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CHAPTER 2
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 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

ACUTE INFLAMMATION
•“PROTECTIVE”
RESPONSE
•NON-specific

Neutrophilic Granulocyte • “MEDIATORS” . “POLY”.ACUTE INFLAMMATION • VASCULAR EVENTS • CELLULAR EVENTS (PMN or PolyMorphonuclear Neutrophil. Neutrophil. Granulocyte. Leukocyte?.

Neutrophilic granulocyte “Poly-” Polymorph . PMN. PML “Leukocyte” Granulocyte. ACUTE INFLAMMATION Neutrophil Polymorphonuclear Leukocyte.

3000 BC) Rubor Calor Tumor Dolor 5th (functio laesa) . HISTORICAL HIGHLIGHTS (Egypt.

STIMULI for acute inflammation • INFECTIOUS • PHYSICAL • CHEMICAL • Tissue Necrosis • Foreign Bodies (FBs) • Immune “responses”. or “complexes” .

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 .

LEAKAGE OF PROTEINACEOUS FLUID ( EXUDATE. NOT TRANSUDATE) .

EXTRAVASATION of PMNs • MARGINATION (PMN’s go toward wall) • ROLLING (tumbling and HEAPING) • ADHESION • TRANSMIGRATION (DIAPEDESIS) .

ADHESION MOLECULES (glycoproteins) affecting ADHESION and TRANSMIGRATION • SECRETINS (from endothelial cells) • INTEGRINS (from many cells) .

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 – 2) Undergo DEGRANULATION – 3) Secrete CYTOKINES .

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 • PLATELET • HISTAMINE ACTIVATING • SEROTONIN FACTOR (PAF) • COMPLEMENT • CYTOKINES • KININS • /CHEMOKINES • CLOTTING • LYSOSOME FACTORS CONSTITUENTS • EICOSANOIDS • FREE RADICALS • NITRIC OXIDE • NEUROPEPTIDES .

HISTAMINE • Mast Cells. basophils • POWERFUL Vasodilator • Vasoactive “amine” • IgE on mast cell .

but more indirect • Evokes N. SEROTONIN • (5HT.O. 5-Hydroxy- Tryptamine) • Platelets and EnteroChromaffin Cells • Also vasodilatation. synthetase (a ligase) from argenine .

COMPLEMENT SYSTEM • >20 components. in circulating plasma • Multiple sites of action. but LYSIS is the underlying theme .

NON vascular –PAIN .KININ SYSTEM • BRADYKININ is KEY component. 9 aa’s • ALSO from circulating plasma • ACTIONS – Increased permeability – Smooth muscle contraction.

i. CLOTTING FACTORS • Also from circulating plasma • Coagulation.e. production of fibrin • Fibrinolysis ..

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EICOSANOIDS (ARACHIDONIC ACID DERIVATIVES) • Part of cell membranes • 1) Prostaglandins (incl. Thromboxanes) • 2) Leukotrienes • 3) Lipoxins (new) MULTIPLE ACTIONS AT MANY LEVELS .

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Prostaglandins (thromboxanes included) • Pain • Fever • Clotting .

Leukotrienes • Chemotaxis • Vasoconstriction • Increased Permeability .

Lipoxins • INHIBIT chemotaxis • Vasodilatation • Counteract actions of leukotrienes .

like eicosanoids • ACTIVATE PLATELETS. Platelet-Activating Factor (PAF) • Phospholipid • From MANY cells. powerfully .

CXC. XC families. numerous roles in acute and chronic inflammation –TNFα. IL-1.. CX3C.CYTOKINES/CHEMOKINES • CYTOKINES are PROTEINS produced by MANY cells. CC. e. PF-4. but usually LYMPHOCYTES and MACROPHAGES. IL-8 . by macrophages • CHEMOKINES are small proteins which are attractants for PMNs (>40).g.

NITRIC OXIDE • Potent vasodilator • Produced from the action of nitric oxide synthetase from arginine .

or NON-specific • Lactoferrin • Lysozyme • Myeloperoxidase • Alkaline Phosphatase • Lysozyme (Bact.) • Collagenase • Acid Hydrolases .LYSOSOMAL CONSTITUENTS • PRIMARY • SECONDARY • Also called • Also called SPECIFIC AZUROPHILIC.

(HYDROXYL RADICAL) •VERY VERY DESTRUCTIVE .FREE RADICALS • O2 – (SUPEROXIDE) •H2O2 (PEROXIDE) •OH.

NEUROPEPTIDES • Produced in CNS (neurons) • SUBSTANCE P • NEUROKININ A .

OUTCOMES OF ACUTE INFLAMMATION • 1) 100% complete RESOLUTION • 2) SCAR • 3)CHRONIC inflammation .

rich in FIBRIN) •Suppurative (PUS) •Ulcerative . Morphologic PATTERNS of Acute INFLAMMATION (EXUDATE) •Serous (watery) •Fibrinous (hemorrhagic.

SEROUS . i.. “Watery”.e.BLISTER.

FIBRINOUS .

PUS = PURULENT ABSCESS = POCKET OF PUS = NEUTROPHILS .

PURULENT. FIBRINOPURULENT .

ULCERATIVE .

Killing (degradation or digestion)  • TERMINATION  • 100% RESOLUTION. ADHESION  • TRANSMIGRATION (DIAPEDESIS)  • CHEMOTAXIS  • PMN ACTIVATION  • PHAGOCYTOSIS: Recognition. SEQUENCE OF EVENTS • NORMAL HISTOLOGY  • VASODILATATION  • INCREASED VASCULAR PERMEABILITY  • LEAKAGE OF EXUDATE  • MARGINATION. SCAR. Attachment. Engulfment. or CHRONIC inflammation . ROLLING.

CHRONIC INFLAMMATION (MONOS) “MONO”CYTE MACROPHAGE LYMPHOCYTE HISTIOCYTE APC .

CAUSES of CHRONIC INFLAMMATION • 1) PERSISTENCE of Infection • 2) PROLONGED EXPOSURE to insult • 3) AUTO-IMMUNITY .

Cellular Players •LYMPHOCYTES •MACROPHAGES (aka. HISTIOCYTES) • PLASMA CELLS • EOSINOPHILS • MAST CELLS .

MORPHOLOGY • INFILTRATION • TISSUE DESTRUCTION • HEALING .

GRANULOMAS GRANULOMATOUS INFLAMMATION 4 COMPONENTS FIBROBLASTS LYMPHS HISTIOS “GIANT” CELLS .

GRANULOMAS GRANULOMATOUS INFLAMMATION CASEATING (TB) NON-CASEATING .

LYMPHATIC DRAINAGE • SITE REGIONAL LYMPH NODES .

CHILLS • C-Reactive Protein (CRP) • “Acute Phase” Reactants. SYSTEMIC MANIFESTATIONS (NON-SPECIFIC) • FEVER. e. Blood Pressure • Cytokine Effects. i. α1-α2 • Erythrocyte Sedimentation Rate (ESR) increases • Leukocytosis • Pulse..e.. IL-1 .g. TNF(α).

. “acute phase” reactants.NORMAL SPE Serum Protein Electrophoresis In ACUTE Inflammation Alpha-1 & alpha-2 are increased.e. i..