Inflammation

Coordinator: Stephen Russell, D.V.M., Ph.D.

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SUPPLEMENTAL IMAGE DATABASE

INTRODUCTION:

Definition of inflammation
Key role of vascular changes and source of inflammatory components

ACUTE vs. CHRONIC INFLAMMATION:

ACUTE INFLAMMATION:

Vascular permeability and edema (text pp 37-39):
- Normal regulation of fluid transport.
- Noninflammatory edema.
- Inflammatory edema:
  - Attendant alterations in the microvasculature (Fig. 2-6)
  - Interactions of mediators (generated from cells and plasma components) with endothelial cells (Figs. 2-6 and 2-7).
  - Postcapillary venule as the target vessel.
  NOTE: The changes above are transient, to be distinguished from direct, irreversible injury, which can also lead to edema.
Clinically relevant consequences of acute inflammation:
- Effusion
- Transudate
- Exudate
- Serous exudate
- Serosanguinous exudate
- Fibrinous exudate(Fig. 2-8)
- Purulent exudate (Fig. 2-4; 2-9)
- Suppurative inflammation
- Abscess
Mediators of increased permeability in inflammatory edema (Fig. 2-13):
NOTE: There are two sources of inflammatory mediators - cells and components of plasma (see Figure 2-7).
- Cell-derived sources of vasoactive mediators (text pp 40-45):
  - Platelets (Fig. 2-11 and 2-13)
  - Endothelial cells (Fig. 2-6)
  - Mast cells in tissues (Fig. 2-12)
  - Leukocytes (neutrophils, monocytes, lymphocytes, basophils, eosinophils)
  - Eosinophils and Macrophages (histiocytes) in tissues
  - Parenchymal cells in the tissue that is affected
- Among cells, there are several sources of mediators, e.g., cellular lipids and intracytoplasmic storage granules:
  - Phospholipid metabolism:
    - Arachidonic acid metabolites (eicosanoids):
      
      NOTE:There are two enzymatic pathways through which inflammatory mediators are generated from arachidonic acid (Fig. 2-7).
      
      Cycloxygenase pathway metabolites (prostanoids) (Fig. 2-10; Table 2-1):
      Thromboxanes
      Prostaglandins
      
      Lipoxygenase pathway (Fig. 2-10; Table 2-1):
      HETEs
      Leukotrienes
      
      Platelet activating factor (PAF)
  - Intracytoplasmic storage granules (Fig. 2-25, 2-30):
    - Different cell types contain different kinds of granules.
    - Different kinds of granules contain a different spectrum of inflammatory mediators (and other entities).
    NOTE: Degranulation of inflammatory cells into the extracellular environment is a key event with respect to stored mediators becoming available.
    
    Plasma-derived vasoactive mediators (text pp 45-49):
    
    Hageman factor and the kinins (Fig. 2-14, 2-15)
    Complement system (classical & alternative pathways; Fig. 2-16, 2-17, & Table 2-2)
- Cellular recruitment at the site of inflammation (text pp 49-53):
  NOTE: Second phase of the inflammatory response, beginning primarily with neutrophils (the most numerous kind of polymorphonuclear leukocyte) - Fig. 2-25
  - Chemotactic factors, esp. C5a
  - Margination and Adherence of Leukocytes to vessel walls (Fig. 2-18).
  - Cell adhesion molecules (Fig. 2-19)
  - Leukocyte exudation (Fig. 2-18)
  - Cytokine networks in acute inflammation (Fig. 2-20)
  Mechanisms of inflammatory cell functions:
  
  Phagocytosis (Fig. 2-24):
  Recognition
  Internalization
  Killing and Digestion
  
  Bactericidal activity of inflammatory cells:
  
  NOTE: Degranulation into phagosomal vacules is key to killing of ingested microorganisms (Fig. 2-24).
  
  Killing through activated oxygen species (Table 2-3):
  Superoxide
  Hydrogen peroxide
  Hypochlorous acid
  Hydroxyl radical
  
  Nonoxidative bacterial killing (text page 59):
  Lysosomal hydrolases
  Bactericidal/permeability-increasing protein
  Defensins
  Lactoferrin
  Lysozyme
  Bactericidal proteins of eosinophils (MBP & ECP)
  Tissue injury by inflammatory cells:
  
  NOTE: Due to the release of enzymes and activated oxygen species, especially directly against the surface of a target ("frustrated phagocytosis").
  
  Phagocytic cell adherence (text p 60)
  Lysosomal enzymes (text p 59)
  Activated oxygen species (text p 60)
  
  Diseases associated with defects in phagocytosis
  
  Congenital diseases (Table 2-4; compare chronic granulomatous disease with events depicted in (Fig. 2-24)
  Acquired defects (Table 2-5)

CHRONIC INFLAMMATION:

These four slides depict for you the process and consequences of chronic (i.e., persistent) inflammation.

NOTE: Inflammation is a dynamic continuum, and chronic inflammation is usually seen as the sequel to acute inflammation. It primarily serves to contain and remove the agent that was the inciting stimulus.

Cellular components of the chronic inflammatory response:
- Macrophage (Figs. 2-26)
- Lymphocyte (Fig. 2-29)
- Plasma cell (Fig. 2-28)
- Eosinophils (Fig. 2-30) in special kinds of chronic inflammatory reactions
Chronic inflammation as a primary response - seen in special circumstances
Granulomatous inflammation (text pp 63-64):
NOTE: This is a special form of chronic inflammation that is designed to eliminate inciting agents that persist, in spite of normal acute and chronic inflammatory responses.
Distinction between a granuloma and granulomatous inflammation.
- Mechanism of granuloma formation (Fig. 2-31)
- Concentric layers of a granuloma.Esquema (Fig. 2-32B)
- Células que se hallan tipicamente en granulomas: Micro
  - Macrophages
  - Epithelioid cells(Fig.2-32B)
  - Multinucleated giant cells[Fig. 2-33] (subtypes: Langhans giant cell; foreign body giant cell [Fig.2-34)
  - Lymphoid cells (Figs 2-32b & 33)
  - Fibroblasts
  - Miscellaneous other inflammatory cell types

SYSTEMIC MANIFESTATIONS OF INFLAMMATION:

Fever (due to pyrogens)
Leukocytosis:
- Accelerated release of leukocytes from the bone marrow
- Accelerated production of leukocytes
- Special terms used to describe leukogram, e.g.:

ACUTE PHASE RESPONSE:

Clinical signs and symptoms
Acute phase proteins (Table 2-6)
Clinical consequence of elevated plasma levels of some acute phase proteins