ACUTE INFLAMMATION
Objectives: To define: 1) the purpose and
consequences of acute inflammation, 2) the hallmark cells and events in acute
inflammation, 3) the role of vasopermeability in acute inflammation, 4) the role of
leukocytes in acute inflammation, and 5) the possible outcomes of acute inflammation.
SUMMARY
Mechanistically, acute inflammation can be generally divided into two broad categories:
vascular events and white blood cell events. Vascular events can be separated into three
distinct steps: (1) vasoconstriction, (2) vasodilation, and (3) vasopermeability. In
response to the initial trauma, a neurologic response results in vasoconstriction of the
blood vessels leading to the injured tissue, with resultant in decrease of blood flow.
This vasoconstriction is followed almost simultaneously by vasodilation which allows an
increase of blood flow into the traumatized tissue. Associated with the vasodilation is
increased vasopermeability or leakiness of the blood vessels, with the resulting
outpouring of plasma proteins and fluids into the tissue. This increased vasopermeability
is likely important in a variety of ways, including the dilution of microbial toxins at
the sites of infection allowing access of important serum proteins, such as complement and
antibodies to enter the tissue site to promote antimicrobial and phagocytosis by
leukocytes, as well as the influx of fibrinogen, and resultant fibrin formation to limit
the spread of infection.
In addition to vascular events, trauma triggers a series of characteristic white blood
cell events which include: (1) margination/pavementing, (2) emigration of leukocytes, (3)
aggregation of leukocytes, and (4) phagocytosis. These events are initiated as a result of
the increased vasopermeability of the blood flow in the bloodstream slow, white blood
cells begin to move to the periphery of the blood vessel and begin to stick to the
vascular endothelium. This process, known as margination/pavementing, represents the first
step in the movement of white blood cells from the lumen of the vessel into the tissue.
Once the leukocytes have adhered to the vascular endothelial cells, they then migrate
between endothelial cells and into the tissue by a process known as emigration. Once in
the tissue, the leukocytes begin to migrate towards the site of trauma in response to the
generation of a gradient of chemical signals known leukocyte chemotactic factors. The
migrating leukocytes next begin to accumulate or aggregate at the sites of trauma and
begin to ingest both microorganism, as well as tissue debris. This ingestion is referred
to as phagocytosis. Phagocytosis can be divided into three distinct steps: (1) attachment
of particle to the leukocyte, (2) ingestion and degranulation, and (3) microbicidal
activity and degradation. These three steps result in both the removal and destruction of
both microorganisms, as well as tissue debris within the traumatized site and are critical
factors in not only host defense, but also the ultimate resolution of the inflammatory
process.
ACUTE INFLAMMATION OUTLINE
I. Purpose, Definition and Causes
II. Hallmarks of Acute Inflammation
A. Time
B. Cells
III. Vasopermeability (VP)
A. Role of vascular endothelium
B. Role of VP factors
IV. Major Leukocyte Events in Inflammation
A. Adherence/margination
B. Migration/chemotaxis
C. Phagocytosis
D. Killing and degradation
A. Margination of Leukocytes
1. Role of chemotactic factors
2. Role of adhesion molecules
B. Migration/Chemotaxis
1. Chemotactic factors
2. Chemotactic factor receptors
C. Phagocytosis
1. Recognition
2. Engulfment/ingestion
3. Degranulation
D. Killing Mechanisms
1. Oxygen independent
2. Oxygen dependent
E. Degradation
1. Proteases
2. Hydrolases
V. Regulation of Leukocyte Function
1. Stimulus-receptor coupling to biological response
VI. Other Roles of Leukocytes
1. Regulation
2. Repair
Required Reading: Pathologic Basis of Disease (PBD), Robbins et al., pp. 51-92.
Optional Reading: Pathology, Rubin and Farber, pp. 36-58.