1. Dr Shoaib Raza

2. Acute inflammation is morphologically characterized by – Dilatation of small blood vessels – Slowing of blood flow – Leukocyte infiltration – Fluid accumulation in interstitial space Special morphologic patterns are seen – Severity of reaction – Specific cause of reaction – Particular tissue/site involved

3.  Marked by Outpouring of thin fluid derived from  Plasma  Secretions of mesothelial cells Accumulation of fluid in these cavities is called as EFFUSION Skin blister represent accumulation of serous fluid

4. Characterized by deposition of fibrin in the extracellular spaces Fibrinous exudate develops when – Vascular leaks are large, or – Local procoagulant stimulus Fibrinous exudate is characteristic of: – Inflammation in the lining of body cavities Conversion to fibrous tissue (organization) within pericardial sac leads to fibrous thickening (Fibrinous pericarditis)

5. Characterized by production of large amounts of pus (purulent exudate), consist of – PMN, liquefactive necrosis, edema fluid Pyogenic bacteria produce this Abscess are localized collection of purulent inflammatory exudate – Suppuration buried in an organ, tissue or confined space Central necrotic area Preserved PMN around this necrotic focus Vascular dilatation, parenchymal and fibroblastic proliferation occurs peripherally

6. A local defect or excavation, of the surface of an organ or tissue, produced by the sloughing (shedding) of inflamed necrotic tissue Occur when tissue necrosis and inflammation exist on or near a surface Encountered in – Mouth, stomach, intestine, genital or urinary tract – Skin & subcutaneous tissues

8.  Complete resolution  Healing by connective tissue replacement Fibrosis, organization, scar formation  Progression to chronic inflammation

9.  Inflammation of the prolonged duration (weeks or months) in which inflammation, tissue injury and attempts at repair coexist  It may Follow acute inflammation Begin insidiously as low grade smoldering response without any manifestation of the acute reaction

10.  Chronic inflammation arises in following settings: Persistent infection by microorganism  Mycobacteria, fungi, viruses, parasites etc Immune mediated inflammatory diseases  Autoimmune diseases (Allergic disorders) Prolonged exposure to potentially toxic agents  Exogenous  Silica, carbon  Endogenous  Atherosclerosis

11.  Chronic inflammation is characterized by: Infiltration with mononuclear cells  Macrophages, lymphocytes, plasma cells Tissue destruction  Induced by persistence of offending agent Attempts at healing by connective tissue replacement of damaged tissue  Proliferation of small blood vessels (Angiogenesis)  Fibrosis

12.  Macrophages are the predominant cells of chronic inflammation Component of mononuclear phagocyte system  LiverKupffer cells  Spleen & Lymph nodesSinus histiocytes  LungAlveolar macrophages  CNSMicroglia  BoneOsteocytes Arise from common precursor in bone marrow Monocytes enter tissue & differentiate into macrophages

13.  Migration begins early in acute inflammation  Predominant cells after 48 hours  Macrophages activation occur via: Microbial products via TLRs IFN- γ secreted by sensitized T Cells, NK cells,  Activation results in: Increased level of lysozyme ROS & NO production Production of cytokines, growth factors, etc

14.  Activation of macrophages result in: Toxicity to microbes & host cells Release of protease etc Influx of other cell types via cytokines Fibroblast proliferation Angiogenesis  Arsenal of mediators make them powerful allies in the defense, but the same weaponry can induce tissue destruction

15.  In acute inflammation: If irritant is eliminated, macrophages disappear  Either dying off  Drain to regional lymph nodes via lymphatics  In chronic inflammation: Accumulation of macrophages persists  As a result of continuous recruitment from the circulation and local proliferation at the site of inflammation

16.  Lymphocytes: Cell mediated or antibody mediated reactions Selectins, integrins and chemokines help in their recruitment TNF, IL-1, etc promote leukocyte recruitment,  Persisting the inflammatory response Macrophages present antigens to T Cells  Plasma cells May transform the inflammatory site into tertiary lymphoid organ

17.  Eosinophils: Abundant in immune reaction mediated by IgE and parasitic infestations (infections) Eotaxin is a potent chemotactic agent for eosinophil Eosinophil produce:  Major Basic Proteins  Mast Cells: Widely distributed in connective tissue Participate in both acute & chronic inflammation Express Fc ε RI Release histamine, prostaglandins, serotonin Cytokines production

18.  Distinctive (Specific) pattern of chronic inflammation  Immune reactions are usually involved in granuloma formation  Granuloma is an attempt to contain an offending agent  Granuloma composed of: Modified macrophages (epitheliod cells) Collar of lymphocytes Giant cells (multinucleated cells) + Necrosis (caseous)  Granulomas are of two main types: Foreign body granuloma Immune granulomas  Delayed type hypersensitivity reactions

19. Fungal Infections: Histoplasmosis Blastomycosis Metal/Dust Berylliosis Silicosis Foreign body Splinter Suture Graft material Sarcoidosis Bacteria: Tuberculosis Leprosy Parasites: Schistosomiasis

24.  Acute Phase Response (systemic inflammatory response syndrome) Fever:  Usually seen in infections  Pyrogens stimulate hypothalamus to form PG Acute Phase proteins:  CRP, Fibrinogen, Serum Amyloid A (SAA) Leukocytosis:  Leukemoid reactions, leukopenia Others:  Increased pulse rate, Increased blood pressure, decreased sweating, rigors, chill, anorexia, somnolence, malaise

25. Pain is perfect misery, the worst of evils, and excessive, overturns All patience. - John Milton,

26.  Defective Inflammation: Increased susceptibility to infections Delayed wound healing  Excessive Inflammation: Hypersensitivity reactions Autoimmune disorders Other non-immune related disorders  AS, CHD, Alzheimer’s Disease Pathology in many infections, metabolic disorders, etc.