Inflammation Flashcards
Inflammation
Reaction of vascularized tissue to injury
3 main functions of inflammation
Bring exudate to help in tissue healing
Bring exudate to tissue to destroy causative agent
Bring exudate to tissue to mediate local defense
2 types of inflammation
Acute
Chronic
Reaction phases of inflammation
Vascular
Cellular
Causes of inflammation
Microbial infections
Hypersensitivity
Physical agents
Irritants and corrosives chemicals
Tissue necrosis
Cardinal sign of acute infection
Redness (rubor) Heat ( calor) Swelling (tumor) Pain (dolor) Loss of function
Typical lab findings of inflammation
High neutrophil
High ESR
High acute phase proteins
Constitutional symptoms of inflammation
Pyrexia
Malaise
Anorexia
Nausea
Hematological change of inflammation
Increased erythrocytes sedimentation rate
Leukocytosis
When do you have eosinophilia
Allergic disorders and parasitic infections
When do you have lymphocytosis
Chronic infection
Viral infection
Whooping cough
When do you have monocytosis
Infectious mononucleosis
Bacterial infections
Why would you have anemia in inflammation
Inflammatory exudate with blood loss
Haemolysis ( bacterial toxins)
Anemia of chronic disorders
Why is there amyloidosis in inflammation
Happens in chronic inflammation with elevated serum amyloid A protein deposited in all tissues
Acute inflammation
Rapid onset and short duration inflammation with exsudation of protein rich fluid with a lot of neutrophils
Steps of acute inflammation
Transient vasoconstriction Vasodilation Increased blood flow to area with transient transsudation Increased fluid exudate Increased viscosity Stasis Margination Pavementing of leucocytes Emigration of leucocytes Chemotaxis Phagocytosis
Where does vasodilation happens ?
Precapillary arterial level
What causes calor and rubor
Hyperemia due to increased blood flow
What molecules cause vasodilation in acute inflammation?
Histamine
Nitric oxide
How is plasma able to escape into tissue ?
Thanks to increased vascular permeability
Why does viscosity of blood increases ?
Fluid loss in tissue makes RBC concentration higher
Immediate transient response
When mild injury , increased permeability at venules and small veins
Fast , short lived
Mediators of immediate transient response
Bradykinin
Histamine
Leukotriene
Delayed prolonged response
In moderate injury
After 2-12h
Last for hours to days
Affects venules and capillaries
Immediate sustained response
After severe injury
Cause cell death and detachment
All levels of micro circulation affected
Fluid leaked immediate and last for days
Mechanism of increased permeability
(Immediate transient)Endothelial gaps in venules due to myosin contraction caused by histamine bradykinin leukotrienes substance p c5a and c3a
(Delayed response)Structural reorganization of cytoskeleton due to endothelial cell retraction by IL1 TNF INFgamma
( immediate sustained injury )Direct endothelial injury with necrosis and detachment
(Leucocyte mediated injury-immediate sustained )neutrophils adhering to endothelium causing injury
Main cell of acute inflammation
Neutrophils
During acute inflammation , how is the number of developing neutrophils increased
Growth factors derived from inflammation stimulate myeloid precursors division
Steps of neutrophils action in acute inflammation
Margination
Rolling
Adhesion To Endothelium
Migration to interstitium with chemotactic gradient
Margination in acute inflammation
Stasis causes movement of leucocytes to periphery of endothelium
Neutrophils pavementing in acute inflammation
Neutrophils adhere to endothelium through adhesion molecules (rolling)
Endothelium lined with neutrophils
Emigration of neutrophils in acute inflammation
Motile leucocytes escape from blood
Occur mostly in venules except in lungs
Neutrophils life span
13 days
First leucocyte you move in viral and ricketsial infection
Lymphocytes
Dominant leucocyte in type I hypersensitivity
Eosinophils
Predominant leucocyte in typhoid fever
Macrophages
Chemotaxis in acute inflammation
Leucocyte migrate towards site of injury by chemotactic agents ( C5a, arachidonic acid, IL8)
Phagocytosis
A process in which a cell ingest solid particles
Stages of phagocytosis
Recognition and attachment
Engulfment
Killing and degradation
Opsonization
Particles are coated by serum proteins to enhance phagocytosis
Major opsonins
IgG
Fibronectin
C3b
2 types of bacterial killing mechanism
Oxygen dépendant mechanism
Oxygen independent mechanism
Species involved in oxygen dépendant phagocytosis
Hydrogen peroxide
Toxic Hypohalite ions (halogen and oxidase action to kill constituents)
Peroxide anions
Hydroxyl radicals
Nitric oxide
Oxygen independent phagocytosis
Phospholipase Lactoferrin (iron binding protein) Lysozyme muraminidase Defensins Low pH
Chronic granulomatous disease
Deficient oxygen dependent phagocytosis due to defects in gene
Lead to recurrent bacterial infections
Cell derived mediators of inflammation
Vasoactive amines Arachidonic acid Cytokines Lysosomal cpds Nitric oxide
Plasma derived mediators of inflammation
Plasma processes
clotting systems
Kinin systems
Preformed mediators
Histamine
Serotonin
Lysosomal enzymes
Histamine action (vasoactive amines)
Vascular dilatation
Immediate transient
IgE mediate hypersensitivity
Stored in mast cells basophils eosinophils platelets
Endothelial cell contraction
Increased membrane permeability
Makes endothelium sticky
Histamine release is stimulated by
Complement c3a, c5a and lysosomal proteins
Serotonin
Found in platelet
Acts like histamine
Serotonin release mediated by
Platelet aggregation Collagen Thrombin ADP antigen antibody complexes
Platelet activating factor action
Platelet aggregation
Vasoconstriction
Bronchoconstriction
Vasodilation at low concentration
Leucocyte adhésion
Chemotaxis
Oxidative burst
Arachidonic acid metabolism
Prostaglandins - vasodilators , pain , fever
Leucotrienes - neutrophils aggregation and chemotaxis ( LTB4) , increased vascular permeability ( SRS A) , endogenous negative regulators (lipoxins)
What type of drugs inhibit COX
NSAIDs like aspirin
What are the molecules inhibited by glucocorticoids to repress inflammation
Cox 1 Cox 2 Il1 TNF NO AA
Role of pro inflammatory cytokines
Growth Differentiation Chemotaxis Activation Cytotoxicity Immune regulation
Chemokines types
CXC a-chemokines (neutrophils)
CC b-chemokines (monocytes, eosinophils, basophils, lymph’s)
C y-chemokines (lymphocytes)
Nitric oxide
Vasodilatation
Reduces platelet aggregation and adhesion
Plasma protease types
Complement system - act on vessel wall, form MAC for lysis of microbes
Kinin system- produce bradykinin ( vascular permeability, vascular dilatation, smooth muscle contraction and pain )
Clotting system - fibrin in exudate, thrombin increase leucocyte adhésion, coagulation factor xii activate coagulation
Effect of c3a and c5a
Anaphylatoxins
Vasodilation
Release histamine
Chemotaxis (c5a)
C3b action
Opsonins
What molecules participate in termination of acute inflammation
Anti inflammatory cytokines ( il4, th2, il10, tgfb,
Glucocorticoids
Protein c
Morphologic patterns of acute inflammation
Serous inflammation
Fibrinous inflammation
Suppurative inflammation
Abcess
Empyema
Haemmorhagic inflammation
Catarrhal inflammation
Pseudomembranous inflammation
Membranous inflammation
Gangrenous inflammation
Serous inflammation
Proteinaceous exudates with few cells
Fibrinous inflammation
Fibrin rich exudate with shaggy strands
Suppurative inflammation
Numerous polymorphes and cell debris
Abcess
Localised collection of pus
Empyema
Collection of pus in a natural body cavity
Hemorrhagic inflammation
Vascular damage by highly virulent organisms and ischaemia
Catarrhal inflammation
Watery fluid secretion from epithelial surface with acute inflammation seen in common cold
Paeudomembranous inflammation
Superficial mucosal ulceration with formation of membrane like surface containing fibrin mucus and inflammatory cells but no epithelial cells
Membranous inflammation
Epithelial surface coated by fibrin , desquamated epithelial cells
Gangrenous inflammation
Vascular stasis leading to thrombus leading to necrosis. Inflammatory response against nécrose
How are drugs transported to site of infection
Through exudate
