Cell Pathology 3

• Mechanical injury • Bacteria, viruses, parasites • Ischaemia • Chemical injury • Temperature • Radiation • Immune mechanism • Foreign body

Note s

• Microvasculature changes • Vasodilation → Redness & heat •  Permeability → Swelling • Inflammatory exudate • Fluid • Cells → Chemical mediators

• Peaking at 5-10 minutes • Lasts 15-30 minutes • Produced by chemical mediators • Nettle stings or insect bits

• Direct endothelial damage • Peaking at around 1h • Lasts until thrombus plugs vessel • Severe direct injury e.g. burns

• Subtle endothelial damage • Leakage starts 18-24hr later • Last 36h or more Causes include; • Sunburn • Radiotherapy • Bacterial toxins

• ChangesinBloodflow • White cells fall to edge of vessels • Adhesion molecules allow attachments between endothelial cell and leukocyte Emigration • Pseudopodiaform • Push between endothelial cells • Proteasesreleased • Digestbasementmembrane • Leukocytemigratesbetween endothelial cells • Basementmembraneseals behind them • Cellsmovetowardschemical signal • Towardsinflammatory mediator

-Phagosome engulfs foreign material -kill foreign material -damage to surrounding tissue

Neutrophils > lymphocytes>monocytes>eosinophils >basophils

• Mediatesmajorityofacuteinflammatoryeffects • Granulecontentsincreasevascularpermeability • Migrate to damaged area by chemotaxis • Phagocytic

> Eosinophils • Allergic/parasitic conditions • Granules include major basic protein Basophils • Give rise to mast cells • Granules include histamine

• Derived from monocytes • Migrate to damaged area (later than neutrophils) • Low numbers which increase with time • Survive much longer than neutrophils

> TCells - Antigen recognition and presentation • Cell killing • >Bcells • Give rise to plasma cells • Synthesize immunoglobulin’s

• Vasoactive amines (histamine and serotonin) • Arachidonic acid derivatives (prostaglandin and leukotrienes) • Cytokines (interleukins, interferons, chemokines and GFs) • Platelet activating factor • Nitric oxide • Lysosomal conten

• Kinin system (bradykinin) • Coagulation and fibrinolytic system (plasmin/fibrin degradation products) • Complement system (C3a and C5a)

• Systemic effects • Leukocyte production • Fever • Tachycardia • lower Blood pressure • lossofappetite • vomiting • skeletalweakness • aching

• Short duration • Minutes to days • Sequential process • Neutrophil and macrophage driven • Protective and reparative mechanism • Sometimes inflammatory response more harmful than initial tissue damage/infection

• Persistent (months or years) • Defined by type of cell present (Lymphocyte, macrophage and plasma cell) • Necrotic cell debris • Tissue granulation • Fibrosis • Balance between repair and continues tissue damage Macrophage are the main effector cells in chronic inflammation: • Antigen presentation (to lymphocytes) • Scavenging • Phagocytosis • Giant cell formation • Harbouring of organisms • Secretion • Reactive oxygen metabolites • Proteases • Arachidonic acid metabolites • Cytokines • Growth factors

➢Occurs following infection ➢Lymphocyte and plasma cell

➢Continued neutrophil production and recruitment ➢Surrounded by fibrous tissue & poorly vascularized ➢Eosinophil-rich

➢Agents difficult to destroy using lysosomal enzymes

• Collection of macrophages frequently surrounded by lymphocytes • Macrophagefuseforming multi-nucleated giant cell or epitheliod cell • Micro-organismswhichexcite an immune response eg mycobacteria • Non-living foreign material

• Primary • Never affected before • Produce lesions • Neutrophil inflammatory response → macrophage influx • Macrophage ingest bacilli → present antigen to lymphocytes • Proliferation of specific T lymphocytes → attract macrophage → Granuloma • Caseating necrosis • Secondary • Patients previously sensitized • Largely due to reactivation of latent mycobacteria • More common in immune compromised e.g. steroid treatment, HIV/AIDS • Miliary • Extensive caseous necrosis • Tissue destruction • Bacilli may enter bloodstream • Granulomas appear in other organs

• Chronic inflammation • Affectsalllayersofthebowelwall • Unknownaetiology • Non-caseatinggranulomas