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



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+




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

:



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



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+



&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&!




> 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.



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!




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



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




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



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




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



> 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



*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



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



LYMPHATIC TISSUE DISORDERS


Tonsilitis -ascula" and *m!hatic "gans

Infection of the tonsils

CLOTTING DISORDERS/BLOOD TRANSFUSIONS


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



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



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



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$

Disease Chart I3-1 (Emmeline).docx

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