Chapter 4. Inflammation

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• Chapter 4. Inflammation

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CHAPTER CONTENTS

• Introduction to inflammation
• Acute inflammation
• Chronic inflammation

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INTRODUCTION TO INFLAMMATION

• CONCEPTION
• Inflammation is a complex reaction to injurious
  agents that consists of vascular response,
  cellular reaction, and systemic reactions.
• a defensive response fundamentally
• be divided into acute inflammation and chronic
  inflammation

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INTRODUCTION TO INFLAMMATION

• CARDINAL CLINICAL SIGNS
• acute inflammation has 5 cardinal signs
• redness (rubor)
• heat (calor)
• swelling
• pain (dolor)
• loss of function

increased blood flow to the inflamed area
accumulation of fluid
release of chemicals that stimulate nerve endings
a combination of factors
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redness heat swelling pain
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INTRODUCTION TO INFLAMMATION

• SYSTEMIC CLINICAL SIGNS
• in acute inflammation
• A. fever
• B. changes in the peripheral white blood cell
  count
• neutrophils leukocytosis
• neutrophil nucleus shift to the left
• lymphocytosis
• neutropenia
• C. changes in plasma protein levels
• the levels of certain plasma proteins increase

entry of pyrogens and release prostaglandins
bone marrow release or production
viral infection
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mature
immature
neutrophil nucleus shift to the left
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ACUTE INFLAMMATION

• the early response of a tissue to injury
• the first line of defense against injury
• nonspecific
• changes in the microcirculation
• exudation of fluid emigration of
  leukocytes
• the causative factors (6 points)

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MORPHOLOGIC AND FUNCTIONAL CHANGES

• the two main components of the acute
  inflammatory
• the microcirculatory response
• the cellular response

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The microcirculatory response

• vasodilation and stasis
• increased permeability
• exudation of fluid

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The microcirculatory response

• A. vasodilation and stasis
• in the microcirculation
• a transient vasoconstriction
• (induced by action of mediators)
• dilation of arterioles, capillaries, and
  venules
• (hyperemia)
• stasis

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The microcirculatory response

• B. increased permeability
• in venules and capillaries
• active contraction of actin
• filaments in endothelial cells
• direct damage to endothelial
• cells
• leukocyte-mediated
• endothelial injury
• transcytosis increased

permeability increase (reversible)
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The microcirculatory response

• B. increased permeability
• in venules and capillaries
• three phases of increased permeability in acute
  inflammation
• (1) an immediate phase
• (2) a delayed response
• (3) a prolonged response
• these permeability changes are effected by
  various chemical mediators

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The microcirculatory response

• C. exudation of fluid
• exudation increased passage of fluid out of the
  microcirculation because of increased vascular
  permeability
• the composition of an exudate approaches that of
  plasma, but rich in proteins
• fibrinogen is converted to fibrin rapidly
• exudation should be distinguished from
  transudation

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Grossly, fibrin is seen on an acute inflamed
serosal surface that changes to a rough,
yellowish bread and butter-like surface, covered
by fibrin and coagulated proteins.
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The microcirculatory response

• C. exudation of fluid
• the functions of exudation
• (1) dilute the offending agent
• (2) cause increased lymphatic flow, conveying
  noxious agents to the draining lymph nodes to
  facilitating a protective immune response
• (3) flood the area with plasma, which contain
  numerous defensive proteins

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The cellular response

• leukocyte infiltration plays an important role
• in limiting the spread of injury
• in defending the host tissue
• Acute inflammation is characterized by the active
  emigration of inflammatory cells from the blood
  into the area of injury.

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The cellular response

• extravasation the process of the leukocytes from
  the vessel lumen to the interstitial tissue.
• 3 steps of extravasation
• (1) margination, rolling and adhesion to
  endothelium in the lumen
• (2) transmigration across the endothelium
• (3) migration toward the site of injury

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The cellular response

• A. types of cells involved
• neutrophils
• (polymorphonuclear leukocytes)
• phagocytic cell of the macrophage system
• lymphocytes and plasma cells

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The cellular response

• B. margination, adhesion and transmigration of
  neutrophils

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The cellular response

• C. emigration of neutrophils
• take 2-10minutes

intercellular junctions
basement membrane
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The cellular response

• D. chemotactic factors
• chemotaxis In the interstitial tissue,
  neutrophils move toward the site of injury,
  oriented along a chemical gradient.
• chemotactic factors Govern the active emigration
  of neutrophils and the direction in which they
  move.

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The cellular response

• E. phagocytosis
• recognition
• opsonization the agent has been coated with
  immunoglobulin or complement factor 3b
  (opsonins).
• engulfment
• the agent opsonins
  phagosome
• microbial killing
• phagosome fuses with lysosomes, therefore
  the enzymes can access to the engulfed
  microorganism and kill them

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Process of phagocytosis
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The cellular response

• F. erythrocyte
• the orderly flow of blood is disturbed in the
  dilated vessels
• erythrocyte form heavy aggregates and sludging
• erythrocyte enter an inflamed area passively
• diapedesis
• hemorrhagic inflammation

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MEDIATORS OF ACUTE INFLAMMATION

• A variety of endogenous chemical mediators play
  some important roles in the modulation of
  inflammatory response.
• originated from cells or plasma
• cell-derived mediators
• sequestered in intracellular granules and
  synthesized in response to a stimulus
• plasma-derived mediators
• present in precursor form and activated by
  proteolytic cleavage

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summary of inflammatory mediators

• Function Major mediators
• Vasodilation 5-HT,histamine,
  bradykinin ,PGE2
• Permeability 5-HT,histamine, C3a,
  C5a, PAF
• Chemotaxis C5a, LTB4, cytokins
• Fever Cytokines( IL-1, 6,
  TNF), PG
• Pain PGE2 , bradykinin
• Tissue damage Lysosomal enzymes , NO

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TYPES OF ACUTE INFLAMMATION

• A. serous inflammation
• B. fibrinous inflammation
• C. suppurative (purulent inflammation)
• D. hemorrhagic inflammation

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TYPES OF ACUTE INFLAMMATION

• A. serous inflammation
• occur in skin, and in peritoneal, pleural and
  pericardial cavities
• accumulation of excessive clear watery fluid
  with a variable protein content
• Catarrhal inflammation is a mild exudative
  inflammation of a surface mucous membrance
  without apparent tissue destruction.

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burn blisters
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Serous inflammation of skin
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TYPES OF ACUTE INFLAMMATION

• B. fibrinous inflammation
• large amounts of fibrinogen pass the vessel
  wall, and fibrins are formed in the extracellular
  spaces
• Pseudomembranous inflammation is the
  fibrinous inflammation occurred on a mucosal
  surface, and a membranous film consisting mainly
  of fibrin mixed with necrotic cells appears on
  the surface of the affected mucosa.

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Fibrinous pericarditis
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Fibrinous pericarditis
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pseudo-membranous inflammation
bacillary dysentery
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pseudo-membranous inflammation
diphtheria
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TYPES OF ACUTE INFLAMMATION

• C. suppurative (purulent inflammation)
• the formation of purulent exudates or pus
• Pus is made up of neutrophils, necrotic cells
  and edema fluid.
• Abscess is a localized collection of purulent
  inflammation accompanied by liquefactive necrosis.

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Abscess of kidney
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Abscess of brain
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Abscess of liver
Abscess of kidney
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TYPES OF ACUTE INFLAMMATION

• D. hemorrhagic inflammation
• marked hemorrhage is the predominant
  pathological change

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COURSE OF ACUTE INFLAMMATION

• A. resolution
• B. repair
• C. suppuration
• D. chronic inflammation

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DIAGNOSIS OF ACUTE INFLAMMATION

• surface structures
• local cardinal signs permit diagnosis
• internal organs
• systemic changes may first manifest
• rarely, examine a fluid exudates or tissue sample

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CHRONIC INFLAMMATION

• the sum of the responses mounted by tissue
  against a persistent injurious agent
• commonly show
• A. immune response
• B. phagocytosis
• C. necrosis
• D. repair

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CHRONIC INFLAMMATION

• the main features include
• (1) mononuclear cell infiltration
• macrophages play dominant rolls
• (2) tissue destruction
• (3) granulation tissue formation and fibrosis
• be distinguished from acute inflammation

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CHRONIC INFLAMMATION IN RESPONSE TO ANTIGENIC
INJURIOUS AGENTS

• mechanisms

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CHRONIC INFLAMMATION IN RESPONSE TO ANTIGENIC
INJURIOUS AGENTS

• morphologic types
• A. granulomatous chronic inflammation
• B. nongranulomatous chronic inflammation

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granulomatous chronic inflammation

• a special type of chronic inflammation
• character the formation of granuloma
• granuloma an aggregate of macrophages
• two types
• epithelioid cell granuloma
• foreign body granuloma

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granulomatous chronic inflammation

• characteristic features
• the formation of epithelioid cell granuloma
• epithelioid cell activated macrophages that
  appear as large cells with abundant pale, foamy
  cytoplasm
• langhans-type giant cell derived from fusion of
  macrophages and characterized by 10-50 nuclei
  around the periphery of the cell

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granulomatous chronic inflammation

• Granulomas are usually surrounded by lymphocytes,
  plasma cells, fibroblasts, and collagen.

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granulomatous chronic inflammation

• causes
• (1) When macrophages have successfully
  phagocytosed the injurious agent but it survives
  inside them
• (2) When an active T lymphocyte-mediated cellular
  immune response occurs

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granulomatous chronic inflammation

• changes in affected tissues
• granulomas expand and fuse with adjacent
  granulomas to
• form large
• masses

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granulomatous chronic inflammation

• changes in affected tissues
• in many infectious granulomas, central caseous
  necrosis is a common feature

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granulomatous chronic inflammation

• caseous necrosis
• gross yellowish-white and resembles crumbly
  cheese
• microscopic finely granular, pink, and amorphous

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nongranulomatous chronic inflammation

• characteristic features
• The accumulation of sensitized lymphocytes,
  plasma cells, and macrophages in the injured
  area.
• These cells are scattered diffusely throughout
  the tissue.
• Scattered tissue necrosis and fibrosis are
  common.

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nongranulomatous chronic inflammation

• causes and changes in affected tissues
• A. chronic viral infections
• B. chronic autoimmune diseases
• C. chronic chemical intoxications
• D. chronic nonviral infections
• E. allergic inflammation and metazoal infections

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CHRONIC INFLAMMATION IN RESPONSE TO NONANTIGENIC
INJURIOUS AGENTS

• characteristic features
• the formation of foreign body granuloma
• foreign body giant cells numerous nuclei
  dispersed throughout the cell
• foreign material is usually identifiable in the
  center of the granuloma
• tissue necrosis is not an associated feature
• (figure 4-19)

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Foreign body granuloma
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FUNCTION AND RESULT OF CHRONIC INFLAMMATION

• function of chronic inflammation
• serves to contain and remove an injurious
  agent that is not easily eradicated by the body
• dependent on immunologic reactivity
• (1) direct killing by activated lymphocytes
• (2) interaction with antibodies
• (3) activation of macrophages

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FUNCTION AND RESULT OF CHRONIC INFLAMMATION

• result of chronic inflammation
• associated with tissue necrosis and implies
  serious illness
• associated fibrosis a repair mechanism and
  perhaps another side effect

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MIXED ACUTE AND CHRONIC INFLAMMATION

• chronic inflammation may follow acute
  inflammation
• or result from repeated bouts of acute
  inflammation
• features of both types of inflammation may
  coexist in certain circumstances

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CHRONIC SUPPURATIVE INFLAMMATION

• It is difficult to remove the large amounts of
  pus associated with chronic suppurative
  inflammation.
• The surrounding viable tissue responds with a
  longstanding inflammatory process in which areas
  of suppuration alternate with areas of chronic
  inflammation and fibrosis.

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CHRONIC SUPPURATIVE INFLAMMATION

• The difference between an acute and chronic
  abscess lies in the thickness of the fibrous
  wall both form are filled with pus.

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Abscess of liver
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RECURRENT ACUTE INFLAMMATION

• if there is predisposing cause, repeated attacks
  of acute inflammation may occur
• Each attack of acute inflammation is follwed by
  incomplete resolution that leads to a
  progressively increasing number of chronic
  inflammatory calls and fibrosis.
• subacute inflammation
• acute-on-chronic inflammation

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CLINICAL AND PATHOLOGIC DIAGNOSIS

• difficult
• Precise diagnosis usually requires recourse to a
  full range of clinical and pathologic studies.
• table 4-9