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Acute inflammation handouts 30 9-2016
1.
2. • Definition of inflammation
• Cardinal signs of inflammation
• Clinical examples of inflammation
• Chemical mediators of inflammation
• Morphology of acute inflammation
3. OBJECTIVES
• MENTION THE CHEMICAL MEDIATORS OF
INFLAMMATION[5M]
• ENUMERATE THE DIFFERENCE BETWEEN TRANSUDATE
&EXUDATE[2M]
• WRITE A NOTE ON VASCULAR &CELLULAR EVENTS OF
INFLAMMATION[5M]
• WRITE A NOTE ON PHAGOCYTOSIS[2M]
• WHAT IS OPSONIZATION[2M]
• WRITE A NOTE ON FATE OF ACUTE INFLAMMATION
• Write a note on cytokines
• Write a note on prostaglandins
4. Inflammation
Inflammation is the response of body
tissues to injury from any agent which could be microbial,
immunological, physical or chemical agents.
Inflammation is of 2 types:
Acute Inflammation
due to early response by the body
short duration
Chronic Inflammation
occurs after delay
it is for longer duration
Characterised by response by chronic inflammatory cells.
5. • Tissues & cells involved in infalmmation
are: fluid and proteins of plasma,
• circulating cells,
• blood vessels,
• Extracellular matrix
• Connective tissue
19. • Acute inflammation has three major components:
(1) alterations in vascular caliber that lead
to an increase in blood flow;
• (2) structural changes in the
microvasculature that permit plasma proteins
and leukocytes to leave the circulation; and
• (3) emigration of the
leukocytes from the microcirculation, their
accumulation in the focus of injury, and their
activation to eliminate the offending agent.
28. WHAT POST-CAPILLARY VENULAR CHANGES OCCUR
WITH ACUTE INFLAMMATION?
Injury / infection Stimulus
Post-capillary venular Responding element
endothelial cells
I. Increased venular permeability Response (1)
AND
II. Attraction of leukocytes to injury Response (2)
Exudation** Consequence
-Plasma protein exudation (1st)
-Leukocyte emigration (2nd)
Swelling (EDEMA) Clinical observation
29. (Histamine, serotonin, bradykinin,
PAF, SRS-A (leukotrienes)
Contraction of
endothelial cells
Normal post-capillary venules: endothelial cells are in contact
B) Changes in venules w/ acute inflammation
Mediators of inflammation
Chemoattraction,
chemotaxis
Plasma entry
into interstitial space
(William E. Winter, MD)
30.
31. Arteriolar Incr. venular Major
Molecule dilatation permeability source(s)
Histamine yes yes mast cells
Serotonin yes yes platelets
Bradykinin yes yes plasma
PAF yes yes various cells,
plts, endothel.
Leukotrienes yes various cells,
(SRS-A) mast cells,
macrophages
What chemical mediators are responsible for
VASCULAR CHANGES w/ acute inflammation?
Note: PAF = platelet activating factor
33. In acute inflammation how do exudates form?
Contraction of post-capillary venular endothelial cells
Increased inter-cellular spaces
Protein-rich fluid leaks outside the vasculature
[ A N D ]
Attraction of leukocytes to the site of injury
Leukocytes leave circulation (easier access b/c of
increased inter-cellular spaces)
Result: Leukocyte-rich Exudate
47. 1) Cellular injury (e.g., necrosis, infection) +/- hemorrhage
(initiators of inflammation)
2) Vascular changes:
Hyperemia & incr. vascular permeability* (occur
concurrently)
3) Leukocyte emigration* & leukocyte actions
4) Healing w/ return to nl structure (resolution) or scar
What Is The Normal Sequence Of Events In Inflammation?
* Initial exudate: protein-rich
Later exudate: protein-rich & leukocyte-rich
(William E. Winter, MD)
48.
49. ACUTE INFLAMMATION - CELLULAR EVENTS:
LEUKOCYTE EXTRAVASATION AND PHAGOCYTOSIS
• The sequence of events of moving leukocytes from the vessel lumen
to the interstitial tissue, called EXTRAVASATION, can be divided into :
1. Events in the vascular lumen:
i. MARGINATION because blood flow slows early in inflammation
(stasis), the endothelium can be virtually lined by white cells
(pavementation)
ii. ROLLING
iii. ADHESION to endothelium
(Vascular endothelium normally does not bind circulating cells)
2. Transmigration across the endothelium (also called DIAPEDESIS)
3. Migration in interstitial tissues toward a chemotactic stimulus
50. • WHICH FACTORS HELP IN ROLLING,
ADHESION AND
TRANMIGRATION[DIAPEDESIS]
• IS IT SAME CHEMICAL MEDIATORS?
52. Role of endothelial molecules in acute inflammation
Endothelial molecule Major role
P-selectin Rolling
E-selectin Rolling and Adhesion
ICAM-1 (Integrin – β1) Adhesion, Arrest
VCAM-1 (Integrin – β2) Adhesion
PECAM-1 (CD-31) Diapedesis
53. Fig 2-4 (p48)
THE MULTISTEP PROCESS OF LEUKOCYTE MIGRATION
THROUGH BLOOD VESSELS (Margination & Rolling-
Adhesion-Transmigration-Chemotaxis)
56. • In most forms of acute inflammation,
NEUTROPHILS predominate in the
inflammatory infiltrate during the first 6 to 24
hours, then are replaced by MONOCYTES in 24
to 48 hours
• In viral infections, lymphocytes may be the first
cells to arrive
• In some hypersensitivity reactions, eosinophil
may be the main cell type
61. Phagocytosis
There are 2 main types of phagocytic cells:
i. Polymorphonuclear neutrophils (PMNs) which
appear early in acute inflammatory response.
ii. Circulating monocytes and fixed tissue
mononuclear phagocytes, commonly called as
macrophages.
62. Phagocytosis
Neutrophils and macrophages upon reaching the tissue spaces produce
several proteolytic enzymes—
• Lysozyme
• Protease
• Collagenase
• Elastase
• Lipase
• Proteinase
• Gelatinase
• Acid hydrolases.
These enzymes degrade collagen and extracellular matrix.
76. MORPHOLOGIC PATTERNS OF ACUTE
INFLAMMATION
Serous inflammation
• Accumulation of excessive clear
watery fluid with a variable protein
content.
• Occurs in skin, and in peritoneal,
pleural and pericardial cavities
• eg The skin blister resulting from a burn
or viral infection is a good example of
the accumulation of a serous effusion
either within or immediately beneath the
epidermis of the skin
77. MORPHOLOGIC PATTERNS OF ACUTE
INFLAMMATION
Fibrinous inflammation
• Large amounts of
fibrinogen pass the vessel
wall, and fibrins are
formed in the fluid
exudate of extracellular
spaces.
• eg Fibrinous pericarditis
in which fibrin is
deposited on the
pericardium.
78. MORPHOLOGIC PATTERNS OF ACUTE
INFLAMMATION
Suppurative (purulent)
inflammation
• The formation of purulent
exudates or pus.
• Pus is made up of neutrophils,
necrotic cells and edema fluid.
• Abscess is a localized
collection of purulent inflammation
accompanied by liquefactive
necrosis.
• eg Multiple bacterial abscesses in
the lung (arrows) in a case of
bronchopneumonia
81. TABLE 2-6 -- Cytokines in Inflammation
Cytokine Principal Sources
Principal Actions in
Inflammation
IN ACUTE INFLAMMATION
TNF Macrophages, mast
cells, T lymphocytes
Stimulates expression of
endothelial adhesion
molecules and secretion of
other cytokines; systemic
effects
IL-1 Macrophages,
endothelial cells, some
epithelial cells
Similar to TNF; greater role
in fever
IL-6 Macrophages, other
cells
Systemic effects (acute-phase
response)
Chemokines Macrophages,
endothelial cells, T
lymphocytes, mast cells,
other cell types
Recruitment of leukocytes to
sites of inflammation;
migration of cells to normal
tissues
IN CHRONIC INFLAMMATION
IL-12 Dendritic cells,
macrophages
Increased production of IFN-
γ
IFN-γ T lymphocytes, NK cells Activation of macrophages
(increased ability to kill
microbes and tumor cells)
IL-17 T lymphocytes Recruitment of neutrophils
and monocytes
Table 2-6 (p61)
82. CYTOKINES : SYSTEMIC EFFECTS OF
INFLAMMATION ( MOSTLY MEDIATED BY IL-1;TNF)
-FEVER ( IL-1 ; TNF ; Exogenous Pyrogens Like Bacterial LPS) :-
Convert AA to Prostaglandins (Esp PGE2) → cAMP Production→
Hypothalamic Temperature Set Point Reset
-INCREASED PRODUCTION OF ACUTE-PHASE PROTEINS (
Eg. CRP ; SAA Protein ; Fibrinogen) :
-LEUKOCYTOSIS ( Neutrophilia ; Left Shift)
-SEPTIC SHOCK
- CANCER CACHEXIA
86. EXAM QUESTIONS
• MENTION THE CHEMICAL MEDIATORS OF
INFLAMMATION[5M]
• ENUMERATE THE DIFFERENCE BETWEEN TRANSUDATE
&EXUDATE[2M]
• WRITE A NOTE ON VASCULAR &CELLULAR EVENTS OF
INFLAMMATION[5M]
• WRITE A NOTE ON PHAGOCYTOSIS[2M]
• WHAT IS OPSONIZATION[2M]
• WRITE A NOTE ON FATE OF ACUTE INFLAMMATION
• Write a note on cytokines
• Write a note on prostaglandins
