Inflammation and repair

							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
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.
Dr.Maha Arafah:


Dr.Maha Arafah:
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
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).
Inflammation and repair
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
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;      Bacterial infections; response to cell necrosis of any
                        neutrophil leukocytosis in blood.                      cause.


  Acute inflammation    Paucity of neutrophils in exudate; lymphocytes and     Viral and rickettsial infections (immune response
  without neutrophils   plasma cells predominant; neutropenia, lymphocytosis   contributes).
                        in blood.

  Allergic acute        Marked edema and numerous eosinophils;                 Certain hypersensitivity immune reactions
  inflammation          eosinophilia in blood.


  Serous                Marked fluid exudation.                                Burns; many bacterial infections.
  inflammation
  (inflammation in
  body cavities)

  Catarrhal             Marked secretion of mucus.                             Infections, eg, common cold (rhinovirus); allergy
  inflammation                                                                 (eg, hay fever).
  (inflammation of
  mucous
  membranes)
  Fibrinous             Excess fibrin formation.                               Many virulent bacterial infections.
  inflammation
  Necrotizing           Marked tissue necrosis and hemorrhage.                 Highly virulent organisms (bacterial, viral, fungal),
  inflammation,                                                                eg, plague (Yersinia pestis), anthrax (Bacillus
  hemorrhagic                                                                  anthracis), herpes simplex encephalitis,
  inflammation                                                                 mucormycosis.

  Membranous            Necrotizing inflammation involving mucous              Toxigenic bacteria, eg, diphtheria bacillus
  (pseudomembranou      membranes. The necrotic mucosa and inflammatory        (Corynebacterium diphtheriae) and Clostridium
  s) inflammation       exudate form an adherent membrane on the mucosal       difficile.
                        surface.

  Suppurative           Exaggerated neutrophil response and liquefactive       Pyogenic bacteria, eg, staphylococci, streptococci,
  (purulent)            necrosis of parenchymal cells; pus formation. Marked   gram–negative bacilli, anaerobes.
  inflammation          neutrophil leukocytosis in blood.
                           Inflammation


                                           Acute


 Causative agent                  Pathogens, injured tissues


                         Neutrophils, mononuclear cells (monocytes,
Major cells involved
                                       macrophages)


Primary mediators              Vasoactive amines, eicosanoids


      Onset                               Immediate


     Duration                             Few days



    Outcomes           Healing, abscess formation, chronic inflammation