патхологѕ

2. 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

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
inflammation

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
INFLAMMATION are the three possible outcomes

5. ACUTE INFLAMMATION
•“PROTECTIVE”
RESPONSE
(Evolutionary?)
•NON-specific

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

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

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

9. STIMULI
for acute inflammation
•INFECTIOUS (B>V)
•PHYSICAL
•CHEMICAL
• Tissue Necrosis
• Foreign Bodies (FBs)
• Immune “responses”, or “complexes”,
but usually CHRONIC

10. Vascular Changes
• Changes in Vascular Flow
and Caliber
• Increased Vascular
Permeability

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

12. LEAKAGE OF
PROTEINACEOUS FLUID
(EXUDATE, NOT
TRANSUDATE)

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

14. ADHESION MOLECULES (CAMs)
(glycoproteins) affecting
ADHESION and TRANSMIGRATION
• SELECTINS (from
endothelial cells): L,P,E
• INTEGRINS (from many
cells): ~8 types

15. CHEMOTAXIS
PMNs going to the site of “injury”
AFTER transmigration

16. LEUKOCYTE
“ACTIVATION”
• “triggered” by the offending stimuli for PMNs to:
–1) Produce eicosanoids (arachidonic acid
derivatives, 20 carbon chains)
• Prostaglandin (and thromboxanes)
• Leukotrienes
• Lipoxins
–2) Undergo DEGRANULATION
–3) Secrete CYTOKINES (“STORM”)?

17. PHAGOCYTOSIS
• RECOGNITION
• ENGULFMENT
• KILLING
(DEGRADATION/
DIGESTION)

18. CHEMICAL MEDIATORS
• From plasma or cells
• Have “triggering” stimuli
• Usually have specific
targets
• Can cause a “cascade”
• Are short lived
• Many are α-1 and α-2!

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

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

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

22. COMPLEMENT SYSTEM
• >20
components,
in circulating
plasma
• Multiple sites
of action, but
LYSIS is the
underlying
effect
CASCADE!!!

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

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

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

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

29. Leukotrienes
•Chemotaxis
•Vasoconstriction
•Increased Permeability

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

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

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
• CHEMOKINES are small proteins which are
attractants for PMNs (>40)

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

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

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

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

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

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

39. BLISTER, “Watery”, i.e., SEROUS

40. FIBRINOUS

41. PUS
=
PURULENT
ABSCESS
=
POCKET
OF
PUS
=
NEUTROPHILS

42. PURULENT, FIBRINOPURULENT

43. ULCERATIVE

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 
• 100% RESOLUTION, SCAR, or CHRONIC
inflammation

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

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

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

48. MORPHOLOGY
•INFILTRATION
•TISSUE DESTRUCTION
•HEALING
•FIBROSIS (SCARRING)

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

50. GRANULOMAS
GRANULOMATOUS INFLAMMATION
CASEATING (TB)
NON-CASEATING

51. LYMPHATIC
DRAINAGE (SPREAD?)
• SITE REGIONAL LYMPH NODES
SAME AS TUMOR!!!!!

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
• Cytokine Effects, e.g., TNF(α), IL-1

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