Acute Inflammation

Inflammation & Healing

Recognition of injury Removal of injurious stimulus Repair of any damage

Injurious stimuli
Trauma Infection Physical (irradiation, thermal) Chemical Ischaemia (lack of blood i.e. oxygen) Immune reactions

Cell Injury Acute Inflammation Chronic Inflammation

Healing & Repair

Acute inflammation
Stereotyped response Delivers molecules and cells to site of injury

Acute inflammation
Vascular reaction leading to increase in blood flow, exudation of plasma proteins into tissues and emigration of neutrophil polymorphs into tissue

Acute myocardial infarction

Vascular changes
Vasodilatation & increased blood flow

Increased vascular permeability

Vascular permeability
Endothelial cell contraction Direct injury Leukocyte dependent injury Increased transcytosis Vascular neogenesis

Increase in vascular permeability

Loss of oncotic pressure in capillaries as vessels permeable to protein Excess fluid in tissues oedema fluid (protein rich exudate) swelling Precursors of protein mediators Fibrin scaffolding for effector cells Immunoglobulins

Polymorphonuclear neutrophil granulocytes

Mediator cells release inflammatory mediators Effector cells kill bacteria and fungi Attracted to site of inflammation and activated by chemotactic factors

How do neutrophil polymorphs get to site of inflammation?

Move in marginal zone of blood flow Changes in vessel wall - integrins, ICAM-1 & VCAM-1(leukocytes) & selectins (endothelial cells) induced by IL-1 & TNF Chemotaxis in tissues

Chemotactic Agents
N-formylmethionine peptides from bacteria C5a Leukotriene B4 IL-8

Leukocyte Activation
Production of arachidonic acid metabolites Degranulation & activation of oxidative burst Secretion of cytokines Modulation of adhesion molecules Expression of surface receptors for bacterial products, cytokines, C3b & Fc

Phagocytosis
Recognition lectins (mannose), Fc, C3b, Engulfment Killing oxygen dependent reactive oxygen intermediates (ROI) (H2O2 & myeloperoxidase) : oxygen independent lysosyme, elastase etc

Chemical Mediators Control Inflammation

Cell derived endogenous and newly synthesised Plasma derived

Cell derived endogenous (pre-formed)

Histamine (vasodilator, increases vascular permeability) mast cells Serotonin platelets Lysosomal enzymes neutrophils

Mast cells
Found along blood vessels Degranulate in response to physical injury (heat, cold, trauma), immune reactions (IgE), C3a & C5a, cytokines (IL-1 & IL-8), etc. Sentinel cells

Newly synthesised mediators

Arachidonic acid metabolites prostaglandins, thromboxanes, leukotrienes, lipoxins.(cell membranes) Platelet activating factor (mast cells) Tumour necrosis factor, IL-1 (macrophages) Nitric oxide (leukocytes) Oxygen metabolites (leukocytes)

Plasma enzyme cascades preformed in blood

Clotting Fibrinolysis Complement Kinin

Plasma Enzyme Cascades

enzyme A

Inactive enzyme B

Active enzyme B

+ fragment B

Inactive enzyme C

Active enzyme C + fragment C

Inactive enzyme D

Active enzyme D + fragment D

XIIa Kinin system: Bradykinin kallikrein Fibrinolysis: Fibrin degradation products plasmin Coagulation: fibrinopeptides thrombin

Complement: C3a, C5a, MAC

Vasodilatation
Prostaglandins Nitric oxide Histamine

Increased vascular permeability

Histamine & serotonin C3a & C5a Bradykinin LTC4, LTD4, LTE4 PAF

Chemotaxis
C5a LTB4 IL-1, TNF

Fever
IL-1 TNF Prostaglandins

Pain
Prostaglandins Bradykinin

Tissue damage
Neutrophil & macrophage lysosomal enzymes Oxygen metabolites Nitric oxide

Mast cell

Blood vessel

Plasma enzyme cascade Neutrophil polymorph

Macrophage

Can you explain signs of acute inflammation?

Rubor (redness) Calor (heat) Dolor (pain) Tumor (swelling) Functio laesa (loss of function)

Outcomes of acute inflammation

Resolution Healing by organisation (scarring) Progression to chronic inflammation Death

Plasma enzyme cascades

Mast cells

Bacterial products

Blood vessels

Neutrophil polymorphs

vasodilatation oedema

Neutrophil polymorphs in tissue