GP 06 - Acute Inflammation Flashcards
What are the two major phases of acute inflammation?
- Vascular changes
- Cellular events
What are the major vascular changes that take place during acute inflammation? What is the purpose of these changes?
- Changes in vascular diameter
- Changes in blood flow
- Changes in vascular permeability
These changes are designed to maximize the movement of plasma proteins and leukocytes out of circulation and into the site of infection or injury
What is exudate?
Fluid that has entered the tissues from the circulation during acute inflammation
How does vascular diameter change during acute inflammation? What causes this? What is the result? When does this occur?
Vasodilation begins early after injury and is induced by the activation of several mediators, notably histamine, on vascular smooth muscle. The result is increased blood flow.
What causes the heat and erythema (redness) at the site of inflammation?
The increased blood flow
How does vascular permeability change during acute inflammation? What causes this? When does it happen? What is the result?
Increased vascular permeability occurs shortly after vasodilation occurs. This happens by one of four mechanisms:
- Endothelial cell contraction in the postcapillary venule
- Direct endothelial injury by the injurious agent
- Endothelial injury by adherent leukocytes
- Increased transcytosis
The increased permeability and vasodilation lead to a loss of fluid, slower more turbulent blood flow, and increased viscosity, causing stasis. This allows for leukocytes to accumulate on and adhere to the epithelium, helping them to migrate through the vascular wall.
What changes occur with the lymph vasculature during acute inflammation?
Since lymph vessels are found in the interstitial spaces near sites of injury they may become dilated or inflammed (lymphangitis). If microorganism makes its way into the lymph vessel, it could travel all the way to a lymph node and cause an inflammation reaction known as lymphadenitis.
What are the two major cellular events that occur during acute inflammation?
- Leukocyte recruitment
- Leukocyte activation
What are the phases involved in leukocyte recruitment? What is the predominant leukocyte recruited during acute inflammation?
- Margination, Rolling, and Adhesion
- Migration across the endothelium and vessel wall
- Migration into the tissues toward a chemotactic stimulus
Neutrophils
What is and what causes margination?
Margination is movement of leukocytes towards the endothelial surface of a blood vessel, caused by blood flow stasis.
What causes leukocyte rolling?
Selectins expressed on leukocytes (L-selectin) and the vessel endothelium (E-selectin) transiently bind to each other, detach, and bind again. This causes the leukocyte to roll along the vessel wall.
What causes the expression of selectins?
Cytokines
When and how does leukocyte adhesion occur?
Leukocyte rolling interactions slow the leukocyte down so that integrins expressed by the leukocyte can firmly bind to the following ligands expressed on the endothelial surface:
- Vascular Cell Adhesion Molecule 1 (VCAM-1)
- Intercellular Adhesion Molecule 1 (ICAM-1)
Where and how do leukocytes migrate across the endothelium and vessel wall?
After adhesion, platelet endothelial cell adhesion molecule 1 (PECAM-1) aids the leukocyte in squeezing between endothelial cells. When the leukocyte reaches the basement membrane, it pierces it by secreting collagenases, and then enters the extravascular tissues.
Once in the extravascular tissue, how do leukocytes make their way to the injurious agent?
By chemotaxis
The chemotactic gradients they follow are to the following factors:
- Bacterial products
- Cytokines, IL-8
- C5a
- Leukotriene B4 (LTB4)
What activates leukocytes and what does leukocyte activation even mean?
Leukocyte activation means that the leukocyte can now perform the following functions:
- Phagocytosis
- Intracellular killing of engulfed pathogens
- Production of mediators that amplify the inflammatory reaction
Leukocytes become activated when bind to a microbe or dead cell
What are the primary ways leukocytes carry out intracellular killing?
- With ROSs
- Directly with enzymes
How do leukocytes sometimes damage the surrounding tissue during an inflammatory response?
- Accidental leakage of lysosomal contents to the extracellular space
- Phagosome leakage (regurgitation during feeding)
- Futile phagocytosis (molecule too large for phagocytosis)
- Engulfment of a cytotoxic material that results in phagocyte disintegration
What are the beneficial effects of inflammation derived from the cellular infiltrates and fluid exudate?
- Cellular Infiltrates - phagocytosis, microbial killing, release of mediators
- Exudate - toxin diultion, delivery of protective antibodies, firbin formation (fibrinogen), activation of plasma mediator system, cell nutrition, general promotion of immunity
What is serous inflammation? Give some common examples of serous inflammation
Exudation of cell poor fluid into spaces created by cell injury or into body cavities.
Examples:
- Blisters following burns or viral infections
- Pleural an pericardial effusions
- Ascites
What is fibrinous inflammation and where is it usually seen?
When vascular leakage during inflammation leaks fibrinogen as well, leading to the formation and deposition of fibrin in the extracellular space.
Typically seen when body cavity linings like the meninges, pericardium, or pleura becom inflammed
What is suppurative (purulent) inflammation and when does it usually occur? Give major examples of this
When the exudate contains large numbers of neutrophils, liquefied debris or necrotic cells, and edema fluid. Typically seen in inflammations caused by pyogenic bacteria that cause liquefactive tissue necrosis, such as staphylococci
Major examples are boils, furuncles, and abscesses
What is and what causes an ulcer? Do they usually occur with acute or chronic inflammations?
- An ulcer is a local defect, or excavation, of the surface of an organ or tissue that is produced by the sloughing of inflamed necrotic tissue
- Can be seen with both acute and chronic inflammations
What are the primary outcomes of acute inflammation?
- Complete resolution
- Progression to chronic inflammation
- Abscess formation
- Scarring (fibrosis)
What happens to the inflammation products after the insult has been resolved?
- The blood vessel heals itself
- Neutrophils undergoe apoptosis and get phagocytosed by macrophages
- Everything else gets absorbed by the lymphatics
What are the primary chemical mediators of inflammation and where do they come from?
- Plasma derived mediators are produced by the liver
- Cell derived mediators are produced at the site of inflammation by:
- endothelial cells at the site of inflammation
- tissue macrophages
- mast cells
- recruited leukocytes
How are the chemical mediators of inflammation deactivated?
- Spontaneous decay
- Enzymatic degradation
- Elimination
- Inhibition
List the major cell-derived and plasma-derived mediators?
- Cell-derived Mediators - vasoactive amines, arachidonic acid metabolites (e.g. - prostaglandins, leukotrienes, etc.), cytokines, ROSs, lysosomal enzymes
- Plasma-derived Mediators - complement system, coagulation & fibrinolytic systems, kinin system
Which mediator is responsible for the pain felt during inflammation?
Bradykinin
What is this an image of?
A blister
