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Lecture on pathomorphology forLecture on pathomorphology for
the 3-rd year studentsthe 3-rd year students
By T.G. FilonenkoBy T.G. Filonenko 1
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TuberculosisTuberculosis
TuberculosisTuberculosis is a chronicis a chronic
communicable disease withcommunicable disease with
specifc granulomatousspecifc granulomatous
inammationinammation caused by acaused by a
variety o tubercle bacilli,variety o tubercle bacilli,especiallyespecially MicobacteriumMicobacterium
tuberculosis hoministuberculosis hominis andand M.M.
t. bovis.t. bovis. 2
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Mode of transmissionMode of transmission
• By inhalation into the respiratory tract.By inhalation into the respiratory tract.• Ingestion. Through ingestion into GIIngestion. Through ingestion into GI
tract leads to development to tonsillartract leads to development to tonsillar
or intestinal tuberculosis.or intestinal tuberculosis.• Inoculation. Through mucousInoculation. Through mucous
membranes o mouth and throat, sin.membranes o mouth and throat, sin.
• Transplacental route Transplacental route results inresults indevelopment o congenital tuberculosisdevelopment o congenital tuberculosis
in etus rom inected mother.in etus rom inected mother.
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Classication ofClassication of
tuberculosistuberculosis 1.1. Primary tuberculosisPrimary tuberculosis
2.2. Post primary tuberculosis:Post primary tuberculosis:a)a) Hematogenous tuberculosisHematogenous tuberculosis
b) b) Secondary tuberculosisSecondary tuberculosis
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PostprimaryPostprimary
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Pathogenesis ofPathogenesis of
TuberculosisTuberculosis• !s the most common portal o entry is the!s the most common portal o entry is the
respiratory tract by inhalation.respiratory tract by inhalation.
• The inhaled organism enters into alveoli and is The inhaled organism enters into alveoli and isingested by the alveolar macrophage.ingested by the alveolar macrophage.
• The "T can either be illed by the macrophage# The "T can either be illed by the macrophage#its growth inhibited or multiplies inside theits growth inhibited or multiplies inside themacrophage.macrophage.
• "T lives in symbiosis with the cell."T lives in symbiosis with the cell.
•$uring the course o the ne%t & to ' wees both$uring the course o the ne%t & to ' wees bothcell(mediated immunity and the delayed type ocell(mediated immunity and the delayed type ohvpersensitivity develop in the host and thesehvpersensitivity develop in the host and theseater the host response to the inection andater the host response to the inection andresult in the ormation o the classic tubercle.result in the ormation o the classic tubercle.
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y v yimmunity inimmunity in
tuberculosistuberculosis Hypersensiti!ity or allergy" and immunity orHypersensiti!ity or allergy" and immunity orresistance" plays a ma#or role in t$e de!elopmentresistance" plays a ma#or role in t$e de!elopment
o% lesions in tuberculosis.o% lesions in tuberculosis.
&issue c$anges seen in tuberculosis are not t$e&issue c$anges seen in tuberculosis are not t$e
result o% any e'oto'in or endoto'in but areresult o% any e'oto'in or endoto'in but are
instead t$e result o% $ost response to t$einstead t$e result o% $ost response to t$e
organism" ($ic$ is in t$e %orm o% de!elopmentorganism" ($ic$ is in t$e %orm o% de!elopment
o% cellmediated $ypersensiti!ity *or type +,o% cellmediated $ypersensiti!ity *or type +,
$ypersensiti!ity) and immunity.$ypersensiti!ity) and immunity.-
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Features of PrimaryFeatures of Primary
TuberculosisTuberculosis• $evelopment o disease at the frst getting o the$evelopment o disease at the frst getting o the
activator into the organism.activator into the organism.
• )ensibili*ation and allergy o +IT +ypersensitivity o)ensibili*ation and allergy o +IT +ypersensitivity o
Immediate Type-Immediate Type- ..
• revalencerevalence o the e%udative ( necrotic changes.o the e%udative ( necrotic changes.• Tendency to hematogenous and lymphogenous Tendency to hematogenous and lymphogenous
generali*ation and also to chronic duration.generali*ation and also to chronic duration.
• araspecifc reactions such as/ vasculitis, nodousaraspecifc reactions such as/ vasculitis, nodous
erythema, arthritis.erythema, arthritis.• rimary Tuberculosis used to be ound most oten inrimary Tuberculosis used to be ound most oten in
young children, but in industriali*ed countries it hasyoung children, but in industriali*ed countries it has
become more common in the elderly and debilitated,become more common in the elderly and debilitated,
in alcoholics, and in high(ris racial groups.in alcoholics, and in high(ris racial groups.
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"Ghon complex""Ghon complex" is theis the
characteristic gross appearancecharacteristic gross appearancewith primary tuberculosiswith primary tuberculosis
The primary complex isThe primary complex islocated inlocated in
the lo!er part of the right the lo!er part of the right
upper lobes orupper lobes or the upper part of the lo!er the upper part of the lo!er
lobes in # $# %# &'lobes in # $# %# &'
segments usually(segments usually( 1/
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P)*M+), C-MP./0 -F T12/)C1.-3*3P)*M+), C-MP./0 -F T12/)C1.-3*3
"Ghon complex4"Ghon complex4
consists of consists of *(*( PulmonaryPulmonary
component socomponent so
calledcalled PrimaryPrimary
a5ect ora5ect or primaryprimary
focus or Ghon6sfocus or Ghon6s
focus(focus(
**( .ymphatic vessel**( .ymphatic vessel
component occurscomponent occurs byby TuberculousTuberculous
lymphangitis(lymphangitis(
***( .ymph node***( .ymph nodecomponent occurscomponent occurs
+++
+
++
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There is There is smallsmalltan(yellowtan(yellow
subpleuralsubpleural
granuloma ingranuloma in
the mid(lungthe mid(lungfeld on the rightfeld on the right 0-0-. In the hilum. In the hilum
is a small yellowis a small yellow
tan granulomatan granuloma
in a hilar lymphin a hilar lymph
node ne%t to anode ne%t to a
bronchusbronchus 1-1-..
P)*M+), C-MP./0 -F T12/)C1.-3*P)*M+), C-MP./0 -F T12/)C1.-3*
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It isIt is 0(1 cm0(1 cm
solitary area osolitary area ocaseouscaseous
pneumoniapneumonia
surrounding bysurrounding by
periocal serousperiocal serous
inammation.inammation. !! central area ocentral area o
necrosis appearsnecrosis appearsirregular,irregular,
amorphous, andamorphous, and
pin. Grossly,pin. Grossly,
areas oareas o
Microscopical picture ofMicroscopical picture of
Primary a5ectPrimary a5ect
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)een here in a)een here in ahilar lymphhilar lymph
nodenode is ais a
2caseating22caseating2
granuloma.granuloma.Granulomas haveGranulomas have
prominentprominent
caseous necrosis.caseous necrosis.
Grossly, areas oGrossly, areas ocaseation appearcaseation appear
cheese(lie.cheese(lie.
TuberculousTuberculous lymphadenitislymphadenitis
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CASEATING LYMPHCASEATING LYMPH
NODE TUBERCULOSISNODE TUBERCULOSIS
PRODUCTIVEPRODUCTIVE
TUBERCULOSISTUBERCULOSIS
OF THE LYMPH NODESOF THE LYMPH NODES 15
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In the case oIn the case oprimaryprimary
tuberculosis otuberculosis o
alimentary tractalimentary tract
due to ingestiondue to ingestion
o tubercleo tubercle
bacilli, a smallbacilli, a small
primary ocus isprimary ocus isseen in theseen in the
intestine. It isintestine. It is
tuberculoustuberculous
Primary tuberculosis of alimentary trPrimary tuberculosis of alimentary tr
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The lymph nodes in this The lymph nodes in this
mesenterymesentery are enlargedare enlargedand have cut suracesand have cut suraces
that appear yellow(tan.that appear yellow(tan.
These nodes are flled These nodes are flled
with sheets owith sheets o"ycobacterium avium("ycobacterium avium(
comple% "!3-comple% "!3-
organisms, and theorganisms, and the
immune response is soimmune response is sopoor in this !I$) patientpoor in this !I$) patient..
The enlarged and The enlarged and
caseous mesentericcaseous mesenteric
4ymph nodes may4ymph nodes may
rupture into peritonealrupture into peritoneal
Tuberculous mesenterial lymphadeni Tuberculous mesenterial lymphadeni
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7uration of Primary7uration of Primary
tuberculosistuberculosisIn course o time, the primary lesion canIn course o time, the primary lesion canheal, expand locally or lead to disseminatedheal, expand locally or lead to disseminated
disease.disease.
This can occur at both the This can occur at both the
sites/ the lung and the lymph nodes.sites/ the lung and the lymph nodes.
5 variants o the duration o rimary5 variants o the duration o rimarytuberculosis are probable/tuberculosis are probable/
• healing o primary comple%#healing o primary comple%#• generali*ation o process lymphogenousgenerali*ation o process lymphogenous
and hematogenous-#and hematogenous-#
• chronic duration.chronic duration.1-
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Healing of the Primary comHealing of the Primary com
+ealing o primary+ealing o primary
comple% begins atcomple% begins atinitial a6ect/initial a6ect/
0. eriocal0. eriocal
inammation resoluteinammation resolute
and e%udativeand e%udativeinammationinammation
replaces by fbrousreplaces by fbrous
capsule 0-#capsule 0-#
1. 3aseous masses1. 3aseous masses
are being dehydratedare being dehydratedand petrifcated, andand petrifcated, and
then ossifcated 1-.then ossifcated 1-.
)uch healed initial)uch healed initial
ocus is calledocus is called
1
2
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3alcifed pulmonary lymph3alcifed pulmonary lymph
nodes in tuberculosisnodes in tuberculosis
+ealing in+ealing in
lymphatic nodes islymphatic nodes is
similar tosimilar to
pulmonary center.pulmonary center.
0alci%ication
2/
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Hematogenous generali8ationHematogenous generali8ation
of primary tuberculosisof primary tuberculosis• The most serious immediate complication is The most serious immediate complication is miliarymiliary
tuberculosis#tuberculosis# in which there is invasion o thein which there is invasion o thebloodstream bybloodstream by MTMT and dissemination throughout theand dissemination throughout thebody.body.
• This occurs when the parenchymal part o the Ghon This occurs when the parenchymal part o the Ghoncomple% involves a pulmonary artery or vein andcomple% involves a pulmonary artery or vein and
discharges its inected contents into the blood.discharges its inected contents into the blood.• "ultiple miliary granulomas develop in many organs o"ultiple miliary granulomas develop in many organs othe body.the body.
• 4arger nodules may have central necrosis nown as4arger nodules may have central necrosis nown ascaseation((a process o necrosis that includes elements ocaseation((a process o necrosis that includes elements o
both li7ueactive and coagulative necrosis.both li7ueactive and coagulative necrosis.• 8ew organs are spared# those most oten involved are the8ew organs are spared# those most oten involved are the
lung mainly by recirculation o the organisms-, spleen,lung mainly by recirculation o the organisms-, spleen,liver, idney, meninges, and bone marrow.liver, idney, meninges, and bone marrow.
• The most serious complication and cause o death can be The most serious complication and cause o death can be
tuberculous leptomeningitis.tuberculous leptomeningitis. 21
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The lesions are The lesions areclassically 9.: mmclassically 9.: mm
to 1 mm into 1 mm in
diameter,diameter, frm andfrm and
tantan
, and evenly, and evenly
distributed throughdistributed through
the a6ected organ.the a6ected organ.
The name 2miliary2 The name 2miliary2
derives rom theirderives rom their
supposedsupposedresemblance toresemblance to
millet seeds. !millet seeds. !
punctate area opunctate area o
necrosis may benecrosis may beseenseen in the center.in the center.
Hematogenous generali8ation ofHematogenous generali8ation of
Primary TPrimary Tuberculosisuberculosis
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+ere are two+ere are twopulmonarypulmonary
granulomas.granulomas.
GranulomatousGranulomatous
inammationinammation
typically consiststypically consists
o epithelioido epithelioid cells,cells,macrophagemacrophage
s, giant cells,s, giant cells,
lymphocytes,lymphocytes,plasma cells, andplasma cells, and
fbroblasts. Therefbroblasts. There
may be somemay be some
neutrophils.neutrophils.
Microscopical featuresMicroscopical features
of Miliary Tuberculosisof Miliary Tuberculosis
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iant cells are aiant cells are a
committee o%committee o%epit$elioidepit$elioid
mmacrop$ages. Seenacrop$ages. Seen
$ere are t(o$ere are t(o
ang$ans type giantang$ans type giant
cells in ($ic$ t$ecells in ($ic$ t$e
nuclei are lined upnuclei are lined up
around t$e perip$eryaround t$e perip$ery
o% t$e cell. dditionalo% t$e cell. dditional
pin epit$elioid pin epit$elioidmacrop$agesmacrop$ages
compose most o% t$ecompose most o% t$e
rest o% t$e granuloma.rest o% t$e granuloma.
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These are epithelioid cells around These are epithelioid cells around
thethe center o a granuloma. They getcenter o a granuloma. They gettheir name rom the act that theytheir name rom the act that they
have lots o pin cytoplasm similarhave lots o pin cytoplasm similar
to s7uamous epithelial cells. Theirto s7uamous epithelial cells. Their
nuclei tend to be long and stringy.nuclei tend to be long and stringy.25
.ymphogenous.ymphogenous
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.ymphogenous.ymphogenous
generali8ationgenerali8ation +t is c$aracteried by in!ol!ement t$e ne( groups o%+t is c$aracteried by in!ol!ement t$e ne( groups o%
lymp$ nodes" suc$ as: paratrac$eal" supracla!icular "lymp$ nodes" suc$ as: paratrac$eal" supracla!icular "subcla!ian" cer!ical and de!elopment o% tuberculoussubcla!ian" cer!ical and de!elopment o% tuberculousmeadenitis.meadenitis.
&$e enlargement o% t$e bronc$ial lymp$ nodes may cause&$e enlargement o% t$e bronc$ial lymp$ nodes may causee'trinsic compression on t$e bronc$us or erode into t$ee'trinsic compression on t$e bronc$us or erode into t$ead#acent structures.ad#acent structures.
&$e e%%ect o% e'ternal compression o% t$e ymp$ nodes&$e e%%ect o% e'ternal compression o% t$e ymp$ nodes
on t$e bronc$us is similar to ($at $appens in t$eon t$e bronc$us is similar to ($at $appens in t$eretrograde in!ol!ement %rom t$e parenc$yma o% t$e lung"retrograde in!ol!ement %rom t$e parenc$yma o% t$e lung"complete or partial obstruction. &$e enlargement o% t$ecomplete or partial obstruction. &$e enlargement o% t$elymp$ nodes may produce a ($eee by compressing t$elymp$ nodes may produce a ($eee by compressing t$e
bronc$us. bronc$us.
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Growth of primary parenhymalGrowth of primary parenhymal
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Growth of primary parenhymalGrowth of primary parenhymal
injury injury • Progressive primary tuberculosis most commonly occurs inpatients !ith suppressed or defective immunity(
• The primary Ghon focus in the lung enlarges rapidly# erodes
the bronchial tree# and spreads# a se9uence that results inad:acent 4satellite; lesions(
• The lesion may enlarge in si8e and li9uefy !ith a cavityformation as in an adult or produce an area of consolidation(
• The caseous material can enter into a bronchus and thenspread to other parts of the lung or the opposite lung#
resulting in a tuberculous bronchopneumonia(•
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;hen there is;hen there is
e%tensivee%tensive
caseation and thecaseation and the
granulomasgranulomas
involve a largerinvolve a larger
bronchus, it isbronchus, it is
possible or muchpossible or much
o the sot,o the sot,necrotic center tonecrotic center to
drain out anddrain out and
leave behind aleave behind a
cavity. 3avitationcavity. 3avitationis typical or largeis typical or large
tuberculotuberculouuss
granulomas.granulomas.
3avitation is more3avitation is more
common in thecommon in the 2-
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HematogenousHematogenous
TuberculosisTuberculosis
Conditions of the development :Conditions of the development :t$e presence o% sensibiliation to tuberculinstrongly pronounced immunity
t$e presence o% %oci are $ealed a%ter$ematogenous generaliation o% primary
tuberculosis *si%ting)absence o% tuberculous lymp$adenitis.
Hematogenous tuberculosis is c$aracteried
by proli%erati!e reaction or %ormation o% t$e
granulomas and $ematogenous spreading. 2
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;ith a poor immuneresponse to theagents producing
granulomatousinammation, thereis e%tensive spreado inection with the
production o a2miliary2 pattern ogranulomas as seenhere in the lung o apatient with miliary
tuberculosis. The 0to 1 mmgranulomas arescattered around
lie millet seeds. 3/
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The ocal The ocal
nature onature ogranulomatogranulomato
usus
inammationinammation
isisdemonstratedemonstrate
d in thisd in this
microscopicmicroscopic
section osection o
lung in whichlung in which
there arethere are
scatteredscatteredranulomas
"iliary pulmonary tuberculosis"iliary pulmonary tuberculosis
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ClassificationsClassifications
of h!ato"no#s t#$%c#losisof h!ato"no#s t#$%c#losis• Generalized hematogenous tuberculosis:Generalized hematogenous tuberculosis:
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8eatures8eatures oo hematogenous(hematogenous(
disseminative tuberculosis/disseminative tuberculosis/• may by in adults only#may by in adults only#• prevalenceprevalence ape%( plural locali*ationape%( plural locali*ation##
• prolierative tissue reactionprolierative tissue reaction##
• development o the pneumosclerosisdevelopment o the pneumosclerosisand emphysema o lungsand emphysema o lungs##
• ??cor pulmonale@cor pulmonale@ hypertrophy o righthypertrophy o right
ventricle o heartventricle o heart-#-#• simmetrical small cavernes#simmetrical small cavernes#
• presence o unpulmonary tubercularpresence o unpulmonary tubercularoci.oci.
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An closer inspection,An closer inspection,
thethe granulomas havegranulomas have
areas o caseousareas o caseousnecrosisnecrosis withwith
ormation o theormation o the
small cavernes.small cavernes. This This
is very e%tensiveis very e%tensive
granulomatousgranulomatousdisease.disease. This pattern This pattern
o multiple caseatingo multiple caseating
granulomas primarilygranulomas primarily
in the upper lobes isin the upper lobes ismost characteristic omost characteristic o
postprimarypostprimary
hematogenoushematogenous reactivation-reactivation-
tuberculosis.tuberculosis. 34
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&89;08
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T#$%c#lo#s n&o!t%itisT#$%c#lo#s n&o!t%itis
pit$elioid cells
ang$ans cell
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&uberculosis&uberculosis
o% t$e testis *1)o% t$e testis *1)
andand
epididymus *2)epididymus *2)
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T#$%c#lo#s !nin"itisT#$%c#lo#s !nin"itis
3-
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RENAL TUBERCULOSISRENAL TUBERCULOSIS
arge %oci o%
caseous necrosis
3
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=++;> &89;08 &89;08
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Milia%' t#$%c#losis of th s(lnMilia%' t#$%c#losis of th s(ln
41
CharacteristicsCharacteristics
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CharacteristicsCharacteristics
of the Secondaryof the Secondary
TuberculosisTuberculosis• "ay be in adults only with
postprimary disease or reinection-#
• Anly ulmonary locali*ation oten 0(st and 1(nd segments so called?)imons oci@-#
• 3ontact and intracanalicular
spreading#• )hits o the clinical(morphological
orms.
42
Forms or stagesForms or stages
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Forms or stagesForms or stages
of the secondaryof the secondary
tuberculosistuberculosis::)*)*Ac#t local t#$%c#losis*Ac#t local t#$%c#losis*
+*+*Fi$%o#s,local t#$%c#losis*Fi$%o#s,local t#$%c#losis*
-*-*Infilt%ati. t#$%c#losis*Infilt%ati. t#$%c#losis*
/*/*T#$%c#lo!a*T#$%c#lo!a*
0*0*Caso#s (n#!onia*Caso#s (n#!onia*
1*1*Ac#t ca.%no#s t#$%c#losis*Ac#t ca.%no#s t#$%c#losis* 2*2*Fi$%o#s 3 ca.%no#s t#$%c#losis*Fi$%o#s 3 ca.%no#s t#$%c#losis*
4*Ci%%hotic4*Ci%%hotic t#$%c#losis*t#$%c#losis*
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+pical pulmonary tuberculosis+pical pulmonary tuberculosis
There are There are
several 0 cmseveral 0 cmdiametdiameteer,r,
partiallypartially
calcifed ocicalcifed oci
dry,dry,
crumbly,crumbly,
and white-and white-
that arethat aresurroundedsurrounded
by slaty,by slaty,
induratedindurated
scar tissue.scar tissue. 44
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ung, tuberculosis, secondary
(reactivation) - Gross, cut surface, and
radiograph
44a
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Caseous# partly gelatinous pneumoniaCaseous# partly gelatinous pneumonia
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Fresh tuberculous cavityFresh tuberculous cavity
reyis$($ite
(all o% t$eca!ity 2 to 3
mm t$ic
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@ibrotic scar in t$e (all o%
tuberculous ca!ity consists o%
%ibroblast" collagen" and
scattered anger$ans giant cells
&$e (all o% tuberculous ca!ity
contains %oci o% calci%ication
replacing t$e caseating
granulomas 47
C li i d fC li ti d f
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Complications and causes ofComplications and causes of
deathdeath Scarring and calci%ication.Scarring and calci%ication.
Pneumot$ora'.Pneumot$ora'.
mpyema.mpyema.
Pleural %ibrosis and ad$esions" (it$ associatedPleural %ibrosis and ad$esions" (it$ associated
pleurisy" s$arp pleuritic pain" and s$ortness o% breat$. pleurisy" s$arp pleuritic pain" and s$ortness o% breat$.
0$ronic respiratorycardiac insu%%iciency due to0$ronic respiratorycardiac insu%%iciency due to
de!elopment Acor pulmonaleB.de!elopment Acor pulmonaleB.
cute $emorr$age due to erosion o% !essels.cute $emorr$age due to erosion o% !essels. 0$ronic renal insu%%iciency due to de!elopment o%0$ronic renal insu%%iciency due to de!elopment o%
amiloidosis o% idneys.amiloidosis o% idneys.