Inflammation and the Acute Inflammatory Response

Question 1

Inflammation is basically

Answer 1

Rxn of vascularized tissue to injury

Question 2

Types of edema

Answer 2

Exudate - inflammatory edema…high protein content, specific gravity > 1.020…from increase in blood vessel permeability that is characteristic of inflammation **contains cellular and chemical mediators critical to inflammation

Transudate - low protein content and specfic gravity < 1.012…filtrate of plasma caused by increase in hydrostatic pressure or decrease in plasma oncotic pressure…no association with vascular permeability

Question 3

Vascular flow change - acute inflammation

Answer 3

Vasodilation…increased blood flow to affected tissue

Question 4

Vascular permeability - acute inflammation

Answer 4

Increases in microvasculature…escape of exudate to injured tissue…blood remaining in vessels is concentrated and moves slows

Question 5

2 mechanisms to increase vascular permeability

Answer 5

Endothelial cell contraction (retraction)

Leukocyte mediated endothelial injury

Question 6

Retraction

Answer 6

Mainly in venules
Endothelial cells shorten, leading to widening of junctions…exudate through gaps
Rapid
Mediated by lots of chemical mediators

Question 7

Leukocyte mediated endothelial injury

Answer 7

Mostly in venules
Leukocytes adhere to endothelial cells and become activate…release toxic substances that cause endothelial injury and detachment of cells from inner wall of blood vessels

Delayed onset

Question 8

Adhesion

Answer 8

When stasis occurs, leukocytes within blood stream move toward inner wall of blood vessels (margination)

Rolling leads to adhesion

Adhesion molecules are mediators that bind…selectins involved in rolling, integrins promote firm adhesion

Modulation of adhesion molecules necessary to promote binding to one another

Question 9

Redistribtuion of adhesion molecules from within cytoplasm to cell surface where they are available for binding example

Answer 9

P-selectin normally bound to Weibel-Palade bodies in endothelial cytoplasm…chemical mediators cause migration to endothelial membrane

Question 10

Induction of adhesion molecule synthesis example

Answer 10

E-selectin…not found within endothelial cells unless induced by chemical mediator of inflammation…not immediately available

Question 11

Increase in binding affinity of adhesion molecules example

Answer 11

LFA-1/ICAm-1 interaction…leukocyte activation leads to conformational changes of adhesion molecules

Question 12

Transmigration across endothelium

Answer 12

Diapedesis

Leuko squeezes through gaps and into tissues…homophilic adhesion to PECAM-1 …**neutrophil is predominant cell that transmigrates in acute

Question 13

Two types of chemoattractants

Answer 13

Exogenous - from bacteria

Endogenous - produced by injured host

Question 14

Mechanism of chemotractant inducement of movement

Answer 14

Chemoattractant binds receptor on leukocyte membrane…activates intracellular phospholipase C which triggers series of events increased intracellular calcium…causes cross linked of actin…forms pseudopod and moves in direction of density gradient…process of pseudopod formation occurs repeatedly until it reaches sources

Question 15

Phagocytosis steps

Answer 15

Recognition and attachment
Engulfment
Killing

Question 16

Recognition - phago

Answer 16

Enhanced by coating of object with opsonins (fragment of IgG and compllement C3b)…opsonins bind to leukocyte

Question 17

Engulfment - phago

Answer 17

FOrms phagosome…lysosomes fuse to form phagolysosome

Question 18

Killing and degradation options

Answer 18

Oxygen dependent killing - consumption of oxygen in phagolysosome causes oxidative burst…involves peroxide-myeloperoxidase-halide system which is covalent insertion of halide into bacterial molecules

Oxygen independent killing - involves other substances in lysosomes that don’t need oxygen (BPI, lysozyme, lactoferrin)

Acid hydrolases degrade

Question 19

Vasoactive amines

Answer 19

Histamine and serotonin

Question 20

Histamine

Answer 20

Preformed and immediately available
Found in mast cells
Dilations of arterioles, increase vascular permeability, redistribute P-selectin
Causes some tissue damage

Question 21

Serotonin

Answer 21

Found iwhtin platelet granules…preformed and similar to histamine

Question 22

Complement system

Answer 22

Lyses microorganisms by generating membrane attack complex
C3a and C5a cause vasodilation and increase permeability…also help release histamine from mast cells
C5a - potent chemoattactant and stimulates movement of leukocytes
C3b - opsonin

Question 23

Kinin system

Answer 23

When factor 12 (Hageman factor) of clotting system comes in contact with injured tissue, becomes activated and activates cascade

Bradykinin- increases vascular permeability…contributor to pain
Kallikrein - activates Hageman factor and produces more brady kinin…also chemoattractant

Question 24

Clotting system

Answer 24

Triggered by factor 12

Produces thrombin…binds to protease activated receptors (PARs) on membranes of cells…redistribtuing of P-selectin and production of prostaglandins

Question 25

AA metabolites

Answer 25

Phospholipases that have been activated will release AA into cells…metabolized by 1 of 2 pathways

Question 26

Cyclooxygenase pathway

Answer 26

Produces prostaglandins

Question 27

Prostacyclin

Answer 27

PGI2

Vasodilation…inhibits aggregation

Question 28

Thromboxane A

Answer 28

Vasoconstriction and promotes aggregation

Question 29

PGD2 and PGE2

Answer 29

Vasodilation and increased permeability of post-cap venules…PGD2 is chemoattractant for neutrophils

Question 30

Prostaglandins can cause

Answer 30

Pain ad fever

Question 31

Lipooxygenase pathway

Answer 31

Produces leukotrienes and lipoxins

Question 32

Leukotriene B4

Answer 32

Chemoattractant

Question 33

Leukotriends C4,D4, and E4

Answer 33

Increase permeability
Vasoconstriction
Bronchospasm

Question 34

Lipoxins A4 and B4

Answer 34

INhibit neutrophil chemotaxis and ability of neutrophil to adher to endothelium…terminates

Question 35

Cytokines

Answer 35

Synthesizes by activated leukocytes

Question 36

Interluekin 1

Answer 36

Similar to TNF

Promote leukocyte adhesion
Promote synthesis of prostaglandins and others
Cause fever, loss of app, increased sleep

Question 37

Interleukin 8

Answer 37

Member of chemokines (powerful chemo attractant)…chemotaxis for neutrophils

Question 38

Nitric oxide

Answer 38

SOluble gas released by endothelial and macrophages

Vasodilator
Interacts with Oxygen free rads to produce antimic substances

Inhiits some of cellular events of inflammation and keeps response under control