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- 3. ABRIEFHISTORYOFTUBERCULOSISIN
DEVELOPMENTOFITSDIAGNOSISANDTREATMENT
Tuberculosis(fromLatin,Tuberculum—tubercle)—generalinfec-
tiousdiseasecausedbyMycobacteriumtuberculosis.FromtheGreekword
(phthisis—consumption—«exhaustionofabody»thewordphthisiologyis
derived—scientificstudyoftuberculosis.
Thenumeroushistoricaldocumentsandmedicaldatatestifytouniver-
saldistributionoftuberculosisinthefarpast.Themostancientdiscovery
indicatingtuberculardiseaseamongpeople,settledintheancienttimesin
Europe,belongstoBartels.In1904atinspectionoftheskeleton,foundnear
toHeidelberg,ofthemanlivinginstonecentury(approximatelyfor5000
B.C.),hehasestablishedatuberculardefeatofchestvertebrawithhump
formation.
Duringforeseeablehistoricaltimealreadyforalongtimestimulate
attentiondependenceoftuberculosisonsocioeconomicconditionsoflife,of
variousgroupsofthepopulation.Hungerandunemployment,theeconomic
crisis,asarule,wereaccompaniedbymortalitygrowthfromtuberculosis.
Especiallysignificantwerethedrasticraiseoftuberculosisprevalenceat
timeofnumerouswars.
Hippocrates—400–350B.C.Thefirstsystemicdescriptionoftheclini-
calmanifestationsandepidemiologicalfeaturesofphthisiswasrecordedin
the«HippocraticCollection».Inhisbook«Thecausesandsymptomsof
chronicdiseases»Hippocratesgaveaveryaccuratedescriptionofthedis-
ease,whichlaterrefertotuberculosisandmentionedthatfever,sweating,
fatigueandlassitudeweresymptomsoftuberculosis.
Thesuppositionaboutinfectiousnessofconsumptionstatedbystill
Aristotle(384–322B.C.),pointingout,thatinairaroundconsumptive
patientthereisamorbidsource.Fromthattimethehugeamountofevidenc-
eswerecollectedthatthebasicsourceofconsumptiondistributionisthe
patientallocatingsputum,whichparticlesinfectair,linen,platesanddishes,
furniture,habitation.Atthosetimes,manydoctorsconnectedtoinfection
comparativelymoreoftenmorbidityamongspousesandpersonslivinginone
dwellingwithconsumptivepatients,amongstudentsanddoctorsmaking
postmortemexaminationsofpersonsdiedfromthisillness.
GirolamusFracastorius(1483–1553)forthefirsttimeraisedthe«germ
theory»andbelievedthatconsumptionwascontagious.Hesystematically
describedthreemajormodesoftransmittinginfectioninhisbook«Decon-
tagioni»:
1)spreadbydirectcontact;
2)spreadbyintermediarysubjects(fomites)beingincontactwithpatho-
genicmicroorganisms;
3)infectionatadistance.
Healsomentionedaboutneedofantisepticsforconsumptionpreven-
tion.
BenjaminMarten(1704–1782)inhisbook«Anewtheoryofconsump-
tion»conjecturedthatthediseasecouldbecausedby«certainspeciesof
microorganism(virus)»,which,oncetheyenterinthebody,couldgenerate
thelesionsandsymptomsofthedisease.
JeanAntoneVillemanfrenchphysicianofmilitaryservicebegana
seriesofexperimentsin1865thatbefore20yearsofKoch’sdiscoveryof
Mycobacteriumtuberculosis.Takinglungtissueandbloodandpusfrom
cavitiesoftuberculouspatients,Villemininoculatedrabbitsandwasableto
demonstratedisseminatedtuberculosisinall.
Inparalleltostudyofaroleofinfectiouscauseoftuberculosis,thedata
werecollected,aboutpeculiaritiesofclinicalandpathomorphologicdisplays
oftuberculosis.
Thelongempiricalperiodofobservationanddiagnosticsofthedisease,
when,onwordsofHippocrates,«…thejudgmentsaredonebymeansofeyes,
ear,nose,mouthandotherways,knownforus,i.e.bysight,touch,hearing,
smellandtaste»,wasreplacedbyaclinical-anatomicaldirection,whichpro-
motedrationalunderstandingoftheillness.
AndreasVesalius(1514–1564)madethepioneeringeffortsofpost-
mortemexaminations.Thismethodofdiseasesstudyfacilitatedtheunder-
standingofthepathologicalfindingssuchaslungcavities,empyemaamong
others.
FranciscusSylviusdelaBoe(1614–1672)forthefirsttimeassociated
smallhardnodulesdiscoveredinvarioustissuesatautopsywiththesymp-
tomsofconsumption.
JohnJacobMongetin1700gavethedescriptionofclassicalmiliary
tuberculosis.
GaspardLaurentBayle(1774–1816)performedaprodigiousnumber
ofautopsiesonphthysicpatient.Notably,thenecropsieswereaccompanied
bydetailedantemortemhistoriesoftheillness,enablingphysicianstomake
clinical-pathologicalcorrelations.
ReneTheophileHyacintheLaenecc(1781–1826),thefrenchdoctor
carriedoutnumerousclinical—anatomicalstudiesandstatedin1819the
doctrineabouttuberculosisin«Treatiseaboutauscultationorrecognition
7Abriefhistoryoftuberculosisindevelopmentofitsdiagnosisandtreatment
- 4. oflungandheartdi-seases».IntheTreatiseheforthefirsttimehasentered
theterm«tuberculosis».Laeneccgavethedescriptionclosetoourconcep-
tionabouttuberculumasasourceoftuberculosis,notedexistenceofisolated
«infiltrativetuberculum».Heunitedvariousmorphologicaldisplaysinthe
uniformdoctrineaboutphthisis.Tothesedisplayshereferredscrofulous
[tuberculous]changesoflymphaticnodes,contactdiseaseofbronchi,the
cavityformedasaresultoftissuesofteningandwhichislookinglikecheese
(caseosis).Laeneccmanagedtoseeconnectionexistingbetweenvarious
displaysoftubercularcharacterinorgans,andtocombineintoonedisease,
knowninthattimedamageofthelungandlymphaticsystem.
TheRussiansurgeon,brilliantphysicianandscientistN.I.Pirogov
(1810–1881)hadplayedanimportantroleindevelopmentandbroadening
ofconceptionabouttuberculosisasasystemicdisease.N.I.Pirogovhad
describedaclinicalpathologicalpictureofacutegeneralizedtuberculosis,
hasnotedanopportunityofsimultaneousexistenceofmiliaryeruptions
andofconfluentchangesatthesamepatient.Hefirsthadpaidattention
togiganticcellsintubercularnodules,receivedthennameofPirogov-
Langhance.
On24thMarch1882RobertKochannouncedthediscoveryofthetuber-
clebacillus(bacteriumofKoch).So,itwasRobertKoch—Germanscientist
whofinallydemystifiedthesecretofthecauseoftuberculosis.Kochrepre-
sentedproofthattuberculosisisbroughtaboutbythetuberclebacillus—
mycobacteriumtuberculosis(MBT).
AfterwardsKoch’sdiscoveryservedasthescientificgroundindevelop-
mentofmethodsfordiagnosisandpreventionoftuberculosisasinfectious
disease.Theseare:
1)Koch’sdevelopmentoftuberculinanditsapplicationasanimmuno-
logicaldiagnosticumfordefinitionoftuberculosisinfection;
2)improvementbyZiehlandNeelsenofstainingofMBTatmicros-
copy;
3)creationbyCalmetteandGuerin,humanvaccine(BacillusCalmette-
Guerin,BCG).
Itwasproved,thatmycobacteriaoftuberculosisconcernstoasort
Mycobacterium.Mycobacteriaarewidelydistributedinanenvironment,
amongthempathogenicandnonpathogenicformsaremet.Forthehumans,
basically,pathogenic(capabletocauseatuberculosis)arebeingmycobacte-
riumtype(humanus)and(bovinus).
SoonafterKoch’sdiscoveryoftypicalKoch’smycobacteriumtheRussian
scientistMechnikovI.I.hasinformed,thatincultures,therearepolymor-
phicformsofmycobacteriumtuberculosis.Thepolymorphismbecomes
apparentbydevelopmentofrodelike,granularandcoccusforms.Thereby
MechnikovI.I.hasspecifiedtheabilityofMBTtovariability.
Fromthistimetheconceptionsabouttuberculosiswerealreadybasedon
exactknowledgeofmethodsofdiagnosticsofthecausativeagentandlocali-
zationoftuberculosisinvariousorgans.
WiththediscoveryofX-raysbyW.C.Roentgenin1895thetechnique
ofradiologicalimagingofdifferentorgansbecameavailableincludingthe
lungs.Thusbeganaccessibletocomparepathomorphologicalmanifestation
oftuberculosistolifetimetubercularchangesinvariousorgans.
Evenlongbeforediscoveryofmycobacteriumtuberculosisthevarious
methodswereappliedfortreatmentofthisdisease.
Themedicineofancienttimeswasbasedonabeliefthatdiseasewas
anaturalphenomenonanditsremediesarederivedfromnaturalsources.
Dietaryenrichmentsofvariousformswerepopular,includingmilkfrom
varioussources.Generallyrecognizedremedieswereusedatthosetimes
suchasbleeding,purging,emetics,orotherinterventions.
Variouschemicalpreparationswereempiricallyusedsuchascombina-
tionsofmercury,silver,cupper,calcium,bismuth,iodine,anti-infective
agents,dyesetc.
Forthetuberculouspatientstheyoftenweremorbidatbestandmortal
intheextreme.
Koch’sdiscoveryoftuberculouspathogenstimulateddevelopmentofspe-
cificmethodsoftreatment,withapplicationofactiveantibioticsandchemi-
calcompoundsagainstmycobacteriumtuberculosis.
Introductionin1950sand1960sofnumerousanti-tuberculosisdrugs:
isonazid,aminglycosides,viomycin,capreomycin,pyrazinamid,ethiona-
mide,cycloserine,ethambutolandrifampicin,ensureeffectiveandpredica-
bletreatmentoftuberculosis.
Nowphthisiologyisarmedwithanumberoftreatmentmethods,effective
atvariousformsoftuberculosis.Simpleormorecomplexschemes,basedon
variousprinciplesandsimultaneousassignmentofseveralanti-tuberculosis
preparationsstrengthentherapeuticeffectandpreventdevelopmentofdrug
resistanceofmycobacteria.
Thechemotherapyoftuberculosisexpandedindicationstosurgical
methodsoftreatmentofthedisease.Tothoseareconcerned:extrapleural
pneumothorax,oleothorax,thoracoplasty,surgeryontheperipheralnerves.
Widelyappliedlungresectionsare:limitedcuneiformresections,segmentec-
tomy,lobectomyandpulonectomy—removalthewholelung.
Abriefhistoryoftuberculosisindevelopmentofitsdiagnosisandtreatment89Abriefhistoryoftuberculosisindevelopmentofitsdiagnosisandtreatment
- 5. Butsuchonlymedicalmeansoffightwithtuberculosiscouldnotbesuc-
cessfulbecauseoflargequantityofthepatients.Anobstacleforthetuber-
culosispreventionisitslongandchroniccourseandmanyfactorssuchas
conditionsoflife,economic,ofmoralandpsychologicalorderconnectedto
thelargematerialspending.Duringallhistoryoffightwithtuberculosis,the
necessityrealizedofconductingofeffectivewidespreadmeasuresofpublic,
sanitaryandpersonalpreventionunderconditionsofcommunallife,devel-
opmentofspecializedanti-tuberculosisservice.
Thetuberculosisdispensarieswereorganizedtocarryoutsomeof
thesemeasures.SuchestablishmentswereorganizedinFrance(inLille)
undertheinitiativeKallmette,inEdinburghundertheinitiativeR.Philip,
etc.Howeverquantityofsuchestablishmentswasinsufficientearlierand
remainsthesamenow.Thosetreatmentfacilitiesdidnotplaytheroleof
organizationalestablishments.
Longbefore,whentheetiologyofthediseasewasunknown,butasthe
infectivenatureoftuberculosissuspected,hasripenednecessityforwider
sanitary—preventivemeasures.Insomecountries,forexampleinPersiaand
Italy,becauseofsignificantdistributionoftuberculosisattemptsweremade
toisolatethepatientsforbadetothemtocommunicatewiththepopulation,
toenteramarriage.FurtherinSpainin1751,inItalyin1782,andthenin
Portugalandinothercountriesthelawswereissuedonobligatoryregis-
trationofallpatientswithphthisisandtheirhospitalization,disinfection
oftheirdwellings,annihilationofclothes,homebelongings.
Fromthegivenmaterialsitisbecomingobviousasignificantdevelop-
mentoftheoreticalknowledgeabouttuberculosis.Thesesuccessesare
achievedbyworksofmanyscientistsofvariouscountries.Amongthemthe
largemeritbelongsalsotoRussianresearchersandpublichealthorganizers,
fromwhichmanywerethefoundersofdevelopmentofmajormethodsof
tuberculosiscontrol.
Onphilanthropicbaseandintheextremelyinsignificantscalesanti-
tuberculosismeasureswerecarriedoutinpre-revolutionaryRussia.On
thepeople’sfundsandprivatedonationsthesmallnetworkofambulance
stations,sanatoriumsandhospitalswascreated.Notonlypreventive,sani-
tary—educational,healthimproving,butalsomedicalpracticecarriedout
byorganizeddispensariesinvariouscities.Clinical,organizationaland
methodicalexperienceonstrugglewithtuberculosisherewasaccumulated
tosomeextend.
RussianscientistsA.I.Abrikosov,V.U.Shtevko,A.I.Strukov,A.N.Chis-
tovich,V.I.Pusikandtheirnumerousfollowershavemadelargecontribution
tothestudyofpathogenesisandpathologicalanatomy,morphogenesisof
tuberculosis.
Itwasfoundout,thatthelargeorsmallerdegreebacillemiacanarise
independentlyinparallelwiththelunglymphaticfocusesbeforeorafter
theirformation(A.I.Chistovich,N.N.Georgadze,M.D.Krilov,Z.A.Lebe-
devaetc.).
RussianpediatriciansledbytheprofessorA.A.Kiselhavecreatedin
30thoftheXXcenturythedoctrineaboutchronictubercularintoxication.
Laterin40–50years,thedoctrinecreatedaboutearlytubercularintoxica-
tionofchildren,forthefirsttimeinfectedbytuberculosis(N.O.Vasilevich,
A.I.Kudrjavceva,andE.Z.Sorkina).Thisperiodofintoxicationisdesignat-
edbyratherearlymorphologicalandbacteriologicaldisplaysoftuberculosis
infectioninbonemarrow,inlymphaticnodes.
BytheprofessorA.I.Kagramanovthepresenceofbacillemiawithsmall
morphologicaldisplaysinvariousorgansandsystemsnotaccessibletoX-ray
diagnosisisprovedatpostmortemexaminationsofchildrenwhohavedied
notfromtuberculosis.Afterdiscoveryofanti-tuberculosispreparations,the
knowledgeaboutearlybacillemiahasformedthebasisfortheirapplication
inchemoprophylaxis.
AtthisperiodinRussiaanewmedicalspecialty—phthisiatriawas
graduallydevelopedandspecializedphthisiatric(anti-tuberculosis)service
createduniqueintheworld.Thephthisiatricsystemconsistsofanetwork
ofstate,specializedmedicalestablishments,whosebasictaskisthestruggle
againsttuberculosisandtoprovidemedicalhelpfortuberculouspatientson
freeofchargebasisonthewholeterritoryofRussia.
Formanagementandcoordinationofactivityphthisiatricservicethe
specialdepartmentwascreatedintheRussianMinistryofhealth.
Anti-tuberculosisdispensaryistheleadingestablishmentofthisnet-
work.Dispensaryprovidestreatment-diagnostichelptotheinhabitants
ofthegivenarea,andalsotoallworkersandemployeesoftheenterprises,
establishmentsandeducationalinstitutionslocatedwithinthejurisdiction
ofthedispensaryterritory.
Fortheregistrationandtreatmenttheclinicalclassificationoftubercu-
losiswascreated.Theclinicalclassificationisasbasefortheregistration
ofthetuberculouspatients,bymeansofdivisionofthemontodispensary
groups.Theclassificationprovidesanopportunityforearlyrevealingand
continuityoftreatmentoftuberculouspatientsunderthesupervisionof
tuberculosisdispensaryinhospital,sanatorium,inahealthresortandin
polyclinic.
Abriefhistoryoftuberculosisindevelopmentofitsdiagnosisandtreatment1011Abriefhistoryoftuberculosisindevelopmentofitsdiagnosisandtreatment
- 6. Thescientificdevelopmentofmethodsofstrugglewithtuberculosishad
receivedspecialsignificance.ThelargecollectivesinRussiananti-tubercu-
losisscientific-researchinstitutesconstantlystudypathogenesisoftubercu-
losis,developmethodsoforganizationoffightwithtuberculosis,testnew
anti-tuberculosisdrugsandmeansoftheiruse.
Inmedicalinstitutes,andatmedicalfacultiesofUniversitiesthechairs
oftuberculosisarecreated,whosetaskistrainingmedicalstudentsabout
diagnosticsandtreatmentoftuberculosis.Atthesametimecollectivesof
suchfacultiesconductscientificwork.
Inmanyindustrializedcountries,sufficientfunding,resources,highliv-
ingstandards,andwideexpansionofchemotherapyinthelast40yearshave
helpedtoreducetuberculosistoarelativelyminorproblem.Butinpoorer
countriesinAsia,Africa,LatinAmericaitremainsalmostasbigaproblemas
ever.Indeed,astheirpopulationshaveincreasedandtheirtuberculosisrates
haveonlyslightlydecreased,thereareprobablymoretuberculosispatients
intheworldtodaythantherewere20yearsago.
WorldHealthOrganization(WHO)hasestimatedthatthetotalnumber
ofcasesintheworldwillrisefrom7,5millionin1990to10,2millioninthe
year2000.Totaldeathswillrisefrom2,5to3,5million.Therisewillbedue
partlytoincreasesinpopulationindevelopingcountriesandpartlytothe
prevalenceincreaseoftheHIVanddrugresistantMBT.
Thenumberofdeathscausedbytuberculosisannuallyessentiallyexceeds
thenumberofcasesofdeathcausedbyanyotherpathogenicmicroorgan-
ism.Tuberculosis,affectsmainlyadultsinthemostproductiveperiodoflife,
entailsenormouseconomiccosts.
WHOisaworld-coordinatingcenterforfightingwithtuberculosis?Ina
baseforfightingwithtuberculosistheorganizationofnationaltuberculosis
programs(NTP)arelaid.Treatmentoftuberculosisisthecornerstoneof
anyNTP.
Eachdoctor,withouttakingconsiderationofhisspecialty,shouldknow
principlesofpreventivemeasures,diagnosticsandtreatmentoftubercu-
losis.
Aqualifieddoctorshouldinpropertimesuspecttuberculosisinthe
patientandaccordingtothecircumstancescarryoutcompetentdiagnostics
andifthereareindicationssendthepatienttophthisiatristsortoanextra
pulmonarytuberculosisexpert.
Ineachcountry,ifthecountryisamember-stateofWHO,thereisa
nationalprogramofstrugglewithtuberculosis.Anydoctorshouldknow,
howthestrugglewithtuberculosisisorganizedinhiscountry,basicdirec-
tionsofthisprogram,establishmentswhichareresponsibleforitsperform-
anceandwheneverpossibletoparticipateinthisprogram.
Abriefhistoryoftuberculosisindevelopmentofitsdiagnosisandtreatment1213Abriefhistoryoftuberculosisindevelopmentofitsdiagnosisandtreatment
- 7. 15Etiologyandpathogenesisoftuberculosis
Chapter1
Etiologyandpathogenesisoftuberculosis
1.1.CHARACTERISTICSOFTHETUBERCLEBACILLI
Mycobacteriumtuberculosis(MBT)—facultativeintracellularpara-
site.
Mycobacteriumtuberculosis(MBT)belongstothefamilyof
Mycobacteriacae,oforderActinomycetalis,andgenusMycobacterium.The
genusofMycobacteriacaecomprisemorethan100species,themajorityof
themaresaprophyteswidespreadinenvironment.
Etymologically,«mycobacterium»isderivedfromtheGreekwords
‘myces’forfungusand‘bakterium’meaningsmallrod.Thename«fungus»
derivesfromthetendencyofthesemicroorganismstospreaddiffuselyover
thesurfaceofliquidmediuminamoldlikegrowthpattern.
Accordingtothemodernconceptofclinicalmedicine,theterm
«Mycobacteriumtuberculosis»whichwasdiscoveredbytheGermansci-
entistRobertKochintheyear1882,unitesthemycobacteriumcomplex
including:M.tuberculosis(MBT),M.bovisanditsBacilliCalmette-Guerin
(BCG)variant—M.bovisBCG,M.africanum,M.microti,M.cannetii,
M.pinnipedii,M.caprae.Thereisahighdegreeofgeneticrelatednessinthis
group.
Mycobacteriumtuberculosisisthemajorcauseoftuberculosisupto95%
inmandeppendingofresidenceterritory.AtthesametimeM.bovisand
M.africanumcancauseadiseaseclinicallyindistinguishablefromclassical
tuberculosis.
MycobacterianotincludedintotheM.tuberculosiscomplexcancause
diseases—mycobacteriosis.Suchmycobacteriaarecombinedintocomplex-
es:M.avium,M.fortinatumиM.terrae,M.leprae,M.ulcerance.
Thegivenmaterialabout«Tuberculosis»inthistextbookrefersonlyto
thediseasecausedbyM.tuberculosis(MBT)ortuberclebacilliofKoch
(BK),M.tuberculosis(typushumanus).
ThenaturalreservoirsofMBTare—human,domesticandwildanimals,
birds.
MBTareslender,curvedrodsthatareresistant(fast)toacids,alkalis,
anddehydration.Thecellwallcontainscomplexwaxesandglycolipids.
MBTcanmultiplywithinmacrophages,andalsoextra-cellular.
MultiplicationofMBTiscomparativelyslow,withmeansofsimple
celldivision.Intheenrichedmedia,doublemultiplicationlastsfrom18to
24hours.ClinicalstrainsofMBTmayrequire4to6weekstogrowinthe
medium.
GeneticstructureofMBTisdeterminednow.Thesequenceandanno-
tationhavebeenpublishedintheinternationaldatabases.Thesequenceof
MBTis4,411,529b.p.long.
TheMBTisnotmotile.Thetemperaturebordersorgrowtharebetween
29–42°C(optimumbetween37–38°C).MBTisresistanttophysicaland
chemicalagents.MBTcanendureverylowtemperaturesandresisttem-
peraturesashighas80°Cfordurationof5minutes.
MBTcansurviveforabout150daysinwetenvironment.Whendry,
MBTcancauseTBinGuineaPigsafteranincubationperiodof1–1,5years.
MBTinthelyophilizedandfrozenstatehasaviabilityofabout30years.
MBT‘sviabilityissignificantlyreducedunderintensivesunlightand
underahightemperatureenvironment.However,itsviabilityremains
significantlyhighwhensubmittedtoadampanddarkenvironment.MBT
remainsviableforseveralmonthswhenexposedoutsidehostorganism,espe-
ciallyindarkanddamprooms.
MBThasacidresistance(acid-fastness)thatdifferthemfrommany
othercausativeagentsoftheinfection.ZiehlandNeelsenin1883developed
aspecialmethodofMBTstaining,basedonacid-fastnessofMBT.Afilm
preparationstainedbycarbol-fuchsinedyeisdecolorizedbysulphuricacid
andwashingwithwaterisprocessedbyfinishdyeingwithmethyleneblue
(Ziehl–Neelsenmethod).Incontrasttonotacid-resistingbacteriaMBT
becomesapparent(havingredcolor)atpreservationofthecoloringeven
afterdiscolorationbyacidsandwellstandoutagainstbluebackgroundat
microscopy.Ziehl–Neelsenmethodisstillemployedtoday.
ResistanceofMBTtoacids,alkalineandspiritsrelatedwithlipidfrac-
tionofexternallayerofMBTmembrane.
MorphologicalchangesofMBT.ThemorphologyandthesizesofMBT
arenotconstant,dependingontheageofbacteriaand,especially,onthe
conditionoftheirenvironmentandcontentoftheirnutrientmedium.
Thecord-factor.ThelipidsoftheexternalmembraneofMBTdetermine
itsvirulenceandformationofplait-likecongestions(cord-factor)innutrient
medium.
Kochnotedaboutcord-factorinhisinitialreportontheetiologicalagent
oftuberculosis.Firstofallcord-factorrelatedwithvirulenceofM.tuber-
- 8. Chapter11617Etiologyandpathogenesisoftuberculosis
culosis.Formationofplait-likecongestionswassubsequentlyobservedto
occuramongothermycobacterialspeciesoflesserorhavingnovirulence.
Cord-factorwaslateridentifiedasahighlyunusualbiologicalcompound,
trehalose6,6-dimycolate,wasobservedtocausehighlyvirulence,often
lethalconsequenceswheninjectedintoexperimentalanimals.However,the
roleofthiscompoundinthepathogenesisoftuberculosisisunclear.
L-forms.OneoftheimportantfeaturesofMBTisitsabilitytoproduce
L-formsTheL-formsarecharacterizedbyreducedlevelofmetabolismand
weakvirulence.RemainingviableL-formscansurviveforalongtimeand
produceanti-tubercularimmunity.
TheL-formdiffersfromusualMBTbytheexpressedfunctionaland
morphologicalalterations.Ithasbeendiscovered,thatthetransformation
ofMBTintotheL-formsacceleratedunderlonganti-bacterialtherapyand
underotherfactors,whichinhibittheMBTgrowth,duplicationandcell
membraneformation.
Ithasbeenestablished,thatL-formscanbefoundinthesputumof
«MBT-negative»patientswithdestructiveformoftuberculosis,capable,
undertheappropriateconditions,tobemodifiedinrode-likevariantwhich
maycausereactivationofthetubercularprocess.Hence,eliminationofMBT
fromcavitiesofsuchpatientsyetdoesnotmeantheirsterilizationfrom
MBT.
MBTisresistant(tolerant)tomanyantibiotics.Thispropertyiscon-
nectedfirstofallwithhighlyhydrophobiccellsurface,whichservesasa
physicalbarrierforchemicalagentsandantibio-tics.Themainreasonof
resistanceiscodedintheMBTgenome.
MBTcanbecomeresistanttoanti-tuberculardrugs.Combinedresist-
anceoftheMBTtoseveraldrugsconsiderablyreducesefficiencyoftreat-
mentoftuberculosisforlastyears.
Asaresult,themodernpublichealthservicesdealsnotonlywiththe
dangerousinfectionoftuberculosisagentbutalsowiththewholesetof
strainswhichareresistantagainstdifferentdrugs.Inpractice,fororganizing
ofeffectivetuberculosistreatment,itisimportantnotonlytodiscoverMBT,
butinparallel(fastenough)topromptlydetermineitsresistance—within
two-threedaysinordertoontimeprescribeaneffectivechemotherapy.
Duringthelate80softhelastcenturyanewmethodwasdiscovered
shorteningtheanalysisprocessmentionedabove.Thenewdiagnostictestis
basedonselectiveamplificationofnucleicacids(DNAorRNA)invitrowith
thehelpofpolymerasechainreaction(PCR).
ThisPCRmethodhasawidespectrum(thelargeopportunities)and
servesasthebaseofexactDNA-diagnostics,whichallowstoidentifyany
strainofMBTandtodefinethereasonofthedrugresistance.
ThelaboratoryresearcheshaveshownthattheoccurrenceofMBT
resistanceisconnectedwithnucleotidereplacements(mutations)ingenes,
encodingvariousenzymes,whichdirectlyinfluencewithdrugs.The
M.tuberculosisresistanttoRifampicinhavemutatationsinrpoBgeneat
codons531,526,533,516.
MutationsinthegenekatG,resultinginreplacementofsomeaminoacids
inenzymescatalaseandperoxidaseareassociatedwithresistanceofsome
MTBstrainstoIsoniazid.
TheresistanceofMBTtoStreptomycinisconnectedwithmissensmuta-
tioninagenerpsL,codingS12mitochondrialprotein,orwithnucleotide
replacementsinagenerrs,coding16SRNA.
TheabovesubmittedmutationsinMBTgenomearetheonlylimited
examplesofformationofitsresistancetoanti-tuberculosisdrugs.Onthis
basisitispossibletomakethefollowingconclusion:introductionofnew
drugsinchemotherapyoftuberculosisleadstonewmutationsinМBT,
resultingtoresistancewithoutexceptionofalluseddrugsandinthiscir-
cumstanceitisnecessarytoconstantlytakeintoconsiderationthetacticsof
tuberculosistreatment.
1.2.WAYSANDMEANSOFTRANSMISSIONOF
TUBERCULOSISINFECTION
Thesourceofinfection.ThebasicsourceofMBTisthetuberculous
patient,spreadingMBT(bacillaryexpectorator/case).
Thefocus(place)oftubercularinfectionbecomesdangerousincase
whenthepatientissufferingfromthe«Openform«ofTBthatiswhenthe
patientexpectoratesMBT.Infectionoccurswithdirect,longdurationand
closecontactwithaMBTpositivepatient.Infectionsmostlyoccurwithin
families,apartmentsorcommunitieswhereatuberculouspatienthasbeen
coughingMBTforalongtime.Thedangerofdisseminationoftheinfectious
agentiseliminatedifMBTexpectoratorisdetectedandisolatedontime.
Occurenceandcourseoftheinfectiondependnotonlyfromtheviru-
lenceoftheagent,butalsoontheconditionofresistanceandreactivity
ofthehost.
- 9. Chapter11819Etiologyandpathogenesisoftuberculosis
TheplaceofMBTpenetrationintothehostismostimportantbecausein
thissitetheprimarycontactbetweenMBTandahosttakesplace(entrance
gatesofinfection).Thefollowingchannelsoftuberculosisinfectiontrans-
missionaredistinguished:
1)air-born;
2)alimentary(digestive);
3)contact;
4)intrauterinetuberculosisinfection.
Air-borntuberculosisinfection
MBTaredistributedintheairwithcoughdroplets,sneezingandcon-
versationbyapatientwithactiveTBseefigure1-2).Inhalationofthese
infecteddropletscanpenetrateintohealthylungs.Thistypeofinfectionis
knownasair-dropletinfection(Air-borninfection).
DependingontheforceofcoughimpulsesandofthedropletssizesMBT
canbedispersedwithairondifferentdistancesfromthepatient,upon
coughing—upto2m,uponsneezing—upto9m.Thebasicmovementof
sputumthrowingparticlesoccursondistanceof1mdirectlyinfrontofthe
patient.
Tubercularsputumdroplets,accumulatedonfloors,dryupandturnto
dustparticles.MBTbeinginsideofthemotesforsometimeremainsviable.
Ithasbeenestablished,thatonthe18-thdayofdriedupsputum,andthere
arestillabout1%ofviablebacteria.Intensiveairflow,floorsweeping,daily
locomotionandanyothertypeofmovementswillraisetheMBTcontain-
ingmotesintheair,whichcanpotentiallypenetrateintolungsandcause
infection.
Infectionthroughdigestive(alimentary)tracts
Specialexperimentsonanimalsshow,thatmuchmoreMBTareneces-
saryforalimentarywayoftransmissioncomparedtoair-borninfection.For
infectionofthehostthroughair-tractsitisneededonlyoneortwomycobac-
teriumtuberculosis,butforinfectionperoshundredsofMBTareneeded.
ThewayofMBTdisseminationinahostatalimentaryinfectionby
tubercularculturewasdemonstratedbytheresultsofpost-mortemexami-
nationspublishedinconnectionwithjudicialprocessinLuebeck.Bymis-
take252infantsatvaccinationthroughfeedingwiththetubercularculture
(Kielstrain)insteadofBCGwasentered.Owingtoinfection68children
diedfromtuberculosisand131childrenwereill;53childrenhadremained
healthy.
Atpostmortemexaminationsof20childrenwhoweredead,itwasdis-
coveredthatinthemajorityofcases,thedamagewasinperitonealcavity.
Therefore,theentranceofinfectionwasthedigestiveorgans.
Oneofthefeaturesofthiswayofinfectionofinfantsisfrequentdamage
ofmesenteriallymphaticnodesbytuberculosis.
ItisnecessarytotakeintoconsiderationthatMBTpenetrationintothe
intestinecanoccuratswallowingbythelungtiberculouspatientsownspu-
tumthatprovedbythepresenceofMBTinsignificantquantityinstomach
flushwaters.
ContactwaysofMBTpenetrationintothehost
Casesofinfectionthroughaconjunctivawereobservedamongchildren
andadults;acuteconjunctivitisandinflammationofthelachrymalsacwere
sometimeseeninthesepatient.
Thetuberculousinfectionthroughtheskinisrare.Thecasesoftuber-
culosisinfectedmilkmaidsaredescribed,atMBTpenetrationthroughthe
injuredskinofhandsfromthecowsinfectedbytuberculosis.
Intrauterinetuberculosisinfection
Thepossibilityoftubercularinfectionofthefetusduringintrauterine
periodoflifewasprovedonsection,ofnewbornsdiedduringthefirstdays
afterbirth.Theinfectionoccursattuberculosislesionofplacentaorataffec-
tionofinjuredplacentaduringdeliverybythetuberculosis-infectedmother.
Suchwayoftubercularinfectionoccursveryrare.
1.3.ETIOLOGYANDIMMUNITY
Themorphologicalandbiochemicalcomponentsofmicrobialcellscause
variousreactionsinthehost.
ThebasicbiochemicalcomponentsofМВТare:
–proteins;
–carbohydrates;
–lipids.
Proteins(tuberculoproteids)isthebasiccarrierofМВТantigenic
properties.
Tuberculin—oneofthetuberculoproteidsiswidelyusedinpracticefor
revealingMBTinfection.(Detaileddescriptionisseeninthesection2.3.
Tuberculintesting).
- 10. Chapter12021Etiologyandpathogenesisoftuberculosis
Delayed-typehypersensitivity(DTH)
Thesubstances,whichareincludedintheMBTwallstructure,inducetis-
suespecificinflammationreactionandgranulomaformation,withthedevelop-
mentofthedelayed-typehypersensitivity(DTH),whichcouldbedetected
byapositivetuberculintestreaction,andaweakantibodyformation.
Ingeneral,termDTHisusedforcharacteristicsofatypeIVimmune
response(indurationatthesiteofintradermalinjectionoftuberculindevel-
opsafter48hours)amongindividualswhoareinfectedwithMycobacterium
tuberculosis.DTHistobeconcernedasanimmuneresponsefromthe
damagedtissuefactors.
Relationshipbetweentheimmuneresponseandpathogenesis
Localandgeneraltuberculosislesionscanbedeterminedbythehost’s
immuneresponseagainsttheMBT.
Inthedescriptionofthismostcomplexprocess,wewilllimitourselves
tothesimpleenumerationoftheevents,proceedingfromthemomentof
primarypenetrationofMBTintothealveoli,totheresultsofactualbattle
betweenthemacroorganismandtheMBT.Thisprocessdeterminesthefate
ofatleastonethirdoftheworldpopulationinfectedwithmycobacterium
tuberculosis.
ThecycleoftuberculosisdevelopmentfromMBTcontaminationtillthe
occurrenceofitsclinicalmanifestationsanddistributionofMBTinenvi-
ronmentconditionallyisclassifiedinto5stages.
Stages
1.Spreadingofinfection(contamination).
2.Beginningofinfection,proliferationanddisseminationinaninfected
host.
3.Formationofimmunereactioninthehost.
4.Formationofcaseousnecrosis,andproliferationofbacteria.
5.Secondaryspreadingofinfection(abilitytoinfect).
Briefdescriptionofeachstage
Stage1.Spreadingofinfection.
1.1.PatientproducesMBT-containingaerosol.
1.2.Smallerparticlesofaerosoldehydrateandformdropletparticles.
1.3.Mycobacterium-containingdropletparticlesaresubsequently
inhaled.
1.4.Dropletparticlespenetrateintobronchianddepositintoalveoli.
1.5.Mycobacteriumisswallowedbythealveolarmacrophagesofthenon
immunizedorganism.
1.6.IfalveolarmacrophagesareabletokilltheMBT;Infectionwillnot
occur.
Stage2.Beginningofinfection,proliferationanddissemination.
2.1.MBTsurviveswithinalveolarmacrophagesandproliferates.
2.2.ProliferatingMBTkillsthealveolarmacrophagesandthelattercon-
sequentlyreleasechemokines,freedchemokinesinteractwiththenewcells.
2.3.Newalveolarmacrophagesandmonocytesactivateandingest
MBT.
2.4.KillercellsandTlymphocytesbegintoaccumulateinthelesions.
2.5.MBTcontinuestoproliferate,killinghostcellsandspreading
locally.
2.6.MBTistransportedtotheintrathoraciclymphnodesandfromthere
theyspreadsystemically.
Stage3.Formationofimmuneresponseofthehost.
FormationofprocessoftuberculosisintheStage3canoccurintwo
ways.
1stvariant:MostpatientswhoenterStageIIIdevelopsufficientimmu-
nitytocontrolthetuberculosisforlifetime.
3.1.1.MBTproliferationhaltedandthebacillarypopulationfallssub-
stantially.
3.1.2.Theprimarylesionandmetastaticfociinvolutes,leavingminimal
residuals.
3.1.3.Thetuberculinskintestbecomesreactive.
2ndvariant(unfavorable).Inthecaseofinsufficientimmuneresponse,
aprogressivetuberculosisprocesswilldevelop.Thissituationisoften
observedamongchildren,AIDSpatientsandthosewhohaveapredisposi-
tiontotuberculosis.
However,someundergoreactivationoflatentinfection:whichmayoccur
atextrapulmonarysite(s)orinthelung.Reactivationofdiseasemayаnd
intotissuelesions,cavityformationandse-condaryMBTproliferation.
OnthecelllevelunfavorablevariantoftheStage3ischaracterizedby
thefollowingpro-cesses.
3.2.1.Immuneresponseofmacroorganism:macrophagessubmittubercu-
losisantigenstoTlymphocytes;Tcellsreleasecytokines.
3.2.2Cytokinesrecruitandactivatemacrophages;resultinginimmune
responsethatincludesprotectivecellularandtissue-lesions.
3.2.3.Theseresponseslimitproliferationand/orkill,MBT,resulting
intoinvolutionoftheprimarylunglesionandtheremote,extrapulmonary
foci,or
- 11. Chapter12223Etiologyandpathogenesisoftuberculosis
3.2.4.IfthehostisunabletorespondeffectivelyagainstMBT,progres-
sionofprimarydiseaseproceeds.
StageIV:CaseationandacceleratedMBTproliferation.
4.1.Pulmonaryfocusreactivatesandundergoesnecrosis(caseation)
resultingintocavityformation.
4.2.MBTlocatedintheextracellularspaceexponentiallymultiplies.
Stage5.Retransmissionoftheinfection.
5.1.PatientexpectoratesMBTinsputum;anotherpersoninhalesthem.
Inthatway,theprocessoftuberculosisinfectionwithsubsequentMBT
expectorationintoexternalenvironmentisaccomplished,therebythe
spreadingofMBTprolongintothesurrounding.
Awholesetofcontributingfactorspredisposethedevelopmentofthe
clinicalmanifestationsofTB.Itisknownthatvirulenttuberculosismyco-
bacteriumcanbefoundamonghealthyindividualsandthosemanifesting
tuberculosisclinicalsymptomsaremorethaninmerecarriers.Conditions
inwhichvariousadverseexternalandinternalcontributingfactors,cause
asharpdecreaseofthehost’sresistance,tuberculosisinfectioncanproceed
intoadisease,namelytuberculosis.Atthesametime,thetuberculosiscon-
taminationcanbeterminatedassocalledlatentinfectionwithoutserious
consequences.
Thelatentinfection
Thelatentinfectionissuchinfectiousprocess,atwhichtherearenoclini-
caldisplaysoftheillnesswhenmycobacteriaispresentinthehost.Theexist-
enceoftheprocessatlatentinfectioncanbeestablishedbymeansofpatho-
morphologicalexaminationorwiththehelpimmunobiologicalreactions.
Thetuberculosislatentinfectionisaconsequence:
1)oftheundevelopedprimaryinfection,atwhichMBTcontinueto
remaininthehost;
2)oftheunfinishedprocessofthetransferredtuberculosisinpast.
Inanycase,MBTexistsinahost,butconditionsofthelatentinfection
occurrencearediffe-rent.Inthefirstsituationthelatentinfectionarisesat
presenceofsomeinherentofthehost’sresistance,duetowhichtheinfectious
focusdoesnotdevelop.Insecond—itisaconsequenceofdevelopedimmu-
nityduringillness,whenthereisalatentfocus.Inbothcasesthereactionof
thehostisinsufficienttodestroyMBT.
Hence,theoccurrenceofthetuberculosislatentinfectiondependsboth
onadegreeofMBTvirulence,andfromaconditionofhost’stoleranceand
immunobiologicalreactivity.Theinfluenceofexternalenvironmenthasalso
beenprovedtobeimportant.
1.4.PATHOLOGICANATOMYOFTUBERCULOSIS
Thelungsarethebasicorgansaffectedbytuberculosis.
Thelungsarecomprisedoflobes.Therightlunghas3lobes,(superior,
medial,inferior),left—2lobes(superiorandinferior).Thelobesaredivided
intosegments.Intherightlungthereare10segmentsandinleftlungthere
are9(fig.2).Thesegmentsarecomprisedfromlobules.Inbothlungs,there
areabout1000lobules.Ingeneralthesizeoflobuleis1–1,5cm.Thecol-
lectionofthelobulescomprisesub-segment.Severalsub-segmentsforma
segment.
Figure1-3.Thelungssegmentstopography(lateralviewandgeneralview)
RightlungLeftlung
Table1-1.Nomenclatureofsegments
RightlungLeftlung
Thesegmentsofthesuperiorlobe:
1.apical.
2.posterior.
3.anterior.
Thesegmentsofthemiddlelobe:
4.lateral.
5.medial.
Thesegmentsoftheinferiorlobe:
6.superior.
7.medialbasal.
8.anteriorbasal.
9.lateralbasal.
10.posteriorbasal.
Thesegmentsofthesuperiorlobe:
1.apical.
2.posterior.
3.anterior.
Thesegmentsofthemiddlelobe:
4.lingualsuperior.
5.lingualinferior.
6.superior.
Thesegmentsoftheinferiorlobe:
8.anteriorbasal.
9.lateralbasal.
10.posteriorbasal.
- 12. Chapter12425Etiologyandpathogenesisoftuberculosis
Eachlungsegmentcontainsabronchusandarterythatarealmost
arrangedinaparallelorder.Thebronchi-lungsegmentshaveatriangular
shapewiththeapexfacingmediallyandthebasefacingperipherally.The
segments7and8iftheleftlunghavecommonbronchusinmajoritycases.
Eachlungsegmentisseparatedfromoneanotherbyalayerofconnecting
tissue.
Bronchialairways.Thetwobronchiproceedfromthebifurcationofthe
tracheaoppositetothe4-ththoracicvertebratotheircorrespondinglungs.
Uponenteringthelungs,thebronchidivideintobranchesinwhicheachof
thesebranchesdivideandsubdividedichotomouslytotheirultimatetermi-
nation(smallestbronchi)seeFigure1-4.
Thestructureofthelungparenchyma.Thefinniest,independentfunc-
tionalunitofthelungparenchymaisanacinus.Itisaminiaturelungabout
1,5mmindiameter.
Theacinusisventilatedbythesmallestbronchioles(bronchiolusor
bronchulusterminalis)—finniestbranchingofthebronchialtree.
Thegroupofacinusformslobulus,whosediameterreaches1–1,5cm.The
mucousmembraneliningthebronchihasaciliatedcolumnarepitheliumas
farastheirtermination.However,inthealveolarpassagesandair-cellsthe
mucousmembranebecomesthinandtransparentcoatedwithasquamous
epithelium.Thelungbloodvessels.Thepulmonaryartery,conveyingthe
venousbloodtothelungs,accompaniesthebronchitothelung,anddivides
alongwiththebronchi.Thebranchesterminateintoathickcapillarynet-
workaroundthealveoli.Airexchangeoccursbetweenthealveoliandvenous
blood.Consequently,oxygenatedbloodreturnstotheleftauricleofthe
heartthroughthePulmonaryvein.Intheircoursethroughthelung,the
arteryiscommonlyfoundaboveandbehindthebronchialtube,whilethe
veinisbelowandanterior.
Pleura.Eachlungisenclosedanditsstructuresupportedbyaserous
membrane,thepleura,whichinvestsitasfarastheroot,andisthenreflected
ontheparietalsofthechest.Thatportionofthemembranewhichisin
relationwiththelungiscalled(pleuravisceraliss.pleurapulmonalis),and
thatincontactwiththeparietes,pleuracostalis,pleuradiaphragmatica
and(pleuramediastinalis).Thepulmonarypleuraisverythin,elastic,and
inseparablyconnectedwiththestructureofthelung;thecostalpleurais
thickandstrong,hasverylittleelasticity,andcanbereadilystrippedoffthe
ribsandintercostalmuscleswhichitcovers.
Thelymphaticlungsystem.Thelungsurfaceisformedofathinsub-pleu-
ralnetworkoflymphaticvesselsthatcommunicatewiththepleuralcavity
byasystemofpores.
Thelungparenchymaconsistsof2typesoflymphaticstructures.
The1sttypeformsanelaboratenetworklocatedbeneaththebronchi’s
mucousmembrane.
The2ndtypeoriginatesinthecapillariesbetweenalveolarductsand
alveolarsacs.
Lymphaticvesselsofbothtypesterminateinthebroncho-pulmonary
nodesinthehilusofthelung.Thesenumerousandlargenodesarelocated
aroundthebronchiandwithinthetrachealbifurcation(Figurefig.1-5).
Thelungnervesarederivedfromtheparasympatheticandsympathetic
nervoussystem.Theyform2plexuses:
1.Anteriorpulmonaryplexus,whichislocatedintheanteriorpartofthe
hilusandismainlycomposedofthefilamentsofthedeepcardiacplexus;
2.Posteriorpulmonaryplexus,whichislocatedintheposteriorpartof
thehilusandiscomposedprincipallyofbranchesofn.vagus.
Thebranchesfrombothplexusesfollowthecourseofthebronchi,andare
thendistributedwithinthewallsofthealveolarductsandalveolarsacs.
Mediastinum.Thetwopleuralsacsdonotcommunicatewitheachother,
buthavebetweenthemaspacewhichcontainsallthevisceraofthechest
Figure1-4.Acinus.
1–thеsmallestbronchia;2–bronchioliorbrochulirespiratorii;3,4–аalveolar
passagesandaircells;5–alveolarsac.(РозенштраухЛ.С.идр.,1987)
- 13. Chapter12627Etiologyandpathogenesisoftuberculosis
(thorax)withtheexceptionofthelungs.Thisiscalledtheintra-pleuralspace
ormediastinum.Themediastinumisdividedinto:anterior,middle,posterior,
andsuperiorportions(parts).
Lungfunction.Thefunctionsoflungsarecloselyconnectedtothe
featuresoftheirstructure.Duetothepresenceofhundredsandmillionsof
alveoli,thetotalsurfaceofwhichreaches100м2andthenetworkofcapillar-
ieswithasurfaceareaupto80м2,togetherwiththecomponentsofalveolar-
capillarymembrane.Thelungsdonotonlyplayaroleinthebreathingbut
alsoinexpectorationandinthemaintenanceofaconstantbodytempera-
ture.Thelungsalsoproducesubstanceswhichparticipateintheregulation
ofbloodcoagulation,protein,fatandcarbohydratesmetabolism.
Thetubercularinflammation
Thetubercularinflammation,likeanyotherinflammationisamanifes-
tationofalteration,exudation,proliferation,leadingtotheformationof
tuberculargranuloma(tuberculum,tuberculartumor).Thetermgranu-
lomaisderivedfromthediminutiveoftheLatintermforagrain,granulum,
whichwasfirstusedbyRudolfVirchov[1818]todescribetumorsthatmay
ulcerateandgiverisetogranulationtissue.
Thetuberculargranulomaisnotamerecollectionofinflammatorycells
butisanactivesiteofactionofnumerousenzymesandcytokinesinthevery
complexprocessofremovingthecausativeagentMBT.
Hematogenicelements(lymphocytes,monocytes,polymorphonuclear
leucocytes)andhistiogenicelements(histocytes,macrophages,fibroblasts,
reticularcells,endotheliumofbloodvessels,plasmaticandmastcells),par-
ticipateintheformationoftuberculargranuloma.
Thetuberculargranulomahasthefollowingstructure.Thecenterconsists
ofamorphoustissuedetritus(duetoalterationandnecrosis),theperipheral
regioncontainsseverallayersofepithelialcells.Lymphoidandplasmacells
arepresentintheexternallayersofthetuberculum.Giantmultinucleated
Pirogov–Langhanscellscanbeseenamongtheepithelialcells.
Thetuberculumhistogenesisdependsonthedevelopmentoftheinflam-
mationprocess,whichiseitherprogressiveorregressive.Whenthereis
adecreasedhostresistancetotuberculosis,progressionofthetubercular
inflammationtakesplace.Thetissueexudativereactiondevelopswiththe
formationofcheesynecrosiswhichmightdevelopwithinthetuberculum
andsurroundingtissues.Thesetissueswillgenerallybeimpregnatedwith
serous-fibrinousexudates.
Variousfociofdifferentsizesofcheesynecrosisariseduringthefurther
progressionofspecifictubercularinflammation.Fociofcheesynecrosiscan
spreadandmergeintobiggerfocifromwhichfociwithsitesofcaseation
(infiltrates)areformed.Caseationisdilutedundertheactionofproteolytic
enzymesandiscoughedoutthroughthebronchi.Cavitiesofdisintegration
appearinthesesitesofthelungsbutulcersappearonthemucousmembrane
andskin.Thecavityformedduringthedisintegrationofcaseationwillbe
thesourceofdisseminationofMBTinotherpartsofthelungsandformation
ofnewfociandcavities.
Atchronicdevelopmenttakesplacethereversedevelopmentofinflam-
mationprocess(regression).Theepitheliumcellsareturnedintofibrob-
lasts,granulomaturnstoscarring.Inthefurtherdevelopmentthefocusof
necrosiscandissolve,undergofibrosis,calcificationandossification(see
colorfigure1-9).
Theparticulardangerisrepresentedbyvascularblooderosionsup-
plyingsitesoflungswherecaseousdegenerationoccurred.Duringcavity
formation,bloodfromthedamagedvesselspenetratesthebronchiandfrom
there,eitherpenetratesotherpartsoflungsorisexpectoratedexternally.
Reversibledevelopmentofprocess(regression)occursduringhighresist-
anceoftheorganismthetuberculumwillbesubstitutedbyfibrosisand
calcification.
Рис.1-5.Схемалимфатическихузловсредостенияипутейоттокалимфы
излегких(РозенштраухЛ.С.идр.,1987)
1–paratrachealnodes;2–tracheo-bronchialnodes;3–bifurcationnodes;
4–bronchial-pulmonicnodes.
- 14. Chapter12829Etiologyandpathogenesisoftuberculosis
Pathologicalanatomyoftheprimarypulmonarytuberculosis
Primarytuberculosisdevelopsafterthefirstcontactofmacroorganism
withMBT.MBTfillintheperipheralpartsofthelungswhentinyparticles
containingMBTareinhaledthroughthesuperiorrespiratorytract.The
mycobacteriumremainsthereandreproducesslowlyformingtheprimary
pulmonaryaffection(focus).Inthisway,mycobacteriumfallingintothe
lymphthroughwhichtheyaretransportedtothelymphnodes.Theclassical
formofmorphologicalmanifestationofprimarytuberculosisistheprimary
tuberculosiscomplex(seecolorfigure1-10).In90%ofcases,theformation
oftheprimarytuberculosiscomplexarelocatedinthesuperiorandmiddle
partsofthelungsbutcanbefoundinthesmallintestine,bones,etc.
Intheprimarylungfocus,alveolitisdevelops,whichisquicklyreplaced
bythetypicaldevelopmentofcaseosisnecrosis.Inthecentreofprimary
focus,caseosisformsbutintheperiphery—elementsofnonspecificinflam-
mationoccur.Theprimarylungaffectlocalizesmoreoftenjustunderpleura,
thereforefrequentlypleuraisinvolvedintheinflammationprocess.The
lymphaticvesselsexpand,theirwallsbecominginfiltratedandtubercles
appear.Intheregionallymphaticnodes,thereareelementsofinflammations
convertingintospecificcaseouschangeswithnecrosis.Theinflammative
changesinthelung(1)and(2)inthelymphnodes(lymphadenitis)and
lymphpaths(lymphangitis)aretogetherknownasthePrimarytuberculo-
siscomplex.Inthefourthphase,intheplaceofbroncho-lobularpneumonia
(3)calcificationbecomecompact,thefocusgetsroundedformandregular
precisecontours,itssizedoesnotexceed3–5mm.Thisformationifcalled
Gohn’sfocus(figure1-12b).
Perifocalinflammationaroundthelymphnodeswillspreadinthemedi-
astinumandsurroundthelungtissues.Theinflammationprocesswithinthe
lymphnodesismostintenseintheprimaryaffectionarea.Therefore,repara-
tivechangesinthelymphnodeswillbeslower.
Thedynamicstudyofprimarypulmonaryprocessesamongchildrenhas
allowedtoallot4phasesoftheprimarytuberculosiscourse(Figure1-11):
1)pneumonic;
2)phaseofdissolving;
3)phaseofcondensation;
4)formationofGohn’sfocus.
Inthefirstphase(pneumatic)thefocusofbroncho-lobularpneumonia
(3)isdeterminedwithasizeof1,5–2till5cmFigure1-11a.Theformofthe
lungfocus(3)isroundorirregular,withheterogenouscharacteranddim
contours.Enlargedregionallymphaticnodes(1)aredeterminedsimultane-
ously(thepictureofinfiltrativebronchoadenitis)andthereisanamplifica-
tionofbronchialvesselspicture—lymphangitis(2)betweenthefocusand
thelungroot.
Theinflammativechangesinthelungandinthelymphnodes(lym-
phadenitis)andlymphpaths(lymphangitis)aretogetherknownasthe
Primarytuberculosiscomplex.Thus,thepictureofprimarytubercular
complexconsistsofthreecomponents:changesinthelungs(3),lymphangi-
tis(2)andlymphadenitis(1)(seefig.1-11).
Inthesecondphaseofdissolving(bipolarity)thereductionofthe
perifocalzoneofinflammation(3)isobserved(Figure1-11b).Thecentrally
locatedcaseousfocusbecomesmoreprominent.Thesignsofinflammation
inregionallymphaticnodes(1)andinthezoneofbronchopulmonaryvessels
aredecreaseding(2).
Inthethirdphase,thephaseofcondensation:theprimaryfocusiswell
outlined(3),itscontoursarecleared,onperipheryofthefocusthereisthe
Figure.1-11.Phasesoftheprimarytuberculosiscourse:
(a).Phase1(pneumonic)ofprimarycomplexformation;(b).Phase2ofdissolving
(bipolarity);(c).Phase3–condensation;(d).Phase4formationofGohn’sfocus
- 15. Chapter13031Etiologyandpathogenesisoftuberculosis
beginningofcalcificationasfinepieces;atperipheralregionsoflungbron-
chiallymphaticnodescalcificationisalsopresent(1)(Figure1-11c).
Inthefourthphase,intheplaceofbroncho-lobularpneumonia(3)cal-
cificationbecomecompact,thefocusisroundwithregularprecisecontours,
itssizedoesnotexceed3–5mm.ThisformationiscalledGohn’sfocus
(Figure1-11d).
Outcomesoftheprimarytubercularcomplexmaybeinthefollowing
way:
1)healingwithencapsulation,calcificationorossification;
2)progressionandgeneralizationoftheinflammationprocess.Itmay
beaccompaniedwithadditionalcomplicationssuchasatelectasis,pneumo-
sclerosis,etc.
Thereare3typesofgeneralizationofthetubercularcomplexpro-
gression:
1)hematogenic;
2)lymphogenic
3)bronchogenic(figure1-13).
HematogenicgeneralizationdevelopswhenMBTpenetratesblood
circulation.Aprerequisiteforhematogenicgeneralizationtooccuris
hyperergia.Twotypesofearlygeneralizationpro-cesshavebeenidentified
dependingontheconditionoftheprimarytubercularcomplex:
1)generalizedmiliarytuberculosiswithmassivedisseminationofthe
productiveorexudativenodesinallorgans;
2)focaltuberculosiswithformationofcaseousfoci,withthesizeupto
1cm.
Thefociofhematogenicgeneralizationmightbecomeasourceforthe
developmentoftuberculosisindifferentorgans.
Atprogressionofhematogenousdisseminatedtuberculosisthecavities
areformed.Theformationofcavitiesistheresultofcheesydisintegration
anddissolutionofnecroticmasses.Thecavitiesareusuallythin-walled,
multipleandsettleddownsymmetricallyinbothlungs.Inanoriginofsuch
cavities,importantroleplaysdamageofbloodvessels,theirthrombosisand
obliteration.Thebloodsupplyofthesefocusesisdisturbedinlungsand
destructionisformedresemblingtrophiculcers.Duringtheformationofthe
cavities,thepossibilityofbronchogenicdisseminationofhealthyregionsof
lungscanappear.
Hematogenicdisseminationofmycobacteriumisalwayscombinedwith
lymphogenic.ThusMBTnotnecessarilypenetrateintothebloodatone
timeatthedestructionofthelargefocalnecrosis.Theycanpenetraterepeat-
edlybysmallportions,passinginthebeginningthroughthelymphaticves-
sels.SuchgenesisgivesdifferentclinicalandX-raydisplayofhematogenic
disseminatedformswithvariouscourses,durationofthediseaseandwith
heavyoutcomeorrecovery.
Thetubercularfocusesinlymphaticnodesarepoorlyaccessibletoaction
ofantibacterialdrugs,buttheyarethesourceofseriouscomplications:such
asdistributionofthetubercularprocessonthemediastinumorgans;joining
ofasecondaryinfection;developmentofamyloidosisofinternalorgans.
Morecommonly,theprimarylesionremainsinactive(quiescent)andmay
remainsofordecadesorforthewholeindividual’slife.Theprecisemecha-
nismsunderlyingthisphenomenonhavenotyetbeenclarified.However,
reactivationorreinfectionoftuberculosismayoccurduetomalnutrition,
malignantdisease,HIVinfection,useofimmunosuppressivedrugsand
intercurrentinfections.
Pathologicalanatomyofsecondarytuberculosis
Theprogressionoftuberculosisisdividedinto2separateconsecutive
periodsreflectingdifferentclinicalandpathomorphologicalpictureofthe
disease.
Post-primary(secondary)tuberculosis—thisdefinitionisusedfor
tuberculosis,whichhasbeendevelopedinorganismwitholdpostprimary
Figure1-13.Generalizationofthetubercularcomplexprogression
- 16. Chapter13233Etiologyandpathogenesisoftuberculosis
lesions,whichwerepartiallyhealed.Occurrenceanddevelopmentofsecond-
arytuberculosiscanriseintwoways:
1)endogenoussuperinfection—reactivationoftheresidualpostpri-
maryfocuses(partiallycalcifiedlymphaticnodes);
2)exogenoussuperinfection(reinfection)—repeatedtuberculosis
infection.
Secondarytuberculosis(90%ofmostcases)—ispulmonarytubercu-
losis.Thetubercularchangesofthesecondaryperiodinlungsquiteoftenare
detectedatfluorographyorX-ray,thataremadeduringpreventivecheckup
withoutanycomplaintsofthepatients.Thistendencyisoneoftheindirect
proofsthatthepatientdoesnotfeeltheillnessasitdevelopedasymptomati-
cally.Insuchcases,X-raytubercularaffectionsappearasamedium-sized
fociinlungsorintheotherorgans.However,inlungstheyseenmoreoften.
Duringthesecondarytuberculosisthespreadofinfectionasarule
proceedsthroughthebronchialairways.
Themostimportanteventthatdeterminesifthepatient,especiallythe
adultpatient,willhavesignificantclinicaltuberculosisisthesofteningand
liquefactionofthecaseousnecroticmaterial.Duringliquefaction,thereisa
massiveincreaseinthenumberofbacilliwhichgrowextracellularinthis
situation.
Evolutionofsecondarytuberculosisispossibletodivideintophases
(figure1-15):
Calcificationstartstooccurduringthebeginningstagesoftubercular
focidevelopmentinapicallesions.Butthecavitiescanbestillopen.This
typeofchronictuberclosisisamajorsourceofinfection.
Thediversityofpathomorphologicalmanifestationsinlungsareusedas
abasistoclassifytuberculosisofbreathorgansontheforms:
–focuspulmonarytuberculosis;
–infiltrative-pneumonicpulmonarytuberculosis;
–caseouspneumonia;
–lungtuberculoma;
–cavernouspulmonarytuberculosis;
–fibrotic-cavernouspulmonarytuberculosis;
–cirrhoticpulmonarytuberculosis;
–tubercularpleurisy;
–tuberculosisofbronchi,trachea,upperrespiratorytract;
–tuberculosiscombinedwithprofessionallungdiseases.
Focuspulmonarytuberculosis
Thefocuspulmonarytuberculosisreferredtothemanifestationof
secondarytuberculosis.Itistheinitialformofpulmonarytuberculosisin
anadult.Tothistypeoftuberculosisrefer:freshorsoftfocaltuberculosis;
Figure1-15.Evolutionofsecondarytuberculosisofadults:
a–lesionformationinupperpartsoflungsinadults.Itisoftenintheupperpart
ofthelung.Thelesionsinthehilarlymphnodesusuallyabsent(thoughsome-
times–amongAfricans,AsiansorpatientswithHIVinfection–thenodesmay
begreatlyenlarged).Thelungandlymphnodelesionsoftenhealandmaylater
becalcified;b–gradualenlargementofthelunglesions;c–caseation(necrosis).
Liquefiedcaseousmaterialmaybecoughedup.Thisresultsinacavity.Spread
ofTBfromthecavitytoproducefurtherlesionsinthesameandintheopposite
lungwithafurthercavitydevelopinginthatlung;d–afterayearortwoof
effectivetreatment(ifthepatientsurvives)intheplacesofspecificlesionsfibrosis
(scarring)ofcavitiesdevelopswhichpullsupthehilumandthetracheatotheside
ofbiggestdamage.
ab
cd
- 17. Chapter13435Etiologyandpathogenesisoftuberculosis
fibroticfocaltuberculosis;long-standingtuberculosiswithfocioflessthan
1cmindiameter.
Softfocuspulmonarytuberculosismorphologicallyrepresentedbythe
developmentofendo-andperi-bronchitisofthefineapicalbranches(1-stand
2-ndorderofthesegmentalbronchi).Thereissubsequentcaseousnecrosisin
thebronchiwalls.Theinvolvementofthenearbyalveoliresultsintheforma-
tionofcaseousacinusorlobularbronchialpneumonia.
Foralongperiodoftime,theprocesswithinthelungswillbelimited
withintheaciniorlobules.Astheprocessprogresses,newfociwillappear
neartheoriginalfocus,developingbycontactwithinthelimitsofthesame
lungsegment.Lymphostasiswilldevelopinthelymphaticvessels,fibrotic
tissuelayers,peribronchialandperivasculartissues,passingonthelung
hilum.
Thetypicalpathofthelungfocaltuberculosisprogressionisabron-
chogenicprogression.Newbronchialpneumonicfociwillformfromthis
progression.Howeverdamageoflymphnodesisnotcharacteristic.
Atfavorablecoursethebronchopneumonicfocusesareexposedtoencap-
sulation,calcification,fibrosisorhyalinosis.
Thefocuses(«reinfects»)havecharacteroflatentdevelopmentatthefibrotic
focuspulmonarytuberculosis,butunderadverseconditions,theiraggravation
possiblewithexudativereactionsandgrowthofazoneofnecrosis.
AttuberculardamageofbronchialtreewithMBTexpectorationthe
destructive(cavitary)formofpulmonarytuberculosisdevelops.
Atreversetubercularprocessquiteoftendiffusesclerosisdevelopsofthe
topsegments.
Infiltrative-pneumonicpulmonarytuberculosis
Theinfiltrativepulmonarytuberculosisknownforalongtime.T.H.Lae-
nec(1781–1926)onthebasisofthesectiondatahasdescribeditasgelati-
nouspneumonia.
Theinfiltrationdevelopsbecauseofexacerbationofencapsulatedfocuses,
whichcanbenotonlyinlungs,butalsointheintrathoraciclymphatic
nodes.
Whenaninfiltrativefocusdevelopsintheunalteredtissue,thenaround
freshtubercularfocusorfusedseveralfocusesperifocalinflammationis
developed.
Infiltrativepulmonarytuberculosischaracterizedbythepresencein
lungsinflammatorychanges,mainlyofexudativecharacterwithcaseous
necrosisandwiththepresenceorabsenceoflungtissuedestruction.
Theetiologyofinfiltrativepulmonarytuberculosiscanbeofvariousori-
gins.Insomegroupsofpatients,infiltrativefocusesaredevelopedasaresult
ofbronchogenicdisseminationofMBTtohealthypulmonarytissuefrom
inflamedlatentapicalfocuses.Whileinothergroupsofpatientstheinfiltra-
tionsrepresentaperifocalinflammationofsmallinfiltrativefocusesofolder
origin,whichconsequentlyradiographicallydifficulttobedetermined.
Thepathological-anatomicalpictureoftheinfiltrativepulmonary
tuberculosisischaracterizedbypresenceoneorseveralfinefocusesof
cheesynecrosis,withdifferenttimedurationwithazoneofperifocalinflam-
mation,whichvolumeexceedstheirsizesinseveraltimes.
Thecharacteroftheexudateisvariousatthisform:serous,serous-fibri-
nous,sometimesasdesquamativealveolitis,caseousinfiltration.Accor-ding
toextenttheprocesscanbelimitedbylo-bule,butcanoccupythewhole
lobeofalung.
Proliferativereactioncomestoanendbydevelopmentofaconnective
tissue,givingtheappearanceinterstitiallyindurativefibroidfields.
Outcomesoftheinfiltrativepulmonarytuberculosis:
1.completeresorptionoftheperifocalzoneorcarnificationofthedam-
agedfocuswithencapsulationandcalcification(transitiontofibroticfocus
form).
2.caseationoftheperifocalzoneofinflammation,joiningofdisintegra-
tion,sequestrationandtransitionintotheacutecaseouspneumoniaorcav-
ernouspulmonarytuberculosis.
3.atpredispositionofinfiltrationtodevelopmentofcaseousnecrosis
theinfiltrationisexposedtocompleteorpartialdisintegration.Asaresult
ofcaseousmassdischargethepneumogeniccavityisformedwhichsize
dependsonavolumeofinfiltrativepneumonicfocusandnecrosis
Caseouspneumonia
Thecaseouspneumoniaarisesmoreoftenasaresultofprogressionof
theinfiltrativepulmonarytuberculosis,butcanaggravatethedevelopment
ofanyformofpulmonarytuberculosis.Thebasicmorphologicalattributeof
thecaseouspneumoniaisprevalenceofcaseouschangesaboveunspecific
perifocal.Dependingonthesizeofthelungvolumethefollowingcaseous
pneumoniaaredistinguished:
1)acinous;
2)lobularconfluent;
3)segmental;
4)lobarcaseous.
- 18. Chapter13637Etiologyandpathogenesisoftuberculosis
Duringtheprogressionofcaseouspneumonia,thepulmonarytuberculo-
sisdevelopswithnumerouscavities.
Lungtuberculoma
Thesourceoftuberculomaformationbasicallytwoformsofpulmonary
tuberculosisareserved:infiltrativeandfocus.Besidestuberculomacouldbe
formedfromcavernouspulmonarytuberculosisbymeansoffillingofcavity
withcaseousmasses.
Thefilledcavitiesrefertotuberculomaonlyconditionally,asthefilling
ofacavityoccursmechanically,whiletuberculoma—itisanoriginalphe-
nomenoninlungtissue.
Tuberculemacanbesolitary(homogeneousа)andoflayeredstructure
seeingonasection(б),multipleandв)conglomerated,consistingfromgroup
ofthefocuseswithcommoncapsule(seecolorfigure1-20).
Variantsofthetuberculemaaggravation:
1)developmentoftheperifocalinflammation;
2)cavitation—dischargeofthecaseousmassesfromacavity,through
drainingbronchus.
Cavernouspulmonarytuberculosis
Cavernoustuberculosisischaracterizedbythepresenceofathin-walled
cavity,withoutperifocalinflammation,withsolitaryfocusesinsurrounding
tissue.
Cavernouspulmonarytuberculosisoriginatefrom:
1)dischargeofthecaseousmasses,fromthetuberculousinfiltrative-
pneumonicfocusinlungs(thepneumogenicacutecavity);
2)fromthefocuswithacapsule(tuberculoma),duetodischargeof
caseousmasses).
Figure1-21-1.Macroview.showingthethin-walledcavitywithcapsule,
3,5cmindiameter,withoutperifocalinflammation,withisolatedfocuses
insurroundingtissue.Remnants(a)ofcaseationareplacedalonginternal
borders(b)ofthecavitywithemptyspaceinthecenter.
Complicationsofthecavernoustuberculosis.Forthecavernouspul-
monarytuberculosisbronchogenicwayofprogressingistypical.Concerning
complicationsofthecavernoustuberculosisitisnecessarytonotean
opportunityoftheprofusehemorrhage.Thecavernoustuberculosisatthe
furtherdevelopmentconvertsintothefibrotic-cavernousone.
Fibrotic-cavernouspulmonarytuberculosis
Fibrotic-cavernouspulmonarytuberculosisdevelopsfromanyprogress-
ingformofpulmonarytuberculosiswithformationofthecavity,inwhich
thewallexpressedbyfibroticcomponent.Certainly,itisnoteasytodefine
whichprocesswasasourceandservedasthereasonfordevelopmentoffar
advancedfibrous-cavernouspulmonarytuberculosis.
Figure1-21-2.Atfibrotic-cavernoustuberculosisthreelayersbegin
clearlytobedefinedinthewallofthecavity:а)aninternalnecroticlayer;
b)middle—asthelayeroftuberculargranulationtissue;c)theexternal,
layerofacavitywallconsistsofafibrousconnectingtissue.
Thetransitionfromsharpcavernoustofibrotic-cavernoustuberculosis
morphologicallyconsistsindevelopmentofscleroticchangesasinthecavity
wall,soinsurroundinglungtissue.Withtimethestructureofawallanda
cavityappea-ranceschange.Theexternallayercanbeofvariousthickness,
asitsstructurecancompriseofadjacentatelectaticlungtissue.
Forfibrotic-cavernoustuberculosis,thefocusesofrepeatedbronchogenic
disseminationofvariousremotenessofeventsarecharacteristic.Asarule,
thecavitydrainagebronchusisda-maged.Othermorphologicalchanges
developalsoinlungssuchaspneumosclerosis,emphysemabronchoectasia.
Thewayofprogressionofthefibrotic-cavernouspulmonarytubercu-
losisisdevelopedbycontactalongbronchiindirectionfromthetopofthe
lungstotheirbase.Thedamageofthebronchialtreerevealinallcasesof
fibrotic-cavernouspulmonarytuberculosis.
Thedamageextentinlungscanbevarious.Theprocesscanbeunilat-
eralandbilateralwithpresenceofoneormultiplecavities.
Cirrhoticpulmonarytuberculosis
Thelungcirrhosisrepresentsactivestageofpulmonarytuberculosis
progression,arisingbecauseofgrowthlungconnectingtissue.Massive
sclerosisdevelopsatinfiltrativepneumoniccarnificationprocesses,dissemi-
natedorfibrous-cavernouspulmonaryfibrosisasaresultoflongdeveloping
tubercularatelectasis.
Atthedevelopmentofcirrhoticpulmonarytuberculosis,alongwithmas-
sive,overgrowthoftheconnectingtissueofdiffusecharacter,deformation
ofalungtissueandbronchectasisdevelopmenttakeplace.Thecavitiesare
absentortheylooklikenarrowslit-likecavities.
Atinvolutionofinfiltrationorfibrous-cavernoustuberculosisthecir-
rhosiscanbeunilateralandbilateral.Atsignificantvolumeofthesclerotic
changeshypertensionofthebloodpulmonarycircuit,corpulmonaleand
- 19. Chapter13839Etiologyandpathogenesisoftuberculosis
lung-heartinsufficiencydevelop.Tothebasiccomplicationsconcern:the
amyloidosisofinternalorgansandtromboembolismofthelungartery.
Thevicariousemphysemaaccompanycirrhoticprocessinlungs,
whichdevelopsintheundamagedpartsofthelungs.Replacementoflung
normaltissuebyscarringmaterial,deformationofbronchiallumendamage
ofbronchialfunctionresultinaccumulationofthebiologicalfluidinbronchi,
whereMBTcanmultiply.Thedeformationofbronchiresultsindevelopment
bronchectasis.Deformation,narrowingandobliterationofvesselsdevelop
underinfluenceofpneumosclerosis.
Thestructuralchangesofbronchi,reductionofrespiratoryexcursions
becauseofpleuralknittingandemphysemaresultininfringementofbreath
function.Themassdestructionofalveoliandlungcapillariesdamagealveoli
gasexchange.Hypoxiaandhypoxemiaarebeingdeveloped.
Therespiratoryinsufficiencyiscompensatedbymusclehypertrophyof
theheart’srightparts.Whenheartcompensatoryabilitiesarediminishing,
torespiratoryinsufficiencyjoinsheartinsufficiencyandsyndrome«Cor
pulmonale»develops.
Inthelaterstagesofcirrhosisdevelopmenttotherightheartinsuffi-
ciency,theinsufficiencyoftheleftventriclejoins.Oneofthebasicreasons
ofdeathofthepatientswithcirrhoticpulmonarytuberculosisistheinsuf-
ficiencyofbloodcirculation.
Tubercularpleurisy
Thepleurisy,istheinflammationofpleura.Twobasicformsofpleurisy
aredistinguished:dryorfibrinous(pleuritissicca,fibrinosa),andexudative
(pleuritisexudativa).
Duringtuberculosisthepleuraisinvolvedintheprocessofinflamma-
tionatpenetrationinitinfectionbythecontactway,throughthelymph
ortheblood.Theinvolvementofpleurainvariouspathologicalprocesses
isconditionedbycloseanatomictopographicalconnectionsofvisceraland
parietalpleurawithlungtissue,intrathoraciclymphaticnodes.Thepleura,
havingbarrierfunction,reactstovariouspathophysiologicalchangesofthe
body.Therefore,thedevelopmentsofinflammativeorallergicprocessestake
place.
Exudativeinflammativereactionofthepleuraisconnectedwith
increasedpermeabilityofthebloodandlymphaticcapillariesofthelung
corticallayerandpleuraitself.Thesecapillariesmakewayforaliquidpart
ofbloodintointratissuefissures,superficiallayersofpleuraandtherefrom,
withthehelpnegativepressure,intopleuralcavity.
Lymphagenicpleurisy.Thetubercularinfectioncanaffectsubpleural
lymphaticnodes.AccumulatinginthenodesMycobacteriumtuberculosis,
somearebrickedupandareeliminatedandtherestofMBT,keepingtheir
virulence,aredistributedalonglymphvesselscausesubpleuralcorticallym-
phangitisortheexudativepleurisy.
Hematogenicpleurisy.ThehematogenicspreadingofMBTintothe
pleuralcavitypromotesdevelopmentoftuberclesonthepleura.Theinitial
focusisanactivetubercularprocessinmediastinumlymphaticnodes.
ThecontactwayofMBTdisseminationarisesatactivetuberculosisof
lymphaticmediastinumnodes,withdefeatofvisceralpleura.
Fibrinouspleurisy(drypleurisy).Atthefibrinouspleurisyonthepleura
atfirst,gentlelayeroccurs,offibrinousstructure,whichcouldeasilyremove.
Furtherthefibrinouspellicleofyellowishoryellowish-graycolorisformed.
Purulentpleurisy(empyema)fromtheverybeginningarisesaspuru-
lentveryrare,butmoreoftenitdevelopsafterserous-fibrinousinflamma-
tionofthepleura.Theprocessusuallyhappensunilateralandmainlysettles
downinbasalorposteriorpartofthepleuralcavity.Thepurulentpleurisyis
observedatburstingoutofcaseousmassesfromlungintothepleuralcavity,
broncho-pleuralfistulasandetc.
Hemorrhagicpleurisyaccompaniedbypenetrationofexudatescontain-
ingasignificantimpurityoferythrocytesintopleuralcavity.
Outcomeofpleurisy
Inoverwhelmingmajorityofcasesthefibrinousexudatesdissolvesonly
partially,andbasicallyissubjectedtotransformation,thatleadstodevelop-
Figure1-23.Thetypicallocalizationofpleurisiesinlungs:
a)costal-diaphragmatic;b)diaphragmatic;c)costal;d)interlobe;e)parame-
distinal;f)apical
- 20. Chapter14041Etiologyandpathogenesisoftuberculosis
mentofcommissuraljoints,fibroticthicke-ningofthepleura,toobliteration
ofthepleuralcavities.
Purulentexudateseldomisexposedtocompletedissolution,moreoften
theencapsulationoftheinflammativeeffusionisdeveloped.Theinflamma-
tiveprocessatpleuralempyemacanpassoninterstitiallungtissues(puru-
lentpneumonia).
Chronicpleurisy
Moreoftenchroniccourseofthepleurisyisobservedatpleuralempyema.
Inthesecasesexudatescondense,dissociate,turnincheesymassorthin
gruelwithpresenceofcholesterolcrystals;themicroorganismscandisap-
pear.Thepleuralmembranesareconsiderablythickenedanddense,some-
timeswithfocalpetrificationandevenossification.Thesignificantsedi-
mentsofcalcifiedmassesareespeciallytypicalfortubercularempyema.The
pleuralempyemacanleadtopurulent—resorptionfever,sepsis,exhaustion,
amyloidosisofinternalorgans.Sometimeslong,chroniccurrentisobserved
atserous-fibroticandfibroticpleurisy.
Duringacuteandchronicpleurisiesthesignificantaccumulationofexu-
datesinthepleuralcavitycausestheatelectasisinappropriatelungandthe
mediastinumorgansaredisplacedintheoppositeside.
Tuberculosisofbronchi,trachea,upperrespiratorytract
Tuberculosisofbronchi,trachea,upperrespiratorytractandother
organs:(nose,buccalcavity,pharynx)arethecomplicationsofprimary
andsecondarypulmonaryandofintrathoraciclymphnodestuberculosis.
Sometimestheseformsespeciallybronchituberculosiscanbeisolated.
Pathologoanatomicalchangesintuberculosisofbronchi,trachea,upper
respiratorytractetc.(nose,oralcavity,andpharynx)arecharacterizedby
formationoftypicalepithelioidtubercleswithLanghancegiganticcells
withproliferationofconnectivetissue.Theformationofthefociofnecrosis,
cheesydisintegration,edemaswithMBTexistence,revealedathistological
investigations,characterizespredominantlyexudativetypeofthereaction.
Theepithelioidtuberclesarelocatedmoreoftensuperficiallyanddirectly
undertheepithelium.Owingtocheesydisintegrationatprogressingdevel-
opmentofinfiltrates,tuberclesarrangedunderanepitheliumtherecomes
formationofulcers.
Pathomorphologyofhealingprocessesarecharacterizedbyintensive
developmentoffibrousconnectivetissuegrowsthroughtuberclesandencap-
sulatingthem.
1.5.EPIDEMIOLOGYOFTUBERCULOSIS
Tuberculosisinfectionanddiseasepatternsamongdifferentpopulations
areheterogeneous.Understandingtheepidemiologyofthisdiseaseis,there-
fore,vitallyimportantasanaidtodiagnosis,prevention,andpublichealth
programdevelopment.
Tasksoftuberculosisepidemiology:
1.Identifiablepopulationsatrisk.
2.Thescopeandimpactoftheinfection.
3.Temporaltrendsininfectionpatterns.
4.Geographicallocations.
5.Reservoirsandmechanismsoftransmission.
6.Riskfactors—whydosomebecomeinfectedand/ordiseasedandoth-
ersnot?
Epidemiologicaldefinitions(terms)
Epidemiologicalsituationconcerningtuberculosisischaracterizedbythe
followingstatisticaldata:infection;incidence;prevalence;mortality.
Infection(infected/contaminated)—percentageofpersonswithposi-
tivetuberculinreactions,ifthereactionsarenotduetovaccination.
IncidenceRate(incidenceofnewcases).Theincidencerateisthe
numberofnewcasesofactivedisease(events)occurringinanidentified
populationoveratimeperiod.Generally,tuberculosismorbidityisreferred
toineventsper100000populationsperyear.
Prevalenceoftuberculosis.Prevalenceisthenumberofpatientswith
activeformsoftuberculosisinapopulationattheendoftheyearper100000
population,thespecialimportancehastheprevalenceindexofactive(MBT
positivecasesofpulmonarytuberculosis).Prevalencethusreflectsthe
cumulativemorbidityfromtuberculosis.Ifallnewcaseswerepromptly
«cured»bytreatment,theincidenceandprevalenceofdiseasewouldbe
closelyapproximate.Butifpatientsarelostfromtherapyorpartiallytreated,
casesofchronictuberculosiswillaccumulate,causinggrossdisparitiesinthe
incidenceandprevalencevalues
Mortalityfromtuberculosis—numberofpatientsdiedbecauseoftuber-
culosisper100000populations.
Smear-Positive(Bacillary,MBT+)caseofpulmonarytuberculosis,
thisreferstoapatientwithtuberculosisoftherespiratorytractwhose
airwaysecretions,whenexaminedbyspecialstainsandmicroscopy,demon-
stratetuberclebacilli.Someauthoritiesrefertotheseas«bacillary»cases.
- 21. Chapter14243Etiologyandpathogenesisoftuberculosis
Smear-NegativePulmonaryCase(MBT-).
Thisreferstoapatientwithpulmonarydiseasewhosesputummicro-
scopyexaminationfailstodemonstratebacilli.Thediagnosisofdiseaseis
establishedbysymptomatology,positivecultures,progressivechangeson
chestradiographdeemedtoreflectdiseaseactivity,and/orothersupporting
datasuchaspositivetuberculinskintestreactivity,epidemiologicalfeatures,
and—forinfantsandchildren—ahistoryofexposuretotuberculosis.
Extrapulmonarydisease.Thisisthecaseofapatientwhoseclinical
illnesspresentswithactiveinflammatorytuberculosisinorgansoutsidethe
lungs.Mostpatientshaveeitherpulmonaryorextrapulmonarytuberculo-
sis;aminoritymanifestssimultaneousdiseaseinbothsystems.Although
extrapulmonaryandsmear-negativepulmonarycasesarebothclearlycom-
ponentsoftheoverallmorbidityoftuberculosis,theyarelesssignificantepi-
demiologicallythansputumsmear-positivecases,whichactastheprimary
vectorsoftransmissiontoothers.
AnnualRateofInfection(ARI).
Theannualrateofinfection(ARI)isyearlyincidenceofnewtuberculous
infectionsamong«eligible»(tuberculin-negative,notpreviouslyinfected)
membersofapopulation,manifestedprimarilybytuberculinskintestcon-
versionrates.
TheARIhasbeenemployedasindirectorinferentialmarkerofthepreva-
lenceofsputumsmear-positive(communicable)cases;withinapopulation.
Byfollowingagroupindividualsknowntobenonreactivetotuberculinand
observingthefrequencywithwhichtheirskintestsbecomereactivethrough
timeauthoritieshaveattemptedtoestimatethetotaltuberculosismorbid-
itywithinthatcommunitybycomparisonwithestablisheddatabases.This
techniquehasbeenemployedprimarilyindevelopingnationsthatlackthe
resourcesforconsistentdiagnosisandcasetabulations.
Tuberculosisinfected.Thisisthestateofharboringviabletubercle
bacilliwithinone’sbodywithoutmanifestingsignsorsymptomsofovert
di-sease.Thegreatmajorityofnormalindividualswhoareexposedtoand
infectedwithMBTenjoythisstatusthroughouttheirentirelives.
Diseasedtiberculouspatients.Thisisthestateofsufferingfromactive,
progressiveinvasionofanorganororgansbyMBT.Thistypicallyismani-
festedbyconstitutionalsymptomsorsignsorsymptomsthatrelatetoaspe-
cificorgansystem.Inmostcases,atuberculinskintestisreactive,butthis
testisneitherspecificnorsensitivefordiseasestatus.Themostimportant
bacteriologicalconfirmationiscultivationofMBTfromthesputum,orfrom
thetissuesofdifferentorgans.
Largelyforpublichealthcommunicationandreporting,WorldHealth
Organizationrecommendsasystemtoclassifypersonswithknownor
suspecteddiseaseandindividualsbeingevaluatedincontactinvestigations
surroundingnewcases.
Informationgatheredinthissystemformsthebackboneofcasereport-
ingintheworld.Asamorbidcaseoftuberculosis—isacceptedadisease
confirmedbydetectionofmycobacteriumtuberculosis,allocatedfromthe
affectedfocus,(withsputum,urineetc.)orreceivedfromtissuesbybiopsy.
Accordingtothisclassificationthepatientsaredividedinto6groups.
Group0.NoknownexposuretoTBandanegativetuberculintest.
Group1.Tuberculosisexposure,withnoevidenceofinfection.Person
knowntohavebeenexposedbuttuberculintestisnegative.Ifinfant,mayalso
includenegativechestx-ray.Mayrequirefollow-upat3monthstoconfirmthe
disease.
Group2.Tuberculousinfection,withoutdisease.Personswithsignificant
tuberculinreactionbutwithoutclinical,radio-graphic,orbacteriologicevi-
denceofdisease.
Group3.ThisgroupIncludesallpatientswithclinicallyactivetubercu-
losiswhosediagnosticstu-diesisadequatetoconfirmthediagnosis;ifincon-
clusive,shouldlistasclass5.
Group4.Tuberculosis,notclinicallyactive.
Ahistoryofpreviousepisode(s)oftuberculosisorabnormalbutstable
chestx-ray,positivetuberculintest,negativebacteriology(ifdone),andno
clinicalorradiographicsignsofdisease.Untilactivediseaseisexcluded,
shouldlistasclass5.
Group5.Tuberculosissuspects(diagnosispending).
Personsinwhomactivetuberculosisissuspectedonbasisofclini-
cal,radiographic,and/orepidemiologicfactors.Usethisstatusforupto
3monthswhilecompleteevaluationispending.
Globalandcontinentalepidemiology.Theprofileoftuberculosisinthe
worldtodayhasbeendevelopedbyamixofdirectobservationsandinfer-
entialmeanssuchastheannualriskofinfection(ARI),asdetailedabove.
Becausetuberculosisismostextensiveinimpoverishednations,whichtypi-
callyhaveinadequatehealthinformationsystems,muchoftheinformation
isindirect.
Becauseofdeficienciesinreportingintheareaswheretuberculosisis
mostprolific,thesenumbersarefarlower.Lookingatlongitudinaltrends
fortuberculosis,itcouldbenotedacleardivergencebetweentheindustrial-
izednations,whereincidentcasenumbersandratessteadilyandsubstan-
- 25. Chapter15051Etiologyandpathogenesisoftuberculosis
2)prevalenceofcaseousnecrosis;
3)moreoftendisintegration;
4)predispositiontobronchogenicdissemination;
5)lesionoflargebronchialtubes.
Tuberculomaoflungsisrepresentedby:
1)focusofcaseousnecrosisinthesizemorethan10mmsurrounded
withazonespecificgranulatedtissue;
2)caseousfocusofnecrosiswiththesizemorethan10mm,
surroundedwithazoneofspecificandnonspecificinflammation;
3)centerofcaseousnecrosisinthesizemorethan10mmsurrounded
withcapsuleofconnectivetissuecapsulewithinclusionofcellular
elementstuberculosisgranulema.
2
Tocavernousformitisnecessarytorefer:
1)freshdestructivetuberculosis,ofthelimitedextentwithacavity,
withoutsharplyexpressedperifocalreaction;
2)freshdestructivetuberculosis,undergonetreatmentwith
preservationofcavityofdisintegrationbytheendofthebasiccourse
ofchemotherapy.
1
Fibrouscavernouspulmonarytuberculosisis:
1)tubercularprocesscharacterizedbypresenceinlungsfibrous
cavity(cavities)andexpressedbyfibrosisinsurroundingtissues;
2)chronicdestructivetuberculosisbeingcharacterizedby
mycobacteriumexpectorationwith(oftenwavy)course.
1
2
Cirrhoticpulmonarytuberculosisisformedfromformslisted
below,exceptfor:
1)tuberculosisofmediastinallymphnodes,complicatedbylesionsof
bronchialtubesfocaltuberculosisandbroncholobularinfiltration;
2)disseminatedandfibrous-cavernouspulmonarytuberculosis;
3)lobarandcaseouspneumoniatuberculosisofpleura.
2
Thebasicdifferenceofcirrhosisfromapneumosclerosisis:
1)biggervolumeofaffectedpartoflungs;
2)volumetricreductionofthedamagedsiteoflungswithlossofits
ventilation;
3)fullstructuralreorganizationofanorganoritspartwithlossofits
function.
1
2
3
Thetubercularpleurisyisaninflammationofpleuratubercular
etiology.Suchdefinition:
1)iscorrect;
2)incorrect;
3)notsure.
1
Moreoftenthesourceofdamagebytuberculosisofpleurais
located:
1)inbronchialtubes;
2)inintrathoraciclymphnodes;
3)incorticalpartsoflungs;
4)extrapulmonary.
2
3
Thetuberculosisinfectionisdistributedinpleurabyalllisted
ways,exceptfor:
1)lymphogenic;
2)hematogenic;
3)bronchogenic;
4)contact;
5)abnormalitiesoflungsintegrity.
3
Epidemiologyoftuberculosis
Caseoftuberculosis—is:
1)chronicdiseaseaccompaniedbyrecurrentcough,sputum
expectorationandspecificchangesonX-ray;
2)diseaseaccompaniedbychangesonX-rayintheupperlungfields,
andalsoinroot’softhelymphnodes;
3)diseaseconfirmedbydetectionofmycobacteriumtuberculosis,
allocatedfromtheaffectedfocus,(withsputum,urineetc.)or
receivedfromtissuesbybiopsy.
3
Annualincreaseininfectionbytuberculosispatients,in
certainpopulation,estimatedaccordingtoskintuberculintest
significativeforhighratetuberculosisinfectionbegins:
1)with20%andmore;
2)with10%andmore;
3)with1%andmore;
4)with0,1%andmore.
3
TuberculosisincidenceRate(incidenceofnewcases)isnumber:
1)oftubercularpatientsper10000population;
2)oftubercularpatientsinpercentsfromallopulation;
3)oftubercularpatientsper1000population;
4)oftubercularpatientswithpositiveMantouxtest;
5)newlyrevealedpatientsincertainyearthisper100000
population.
5
Inhighincidencerateoftuberculosis,itispossibletorefer:
1)20diseasedforapopulationof100000;
2)30–50diseasedforapopulationof100000;
3)100diseasedforapopulationof100000.
3
- 26. Chapter152
Chapter2
Themethodsoftuberculosisdiagnostics
2.1.SETTINGQUESTIONS
Themajorityofcasesoftuberculosisgenerallydiscoveredwhenthe
patientvisitshis/hergeneralpractitioner.
Thepatientfeelingsometypeofdiscomfortdoesnotimmediatelyreferto
thedoctor.Patientcomplainsofasomewhatconstantsub-febriletempera-
tureupto37,5°C.Drycoughwithoccasionalpresenceofsputumappearsin
caseofadvancedTB.Heavysmokersdonotpayadequateattentiontotheir
coughingandrelatestheircoughingtosmokingratherthanTB.
MedicalprofessionalswhatevertheirspecialtymustbeawareoftheTB
prevalence.Hereisasetofquestionsthataretobeaddressedinthecasea
doctorisfacedwithatuberculouspatient:
1.Whetherthegivenpatientwaspriorinfectedbytuberculosis?
2.Whetherhis/herrelativeswereinfectedbytuberculosis?
3.Whetherthepatienthadcontactwithtuberculouspatientsoranimals
(household,professional,industrialcontact)?
4.Whetherthepatientisregisteredinatuberculosisdispensarydueto:
tuberculintestingorhypersensitivereactiontothetest,contactwithtuber-
culouspatients,andnocleardiagnosisoftuberculosis.
5.WhenthepatienthadtheX-rayexamination?
6.WhetherthepatientwasinvitedaftertheX-rayexaminationforaddi-
tionalresearch?
7.Whetherhewasinaprisonorlivedwithsomeonewhowasinapris-
on.
8.Whetherthepatientishomeless,arefugee,migrantorbeinginunfa-
vorablesocialconditions?
Intherecentyears,AIDShasbecomeoneofthemostpowerfulincreas-
ingfactors,ofTBinfection.PatientssimultaneouslyinfectedwithHIVand
MBT,havea50%increasedchanceofdevelopingTB.
Athoroughanamnesismustbeperformed,asitisnecessarytopayat-
tentiontothefrequencyofrepeatedrespiratoryinfections.Therespiratory
infectionswillusuallybedescribedasthecommoncold.Ifapatientcon-
tractedinfluenzaandstillhasalong-standingsubfebrilebodytemperature
Overallpooloftuberculosisinfectedintheworld:
1)decreases;
2)increases;
3)remainpermanent.
2
OneuntreatedMBTbacillarytuberculosispatientinfectinone
yearabout:
1)20persons;
2)10persons;
3)3–5persons.
1
Amonginfectiousdiseases,tuberculosis,asthereasonofdeath
occupies:
1)1stplace;
2)5thplace;
3)6thplace;
4)8thplace.
1
- 27. Chapter25455Themethodsoftuberculosisdiagnostics
accompaniedwithcoughing,thenweshouldnotsuspectInfluenzabut
ratheroneofTB’smanifestations.
Ifapatienthadsufferedfromexudativeordrypleuritis,thismightbe
anindicationforthepresenceoftuberculosisinpast.
Upongatheringanamnesisamongteena-gers,adultsandelderlypatients,
itisveryessentialtoobtainthefollowinginformationwhethertheyhad
sufferedfromchronicconjunctivitis;erythemanodosum;otherpoorly
displayedsignsoftubercularintoxication.
Upongatheringanamnesis,itisalsonecessarytofindout,whenthe
tuberculintestreactedpositiveforthefirsttime.
Afterawell-collectedanamnesis,itiseasierforthedoctortoconfirmhis
assumptionofpresenceoftubercularprocess.
2.2.SYMPTOMSOFTUBERCULOSIS
Ifapatienthasanyofthefollowing,considerhima‘Tuberculosis
Suspect’:
1.Coughforover3weeks.
2.Haemoptysis.
3.Paininthechestforover3weeks.
4.Feverforover3weeks.
Allthesecanbeduetosomeotherdi-seasesbutsputummustbetested
ifanyofthesymptomsarepresent.
Coughandsputumisverycommoneverywhere.Muchofthisisdueto
acuterespiratoryinfectionsandlastsonlyaweekortwo.
Thereisalsomuchchroniccoughduetochronicbronchitis(sometimes
called«ChronicObstructivePulmonaryDisease»(COPDorothernames).
Thisismostlyduetotobaccosmoking,butmayalsooccurfromatmospheric
pollution(eitherduetocookingorheatingfiresorinsomeplacesdueto
industrialpollution).
Asweshallsee,certainadditionalsymptomsmaysuggesttuberculosis.
However,oftenthisisnotobvious:theonlywaytoconfirmthediagnosis
istoexaminethesputumforMBTpresenceatleast3times,ineveryone
whohavehadacoughformorethan3weeks.
Herearesomeguidelinesfortheproperdiagnosisofpulmonarytuber-
culosis.
GeneralSymptoms:
++—Lossofweight.
++—Feverandsweating.
+—Lossofappetite.
+—Breathlessness.
RespiratorySymptoms:
+++—Cough.
+++—Sputum.
++—Blood-spitting.
+—Tiredness.
+—Chestwallpain.
+—Localizedwheezeinlungs.
+—Frequentcolds.
(Thenumberofplus(+)signshowwhichsymptomsaremostimportant
fortuberculosis.)
Itisimportanttorememberthatallthesymptomscouldbedueto
otherillnesses.
Oneofthemostimportantsigns,thatshouldraisesuspicionofpossible
tuberculosis,isthatthesymptomshavedevelopedgraduallyoverweeks
ormonths.
Cough,ofcourse,isacommonsymptomafteracuterespiratoryinfec-
tions.Itisalsocommoninsmokers.Itiscommoninsomeareaswherethe
housesorhutshavenochimneysandthehousesareoftenfullofsmokewhen
firesmaybeusedforheatingaswellascooking.
Bothtobaccoanddomesticsmokeleadtochronicbronchitis.Cough
maydevelopgraduallyinapatientwithlungcancer,whichisbecoming
commonerincountrieswithincreasingcigarettesmoking.
Bronchiectasisiscommoninsomecountries:thepatientmayhave
hadachroniccoughwithpurulentsputumsincechildhood.However,
ifapatienthashadacoughformorethan3weeksyoumustgethis
sputumexaminedforТВtomakesurethatthecoughisnotdueto
tuberculosis.
Thereisnothinginthesputumwhichitselfsuggeststuberculosis:itmay
bemucoid,purulentorcontainblood.Intuberculosis,bloodinthesputum
mayvaryfromafewspotstoasuddencoughingofalargeamountofblood.
Occasionallythisbloodlossissohighthatthepatientquicklydies,usually
fromasphyxiaduetoaspiratedblood.
PresenceofbloodinsputumcallsforsputumexaminationforMBT.
Painsinthechestoccuroftenintuberculosis.Sometimesitisjustadull
ache.Sometimesitisworstonbreathingin(duetopleurisy).Sometimesitis
duetomusclestrainfromcoughing.
- 28. Chapter25657Themethodsoftuberculosisdiagnostics
Breathlessnessintuberculosisisduetogeneralinfectionofthelungtis-
sues,ortopleuraleffusioncomplicatingthelungtuberculosis.
Sometimespatientsseemtohavedevelopedacutepneumonia.However,
suchpneumoniamaynotgetbetterwithroutineantibiotics.Thecoughand
fevermaypersist.Thepatientremainsill.Ifyouquestionhimclosely,you
mayfindthathehashadcoughandlossofweightforweeksormonthsbefore
thepneumoniadeveloped.
Oneshouldrememberthat,inanoldersmoker,coughandlossofweight,
whichcomesongradually,maybeduetolungcancer.Ho-wever,onemust
checkfortuberculosisbyexa-miningthesputum.
Womenwhodeveloptuberculosismaystophavingmenstruation(amen-
orrhea).
Physicalsigns.Oftenthesedonothelpmuch.Butdoexaminethe
patientcarefully.Thepathogenoussignscouldberevealed.
1.Generalcondition.Sometimesthepatientappearstobeingoodhealth
despiteadvanceddisease.
2.Theremaybedifferenttypeoffevers.Theremaybeonlyslightrise
oftemperatureintheevening.Thetemperaturemaybehighorirregular.
Oftenthereisnofever.
3.Pulseisusuallyraisedinproportiontofever.
4.Fingerclubbing.Thissymptommaybeencountered,especiallyin
patientswithextensivedisease.Oneshouldkeepinmindthatclubbingis
commoninlungcancer.
5.Examinationofchest.Oftentherearenoabnormalsigns.Thecom-
monestisfinecrepitations(crackles)intheupperpartofoneorbothlungs.
Theseareheardparticularlyontakingadeepbreathaftercoughing.Later
theremaybedullnesstopercussionorevenbronchialbreathinginthe
upperpartofbothlungs.Occasionallythereisalocalizedwheezedueto
localtuberculousbronchitisorpressurebyalymphnodeonabronchus.In
chroniclungtuberculosis,withmuchfibrosis(scarring),thescarringmay
pullthetracheaortheheartovertooneside.Atanystagethephysicalsigns
ofpleuraleffusionmaybepresent.
However,oftenyouwillfindnothingabnormalinthechest.
2.3.TUBERCULINTESTING
Introduction.Tuberculintestisavaluablesupplementarymethodfor
clinicaldiagnosisoftuberculosis.Itspecifiesthepresenceofspecificsen-
sitivitycausedbyvirulentMBTorBCGvaccine.
Tuberculinappliesfortuberculintests.Forthefirsttimetuberculinwas
isolatedfromproductsofmycobacteriumtuberculosisbyR.Kochin1890.
Tuberculiniswater-glycerinextractionfrombrothcultureofmycobacterium
tuberculosis.
Tuberculinhasincompleteantigenicpropertiesi.e.itisnotsensitize
healthyorganismandformanti-tubercularimmunity.Itseffectiveagent
istuberculoproteid.Themainthermostablecomponentoftuberculinis
referredtoasantigenA60.
Tuberculinprovokesreciprocalreactiononlyamongpeoplewhoalready
sensibilizedbyMBTorBCGvaccine.Whentuberculinisinjectedinto
theskin,adelayedlocalallergicreactiondevelopswithin24–48hours.
Pathomorphologyoftheinfiltrationischaracterizedbyedemaofalllayersof
theskinwithmononuclearandhistiocytereaction.Thereactioncharacter-
izesthedegreeofallergyandNOTthedegreeofimmunity.
Tuberculinpreparations
Tuberculinpreparationsarethefollowing:PPD-L(purifiedprotein
derivativenamedafterM.Linnikova),tuberculardiagnosticumerythrocyte
dryandimmune-enzymeanalysis—systemforidentifyingofantibodiesto
theMBT.
InRussia2kindsofPPD-Ltuberculinareproduced:
1.Intheformofsolution,readytouse-liquidformoftubercularaller-
genpurifiedinstandardsolutionforintradermalapplication(purified
tuberculininstandarddilution).
2.Drytubercularpurifiedallergen(drypurifiedtuberculin).
Tuberculin—liquidallergenrepresentsasolutionoftuberculinin0,85%
solutionofNaClwithphosphatebuffer,withthetwin—80asthestabilizer
andphenolasaconservator.Thepreparationisproducedinampoulesas
asolutioncontaining2TU(tuberculinunits)PPD-Lin0,1ml,colorless
transparentliquid.Itisproducedin5TU,10TUin0,1mlandothersolu-
tions.Expirydate—1year.
Purifiedtuberculininstandardsolutionisusedforperformanceofuni-
formintradermaltuberculintest(testMantoux).Theindustrialproduction
ofPPD-Lsolutionallowsusageofstandardpreparationsformasstuberculin
testing.Itisalreadydilutedandthereforeavoidserrorsoftuberculindilu-
tion.
Tubercularallergenpurifieddry(drypurifiedtuberculin)lookslikea
driedcompactmassorawhitecoloredpowder(slightlygrayishorcream),
easilysolubleintheappliedsolvent—carbolatedphysiologicalsolution.Itis
producedinampoules.Eachampoulecontains50000TU.Termofvalidity
- 29. Chapter25859Themethodsoftuberculosisdiagnostics
is5years.Drypurifiedtuberculinisusedfordiagnosisoftuberculosisand
tuberculintherapyonlyintuberculosisdispensariesandclinics.
Thespecificactivityoftuberculinpreparationsisestablishedandsuper-
visedaccordingtothenationalstandardsoftheappropriatetypesoftuber-
culin.
TheWHOandtheInternationalUnionAgainstTuberculosisandLung
DiseaserecommendusingPPD-RT23.Thisispurifiedtuberculin.
Mantouxtest
TheMantouxtestisperformedasfollows:theinnerthirdsurfaceof
theforearm’sskinisdisinfectedwith70%ethanolandisdriedbysterile
cotton.
Athinneedlepenetratestheskinintradermallyparalleltoskinsurface
withitsaperturefacingupward.Afterintroducingtheneedleintotheskin,
immediatelyinject0,1mloftuberculinsolution-onedose,containing2TU
PPD-L(seecolorfigure2-1).
AcorrectlyperformedMantouxtestwillpresenta«lemonpeel»appear-
ingwhitepapuleonskinwith7–8mmindiameter(Figure2-1).
Aqualifiednurseunderadoctor’sprescriptioncanperformthe
Mantouxtest.
Adoctororaspeciallytrainednursecanevaluatetheresultsofthe
tuberculintest.
TheestimationofMantouxreactioniscarriedoutafter72hours.Itstarts
withavisualinspectionoftheplaceoftuberculininjectiononforearm.Thus,
itispossibletoestablishabsenceofthereactionandthepresenceofhyper-
emiaorinfiltrate.Itisnecessarytodistinguishaninfiltratefromhyperemia.
Forthispurpose,inthebeginningpalpatethedepthofskinfoldofforearmin
healthyskin,then—intheplaceoftuberculinintroduction.Theskinfoldin
theinfiltrationpartthickercomparedwithhealthypart.Atthehyperemia,a
skinfoldisidenticalwithhealthypart.Afterthat,surfaceestimationmeas-
urementofreactioniscarriedoutbyatransparentrulerin(mm).
ResultoftheMantouxtestisreadafter72hours.Measuretheinfiltrate
inmmwithtransparentrulerandregisterthediameterofinfiltrate
Theresponsetoatuberculincanbe:
1)negative—absenceoftheinfiltrationandhyperemiaorotherwise
prickedreaction(0–1mm);
2)doubtful—availabilityofaninfiltrateinthesizeof2–4mmoronly
hyperemiaofanysize;
3)positive—availabilityofaninfiltrateinthesizeof5mmandmore.
Positivereactionsontuberculinaredifferentiatedaccordingtothesize
ofinfiltrateindiameter:
–weaklypositive—sizeofaninfiltrate5–9mm;
–mediumintensity—10–14mm;
–marked(prominent)—15–16mm;
–hyperergicforchildrenandadolecents—17mmandmore,foradult
21mmandmore,andalsovesicular-necroticreactionsirrespectiveofthesize
ofaninfiltratewithalymphangitisorwithoutit;
–intensifiedreactiontotuberculinisconsideredwiththeincreaseinthe
sizeoftheinfiltrateby6mmormoreincomparewithpreviousreaction.
Purposeofthetuberculintestapplication
Tuberculintestasthespecifictestisappliedinmassexaminationofthe
populationfortuberculosis(masstuberculintesting),andalsoinclinical
practicefordiagnosingthestagesoftuberculosis(individualtuberculin
testing).
Tuberculintestisappliedfor:
1.TorevealgroupsofhighTBinfectionrisk,towhichchildrenandado-
lescentsarereferred:
1.1.primaryinfectedwithMBT;
1.2.morethan1yearpastafterMBTinfectionwithhyperergicreac-
tions;
Figure2-3.Measurementinfiltrationsizeaftertuberculinintroduction