopoiesis by B12
Aragon-Ching
Defciency in vitamin B1 !usually due to absorption"# resultin$ in inactive
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methionine synthase to convert olate into its active orm. Homocysteine levels
elevated. %n addition# methionine is not recycled and no &A' can be produced →
lac( o methylation on myelin sheaths → myelin de$eneration.
Meth!lmalon!l.CoA m%tase also inacti,e Meth!lmalonic acid le,els ele,ated
Anemia s!m&toms co%&led #ith ne%rolo*ical &roblems and meth!lmalonic acid%riaTreat ,ia IM inection of h!dro0!cobalamin/B12
Hereditary hemochromatosis Regulation of Hematopoeisis by Iron
)*+ mutation in H,- $ene → Decreased hepcidin epression in liver despite hi$h
,e levels → -cess iron in circulation → )an poison or$ans due to ,enton reaction
!/H0 production".
3oint &ain+ fati*%e+ diabetes+ loss of libido+ im&otence+ cardiom!o&ath!+ heart fail%re+ li,er
cirrhosis
T
reat ,ia &hlebotom! Iron deficienc! anemia Re*%lation of Hemato&oeisis b! Iron Aragon-Ching
Im&aired *ro#th and de,elo&ment+ fati*%e+ #ea4ness+ tach!cardia+ shortness of breath+
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Condition Name Associated Issue/Pathogenesis Patient Sm!toms/T"eatment
Defciency caused by many actors !see )linical ,indin$s )hart" includin$ issues
ith diet# absorption# and chronic bleedin$. → unable to ma(e heme → unable to
ma(e Hb → lac( o hemo$lobinziation
in RBCs
Smear has increased central &allor+ microc!tosis+ anisoc!tosis+ &encil cells+ and tar*et cells
di55iness+ irritabilit!+ decreased #or4 &rod%cti,it!+ 6ICA "ice and cla! es&eciall!$+ an*%lar
stomatitis "inflammation of li& corners$+ 4oilon!chiae "thin/s&oon nails$
Treat the %nderl!in* ca%se 6t ma! or ma! not be res&onsi,e to iron s%&&lement "#ith oran*e
%ice$ Ma! need I7 inection if absor&tion &roblem . Oral s%&&lement side effects8
d
iarrhea+ consti&ation+ cram&s 9.lin4ed sideroblastic anemia Re*%lation of Hemato&oiesis b! Iron
Defciency in A2A&3 → no heme synthesis → iron accumulates in
mitochondria4surrounds nuclei. )an be caused by B
:
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6t ma! or ma! not be res&onsi,e to B
:
treatment
deficienc! or ALAS.2 m%tation/deficienc! A&lastic anemia Hemato&oeisis
Total fail%re of bone marro# to &rod%ce er!throblasts for RBCformation Hereditar! s&heroc!tosis Hemato&oeisis
5B) ehibit spherocytosis !loss o biconclave" → prone to rupture causin$ hemoltyic
anemia and lac( o / delivery 'yelophthisic anemia Hematopoeisis
S&ace.occ%&!in* bone marro# lesions &re,entin* RBC formation "fibrosis+ t%mors+ *ran%lomas$
Tear dro& cells in blood smear
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Condition Name Associated Issue/Pathogenesis Patient Sm!toms/T"eatmentSe)e"e "enal &ailu"e 'emato!oeisis
B%rr cells in blood smear
Sicle cell anemia !e"elopment# School-Aged Child $ith Sicle Cell
Hemaglobinopathies
Most commonl! identified disease in ne#born screen "1/-;; African Americans$
&&6 Beta $lobin $ene missense mutation6 $lutamic acid → valine )ells are
hetero$enous and orms sic(les durin$ episodes. Durin$ deoy$enated states# Hb
stac(s upon each other and a$$re$ate into the sic(le orm. → )an cause vaso3
occulation.
Other types: SC, Sβ
thal+
6ainf%l crisis+ ac%te chest s!ndrome+ ris4 for silent cerebral infarct+ s&leen enlar*ement+
a,asc%lar necrosis+ hand/foot s!ndrome+ com&lications from infection+ renal iss%es+
osteonecrosis of hi& and sho%lders+ &roliferati,e retino&ath! "Hb SC$+ le* %lcers+ cholec!stisis+
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&ria&ism
Life s&an8 ';.-; !rs for SS< :;.=; for SC
Treatment
> Earl! inter,ention from birth ? : !rs8 &enicillin &ro&h!la0is+ con%*ate &ne%mococcal ,accine+
a**ressi,e e,al%ations of an! fe,er
> Transf%sions
> 6ain medicine and fl%ids
> H!dro0!%rea
>
Bone marro# trans&lant Anemia of chronic disease/chronic inflammation
SD
Aragon-Ching
H!&o&roliferati,e anemia d%e to chronic non.hematolo*ic condition "inflammator! res&onse$Conditions can be infectio%s+ mali*nant+ imm%nolo*ic+ tra%matic
> Infectio%s8 TB+ l%n* abscess+ endocarditis+ &%lmonar!+ f%n*al AIDS
Treat %nderl!in* &rocess #hile correctin* an! co.e0istent )e deficienc! Some 6ts also benefit
from E6O thera&!
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Condition Name Associated Issue/Pathogenesis Patient Sm!toms/T"eatment
> Inflammator!8 rhe%matoid arthritis+ rhe%matic fe,er+ s!stemic l%&%s+ re*ional enteritis+
%lcerati,e colitis+ ,asc%litis
> Mali*nancies8 carcinomas+ metastatic CA+ 'od*4in@s+ NHL+ m%lti&le m!eloma
0 'isc6 liver disease# thrombophlebitis# sterile abscesses# isch. Heart disease →
/verhelmin$ presence o in7ammatory cyto(ines hich suppress erythropoiesis
and -8/ production4response# also altered iron metabolism → decreased utilization
o ,e !hi$her stora$e" Hemolytic anemia !$eneral" Ara$on3)hin$
)auses6 inherited intrinsic 5B) deect or ac9uired deect 8remature4accelerated
peripheral 5B) destruction → increased bilirubin# 2DH# and decreased hapto$lobin
Smear8 s&heroc!tes+ schistoc!tes+ &ol!chromasia+ immat%re n%cleated RBCs Marro#8 er!throid
h!&er&lasia+ thinnin* in bones Hemol!tic anemia d%e to :6D deficienc!
Aragon-Ching
:;8D protects 5B)s rom oidative dama$e and maintains NAD8H level. De <
hi$her oidative dama$e. → Hemolysis.
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9.lin4ed inheritance )orms8
> A. ? 1;.1- African Americans< retics are stress.resistant< milder
> Mediterranean ? most common in #hites< lo# retic le,els< ac%te and fatal
Smear ? Hein5 bodies+ bite cells Hereditar! s&heroc!tosis
Ara*on.Chin*
AD inheritance M%tant in band '1 &rotein res%ltin* in decreased s&ectrin e0&ression in RBC
"s4eletal com&onent of membrane$
Chronic anemia+ s&lenome*al!+ *allstones+ a&lastic crisis
Treat ,ia s&lenectom!
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Condition Name Associated Issue/Pathogenesis Patient Sm!toms/T"eatment
Smear ? s&heroc!tes+ increased osomotic fra*ilit! arm.
reactin* imm%ne hemol!sis
Aragon-Ching
%$: antibodies bind to 5B)s in arm temperatures !=>)" → pha$ocytosis. 8ositive
)oomb?s test.
Smear ? &ol!chromasia+ micros&heroc!tes
Ind%ced b! idio&athic reasons+ ,ir%s+ neo&lasia+ connecti,e tiss%e disorders+ &rior blood
transf%sion/bone marro# trans&lant+ dr%*s Dr%*s8 . %inidine8 innocent b!standerF< dr%*
com&le0es #ith Ab and
attaches nonspecifc to 5B) → complement pathay activated 3 8enicilin6 attaches
to 5B) membrane and serves as a hapten a$ainst
Ab #hich directs them to the RBC . Meth!ldo&a8 alters RBC membrane to become an
anti*en and
imm%no*enic "tr%e a%toimm%ne$ . Others e0am&les incl%de s%lfonamides+ ce&halos&orins
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7aries from mild to se,ere s!m&toms< he&atos&lenomal*! in 1/G+ thrombo&hlebitis+ a%ndice+
&allor+ cardio&%lmonar! colla&se
Treat ,ia discontin%in* all dr%*s+ search for &otential l!m&homa or le%4emia+ control l!sis #ith
corticosteroids s&lenectom! if all else fails
Cold.reactin* imm%ne hemol!sis Ara*on.Chin*
%$' only bind to 5B)s at lo temperatures!@=1)" → pha$ocytosis by liver
macropha$es 8ositive Donath32andsteiner test.
Ind%ced b! idio&athic reasons+ l!m&ho&roliferati,e diseases+ certain infections
7asc%lar occl%sion "&ain/%lceration in toes and fi*%res$
Treat ,ia %nderl!in* disorder+ &lasma e0chan*e+ and and a,oidin* e0&os%re to cold
Transf%sions m%st be done thro%*h a blood #armer Carbon mono0ide "CO$ &oisonin*
Hemoglobin
Hi$h anity bindin$ to Hb → unable to deliver /
2
Treat ,ia 1;; o0!*en thera&!
E,ol%tionar! &rotection of distal histidine =
&re,ents CO from bindin* linearl! li4e it &refers "lo#ers affinit!$ 6oisonin* occ%rs #hen
concentration/&ress%re of CO is hi*her than O
2
Methemo*lobin Hemo*lobin Chocolate c!anosis+ chocolate
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Condition Name Associated Issue/Pathogenesis Patient Sm!toms/T"eatment
Hb ith ,e= rather than ,e in heme. → /
2
co,ered blood+ c!anotic cannot bind
s!m&tomolo*! Red%ction
of iron d%e to o0idi5in* molec%les "nitrates+ ROS$+ dr%*s+ and decreased NADH.c!tochrome B
-
red%ctase "NADH.methemo*lobin
Treat ,ia meth!lene bl%ered%ctase$
Inf%sions are hel&f%l for c!anide &oisonin* Thalassemia
Hemo*lobin
3 'utation in locus o control re$ion → no epression o $lobin $enes 3 8oint
mutation causin$ alternative splice site → etension in second intron causin$
additional > amino acids added to Hb
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Tar*et cells in blood smear thalassemia Hemo*lobino&athies
'utation or deiciency in beta chain → decreased 5B) Hb → increased ree C chains
→ precipitate out → ineective erythropoiesis# hemolysis# marro epansion#
etramedullary hematopoiesis
Hereditar! &ersistence of Hb ) as a #a! to com&ensate deficienc!T!&es
0 E3thal F $enes or beta Hb deleted → no epression
0 3thal F $enes mutated → disease severity varies dependin$ on amount o Hb A
produced and the problem
0 G F no or G chain → no Hb A
2
• Hemoglobin Lepore – δβ hybrid chain replaces typical β chain in Hb
Se,ere anemia+ hi*h o%t&%t con*esti,e fail%re+ chi&m%n4 faces+ bones/s4%ll h!&ertro&h!
More s!m&toms #ith maor ? diabetes+ h!&o&arath!roidism+ h!&o*onadism+ infections from
transf%sion+ alloimm%ni5ation from transf%sion
Treat ,ia transf%sions+ com&rehensi,e thalassemia center+ h!dro0!%rea "for increased Hb )
&rod%ction$+ iron chelation thera&! "red%ces &otential for hemochromatosis or*an dama*e$+
stem cell trans&lant thalassemia Hemo*lobino&athies
8oint mutation or deletion in alpha chains → decreased 5B) Hb → increased ree
chains → ormation o abnormal Hb that have hi$h
Hb H8 microc!tic anemia+ s&lenome*al!+ iron.loadin*+ ineffecti,e er!thro&oiesis+ bris4 hemol!sis
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Condition Name Associated Issue/Pathogenesis Patient Sm!toms/T"eatment
affinit! for O
2
"Hb barts ? J
'
< Hb H ? K
'
$
,our $enes code or alpha chains. → 'utation leads to specifc type.> Thal trait ?t#o *enes nonf%nctional< no.mild s!m&toms+ 2.1; Hb Barts in ne#borns
o Homozy$ous C thal !C34C3" → > o Aricans o Heterozy$ous CE thal !CC433" →
common in &- Asia
0 Hb H disease4C thal maIor F three $enes nonunctional !C3433" → unstable Hb
o 2;.'; Hb Barts in ne#born< -.'; Hb H in ad%lts
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> Hb Barts/; ? homo5!*o%s ../..+ no f%nctional al&ha *enes
o Leads to eclam&sia in mother and stillbirth
Hb Barts8 Leads to eclam&sia in mother and stillbirth
Sicle cell disease Hemoglobinopathies
See abo,e
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*AB DIA+NSIS (% ANE#IAS
Condition (e TIBC T& T&
Sat
(tn *D' %BC '$ 'ct #C- %D. P*T %etic the"
Iron deficienc! anemia
J K K J J J J J J K K N
Me*aloblastic anemia N or
K
LB)6 J Hapt6 J Bili6 K Anemia o chronic disorders
N or
N or
N or
N or
K J J J K K J N or J
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J
K
K
J
Hapt6 N Bili6 N LB)6 N Hemolytic anemia K K K Hapt6 J
B
ili6 K Hemochromatosis K J J K K N &ideroblastic anemia K J J K K J
Mhalessemia K J J K K J
)e ser%m iron TIBC total iron.bindin* ca&acit! Tf ser%m transferrin Tf Sat transferrin sat%ration
)tn ser%m ferritin LDH ser%m lactate deh!dro*enase RBC red blood cell co%nt Hb ser%m
hemo*lobin Hct hematocrit "&ac4ed RBC ,ol%me$ MC7 mean cor&%sc%lar ,ol%me RD red blood
cell distrib%tion #idth ",ariation in RBC si5es$ Retic retic%loc!te co%nt 6LT &latelet co%nt BC #hite
blood cell co%nt Ha&t ser%m hat&o*lobin Bili ser%m bilir%bin
J J J J N or
N K N or
N N or K
J
J
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LYMPHATIC TISSUE DISORDERS
Condition Name Associated Issue/Pathogenesis Patient Sm!toms/T"eatment
Tonsilitis -ascula" and *m!hatic "gans
Infection of the tonsils
CLOTTING DISORDERS/BLOOD TRANSFUSIONS
Condition Name Associated Issue/Pathogenesis Patient Sm!toms/T"eatment
Be"na"d Soulie" Snd"ome Platelets
Glanzmanns thrombasthenia
Defects in cell membrane Chedia4 He*ashi disease 6latelets&tora$e pool disease → decrease4absence o dense $ranules causin$ diminished
platelet a$$re$ation Mhrombocytopenia 8latelets
Decreased &latelet n%mber Can be d%e to *enetic disorders . Tar bab! s!ndrome+ iscott.
Aldrich s!ndrome+ Ma!.He**lin anomal!+ Al&ort s!ndrome+ and ac%ired ame*a4ar!octic
thromboc!to&enic &%r&%ria "AAT6$ Or d%e to ac%ired factors ? radiation e0&os%re+ dr%*s+
chemicals "es&eciall! ben5enes$+ infections+ bone marro# d!sf%nction
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OR increased destr%ction8 dr%* ind%ced+ IT6+ TT6+ DIC+
h!&ers&lenism Imm%ne thromboc!to&enic &%r&%ra "IT6$
Platelets
%$ hich binds to :8%%b4%%ia# :81b4% → no platelet adhesion or a$$re$ation# rapid
destruction in 5- system !spleen". Also %$ to me$a(aryocytes → suppression o
thrombopoeisis.
Ac%te IT68 es& in children '.: bo!s and *irls after infection< s&ontaneo%s d%ration Chronic IT68
ad%lts in #omen es& &rior to meno&a%se< not d%e to infection
E,idence of m%co%sal bleedin*+ eas! br%isin*+ menorrha*ia+ *in*i,al bleedin*+ intracranial
bleedin*
Treat ,ia corticosteroids and s&lenectom! Ne#er trials incl%de I7I+ Rit%0imab+ and
s!nthesi5ed T6O
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Condition Name Associated Issue/Pathogenesis Patient Sm!toms/T"eatmentTh"om$otic th"om$octo!enia !u!u"a TTP0
Platelets
%$ a$ainst ADA'M&31= metalloproteinase hich cleaves OL, into its active orm. →
No clippin$ o OL, → %ncreased platelet adhesion but no coa$ulation. → '%s4death
easily occur.
Thromboc!to&enia+ microan*io&athic hemol!tic anemia+ renal fail%re+ fe,er+ CNS s!m&toms
"conf%sion+ loss of conscio%sness$
Treat ,ia hi*h doses of corticosteroids to s%&&ress Ab &rod%ction and &%t &atients on &lasma
e0chan*e He&arin ind%ced thromboc!to&enia "HIT$
Platelets
%$ orm a$ainst unractionated heparin !H'L" and ,%O → orm immune complees
hich deposit on platelet?s surace. → 8latelets bind to$ether and cause small
clots4$et destroyed by 5- system.
se other anti.coa*%lants rather than he&arin
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6reeclam&sia 6latelets
Hi*h B6 and &rotein%ria
-.1- of &re*nancies
D
eli,er ASA6 HELL6 s!ndrome 6latelets
6re*nanc!.related Incl%des hemol!sis+ ele,ated bili and SOT+ li,er en5!mes &resent in blood+
lo# &latelets
Na%sea+ malaise+ abdominal &ain
Deli,er ASA6
Neonatal alloimm%ne thromboc!to&enia "NAIT$
Platelets
,etal inheritance o platelet anti$ens not present in mother → cross into placenta
and mother develops %$
Treat ,ia inf%sion of #ashed maternal &latelets+ earl! C. section
Hemophilia A Coagulation
3lin(ed recessive inheritance# more common. ,actor * defciency → prolon$ed 8MM
Hemarthrosis+ m%scle bleeds+ m%c%taneo%s bleeds+ intracranial bleeds+ &ost dental/s%r*ical
bleeds Normal bleed after minor c%t
Treat ,ia &lasma/recombinant )7III or DDA76 "to stim%late )7III release$