INFLAMATION

Ref: Localized response of vascularized tissue to

injurious agent.
Purpose: A protective response which serves;
Eliminate or limit spread of initial injurious agent (eg
bacteria toxins)
Remove consequence of such injury e.g removal of
necrotic cells and tissues.
Without inflammation; injury eg infection wound
continue unchecked.
Healing will not occur.
Inflammation is closely linked with process of repair.
Repair begins during early phase of inflammation.
Repair reaches completion usually when injurious
influence is neutralized.
Repair reaches completion usually when injurious
influence is neutralized.
Unique feature of inflammatory process reaction
of blood vessels leading to accumulation of fluid
and leukoctes in extravascular tissue.
UNDERLIES PATHOLOGIC CONDATIONS
Rheumatoid arthritis
Lung fibrosis
Life threatening hypersensitivity reactions – insect
bites, drug reaction, toxins.
Repair also underlies;
Disfiguring scars, fibrous bands(intestinal
obstruction
Keloid.
Causes of inflammation
Physical agents – organic and inorganic
Infective agents
Immunologic agents such as cell-mediated antigen
HISTORIC AL BACKGROUND.
The four cardinal signs of inflammation were first
listed Roman writer of first century AD “CELSUS”
Were listed as:
Rubor, tumor, calor, dolor (redness, swelling heat
and pain).
These signs are more prominent in acute
inflammation than chronic inflammation.
A fifth clinical sign, loss of function (functio laesa)
was later added by virchow.
In 1793 John Hunter (Scottish surgeon) noted what
is now considered obvious;
Inflammation is not a disease but a non-specific
response that has beneficial effect on its host.
Julius cohnheim first used the microscope to
observe inflammed blood vessels.
He noted;
initial changes in blood flow
Subsquent Oedema caused by increased
vascular permeability.
Characteristic leukocytes emigration.
He wrote these description of inflammation
which we can hardly improve on.
1880s Russian biologist ELIE Metchnikoff
discovered process of phagocytosis.
Observe ingestion of bacteria by leukocytes.
He concluded that the purpose of inflammation
was to bring phagocyte cells to injured area to
engulf bacteria.
His conclusion contradicted prevailing theory
(Paul Ehrlich) that purpose of inflammation was
to bring serum factors to neutralize infections
agent.
It then became clear that both cells
(phagocytes) and serum factors (antibodies) were
critical in defense against microorganism.
Both scientists shared the Nobel prize of 1908.
SIR THOMAS LEWIS – Simple experiments studying
inflammatory response in skin.
Proposed that chemical substances such as
Histamine locally induced by injury, mediate vascular
changes of inflammation.
Importance – Lead to discovery of many chemical
mediators of inflammation
Use of anti-inflammatory agents in clinical
medicine.
TYPES OF INFLAMMATION.
Inflammation is classified as acute or chronic
A Acute inflammation
Is an inflammation of short duration and represents
early body reaction.
Is usually followed by repair
Characteristics;
Main features of acute inflammation;
Accumulation of fluid and plasma at the affected site.
Accumulation of inflammatory cells at the site.
Chronic inflammation
Longer duration
(T0 discuss later)
Acute inflammation
The changes in acute inflammation is better described
under the follow 2 headings.
Vascular events
Cellular events.
VASCULAR EVENTS:
One of the earliest events in response to tissue injury
is alteration in microvasculature.
Microvasculature (arterioles, capillaries and venules)
These alteration include;
Haemodynamic changes.
Changes in vascular permeability.
haemodynamic changes:
A Transient vascular contraction is the first response
irrespective of type of injury.
oIs short lived, seconds;
oNeurogenic in origin.
B Vasodilation.
oThis is the next event.
oMainly involves arterioles but other component of
venues affected to a lesser component.
oVasodilatation results into increase blood volume in
microvasculature of affected site.
oIs responsible for redness (rubor) and warmth
(color) at the site of acute inflammation.
 Chemical mediation of vasodilatation will be
discussed later.
INCREASED VASCULAR PERMIABILITY.
Vasodilation is quickly followed by increased
vascular permeability.
This leads to outpouring of protein rich fluid into
extravascular tissue (swelling = Odema= tumor).
slowing of blood flow = stasis
Loss of fluid result’s in concentration of red cell in
small vessels (viscosity).
Viscosity reflected by dilated small vessels packed
with red blood vessels and slower blood flow
condition called stasis.
As stasis develops leukocytes (predominantly
neutrophils) accumulates along vascular
endothelium
Soon after migrated through vascular wall to
interstial tissue (discussed and vascular events)
INCREASED VASCULAR PERMIABILITY
(vascular leakage).
Normal fluid exchange and microvascular
permeability is dependent on normal intact
endothelium
STARLINGS HYPOTHESIS.
Fluid balance between vascular and interstitial
tissue.
The balance maintained by two opposing
forces.
A) Forces that causes outward movement of
fluid from microcirculation.
 (HIGH)Intravascular hydrostatic pressure and
 (LOW)Osmotic pressure of interstitial fluid
B) Forces that causes inward movement of
interstitial fluid into circulation.
 HIGH)Intravascular osmotic pressure and
Hydrostatic pressure of interstitial fluid.

HP
OP

arteriolar end venular end

At arteriolar end high hydrostatic pressure forces
fluid movement into interstitial tissue (transudate)
At venular end low HP and high osmotic pressure
favours movement of fluid into blood vessels.
Whatever small fluid that remains is removed by
lymphatic.
END RESULT No accumulation of fluid in the
During inflammation the endothelium becomes
leaky.
Allow micromolecules – protein rich fluid to leak.
The high hydrostatic pressure and protein rich
fluid (Osmotic pressure in tissue) leads to massive
outflow of fluid in interstitial tissue (Oedema) =
tumor)
How does endothelium becomes leaky in
inflammation = mechanism:
A) Formation of endothelial gaps in venues
 Most common mechanism of vascular leakage
 Elicited by histamine, bradykinin, leukotrienes
and other chemicals.
 Occurs rapidly after exposure to mediator .
 Usually reversible and short-lived (15-30
minutes)
 Thus called immediate and transient response.
Binding of mediator – contraction of contractile
and cytoskeleton proteins (contraction of
endothelial cells)
B) Direct injury – Endothelial cell necrosis and
detachment.
Occur following damage to injurious stimuli such
burns or lytic bacterial infection.
Damage occurs immediately after injury and is
sustained until injured vessels are thrombosed or
repaired.
Called immediate sustained response.
All level of micro vasulative affected.
C) DELAYED PROLONGED LEAKAGE.
 A common type of increased permeability.
Occurs after delay of 2-12 hrs
Last for several hours or even days.
Involves venules and capillaries.
 Cause such as moderate Thermal injury radiation,
UV radiation and certain bacterial toxin.
Example late appearing sunburn
Results for delayed endothelial injury cytokines
may be involved.
D) Leukocytes – mediated endothelial injury
leukocytes adheres to endothelium relatively early
during inflammation.
Activated leukocytes produces products that cause
endothelial injury or detachment (toxic 0xgen
species, Enzymes)
C) Leakage from new blood vessels (repair)
- stops when endothelium matures

Cellular Events.
Includes leukocyte extravasation and
phagocytosis.