This document provides information about chronic inflammation: - Chronic inflammation can occur either from an ongoing acute inflammatory response or from the beginning as a chronic response to less toxic agents like bacteria or environmental materials. - It is characterized by mononuclear cell infiltrates like macrophages, lymphocytes and plasma cells that can cause tissue destruction and fibrosis over time. - Macrophages play an important role by secreting enzymes, proteins, and cytokines that perpetuate the inflammatory response and recruit other immune cells.

1. FACULTY OF MEDICINE PRIŠTINA
Institute of pathology
Prof. dr Nebojša Mitić
CHRONIC
INFLAMMATION

2. Chronic inflammation
 It can occur in two ways:
 acute inflammation may follow
 from the very beginning it has the character of
chronic inflammation
 Often, harmful agents that cause chronic
inflammation are less toxic than those that
cause acute inflammation.

3. Chronic inflammation
 Persistent infections with low-toxic intracellular
microorganisms that cause a late-type immune
reaction (TB bacillus, Treponema pallidum, some
types of fungi).
 Prolonged exposure to some undecomposed
inanimate material (silicon crystals, asbestos in the
lungs, other pneumoconioses).
 Immune reactions against own tissues resulting in
autoimmune diseases (systemic connective tissue
diseases).ivica).

5. Characteristics of chronic
inflammations
mononuclear cell infiltrates
(macrophages, lymphocytes and plasma
cells)
tissue destruction
fibrosis.

6. MACROPHAGES
 Component of the mononuclear-phagocytic system-
MFS (formerly reticulo-endothelial-RES).
 MFS - related cells of bone marrow origin including
blood monocytes and tissue macrophages.
 Tissue macrophages are diffusely scattered in the
connective tissue or gathered in certain organs
(Kupffer cells in the liver, alveolar macrophages in
the lungs, sinus histiocytes in the spleen and lymph
nodes). They all originate from a common precursor
in the bone marrow.
 The half-life of blood monocytes is about one day,
and tissue macrophages live for several months,

7. Macrophages
 Besides phagocytosis, macrophages have a
number of important roles in inflammation.
 They can be activated, indicated by:
 increase in cell size,
 an increase in the amount of lysosomal
enzymes,
 significantly more active metabolism and
 greater possibility of phagocytosis.

8. Macrophage activation signals
Lymphokines, the most important ϒ-
interleukin, are secreted by sensitized T-
lymphocytes
bacterial endotoxins
contact with fibronectin coated surfaces
different chemicals that can be produced
during acute inflammation

9. ACTIVATED MACROPHAGES SECRETE
 enzymes (neutral or acid proteases)
 plasma proteins (complement system and
coagulation proteins)
 reactive oxygen metabolites
 lipid mediators (products of arachidonic acid
metabolism and TAF)
 cytokines (IL-1, TNF)
 growth factors (proliferation of various cells).

11. Lymphocytes
 They have a reciprocal relationship with
macrophages in chronic inflammation.
 They are most often activated in contact
with an antigen, whereby the
lymphocyte secretes lymphokines.
 Activated macrophages activate
lymphocytes, closing the circle and
creating conditions for chronic
inflammation.

13. Plasma cells
 they create antibodies directed
against persistent antigens or against
altered tissue components.

14. Eosinophilic leukocytes
 are characteristic of:
immune reactions mediated by IgE and
for
parasitosis.

15. Eozinophilic leukocytes

16. Proliferation of fibroblasts and
accumulation of extracellular matrix
 it is a common occurrence in many
chronic inflammations and is the
cause of permanent loss of function.
 The mechanisms of inflammatory
fibrosis are similar to the mechanisms
during the reparation process.

17. Fibrous adhesions

18. Chronic inflammation
non-proliferative
proliferative

19. Chronic non-proliferative
inflammation
 Long-term lymphoplasmacytic
infiltration of organs with a weak
proliferative component (for example,
chronic persistent hepatitis).
 Chronic exudative inflammation
(chronic purulent osteomyelitis).

20. CHRONIC PROLIFERATIVE
INFLAMMATION
 granulating inflammation
 fibrous and sclerosing
 inflammation with fatty degeneration
and pseudoxanthoma cells.

21.  Chronic atrophic inflammation.
 Chronic hyperplastic
inflammation

22. FORMS OF PRODUCTIVE
INFLAMMATION
 Interstitial
 Granulation
 Parasitic inflammations with granuloma
formation
 Proliferative inflammations in which
proliferate elements of other importance
 Proliferative inflammation in which there is
proliferation of parenchyma and stroma

23. INTERSTITIAL INFLAMMATION
 It is characterized by cellular infiltration
that affects the interstitial supporting
tissue, that is, the stroma of the organ.
 The cellular infiltrate consists of cells
of chronic inflammation.
 A complete cure is possible, but often
there is a fibroblastic reaction and
sclerosis of the organs.
 Causes: viruses, rickettsiae, diphtheria
bacillus, TBC bacillus and treponema.

24. GRANULOMATOUS
INFLAMMATION
 Proliferation of granulation tissue
exclusively in one place in the
interstitium, forming a limited
nodule called a granuloma.
 They are clearly circumscribed
and look like tumors.

25. Characteristic of granuloma
Specific transformation of
histiocytes and tissue
monocytes into histiocytic
macrophages or so-called.
epithelioid cells.

26. Epithelioid cells
 Polygonal cells, with light granular
cytoplasm, usually in close contact to
resemble epithelium, hence the
name epithelioid.

27. TYPES OF GRANULOMA
 Granuloma in sarcoidosis
 Granuloma in TBC
 Syphilis granuloma (gumma)
 Reticuloabscessing granuloma
 Granuloma in actinomycosis
 Granuloma in rheumatic fever
 Granuloma in rheumatoid arthritis (Bang's
granuloma)
 Granuloma around protozoa
 Granuloma around animal parasites
 Granuloma around the foreign body

30. SARCOIDOSIS (Besnier-Beck-
Shaumanova disease)
 Etiology unknown, most likely
immunological in nature.
 A disease similar to TBC.
 Granulomas in the lungs,
mediastinum or sometimes
diffusely.

31. Histology
 Granuloma composed of epithelioid
cells, giant multinucleated cells of the
Langhans type, lymphocytes and
plasmocytes on the periphery, without
necrosis in the center of the
granuloma.
 Similar granulomas are found in the
intestines in Crohn's disease

32. Giant multinucleated cell
Epiteloid cells

33. Langhans cell
 A giant cell with several nuclei around
the periphery of the cell in the form of
a wreath or horseshoe.
 In the cytoplasm of giant cells in
sarcoidosis, inclusion Schaumann
corpuscles are found, important in the
differential diagnosis with TBC.

34. Schaumann asteroid corpuscle in giant cell

35. Tuberculous granuloma
 In the center of the granuloma, there
is often a structureless, necrotic
mass, similar to cheese or dry plaster
(cheesy or caseous necrosis).
 Around the caseous necrosis, a band
of epithelioid and giant cells of the
Langhans type, and on the periphery
a non-specific part of granulation
tissue or mature connective tissue.

36. Caseous necrosis

40. TBC ostemyelitis

41. Syphilis granuloma (gumma)
 Similar to TBC, except that
vascularization is maintained
longer in its center, and
plasmocytes dominate in the
periphery.

42. Syphilis granuloma

43. Reticuloabscessing granuloma
 A central zone with a mass of leukocytes,
i.e. an abscess, and around the central
part initially reticular cells, and later
epithelioid cells arise from them.
 It is found in brucellosis, tularemia,
pseudotuberculosis, inguinal granuloma,
cat scratch disease.

44. A: Liver fragment with brucellosis granuloma
B and C: histological images of granulomas

45. Inguinal granuloma

46. Inguinal granuloma

47. Inguinal granuloma

49. Tularemia, ulcer on the hand at the site of entry of Francisella tularensis

50. Glandular type of tularemia

51. An irregular granulomatous structure with a star-shaped abscess and central necrosis
surrounded by an inner layer of palisade-arranged histiocytes (arrows), a row of
lymphocytes in the middle (arrowhead) and on the outside a zone of fibrosis (asterisks) in
the middle stage of the development of "cat-scratch disease" (H-E x100 ).

52. The inflammatory and necrotic region is replaced and surrounded by spindle-
shaped collagen-producing cells, fibroblasts, and fibrocytes (asterisks), in late-
stage "cat-scratch disease" (H-E, ×100).

54. Cat scratch disease

55. Actinomycosis granuloma
 It is made up of epithelioid cells, small
round cells, giant and xanthoma cells.
 In the center of the granuloma, there is
often an abscess, where there are fibers
or micelles of acinomycetes.
 It appears in three forms:
 facial
 pulmonary
 inguinal granuloma

58. Granuloma with actinomycetes in the center

62. Rheumatic fever granuloma
(Aschoff's granuloma)
 Aschoff bodies in the myocardium, usually
around blood vessels and subendocardial.
 In the center there is fibrinoid necrosis,
 Anichkov's myocytes (cells that are not of
muscle origin even though they are called
myocytes) and Aschoff's giant cells
proliferated around the necrosis.
 On the periphery of the granuloma are
lymphocytes.

68. Rheumatoid arthritis granuloma
(Bang granuloma)
 Fibrinoid necrosis in the center,
histiocytes arranged in a palisade
around the necrosis, and around it is
connective tissue.

69. Rheumatoid subcutaneous nodule with a field of necrosis surrounded by
macrophages in a palisade arrangement and scattered cells of chronic inflammation

70. Protozoa granuloma
(toxoplasmosis)
 Necrosis with precipitated calcium salts
around which macrophages are located,
and parasites in them.
 Some macrophages turn into pseudocysts.
 At the very periphery, there is non-specific
granulation tissue.

72. Toxoplasma gondi

73. Granuloma in the spleen in
toxoplasmosis

74. Granuloma around the foreign body
 It is created around exogenous (most often surgical
thread) or endogenous material (gout and
thesaurism).
 In the center of the granuloma there is a foreign
body.
 Around the foreign body is a band of macrophages,
tissue histiocytes and giant multinucleated cells of
the "foreign body" type, which have multiple nuclei
diffusely scattered throughout the cytoplasm or
clustered in the center of the cell.
 On the periphery of the granuloma there is
granulation and connective tissue.

75. Granuloma corporis alieni

76. Granuloma corporis alieni

78. INFLAMMATION WITH SECOND ORDER ELEMENTS
PROLIFERATION
 They occur in lymphatic organs, lymph nodes,
tonsils, spleen, that is, in organs that contain
lymph follicles. The tissue that multiplies in
this case is lymphatic tissue and there is no
proliferation of connective tissue.
 Proliferated lymphoid elements, sinus
histiocytes, reticular cells, lead to an increase
in the organ as a whole or individual
lymphatic structures. This is why these
inflammations are hyperplastic.

79. Hiperplastični germinativni centri u limfoidnom tkivu

80. PROLIFERATIVE INFLAMMATIONS IN WHICH THE STROMA AND
PARENCHYMA PROLIFERATE AT THE SAME TIME
 Lymphoplasmacytic infiltration in the stroma and
simultaneous proliferation of parenchymal
elements, mainly epithelium.
 On mucous membranes lined with cylindrical
epithelium, growths with a stalk, inflammatory
polyps.
 On mucous membranes lined with squamous
epithelium of papillomatous structure
(papillomatous laryngitis).
 These changes should be distinguished from
true tumor proliferations.

81. Nasal polyp

83. Nasal polyp

84. Nasal polyp

85. Laryngeal papillomatosis

86. Laringealni papilom

87. Laringeal papilloma

89. Thank you for your attention