1. Tuberculosis is caused by the bacterium Mycobacterium tuberculosis and mainly affects the lungs. It is observed that 10 million active TB cases occur globally each year, with India reporting approximately 2.3 million cases. 2. Tuberculosis is transmitted when people inhale droplets from the coughs or sneezes of people with active pulmonary or laryngeal TB. It can also occur through ingesting milk from cows with bovine tuberculosis. 3. Granulomatous inflammation is the body's protective response to chronic infections or foreign material like tuberculosis bacteria. It forms structures called granulomas that wall off the pathogen to prevent spread while also destroying tissue over time.

1. Nem Kumar Jain
MS (Pharm.) Pharmacology & Toxicology
Assistant Professor
School of Pharmacy
ITM University Gwalior
Pathophysiology of Tuberculosis
(TB)

2.  Observed on 24 March each year, is designed to
build public awareness about the
global epidemic of tuberculosis (TB) and efforts to
eliminate the disease.
 24th March memorialize the day in 1882, when Dr.
Robert Koch declared that he had discovered the
causative factor of Tuberculosis- Mycobacterium
Tuberculosis
 In 1995 WHO start recognizing World Tuberculosis DAY and

3. Granulomatous inflammation
 Granulomatous inflammation is a distinctive pattern of chronic
inflammatory reaction.
 The formation of Granuloma is a protective defense reaction by
the host to chronic infection or foreign material, preventing
dissemination and restricting inflammation but eventually causes
tissue destruction because of persistence of the poorly digestible
antigen
 Causative Factors: Infectious or non-infectious
 Ex. Tuberculosis and Syphilis etc

4. s
Introduction
 TB is caused by
bacteria,belonging to the
genus Mycobacterium.
 It mainly affects the lungs, but
it can affect any part of the
body, including the abdomen,
glands, bones and nervous
system.
 As per WHO reports(2018),
approx. 10 million active TB
cases globally
 India: 2.3 million cases
 Other common names
included “wasting disease”
and the “white plague”.
Sign and Symptoms
 Cough for more than 3 weeks
 Weight loss/anorexia
 Malaise
 Fatigue
 Low grade Fever
 Night sweats
 Hemoptysis (blood stained
mucus)
 Chest pain

5.  These form a large group but only three
relatives (Mycobacterium tuberculosis
complex) are obligate parasites that can
cause TB disease.
 Mycobacterium: aerobic atypical slender,
rod shaped bacteria
 M. tuberculosis complex: M.
tuberculosis, M. bovis, M. africanum
 They have been found in soil, milk and
water (atypical mycobacteria)
 Mycobacterium leprae: The cause of
leprosy.
 Other strains which causes TB are
 M. Avium Complex (MAC): M.
avium & M. intracellulare
 M. bovis, M. hominis
• Less common strains which causes TB
are
 M. africanum
 M. microti
 M. pinnipeddi
 M. cannetti
• Less pathogenic strains are
 M. abscessus
 M. fortuitum
 M. chelonae
 M. ulcerans
• Non pathogenic strains are M.
smegmatis
• M.tuberculi also called as Koch’s bacilli
or Acid Fast bacilli
Etiology

6.  Based on anatomical side:
 Pulmunary TB (lungs)
 Milliary (Spleen, kidney, liver,
brain etc)
 Based on presence of
signs and symptom:
 Active TB (only shows signs
and symptoms).
 Latent TB (Signs and
symptoms absent, Dormant)
 Based on type of tissue
response
 Primary TB: First time,
Childhood TB, Ghon’s
complex
No Immunization or infection
 Secondary TB: Re-infection
 Characteristics of
Mycobacterium sp. which
makes resultant disease
Chronic and necessitates
prolong treatment
 Slow growing
 Intracellular infection
 Formation of slow growing
granuloma results in
destruction of host tissue
 Biology of Mycobacterium:
distinct populations
 Rapidly growing with high
bacillary load
 Slow growing
 Spurters
 Dormant
Types and some facts of Tuberculosis

7. MODE OF TRANSMISSION.
 Human beings acquire infection with tubercle bacilli by
one of the following routes:
 Inhalation of organisms present in fresh cough droplets
or in dried sputum from an open case of pulmonary
tuberculosis.
 Ingestion sputum of an open case of pulmonary
tuberculosis, or ingestion of bovine tubercle bacilli from milk
of diseased cows.
 Inoculation of the organisms into the skin may rarely
occur from infected postmortem tissue.
 Transplacental route results in development of congenital
tuberculosis in foetus from infected mother and is a rare
mode of transmission.

8. TYPES OF TUBERCULOSIS
 Lung is the main organ affected in tuberculosis.
 Depending upon the type of tissue response and
age, the infection with
 tubercle bacilli is of 2 main types:
 Primary tuberculosis
 Secondary tuberculosis

9. PRIMARY TUBERCULOSIS
 The infection of an individual who has not been
previously infected or immunised is called
primary tuberculosis or Ghon’s complex or
childhood tuberculosis.
 The most commonly involved tissues for primary
complex are lungs and lymph nodes.
 Other tissues are tonsils and cervical lymph
nodes, lesions may be found in small intestine
and mesenteric lymph nodes.
 Progressive primary tuberculosis is particularly
high in immunocompromised host e.g. in patients
of AIDS. in

10. SECONDARY TUBERCULOSIS
 The infection of an individual who has been
previously infected or sensitised is called
secondary, or post-primary or reinfection, or
chronic tuberculosis.
 The infection may be endogenous source such
as reactivation of dormant primary complex.
 exogenous source such as fresh dose of
reinfection by the tubercle bacilli.
 Secondary tuberculosis occurs most commonly in
lungs in the region of apex. Other sites and
tissues which can be involved are tonsils,
pharynx, larynx, small intestine and skin.

11. EXTRA PULMONARY / miliary
TUBERCULOSIS
 RESPIRATORY TUBERCULOSIS
 PERIPHERAL LYMPH NODES TUBERCULOSIS
 BONE TUBERCULOSIS
 JOINTS TUBERCULOSIS
 PERICARDIAL TUBERCULOSIS

12. HIV-ASSOCIATED
TUBERCULOSIS
 Moreover, HIV-infected individual on acquiring
infection with tubercle bacilli develops active
disease rapidly (within few weeks) rather than
after months or years.
 Extra-pulmonary tuberculosis is more common in
HIV disease and manifests commonly by
involving lymph nodes, pleura, pericardium, and
tuberculous meningitis.
 Infection with M. avium- intracellulare (avia or bird
strain) is common in patients with HIV/AIDS.

13. Pathogenesis: Evolution of tubercle

14.  When ever the Mycobacterium tuberculi enters body.
As it is strictly aerobic it resides in alveoli of lungs.
 After about 12 hours, there is progressive infiltration
by macrophages (C2a C2b) as opsonins
 The macrophages start phagocytosing the tubercle
bacilli and either kill the bacteria or die away
themselves.
 In the latter case, they further proliferate locally as
well as there is
 increased recruitment of macrophages from blood
monocytes.

15. As a part of body’s immune response, T and B cells
are activated.
Activated CD4+T cells develop the cell-mediated
delayed type hypersensitivity reaction, while B
cells result in formation of antibodies which play
no role in body’s defence against tubercle bacilli.
In 2-3 days, the macrophages undergo structural
changes as a result of immune mechanisms to
epithelioid cells.

16.  The epithelioid cells in time aggregate into tight
clusters or granulomas. Release of cytokines in
response to sensitized CD4+T cells and some
constituents of mycobacterial cell wall play a role
in formation of granuloma.
 Some of the macrophages form multinucleated
giant cells by fusion of adjacent cells. The giant
cells may be Langhans’ type having peripherally
arranged nuclei in the form of horseshoe or ring

17.  Around the mass of epithelioid cells and giant
cells is a zone of lymphocytes, plasma cells and
fibroblasts.
 The lesion at this stage is called hard tubercle
due to absence of central necrosis.
 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 tuberculous lesions.

18.  The development of caseation necrosis is possibly
due to interaction of mycobacteria with activated T
cells (CD4+ helper T cells via IFN-γ and CD8+
suppressor T cells directly)
 Microscopically, caseation necrosis is structure
less, eosinophilic and granular material with
nuclear debris.
 The soft tubercle which is a fully-developed
granuloma with caseous centre does not favour rapid
proliferation of tubercle bacilli.
 Acid-fast bacilli are difficult to find in these lesions and
may be demonstrated at the margins of recent
necrotic foci and in the walls of the cavities.

19. Fate of granuloma
 The caseous material may undergo liquefaction,
extend , discharge.: Trsnsmission through sputum
 In tuberculosis of tissues like bones, joints, lymph
nodes and epididymis, sinuses are formed and the
sinus tracts are lined by tuberculous granulation
tissue: Miliary Tuberculosis
 May coalesce together enlarging the lesion which is
surrounded by progressive fibrosis.
 In the granuloma enclosed by fibrous tissue, calcium
salts may get deposited in the caseous material
(dystrophic calcification) and sometimes the lesion
may even get ossified over the years.