Inflammation (1) pdf - MSc Noor S. Dalis

Lec 1 Theory Physiology Dr. Noor
Salman

MSc.Noor S. Dalis

Lec 1 Theory Physiology Dr. Noor Salman

Inflammation

is part of the complex

biological response of vascular tissues

to harmful stimuli, such as pathogens,

damaged cells, or irritants.

What is the aim of inflammation?

1.To eliminate the initial cause of cell injury

2.Diluting, destroying and neutralizing the
harmful agents

3.limit tissue injury

4.Generate new tissue

Lec 1 Theory Physiology Dr. Noor Salman

The inflammatory response

1. to immune reaction

2. to injury

3. to ischemic damage

• Inflammation is not a synonym for infection, even

in cases where inflammation is caused by infection.

• Although

infection is caused by a microorganism,

• inflammation is one of the responses of the

organism to the pathogen.

inflammation  is  a  stereotyped  response,  and
therefore  it  is  considered  as  a  mechanism  of  innate
immunity, as compared to adaptive immunity,  which
is specific for each pathogen.

Lec 1 Theory Physiology Dr. Noor Salman

• Infections are caused by microorganisms such as

viruses, prions, bacteria, and larger organisms like
parasites and fungi.

• Hosts can fight infections using their immune system.

• Mammalian hosts react to infections with an innate

response, often involving inflammation, followed by an
adaptive response’.

The classic signs of inflammation

1. Redness

2. Swelling

3. Heat

4. Pain or discomfort

5. loss of function

Lec 1 Theory Physiology Dr. Noor
Salman

Causes of inflammation:

A. Exogenous

• Mechanical

• Physical

• Chemical

• Biological

B. Endogenous

• Circulatory disorder, hypoxia

• Endogenous protease release

• Immune complex formation

Lec 1 Theory Physiology Dr. Noor Salman

Systemic symptomatology

• fever (irritation of center of thermoregulation)

tumor necrosis factor (TNF) & interleukin1 (IL-1) and IL-6
interleukin6

• High erythrocyte sedimentation rate

• leukocytosis - increased number of WBC

1. bacteria – neutrophils

2. parasites – eosinophils

3. viruses - lymphocytosis

• leucopenia - decreased

WBC

• viral infections, salmonella infections, rickettsiosis

• immunologic reactions - increased level of some substances

(C-reactive protein)

Lec 1 Theory Physiology Dr. Noor
Salman

Types of Inflammation

Lec 1 Theory Physiology Dr. Noor Salman

Types of inflammation

• 1- Acute inflammation.

• 2- Chronic inflammation

A. Acute inflammation (AI) :

is of short duration lasting from

few minutes up to few days .

• The major local manifestations of acute inflammation:

A- Vascular changes : vascular dilation causing redness

(erythema) and warmth and extravasation of plasma fluid
and proteins (edema)

B- Cellular events :leukocyte emigration and accumulation in

the site of injury .

Lec 1 Theory Physiology Dr. Noor Salman

Acute inflammatory reactions are
triggered by a variety of stimuli:

1. Infections (bacterial, viral, parasitic) .

2. Trauma (blunt and penetrating)

3. Physical and chemical agents (thermal injury,

e.g., burns and irradiation)

4. Tissue necrosis (from any cause)

5. Foreign bodies .

6. Immune reactions (also called hypersensitivity

reactions)

Lec 1 Theory Physiology Dr. Noor Salman

Vascular changes

A. Vasodilatation, which first involves the arterioles & then
results in opening of new microvascular beds in the area. The blood
flow thus will be increased in the injured area , this is called active
hyperemia. This is the cause of heat & redness observed clinically.

•increased permeability of vessels due to widened intercell.

•junctions and contraction of endothelial cells (histamin,
bradykinin)

•protein poor transudate (edema)

•protein rich exudate

• leukocyte-dependent endothelial

injury

• •proteolysis – protein leakage

• •→ platelet adhesion→ thrombosis

Lec 1 Theory Physiology Dr. Noor Salman

B. Cellular events

• leukocytes margination

• neutrophils (1-2 days)

• monocytes (2-3 days)

• •chemotaxis

1. •endogenous signaling molecules - lymphokines

2. •exogenous - toxins

• •phagocytosis - lysosomal enzymes, free radicals,

oxidative burst

Lec 1 Theory Physiology Dr. Noor Salman

C. Phagocytosis

• adhesion and invagination into cytoplasm

• engulfment

• lysosomes - destruction

• in highly virulent microorganisms can die leucocyte and

not the microbe

• in highly resistant microorganisms - persistence

within macrophage - activation after many years

Lec 1 Theory Physiology Dr. Noor Salman

Out comes of acute inflammation

1-Complete resolution

: When the injury is limited or short

lived, when there has been little tissue destruction and when the
tissue can regenerate, the most usual outcome is restoration to
histologic & functional normalcy. The lymphatic drainage &
macrophages lead to the clearance of edema, inflammatory cells
and necrotic debris.

2-Scarring or fibrosis

:results when inflammation occur in

tissue that don't regenerate or after sever tissue destruction.

Abscess formation

may occur in the setting of certain

bacterial or fungal infection (these organisms called pyogenic or
pus forming).

4- Progression to chronic inflammation.

Lec 1 Theory Physiology Dr. Noor Salman

B. Chronic inflammation

Chronic inflammation is of prolonged duration; it lasts for
weeks, months or years, in which active inflammation,
tissue injury & healing proceed simultaneously occur .

Vascular stages

leads to an increased in blood flow

-changes in the small blood vessels of the microcirculation

• characterized – response triplet

1. momentary vasoconstriction (seconds)

2. vasodilatation – arterioles, venules (minutes)

3. increased capillary permeability

• consequences

:•swelling

•mediator release

•increased viscosity

•Increased blood clotting (hours)

• mediators: histamine

Lec 1 Theory Physiology Dr. Noor Salman

Cellular stages

• leads to the migration of leukocytes from the circulation

• their activation to eliminate the injurious agent

The stages is

1. Rolling

2. margination

3. adhesion

4. transmigration across the endothelium – diapedesis

5. chemotaxis - migration

6. formation of inflammatory barrier

7. opsonization

8. phagocytosis

9. killing

10. digestion of bacteria

Lec 1 Theory Physiology Dr. Noor Salman

Chronic inflammatory response

-Infiltration

1. macrophages

2. lymphocytes

3. fibroblasts

leading to→

• persistent inflammation

• fibroblast proliferation

• scar formation

Lec 1 Theory Physiology Dr. Noor Salman

A/Important inflammatory

B/Important inflammatory

mediators I.

mediators II.

1. classic mediators:

complement and derivatives

Histamine, serotonin,

adhesive proteins

: selectin

prostaglandins and derivate

group - antiflamin

and other thrombocyte

derivate

3. antibodies

2. oxidant agents:

neurogene

mediators:

superoxide derivatives

substance P, CGRP

3. cytokines

5. other factors

4. Chemokines

growth factor (somatomedins)

5. proteases: Hagemann -

colony stimulating factor (CSF)

factor

Lec 1 Theory Physiology Dr. Noor
Salman