Acute Inflammation Study Resources

Acute inflammation Types • • Serous: large fluid volume leaked form plasma e.g. skin blister Fibrinous: triggered by a severe injury, leakage of fibrinogen (then activated to fibrin) e.g. fibrinous pericarditis • Suppurative: abundance of living and dead neutrophils + dead cell/tissue debris = abscess (localised collection of pus) e.g. suppuratives meningitis • Ulcerative: occurs at or near tissue surface with local death followed by a local defect e.g. ulcerative gastritis (peptic ulcer) Causes • Infections: micro-organisms e.g. bacteria, viruses, fungi, parasites (pathogens) • Toxins: exogenous chemicals or endogenous agents produced by organisms e.g. gas gangrene • Physical agents: trauma, thermal, radiation • Foreign bodies: e.g. splinters, dirt, sutures – may have physical, chemical and infectious components • Ischaemia e.g. dead cardiac muscle after coronary artery occlusion • Immunological (hypersensitivity) reactions – misdirected Gross signs • Local features recognisable to naked eye o Skin, subcutaneous tissue o Internal organs (intra-operatively) • May or may not be a systemic response o Malaise (feeling sick) o Pyrexia (fever) o Changes in blood e.g. increased leukocyte count, changes to proteins • May or may not be localised e.g. pain in right iliac fossa in acute appendicitis • Five principal changes: redness, swelling and heat (due to changes in blood vessels), pain and loss of function (cause/consequence of injury) Microscopic Vascular events physiology • ↑ blood vessel diameter and blood flow → dilation of arteries and capillaries • ↑ blood vessel permeability o Mostly venules o Leakage of fluid (oedema) o Leakage of fibrin (exudate) o Leakage of red blood cells (diapedesis) Cellular events • Neutrophils from blood adhere to vessel walls (margination, rolling, adhesion) → emigrate between endothelial cells → move through injured tissue (chemotaxis) → take up pathogens, dead cells (phagocytosis) • Sometimes other leukocytes are involved e.g. inflammation due to a virus or autoimmune reaction trigger lymphocytes Molecular events • Many chemically diverse mediates effect the changes in cellular and vascular activity • Different mediators may have similar effects, but at different stages, while a mediator can have a variety of effects • Inflammatory mediator: pre-formed, synthesized after injury or plasma derived Inflammatory mediators • Pre-formed e.g. histamine, serotonin (platests, mast cells) – cause vasodilation, ↑ permeability • Newly synthesised: o Prostaglandins – vasodilation, pain, fever o Cytokines (e.g. TNF, IL-1) – chemotaxis, fever, appetite loss, ↑neutrophils o Nitric oxide – vasodilation, ↑permeability, chemotaxis • Outcomes Plasma derived o Kinins – generate vasoactive proteins o Complement – ↑permeability o Clotting factors –release other mediators from platelets, endothelium • Others: Selectins and Integrins – adhesion molecules for margination and transmigraton of neutrophils in blood vessels Complete resolution • Injuring agent and dead tissue are eliminated • Vascular and cellular events reverse • Normal structure and function is returned Extensive tissue loss – death • Injuring agent cannot be overcome • Inflammation progresses • Tissue dies, then putrefies → gangrene • Vital organs and cardiovascular system are overwhelmed by toxins → septic shock → death Healing by scarring • Defect filled with dead tissue, neutrophils and exudate • In-growth of new blood vessels & fibroblasts = granulation tissue • Granulation tissue matures → ↓ blood vessels & cells, ↑ collagen = scar/fibrosis Becomes chronic inflammation • Persistent inflammatory response • May or may not involve granulation tissue and fibrosis