Chapter Four Inflammation

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Chapter FourInflammation

• Su Min (??)

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• Definition
• Inflammation is the protect response of living
  tissue which developed blood system to injury.
• It involves- vascular, neuralgic, humoral and
  cellular response at the site of injury.

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Section 1 Causes manifestion of Inflammation
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Causes

• Physical agents trauma, extremes of heat or
  cold, radiant ray, etc.
• Chemical agents
• exogenous substances
• endogenous substances

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Causes

• Microbiologic agents Viruses, bacteria, fungi,
  protozoa, etc.
• Necrosis tissue
• Immunological reactions

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Manifestion

• 1. Local signs
• (1) Redness
• (2) Swelling
• (3) Heat
• (4) Pain
• (5) Loss of function

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Manifestion

• 2. General responses
• (1) Fever
• (2) Leukocytosis
• (3) Proliferation of the mononuclear phagocyte
  system
• (4) Injury of parenchyma organs.

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Section 2 Basic Pathologic Changes
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• The basic pathologic changes of inflammation in
  the site of injury are alteration, exudation, and
  proliferation.
• 1. Alteration
• (1) Definition The tissues or cells in the
  inflammatory site become degeneration and/or
  necrosis.

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• (2) Causes and mechanism
• Be damaged by inflammatory factors directly.
• Local blood circulation disturbance
• Be affected by inflammatory mediators.
• (3) Morphology
• Parenchyma cells edema, fatty change, necrosis
  etc.
• Interstitium edema, mucoid degeneration,
  fibrinoid degeneration, necrosis, etc.

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• 2. Vascular changes
• (hyperemia and exudation)
• (1) Changes in vascular flow and caliber
• ? Changes in caliber
• Transient arteriolar constriction
• Persistent vasodilatation

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• ? Changes in flow
• a. Initially rapid as a result of vasodilatation
  (active hyperemia)
• b. Slowing and disturbance of axial flow as a
  result of increased blood viscosity secondary to
  loss of plasma into the tissue (congestion and
  edema)

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• ? Changes in the endothelium
• Increased vascular permeability leading to the
  escape of a protein-rich fluid (exudates) into
  the interstitium.
• a. Endothelial cell contraction, or increased
  transcytosis across the endothelial cytoplasm.
• b. Direct endothelial injury, resulting in
  endothelial cell necrosis and detachment
• c. Leakage from regenerating capillaries

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• (2) Fluid exudate
• Normally the walls of small blood vessels are
  freely permeable to water and crystalloids but
  relatively impermeable to plasma proteins. The
  formation of protein-rich fluid exudates is
  facilitated by separation of the intercellular
  junction of the endothelium.

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• The fluid exude carries into the inflamed area
  the following important constituents
• ? Serum bactericidal factors
• a. Antibodies which act by opsonising bacteria
  prior to phagocytosis and by neutralizing
  exotoxins
• b. Components of the complement system

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• ? Interferon a non-specific antiviral agent
• ? Fibrinogen which is converted to fibrin. Fibrin
  is important in providing
• a. Cement substance uniting severed tissues
• b. Scaffold for repair processes
• c. Barrier to the spread of organisms
• d. Surface against which phagocytosis of
  adherent organisms is enhanced
• ? Therapeutic agents-antibiotics,
  anti-inflammatory drugs, etc.

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• (3) Leukocyte exudates and phagocytosis
• ? Leukocytic margination,rolling
• ? Adhesionby the binding of adhesion
• molectures (selectins, immunoglobulins,
• intergrins, mucin-like glycoproteins)

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• ? Emigrating
• It refers to the process by which motile white
  cells migrate out of blood vessels.
• Although all leukocytes are more or less
  motile, the most active are the neutrophils and
  monocytes the most sluggish are the lymphocytes.
• While cell emigration is an active,
  energy-dependent process.
• Red blood cell out of blood vessels, called
  diapedesis, is believed to be passive loss of red
  blood cells through the points of rupture
  (blooding).

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White cell transmigration

• It is include following handings
• ?WBC margination
• ?
• ?WBC adhesion with endothelial surface adhesion
  molecule
• ?
• ?WBC transmigration
• 2-12 minute

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• ? Chemotaxis
• Following extravasations, leukocytes emigrate
  in tissues toward the site of injury by a process
  called chemotaxis.
• Exogenous chemo attractants bacterial products,
  etc.
• Endogenous chemo attractants components of the
  (LTB4), cytokines, etc.

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• ? Phagocytosis
• Recognition and attachment of the particle to
  the surface of the phagocyte? engulfment? killing
  and degradation

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• Types of leukocyte (inflammatory cells)
• Leukocytes are out of blood vessels that are
  known as inflammatory cells.
• a. Neutrophils
• Small phagocytic cell
• The two types of granules in the cytoplasm
• Azurophil granules and specific granules.
• The first cells to appear in perivascular
  spaces are the neutrophils.
• Commonly seen in early stage of inflammation,
  and acute inflammation, and purulent inflammation.

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• b. Macrophages
• Tissue macrophages are derived from blood
  monocytes that emigrate from blood vessels under
  influence of chemotactic factors.
• Commonly seen in later stage of inflammation,
  chronic inflammation, non-purulent inflammation,
  and viral, or protozoal, or fungal infections.
  And macrophages are also related to specific
  immune response.

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• dusty cell
  Langhans giant cell
• foamy cell
• Macrophages could epithelioid cell
• Formation heart failure cell
• 
  Multinucleate giant-cells foreign-body giant
  cell

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• c. Eosinophilia
• Commonly seen in hypersensitivity reaction and
  human parasitological infections.
• d. Lymphocytes and plasma cells
• Commonly seen in virus infection and chronic
  inflammation.
• e. Basophilic and mast cell

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MacrM
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• 3. Proliferation
• Proliferate constitution
• Endothelium, macrophages, and fibroblasts
  commonly seen in later stage of inflammation

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• Section 3
• Inflammatory Mediator

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• 1. Definition
• It is the chemical substances which cause or
  participate in inflammation
• (1) Mediators originate either from plasma or
  cells
• (2) Most mediators perform their biologic
  activity by initially binding to specific
  receptors on target cells.
• (3) A chemical mediator can stimulate the release
  of mediators by target cells themselves.

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• (4) Mediator can on one or few target cell types,
  or have widespread targets, or may even have
  differing effects, depending on cell and tissue
  types.
• (5) Once activated and released from the cell,
  most of these mediators are short-lived
• (6) Most mediators have potential harmful
  effects.

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2. Types of mediator

• (1) Cell produce
• serotonin
• Arachidonic acid metabolic products
  LTB4?LTC4?LTD4?LTE4
• Cell products O2-, H2O2, acid protease, neutral
  proteinase.
• Cytokine IL-1ß, 2,3,4,6,7,10,12, IFN-?, TNF-a,
  CSF.
• Platelet activating factor( PAF)
• nitric oxide(NO)

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2. Types of mediator

• (2) body fluid produce
• Kinin system
• Complement system
• Clotting system

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2. Types of mediator Summary of mediators of
acute inflammation
Mediator Source Action Action Action
Mediator Source Vascular Leakage Chemotaxis Other
Histamine and serotonin Mast cells, platelets _  
Bradykinin Plasma substrate _ Pain
C3a Plasma protein via liver _ Opsonic fragment (C3b)
C5a Macrophages Leukocyte adhesion, activation
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Mediator Source Action Action Action
Mediator Source Vascular Leakage Chemotaxis Other
Prostaglandins Mast cells from membrane phospholipids Potentiate other mediators _ Vasodilation, pain, fever
Leukotriene B4 Leukocytes _ Leukocyte adhesion, activation
Leukotriene C4, D4, E4 Leukocytes, mast cells _ Bronchoconstriction, vasoconstriction
Oxygen metabolites Leukocytes _ Endothelial damage, tissue damage
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Mediator Source Action Action Action
Mediator Source Vascular Leakage Chemotaxis Other
PAF Leukocytes, mast cells Bronchoconstriction, leukocyte priming
IL-1 and TNF Macrophages, other _ Acute phase reactio- ns, endothelial act- evasion
Chemokines Leukocytes, others _ Leukocyte activation
Nitric oxide Macrophages, endothelium Vasodilation, cytotoxicity
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Main mediators function
Function Types of mediator
Vasodilation Histamine, Bradykinin, Nitric oxide, Prostaglandins PGE2, PGD2,PGF2, PGI2
Vascular Leakage Histamine, Bradykinin, C3a, C5a, PAF, active oxygen metabolic products, Leukotrienes C4, D4, E4 Substance P
Chemotaxis C5a, LTB4, bacterial products, IL-8, TNF.
Fever IL-1, IL-6, TNF, PG.
Pain PGE2, Bradykinin
Tissue damage Neutrophil and macrophage lysosomal enzymes Oxygen metabolites, Nitric oxide
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• Section 4
• Types of Inflammation

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• 1. Classification according to duration
• (1) Super-acute inflammation
• Hoursdays
• (2) Acute inflammation
• Daysone month
• (3) Sub-acute inflammation
• One monthmonths
• (4) Chronic inflammation

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• 2. Classification according to pathologic changes
• (1) Alterative inflammation
• ? Alterative changes are the most obviously,
  exudative and proliferate changes are slighter.
• ? Commonly seen in parenchyma organs
• ? Causes virus, toxin, chemical poison, etc.
• ? e. g fulminant hepatitis, type B epidemic
  encephalitis, poliomyelitis, caseous pneumonia,
  etc.

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• (2) Exudative inflammation
• Excess of a particular component of the
  inflammatory exudates imparts distinctive
  features.
• ? Serous inflammation
• Watery, low protein content, derived from blood
  or aerosol lining cells.

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• Commonly seen in mucous membrane, serosa, lung,
  loose connective tissue, skin.
• Examplesblister formation following
  burning, or scalding
• 2 the pleural effusion associated with
  tuberculosis, common cold, etc.

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• ? Fibrinous inflammation
• a. Much fibrin due to coagulation of large
  fibrinogen outpouring.
• b. Causes Shigellosis
• Streptococcus pneumonias
• Corynebacterium diphtherias
• Hg poison
• Uremia

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• c. Commonly seen in
• (i) Serosa
• (ii) Mucous membrane Pseudo-membrane
• (iii) Lung
• d. Examples rheumatic pericarditis, dysentery,
  diphtheria, lobular pneumonia, etc.

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Hairy heart
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diphtheria
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Bacillary dysentery
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• ? Suppurative inflammation
• a.Definition Much exudates with lots of
  neutrophils and liquefied necrotic tissue (pus).
• Pus composed of dead and dying neutrophils,
  liquefied tissue, pyogenic organisms.
• b. Causes staphylococci, pneumococcus,
  gonococci, gram-negative rods, and some
  nonhemolytic streptococci.

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• c. Types
• (i) Abscess a localised collection of pus in an
  organ or tissue.
• Abscess could formation
• Ulcer localized defect in an epithelial surface
  due to necrosis.
• Sinus a abnormal tract leading from a cavity to
  the surface.
• Fistula a tract open at both ends, through which
  abnormal communication between two surface is
  established.

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multi-abscess of kidney
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abscess
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fistula
abscess
sinus
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• (ii) Phlegmonous inflammation
• Definition wide-spread purulent inflammation in
  loose tissue, and appendix
• Causes hemolytic streptococci

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• (iii) Surface purulent inflammation and Empyema
• Surface purulent inflammation
• purulent inflammation of mucosal or serosa
  surface.
• Empyema
• a collection of pus in a hollow viscus, e. g.
  in the gall-bladder or appendix.

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• ? Haemorrhage inflammation
• Inflammation associated with conspicuous
  haemorrhage as a result of vascular damage, e. g.
  meningococcus.
• ? Catarrhal inflammation
• Inflammation of mucosal surfaces with
  hypersecretion of mucus, e. g. common cold

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• (3) Proliferative inflammation
• ? General proliferative inflammation
• Proliferative constitutions
• Fibroblasts, endothelium, macrophage, and
  sometimes coated-epithelium, adenocytes,
  parenchyma cells, etc. commonly seen in chronic
  inflammation

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• ? Special types
• a. Inflammatory granuloma (granulomatous
  inflammation)
• Definition Nodular area of histocytes
  (macrophages)
• Proliferation that have been transformed into
  epithelioid cells, surrounded by a collar of
  lymphocytes, occasionally fibroblasts and plasma
  cells.

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• Types
• (i) Infective granuloma
• Tuberculosis, syphilis, sarcoidosis,
  cat-scratch fever, leprosy, brucellosis, some of
  the mycotic infections, etc.
• Example granuloma of tuberculosis Focal
  aggregation of monocyter that have undergone
  alteration to epithelioid cells. These is caseous
  necrosis in the center. The enclosing wall
  contains several large multinucleate giant cells
  to the Longhand type, with peripheral orientation
  of the nuclei. And also lots of lymphocytes and
  some of fibroblasts.

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Tuberculous granuloma, tubercle
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Langhans giant cell
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• (ii) Foreign bodys granuloma
• Features foreign bodies
• Foreign body giant cell seen in association
  with particulate insoluble material. Nuclei
  scattered throughout cytoplasm. No caseous
  necrosis

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Foreign body giant cell of brain
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• b. Inflammatory polyp

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Nasal polyp
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c. Inflammatory pseudo-tumor
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Inflammatory pseudo-tumor
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• Sections 5
• Course outcome of Inflammation

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Course

• (1) Acute inflammation
• (2) Chronic inflammation

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Outcomes

• (1) Healing
• (2) Delay and Persistence
• (3) Spread
• ?Direct
• ? Lymphatic
• Lymphangitis progressing to acute
  lymphadenitis.

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• ? Blood vessels
• Bacteria Organisms? blood
• Toxemia Toxin? blood
• Septicemia ??
• Multiplication of organisms in the blood
  stream.
• Pyaemia, spread of pyogenic organisms in infected
  micro-thrombi via the blood-stream possibly
  giving rise to metastatic abscesses.

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• (4) Death resulting from
• Toxaemia Bacteria e. g. endotoxic shock and
  its complications.
• Involvement of vital organs, e. g. encephalitis,
  myocarditis.

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• Sections 6
• Significances of Inflammation

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1. Significances

• (1) Inflammation is fundamentally a protective
  response whose ultimate goal is torid the
  organism of both the initial cause of cell injury
  and the consequences of such injury, the necrotic
  cells and tissues.
• (2) Inflammatory response is closely
  intertwined with the process of repair.

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• (3) The inflammatory response occurs in the
  vascularized connective tissue.
• (4) Inflammatory response of both vascular and
  cellular responses are mediated by inflammatory
  mediators chemical factors derived from plasma or
  cells and triggered by the inflammatory stimulus.
• (5) However, inflammatory responses are not
  perfect that may be potentially harmful.

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2. Aspects of inflammation

• (1) Many systemic and local host factors
  influence the adequacy of the inflammatory-
  reparative response.
• ? Nutrion condition
• ? Immune condition
• ? Endocrine condition
• ? Characteristics of inflammatory organ or
  tissue

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• (2) The aspects of inflammatory factors
• ? Character
• ? Quantity
• ? Duration of injury