Inflammation

(1)

(2)

Inflammation

(5 OBJECTIVES)

1) (Concept) Understand the chain,

progression, or sequence of

(3)

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

(4)

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

(5)

ACUTE INFLAMMATION

• _{“PROTECTIVE”}

RESPONSE

(6)

ACUTE INFLAMMATION

• _VASCULAR

_VASCULAR

EVENTS

• _CELLULAR

_CELLULAR

EVENTS (PMN or

PolyMorphonuclear Neutrophil,

Leukocyte?, “POLY”, Neutrophil,

Granulocyte, Neutrophilic

Granulocyte

(7)

ACUTE

INFLAMMATION

Neutrophil

Polymorphonuclear Leukocyte, PMN, PML “Leukocyte”

Granulocyte, Neutrophilic granulocyte

“Poly-”

(8)

Rubor

Calor

Tumor

Dolor

5

th

_{(functio laesa)}

HISTORICAL

(9)

STIMULI

for acute inflammation

• _INFECTIOUS

_INFECTIOUS

• _PHYSICAL

_PHYSICAL

• _CHEMICAL

_CHEMICAL

• _{Tissue Necrosis}

• _{Foreign Bodies (FBs)}

(10)

Vascular Changes

• _{Changes in Vascular Flow}

and Caliber

• _{Increased Vascular}

(11)

INCREASED PERMEABILITY

• _DILATATION

• _{Endothelial “gaps”}

• _{Direct Injury}

• _{Leukocyte Injury}

(12)

LEAKAGE OF

PROTEINACEOUS FLUID

(

EXUDATE

,

NOT

(13)

EXTRAVASATION of

PMNs

• MARGINATION

(PMN’s go toward

wall)

• ROLLING

(tumbling

and HEAPING)

• ADHESION

• TRANSMIGRATION

(14)

ADHESION MOLECULES

(glycoproteins) affecting

ADHESION and TRANSMIGRATION

• _SECRETINS

_(from

endothelial cells)

• _INTEGRINS

_{(from many}

(15)

CHEMOTAXIS

(16)

LEUKOCYTE

“ACTIVATION”

• “triggered” by the offending stimuli for PMNs to:

–

1)

Produce eicosanoids

(arachidonic acid

derivatives)

• Prostaglandin (and thromboxanes) • Leukotrienes

• _Lipoxins

(17)

PHAGOCYTOSIS

• _RECOGNITION

• ENGULFMENT

• KILLING

(18)

CHEMICAL MEDIATORS

• _{From plasma or cells}

_{From plasma or cells}

• _{Have “triggering” stimuli}

_{Have “triggering” stimuli}

• _{Usually have specific targets}

_{Usually have specific targets}

• _{Can cause a “cascade”}

_{Can cause a “cascade”}

(19)

CLASSIC MEDIATORS

• _HISTAMINE

• _SEROTONIN

• COMPLEMENT

• _KININS

• _CLOTTING

FACTORS

• _EICOSANOIDS

• NITRIC OXIDE

• PLATELET

ACTIVATING

FACTOR (PAF)

• _CYTOKINES

• _/CHEMOKINES

• LYSOSOME

CONSTITUENTS

(20)

HISTAMINE

• _{Mast Cells,}

basophils

• _POWERFUL

Vasodilator

• _Vasoactive

“amine”

• _{IgE on mast}

(21)

SEROTONIN

• _(5HT_,

5 _-

H

ydroxy-T

ryptamine

) • Platelets and

EnteroChromaffin Cells • Also vasodilatation, but

more indirect

(22)

COMPLEMENT SYSTEM

• >20

components,

in circulating

plasma

(23)

KININ SYSTEM

• BRADYKININ is KEY component, 9 aa’s

• ALSO from circulating plasma

• ACTIONS

– Increased permeability

– Smooth muscle contraction, NON vascular

(24)

CLOTTING

FACTORS

• _{Also from circulating plasma}

• _{Coagulation, i.e., production of}

fibrin

(25)

(26)

EICOSANOIDS

(ARACHIDONIC ACID DERIVATIVES)

• _{Part of cell membranes}

• ₁₎

₁₎

_{Prostaglandins}

_(incl.

Thromboxanes)

• ₂₎

₂₎

_Leukotrienes

• ₃₎

₃₎

_Lipoxins

_(new)

(27)

(28)

Prostaglandins

(thromboxanes included)

• _Pain

• _Fever

(29)

Leukotrienes

• _Chemotaxis

• _{Vasoconstriction}

(30)

Lipoxins

• _{INHIBIT chemotaxis}

• _{Vasodilatation}

• _{Counteract actions of}

(31)

P

latelet-

A

ctivating

F

actor

(PAF)

• _Phospholipid

• _{From MANY cells,}

like eicosanoids

• _ACTIVATE

(32)

CYTOKINES/CHEMOKINES

• CYTOKINES

are PROTEINS produced by

MANY cells, but usually LYMPHOCYTES

and MACROPHAGES, numerous roles in

acute and chronic inflammation

–

_TNFα

,

IL-1

,

by

macrophages

(33)

N

ITRIC

O

XIDE

• _{Potent vasodilator}

• _{Produced from the action}

(34)

LYSOSOMAL CONSTITUENTS

• PRIMARY

• Also called

AZUROPHILIC, or

NON-specific

• Myeloperoxidase

• Lysozyme (Bact.)

• Acid Hydrolases

• SECONDARY

• Also called

SPECIFIC

• Lactoferrin

• Lysozyme

• Alkaline Phosphatase

(35)

FREE RADICALS

• _O

₂

–

_(SUPEROXIDE)

• _H2O2

(PEROXIDE)

• _OH

-

(HYDROXYL RADICAL)

(36)

NEUROPEPTIDES

• _{Produced in CNS (neurons)}

(37)

OUTCOMES OF

ACUTE INFLAMMATION

• ₁₎

_{100% complete}

RESOLUTION

• 2)

SCAR

(38)

Morphologic PATTERNS

of Acute INFLAMMATION

(EXUDATE)

• _Serous

_Serous

(watery)

• _Fibrinous

_Fibrinous

(hemorrhagic,

rich in FIBRIN)

• _Suppurative

_Suppurative

(PUS)

(39)

(40)

(41)

PUS

=

PURULENT

ABSCESS =

POCKET OF

PUS =

(42)

(43)

(44)

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_

(45)

CHRONIC INFLAMMATION

(MONOS)

LYMPHOCYTE

“MONO”CYTE MACROPHAGE

(46)

CAUSES of

CHRONIC INFLAMMATION

• ₁₎

_PERSISTENCE

_of

Infection

• ₂₎

_PROLONGED

EXPOSURE

to insult

(47)

Cellular Players

• _LYMPHOCYTES

_LYMPHOCYTES

• _MACROPHAGES

_MACROPHAGES

(aka, HISTIOCYTES)

• PLASMA CELLS

• EOSINOPHILS

(48)

MORPHOLOGY

• _INFILTRATION

• _{TISSUE DESTRUCTION}

(49)

GRANULOMAS

GRANULOMATOUS INFLAMMATION

4 COMPONENTS

FIBROBLASTS

LYMPHS

HISTIOS

(50)

GRANULOMAS

GRANULOMATOUS INFLAMMATION

CASEATING (TB)

(51)

LYMPHATIC

DRAINAGE

(52)

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

(53)

NORMAL SPE

Serum

Protein

Electrophoresis

In ACUTE

Inflammation

Alpha-1 & alpha-2

are increased, i.e.,

“acute phase”