TUBERCULOSIS OF THE LUNG AND EXTRAPULOMARY .ppt

Primary and Secondary Tuberculosis

1. TUBERCULOSIS
Chronic infectious disease causing
granulomatous inflammation
Causative organism is the Tubercle bacilli called
Mycobacterium tuberculosis
Typically infects the lungs, but except hair and
nails, all the other organs of the body can be
infected

2. Mycobacterium tuberculosis
Slender Rod like bacilli, discovered in 1882
Strict aerobe
Thrives well in tissues rich in O2
5 pathogenic strains
(M.hominis, M.bovis, M.avium, M.murine & cold
blooded vertebrate strain)
Non-pathogenic 6
th
strain – M.smegmatis is
non-infective to humans

3. Methods to demonstrate
M. hominis
Acid-fast staining by Ziehl-Neelsen stain
Waxy cell wall does not allow normal stains but allows heated carbol
fuschin. Thus the organism is stained pink to red in color. Once
stained, it does not give up the color even on addition of acid and
alcohols (hence called acid fast bacilli - AFB). Methylene blue acts
as a counterstain to demonstrate the background and cells.
Fluorescent dye methods
Culture in L-J medium for 6 weeks / Bactest
Guinea pig inoculation
 PCR / RT-PCR
FISH technique

4. Atypical mycobacteria
These are usually non-pathogenic to humans and
are resistant to the usual ATT.
They infect humans when the immunity is lowered
as in AIDS
There are 4 groups
Group 1: Photochromogens(yellow pigments in light)
Group 2: Scotochromogens (pigments in light or
dark)
Group 3: Non-chromogens ( no pigments)
Group 4: Rapid growers ( fast growth but less virile)

5. Atypical mycobacteria
M.kansasii & M.avium-intracellulare –
Pulmonary disease
M.avium intracellulare & M.scrofulaceum
– Lymphadenitis
M.ulcerans & M.marinum – Skin lesions
M.fortuitum & M.chelonei – Abscess
M.avium intracellulare in AIDS -
Bacteremia

6. Modes of transmission of TB
1. Inhalation of cough droplets or from
dried sputum from an open case.
2. Ingestion by self swallowing of sputum
or consumption of cows milk.
3. Inoculation by accidental prick into the
skin
4. Trans-placental from mother to fetus

7. Modes of spread of TB
Local spread by macrophages
Lymphatic spread
Hematogenous spread – Miliary TB
By natural passages
eg: Lung to pleura
Intestinal to Peritoneal cavity
Heart to Pericardial cavity

8. Immune response in TB
Tuberculosis is a killer disease BUT…..
Is the tubercle bacilli really responsible for the changes it
brings about in the body???
What toxins are produced by the bacilli to bring about
tissue destruction leading to death???

9. Immune response in TB
The answer is NOTHING…..
TB bacilli do not produce any toxins…..
So, Who is the culprit then????

10. Our IMMUNE SYSTEM is the culprit
Our defence mechanism launches cell
mediated hypersensitivity against the lipids
present on the cell wall of the tubercle
bacilli which is responsible for tissue
destruction.

11. There are 2 basic lipids on the tubercle
bacilli cell wall
–Mycosides – cord factor
–Glycolipids – Wax D

12. The Tuberculin skin test
Aka Mantoux test
O.1ml of tuberculoprotein injected INTRADERMALLY
Delayed type hypersensitivity occurs in individuals who
are infected or previously infected with the bacilli.
Positive reaction is occurrence of indurated area > 15mm
at the site of injection after
72 hrs.
Test does not distinguish between infection and disease

13. Vaccination against TB
Injection
Attenuated strains of bovine type of TB bacilli
called Bacille Calmette-Guerin (BCG)
The vaccinated person develops cell mediated
delayed hypersensitivity.
This person will show positive reaction to
Mantoux test.

14. Evolution of the Tubercle
Entry of the bacilli by inhalation or ingestion
Initial defence response is by neutrophils which is
unsuccessful.
After 12hrs, macrophages move in with progressive
infiltration (they smell the C3b & C2a opsonins which
coat the bacilli)
Phagocytosis of the TB bacilli occurs – sometimes the
organisms die; other times the macrophages die
Now the T and B lymphocytes are activated.
CD4+ T cells are responsible for the delayed
hypersensitivity reaction.
B lymphocytes produce antibodies that are useless
against TB bacilli.

15. Evolution of the Tubercle
After 2-3 days, the macrophages undergo structural changes –
cytoplasm becomes pale and the nuclei becomes elongated and
vesicular. These modified macrophages are called EPITHELIOID
CELLS
Some epithelioid cells aggregate and fuse together to form a
multinucleated giant cell – LANGHANS GIANT CELL
 The combination of epithelioid cells, Langhans giant cells,
peripheral lymphocytes and plasma cells into a nodular formation
is called a GRANULOMA. This is called a HARD TUBERCLE.
After 10-14 days, the central part of the granuloma undergoes
CASEOUS NECROSIS. This is called a SOFT TUBERCLE.

16. Evolution of the Tubercle

17. Fate of a Granuloma
Cold abscess formation – caseous necrosis
undergoes liquefaction and discharges its
contents on the surface
Sinus tract formation
Coalition of adjacent granulomas
Dystrophic Calcification

18. Types of Tuberculosis
Primary TB – infection of an individual
who is exposed to the bacilli for the first
time.
Secondary TB – Infection of an individual
who has been previously infected or
sensitised. Aka post-primary, reinfection or
chronic TB

19. Primary Tuberculosis
Aka Primary complex, Ghons complex or childhood TB
It is the lesion produced at the site of entry + draining lymphatics + draining
lymph nodes
Most common involvement is the
Focus in the lung (1-2cm granuloma)
+ Hilar lymphatics
+ Hilar lymph nodes.
Fate of Primary TB :
1.Healing by fibrosis
2.Calcification / Ossification
3.Progressive primary TB – other areas of the same lung or other lung
4.Miliary TB - Bacilli enters into circulation by eroding blood vessels and is
carried to organs like kidney, liver, spleen brain etc
5.Healed lesions can get reactivated when immunity gets lowered – progressive
secondary TB

25. Secondary Pulmonary TB
Begins as an area of consolidation in the apical
segments of the lung
Very common in patients with lowered
immunity like AIDS
Fate :
1. Healing with scarring and calcification
2. Coalition
3. Fibrocaseous tuberculosis
4. Tuberculous caseous pneumonia
5. Miliary TB

34. LEPROSY
Aka Hansen’s disease discovered 1874
Affects mainly cooler parts of the body
such as skin, mouth, R.S, peripheral
nerves, lymph nodes and testis
Causative organism – Mycobacterium
leprae.

35. Methods of Demonstration
Organisms are arranged in globi or
cigarettes in pack arrangement
Ziehl-Neelsen stain – less acid fast
Fite-Faracco stain
Gomori Methenamine silver (GMS)
Bacterial Index (BI) 1+ to 6+ 1-10 bacilli
per 100 fields to > 1000 per 100 fields

36. Modes of transmission
Leprosy is a slow communciable disease
Incubation period – 2 to 20 years
Direct contact of secretions from damaged
skin, nasal secretions, mucous membranes
Materno-fetal transmission
Breast feeding to infant

37. Ridley & Joplings Classification
There are 2 main types - POLAR TYPES
–Lepromatous leprosy ( low resistance)
–Tuberculoid leprosy ( high resistance)

38. Reactions in Leprosy
Lepra reactions are of 2 types
–Type 1 (borderline reactions)
Occurs in patients who are on the borderline
Maybe upgrading reaction or downgrading
reaction
–Type 2 (erythema nodosum leprosum)
Occurs is patients after treatment. Patients
develop tender cutaneous nodules, fever,
iridocyclitis, synovitis, etc.

39. Clinical features
Lepromatous Leprosy – Symmetrical,
multiple, hypopigmented macules, papules
or nodules. Affected area is hypoaesthetic
or anesthetic
Tuberculoid leprosy – Asymmetrical, one
or few, hypopigmented lesion with
DISTINCT SENSORY IMPAIRMENT .

40. Histopathology - Lepromatous
Leprosy
The dermis shows a proliferation of
macrophages containing bacteria – foam
cells or lepra cells or Virchow cells. There
is a clear zone between the involved dermis
and the epidermis
Epidermis over the lesion is thinned out or
ulcerates

41. Lepromatous leprosy

42. Histopathology - Tuberculoid
leprosy
The dermis shows a granuloma resembling
hard tubercles composed of epithelioid
cells, Langhans giant cells, peripheral
lymphocytes.
Granulomas affect dermal nerves causing
sensory impairment
No clear zone seen between the epidermis
and dermis
Few bacilli are seen

43. Tuberculoid Leprosy

44. Lepromin test
It is not a diagnostic test
It is done for classifying leprosy patients
It will be positive only in patients with good
immunity – ie, Tuberculoid Leprosy
Early response 24-48 hrs to intradermal
injection of Lepromin is called Fernandez
reaction
Delayed response 1 month is called Mitsuda
reaction

46. SYPHILIS
It is a sexually transmitted disease
Causative organism – Treponema pallidum,
a spirochaete.
It is a coiled spiral filament 10 microns
long, motile in fresh preparations
Demonstrated by Dark ground illumination,
silver stains and fluorescent stains.

47. Immunology
The organism does not produce any toxins
The lesions are produced by host reaction
Antibodies produced against the organisms
are
–Wassermann antibodies – VDRL test
–Treponemal antibodies – against treponemal
protein

48. Mode of transmission
Sexual intercourse
Intimate person to person contact
Blood transfusion
Materno-fetal transmission

49. Stages of Syphilis
Primary Syphilis
Secondary syphilis
Tertiary syphilis

50. Primary syphilis
Typical lesion is called CHANCRE
Appears on the genitals or extragenital site
in 2- 4 weeks following exposure
Painless papule, which ulcerates in the
center, with regional lymph node
enlargement
Heals completely even without treatment
Micros – dense infiltrate of lymphocytes,
plasma cells and a few macrophages

51. Secondary syphilis
Inadequately treated patients develop muco-
cutaneous lesions and painless
lymphadenopathy in 2-3 months
Mouth, vagina, pharynx are involved
Ano-genital region may show condyloma
lata

52. Tertiary syphilis
Appears after 2-3 years
Syphilitic gumma – solitary, localised,
rubbery lesion with central necrosis affects
organs like liver, testis, brain, bone
Diffuse lesions – affects CVS causing AI,
aneurysm. Neurosyphilis producing tabes
dorsalis, meningo-vascular syphilis.

53. Congenital syphilis
Affects fetus > 16 weeks
Child may be born dead
Child may be born alive with manifestation
– saddle nose deformity
Child may manifest disease later –
Hutchinson’s teeth

54. Histopathology of Syphilis

55. ACTINOMYCOSIS
It is a chronic suppurative disease caused by
anaerobic bacteria, Actinomycetes israeli.
The organisms are commensals in the oral
cavity, alimentary tract and the vagina.
The infection occurs when there is a
decreased immunity or some underlying
disease.

56. Histopathology of Actinomycosis

57. Types of Actinomyosis
There are 4 types
–Cervico-facial
–Thorasic
–Abdominal
–Pelvic

58. Morphology of Actinomycosis

59. Pathological changes
Cervico-facial :
Commonest form, best prognosis
Infection from tonsils, carious teeth, peri-odontal
disease or trauma following tooth extraction.
Initially a firm swelling develops in the lower jaw
“lumpy jaw”.In time the mass breaks down and
abscesses and sinuses are formed. The discharging pus
contains yellow sulphur granules. The infection spreads
to the soft tissue and bone.

60. Pathological changes
Thoracic :
Infection in the lungs
Occurs due to aspiration of the organism from oral
cavity or extension from abdominal or hepatic lesions.
Initially there is patchy pneumonia like picture but the
lesion extends into the whole lung, pleura, ribs and
vertebrae.

61. Pathological changes
Abdominal :
Common in appendix, caecum, liver
Occurs due to swallowing of organisms or extension
from thorasic cavity
Pelvic :
Occurs as a complication of IUCD device

62. SARCOIDOSIS
It is a systemic disease
Etiology unknown
20 to 40 yrs affected
Characterised by non-caseating granulomas
affecting mostly the lymph nodes and lungs

63. Histopathology