Acute and Chronic

Inflammation
Part 1: Acute Inflammation
Samer Nassif, MD

Inflammation :
Definitions
Inflammation is the primary host response to injury.
It is a defensive mechanism.
It is a protective response:
Destruction of injurious agent if possible.
Isolation of the injurious agent if not rapidly eliminated.

Stimuli Causing
1- Infections:
bacteria, viruses, parasites, fungi, toxins.
Inflammation
2- Tissue necrosis: ischemia, infarct, hypoxia, trauma,
chemical injury, irradiation, burns.
3- Foreign bodies may cause trauma + necrosis, or
carry germs to trigger inflammation.
4- Immune reactions, acute (hypersensitivity) or
chronic
(autoimmune diseases).

Acute Inflammation: Progressive

Kinesis of Vascular & Cellular
Events

Inflammation & Repair work in

parallel
Inflammatory reaction

may be too strong

Hypersensitivity.
Inflammatory reaction
may persist at low
grade.
Chronic injury of tissue
will occur in long term
inflammation.

Repair may be too

excessive fibrous
scars will form.
Repair is incomplete
granulomas or abcess
will be formed.
Tissue remodeling will
occur when repair is
delayed.

Acute Inflammation is an
immediate response

Rapid in onset
Short in
duration

Components of Acute Inflammat

Two major progressive

components
of
acute
inflammation

Vascular:

1.Change in caliber

Cellular:

Leukocytes undergo
vasodilatation
1.Margination
2.Rolling
2. Change in structure
3.Adhesion
increased permeability 4.Migration
5.Activation

Physiopathology of Acute
Inflammation
Immediate changes in vascular caliber are

induced by histamine: dilatation involves arterioles

at first, then capillaries.
Cardinal signs of inflammation are: rubor, tumor,

calor, dolor, and loss of function.

Physiopathology of Acute
Inflammation
(contd)
Increased vascular permeability causes

outpouring of serum & cells into surrounding

tissues:
Transsudate is an osmotic leakage of serum

fluid;
Exudate is leakage of plasma protein & cells.
Purulent exudate (pus) contains necrotic cells
& bacteria.

Acute Inflammation: Leakage of

Fluid
into Surrounding Tissues

Increased Vascular Permeability

WHY?
1- Normal: no gaps
2- Immediate transient
response: venules
3- Direct endothelial
injury: all vessels
4- Leukocytes-mediated
cell injury: venules
5- Increased traffic in ECs
(transcytosis): VEGF
6-Repair processes:
Leaky new vessels

Inflammation: Cellular
Events

Chemotaxis of Leukocytes in Acute

Inflammation
Selectins and Integrins mediate adhesion of

leukocytes over endothelial cells.

Cytokines( Histamine, TNF, IL-1) lead to
expression & activation of such adhesion.
Adhesion molecules in intercellular junctions of
endothelial cells guide WBC migration.
Collagenases pierce basement membrane of
blood vessels to reach extravascular tissue.
Tissue integrins in ECM help leukocytes to
migrate & bind to injurious agent in ECM.

Leukocyte Chemotaxis
Locomotion oriented with a chemical gradient:
Exogenous chemoattractants are bacterial products.
Endogenous chemical mediators are complement
components (C3a, C5a), leukotriene B4, & cytokines
(TNF, IL-1, IL-8).
Activated leukocytes extend filopodia through

actin reorganization for locomotion.

Leukocyte integrins attach to extracellular matrix

glycoproteins.

Activation of Leukocytes
Recognition of injury:
-Receptors for microbes
over cell surface: (TLRs)
-Receptors to
chemokines and lipids
(G-proteins)
-Receptors for opsonins
which coat microbes
-Receptors for cytokines
after contact + microbes

Removal of
injury:
-Increase in Ca++
-Activation of
enzymes (protein
Kinase C,
Phospholipase A)
-Phagocytosis
follows

Acute Inflammation:Functions of
Leukocytes Receptors

Phagocytosis
Recognition
Attachment
Engulfment
Killing (respiratory

oxidative burst)
Degradation
(Reactive oxygen
and nitrogen
species generate
free radicals)

http://sphweb.bumc.bu.edu/otlt/mph-modules/eh/eh_immunity_b/eh_immunity_b3.html

http://sphweb.bumc.bu.edu/otlt/mph-modules/eh/eh_immunity_b/eh_immunity_b3.html

Defects in Leukocyte Function

Defects in leukocyte adhesion (integrins & selectins)

cause vulnerability to recurrent bacterial infections.

-LAD1: Defect of beta chain (CD11/CD18) of integrin.
-LAD2: Mutation of the sialylated oligosaccharide which is
the anchoring system for E-selectin.

Defects in phagolysosome function: Chediak-Higashi

syndrome induces delayed microbial killing, defective

degranulation, giant neutrophil granules and
immunodeficiency.

Defects in microbicidal activity: Chronic granulomatous

disease has impaired oxidative burst from defective NADH

oxidase: membrane (X-linked) or cytoplasmic (AR)
mutations.

Acquired defects, due to thermal injury, bone marrow

suppression, cancer, immunodeficiencies, diabetes mellitus,

hemodialysis or sepsis.