Pathology Lecture (3-4) PDF

 2- Cellular events Transmigration of leucocytes First chemotaxis Second phagocytosis Last Transmigration of leucocytes in the end of this process formation of cellular exudate N.B :- inflammatory exudate Consists o...

 2- Cellular events Transmigration of leucocytes First chemotaxis Second phagocytosis Last Transmigration of leucocytes in the end of this process formation of cellular exudate N.B :- inflammatory exudate Consists of both fluid and cellular exudate  Chemotaxis Definition :- Movement of leukocytes toward the inflammatory area along a chemical gradient Chemotactic agents for leukocytes include:- 1. Exogenous factors: - Products from bacteria - Toxins 2. Endogenous factors: - Cytokines, especially chemokine, lymphokines - Complement components especially C5a. - leucotriens B4 (LTB4).  Phagocytosis Definition :- It is the ingestion and destruction of solid particles (tissue debris, living or dead bacteria and other foreign cells) by phagocytic cells mainly neutrophils and macrophages (monocytes) Two main types of phagocytic cells 1- Polymorphonuclear neutrophils (PMNs) : Seen in early in acute inflammation (1-2 days), called microphages( phagocytosis of small particles) 2- Macrophages : Seen in late in acute inflammation (2-3 days)& In chronic inflammation phagocytosis of small& large particles Steps of Phagocytosis 1. Recognition and attachment is facilitated by Opsonization which is the coating of particles for recognition & attachment by phagocytic cells. The most important opsonins are IgG and C3b  IgG are bound to the phagocytic cell surface receptor Fc portion.  C3b bind to cellular receptors for C3b 2. Engulfment ingesting of the attached opsonized particle by pseudopodial extensions from the surface of the leucocyte in this step result in fromation of phagosome which is a membrane-bound vesicle that encloses opsonized particle 3. Degradation &killing Phagosomes fuse with cytoplasmic lysosomes and form phagolysosomes then degradation &killing occurs either by 1. Oxygen dependent mechanism the most important 2. oxygen independent mechanism much less effective 1. Oxygen dependent mechanism(oxidative burst) Formation of phagolysosomes →rapid increase in oxygen consumption & activates of 1. NADPH oxidase lead to production of the oxygen metabolites(hydrogen peroxide (H2O2) hydroxyl radical (HO).) 2. leucocyte enzyme myeloperoxidase 2. oxygen independent mechanism The pH of the phagolysosome is low as 4.0 inhibit the growth of many types of microorganisms and activation of many proteins and enzymes include e.g 1. Lysosyme 2. Lactoferrin 3. Major basic protein of eosinophils. 4. Other proteins as defensins  Chemical Mediators Of Acute Inflammation Definition:-any substances that secreted and activated to help inflammatory process Chemical mediators that are responsible for vascular and cellular events. Sources of chemical mediators Exogenous Bacterial as E.coli Endotoxins 2- Endogenous 1- Cell -Derived chemical mediators produced locally by cells at the site of inflammation – Leukocytes ,Endothelial cell...... etc (e.g Histamine) 2- Circulating plasma proteins “synthesized by liver”, C3b and C5a) )  Biologic effects of mediators 1. Vascular phenomena: Vasodilatation→histamine, nitro oxide & prostaglandins Increase vascular permeability→Histamine,sertonin & Bradykinins 2. chemotaxis:→C5a, leukotriene B4 and lysosomal & bacterial products 3- Phagocytosis → C3b and Opsonins. 4. Pain →bradykinin and prostaglandins 5- Fever prostaglandins, IL6, TNF. 6- Tissue damage lysosomal enzymes , oxygen free radicals, Nitric oxide  Fate of Acute Inflammation 1. Resolution 2. Spread (Septicaemia , toxemia, lymphangitis, Thrombophlebitis, lymphadenitis) 3. Fibrosis (Scarring) 4. Abscess Formation 5. Progression to Chronic Inflammation Resolution of acute inflammation 1. Inflammatory fluid:- passes into lymphatics 2. Dead cells :- Phagocytosis 3. Repair by regeneration is the replacement of damaged cells by new cells.  Acute inflammation Suppurative Non-suppurative (purulent ) (Without pus ) (With pus) 1- Serous …..excess clear fluid in Localized Diffuse exudate 2- Fibrinous….. excess fibrin in exudate 3- Serofibrinous.. excess both fluid &fibrin 4- Catarrhal ……excess mucus - Abscess - Cellulitis 5- Pseudomembranous (fibrino- necrotic) - Furuncle - Suppurative 6- Hemorrhagic….. B.V. damage - appendicitis - anthrax. - Diffuse septic 7- Necrotizing/ gangrenous Carbuncle peritonitis 8- Allergic  PUS Definition is purulent inflammatory exudate Characters of pus Thick, turbid yellowish fluid Composition of pus 1. Large number of neutrophils and pus cells 2. The liquefied necrotic material 3. bacteria 4. Fluid exudates Abscess Definition:-acute localized suppurative inflammation with pus fromation Sites:- common in skin, subcutaneous tissue and may occurs internal organs like brain, lung, liver, kidney,……. Cause:- Staphlococcus aureus secreted coagulase enzyme that lead localization  Pathogenesis of abscess I. The virulence of pyogenic organisms cause: 1) Marked tissue destruction 2) Attraction of large number of neutrophils. 3) Death of many neutrophils (pus cells)  release their lyzosomal enzymes II. The Lyzosomal enzymes that release from pus cells Lead to Liquefaction of necrotic tissue and fibrin, result in PUS formation Pathological Features - Early: Two zones - Later : Three zones a) A central necrotic core. b) A mid zone of pus. c) The peripheral zone : pyogenic membrane which is formed by fibrin and help in localize the infection. - Further enlargement Fate of abscess 1-Small abscess: Pus is may be absorbed, followed by healing. 2- Large abscess:  pointing & rupture (spontaneous evacuation)  healing. Or surgical drainage 3-- Complications Complications: 1-Spread of infection → lead to enlarged size 2- Complications of evacuation and healing: a)Ulcer b)Sinus. c)Fistula. e) Hemorrhage e.g. hemoptysis with lung abscess. f) Rupture: e.g. brain abscess. 3-Chronicity. Chronic breast abscess 4- Compression effects: e.g. in case of brain abscess Ulcer: local defect of the epithelial surface due to defect healing Sinus: it is blind ended tract between abscess and epithelial surface due to chronic discharge to surface Fistula: is a track connecting two epithelial lined surfaces  Carbuncle - It is multiple communicating deep subcutaneous abscesses, opening on skin by multiple sinuses - occurs in special sites in the back of the neck and scalp, where the skin and subcutaneous tissues are thick and tough due to dense fibrous septa dividing the subcutaneous tissue into compartments, - Common in Special patient= diabetics (low immunity).. - Furuncle or boil :- - It is a small abscess related to hair follicles.  Cellulitis Definition it is diffuse acute suppurative inflammation Cause :- Strept haemolyticus  secreted enzymes as 1. Hyaluronidase (spread factor) 2. Streptokinase(fibrinolysin) which dissolve fibrin and facilitate the spread of infection. Sites:- Loose subcutaneous tissue & Areolar tissue; orbit, pelvis, … Common in Special patient= diabetics (low immunity)..  Abscess Cellulitis Localized Diffuse suppurative Type suppurative inflammation inflammation Cause Staph aureus--> Strept hemolyticus  organism secreted organism secreted coagulase enzyme hyaluronidase & Pathogenesis that lead to fibrin streptokinase enzymes deposition that dissolve the fibrin localization Site Any tissue Loose connective tissue Thick, less red cells, Thin, sanguineous, and Pus few necrotic tissue extensive necrosis Spread Less More  Non- suppurative(non-purulent) inflammation 1-Serous Inflammation Characterized by excessive serous fluid poor in fibrin. Examples: 1. Skin blisters due to skin burns. 2. Epidermal vesicles due to herpes simplex viral infection. 3. Inflammation of serous membranes (pleura, pericardium and peritoneum)  2- Fibrinous Inflammation  Characterized by an exudate rich in fibrin, with a little fluid component.  Examples:  Lobar pneumonia  Inflammation of serous membranes. e.g fibrinous pericarditis 3- Serofibrinous Inflammation Inflammation of serous membranes rich in both fluid exudate & fibrin,  4- Catarrhal Inflammation Characteristics: A mild form of acute inflammation of mucous membranes  excess mucus secretions Examples: 1. Catarrhal rhinitis (common cold) 2. Catarrhal appendicitis. 5- Pseudomembranous (Membranous) Inflammation  Characteristics & pathogenesis:  A severe form of acute inflammation of mucous membranes characterized by replacement of the normal mucous membrane by a false membrane composed of patches of necrotic tissue & fibrin  Virulent bacteria secreting exotoxins  mucosal necrosis and marked inflammation  false membrane  Examples: 1- Diphtheria 2-Bacillary dysentery. 5- Pseudomembranous (Membranous) Inflammation  Defintion :- Inflammation of prolonged duration “weeks to years ” in which: inflammation, tissue destruction & healing occurs in same time. Causes  follow acute inflammation due to failure of immunity  start chronic by gradual onset due to one or more of the following: 1. Infection with resistant organisms e.g. T.B. 2. Non-living irritants as foreign bodies e.g. silicosis (inhalation of silica particles into lungs) 3. Development of autoimmunity e.g. rheumatoid arthritis.  Types Of Chronic Inflammation  Chronic Non-specific Inflammations:  Usually follow acute inflammation, e.g. chronic abscess.  Why termed "nonspecific“??? 1. All show the same microscopic features of chronic inflammation (chronic inflammatory cells, fibrosis….) 2. We can’t identify the cause.  Chronic Specific Inflammations:  Usually start chronic.  Show microscopic features of chronic inflammation with additional features specific for each type as (bilharzia ova in cases of bilharziasis).  The majority of chronic specific inflammations occur in the form of granulomas.  Granulomas Definition & Pathological Characteristics:  A special form of chronic inflammation characterized by nodular collections of many macrophages with lymphocytes, plasma cells, giant cells and fibrosis.  The macrophages commonly change into  epithelioid cell ( enlarged macrophage)  multinucleated giant cells( fused of many macrophages  Some granulomas may exhibit central necrosis. Types Of Granulomas:  Infectious granulomas: Most of these granulomas are necrotizing. Examples: T.B, leprosy, bilharziasis  Foreign body granulomas: Mostly non-necrotizing granulomas. Examples: silicosis  Granulomas of unkown aetiology: Mostly non-necrotizing granulomas. Examples: Sarcoidosis & Crohn's disease.  According to type of inflammation 1-Acute inflammatory cells  Neutrophils. Pyogenic. Dead neutrophils = pus cells.  Macrophages. They are derived from blood monocytes & tissue histiocytes  Possible variations e.g.  Eosinophils in allergic inflammation  Lymphocytes & plasma cells in viral infections  Few neutrophils in bacillary infections as Typhoid 2-Chronic inflammatory cells  Lymphocytes. Plasma cells  Macrophages  Giant cells. They are most commonly seen in granulomas  Eosinophils in chroinc parasitic infection e.g bilharziasis