TUBERCULOSIS

Dr G.O OGUN
Dept of pathology
College of Medicine
University of Ibadan
 Introduction
 Estimated to affect 1.7 billion people
world wide- about a third of the
world’s population
 8-10 million cases each year
 1.7 million deaths each year
 2nd leading infectious cause of death
after HIV
 Infection with HIV makes people
susceptible to rapidly progressive
tuberculosis
The disaster called T.B
 Introduction -2
 Tuberculosis thrives where there is poverty
and ignorance completes the cycle.
 Diseases that increase the risk for TB are
3. Diabetes mellitus
4. Hodgkin's lymphoma
5. Chronic lung disease like – Silicosis
6. Chronic renal failure
7. Malnutrition
8. Alcoholism
9. Immunosuppresion
 Microbiology of TB
 Itis caused by M. tuberculosis which
belong to the genus Mycobacterium
 They are slender aerobic rods that
grow in straight or branching chains.
 Mycobacterium have a waxy cell wall
composed of mycolic acid which
makes them acid fast
 This implies they retain the red
colour of carbol fushin even after
treatment with acid alcohol during
ZN staining
 Pathogenesis
 Is Based on the immune status and
immune response of an individual who
inhales the organism

 Non – Immune – Previously unexposed

individual- PRIMARY T.B (Source of
organism is always exogenous)

 Immune- previously exposed -

SECONDARY T.B
 TB Pathogenesis
 The effector cells that mediate
immunity also mediate
hypersensitivity and tissue
destruction
 Therefore the state of
hypersensitivity also signals
acquisition of immunity to the
organism
 TB Pathogenesis
 Macrophages are the primary cells
infected by M.tuberculosis
 Enters macrophages by
endocytosis
3. Mannose receptor bind
lipoarabinomannan(LAM) on the
organism
4. Complement receptor (CR) bind
opsonised mycobacteria
 TB pathogenesis
 Inside the pulmonary alveolar
Macrophage/ air spaces
2. It replicates within the phagosome
formed by blocking fusion with the
lysosome.
3. It blocks calcium signal and block
protein assemblage involved in
phagolysosome formation.
4. Prevent acidic pH in the phagosome
5. Maturation arrest of the phagosome
 TB Pathogenesis
 Other factors come into play in the
proliferation of the mycobacterium in the
macrophage
 NRAMP 1 gene polymorphism
 Complement activated on the surface of
M.tuberculosis opsonise the organism
and facilitate its uptake by CR3 without
triggering respiratory burst necessary to
kill the organism
 EQUENCE OF EVENTS IN PRIMARY PULMONAR
SEQUENCE
TUBERCULOSIS
IL12 IFN -ç iNOS TNF,Chemo
APC  To Th1  Ac Mac Monocyte
TBag
Presentation
TCR HS  recruitment
Class II MHC NO 
Free radicals Granuloma
 formation
Bactericidal HS
(Immunity)

HS- Hypersensitivity
TCR- T-cell receptor
TBag- M.Tuberculosis antigen
Tuberculous Granuloma
 Primary TB
 In a non immunized individual – typically
children
 Lesion typically in subpleural zones of lung
–(distal airspace in the lower part of upper
lobe or upper part of lower lobe )- can be
at other sites
 Brief acute inflammation – neutrophils.
 Within 3 weeks of infection, granuloma
formation occurs
 Ghon focus- a 1-1.5cm area of
consolidation and hilar lymph node 
Ghon complex
 Develop immunity – Mantoux positive
 Ghon’s Complex

 Primary
tuberculosis is the
pattern seen with
initial infection with
tuberculosis in
children.
 Primary Tuberculosis
In Non Immunized individuals
(Children)
 Primary Tuberculosis:
Self
Limited disease
Ghons focus, Ghon complex or Primary
complex.
 Primary Progressive TB
MiliaryTB and TB Meningitis.
Common in malnourished children
10% of adults, Immuno-suppressed
individuals
 PRIMARY TB AND OUTCOME

 Primary complex can become

3. Healed (organism dead)
4. Latent lesion( organism dormant-
pulmonary and extrapulmonary)
5. Progressive Primary T.B
 Secondary Tuberculosis:
 Post Primary in immunized
individuals.
 Cavitary Granulomatous response.
 Reactivation or Reinfection
 Apical lobes or upper part of lower
lobes – O2
 Caseation, cavity formation
 Pulmonary or extra-pulmonary
 Local or systemic spread / Miliary
Vein – via left ventricle to whole body
Artery – miliary spread within the lung
 SECONDARY TB
 Results from
2. Reactivation of latent lesions of primary
TB especially when host resistance is
weak. Commoner in low-prevalence
areas.
3. Reinfection – due to waning of protection
offer by the primary disease or from a
large innoculum. Especially in areas of
high prevalence
 MORPHOLOGY
 LYMPHADENITIS- Is the most frequent form
of extra-pulmonary TB
 In HIV- negative patients,
lymphadenopathy tends to be unifocal and
patients do not usually have features of
ongoing extranodal disease
 In HIV- positive patients, there is multifocal
disease, systemic symptoms and either
pulmonary and other organ involvement
by active tuberculosis
 Cervical lymph node with a discharging
sinus- Scrofula
 MORPHOLOGY
 Progressive Primary TB- occur in the
elderly and immunosupressed.
 Apical lesion expands
 Erosion into a bronchus evacuates
caseous material creating an
irregular ragged cavity poorly walled
off by fibrous tissue.
 Erosion into blood vessel leads to
haemoptysis.
 Treatment call halt this leading to
healing by fibrosis.
 Progressive Primary TB
 If treatment is inadequate or host
defence is impaired, then infection
can spread by direct expansion by
2. Airways
3. Lymphatics
4. Vascular system
Lung TB - Cavitation
Typical cavitating granuloma
 Pulmonary
Miliary TB
 Microscopic or Small
(2mm) foci of
yellowish- white
consolidation through
out the whole lug
parenchyma.
 Thru lymphatics into
lymphatic ducts to
right side of the heart
blood or bronchial
spread
 Low immunity
 Pulmonary or
Systemic types.
Miliary TB
 SYSTEMIC MILIARY TB
 Occurs when infective foci in the
lungs seed or rupture into one of the
branches of the pulmonary venous
return to the heart.
 Organism subsequently disseminate
via systemic arterial circulation
 Typically affects- liver, bone marrow,
spleen, adrenals, meninges, kidneys,
fallopian tubes and epidydymis
 Cavitary Tuberculosis
 When necrotic
tissue is coughed
up  cavity.
 Cavitation is typical
for large
granulomas.
 Cavitation is more
common in the
secondary
reactivation
tuberculosis -
upper lobes.
Cavitary Secondary TB
 Complication of Post primary
TB/cavitations in the lungs
 Haemorrhage
 Possibility
of Aspergillus infection of a
pulmonary cavity in healed tuberculosis
forming aspergilloma.
 Pneumothorax
 Bronchietasis
 Progressive pulmonary fibrosis
 Lung destruction
 Systemic amyloidosis possible
 PLEURA
 Progressive pulmonary Tuberculosis
typically can cause involvement of
the pleura as
2. Serous pleura effusions
3. Tuberculous empyema
4. Obliterative fibrous pleuritis
 UPPER AIRWAY TB
 Endobronchial, Endotracheal and
laryngeal TB
 Typically develops when infective
material is spread through the
lymphatic channels or from
expectorated infectious material
Tuberculous Granuloma
Epitheloid cells in Granuloma
Systemic Miliary TB
Adrenal TB - Addison Disease
TB Epididymitis / Orchitis.
TB Peritonitis + liver Miliary TB
TB Brain – Caudate n.
TB Intestine
Prostate TB
Spinal TB - Potts Disease
 MORPHOLOGY - Contd
 Tuberculous meningitis and Tuberculomas-
In TB meningitis the pus gravitate mainly
basally. (basal meningitis) .Other causes of
basal meningitis are fungal aetiology and
H.infuenza. The tuberculomas are mainly
found in the temporal lobe.

 Tuberculous pericarditis – Either by direct

spread from the lung or by
haematogenous route. Calcification and
fibrosis typically leads to profound
features of right heart failure

 Liver-
can present with deranged liver
enzymes
 Morphology - contd
 Bones – osteomyelitis, TB arthritis- Knee
and hip joint are the most commonly
affected joints.
 Ovary, Fallopian tubes and endometrium-
TB of Female genital tract typically start
from the fallopian tubes. The organism
arriving there by the blood stream.
 TB epididymitis is most frequent site in the
male genital tract. Tb orchitis is rare
 Intestine – typically occur in children. The
children are usually malnourished. Ulcers
formed are typically transverse ulcers in
the terminal ileum but most are irregular
in shape.
 Tuberculous peritonitis can occur either
 Morphology- Contd
 Potts disease- typically involve children and T9-
T11 thoracic vertebrae are most frequently
involved. Cervical spine involvement is more
common than Lumbar involvement.
 In Potts disease there is destruction of the
vertebra body resulting in collapse causing
formation of Gibbus or Kyphosis, causing pain and
local tenderness.
 Paraspinal cold abscesses in patients with potts
disease may track along tissue planes to present
as an abdominal mass or pelvic mass.
 Paraplegia complicate potts disease which is
spastic . The pathogenesis of the paraplegia is a
combination of spinal angulation, paravetebra
abscess compression and more importantly,
tuberculous vasculitis of the spinal blood vessels
resulting in infarcts and necrosis of the spinal
cord
 Diagnosis of TB
 Clinical and radiographic features are not
confirmatory.
 Fine needle aspiration of lymph nodes
 ZN Stain - 1x104/ml, 60% sensitivity
 Auramine - Rhodamine by florescence
 3 negative smears to assure low infectivity*
 Culture most sensitive, specific and the Gold
standard
 Conventional Lowenstein Jensen media up to
10 wks
 Liquid media culture 2weeks

 Animal innoculation- 9 band armadillo

 PCR is available
Caseation Necrosis
AFB - Ziehl-Nielson stain
Colony Morphology – LJ Slant
 Granuloma or LH giant cell is not pathognomonic
of TB…!
 Foreign body
granuloma.
 Fat necrosis.
 Fungal infections.
 Sarcoidosis.
 Crohns disease.
 What is New…?
 14-30% of TB patients also HIV
infected.
 New drugs - Rifapentine, Interferons,
Thalidomide.
 Immune therapy : Killed M. vaccine
stimulates CD8 cells (increased INF
and IL-12).
 The genome of TB has been
identified (~4000 genes) potential
to develop new vaccines and tests.