5 OBJECTIVES
1.Understand the concept, progression, or sequence of vascular and cellular events in acute inflammation
2.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

• “PROTECTIVE”RESPONSE
• “NON”-Specific

• VASCULAR
EVENTS
• CELLULAR
EVENTS (PMN or
P oly M orphonuclear N eutrophil)
• “MEDIATORS”

Neutrophil (PMN)
Polymorphonuclear
Leukocyte(PML)

HISTORICAL
HIGHLIGHTS
(SIGNS OF
INFLAMMATION)
Rubor
Calor
Tumor
Dolor
5 th (functio laesa)

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

• Changes in Vascular Flow and
Caliber
• Increased Vascular
Permeability

INCREASED PERMEABILITY
• DILATATION
• Endothelial “gaps”
• Direct Injury
• Leukocyte Injury
• Transocytosis (endo/exo)
• New Vessels

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

PMNs going to the site of “injury”
AFTER transmigration

• “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

• RECOGNITION
• ENGULFMENT
• KILLING
(DEGRADATION/DIG
ESTION)

• From plasma or cells
• Have “triggering” stimuli
• Usually have specific targets
• Can cause a “cascade”
• Are short lived

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

(thromboxanes included)
• Pain
• Fever
• Clotting

• Chemotaxis
• Vasoconstriction
• Increased Permeability

P lateletA ctivating F actor
(PAF)
• Phospholipid
• From MANY cells, like eicosanoids
• ACTIVATE PLATELETS, powerfully

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

N
O
• Potent vasodilator
• Produced from the action of nitric oxide synthetase from arginine

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

• O
2 –
(SUPEROXIDE)
• H2O2 (PEROXIDE)
• OH
-
(HYDROXYL RADICAL)
VERY VERY
DESTRUCTIVE

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

Morphologic PATTERNS of Acute INFLAMMATION
(EXUDATE)
•
(watery)
•
(hemorrhagic, rich in FIBRIN)
•
(PUS)
•

BLISTER, “Watery”, i.e., SEROUS

FIBRINOUS

PUS
=
PURULENT
ABSCESS
=
POCKET
OF
PUS
=
NEUTROPHILS

PURULENT, FIBRINOPURULENT

ULCERATIVE

Systemic effects
• Fever
• Leukocytosis
• Acute phase proteins
• Others –sleepiness, hypotension, lipolysis

CHRONIC INFLAMMATION
LYMPHOCYTE
“MONO”CYTE
MACROPHAGE
HISTIOCYTE
APC

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

•
•
• PLASMA CELLS
• EOSINOPHILS
• MAST CELLS

• INFILTRATION
• TISSUE DESTRUCTION
• HEALING

GRANULOMATOUS INFLAMMATION
4 COMPONENTS
FIBROBLASTS
LYMPHS
HISTIOS
“GIANT” CELLS

GRANULOMATOUS INFLAMMATION

• SITE  REGIONAL LYMPH NODES

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