11 chronic n granulomatous INFLAMMATION.new - Copy.ppt

This is the PDF of pathology...iflmmatiom..it which there are diseqses too

1. Dr.Kamini Patel
Dept of pathology
GMERS medical college
valsad

2. Acute inflammation
Chronic inflammation
RepairResolution
Abscess
Injury

3. It is the inflammation of prolonged duration
(weeks or months).
In which tissue distruction and inflammation
occur at the same time.
It is occurred :
Following acute inflammation
incidentally as active inflammation.

4. 1.Viral infection
2.Persistent infections by certain
microorganisms, e.g. tubercle bacilli,
Treponemapallidum, fungi, and parasites.
3.Prolonged exposure to potentially toxic
agents, either exogenous or endogenous
e.g. of exogenous agent is particulate silica, when inhaled
for prolonged periods, results in silicosis
e.g. of endogenous agent is atherosclerosis (a chronic
inflammatory process of the arterial wall induced by
endogenous toxic plasma lipid components)
4.Autoimmunity:immune reactions develop
against the individual's own tissues
In these diseases, autoantigensevoke immune
reaction that results in chronic tissue damage and
inflammation e.g. rheumatoid arthritis and lupus
erythematosus

5. 1.Infiltration with mononuclear cells include
Macrophages
Lymphocytes
Plasma cells
2.Tissue destruction
induced by the persistent offending agent or by
the inflammatory cells.
3.Healing
by connective tissue replacement of damaged
tissue, accomplished by proliferation of small
blood vessels (angiogenesis) and, in particular,
fibrosis

6. MONONUCLEAR CELL INFILTRATION
Macrophages
The dominant cellular player in chronic inflammation
Component of mononuclear phagocyte system
(sometimes called reticuloendothelialsystem)
Originating from bone marrow.

7. mononuclear phagocyte system

8. Blood monocyte Tissue macrophage (RES)
migrate into tissue
within 48 hours
after injury
and
differentiate

9. The roles of activated macrophages in chronic inflammation.
Acute
&
Chronic inflam.
persist

10. In chronic inflammation, macrophage
accumulation persists, this is mediated by
different mechanisms:
1.Recruitment of monocytes from the circulation, which results
from the expression of adhesion molecules and chemotactic
factors
2.Local proliferation of macrophages after their emigration
from the bloodstream
3.Immobilization of macrophages within the site of
inflammation

13. ◦Both T & BLymphocytesmigrates into inflammation site
◦From activated B lymphocytes, plasma cell is develop.

14. EOSINOPHILS
Are abundant in immune reactions mediated by IgE and in parasitic
infections.

15. MAST CELLS
◦are widely distributed in connective tissues.
◦Participate in both acute and chronic inflammatory reaction.
◦Mast cells express on their surface the receptor that bindss the
Fc portion of IgE antibody.
◦the cells degranulate and release mediators, such as histamine
and products of AA oxidation.

17. Definition:
Granulomatousinflammationisadistinctive
patternofchronicinflammatoryreaction.
Itisaprotectiveresponsetochronicinfection
orforeignmaterial,preventingdissemination
andrestrictinginflammation.
Involvedcells -activatedmacrophage
-lymphocyte
-plasmacells

18. Bacterial -Tuberculosis,Leprosy,syphilis
Parasites-Schistosomiasis
Fungi -Histoplasmosis,Blastomycosis
Miscellaneous–Berylliosis
-Silicosis
-sarcoidosis
-crohn`sdisease

20. Microscopic aggregation of
macrophages that are transformed
into epithelium-like cells (epitheloid
cells) surrounded by a collar of
mononuclear leukocytes, principally
lymphocytes and occasionally plasma
cells.

21. Epithelioid cells fuse to form giant cells
containing 20 or more nuclei.
The nuclei arranged either peripherally
(Langhans-type giant cell) or
haphazardly (foreign body-type giant
cell).
These giant cells can be found either at the
periphery or the center of the granuloma.

22. Fibrous connective tissue often surrounds
granulomas (remodeling of tissue)
Areas within the granuloma can undergo
necrosis (prototype: caseous necrosis in
tuberculosis).
Necrosis can lead to calcification or
liquefaction and formation ofa cavern if
drained.

23. Langhans Giant Cell
Caseous Necrosis
Epithelioid Macrophage
Lymphocytic
Rim

25. 1.Foreign body granulomas–form when
material such as talc, sutures, or other
fibers are large enough to preclude
phagocytosis by a single macrophage.

26. 2.Immune granulomas-
caused by insoluble particles that are capable
of inducing a cell-mediated response.
Macrophages engulf the foreign material and
responding T cells
produce cytokines, such as IL-2 which
activates other T cells and IFN-which is
important in transforming macrophages into
epithelioid cells and multinucleate giant cells.

29. Presence of indigestible organisms
or particles (Tb, mineral oil, etc)
Cell mediated immunity (T cells)

30. Langhans Giant Cell
Caseous Necrosis
Epithelioid Macrophage
Lymphocytic
Rim

31. Tuberculosis
leprosy
syphilis

32. Tuberculosis is a chronic
communicable disease in which
the lungs are the prime target,
although any organ may be
infected.

33. Caused by tubercle bacillus.
Infects one third of world population..!
3 million deathsdue to TB every year
Crowding, Poverty, malnutrition
incidence is increasing in patient of
Immunosuppressed patients -AIDS,
Diabetes,, Drug resistance.

34. Inhalation
Ingestion
Inoculation
Transplacental route

35. Local spread
Lymphatic spread
Hematogenous spread
By natural passages
1) lung lesion into pleura (tuberculous pleurisy)
2) Infected sputum into larynx

36. TB bacilli injected IV in guinea pig
Bacilli lodge in pulmonary capillary
Initial response of neutrophilsis evoked , which rapidly
destroyed by organisms
After 12 hr. progressive infiltration by macrophges
Macrophage start phagocytosingTB bacilli

37. Then T & B cells activated
Activated T cell develops cell mediated delayed hypersensitivity reaction
And activated B cell form antibodies against TB bacilli
After 2 –3 days macrophages undergo structural change and form
epitheloidcell
Epitheloidcells aggregate in to tight cluster and form granuloma
Some of macrophages form multineucleatedgiant cells by fusion of
adjacent cells.
Giant cells may be lenghanstype or foreign body type.

38. Around the mass of epitheloidcells and giant cells there is a
zone of lymphocyte, plasma cells and fibroblast.
It is called a HARD TUBERCLE.
(Absence of central Caseousnecrosis)
Within 10 to 14 days center of cellular ma undergo caseation
necrosis
It is called a SOFT TUBERCLE.
(A hallmark of TUBERCULOSIS)

40. Development of caseous necrosis is due to
Interaction of mycobacteria with activated T cells
Direct toxicity of mycobacteria on macrophages.
Microscopically :
Caseous necrosis is
structure less, eoinophilic, and granular
material with nuclear debris.

41. Cold abscess:
caseous material undergo lequification and discharging
the content on the surface.
Sinus tract formation:
in bone, joint, LN, soft tissue.
Progressive fibrosis
Dystrophic calcification:
calcium salt deposited in caseous material.

42. Primary TB
SecondaryTB
Progressive pulmonary TB
Miliary TB

43. Primary tuberculosis is the form of disease
that develops in a Previously unexposed and
Unsensitizedperson.
Tuberculosisisatypeofdelayedtissue
hypersensitivitytothetuberculousbacillus
whichelicitacell-mediatedimmune
responsewhichwillresiststhegrowthand
spreadofthemycobacterium.

44. Inhalationofinfectiousagentinapreviously
Unexposedimmunocompotent individualare:
mycobacterium willgainaccesstoalveolar
macrophagethroughreceptors.
microbacteriumareinsidethecytoplasmofthe
macrophageitwillinhibitthemicrobicidal
responseofthemacrophage
(ineffectivephagolysosome).

46. Multiplicationoftheorganisminsidethe
alveolarmacrophage
processing&presentationoftheantigenon
thesurface
AcloneofsensitizedT-cellsproliferate,
producegammaINT.
Activationofthemacrophages(augmenting
theircapacitytokillmycobacteria)

47. The lytic enzymes of the activated
macrophages if released, also damaged host
tissues.
This activation of macrophages and
destruction of mycobacteria comprises the
cell mediated immunity.

49. In immunocompromised persons granulomas
are poorly formed or not formed at all and
the infection progress at the primary site in
the lung ,lymph nodes or in multiple sites---
------progressive primary
tuberculosis.

50. Ghon complex
Is characterized by:
GhonFocus-----
involves upper
segments of the lower
lobes or lower seg. of
the upper lobe of
LUNG.
Ghoncomplex
Microscopically the
classic lesion of TB is a
caseousgranuloma

52. Occur by ingestion of cow’s milk infected
with M.Tuberculosis,involved ileocaecal
regionof intestine
Due to Ingetion of TB bacilli, a small primary
focusseen in Intestine is involved with
enlarged mesentric Lymph nodes producing
TABES MESENTRICA
The enlarged and caceous mesentric LN
rupture into peritoneal cavity and cause TB
PERITONITIS.

55. Healing by fibrosis and calcification.
Prograssive primary tuberculosis –
spreading to the other area of lung or
opposite lung.
Milliary spread –to lungs , liver , spleen
,kidneys , and brain.
Progessive secondary pulmonary
tuberculosis

56. Is the pattern of disease that arises in a
previously sensitized host.
ENDOGENOUS SOURCE -reactivation of
dormant primary lesionswhen the host
resistance is lowered.
EXOGENOUS SOURCE -reinfectionby a
high dose of virulent bacilli which occur more
commonly in endemic areas.

57. Insecondarypulmonarytuberculosis,the
lesionsinvolvestheapicesofbothlungsand
appeargrosslyassharplycircumscribedfirm
areaswithcentralcaseationandcavitation
surroundedbyfibrouswall.
Itcanhealbyfibrosisleavingaresidual
apicalscar.
Histologically,epithelioidgranulomaswith
centralcaseationandLanghan’stypegiant
cells.

58. Healing by Scarring &calcification
Non-cavitary (fibrocaseous)
tuberculoisis
Cavitary tuberculosis
Tuberculous caceous pneumonia
Milliary tuberculosis

60. lympho-haematogenous spread
of tuberculous infection from
primary focus.
Lesion are :
millet seed sized (1 mm dia )
yellowish,firm areas without
grossly visible caseation necrosis.

61. Miliary tuberculosis is most prominent in :
the liver,
bone marrow,
spleen,
adrenals,
meninges, kidneys, fallopian tubes, and
epididymis.

65. DIAGNOSIS OF TB

66. Medical history
Physical examination
Mantoux tuberculin skin test
Chest radiography
Culture
Haematological examination
Cytopathological examination
Histopathological examination
PCR

70. AFB -Ziehl-Nielson stain

72. Known as hansen’ s diseases
Affecting skin & peripheral nerves
(coolest part of body) resulting in
disabling deformities
Caused by M. leprae

73. Direct contact with untreated
leprosy patient
Materno –foetal transmission.

74. Tuberculoid leprosy
Lepromatous leprosy

75. T cell mediated immune response
Localized skin lesions –
assymetricle,single,hypopigmented,erythematous
macular.
Neuronal involvement is dominant.
Nerve degeneration cause skin anesthesia & muscle
atrophy.
Lepromintest is positive.
Microscopy: Grenulomatouslesion in nerve sheaths.
granulomascontain epithelioid
macrophage, giant cells &
lympgocytes.

77. Lack of T cell mediated immune response
Skin lesion –
symmetrical,multiple,hypopigmented,
erythematous, maculopopularor nodular
lesion (Leonine face).
Antigen antibody complex leads erythema
nodosumleprosum, vasculitis&
glomerlonephritis.
More infectious than Tuberculoid leprosy.
Microscopy: large aggregates of lipid laden
macrophage filed with masses of AFB (Globi)

81. Venereal disease
Caused by treponema pallidium
Detected by silver stain, dark field examination
& immunoflorescence technique.

82. Person to person contact
Sexualy transmission
Transfusion of infected blood
materno foetal transsmission

83. Primary stage:
3 weeks after contact
Single, firm, non tender, raised, red lesion call
CHANCRE, located on penis, cervix, vaginal
wall or anus
Chancre shows intense inflammation

84. 2-10 weeks after chancre.
Diffuse rash with macular, follicular, postural,
annular or scaling lesions on palms & soles.
Fever, lymphadenopathy, headache & arthritis
More infectious stage.
Inflammation is less intense

85. Occurs years after primary lesion.
Acute inflammatory lesion of aorta, CNS or
gumma in liver, bone & skin
In aortitis, inflammatory scarring of tunica
media, widening & incompetence of aortic valve
ring & narrowing of the mouths of the coronary
ostia occur.

86. Several forms:
Meningovascular syphilis
Tabes dorsalis
General paresis

87. Histological hallmarks of syphilis are
periarteritis, endarteritis & plasma cell rich
mononuclear infiltration.
Exudate show lymphocytes, histiocytes
&plasma cells

88. Thank you