1. CHRONIC INFLAMMATION
HA MWAKYOMA, MD

2. CHRONIC INFLAMMATION:
THE OUTCOME (FATE) OF ACUTE INFLAMMATION:
This is the evolution of acute inflammation
Acute inflammatory process can culminate in one of the following 4 outcomes.
Resolution
Healing and scarring
Progression to suppuration – spread through lymphatics (lymphangitis, reactive lymphadenitis) and systemic spread e.g. septicaemia, toxaemia
Progression to chronic inflammation

3. THE OUTCOME (FATE) OF ACUTE INFLAMMATION: cont--
RESOLUTION:
It means complete return to normal tissue following acute inflammation.
This occurs when tissue changes are slight and the cellular changes are reversible e.g. resolution of lobar pneumonia.
HEALING BY SCARRING:
This takes place when the tissue destruction in acute inflammation is extensive so that there is no tissue regeneration but actually there is healing by fibrosis

4. THE OUTCOME (FATE) OF ACUTE INFLAMMATION: cont--
SUPPURATION:
When the pyogenic bacteria causing acute inflammation results in severe tissue necrosis, the process progresses to suppuration.
Subsequently, there is a mixture of :-
Neutrophils;
Bacteria;
Fragments of necrotic tissue;
Cell debris and
Fibrin, ALL of these comprise PUS which is contained in a cavity to form an ABSCESS.

5. THE OUTCOME (FATE) OF ACUTE INFLAMMATION: cont--
CHRONIC INFLAMMATION:
The acute inflammation may progress to chronic inflammation in which the process of inflammation and healing proceed side by side.

6. II: CHRONIC INFLAMMATION:-
Definition:
Chronic inflammation is defined as prolonged process in which tissue destruction and inflammation occur at the same time.
Causes:
Chronic inflammation can be caused by one of the following 3 ways:-

7. Causes of CI: Persistence of acute inflammation (AI).
This is a chronic inflammation following acute inflammation
This occurs when the tissue destruction is extensive, or the bacteria survive and persist in small numbers at the site of acute inflammation e.g. osteomyelitis, acute lobar pneumonia terminating in lung abscess.

8. Causes of CI: Recurrent attacks of acute inflammation.
This occurs when there is repeated bouts of acute inflammation culminating in chronicity of the process. Examples are:--
-- Recurrent urinary tract infection leading to chronic pyelonephritis.
-- Repeated acute infection of gall bladder leading to chronic cholecystitis
-- Immunologic inflammation due to persistence of immune complexes or auto-antigens – e.g. chronic thyroiditis

9. Causes of CI:
Chronic inflammation starting de novo (de novo CI by passing AI (e.g. TB).
This occurs when the infection with organisms of low pathogenicity is chronic from the beginning e.g. Mycobacterium tuberculosis.

10. General Features of Chronic Inflammation:
There are may be differences in chronic inflammatory response depending upon the tissue involved and causative organisms,
Also there are some basic similarities amongst various types of chronic inflammation.
The following general features characterize any chronic inflammation.

11. General Features of Chronic Inflammation:
MONONUCLEAR CELLINFILTRATION:
Chronic inflammatory lesions are infiltrated by mononuclear inflammatory cells like phagocytes and lymphoid cells.
Phagocytes are represented by:
Circulating moocytes
Tissue macrophage
Epithelioid cells and sometimes
Multinucleated giant cells

12. MONONUCLEAR CELL INFILTRATION:cont----
The macrophages comprise the most important cells in chronic inflammation
The macrophages may appear at the site of chronic inflammation from:-
Chemotactic factors of macrophage (continued recruitment).
Local proliferation of macrophage and
Longer survival of macrophages at the site of inflammation (Immobilization).

13. The macrophages
The blood monocytes on reaching the extravascular space, transform into tissue macrophages.
Besides phagocytosis, macrophages may get activated in response to stimuli such as Cytokines (lymphokines) and bacterial endotoxins

14. The macrophages
On activation macrophages release several biologically active substances e.g. acid and neutral proteases, oxygen-derived reactive metabolites and cytokines
These products bring about tissue destruction, neovascularization and fibrosis

15. OTHER Chronic inflammatory cells
OTHER Chronic inflammatory cells include:-
Lymphocytes
Plasma cells
Eosinophils and
Mast cells
NB: In chronic inflammation, lymphocytes and macrophages influence each other and release mediators of inflammation.

16. TISSUE DESTRUCTION AND NECROSIS:
Tissue destruction and necrosis are common in many chronic inflammatory lesions and
are brought about by activated macrophages by release of a variety of biologically active substances.

17. PROLIFERATIVE CHANGES:
As a result of necrosis, proliferation of small blood vessels and fibroblasts are stimulated resulting in formation of inflammatory granulation tissue.
Eventually healing by fibrosis and collagen laying takes place.

18. TYPES OF CHRONIC INFLAMMATION:
Conventionally, chronic inflammation is subdivided into 2 type
Non-Specific Inflammation:
This occurs when the irritant substance produces a non-specific inflammatory reaction with formation granulation tissue and healing by fibrosis, e.g. chronic osteomyelitis, chronic ulcer.

19. TYPES OF CHRONIC INFLAMMATION:cont--
Specific Inflammation:
This results when the injurious agent causes a characteristic histologic tissue response e.g. tuberculosis, leprosy Syphilis etc.
However, for a more descriptive classification, histological features are used for classifying chronic inflammation into 2 corresponding types:-

20. CHRONIC NON-SPECIFIC INFLAMMATION.
Is characterized by non-specific inflammatory cell infiltration e.g. chronic osteomylitis, lung abscess.

21. CHRONIC GRANULOMATOUS INFLAMMATION.
Is characterized by formation of granulomas e.g. TB, Leprosy, Syphilis, actinomycosis, Sarcoidosis etc.
GRANULOMATOUS INFLAMMATION:
Definition:
Is a special type of chronic inflammatory reaction which is characterized by the local accumulation of large numbers of macrophages, some of which may have undergone striking morphological and functional changes (Epithelioid cells) and rimmed at the periphery by the lymphoid cells (see fig )

22. A typical granuloma (Tubercle)

23. A Granuloma: Epithelioid cells:-
are so called because of their epithelial like appearance
Are modified macrophages which are somewhat elongated, have pale-staining abundant cytoplasm, lightly-staining slipper shaped nucleus.
They are weakly phagocytic and more secretory in function
Besides the presence of epithelioid cells and lymphoid cells, granulomas may have giant cells, necrosis and fibrosis

24. GIANT CELLS These cells may occur under pathological and physiological
conditions.
Are formed by fusion of adjacent epithelioid cells and may have 20 or more nuclei.

25. Giant cells: (see diagram )

26. Pathological giant cells.
Langhans’ giant cells:-
Have peripheral arranged nuclei like horse shoe or ring clustered at the two poles
Are commonly seen in tuberculosis
Foreign body giant cells:-
Have centrally arranged nuclei
Are commonly seen in foreign body tissue reactions

27. Langhans’ Giant cell

28. FB giant cell

29. PATHOLOGICAL GIANT CELLS
Viral type giant cells:
Fused epithelial cells
Commonly seen in viral infections especially myxoviruses, e.g. in measles

30. NumerousWarthin-Finkeldey's giant cells. (measles lymphadenitis)

31. PATHOLOGICAL GIANT CELLS
Touton giant cells:-
Fused tumour cells
Commonly seen in nevi, Reed Sternburg cells (RS cells) in Hodgkin’s disease.

32. Tuton giant cell

33. Physiological giant cells.
Osteoclasts:-
Fused macrophages
Centrally located nucleus

34. OSTEOCLASTIC like GIANT CELLS

35. Osteoclastic like giant cells

36. Syncytiotrophoblasts:-
Mesodermal cells covering chorionic villi.
: Like epithelioid cells, the giant cells are weakly phagocytic but produce secretory products which help in removing the invading agents.

37. Syncytiotrophoblasts giant cells

38. NECROSIS
May be a feature of some granulomatous conditions e.g. central caseation necrosis of tuberculosis, so called because of cheese-like appearance and consistency of necrosis.
FIBROSIS:-
Is due to proliferation of fibroblasts at the periphery of granuloma

39. Tuberculos lymphadenitis(Caseous necrosis)

40. FACTORS FAVOURING FORMATION OF GRANULOMA
The following 2 factors favour the formation of granulomas.
Presence of poorly digestible irritant:-
These may be organisms like Mycobacterium tuberculosis, particles of talc etc.
Presence of cell-mediated immunity to the irritants
- This imply the role of hypersensitivity in granulomatous inflammation.

41. EVOLUTION OF GRANULOMA.
The Mechanism of evolution of granuloma.
The classical example of granulomatous inflammation is the tissue response to tubercle bacilli which is called TUBERCLE
The initiating event in granuloma formation
is believed to be the deposition within tissue of a relatively indigestible antigenic material which initiates a delayed type (Type IV) hypersensitivity reaction.

42. EVOLUTION OF GRANULOMA.
The complex interaction between antigen- presenting  mononuclear phagocytes and T lymphocytes, mediated by a variety of cytokines, initially results in T lymphocyte proliferation and activation at sites of antigen deposition.
The lymphocytes are predominantly T-helper cells

43. EVOLUTION OF GRANULOMA.
Recruitment of  macrophages from the circulation, their attraction to and retention at sites of antigen deposition, their maturation into epithelioid cells, and the ultimate formation of mature granulomas occurs under the influence of lymphokines produced by  activated T-helper cells.

44. EVOLUTION OF GRANULOMA.
Granulomas may either involute (resolve) or undergo fibrosis.  It has been suggested that  emigration of cells, reversion of  mature mononuclear phagocytes to less mature forms, and apoptosis play a role in involution.
Fibrosis usually begins at the periphery of the granuloma and progresses towards the center ultimately resulting in formation of a scar

45. CLASSIFICATION OF GRANULOMATOUS CONDITIONS -aetiologic
BACTERIAL:
Tuberculosis
Leprosy
Syphilis
Granuloma inguinale (donovanosis)
Brucellosis
Cat scratch disease
Tularaemia

46. CLASSIFICATION OF GRANULOMATOUS CONDITIONS -aetiologic
FUNGAL:
Blastomycosis
Cryptococcosis
Actinomycosis
Coccidiomycosis
PARASITIC:
Schistosomiasis
(Bilharziasis)

47. CLASSIFICATION OF GRANULOMATOUS CONDITIONS -aetiologic
MISCELLANEOUS:
Sarcoidosis
Crohn’s disease (Regional enteritis)
Silicosis
Berylliosis
Foreign body granulomas;-
Talc, Suture, wood, splinter etc