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