5 Key Concepts of Inflammation

Ans:1. Recognition of injurious agent

2. Recruitment of leukocytes
3. Removal of the agent
4. Regulation of the Response
5. Resolution/repair of any damaged tissue
What is inflammation?
Ans:It is a complex reaction to an injurious agent involving both vascular event
s and cellular events that lead to the accumulation of fluid and WBCs in the inj
ured area. It is a protective response.
Acute Inflammation vs Chronic Inflammation (general characteristics)
Ans:Acute inflammation? Rapid onset, short duration (hours to days), fluid accum
ulation (edema) and neutrophils.
Chronic inflammation? Variable onset, longer duration (weeks, months, years), ma
crophages and lymphocytes and new vessel formation and fibrosis.
Exudate vs Transudate vs Edema vs Pus
Ans:
- Exudate: Inflammatory extracellular fluid that is rich in protein, cellular de
bris and has a specific gravity above 1.020 (goes along with structural changes
in the vessel that occur with inflammation).
- Transudate: A fluid with low protein, few cells and a specific gravity less th
an1.012. (This is really an ultra filtrate of blood plasma).
- Edema: Excess of fluid in the interstitial spaces or in serous cavities- can b
e either an exudate or transudate. (effusion in the lungs, ascietes in the abdom
en)
- Pus: Also referred to as a purulent exudate- rich in neutrophils, making it ap
pear whitish clinically.
Stimuli for acute inflammation
Ans:
1. Infection- these are typically bacterial and fungal. Occasionally, viruses an
d parasites can initiate an acute response with neutrophils. (see gross image be
low)
2. Trauma- physical and chemical
3. Tissue necrosis -Often secondary to ischemia, but from all causes (see micros
copic image below)
Three Components of Acute Inflammation:
Ans:
1. Vascular Response
2. Cellular Response
3. Chemical Mediators
Vascular Response of Acute Inflammation
1. Vasodilation: There is a very transient period of vasoconstriction; then the
vessel dilates to allow more blood and blood components to get to the site of in
jury. (First in arterioles, then in capillaries.) This is the cause of a warm an
d red area in the case of subcutaneous or superficial injury. Induced by several
mediators including histamine and nitric oxide that act on the vascular smooth
muscle.

2. Increased permeability: The normally intact endothelium becomes leaky during

acute inflammation to allow for various proteins and cells to escape into the in
jured tissue. This essentially results in edema. The immediate transient respons
e refers to the formation of endothelial gaps in venules, one of the first event
s to occur and lasts between 15 and 30 minutes. Certain chemical mediators act o
n these vessels leading to endothelial cell contraction.
- Neutrophils can release several toxic oxygen species and proteolytic enzymes t
hat cause endothelial detachment.
Transient Response vs Delayed Response
Ans:
1. Transient response mediated by histamine and leukotrienes.
2. Delayed response starting about 2 hours and lasting about 12 hours mediated b
y kinins and complement.
3. Delayed prolonged responses typically occurring after a burn (thermal injury)
.
Cellular Events in Acute Inflammation
Ans:
Neutrophils predominate in the first 24 hours eventually to be replaced by macro
phages (after 24 hours through 48 hours). Leukocytes ingest and kill bacteria an
d other microbes. Eventually, the macrophages clean up the debris.
Review of events as the leukocytes travel to sight of injury (6 Steps)
Ans:
1. Margination: Collection of leukocytes near the endothelial surface within the
vessel lumen. The slowing down of the blood flow during inflammation helps this
process as more cells are concentrated at the periphery of the vessel lumen.
2. Adhesion: Complicated process mediated by several types of molecules: selecti
ns, immunoglobulin family, integrins and mucin-like glycoproteins. Complimentary
molecules are exposed on leukocytes and the endothelium. The process is mediate
d by cytokines.
3. Diapedesis: Transmigration of leukocytes across the endothelium. This is enha
nced by the presence of adhesion molecules present in the intercellular junction
s (PECAM or CD 31).
4. Chemotaxis: Process whereby leukocytes move in the tissue to the exact site o
f injury via a concentration gradient. This occurs via chemoattractants such as
complement, leukotrienes, as well as cytokines.
5. Recognition: When leukocytes arrive at their destination, they express severa
l receptors that recognize external stimuli. The stimuli include bacterial produ
cts, opsonins and cytokines.
6. Removal: This occurs primarily through phagocytosis
Types of Adhesion Molecules Involved in Acute Inflammation
Ans:
Selectins
- Selectins bind through their lectin domain.
- Three different proteins that all act to mediate the adhesion of leukocytes to
endothelium.
- Many of these are only expressed on cytokine-activated endothelium.
- Mediate the 'rolling' of leukocytes
Immunoglobulin family
- These include ICAM-1 (Serves as ligand for integrins and has a major role in a
dhesion, arrest and transmigration).
- VCAM-1 (Mediates adhesion of eosinophils, monocytes and lymphocytes).
Integrins
- Large family of proteins that mediate cellular interactions between other cell
s or between the extracellular matrix (surrounding tissue).

- Integrins are expressed on leukocytes and platelets.

What are the chemical mediators involved in acute inflammation?
Ans:
Histamine, Seratonin, Complement, Kinin System, Clotting System, Platelet activa
ting factor (PAF), Cytokines, Chemokines, Nitric oxide
Histamine and Acute Inflammation
Ans:
Preformed and present predominantly in mast cells, but also in basophils and pla
telets. Degranulation of mast cells occurs with physical injury, as well as with
several types of immune reactions. Histamine causes vasodilation of arterioles
and increased permeability of venules and mediates the immediate transient respo
nse
Seratonin and Acute Inflammation
Ans:
Present in platelets and neuroendocrine cells. It has similar effects as that of
histamine and is released when platelets aggregate after contact with collagen
(often exposed with injury). PAF also stimulates the release of serotonin from p
latelets.
Kinin System and Acute Inflammation
Ans:
This is also a system of factors and reactions that act to ultimately cause vas
odilation during inflammation. It consists of plasma proteins that release vasoa
ctive peptides (bradykinin). This substance increases vascular permeability, vas
odilation and pain.
Platelet activating factor (PAF) and Acute Inflammation
Ans:
This is released from activated basophils (also from platelets and other leukocy
tes) and has multiple effects: stimulates platelets, causes vasoconstriction and
bronchoconstriction and at very low concentrations causes vasodilation and incr
eased permeability. It also enhances leukocyte adhesion and chemotaxis.
Major Cytokines of Acute Inflammation
Ans:
Major functions of TNF and IL-1
- Induce synthesis of endothelial adhesion molecules
- Induce synthesis of other chemical mediators
- Induce enzymes involved with matrix remodeling
- Increase the thrombogenicity of enodothelium
- TNF acts to prime neutrophils
NO and Acute Inflammation
Ans:
Nitric oxide:
- Potent vasodilator
- Some antimicrobial actions
- Reduces platelet aggregation and adhesion
- Regulates leukocyte recruitment and other aspects of inflammation
Patterns of Acute Inflammation
Ans:
- Congestion (increased blood in vessels)
- Edema (fluid in interstitial spaces)
- Influx of neutrophils and often tissue necrosis.
- Depending on the timing of the lesion, one may also see evidence of repair alr
eady in progress (to be discussed later).

Serous inflammation
Ans:
Characterized by accumulation of thin fluid derived from the mesothelial lining
of a given cavity (peritoneal, thoracic) or from plasma. A blister on your foot
is a good example.
Fibrinous inflammation
Ans:
This occurs in the setting of greater vascular permeability so that larger prote
ins can escape, such as fibrin. Also, fibrinous inflammation can occur in the se
tting of cancer with procoagulant stimuli. A fibrinous exudates appears red and
granular grossly and histologically appears as pink threads. Pericarditis can be
fibrinous.
Suppurative or purulent inflammation
Ans:
This describes the accumulation of pus, often in the setting of pyogenic (bacter
ial) infection. Pus includes neutrophils, necrotic cells and edema fluid. An abs
cess is also the accumulation of pus in a localized area within a tissue (see be
low).
Outcomes of Acute Inflammation
Ans:
- Complete resolution: The inflammatory process is complete; there is cessation
of leukocyte infiltration, return of normal vascular permeability and normal tis
sue.
- Healing by fibrosis: With more extensive inflammation and tissue necrosis, con
nective tissue replacement occurs (scar).
- Progression to chronic process: There are no exact measurements or criteria to
say why some acute inflammatory reactions become chronic problems. Often the st
imulus is not removed adequately or there is some block or interference with the
normal acute reaction/resolution. Realize that most chronic inflammatory proces
ses begin as a chronic problem and do not necessarily arise secondary to an acut
e problem.
Complications of Acute Inflammation
Ans:
- Abscess: An abscess is defined as an area of pus with marked underlying tissue
destruction. The collection of acute inflammatory cells (that make up the pus)
is characteristically walled off making it more difficult to treat with systemic
antibiotics. Abscesses often need to be surgically drained.
- Ulcer: An ulcer is a superficial epidermal or mucosal defect. The skin or epit
helium is sloughed off (falls off); the area directly underneath this defect con
tains numerous neutrophils, cellular debris and fibrin. The deeper areas consist
of macrophages, new vessels and fibroblasts indicative of repair. Ulcers can be
found on any mucosal surface and on the skin.