INFLAMMATION AND REPAIR PATHOLOGY

1. 2nd Yr Pathology 2010
Inflammation and cellular
responses
Prof Orla Sheils

2. 2nd Yr Pathology 2010
Inflammation
 Is a protective response
 The body’s response to injury
 Interwoven with the repair process

3. 2nd Yr Pathology 2010
Inflammation
 Types
 Acute (sec, mins, hrs)
 Chronic (days, weeks, months, yrs)

4. 2nd Yr Pathology 2010
Causes of inflammation
 Bacterial
 Viral
 Protozoal
 Metazoal
 Fungal
 Immunological
 Tumours
 Chemicals, toxins etc
 Radiation

5. 2nd Yr Pathology 2010
Acute inflammation

6. 2nd Yr Pathology 2010
Inflammation
 The Cardinal Signs of Acute
Inflammation
RUBOR
CALOR
TUMOR
FUNCTIO LAESA

7. 2nd Yr Pathology 2010
Cardinal signs of inflammation

8. 2nd Yr Pathology 2010
Cardinal signs of inflammation

9. 2nd Yr Pathology 2010
Cardinal signs of inflammation

10. 2nd Yr Pathology 2010
Cardinal signs of inflammation

11. 2nd Yr Pathology 2010
Cardinal signs of inflammation

12. 2nd Yr Pathology 2010
Cardinal signs of inflammation

13. 2nd Yr Pathology 2010
Inflammation
The basis of the five cardinal signs
 Increased blood flow due to vascular dilatation gives
redness and heat.
 Increased vascular permeability gives oedema
causing tissue swelling.
 Certain chemical mediators stimulate sensory nerve
endings giving pain. Nerves also stimulated by
stretching from oedema.
 Pain and swelling result in loss of function.

14. 2nd Yr Pathology 2010
Components of acute and chronic inflammation

15. 2nd Yr Pathology 2010
Cell of the acute inflammatory
response
 Polymorphonuclear leukocyte

16. 2nd Yr Pathology 2010
The process of inflammation

17. 2nd Yr Pathology 2010
The phases of inflammation
 FIRST THERE IS VASCULAR DILATATION
followed by exudation of protein-rich oedema
fluid which floods the area, dilutes toxins, allows
immunoglobulins to opsonise bacteria and
provides substrate (fibrinogen) for fibrin scaffold.
 SECOND THERE IS ACTIVE EMIGRATION OF
POLYMORPHS through vessel wall and along the
chemotactic gradient to the site of injury

18. 2nd Yr Pathology 2010
 THE VASCULAR PHASE OF INFLAMMATION
Fluid escapes from vessels because of endothelial cell (EC)
retraction, opening up gap-junctions.
The vessels which are normally involved are the post-capillary
venules where the EC have high affinity receptors for histamine.
Severe EC injury leads to leakiness of all vessels
capillaries, venules and arterioles - giving acute local oedema,
e.g. blister formation after a burn.
The phases of inflammation

19. 2nd Yr Pathology 2010
Local vascular manifestations of acute inflammation

20. 2nd Yr Pathology 2010
Leukocyte migration in inflammation

21. 2nd Yr Pathology 2010
Molecules modulating endothelial-neutrophil interactions
LFA-1 and MAC-1
(activated integrins)

22. 2nd Yr Pathology 2010
Acute inflammation: tissue effects
Pavementation and diapedesis

23. 2nd Yr Pathology 2010
Acute inflammation: tissue effects
Inflammatory cells in protein exudate

24. 2nd Yr Pathology 2010
Acute inflammation: tissue effects
Blood vessel involved in the acute inflammatory process

25. 2nd Yr Pathology 2010
Acute inflammation: tissue effects
Bronchopneumonia

26. 2nd Yr Pathology 2010
Acute inflammation: tissue effects
Abscess: collection of acute inflammatory cells

27. 2nd Yr Pathology 2010
Acute inflammation: tissue effects
Multiple splenic abscesses

28. 2nd Yr Pathology 2010
 Vasoactive amines
 Histamine
 Serotonin (5-HT)
 Neuropeptides
 Substance P
 Plasma proteases and the complement system
 Action of Hageman factor
 Arachidonic acid metabolites
 Prostaglandins
 Leukotrienes
 Lipoxins
 Cytokines
 IL-1, TNF etc.
 Chemokines (CXC and CC)
 Nitric oxide and oxygen-derived free radicals
Chemical mediators of inflammation

29. 2nd Yr Pathology 2010
Chemical mediators of inflammation
 PREFORMED
Histamine, Serotonin
 NEWLY SYNTHESISED
Prostaglandins
Leucotrienes
Platelet activating factor
Cytokines
Nitric oxide
 LOCAL AND SYSTEMIC

30. 2nd Yr Pathology 2010
Chemical mediators of inflammation
(local and systemic)

31. 2nd Yr Pathology 2010
Plasma proteases

32. 2nd Yr Pathology 2010
The complement system

33. 2nd Yr Pathology 2010
Arachidonic acid metabolites
HETE = hydroxyeicosatetraenoic acid
HPETE = hydroperoxyeicosatetraenoic acid

34. 2nd Yr Pathology 2010
Cytokines (IL-1 and TNF)

35. 2nd Yr Pathology 2010
Nitric oxide (NO)

36. 2nd Yr Pathology 2010
Effects of mediators of inflammation
Vasodilation:
Prostaglandins, NO
Increased vascular permeability:
Histamine, serotonin, C3a, C5a, bradykinin,
Leukotrienes C4, D4, E4, platelet activating factor
Chemotaxis, leukocyte activation:
C5a, leukotriene B4, bacterial products, chemokines (IL-8)
Fever:
IL-1, IL-6, TNF, prostaglandins
Pain:
Prostaglandins, bradykinin
Tissue damage:
Neutrophil and macrophage lysosomal enzymes, oxygen metabolites
NO

37. 2nd Yr Pathology 2010
Phagocytosis
Phagocytosis of bacteria by polymorphs

38. 2nd Yr Pathology 2010
PHAGOCYTOSIS
Recognition and attachment
Foreign objects coated with opsonins IgG and C3b which attach to
receptors on polymorph surface.
Engulfment
Cell membrane fuses around an object: at the some time
lysosomes
empty into the vacuole, often before vacuole has time to seal - this
gives
rise to 'regurgitation during feeding' and enzymatic damage to
surrounding
tissue.
Killing or degradation
H2O2, hypohalous acid (HOC1) produced by myeloperoxidase and
superoxides kill bacteria. Lysozyme digests them.

39. 2nd Yr Pathology 2010

40. 2nd Yr Pathology 2010
Chronic inflammation

41. 2nd Yr Pathology 2010
Cells of the chronic inflammatory
response
 Lymphocytes
 Monocytes/ macrophages
 Plasma cells

42. 2nd Yr Pathology 2010
Maturation of circulating monocytes
to macrophages

43. 2nd Yr Pathology 2010
Macrophage-lymphocyte interactions
in chronic inflammation

44. 2nd Yr Pathology 2010
Cellular interactions in chronic
inflammation

45. 2nd Yr Pathology 2010
Chronic inflammation: tissue
effects
Knee joint in rheumatoid arthritis

46. 2nd Yr Pathology 2010
Chronic inflammation: tissue
effects
Chronic cervicitis

47. 2nd Yr Pathology 2010
Chronic inflammation: tissue
effects
Lung abscess

48. 2nd Yr Pathology 2010
Granulomatous
inflammation:
a special form of
chronic inflammation

49. 2nd Yr Pathology 2010
Granuloma
 Definition
 A collection of macrophages, lymphocytes,
mononuclear cells and fibroblasts with or
without giant cell formation and constitutes
a special form of chronic inflammation

50. 2nd Yr Pathology 2010
Granulomatous inflammation
Bacterial:
TB, Leprosy, Syphillis, cat-scratch disease
Parasitic:
Schistosomiasis
Fungal:
Histoplasma, blastomycosis, cryptococcus
Inorganics, metals, dusts:
Silicosis, berrylliosis
Foreign body
Unknown:
Sarcoidosis

51. 2nd Yr Pathology 2010
Granulomatous inflammation:
tissue effects

52. 2nd Yr Pathology 2010
Granulomatous inflammation:
tissue effects

53. 2nd Yr Pathology 2010
Granulomatous inflammation:
tissue effects

54. 2nd Yr Pathology 2010
Granulomatous inflammation:
tissue effects
Epithelioid cells

55. 2nd Yr Pathology 2010
Granulomatous inflammation:
tissue effects
Talc granulomas in the lung

56. 2nd Yr Pathology 2010
Healing and repair

57. 2nd Yr Pathology 2010
Wound healing: critical steps

58. 2nd Yr Pathology 2010
The cell cycle

59. 2nd Yr Pathology 2010
Cyclins, cyclin dependent kinases and
cyclin dependent kinase inhibitors

60. 2nd Yr Pathology 2010
Cell-cell interactions in repair

61. 2nd Yr Pathology 2010
Cell surface receptors in healing
and repair

62. 2nd Yr Pathology 2010
The major components of the
extracellular matrix (ECM) required for
healing and repair

63. 2nd Yr Pathology 2010
Extracellular matrix re-modelling occurs by the action of
Matrix metalloproteinases

64. 2nd Yr Pathology 2010
Matrix metalloproteinase
regulation

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Critical steps in angiogenesis

66. 2nd Yr Pathology 2010
Major growth factors in
wound healing

67. 2nd Yr Pathology 2010
Wound healing: critical steps

68. 2nd Yr Pathology 2010
Granulation tissue

69. 2nd Yr Pathology 2010
Granulation tissue

70. 2nd Yr Pathology 2010
Scar tissue
Skin

71. 2nd Yr Pathology 2010
Scar tissue
Lung

72. 2nd Yr Pathology 2010
Outcome of healing and repair

73. 2nd Yr Pathology 2010
When healing goes wrong
Keloid scar