Inflammation 2 PDF

Inflammation 2 By Dr/ hend salah abo safia Assistant professor of pathology  Leukocyte Recruitment and Activation The sequence of events in the recruitment of leukocytes from the vascular lumen to the extravascular space consists of (1) margination and rolling a...

Inflammation 2 By Dr/ hend salah abo safia Assistant professor of pathology  Leukocyte Recruitment and Activation The sequence of events in the recruitment of leukocytes from the vascular lumen to the extravascular space consists of (1) margination and rolling along the vessel wall; (2) firm adhesion to the endothelium; (3) transmigration between endothelial cells; (4) migration in interstitial tissues toward a chemotactic stimulus. o Rolling, adhesion, and transmigration are mediated by the interactions of adhesion molecules on leukocytes and endothelial surfaces.  Margination: This process of leukocyte accumulation at the periphery of vessels Rolling :The cells bind and detach and thus begin to tumble on the endothelial surface The weak and transient interactions involved in rolling are mediated by the selectin family of adhesion molecules (Selectins ) E-selectin expressed on endothelial cells; P-selectin present on platelets and endothelium; L-selectin on the surface of most leukocytes.  Adhesion: The firm adhesion is mediated by integrins expressed on leukocyte cell surfaces interacting with their ligands on endothelial cells. Integrins are normally expressed in a low-affinity form and do not adhere to their specific ligands until the leukocytes are activated by chemokines. TNF and IL-1 activate endothelial cells to ↑expression of ligands for integrins. Engagement of integrins by their ligands delivers signals to the leukocytes that lead to cytoskeletal changes that mediate firm attachment to the substrate.  oTransmigration. leukocytes migrate through the vessel wall primarily by squeezing between cells at intercellular junctions. This extravasation of leukocytes, called diapedesis Migration of leukocytes is driven by chemokines produced in extravascular tissues, which stimulate movement of the leukocytes toward their chemical gradient. After passing through the endothelium, leukocytes secret collagenases that enable them to pass through the vascular basement membrane.  Chemotaxis leukocytes movement toward sites of infection or injury along a chemical gradient Chemotactic agents: Both exogenous and endogenous substances can be chemotactic for leukocytes, including Bacterial products and pathogenic organisms Cytokines, especially chemokines Components of the complement system ***** C5a Leukotrienes from neutrophils  Type of Emigrating Leukocytes : Cocci attract PMNL. Bacilli attract monocytes. Viruses attract lymphocytes. Parasites and hypersensitivity reactions attract eosinophils  Phagocytosis and Clearance of the Offending Agent Phagocytosis means ingestion of particulate material by cells. Phagocytosis consists of three steps (1) recognition and attachment of the particle to the ingesting leukocyte; (2) engulfment, with subsequent formation of a phagocytic vacuole; (3) killing and degradation of the ingested material Most important phagocytes: neutrophils (microphages) and macrophages ↑↑↑ efficiency by opsonization of the microbes Opsonins: coat microbes and target them for phagocytosis a) Antibodies b) C3b cleavage product of complement c) plasma lectins called collectins  Intracellular Destruction of Microbes and Debris Reactive oxygen species (ROS) (oxidative burst) Reactive nitrogen species derived from nitric oxide [NO] Lysosomal enzymes (acid hydrolases and elastase)  Neutrophil Extracellular Traps (NETs). Definition: These traps are extracellular fibrillar networks that are produced by neutrophils in response to : infectious pathogens (mainly bacteria and fungi) inflammatory mediators (such as chemokines, cytokines, complement proteins, and ROS). NETs contain a framework of nuclear chromatin with embedded granule proteins, such as antimicrobial peptides and enzymes.  Role The traps provide a high concentration of antimicrobial substances at sites of infection prevent the spread of the microbes by trapping them in the fibrils. Formation: In the process, the nuclei of the neutrophils are lost, leading to death of the cells. NETs also have been detected in blood neutrophils during sepsis. The nuclear chromatin in the NETs, which includes histones and associated DNA, has been postulated to be a source of nuclear antigens in systemic autoimmune diseases, particularly lupus, in which affected persons react against their own DNA and nucleoproteins  Types of acute inflammation: 1- Abscess. Localized 2- Furuncle (boil). Suppurative 3- Carbuncle. Diffuse Cellulitis( Phlegmonous ) Types Non-suppurative  Catarrhal  Pseudo-membranous  Serous inflammation  Fibrinous inflammation  Serofibrinous inflammation  Hemorrhagic  Allergic  I – Non suppurative inflammation: Catarrhal inflammation: *Affect the mucous membranes (mild type). *The best example is common cold or coryza. *characterized by formation of abundant exudates rich in mucous. *Microscopically: The mucous lining cells are swollen, some cells are ruptured. The submucosa shows hyperaemia, oedema and cellular infiltration with leucocytes.  Pseudo-membranous inflammation :  This is a severe type of acute inflammation characterized by formation of a membrane like structure on the affected area.  Examples: Diphtheria and bacillary dysentery.The causative bacteria remain on the mucosal surface and produce powerful exotoxin which causes patchy mucosal necrosis. *Grossly: the mucosa is congested and shows a yellowish pseudo-membrane which is adherent to the underlying structures and if it is removed it leaves a bleeding surface. *Microscopically:  The pseudomembrane is formed of fibrin threads, causative microorganisms, necrotic mucosal cells, acute inflammatory cells and some RBCs.  The submucosa is hyperaemic, oedematous and infiltrated by polymorphs.  Serous inflammation :  Characterized by the formation of abundant fluid exudate rich in proteins in serous sacs.  Examples: Pleural effusion and epidermal blisters following burns.  Fibrinous inflammation :  In this type the exudate is rich in fibrin.  Increased vascular permeability → fibrinogen accumulates within exudates. →fibrin forms.  In inflammation of the lining of body cavities: meninges, pericardium, and pleura.  Histologically: Fibrin = eosinophilic meshwork of threads or as an amorphous coagulum  Resolution through fibrinolysis + clearance by macrophages  If not resolved: organization → scarring→ deleterious effect. within the pericardial cavity→restrictive cardiomyopathy Hemorrhagic inflammation: The exudate is rich in blood and is caused by virulent organisms that cause damage of blood vessels as in cases of small pox. Hemorrhagic enteritis Hemorrhagic pneumonia  Allergic inflammation It is characterized by exudation of abundant fluid containing eosinophils e.g. urticaria. It is caused by antigen antibody reaction.  Suppurative inflammation *Definition: it is a severe type of acute inflammation which is characterized by formation of pus. It may be primary or complicate any other type of inflammation. *Causative organism: staphylococci, streptococci, gonococci and meningococci. *Pathogenesis of pus formation:  Bacterial toxins necrosis of the tissue particularly in the center.  The causative bacteria strongly chemotactic, they attract a large number of polymorphs.  Some polymorphs will be killed in the battle against the microorganism  pus cells (Pus cell is a dead polymorph).  The dead polymorphs and bacteria release proteolytic enzymes which liquefy necrotic tissues and result in the formation of pus.  Pus is composed of: Living and dead microorganisms Living and dead polymorphs. Liquefied Necrotic tissues. Some blood cells and globules of fat. Inflammatory exudate.  A- Localized suppurative inflammation: 1- Abscess: *Definition: localized area of suppurative inflammation. *Causative organism: pyogenic microorganisms particularly: staphylococci produce coagulase enzymes  fibrin threads  surround and localize the area of inflammation. Its center is a mass of necrotic leukocytes and tissue cells. Rim of preserved neutrophils around the necrotic focus Surrounded by vascular congestion and parenchymal and fibroblastic proliferation  *Fate of abscess:  If the abscess is not evacuated it will rupture at the point of least mechanical resistance.  If the abscess is evacuated the swelling subsides, cavity collapses , healing by granulation tissue. *Complications of abscess: 1-Complications of healing: a- Ulcer: Which is an area of epithelial discontinuity. b- Sinus: Which is blind ended tract opening to the surface and discharging pus. c- Fistula: which is a tract with two openings e.g. one to the surface and the second to a mucous membrane. 2 -Chronicity: If the abscess is not completely drained. 3-Spread of infection by: a- Lymphatics causing lymphangitis and lymphadenitis. b- Blood causing toxaemia, or septicaemia. c- Septic thrombophlebitis causing pyaemia.  2 - Boil or Furuncle: It is a localized suppuration in hair follicle or sebaceous gland. 3 - Carbuncle:  It is a type of localized suppuration in the subcutaneous tissue, particularly in the region of the back.  It is characterized by formation of multiple loculi containing pus which open on the surface by multiple openings (sinuses).  It is a serious condition and it occurs in diabetic patients.  B- Diffuse suppurative inflammation: Phlegmonous inflammation:  It is a diffuse form of acute inflammation which occurs in the subcutaneous tissues (cellulitis) and mucous membranes e.g. the appendix.  It is caused by streptococcal infection  spreading factor (hyaluronidase enzyme and fibrinolysin) dissolve fibrin, thus helping the spread of infection.