Inflammation and Repair

Part 1
Udessa G (MSc)
Nursing Department
1
Institute of Health
Bule Hora University

Udessa G (MSc) 2/25/2023

 Learning objectives
 After completing this section, the learner will be able
2
to meet the following objectives:
Define inflammation
Identify five cardinal signs of acute inflammation
 Describe the vascular and cellular changes in an
acute inflammatory response.
List four types of inflammatory mediators and state
their function.
Contrast acute and chronic inflammation.
Distinguish the systemic manifestation of
inflammation
 Describe role of inflammation in wound healing
process
Udessa G (MSc) 2/25/2023
 What is Inflammation?
3 Inflammation is the body’s response to injury and is
considered one of the body’s defensive mechanisms.
Fundamentally a protective response
It will only occur along borders of injury where blood
supply is maintained, i.e. gangrene
Destroys, dilutes, or walls off the injurious agent
Initiates the repair process
Reaction of blood vessels leads to:
Accumulation of fluid and leukocytes in extra vascular
tissues
Udessa G (MSc) 2/25/2023
 What is Inflammation?
4
May be potentially harmful
Hypersensitivity reactions to insect bites, drugs,
Chronic diseases: arthritis, atherosclerosis
Disfiguring scars, visceral adhesions
Consists of two general components
Vascular reaction
Cellular reaction
Controlled by a variety of chemical mediators
Derived from plasma proteins
Derived from cells inside and outside of
blood vessels
Udessa G (MSc) 2/25/2023
 Inflammation vs. Infection
5

Where as inflammation is a response to injury, infection

is the invasion of living tissue by pathogens.

An infection causes inflammation, but tissue that is

inflamed may not be infected. Therefore, inflammation
may exist without the presence of microbial pathogens,
i.e. sunburn

Udessa G (MSc) 2/25/2023

6
Without inflammation
Infections would go unchecked
Wounds would never heal
Injured organs remain permanent sores
Although it is a protective response it can
cause considerable harm
E.g. Common chronic diseases such as
rheumatoid arthritis ,hypersensitivity
reactions.
Udessa G (MSc) 2/25/2023
 Harmful consequences of inflammation
7

Protective inflammatory reactions to infections are

often accompanied by local tissue damage and its
associated signs and symptoms (e.g., pain and
functional impairment)
Typically, however, these harmful consequences are
self-limited and resolve as the inflammation abates,
leaving little or no permanent damage.

Udessa G (MSc) 2/25/2023

 There are many diseases in which the inflammatory reaction
8 is misdirected
Against self tissues in autoimmune diseases
Occurs against normally harmless environmental
substances (e.g., in allergies), or is inadequately controlled
In these cases, the normally protective inflammatory
reaction becomes the cause of the disease, and the damage
it causes is the dominant feature.
In clinical setup, great attention is given to
the injurious consequences of inflammation.
Udessa G (MSc) 2/25/2023
9

Listed are selected examples of diseases in which the inflammatory response plays a significant
role in tissue injury
Some, such as asthma, can present with acute inflammation or a chronic
Udessa G (MSc) 2/25/2023
illness with repeated bouts of acute exacerbation
 Types of Inflammation
10
Acute inflammation Chronic inflammation
Short duration Longer duration
Edema Lymphocytes & macrophages
Mainly neutrophils predominate
Fibrosis
Granulomatous
inflammation New blood vessels
(angiogenesis)
Distinctive pattern of
chronic inflammation
Activated macrophages
(epithelioid cells)
predominate
+/- Multinucleated giant
Udessa G (MSc) 2/25/2023
11 Acute Inflammation

Acute inflammation is a rapid host response that

serves to deliver leukocytes and plasma proteins
to sites of tissue injury.

Udessa G (MSc) 2/25/2023

 Causes of acute inflammation
12

 Microbial infections; bacteria, viruses, fungi, protozoa,

parasite
 Hypersensitivity reactions
 Physical agents e.g., trauma, heat, electricity,
irradiation…
 Chemicals e.g., drugs, acid, alkaline
 Tissue necrosis (ischemia), ...
 “All causes of cellular injury ”
Udessa G (MSc) 2/25/2023
13
Events in Acute Inflammation
Increased blood flow due to dilation of blood vessels
(arterioles) supplying the region

Increased permeability of the capillaries, allowing

fluid and blood proteins to move into the interstitial
spaces

Migration of neutrophils (and perhaps a few

macrophages) out of the venules and into interstitial
spaces
Udessa G (MSc) 2/25/2023
14 Five “cardinal signs” of inflammation:
Redness— The redness that occurs as a result of the
increased blood flow to the inflamed area.
Swelling — Swelling of the inflamed tissue as a result of
increased capillary permeability and fluid accumulation.
Heat — The increase in temperature (heat) that occurs in the
inflamed area as a result of increased blood flow.
Pain— Pain that occurs in the inflamed area as a result of
stimulation of sensory neurons.
Loss of function — Alteration or loss of function in the
inflamed tissues.
Udessa G (MSc) 2/25/2023
15

Heat
Udessa G (MSc)
Redness Swelling Pain Loss Of Func. 2/25/2023
 Acute inflammation of Skin
16

Udessa G (MSc) 2/25/2023

17
The major local manifestations of
acute inflammation, compared to
normal.
(1) Vascular dilation and
increased blood flow (causing
erythema and warmth);
(2) extravasation and
extravascular deposition of
plasma fluid and proteins
(edema);
(3) leukocyte emigration and
accumulation in the site of injury.

Udessa G (MSc) 2/25/2023

18

Vascular Response to Acute Inflammation :

Normal fluid exchange in vascular beds depends on an
intact endothelium and is modulated by two
opposing forces:

• Hydrostatic pressure causes fluid to move out of the

circulation.

• Plasma colloid osmotic pressure causes fluid to move

into the capillaries.
Udessa G (MSc) 2/25/2023
 Edema is excess fluid in interstitial tissue or body cavities and can be
19
either an exudate or a transudate.

Transudate is excess, extravascular fluid with low protein content

(specific gravity of 1.012 or less); it is essentially an ultrafiltrate of
blood plasma resulting from increase hydrostatic pressure or
diminished plasma osmotic forces.

Exudate is an inflammatory, extravascular fluid with cellular debris and

high protein concentration (specific gravity of 1.020 or more),.
Occurred due to increase permeability of capillaries

Pus is a purulent inflammatory exudate rich in neutrophils and cell

Udessa G (MSc) 2/25/2023

debris.
 Formation of exudates and transudates
20

Udessa G (MSc) 2/25/2023

 A- Changes in Vascular Flow and Caliber:

21
 After transient time (seconds) from cell injury, there is
vasoconstriction.
 Then there is vasodilation which is induced by the action of
several mediators, mainly histamine, on vascular smooth
muscle.
 Vasodilation first involves the arterioles and then leads to
opening of new capillary beds in the area. The result is
increased blood flow, which is the cause of heat and redness
(erythema) at the site of inflammation.
 Vasodilation is quickly followed by increased permeability of
the microvasculature, with the outpouring of protein-rich fluid
into the extravascular tissues .

Udessa G (MSc) 2/25/2023

22 A- Changes in Vascular Flow and Caliber-continue
 The loss of fluid and increased vessel diameter lead to slower blood
flow, increased concentration of red cells in small vessels, and
increased viscosity of the blood.

 These changes result in engorgement of small vessels with slowly moving

red cells, a condition termed stasis .

 Mic. You can see the tissue having numerous dilated small vessels
packed with RBCs.

 After stasis leukocytes (Neutrophils) change their normal flow in vessels,

& begin to accumulate along the vascular endothelial surface (and
then cellular changes developed).
Udessa G (MSc) 2/25/2023
23 B-Increased Vascular Permeability (Vascular Leakage)
 Several mechanisms are responsible for the increased permeability of postcapillary
venules, a hallmark of acute inflammation

1-Retraction of endothelial cells

 resulting in opening of inter-endothelial spaces is the most common

mechanism of vascular leakage.

 It is elicited by histamine, bradykinin, leukotrienes, and other chemical

mediators.

 It is called the immediate transient response because it occurs rapidly after

exposure to the mediator and is usually short-lived (15 to 30 minutes). This is
to be distinguished from the delayed prolonged response that follows
endothelial injury, described next
Udessa G (MSc) 2/25/2023
 2- Endothelial injury
24
 Endothelial injury, resulting in endothelial cell necrosis and
detachment.

 Direct damage to the endothelium is encountered in severe

injuries, for example, in burns, or is induced by the actions of
microbes and microbial toxins that target endothelial cells.

 Neutrophils that adhere to the endothelium during inflammation

may also injure the endothelial cells and thus amplify the reaction.

 In most instances leakage starts immediately after injury and is

sustained for several hours until the damaged vessels are
Udessa G (MSc) 2/25/2023

thrombosed or repaired
25
 Although these mechanisms of increased vascular
permeability are described separately, all probably
contribute to varying degrees in responses to most stimuli.
For example, at different stages of a thermal burn, leakage
results from chemically mediated endothelial retraction
and direct and leukocyte-dependent endothelial injury.

 The vascular leakage induced by these mechanisms can

cause life-threatening loss of fluid in severely burned
patients.
Udessa G (MSc) 2/25/2023
26

Principal
mechanisms of
increased
vascular
permeability in
inflammation
and their
features and
underlying
causes.
Udessa G (MSc) 2/25/2023
27

Responses of Lymphatic Vessels and Lymph Nodes

 In addition to blood vessels, lymphatic vessels also participate in
acute inflammation.
 The system of lymphatics and lymph nodes filter the extravascular
fluids. Lymphatics drain the small amount of extravascular fluid
that leaks out of capillaries in the healthy state.
 In inflammation, lymph flow is increased and helps drain edema
fluid that accumulates because of increased vascular
permeability.
 In addition to fluid, leukocytes and cell debris, as well as microbes,
may find their way into lymph. Lymphatic vessels, like blood
vessels, proliferate during inflammatory reactions to handle the
increased load.
Udessa G (MSc) 2/25/2023
 Responses of Lymphatic Vessels and Lymph Nodes-continue
28

 The lymphatics may become secondarily inflamed (lymphangitis), as

may the draining lymph nodes (lymphadenitis).

 Inflamed lymphatic vessels appear as red lines spreading from the

wound

 Inflamed lymph nodes are often enlarged because of

hyperplasia(increased cellularity of the lymph node)of the lymphoid
follicles and increased numbers of lymphocytes and macrophages.
This pathological change is termed reactive ( inflammatory)
lymphadenitis
Udessa G (MSc) 2/25/2023
29
Cellular changes of acute inflammation.
 A critical function of inflammation is to deliver leukocytes to sites
of injury (recruitment), especially those cells capable of
phagocytosing microbes and necrotic debris (e.g., neutrophils
and macrophages).
 The type of leukocyte that ultimately migrates into a site of injury
depends on the age of the inflammatory response and the
original stimulus.
 In most forms of acute inflammation, neutrophils predominate
during the first 6 to 24 hours and are then replaced by
monocytes after 24 to 48 hours.
Udessa G (MSc) 2/25/2023
30

 There are several reasons for this sequence:

 neutrophils are more numerous in blood than monocytes, they

respond more rapidly to chemokines, and they attach more firmly
to the particular adhesion molecules that are induced on
endothelial cells at early time points.

 After migration, neutrophils are also short-lived; they undergo

apoptosis after 24 to 48 hours, whereas monocytes survive longer.

Udessa G (MSc) 2/25/2023

31
Cells of acute inflammation:
1. Neutrophils: Most prominent cells in acute inflammation during first 6hrs -24hrs.

2. monocytes----macrophages: These cells replaced neutrophils in area of acute

inflammation after 2-3days.

3. Eosinophils: These cells are prominent in acute inflammatory allergic diseases &
parasitic infestation.

4. Mast cells & basophils: they are the main source of histamine in acute
inflammation.

5. Lymphocytes: These cells are the most important cells of chronic inflammation,
but also increased in acute inflammation due to viral diseases like influenza,
Udessa G (MSc) 2/25/2023
mumps.
32
The main acute inflammatory
cells are :
Neutrophils and macrophages

Udessa G (MSc) 2/25/2023

  The journey of leukocytes from the vessel lumen to the tissue
33
interstitium is called extravasation, it is a multistep process that is
mediated and controlled by adhesion molecules and cytokines
called chemokines.

 It is divided into 4 steps:

1. Margination & Rolling

2. Adhesion & Transmigration:

3. Chemotaxis & Activation:

4. Phagocytosis & Degranulation of leukocytes

Udessa G (MSc) 2/25/2023

 1. Margination & Rolling:
34  normally flowing blood in venules, red cells are
confined to a central axial column, displacing the
leukocytes toward the wall of the vessel.
Because of dilation of inflamed post-capillary venules,
blood flow slows (stasis), and more white cells take a
peripheral position along the endothelial surface.
This process of leukocyte redistribution is called
margination.
Subsequently leukocytes tumble on the endothelial cell
surface, which is called Rolling of WBCs. (Rolling is
occurred due to interaction between selectin receptors
on leukocytes & the endothelial cells).
Udessa G (MSc) 2/25/2023
35
Mic . Of margination

Udessa G (MSc) 2/25/2023

36
2. Adhesion & Transmigration:
 WBC stick to the surface of endothelial cells, this
is called Adhesion, which is achieved by
interaction between Immunoglobulin molecules
on endothelial cells & integrins on the leukocytes (
adhesive molecules) .
Then Crawling of WBCs between endothelial cells
& through basement membrane into the
extravascular space is called Transmigration &
movement of WBC during this process is called
diapedesis .
Udessa G (MSc) 2/25/2023
37 3. Chemotaxis & Activation:
After extravasation of WBCs; they will migrate toward
sites of injury along a chemical gradient, this is called
Chemotaxis.
Chemical gradient is more at the site of injury.
Movement of WBC during Chemotaxis toward the sites
of injury is achieved by pseudopodia (by actin
filaments within WBC).

Udessa G (MSc) 2/25/2023

  Chemoattractants these are proteins present at the site of injury
38 attract WBC to this site), like Soluble bacterial proteins, complement
system components like C5a, Cytokines (IL-8) , leukotriene B4.

Activation of WBC is stimulated by the above Chemotactics, &

include the followings:
I. Degranulation & secretion of lysosomal enzymes.
II. Production of Arachidonic Acid metabolites (chemical mediators).
III. Modulation of leucocytes adhesive molecules (increased or
decreased).

Udessa G (MSc) 2/25/2023

 4. Phagocytosis & Degranulation of leukocytes, which
39
include three steps:

a- Recognition & attachment of injurious particles to the

ingesting leukocytes (by Opsonization)

Opsonization is the process by which injurious particles

are coated by specific plasma particles that are called
opsonins, to facilitate the recognition & attachment of
injurious particles to the killer leukocytes.

opsonins include IgG & C3b .

Udessa G (MSc) 2/25/2023
40

b. Engulfment of injurious particle & formation of

phagocytic vacuole by Pseudopods of WBC, &
then fusion of these vacuoles with the
membrane of lysosomes.
C. killing & degradation of injurious particles by
production of free radicals.

Udessa G (MSc) 2/25/2023

 Emigration of neutrophils

41

Sequence of events in leukocytes emigration in inflammation:

1. Margination 2. rolling 3. adhesion 4. transmigration and movement
Udessa G (MSc) 2/25/2023

toward injurious agent (stimulus)

42

Udessa G (MSc) 2/25/2023

43

Udessa G (MSc) 2/25/2023

 Sequence of events in an inflammatory
reaction-Summary
44

Udessa G (MSc) 2/25/2023