Acute and Chronic Inflammation

Part 1: Acute Inflammation

Samer Nassif, MD

Inflammation : DefinitionsInflammation is the primary host response to injury.

It is a defensive mechanism.

It is a protective response: Destruction of injurious agent if possible.Isolation of the injurious agent if not rapidly eliminated.

Stimuli Causing Inflammation1- Infections: bacteria, viruses, parasites, fungi, toxins.

2- Tissue necrosis: ischemia, infarct, hypoxia, trauma, chemical injury, irradiation, burns.

3- Foreign bodies may cause trauma + necrosis, or carry germs to trigger inflammation.

4- Immune reactions, acute (hypersensitivity) or chronic (autoimmune diseases).

Acute Inflammation: Progressive Kinesis of Vascular & Cellular Events

Inflammation & Repair work in parallelInflammatory reaction may be too strong Hypersensitivity.Inflammatory reaction may persist at low grade.Chronic injury of tissue will occur in long term inflammation.

Repair may be too excessive fibrous scars will form.Repair is incomplete granulomas or abcess will be formed.Tissue remodeling will occur when repair is delayed.

Acute Inflammation is an immediate responseRapid in onset

Short in duration

Components of Acute Inflammation

Two major progressive componentsof acute inflammationVascular:

Change in caliber vasodilatation

2. Change in structure increased permeabilityCellular: Leukocytes undergoMarginationRollingAdhesionMigrationActivation

Physiopathology of Acute InflammationImmediate changes in vascular caliber are induced by histamine: dilatation involves arterioles at first, then capillaries.

Cardinal signs of inflammation are: rubor, tumor, calor, dolor, and loss of function.

Physiopathology of Acute Inflammation (contd)Increased vascular permeability causes outpouring of serum & cells into surrounding tissues: Transsudate is an osmotic leakage of serum fluid; Exudate is leakage of plasma protein & cells. Purulent exudate (pus) contains necrotic cells & bacteria.

Acute Inflammation: Leakage of Fluid into Surrounding Tissues

Increased Vascular Permeability: WHY?1- Normal: no gaps2- Immediate transient response: venules3- Direct endothelial injury: all vessels4- Leukocytes-mediated cell injury: venules5- Increased traffic in ECs (transcytosis): VEGF6-Repair processes: Leaky new vessels

Inflammation: Cellular Events

Chemotaxis of Leukocytes in Acute InflammationSelectins and Integrins mediate adhesion of leukocytes over endothelial cells.Cytokines( Histamine, TNF, IL-1) lead to expression & activation of such adhesion.Adhesion molecules in intercellular junctions of endothelial cells guide WBC migration.Collagenases pierce basement membrane of blood vessels to reach extravascular tissue.Tissue integrins in ECM help leukocytes to migrate & bind to injurious agent in ECM.

Leukocyte ChemotaxisLocomotion oriented with a chemical gradient: Exogenous chemoattractants are bacterial products.Endogenous chemical mediators are complement components (C3a, C5a), leukotriene B4, & cytokines (TNF, IL-1, IL-8).

Activated leukocytes extend filopodia through actin reorganization for locomotion.

Leukocyte integrins attach to extracellular matrix glycoproteins.

Activation of LeukocytesRecognition of injury: -Receptors for microbesover cell surface: (TLRs)-Receptors to chemokines and lipids (G-proteins)-Receptors for opsonins which coat microbes-Receptors for cytokines after contact + microbesRemoval of injury:-Increase in Ca++-Activation of enzymes (protein Kinase C, Phospholipase A)-Phagocytosis follows

Acute Inflammation:Functions of Leukocytes Receptors

PhagocytosisRecognitionAttachmentEngulfmentKilling (respiratory oxidative burst)Degradation (Reactive oxygen and nitrogen species generate free radicals)

http://sphweb.bumc.bu.edu/otlt/mph-modules/eh/eh_immunity_b/eh_immunity_b3.html

http://sphweb.bumc.bu.edu/otlt/mph-modules/eh/eh_immunity_b/eh_immunity_b3.html

Defects in Leukocyte FunctionDefects in leukocyte adhesion (integrins & selectins) cause vulnerability to recurrent bacterial infections. -LAD1: Defect of beta chain (CD11/CD18) of integrin. -LAD2: Mutation of the sialylated oligosaccharide which is the anchoring system for E-selectin.

Defects in phagolysosome function: Chediak-Higashi syndrome induces delayed microbial killing, defective degranulation, giant neutrophil granules and immunodeficiency.

Defects in microbicidal activity: Chronic granulomatous disease has impaired oxidative burst from defective NADH oxidase: membrane (X-linked) or cytoplasmic (AR) mutations.

Acquired defects, due to thermal injury, bone marrow suppression, cancer, immunodeficiencies, diabetes mellitus, hemodialysis or sepsis.