Inflammation

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Inflammation

• Comprehensive Approach

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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

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Inflammation and repair

• Neutrophils, monocytes, eosinophils, lymphocytes,
  basophils, and platelets.
• Mast cells, fibroblasts, resident macrophages
  and lymphocytes.
• The extracellular matrix

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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. Shem-e-met "
  Inflammation and ends in a symbol called a
  determinative, a "flaming brazier". This brazier
  is a device heated with fire.

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Dr.Maha Arafah
Dr.Maha Arafah
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Inflammation and repair

• Leukocyte extravasation
• Leukocyte localisation and recruitment to the
  endothelium local to the site of inflammation
  involving margination and adhesion to the
  endothelial cells

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Inflammation and repair

• 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).

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Inflammation and repair
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Inflammation

• 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

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Acute InflammationAcute inflammation is a rapid
response to an injurious agent that serves to
deliver mediators of host defenseleukocytes and
plasma proteinsto 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
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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)
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Acute InflammationWhen 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.
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Acute Inflammation - continuedAs 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.
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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.
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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).
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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.
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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.
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Leukocytes Rolling Within a Venule
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Neutrophil Pavementing (lining the venule)
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Table 32. Mediators of Acute Inflammation.

             
Mediator Vasodilation Immediate Sustained Chemotaxis Opsonin Pain
Histamine
Serotonin (5HT)
Bradykinin
Complement 3a
Complement 3b
Complement 5a
Prostaglandins ?  
Leukotrienes ?
Lysosomal proteases 1 
Oxygen radicals 1 
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Resolution of Acute Inflammation
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Table 34. 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 (pseudomembranous) 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, gramnegative bacilli, anaerobes.
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Inflammation Inflammation 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
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