Chronic

inflammation
 Definition:
It is prolonged process in which tissue
destruction and inflammation occur at
the same time.
or
Inflammation of prolonged duration
(weeks to months to years), in which
active inflammation, tissue injury and
healing occur at the same time.
 Systemic effects of chronic
inflammation SIGNS &
•Fever: SYMPTOMS
•Anaemia:
•Leucocytosis
•ESR: is elevated
•Amyloidosis:
 Types of chronic inflammation
1.Chronic Non-specific – when the
irritant substance produces a non
specific inflammatory reaction with
formation of granulation tissue and
healing by fibrosis.
Eg. Chronic osteomyelitis, chronic ulcer.
2. CHRONIC GRANULOMATOUS
INFLAMMATION
It is characterized by formation of
granulomas.
Eg: tuberculosis, leprosy, syphilis,
actinomycois, sarcoidoisis etc.
Granuloma:
Circumscribed tiny lesion, about 1
mm in diameter, composed
predominantly of collection of
modified macrophages called
epitheloid cells, and rimmed at
the periphery by lymphoid cells.
 Pathogenesis of granuloma formation
1. Engulfment of macrophage :
Macrophage and monocytes engulf
the antigen to be destroyed. Since it
is poorly digestible, macrophage
undergoes morphological change to
epitheloid cell
2.Cd4+ T cell: As macrophages
fail to deal with antigen,
lymphocytes get activated and
elaborates lymphokines (IL -1,IL-
2, interferon –y, TNF-a)
 3.Cytokines:
Various cytokines are formed by activated CD4+ T
cells and macrophages .
These cytokines plays the following role in
formation of granuloma:
a.IL-1 and IL-2 stimulate proliferation of more
T cells
b. Interferon-y activates macrophage
c.TNF-ἁ promotes fibroblast
proliferation which leads to
secretion of prostaglandins which
has role in vascular response of
inflammation.
d. Growth factor : Activated
macrophages stimulate fibroblast
growth
• Thus a granuloma is formed of
macrophages modified as epithelioid
cells in center,
• (with some interspersed multinucleate
giant cells),
• surrounded peripherally by
lymphocytes(mainly T cells), and healing
by fibroblast or collagen depending
upon the age of granuloma.
• Flow chart.mechanism of evolution of
granuloma
 Composition of granuloma
1. Epitheliod cells: modified
macrophages.
2. Multinucleate giant cells—
( horseshoe or ring, Langhans or
foreign body)
3. Lymphoid cells
4. Necrosis: eg: cheese-like in tb
5. Fibrosis : periphery of granuloma.
Chronic granulomatous inflammation:
It is characterised by formation of
granulomas.
Eg:
1. Tuberculosis
2. leprosy
3. Syphilis
4. actinomycosis
5. sarcoidosis
1.Tuberculosis
 CAUSATIVE ORGANISM
Tubercle bacillus or Koch’s bacillus
(named after Robert Koch )
Mycobacterium tuberculosis causes
tuberculosis in the lungs and other
tissues of the human body.
TUBERCLE BACILLI
• Out of various pathogenic strains
for human disease included in
Mycobacterium tuberculosis
complex, currently most common
is
• M. tuberculosis hominis (human
strain)
• M. tuberculosis bovis (bovine
strain) used to be common
pathogen to human beings during
the era of consumption of
unpasteurised milk but presently
constitutes a small number of
human cases.
 METHODS OF DEMONSTRATION
1. Acid fast (Ziehl-Neelsen) staining.
The acid fastness of the tubercle bacilli is
due to mycolic acids, cross-linked fatty
acids and other lipids in the cell wall of
the organism making it impermeable to
the usual stains.
• It takes up stain by heated carbol fuschin .
2. Fluorescent dye methods.
3. AFB sputum smear (for 3 consecutive
days)
4. Culture of the organism from sputum
in Lowenstein- Jensen (L.J.) medium.
6. Guinea pig inoculation method by
subcutaneous injection of the organisms.

7. Molecular methods such as nuclear acid

amplification (eg.PCR) are the most recent
methods.
8.FNAC Fine needle aspiration cytology-to
diagnose & confirm TB from enlarged lymph
nodes
FACTORS CONTRIBUTING
(ETIOLOGY)
• Malnutrition
• Inadequate medical care
• Poverty
• Crowding
• Chronic uncontrolled diabetes
• Alcoholism
• Immunocompromised states like AIDS.
• Low socio-economic status
 PRIMARY SITES TO BE AFFECTED IN TB
• Lung
• Cervical lymph nodes
• Pharynx
• Bronchi
• Intestine
• Regional lymph nodes
• Larynx
• Tonsils
• Trachea
• skin
 SECONDARY SITES
LIVER
KIDNEY
SPLEEN
BONE MARROW
 MODE OF TRANSMISSION

1. Inhalation of organisms
present in fresh cough
droplets or in dried sputum
from an open case of
pulmonary tuberculosis.
2. Ingestion of the organisms leads to
development of tonsillar or intestinal
tuberculosis.
This mode of infection of human tubercle
bacilli is from self-swallowing of infected
sputum of an open case of pulmonary
tuberculosis, or ingestion of bovine
tubercle bacilli from milk of diseased cows.
3. Inoculation of the organisms into the
skin may rarely occur from infected
postmortem tissue.
4. Transplacental route results in
development of congenital tuberculosis
in foetus from infected mother and is a
rare mode of transmission
 Spread of tuberculosis
1. Local spread: macrophages carry
the bacilli into the surrounding
tissues.
2. lymphatic spread: the bacilli may
pass into various lymphoid
follicles.
3. haematogenous spread: this produces
millet seed-sized lesions in different
organs.
4. By natural passages:
 lung lesion into pleura
 transbronchial spread into adjacent lung
segments
Depending upon the type of tissue
response:
 PRIMARY TUBERCULOSIS
 SECONDARY TUBERCULOSIS
 MILIARY TUBERCULOSIS
 PRIMARY TUBERCULOSIS
DEFINITION:
The infection of an individual who has
not been previously infected or immunized
is called primary tuberculosis.

SYNONYMS: GHON’S COMPLEX

CHILDHOOD TUBERCULOSIS
Ghon’s complex consists
of 3 components:
• Pulmonary component
• Lymphatic vessel
component
• Lymph node
component
Pulmonary component:
• Lesion in the lung is the called
the Primary focus or Ghon’s focus.
• Microscopically : the lesion
consist of Tuberculous
granulomas with caseation
necrosis.
• Lymphatic vessel component:
the lung lesion, contain
phagocytes containing bacilli,
may develop miliary tubercles
Lymph node component:
this contains enlarged lymph nodes and they
show caseation necrosis
Microscopically: caseation, tuberculous
granulomas and fibrosis.
 FATE OF PRIMARY TB
1. Healing by fibrosis , calcification
& even ossification
2. Disseminated of caseous
material through bronchi to other
parts of the same lung or to the
opposite lung. This is called
progressive primary TB.
FATE OF PRIMARY TUBERCULOSIS:
3. Bacilli may enter the circulation
through erosion in the blood vessel and
spread to various tissues and organs-
primary miliary TB.
4. In lowered resistance and
increased hypersensitivity of
the host, the healed lesions of
primary TB may get
reactivated-to form progressive
secondary TB.
 SECONDARY TUBERCULOSIS:
DEFINITION:
The infection of an individual who has
previously infected or sensitized is called
secondary tuberculosis
SYNONYMS: Post primary/ Re infection/
Chronic tuberculosis.
SOURCES OF INFECTION
Secondary pulmonary tb:
Secondary tb occurs most commonly in
lungs in the region of apex.
It occurs by haematogenous spread of
infection from primary complex to the
apex of the affected lung.
Microscopically : the appearance is
typical of tb granulomas with caseation
necrosis.
FATE OF SECONDARY TUBERCULOSIS:
1. Healing with fibrous scarring (In older
people) and calcification (Young
people)
2. Coalesce to form larger area of
progressive secondary pulmonary
tuberculosis with pulmonary and
extrapulmonary involvements:
 Fibrocaseous tuberculosis
 Tuberculous caseous
pneumonia
 Miliary tuberculosis
 FIBROCASEOUS TUBERCULOSIS
Definition:
• The original area of tuberculous
pneumonia undergoes massive
central caseation necrosis
 TYPES:
–Cavitary/open fibrocaseous
tuberculosis
–Non cavitary/ chronic
fibrocaseous tuberculosis
Cavitary or open fibrocaseous TB:
It either breaks into a bronchus
from a cavity
Non cavitary lesion:
remains as a soft caseous lesion
without drainage into a bronchus
or bronchiole (chronic fibro
caseous TB)
• The cavity favours TB bacilli
proliferation due to high oxygen
tension. The cavity communicates
with bronchial tree and becomes
the source for spread of infection
(open TB)
 Grossly
Cavity is sperical with thick fibrous wall,
lined by yellowish,caseous,necrotic
material.
Around the cavity it is foci of
consolidation.
• Microscopically
The wall of cavity shows eosinophilic,
granular, caseous material.
The outer wall of cavity shows fibrosis
along with TB granuloma formation
composed of epitheliod cells langhans
gaint cells and periphery composed of
lymphocytes and central caseous
necrosis
 TUBERCULOUS CASEOUS PNEUMONIA

DEFINITION:
secondary tuberculosis in an
individual with high degree of
hypersensitivity may spread to rest
of lung producing caseous
pneumonia.
 Microscopically

 The lesions show exudative reaction .

 They are oedema ,fibrin ,polymorphs &
monocytes
 Numerous tubercle bacilli can be
demonstrated in the exudates.
 MILIARY TUBERCULOSIS
DEFINITION:
This is lymphohematogenous spread
of tuberculous infection.
The miliary lesions are millet seed-sized
(1mm diameter), yellowish, firm areas
without grossly visible caseation necrosis.
The spread is either by entry into pulmonary
vein or pulmonary artery.
The organs affected are: liver, spleen, kidney,
brain, and bone marrow.
 microscopically
 The lesions show the structure of
tubercles with minute area of
caseation necrosis
Diagnosis of TB:
1. Positive Mantoux skin test.
2. positive sputum for AFB(on smear
or culture)
3. complete haemogram
4. Chest x-ray
5. fine needle aspiration cytology
 Pathogenesis of tb/ evolution of
tubercle
• Tb bacilli do not as such produce any
toxins.
• Tissue changes seen in tb are due to
result of host response to the
organism namely delayed type of
hypersensitivity and immunity.
The events that take place when tb
bacilli are introduced into the
tissue are:
1. When the tb bacilli are lodged in
pulmonary capillaries an initial
response of neutrophils is evoked
which are rapidly destroyed by
the organism
2. After 12 hours there is progressive
infiltration of macrophages.
3. Macrophages start phagocytosing the tb
bacilli and either kill the bacterial or die
away themselves.
4. As a part of body’s immune response, T
and B cells are activated. Cytokines
determine the host response by
infiltrating macrophage-monocytes and
develop the cell-mediated delayed type
hypersensitivity reaction.
5.In 2-3days the macrophages undergo
structural changes as a result of
immune mechanisms called
epitheliod cells.
6. These epitheliod cells aggregate into
tight clusters or granulomas.(cytokines
by CD4+T CELL)
7. Some of the macrophages, unable
to destroy tb bacilli, fuse together
and form multinucleated giant cells.
8. Around the cluster of epitheloid cells a few
giant cells, a zone of lymphocytes and plasma
cells is formed which is further surrounded by
fibroblasts. The lesion at this stage is called
hard tubercle due absence of central necrosis.
9. Within 10-14 days, the centre of the cellular
mass begins to undergo caseation necrosis,
characterised by cheesy appearance and high
lipid content. This stage is called soft tubercle
which is the hallmark of tb lesions.
Figure 5.21