Dr Shoaib Raza

• 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

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

• 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)

• 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

• 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

Complete resolution Healing by connective tissue

replacement• Fibrosis, organization, scar formation

Progression to chronic inflammation

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

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

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

Macrophages are the predominant cells of chronic inflammation• Component of mononuclear phagocyte system

Liver Kupffer cells Spleen & Lymph nodes Sinus histiocytes Lung Alveolar macrophages CNS Microglia Bone Osteocytes

• Arise from common precursor in bone marrow• Monocytes enter tissue & differentiate into

macrophages

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

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

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

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

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 FcεRI• Release histamine, prostaglandins, serotonin• Cytokines production

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

Fungal Infections:• Histoplasmosis• BlastomycosisMetal/Dust• Berylliosis• SilicosisForeign body• Splinter• Suture• Graft materialSarcoidosis

Bacteria:• Tuberculosis• Leprosy

Parasites:• Schistosomiasis

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

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.