Docstoc

Ch 2 - Inflammation - OH

Document Sample
Ch 2 - Inflammation - OH Powered By Docstoc
					 LFS 319 – Pathophysiology                         Chapter 2: Inflammation

                         Chapter 2: Inflammation
                          1. Acute Inflammation
Introduction
   Inflammation is the response of living tissue to damage.
   Short-lasting (few days)
   The acute inflammatory response has 3 main functions.
           1. The affected area is occupied by exudate
                 helps mediate local defences
           2. Removal of causative agent (e.g. bacteria
           3. Removal of damaged tissue & debris from the site
              of damage.
Causes of acute inflammation:
     Physical damage
     Chemical substances
     Micro-organisms
     Other agents
The inflammatory response consists of:
        1. Changes in blood flow
        2. Increased permeability of blood vessels
   Examples of acute inflammation?


                   Definition of inflammation
"inflammation is complexly orchestrated response to injury that
 serves to destroy the source of injury, remove the accumulated
          debris, and trigger the repair process" Page 28

                                                                             1
 LFS 319 – Pathophysiology                       Chapter 2: Inflammation

Cardinal signs:
      Redness (rubor)
      Heat (calor)
      Swelling (tumor)
      Pain (dolor)
      Loss of function


Normal vascularised connective tissue
   The inflammatory process is focused in the vascularised
    loose connective tissue (ECM).
   The vessels that participate in the inflammatory response
    are the venules.
   Inflammation loosens endothelial junctions within
    postcapillary venules.
   Connective tissue contains fibroblasts, macrophages &
    mast cells

Formation of tissue fluid (Fig. 2.3, P 30):

4 forces control fluid movement between blood and tissue
spaces:
           a. Blood hydrostatic pressure (BHP)
           b. tissue hydrostatic pressure (THP)
           c. blood osmotic pressure (BOP)
           d. tissue osmotic pressure (TOP)

      fluid leaving blood vessels at the arteriolar end = fluid
                       entering at venule end
                                                                           2
 LFS 319 – Pathophysiology                       Chapter 2: Inflammation

 Normal fluid shift: (Fig. 2.3 a):

   At the arteriolar end of the capillary:

                  BHP + TOP > BOP + THP
                               
      Fluid shifts from blood vessels to interstitial spaces.

   At the venule end of the capillary:

                  BOP + THP > BHP + TOP
                                 
       Fluid shifts from interstitial spaces to blood vessels

 In acute inflammation, 2 changes occur (Fig. 2.3 b&c):

        1. Hyperaemia due to dilation of arterioles   BHP
            increased fluid filtration  transudate
        2.  Permeability (esp. venules)  filtration of blood
           proteins  exudate

   Explain how high tissue osmotic pressure contributes to
                         swelling?

    Net effect: low blood volume, high viscosity  Stasis

How do permeability changes differ in mild to moderate injury
            from that in more severe injury?

                                                                           3
 LFS 319 – Pathophysiology                      Chapter 2: Inflammation


What are the benefits of accumulation of fluid and plasma
proteins at an injury site?

        1. dilution of toxins
        2. limitation of use of affected part because of pain
        3. presence of antibodies
        4. stimulation of phagocytosis (by exudates proteins)

Descriptive classification of acute inflammation:

  1. Serous inflammation
      Only fluid escapes from capillaries
      Occurs in minor injuries, e.g. blisters of mild burns

  2. Fibrinous exudates
      Presence of fibrinogen (a plasma protein) in the
       exudates
      Results in coagulation of exudates
      E.g. in pericarditis and pleurisy (seen in pneumonia)

  3. Purulent (suppurative) inflammation:
     a. Caused by more severe injury
     b. Results in formation of Pus
     c. Pus is: Neutrophils, necrotic debris & fluid exudates
     d. Cellulitis: diffuse suppurative inflammation
     e. Abscess: localised accumulation of pus
     f. Cyst: a fluid-filled sac may remain after removal of
        injurious agent

  4.    Hemorrhagic inflammation
                                                                          4
 LFS 319 – Pathophysiology                    Chapter 2: Inflammation

The formation of exudate: Cellular factors:

Stages of movement of Leukocytes from blood vessels to tissue
spaces:

  1.    Migration: movement towards vascular endothelium
  2.    Rolling, pavementing and adhesion: attachment to
        endothelium
  3.    Transmigration: movement of leukocytes from blood to
        tissue spaces

Phagocytosis:

Effective phagocytic activity involves:

  1.    Activation (chemotaxis)
  2.    Recognition & Attachment
  3.    Engulfment & destruction




                                                                        5
 LFS 319 – Pathophysiology                            Chapter 2: Inflammation

  4. Chemical Mediation of Inflammation:
Answer the following questions:

    a. What triggers the dilation and permeability changes that
       occur during acute inflammation?
    b. What activates phagocytic cells?
    c. How are these responses linked to the original injury?

                            Injury
                               ↓
        Chemicals released or produced at site of injury
                               ↓
                 Acute inflammatory changes

Acute inflammation starts with triggering events, also called
initiators (Table 2.1, page 38).

                                Initiator(s)
                                     ↓
                           Chemical mediators
                                     ↓
                         Vascular & cellular events
                         (Inflammatory response)




                                                                                6
                 LFS 319 – Pathophysiology                             Chapter 2: Inflammation
Cell-Derived Mediators:

   Chemical         Released from               Triggered by                          Causes
Histamine            Mast cells             Cold, heat, trauma,   Rapid, brief increase in
[binds to H1         Platelets              foreign antigens      postcapillary venule permeability
receptors]

Serotonin            platelets              Contact with of   Same as above
                                             platelets with
                                             basement membrane
                                             collagen fibres
Eicosanoids          All                    Injury                   Coagulation
                      Leukocytes                                      Pain
[Metabolic            especially                                      Swelling
transformation        mast cells                                      Tissue damage
of arachidonic
acid (AA)]



                                                                                                   7
           LFS 319 – Pathophysiology                       Chapter 2: Inflammation

Plasma Cascades
                                                        Bradykinin: contributes to pain
                                        Inflammation    of inflammation.
Kinin


Fibrinolytic                           Inflammation &   Function in both inflammation
                                         Coagulation    and blood loss prevention

Coagulation
                                                        The complement system consists of
                                                        20 circulating proteins. Upon
                                   Inflammation &
                                                        activation, a complex of 5 proteins
Complement                             immune           is formed called the membrane
                                                        attack complex (MAC), which can
                                                        destroy microorganisms by
All four cascades can be directly or indirectly         producing holes in their membranes.
triggered by the presence of the active form of         They also promote chemotaxis,
circulating protein known as Hageman factor             dilation, permeability changes, and
(clotting factor no. XII)                               phagocytosis and histamine release
                                                        by mast cells.
                                                                                          8
 LFS 319 – Pathophysiology                    Chapter 2: Inflammation

Systemic effects of acute inflammation:

     Fever
     Loss of appetite
     Rapid weight loss
     Fatigue
     Lymphadenitis
     Bacteremia
     Leukocytosis
Therapeutic modification of acute inflammation:

a. Temperature:
    Application of cold to damaged area  ↓ swelling (how?)
   Application of heat   phagocytosis

      Q. Explain why cold should not be applied for more than
                            10 minutes.
       Q. Explain why cold should be applied first then heat.

b. Elevation and pressure:

   Elevation of a limb reduces swelling.
   Constrictive wrapping reduces exudate formation




                                                                        9
 LFS 319 – Pathophysiology                  Chapter 2: Inflammation

c. Drug Therapy:

   Antihistamines  block the action of histamine at its
    blood vessel receptors.
   NSAIDs   prostaglandin synthesis, bradykinin
   Steroid    prostaglandin synthesis 
                ↓ vasodilation
                ↓ swelling
                ↓ phagocytic activity  ↓ tissue damage
                ↓ release of lysosomal enzymes  ↓ damage


Potential complications of anti-inflammatory therapy:

   Interference with the healing process

   Greater susceptibility to infection




                                                                      10
 LFS 319 – Pathophysiology                        Chapter 2: Inflammation

2. Chronic Inflammation


Subacute:         Inflammation lasting > 1 week
Chronic:          Inflammation lasting > 6 weeks – months or years

Development of chronic inflammation

                   Injurious agent enters body
                                
                 Acute inflammatory response
                  (both vascular and cellular)
                                
                Agent not destroyed or removed
                                
           Vascular response diminishes (↓ exudate)
& cellular response dominates (↑ phagocytes and lymphocytes
                             activity)
                                
   Injurious agent attacks and defences = host attacks and
                            defences
                                
               Inflammatory response prolonged
                                
                      Chronic inflammation
                                
                         Tissue damage




                                                                            11
 LFS 319 – Pathophysiology                     Chapter 2: Inflammation



Pathogenesis of chronic inflammation: (Fig. 2.20, P 47)

               Acute inflammatory response
                             
        Response unable to eliminate injurious agent
                             
        Lymphocytes are also attracted to the scene
  (so now both macrophages and lymphocytes are present)
                             
         Injurious agent not destroyed or removed
                             
   Lymphocytes (T-Helper)  Lymphokines (MAF, MIF)
                             
               Accumulation of macrophages
                                     
                  Diffuse           Focal
                                     
                        Chronic        Chronic
                      Nonspecific   Granulomatous
                     inflammation   inflammation.
                           .




                                                                         12
 LFS 319 – Pathophysiology                       Chapter 2: Inflammation



Explain how acute and chronic inflammation processes differ
               in the sequencing of healing.


Classification of chronic inflammation:

There are two patterns:

    a. Nonspecific chronic inflammation (most common):

           Diffuse accumulation of macrophages and
           lymphocytes at site of injury.

    b. Granulomatous inflammation:

            Focal accumulation of macrophages and
             lymphocytes  granuloma
            Formation of a mass of epithelioid cells surrounded
             by lymphocytes and fibroblast.
            Central mass of necrotic tissue
            Multinucleated giant cells


          Give examples of agents that may cause chronic
                          inflammation.




                                                                           13

				
DOCUMENT INFO
Shared By:
Categories:
Tags:
Stats:
views:14
posted:11/17/2011
language:Swedish
pages:13