1. General Pathology Inflammation II Healing processes Classification Jaroslava Dušková Inst. Pathol.,1st Med. Faculty, Charles Univ. Prague

2. Inflammation Definition: complex reaction of organism to damage (aim: homeostasis maintenance)

3. Inflammation Sense defensive – agent elimination reparative – damage reparation

4. Inflammation Celsus´ features: v rubor v tumor v calor v dolor v functio laesa

5. Inflammation - Classification: Time view v acute (days) v subacute (weeks) v chronic (months-years )

6. Phases of Inflammatory Response Alteration Exsudation Proliferation

7. Healing of Inflammation

8. Progressive Changes Def.: processes leading to  lost or damaged tissue substitution or  adaptation to the organism or environment changed conditions

9. Progressive Changes  Regeneration (restitution )  Reparation (substitution )  Hypertrophy  Hyperplasia  Metaplasia  Adaptation

10. Progressive changes 1.  Regeneration - restitution of former status u Reparation – substitution with a less specialised tissue u Hypertrophy – enlargement of the organ through cell enlargement

11. Angiogenesis Endogenous Promotors u VEGF - A,B,C,D u Angiopoietins u Angiogenin u basic FGF bFGF u Hepatocyte Growth Factor HGF u Interleukin-8 u PDGF u Transformation Growth Factor ß TGF ß u TNF 

12. Angiogenesis Endogenous Inhibitors u Angiostatin u Brain Angiogenesis Inhibitor 1 BAI1 u Endostatin u Interferons u Platelet factor-4 cleavage products u Prolactin fragment (16kd) u Thrombospondin-1 u VEGI u Vasostatin

13. Progressive changes 2. u Hyperplasia – enlargement of the organ through cell multiplication  Metaplasia – transformation of one differentiated tissue into another differentiated tissue  Adaptation - functional adjustment It is done by means of metaplasia, hypertrophy, hyperplasia, metalaxia, (rebuilding).

14. Healing Processes 1. u wounds – per primam intentionen (wounds without infection, dislocation, foreign bodies) – per secundam intentionen u hematoma organisation u thrombus organisation (possible recanalisation)

15. Proliferation - steps  dissolution of exsudate & necrotic tissue  granulation tissue fibronectin formation, fibroblasts & endothelia organisation  collagen production  scar maturation  scar contraction myofibroblasts

16. Wound Healing - steps Day 0: fibrin – fibronectin gel Day 1: neutrophils Day 1-2: macrophages Day 2-4: fibroblasts, myofibroblasts, capillaries

17. Granulation Tissue Growth  PDGF from: mf, endoth., platellets causes: fbl proliferation, proteosynthesis  Transforming GF from: mf, epithelia causes: fbl proliferation, angiogenesis  IL- 1 from: mf, epithelia causes: fbl proliferation, endogenous pyrogen  TNF α from: mf causes: endothelial growth, killing bacteria, cachexia

18. Healing Processes 2. u ischemic and traumatic necroses u foreign bodies healing u bone fractures

19. Factors Influencing Wound Healing  age  nutrition status – protein deficit  vitamins A,C – collagen, epithelisation  Zinc – enzyme function  steroids  local factors  infection  necrosis  foreign bodis  patient´s motility  arterial perfusion  venous drainage

20. Inflammation - Classification: According to the dominant phase : v alterative v EXSUDATIVE v proliferative

21. Inflammation - localisation u superficial v mucous membranes v serous membranes v skin u interstitial

22. Inflammation - Classification: Type of exsudate:  serous  nonpurulent – lymphoplasmocellular  purulent  fibrinous  gangrenous

23. Interstitial fibrinose inflammation u fibrin exsudation & fibrinoid change of the collagen containing connective tissue

24. Fibrinoid Change of Collagen u vessels and connective tissue damage u plasmorrhagia (leakage of plasma) u deposits of Ag-AB complexes u staining characteristics fibrin - like

25. Significance of Fibrinoid Change u diminished quality of the collagen ( firmness, permeability) u tendency to thrombosis in the vessels, aneurysms formation

26. Inflammation - Classification: Type of exsudate:  serous  nonpurulent – lymphoplasmocellular  purulent  fibrinous  gangrenous

27. Gangrenous Inflammation u tends to be interstitial u putrefactive bacteria u severe alteration