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Acute and Chronic
Inflammation
Referrence
 Chapter 2, “Acute and Chronic
Inflammation” in Robbins’ Basic
Pathology, pages 31-57
Introduction
 Inflammation is a defensive host
response to foreign invaders and
necrotic tissue.
 Can be acute or chroni...
Acute inflammation
Acute inflammation
 Immediate and early response to tissue
injury (physical, chemical, microbiologic, etc.)
 Acute infla...
Vascular change
Vascular change
 The main vascular reactions of acute
inflammation are increased blood flow
followed by vasodilation and ...
Increased vascular permeability
 This will leads to the movement of
protein-rich fluid and blood cells into the
extravasc...
Vascular leakage
 several mechanisms may contribute to
increased vascular permeablity:
 Endothelial cell contraction tha...
Vascular leakage
 Cytokine mediators (TNF, IL-1) induce
endothelial cell junction retraction through
cytoskeleton reorgan...
Vascular leakage
 Endothelial injuries result in vascular
leakage by causing direct endothelial cell
necrosis, detachment...
Vascular leakage
 Certain mediators such as vascular
endothelial growth factor (VEGF) may
cause increased transcytosis vi...
Leukocyte cellular events
Leukocyte cellular events
 Leukocytes leave the vascular lumen to the
extravascular space through the following
sequence ...
Margination and Rolling
 With increased vascular permeability, fluid
leaves the vessel causing leukocytes to
settle-out o...
Margination and Rolling
 Early rolling adhesion mediated by
selectin family of adhesion molecules:
 E-selectin (on endot...
Adhesion
 The rolling leukocytes are able to sense
change on the endothelium that initiate the
next step in the reaction ...
Transmigration (diapedesis)
 Is the movement of leukocyte across
the endothelial surface
 Occurs after firm adhesion and...
Chemotaxis
 Leukocytes follow chemical gradient to site of
injury this process called (chemotaxis)
 Chemotactic factors ...
Phagocytosis
 Phagocytosis is the ingestion of
particulate material by phagocytic cell
 neutrophils and monocytes-macrop...
 Phagocytosis consists of three steps:
 Recognition and attachment of the particle
 Engulfment (form phagocytic vacuole...
Defects of leukocyte function
 Defects of leukocyte adhesion:
 Leukocyte adhesion deficiency type I :
is associated with...
Defects of leukocyte function
 Defects of chemotaxis/phagocytosis:
 Microtubule assembly defect leads to
impaired locomo...
Possible outcomes of acute
inflammation
Possible outcomes of acute
inflammation
 Complete resolution of tissue structure
and function:
 When the injury is limit...
Outcomes (cont’d)
 Abscess formation occurs with some
bacterial or fungal infections
 Progression to chronic inflammatio...
Chronic inflammation
Chronic inflammation
 Is inflammation of prolonged duration (week
to years) in which continuing inflammation,
tissue inju...
Chronic inflammation
 Is characterized by a different set of
reactions:
 Lymphocyte, macrophage, plasma cell
(mononuclea...
 Chronic inflammation may arise in the
following setting :
 Persistent injury or infection (ulcer, TB)
 Prolonged toxic...
Chronic inflammatory cells
and mediators
Chronic inflammatory cells
and mediators
 Macrophages
 The dominant cells.
 Scattered all over (Kupffer cells, sinus
hi...
Chronic inflammatory cells
and mediators
 Two majors pathways of macrophage
activation:
 Classical macrophage activation...
Chronic inflammatory cells
and mediators
 Macrophages have several roles in host
defense and inflammatory reaction:
 Ing...
Chronic inflammatory cells
and mediators
 Lymphocytes (T - B )
 Antigen-activated (via macrophages and dendritic
cells)
...
Chronic inflammatory cells
and mediators
 Eosinophils
 Found especially at sites of parasitic
infections, and as part of...
Granulomatous Inflammation
Granulomatous Inflammation
 Is a distinctive pattern of chronic
inflammation characterized by
aggregates of activated mac...
 Granulomatous Inflammation can form
under three setting :
 Persistance T-cell response to certain
microbes (such as TB)...
Systemic effects
Systemic effects
 Fever
 The most prominent manifestation of acute-phase
response.
 Fever is produced in response to py...
Systemic effects (cont’d)
 Leukocytosis
 Is a common feature of inflammatory reaction,
espicially those induced by bacte...
Thank you
Acute and chronic inflammation
Acute and chronic inflammation
Acute and chronic inflammation
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Acute and chronic inflammation

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Dr salem

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Acute and chronic inflammation

  1. 1. Acute and Chronic Inflammation
  2. 2. Referrence  Chapter 2, “Acute and Chronic Inflammation” in Robbins’ Basic Pathology, pages 31-57
  3. 3. Introduction  Inflammation is a defensive host response to foreign invaders and necrotic tissue.  Can be acute or chronic.
  4. 4. Acute inflammation
  5. 5. Acute inflammation  Immediate and early response to tissue injury (physical, chemical, microbiologic, etc.)  Acute inflammation has two major components :  Vascular changes  Cellular events
  6. 6. Vascular change
  7. 7. Vascular change  The main vascular reactions of acute inflammation are increased blood flow followed by vasodilation and increased vascular permeability:  warmth and redness  Opens microvascular beds and protein-rich fluid moves into extravascular tissues  Migration of leukocytes (principally neutrophils)
  8. 8. Increased vascular permeability  This will leads to the movement of protein-rich fluid and blood cells into the extravascular tissue.  The resulting protein-rich accumulation is called an exudate.  Increases interstitial osmotic pressure contributing to edema.
  9. 9. Vascular leakage  several mechanisms may contribute to increased vascular permeablity:  Endothelial cell contraction that leading to intracellular gaps of venules This occur after binding of histamines and bradykinins, and many other mediators and is usually short-lived (15 – 30 min.)
  10. 10. Vascular leakage  Cytokine mediators (TNF, IL-1) induce endothelial cell junction retraction through cytoskeleton reorganization  This reaction may take 4 – 6 hrs to develop ,and lasting for 24 hrs or more
  11. 11. Vascular leakage  Endothelial injuries result in vascular leakage by causing direct endothelial cell necrosis, detachment making them leaky until they are repaired or may cause delayed damage as in thermal, certain bacterial toxins or Ultraviolet injury.
  12. 12. Vascular leakage  Certain mediators such as vascular endothelial growth factor (VEGF) may cause increased transcytosis via intracellular vesicles which travel from the luminal to basement membrane surface of the endothelial cell  All or any combination of these events may occur in response to a given stimulus
  13. 13. Leukocyte cellular events
  14. 14. Leukocyte cellular events  Leukocytes leave the vascular lumen to the extravascular space through the following sequence of events:  Margination and rolling along the vessel wall  Firm adhesion and transmigration between endothelial cells  Chemotaxis and activation
  15. 15. Margination and Rolling  With increased vascular permeability, fluid leaves the vessel causing leukocytes to settle-out of the central flow column and “marginate” along the endothelial surface  Endothelial cells and leukocytes have complementary surface adhesion molecules which briefly stick and release causing the leukocyte to roll along the endothelium until it eventually comes to a stop as mutual adhesion reaches a peak
  16. 16. Margination and Rolling  Early rolling adhesion mediated by selectin family of adhesion molecules:  E-selectin (on endothelium cell)  P-selectin (present on platelets, endothelium)  L-selectin (on the surface of most leukocytes)
  17. 17. Adhesion  The rolling leukocytes are able to sense change on the endothelium that initiate the next step in the reaction of leukocytes, which is firm adhesion to endothelial surface  Occur as leukocytes adhere to the endothelial surface and is mediated by the interaction of integrins on leukocytes binding to IG-family adhesion proteins on the endothelium.
  18. 18. Transmigration (diapedesis)  Is the movement of leukocyte across the endothelial surface  Occurs after firm adhesion and mediated by palatelete endothelial cell adhesion molecules-1 (PECAM –1) on both leukocyte and endothelium
  19. 19. Chemotaxis  Leukocytes follow chemical gradient to site of injury this process called (chemotaxis)  Chemotactic factors for neutrophils, produced at the site of injury, include:  Bacterial products  Components of complement system especially (C5a)  Cytokines.
  20. 20. Phagocytosis  Phagocytosis is the ingestion of particulate material by phagocytic cell  neutrophils and monocytes-macrophages are the most important phagocytic cells
  21. 21.  Phagocytosis consists of three steps:  Recognition and attachment of the particle  Engulfment (form phagocytic vacuole)  Killing and degradation of the ingested materials.
  22. 22. Defects of leukocyte function  Defects of leukocyte adhesion:  Leukocyte adhesion deficiency type I : is associated with recurrent bacterial infections.  Leukocyte adhesion deficiency type 2 : is associated with recurrent bacterial infections and result from mutations in the gene that required for the synthesis of sialyl-lewis X on neutrophils.
  23. 23. Defects of leukocyte function  Defects of chemotaxis/phagocytosis:  Microtubule assembly defect leads to impaired locomotion and lysosomal degranulation (Chediak-Higashi Syndrome)
  24. 24. Possible outcomes of acute inflammation
  25. 25. Possible outcomes of acute inflammation  Complete resolution of tissue structure and function:  When the injury is limited or short-lived.  There has been no or little tissue damage  When the injured tissue is capable of regeneration  Scarring (fibrosis):  When inflammation occur in tissues that do not regenerate  The injured tissue is filled with connective tissue
  26. 26. Outcomes (cont’d)  Abscess formation occurs with some bacterial or fungal infections  Progression to chronic inflammation.
  27. 27. Chronic inflammation
  28. 28. Chronic inflammation  Is inflammation of prolonged duration (week to years) in which continuing inflammation, tissue injury, and healing, often by fibrosis, proceed simultaneously.
  29. 29. Chronic inflammation  Is characterized by a different set of reactions:  Lymphocyte, macrophage, plasma cell (mononuclear cell) infiltration  Tissue destruction by inflammatory cells  Repair with fibrosis and angiogenesis (new vessel formation)
  30. 30.  Chronic inflammation may arise in the following setting :  Persistent injury or infection (ulcer, TB)  Prolonged toxic agent exposure (silica)  Autoimmune disease states (RA, SLE)
  31. 31. Chronic inflammatory cells and mediators
  32. 32. Chronic inflammatory cells and mediators  Macrophages  The dominant cells.  Scattered all over (Kupffer cells, sinus histiocytes, alveolar macrophages, etc.  Derived from circulating blood monocytes and reach site of injury within 24 – 48 hrs and transform to macrophages.
  33. 33. Chronic inflammatory cells and mediators  Two majors pathways of macrophage activation:  Classical macrophage activation: induced byT cell-derived cytokines, endotoxins, and other products of inflammation  Alternative macrophage activation: induced by cytokines produced by T lymphocytes and other cell including mast cell and eosinophils
  34. 34. Chronic inflammatory cells and mediators  Macrophages have several roles in host defense and inflammatory reaction:  Ingest and eliminate microbes and dead tissue.  Initiate the process of tissue repair.  Secrete mediators of inflammation such as cytokines.
  35. 35. Chronic inflammatory cells and mediators  Lymphocytes (T - B )  Antigen-activated (via macrophages and dendritic cells)  Lymphocytes and macrophages interact in a bidirectional way and these interaction play an important role in propagating chronic inflammation lymphocyte release macrophage-activating cytokines (in turn, macrophages release lymphocyte-activating cytokines until inflammatory stimulus is removed)
  36. 36. Chronic inflammatory cells and mediators  Eosinophils  Found especially at sites of parasitic infections, and as part of immune reaction mediated by IgE  Typically associated with allergies.
  37. 37. Granulomatous Inflammation
  38. 38. Granulomatous Inflammation  Is a distinctive pattern of chronic inflammation characterized by aggregates of activated macrophages and scattered lymphocytes.
  39. 39.  Granulomatous Inflammation can form under three setting :  Persistance T-cell response to certain microbes (such as TB)  In some immune mediated inflammatory diseases (Crohn disease)  In sarcoidosis disease in response to relatively inert foreign bodies(suture or splinter)
  40. 40. Systemic effects
  41. 41. Systemic effects  Fever  The most prominent manifestation of acute-phase response.  Fever is produced in response to pyrogens which stimulate prostoglandine synthesis.  PGE stimulate the production of neurotransmitters to reset the temperature at a higher level.
  42. 42. Systemic effects (cont’d)  Leukocytosis  Is a common feature of inflammatory reaction, espicially those induced by bacterial infection  Elevated white blood cell count.  Other manifestations include:  Increased heart rate and blood pressure.  Decreased sweating.  Sepsis in severe bacterial infection.
  43. 43. Thank you

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