Inflammation Lecture 4 PDF

Inflammation  Intended Learning Outcomes (ILOs)  By the end of this lecture students should be able to: - Define inflammation and recognize the clinical manifestations of inflammation and its systemic effects. - Explain the vascular and cellular events in acute inflammation and describe its...

Inflammation  Intended Learning Outcomes (ILOs)  By the end of this lecture students should be able to: - Define inflammation and recognize the clinical manifestations of inflammation and its systemic effects. - Explain the vascular and cellular events in acute inflammation and describe its morphology. - Compare/contrast acute inflammation with chronic inflammation. - Recognize different types of acute inflammation and examples on each type. - Recognize the pathologic changes in acute and chronic osteomyelitis  It is a vital process by which living tissues react to injury as a protective response to: - Localize and - Eliminate the cause of cell injury.  Types of Inflammation Acute Chronic ▪ Rapid onset ▪ Gradual onset ▪ Short duration (minutes- ▪ Longer (days-years) days) ▪  productive ▪  exudative (granulation tissue) ▪ fibrosis Acute inflammation  Causes Physical : Chemicals: Infective: Trauma acids & alkalies bacteria, heat viruses, cold parasites irradiation fungi Tissue injury Inflammation  A. Acute inflammation Reactive changes in the first few minutes after tissue injury 1. Vascular changes including: Transient vasoconstriction followed by vasodilatation. Increased vascular permeability : d.t the effect of chemical mediators on the arterioles, capillaries, post capillary venules → Inflammatory exudate →swelling of the affected site 2. Leucocyte emigration: from the microcirculation & accumulation in the focus of injury Steps of leucocyte emigration: 1-Leucocyte margination 2-Rolling mediated by: selectins 3- Adhesion mediated by : Integrins 4- transmigration 5- chemotaxis 6- phagocytosis  Leucocyte emigration 3 1 2 4 5 C3a, C5a chemotaxis 0 6 Coating by IgG, C3b N.B: Some RBCs come out through inter endothelial gaps (Diapedesis) Chemotaxis Certain bacterial products & inflammatory substances (chemotaxins) are able to attract leucocytes towards them Both exogenous and endogenous substances can be chemotactic for leucocytes as: - Soluble bacterial products. - Components of the complement system, (particularly C5a and C3a). - Products of arachidonic acid (AA) metabolism, (leukotriene B4"LT-B4"). Phagocytosis  It is a process by which neutrophils and macrophages ingest bacteria and foreign particles.  Steps: - Opsonization:Specific surface receptors recognize components of the micro-organisms and dead cells or host proteins ( called opsonins) coat micro-organisms and target them for phagocytosis Most important opsonins are IgG and C3b. - Engulfment. - Killing and Degradation of Micro-organisms The most important microbicidal substances involved are : Reactive oxygen species (ROS), Reactive nitrogen species, particularly NO, Lysosomal enzymes.  Inflammatory exudate Pathogenesis Vascular permeability Arteriolar V.D Osmotic pressure of interstitial fluid Composition Fluid Cells Plasma fluid rich in fibrinogen (subjected to clotting, Ptn.4gm%, Sp.gr.1018) Neutrophils Macrophages Function: Function: 1.Dilute bacterial toxins 1- Phagocytosis 2.Bring antibodies to area of inflammation 2- Killed PNLs (pus cells) -Bacteriolysins -Aggluinins ( to fix the organism) Proteolytic enzymes -Opsonins( to coat the organism) 3. Fibrinogen fibrin Liquefy necrotic debris -Facilitate leukocyte movement -Localize infection Prepare area for repair  Chemical mediators of inflammation Types: vasodilatation Histamine, Prostaglandin, a) Cell derived mediators Nitric oxide b) Plasma derived Increased vascular Histamine, mediators permeability serotonin, substance P, bradykinin Leukocyte C3a, C5a recruitment (chemotaxis) fever IL1, TNF, Prostaglandin pain Prostaglandin, bradykinin  Signs of acute inflammation Red Hot Local pain Swelling Loss of function Fever, anorexia , headache , malaise ( FAHM) Leukocytosis Elevated acute phase proteins (CRP, systemic serum amyloid associated protein (AA), finbrinogen (leads to increased ESR) Lymphangitis and lymphadenitis Shock: with severe bacterial infection  Local signs in acute inflammation: Redness Hotness Swelling Pain d.t stretching of tissues by inflammatory exudates with irritation of nerve endings Loss of function Test yourself Opsonization by C3b is an important step in mediating which of the following leukocyte function: A. Chemotaxis B. Transmigration C. Margination D. Phagocytosis E. Exudation Opsonization by C3b is an important step in mediating which of the following leukocyte function: A. Chemotaxis B. Transmigration C. Margination D. Phagocytosis E. Exudation Which of the following factors participates in the formation of inflammatory fluid exudate: A. Increased intravascular osmotic pressure B. Increased vascular permeability C. Vasoconstriction D. Decreased osmotic pressure of the interstitial tissue Which of the following factors participates in the formation of inflammatory fluid exudate: A. Increased intravascular osmotic pressure B. Increased vascular permeability C. Vasoconstriction D. Decreased osmotic pressure of the interstitial tissue Types of acute inflammation Non Suppurative suppurative Localized -Serous Abscess -Serofibrinous Boil - Membranous Carbuncle -Catarrhal -Allergic Diffuse cellulitis -Hgic -Necrotizing A-Non suppurative inflammation 1-Serous inflammation: cc by: excessive clear watery fluid exudates with: Few protein content Few cellular content e.g.:- Blister following skin burns - Vesicles of herpes simplex 2-Serofibrinous inflammation: Exaudate: Rich in serous fluid & fibrin Ex. - Inflammation of serous sacs ( PPP) eg ; acute fibrinous pericarditis, fibrinous pleurisy -Lung alveoli in acute lobar pneumonia -gross : bread and butter appearance - fate: resolution or organization 3-Catarrhal inflammation: Exaudate: Excess mucous secretion Ex. Common cold 4-Membranous inflammation: ( pseudo membranous) Examples 1-Diphtheria 2-Bacillary dysentery of large intestine Pathogenesis Bacteria remains on the mucosal surface → powerful exotoxin Exotoxin→ diffuse to submucosa→ acute inflammation → exudates rich in fibrin → mixes with necrotic parts of mucosa membrane Grossly: Greyish white dirty membrane loosely attached and can be easily removed. 5-Allergic inflammation: Exudates: excess eosinophils Tissue & blood eosinophilia Ex. -Eczema -Urtecaria -Allergic rhinitis -Nasal polyps -Bronchial asthma 6-Haemorrhagic inflammation 7-Necrotizing inflammation B- Suppurative inflammation: Pathogenesis of pus formation: -Pyogenic organisms→ marked tissue destruction -Many PNL are killed by bacteria → pus cells → proteolytic enzymes→ liquefaction of necrotic tissue → fluid material mixes up with elements of inflammatory exudate→ pus Composition of pus: 1. Living and dead microorganisms 2. Liquefied necrotic tissue. 3. PNL and, many pus cells 4. Some RBCs. 5. Inflammatory fluid exudates  Localized suppurative inflammation 1- Abscess -Definition: Localized suppurative inflammation →cavity containing pus -Cause Pyogenic bacteria as staph. aureus -Site Subcutaneous tissue (most common)  Pathogenesis of abscess 1- Pyogenic organisms→ marked tissue destruction 2- Many PNL die → proteolytic enzymes →liquefy the periphery of the necrotic area →pus The abscess is formed of 3 zones Central zone : necrotic tissue Mid zone : pus Peripheral zone: (pyogenic membrane = congested vessels+ PNLs+ organism ) 3-The abscess enlarges by further necrosis & liquefaction of the surrounding inflamed zone until staph. Bacteria ( staphylococcus) produce coagulase enzyme which helps localization 4-The tension inside the abscess cavity gradually ↑d.t increase in the amount of fluid →increased tension →pain 5-The abscess always tries to open & discharge its contents outside e.g.; Abscess in subcutaneous tissue → narrow tract which connects abscess cavity with surface outside (sinus) (blind end deeply & open end on the surface ) 2- Furuncle (boil): Small abscess Related to hair follicle or sebaceous gland Site: Face, back of neck ,axilla 3-Carbuncle: Multiple loculi of pus separated by fibrous tissue strands Open on the surface by multiple openings Site: Back of neck & scalp Common predisposing factor→ Diabetes Causative organism → Staph. aureus  Abscess “Complications” -Chronic abscess: if acute abscess is not drained -Blood spread: toxaemia, septicaemia, pyaemia -Lymphatic spread: lymphangitis, lymphadenitis -Complications of healing: ulcer, keloid, sinus, fistula Skin Ulcer  Sinus Narrow tract which connects abscess cavity with surface outside ( It has a blind end deeply & open end on the surface )  Fistula Definition: Abnormal tract lined by septic granulation tissue connecting 2 cavities or between hollow viscera & the surface  Diffuse suppurative inflammation Cellulitis Definition: Diffuse type of suppurative inflammation Sites: Subcutaneous tissue→ cellulitis Mucous membrane → Phlegmonous inflammation Cause Streptococci secrete →fibrinolysins, streptokinase, hyaluronidase →spread of infection Acute hematogenous osteomyelitis Acute hematogenous osteomyelitis  Predisposing factors: - Age: common in children (3-10 years) - Sex: more in boys - Trauma: forms hematoma  Causative organism: staphylococcus aureus (commonest), also may be streptococci, Haemophilus influenza  Route of infection: via blood stream  Source of infection: it follows bacteraemia from septic focus as tonsillitis, upper respiratory tract infection, abscess  Bones affected: any bone especially femur, tibia, and humerus  Site of infection: metaphysis of long bones is more affected as it is more exposed to trauma and blood circulation is slow  Fate of Acute Inflammation Healing/Repair Tissue destruction and scarring Acute Chronicity Resolution Inflammation Injurious agent persists (TB) Interference with healing Restoration of normal Progression - Local -Lymphatic (lymphangitis and lymphadenitis) -Blood (bacteraemia, septicaemia, pyaemia) - Natural passages (ureter)  B. Chronic inflammation: If persists for weeks or months after initial injury Cause: -Progression from acute inflammation -Recurrent episodes of acute inflammation -Chronic inflammation de novo Types: 1-Chronic non specific inflammation 2-Chronic specific inflammation (granulomas) Cloaca Involucrum  Differences between acute & chronic inflammation Acute inflammation Chronic inflammation Onset Sudden Gradual Duration Short Long Vascular phenomenon Prominent Less prominent Local (cardinal)signs Prominent Less prominent Toxaemia Acute Chronic Cells Neutrophils - Lymphocytes, plasma cs, macrophages macrophages, fibroblasts Fate Healing Fibrosis Progression Chronic Test yourself  A 95-year-old woman touches a pot of boiling water. Within 2 hours, she has marked erythema of the skin of the fingers of her hand, and small blisters appear on the finger pads. This has led to which one of the following inflammatory responses? A Fibrinous inflammation B Granulomatous inflammation C Purulent inflammation D Serous inflammation E Ulceration  A 95-year-old woman touches a pot of boiling water. Within 2 hours, she has marked erythema of the skin of the fingers of her hand, and small blisters appear on the finger pads. This has led to which one of the following inflammatory responses? A Fibrinous inflammation B Granulomatous inflammation C Purulent inflammation D Serous inflammation E Ulceration Which of the following is true about pseudomembranous inflammation: a. A severe form of suppurative inflammation affecting mucus membranes b. It develops in the intestine in case of amoebic dysentery c. It develops in the throat in case of diphtheria d. Characterized by an exudate rich in eosinophils e. It is formed of a true membrane that is firmly adherent to the underlying tissue Which of the following is true about pseudomembranous inflammation: a. A severe form of suppurative inflammation affecting mucus membranes b. It develops in the intestine in case of amoebic dysentery c. It develops in the throat in case of diphtheria d. Characterized by an exudate rich in eosinophils e. It is formed of a true membrane that is firmly adherent to the underlying tissue Thank you