Pathophysiology

1. PULMONARY TUBERCULOSIS
DR. NSOBYA GEORGE
PATHOLOGY SHO II

2. Learning Objectives:
1.Know Etiology of tuberculosis
2. Know Pathogenesis of
tuberculosis
3. to know the events of Primary
and Secondary infection
(tuberculosis)
4. Morphology of tuberculosis

3. Pulmonary tuberculosis
• Pulmonary tuberculosis (TB) is a chronic granulomatous infection of the lung caused by
Mycobacterium tuberculosis
• Most common cause of death resulting from a single infectious agent(WHO)
• 1.7billion infections worldwide; 10.4million new cases/year; 1.7million deaths; M: 6.3million
F:3.2million(WHO 2017)
• Tuberculosis flourishes under poverty, crowding and chronic debilitating illness
• Infection with HIV makes people susceptible to rapidly progressive tuberculosis; 13% of the people
who developed tuberculosis in 2011 were HIV-positive.
• In developed world, its mainly a disease of older adults, immigrants from high-burden countries,
racial and ethnic minorities, and people with AIDS.

4. Pulmonary Tuberculosis
The introduction of antibiotics in the 1950s, the
United States and other Western countries enjoyed
a long decline in the number of infections until the
mid-1980s. Since that time, the rate of infection has
increased, particularly among people with the
human immunodeficiency
virus (HIV).
Tuberculosis affects the lungs more often than any
other organ.

5. Pulmonary Tuberculosis
Mycobacterium tuberculosis.
are slender, rod shaped, aerobic bacteria that do not form spores and thrive
in an oxygen rich environment. This explains their tendency to cause disease
in the upper lobe or upper parts of the lower lobe of the lung, where
ventilation is greatest.
They are similar to other bacterial organisms except for an outer waxy
capsule that makes them more resistant to destruction.
The waxy coat also causes the organism to retain red dye when treated with
acid in acid fast staining.
The mycobacteria are often referred to as acid-fast bacilli. Although M.
tuberculosis can infect practically any organ of the body, the lungs are most
frequently involved.

6. TUBERCULOSIS MYCOBACTERIUM.
ZIEHL NEELSEN STAIN

7. Is an airborne infection spread by minute, invisible
particles, called droplet nuclei, that are harbored in the
respiratory secretions of persons with active tuberculosis.
Coughing, sneezing, and talking all create respiratory
droplets; these droplets evaporate, leaving the organisms
(droplet nuclei),which remain suspended in the air and
are circulated by air currents. Living in crowded and
confined conditions increases the risk for spread of the
disease.
milk contaminated with M. bovis is rare in countries
where milk is routinely pasteurized, but it is still seen in
countries that have tuberculous dairy cows and
unpasteurized milk.
Pulmonary Tuberculosis

8. The tubercle bacillus incites a distinctive chronic
inflame response referred to as granulomatous
inflammation.
Cell-mediated immunity and hypersensitivity
reactions contribute to the evolution of the disease.
Tuberculosis can manifest as a primary or reactivated
infection.

9. 9
Risk factors
• Contact with smear +/ potential individuals
• Poverty: poor socio-economic status
• Alcoholism & smoking
• Immuno compromised individuals ( HIV/AIDS & immune supressive
therapy)
• Malnutrition
• Other risk factors are diabetes mellitus, Hodgkin lymphoma,
chronic lung disease (particularly silicosis), chronic renal failure,

10. 10
Modes of transmission
• Inhalation of the mycobacterium in aerosol & dust
• Ingestion of unpasteurised milk

11. Pathogenesis
• The destructive effects of infection are entirely due to the hypersensitivity reaction of the host
directed against bacterial cell-wall constituents.
• The following sequence of events occurs:
1. 0–10 days—mycobacteria excite a transient but marked acute inflammatory response. Neutrophils
phagocytose the organisms but are unable to destroy them, as the cell walls are resistant to
degradation. Instead, engulfed bacteria are drained into local lymph nodes

12. 2. After 10 days—development of a T-cell-mediated immune response (type IV hypersensitivity
reaction) to the bacillary cell-wall constituents results in cytokine release and macrophage activation.
Gradually a chronic inflammatory pattern develops, which is dominated by aggregates of macrophages
called epithelioid cells, which form variable numbers of granulomas with a central core of necrotic
caseous tissue containing viable mycobacteria.
Tuberculous granulomas are termed tubercles.
Macroscopically, the granulomas appear as pinhead sized white or greyish foci (tubercles) in the tissues.

13. • Microscopically, granulomas are the histological hallmark of TB infection.
• A granuloma consists of a central area of amorphous caseous necrosis, surrounded by
three cellular layers:
1. An inner layer of activated macrophages (epithelioid cells) with Langhans’ giant cells
2. A middle layer of lymphocytes
3. An outer layer of fibroblastic tissue, which merges with surrounding structures and increases with
the age of the lesion

14. CLINICAL FEATURES
• Two important pathophysiologic types:
1. Primary tuberculosis, which occurs in the nonimmune host.
2. Secondary tuberculosis, which occurs in the host who is immune
to M. tuberculosis.

15. 15
• Systemic symptoms include
a. Malaise
b. Anorexia
c. Weight loss
d. Fever ( low grade & remittent)
e. Night sweats
f.  amount of sputum
g. Hemoptysis
h. Pleuritic pains
• Extrapulmonary manifestations depend on organ
system involved.

16. Occurs in a person lacking previous contact with the
tubercle bacillus.
It typically is initiated as a result of inhaling droplet
nuclei that contain the tubercle bacillus
Inhaled droplet nuclei pass down the bronchial tree
without settling on the epithelium and implant in a
respiratory bronchiole or alveolus beyond the mucociliary
system. Soon after entering the lung, the bacilli are
surrounded and engulfed
by macrophages.

17. The tubercle bacillus grows slowly, dividing
every 25 to 32 hours in the macrophage.
As the bacilli multiply, the macrophages
degrade some mycobacteria and present
antigen to the T lymphocytes for development
of a cell-mediated immune response.
The organisms grow for 2 to 12 weeks until
they reach sufficient numbers to elicit a
cellular immune response

18. In persons with intact cell-mediated immunity,
this action is followed by the development of a
single, gray-white, circumscribed granulomatous
lesion, called a Ghon’s focus, that contains the
tubercle bacilli, modified macrophages, and other
immune cells.

19. Within 2 to 3 weeks, the central portion of the
Ghon’s focus undergoes soft, caseous (cheeselike) necrosis.
This occurs at approximately the time that the tuberculin test
result becomes positive, suggesting that the necrosis is caused
by the cell-mediated hypersensitivity immune response.
During this same period, tubercle bacilli, free or
inside macrophages, drain along the lymph channels to the
tracheobronchial lymph nodes of the affected lung and there
evoke the formation of caseous granulomas.
The combination of the primary lung lesion and lymph
node granulomas is called Ghon’s complex

20. When the number of organisms inhaled is small and
the body’s resistance is adequate, scar tissue forms
and encapsulates the primary lesion. In time, most of
these lesions become calcified and are visible on a
chest radiograph. *ranke complex*
Primary tuberculosis usually is asymptomatic, with the
only evidence of the disease being a positive tuberculin
skin test result and calcified lesions seen on the chest
radiograph.

21. Occasionally, primary tuberculosis may progress,
causing more extensive destruction of lung tissue and
spreading through the airways and lymphatics to
multiple sites within the lung.
As the disease spreads, the organism gains access to
the sputum, allowing the person to infect others.
In rare instances, tuberculosis may erode into
a blood vessel, giving rise to hematogenic
dissemination. Miliary tuberculosis

23. TUBERCULOUS GRANOLOMA

24. EPITHELIOD CELLS
FIBROBLASTS
GIANT CELL TYPE
LANGHANS
LYMPHOCYT
ES
TUBERCULOUS GRANULOMA

26. Secondary tuberculosis represents either
reinfection from inhaled droplet nuclei
or
reactivation of a previously healed primary
lesion.

27. The re-infection lesion results from proliferation of Mycobacterium
tuberculosis in the wall of a bronchiole or alveolus.
Tubercle follicles develop and the lesion enlarges by formation of
new tubercles at the margin and in the adjacent lung tissue, they
have many caseous material.
The progress of the lesion is slow, the tubercles are well developed
and there is formation of fibrous tissues at the periphery.
The lesion may become encapsulated by fibrous tissues or the
caseous material may be gradually discharged along the bronchus,
leaving a small cavity.

28. In secondary tuberculosis, the hypersensitivity reaction
can be an aggravating factor, as evidenced by the
frequency of cavitation and bronchial dissemination.
The cavities may coalesce to a size as large as 10 to 15
cm in diameter.
Pleural effusion and tuberculous empyema are common
as the disease progresses.

29. The common sites are the posterior or apical segment of the
upper lobe and the superior segment of the lower lobe.
It often occurs in situations of impaired body defense
mechanisms. The partial immunity that follows primary
tuberculosis affords protection against reinfection and to
some extent aids in localizing the disease should
reactivation occur.

30. Clinical manifestation: low-grade fevers, night sweats,
easy fatigability, anorexia,
and weight loss.
A cough initially is dry but later becomes productive
with purulent and sometimes blood-tinged sputum.
Dyspnea and orthopnea develop as the disease
advances.

31.  The initial lesion is usually a small focus of consolidation, less
than 2cm in diameter, within 1 to 2cm of the apical pleura.
 Are sharply circumscribed, firm and gray-white to yellow in
color with variable degrees of central caseation and
peripheral fibrosis.
 In immunocompetent individuals, the initial parenchymal
focus undergoes progressive fibrous encapsulation, leaving
only fibrocalcifc scars.
 Histologically, the active lesions show characteristic
coalescent tubercles with central caseation.

32.  AAF bacilli can often be identified with acid-fast stains in
early exudative and caseous phases of granuloma formation
but are usually too few to be found in the late, fibrocalcifc
stages.
 Localized, apical, secondary pulmonary tuberculosis may heal
with fibrosis either spontaneously or after therapy, or the
disease may progress and extend along several different
pathways.

33.  Seen in older adults and immunosuppressed people.
 The apical lesion expands into adjacent lung and eventually
erodes into bronchi and vessels. This evacuates the caseous
center, a cavity.
 Erosion of blood vessels results in hemoptysis.
 The cavities, now free of inflammation, may persist or
become fibrotic.
 If the host defenses are impaired, the infection may spread
via airways, lymphatic channels, or the vascular system
causing miliary TB.

34.  AAF bacilli can often be identified with acid-fast stains in
early exudative and caseous phases of granuloma formation
but are usually too few to be found in the late, fibrocalcifc
stages.
 Localized, apical, secondary pulmonary tuberculosis may heal
with fibrosis either spontaneously or after therapy, or the
disease may progress and extend along several different
pathways.

35.  Miliary pulmonary disease occurs when organisms draining
through lymphatics enter the venous blood and circulate
back to the lung.
 Individual lesions are either microscopic or small, visible (2-
mm) foci of yellow-white consolidation scattered through
the lung parenchyma.
 Miliary lesions may expand and coalesce, resulting in
consolidation of large regions or even whole lobes of the
lung.
 With progressive PTB, the pleural cavity is invariably
involved, and serous pleural effusions, tuberculous
empyema, or obliterative fibrous pleuritis may develop.

36.  Progressive PTB that occurs in ISS individuals spreads in a
similar manner.
 Endobronchial, endotracheal, and laryngeal tuberculosis
may develop by spread through lymphatic channels or from
expectorated infectious material.
 The mucosal lining may be studded with minute
granulomatous lesions that may only be apparent
microscopically.

37.  Systemic miliary tuberculosis occurs when bacteria
disseminate through the systemic arterial system.
 Miliary TB is most prominent in the liver, bone marrow,
spleen, adrenals, meninges, kidneys, fallopian tubes, and
epididymis, but could involve any organ.
 Isolated tuberculosis may appear in any of the organs or
tissues seeded hematogenously and may be the presenting
manifestation.
 Commonly involves the meninges (tuberculous meningitis),
kidneys (renal tuberculosis), adrenals (important cause of
Addison disease), bones (osteomyelitis), and fallopian tubes
(salpingitis)

38.  Pott disease is when vertebrae are affected.
 Paraspinal “cold” abscesses in these patients may track along
tissue planes and present as an abdominal or pelvic mass.
 Lymphadenitis is the most frequent presentation of XPTB,
usually occurring in the cervical region (“scrofula”).
 In HIV-negative individuals, lymphadenitis tends to be
unifocal and localized.
 HIV-positive people, on the other hand, almost always have
multifocal disease, systemic symptoms, and either
pulmonary or other organ involvement by active
tuberculosis.

39.  Intestinal tuberculosis due to drinking of milk contaminated
by bovine TB or swallowing of coughed-up infective material
in patients with advanced pulmonary disease.
 Organisms are seeded to mucosal lymphoid aggregates of the
small and large bowel, which then undergo granulomatous
inflammation that can lead to ulceration of the overlying
mucosa, particularly in the ileum.
 Healing creates strictures.

40. Occurs when a large number of mycobacteria gain
entrance to the bloodstream.
The lesions are usually more numerous in the lung
than in any other organ.
They consist of grey tubercles which may be too
small to be visible by the naked eye or up to 3 mm in
diameter.

43. 1. Bones
2. Kidneys
3. Lymphonodes (in tuberculous lymphadenopathy,
the nodes may discharge into the skin, forming a
tuberculous sinus (‘scrofula’)
4. Pericardium
5. Small Intestine (the inflammation involves the
Peyer’s patches) The ulceration is typically
circumferential

44. The primary drugs used in the treatment of tuberculosis are:
Isoniazid (INH), Rifampin, Pyrazinamide, Ethambutol, and
Streptomycin.
Two groups meet the criteria established for the
use of anti mycobacterial therapy for tuberculosis:
(1) persons with an active form of the disease
(2) those who have had contact with cases of active
tuberculosis and who are at risk for development of active
tuberculosis.