Lecture 3

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 Acute – up to days (rapid onset &
short duration).

 Chronic - Weeks to Months or

Years (gradual onset & long
duration)
 Subacute - Grades of inflammation
between acute and chronic

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1. LOCAL TISSUE DAMAGE

◦ Cellular degeneration & necrosis

◦ Activated Macrophages and Mast
cells at the damaged tissue

chemical mediators (eg. Histamine)

promoting vascular & cellular changes
in inflamed area.
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 Vasoconstriction / action of irritant on
vessel wall
 Vasodilatation of the arterioles followed by
the capillaries ( histamine and nitric oxide) &
the venules dilate passively
 Increased blood flow (hyperaemia) ??
 Increased capillary permeability
(formation of fluid exudates (outpouring of
protein rich exudate)
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 Increased viscosity (Loss of fluid leads to
Concentration of red cells) of the blood
leading to slowing of blood stream (stasis).

 Formation of fluid exudate is accompanied

and followed by formation of cellular
exudate.

 Stasis leads to accumulation, then sticking of

leukocytes along the endothelium, then its
migration through the vascular wall into the
interstitial fluid.
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 Increase in the hydrostatic pressure,
leading to escape of fluid outside the
capillaries.
 Increased vascular permeability → escape
of a protein-rich fluid (exudate)
 The loss of protein from the plasma
reduces the intravascular osmotic
pressure & increases the osmotic
pressure of the interstitial fluid
 All of the above leads to oedema.
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 Mechanism of Extravasation:

1- Activation of leukocyte

2- Margination & pavementation of leukocytes:

Leukocytes leave the axial blood stream (margination)

followed by rolling then adhesion (pavementation) of
these leukocytes to the sticky endothelial surface.

3- Migration of leukocytes: by means of pseudopodia

(amoeboid movement).

 Neutrophils migrate first followed by monocytes.

 Diapedesis of RBC’s: passive escape of red blood cells

(small in size) outside the capillary

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 Dilute of microorganism / toxins
 Bring antibodies and chemical mediators, to the inflamed
area.
 Bring leukocytes to engulf m.o.
 Bring fibrinogen, helping in trapping the m.o. and
localization of infection.

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 Migration of leukocytes toward the injurious
agent mediated by chemical stimuli.

 Exogenous agents are bacterial products

 Endogenous agents :
(1) Component of complement system,
particularly C3a & C5a

(2) Cytokines: proteins produced by many cell

types, principally activated lymphocytes and
macrophages; endothelium, epithelium….

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 Phagocytosis: process by which the
phagocytic cells:
- Recognize
- Engulf abnormal particles (bacteria, dead
cells and foreign bodies)
- kill & degrade abnormal particles

 Types of phagocytic cells in acute

inflammation:
1. Neutrophils
2. Macrophages= monocytes & tissue
histiocytes
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1. Recognition & attachment:
specific proteins (opsonins e.g.
antibodies IgG & C3b) coat
microbes

2. Engulfment: The leukocytes

surround the bacteria by
pseudopodia and engulf them
inside vacuoles, phagosomes.

3. The phagosomes fuse with the

membrane of lysosomal granules
phagolysosome, where the bacteria
are destroyed by the lysosomal
digestive enzymes.

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 Killing and degradation:
Killing of infectious agents within neutrophils and
macrophages
 Oxygen-dependent mechanisms: hydrogen peroxide
or superoxide which are bactericidal
 Oxygen-independent mechanisms: by lysosomal
enzymes
 After killing, hydrolytic enzymes such as lipases,
nucleases etc..., degrade the microbes within
phagolysosomes, at acid pH 4-5 which is optimum for
the action of these enzymes.

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 Bacteria may remain alive within phagocyte e.g.
tubercle bacilli.

 Bacterial toxins, may kill phagocytic cells.

 The efficiency of phagocytosis is dependent on

◦ Patient’s immunity
◦ Virulence of bacteria
◦ Presence of opsonins
◦ Nature of inflamed tissues. Phagocytosis is less
efficient in loose tissues as serous sacs.

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 Late in acute inflammation neutrophils
become few (short life span);

 Tissue histiocytes enlarge and becomes

phagocytic + monocytes macrophages

 They phagocytose dead bacteria, necrotic

debris, pus cells, foreign bodies, pigments,
fibrin /preparing the tissue for the repair
process.
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 Cells producing the  Plasma derived
mediators (neutrophils,
monocytes, macrophages,  Complements
mast cells, fibroblasts &  Coagulation system
platelets)
 Fibrinolytic system
 Histamine  Bradykinin
 Lysosomal components
 Cytokines
 Serotonin
 Prostaglandins
 leukotrienes

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 Some have direct enzymatic activity (lysosomal
enzymes) or mediate oxidative damage
(reactive oxygen and nitrogen intermediates).
 One mediator can stimulate the release of
other mediators, or counteract the initial
mediator action.
 Mediator can act on one target or diverse
targets or may even have different effects on
different types of cells.

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 Vasodilatation: Histamine, nitric oxide,
prostaglandins

 Increased vascular permeability: Histamine,

bradykinin, C3a, C5a

 Leukocyte activation, adhesion & Chemotaxis:

Leukotrienes, cytokines, C5a and bacterial
products

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 Pain: Prostaglandins & bradykinin

 Tissue damage: Nitric oxide, oxygen

metabolites, lysosomal enzymes.

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