CLINICAL

CLASSIFICATION
OF TUBERCULOSIS.

PRIMARY TUBERCULOSIS
 Tuberculosis is an infectious disease
caused by bacteria (Mycobacterium
tuberculosis) characterized by the
formation of specific granulomas in
various organs and tissue (tuberculous
specific inflammation) in association
with non-specific and paraspecific
reactions, with polymorphic clinical
manifestations in addiction on the
form, stage, location and extension of
the process
 Cases of TB are classified
according to:
 anatomical site of disease
 phase of process
 history of previous treatment
 drug sensibility
 HIV status
 Pulmonary tuberculosis (PTB)
 Pulmonary tuberculosis (PTB) refers to a case
of TB (defined above) involving the lung
parenchyma
 Miliary tuberculosis is classified as pulmonary TB
because there are lesions in the lungs
 Tuberculous intrathoracic lymphadenopathy
(mediastinal and/or hilar) or tuberculous pleural
effusion, without radiographic abnormalities in
the lungs, constitutes a case of extrapulmonary
TB
 A patient with both pulmonary and
extrapulmonary TB should be classified as a case
of pulmonary TB
 Extrapulmonary TB (EPTB)
 Extrapulmonary tuberculosis (EPTB) refers to
a case of TB (defined above) involving organs
other than the lungs, e.g., pleura, lymph nodes,
abdomen, genitourinary tract, skin, joints and
bones, meninges
 EPTB cases could be either bacteriologically
confirmed or clinically diagnosed
 Identification of M. tuberculosis (as opposed to
histology) should be the basis of bacteriological
confirmation of EPTB
 The case definition of an EPTB case with several
sites affected depends on the site representing
the most severe form of disease
 Pulmonary tuberculosis
 Primary tuberculosis complex
 Disseminated pulmonary tuberculosis
 Nodulary pulmonary tuberculosis
 Infiltrative pulmonary tuberculosis
 Fibrous-cavernous pulmonary
tuberculosis
 Tracheobronchial tuberculosis
Extrapulmonary tuberculosis
 Pleural tuberculosis
 Tuberculosis of intrathoracic lymph nodes
 Other forms of upper airway tuberculosis
 Tuberculosis of central nervous system
 Skeletal tuberculosis (bone and joint)
 Intestinal tuberculosis, tuberculous
peritonitis,
 Lymph node tuberculosis
 Genitourinary tuberculosis
 Cutaneous tuberculosis
 Confirmation of the diagnosis
 direct microscopy of samples
 cultures
 histopathological examination
 clinic-radiological examination
Characteristics of tuberculous process
 Localization and extension:
 in the lungs: limited (1, 2 segments) and
extended (3 and more segments)
 in other organs
 Phase

 progressing (infiltration, destruction,

dissemination)
 regressing (desorption, consolidation)
 stationary (without roentgenological
dynamics)
 stabilization (recovery)
 Complications

 haemoptysis
 spontaneous pneumothorax
 respiratory failure
 pulmonary heart
 atelectasis
 amyloidosis
 fistula
 insufficiency of affected organs
Primary Tuberculosis
 The pathogenesis of TB
 infectious process evolves into a concrete
organism
 represents a complex interaction between
macro- and micro-organisms depending on
the a number of factors
 Virulence and pathogenity
M. tuberculosis
 Virulence is the ability of a pathogen to
penetrate, to adapt, multiply and spread into
the tissues of the host organism
 virulence may essential change under the action of
environmental factors and expressed differently
depending on the macro condition
 Pathogenicity is the ability to produce
inflammation, is a characteristic of the species
 On the basis of pathogenicity underlying genetic
structure and chemical peculiarities of M.
tuberculosis

 The degree of pathogenicity is expressed by

virulence
 The pathogenesis of TB

 In the evolution of TB - two periods with cellular

response of the macroorganism to penetration of M.
tuberculosis, strictly differentiated immunological,
clinical and morphological
 The reaction of macroorganism to a primary
exogenous infection is defined as primary
tuberculosis
 The reaction of macroorganism to an repeated
exogenous infection (superinfecţia exogenous) or
reactivation of already cured postprimary sequelae
(endogenous infection) - called secondary
tuberculosis
 The pathogenesis of TB

 Primary infection is established by

converting of the tuberculin skin
test – Tuberculin conversion
 This period with positive IDR
Mantoux 2UT is asymptomatic -
Latent primoinfection
 Primary TB
 90% of infected people remain in latent tuberculosis
infection stage, only 10% of those infected will
develop TB- disease

 TB- disease, occurring as a result of infection in

individuals previously uninfected - primary
tuberculosis
 Pathogenesis of TB

Infection - Immunity
The natural evolution of TB infection

50-70%
30-50%

90% 10%
 Overview of TB pathogenesis

90% no sequellae

Primary WHY?
infection
(tuberculin 5% primary TB
positive) (within 2 years)

GET IN 5% reactivation
(later in life)
STAY IN GET OUT
 Human tuberculosis:
Natural History

Infection Initial containment – 95%

Early Progression -
5%
 Tuberculosis: Transmission and
Natural History

Self-Cure – 90%

Infection Initial containment – 95%

Early Progression - Late Progression -

5% 5%
 Background
 Tuberculosis (TB) is increasing among
adults in many areas
 TB is major cause of childhood morbidity
and mortality worldwide
 Limited information on epidemiology of TB
in children
 Features of primary tuberculosis

 Primary tuberculosis develops after the

child's first contact with the
Mycobacterium tuberculosis
 It is mainly in children and adolescents
 With conversion of tuberculin test
 Develop delayed-type hypersensibility,
so appear hyperergical tuberculin tests
 Features of primary tuberculosis
 In most cases, tuberculosis in children is a
mild disease and may heal on its own
without treatment
 The record multidrogresistent primary
M.tuberculosis to antituberculosis drugs
 Features of primary tuberculosis
 In the pathologic process is involved lymphatic
system
 Tuberculosis in infants and children younger than
3 years old is much more likely haematogenous
dissemination of the organisms occurs and
spreads the organisms throughout the body,
leading to acute disseminated TB (milliary TB)
and tuberculosis meningitis, a very dangerous
forms of the disease
 Paraspecifical reactions
 Immune reactions of interaction and awareness
of macrophages and activated lymphocytes and
their accumulation to develop logical end
(granulomma formation) contribute to the
development of reactions in various organs,
called by A. Strucov para-specific reactions
 They have a toxico-allergic origin,
polymorphic mononuclear type
 After character of cellular reactions the first
3 types - delayed hypersensitivity reaction,
4th – immediately type and 5th - mixed
type
 Features of primary tuberculosis
 Paraspecifical reactions are
characteristic :
 erythema nodosum
 phlyctenular conjunctivitis
 poliarticular syndrome (Poncet’s
rheumatism is an “allergic” type of joint
swelling which may disappear in two to
three weeks, and does not indicate the
presence of tubercle bacilli in the joint
space)
Erythema nodosum
 Mucocutaneous manifestations

 Erythema nodosum appears in the

form of bluish red tender subcutaneous
nodules several millimeters to several
centimeters in diameter on the shins,
sometimes on the backs of the arms
and rarely on the front, in two to three
bursts
 They are painful, raised lesions that
may turn purple and take on the
appearance of a bruise
 Mucocutaneous manifestations
 Phlyctenular conjunctivitis begins with
generalized pain and irritation in one eye
accompanied by watering and photophobia
 On examination, grey or yellow lesions can be
observed where the cornea joins the white of the
eye; a number of blood vessels enter the lesions,
giving an appearance of vascular engorgement of
the conjunctiva
 Each lesion persists for about a week, and then
disappears, to be replaced by others
 In severe cases the cornea may ulcerate
Phlyctenular conjunctivitis
 Pathogenesis of TB

Infection - Immunity
 Overview of TB pathogenesis

90% no sequellae

Primary WHY?
infection
(tuberculin 5% primary TB
positive) (within 2 years)

GET IN 5% reactivation
(later in life)
STAY IN GET OUT
 Pathogenesis
 Inhalation -> phagocytosis by alveolar
macrophages
 Bacterial multiplication occurs intracellularly
 Lymphatic spread to regional lymph nodes or
hematogenous dissemination
 Immune response results in granuloma
formation (containment of infection)
 Cell death in the granuloma results in
caseous necrosis
 Bacteria can remain dormant in the
granuloma
 Pathogenesis of Tuberculosis
 Dissemination of infected
macrophages through the draining
lymphatics into the circulation
 Development within 3-8 weeks of a
CD4+ T cell dependent cell-mediated
immune response with granuloma
formation and macrophage activation
at sites of infection
 Immunity in Tuberculosis
 Antigen-specific activation of CD4+ T
lymphocytes with secretion of IL-2,
increased expression of IL-2
receptors, and secretion of IF-
 Antigen-driven clonal expansion of
CD4+ T lymphocytes by IL-2 acting
via autocrine and paracrine
mechanisms
 Activation by IF- of Mycobacterium
tuberculosis killing by macrophages
Delayed-type hypersensitivity
 HSV is the result of the interaction between
T helper 1 (TH1) lymphocytes (CD4
phenotype) with the macrophage immune
complex - MHC (Major Histocompatibility
Complex)
 As a result of this interaction one helper T
lymphocytes secrete a number of cytokines
(IFNγ, FNTα, IL 2) that leads to specific
inflammatory reaction
The human tuberculous granuloma
 Histopathological Features of TB

 Granulomas: Focal tissue aggregates of

epithelioid cells (activated macrophages),
Langhans’ giant cells, lymphocytes, and
granulation tissue (tubercles)
 Langhans’ giant cells reflect the most
successful host tissue response in
tuberculosis, absent in fulminant
tuberculosis (especially AIDS patients)
Tuberculous Granulomas
Caseation Necrosis
Epitheloid cells in Granuloma
Cells in Granuloma
The human tuberculous granuloma
Pathogenesis of infection with
Mycobacterium tuberculosis
 Clinical forms of primary TB

 Primary Tuberculosis Complex

 TBof intratoracic lymphatic

nodes
 PRIMARY TUBERCULOSIS COMPLEX

 is a form of primary tuberculosis in

children and adolescents with
morphological substrate - specific
inflammation of lung parenchyma
(primary focus), involved in the
process of lymphatic routes
(lymphangitis) and mediastinal
lymphadenopathy
Lesions associated with primary tuberculosis

 Initial infection with Mycobacterium tuberculosis

in an immunocompetent individual usually
occurs in an upper region of the lung producing
a sub-pleural lesion called a Ghon focus
 Granulomatous involvement of peribronchial
and/or hilar lymph nodes is frequent in primary
tuberculosis due to lymphangitic spread from
the Ghon focus
Lesions associated with primary tuberculosis

 The early Ghon focus together with the

lymph node lesion constitutes the Ghon
complex
 These lesions undergo healing and over
time usually evolve to fibrocalcific nodules
 The combination of late fibrocalcific lesions
of the lung and lymph node which evolved
from the Ghon complex is referred to as
the Ranke complex
 Clinical manifestations
of intoxication syndrome
 the central nervous system - general
weakness, asthenia, excitability, headaches,
sleep disturbances, feverish, night sweats
 endocrine system - the growing disorder
children, the dysfunction of the thyroid gland in
the age of puberty (hyperplasia of gr. II-III,
hyperfunction), the disorder of the ovarian
function (primary or secondary irregular of the
menstrual cycle), decreased of the function
adrenal glands (adynamy, hypotonia)
 Clinical manifestations
of intoxication syndrome
 immune system - children are frail, often
respiratory tract infection (influenza,
recurrent bronchitis and pneumonia),
reactivation of chronic infections (sinusitis,
tonsillitis, pyelonephritis etc.)
 the heart – toxico-allergic myocarditis
(tachycardia, cardiac tone I reduced,
apical systolic functional murmur)
 digestive system – diminished appetite
and progressive weight loss, subacid
gastritis
 Pulmonary syndrome

 Cough - is most frequently, usually more

marked in the morning and is commonly
productive
 Chest pain – may result from
involvement of the pleura
 Dyspnoea – due to consolidation,
cavitation, fibrosis and pleural affection
 Haemoptysis - appears in complicated
cases with primary cavity, most common
in adolescents
 Local symptoms

 Often the chest physical examination -

normal, with radiological discrepancy
 Notice any limitation of movements on
the affected part
 Dullness
 Harsh vesicular breathing and many
diffuse rales of small caliber
 Radiographic picture of a primary
tuberculosis complex
 The primary complex has four stages of
development. There are four stages of
primary complex development :
1. I stage – pneumonic
2. II stage - resorption
3. III stage - condensation
4. IV stage - calcination
 Pneumonic stage
 consists of a small area of
infiltration at any location in the
lung parenchyma, accompanied by
unilateral mediastinal
lymphadenopathy
 The infiltration forms when the
bacilli are first inhaled (as a
defence reaction around the
location at which the bacilli first
deposit); it is characteristically
small (3 to 10mm in diameter)
 This nodular shadow is sometimes
surrounded by a lighter, less
dense shadow with irregular edges
 On lateral X-ray, mediastinal
lymphadenopathy appears as a
rounded or oval latero-tracheal or
hilar shadow
Pneumonic stage
 On X-ray general view three
components of a complex are
visible:
1) the focus in lung tissue by
the size 2-4 cm. in diameter or
more, of oval or irregular form,
various intensity (more often -
average and even high), with an
indistinct, obscure contour;
 2) the flow out to a root -
lymphangitis, which is defined
as linear tension bars from focus
to the hilum;
 3) in a hilum - enlarged
infiltrated lymphatic nodes.
The hilum is represented to be
extended, it’s structure) is
blurry, the intensity is increased.
The contours outlining lymphatic
nodes, or are dim, or more
precisely depict the increased
nodes.
 Stage of resorption

 The radiological
picture is that of a
primary focus in the
lung with
accompanying
mediastinal lymph
nodes enlargement
united by an opaque
tape (lymphangitis –
the draining
lymphatics become
beaded by
tubercles, distended
and tortuous)
Stage of resorption
 The size of the focus
in lung tissue
decreases, its
intensity raises, the
contours become
precise
 The flow out to a
hilum and infiltration
of lymphatic nodes
decreases
 Stage of condensation
 On a place of focus area
remains with the size up to
1 cm, inside of it inclusions
of calcinations appear as
fine spots of sharp
intensity
 Same spots of calcinations
are noticeable and in
lymphatic nodes of the
lung hilum
 Thin tension bars are
determined between the
focus and the hilum
Stage of condensation
 Calcination-stage
 The focus in lung tissue
becomes even smaller, more
densely, of high intensity, with
distinct contour, frequently
rugged and rough
 Calcinations are intensified
also in hilum lymphatic nodes
 Calcinations in certain cases
are represented by solid,
dense formations, in others -
they have less intensive
shadows of inclusions, which
testify about incomplete
calcifications of the focus and
preservation of caseous
regions in it
 Outcome of primary TB complex
 At favorable course of primary tuberculous
complex with time calcification increases up to
ossification at the place of former caseosis
located in peripheral parts of lungs. This is
Gohn's focus
 When primary complex is revealed in time and
the patient receives valuable treatment,
frequently could be achieved complete dissolution
of pathological changes in lung tissue and in root,
with complete restoration of their initial structure
Gohn's focus

 The lesion is small and

usually cannot be detected
during its active stage;
not until calcium salts are
deposited in the healed
lesion can its presence be
detected
 In a large majority of
instances healing takes
place with fibrosis and
calcification (Gohn's focus
pointed be arrow)
 TUBERCULOSIS
OF INTRATORACIC
LYMPHATIC NODES
 Definition
 is a primary form of
extrapulmonary tuberculosis with
specific inflammation of
intratoracic lymphatic nodes, in
children and adolescents
 It affects mostly lymph nodes after
Suchenicov - Esipov scheme
(paratracheal, tracheo-bronchial,
interbronchial, bronho-pulmonary
lymph nodes) and Engel (para-aortic
lymph nodes)
 TB of intratoracic lymphatic nodes
• On chest x-ray the
shadow of the lung
hilum is extended, the
outside contour is
unclear, the structure is
heterogeneous and
intensity is increased

• S-m of enlarged hilum

TB of intratoracic lymphatic nodes
TB of intratoracic lymphatic nodes
 The diagnosis can be established
on the following considerations

 history of contact with case of

pulmonary tuberculosis
 significant reaction to the tuberculin skin
test
 absence of elevated white cell count in
the blood
 absence of clinical and/or radiological
improvement after treatment with a
broad-spectrum antibiotics
 The tuberculin skin test

 in most cases is hyperergical and

coincides with a tuberculin conversion
 Bacteriologic diagnosis
 Sputum can rarely be collected from
children
 Can try sputum induction in older children
 Bronchoalveolar lavage is invasive,
expensive and should be reserved for
situations where the diagnosis is in question

 Gastric aspirates
• people swallow mucus in their sleep
• collect gastric contents before the stomach empties
 Local complications of primary tuberculosis

 Fistulation of the lymph node into the

bronchi: the lymph node swells and
erodes into the bronchus (usually between
the 4th and 7th month of development)
 This can be a serious event for small
infants, where the caseous material can
create acute bronchial obstruction; in
older children it usually causes cough
 Local complications of primary tuberculosis

 The formation of a primary

tuberculous cavity at the site of
infiltration is a more unusual complication
 Delayed local complications
 Bronchiectasis may develop in the
poorly ventilated area of the lung,
creating bronchial superinfections and
repeated episodes of haemoptysis.
 The most characteristic feature of this
type of sequelae is “hilar disease” or
“right middle lobe syndrome”:
 Atelectasis
 hilar calcification
 recurrent haemoptysis.
Atelectasis
 Differential diagnosis

 sarcoidosis,
st. I
 lymphogranulomatosis
 lymphosarcoma
 leukemia
 adenopathy nonspecific
 Infants may have acquired TB
• by trans placental spread through the
umbilical vein to the fetal liver
• by aspiration or ingestion of infected
amniotic fluid
• via airborne inoculation from close
contacts (family members or nursery
personnel)
• About 50% of children born to mothers
with active pulmonary TB develop the
disease during first year of life if
chemoprophylaxis or BCG vaccine is
not given
 Neonatal TB

 The clinical presentation nonspecific

 Multiple organ involvement
 Usually fever, lethargy, respiratory
distress, hepatosplenomegaly, or failure to
thrive may indicate TB in an infant with a
history of TB exposure
 For diagnosis: culture and smear of
tracheal aspirates, urine, gastric washings
for acid-fast bacilli, chest x-ray (milliary
infiltrates)
 Biopsy of the liver, lymph nodes, or lung
and pleura may be needed
 Skin test results may be negative
Cerebrospinal fluid analysis in TB meningitis

 CSF is clear or opalescent, pressure is elevated

 CSF pleocytosis with lymphocytic
predominance: presence of more than 50 white cells/mm³
on microscopic examination of the CSF, with more
lymphocytes than polymorphonuclear cells
 Decreased CSF glucose: value of CSF glucose 50% or
less than simultaneous serum glucose determination.
 Increased CSF protein: value of CSF protein more than
the upper limit of normal of the performing laboratory's
reference values, i.e. > 0.45 mg/dl.
 Abnormal CSF: presence of all 3 of the above CSF findings
(CSF pleocytosis with lymphocytic predominance +
decreased CSF glucose + increased CSF protein.
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