Acute and chronic inflammation

Inflammation and tissue response to injury

3. BY
DR. IKRAM UL HAQUE
ASSOCIAT PROFESSOR
AND CONSULTANT
HISTOPATHOLOGY
A N M C, LAHORE

5. EDUCATION IS
HANGING
AROUND
UNTIL YOU’VE
CAUGHT ON
Charles Darwin

7. INFLAMMATION
Reaction of a tissue and its microcirculation
to a pathogenic insult or it is a reaction
which is characterized by the generation of
inflammatory mediators and amount of
fluid and leucocytes from the blood into
extra vascular tissue

8. FOUR CARDINAL SIGNS OF
INFLAMMATION
•Rubor (redness)
•Color (heat)
•Tumor (swelling)
•Dolar (pain)
Aulus Celsus
Roman Encyclopedist

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

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

17. ACUTE INFLAMMATION
•“PROTECTIVE”
(RESPONSE)
•NON-specific

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

20. ACUTE INFLAMMATION
•VASCULAR EVENTS
•CELLULAR EVENTS
(PolyMorphonuclearNeutrophil,
Leukocyte?, “POLY”, Neutrophil,
Granulocyte, Neutrophilic
Granulocyte
•“MEDIATORS”

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

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

35. LEAKAGE OF
PROTEINACEOUS FLUID
(EXUDATE ,
NOTTRANSUDATE)

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

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

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

39. 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

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

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

43. CLASSIC MEDIATORS
•HISTAMINE
•SEROTONIN
•COMPLEMENT
•KININS
•CLOTTING
FACTORS
•EICOSANOIDS
•NITRIC OXIDE
•PAF
•CYTOKINES
•/CHEMOKINES
•LYSOSOME
CONSTITUENTS
•FREE RADICALS
•NEUROPEPTIDES

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

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

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

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

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

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

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

53. Leukotrienes
•Chemotaxis
•Vasoconstriction
•Increased Permeability

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

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

56. CYTOKINES/CHEMOKINES
•CYTOKINESare 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)

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

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

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

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

61. OUTCOMES OF
ACUTE INFLAMMATION
•1) 100% complete
RESOLUTION
•2) SCAR
•3)CHRONICinflammation

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

63. BLISTER, “Watery”, i.e., SEROUS

64. FIBRINOUS

65. PUS
=
PURULENT
ABSCESS
=
POCKET
OF
PUS

66. PURULENT, FIBRINOPURULENT

67. ULCERATIVE

69. 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

70. CHRONIC INFLAMMATION
(MONOS)
LYMPHOCYTE
MONOCYTE
MACROPHAGE
HISTIOCYTE

72. CAUSES of
CHRONIC INFLAMMATION
•1) PERSISTENCEof
Infection
•2) PROLONGED
EXPOSUREto insult
•3) AUTO-IMMUNITY

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

74. MORPHOLOGY
•INFILTRATION
•TISSUE DESTRUCTION
•HEALING

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

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

77. LYMPHATIC
DRAINAGE
•SITEREGIONAL LYMPH NODES

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

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