Body Response To Tissue Damage: Acute Inflammation Flashcards
Stimuli of acute inflammatory response
Microorganisms especially bacteria Trauma Ischaemic necrosis Radiation damage Chemical damage
Define acute inflammatory response
The most common response of the body tissues to an area of nearby damage
Purpose of acute inflam response
Destroy/neutralise the damaging agent
Liquefy and remove dead tissue
Prepare the damaged area for healing
Inflammatory exudate
Facilitates inflammatory response
Derived from blood components:
Fluid
Fibrin
Neutrophils
Few macrophages and lymphocytes
-> fluid dilutes toxins, carries nutrients, mediates antibodies
-> fibrin, activated from soluble fibrinogen by the coagulation cascade
-> neutrophils phagocytosis of tissue and necrotic debris
Stages of exudate formation
1) small blood vessels adjacent to the area become dilated with increase blood flow, blood flow then slows. Dilation and loss of axial flow caused by substances released by dead tissue.
2) endothelial cells swell and partially retract-> internal capillary lining no longer intact
3) vessels become leaky-> water, salts and some small plasma proteins get through.-> exudatation. Tissue becomes swollen. Especially fibrinogen.
4) circulating neutrophil polymorphs initially adhere to the swollen endothelial cells (margination) then actively migrate through the vessel basement membrane (emigration) to the area of damaged tissue.
Stages of neutrophil margination, emigration and migration
1) rolling-> neutrophils roll along the endothelium in close contact
2) adhesion-> neutrophils firmly adhere to the endothelium
3) aggregation-> adjacent neutrophils adhere to each other and undergo shape change
4) emigratatin-> through vessel walls down a conc gradient of chemotactic factors
Endothelium activation
IL-1 TNF and chemo lines increase the expression of adhesion molecules on the endothelium. Eg selectins which cause neutrophil rolling
Chemokines on the endothelial surface bind receptors on neutrophils and signal leukocyte expression of integrins
Intercellular adhesion molecule 1 promotes adhesion of neutrophils and lymphoid cells
Vascular cell adhesion molecule 1 promotes adhesion of lymphoid and monocyte cells
Increased synthesis of platelet activating factor-> vascular permeability
Increase synthesis of nitric oxide-> vascular dilation
C5a fragments of complement induce increased expression of complementary cell adhesion molecules on neutrophils
Variants of inflammatory exudate composition
Purulent-> neutrophils dominate the composition-> material is liquified to form pus. Contains both active and dead neutrophils, fibrinogen and necrotic cells. More server infections
Serous-> when fluid is the major component-> swelling
Fibrinous-> mainly fibrin, often seen in relations to serous surfaces eg pericardium.
Catarrhal-> high mucous content
Functions of exudate components
Fluid-> dilute/buffer locally produced toxins, allow diffusion of mediators, flowing so removing and bringing
Fibrin-> forms a network of fibrin threads-> scaffold for lymphocytes to migrate?
Neutrophils-> kill Microorganisms and break down damaged tissue via phagocytosis
Macrophages-> present in small numbers initially, phagocytosis of dead material and produce growth factors and Chemokines also assist repair.
Role of histamine
Cellular mediator
Pre formed
Released from mast cells, basophils and platelets
Mast cells activated by trauma, the contents of damaged cells, IgE (allergy), C3a, C5a
->transient dilation of arterioles
->increases permeability in venues
Role of prostaglandins
Cellular mediator
Derived by local synthesis from arachidonic acid
COX pathway:
COX1-> normally present in cells
COX 2-> induced for inflammation
Thromboxane TXA2-> aggregates platelets and causes vasoconstriction
Prostacyclin PGI2-> inhibits platelet aggregation and dilated vessels
Stable prostaglandins, PGE2, PGF, PGD2-> vasodilation and increased vascular permeability. PGE-> pain.
Role of leukotriens
Cellular mediator Lipoxygenase pathway Leukotrienes-> LTC4, LTD4, LTE4 Vasoconstriction and increased permeability in venues LTB4-> leukocyte adhesion to endothelium
Role of platelet activating factor
Cellular mediator Synthesised by mast cells and basophils -> stimulated by IgE release Also synthesised by platelets, neutrophils, monocytes and endothelium -> vasoconstriction -> increased vascular permeability -> platelet aggregation -> stimulates arachidonic pathway 1000x more potent than histamine
Role of Chemokines
Cellular mediators
Secreted by leukocytes and endothelial cells in response to tissue damage
Locally bound to extra cellular matrix and heparin-sulphate protecoglycans of cells
Establish a concentration gradient away from the focus of inflammation
Rolling neutrophils encounter Chemokines on the endothelial cells-> activates Chemokines receptors-> signals activate leukocyte integrins-> mediate adhesion and emigration
Role of nitric oxide
Cellular mediator
Locally synthesised by the endothelium and macrophages via nitric oxide synthase
-> vasodilation
-> increases vascular permeability
-> reactive oxygen intermediate-> cell and bacterial killing
Role of the complement system
Plasma derived mediators
C3a-> increases vascular permeability by liberating histamine
C5a-> increases vascular permeability by liberating histamine, chemotactic to neutrophils, induces endothelial cell adhesion molecules
C345-> chemo attractive to neutrophils
C3b-> opsonises bacteria and facilitates neutrophil phagocytosis
Role of the kinins
Plasma derived mediators From precursors by proteolytic cleavage Activated by Hageman factor (factor XII) of the coagulation cascade-> cleaves prekallikrein to kallikrein-> stimulate kinnogen to form bradykinin -> increased vascular permeability -> pain -> activated complement system
Role of the thrombolytic pathway
Plasma derived mediator Plasmin -> activated the complement system -> activates Hageman factor -> lyses fibrin to fibrin degradation products-> increase permeability of vessels
Mediators of vasodilation
Histamine Prostaglandins Nitric oxide Bradykinin PAF
Mediators of increased permeability
Histamine C3a C5a Bradykinin Leukotrienes PAF Nitric oxide
Neutrophil adhesion
IL-1 TNFa PAF LTB4 C5a Chemokines
Mediators of neutrophil chemotaxis
C5a
LTB4
Bacterial components
Chemokines
Mediators of fever
IL-1
TNF
Prostaglandins
Mediators of pain
Prostaglandins
Bradykinin
Tissue necrosis mediators
Neutrophil lysosomal granule contents
Free radicals generated by neutrophils
Drug therapy of acute inflammation
Steroids-> inhibit phospholipase A2-> limits arachidonic acid production etc
Aspirin and indinethacin-> inhibit the COX pathway
The four cardinal signs of inflammation
Calour-> heat
Dolor-> pain
Rubor-> redness
Tumour-> swelling
Clinical signs of acute inflammation
Malaise Fever Pain Rapid pulse Neutrophil leukocytosis Elevated ESR Increased acute phase proteins-> IL-1 induced
