Assist. Prof.Dr. Baydaa H. Abdullah Acute inflammation Assist. Prof.Dr. Baydaa H. Abdullah

The body’s response to injury Inflammation Is a protective response The body’s response to injury Interwoven with the repair process

Inflammation Types Acute (sec, mins, hrs) Chronic (days, weeks, months, yrs)

Causes of inflammation Bacterial Viral Protozoal Metazoal Fungal Immunological Tumours Chemicals, toxins etc Radiation

The Cardinal Signs of Acute Inflammation RUBOR CALOR TUMOR FUNCTIO LAESA

Cardinal signs of inflammation

Cardinal signs of inflammation

Cardinal signs of inflammation

Cardinal signs of inflammation

Cardinal signs of inflammation

Cardinal signs of inflammation

Inflammation The basis of the five cardinal signs Increased blood flow due to vascular dilatation gives redness and heat. Increased vascular permeability gives oedema causing tissue swelling. Certain chemical mediators stimulate sensory nerve endings giving pain. Nerves also stimulated by stretching from oedema. Pain and swelling result in loss of function. 2nd Yr Pathology 2010

Components of acute and chronic inflammation 2nd Yr Pathology 2010

Cell of the acute inflammatory response Polymorphonuclear leukocyte

The process of inflammation

The phases of inflammation FIRST THERE IS VASCULAR DILATATION followed by exudation of protein-rich oedema fluid which floods the area, dilutes toxins, allows immunoglobulins to opsonise bacteria and provides substrate (fibrinogen) for fibrin scaffold. SECOND THERE IS ACTIVE EMIGRATION OF POLYMORPHS through vessel wall and along the chemotactic gradient to the site of injury

The phases of inflammation THE VASCULAR PHASE OF INFLAMMATION Fluid escapes from vessels because of endothelial cell (EC) retraction, opening up gap-junctions. The vessels which are normally involved are the post-capillary venules where the EC have high affinity receptors for histamine. Severe EC injury leads to leakiness of all vessels capillaries, venules and arterioles - giving acute local oedema, e.g. blister formation after a burn.

Recognition and attachment PHAGOCYTOSIS Recognition and attachment Foreign objects coated with opsonins IgG and C3b which attach to receptors on polymorph surface. Engulfment Cell membrane fuses around an object: at the some time lysosomes empty into the vacuole, often before vacuole has time to seal - this gives rise to 'regurgitation during feeding' and enzymatic damage to surrounding tissue. Killing or degradation H2O2, hypohalous acid (HOC1) produced by myeloperoxidase and superoxides kill bacteria. Lysozyme digests them. 2nd Yr Pathology 2010

Summary of acute inflammation Stimulated by physical injury, infection, foreign body Resident macrophages and/or damaged endothelium, mast cells—IL-1, TNF, endothelin, histamine Vascular response: vasodilation, endothelial contraction, exudation of plasma Neutrophils: marginate (selectin-glycoprotein), adhere (integrin-CAM), extravasate (CD31), migrate (IL-8, chemotactic stimuli) Phagocytosis: recognition, engulfment, killing Phagocytosis receptors bind mannose, oxidized lipids, lipopolysaccharides, lipoteichoic acids, opsonins Killing is O2-dependent (respiratory burst, NADPH oxidase generated H2O2; myeloperoxidase generated HOCl; iNOS generated NO) or independent (lysozyme, lactoferrin, defensins) Responding leukocytes cause pain and loss-of-function via prostaglandins, enzymes Complete resolution; fibrosis, organization or scarring; abcess formation; progression to chronic inflammation Acute inflammation is a stereotyped response to a septic or sterile stimulus. Circulating neutrophils respond first. Response is receptor-mediated. Outcome varies according to the type and severity of initiating stimulus. Acute inflammation may progress to chronic inflammation, but more often chronic inflammation is not easily associated with an initial bout of acute inflammation.

Outcomes of Acute Inflammation Resolution of tissue structure and function with elimination of stimulus Tissue destruction and persistent inflammation Abscess pus-filled cavity (neutrophils, monocytes and liquefied cellular debris) walled off by fibrous tissue and inaccessible to circulation tissue destruction caused by lysosomal and other degradative enzymes Ulcer loss of epithelial surface acute inflammation in epithelial surfaces Fistula abnormal communication between organs or an organ and a surface Scar Causes distortion of structure and sometimes altered function Chronic inflammation Marked by replacement of neutrophils and monocytes with lymphocytes, plasma cells and macrophages Accompanied by proliferation of fibroblasts and new vessels with scarring

Outcomes of Acute Inflammation Resolution of tissue structure and function with elimination of stimulus Tissue destruction and persistent inflammation Abscess pus-filled cavity (neutrophils, monocytes and liquefied cellular debris) walled off by fibrous tissue and inaccessible to circulation tissue destruction caused by lysosomal and other degradative enzymes Ulcer loss of epithelial surface acute inflammation in epithelial surfaces Fistula abnormal communication between organs or an organ and a surface Scar Causes distortion of structure and sometimes altered function Chronic inflammation Marked by replacement of neutrophils and monocytes with lymphocytes, plasma cells and macrophages Accompanied by proliferation of fibroblasts and new vessels with scarring

Outcomes Resolution The complete restoration of the inflamed tissue back to a normal status. Inflammatory measures such as vasodilation, chemical production, and leukocyte infiltration cease, and damaged parenchymal cells regenerate. In situations where limited or short lived inflammation has occurred this is usually the outcome. Fibrosis Large amounts of tissue destruction, or damage in tissues unable to regenerate, can not be regenerated completely by the body. Fibrous scarring occurs in these areas of damage, forming a scar composed primarily of collagen. The scar will not contain any specialized structures, such as parenchymal cells, hence functional impairment may occur.

Outcomes Abscess formation A cavity is formed containing pus, an opaque liquid containing dead white blood cells and bacteria with general debris from destroyed cells. Chronic inflammation In acute inflammation, if the injurious agent persists then chronic inflammation will ensue. This process, marked by inflammation lasting many days, months or even years, may lead to the formation of a chronic wound. Chronic inflammation is characterised by the dominating presence of macrophages in the injured tissue. These cells are powerful defensive agents of the body, but the toxins they release (including reactive oxygen species) are injurious to the organism's own tissues as well as invading agents. Consequently, chronic inflammation is almost always accompanied by tissue destruction.

Patterns of Inflammation Serous Inflammation Marked by outpouring of thin fluid From blood serum, e.g. burn blisters Effusion from mesothelial cells lining the pleural, peritoneal and pericardial cavity Fibrinous Inflammation A feature of pericardial and peritoneal inflammation Vascular permeability allows larger molecules like fibrin to pass or procoagulant stimulus exists in the interstitium (e.g. cancer cells) Suppurative Inflammation Characterized by production of large amount of pus composed of neutrophils, necrotic cells and edema fluid Involves pyogenic bacteria e.g. Streptococci and Staphylococcus aureus Abscesses are focal localized collections of purulent inflammatory tissue caused by suppuration. Ulcers Local defect or excavation of the surface of an organ or tissue by sloughing of inflammatory necrotic tissue Acute stage - intense polymorphonuclear infiltration and vascular dilation in margin Chronic stage - margin and base develop fibroblastic proliferation, scarring and accumulation of lymphocytes, plasma cells and macrophages

Systemic inflammatory response Acute Phase Response Fever Acute-phase protein secretion from liver Leukocytosis Tachycardia, increased blood pressure Shivering, chills Anorexia, somnolence, malaise Septic shock