Transcript 08-Inflammation and repair,hala

Comprehensive Approach
Inflammation and repair
Inflammation is fundamentally a
protective response
 Inflammation and repair may be
potentially harmful
 The inflammatory response consists of
two main components, a vascular
reaction and a cellular reaction

Inflammation and repair
Neutrophils, monocytes, eosinophils,
lymphocytes, basophils, and platelets.
 Mast cells, fibroblasts, resident
macrophages and lymphocytes.
 The extracellular matrix

Inflammation and repair
Acute inflammation
 Chronic inflammation
 The vascular and cellular reactions of
both acute and chronic inflammation are
mediated by chemical factors
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Inflammation and repair
Historical Perspective:
 (Latin, inflamatio, to set on fire)
 The word "inflammation" goes back at
least to ancient Egyptian times. “Sheme-met " : Inflammation and ends in a
symbol called a determinative, a
"flaming brazier". This brazier is a device
heated with fire.
Dr.Maha Arafah:
Dr.Maha Arafah:
Inflammation and repair
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Leukocyte extravasation
Leukocyte localisation and
recruitment to the endothelium local
to the site of inflammation –
involving margination and adhesion
to the endothelial cells
Inflammation and repair
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Greek for flame, and indeed an inflamed
body part may feel ‘on fire’. In its
traditional clinical description,
inflammation has four characteristics:
calor (heat), rubor (redness), tumor
(swelling and dolor (pain).
Inflammation and repair
Inflammation
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Overview of Cellular Mechanisms Involved
in Acute Inflammation
Chemical Mediators of Acute Inflammation
Examples of Acute Inflammatory
Responses
Differences Between Acute and Chronic
Inflammation
Examples of Chronic Inflammation
Discussion of Potential Roles of Nutrition in
Inflammation
Acute Inflammation
Acute inflammation is a rapid response to an injurious agent
that serves to deliver mediators of host defense—leukocytes
and plasma proteins—to the site of injury. Acute
inflammation has three major components: (1) alterations in
vascular caliber that lead to an increase in blood flow; (2)
structural changes in the microvasculature that permit
plasma proteins and leukocytes to leave the circulation; and
(3) emigration of the leukocytes from the microcirculation,
their accumulation in the focus of injury, and their activation
to eliminate the offending agent
Acute inflammatory reactions are triggered by a
variety of stimuli:
• Infections (bacterial, viral, parasitic) and microbial
toxins
• Trauma (blunt and penetrating)
• Physical and chemical agents (thermal injury, e.g.,
burns or frostbite; irradiation; some environmental
chemicals)
• Tissue necrosis (from any cause)
• Foreign bodies (splinters, dirt, sutures)
• Immune reactions (also called hypersensitivity
reactions)
Acute Inflammation
When a host encounters an injurious agent, such as an
infectious microbe or dead cells, phagocytes that reside in all
tissues try to get rid of these agents. At the same time,
phagocytes and other host cells react to the presence of the
foreign or abnormal substance by liberating cytokines, lipid
messengers, and the various other mediators of inflammation.
Some of these mediators act on endothelial cells in the vicinity
and promote the efflux of plasma and the recruitment of
circulating leukocytes to the site where the offending agent is
located.
Acute Inflammation - continued
As the injurious agent is eliminated and anti-inflammatory
mechanisms become active, the process subsides and the
host returns to a normal state of health. If the injurious
agent cannot be quickly eliminated, the result may be
chronic inflammation. The recruited leukocytes are activated
by the injurious agent and by locally produced mediators,
and the activated leukocytes try to remove the offending
agent by phagocytosis.
The vascular phenomena of acute inflammation are characterized
by increased blood flow to the injured area, resulting mainly from
arteriolar dilation and opening of capillary beds induced by
mediators such as histamine. Increased vascular permeability
results in the accumulation of protein-rich extravascular fluid,
which forms the exudate. Plasma proteins leave the vessels, most
commonly through widened interendothelial cell junctions of the
venules. The redness (rubor), warmth (calor), and swelling (tumor)
of acute inflammation are caused by the increased blood flow
and edema.
Circulating leukocytes, initially predominantly
neutrophils, adhere to the endothelium via adhesion
molecules, transmigrate across the endothelium, and
migrate to the site of injury under the influence of
chemotactic agents. Leukocytes that are activated by the
offending agent and by endogenous mediators may
release toxic metabolites and proteases extracellularly,
causing tissue damage. During the damage, and in part
as a result of the liberation of prostaglandins,
neuropeptides, and cytokines, one of the local
symptoms is pain (dolor).
Changes in vascular flow and caliber begin early after injury and develop at
varying rates depending on the severity of the injury. The changes occur in
the following order:
• Vasodilation. Increased blood flow is the cause of the heat and the
redness. Vasodilation is induced by the action of several mediators, notably
histamine and nitric oxide on smooth muscle.
• Increased permeability of the microvasculature.
• Stasis. The loss of fluid results in concentration of red cells in small
vessels and increased viscosity of the blood.
A hallmark of acute inflammation is increased vascular
permeability leading to the escape of a protein-rich fluid
(exudate) into the extravascular tissue. The loss of protein from
the plasma reduces the intravascular osmotic pressure and
increases the osmotic pressure of the interstitial fluid. Together
with the increased hydrostatic pressure owing to increased
blood flow through the dilated vessels, this leads to a marked
outflow of fluid and its accumulation in the interstitial tissue.
The net increase of extravascular fluid results in edema.
Leukocytes Rolling Within a Venule
Neutrophil Pavementing (lining the
Table 3–2. Mediators of Acute Inflammation.
Mediator
Vasodilation
Immediate
Sustained
Chemotaxis
Opsonin
Pain
Histamine
+
+++
–
–
–
–
Serotonin (5–HT)
+
+
–
–
–
–
Bradykinin
+
+
–
–
–
++
Complement 3a
–
+
–
–
–
–
Complement 3b
–
–
–
–
+++
–
Complement 5a
–
+
–
+++
–
–
Prostaglandins
+++
+
+?
–
–
Leukotrienes
–
+++
+?
+++
–
–
Lysosomal proteases
–
–
++1
–
–
–
Oxygen radicals
–
–
++1
–
–
–
Resolution of Acute Inflammation
Table 3–4. Types of Acute
Inflammation.
Type
Features
Common Causes
Classic type
Hyperemia; exudation with fibrin and neutrophils;
neutrophil leukocytosis in blood.
Bacterial infections; response to cell necrosis of any
cause.
Acute inflammation
without neutrophils
Paucity of neutrophils in exudate; lymphocytes and
plasma cells predominant; neutropenia, lymphocytosis
in blood.
Viral and rickettsial infections (immune response
contributes).
Allergic acute
inflammation
Marked edema and numerous eosinophils;
eosinophilia in blood.
Certain hypersensitivity immune reactions
Serous
inflammation
(inflammation in
body cavities)
Marked fluid exudation.
Burns; many bacterial infections.
Catarrhal
inflammation
(inflammation of
mucous
membranes)
Marked secretion of mucus.
Infections, eg, common cold (rhinovirus); allergy
(eg, hay fever).
Fibrinous
inflammation
Excess fibrin formation.
Many virulent bacterial infections.
Necrotizing
inflammation,
hemorrhagic
inflammation
Marked tissue necrosis and hemorrhage.
Highly virulent organisms (bacterial, viral, fungal),
eg, plague (Yersinia pestis), anthrax (Bacillus
anthracis), herpes simplex encephalitis,
mucormycosis.
Membranous
(pseudomembranou
s) inflammation
Necrotizing inflammation involving mucous
membranes. The necrotic mucosa and inflammatory
exudate form an adherent membrane on the mucosal
surface.
Toxigenic bacteria, eg, diphtheria bacillus
(Corynebacterium diphtheriae) and Clostridium
difficile.
Suppurative
(purulent)
inflammation
Exaggerated neutrophil response and liquefactive
necrosis of parenchymal cells; pus formation. Marked
neutrophil leukocytosis in blood.
Pyogenic bacteria, eg, staphylococci, streptococci,
gram–negative bacilli, anaerobes.
Inflammation
Acute
Causative agent
Pathogens, injured tissues
Major cells involved
Neutrophils, mononuclear cells (monocytes,
macrophages)
Primary mediators
Vasoactive amines, eicosanoids
Onset
Immediate
Duration
Few days
Outcomes
Healing, abscess formation, chronic inflammation