● SPECI

ALPATHOLOGYNOTES

a
pa
ya
Si
SPECI
ALPATHONot
es

Dat
acol
l
ect
edf
rom Robbi
nspat
hol
ogyy
oudontev
enNeedt
ocr
osscheck

#Chap1

BLOODVESSELS
.Vascul
ardi
seasedev
elopst
hrought
wopr
inci
pal
mechani
sms:

•Nar
rowi
ngorcompleteobst
ruct
ionofvessel
lumina,
occurr
ingei
therpr
ogr
essi
vel
y(e.
g.,
by
at
her
oscl
erosi
s)oracut
ely(
e.g.
,bythr
ombosisoremboli
sm)

•Weakeni
ngofv
essel
wal
l
s,causi
ngdi
l
ati
onand/
orr
upt
ure

Vesselwal
lsareorgani
zedint
othr
eeconcent
ri
clay
ers:
inti
ma, media,
andadventi
ti
a.These
a
l
ayersarepresenti
nall
vessel
sbutar
emostapparenti
nlargervessel
sandpart
icul
arl
yart
eri
e
pa

●CONGENI
TALANOMALI
ES
ya

Ber
ryaneur
ysmsa r
et hi
n-wal
ldart
erial
outpouchingsincerebr
alvessel
s,classi
cal
lyatbr
anch
Si

poi
ntsar
oundthecir
cleofWil
li
s;t
heyoccurwher ethear t
eri
almediaiscongenit
all
yatt
enuat
ed
andcanspont
aneousl
yruptur
ecausingfat
alint
racerebralhemorr
hage

Ar
teri
ovenous(AV)fi
stul
asareabnormalconnect
ionsbetweenar
ter
iesandvei
nswi
thoutan
i
nter
veningcapi
ll
arybed.Theyoccurmostcommonl yasdevel
opmental
defect
s

Fi
bromuscul
ardyspl
asi
aisaf
ocali
rr
egul
art
hickeni
ngofthewal
lsofmedium-
sizedandl
arge
muscul
arart
eri
esduetoacombi
nati
onofmedialandi
nti
malhyper
plasi
aandf
ibrosi
s

occur
smostf
requent
lyi
nyoungwomen

i
nther
enal
art
eri
es,
itcanl
eadt
orenov
ascul
arhy
per
tensi
on

●Bl
oodpr
essur
eregul
ati
on

Bl
oodpr
essur
eisdet
ermi
nedbyv
ascul
arr
esi
stanceandcar
diacout
put
.

Car
diacoutputi
sdeter
minedbyheartr
ateandst
rokevol
ume, whi
chisstr
onglyi
nfl
uencedby
bl
oodvolume.Bloodvol
umeintur
nisregulat
edmai
nlybyrenal
sodium excr
eti
onorresor
pti
on.

Reni
n,amaj
orr
egul
atorofbl
oodpr
essur
e,i
ssecr
etedbyt
heki
dney
sinr
esponset
o
decr
easedbl
oodpr
essur
einaf
fer
entar
ter
iol
es

●Hy
per
tensi
on

•Hypertensi
onisacommondi sorderaffect
ing25%ofthepopul
ati
on;
iti
samaj
orr
iskf
act
or
f
oratheroscler
osi
s,congest
iveheartfail
ure,andrenal
fai
l
ure.

•Essent
ialhy
pert
ensi
onrepresents95%ofcasesandi
sacompl
ex,mul
ti
factor
ialdi
sor
der
,
i
nvolv
ingbothenvi
ronment
alinfl
uencesandgeneti
cpol
ymor
phi
smsthatmayinfl
uencesodi
um

r
esor
pti
on,
aldost
eronepat
hway
s,andt
her
eni
n–angi
otensi
nsy
stem.

•Hypert
ensionoccasional
lyiscausedbysingl
e-genedi
sorder
sori
ssecondar
ytodi
seases
a
oftheki
dney,adrenal
,orotherendocri
neorgans.
pa

Hy
ali
near
ter
iol
oscl
erosi
sisassoci
atedwi
thbeni
gnhy
per
tensi
on
ya

I
ntheki
dney
s,theart
eri
olarnar
rowingcausedbyhyali
neart
eri
oscl
erosi
sleadst
odi
ff
use
v
ascul
arcompromiseandnephroscl
erosi
s(glomer
ularscar
ri
ng)
Si

Hyperpl
ast
icar
ter
iol
oscl
erosi
sismor
ety
pical
ofsev
erehy
per
tensi
on.Vessel
sexhi
bit
“
onionski
n,
”

.I
nmal
i
gnantHTN (
necr
oti
zi
ngar
ter
iol
i
tis)
,whi
char
epar
ti
cul
arl
ypr
omi
nenti
ntheki
dney

●At
her
oscl
erosi
s

•Ather
osclerosi
si saninti
ma-basedlesi
oncomposedofafi
brouscapandanather
omatous
(l
i
teral
l
y,“
gr uel
-l
ike”)core;
theconsti
tuent
softhepl
aquei
ncl
udesmoot hmuscl
ecell
s,ECMs,
i
nflammatorycells,l
ipi
ds,andnecrot
icdebri
s.

●ANEURYSMSANDDI
SSECTI
ONS

Aneur
ysmsar
econgeni
tal
oracqui
reddi
l
ati
onsofbl
oodv
essel
sort
hehear
t

Tr
ue”aneur
ysmsi
nvol
veal
lthr
eel
ayer
soft
hear
ter
y(i
nti
ma,
medi
a,andadv
ent
it
ia)ort
he

at
tenuatedwal
loft
heheart
;theseincl
udeather
oscler
oti
candcongeni
talvascularaneur
ysms,
aswellasvent
ri
cul
araneur
ysmsr esul
ti
ngfr
om transmural
myocardi
ali
nfarcti
ons.
 f
alseaneur
ysm (
pseudoaneur
ysm)r
esul
tswhenawal
ldef
ectl
eadst
othef
ormat
ionofan

ext
rav
ascul
arhemat
omat
hatcommuni
cat
eswi
tht
hei
ntr
avascul
arspace(
“pul
sat
ing
hematoma”
)

I
N art
eri
aldissect
ions,
pressur
izedbl
oodgai
nsent
ryt
hear
ter
ial
wal
lthr
oughasur
face
def
ectandthenpushesaparttheunderl
yi
ngl
ayer
s.

Saccul
araneur
ysmsarediscr
eteout
pouchi
ngsr
angi
ngf
rom 5t
o20cm i
ndi
amet
er,
oft
en
wi
thacont
ainedt
hrombus.

Fusi
for
m aneury
smsarecir
cumferent
ial
dil
ati
onsupto20cm i
ndi
ameter
;thesemost
commonlyinv
olvetheaor
ti
carch,
theabdominalaor
ta,
ort
heil
i
acart
eri
es

AbdominalAort
icAneur
ysm At
her
oscl
erot
icaneur
ysmsoccurmostf
requent
lyi
nthe
abdominalaor
ta,

Thoraci
cAort
icAneur
ysm Thor
aci
caor
ti
caneur
ysmsmostcommonl
yar
eassoci
atedwi
th
hy
pertensi
onandMarfansy
ndrome,

Aor
ti
cDissect
ionAor
ti
cdi ssect
ionoccurswhenbl
oodspl
aysapar
tthel
ami
narpl
anesoft
he
a
pa
medi
atoform abl
ood-f
il
ledchannelwithi
ntheaor
ti
cwall

Themostfrequentpr
eexi
sti
nghi
stol
ogi
cal
l
ydet
ect
abl
elesi
oni
sthecy
sti
cmedi
al
ya

degener
ati
on
Si

Themostcommoncauseofdeat
hisr
upt
ureoft
hedi
ssect
ioni
ntot
heper
icar
dial
,pl
eur
al,
or
per
it
oneal
cavi
ty

●VASCULI
TIS

Vascul
i
tisi
sagener
alt
ermf
orv
essel
wal
li
nfl
ammat
ion.

Thet
womostcommonpat hogeni
cmechani
smsofv asculi
ti
sareimmune-
medi
ated
i
nfl
ammati
onanddi
rectv
asculari
nvasi
onbyi
nfect
iouspathogens.

Giantcell
(temporal)ar
ter
it
isi
sthemostcommonf
orm ofv
ascul
i
tisamongt
heel
der
lyi
n
developedcountr
ies.

I
ttakestheform ofchr
onic,
typi
cal
lygr
anulomatous,
infl
ammati
onoflar
get
osmal
lsi
ze
ar
ter
ies,mainl
ythosesupply
ingthehead—especi
all
ythetempor
alart
eri
es

canl
eadt
osuddenandper
manentbl
i
ndness,

Diagnosisdependsonbi
opsyandhi
stol
ogy
;Cor
ti
cost
eroi
dorant
i-
TNFt
herapi
esar
e
ef
fecti
vetreatments.
●Takay
asuArt
eri
ti
scharacter
izedpri
nci
pal
l
ybyocul
ardist
urbancesandmarkedweakeni
ngof
thepul
sesi
ntheupperextr
emi t
ies(
hencet
heal
ter
natename, pul
sel
essdi
sease)

Takay
asuar
ter
it
iscl
assi
cal
l
yaf
fect
stheaor
ti
car
chandar
chv
essel
s

Pul
monar
yar
ter
iesar
einv
olv
edi
n50%ofpat
ient
s,andr
enal
andcor
onar
yar
ter
iesal
socan
beaff
ect
ed

●Pol
yarter
it
isNodosa: Cl
assicPANi sasegmentalt
ransmural
necrot
izi
nginf
lammati
onof
smallt
omedi um-si
zedarter
ies,
oft
enwithsuperi
mposedthrombosi
s.Kidney,
hear
t,l
i
ver,
and
gast
roi
ntesti
nalt
ractvessel
sareaffect
edindescendi
ngorderoff
requency

Therei
snoassoci
ati
onwi
thANCAs,
butat
hir
doft
hepat
ient
shav
echr
oni
chepat
it
isB
i
nfect
ion

I
ntheacut
ephasef
ibr
inoi
dnecr
osi
sandl
umi
nal
thr
ombosi
s

Ol
derl
esi
onsshowf
ibr
oust
hickeni
ngoft
hev
essel
wal
lext
endi
ngi
ntot
headv
ent
it
ia

A“cl
assi c”presentat i
oncani nvol
vesomecombi nat
ionofrapidl
yacceler
atinghyper
tensi
on
duetor enal art
eryinv ol
vement;abdominalpai
nandbloodystoolscausedbyv ascul
ar
a
pa
gastroi
nt esti
nallesions;di
ff
usemuscul arachesandpai
ns;andper i
pheral
neuriti
s,
predomi nantlyaffecti
ngmot ornerves
ya

●KawasakiDi
seaseisanacute,
febri
l
e,usual
lysel
f-
li
mit
edi
l
lnessofi
nfancyandchi
l
dhood(
80%
Si

oft
hepatient
sareyoungert
han4y earsofage)

associat
edwithanart
eri
ti
sofmainl
ylar
getomedi
um-
sizedv
essel
s.I
tscl
i
nical
signi
fi
cance
st
emsf rom thei
nvol
vementofcor
onaryar
ter
ies

cer
vical
lymphnodeenl
argement(
hencei
tsot
hername,
mucocut
aneousl
ymphnode
sy
ndrome).

●Micr
oscopi
cpolyangi
it
isisanecr
oti
zi
ngv
ascul
i
tist
hatgeneral
l
yaf
fect
scapi
l
lar
ies,
aswel
las
small
art
eri
olesandvenules.

I
tal
soi
scal
l
edhy
per
sensi
ti
vi
tyv
ascul
i
tisorl
eukocy
tocl
ast
ic

necrot
izi
nggl
omer
ulonephr
it
is(
seeni
n90%ofpat
ient
s)andpul
monar
ycapi
l
lar
it
isar
e
par
ticul
arl
ycommon

mostcasesar
eassoci
atedwi
thMPO-
ANCA.

maj
orfeat
uresi
ncludehemoptysi
s,hematur
ia,
prot
einuri
a,abdomi
nal
pai
norbl
eedi
ng,
muscl
epainorweakness,andpal
pablecut
aneouspurpura
●Wegenergr
anul
omat
osi
sisanecr
oti
zi
ngv
ascul
i
tischar
act
eri
zedbyaspeci
fi
ctr
iadof
fi
ndi
ngs:

•Granulomasofthelungand/
ortheupperrespir
atoryt
ract(ear,
nose, si
nuses,
throat)
•
Vasculi
ti
sofsmalltomedium-si
zedvessel
s(capill
ari
es,v
enules,art
eri
oles,andart
eries)
,most
pr
omi nent
lyint
helungsandupperrespi
rat
orytract

•Gl
omer
ulonephr
it
is

PR3-
ANCAsar
epr
esenti
nal
most95%ofcases

Classi
cpresent
ationsincl
udebi
lat
eralpneumoni
ti
swi thnodul
esandcavit
aryl
esions(95%),
chr
onicsinusi
ti
s(90%) ,
mucosalul
cerati
onsofthenasopharynx(
75%),andrenal
disease(80%);
pat
ientswithl
ow-graderenali
nvol
vementmaydemonst rateonl
yhematuri
aandpr ot
einur
ia

●Churg-St
raussSyndrome(
alsocal
l
edal
l
ergi
cgr
anul
omat
osi
sandangi
i
tis)i
sasmal
lvessel
necr
otizi
ngv ascul
i
tis

classi
cal
l
yassociatedwi
thasthma,
aller
gicr
hinit
is,l
unginfi
lt
rat
es,per
ipher
aleosinophi
li
a,
extr
avascul
arnecrot
izi
nggr
anulomas,andastr
ikinginfi
l
trat
ionofvessel
sandperi
vascular
a
ti
ssuesbyeosinophi
ls.
pa

MPO-ANCAsarepr
esenti
nami
nor
it
yofcases,
suggest
ingt
hatt
hedi
sor
deri
spat
hogeni
cal
l
y
ya

het
erogeneous
Si

●Thromboangii
ti
sOblit
erans(Buer
gerdi
sease)ischaracteri
zedbyfocal
acuteandchroni
c
i
nflammationofmedium-sizedandsmal
lart
eri
es,especiall
ythet
ibi
alandradi
alar
ter
ies,
associ
atedwit
ht hr
ombosis;

incr
easedpr
eval
enceincer
tai
nethni
cgr
oups(
Isr
ael
i
,Indi
ansubcont
inent
,Japanese)andan
associ
ati
onwit
hcertai
nHLAhaplot
ypes

Earl
ymanifestat
ionsincludecol
d-i
nducedRaynaudphenomenon,
instepf
ootpai
ninduced
byexerci
se(
instepclaudicati
on),
andasuperfi
cial
nodul
arphl
ebi
ti
s(venousi
nfl
ammation)
.

●Ray
naudPhenomenon

Ray
naudphenomenonresult
sfrom exaggerat
edvasoconst
ri
cti
onofar
teri
esandar t
eri
olesin
t
heextremi
ti
es,
part
icul
arl
ythefi
ngersandt oes,
butal
sosomet i
mesthenose,ear
lobes,orli
ps.

Pri
mar yRaynaudphenomenon(previ
ousl
ycal
ledRay
nauddi
sease)i
scausedbyexagger
ated
cent
ralandlocalvasomotorr
esponsestocol
doremoti
on;

SecondaryRaynaudphenomenonrefer
stovascul
ari
nsuffici
encyduet oart
eri
aldi
sease
causedbyotherentit
iesincl
udi
ngsy
stemicl
upusery
thematosus,scl
eroderma,Buer
gerdisease,
orevenatheroscl
erosis
●Var
icoseVei
nsoft
heExt
remi
ti
es

Vari
cosevei
nsareabnor
mal
l
ydi
l
atedt
ort
uousv
einspr
oducedbychr
oni
cal
l
yincr
eased
i
ntr
aluminal
pressur
e

Thesuper
fi
cial
vei
nsoft
heupperandl
owerl
egt
ypi
cal
l
yar
einv
olv
ed

Obesi
tyi
ncr
easesther
isk,el
evat
ioni
nv enouspr
essur
ecausedbycompr
essi
onoft
hei
nfer
ior
v
enacavabythegrav
idut
er usduri
ngpregnancy

Themostdi
sabli
ngsequelaeincl
udeper
sist
entedemai
ntheext
remi
tyandsecondar
y
i
schemi
cskinchanges,
incl
udingstasi
sder
mat i
ti
sandul
cer
ati
ons.

Ofnote,
embolism f
rom t
hesesuper
fi
cial
vei
nsisveryr
are,
incont
rastwi
tht
her
elat
ivel
y
f
requentembol
ithatari
sefr
om thr
om boseddeepvei
ns

Vari
cosit
iesofOt
herSi
tesEsophagealvari
ces.Li
verci
rr
hosi
s(lessfr
equent
ly,
por
tal
vei
n
obst
ructi
onorhepat
icvei
nthrombosis)causesport
alvei
nhyper
tension

Hemor
rhoi
dsar
evar
icosedi
l
ati
onsoft
hev
enouspl
exusatt
heanor
ect
alj
unct
ion
a
Thr
ombophl
ebi
ti
sandPhl
ebot
hrombosi
s
pa

Thr
ombosisofdeepl
egv
einsaccount
sformor
ethan90%ofcasesoft
hrombophl
ebi
ti
sand
ya

phl
ebothr
ombosi
s.
Si

I
ndeepvenoust
hrombosi
s(DVT)oft
hel
egs,
prol
ongedi
mmobi
l
izat
ionr
esul
ti
ngi
nvenous
st
asi
sist
hemostimport
antri
skfact
or

Pul
monar
yembol
i
sm i
sacommonandser
iouscl
i
nical
compl
i
cat
ionofDVT

○●Super
iorandI
nfer
iorVenaCav
aSy
ndr
omes

Thesuperi
orv enacav asyndr
omeusual l
yiscausedbyneopl asmst hatcompressori
nvade
thesuperiorvenacav a,suchasbronchogeni
ccarcinomaormedi ast
inally
mphoma.The
resulti
ngobstructi
onpr oducesacharact
eri
sti
ccli
nicalcomplexconsi st
ingofmarkeddil
ati
onof
thev ei
nsofthehead, neck,andarmsassociatedwithcyanosis.Pulmonaryvessel
salsocanbe
compr essed,
causi ngrespir
ator
ydist
ress.

Theinfer
iorv
enacavasyndromecanbecausedbyneopl asmst hatcompressorinvadet
he
i
nfer
iorvenacavaorbyathrombusfrom t
hehepati
c,r
enal
,orlowerextremi
tyveinsthat
pr
opagatesupward.Cer
tai
nneoplasms—part
icul
arl
yhepat
ocellul
arcarci
nomaandr enalcel
l

car
cinoma—canoccul
deI
VC

Ly
mphangi
ti
sref
erst
oanacut
einf
lammat
orypr
ocesscausedbybact
eri
alseedi
ngoft
he
l
ymphat
icv
essel
s

Pr
imaryl
ymphedemacanoccurasanisolat
edcongenit
aldefect(
simplecongeni
tal
l
ymphedema)orasthef
amil
i
alMilr
oydisease(her
edofamil
ial
congenital
lymphedema)

Secondar
yorobstr
ucti
velymphedemastemsfr
om t
heaccumul
ati
onofi
nter
sti
ti
alf
lui
d
behi
ndanobstr
ucted,pr
eviousl
ynormal
lymphat
ic

mil
kyaccumulati
onsoflymphinvar
iousspacesdesi
gnat
edchy
lousasci
tes(
abdomen)
,
chy
lot
horax,andchyl
oper
icardi
um.

●TUMORS

Nevusfl
ammeus( a“bi
rt
hmar
k”)
,themostcommonf
orm ofv
ascul
arect
asi
a,
onheadand
neckr
egressspont
aneousl
y

Theso-
cal
l
edpor
twi
nest
aini
saspeci
alf
orm ofnev
usf
lammeus.

l
esi
onsoccurr
ingi
nthedi
str
ibut
ionofthetri
geminalner
veareassoci
atedwi
tht
heSt
urge-
Webersy
ndrome(al
socal
l
edencephalotr
igeminal
a angi
omatosi
s

l
argefaci
altel
angi
ect
asiai
nachildwi
thment
aldef
ici
encymayi
ndi
cat
ethepr
esenceof
pa

addi
ti
onalvascul
armalf
ormat
ions.
ya

Spi
dert
elangi
ect
asi
asar
enon-
neopl
ast
icv
ascul
arl
esi
ons
Si

Heredi
tar
yhemor
rhagi
ctel
angi
ect
asi
a(Osl
er-
Weber
-Rendudi
sease)i
sanaut
osomal
dominant

Beni
gnTumor

●Hemangi
omasar
ever
ycommont
umor
scomposedofbl
ood-
fi
ll
edv
essel
s

mostarepresentf
rom bi
rt
handi
nit
ial
l
yincr
easei
nsi
ze,
butmanyev
ent
ual
l
yregr
ess
spont
aneously

Ty
pesofhemangi
oma

Capil
lar
yhemangiomasar
ethemostcommontype;t
heseoccuri
ntheski
n,subcut
aneous
ti
ssues,andmucousmembranesoft
heor
alcav
iti
esandli
ps,

Juveni
l
ehemangi
omas(
so-
cal
l
edst
rawber
ryhemangi
omas)oft
henewbor
nski
nar
eext
remel
y
common

growrapi
dlyf
oraf
ewmonthsbutt
henfadebyt heageof1t
o3y
ear
s,wi
thcompl
ete
r
egressi
onbyage7inthev
astmaj
ori
tyofcases.
 •Pyogenicgranul
omasarecapi
ll
aryhemangiomast
hatmani
festasr
api
dlygr
owi
ngr
ed
peduncul
atedlesi
onsontheski
n,gi
ngival
,oror
almucosa

Pr
egnancytumor(gr
anul
omagravi
darum)i
sapyogeni
cgr
anul
omat
hatoccur
sinf
requent
ly
(
1%ofpatient
s)int
hegingi
vaofpr
egnantwomen.

Caver
noushemangi
omasarecomposedoflarge,
dil
atedv ascul
archannel
s,
Cav
ernous
hemangi
omasconsti
tut
eonecomponentofvonHippel-
Lindaudisease

Ly
mphangi
omasar
ethebeni
gnl
ymphat
iccount
erpar
tofhemangi
omas.

•Si
mpl
e(capi
l
lar
y)l
ymphangi
omasar
esl
i
ght
lyel
evat
edorsomet
imespeduncul
atedl
esi
ons

di
sti
ngui
shedf
rom capi
l
lar
ychannel
sonl
ybyt
heabsenceofbl
oodcel
l
s.

Cav
ernousl
ymphangi
omas(
cyst
ichy
gromas)t
ypi
cal
l
yar
efoundi
ntheneckoraxi
l
laofchi
l
dren

cav
ernousl
ymphangi
omasoft
heneckar
ecommoni
nTur
nersy
ndr
ome.

Gl
omusTumor
s(Gl
omangi
omas)
arebeni
gn,
exqui
sit
elypai
nful
tumor
sar
isi
ngf
rom speci
ali
zed
smoot
hmuscl
ecel
l
sofgl
omusbodi
es
a
pa
Theymostcommonl
yar
efoundi
nthedi
stal
por
ti
onoft
hedi
git
s,especi
all
yundert
he
fi
nger
nai
ls.
ya

Baci
llar
yAngiomatosi
sisavascularprol
i
ferat
ionini
mmunocompr omisedhost
s(e.
g.,pati
ents
Si

wit
hAI DS)causedbyopport
unist
icgram-negati
vebaci
l
lioft
heBar
tonel
lafami
ly
.Thelesions
caninvol
vetheskin,
bone,br
ain,

Rol
eof2speci
esi
nthi
s

Bart
onel
lahensel
ae,
whosepr
inci
pal
reser
voi
rist
hedomest
iccat
;thi
sor
gani
sm causescat
-
scr
atchdi
sease

Bart
onell
aquint
ana,whi
chi
str
ansmi
tt
edbyhumanbodyl
i
ce;
thi
smi
crobewast
hecauseof
“
trenchfev
er”i
nWor l
dWarI

I
nter
medi
ate-
Grade(
Bor
der
li
ne)Tumor
s

Kaposi
Sar
comai
sav
ascul
arneopl
asm causedbyKaposi

sarcomaher
pesv
irus(
KSHV,alsoknownashumanher
pesvi
rus-8,
orHHV-
8).Al
thoughi
t
occursi
nanumberofcont
exts,i
tisbyf
armostcommoni
npatient
swit
hAIDS

Classi
cKSisadisor
derofoldermenofMedi
ter
ranean,
Middl
eEast
ern,
orEast
ernEur
opean
descent(
especi
all
yAshkenazi
cJews)
 Endemi
cAf
ri
canKSt
ypi
cal
l
yoccur
siny
ounger(
underage40)

Hemangi
oendot
hel
iomaswel
l-di
ffer
enti
atedhemangi
omasandaggressi
vel
ymali
gnant
angi
osar
comas.
Asanexample,epit
hel
ioi
dhemangioendothel
iomai
savascul
artumorof
adul
tsar
isi
ngi
nassoci
ati
onwithmedium sizedt
olargeveins

Mal
i
gnantTumor
s

Angi
osar
comasar
emal
i
gnantendot
hel
i
alneopl
asm

Ol
deradul
tsar
emor
ecommonl
yaf
fect
ed

.Ther
eisnogenderbi
as,
and

l
esi
onscanoccuratanysi
te,
butmostof
teni
nvol
vet
heski
n,sof
tti
ssue,
breast
,andl
i
ver
.

Hepaticangiosarcomasar eassociat
edwithcer
tai
ncarcinogens,i
ncl
udi
ngarsenicalpesti
cides,
Thorotrast(
ar adioact
ivecontr
astagentf
ormerl
yusedf orr
adi
ologi
cimagi
ng)
, andpolyviny
l
chl
oride( awidelyusedplast
ic,andoneofthebestknownexamplesofhumanchemi cal
car
cinogenesi s) a
Angiosar
comasalsocanari
seinthesett
ingofl
ymphedema,cl
assi
cal
l
yi ntheipsi
l
ateralupper
pa

extr
emitysev
eral
y ear
saf
terradi
calmastect
omy(i
.e.
,wit
hly
mphnoder esecti
on)forbreast
cancer
ya

Angi
osarcomasal
socanbeinducedbyradiati
onandr
arel
yar
eassoci
atedwi
thl
ong-
ter
m
Si

(y
ear
s)indwel
li
ngfor
eignbodi
es(e.
g.,
catheters)
.

Cl
i
nical
l
y,angi
osar
comasar
eaggr
essi
vet
umor
sthati
nvadel
ocal
l
yandmet
ast
asi
ze

Hemangi
operi
cy t
omasThesetumorsderi
vethei
rnamefrom thecel
l
sofor
igi
n,t
heper
icy
tes,
myof
ibr
oblast
-l
ikecel
l
sthatsurr
oundcapi
ll
ari
esandvenules

Vascul
arRepl
acement

Sy
ntheti
corautol
ogousv
ascul
argr
aft
scommonl
yar
eusedt
orepl
acedamagedv
essel
sor
by
passdiseasedart
eri
es

themorethan400,000cor onar
yarter
ybypasssurger
iesperyear)
,gr
aft
sgener al
l
yare
composedofeitherautol
ogoussaphenousv ei
n(t
akenfrom thepati
ent
’sownleg)orlef
t
i
nternalmammar yart
ery(owingtoit
sproximit
ytotheheart
).Thelong-
ter
m patencyof
saphenousvei
ngr af
tsisonly50%at10y ears.

Thesegr
aftsoccl
udeasaconsequenceoft
hrombosi
s(t
ypi
cal
l
year
ly)
,int
imal
thi
ckeni
ng
(
monthstoyearspost
oper
ati
vel
y),
and
v
eingr
aftat
her
oscl
erosi
s

Bycont
rast
,mor
ethan90%ofi
nter
nal
mammar
yar
ter
ygr
aft
sar
epat
entaf
ter10y
ear
s.

Hear
t
Hear
tFai
l
ure

Hear
tfai
l
uregener
all
yisr
efer
redt
oascongest
ivehear
a tfai
l
ure(
CHF)

r
esul
tbot
hfr
om sy
stol
i
c&di
ast
oli
cdy
sfunct
ion
pa

●l
eftsi
dedhear
tfai
l
uershowsl
eftv
ent
ri
cul
arhy
per
trophy
ya

●Lungsshowsedemaaswellaspl
eur
alef
fusi
onduet
oani
ncr
easei
nhy
drost
ati
cpr
essur
ein
Si

thevenul
esoft
heviscer
alpl
eur
a.

●Lungsalsoshowsbreakdownofredcell
sandhemoglobinleadst
otheappear
anceof
hemosideri
n-l
adenal
veol
armacrophages—so-
cal
ledheartfai
lur
ecell
s

●Dy
sneai
smostsi
gni
fi
cantsy
mpt
om ofl
eftsi
dedhear
tfai
l
ure,
coughi
sal
socomon

●LHFi
nchr
oni
ccasescangi
ves3hear
tsounds,
atr
ial
fibr
il
lat
ionwi
thi
rr
egul
arl
yir
regul
arbeat

Al
sohy
poxi
cencephal
opat
hy

●Ri
ghtsi
dedhear
tFai
l
urecancausemostcomonl
ypul
monar
yHTN

Cent
ri
lobul
arcongest
ionofl
i
veri
sassoci
atedwi
tht
his

I
fRHFi
sassoci
atedwi
thLHFt
heni
tshowscent
ri
lobul
arnecr
osi
s

Congeni
tal
Hear
tDi
seas

●VSDmostcomoncongeni
tal
def
ectofhear
t

Vsd>ASD>pul
monar
yst
enosi
s>PDA>Tet
ral
ogyofFal
l
ot>Coar
ctat
ionof
aort
a>Atr
iov
entri
cul
arseptaldef
ect>Aor
ti
cst
enosi
s>Tr
ansposi
ti
onofgr
eatar
ter
ies>Tr
uncus
art
eri
osus>Tri
cuspi
datresia

●cy
anosi
sisnotear
lyf
eat
urei
nlef
ttor
ightsi
dedshunt
sbuti
tisear
lyi
nri
ghtt
olef
t

●Tet
ral
ogyofFal
l
ot

Tet
ral
ogyofFal
l
oti
sthemostcommoncauseofcy
anot
iccongeni
tal
hear
tdi
sease

●Aort
icCoarct
ati
onCoarct
ati
on(narr
owi
ng,orconstr
icti
on)oftheaor
tai
sacommonf
orm of
obst
ruct
ivecongeni
tal
heartdi
sease.
.Mal
esareaffectedtwiceasoft
enasf
emal
es

➡ Pr
educt
alcoar
ctat
ionwi
thaPDAusual
l
ypr
esent
sear
lyi
nli
fe,
classi
cal
l
yascy
anosi
s

➡ Post
duct
alcoar
ctat
ionwi
thoutaPDAusual
l
yisasy
mpt
omat
ic

●I
SCHEMI
CHEARTDI
SEASE

I
nmor ethan90%ofcases,I
HDisaconsequenceofr
educedcor
onar
ybl
oodf
lowsecondar
yto
obst
ruct
iveat
heroscl
erot
icv
ascul
ardi
sease

Angi
naPect
ori
s
a
pa

Angi
napect
ori
sisani
nter
mit
tentchestpai
ncausedbyt
ransi
ent
,rev
ersi
blemy
ocar
dial
i
schemi
a.
ya

●Ty
pical
lst
abl
eangi
na
Si

Thepainusual
lyisrel
i
evedbyrest(
reduci
ngdemand)orbydr
ugssuchasni
tr
ogl
ycer
in,
a
v
asodi
latort
hatincr
easescor
onaryperf
usi
on.

●Pr
inzmet
alorv
ari
antangi
na

Pri
nzmetalangi
naty
pical
l
yrespondspr
ompt
lyt
ovasodi
l
ator
ssuchasni
tr
ogl
ycer
inandcal
cium
channel
blocker
s.

●Unst
abl
eangi
na(
alsocal
l
edcr
escendoangi
na)

●My
ocar
dial
Inf
arct
ionMyocar
dial
inf
arct
ion(
MI)
,al
socommonl
yref
err
edt
oas“
hear
tat
tack,
”
i
snecr
osi
sofhear
tmuscl
eresul
ti
ngf
rom i
schemi
a

LAD)ar
ter
yisthecauseof40%to50%ofal
lMI
sandt
ypical
l
yresul
tsi
ninf
arct
ionoft
he
ant
eri
orwall
ofthelef
tvent
ri
cle,

acut
eoccl
usi
onoft
hepr
oxi
mal
lef
tci
rcumf
lex(
LCX)ar
ter
y(seeni
n15%t
o20%

ofMIs)wil
lcausenecr
osi
softhelat
eral
lef
tvent
ri
cle,andproxi
mal ri
ghtcoronar
yarter
y( RCA)
occl
usion(
30%t o40%ofMIs)aff
ectsmuchoftherightvent
ri
cle.Theposteri
ort
hir
doft he
sept
um

4–12hour
sBegi
nni
ngcoagul
ati
onnecr
osi
s;edema;
hemor
rhage

12-
24hrnecr
osi
spl
usst
artofneut
rophi
l
ls

1-
3day
scompl
etenecr
osi
spl
usneut
rophi
l
s

El
ectrocardi
ographicabnor
mali
ti
esar
eimport
antf
orthediagnosi
sofMI;thesei
ncludeQ
waves,STsegmentchanges, andTwaveinv
ersi
ons(
thelat
tertworepr
esentingabnormal
it
ies
i
nmy ocardialr
epolar
izati
on

Arr
hythmiascausedbyel
ect
ri
cal
abnor
mal
i
tiesi
nischemi
cmy
ocar
dium andconduct
ion
sy
stem arecommon; i
ndeed

Tr
oponi
nsandCK-
MBhav ehi
ghspeci
fi
cityandsensi
ti
vi
tyf
ormy ocar
dialdamage. •CK-MB
r
emainsaval
uabl
emarkerofmy
ocardi
ali
njury
,secondonl
ytothecardi
ac-speci
fi
ctr
oponi
ns,

Althoughcardi
act r
oponi
nandCK-MBar eequal
l
ysensi
ti
vemar
kersoftheear
lystagesofan
MI,persi
stenceofelevat
edtr
oponi
nlev
elsforappr
oxi
matel
y10daysal
lowsthediagnosi
sofan
acuteMIlongaf t
erCK-MBlevel
shaveret
urnedtonor
mal
a
pa

•Ar
rhy
thmi
ascanbecausedbyi
schemi
corst
ruct
ural
changesi
ntheconduct
ionsy
stem or
bymyocyt
eel
ect
ri
cali
nst
abil
it
y
ya

.I
nstruct
ural
l
ynormal
heart
s,ar
rhyt
hmiasmor eof
tenar
eduet
omut
ati
onsi
nionchannel
s
Si

t
hatcauseaberr
antr
epol
ari
zat
ionordepol
ari
zat
ion.

•SCD(suddencar
diacdeat
h)mostf
requent
lyi
sduet
ocor
onar
yar
ter
ydi
seasel
eadi
ngt
o
i
schemia.

●Sy
stemi
c(Lef
t-
Sided)Hy
per
tensi
veHear
tDi
sease

Thecri
ter
iaforthedi
agnosi
sofsy st
emi chypertensi
vehear
tdiseaseare(1)lef
tventri
cul
ar
hy
pertr
ophyintheabsenceofothercardi
ovascularpathol
ogy(e.
g.,val
vul
arstenosi
s),and(2)a
hi
stor
yorpathologi
cevi
denceofhy per
tension

Theessenti
alf
eatureofsystemichy
pertensi
vehear
tdi
seasei
slef
tvent
ri
cul
arhy
per
trophy
,
t
ypical
l
ywithoutvent
ri
culardi
lati
onunti
lveryl
atei
nthepr
ocess

Micr
oscopical
l
y,t
hetransv
ersediameterofmy ocyt
esisincr
easedandther
eisprominent
nucl
earenl
argementandhyperchr
omasia(“boxcarnuclei
”)
,aswellasi
nter
cel
lul
arf
ibr
osis

Corpulmonaleresul
tsfr
om pulmonaryhypert
ensionduetopri
marylungparenchy
mal or
vascul
ardisor
ders.Hyper
trophyofbothther
ightventr
icl
eandtheri
ghtatr
ium i
scharact
eri
sti
c;
dil
ati
onalsomaybeseenwhenf ail
uresuper
venes.
●VALVULARHEARTDI
SEASE

St
enosisisthefai
lureofaval
vetoopencompl etel
y,obst
ructi
ngf
orwardfl
ow.Val
vul
ar
st
enosi
sisalmostal waysduetoapri
mar ycuspalabnormal
ityandi
svir
tual
l
yalwaysachr
oni
c
pr
ocess(e.g.
,cal
cifi
cati
onorval
vescarr
ing).

•Insuffici
encyr esult
sfrom fai
lureofav alvetoclosecompletel
y ,
ther
ebyal l
owing
regur git
ation(backflow)ofblood.Val v
ularinsuf
fici
encycanresultfrom ei
therint
ri
nsicdisease
oft hev al
v ecusps( e.g.
,endocardit
is)ordisrupt
ionofthesuppor t
ingstr
uctures(e.g.
,theaorta,
mitr alannulus,tendinouscords,papill
arymuscles,orventr
icul
arfreewal l
)withoutpri
mar y
cuspal i
njury

●Degener
ati
veVal
veDi
sease

Degener
ati
veval
vediseaseisat
erm usedtodescr
ibechangesthataf
fectt
hei
ntegr
it
yof
val
vul
arext
racel
l
ularmatri
x(ECM).Degener
ati
vechangesincl
ude

•Calci
fi
cat
ions,whichcanbecuspal
(typi
cal
l
yint
heaor
ti
cvalv
e)orannular(inthemi
tr
al
v
alve)Themitralannul
arcal
cif
icat
ionusual
lyi
sasy
mptomat
a i
cunlessi
tencroachesont
he

adj
acentconduct
ionsy
stem
pa

•Decr
easednumber
sofv
alv
efi
brobl
ast
sandmy
ofi
brobl
ast
s
ya

Cal
cif
icAor
ti
cSt
enosi
sCal
cif
icaor
ti
cdegener
ati
oni
sthemostcommoncauseofaor
ti
c
Si

st
enosi
s

Thehal
l
mar
kofcal
cif
icaor
ti
cst
enosi
sisheaped-
upcal
cif
iedmassesont
heout
fl
owsi
deof
t
hecusps

●My
xomat
ousMi
tr
alVal
ve

I
nmy xomat
ousdegener
ati
onoft
hemi
tr
alv
alv
e,oneorbot
hmi
tr
all
eaf
let
sar
e“f
loppy
”and
pr
olaps

●Rheumat
icVal
vul
arDi
sease

Rheumat
icfev
erisanacute,
immunologi
call
ymediat
ed,mul
ti
syst
em i
nfl
ammat
orydi
seaset
hat
occur
saf
tergroupAβ-hemolyt
icst
rept
ococcal
inf
ecti
ons

Iti
sassoci
atedwit
hinf
lammati
onofallpar
tsofthehear
t,butv
alv
ulari
nfl
ammat
ionand
scarr
ingpr
oducesthemostimpor
tantcl
i
nical
feat
ure

Themyo-car
dial
inf
lammat
oryl
esi
ons—cal
l
edAschof
fbodi
es—ar
epat
hognomoni
cfor
r
heumati
cfever
 Themosti mportantfunct
ionalconsequenceofrheumat i
cheartdi
seaseisv al
v ul
arst
enosis
andregur
gitat
ion;stenosi
stendstopr edominat
e.Themi tr
alval
vealoneisinvolvedin70%of
cases,wi
thcombinedmi t
ralandaorti
cdiseaseinanother25%;thetr
icuspi
dv alv
eusuallyisl
ess
fr
equentl
y(andlesssev er
ely
)involved;andthepul
moni cvalv
ealmostalway sescapesinjur
y

Ear
lyl
esi
oncausesmi
tr
alr
egur
git
ati
on

Whi
l
elat
elesi
oncausesmi
tr
alst
enosi
s

Cl
i
nical
Feat
ures

Acuterheumat
icf
everoccur
smostof
teni
nchi
l
dren;
thepr
inci
pal
cli
nical
mani
fest
ati
oni
s
car
dit
is.

Never
thel
ess,
about20%off
ir
stat
tacksoccuri
nadul
ts,
wit
har
thr
it
isbei
ngt
hepr
edomi
nant
f
eat
ure.

Al
thoughcul
tur
esar
enegat
ivef
orst
rept
ococci
att
het
imeofsy
mpt
om onset
,ser
um t
it
ers

t
ooneormor
est
rept
ococcal
ant
igens(
e.g.
,st
rept
oly
sinOorDNAase)usual
a l
yar
eel
evat
ed

Thedi
agnosisofacut
erheumaticfev
erismadebasedonser
ologi
cevi
denceofpr
evi
ous
pa

st
rept
ococcal
infect
ioni
nconjunct
ionwithtwoormoreoft
heso-
call
edJonescr
it
eri
a:
ya

(
1)cardi
tis;
(2)migr
atorypol
yarthr
it
isoflar
gejoi
nts;
(3)subcut
aneousnodul
es;
(4)er
ythema
margi
natum ski
nrashes;and(5)Sydenham chor
ea,
Si

Minorcri
ter
iasuchasfever
,ar
thr
algi
as,
ECGchanges,
orel
evat
edacut
ephaser
eact
ant
sal
so
canhelpsupportt
hediagnosi
s.

●I
nfect
iveEndocar
dit
is

Micr
obial
invasi
onofhear tval
vesormuralendocar
dium—oft
enwi t
hdestr
uct
ionoft
he
under
lyi
ngcardi
actissues—charact
eri
sti
cal
l
yr esul
tsi
nbulky
,fr
iabl
eveget
ati
onscomposedof

necr
oti
cdebr
is,
thr
ombus,
andor
gani
sms.

Acut
eendocar
dit
ishi
ghl
yvi
rul
entor
gani
sm at
tacki
ngapr
evi
ousl
ynor
mal
val
ve,

acut
eendocardi
ti
sthemorevi
rul
entS.aur
eus(
commont oski
n)canat
tackdef
ormedaswel
l
asheal
thyval
vesandisr
esponsi
blef
or10%to20%ofcasesover
a

Subacuteendocar
diti
sreferstoi
nfect
ionsbyorgani
smsoflowv i
rul
enceinvolv
inga
previousl
yabnormalheart,especi
all
yscarr
edordeformedval
vesFift
ypercentto60%ofcases
ofendocarditi
soccurr
ingondamagedordef or
medv al
vesarecausedbyStrept
ococcusvi
ri
dans,

Addi
ti
onal
bact
eri
alagent
sincl
udeent
erococci
andt
heso-
cal
l
edHACEKgr
oup(
Haemophi
l
us,
Act
inobaci
l
lus,
Car
diobact
eri
um,
Eikenel
l
a,andKi
ngel
l
a)

Cl
i
nical
Feat
ures

Fev
eri
sthemostconsi
stentsi
gnofi
nfect
iveendocar
dit
is.

Howev er
,insubacutedisease(particularl
yi ntheelderly),
f ev ermaybeabsent ,andtheonly
manif
estati
onsmaybenonspeci fi
cf atigue,wei ghtloss,andaf lul
ikesyndrome;
spl
enomegal yalsoiscommoni nsubacut ecases.Bycont r ast ,acut
eendocarditi
soften
manif
estswithast ormyonsetincludingr apidlydev el
opingf ev er ,
chill
s,weakness,andlassi
tude.
Murmursarepr esenti
n90%ofpat i
ent swi t
hl eft-
sidedlesions

●Noni
nfect
edVeget
ati
ons

●Nonbact
eri
alThr
ombot
icEndocar
dit
is

Nonbact
eri
alt
hromboti
cendocar
dit
is(
NBTE)i
schar
acteri
zedbythedeposit
ionofsmal
l(1t
o
5mm indiameter
)thr
omboti
cmassescomposedmainl
yoffi
bri
nandplat
elet
s

theconditi
onusual
lyisfoundonpreviousl
ynormal v
alv
es.Rat her,
hypercoagul
abl
estat
esare
theusualprecur
sortoNBTE; NBTElesionscanbecomecl i
nicall
ysigni
fi
cantbygiv
ingri
set
o
a
embolithatcancauseinfar
ctsi
nthebr ai
n,hear
t,andotherorgan
pa

●Li
bman-
SacksEndocar
dit
isLi
bman-
Sacksendocar
dit
isi
schar
act
eri
zedbyt
hepr
esenceof
ya

ster
il
evegetat
ionsontheval
vesofpat
ient
swithsy
stemiclupuser
ythemat
osust
hisi
sasa
Si

consequenceofimmunecomplexdeposit
ionSi
mil
arlesi
onscanoccurint
heset
ti
ngof
anti
phospholi
pidant
ibodysy
ndrome

●Car
cinoi
dHear
tDi
sease

Thecarci
noi
dsyndr
omer
esul
tsf
rom bi
oact
ivecompoundssuchasser
otoni
nrel
easedby
car
cinoi
dtumor
s

sy
stemi
cmani
fest
ati
onsi
ncl
udef
lushi
ng,
diar
rhea,
der
mat
it
is,
andbr
onchoconst
ri
cti
on

Themediator
selaboratedbycarci
noi
dtumor
sincl
udeserotoni
n(5-
hydr
oxy
try
ptami
ne)
,
kal
li
krei
n,br
adyki
nin,
histamine,
prost
agl
andi
ns,
andtachy
kinins.

●Pr
ost
het
icCar
diacVal
ves

Mechani
calv
alv
esarenowmostcommonl ydoubl
eti
l
tingdi
skdev
icesmadeofpy
rol
yti
c
car
bonbutr
equi
rechr
onicant
icoagul
ati
on,

Bi
oprosthet
icv
alv
esar
emanuf actur
edf
rom gl
utaral
dehyde-
fi
xedpor
cineorbov
inet
issues,
orcr
yopreserv
edhumanval
ves.Thesedonotr
equireanti
coagul
ati
on
 Inmechanicalval
ves,i
nfecti
veendocardi
ti
stypi
cal
lyinv
olv
esthesut
ureli
neandadjacent
peri
valvul
arti
ssue;t
heassociatedti
ssuechangescancausetheval
vet
odetach(paraval
vul
ar
l
eak).Inbiopr
osthet
icval
ves,theval
veleafl
etsaswel
l ast
heperi
val
vul
arti
ssuescanbecome
i
nfected.

●Car
diomy
opat
hy •Car
diomy
opat
hyi
sint
ri
nsi
ccar
diacmuscl
edi
sease;
ther
emaybe
speci
fi
ccauses,
ori
tmaybei
diopat
hic.

•Thet
hreegener
alpathophysi
ologiccategori
esofcardi
omyopat
hyar
edi
l
ated(
account
ing
f
or90%ofthecases),
hypertr
ophi
c, andrestri
cti
ve(
leastcommon).

•DCM r esult
si nsyst
oli
c(contr
acti
le)dysf
unct
ion.Causesi
ncl
udemyocar
dit
is,
toxi
c
exposures(e.g.,
alcohol
),andpregnancy.I
n20%to50%ofcases, mut
ati
onsaff
ecti
ng
cytoskel
etalproteinsar
eresponsibl
e.

•HCM resul
tsindiast
oli
c(relaxat
ion)dy
sfunct
ion.Vi
rt
uallyal
lcasesareduetoautosomal
dominantmutati
onsintheproteinsthatmakeupthecontracti
l
eapparatus,
inparti
cularβ-
myosinheavychain.
a
pa
•Restr
ict
ivecardi
omy opathyresul
tsi
nastiff
,noncompli
antmyocardi
um andcanbeduet
o
deposi
ti
ons(e.g.,
amy l
oid),
increasedi
nter
sti
ti
alfi
brosi
s(e.
g.,
duetoradi
ati
on),ort
o
ya

endomyocardial
scarr
ing.
Si

•●Myocar
dit
isi
smy ocar
dial
damagecausedbyi
nfl
ammat
oryi
nfi
l
trat
essecondar
ytoi
nfect
ions
orimmunereact
ions.

Coxsacki
evi
rusesAandBaret
hemostcommonpathogensintheUnit
edStat
es.Cl
i
nical
l
y,
myocardi
ti
scanbeasymptomat
ic,
giv
eri
set
oacut
ehear tf
ail
ure,orev
olv
etoDCM.

●Per
icar
dit
is

I
tmostoft
enisduet
ovir
ali
nfecti
on(ty
pical
l
ywi
thconcur
rentmy
ocar
dit
is)
,al
thoughbact
eri
a,
f
ungi
,orpar
asi
tesmayal
sobei nv
olv
ed.

I
nmostcases,peri
cardi
ti
sissecondaryt
oacut
eMI,cardi
acsurger
y,radi
ati
ontot
he
mediast
inum,
orprocessesinv
olv
ingothert
hor
aci
cst
ructures(
e.g.
,pneumoniaorpl
eur
it
is)
.

Ur
emi
aist
hemostcommonsy
stemi
cdi
sor
derassoci
atedwi
thper
icar
dit
is

Cl
i
nical
Feat
ures

Per
icar
dit
iscl
assi
cal
l
ymanif
est
swithaty
pical
chestpai
n(notr
elat
edt
oexer
ti
onandwor
se
i
nrecumbency),
andapromi
nentf
ri
cti
onrub
 P-
Rdepr
esssi
oni
scomonl
yseen,
STel
evat
ioni
sal
sopr
esent

●Per
icar
dial
Eff
usi
ons

Nor
mal l
y,t
heperi
car
dialsaccontai
nsatmost30t o50mLofcl
ear
,ser
ousfl
uid.Ser
ousand/or
f
ibr
inouseff
usi
onsinexcessofthisamountoccurmostcommonl
yint
heset
tingofper
icar
dial
i
nfl
ammat i
on

•Ser
ous:
congest
ivehear
tfai
l
ure,
hypoal
bumi
nemi
aofanycause

•Ser
osangui
neous:
bluntchestt
rauma,
mal
i
gnancy
,rupt
uredMIoraor
ti
cdi
ssect
ion

•Chy
lous:
medi
ast
inal
lymphat
icobst
ruct
ion

sl
owl
yaccumul
at-
ingef
fusi
ons—ev
enasl
argeas1000mL—canbewel
l
tol
erat
ed.

Bycont
rast
,rapi
dlydev
elopingcol
lect
ionsofasl
itt
leas250mL(e.
g.,
ruptur
edMIorr uptured
aorti
cdissect
ion)cansorestr
ictdi
astol
i
ccardiacf
il
li
ngastopr
oducepotenti
all
yfat
alcardiac
tamponade.
a
pa

●Met
ast
ati
cNeopl
asms
ya

Tumormetast
asesconst
it
utet
hemostcommonmalignancyoft
hehear
t;met
ast
ati
ccar
diac
l
esi
onsoccuri
nabout5%ofpati
ent
sdyi
ngofcancer
.
Si

Al
thoughanymal
i
gnancycansecondar
il
yinv
olv
ethehear
t

ndescendi
ngor derthesear
elungcancer,l
ymphoma,
breastcancer
,leukemi
a,mel
anoma,
hepat
ocell
ularcarci
noma,andcoloncancer

●Pr
imar
yNeopl
asms

Pri
marycar
diact
umorsar
euncommon; moreov
er,
mostalsoar
e(for
tunat
ely
)beni
gn.Thefiv
e
mostcommonhav enomal
ignantpot
ent
ial
andaccountf
or80%to90%ofallpr
imaryhear
t
tumor
s

.Indescendi
ngorderoffr
equency
,thesear
emy
xomas,
fibr
omas,
li
pomas,
papi
l
lar
y
f
ibroel
astomas,andrhabdomyomas.

Angi
osar
comasconst
it
utet
hemostcommonpr
imar
ymal
i
gnantt
umoroft
hehear
t

Myxomasarethemostcommonprimar
ytumor
soft
headul
thear
t.Roughl
y90%ar
eat
ri
al,
wi
tht
hel
eftat
ri
um account
ingf
or80%oft
hose

Rhabdomy
omasar
ethemostf
requentpr
imar
ytumor
soft
hehear
tini
nfant
sandchi
l
dren
●CARDI
ACTRANSPLANTATI
ON

Alt
houghpermanentventr
icularassistdeviceimplantati
onisincr
easi
nglyanopti
onfor
managementofend-stagehear tdisease,
cardiactransplant
ati
onremainsthet
reatmentof
choi
ceforpati
ent
swi t
hintractableheartfail
ure.

Theimmunosuppressi
onr
equir
edf
orall
ograftsur
viv
al al
soincr
easestheriskof
oppor
tuni
sti
cinf
ect
ionsandcer
tai
nmali
gnancies(e.
g.,Epst
ein-
Barrvi
rus–associ
ated
l
ymphoma)

Rej
ect
ioni
sdi
agnosedbyendomy
ocar
dial
biopsyoft
het
ranspl
ant
edhear
t.

Rej
ect
ioni
schar
act
eri
zedbyani
nter
sti
ti
all
ymphocy
tici
nfl
ammat
ion,
associ
atedmy
ocy
te
damage

•All
ogr
aftarteri
opathyi
sthesinglemostimportantl
ongter
ml i
mitat
ionforcardiac
t
ranspl
antat
ion.Iti
sacondi t
ionoflat
e,pr
ogressi
ve,dif
fusel
ystenosi
ngint
imal proli
fer
ati
oni
n
t
hecoronaryarteri
esleadi
ngt oi
schemici
njury
a
BLOODPATHOLOGY
pa
ya

REDCELLDI
SORDERS

pol
ycy
themi
a(ani
ncr
easei
nredcel
l
sal
soknownaser
ythr
ocy
tosi
s)
Si

Anemi
aisdef
inedasar
educt
ioni
ntheoxy
gen-
tr
anspor
ti
ngcapaci
tyofbl
ood,
whi
chusual
l
y

st
emsf
rom adecr
easei
nther
edcel
lmasst
osubnor
mal
lev
els

. Anemiacanr
esul
tfr
om bl
eedi
ng,
incr
easedr
edcel
ldest
ruct
ion,
ordecr
easedr
edcel
l
pr
oduct
ion

Mor
phol
ogy

•Mi
crocy
tic(
ir
ondef
ici
ency
,thal
assemi
a)

•Macr
ocy
tic(
fol
ateorv
itami
nB12def
ici
ency
)

•Nor
mocy
ticbutwi
thabnor
mal
shapes(
her
edi
tar
yspher
ocy
tosi
s,si
ckl
ecel
ldi
sease)

Cl
i
nical
Mani
fest
ati
ons

•Acut
e:shor
tnessofbr
eat
h,or
ganf
ail
ure,
shock

•Chr
oni
cPal
l
or,
fat
igue,
lassi
tudeWi
thhemol
ysi
s:j
aundi
ceandgal
l
stonesWi
thi
nef
fect
ive
er
ythr
opoi
esi
s:i
ronov
erl
oad,
hear
tandendocr
inef
ail
ure

HEMOLYTI
CANEMI
AS

hemol
yti
canemiasar
eassoci
atedwi
thery
throi
dhy
per
plasi
aint
hemar
rowandi
ncr
eased
number
sofret
icul
ocy
tesi
ntheperi
pher
alblood

Destr
ucti
onofr
edcel
lscanoccurwit
hint
hevascularcompar
tment(
int
rav
ascul
arhemol
ysi
s)or
wit
hinti
ssuemacr
ophages(
extr
avascul
arhemoly
sis).

i
ntravascul
arhemoly
sisleadstohemoglobinemia,
hemogl
obi
nur
ia,
andhemosi
der
inur
ia,
heptaglobi
niscompl
etel
ydeplet
edfrom theplasma,

Ext
rav
ascul
arhemol
ysi
s,t
hemor
ecommonmodeofr
edcel
ldest
ruct
ion,

Ext
ravascul
arhemolysi
sisnotassoci
atedwit
hhemoglobi
nemiaandhemogl
obi
nuri
a,but
of
tenproducesjaundi
ce,f
ormati
onofbil
lurbi
nri
chgal
lst
ones,hept
agl
obini
sdecr
eased

Her
edi
tar
ySpher
ocy
tosi
s

Her
edi
tar
yspher
ocy
tosi
siscausedbyabnor
mal
i
tiesi
nthemembr
aneskel
eton
a
pa
,
Themaj
ormembr
aneskel
etonpr
otei
nisspect
ri
n,

Themut
ati
onsi
nher
edi
tar
yspher
ocy
tosi
smostf
requent
lyi
nvol
veanky
rin,
band3,
and
ya

spect
ri
n
Si

Thecr
it
icalr
oleofthespl
eeni
sil
l
ustr
atedbythebenef
ici
aleff
ectofspl
enect
omy
;al
though
t
heredcel
l def
ectandspher
ocyt
esper
sist
,theanemi
aiscorrect
ed.

Splenomegal
yismor
ecommonandprominenti
nheredi
taryspherocy
tosi
schol
eli
thi
asi
s,
whichoccur
sin40%to50%ofpat
ient
swi
thheredi
tar
yspherocytosi
s.

e, redcell
sinher
edi
taryspher
ocytosi
shaveincr
easedosmoticf
ragi
l
itywhenpl
aced
i
nhy
potonicsal
tsol
uti
ons,acharact
eri
sti
cthatcanhel
pestabl
i
shthediagnosi
s

Thecl
ini
calcourseof
tenisstabl
ebutmaybepunct
uat
edbyaplasti
ccrises.Themostsev
ere
cr
isesar
etri
ggeredbyparvovi
rusB19,whi
chi
nfect
sanddest
roy
ser y
throblast
s

Si
ckl
eCel
lAnemi
a

•Autosomalr
ecessi
vedisor
derresul
ti
ngfr
om amutat
ioni
nβ-gl
obi
nthatcauses
deoxy
genatedhemoglobi
ntoself
-associ
atei
ntol
ongpol
ymerst
hatdi
stor
t(si
ckle)t
her
edcel
l

•Bl
ockageofv
essel
sbysi
ckl
edcel
l
scausespai
ncr
isesandt
issuei
nfar
cti
on,
par
ti
cul
arl
yof
t
hemar r
owandspleen
 •Redcel
lmembr anedamagecausedbyr
epeat
edbout
sofsi
ckl
i
ngr
esul
tsi
namoder
atet
o
sever
ehemoly
ticanemia

normaladul
tredcel
lcontai
ns96%HbA( α2β2)
,3%HbA2(α2δ2)
,and1%fet
alHb(HbF,α2γ2)
.
HbSisproducedbythesubsti
tut
ionofv
ali
neforgl
utami
caci
datthesixt
haminoaci
dresi
dueof
β-
globi
n

Si
ckl
ecel
lanemi
aist
hemostcommonf
ami
l
ial
hemol
yti
canemi
aint
hewor
ld.

si
gni
fi
cantpr
otect
iveef
fectofHbSagai
nstPl
asmodi
um f
alci
par
um mal
ari
a.

●Twomaj
orconsequencesar
isef
rom t
hesi
ckl
i
ngofr
edcel
l
s

chr
oni
chemol
yti
canemi
a

mi
crov
ascul
arobst
ruct
ions,
whi
chr
esul
tini
schemi
cti
ssuedamageandpai
ncr
ises

Cr
ewcutappear
anceonskul
l
,moder
atespl
eenomegal
y,gal
lst
oneshemosi
der
osi
s

Themostser
iousofthesearet
hevaso-
occlusi
ve,
orpai
n,cr
isesmostcommonl
yint
hebone
marrow,
wherei
toftenprogr
essestoi
nfar
cti
on.
a
pa
Afearedcompli
cati
onist
heacutechestsy
ndr
ome,
whi
chcanbet
ri
gger
edbypul
monar
y
i
nfect
ionsorfatembol
ifr
om i
nfar
ctedmarrow
ya

t
heacut
echestsy
ndr
omeandst
rokear
ethet
wol
eadi
ngcausesofi
schemi
a-r
elat
eddeat
h.
Si

si
ckl
ecel
ldi
seasear
epr
onet
oinf
ect
ionspneumococal
l
,sal
monel
l
a

Pr
enat
aldi
agnosi
sofsickl
ecellanemiacanbeper
for
medbyanal
yzi
ngf
etal
DNAobt
ainedby
amni
ocent
esi
sorbiopsyofchor
ionicvi
ll
i
.

pr
ophy
lact
ict
reat
mentwi
thpeni
cil
l
int
opr
eventpneumococcal
inf
ect
ions.

Amai
nst
ayoft
her
apyi
shy
droxy
urea,
a“gent
le”i
nhi
bit
orofDNAsy
nthesi
s.

Thal
assemi
a

Thethal
assemi
asar
einher
it
eddi
sor
der
scausedbymut
ati
onst
hatdecr
easet
hesy
nthesi
sofα-
orβ-
globi
nchai
ns

commonamongpopul
ati
onsi
nMedi
ter
ranean,
Afr
ican,
andAsi
anr
egi
onsi
nwhi
chmal
ari
ais
endemi
c

β-
Thal
assemi
a

:
(1)β0,
inwhi
chnoβ-
globi
nchai
nsar
epr
oduced;
and(
2)β+,
inwhi
cht
her
eisr
educed(
but
det
ect
abl
e)β-
globi
nsy
nthesi
s.

Personsinher
it
ingoneabnormal
all
elehav
eβ-
thal
assemi
ami
nor(
alsoknownasβ-
t
halassemiatrai
tasymptomati
c

Mostpeopl
einher
it
inganyt
woβ0andβ+al
l
eleshav
eβ-
thal
assemi
amaj
or;

per
sonsi
nher
it
ingt
woβ+al
l
eleshav
eami
l
derdi
seaset
ermedβ-
thal
assemi
aint
ermedi
a.

Mut
ati
onsl
eadi
ngt
oaber
rantRNAspl
i
cingar
ethemostcommoncauseofβ-
thal
assemi
a

Twomechani
smscont
ri
but
etot
heanemi
ainβ-
thal
assemi
a

(hypochromic)andsmall
insize(
micr
ocy
tic)
.Ev
enmor
eimpor
tanti
sthei
mbal
ancei
nβ-
globi
n
andα-globi
nchainsynt
hesis,

i
nef
fect
iveer
ythr
opoi
esi
s,ext
rav
ascul
arheamol
ysi
s,i
ronov
erl
oad

α-
Thal
assemi
a

Unl
ikeβ-t
hal
assemi
a,α-
thal
assemi
aiscausedmai
nlybydel
eti
onsi
nvol
vi
ngoneormor
eof
a
t
heα-globi
ngenes.
pa

Excessβ-gl
obi
nandγ-
globi
nchai
nsf
ormr
elat
ivel
yst
abl
eβ4andγ4t
etr
amer
sknownasHbH
ya

andHbBar t
Si

Tar
getcel
l
sar
epr
esen

CLI
NICALMANI
FESTATI
ON

●-Thalassemi
aminorandα-
thal
assemi
atr
ait(
causedbydel
eti
onoft
woα-
globi
ngenes)ar
e
of
tenasymptomati
c

β-Thal
assemiamajormanif
est
spost
nat
all
yasHbFsy
nthesi
sdi
mini
shes.Theyar
esust
ained
byrepeat
edbloodtr
ansfusi
ons,

Unlesspati
ent
saret
reatedaggr
essi
vel
ywi
thi
ronchel
ator
s,car
diacdy
sfunct
ionf
rom
secondaryhemochr
omatosis

Whenf
easi
ble,
bonemar
rowt
ranspl
ant
ati
onatanear
lyagei
sthet
reat
mentofchoi
ce

.HbHdisease(
causedbydelet
ionoft
hreeα-
globi
ngenes)andβ-
thal
assemi
aint
ermedi
aar
e
notassev
ereasβ-thal
assemi
amaj or
,

BetathalasemiaHbelect
rophor
esi
sshowspr
ofoundreduct
ionorabsenceofHbAand
i
ncreasedlevelsofHbF.TheHbA2level
maybenormalorincr
eased
 Pr
enat
aldi
agnosi
sofβ-
thal
assemi
acanbemadei
nspeci
ali
zedcent
ersbyDNAanal
ysi
s.

Thediagnosi
sofβ- t
hal
assemiaminori
smadebyHbel ectr
ophoresi
s,whi
chtypi
cal
l
yrev
eal
s
areducedlevel
ofHbA( α2β2)andanincr
easedlevelofHbA2(α2δ2).HbHdi
seasecanbe
di
agnosedbydet ect
ionofβ4tetr
amersbyelect
rophoresi
s.

Gl
ucose-
6-Phosphat
eDehy
drogenase

(
G6PD)Def
ici
ency

•X-
li
nkeddisor
dercausedbymutati
onsthatdest
abi
l
izeG6PD,
maki
ngr
edcel
l
ssuscept
ibl
e
t
ooxidantdamage,hei
nzbody,bi
tecel
lpr
esent

Par
oxy
smal
Noct
urnal
Hemogl
obi
nur
ia

acqui
redmut
ati
onsi
ngenePI
GA,
whi
chi
srequi
redf
ort
hesy
nthesi
sofphosphat
idy
li
nosi
tol
gl
ycan(PIG)
,

inor
dinat
elysensi
ti
vetocomplement
-medi
atedly
sisAnot
hercompl
i
cat
iont
hati
sof
ten
ser
iousandsomet i
mesfatal
isv
enousthrombosi
s
a
I
mmunohemol
yti
cAnemi
as
pa

Thedi
agnosi
sofimmunohemol
yti
canemiasdependsonthedetecti
onofant
ibodi
esand/or
ya

compl
ementonredcel
l
s.Thi
sisdonewit
hthedirectCoombsantigl
obul
i
ntest&indi
rect
coomb'
stest
Si

Warm ant
ibodyimmunohemol y
ticanemi
asar
ecausedbyi
mmunogl
obul
i
nG(
IgG)or
,rar
ely
,IgA
ant
ibodi
esthatareact
iveat37°C.

Coldant
ibodyimmunohemolyti
canemiasusual
lyarecausedbylow-
aff
ini
tyI
gM anti
bodi
est
hat
bindt
oredcellmembranesonlyattemper
atur
esbelow30° C,
suchasoccuri
ndistal
part
sof
thebody(e.
g.,
ear
s,hands,andtoes)i
ncol
dweat her

Microangi
opathi
chemol y
ticanemi
aisobser
vedi
npat
hologicstatesi
nwhichsmall
v essel
s
becomepar t
ial
lyobst
ructedornar
rowedbyl
esi
onst
hatpredisposepassi
ngredcel
lsto
mechanicaldamage

Mal
ari
a

themostimpor
tantisPlasmodium fal
ciparum,whichcausestert
ianmalari
a(fal
cipar
um
malari
a),
aseri
ousdisorderwi
thahi ghfatal
it
yrate.Theothert
hreespeciesofPl
asmodi um t
hat
i
nfecthumans—Pl
asmodi um malari
ae,Plasmodium viv
ax,andPlasmodium oval
e—cause
r
elati
vel
ybeni
gndisease.

Tr
opozoi
tthespeci
esofmal
ari
athati
sresponsi
blef
orani
nfect
ioncanbei
dent
if
iedi
n
appr
opr
iat
elyst
ainedt
hicksmear
sofper
ipher
albl
ood.

Fat
alf
alci
par
um mal
ari
aof
teni
nvol
vest
hebr
ain,
acompl
i
cat
ionknownascer
ebr
almal
ari
a

Anemi
asofDi
mini
shedEr
ythr
opoi
esi
s

I
ronDef
ici
encyAnemi
a

•Causedbychr
onicbleedi
ngorinadequat
eir
oni
ntake;
resul
tsi
ninsuf
fi
cienthemogl
obi
n
sy
nthesi
sandhypochromic,micr
ocyti
credcel
ls

Thenor
mal
tot
albodyi
ronmassi
sabout2.
5gf
orwomenand3.
5gf
ormen.

serum f
erri
ti
nlev
eli
sagoodmeasur
eofi
ronst
ores.Assessmentofbonemar
rowi
roni
s
anotherrel
iabl
e

I
ronbal
anceismai
ntai
nedl
argel
ybyr
egul
ati
ngt
heabsor
pti
onofdi
etar
yir
on,
I
roni
sabsor
bed
i
ntheduodenum

Wit
hl ong-
standi
nganemia,
abnormal
it
iesoft
hefinger
nail
s,i
ncl
udi
ngt
hinni
ng,
flat
teni
ng,
and
“
spooning,”mayappear
,PICAisanot
hercompli
cat
ionofit
a
pa
Diagnost
iccr
iter
iai
ncludeanemia,hy
pochr
omicandmicr
ocyt
icredcelli
ndi
ces,l
owser
um
f
erri
tinandi
ronlevel
s,l
owt r
ansfer
ri
nsatur
ati
on,
incr
easedt
otal
iron-
bindi
ngcapaci
ty,
ya

Anemi
aofChr
oni
cDi
sease
Si

•Causedbyinfl
ammator
ycy
toki
nes,
whichi
ncreasehepcidi
nlevel
sandt
her
ebysequest
er
i
roninmacrophages,
andal
sosuppr
esser
ythr
opoiet
inproduct
ion

Unl
i
keirondef
ici
encyanemi
a,however,st
oragei
ronint
hebonemar rowisi
ncreased,
the
ser
um fer
ri
ti
nconcent
rat
ioni
selev
ated,andthetot
ali
ron-
bindi
ngcapacit
yisr
educed

Megal
obl
ast
icAnemi
a

•Causedbydefi
cienci
esoffol
ateorvi
tami
nB12t
hatl
eadt
oinadequat
esy
nthesi
sof
t
hymidineanddef
ectiveDNArepl
icat
ion

•Resul
tsinenlar
gedabnor mal
hematopoi
eti
cpr
ecursors(megal
obl
ast
s),
inef
fect
ive
hematopoi
esis,
macr ocy
ticanemi
a,and(i
nmostcases)pancyt
openi
a

Tet
rahy
drof
olat
eact
sasanaccept
oranddonorofone-
car
bonuni
tsi
n

Unl
i
keb12deganemi
a,i
nfol
atedefanemi
aneur
ologi
cabnor
mal
i
tiesdonotoccur

Per
nici
ousanemi
aist
hemostf
requentcauseofv
itami
nB12def
ici
ency
 I
nb12demy
eli
nat
ionoft
hepost
eri
orandl
ater
alcol
umnsoft
hespi
nal
cor
d,

Thediagnost i
cf eaturesofperni
ciousanemiaincl
ude(1)lowser um vi
tami nB12l evel
s,(
2)
normal orelev at
edser um folat
elevels,
(3)ser
um anti
bodiestointr
insicfactor,(
4)moder at
eto
sev er
emegal oblasti
canemi a,(
5)leukopeniawit
hhypersegmentedgr anulocytes,and(6)a
dramat i
creticulocyti
cr esponse(wit
hin2t o3days)t
opar ent
eraladmi ni
strati
onofv it
aminB12.

Apl
ast
icAnemi
a

•Causedbybonemar rowfail
ure(hypocel
lul
ari
ty)duet
odiv
ersecauses,i
ncl
udi
ngexposures
t
ot oxi
nsandradi
ati
on,idi
osyncr
aticreact
ionstodrugsandv
iruses,
andinher
it
eddef
ectsin
t
elomeraseandDNAr epair

multi
pot
entmyel
oidstem cel
l
sar
esuppr
essed,
leadi
ngt
obonemar
rowf
ail
ureand
pancy
topeni
a.My
elophthi
sicAnemi
a

•Causedbyr
eplacementoft
hebonemar
rowbyi
nfi
l
trat
ivepr
ocessessuchasmet
ast
ati
c
car
cinomaandgranul
omatousdisease

•Leadstotheappear
anceofearl
yerythr
oidandgranulocy
ticprecursor
s
a
(
leukoer
ythr
oblast
osi
s)andtear
dropshapedredcel
lsintheperipheral
blood
pa

POLYCYTHEMI
A
ya

Pol
ycy
t hemi
a,orer
ythr
ocyt
osi
s,denotesanincr
easei
nr edcel
lsperuni
tvolumeofper
ipher
al
Si

bl
ood,usual
l
yinassoci
ati
onwit
hani ncreasei
nhemoglobinconcent
rat
ion

absol
ute(
def
inedasani
ncr
easei
ntot
alr
edcel
lmass)

Rel
ati
ve(
Reducedpl
asmav
olume(
hemoconcent
rat
ion)

Absol
utepol
ycy
themi
aisdescr
ibedas

pri
marywhentheincr
easedr
edcel
lmassr
esul
tsf
rom anaut
onomouspr
oli
fer
ati
onof
er
ythr
oidpr
ogeni
tor
s,and

secondar
ywhent
heexcessi
vepr
oli
fer
ati
onst
emsf
rom el
evat
edl
evel
sofer
ythr
opoi
eti
n

PLASMA RBCMass 02 EpOl

evel Associ
ati
on
VOLUM Sat
urat
ion

Rel
ati
ve ⬇ Dehy
drat
ion,
bur
ns

Appropri
ate ⬆ ⬇ ⬆ l
ung
absolut
e di
sease,congeni
tal
heartdi
seas,hi
gh
2ndar
ypol
y al
tit
ude
Inappropr
iat
e ⬆ ⬆ r
enal
cel
lca,
HCC
absolute
Hydr
onephrosi
s,
2ndar
y duet
oect opi
c
pol
ycyt
hemi
a EPOsecreti
on

Pol
ycy
themi
a ⬆ ⬆⬆ ⬇ EPO⬇ i nPCV
ver
a duetonegative
feedback
Pr
imar
y supressi
ngrenal
EPOpr oduct
ion

NON-
NEOPLASTI
CDI
SORDERSOFWHI
TECELLS

Leukopeni
aresul
tsmostcommonl
yfr
om adecr
easei
ngr
anul
ocy
tes,
themostnumer
ous
ci
rcul
ati
ngwhitecel
l
s.

Lymphopeniaismuchl esscommon;i
tisassoci
atedwi
thr
arecongeni
tal
immunodef
ici
ency
di
seases,advancedhumani mmunodef
ici
encyvi
rus(HI
V)i
nfect
ion,
andtreat
mentwi
thhigh
a
pa
dosesofcorti
coster
oids.

Absol
utel
ymphocy
tecount<1500cel
l
s/mm3
ya

(
<3000cel
l
s/mm³i
nchi
l
dren
Si

Neut
ropeni
a/Agr
anul
ocy
tosi
s

Areducti
oni
nthenumberofgr
anul
ocy
tesi
nbl
oodi
sknownasneut
ropeni
aor
,whensev
ere,
agr
anulocy
tosi
s

Absol
uteneut
rophi
lcount<1500cel
l
s/mm3

Sev
erei
nfect
ionst
ypi
cal
when<500cel
l
s/mm3

Decr
easedgranul
ocyt
eproduct
ion.Cl
i
nical
lyi
mportantr
educt
ionsi
ngr
anul
opoi
esi
sar
emost
of
tencausedbymarrowfai
l
ure(asoccursinapl
ast
icanemia)

I
ncreasedgranul
ocy
tedest
ructi
on.Thi
scanbeencounteredwithi
mmune- mediatedinj
ury
(
tri
ggeredinsomecasesbydrugs)ori
noverwhel
mingbacteri
al,
fungal
,orr
icket
tsiali
nfect
ions

Mar
rowhypercel
l
ular
it
yisseenwhentherei
sexcessi
veneut
rophi
ldest
ruct
ionori
nef
fect
ive
gr
anul
opoi
esi
s,suchasoccursinmegal
oblast
icanemia

necrot
izi
nglesi
onsofthegingi
va,f
loorofthemout
h,buccal
mucosa,
phar
ynx,
orot
hersi
tes
wi
thi
ntheoral
cavit
y(agr
anulocyt
icangina)
t
reat
mentef
for
tsmayal
soi
ncl
udegr
anul
ocy
tecol
ony
-st
imul
ati
ngf
act
or,

React
iveLeukocy
tosi
s

Ani
ncr
easei
nthenumberofwhi
tecel
l
sint
hebl
oodi
scommon

Such“
leukemoi
d”r
eact
ionsmustbedi
sti
ngui
shedf
rom t
ruewhi
tecel
lmal
i
gnanci
es

●I
nfect
iousMononucl
eosi
s

I
nfecti
ousmononucleosisisanacute,sel
f-
li
miteddiseaseofadolescent
sandy oungadult
s
thatiscausedbyEpstei
nBar rvi
rus(EBV),amemberoft heherpesv
irusfamil
y.Theinfect
ioni
s
character
izedby(
1)fever,sorethroat
,andgeneral
izedlymphadeni
ti
sand( 2)alymphocytosi
s
ofactivat
ed,CD8+Tcells

Tr
ansmi
ssi
ont
oaser
onegat
ive“
kissi
ngcousi
n”usual
l
yinv
olv
esdi
rector
alcont
act

Bcel
l
sthatar
elat
ent
lyi
nfect
edwi
thEBVunder
gopol
ycl
onal
act
ivat
ionandpr
oli
fer
ati
on,

Vi
russpecif
icCD8+Tcell
sappeari
ntheci
rcul
ati
onasat
ypi
cal
lymphocy
tes,
afi
ndi
ngt
hati
s
char
acter
ist
icofmononucl
eosi
s.
a
pa
Lymphadenopat
hyi
scommonandi
smostpr
omi
nenti
nthepost
eri
orcer
vical
,axi
l
lar
y,and
gr
oinregi
ons
ya

di
agnosisdependsont hefol
lowingfi
ndings,i
ni ncr
easingorderofspeci f
ici
ty:
(1)
Si

l
y mphocytosiswit
hthecharacteri
sti
catypi
cal l
ymphocy tesintheper i
pheralbl
ood,(2)aposit
ive
heterophi
lreact
ion(Monospottest),(
paulbunnel t
est)
and( 3)ar i
singti
terofanti
bodiesspeci
fic
forEBVant i
gens(vir
alcapsidanti
gens,ear
lyantigens,orEpstein-
Barrnuclearanti
gen).

EBVcausestypesofBcel
ll
ymphoma.Aseri
ouscompl
icati
oni
nthosel
ackingTcell
i
mmunity(suchasorganandbonemar
rowt
ranspl
antr
eci
pient
sandHIVi
nfect
edindi
vi
dual
s)

●acutemyeloidleukemi
as,i
nwhichimmatureprogeni
torcell
saccumulateint
hebonemar
row;
myelopr
oli
ferati
vedisor
der
s,inwhi
chaninappropri
ateincr
easeintheproduct
ionof
for
medbloodel ementsl
eadstoel
evatedbl
oodcellcounts;

●myel
odysplast
icsyndromes,whi
char
echar
act
eri
sti
cal
l
yassoci
atedwi
thi
nef
fect
ive
hemat
opoiesisandcytopeni
as.

●Hi
sti
ocy
ticneopl
asmsi
ncl
udepr
oli
fer
ati
vel
esi
onsofmacr
ophagesanddendr
it
iccel
l

Ly
mphoi
dNeopl
asms

●l
eukemi
as,
wit
hinv
olv
ementoft
hebonemar
rowandt
heper
ipher
albl
ood

●l
ymphomas,
tumor
sthatpr
oducemassesi
nly
mphnodesorot
hert
issues
 Becauseofthei
rov
erl
appingcli
nical
behavi
or,thevar
iousl
ymphoidneoplasmscanbe
distingui
shedwit
hcer
tai
ntyonlybythemorphologicandmolecul
archar
acteri
sti
csoft
hetumor
cells.

Twogr
oupsofl
ymphomasar
erecogni
zed:
Hodgki
nly
mphomasandnon-
Hodgki
n
l
ymphomas

Hodgki
n Non-
Hodgki
n

Locali
zed,singl
egroupofnodes;cont
iguous Mult
iplel
ymphnodesi
nvol
ved;
extranodal
spread(stageisst
rongestpr
edict
orof i
nvol
v ementcommon;
noncont
iguousspread
prognosis

Char
act
eri
zedbyReed-
Ster
nber
gcel
l
s Majori
tyi
nvol
veBcel
l
s;af
ewar
eofT-
cel
l
l
ineage

Bimodaldist
ributi
on–youngadul
thoodand> Canoccuri
nchi
l
drenandadul
ts.
55years;morecommoni nmenexceptfor
nodul
arsclerosingty
pe a
Associ
atedwi
thEBV. Maybeassoci
atedwi
thHI
Vandaut
oimmune
pa
di
sease
ya
Si

Nodul
arscl
erosi
sMostcommon

Ly
mphocy
ter
ichBestpr
ognosi
s

Ly
mphocy
tedepl
etedSeeni
nimmunocompr
omi
sedpat
ientwr
ostpr
ognosi
s

●Foll
i
cularLymphoma•Tumorcel
lsrecapi
tulat
ethegrowt
hpatter
nofnormalger
minalcenterB
cel
ls;mostcasesar
eassoci
atedwit
ha( 14;18)tr
ansl
ocat
iont
hatresul
tsi
ntheover
expressi
on
ofBCL2

●Mant l
eCellLymphoma•Thi
stumorofmatur
eBcellsAnassoci
ati
onwi t
han(11;
14)
transl
ocati
onthatr
esul
tsi
noverexpr
essi
onofcy
cli
nD1,aregul
atorofcel
lcy
clepr
ogressi
on,
is
recognized

●Di
ff
uselar
geB-
cell
lymphomav
Usuall
yol
deradul
ts,
but20%i
nchi
l
drenAl
ter
ati
onsi
nBcl
-2,
Bcl
-
6Mostcommontypeofnon-
Hodgki
nlymphomainadul
ts.

●Burki
ttl
ymphomaAdolescent
sory oungadul
tst
(8;
14)
—tr
ansl
ocat
ionofc-
myc(
8)andheav
y-
chai
nIg(14)
“Star
rysky
”appearance
●Mult
ipl
emy
elomaThemostfr
equentM pr
otei
nproducedbymyelomacell
sisIgG(
60%)
,
fol
l
owedbyI
gA(20%to25%)
;onlyr
arel
yareIgM,I
gD,orIgEM pr
otei
nsobserv
ed

Renal
dysf
unct
ioni
sacommon,
ser
iouspr
obl
em i
nmy
eloma.
areseen.

I
ncont
rastwi
thmul
ti
plemy
eloma,
lymphopl
asmacy
ticl
ymphomai
snotassoci
atedwi
th
l
yti
c

skel
etal
lesi
ons

Electr
ophoresi
soft heser
um anduri
nei sanimpor
tantdi
agnosti
ctool
.In99%ofcases,
ei
theramonocl onalcomplet
eimmunogl obul
inoramonoclonalf
reeimmunoglobul
inli
ght
chai
ni spresenti
ntheserum,theuri
ne,orboth

●Acutemyel
oidl
eukemias(
AMLs)Aggressi
vetumorscompri
sedofi
mmat
uremy
eloi
dli
neage
bl
ast
s,whi
chrepl
acethemarrowandsuppressnor
mal hemat
opoi
esi
s

●My el
oproli
ferati
vedi
sor der
sMy el
oidtumorsinwhichproducti
onofformedmy el
oidel
ement
s
i
si ni
ti
all
yincreased,l
eadingtohighbloodcountsandextramedull
aryhemat
opoiesi
sThemost
commonpat hogenickinasesareBCR-ABL(associat
edwi t
hCML)andmut atedJAK2
a
(associ
atedwi thpol
ycyt hemiaveraandpri
mar ymyelof
ibrosi
s
pa

Pr
othr
ombi
nti
me(
PT)
.Thi
stestassessest
heext
ri
nsi
candcommoncoagul
ati
onpat
hway
ya

Apr
olongedPTcanr
esul
tfr
om adef
ici
encyoff
act
orV,
VII
,orXorpr
othr
ombi
norf
ibr
inogen
Si

Prol
ongati
onofPTTcanbecausedbyadef
ici
encyoff
act
orV,
VII
I,
IX,
X,XI
,orXI
Ior
pr
othrombinorf
ibr
inogen

Par
ti
alt
hrombopl
ast
int
ime(
PTT)
.Thi
stestassessest
hei
ntr
insi
candcommoncoagul
ati
on
pat
hways

def
ici
enci
esofpl
atel
ets(
thr
ombocy
topeni
a)ar
eani
mpor
tantcauseofbl
eedi
ng.

●.DICiscausedbyt hesystemi cactiv

ationofcoagul
ati
onandr
esul
tsintheformati
onof
thr
ombi t
hroughoutthemi crocir
culati
on.Asaconsequence,pl
atel
etsandcoagul
ati
onf
actor
s
areconsumedand, secondar i
l
y,fi
brinoly
sisisact
ivat
ed

I
nDI
CInv
olv
ementoft
headr
enal
glandscanpr
oducet
heWat
erhouse-
Fri
der
ichsensy
ndr
ome

DI
Cmaycont
ri
but
etot
hedev
elopmentofSheehanpost
par
tum pi
tui
tar
ynecr
osi
s

acuteDI
C( e.
g.,t
hatassoci
atedwithobst
etri
ccompli
cat
ions)i
sdominat
edbyableedi
ng
di
athesi
s,whereaschroni
cDIC( e.
g.,
asoccursint
hosewit
hcancer)t
endstomani
festwi
th
si
gnsandsy mptomsr el
atedt
ot hr
ombosis.
 Laborat
oryev
aluati
oninDICthrombocytopeni
aandprolongat
ionoft
hePTandt
hePTT
(
from depl
eti
onofplat
elet
s,cl
ott
ingfact
ors,andf
ibr
inogeBT⬆ ⬆ ⬆

●Isolat
edt
hrombocytopeni
aisassoci
atedwi
thabl
eedi
ngt
endencyandnor
mal
coagul
ati
on
tests⬇ pl
etel
etcount⬆ BT

t
hrombocy
topeni
aisoneoft
hemostcommonhemat
ologi
cmani
fest
ati
onsofAI
DS

Acut
eITPi
sasel
f-
li
mit
edf
orm seenmost
lyi
nchi
l
drenaf
terv
iral
inf
ect
ions.

Ant
ibodi
esdi
rect
edagai
nstpl
atel
etmembr
anegl
ycopr
otei
nsI
Ib/
II
IaorI
b/I
Xcompl
exescan
bedet
ectedinr
oughl
y80%ofcauseofchr
oni
c

Thespleeni
sanimpor
tantsi
teofanti
plat
eletant
ibodypr
oduct
ionandt
hemaj
orsi
teof
dest
ruct
ionoft
heIgG-
coatedpl
atel
ets

COAGULATI
ONDI
SORDERS

●VwD

Theclassicandmostcommonv ar
iantofvonWill
ebr
anddi
sease(t
ypeI
)isanaut
osomal
a
dominantdisor
deri
nwhichthequant
ityofci
rcul
ati
ngvWFisr
educed.
pa

TypeII(
vwb)i
sdi
vi
dedi
ntosever
alsubt
ypeschar
act
eri
zedbyt
hesel
ect
ivel
ossofhi
gh
ya

molecul
ar-
wei
ghtmul
ti
mer
sofv WF
Si

●Hemophili
aA(VI
II
)isthemostcommonher
edit
arycauseofser
iousbl
eedi
ng.I
tisanX-
li
nked
recessi
vedi
sor
dercausedbyr
educedf
act
orVII
Iact
ivi
ty.

Hemophi
ll
i
aAeasybr
uisi
ngandmassi
vehemor
rhageaf
tert
raumaoroper
ati
vepr
ocedur
es.
Pat
echi
aear
eabsent

Speci
fi
cassay
sforf
act
orVI
IIar
eusedt
oconf
ir
mthedi
agnosi
sofhemophi
l
iaA,

PTT⬆ ⬆ ⬆

Hemophi
l
iaAi
str
eat
edwi
thf
act
orVI
IIi
nfusi
ons.Hi
stor
ical
l
y,f
act
orVI
IIwaspr
epar
edf
rom
humanpl
asma

●Hemophi
li
aB—FactorI
XDefi
ciencyX-l
inkeddisorderePTTi
sprol
onged.Thedi
agnosi
sis
madeusi
ngspeci
fi
cassaysoff
actorIX.Iti
streatedbyinf
usi
onofr
ecombinantf
actorI
X.

TTP: Causedbyacquir
edori
nher
it
eddef
ici
enci
esofADAMTS13,
apl
asmamet
all
opr
otease
⬇ pl
eteletcount⬆ BT

Ber
nard-
Soul
i
ersyndromeDef
ectinplatel
etpl
ugf
ormat
ion.Lar
gepl
atel
ets.
GpI
bdef
ecti
n
pl
atel
et-
to-
vWFadhesi
on⬇ plet
eletcount⬆ BT
 Massi
vespl
enomegal
y(wei
ghtmor
ethan1000g)

•My
elopr
oli
fer
ati
vedi
sor
der
s(chr
oni
cmy
elogenousl
eukemi
a,pr
imar
ymy
elof
ibr
osi
s)

●Thy
micHy
per
plasi
a

Thymicenl
argementof
tenisassoci
atedwit
hthepresenceofl
ymphoidf
olli
cles,
orger
minal
cent
ers,
wit
hinthemedull
a.Thesegerminal
cent
erscontainr
eact
iveBcel
ls,

●Thy
momasar
etumor
soft
hymi
cepi
thel
i
alcel
l
s

Beni
gnorencapsul
atedt
hymoma:
cyt
ologi
cal
l
yandbi
ologi
cal
l
ybeni
gn •Mal
i
gnant
t
hymoma

Ty
peI
:cy
tol
ogi
cal
l
ybeni
gnbuti
nfi
l
trat
iveandl
ocal
l
yaggr
essi
ve

Ty
peI
I(t
hymi
ccar
cinoma)
:cy
tol
ogi
cal
l
yandbi
ologi
cal
l
ymal
i
gnant

mostcommonlymy
ast
heni
agr
avi
s,i
nwhi
chaconcomi
tantt
hymomawasdi
scov
eredi
n15%
t
o20%ofpati
ents. a
Bl
oodt
ransf
usi
ont
her
apy
pa

PackedRBCsHbandO2car
ryi
ngcapaci
tyAcut
ebl
oodl
oss,
sev
ereanemi
a
ya

Pl
atel
etsplateletcount(∼5000/
mm3/
uni
t)St
opsi
gni
fi
cantbl
eedi
ng(
thr
ombocy
topeni
a,
Si

qual
i
tati
veplateletdefect
s)

Fr
eshfrozenplasma/pr
othrombincompl exconcentratecoagul
ati
onfact
orlevel
s;FFP
cont
ainsal
lcoagul
ati
onfactor
sandpl asmapr otei
ns;PCCgener al
l
ycontai
nsfactorsI
I,VI
I,
IX,
andX,aswellasprot
einCandSDI C,cirr
hosis,i
mmedi ateanti
coagul
ati
onreversal

Cryopr
ecipit
ateContainsf
ibr
inogen,
fact
orVI
II
,factorXI
II
,vWF,
andf
ibr
onect
inCoagul
ati
on
f
actordefi
cienci
esinvolv
ingfi
bri
nogenandfact
orVIII

Bl
oodtransf
usionri
sksincl
udeinf
ecti
ontr
ansmissi
on(
low)
,tr
ansf
usi
onr
eacti
ons,i
ron
ov
erl
oad(mayl eadto2°hemochromatosi
s),
hypocal
cemi
a(ci
tr
atei
saCa2+chel
ator
),and
hy
perkal
emia(RBCsmayl yseinol
dbloodunit
s

Lungs

●Thehi
stol
ogi
cmani
fest
ati
onofARDSi
nthel
ungsi
sknownasdi
ff
useal
veol
ardamage(
DAD

Neut
rophi
l
sar
ethoughtt
ohav
eani
mpor
tantr
olei
nthepat
hogenesi
sofARDS

I
nARDsThemostcharact
eri
sti
cfi
ndi
ngi
sthepr
esenceofhy
ali
nemembr
anes,
par
ti
cul
arl
y
l
i
ningt
hedi
stendedal
veol
arduct
s
●hemaj
ordi
ff
useobst
ruct
ivedi
sor
der
sar
eemphy
sema,
chr
oni
cbr
onchi
ti
s,br
onchi
ect
asi
s,and
ast
hma.

I
N obstructi
vedi
sordersFEV1)
,issi
gni
fi
cant
lydecr
eased.Thus,
ther
ati
oofFEVt
oFVCi
s
charact
eri
stical
l
ydecreased.

i
ndi
ff
user
est
ri
cti
vedi
seases,
FVCi
sreducedandr
ati
oofFEVt
oFVCi
snearnor
mal
.

●Emphy sema( pi
nkpuf
fer
)ischar
acteri
zedbyabnormalper
manentenl
argementoft
heair
spacesdist
altotheter
minalbr
onchi
oles,accompani
edbydest
ruct
ionofthei
rwal
l
swit
hout
si
gnifi
cantfi
brosi
s.

Cent
ri
LobularEmphysemaThecentr
alorproxi
malpar
tsoft
heaci
ni,
for
medbyr
espi
rat
ory
br
onchi
oles,
areaffect
ed,whi
l
edist
alal
veoli
arespar
ed

Centr
iLobul
arEmphy
semamostcommonl
yseenasaconsequenceofci
gar
ett
esmoki
ngi
n
peopl
e

I
npanacinar(
panl
obular)emphysema,t
heaci
niar
euni
for
mlyenl
arged,
from t
hel
evel
oft
he
r
espir
ator
ybronchi
olet
ot heter
minalbl
i
ndalv
eoli
a
panaci
narmorecommonl yi
nthel
owerl
ungzonesandi
sthet
ypeofemphy
semat
hatoccur
s
pa

i
nα1-anti
tr
ypsi
ndefi
ciency
ya

I
ndist
alaci
nar(
paraseptal
)emphy
sema,
thepr
oxi
mal
por
ti
onoft
heaci
nusi
snor
mal
butt
he
Si

di
stal
parti
spri
mari
lyinvol
ved

Lossofel
ast
icTi
ssuei
nemphy
sema,
Dyspneausual
l
yist
hef
ir
stsy
mpt
om

●Chroni
cBronchi
ti
s( bl
uebl
oat
er)def
inedbythepresenceofaper
sist
entpr
oduct
ivecough
foratl
east3consecuti
vemont
hsinatleast2consecut
ivey
ear
s.

Ci
gar
ett
esmoki
ngi
sthemosti
mpor
tantunder
lyi
ngr
iskf
act
or;
airpol
l
utant
sal
socont
ri
but
e.

Chr
oni
cobstruct
ivecomponentl
argel
yresul
tsf
rom smal
lai
rwaydi
sease(
chr
oni
c
br
onchi
oli
ti
s)andcoexi
stentemphy
sema.

•Histol
ogicexaminat
iondemonstrat
esenl
argementofmucus-
secr
eti
nggl
ands,
gobl
etcel
l
metaplasi
a,andbronchi
olarwal
lfi
brosi
s.

●AsthmaThehal l
mar ksofthediseasear
eintermit
tentandrev
ersibl
eai
rwayobst
ruct
ion,
chroni
cbronchi
alinf
lammat ionwitheosi
nophil
s,br
onchialsmoothmusclecel
lhy
pert
rophyand
hyperr
eact
ivi
ty,
andincreasedmucussecr et
ion

Eosi
nophil
sar
ekeyi
nfl
ammatorycel
l
sfoundinalmostal
lsubt
ypesofasthma;eosi
nophil
pr
oductssuchasmaj
orbasi
cpr
oteinar
eresponsi
blef
orair
waydamage.Presenceofchar
cot
l
aydoncel
l
s

char
act
eri
sti
cmor
phol
ogi
cchangesi
nast
hma,
col
l
ect
ivel
ycal
l
ed“
air
wayr
emodel
i
ng,
”

●Bronchi
ect
asisistheper
manentdil
ationofbronchiandbr
onchiol
escausedbydest
ruct
ionof
themuscleandthesupport
ingel
asti
ctissue,
result
ingfr
om orassoci
atedwi
thchr
onic
necrot
izi
nginf
ecti
onsitaf
fect
slowerlobe

Thecondi
ti
onst
hatmostcommonl
ypr
edi
sposet
obr
onchi
ect
asi
sincl
ude:

•Bronchi
alobstr
ucti
on.Incysti
cfi
brosi
s,I
nimmunodefi
ciencystat
esKartagenersy
ndr
ome
Necroti
zi
ng,orsuppurat
ive,
pneumonia,part
icul
arl
ywi
thv i
rul
entorgani
smssuchas
Staphyl
ococcusaureusorKlebsi
ell
aspp

●Idi
opathi
cpul monaryfi
brosi
s(I
PF),alsoknownascryptogenicf
ibr
osi
ngalveol
it
is,
ref
erstoa
pulmonarydisorderofunknowneti
ology.I
tischar
act
erizedbypat
chybutpr
ogr essi
vebil
ater
al
i
nterst
it
ialf
ibrosis,

Theradi
ologi
candhistol
ogi
cpatter
noffi
brosi
sisr
efer
redt
oasusual
int
erst
it
ial
pneumoni
a
(
UIP),
whichisrequi
redfort
hediagnosi
sofI
PF
a
I
PFhav
eappear
anceofcobbl
est
oneswi
thl
owerl
obepr
edomi
nance,
(honey
combf
ibr
osi
s)
pa

I
PFhav
echar
act
eri
sti
c“dr
y”or“
Vel
cro”
-l
ikecr
ackl
esdur
ingi
nspi
rat
ion.
ya

●Nonspeci
fi
cInter
sti
ti
alPneumoni
aThefi
brosi
ngpatter
nconsi
stsofdi
ff
useorpat
chy
Si

i
nter
sti
ti
alf
ibrosi
s,wi
thoutthet
empor
alhet
erogenei
tychar
act
eri
sti
cofUIP

●Pneumoconi
osi
sisater
m or
igi
nal
l
ycoi
nedt
odescr
ibet
henon-
neopl
ast
icl
ungr
eact
iont
o
i
nhalat
ionofmi
neral
dust
s.

Tobaccosmoki
ngwor
senst
heef
fect
sofal
li
nhal
edmi
ner
aldust
s

●Pul
monar
yant
hracosi
sist
hemostinnocuouscoal
inducedpul
monaryl
esi
oni
ncoal
miner
s
andal
soi
scommonlyseeni
nal
lurbandweller
sandtobaccosmoker
s.

Si
mpl
eCWPi
schar
act
eri
zedbycoal
macul
esandt
hesomewhatl
argercoal
nodul
e

●Si
li
cosi
sisthemostcommonpneumoconi
osi
sint
hewor
ld,
andcr
yst
all
i
nesi
l
ica(
e.g.
,quar
tz)
i
stheusualcul
pri
t.

Si
l
icosi
sisassoci
atedwi
thani
ncr
easedsuscept
ibi
l
ityt
otuber
cul
osi
s

●Asbest
osi
sismar
kedbydi
ff
usepul
monar
yint
erst
it
ial
fibr
osi
s.

Pleur
alpl
aquesarethemostcommonmani f
est
ati
onofasbest
osexposur
emostf
requent
ly
ontheanter
iorandposter
olat
eral
aspect
soft
hepari
etal
pleur
a
 Cigaret
tesmoki
ngincr
easestheri
skoflungcanceri
ntheset
ti
ngofasbestosexposur
e;
moreover,ev
enfamil
ymember sofworker
sexposedtoasbest
osareati
ncreasedri
skfor
cancer.

●sarcoi
dosi
sisamul
ti
system di
seaseofunknownet
iol
ogychar
act
eri
zedbynoncaseat
ing
granul
omasinmanyt
issuesandorgans

Thediagnost
ichi
stopat
hol
ogi
cfeat
ureofsar
coi
dosi
sist
henoncaseat
ingepi
thel
i
oid
gr
anuloma

ast
eroidbodi
es,
stel
lat
eincl
usi
onsencl
osedwi
thi
ngi
antcel
l
s.Thei
rpr
esencei
snotr
equi
red
f
ordiagnosi
sofsarcoi
dosi

di
ff
useint
erst
it
ial
fibr
osi
s,r
esult
ingi
naso-cal
l
edhoney
combl ung.
Int
rat
hor
aci
chi
l
arand
par
atr
acheal
lymphnodesareenlar
gedin75%to90%ofpati
ent
s,

Er
ythemanodosum,
thehal
l
mar
kofacut
esar
coi
dosi
s,

Cli
nicalmanifest
ati
onsincludelymphnodeenlargement
,eyei
nvol
vement( si
ccasy ndr
ome
[
dryeyes],i
ri
ti
s,orir
idocycl
it
is),ski
nlesi
ons(er
ythemanodosum,pai
nlesssubcutaneous
a
nodul
es),andvisceral(
li
ver
,skin,marrow)i
nvolv
ement
pa

●Unli
kebronchi
alasthma,i
nwhichbronchiar
ethefocusofi
mmunologi
cal
l
ymedi
atedi
njur
y,
ya

thedamageinhypersensi
ti
vi
typneumoniti
soccur
satthelev
elofal
veol
i
Si

Themostst r
iki
nghist
ologi
cfeat
ureofDIPistheaccumulat
ionofl
argenumbersof
macrophageswi t
habundantcyt
opl
asm contai
ningdust
y-br
ownpigment(smoker
’s
macrophages)i
nt heai
rspaces

●Pul
monaryEmboli
sm Moret
han95%ofall
pulmonaryembol
iar
isefrom thr
ombiwit
hinthe
l
argedeepvei
nsofthel
owerl
egs,
typi
cal
l
yorigi
nat
ingint
hepopl
iteal
v ei
nandlar
gervei
ns
abovei
t

•Mostpul monar
yemboli(60%t
o80%)arecli
nical
l
ysi
lentbecauset
heyar
esmal l
,
In5%of
cases,suddendeat
hpat
ient
swhohaveexperi
encedonepulmonaryembol
ism hav
ea30%
chanceofdev el
opi
ngasecond.

Riskf act
orsi
ncl
udeprolongedbedr
est,
legsur
ger
y,sever
et r
auma,
CHF,useoforal
contracepti
ves(
especi
all
ythosewithhi
ghestr
ogencontent
),di
ssemi
nat
edcancer
,andgenet
ic
causesofhy per
coagul
abil
ity

●Pul
monaryhypert
ensi
onmostoftensecondar
ytoadecreaseinthecross-
sect
ional
areaoft
he
pul
monar
yv ascul
arbed,ort
oincr
easedpulmonar
yvascul
arbloodflow

primar
y”i
mmune-mediat
eddi
seasest
hatmani
festast
het
ri
adofhemopt
ysi
s,anemi
a,and
di
ffusepul
monar
yinf
il
tr
ate
●Goodpastur
esyndrome, t
heprot
ot ypedi
sorderofthisgroup,i
sanuncommonbuti nt
rigui
ng
condi
ti
oncharacter
izedbyaproli
ferati
ve,
usuall
yrapidlyprogr
essi
ve,
glomer
ulonephri
ti
sand
hemorrhagi
cint
erst
iti
alpneumoniti
s.

●Pneumoni
acanbev
erybr
oadl
ydef
inedasanyi
nfect
ioni
nthel
ung

Br
onchopneumoniai
mpl
i
esapat
chydi
str
ibut
ionofi
nfl
ammat
iont
hatgener
all
yinv
olv
es
morethanonelobe

LobarPneumoni
ainv
olv
eonel
obeandshowsl
obul
erconsol
i
dat
ion

St
rept
ococcuspneumoni
aei
sresponsi
blef
ormor
ethan90%ofl
obarpneumoni
as

H.i
nfl
uenzaei
sthemostcommonbact
eri
alcauseofacut
eexacer
bat
ionofCOPD

Al
ongwi
thS.pneumoni
aeandH.inf
luenzae,
M.cat
arr
hali
sconst
itut
esoneoft
het
hreemost
commoncausesofot
it
ismedi
a(i
nfect
ionofthemi
ddleear
)inchil
dren.

•S.aur
eusisanimport
antcauseofsecondar
ybact
eri
alpneumoni
ainchi
l
drenandheal
thy
adul
tsaft
ervi
ral
respi
rat
oryi
ll
nesses
a
•K.pneumoni
aei
sthemostf
requentcauseofgr
amnegat
ivebact
eri
alpneumoni
a
pa

Pseudomonaspneumoni
aalsoiscommoninper
sonswhoar
eneutropeni
c,usual
l
y
ya

secondar
ytochemother
apy
;invi
cti
msofext
ensi
veburns;
andi
npat
ientsrequi
ri
ngmechani
cal
venti
l
ati
on
Si

Legionell
apneumoni
aiscommoninpersonswi t
hsomepredi
sposi
ngcondit
ionsuchas
cardi
ac,renal
,i
mmunologi
c,orhemat
ologi
cdisease.Or
gant
ranspl
antr
eci
pient
sareparti
cul
arl
y
suscepti
ble.

Themostcommoncausesofat y
pical
pneumoni
asi
ncl
udethosecausedbyM.pneumoni
ae,
vi
rusesincl
udinginfl
uenzavi
rusest
ypesAandB,humanmetapneumovi
rus,
C.pneumoni
ae,
and
C.burneti
i(agentofQfever
)

S.aureusar
ethemostcommonisol
ates;inhospi
tal
aqui
redpneumoni
aot
her
sar
e,Gr
am-
negat
iverods(
membersofEnt
erobact
eri
aceaeandPseudomonasspp

●Lungabscessref
erst
oalocal
izedareaofsuppur
ati
venecr
osi
swi t
hint
hepul
monar
y
parenchy
ma,resul
ti
ngi
nthefor
mat i
onofoneormor elar
gecav
iti
es.

●Pulmonar
yabscessesr
esul
ti
ngf
rom aspi
rat
ionofi
nfect
ivemat
eri
alar
emuchmor
ecommon
ontheri
ghtsi
de

Anaer
obi
cbact
eri
aar
epr
esenti
nal
mostal
ll
ungabscesses,
 Occasi
onal
ly,
abscessesrupt
urei
ntothepleur
alcav
ityandpr
oducebr
onchopl
eur
alf
ist
ulas,
t
heconsequenceofwhichispneumothoraxorempyema

●Worl
dHealthOrgani
zat
ion(
WHO)est
imat
esthattuber
culosi
scauses6%ofalldeaths
wor
ldwide,
makingitt
hemostcommoncauseofdeathresul
ti
ngfr
om asingl
einfect
iousagent
.

Tubercul
osisi
sachroni
cgr
anul
omatousdiseasecausedbyM.tuber
cul
osi
s,usual
l
y
af
fecti
ngthelungs,
butvi
rt
ual
l
yanyext
rapul
monar yorgancanbei
nvolv
edini
solat
edinf
ect
ion

Thehist
opathol
ogichal
lmar
kofhostr
eact
iontotuber
culosi
sinimmunocompet
entper
sons
i
sthepresenceofgranul
omas,usual
l
ywit
hcentr
alcaseat
ingnecrosi
s

whi
chconsi
stofepi
thel
i
oidhi
sti
ocy
tesandmul
ti
nucl
eat
egi
antcel
l
s.

combinat
ionofpar
enchy
mal
lesi
onandnodal
inv
olv
ementi
sref
err
edt
oast
heGhon
complex

Secondar
ytuber
cul
osi
sist
hepat
ter
nofdi
seaset
hatar
isesi
napr
evi
ousl
ysensi
ti
zedhost

Secondar
ypul
monar
ytuber
cul
osi
siscl
assi
cal
l
ylocal
i
zedt
otheapexofoneorbot
hupper
l
obes.
a
pa

●Nontuberculousmy cobact
eri
amostcommonlycausechronicbutcli
nical
l
ylocal
ized
pul
monar ydiseaseinimmunocompetentper
sons,
mostf r
equentl
yincl
udeMy cobacter
ium
ya

avi
umintracell
ular
e(alsocal
ledM.av
ium compl
ex)
,My cobact
eri
um kansasii,
and
Si

Mycobacterium abscessus

●Pneumocyst
isPneumoni
aP.j
i
rov
eci(
former
lyknownasP.cari
nii
),anopport
uni
sti
cinf
ect
ious
agentf
ormerl
yconsi
der
edtobeaprot
ozoan,
isnowclassi
fi
edasaf ungus.

●Candi
daalbi
cansisthemostcommondisease-
causi
ngf
ungus.I
tisanor
mal
inhabi
tantoft
he
or
alcavi
ty,
gastr
oint
esti
nal
tract
,andv
agi
nainmanypeople

Themostcommonpr esentati
onwithcandidi
asisist
hatofasuper f
ici
ali
nfect
iononmucosal
surf
acesoft
heor
alcavi
ty(thrush),
Candi
dav agini
ti
sisanextremelycommonf orm of v agi
nal
i
nfecti
oni
nwomen,especial
lythosewhoar ediabeti
corpregnantoronoralcont
racept
ivepil
l
s.

Candi
daesophagi
ti
siscommoni
npat
ient
swi
thAI
DSandi
nthosewi
thhemat
oly
mphoi
d
mali
gnanci
es.

●Cr
ypt
ococcosisalmostex
clusi
velymanif
est
sasanoppor
tuni
sti
cinf
ecti
oni
n
i
mmunocompr omisedhost
s,part
icul
arl
ypati
ent
swi
thAIDSorhematol
ymphoi
d

mal
i
gnanci
es

●TheOppor
tuni
sti
cMol
dsMucor
mycosi
sandi
nvasi
veasper
gil
l
osi
sar
euncommoni
nfect
ions
al
mostalwaysli
mitedtoimmunocompromisedhosts,
par
ti
cul
arl
yt hosewit
hhematol
ymphoid
mali
gnanci
esorprofoundneutr
openi
a,t
hoseundergoi
ngcor
ti
costeroidt
herapy
,oral
l
ogenei
c
st
em cel
ltr
anspl
antrecipi
ent
s.

●Aspergi
l
loma( “
fungusbal
l”
)for
mationoccursbycoloni
zati
onofpreexi
sti
ngpul
monar
y
cavi
ti
es(e.g.
,ect
ati
cbronchiorl
ungcyst
s,postt
ubercul
osiscav
itar
ylesi
ons)byt
hef
ungus

●LungTumor
s

Roughl
y95%ofpr i
marylungtumorsarecarci
nomas;ther
emaini
ng5%const
it
utea
miscel
l
aneousgroupthati
ncludescar
cinoi
ds,mesenchy
mal mal
i
gnanci
es(
e.g.
,fi
brosar
comas,
l
eiomyomas),
lymphomas,andaf ewbenignlesi
ons.

Themostcommonbeni gntumorisaspheri
cal,small(3to4cm),di
scret
e“hamartoma”t
hat
oftenshowsupasaso- cal
ledcoi
nlesi
ononchestr adiogr
aphs.I
tconsi
stsmainl
yofmature
carti
lage,butt
hisi
sof
tenadmixedwithfat
,fi
broustissue,andbl
oodvessel
sinvari
ous
proporti
ons

l
ungwereclassi
fi
edint
ot wobroadgr
oups:
smallcel
llungcancer(
SCLC)andnon–small
cel
l
l
ungcancer(
NSCLC) ,wi
ththelat
teri
ncl
udi
ngadenocar
cinomasandsquamousandlarge
a
pa
cel
lcar
cinomas
ya

Thekeyreasonf orthi
shi
stori
caldi
sti
nct
ionwast hatv
irt
uall
yall
SCLCshavemet
astasi
zed
bythet
imeofdi agnosisandhencearenotcurablebysur
gery.Ther
efor
e,t
heyar
ebesttr
eat
ed
Si

bychemotherapy,withorwi
thoutradi
ati
ontherapy

Combinati
onchemother
apyal
soi
savail
abl
eal
ongwithanti
-EGFRther
apyfort
hose
adenocar
cinomaswit
hEGFRmutati
ons,
andALKinhi
bit
orsforthosewi
thALKmutati
ons

Smokingisthemosti
mpor
tantr
iskf
act
orforlungcancer
;inwomenandnonsmoker
s,
adenocar
cinomasar
ethemostcommoncancers.

heavysmoker
sexposedtoasbest
oshav eanappr
oxi
mately55ti
mesgr eaterr
iskf
or
devel
opmentofl
ungcancerthant
hatfornonsmoker
snotexposedtoasbestos.

Squamouscel
lcar
cinomasaremorecommoninmenthani
nwomenandarecl
osely
cor
rel
atedwi
thasmokinghist
ory;
theyt
endt
oari
secent
ral
lyi
nmaj
orbr
onchi
scel
lfeatur
es.

Adenocar
cinomasmayoccurascent
ral
lesi
onsl
i
ket
hesquamouscel
lvar
iantbutusual
l
yar
e
moreperi
pheral
lyl
ocat
ed

Smal
lcel
ll
ungcar
cinomas(
SCLCs)gener
all
yappearaspal
egr
ay,
cent
ral
l
ylocat
edmasses

Hy
per
cal
cemi
amostof
teni
sencount
eredwi
thsquamouscel
lneopl
asms
 Lungcancer
s,par
ticul
arl
ySCLCs,cancausepar
aneopl
ast
icsyndr
omes.
.Cushi
ngsyndrome
(f
rom i
ncr
easedproducti
onofadrenocor
ti
cotr
opi
chormone)
;,sy
ndromeofi
nappr
opri
ate
secr
eti
onofanti
diur
etichor
mone;

●Carcinoi
dtumorsaremal
ignantt
umorscomposedofcel
l
sthatcont
aindense-
core
neurosecret
orygr
anul
esi
nt hei
rcy
topl
asm and,
rar
ely
,maysecr
etehor
monallyact
ive
poly
pept i
des

Theyoccasional
lyoccuraspar
toft
hemult
ipl
eendocri
neneoplasi
asyndr
omeBronchi
al
carci
noidsoccuratanearl
yage(mean40y
ears)andrepr
esentabout5%ofall
pul
monary
neoplasms.

Hist
ologi
cal
l
y ,
typi
calcar
cinoi
ds,
li
kethei
rcount
erpar
tsint
heintest
inalt
ract
,ar
ecomposed
ofnest
sofunifor
m cell
sthathaver
egul
arroundnucl
eiwit
h“sal
t-
and-pepper

Pl
euralEf
fusi
onandPl
eur
it
isWhent
hepl
eur
alf
lui
disat
ransudat
e,t
hecondi
ti
oni
ster
med
hy
drothor
ax

●Pneumot
hor
axr
efer
stopr
esenceofai
rorot
hergasi
nt
a hepl
eur
alsac,

Secondarypneumothor
axi
stheconsequenceofr
upt
ureofanypul
monar
ylesi
onsi
tuat
edcl
ose
pa
tothepleur
alsur
face
ya

Mechani
cal
vent
il
ator
ysuppor
twi
thhi
ghpr
essur
eal
somayt
ri
ggersecondar
ypneumot
hor
ax
Si

Empy
emai
sthusani
mpor
tantcompl
i
cat
ionofpneumot
hor
ax(
pyopneumot
hor
ax)
.

●Hemothor
ax,t
hecollect
ionofwholebl
ood(incontr
astwit
hbloodyeff
usion)i
nthepleural
cav
ity
,isacompli
cat
ionofar upt
uredi
ntr
athoraci
caort
icaneur
ysm t
hatisalmostal
way sfat
al

●Chy
lot
hor
axi
sapl
eur
alcol
l
ect
ionofami
l
kyl
ymphat
icf
lui
dcont
aini
ngmi
crogl
obul
esofl
i
pid.

●Mali
gnantmesot
hel
i
omai
sar
arecancerofmesot
hel
i
alcel
l
s,usual
l
yar
isi
ngi
nthepar
iet
alor
vi
scer
alpleur
a,

Thosewhowor kdi
rect
lywit
hasbestos(
shi
pyardwor
kers,
miner
s,i
nsul
at ors)ar
eatgreatest
ri
sk,butmali
gnantmesot
heli
omashaveappear
edinper
sonswhoseonlyexposurewasli
vingin
proxi
mityt
oanasbestosfact
oryorbei
ngarel
ati
veofanasbest
osworker

●Acut
einfect
ionsoftheupperrespir
ator
ytr
actareamongthemostcommonaf
fl
ict
ionsof
humans,mostfrequent
lymanif
estingasthe“commoncold

St
rept
ococcalt
onsi
l
li
ti
sisimpor
tanttorecognizeandtreatear
ly,
becauseoft
heassoci
ated
pot
enti
alf
ordevel
opmentofper
it
onsil
larabscesses(“qui
nsy”

Acut
elar
yngi
ti
scanr
esul
tfr
om i
nhal
ati
onofi
rr
it
ant
sormaybecausedbyal
l
ergi
●Nasopharyngealcar
cinomai
sar areneopl
asm t
hatmeri
tscommentbecauseof(1)thest
rong
epi
demiologicl
inkstoEBVand(2)thehighfr
equencyoft
hisf
orm ofcanceramongtheChi
nese

●Nonmal
i
gnantLesi
ons

●Vocal
cordnodules(
“pol
yps”)ar
esmoot
h,hemispheri
calpr
otr
usi
ons(
usual
l
ylesst
han0.
5cm
i
ndiameter
)locat
ed,mostoft
en,ont
hetr
uevocalcords.

●Lar
y ngeal
papi
llomaorsquamouspapi
l
lomaoft
hel
ary
nxi
sabeni
gnneopl
asm,
usual
l
y
l
ocatedont het
ruevocal
cords,

●Carci
nomaoft helar
ynxrepr
esentsonl
y2%ofal lcancer
s.I
tmostcommonl yoccursaf
terage
40y ear
sandismor ecommoni nment haninwomen( wit
hagenderrati
oof7: 1)
.
Envi
ronmentali
nfl
uencesarever
yimportantinitscausati
on;near
lyal
lcasesoccuri
nsmokers,
andalcoholandasbest
osexposuremayal soplayroles

About95%oflaryngeal
cancer
sar
ety
pical
squamouscel
lcar
cinomas.
Rar
ely,
adenocar
cinomasareseen

about90%ofgl
ott
ict
umor
sar
econf
inedt
othel
ary
nxatdi
agnosi
s.
a
supragl
otti
clarynxisr
ichi
nlymphat
icspaces,
andnear
lyat
hir
doft
heset
umor
smet
ast
asi
ze
pa

t
or egi
onal(cer
vical)l
ymphnodes
ya

Ki
dneyandI
tsCol
l
ect
ingSy
stem
Si

Azot
emi
aisanel
evat
ionofbl
oodur
eani
tr
ogenandcr
eat
ini
nel
evel
sandusual
l
yref
lect
sa

decr
easedgl
omer
ularf
il
tr
ati
onr
ate(
GFR)
.

Whenazot
emiagi
vesr
iset
ocl
i
nical
mani
fest
ati
onsandsy
stemi
cbi
ochemi
cal
abnor
mal
i
ties,
i
tist
ermeduremi
a.

Nephrit
icsyndromer esul
tsfr
om glomerul
ari
njur
yandisdominat
edbyt heacuteonsetof
usuall
ygrosslyvi
sibl
ehemat uri
a(redbl
oodcell
sandredcel
lcast
si nuri
ne)
,protei
nuri
aofmild
tomoder atedegree,
azotemia,edema,andhyper
tensi
on;
iti
stheclassi
cpresentat
ionofacut
e
postst
reptococcalgl
omer ul
onephri
ti
s

Nephroti
csyndromei
sagl omerul
arsyndromechar
act
erizedbyheavyprot
einur
ia(
excret
ionof
great
erthan3.5gofprot
ein/dayi
nadult
s),hy
poal
buminemia,sev
ereedema, hy
per
li
pidemia,
andli
piduri
a(l
ipi
dint
heurine)

Glomerul
arI
njury•Ant
ibody-
medi
atedi
mmunei njur
yisanimport
antmechanism ofgl
omerul
ar
damage,mainlybywayofcomplementandleukocyt
e-medi
atedpat
hways.Ant
ibodi
esalsomay
bedir
ectl
ycytotoxi
ctocell
sint
heglomerul
us.
 •Themostcommonf
ormsofant
ibody
-medi
atedGNar
ecausedbyt
hef
ormat
ionofi
mmune
complexes

Minimal
-ChangeDi
seaseglomerul
ihav
eanor mal
appear
ancebyli
ghtmicr
oscopybutshow
di
ffuseeff
acementofpodocyt
efootpr
ocesseswhenvi
ewedwit
htheelect
ronmicr
oscope

MMDcomoni nchi
ldhoodb/wagekf1t
o7,
Mor
ethan90%ofchi
l
drenr
espondt
oashor
t
cour
seofcor
ti
cost
eroidther
apy

Focal
segment
algl
omer
uloscl
erosi
s(FSGS)i
schar
act
eri
zedhi
stol
ogi
cal
l
ybyscl
erosi
s
aff
ect
ing

FSGSInassoci
ati
onwithot
hercondi
ti
ons,
suchasHI
Vinf
ect
ion(
HIVnephr
opat
hy)orher
oin
abuse(
heroi
nnephropat
hy

Theinci
denceofhemat ur
iaandhyper
tensi
onishigherinper
sonswit
hFSGSthani
nthose
wi
thminimal-
changedisease;FSGSassoci
atedprot
einuri
aisnonsel
ect
ive;
andi
ngener
althe
r
esponsetocorti
cost
eroidtherapyi
spoor.

MEMBRANOUSNEPHROPATHYmostcommonbet ween30and60y ear

sofage.Iti
s
a
charact
eri
zedmorphol
ogical
l
ybythepr
esenceofsubepi
thel
ial
immunogl
obul
in-
contai
ning
pa
deposit
salongt
heGBM. showdi
ff
usethi
ckeni
ngofthecapil
l
arywal
l
ya

. Spi
keanddomepat
ter
en,
lossofef
facmentpr
ocess
Si

I
nabout85%ofcasesMembranousnephr
opat
hyi
saf
orm ofchr
oni
cimmunecompl
ex
gl
omerul
onephr
it
isi
nducedbyant
ibodi
es,

.MPGNiscausedbyi
mmunecomplexdeposit
ion;densedepositdi
seaseisaconsequence
ofcompl
ementdysr
egul
ati
on.Bot
hmaypresentwit
hnephr ot
icand/ornephr
iti
cfeat
ures.

Acut
eposti
nfecti
ousGN,oneofthemorefrequentlyoccur
ringglomerul
ardi
sorder
s,i
scaused
bygl
omerul
ardeposit
ionofimmunecomplexesr esul
ti
nginpr ol
i
ferat
ionofanddamageto
gl
omerul
arcell
sandinfi
lt
rat
ionofl
eukocy
tes,especial
lyneutr
ophi l
s.

Thecl
assi
ccaseofpostst
reptococcal
GNdev
elopsi
nachi
l
d1t
o4weeksaf
tert
heyr
ecov
er
f
rom agr
oupAstrept
ococcalinf
ection

El
ect
ronmicr
oscopyshowsdepositedimmunecomplexesarr
ayedassubendot
hel
i
al,
i
ntr
amembranous,
or,mostof
ten,subepit
hel
ial
“humps”nest
ledagai
nstt
heGBM

scat
ter
edgr
anul
ardeposi
tsofI
gGandcompl
ement

I
gAnephropat
hyi
soneoft
hemostcommoncausesofrecur
rentmi
croscopi
corgr
oss
hemat
uri
aandist
hemostcommonglomer
ulardi
seaser
eveal
edbyrenalbi
opsyworl
dwi
de.
 Thehal
l
mar
koft
hedi
seasei
sthedeposi
ti
onofI
gAi
nthemesangi
um

Her
edi
tar
ynephr
it
is(
Alportsy
ndrome)i
scausedbymutati
onsingenesencodi
ngGBM col
lagen;
i
tmani
fest
sashematuri
aandslowlypr
ogr
essingpr
otei
nur
iaanddecli
ningr
enalf
unct
ion;

Thecharact
eri
sti
chi
stol
ogi
cfi
ndi
ngassoci
atedwi
thRPGNi
sthepr
esenceofcr
escent
s
(
crescent
icGN)

RPGNmaybei mmune- mediat

ed,aswhenaut oanti
bodi
estotheGBM dev el
opinanti-
GBM
anti
bodydi
seaseorwheni tar
isesconsequentt
oi mmunecompl exdeposit
ion;
ital
socanbe
pauci
-i
mmune, associ
atedwit
hantineut
rophi
lcytopl
asmicant
ibodies.

Tubul
oint
ersti
ti
alnephr
it
is(TIN)ref
erstoagroupofi
nfl
ammat
orydi
seasesoft
heki
dney
sthat
pri
mari
lyi
nv ol
vetheint
erst
it
ium andtubul
es

Acutepy el
onephri
ti
s,acommonsuppur at
iveinfl
ammat i
onoft heki
dneyandt herenal
pel
v i
s,i
s
causedbybact er
iali
nfecti
on(gramanegati
ver ods).I
tisanimpor t
antmanifestat
ionofur
inary
tr
actinfect
ion(UTI)
,Character
isti
cal
l
y,di
scret
e, yel
l
owi sh,r
aisedabscessesaregrossl
y
apparentontherenalsurface a
Chr
oni
cpyel
onephri
ti
susual
l
yi sassociat
edwithurinar
yobst
ruct
ionorr
efl
ux;
resul
tsi
nscar
ri
ng
pa
oft
hei
nvol
vedkidney,
andgradualrenali
nsuf
fi
ciency.

ATIisthemostcommoncauseofacuteki
dneyinj
ury;
itscl
i
nicalmani
festat
ionsar
eel
ect
rol
yte
ya

abnormali
ti
es,
acidosi
s,ur
emi
a,andsi
gnsoffl
uidoverl
oad,of
tenwit
holigur
ia.
Si

ATIi
schar
acter
izedmorphol
ogical
l
ybyi nj
uryornecr
osisofsegmentsofthetubul
es
(
typi
cal
lyt
heproxi
mal t
ubul
es),
protei
naceouscastsindi
stalt
ubules,
andint
erst
iti
aledema

Arter
ionephroscl
erosi
sist
heter
m usedf
orthethickeni
ngandscl
erosi
sofar
ter
ial
wal
l
sandt
he
renalchangesassociat
edwit
hbeni
gnhyper
tension.

Mal
i
gnanthy
per
tensi
on,
def
inedasbl
oodpr
essur
eusual
l
ygr
eat
ert
han200/
120mm Hg

Damaget
othesmal
lvessel
sismani
fest
edasf
ibr
inoi
dnecr
osi
soft
hear
ter
iol
es

wi
despr
eadt
hrombosi
sin

t
hromboti
cmicroangi
opat
hyrefer
stolesi
onsthemicr
oci
rcul
ati
onandcl
i
nical
l
yby
micr
oangi
opat
hichemolyt
icanemia,
thrombocyt
openi
a,

Chil
dhoodHUSi st
hebest
-char
act
eri
zedoft
herenalsyndromesassoci
atedwi
ththr
ombot
ic
microangi
opat
hy.Asmanyas75%ofcasesfol
l
owi nt
estinal
inf
ect
ionwithShi
ga
toxi
n–produci
ngE.col
i
,

Anemergingthemei
nthepat
hophysiol
ogyoft
heheredi
tar
ycyst
icdiseasesist
hatt
he
under
lyi
ngdefecti
sint
heci
li
a–cent
rosomecomplexoftubul
arepi
thel
i
al cel
ls
 Si
mpl
ecy
stsconst
it
uteacommonpost
mor
tem f
indi
ngt
hathasnocl
i
nical
signi
fi
cance.

Adul
tpolycyst
icki
dneydi
seaseisadi
seaseofautosomal
dominanti
nher
it
ancecausedby
mutat
ionsinthegenesencodi
ngpol
ycyst
in-
1or-2.onchr
omosom 16

PCKDADThemosti mport
antcompl
icat
ions,
becauseofthei
rdel
eter
iousef
fectonal
ready
margi
nal
renal
funct
ion,ar
ehypert
ensi
onandurinar
yinf
ecti
on.

PCKDADSaccularaneur
ysmsofthecir
cleofWi l
l
isar
epr
esenti
n10%t
o30%ofpat
ient
sand
ar
eassoci
atedwi
thahi ghi
nci
denceofsubarachnoi
dhemor
rhage

Aut
osomalRessesiv
echil
dhooddiseasPKHD1gene,
codi
ngf
oraput
ati
vemembr
aner
ecept
or
pr
otei
ncal
l
edf i
brocyst
in,
local
i
zedtotheshor
tar
m ofchr
omosome6(6p)

Nephronophthi
sis–medull
arycyst
icdiseasecompl exisbeingincr
easingl
yrecogni zedasa
causeofchronickidneydi
seaseinchil
drenandy oungadults.Ofautosomal recessi v
e
i
nheri
tance,i
tisassociat
edwithmut ati
onsinseveralgenesthatencodeepi t
helialcel
lpr
otei
ns
cal
lednephrocysti
nsthatmaybei nv
olvedincil
iaryfunct
ion;ki
dneysar econtractedandcont
ain
multi
plesmallcysts. a
Symptomaticuroli
thi
asisi
smorecommoni nment haninwomenmostimpor t
antcauseis
pa
i
ncreaseduri
naryconcentr
ati
onofthest
one’sconsti
tuent
s,sot
hati
texceedsthei
rsolubi
l
ity
i
nuri
ne( super
saturat
ion).
ya

Ther
ear
ethr
eemaj
ort
ypesofst
ones.
Si

•About80%ofrenalst
onesar
ecomposedofei
thercal
cium oxal
ateorcal
cium oxal
atemi
xed
wit
hcalci
um phosphat
e.

•Tenper
centar
ecomposedofmagnesi
um ammoni
um phosphat
e.

•Si
xper
centt
o9%ar
eei
therur
icaci
dorcy
sti
nest
ones.

Hydr
onephrosi
srefer
stodil
ati
onofther
enalpel
vi
sandcal
yces,wi
thaccompany
ingat
rophy
oft
heparenchyma,causedbyobstr
uct
iont
otheoutfl
owofur
ine.

Tumor
soft
hel
owerur
inar
ytr
actar
eaboutt
wiceascommonasr
enal
cel
lcar
cinomas

•Cl
earcel
lcar
cinomasar ethemostcommonandareassociatedwit
hhomozy
gousl
ossof
t
heVHLt umorsuppressorprot
ein;
tumor
sfr
equent
lyi
nvadetherenal
vei
n.

•Papil
lar
yrenalcel
lcar
cinomasf
requent
lyar
eassoci
atedwithincreasedexpr
essi
onand
act
ivat
ingmutati
onsoftheMEToncogene;t
heytendt
obebi l
ater
al andmulti
pleandshow
var
iabl
epapill
afor
mat i
on.

•Chr
omophober
enal
cel
lcar
cinomasar
elesscommon;
tumorcel
l
sar
enotascl
earasi
nthe
otherr
enal
cel
lcarci
nomas.t
ri
adofpai
nlesshemat
uri
a,apal
pabl
eabdomi
nal
mass,
anddul
l
fl
ankpaini
schar
acteri
sti
c

Wi
l
msTumort
hir
dmostcommonor
gancanceri
nchi
l
dreny
oungert
han10y
ear
sofage

Or
alCav
ityandGast
roi
ntest
inal
Tract

Aphthousulcer
sar
epai
nful
super
fi
cial
ulcer
sofunknownet
iol
ogymostcomoni
n1st2
decadesofli
fe

Herpessi
mplexv
iruscausesasel
f-
li
mit
edi
nfect
iont
hatpr
esent
swi
thv
esi
cles(
col
dsor
es,
f
everbli
ster
s)

Or
alcandi
diasi
smayoccurwhent
heor
almi
crobi
otai
sal
ter
ed(
e.g.
,af
terant
ibi
oti
cuse)

Fi
bromasandpy
ogeni
cgr
anul
omasar
ecommonr
eact
ivel
esi
onsoft
heor
almucosa

Ther
iskofmal
i
gnantt
ransf
ormat
ioni
sgr
eat
eri
ner
ythr
opl
aki
a(r
elat
ivet
oleukopl
aki
a).

•Amaj
ori
tyofor
alcav
itycancer
sar
esquamouscel
alcar
cinomas.

•Oralsquamouscell
carci
nomasarecl
assical
l
yli
nkedt
otobaccoandal
cohol
use,
butt
he
pa
i
ncidenceofHPVassoci
atedlesi
onsi
sri
sing.
ya

Si
aladeni
ti
s(inf
lammati
onofthesal
iv
arygl
ands)canbecausedbyt
rauma,
inf
ect
ion(
such
asmumps) ,oranautoi
mmunereact
ion.
Si

• Pleomorphi
cadenomaisaslow-gr
owi
ngneopl
asm com posedofahet
erogeneousmi
xtur
e
ofepi
thel
i
alandmesenchy
malcell
s.

•Mucoepi
dermoi
dcar
cinomaisamalignantneopl
asm ofvar
iabl
ebi
ologi
caggr
essi
veness
t
hatiscomposedofami
xtureofsquamousandmucouscel l
s.

Thejawsareacommonsiteofepit
heli
um- l
i
nedcy
stsder
ivedf
rom odont
ogeni
cremnant
s.•
Theodontogeni
cker
atocy
sti
slocal
lyaggressi
ve

Themostcommonodont
ogeni
ctumor
sar
eamel
obl
ast
omaandodont
oma

●ESOPHAGUS

Achalasi
aischaract
eri
zedbyt
het
ri
adofi
ncompl
eteLESr
elaxat
ion,
incr
easedLESt
one,
and
esophagealaper
ist
alsi
s

Themostf
requentsi
teofectopi
cgast
ri
cmucosai
stheuppert
hir
doft
heesophagus,
wher
e
i
tisref
err
edt
oasani nl
etpatch.

Themostcommonesophageal
lacer
ati
onsar
eMal
l
oryWei
sst
ear
s
 Boerhaavesyndrome,
characteri
zedbytr
ansmur
alesophageal
tear
sandmedi
ast
init
is,
occur
sr ar
elyandisacatast
rophicevent

GERDismostcommoni nadul
tsoldert
han40y earsofagebutalsooccur
sininfant
sand
chi
ldr
en.Themostfrequent
lyr
eport
edsy mptomsar ehear
tbur
n,dysphagi
a,and,
lessoften,
not
iceabl
eregur
git
ati
onofsour-t
ast
inggastr
iccontent

Barr
ettesophagusi
sacompl i
cati
onofchr
oni
cGERDt
hati
schar
act
eri
zedbyi
ntest
inal
metapl
asiawithi
ntheesophageasquamousmucosa

Di
agnosisofBarr
ettesophagusrequi
resendoscopyandbi
opsy
,,i
sassoci
atedwi
thi
ncr
eased
r
iskofesophageal
adenocarcinoma.

Esophagealsquamouscellcar
cinomai sassoci
atedwi
thalcohol
andtobaccouse,
pov
ert
y,
caust
icesophageali
njur
y,achal
asi
a, t
ylosi
s,andPlummer
-Vinsonsyndr
ome

I
ncontrastt
othedi
stal
locati
onofmostadenocar
cinomas,
hal
fofsquamouscel
l
car
cinomasoccuri
nthemiddlethi
rdoft
heesophagus

●Acut
eandChr
oni
cGast
ri
ti
s
a
pa
Acut
egast
ri
ti
scanpr
ogr
esst
oacut
egast
ri
cul
cer
ati
on.

Themostcommoncauseofchr
oni
cgast
ri
ti
sisH.py
lor
iinf
ect
ion;
mostr
emai
ningcasesar
e
ya

causedbyaut
oimmunegast
ri
ti
s
Si

H.py
lorigast
ri
ti
stypi
cal
l
yaffectstheantrum andi
sassoci
atedwi
thincr
easedgastr
icaci
d
pr
oduct
ion.Theinducedmucosa-associ
atedlymphoi
dti
ssue(MALT)cantransf
orminto
l
ymphoma.

Aut oi
mmunegast r
iti
scausesatrophyofthegastr
icbodyoxynt
icglands,whichresul
tsi
n
decreasedgastr
icaci
dpr oduct
ion,
antralGcell
hyperpl
asi
a,achl
orhydri
a,andvitaminB12
defi
ciency.Ant
i-
pari
etalcel
landanti–i
ntr
insi
cfact
oranti
bodiesty
pical
lyarepresent.

I
ntest
inal
metaplasi
adevelopsinbot
hfor
msofchr
oni
cgast
ri
ti
sandi
sar
iskf
act
orf
or
dev
elopmentofgastri
cadenocarci
noma.

●Gast
ri
cPol
ypsandTumor
s

Inf
lammat or
yandhyper
plasti
cgastr
icpol
ypsarer
eact
ivel
esi
onsassoci
atedwi
thchr
oni
c
gastr
it
is.Ri
skofdyspl
asi
aincreaseswit
hpolypsi
ze.

Gastr
icadenomasdev el
opinabackgr
oundofchr
onicgastri
ti
sandarepar
ticul
arl
y
associ
atedwit
hintest
inalmet
aplasi
aandmucosal(
glandul
ar)atr
ophy
.Adenocarci
noma
fr
equentl
yari
sesingastri
cadenomas,
 mor
ecommoni
nlowersoci
oeconomi
cgr
oups.

•Gast
ri
cadenocar
cinomasar
ecl
assi
fi
edaccor
dingt
olocat
ionandgr
ossandhi
stol
ogi
c

morphology.Thosewi t
hanintest
inal
hist
ologi
cpatternt
endtofor
m bulkyt
umorsandmaybe
ul
cerated,whereasthosecomposedofsignetri
ngcellst
ypi
call
ydi
splayadif
fusei
nfi
lt
rati
ve
gr
owt hpatter
nt hatmaythi
ckenthegastr
icwall(
li
niti
spl
asti
ca)wi
thoutfor
mingadiscret
e
mass.

•H.pyl
ori
inf
ecti
onisthemostcommoneti
ologi
cagentf
orgast
ricadenocar
cinoma,
but
ot
herassoci
ati
ons,
incl
udingchr
oni
cat
rophi
cgastr
it
isandEBVinf
ecti
o

Pri
marygast
ri
clymphomasmostoftenar
ederi
vedfr
om t
hemucosa-
associ
atedl
ymphoi
d
t
issuewhosedevel
opmenti
sinducedbychr
oni
cgastr
it
is

Gast
rointest
inalst
romalt
umor( GI
ST)i
sthemostcommonmesenchy malt
umorofthe
abdomen,occursmostofteninthest
omach;i
tar
isesfr
om beni
gnpacemakercel
l
s,al
soknown
asthei
ntersti
ti
alcell
sofCaj
al.

Car
cinoi
dtumorsari
sefr
om thedif
fusecomponentsoftheendocri
nesy
stem,
andar
emost
a
commoni nt
hegastr
oint
est
inal
tract
,part
icul
arl
ythesmall
intest
ine.
pa
ya

I
ntest
inalObst
ruct
ion
Si

Hir
schspr
ungdiseaseist
her esul
tofdefect
iveneur
alcr
estcel
lmi
grat
ionf
rom cecum t
o
r
ectum.Itgi
vesr
isetofunct
ionalobstr
ucti
on.

•Abdominalherni
ati
onmayoccurthr
oughanyweaknessordef
ectint
hewallofthe
per
it
onealcavi
ty,i
ncl
udingi
ngui
nalandfemor
alcanal
s,umbi
li
cus,andsi
tesofsur
gicalscar
ri
ng

●Vascul
arDi
sor
der
sofBowel

I
ntest
inal
ischemi
acanoccurasar
esul
tofei
therar
ter
ial
orv
enousobst
ruct
ion.

•Ischemicboweldi
seaseresult
ingfrom hy
poper
fusi
onismostcommonatt
hesplenic
f
lexure,si
gmoidcol
on,andrectum; t
hesearewater
shedzoneswher
etwoar
ter
ial
cir
culat
ions
t
ermi nat
e

. •Syst
emicvascul
i
tidesandi
nfect
iousdiseases(
e.g.
,CMVi
nfect
ion)cancausev
ascul
ar
di
seaset
hati
snotconf i
nedtot
hegastroi
ntesti
nalt
ract
.

•Angi
ody
spl
asi
aisacommoncauseofmaj
orl
owergast
roi
ntest
inal
bleedi
ngi
ntheel
der
ly.

•Hemor
rhoi
dsar
ecol
l
ater
alv
essel
sthatf
ormt
oal
l
owr
esol
uti
onofv
enoushy
per
tensi
on.
●Mal
absor
pti
veDi
arr
hea

Di
arr
heacanbechar
act
eri
zedassecr
etor
y,osmot
ic,
mal
absor
pti
ve,
orexudat
ive.

•Themal absor
pti
onassociat
edwithcyst
icf
ibr
osi
sistheresul
tofpancr
eati
cinsuf
fi
ciency
(
i.
e.,i
nadequatepancr
eat
icdigesti
veenzy
mes)anddefi
cientl
uminalbr
eakdownofnutri
ents.

•Celi
acdiseaseisani
mmune- medi
atedenteropathytrigger
edbytheingesti
onofgl
uten-
contai
ninggrai
ns.Themalabsorpti
vedi
arr
heai nceliacdiseaseisduetolossofbr
ushborder
surf
aceareaand,possi
bly
, def
ici
entent
erocyt
emat urat
ionasar esul
tofimmune-medi
ated
epi
thel
ialdamage.

•Lact
asedef
ici
encycausesanosmot
icdi
arr
heaowi
ngt
othei
nabi
l
ityt
obr
eakdownor
absor
blact
ose.

•I
rr
it
ablebowelsyndrome(I
BS)ischar
act
eri
zedbychr
oni
c,r
elapsi
ngabdomi
nal
pai
n,
bl
oat
ing,andchangesinbowelhabi
ts.

•Thetwoformsofmi croscopi
ccolit
is,col
lagenouscol
it
isandlymphocy
ticcoli
ti
s,bot
h
causechr
oni
cwat erydi
arrhea.Thei
ntestinesaregrossl
ynormal,
andthediseasesare
a
i
denti
fi
edbytheirchar
acteri
sti
chist
ologicfeatur
es.
pa

●I
nfect
iousEnt
erocol
i
tis
ya

Vi
bri
ocholer
aesecr
etesapr
e-formedt oxint
hatcausesmassivechl
ori
desecr
eti
on.Wat
er
Si

f
oll
owstheresul
ti
ngosmoti
cgradient
,leadingt
osecretor
ydi
arrhea.

•Campyl
obacterj
ejuni
isthemostcommonbact
eri
alent
eri
cpat
hogeni
ndev
eloped
count
ri
esandalsocausestr
avel
er’
sdiar
rhea.

Mostisol
atesar
enoninvasi
ve.Salmonel
l
aandShi
gel
l
aspp.ar
einv
asi
veandassoci
atedwi
th
exudat
ivebloodydi
arr
hea(dysenter
y).

Sal
monell
ainf
ect
ionisacommoncauseoff
oodpoi
soni
ng.S.t
yphi
cancausesy
stemi
c
di
sease(
typhoi
dfev
er).

•Pseudomembranouscol
it
isisoft
ent r
igger
edbyant
ibi
oti
cther
apyt
hatdi
srupt
sthenor
mal
mi
crobi
otaandal
l
owsC.diff
ici
letocoloni
zeandgrow

Rotav
irusi
sthemostcommoncauseofsev
erechi
l
dhooddi
arr
heaanddi
arr
heal
mor
tal
i
ty
worl
dwide.

•Di
ver
ti
cul
ardi
seaseoft
hesi
gmoi
dcol
oni
scommoni
nWest
ernpopul
ati
onsov
ert
heageof
60.

●I
nfl
ammat
oryBowel
Disease
 I
nfl
ammat
orybowel
disease(
IBD)i
sanumbr
ell
ater
mforCr
ohndi
seaseandul
cer
ati
vecol
i
tis.

•Crohndi
seasemostcommonl yaf
fect
stheter
minal
il
eum andcecum, butanysi
tewit
hint
he
gast
roint
est
inal
tractcanbei
nvol
ved;
skipl
esi
onsandnoncaseat
inggranulomasarecommon

. •Ulcerati
vecoli
tisi
sli
mit
edtothecol
on,i
scontinuousfr
om ther
ect
um,andrangesi
next
ent
f
rom onlyrectal
diseaset
opancol
i
tis;
nei
therski
plesionsnorgr
anul
omasarepr
esent.

•BothCrohndi
seaseandulcer
ati
vecoli
ti
scanhaveext
raint
esti
nalmanif
est
ati
ons.•Ther
isk
ofcol
onicepit
hel
i
aldyspl
asiaandadenocar
cinomai
sincr
easedinpat
ient
swhohav ehadIBD
formorethan8to10years.

●Col
oni
cPol
yps,
Adenomas,
andAdenocar
cinomas

I
ntest
inalpol
ypscanbeclassi
fi
edasnon-neopl
asti
corneopl
asti
c.Thenon-
neopl
ast
icpol
yps
canbefurt
herdefi
nedasinf
lammat or
y,hamart
omatous,
orhyperpl
ast
ic.

•I
nfl
ammat
orypol
ypsf
orm asar
esul
tofchr
oni
ccy
clesofi
njur
yandheal
i
ng.

• Hamar tomat
ouspolypsoccursporadi
call
yorasapar
tofgenet
icdi
seases.I
nthel
att
er
case,
theyoft
enareassoci
atedwit
hincreasedri
skofmal
i
gnancy.
a
pa

•Hyper
plasti
cpolypsarebenignepit
heli
alprol
if
erat
ionsmostcommonl yfoundinthel
eft
col
onandrectum.Theyar enotreact
iveinori
gin,
incontrastwithgast
ri
chy per
plast
icpol
yps;
ya

havenomalignantpotent
ial
;andmustbedi st
ingui
shedf rom sessi
l
eserrat
edadenomas.
Si

•Benignepit
heli
alneopl
ast
icpol
ypsoftheint
est
inesaret
ermedadenomas.Thehal
l
mark
featureoftheselesi
ons,whi
charet
heprecursor
sofcoloni
cadenocar
cinomas,
iscy
tol
ogi
c
dysplasi
a.

•I
ncontr
astwi
thtr
adi
ti
onaladenomas,sessi
leser
rat
edadenomasl
ackcy
tol
ogi
cdy
spl
asi
a
andshar
emorphol
ogi
cfeat
ureswithhyper
plast
icpol
yps.

•Famil
ialadenomat
ouspoly
posis(FAP)andheredit
arynonpoly
posiscol
orect
alcancer
(HNPCC)arethemostcommonf ormsoff ami
li
alcoloncancer
.FAPiscausedbyAPC
mutati
ons,andpati
ent
stypi
cal
lyhaveover100adenomasanddev el
opcoloncancerbefor
ethe
ageof30.

•HNPCCi scausedbymut at
ionsi
nDNAmi smat chrepairgenes.Pati
entswit
hHNPCChave
farf
ewerpolypsanddevel
opcanceratanolderagethant hattypi
calforpat
ient
swi
thFAPbut
atayoungeragethani
npatientswit
hspor
adiccoloncancer .

•FAPandHNPCCar eex
amplesoftwodisti
nctpat
hway
sofneopl
ast
ict
ransf
ormat
ion,
bot
h
ofwhichcont
ri
but
etospor
adi
ccoloncancer.

•Thev
astmaj
ori
tyofcol
oni
ccancer
sar
eadenocar
cinomas.
●Appendi
x

• Acut eappendici
ti
sismostcommoni nchi
l
drenandadol
escents.I
tisthoughtt
obe
i
nit
iatedbyi
ncreasedintral
uminalpr
essur
econsequentt
oobst
ruct
ionoftheappendi
ceal
lumen,
whichcompromisesv enousoutfl
ow.

•Themostcommont
umoroft
heappendi
xist
hecar
cinoi
d.

•Thecli
nicalpr
esentati
onwit
happendi
ceal
adenocar
cinomacanbei
ndi
sti
ngui
shabl
efr
om t
hat
wit
hacut eappendici
ti
s.

●Li
ver
,Gal
l
bladder
,andBi
l
iar
yTr
act&Pancr
eas

Sur
gicalr
emovalof60%oftheli
veri
nanormalper
soni
sfoll
owedbymini
mal andt
ransi
ent
hepat
icimpai
rment
,withr
est
orati
onofmostofi
tsmassbyregenerat
ionwi
thi
n4t o6weeks

Thehi
stol
ogi
ccor
rel
ateofacut
eli
verf
ail
urei
smassi
vehepat
icnecr
osi
s

Jaundi
ceoccur
swhenr
etent
ionofbi
l
irubi
nleadst
oser
um l
evel
sabov
e2.
0mg/
dL.

hepat
icmachiner
yforconj
ugat
ingandexcret
ingbil
ir
ubindoesnotful
l
ymat ur
eunt
ilabout2
a
weeksofage,al
mosteverynewborndevel
opstr
ansientandmildunconj
ugat
ed
pa

hyper
bil
i
rubi
nemia,t
ermedneonatalj
aundi
ceorphysiol
ogicj
aundiceoft
henewborn
ya

Chol
est
asi
s,char
acter
ist
icl
abor
ator
yf i
ndingi
selevatedserum al
kal
i
nephosphat
ase,
an
enzy
mepresenti
nbil
eductepit
hel
ium andinthecanali
cularmembraneofhepat
ocy
tes.
Si

Hepat
it
isandint
ra-orex
trahepati
cobstr
uct
ionofbil
eflowar
ethemostcommoncausesof
j
aundi
ceinvol
vi
ngtheaccumul at
ionofconj
ugatedbi
l
irubi
n

Hemolyt
icanemiasaret
hemostcommoncauseofj
aundi
cei
nvol
vi
ngt
heaccumul
ati
onof
unconj
ugat
edbili
rubi
n.

Ci
rr
hosisi
sdef
inedasadiff
useprocesscharact
eri
zedbyf
ibr
osi
sandt
heconv
ersi
onof
nor
malli
verar
chi
tect
urei
ntostr
uct
urall
yabnormalnodul
es.

Ci
rr
hosi
smostfr
equentar
echr
oni
chepat
it
isBandCandal
cohol
i
candnonal
cohol
i
c
st
eat
ohepat
it
is.

Themaincompl
i
cati
onsofcir
rhosi
sarerel
atedt
odecreasedli
verfuncti
on,
por
tal
hy
pertensi
on,
andi
ncr
easedri
skfordevel
opmentofhepatocel
l
ularcarci
noma.

Thedominanti
ntr
ahepat
iccausei
sci
rr
hosi
s,account
ingf
ormostcasesofpor
tal
hy
pertensi
on

Asci
tesr
efer
stot
hecol
l
ect
ionofexcessf
lui
dint
heper
it
oneal
cav
ity
.Itusual
l
ybecomes
cl
i
nical
l
ydet
ect
abl
ewhenatl
east500mLhav
eaccumul
ated,

Muchmor ei
mport
antar
etheesophagogast
ri
cvari
cest
hatappeari
nabout65%ofper
sons
wi
thadv
ancedci
rr
hosi
softhel
iv
er,causi
ngmassiv
ehematemesis

Pul
monar
ydy
sfunct
ioni
nchr
oni
cli
verdi
seasei
scommonandmaybel
i
fe-
thr
eat
eni
ng

hepat
icf
ail
uremayleadt
oportopul
monar
yhypert
ensi
onorhepat
opul
monar
ysy
ndr
ome.
;the
mostcommonclini
calmani
fest
ati
onsar
edyspneaonexer
ti
on

mosti
mpor
tantagentt
hatpr
oducest
oxi
cli
veri
njur
yisal
cohol
;

●Vi
ral
Hepat
it
is

•I
ntheal
phabetofhepat
otr
opi
cvi
ruses,
someeasymnemoni
cdev
icesmaybeusef
u

l
: Thev
owel
s(hepat
it
isAandE)nev
ercausechr
oni
chepat
it
is,
onl
yacut
ehepat
it
is

. Onl ytheconsonants(
hepat
it
isB,
C,D)hav
ethepot
ent
ial
tocausechr
oni
cdi
sease(
Cfor
a
consonantandforchroni
pa

). Hepati
ti
sBcanbet
ransmi
tt
edbybl
ood,
bir
thi
ng,
and“
bonki
ng”(
ast
heysayi
ntheUni
ted
ya

Kingdom)
.
Si

Hepati
ti
sCist
hesingl
ev i
rusthati
smoreof
tenchr
onicthannot(
almostnev
erdet
ected
acutel
y;85%ormoreofpat
ientsdevel
opchr
oni
chepati
ti
s,20%ofwhom will
devel
opci
rr
hosis)
.

Hepati
ti
sD,t
hedelt
aagent
,isadef
ect
ivev
irus,
requi
ri
nghepat
it
isBcoi
nfect
ionf
ori
tsown
capaci
tyt
oinf
ectandrepl
i
cat
e

. Hepat
it
isEi
sendemi
cinequat
ori
alr
egi
onsandf
requent
lyepi
demi
c.

•Thei
nfl
ammat or
ycel
lsinbot
hacuteandchr
onicv
iralhepat
it
isar
emai
nlyTcel
l
s;i
tist
he
pat
ter
nofinj
uryt
hatisdi
ff
erent
,nott
henatur
eofthei
nfil
trat
e.

•Bi
opsyassessmenti
nchr
onicvi
ral
hepat
it
isi
smosti mpor
tantforgradi
ngandstagingof
di
sease,
whichareusedt
odecidewhet
herapati
entunder
goesoftenarduousant
ivi
ral
tr
eat
ments.

•Pati
ent
swithlong-
standi
ngHBVorHCVinfect
ionsareatincr
easedri
skfort
hedev
elopment
ofhepat
ocel
lul
arcarci
nomas,ev
enint
heabsenceofestabl
ishedcir
rhosi
s.

•Al
cohol
i
cliv
erdiseasehast
hreemai
nmani
festati
ons:
hepat
icst
eat
osi
s,al
cohol
i
chepat
it
is,
andci
rr
hosi
s,whichmayoccural
oneori
ncombinati
on
. •Consumptionof50to60g/dayofalcohol
isconsi
der
edt
obet
het
hreshol
dfort
he
dev
elopmentofalcohol
i
cli
verdi
sease.

Nonal
cohol
icfat
tyl
i
v erdisease(
NAFLD)isassociat
edwi
tht
hemet
abol
i
csy
ndr
ome,
obesi
ty,
t
ype2diabet
es,anddysli
pidemiaand/
orhyper
tension

Inchi
l
dren(
NAFLD),theappearanceofthehist
ologicinjuri
esi
ssomewhatdif
ferent
:
Inf
lammati
onandscarringtendtobemor eprominentintheport
altr
actsandper
iport
alr
egi
ons,
andmononucleari
nfi
l
tratesrat
herthanneutr
ophi
licinf
il
tratespr
edominat
e.

Reyesy ndr
omehasbeenassoci at
edwi t
haspi r
inadminist
rat
iondur
ingvi
rali
l
lnesses;
whil
ethereisnodef
ini
ti
veevidencethatsal
icyl
atesplayacausal
rolei
nthi
sdisor
der,asa
pr
ecautionaspir
ini
scontr
aindicat
edinchil
dren

specialcategor
ymer i
ti
ngemphasisinvol
vesmi t
ochondr
ial
inj
uryl
eadingt
odi
ff
use,
hepatocellul
armicr
ovesicul
arst
eat
osis,usual
l
yassociat
edwithsever
eandpot
enti
all
yfat
al
acuteli
v erdysf
unct
ion

Prol
ongedconjugat
edhyperbi
l
irubi
nemi
athatl
astsbeyondthef
irst14day
sofl
i
fei
ster
med
neonat
alchol
estasi
s.Themajorcausesar
eextr
ahepati
cbil
iar
yatr
esia,
a
pa
Cholest
asi
sofSepsi
sThemostcommonal t
erat
ioni
scanal
i
cul
archol
est
asi
s,
wit
hbi
l
epl
ugs
wi
thi
npredomi
nant
lycent
ri
lobul
arcanal
i
cul
i
ya

●Pri
marybil
iaryci
rrhosi
s(PBC)i sachronic,progressiv
e, andsomet i
mesf at
alcholest
ati
cli
ver
Si

di
seasecharacter
izedbydest ructi
onofi nt
rahepaticbil
educt s,port
alinf
lammationandscarri
ng,
andthedevelopmentofcir
r hosisandliverfail
ureov eryearstodecadesThecar dinalf
eatur
eof
PBCisanonsuppur at
ivedest ruct
ionofsmal l
andmedi um- si
zedint
rahepat
icbileduct
s.PBC
i
sprimari
lyadiseaseofmi ddle-agedwomen, withpeaki ncidencebetweentheagesof40and
50years

Morethan90%ofpersonswithPBCdemonstrat
ehi
ght
it
ersofaut
oant
ibodi
esdi
rect
ed
agai
nstsever
almi
tochondri
alaci
ddehy
drogenases

●Pri
maryscl
erosingchol
angi
ti
s(PSC)isachronicchol
estat
icdi
sorder
,char
acter
izedby
pr
ogressi
vef
ibrosisanddest
ruct
ionofext
rahepati
candintr
ahepat
icbil
eductsofallsi
zes

PSCcommonl yi
sseeninassoci
ati
onwi
thi
nfl
ammatorybowel
diseasepar
ti
cular
lyul
cer
ativ
e
colit
is,whi
chcoexi
stsi
napproxi
matel
y70%ofaf
fect
edpati
ent
sMalesareaff
ectedmoreoften
thanf emal
es,i
narati
oof2:1

●Hemochromat
osisi
schar act
eri
zedbyaccumul
ati
onofironi
nli
ver
,pancr
eas,
hear
t,pi
tui
tar
y
gl
and,j
oint
sandothert
issues.I
tisusual
l
ycausedbymutat
ionsi
ntheHFEgene

●Wi
l
sondi
seasei
sther
esul
tofaccumul
ati
onofcopperi
nthel
i
ver
,br
ain,
andey
es;
iti
s
causedbyamut
ati
oni
nthemet
ali
ont
ranspor
terATP7B.

•α1-Ant
it
rypsi
n(AAT)def
ici
encyinper
sonsofPiZZgenotypecausespulmonar
y
emphysema( duetoi
ncr
easedelast
aseacti
vi
ty)andl
iv
erinj
ury(
causedbytheaccumul
ati
onof
misf
oldedAAT) .

•Portalv
einobstr
uct
ionbyint
ra-orext
rahepat
ict
hrom bosi
smaycausepor
tal
hyper
tensi
on,
esophagealvar
ices,
andasci
tes.

•Themostcommoncauseofi
mpai
redi
ntr
ahepat
icbl
oodf
lowi
sci
rr
hosi
s.

Themostcommonmal
i
gnantt
umor
soft
hel
i
verar
emet
ast
ati
ccar
cinomas,
mostof
tenf
rom
col
on,l
ung,
andbr
east
.

•Themainet
iol
ogi
cagentsforhepat
ocel
lul
arcar
cinomaar
ehepat
it
isBandC, al
cohol
ic
ci
rr
hosis,
hemochr
omatosi
s,and,morerar
ely,
tyr
osi
nemiaandα1-
ant
it
rypsi
n(AAT)defi
ciency

•I
ntheWester
npopul
ati
on,
about90%ofhepat
ocell
ularcarcinomasdev
elopi
nci
rr
hot
ic
l
i
vers;i
nAsi
a,al
most50%ofcasesdevel
opi
nnoncir
rhoti
clivers.

•Thechroni
cinf
lammationandcell
ularr
egener
ati
onassoci
atedwi
thv
iral
hepat
it
ismaybe
a
pa
pr
edisposi
ngfact
orsfort
hedevelopmentofcarci
nomas.

●Hepati
cadenomai
sabeni
gnhepat
ocell
ularneopl
asm thatusual
l
yoccur
sinwomenofchil
d-
ya

beari
ngagewhohav
eusedoral
cont
racept
ivepil
ls,
anditmayr egr
essondi
sconti
nuanceof
Si

hormoneuse

Gal
l
bladderdi
seasesi
ncl
udechol
eli
thi
asi
sandacut
eandchr
oni
cchol
ecy
sti
ti
s.

•Gall
stonef
ormati
oni
sacommoncondi ti
oni
nWest er
ncountri
es.Thegreatmajori
tyofthe
gal
lst
onesarechol
est
erolst
ones.Pi
gment
edstonescont
aini
ngbili
rubi
nandcalcium ar
emost
commoni nAsi
ancountr
ies.

•Riskf
actorsforthedev
elopmentofchol
est
erol
stonesar
eadv
anci
ngage,
femal
egender
,
est
rogenuse,obesit
y ,
andheredi
ty.

•Cholecyst
it
isal
mostalwaysoccursinassoci
ati
onwi
thchol
eli
thi
asi
s,al
thoughi
nabout10%
ofcasesitoccursi
ntheabsenceofgall
stones.

•Acut
ecal
cul
ouschol
ecy
sti
ti
sist
hemostcommonr
easonf
oremer
gencychol
ecy
stect
omy
.

•Obstr
uctiv
elesi
onsoftheextrahepat
icbil
eductsinadul
tscangi
ver
iset
oascendi
ng
i
nfect
ion(chol
angit
is)andsecondarybi
li
aryci
rrhosi
s

. •I
nfant
sbornwit
hcongeni
tal
bil
i
aryat
resi
apr
esentwi
thneonat
alchol
est
asi
sandr
equi
re
l
i
vert
ranspl
ant
ati
onforcur
e.
●carci
nomaoft hegal
lbl
adderisthemostfrequentmal
ignantt
umorofthebil
iar
ytr
act.I
tis2to
6t i
mesmor ecommoni nwomenandoccur smostfr
equentl
yinthesev
enthdecadeofli
fe.
Carcinomaofthegall
bladderi
smorefrequentint
hepopulat
ionsofMexicoandChi
le,Most
areadenocar
cinomas,

●Chol
angi
ocarci
nomasareadenocarci
nomast
hatar
isef
rom chol
angi
ocy
tesl
i
ningt
he
i
ntr
ahepat
icandext
rahepat
icbi
li
aryducts

Chol
angi
ocarcinomasar
ety
picaladenocarci
nomaswit
hmor eorlesswel
l-
for
medglands
of
tenaccompaniedbyabundantfi
brousstroma(desmopl
asi
a)yiel
dingafi
rm,gri
tt
yconsi
stenc

●Pancr
eas

●Acutepancreat
it
isischar
acteri
zedbyinfl
ammat i
onandr ever
sibl
eparenchymal
damagethat
rangesfr
om focaledemaandf atnecr
osistowidespreadpar
enchymalnecrosi
sand
hemorrhage;t
heclini
calpr
esentat
ionvari
eswidely,
from mil
dabdominalpaintor
api
dlyf
atal
vascul
arcoll
apse.

•Chroni
cpancreati
ti
sischaract
eri
zedbyi
rrever
sibl
eparenchy
mal damageandscarf
ormation;
cl
ini
calpresent
ati
onsincl
udechroni
cmalabsorpt
ion(duetopancr
eati
cexocri
nei
nsuff
ici
ency)
a
anddiabetesmell
it
us(duetoisl
etcel
ll
oss).
pa

Duct
alobst
ruct
ionandl
ong-
ter
m al
cohol
abusear
ethemostcommoncausesi
nbot
hfor
m
ya

Cl
oset
o95%ofmuci
nouscy
sti
cneopl
asmsar
isei
nwomen,
Si

●Serouscyst
adenomasaccountf
orappr
oxi
mat
ely25%ofal
lpancr
eat
iccy
sti
cneopl
asms
female-
tomalerat
ioi
s2:1

●I
ntr
aduct
alpapi
ll
arymuci
nousneoplasms(IPMNs)ar
emucinpr
oducingi
ntr
aduct
alneopl
asms.
I
ncontr
astwit
hmucinouscyst
icneoplasms,I
PMNsoccurmorefr
equentl
yinmenthanin
womenandmor efr
equent
lyi
nvol
vetheheadofthepancr
eas

●Inf
il
tr
ati
ngductal
adenocarci
nomaofthepancreas(mor
ecommonl
yref
err
edt
oas“
pancr
eat
ic
cancer
”)i
sthefourt
hleadi
ngcauseofcancerdeath

Approxi
matel
y60%ofpancr
eat
iccancer
sar
isei
ntheheadoft
hegl
and,
15%i
nthebody
,and
5%inthetai
l;

Obst
ruct
ivej
aundi
cei
saf
eat
ureofcar
cinomaoft
heheadoft
hepancr
eas;

Mal
eGeni
tal
Syst
em andLowerUr
inar
yTr
act

I
nhy
pospadi
as,
themor
ecommonoft
het
wocondi
ti
ons,
theabnor
mal
openi
ngoft
he
ur
ethr
aisont
hev
ent
ral
aspectoft
hepeni
sany
wher
eal
ongt
heshaf
t

I
nepi
spadi
as,
theabnor
mal
uret
hral
ori
fi
cei
sont
hedor
sal
aspectoft
hepeni
s.

Balaniti
sandbalanoposthi
ti
sref
ert
olocal
inf
lammati
onoftheglanspeni
sandofthe
over
lyingprepuce,
respecti
vel
y.wit
haccumul
ati
onsofdesquamat
edepithel
i
alcel
l
s,sweat
,and
debr
is, t
ermedsmegma

Phi
mosisr
epr
esent
sacondi
ti
oni
nwhi
cht
hepr
epucecannotber
etr
act
edeasi
l
yov
ert
he
gl
anspeni
s

Morethan95%ofpeni
l
eneopl
asmsar
iseonsquamousepi
thel
i
um buti
tisuncomoni
n
casesofpeni
s

Squamouscell
car
cinomainsi
tuofthepeni
s(Bowendisease)occur
sinol
derunci
rcumci
sed
malesandappear
sgrossl
yasasoli
tar
yplaqueontheshaf
tofthepenis

I
nvasi
vesquamouscel
lcar
cinomaofthepeni
sappear
sasagr
ay,
crust
ed,
papul
arl
esi
on,
mostcommonlyonthegl
anspenisorpr
epuce

Verr
ucouscarci
nomaisavari
antofsquamouscel
lcar
cinomachar
act
eri
zedbyapapi
l
lar
y
a
pa
ar
chit
ectur
e,v
irt
uall
ynocyt
ologi
catypi
a,

f
ail
ureofdescenti
sassoci
atedwi
tha3-t
o5-
fol
dincr
easedr
iskoft
est
icul
arcancer
ya

Bi
later
alor,
insomecases,
evenuni
l
ater
alcr
ypt
orchi
dism i
sassoci
atedwi
tht
ubul
arat
rophy
Si

andsteri
l
ity
.

Test
icul
art
umor
sar
ethemostcommoncauseofpai
nlesst
est
icul
arenl
argement
.

Germ cell
sar
et hesour
ceof95%oft
est
icul
art
umors,
andtheremai
nderari
sefrom Ser
tol
ior
Leydi
gcells.
Ger
m cellt
umorsmaybecomposedofasi
nglehi
stol
ogi
cpatt
ern(60%ofcases)or
mixedpatter
ns(40%

Semi
noma40–50(
age),
10%ofpat
ient
shav
eel
evat
edhCG

Embr
yonal
car
cinoma20–30(
age)Negat
ive(
pur
eembr
yonal
car
cinoma)

Yol
ksact
umor3(
peakage),
90%ofpat
ient
shav
eel
evat
edAFP

Chor
iocar
cinoma20–30(
age),
100%ofpat
ient
shav
eel
evat
edhCG

Ter
atomaAl
lages,
Negat
ive(
pur
eter
atoma)
(Tumormar
ker
)

Mi
xedt
umor15–30(
age),
90%ofpat
ient
shav
eel
evat
edhCGandAFP

mosthy
per
plast
icl
esi
onsar
isei
nthei
nnert
ransi
ti
onzone,
whi
l
emostcar
cinomas(
70%t
o
80%)ar
isei
ntheper
ipher
alzones.

•Bact
erial
prostat
it
ismaybeacut
eorchr
oni
c;t
her
esponsi
bleor
gani
sm usual
l
yisE.col
ior
anot
hergram-negati
verod.

•Chr
oni
cnonbact
eri
alpr
ost
ati
ti
s(al
soknownaschr
oni
cpel
vi
cpai
nsy
ndr
ome

BPHpref
erent
ial
l
yinvol
vesthei
nnerport
ionsofthepr
ostat
e,t
hemostcommon
manif
est
ati
onsarerel
atedt
oloweruri
naryt
ractobstr
uct
ion

BPHischar
acter
izedbyprol
if
erat
ionofbeni
gnstr
omalandglandul
arel
ements.DHT,
an
andr
ogenderi
vedfr
om test
oster
one,ist
hemajorhor
monalsti
mulusforpr
oli
fer
ati
on

Car
cinomaoft
hepr
ost
atei
sacommoncancerofol
dermenbet
ween65and75y
ear
sofage

Car
cinomasoft
hepr
ost
atear
isemostcommonl
yint
heout
er,
per
ipher
algl
and

Gr
adingofpr
ost
atecancerbyt
heGl
easonsy
stem cor
rel
ateswi
thpat
hol
ogi
cst
ageand
pr
ognosis

Ser
um PSAmeasur ementi
sausef
ulbutimperf
ectcancerscr
eeni
ngt
est
,wi
thsi
gni
fi
cant
a
r
atesoff
alse-
negat
iveandfal
se-
posi
ti
veresul
ts
pa

Evaluat
ionofPSAconcent
rat
ionsaf
tert
reat
menthasgr
eatv
aluei
nmoni
tor
ingpr
ogr
essi
ve
ya

orrecurr
entdi
sease.
Si

Ureter
opel
vi
cjunct
ion(UPJ)obstruct
ion,
acongeni
tal
disor
der,
resul
tsi
nhy
dronephr
osi
s.I
t
usual
lymanif
estsi
ninfancyorchi
ldhood,muchmorecommonl yi
nboys

I
nterst
it
ial
cy st
it
is(
i.
e.,chr
oni
cpelv
icpai
nsy
ndr
ome)i
saper
sist
ent
,pai
nful
for
m ofchr
oni
c
cy
sti
tisoccurr
ingmostfrequent
lyi
nwomen.

Malakopl
akiamostcommonlyoccursint
hebl
adderandr
esul
tsf
rom def
ect
sinphagocy
tic
ordegradat
ivefunct
ionofmacr
ophages

major
it
yofbl
addercancer
s(90%)ar
eur
othel
i
alcar
cinomas.Car
cinomaoft
hebl
adderi
s
morecommoninment haninwomen

Adenocar
cinomasoft hebl
adderar
erar
eandar
ehistol
ogi
cal
l
yident
ical
toadenocar
cinomas
seeni
nthegastroi
ntest
inalt
ract
.Someari
sefr
om ur
achalr
emnant
s

Bl
addert
umor
smostcommonl
ypr
esentwi
thpai
nlesshemat
uri
a.

pri
marysyphi
l
isapai
nlessl
esi
oncal
l
edchancr
edev
elopsont
heext
ernal
geni
tal
i
aal
ongwi
th
r
egional
lymphnodeenl
argement
 .Secondar
ysyphi
l
ismani
festswi
thgener
ali
zedl
ymphadenopat
hyandmucocut
aneous
l
esionscall
edcondyl
omat
alata.

Ter
ti
arysy
phi
l
ismaycausepr
oxi
mal
aor
ti
ti
sandaor
ti
cinsuf
fi
ciency
;Gumma

•Congeni
talsyphi
li
smost
lydur
ingpr
imar
yandsecondar
yst
agesofdi
seasei
nthemot
her
.It
mayleadtosti
l
l bi
rth

Thedi
agnost
icmai
nst
ayisserologi
ctest
ing.Nont
reponemalant
ibodyt
est
s(VDRLandRPR)
ar
eusual
lyposi
ti
vei
near
lydiseasebutnegati
veinadvancedi
seas

GonorrheaisacommonSTDaf
fect
ingt
hegeni
tour
inar
ytr
act•I
nmal
est
her
eisa
sever
e,sy
mpt omati
cur
ethr
it
is

Pregnantwomencant
ransmi
tgonor
rheat
onewbornsdur
ingpassagethrought
hebirt
hcanal
.
•Diagnosi
scanbemadebycul
tur
eoftheexudat
esaswel
l asbynucl
eicacidampl
i
ficat
ion
t
echniques.

NGUandcervi
cit
isar
ethemostcommonf or
msofSTD.Amaj
ori
tyofthecasesar
ecausedby
C.t
rachomat
is,
andther
estbyT.v
aginal
i
s,U.ur
eal
yti
cum,
andM.genit
ali
um.
a
pa
Ly
mphogranul
omaVener
eum,
causedbyC.t
rachomat
isser
oty
pest
hatar
edi
sti
nct
from t
hose
t
hatcauseNGU.
ya

H.ducr
eyi
inf
ect
ioncausesanacut
epai
nful
ulcer
ati
vegeni
tal
inf
ect
ioncal
l
edchancr
oid
Si

Gr
anul
omai
ngui
nal
eisachr
oni
cfi
brosi
ngSTDcausedbyC.gr
anul
omat
is.

Recur
rentl
esionsar
emorecommonwit
hHSV-1thanwi
thHSV-
2inf
ect
ion,
andi
ngener
alar
e
l
espainf
ulandlessext
ensi
vet
hanpr
imar
ylesi
ons

HPVcausesmanyproli
fer
ati
velesi
onsofthegeni
tal
mucosa,
incl
udi
ngcondy
loma
acumi
nat
um, pr
ecancer
ouslesi
ons,andinv
asiv
ecancers.

Femal
eGeni
tal
Syst
em andBr
east

Oneoft hemostcommoncausesofvulv
iti
sisr
eacti
veinfl
ammationi
nresponsetoan
exogenoussti
mulus,whet
herani
rr
it
ant(
contacti
rr
it
antdermati
ti
s)oranal
ler
gen(cont
act
all
ergi
cdermati
ti
s).

Li
chensimplexchr
onicusismar
kedbyepi
thel
i
alt
hickeni
ng(
par
ti
cul
arl
yoft
hest
rat
um
gr
anulosum)andhyperker
atosi
s

Lichenscl
erosusischaract
eri
zedbythinni
ngoftheepi
dermis,di
sappearanceofr
etepegs,
hydropi
cdegenerati
onofthebasalcel
ls,dermal
fibr
osi
s,andascantper
ivascul
ar,
mononuclear
i
nflammatorycelli
nfi
lt
rat
e
 Vul
varPagetdi
seaseischaract
eri
zedbyared,
scal
yplaquecausedbyprol
if
erat
ionof
mali
gnantepi
thel
i
alcel
lswit
hintheepi
der
mis;
usuall
y,t
hereisnounderl
yingcarci
noma,

unl
i
kePagetdi
seaseofni
ppl
e.

•Posi
ti
vest
aini
ngf
orPASdi
sti
ngui
shesPagetdi
seasecel
l
sfr
om mel
anoma

SquamousCel
lCar
cinomaoft
heVul
va

•HPV-r
elat
edv
ulvarsquamouscellcar
cinomasusuall
yarepoorlydif
fer
enti
atedl
esi
onsand
someti
mesaremult
ifocal
.Theyof
tenevol
vef r
om v
ulvari
ntr
aepitheli
alneopl
asi
a(VI
N)

. •Non–HPV- rel
atedvulv
arsquamouscel
lcar
cinomasoccur
inol
derwomen,usual
lyar
ewell
di
ffer
enti
atedandunifocal
,andoft
enar
eassoci
atedwit
hli
chenscl
erosusorot
heri
nfl
ammator
y
condi
ti
ons.

Vagini
ti
sisarelat
ivel
ycommoncondit
ionthati
susuall
ytr
ansientandofnocli
nical
consequence.I
tisassoci
atedwi
thpr
oducti
onofav agi
naldi
scharge(l
eukor
rhea)

cl
earcel
ladenocar
cinoma,aver
yraret
umor,wasident
if
iedi
naclusterofyoungwomen
whosemotherstookdi
ethyl
sti
l
best
roldur
ingpr
egnancytoprev
entt
hreatenedabort
ion
a
pa

C.t
rachomat
isisbyfart
hemostcommonoft
hesepat
hogens,
account
ingf
orasmanyas
40%ofcasesofcerv
ici
ti
s
ya

Mostt
umorsoft
hecerv
ixar
eofepi
thel
i
alor
igi
nandar
ecausedbyoncogeni
cst
rai
nsof
Si

humanpapi
l
lomavi
rus(
HPV).

Ri
skfactorsf
orcervical
carci
nomaarerelat
edtoHPVexposur
e, suchasear
lyageatf
ir
st
i
nter
course,mul
ti
plesexualpart
ner
s,andotherf
act
orsi
ncludi
ngcigarett
e

smoki
ngandi
mmunodef
ici
ency
.

•Near
lyal
lcer
vical
carci
nomasarecausedbyHPVinf
ect
ions,par
ti
cul
arl
yhi
gh-r
iskHPV
ty
pes16,18,
31,and33;t
heHPVv acci
neiseff
ect
ivei
npr
eventi
nginf
ecti
onduetoHPVtypes16
and18

CI
NIi
schar
act
eri
zedbydy
plast
icchangesi
nthel
owert
hir
doft
hesquamousepi
thel
i
um

CINII
,dy
spl
asi
aextendst
othemi
ddl
ethi
rdoft
heepi
thel
i
um andt
akest
hef
orm ofdel
ayed
ker
ati
nocyt
ematur
ati
on.

CI
NI I
I,
ismar
kedbyal
mostcompl
etel
ossofmat
urat
ion,
evengr
eat
erv
ari
ati
oni
ncel
land
nucl
earsi
ze,

Themostcommoncer
vical
car
cinomasar
esquamouscel
lcar
cinomas(
75%)
,fol
l
owedby
adenocar
cinomasandmix
edadenosquamouscarci
nomas(20%)andsmallcel
lneur
oendocr
ine
carci
nomas( l
esst
han5%)
.Al
lofthesety
pesofcarci
nomasarecausedbyHPV.

Endomet
ri
osi
sref
erstoendometri
algl
andsandst
romal
ocat
edout
sidet
heut
erusandmay
i
nvolv
ethepel
vi
corabdominalper
it
oneum

Adenomyosi
sref
erstogr
owthofendometr
ium i
ntot
hemy
omet
ri
um wi
thut
eri
neenl
argement
.
Unl
ikewit
hendometri
osi
s,t
her
eisnocycl
icbl
eeding

Endomet
ri
alhy
per
plasi
aresul
tsf
rom excessendogenousorexogenousest
rogen.

Endomet
ri
oidcarci
nomai
sassoci
atedwit
hestr
ogenexcessandendometri
alhyper
plasi
a.
Ear
lymol
ecul
archangesi
ncl
udei
nact
ivati
onofDNAmismat chrepai
rgenesandthePTENgene

. Serouscar
cinomaoft
heendomet
ri
um ar
isesi
nol
der
womenandusual
l
yisassoci
atedwi
th
endomet
ri
alat
rophy

Ut
eri
neSmoot
hMuscl
eNeopl
asms

•Beni
gnsmoothmuscl
etumors,
cal
ledl
eiomyomas,
arecommonandf
requent
lymul
ti
ple;
t
heymaymanifestwi
thmenor
rhagi
aorasapelv
icmassormaybedet
ect
edasacauseof
a
pa
i
nfer
ti
li
ty

. •Mali
gnantsmoot
hmuscl
etumor
s,cal
l
edl
eiomy
osar
comas,
ari
sedenov
o,notf
rom
ya

l
eiomy
omas.
Si

•Cr
it
eri
aofmal
i
gnancyi
ncl
udenecr
osi
s,cy
tol
ogi
cat
ypi
a,andmi
tot
icact
ivi
ty.

Fal
l
opi
anTubeDi
sease

•Sal
pingi
ti
sisusual
lyacomponentofpel
vi
ci nf
lammator
ydisease;
itr
esul
tsi
nscar
ri
ngof
t
hefall
opiantubel
i
ning,
incr
easi
ngther
iskoftubalect
opi
cpregnancy.

•Fal
l
opiant
ubecar
cinomasusual
l
ymani
festatanadv
ancedst
age,
wit
hinv
olv
ementoft
he
per
it
oneal
cavi
ty.

Poly
cyst
icovar
iandisease(f
ormerl
ycal
ledStei
n-Lev
ent
halsyndr
ome)i
sadisor
deri
nwhi
ch
mult
ipl
ecysti
cfol
li
clesintheovar
iespr
oduceexcessandr
ogensandest
rogens

.
Epi
thel
ialt
umorsaret
hemostcommonmal
i
gnantov
ari
ant
umor
sandar
emor
ecommoni
n
womenolderthan40y
ear
sofage.

•Themajort
ypesofepi
thel
i
altumorsar
eserous,
muci
nous,andendomet
ri
oid.Eachhasa
beni
gn,mal
i
gnant,andborder
li
ne(lowmali
gnantpot
ent
ial
)counter
part
.

•Sexcor
d–st
romal
tumor
smaydi
spl
aydi
ff
erent
iat
iont
owar
dgr
anul
osa,
Ser
tol
i
,Ley
dig,
or
ovar
ianst
romal
cel
l
type.Dependi
ngondi
ff
erent
iat
ion,
theymaypr
oduceest
rogensor
andr
ogens

. •Ger
m cel
ltumors(most
lycy
sti
cter
atomas)ar
ethemost
commonov
ari
ant
umori
nyoung
women;
amajor i
tyar
ebeni
gn

marker
,thepr
otei
nCA-
125,
isel
evat
edi
ntheser
aof75%t
o90%ofwomenwi
thepi
thel
i
al
ov
ari
ancancer

Ect
opicpregnancyInmoret
han90%oft
hesecases,i
mplant
ationoccursi
ntheov
iduct
s
(
tubalpr
egnancy);ot
hersi
tesi
ncl
udet
heovar
iesandtheabdominalcavi
ty

Chr
oni
csal
pingi
ti
swi
thscar
ri
ngi
samaj
orr
iskf
act
orf
ort
ubal
ect
opi
cpr
egnancy
.

Par
ti
almol
es(69xxy)ar
et r
ipl
oidandhav
etwoset
sofpaternalchromosomes.Theyt
ypi
cal
l
y
ar
eaccompani
edbyf et
alt
issue.
Thereisal
owrat
eofper
sistentdisease.

•Complet
emoles(46xx)ar
edi
ploi
d,andal
lchr
omosomesar
epat
ernal
.Noembr
yoni
corf
etal
t
issuesar
eassoci
atedwithcompl
etemole.

•Amongcompletemoles,10%to15%areassoci
atedwi
thpersi
stentdi
seaset
hatusual
ly
a
pa
t
akesthef
orm ofaninv
asivemole.Onl
y2%ofcompletemolesprogresst
ochori
ocar
cinoma

•Gestat
ional
choriocar
cinomaisahi
ghl
yinv
asiv
eandfr
equent
lymet
ast
ati
ctumort
hat
,in
ya

contr
astwithovar
ianchori
ocarci
noma,
isr
esponsi
vet
ochemot
her
apyandcur
ablei
nmost
Si

cases.

Preecl
ampsiai
sduet
oabnormali
ti
esi
nmater
nalandplacental
bloodfl
ow,wit
hresul
tant
pl
acentali
schemi
aandi
nfar
cti
onandabnor
mali
ti
esinpr
oductionofvasodi
lat
ors

Ecl
ampsi
aischar
act
eri
zed,
inaddi
ti
on,
bysei
zur
es.I
tcanbef
atal
whenaccompani
edby
mult
ior
gandamage.

•Fi
brocy
sti
cchangesmaybecl
assi
fi
edasnonpr
oli
fer
ati
ve(
cyst
ic)orpr
oli
fer
ati
ve.

•Prol
if
erat
ivelesi
onsi
ncludeepit
heli
alpr
oli
fer
ati
onsofductsandlobul
es(
withorwit
hout
f
eaturesofatypi
a)andadenosis(
proli
fer
ati
onofter
minalduct
s),someti
mesassoci
atedwit
h
f
ibrosi
s(scl
erosi
ngadenosis)
.

•Atypi
calhyperplasi
a(whetherduct
alorl
obul
ar)i
sassociat
edwi
thaf
ive-
fol
dincr
easei
n
t
heriskofdevelopinglcar
cinoma.

Acutemastit
isdevel
opswhenbact
eri
a,usual
lyStaphylococcusaur
eus,gai
naccesst
othe
breasttissuet
hroughtheduct
s.Thevastmajor
ityofcasesari
seduri
ngtheearl
yweeksof
nursing,
 Fi
broadenomai
sbyf
art
hemostcommonbeni
gnneopl
asm oft
hef
emal
ebr
east
.Iti
sa
bi
phasictumor

phy
ll
odestumor
sar
ebi
phasi
c,bei
ngcomposedofneopl
ast
icst
romal
cel
l
sandepi
thel
i
um-
l
i
nedglands.

•Amaj
ori
ty(
75%)ofbr
eastcancer
sar
edi
agnosedaf
tert
heageof50.

About10%ofal
lbr
eastcancer
sar
ecausedbyi
nher
it
edmut
ati
ons;
BRCA1andBRCA2genes

Duct
alcar
cinomainsit
u(DCI
S)i
saprecur
sortoinvasi
veduct
alcar
cinomaandt
ypi
cal
l
yis
f
oundonmammogr aphi
cexami
nat
ionascal
cif
icat
ions

Lobularcar
cinomainsitu(LCI
S)fr
equentl
yisani
ncidental
findi
ngandusuall
yisnot
associ
atedwithcalci
fi
cat
ions.Whencar
cinomadevel
opsi nawomanwi thaprevi
ousdiagnosi
s
ofLCIS

Est
rogenandpr ogest
eronereceptorst
atusandexpr
essi
onofHER2/
NEUar
eusedpr
imar
il
y
t
odetermineresponsetotreat
ment . a
Est
rogenr
ecept
or–expr
essi
ngt
umor
sar
emor
eli
kel
ytor
espondt
otamoxi
fen.
pa

Themostimportantcauseofhyperestr
ini
sm i
nt hemaleiscir
rhosisandt heconsequent
ya

i
nabil
it
yofthel
ivertometabol
izeest
rogens.Othercausesincl
udeKlinefel
tersyndrome,
anabol
icst
eroi
ds,andsomephar macologi
cagents.
Si

Endocr
ineSy
stem

Themostcommoncauseofhy
per
pit
uit
ari
sm i
sanant
eri
orl
obepi
tui
tar
yadenoma.

•Pitui
tar
yadenomascanbemacr
oadenomas(
great
ert
han1cm i
ndi
amet
er)or
mi
croadenomas

Pr
olact
inomasar
ethemostcommont
ypeofhy
per
funct
ioni
ngpi
tui
tar
yadenoma.

Hy
per
prol
act
inemi
acausesamenor
rhea,
gal
act
orr
hea,
lossofl
i
bido,
andi
nfer
ti
li
ty

Per
sist
enthyper
secret
ionofgr
owt
hhormonest
imulat
esthehepati
csecreti
onofinsul
i
n-l
i
ke
gr
owthfactorI(
somatomedinC),
whi
chcausesmanyofthecl
ini
calmani
festati
ons.

Gr
owthhor
mone( somat ot
rophcel
l
)adenomas:gi
gant
ism (
chi
l
dren)
,acr
omegal
y(adul
ts)
,
andi
mpair
edglucosetol
eranceanddiabet
esmel
li
tus

•Cor
ti
cot
rophcel
ladenomas:
Cushi
ngsy
ndr
ome,
hyper
pigment
ati
on
 •Al
lpi
tui
tar
yadenomas,parti
cul
arl
ynonf
unct
ioni
ngadenomas,
maybeassoci
atedwi
th
masseff
ect
sandhy popi
tui
tar
ism

Hypopi
tui
tar
ism accompani
edbyevi
denceofpost
eri
orpit
uit
arydy
sfunct
ioni
nthef
orm of
di
abetesi
nsi
pidusisalmostal
waysofhypot
hal
amicori
gin.

Sheehansy ndrome,orpostpart
um necr
osi
soft
heant
eri
orpi
tui
tar
y,i
sthemostcommon
f
orm ofcli
nicall
ysigni
fi
cantischemicnecr
osi
soft
heant
eri
orpi
tui
tar
y

Theposteriorpi
tui
tary
,orneurohypophysi
s,i
scomposedofmodi
fiedgli
alcel
l
s(ter
med
pi
tuicyt
es)andaxonal pr
ocessesextendi
ngfrom ner
vecel
lbodi
esi
nt hesupr
aopti
cand
paravent
ri
cularnucl
eiofthehypothal
amus

.Thecl
ini
call
yimpor
tantposter
iorpi
tui
tar
ysyndromesinv
olv
eADHpr
oduct
ion.Theyi
ncl
ude
di
abetesi
nsi
pidusandsecret
ionofinappr
opri
atel
yhighl
evel
sofADH

ADHdef i
ciencycausesdiabet
esinsi
pidus,
acondi
ti
oncharact
eri
zedbyexcessi
veuri
nat
ion
(
polyur
ia)causedbyani nabi
li
tyoft
hekidneytopr
operl
yresor
bwaterfr
om theuri
ne.

Diabetesinsipi
dusfr
om ADHdefici
encyisdesignatedascentral
,todif
fer
ent
iat
eitf
rom
a
nephrogenicdiabetesi
nsi
pidusasaresul
tofrenaltubul
arunresponsiv
enesstoci
rcul
ati
ngADH
pa

I
nt hesyndromeofinappr
opriateADH(
SIADH)secr
eti
on,
ADHexcessi
scausedbysev
eral
ya

ext
racrani
alandint
racr
anial
disorders
Si

ectopi
cthyroi
dti
ssue,mostcommonlylocat
edatt
hebaseoft
het
ongue(
li
ngual
thy
roi
d)or
atothersi
tesabnor
mallyhi
ghintheneck.

Thei
nteracti
onoft hy
roi
dhor monewithi
tsnucleart
hyr
oidhormonerecept
or(TR)r
esul
tsi
n
t
heformationofahor mone-
receptorcompl
exthatbindst
othyroi
dhormoneresponseel
ements
(
TREs)intargetgenes,r
egul
atingthei
rtr
anscr
ipt
ion.

hy
per
thy
roi
dism i
sonl
yone(
albei
tthemostcommon)cat
egor
yoft
hyr
otoxi
cosi
s.

Themeasur
ementofser
um TSHi
sthemostusef
ulsi
ngl
escr
eeni
ngt
estf
orhy
per
thy
roi
dism

Cr
eti
nism r
efer
stohy
pot
hyr
oidi
sm dev
elopi
ngi
ninf
ancyorear
lychi
l
dhood.

Hypot
hyr
oidi
sm dev
elopi
ngi
nol
derchi
l
drenandadul
tsr
esul
tsi
nacondi
ti
onknownas
my
xedema.

Hashimotothyr
oiditi
sisthemostcommoncauseofhypothy
roi
dism i
nareasoftheworl
d
whereiodi
nelevel
sar esuff
ici
entant
it
hyr
oidant
ibodi
es(
anti
thy
rogl
obul
i
n,andanti
thyr
oid
per
oxidaseanti
bodies)

Hashi
mot
othy
roi
dit
iscomest
ocl
i
nical
att
ent
ionaspai
n-l
essenl
argementoft
het
hyr
oid,
usual
l
yassoci
atedwi
thsomedegr
eeofhy
pot
hyr
oidi
sm,
inami
ddl
e-agedwoman.

Hashimot
othyroi
dit
isoft
enhaveot
heraut
oimmunedi
seasesandar
eati
ncr
easedr
iskf
or
t
hedev el
opmentofBcellnon-
Hodgki
nly
mphomas

Subacutegranulomatous(deQuerv
ain)thyr
oidit
isi
sasel
f-
li
miteddisease,
probabl
y
secondar
yt oavirali
nfect
ion,
andischaracter
izedbypai
nandthepresenceofagranulomat
ous
i
nflammationinthethyroi
d.

•Subacut
elymphocyti
cthyroi
dit
isisaself
-l
imi
teddiseasethatoft
enoccursaft
era
pr
egnancy(post
part
um thyr
oidit
is)
,ty
pical
l
yispainl
ess,andischaracter
izedbyl
ymphocy
tic
i
nfl
ammat i
oninthethy
roid.

Grav
esdisease,themostcommoncauseofendogenoushyper
thy
roi
dism,
ischar
act
eri
zed
bythetr
iadofthyr
otoxi
cosi
s,opht
hal
mopat
hy,anddermopathy

Gr
avesdi
seasei
sanaut
oimmunedi
sor
dercausedbyaut
oant
ibodi
est
otheTSHr
ecept
or

•Thethyr
oidi
nGravesdiseaseischaracter
izedbydiff
usehyper
trophyandhyper
plasi
aof
f
oll
icl
esandlymphoi
dinfi
lt
rates;
glycosaminoglycandeposi
ti
onandl y
mphoidinf
il
tr
atesare
a
r
esponsi
blefort
heophthal
mopat hyanddermopat hy.
pa

Di
ff
useandmul
ti
nodul
argoi
ter
sref
lecti
mpai
redsy
nthesi
soft
hyr
oidhor
mone,
mostof
ten
ya

causedbydi
etar
yiodi
nedef
ici
ency
.
Si

t
hedefini
ti
vediagnosi
soft
hyroi
dadenomacanbemadeonl
yaf
tercar
eful
hist
ologi
c
examinat
ionoftheresect
edspeci
men

Fol
l
icul
aradenomasarethemostcommonbeni
gnneopl
asms,
whi
l
epapi
l
lar
ycar
cinomai
s
t
hemostcommonmal i
gnancy.

•Mult
ipl
egeneti
cpathwaysar
einvol
vedinthyr
oidcarci
nogenesi
s.Someoft
hegenet
ic
abnor
malit
iest
hataref
airl
yuni
quetothyr
oidcancersi
ncludePAX8/
PPARGfusi
on

(i
nfoll
i
cularcarci
noma)
,chromosomal
rear
rangementsinvol
vi
ngtheREToncogene(
in
papi
ll
arycancers)
,andmutat
ionsofRET(
inmedull
arycarci
nomas).

•Fol
li
cul
aradenomasandcarci
nomasbothar
ecomposedofwel l
-di
ffer
enti
atedfoll
icular
epi
thel
i
alcel
ls;
thelat
terar
edi
sti
ngui
shedbyevi
denceofcapsul
arand/orvasculari
nvasion.

•Papi
ll
arycarci
nomasar erecogni
zedbasedonnucl earf
eatures(
groundgl
assnuclei,
pseudoi
ncl
usions)evenint
heabsenceofpapi l
lae.Theseneopl
asmstypi
cal
lymetast
asizeby
wayoflymphati
cs,buttheprognosi
sisexcel
lent.

•Anapl
ast
iccar
cinomasar
ethoughtt
oar
isebydedi
ff
erent
iat
ionofmor
edi
ff
erent
iat
ed
neopl
asms.Theyar
ehi
ghl
yaggr
essi
ve,
uni
for
mlyl
ethal
cancer
s.

•Medullar
ycancersarenonepi
thel
i
alneopl
asmsari
singf
rom t
heparafol
l
icul
arCcel
l
sand
canoccurineit
hersporadic(
70%)orfami
li
al(
30%)set
ti
ngs.Amyl
oiddeposi
tsarea
char
acter
isti
chist
ologi
cf i
ndi
ng

Pr
imar
yhy
per
par
athy
roi
dism i
sthemostcommoncauseofasy
mpt
omat
ichy
per
cal
cemi
a.

Thecl
ini
calmanif
estati
onsofhyper
parat
hyr
oidi
sm canbesummar
izedas“
pai
nful
bones,
r
enalst
ones,abdominalgr
oans,andpsychi
cmoans.”

•Secondar
yhyperparat
hyr
oidi
sm mostof
teni
scausedbyr
enal
fai
l
ure,
andt
hepar
athy
roi
d
gl
andsarehyper
plasti
c.

•Mali
gnanciesar
ethemosti
mpor tantcauseofsymptomati
chypercal
cemia,whi
chresul
ts
f
rom ost
eolyt
icmetast
asesorr
eleaseofPTH- r
elat
edprotei
nfr
om nonparat
hyroi
dtumors.

Surgi
call
yinducedhypoparat
hyr
oidi
sm:Themostcommoncausei sinadv
ert
entr
emov
alof
par
athyr
oidsduringthy
roidect
omyorothersur
gical
neckdi
ssect
ions.

•Congeni
tal
absence:Thisoccur
sinconjunct
ionwi
ththy
micaplasi
a(Di
Geor
gesy
ndr
ome)
a
pa
andcardi
acdefect
s,secondar
ytodelet
ionsonchromosome22q11.2

majorcli
nicalmanif
estat
ionsofhypoparat
hyroidism ar
esecondarytohypocalcemiaand
ya

i
ncludeincr
easedneuromuscularir
ri
tabi
li
ty(t
ingli
ng, musclespasms,f
acialgr
imacing,and
Si

sustai
nedcarpopedalspasm ort
etany),
cardi
acar rhythmi
as,and,onoccasi
on,increased
i
ntracr
anial
pr essur
esandseizur
es

Ty pe1di
abetesi
sanautoimmunediseasechar
acter
izedbyprogr
essi
vedest
ructi
onofisl
et
betacell
s,l
eadi
ngtoabsol
uteinsul
i
ndefi
ciency
.Bothautor
eact
iveTcell
sandautoanti
bodi
es
areinvol
ved

. •Ty pe2diabet
esiscausedbyinsul
i
nresi
stanceandbet
acel
ldy
sfunct
ion,
resul
ti
ngi
n
r
elat
iveinsul
i
ndefici
ency.Aut
oimmunit
yisnotinvol
ved.

Thelong-
ter
m compli
cati
onsisatt
ri
but
edtothreeunderl
yi
ngmechani
sms:formati
onofAGEs,
act
ivat
ionofPKC,anddi
sturbancesi
npolyol
pathwaysleadi
ngt
ooxidat
ivest
ress.

Pancreati
cNeur
oendocri
neTumor. PanNETsar emostcommoni nadul
tsandmaybesi ngle
ormult
ifocal
;whentheyar
emal i
gnant,t
heliveri
sthemostcommonsi teofor
ganmetastases.
Thesetumorshaveapropensi
tytoelaborat
epancreat
ichormones,
butsomear enonf
unctiona

Bet
acelltumors(i
nsuli
nomas)arethemostcommont ypeofPanNETandmaybe
responsi
blefortheel
aborati
onofsuff
ici
enti
nsul
int
oinducecli
nical
l
ysigni
fi
canthy
pogl
ycemi
a.
Thecharacteri
sti
ccli
nical
pict
urei
sdomi nat
edbyat
tacksofhypoglycemi
a
 zol
l
ingerandEll
isonfi
rstcal
ledat
tent
iontotheassoci
ati
onofpancreati
cisletcel
ll
esi
ons
wit
hhypersecr
eti
onofgast r
icaci
dandseverepepti
culcer
ati
on,whicharepresentin90%to
95%ofpatient
swithgastri
nomas—thecli
nical
hall
markofZoll
inger
-El
li
sonsy ndrome.

Themostcommoncauseofhy
per
cor
ti
sol
i
sm i
sexogenousadmi
nist
rat
ionofst
eroi
ds

. •Endogenoushypercor
tisol
ism mostof
teni
ssecondar
ytoanACTH-pr
oduci
ngpi
tui
tar
y
mi
croadenoma(Cushingdisease),f
oll
owedbypri
maryadr
enalneopl
asms

ACTH-
independenthyper
cor
ti
sol
i
sm)andpar
aneopl
ast
icACTHpr
oduct
ionbyt
umor
s(e.
g.,
small
cel
llungcancer)
.

bi
l
ater
aldi
ff
useornodul
arhy
per
plasi
a(mostcommonf
indi
ngi
nendogenousCushi
ng
sy
ndrome

I
nsecondaryhyper
aldost
eroni
sm,aldost
eronereleaseoccursinresponsetoacti
vat
ionofthe
r
eni
n-angi
otensi
nsystem.Thiscondi
ti
onischaracteri
zedbyincreasedlevel
sofplasmareni
n

Pri
maryhyperal
dost
eronism,bycontr
ast
,indicatesaprimary,autonomousov erproduct
ionof
aldoster
one,wit
hresul
tantsuppressi
onoft
her enin-angi
otensi
nsy stem anddecreasedplasma
a
reninacti
vi
ty
pa

appr
oxi
mately35%ofcases,
pri
maryhyper
aldost
eroni
sm i
scausedbyasol
i
tar
yal
dost
erone-
ya

secr
eti
ngadenoma,acondi
ti
onref
err
edtoasConnsy ndr
ome.
Si

Thecl
i
nical
hal
l
mar
kofhy
per
aldost
eroni
sm i
shy
per
tensi
on.

Theadrenalcortexcansecreteexcessandr
ogensineitheroftwoset t
ings:adrenocort
ical
neopl
asms( usuall
yv i
ri
li
zi
ngcar ci
nomas)orcongeni
taladrenalhyper
plasia(CAH) . •CAH
consi
stsofagr oupofaut osomalrecessi
vedi
sorder
scharacter
izedbydef ectsinsteroi
d
bi
osynthesi
s,usuallycor
tisol
;themostcommonsubt ypeiscausedbydef i
ciencyoftheenzyme
21-hy
droxyl
ase

Bi
l
ater
alhy
per
plasi
aoft
headr
enal
cor
texi
schar
act
eri
sti
c.

Pri
maryadrenocort
ical
insuf
fi
ciencycanbeacut
e(Wat
erhouse-
Fri
der
ichsensy
ndr
ome)or
chr
onic(
Addisondisease).

•Chroni
cadrenal
insuffi
ci
encyintheWesternworl
dmostof
teni
ssecondar
ytoautoi
mmune
adr
enali
ti
s,whi
choccursint hecont
extofoneoftwoautoi
mmunepol
yendocr
inesy
ndromes:
APS1(causedbymut at
ionsintheAIREgene)orAPS2.

Pri
mar yadr
enocor
ti
cali
nsuffi
ciencyal
soi
schar
act
eri
zedbyhi
ghACTHl
evel
swi
th
associ
atedski
npigmentat
ion.
 10%ofpheochr
omocy
tomasar
eext
raadr
enal
,

•10%ofadr
enal
pheochr
omocy
tomasar
emal
i
gnant
,al
thought
heassoci
atedhy
per
tensi
on

25%ofpersonswit
hpheochr
omocytomasandparagangl
i
omashar
boragerml
inemut
ati
on
i
noneofatleastsi
xknowngenes,
incl
udi
ngRET,NF1,
VHL,SDHB,
SDHC,andSDHD

Neurobl
ast
omaist
hemostcommonextr
acrani
alsol
idt
umorofchi
l
dhood.Theseneopl
asms
occurmostcommonl
ydur
ingt
hefi
rst5y
earsofli
feandmayar
isedur
ingi
nfancy

TheMENsy ndr
omesar
eagroupofinher
it
eddi
seasesresul
ti
ngi
nprol
if
erat
ivel
esi
ons
(
hyperpl
asi
as,
adenomas,
andcar
cinomas)ofmul
ti
pleendocri
neor
gans

MENt y
pe1isinher
it
edi
nanaut osomal
domi
nantpat
ter
n.Thegene(
MEN1)i
slocat
edat
11q13andisat
umorsuppressorgene

Par
athy
roi
d:Pri
mar
yhy
per
par
athy
roi
dism i
sthemostcommonmani
fest
ati
onofMEN-
1(80%
t
o95%ofpatient
s)

Pancr
eas:
Endocr
inet
umor
soft
hepancr
easar
ethel
eadi
ngcauseofdeat
hinMEN-
1.
a
Pi
tui
tar
y:Themostf
requentpi
tui
tar
ytumori
npat
ient
swi
thMEN-
1isapr
olact
in-
secr
eti
ng
pa

macr
oadenoma
ya

commonlyinvol
vedinMENt ype2Aincl
ude•Thyroi
d:Medul
l
arycar
cinomaofthethyroid
commonlyaremulti
focal
,andfociofCcell
hyper
plasi
acanbefoundi
nt headj
acentthy
r oi
d,
Si

adr
enal
medual ,
parathyr
oidgl
andareothers

MEN-
2A,
wit
hthef
oll
owi
ngdi
ff
erences:

•Pr
imar
yhy
per
par
athy
roi
dism doesnotdev
elopi
npat
ient
swi
thMEN-
2B.

•Ex
traendocr
inemani
fest
ati
onsar
echar
act
eri
sti
cinpat
ient
swi
thMEN-
2B.

al
lpersonscarr
yingger
mlineRETmut at
ionsareadvi
sedtohav
epr
ophy
lact
ict
hyr
oidect
omy
t
opreventtheinev
itabl
edevelopmentofmedull
arycar
cinomas

Bones,
Joi
nts,
andSof
tTi
ssueTumor
s

Abnormali
ti
esinasingleorgr
oupofbonesarecall
eddysost
osesandcanr
esul
tint
he
absenceofbones,super
numerarybones,
ori
nappropr
iat
elyf
usedbones;

Abnor
mal
i
tiesi
nboneorcar
ti
lageor
ganogenesi
sar
ecal
l
eddy
spl
asi
as

Achondropl
asi
aandt
hanatophor
icdwarf
ism occurasaconsequenceofconst
it
uti
veFGFR3
act
ivat
ion,
resul
ti
ngi
ndefect
ivecar
ti
lagesy
nthesisatgrowt
hplat
es
. Osteogenesisimperf
ecta(bri
tt
lebonedisease)i
sagroupofdi
sor
derscausedbymut at
ions
i
nthegenesf orty
pe1col l
agenthatint
erf
erewithit
snor
mal pr
oducti
on,wit
hresul
tantbone
f
ragi
l
ityandsusceptibi
l
ityt
of r
actures.

Ost
eopet
rosi
siscausedbymut ati
onsthati
nter
fer
ewit
hosteocl
astf
uncti
onandis
associ
atedwi
thdensebutarchi
tectur
all
yunsoundboneowingt
odefect
iveboner
esorpt
ion.

Osteopor
osisr
esul
tsfr
om decr
easedbonemassandi
scl
i
nical
l
ysi
gni
fi
cantbecausei
t
pr
edisposesbonetof
ract
ure

t
womostcommonf ormsareseni
l
eosteopor
osisduetoagingrelatedlossesofosteobl
ast
f
uncti
on,
andpostmenopausalost
eopor
osisduetoincr
easedosteoclasti
cactivi
tycausedby
t
herel
ati
veabsenceofestr
ogen

Pagetdiseasemayresul
tfr
om aparamy xovi
rusinf
ecti
oningenet
ical
l
ysuscept
ibl
epersons
andiscausedbyaberr
antandexcessi
veost eocl
astacti
vi
ty,
fol
lowedbyexuber
ant—but
str
uctur
all
yunsound—osteobl
astdeposit
ionofbone.

•Pri
maryorsecondary(duetorenalfai
l
ure)ov
erproductionofPTH(hy
perparat
hyr
oidi
sm)
result
sinincr
easedosteoclastact
ivi
tyandboneresorpt
ion,
leadi
ngtof
racturesand
a
deformiti
es
pa

Py
ogeni
cost
eomy
li
ti
sSt
aphy
lococcusaur
eusi
sthemostf
requentcausat
iveor
gani
sm
ya

;
Ent
rappedboner
api
dlybecomesnecr
oti
c;t
hisnon-
viabl
ebonei
scal
l
edasequest
rum.
Si

Thediagnost
icr
adi
ologi
cfi
ndi
ngs:
adest
ruct
ivel
yti
cfocussur
roundedbyedemaanda
scl
erot
icri
m.

Tuber
cul
osi
soft
hev
ert
ebr
albodi
esi
sacl
i
nical
l
yser
iousf
orm ofost
eomy
eli
ti
s

Fi
brouscor
ti
cal
def
ect
/nonossi
fyi
ngf
ibr
oma—spi
ndl
ecel
l
sar
rangedi
nst
ori
for
m pat
ter
n

Fi
brousdy
spl
asi
a—cur
vil
i
neart
rabecul
aeofwov
enbonesur
roundedbybeni
gnf
ibr
obl
ast
s

Ost
eoi
dost
eoma—i
slandsofwov
enbone,
typi
cal
l
yinv
olv
ingt
hepr
oxi
mal
femurort
ibi
a

Ost
eochondr
oma—car
ti
lage-
cappedout
growt
hsatepiphy
seal
growt
hpl
ates

Enchondr
oma—nodul
esofhy
ali
necar
ti
lage

Giantcel
ltumor
—composedofamixt
ureofneopl
ast
icmononuclearcel
l
sandr
eact
ive
ost
eoclast-
li
kegi
antcel
l
s,t
ypi
cal
l
yoccupyi
nglongboneepi
physes

Met
ast
ati
ctumor
sar
ethemostcommonmal
i
gnantt
umor
sinv
olv
ingbone
 Ost
eosar
coma—mal
i
gnantmesenchy
mal
tumorf
ormi
ngbone;
20%ofpr
imar
ybonet
umor
s

Chondr
osar
coma—mal
i
gnantmesenchy
mal
tumorf
ormi
ngcar
ti
lage

Ewi
ngsarcoma—aggr
essi
vesmal
lroundcel
ltumorofadol
escent
swi
thEWSgene
r
earr
angements.

Ost
eoar
thr
it
is,
ordegener
ati
vej
ointdi
sease,
ist
hemostcommonj
ointdi
sor
der
.

personsol
derthan65y ear
sofage.Thef
undament
alf
eat
ureofost
eoar
thr
it
isi
sdegener
ati
onof
thearti
cul
arcart
il
age;

Rheumatoidar
thri
ti
s(RA)isachr
oni
caut
oimmunei
nfl
am mat
orydi
seaset
hataf
fect
smai
nly
t
hejoint
s,especi
all
ysmallj
oint
s,

RAi
scausedbyanaut
oimmuner
esponseagai
nstsel
f-
ant
igen(
s)

.Goutandpseudogout
.Increasedci
rcul
atinglev
elsofuri
caci
d(gout)orcal
cium
py
rophosphat
e(pseudogout)canleadtocrystal
deposit
ionint
hejoi
ntspace.

react
ivetumor
-l
ikel
esi
onssuchasgangl
i
onsandsy
nov
ial
cyst
sar
emuchmor
ecommont
han
a
neoplasms;
pa

Li
pomasar
ebeni
gnt
umor
soff
atandar
ethemostcommonsof
tti
ssuet
umor
sinadul
ts.
ya

Li
posar
comasaremal
ignantneopl
asmswit
hadi
pocy
tedi
ff
erent
iat
ion.Theyoccurmost
Si

commonlyint
hef
if
thandsixt
hdecadesofl
if
e.

Mostl
i
posar
comasar
isei
nthedeepsof
tti
ssuesori
nther
etr
oper
it
oneum

Myosit
isossi
fi
cansisdist
ingui
shedfr
om ot
herfi
brobl
ast
icpr
oli
fer
ati
onsbythepr
esenceof
metapl
asti
cbone.Itusual
l
ydev el
opsint
heproxi
malmusclesoft
heextremi
ti
esinat
hlet
ic
adol
escentsandyoungadult
saf t
ertr
auma

Fibr
osar
comasaremal i
gnantneoplasmscomposedoff
ibrobl
ast
s.Mostoccuri
nadul
ts,
t
ypical
lyi
nthedeept
issuesofthethigh,knee,
andr
etr
oper
it
onealar
ea.

Rhabdomy osar
comaisthemostcommonsof
tti
ssuesar
comaofchi
l
dhoodandadol
escence,
usual
lyappeari
ngbefor
eage20

Beni
gnsmoot
hmuscl
etumor
s,orl
eiomy
omas,
comonl
yinut
erus

Lei
omyosar
comasaccountf
or10%t
o20%ofsof
tti
ssuesar
comas.Theyoccuri
nadul
ts,
morecommonlyf
emales.

.Synovi
alsar
comasaccountf
orapproxi
matel
y10%ofall
softt
issuesar
comas, t
ypical
l
y
occur
ringi
npersonsi
nthei
r20sto40s.Theyusual
l
ydev
elopindeepsoftt
issuesaroundthe
l
argej
oint
soft
heext
remi
ti
es,
wit
h60%t
o70%occur
ri
ngar
oundt
heknee;

Per
ipher
alNer
vesandMuscl
es

•Per
ipher
alneur
opathi
esmayr esul
tinweaknessand/orsensor
ydef
ici
tsandmaybe
sy
mmet ri
corconsi
stofrandom i
nvolv
ementofindiv
idualner
ves.

•Axonalanddemyeli
nat
ingperipher
alneuropat
hiescanbedist
ingui
shedonthebasi
sof
cl
i
nicalandpathol
ogi
cfeat ur
es.Somedi sor
dersareassoci
atedwithamixedpat
ter
nofinj
ury
.

•Di
abet
esi
sthemostcommoncauseofper
ipher
alneur
opat
hy.

•Gui
ll
ain-
Bar
résyndromeandchroni
cidi
opat
hicdemyel
i
nati
ngpoly
neuropat
hyareimmune-
mediat
eddemyeli
nati
ngdiseasest
hatf
oll
owacuteandchr
oni
ccour
ses,r
especti
vel
y.

Myastheniagravi
siscausedbyaut
oanti
bodiesthatbl
ockthef
uncti
onofpost
synapti
c
acet
ylchol
inerecept
orsatmotorendpl
ates,whichresul
tsi
nthedegr
adat
ionanddeplet
ionof
ther
eceptors a
Cl
ini
cal
ly,myastheni
agr
avisfr
equent
lymani
fest
swit
hptosi
s(dr
oopi
ngey
eli
ds)ordi
plopi
a
pa

(
doublevi
sion)duetoweaknessint
heextr
aocul
armuscl
es
ya

Lamber t
-Eat
onsyndr
omei scausedbyautoant
ibodi
esthati
nhibi
tthefunct
ionofpr
esy
napt
ic
cal
cium channel
s,whi
chreducestherel
easeofacetyl
chol
inei
ntothesynapti
cclef
t
Si

I
ncont
rastwi
ththosesuf
fer
ingfr
om myast
heni
agravi
s,pati
ent
swi
thLamber
t-
Eat
on
sy
ndromeexper
iencei
mprovementi
nweaknesswit
hrepeti
ti
vesti
mul
ati
on.

I
nfectionsmaybeassoci
atedwithdefect
sinneur
alt
ransmi
ssi
onandmuscl
econt
ract
ion.
Cl
ostri
dium tet
ani
andClost
ri
dium botul
i
num

Thegenet
icfor
msofmy opat
hyf
alli
ntosever
alf
air
lydi
sti
nctcl
ini
calphenot
ypes,
incl
udi
ng
muscul
ardystr
ophy,
congeni
tal
myopat
hy,andcongeni
tal
musculardystr
ophy.

•Dystr
ophi
nopat
hiesareX-l
inkeddisor
der
scausedbymut at
ionsinthedystr
ophingeneand
di
srupt
ionoft
hedystrophi
n-gl
ycoprot
eincompl
ex.Dependi
ngont hety
peofmut at
iont
he
di
seasemaybesevere,suchasDuchennemusculardystr
ophy,ormil
d( e.
g.,
Beckerdystr
ophy
).

Per
ipher
alNer
veSheat
hTumor
s

•Inmostperi
pher
alner
vesheat
htumor
s,t
heneopl
ast
iccel
l
sshowev
idenceofSchwanncel
l
di
ffer
ent
iat
ion.

•Per
ipher
alner
vesheat
htumor
sar
eimpor
tantf
eat
uresoft
hef
ami
l
ial
tumorsy
ndr
omes
neur
ofi
bromat
osi
sty
pe1(
NF1)andt
ype2(
NF2)
.

•Schwannomasandneur
ofi
bromasar
ebeni
gnner
vesheat
htumor
s.

•Schwannomasareci
rcumscr
ibed,
usual
l
yencapsul
atedt
umor
sthatabutt
hener
veofor
igi
n
andareafeat
ureofNF2.

•Neur
ofi
bromasmaymanif
estasaspor
adicsubcut
aneousnodul
e,asal
arge,
poor
lydef
ined
sof
tti
ssuel
esion,
orasagr
owthwithi
naner
ve.Neurof
ibr
omasareassoci
atedwi
thNF1.

•About50%ofmal i
gnantperi
pher
alnervesheathtumorsoccurdenov
oinotherwi
senor
mal
persons,whi
l
etheremainderar
isefr
om themalignantt
ransf
ormati
onofapreexi
sti
ngNF1-
associat
edneur
ofi
broma.

#Aut
oimune

SLEisasyst
emicautoi
mmunedi
seasecausedbyaut
oant
ibodi
espr
oducedagai
nst
numeroussel
f-
ant
igensandt
hef
ormati
onofimmunecomplexes.

I
nSLEThemostcommoncausesofdeat
har
erenal
fai
l
ure,
int
ercur
renti
nfect
ions,
and
car
diov
ascul
ardi
sease
a
pa

ANAsar
efoundi
nvi
rt
ual
l
y100%ofpat
ient
s,butani
mpor
tantpoi
nti
sthatANAsar
enot
speci
fi
c
ya

I
mmunol
ogi
cdi
sor
der(
ant
i-
dsDNA,
ant
i-
Sm,
ant
iphosphol
i
pid)
Si

Antiphosphol
ipidsyndr ome1°or2°aut oimmunedisorder(mostcommonl yinSLE).
Diagnose
basedoncl i
nicalcri
teriaincl
udinghistor
yofthrombosis(art
eri
alorvenous)orspontaneous
abor
tionalongwi t
hlabor atoryf
indingsoflupusanti
coagulant
,ant
icar
dioli
pin,anti
-β2
gl
ycopr ot
einant
ibodies.Treatwithsy st
emicanti
coagulat
ion.

Sjögrensyndromeisacl i
nicopathol
ogi
centi
tychar
acteri
zedbydryeyes
(keratoconjunct
ivi
ti
ssicca)anddr ymouth(xer
ost
omia),
resul
ti
ngfr
om immune-
medi
ated
destructionofthelacr
imalandsal i
varygl
ands

About60%ofSjögr
enpat
ient
shav eanotheraccompanyi
ngaut
oimmunedi
sor
dersuchas
RA.Not
ably,
ther
eisa40-
fol
dincreasedri
skfordevel
opinganon-
Hodgki
nBcel
ll
ymphoma,

Sj
ögrenpat
ient
shaveAnti
-SSAandanti
-SSBmayalsobeseeni
nSLE.⊕Ant
i-
SSAi
n
pr
egnantwomenwithSLEr
iskofcongeni
talhear
tbl
ockint
henewbor
n.

Ser
onegati
vespondyl
oar
thri
ti
sArt
hri
ti
swit
houtrheumatoi
dfact
or(noant
i-
IgGant
ibody
).
St
rongassoci
ati
onwithHLA-B27(MHCclassIser
otype)
.Subty
pes(PAIR

React
ivear
thr
it
isFor
mer
lyknownasRei
tersy
ndr
ome.Cl
assi
ctr
iad:
Conj
unct
ivi
ti
s,
Uret
hri
ti
s
Ar
thr
it
i

Pol
ymyosi
ti
s/dermatomyosi
ti
sCK,
⊕ANA( nonspecif
ic)
,⊕anti
-Jo-
1(hi
sti
dyl
-t
RNAsy
nthet
ase)
(
speci
fi
c),
⊕anti-SRP(speci
fi
c),
⊕anti
-Mi
-2(
specif
ic)anti
bodi
es

Polymy osi
tisProgressi
vesymmet r
icpr
oximalmuscleweakness,character
izedby
endomy si
al i
nflammat i
onwithCD8+Tcells.Mostof
teninvolv
esshoulders. Der matomy
osit
is
Cli
nical
lysimilartopolymyosi
ti
s,butal
soinvol
vesmalarrash(si
mil
artot hati
nSLEbutinv
olv
es
nasolabi
al f
olds),

Syst
emicscler
osis(SS)i
sani mmunol
ogicdisor
derchar
acter
izedbyexcessi
vefi
brosi
sin
mult
ipl
eti
ssues,obli
ter
ati
vevascul
ardi
sease,
andev i
denceofautoi
mmuni t
y,mainl
ythe
pr
oducti
onofmul t
ipl
eautoanti
bodi
es

Di
ff
usescl
eroder
ma—widespr
eadskininv
olvement
,rapi
dprogr
essi
on,ear
lyvi
sceral
i
nvol
vement
.Associ
atedwi
thanti
-Scl
-70ant
ibody(
anti
-DNAtopoi
someraseIant
ibody)
.

Li
mit
edscl
eroder
ma—l
i
mit
edski
ninv
olv
ementconf
inedt
ofi
nger
sandf
ace.Al
sowi
th

CRESTsy
ndr
ome
a
pa
Cent
ral
Ner
vousSy
stem

Cer
ebraledemai
stheaccumul
ati
onofexcessfl
uidwi
thinthebrai
nparenchy
ma.
ya

Hydr
ocephalusi
sdef
inedasani
ncreasei
nCSFv ol
umewi t
hinall
orpartofthevent
ri
cul
ar
Si

sy
stem.

•I
ncr
easesinbr
ainvolume(asaresul
tofincr
easedCSFv ol
ume,
edema,
hemor
rhage,
or
t
umor)r
aisethepr
essureinsi
dethef
ixedcapaci
tyoftheskul
l.

•Incr
easesinpr
essur
ecandamagethebrai
neit
herbydecr
easi
ngper
fusi
onorbydi spl
acing
t
issueacrossdur
alpar
ti
ti
onsi
nsi
detheskul
lorthr
oughopeni
ngsi
ntheskul
l(her
niat
ions).

St
rokeist
hecli
nicalt
ermforacut
e-onsetneur
ologi
cdef
ici
tsr
esul
ti
ngf
rom hemor
rhagi
cor
obst
ruct
ivev
ascul
arlesi
ons.

•Cerebr
ali
nfar
cti
onfol
lowslossofbloodsuppl
yandcanbewi despr
eadorf
ocal
,oraf
fect
r
egionswit
htheleastr
obustvascul
arsuppl
y(“wat
ershed”i
nfar
cts)
.

•Focalcerebrali
nfarct
saremostcommonlyembol i
c;wit
hsubsequentdi ssolut
ionofan
emboli
sm andr eperf
usion,anonhemorr
hagi
cinf
arctcanbecomehemor rhagic. •Primary
i
ntr
aparenchymal hemor r
hagestypi
cal
l
yareduetoeit
herhy per
tension(mostcommonl yin
whit
emat ter
,deepgr aymatter
,orpost
eri
orf
ossacontents)orcerebral
amy loidangi
opathy
.

•Spont
aneoussubar
achnoi
dhemor r
hageusual
l
yiscausedbyast
ruct
ural
vascul
ar
abnor
mali
ty,
suchasananeurysm orar
ter
iov
enousmalf
ormati
on
 i
njurybothattheori
ginalpoi
ntofcontact(coupinj
ury
)andont
heopposi
tesi
deoft
hebr
ain
(
contrecoupinj
ury)owi
ngt oimpact
swi t
ht heskull
.

Epi
dur
alHematomaDur al
vessel
s—especial
l
ythemiddlemeningeal
art
ery—ar
evul
ner
abl
eto
t
raumati
cinj
ury
.Cli
nical
l
y,pati
ent
scanbel uci
dforsev
eralhour
sbetweenthemomentof
t
raumaandthedevelopmentofneur
ologi
csigns

Subdur al
Hemat omaRapi
dmov ementofthebr ai
nduringtraumacantearthebri
dgi
ngvei
ns
patientswit
hbrai
natrophy,t
hebri
dgingveinsarestret
chedout,andthebrai
nhasaddi
ti
onal
spacewi thi
nwhichtomov e,
account
ingforthehigherrat
eofsubduralhematomasinel
derl
y
persons.

Neur
alTubeDefect
sPar t
ial
fail
ureorrev
ersal
ofneur
altubeclosur
eFol
atedef
ici
encydur
ing
t
heini
ti
alweeksofgestat
ionalsoincr
easesri
skthr
oughuncert
ainmechani
sms;

eachchar
act
eri
zedbyabnor mali
ti
esinvol
vi
ngsomecombi nati
onofneuralt
issue,
meninges,
andover
lyi
ngboneorsoftt
issues.Coll
ect
ivel
y,neur
alt
ubedefect
sconsti
tutet
hemostfrequent
ty
peofCNSmal f
ormati
on

Myel
omeni
ngocel
eisanextensi
onofCNSt i
ssuethr
oughadef
ecti
nthev
ert
ebr
alcol
umn
a
t
hatoccur
smostcommonlyinthelumbosacr
alregi
on
pa

anencephal
yisamalfor
mati
onoftheant
eri
orendoft
heneur
alt
ubet
hatl
eadst
othe
ya

absenceofthebrai
nandthet
opofskull
.
Si

I
ncert
ainmalfor
mations,t
hevolumeofthebr
aini
sabnor
mal
l
ylar
ge(megal
encephal
y)or
smal
l(mi
croencephal
y).Micr
oencephal
y,byf
art
hemorecommonofthet
wo,

Lissencephal
y(agy
ria)or
,wi
thmor
epat
chyi
nvol
vement
,pachy
gyr
ia,
ischar
act
eri
zedby
absentgyrati
on

Hol
opr
osencephal
yischar
act
eri
zedbyadi
srupt
ionoft
henor
mal
midl
i
nepat
ter
ning

Pol
ymi
crogy
riai
scharact
eri
zedbyanincr
easednumberofi
rr
egul
arl
yfor
medgy
rit
hatr
esul
t
i
nabumpyorcobblest
one-l
i
kesurf
ace.

TheAr
nol
d-Chiar
imalfor
mat i
on(Chiarit
ypeIImal
for
mati
on)combi nesasmal l
post
erior
f
ossawit
hami sshapenmidli
necerebell
um anddownwardextensi
onoft hever
misthr
ought he
f
oramenmagnum; hydr
ocephalusandal umbarmyel
omeningocelety
picall
yareal
sopresent.

Thefarmi
l
derChi
ari
typeImal
for
mat
ionhasl
ow-
ly
ingcer
ebel
l
art
onsi
l
sthatext
endt
hrough
t
heforamenmagnum.

Dandy-
Walkermalf
ormati
on,
charact
eri
zedbyanenl
argedpost
eri
orf
ossa,
absenceoft
he
cer
ebell
arver
mis,andalar
gemidl
inecyst
,
 Jouber
tsy
ndrome,i
nwhichther
eisabsenceoft
hevermisandbrai
nst
em abnor
mal
i
ties
r
esul
ti
ngineyemovementprobl
emsanddisrupt
edr
espi
rator
ypatt
erns

expansi
onsoft heependyma-
li
nedcent
ralcanaloft
hecord(hydr
omy el
i
a)ordevel
opmentof
f
lui
d-fi
ll
edclef
tl
ikecavi
tiesi
nthei
nnerpor
tionofthecord(
syri
ngomy el
i
a,syr
inx)
.

Thet
womaj
ort
ypesofi
njur
ythatoccuri
ntheper
inat
alper
iodar
ehemor
rhagesandi
nfar
cts

Meningit
isisaninfl
ammator
yprocessinv
olvi
ngt
heleptomeni
ngeswi
thi
nthesubarachnoi
d
space;
iftheinfect
ionspr
eadsi
ntotheunderl
yi
ngbr
ainiti
ster
medmeningoencephal
i
tis.

Escher
ichi
acol
iandt
hegr
oupBst
rept
ococci
;i
nadol
escent
sandi
nyoungadul
ts,
Nei
sser
ia

meningi
ti
disi
sthemostcommonpat hogen;
andi
nol
deri
ndi
vi
dual
s,St
rept
ococcus
pneumoniaeandLi
ster
iamonocy
togenesaremor
ecommon

Acut
ePyogeni
cMeningit
is(
Bact
eri
alMeni
ngit
is)Lumbarpunctur
erev
ealsanincr
eased
pr
essur
e;exami
nati
onoftheCSFshowsabundantneutr
ophi
ls,
elevat
edprot
ein,
andreduced
gl
ucose

Asept
icmeni
ngi
ti
sisacli
nicalt
ermforani
ll
nesscompr
isi
ngmeni
ngeal
irr
it
ati
on,
fev
er,
and
a
pa
al
ter
ati
onsi
nconsci
ousnessofrel
ati
vel
yacut
eonset.

I
ncont
rastt
opy
ogeni
cmeni
ngi
ti
s,exami
nat
ionoft
heCSFof
tenshowsl
ymphocy
tosi
s,
ya

moder
atepr
otei
nel
evat
ion,
andanor
mal
glucosel
evel
.
Si

Tuberculousmeni ngit
isusuallymanifestswithgener
ali zedsignsandsymptomsof
headache, mal ai
se,mentalconf usi
on,andv omiti
ng.Ther
ei sonlyamoder at
eincr
easeinCSF
cellul
ari
ty,withmononucl earcellsorami xtur
eofpolymor phonuclearandmononucl
earcell
s;
theproteinlevelisel
ev at
ed,oftenstri
kinglyso,andtheglucosecont entt
ypi
cal
lyi
smoder at
ely
reducedornor mal.

Neur
osy
phil
i
s,ater
ti
arystageofsyphi
l
is,occur
sinabout10%ofpersonswit
huntreated
Tr
eponemapal
li
dum i
nfect
ion.Pat
ient
swithHIVinfect
ionar
eati
ncreasedri
skforneurosyphi
l
is,

Neur
oborr
eliosi
srepresent
sinv
olv
ementoft
hener
voussy
stem byt
hespi
rochet
eBor
rel
i
a
bur
gdorf
eri
,thepathogenofLymedisease.

Pri
ondiseasesaretr
ansmit
tedbyanal
ter
edf
orm ofanor
mal
cel
l
ularpr
otei
n.Theycanbe
spor
adic,
transmit
ted,
orinher
it
ed.

MSi sanautoi
mmunedemy el
inat
ingdisordercharacteri
zedbydist
inctepisodesof
neurol
ogicdef
ici
ts,
separ
atedi
ntime,at
tri
butabletowhi tematt
erlesi
onst hataresepar
atedi
n
spaceI
tisthemostcommonoft hedemyelinati
ngdisorders,
 Alzhei
merdisease(AD)i st
hemostcommoncauseofdement iaThediseaseusual
ly
manifest
swiththeinsi
diousonsetofimpai
redhigheri
ntell
ect
ual f
uncti
onandalter
edmood
andbehavior
.Later,
thi
spr ogr
essestodi
sori
entati
on,memoryloss,andaphasi
a,fi
ndings
i
ndicati
veofseverecort
icaldysf
unct
ion

ADisdi
agnosedbythepresenceofpl
aques(
anext
racel
l
ularl
esi
on)
;andneur
ofi
bri
l
lar
y
t
angl
es(anint
racel
l
ularl
esi
on

fr
ontotemporall
obardegenerati
on(FTLD).Thesedisor der
ssharecli
nicalf
eatur
es
(pr
ogressivedet
eri
orati
onoflanguageandchangesi npersonal
it
y)stemmi ngfr
om the
degenerat
ionandatrophyoftemporalandfr
ontallobes;

Parki
nsoni
sm isacl i
nicalsy
ndromecharact
eri
zedbytr
emor,
rigi
dit
y,brady
kinesi
aand
i
nstabil
i
ty,
majorhist
ologicfi
ndingisLewyneur
it
es,dy
str
ophi
cneuri
testhatalsocontai
n
abnormall
yaggregatedα-synuclei
n.

Hunti
ngtondi
sease(HD)i
sanautosomal
dominantmov
ementdi
sor
derassoci
atedwi
th
degener
ati
onofthestr
iat
um (
caudat
eandputamen)
.

Amyot
rophi
clater
alscl
erosi
s(ALS)resul
tsf
rom t
hedeat
hoflowermotorneur
onsinthe
a
spi
nal
cordandbrainst
em, andofuppermotorneur
ons(
Betzcel
ls)i
nthemotorcor
tex.
pa

Themaj
ort
ypesofgl
i
alt
umor
sar
east
rocy
tomas,
oli
godendr
ogl
i
omas,
andependy
momas
ya

Di
ff
useast
rocyt
omasaccountforabout80%ofadul
tgl
iomas.Theyar
emostfrequenti
nthe
Si

f
ourt
hthr
oughthesixt
hdecadesofli
fe.Theyusual
l
yar
efoundinthecer
ebr
alhemispher
es

mutat
ionst
hatal
tertheenzymat
icact
ivi
tyoft
woisof
ormsofthemetabol
i
cenzyme
i
soci
tr
atedehydr
ogenase(I
DH1andIDH2)arecommoninlower
-gr
adeastr
ocyt
omas.

Ol
igodendr
ogli
omasaccountfor5%t
o15%ofgl
i
omasandmostcommonl
yar
edet
ect
edi
n
t
hefourthandfi
ft
hdecadesofli
fe

Ependy momasmostof tenari

senextt ot
heependymalinedventr
icularsy
stem,incl
udingthe
centralcanalofthespinal
cord.I
nthef i
rst2decadesofli
fe,t
heytypicall
yoccurnearthefourt
h
ventri
cleandconst i
tut
e5%t o10%oft heprimarybrai
ntumorsinthisagegroup.Inadults,
the
spinalcordistheirmostcommonl ocati
on;

Medul
l
obl
ast
omaoccur
spr
edomi
nant
lyi
nchi
l
drenandexcl
usi
vel
yint
hecer
ebel
l
um

Meningi
omasarepr
edomi
nantl
ybeni
gntumorsthatar
isefr
om ar
achnoi
dmeni
ngot
hel
i
alcel
l
s.
Theyusual
l
yoccuri
nadul
tsandar
eoftenat
tachedtothedura

Met
ast
ati
clesi
ons,most
lycar
cinomas,
accountforapproxi
matelyonefour
thtoonehal
fof
i
ntr
acr
ani
alt
umors.Themostcommonpr i
marysitesarelung,
breast,ski
n(mel
anoma),ki
dney
,
andgast
roi
ntest
inal
tract
—toget
hert
heseaccountf
orabout80%ofcases

Ski
n

Ur
ti
cari
a(“hi
ves”)i
sacommondi sor
dermediat
edbyl
ocal
i
zedmastcel
ldegr
anul
ati
on,
whi
ch
l
eadstodermalmicrovascul
arhy
per
per
meabil
it
y

Er
ythemamult
ifor
meisanuncommon, usual
l
ysel
f-
li
mit
eddi
sor
dert
hatappear
stobea
hy
persensi
ti
vi
tyr
esponset
ocert
aini
nfect
ionsanddr
ugs.

mostcommonf or
m,contactder
matit
is,i
stri
ggeredbyexposur
etoanenvironment
al
cont
actsensi
ti
zi
ngagent
,suchaspoisonivy
,thatchemical
l
yreact
swit
hself
-pr
otei
ns

Psori
asi
sisacommonchr oni
cinf
lammator
yder
mat
osi
s,psor
iasi
sisassoci
atedwi
than
i
ncreasedr
iskofhear
tat
tackandstr
okes,

Pr
uri
ti
c,pur
ple,
pol
ygonal
,pl
anarpapul
es,
andpl
aques”ar
ethet
ongue-
twi
sti
ng

Impeti
go,oneoft
hemostcommonbacter
iali
nfecti
onsoftheski
n,i
sseenpri
mari
l
yin
chi
ldr
en.Thecausat
iveor
gani
sm i
susual
l
yStaphylococcusaur
eusor,
lesscommonl
y,
Str
eptococcuspy
ogenes,
a
pa

Verrucaear
ecommonlesi
onsofchil
drenandadol
escent
s,al
thoughtheymaybe
encounteredi
nanyagegr
oup.Theyar
ecausedbyhumanpapill
omav i
rus(HPV)
.
ya

Pemphigusi
sar ar
eautoi
mmunebl i
steri
ngdi
sor
derr
esul
ti
ngfr
om l
ossofnormal
Si

i
nter
cel
lul
aratt
achmentswit
hintheepi
dermisandt
hesquamousmucosal
epit
heli
um.
Pemphi
gusv ul
gari
s(themostcommont ype

Bul
l
ouspemphi
goi
dischar
act
eri
zedbysubepi
der
mal
nonacant
hol
yti
cbl
i
ster
s

Dermati
ti
sherpet
if
ormisi
sanothert
ypeofautoimmunebl i
steri
ngdisor
derchar
act
eri
zedby
ext
remelyprur
it
icur
ti
cari
aandgroupedvesi
cles,
granul
ardeposit
sofIgA

SeborrheicKer
atosi
sThesecommonpi gmentedepider
mal t
umorsoccurmostfr
equent
lyi
n
middl
e-agedorolderpersons.ont
het
runk,al
thoughtheextr
emiti
es,
head,andneckal
somay
besit
esofi nvol
vement.

Act
ini
ckerat
osis:
Presentonsun-
exposedski
n,t
hesel
esi
onsshowcy
tol
ogi
cat
ypi
ainl
ower
par
tsofepi
dermisandinfr
equent
lypr
ogresst
ocarci
nomainsi
tu.

Squamouscel
lcar
cinomaisacommontumorar
isi
ngonsunexposedsi
tesi
nol
derpeopl
e.
Thesetumor
shaveahigheri
nci
dencei
nmenthani
nwomen.

Basalcellcar
cinomaisacommonslow-gr
owi
ngcancert
hatrar
elymetast
asizes.Itt
endst
o
occuratsitessubjectt
ochroni
csunexposur
eandi
nli
ghtl
ypigmentedi
ndivi
dualslocal
y
i
nvasi
ve,
Met
ast
asi
sisv
eryr
are.

Dy
splasti
cnev
imaybespor adi
corfami
l
ial
.Thel
att
erar
eimpor
tantcl
i
nical
l
ybecauset
hey
ar
econsider
edpotent
ial
precur
sorsofmel
anoma.

Mi
croscopi
cal
l
y,dy
spl
ast
icnev
iar
emost
lycompoundnev
i

Mel
anomai
slesscommonbutmuchmor
edeadl
ythanbasal
orsquamouscel
lcar
cinoma

Themosti
mpor
tantcl
i
nical
signi
sachangei
nthecol
ororsi
zeofapi
gment
edl
esi
on.

Inmostcases,melanomaprogr
essesfr
om anint
raepi
theli
al(
insi
tu)t
oaninvasi
ve(der
mal
)
for
m.Charact
erist
icsoftheder
maltumorsuchasdepthofinv
asi
onandmi t
oti
cacti
vi
ty
corr
elat
ewit
hsur v
ival
.

Goodl
uck a
#Si
yapaa
pa
ya
Si