Pulmonary

Tuberculosis
Cheng Zhang ， Respiratory
Medicine ， Affiliated Hospital of
Jining Medicine college
23,Feb
 Tuberculosis(TB), a chronic bacterial
infection(infectious) causes more deaths
worldwide than any other infectious disease.TB is
spread through the air and usually infects the
lung(other organs are sometimes involved.some 2
billion people-one-third of the worlds population—
are infected with the TB organism, Mycobacterium
tuberculosis.
 Epidemiology
 Global
 Worldwide ， tuberculosis is second only to HIV in
causes of death by infectious disease among adults
 Many developng countries are suffering dual
epidemics of TB and HIV
 1/3 （ 2 billion ） have been infected
 5% of infacted develop active disease during the the
first years following exposure.
 Eight million new cases each year and three
million deaths
 TB aptly bears the name“The Captain of all
these Men of Death”
 Epidemiology
 CHINA
 a. High infection rate(nearly half)
 b. High mobility rate
 c. High resistance rate(primary 18.6%,acquired
46.5%)
 d. A big death population(130 thousans cases died per
year)
 e. More younger and middle-age population
 f. A big different mobility in different areas
 g. A low mobility
 Mycobacteria belong to the family
Mycobacteriaceae and the order
Actinomycetales.The pathogenic species
are the M. tuberculosis complex,the most
frequent and important agent of human
disease is M. tuberculosis,the others are
M.bovis,M.africanum, and M. microti
 Etiology
the bionomics of mycobacterium tuberculosis
(tubercle bacillus)

1. polymorphism
2. acid résistance
3. Grow slowly: 14~20h
4. Resistance: dry 、 cold 、 acid 、 base
5. constitution complicated ：
adipoid 、 protein 、
polycose
 M. tuberculosis is a rod-shaped ,non-spore-
forming,thin aerobic bacterium measuring
0.5 μm by 3 μm.
 Fast-acid stain can not decolorized with acid
alcohol.
 INTERPERSONAL SPREAD OF TUBERCULOSIS

 SOURCE OF INFECTION
 The patient is the major source of
infection.Tubercle bacilli are expelled into
the air through respiratory secretion of
patients with pulmonary tuberculosis.
 Transmitting Routes
 M.tuberculosis is transmitted by airborne
from person to person via the respiratory
route.Inhalation of droplet nuclei contaning
tubercle bacillus may cause
infection.Transmitting by other ways such as
digestive or skin is rare currently
 Susceptible Population
 The factors that affect susceptibility to
pulmonary tuberculosis include natural
resistance and acquired specific resistance
 The former:heritance ,poor life overcrowded
living accommodations,malnutritious
status,infants,old ages HIV
infection,persons who take immunological
suppressors are susceptible to tuberculosis.
 Influential Factors
 Number of organisms in the expectorated
sputum
 extent of pulmonary disease,

 frequency of cough,

 duration of exposure,

 Density of infected droplet nuclei,

 adequate air ventilation,

 Individural immunity status

 About one-third of the worlds population is
infected with tuberculosis.However,most do
not show signs of disease,bacteria are
inactive (latent ) and can not transmitted to
others.about 10 percent of people with the
inactive form of the disease eventually will
develop active tuberculosis.
 PROGRESSION AND DEVELOPMENT
 PRIMARY INFECTION
 In about 5 percent of people,the immune system can’t
stop the initial tuberculosis infection
 These people develop active tuberculosis within one
year of exposure to the bacteria
 This type of active tuberculosis is most common in
infants and chidren
 PROGRESSION AND DEVELOPMENT
 Primary pulmonary tuberculosis results from an
initial infection with tubercle bacilli
 Infection ,primary infection presented as an
infiltration lesion,follows if the inoculum escapes
alveolar macrophage microbicidal activity,with the
spreading of tubercle bacilli along intrapulmonary
lymphatic ducts to hilar lymph node,the lymph nodes
enlarged
 PROGRESSION AND DEVELOPMENT
 The lesion of primary infiltration,enlargement of
tracheobronchial lymph node is called primary
syndrome or primary tuberculosis
 Cell-mediated specific immunity plays a role in human
body when invasive initially
 Primary infection represent the most common
processes:(1) primary infection rapidly
absorbed;(2)enlarged lymph nodes gradually
smaller;(3)tubercle bacilli spreading to other organs
killed
 PROGRESSION AND DEVELOPMENT
 IMMUNITY AND DELAYED-TYPE
HYPERSENSITIVITY

 Koch phenomenon:
Infection and reinfection: two experiment
The first experiment:
Inoculation some Bacillus tuberculosis Have no obvious
at first

reaction 10~14 days later local flare

ulcer ， disunion Bacillus tuberculosis multiplicity

regional nodes to follow lymph node and blood circulation

intumesce Spreading all over the body

cavia cobaya died (none immunity ）

 The second experiment:

Inoculation the same dose Bacillus

tuberculosis to the cavia cobaya (which Have some different
have been inoculated 4-6weeks ago) reaction

Occurrence high fever ， 2-3days regional nodes have

later ， local site: red swelling 、 none intumesce
ulcer 、 necrosis

do not Spreading all over the body Koch phenomenon

 Secondary Tuberculosis
 Tubercle bacilli have the capacity to remain
dormant,but viable,for long periods in health
subjects.Where primary infection has
healed spontaneously,a proportion of
patients will continue to harbor (hide)
organisms capable of causing disease in
the future.
 Such reactivation to cause secondary
(postprimary) tuberculosis may occur in any
organ,but it is most common in the lung.
 Reactivation is more likely ito occur in
patients with chronic disease causing
general debility,such as
alcoholism,malnutrition and diabetes
mellitus,or with cellular imunodeficiency
 Secondary TB results from endogenous
recrudescence and exogenous reinfection.
 ~presents obvious clinical symptoms,
cavities and bacilli expelled ,and are
infectious.A bad prognosis without
treatment occurs in positive bacilli,which
showa a half death rate will appear in 5
years
 Pthology
 Basic pathological fingdings
 Inflammtory exdative response
 Proliferative response
 Caseous necrosis
 The lesions sometimes change from one type to
another or are a composite of several.which
depens on tuberculin sensitivity of the host and on
the number of tubercle bacilli.
A exudative mainly present local infiltration
of neutrophils,and subsequently
transformed to macrophages and
lymphocytes.
 B proliferation shows typically tubercle

 ~ occurred with strong resistance and

recover stage
C caseous necrosis is described as
caseous because it resembles cheese
,being rather homogeneous, yellow-white
,and rich in lips.~appear in the condition of
presence of strong toxic tuberculous bacilli
in a large number and of hypersensitivity
with weak resistance
（二） turnover

1 absorption
2 fibrosis
3 calcification
4 aggrevation
 Clinical manifestation

Symptom:
1. general symptom(nonspecific,insidious)
low-grade fever 、 debilitation 、 night-
sweat 、 anorexia 、 emaciation(weight loss),general
malaise,fatigue,headache

2.respiratory system symptom

cough 、 expectoration
Hemoptysis(mild,masssive)
chest pain
dyspnea(extensive disease)
 Sign:
quality and circumscription

Inspection: respiratory movement attenuated

Palpitation :increased fremitus(consolidation)

percussion : dullness

Auscultation: breath sound degrade

Allergic manifestation:erythema nodosum

rhochi,moist rales,effusion
 Assistant examinations
 Bacteriological examinations(gold standard)
 It also helps make regimen and check
efficacy of chemotherapy
 Collection of specimens
 Freshlyexpectorated sputum
 Three consecutive morning sputum
specimen
 Sputum induction

 Others(pleural effusion,bronchial
brushings/biopsy/BAL
 Direct examination

 Confirmation of tubercle bacilli

 Demonstration of acid-fast bacilli on smear
can illustrate the presence of anti-acid bacilli
but can not identify M. tuberculosis and
saprophytic nontuberculous mycobacteria
 Culture and susceptibility test
 Confirmationof M.TB
 Determination of susceptibility
 Imaging
 Diagnosis and evaluation
 Favour location:upper lobe (apical ,posterio
segements),lower lobe (superior segement)
 Natures:small homogenous infiltrates,multinodular
infiltration,cavity,satellite nodular lesions,fibrotic
scarring
 more-foci,more-morphology,more-calcification
 Fewer-mass,fewer-cumulation,fewer-intensification
 CT scan offer the evidence of fine or latent
lesions,and detect the infected area and
other confused disorders
PPD （ purified protein derivative ）：
　 0.1ml(5IU) ih left forearm

48~72h measure induration (transverse diameter+ length

wise diameter)/ ２

negative ≦ 4mm
weakly positive 5~9mm
positive 10~19mm
powerful positive≧20mm or <20mm blister and
angiolymphitis
 The tuberculin skin test identifies individuals
who have been infected with M.tuberculosis
but does not distinguish between M
tuberculous infection and tuberculosis.
 Both false-positive and false-negative
tuberculin reactions occur
Types of pulmonary tuberculosis
 A. primary pulmonary tuberculosis(primary
syndrome,intrathoracic lymphatic
tuberculosis)
 B hematogenous pulmonary
tuberculosis(acute,subcute,chronic)
 C postprimary or secondary pulmonary
tuberculosis (infiltrative, chronic fibro-
cavitative and caseous pneumonitis)
D tuberculous pleuritis(dry,exudative
andtuberculous empyema)
 E other extrapulmonary(genitourinary tract,
bones,and joints, meninges,
peritoneum,and pericardium)
 diagnosis
 Diagnostic methods
 exposing history
 clinical manifestations
 imagiological presentations
 bacteriologic findings
 pathological results
 tuberculin skin test and other methods
 Differential diagnosis
1 pneumonia
 2 bronchogenic carcinoma

 3 lung abcess

 4 bronchiectasis
 chemotherapy
 Principle:early,regular,full-
termed,adequate,and combined therapy
 enhance cure rate,lessen recurrent rate
,provide safer ,avoid resistance
 Biological mechanisms of
chenmotherapy
 Differences in mycobacteria metabolic rate
are associated with differences in
susceptibility to anti tuberculosis. only
actively replicating organism are killed by
chenmotherapy.
 Group A living extracellularly, metabolically
very active, rapidly, continuously growing in
a hyperoxic and neutral-pH environment.
susceptible to SM,INH,EMB
 Group B living extracellularly metabolically
less or intermittently active in a hyoxic and
neutral-pH environment. susceptible to
RFP,INH
 Group C living in the acid ,hypoxic
environment of macrophages
,slow,intermittent growth.PZA and RPF are
uniquely effective against these organisms
and INH is less effective.
 Group completely dormant unaffected by
both antimicrobial and cellular immune
mechanisms.
 Antituberculous drugs
A isoniazid(INH)
 Intra and extra cellular bacilli

 INH should be used in all regimens except

when a high proportion of INH-resiastant
organisms are present
 Intravenouslly,intramuscular
nasogastric,oral
 Side effects (toxic manifestations)
 Peripheral neuritis(reversible,treated with
pyridoxine
 toxic hepatitis(including allergic )
 If enzymelevels rise above three times normal
values
 Monthly monitoring of liver enzyme is
recommended.
 Rifampin (RFP)
 Bactericidal against intra-extra cellular

 Dose not pass the blood-brain barrier under

normal conditions
 Distributing well (urine, tears, sweat,and
other body fluids,coloring them to red-
orange
 Major side effects
 gastrointestinal upset
 heptic toxicity
 Appearance pg jaundice is the signal og
cessation of RFP,rifapentin is also available
 INH and RFP together produce heptotoxicity
more frequently than either drug alone
 C pyrazinamide (PZA)
 Nictinic acid derivative similar to isonazid,no
cross-resistance with INH
 Effective against slowly metabolically intracellular
bacilli, important one of short-course regimen
 Adverse reaction heptotoxicity ,hyperurecemia,
rare side effects skin rash,gastrointestinal
intolerance
 D ethambutol (EMB)
 Bacteriostatic agent(limited to M.TB)
 Active against both intra and extra cellular bacilli
 Main toxicity: optic neuritis
 Children are forbidden to administer EMB because
of disbility to identify the visual symptom
 E streptomycin (SM)
 Effective only against extracellular bacterial
 First major antituberculous drug released
 SM must be administered parenterally ,because it
is not absorbed from gut( usually intramuscular)
 Major toxicity irreversible eighth nerve damage
leading to vestibular dysfunction and ,less
frequently ,nephrotoxic
Dosage of common antituberculous
drugs
 Isoniazid daily dosage(g/d) intermittent
 (INH) 0.3 q.d 0.6-0.8 ,2-3/w
 Rifapin 0.4 -0.6 q.d 0.6-0.8 ,2-3/w
 RFP
 Pyrazinamide 1.5-2.0 tid/qid 2.0-3.0,2-3/w
 PZA
 Ethambutol 0.75-1.0 q.d 1.5-2.0,2-3/W
 EMB
 Streptomycin 0.75-1.0 q.d im 0.75-1.02-3/w
 SM