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Inflammation
(5 OBJECTIVES)
1) (Concept) Understand the chain, progression, or sequence of vascular and cellular events in the histologic evolution of acute inflammation
2) (Rote?) Learn the roles of various chemical mediators of acute inflammation 3) Know the three possible outcomes of acute inflammation 4) Visualize the three morphologic patterns of acute inflammation 5) Understand the causes, morphologic patterns, principle cells, minor cells, of chronic and granulomatous inflammation
SEQUENCE OF EVENTS
NORMAL HISTOLOGY VASODILATATION INCREASED VASCULAR PERMEABILITY LEAKAGE OF EXUDATE MARGINATION, ROLLING, ADHESION TRANSMIGRATION (DIAPEDESIS) CHEMOTAXIS PMN ACTIVATION PHAGOCYTOSIS: Recognition, Attachment, Engulfment, Killing (degradation or digestion) TERMINATION 100% RESOLUTION, SCAR, or CHRONIC INFLAMMATION are the three possible outcomes
NON-specific
ACUTE INFLAMMATION
VASCULAR EVENTS CELLULAR EVENTS (PMN or
PolyMorphonuclear Neutrophil,
Leukocyte?, POLY, Neutrophil, Granulocyte, Neutrophilic Granulocyte
MEDIATORS
ACUTE INFLAMMATION
Neutrophil Polymorphonuclear Leukocyte, PMN, PML Leukocyte Granulocyte, Neutrophilic granulocyte Poly- Polymorph
HISTORICAL HIGHLIGHTS
(Egypt, 3000 BC)
Vascular Changes
Changes in Vascular Flow and Caliber Increased Vascular Permeability
INCREASED PERMEABILITY
DILATATION Endothelial gaps Direct Injury Leukocyte Injury Transocytosis (endo/exo) New Vessels
EXUDATE, NOT
TRANSUDATE)
MARGINATION (PMNs go toward wall) ROLLING (tumbling and HEAPING) ADHESION TRANSMIGRATION (DIAPEDESIS)
EXTRAVASATION of PMNs
CHEMOTAXIS
PMNs going to the site of injury AFTER transmigration
LEUKOCYTE ACTIVATION
triggered by the offending stimuli for PMNs to: 1) Produce eicosanoids (arachidonic acid derivatives)
Prostaglandin (and thromboxanes) Leukotrienes Lipoxins
PHAGOCYTOSIS
RECOGNITION ENGULFMENT KILLING (DEGRADATION/ DIGESTION)
CHEMICAL MEDIATORS
From plasma or cells Have triggering stimuli Usually have specific targets Can cause a cascade Are short lived
CLASSIC MEDIATORS
HISTAMINE SEROTONIN COMPLEMENT KININS CLOTTING FACTORS EICOSANOIDS NITRIC OXIDE
PLATELET ACTIVATING FACTOR (PAF) CYTOKINES /CHEMOKINES LYSOSOME CONSTITUENTS FREE RADICALS NEUROPEPTIDES
HISTAMINE
Mast Cells, basophils POWERFUL Vasodilator Vasoactive amine IgE on mast cell
SEROTONIN
(5HT,
5-Hydroxy-
Tryptamine)
Platelets and EnteroChromaffin Cells Also vasodilatation, but more indirect Evokes N.O. synthetase (a ligase)
COMPLEMENT SYSTEM
>20 components, in circulating plasma Multiple sites of action, but LYSIS is the underlying theme
KININ SYSTEM
BRADYKININ is KEY component, 9 aas ALSO from circulating plasma ACTIONS
Increased permeability Smooth muscle contraction, NON vascular
PAIN
CLOTTING FACTORS
Also from circulating plasma Coagulation, i.e., production of fibrin Fibrinolysis
EICOSANOIDS
(ARACHIDONIC ACID DERIVATIVES)
Prostaglandins
(thromboxanes included) Pain Fever Clotting
Leukotrienes
Chemotaxis Vasoconstriction Increased Permeability
Lipoxins
INHIBIT chemotaxis Vasodilatation Counteract actions of leukotrienes
CYTOKINES/CHEMOKINES
CYTOKINES are PROTEINS produced by MANY cells, but usually LYMPHOCYTES and MACROPHAGES, numerous roles in acute and chronic inflammation
TNF, IL-1, by
macrophages
CHEMOKINES are small proteins which are attractants for PMNs (>40)
NITRIC OXIDE
Potent vasodilator Produced from the action of nitric oxide synthetase from arginine
PRIMARY
LYSOSOMAL CONSTITUENTS
SECONDARY
Also called SPECIFIC Lactoferrin Lysozyme Alkaline Phosphatase Collagenase
FREE RADICALS
O2 (SUPEROXIDE)
VERY VERY
NEUROPEPTIDES
Produced in CNS (neurons) SUBSTANCE P NEUROKININ A
Fibrinous (hemorrhagic,
rich in FIBRIN)
FIBRINOUS
PUS = PURULENT
PURULENT, FIBRINOPURULENT
ULCERATIVE
Cellulits = acute skin infection commonly caused by Streptococcus pyogenes or Staphylococcus aureus
Heat
The nomenclature used to describe inflammation in different tissues employs the tissue name and the suffix -itis
e.g pancreatitis meningitis pericarditis arthritis
Type
Classic type
Features
Hyperemia; exudation with fibrin and neutrophils; neutrophil leukocytosis in blood.
Common Causes
Bacterial infections; response to cell necrosis of any cause.
Paucity of neutrophils in exudate; lymphocytes and Viral and rickettsial infections (immune response plasma cells predominant; neutropenia, lymphocytosis in contributes). blood. Marked edema and numerous eosinophils; eosinophilia in Certain hypersensitivity immune reactions blood. Burns; many bacterial infections.
Serous inflammation Marked fluid exudation. (inflammation in body cavities) Catarrhal inflammation Marked secretion of mucus. (inflammation of mucous membranes)
Fibrinous inflammation Excess fibrin formation. Necrotizing inflammation, hemorrhagic inflammation Marked tissue necrosis and hemorrhage.
Many virulent bacterial infections. Highly virulent organisms (bacterial, viral, fungal), eg, plague (Yersinia pestis), anthrax (Bacillus anthracis), herpes simplex encephalitis, mucormycosis.
Membranous Necrotizing inflammation involving mucous membranes. Toxigenic bacteria, eg, diphtheria bacillus (pseudomembranous) The necrotic mucosa and inflammatory exudate form an (Corynebacterium diphtheriae) and Clostridium inflammation adherent membrane on the mucosal surface. difficile. Suppurative (purulent) Exaggerated neutrophil response and liquefactive inflammation necrosis of parenchymal cells; pus formation. Marked neutrophil leukocytosis in blood. Pyogenic bacteria, eg, staphylococci, streptococci, gramnegative bacilli, anaerobes.
Different morphological patterns of acute inflammation can be found depending on the cause and extend of injury and site of inflammation
Serous inflammation
Purulent inflammation
Fibrinous inflammation
ulcers
Pneumonia
Congested septal capillaries
= red hepatization
Red Hepatization
Massive confluent exudation with red cells, neutrophils and fibrin into alveolar spaces Lobes are distinctly red, firm and airless, with liver-like consistency
Gray Hepatization
Follows with progressive disintegration of red cells and persistence of a fibrino-suppurative exudate resulting in grayish dry appearance
Resolution or scarring
Resolution due to clearance of the infection and enzymatic digest of exudate which can be reabosrbed, ingested by macrophages cleared via muco-cilliary escalator Scarring due to organization of exudate, infiltration of fibroblasts and deposition of collagen
Red hepatization
Gray hepatization
Abscess formation
is the result of a suppurative (purulent) necrosis of the parechyma resulting in the formation of one or more cavities it has a central necrosis, rimmed by neutrophils and surrounded by fibroblasts
Occurs in the lung due to: Aspiration of infective material Aspiration of gastric content Complication of necrotizing bacterial pneumonia (e.g Staphylococcus) Septic embolism
Peptic ulcer
An ulcer is a local defect of mucosal lining produced by shedding of necrotic tissue Peptic ulcers are produced by an imbalance between gastroduodenal defense mechanisms and the damaging force 70% of all ulcers are due to H. pyolri infection which initiates a strong inflammatory response
Inflammed Lung
FIBRINOUS INFLAMMATION With more severe injuries and the resulting greater vascular permeability, larger molecules such as fibrinogen pass the vascular barrier, and fibrin is formed and deposited in the extracellular space
Leukocytosis
Neutrophilia and left shift of neutrophils points to bacterial infection Lymphocytosis points to viral infection Eosinophilia point to allergy or parasitic infection
Outcome of acute inflammation Complete restitution Abscess formation (encapsulation and pus) Chronic inflammation Healing with scar formation
SEQUENCE OF EVENTS
NORMAL HISTOLOGY VASODILATATION INCREASED VASCULAR PERMEABILITY LEAKAGE OF EXUDATE MARGINATION, ROLLING, ADHESION TRANSMIGRATION (DIAPEDESIS) CHEMOTAXIS PMN ACTIVATION PHAGOCYTOSIS: Recognition, Attachment, Engulfment, Killing (degradation or digestion) TERMINATION 100% RESOLUTION, SCAR, or CHRONIC inflammation