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Chapter FourChapter Four
InflammatioInflammationn
Su Min (苏敏)
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.
Section 1 Section 1 Causes & manifestion of Causes & manifestion of
InflammationInflammation
CausesCauses
Physical agents: trauma, extremes of heat or cold, radiant ray, etc.
Chemical agents
exogenous substances
endogenous substances
CausesCauses
Microbiologic agents: Viruses, bacteria, fungi, protozoa, etc.
Necrosis tissue
Immunological reactions
ManifestionManifestion
1. Local signs
(1) Redness (2) Swelling (3) Heat (4) Pain (5) Loss of function
ManifestionManifestion
2. General responses
(1) Fever
(2) Leukocytosis
(3) Proliferation of the mononuclear phagocyte system
(4) Injury of parenchyma organs.
Section 2 Section 2 Basic Pathologic Changes Basic Pathologic Changes
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.
(2) Causes and mechanism:Be damaged by inflammatory factors directly.Local blood circulation disturbanceBe affected by inflammatory mediators.
(3) Morphology Parenchyma cells: edema, fatty change,
necrosis etc.Interstitium: edema, mucoid degeneration,
fibrinoid degeneration, necrosis, etc.
2. Vascular changes (hyperemia and exudation)
(1) Changes in vascular flow and caliber
① ① Changes in caliberChanges in caliber
Transient arteriolar constriction
Persistent vasodilatation
② ② Changes in flowChanges 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)
③ ③ Changes in the endotheliumChanges 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
(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.
The fluid exude carries into the inflamed area the following important constituents:
① Serum bactericidal factors
a. Antibodies which act by opsonising bacteria prior to phagocytosis and by neutralizing exotoxins
b. Components of the complement system
② Interferon: a non-specific antiviral agent
③ Fibrinogen which is converted to fibrin. Fibrin is important in providing:
a. Cement substance uniting severed tissuesb. Scaffold for repair processesc. Barrier to the spread of organismsd. Surface against which phagocytosis of adherent
organisms is enhanced
④ Therapeutic agents-antibiotics, anti-inflammatory drugs, etc.
(3) Leukocyte exudates and phagocytosis
① Leukocytic margination,rolling
② Adhesion:by the binding of adhesion molectures (selectins, immunoglobulins, intergrins, mucin-like glycoproteins)
③ 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).
White cell transmigrationWhite cell transmigration
It is include following handings:
WBC margination
WBC adhesion with endothelial
surface adhesion molecule
WBC transmigration 2-12 minute
④ Chemotaxis
Following extravasations, leukocytes emigrate in tissues toward the site of injury by a process called chemotaxis.
Exogenous chemo attractants:Exogenous chemo attractants: bacterial products, etc.
Endogenous chemo attractants:Endogenous chemo attractants: components of the (LTB4), cytokines, etc.
⑤ Phagocytosis
Recognition and attachment of the particle to the surface of the phagocyte→ engulfment→ killing and degradation
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.
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.
dusty cell Langhan’s giant cell
foamy cell
Macrophages could epithelioid cell
Formation heart failure cell
Multinucleate giant-cells foreign-body giant cell
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
MacrM
3. Proliferation
Proliferate constitution:Proliferate constitution:
Endothelium, macrophages, and fibroblasts commonly seen in later stage of inflammation
Section 3
Inflammatory Mediator
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.
(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.
2. 2. Types of mediatorTypes of mediator(1) (1) Cell produceCell produce serotonin Arachidonic acid metabolic products:
LTB4 、 LTC4 、 LTD4 、 LTE4 Cell products: O2
-, H2O2, acid protease, neutral proteinase.
Cytokine: IL-1β, 2,3,4,6,7,10,12, IFN-γ, TNF-α, CSF.
Platelet activating factor( PAF) nitric oxide(NO)
2. 2. Types of mediatorTypes of mediator
(2) body fluid produce
Kinin system
Complement system
Clotting system
2. 2. Types of mediatorTypes of mediator Summary of mediators of acute inflammation
Mediator Source
Action
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
Mediator Source
Action
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
Mediator Source
Action
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
Main mediators functionMain 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
Section 4
Types of Inflammation
1. Classification according to duration
(1) Super-acute inflammation
Hours——days
(2) Acute inflammation
Days——one month
(3) Sub-acute inflammation
One month——months
(4) Chronic inflammation
2. Classification according to pathologic changes
(1) Alterative inflammation
① Alterative changes are the most obviously, exudative and proliferate changes are slighter.
② Commonly seen in parenchyma organs
③ Causes: virus, toxin, chemical poison, etc.
④ e. g: fulminant hepatitis, type B epidemic encephalitis, poliomyelitis, caseous pneumonia, etc.
(2) Exudative inflammation
Excess of a particular component of the inflammatory exudates imparts distinctive features.
① Serous inflammationWatery, low protein content, derived from
blood or aerosol lining cells.
皮肤浆液性炎(水疱)
Commonly seen in:Commonly seen in: mucous membrane, serosa, lung, loose connective tissue, skin.
Examples:Examples:blister formation following burning, or scalding
2 the pleural effusion associated with tuberculosis, common cold, etc.
② Fibrinous inflammation
a. Much fibrin due to coagulation of large fibrinogen outpouring.
b. Causes: Shigellosis
Streptococcus pneumonias
Corynebacterium diphtherias
Hg poison
Uremia
c. Commonly seen in
(i) Serosa
(ii) Mucous membrane: Pseudo-membrane
(iii) Lung
d. Examples: rheumatic pericarditis, dysentery, diphtheria, lobular pneumonia, etc.
Hairy heart
diphtheria
Bacillary dysentery
③ 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.
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.
multi-abscess of kidney
abscess
sinus
abscess
fistula
(ii) Phlegmonous inflammation
Definition: wide-spread purulent inflammation in loose tissue, and appendix
Causes: hemolytic streptococci
(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.
④ Haemorrhage inflammation:
Inflammation associated with conspicuous haemorrhage as a result of vascular damage, e. g. meningococcus.
⑤ Catarrhal inflammation:
Inflammation of mucosal surfaces with hypersecretion of mucus, e. g. common cold
(3) Proliferative inflammation
① General proliferative inflammation
Proliferative constitutions:
Fibroblasts, endothelium, macrophage, and sometimes coated-epithelium, adenocytes, parenchyma cells, etc. commonly seen in chronic inflammation
② Special types
a. Inflammatory granuloma (granulomatous inflammation)
Definition: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.
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.
Tuberculous granuloma, tubercle
Langhans giant cell
(ii) Foreign body’s granuloma
Features: foreign bodies
Foreign body giant cell: seen in association with particulate insoluble material. Nuclei scattered throughout cytoplasm. No caseous necrosis
Foreign body giant cell of brain
b. Inflammatory polyp
Nasal polyp
c. Inflammatory pseudo-tumor
Inflammatory pseudo-tumor
Sections 5 Course & outcome of Inflammation
CourseCourse
(1) Acute inflammation
(2) Chronic inflammation
OutcomesOutcomes
(1) Healing
(2) Delay and Persistence(3) Spread(3) Spread ①Direct ② Lymphatic: Lymphangitis progressing to acute
lymphadenitis.
③ Blood vessels
Bacteria:Bacteria: Organisms→ blood
Toxemia:Toxemia: Toxin→ blood
Septicemia:Septicemia: +① ② 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.
(4) Death resulting from
Toxaemia & Toxaemia & BacteriaBacteria : : e. g. endotoxic shock and its complications.
Involvement of vital organs, e. g. encephalitis, myocarditis.
Sections 6
Significances of Inflammation
1. 1. SignificancesSignificances
(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.
(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.
2. 2. Aspects of inflammationAspects of inflammation
(1) Many systemic and local host factors influence the adequacy of the inflammatory- reparative response.
① Nutrion condition
② Immune condition
③ Endocrine condition
④ Characteristics of inflammatory organ or tissue
(2) The aspects of inflammatory factors
① Character
② Quantity
③ Duration of injury