Acute Inflammation2023.pdf

Acute InflammationDr Emer [email protected] Reading for this course: Learning objectivesAfter this lecture you should be able to:•Define inflammation•List the causes of acute inflammation•Explain briefly the process of acute inflammation•Describe the clinical manifes...

Acute InflammationDr Emer [email protected] Reading for this course: Learning objectivesAfter this lecture you should be able to:•Define inflammation•List the causes of acute inflammation•Explain briefly the process of acute inflammation•Describe the clinical manifestations of acute inflammation (local and systemic)•Classify different patterns of acute inflammation•Mention the outcomes of acute inflammation •The host response (reaction) to cellular injury•The roles of inflammation are: •To contain & isolate injury •To destroy invading microorganisms/ inactivate toxins•To prepare the tissue or organ for healing and repair •Inflammation can sometimes be inappropriately triggered or poorly controlled → problems allergies, chronic diseases •Inflammation in a given site is named by adding the suffix -itisto the name of the organ or tissueWhat is Inflammation? Acute versus chronic inflammation are distinguished by the duration and the type of infiltrating inflammatory cellsInflammation AcuteChronic—Timecourse<48hours>48hours(weeks/months/years)—CelltypeNeutrophilsMononuclearcells:(Lymphocytes)Macrophages,Lymphocytes,Plasmacells Acute Inflammation•Rapid host response to tissue injury•Serves to deliver leukocytes and antibodies to sites of infection or tissue injury •Destroys, dilutes or walls off the injurious agent•Triggers repair•Protective response can be potentially harmful Local Clinical signs of Acute Inflammation•Rubor = redness•Tumor = swelling•Calor = heat•Dolor = pain(described by Celsus 1st. Century AD)•Functio laesa = loss of function(added by R. Virchow in 20thcentury) Heat Redness Swelling Pain Loss of functionCelsus (1 AD)Virchow (1902) Local clinical features of AI Causes of AI•Microbial infections: bacterial, viral, fungal, etc.•Tissue necrosis (ischemia, trauma, physical/chemical)•Foreign bodies •Hypersensitivity reactions Sequence of Events in AI 1) Vascular Changes associated with AI•Increased Vascular Flow •Increased Vascular PermeabilityManifestations of Acute inflammation : Manifestations of Acute inflammation :Alteration of vascular caliberfollowing very brief vasoconstriction (seconds), vasodilation leads to increased blood flow and blood pooling creating redness and warmth (rubor and calor)Changes of microvasculatureincreased permeability for plasma proteins and cells creating swelling (tumor). Fluid loss leads to concentration of red blood cells and slowed blood flow (stasis)Emigration of leukocytes from microcirculationdue to stasis and activation leads migration towards offending agent !Va s c u l a r c h a n g e s a n d f l u i d leakage during acute inflammation lead to edemaiean excess of fluid in the interstitial tissue or serous cavities called exudate!Exudate•A filtra te o f b lo o d p la s m a mixed with inflammatory cells and cellular debris. •permeability of endothelium is usually altered•high protein content.Increased permeability →leakage of plasma proteins Mechanisms of increased vascular permeabilityContraction of endothelial cells elicited by Histamine, leukotrienes, bradykinin etc.Short lived (15-30 mins)Direct damage to endothelium resulting in endothelial cell (EC) necrosis and detachment.Neutrophilsthat adhere to endothelium during inflammation may injure the ECTr a n s c y t o s i sis the increased transport of fluids and proteins thru the EC via channels. ↑blood flowRedness (erythema)Heat"Clinical manifestations ↑vascular permeabilitySwelling (oedema)Loss of function"Clinical manifestationsSwollen kneeSwelling of larynx 2) Cellular component of inflammation!Neutrophils (polymorphonuclear cells)!Phagocytosis -By macrophages (+ non professional)!Release of chemical mediators Leukocyte migration to the inflammatory siteFluid leaves the vessel (edema) causing leukocytes to settle-out of the central flow and role along the endothelial surface followed by penetration through the wall of the vessel. In order forleukocytes to leave the vessel lumen, endothelial cells need to be activated and upregulate adhesion molecules that can interact with complementary adhesion molecules on leukocytesUp-regulation of adhesion molecules on endothelial cells is induced by an array of inflammatory mediators such as TNF, IL-1, histamine and others produced by tissue resident inflammatory cells.Selectins (weak)Integrins (strong) Nature of leukocyte infiltrate varies with timeMyocardium following heart attack and resultant necrosis Leukocytes are attracted towards the site of injury along a chemical gradient of chemo-attractants in a process called chemotaxis.Exogenous (non-self) andendogenous (self) stimuli can act aschemoattractantsExogenous: Bacterial products Endogenous:Components of the Complement systemCytokines (chemokines)Chemotaxis of Leukocytes Neutrophil and macrophage effector functions eliminate pathogens and noxious substances•Phagocytosisof pathogens and noxious agents•Release of bactericidaland cytotoxicmolecules PhagocytosisSteps:1Recognition and attachment2Engulfment and fusion of phagosomeand lysosome3Killing and degradation of ingested material •Phagosomesfuse with Lysosomalgranulesto form phagolysosome: bacteriocidaland cell degrading enzymes digest the microbe/dead cells•Killing of microbes is also achieved by production of Reactive Oxygen and Nitrogen SpeciesKilling and degradation of phagocytosed microbes Thevascular&cellularresponsesofinflammationaremediatedbysolublefactors(derivedfrombloodplasmaorproducedbysomecells)&triggeredbytheinflammatorystimulus.Acute Inflammatory Mediators LOCAL MEDIATORSSYSTEMIC MEDIATORSAcute Inflammatory Mediators Systemic effects of Inflammation:•Fever-elevation of body temp by 1-4°C•Elevated conc of acute-phase proteins (C-reactive protein, fibrinogen and serum amyloid protein)•Leukocytosis (15-20,000cells/µL)•Increased pulse and BP, rigors, chills, malaise•In severe cases "Sepsis Morphologic Patterns of Acute Inflammation (EXUDATE)•Serous(watery)•Fibrinous(hemorrhagic, rich in FIBRIN)Fibrinous exudate•Suppurative(PUS or Purulent exudate)Staphylococci-pyogenic bacteria•Ulcerative (shedding of inflamed necrotic tissue) •SEROUSINFLAMMATION: –Serous inflammation is marked by the outpouring of a thin fluid with proteins but little cells. –e.g.the skin blister resulting from a burn or viral infection represents a large accumulation of serous fluidMorphologic Patterns of Acute Inflammation •FIBRINOUS INFLAMMATION –more severe injuries with greater vascular permeability, larger molecules like fibrinogen pass the vascular barrier, and fibrin is formed and deposited–A fibrinous exudate is characteristic of inflammation in the lining of body cavities, such as the meninges, pericardium and pleuraMorphologic Patterns of Acute Inflammation •SUPPURATIVE or PURULENT INFLAMMATION –Certain bacteria (e.g., staphylococci) produce this localized suppuration and are therefore referred to as pyogenic (pus-producing) bacteria–characterized by the production of large amounts of pus or purulent exudate consisting of neutrophils, necrotic cells, and edema fluidAbscesses: localized collections of purulent inflammatory tissue caused by suppuration buried in a tissue, an organ, or a confined space.Morphologic Patterns of Acute Inflammation }Acute bacterial meningitis}Normal brain •NECROTISING/ULCERATIVE INFLAMMATION –An ulcer is a local defect of the surface of an organ or tissue that is produced by the sloughing (shedding) of inflammatory necrotic tissue–encountered in inflammatory necrosis of the mucosa of the mouth, stomach, intestines, or genitourinary tractMorphologic Patterns of Acute Inflammation OUTCOMES OFACUTE INFLAMMATION Adverse outcomes of inflammation•Resolution(healing)–±Fibrosis–abscess formation•Spread: sepsis•Chronicity (chronic inflammation)Abscess formationFibrosis in heart•Localised collection of pus (neutrophils, necrotic cells, oedema fluid)•Bacterial infection or secondary infection of necrotic tissue•Often require surgical drainage !Acute inflammation:–Causes–Vascular dilation & leakiness, role of neutrophils –Clinical effects: Local and systemic manifestations–Morphology –suppurative/serous/fibrinous/ulcerative–OutcomesSummary