PROCESS OF INFLAMMATION

AND HEALING.
DR KASONDA
PEDIATRICIAN
22/05/2017
 LEARNING OBJECTIVES
a) Define inflammation
b) Explain cardinal signs of inflammation
c) Explain types of inflammation
d) Explain the basic phenomenon in acute
inflammation
e) Explain the basic phenomenon in
chronic inflammation
f) Identify the main chemical mediator of
inflammation
g) Explain the outcome and complication
of inflammation
h) Describe the mechanisms of tissue
healing and repair
 Definition, Causes and Types of
Inflammation
Inflammation
The ability of vascularised living tissue to respond
to any noxious agent or injury.
It is a local response of the living mammalian
tissues to injury due to an agent.
It is a protective response intended to eliminate
the initial cause of cell injury as well as the
necrotic cells and tissues resulting from the
original insult.
It is a complex reaction which involves many
other systemic changes despite of what is
observed locally.
Causes of Inflammation
Physical agents like heat, cold, radiation and
mechanical trauma
Chemical agents like organic and inorganic
poisons
Infective agents like bacteria virus and their
toxins
Immunological agents like cell mediated and
antigen antibody reactions
 Types or Classification of Inflammation
Depending on the different capacity of the
host and duration of response, inflammation
can be classified into acute or chronic.
Acute inflammation represents the early body
reaction and usually followed by repair and is of
short duration.
Chronic inflammation occurs either after the
causative agent of acute inflammation persists for
the long time or the stimulus such as that which it
induces chronic inflammation from the beginning.
It is of long duration.
 Acute Inflammation
It is a rapid response to injury or microbes and
other foreign substances that is designed to
deliver leukocytes and plasma proteins to sites
of injury.
The leukocytes clear the invaders and begin
the process of digesting and getting rid of
necrotic tissues.
Components of Acute Inflammation
Acute inflammation has two major components
which are :
1. Vascular changes
Alterations in vessel caliber resulting in increased
blood flow (vasodilatation) and structural
changes that permit plasma proteins to leave the
circulation (increased vascular permeability)
2.Cellular events
Emigration of the leukocytes from the microcirculation and
accumulation in the focus of injury (cellular recruitment and
activation)
The principal leukocytes in acute inflammation are
neutrophils (polymorphonuclear leukocytes)
 Causes of Acute Inflammation
Infections (bacterial, viral, fungal, parasitic) are among
the most common and medically important causes of
inflammation
Trauma (blunt and penetrating)
Physical and chemical agents (thermal injury, e.g. burns
or frostbite; irradiation; some environmental
chemicals) injure host cells and elicit inflammatory
reactions.
Tissue necrosis (from any cause), including ischemia (as
in a myocardial infarct) and physical and chemical
injury
Foreign bodies (splinters, dirt, sutures)
Immune reactions against environmental substances or
against self tissues (hypersensitivity)
 Clinical Features/Signs of Acute Inflammation
Acute inflammation has five cardinal features as
follows
1.Pain and tenderness (dolour)
- This is an early symptom in acute inflammation
The pain in acute inflammation is due to direct nerve
injury, tissue irritation by chemicals and agents released by
cells involved in acute inflammation and pressure due to
accumulating exudates compressing nerves
2.Swelling (tumour)
- This is due to local accumulation of inflammatory
exudates
Vascular changes occur within the affected area, which
cause accumulation of fluid and white blood cells to
escape from the intravascular compartment to the
interstitial tissue in the inflamed area
3.Redness (rubor)
-This is due to local increase in blood flow to the
inflamed zone, increased permeability and blood flow
give red coloration
The coloration is less prominent feature among dark
skinned individuals
4.Hotness (colour)
- Inflamed area feels warmer than the surrounding areas
due to increased blood flow to the affected area.
5.Loss of function or reduced efficiency (function laesa)
Inflamed tissue or organ cannot perform its function
as efficiently as a normal tissue o Temporary or
permanent structural damage to the tissue may lead to
loss of function.
 Vascular Changes During Acute
Inflammation
Transient Vasoconstriction
This is a very short event lasting for a few seconds

Arteriolar Vasodilatation
This is a predominant feature in acute inflammation.
This occurs due to increased blood flow and
engorgement of the down-stream capillary beds.
This vascular expansion is the cause of the redness
(erythema) and warmth characteristically seen in acute
inflammation.
As the microvasculature becomes more permeable,
protein-rich fluid moves into the extravascular tissues.
 This causes the red blood cells to become more
concentrated, thereby increasing blood viscosity
and slowing the circulation.
These changes are reflected microscopically by
numerous dilated small vessels packed with
erythrocytes and slowly flowing blood, a process
called stasis.
As stasis develops, leukocytes (principally
neutrophils) begin to accumulate along the
vascular endothelial surface, a process called
margination.
This is the first step in the journey of the
leukocytes through the vascular wall into the
interstitial tissue (described later).
 Increased Vascular Permeability
In the early phase of inflammation, arteriolar
vasodilatation and increased volume of blood
flow lead to a rise in intravascular hydrostatic
pressure, resulting in movement of fluid from
capillaries into the tissues.
This fluid, called a transudate, is essentially an
ultra filtrate of blood plasma and contains little
protein.
However, transudation is soon eclipsed by
increasing vascular permeability that allows the
movement of protein-rich fluid and even cells
into the interstitium, this protein rich fluid is
called an exudate.
 The loss of protein-rich fluid into the
perivascular space reduces the intravascular
osmotic pressure and increases the osmotic
pressure of the interstitial fluid.
The net result is outflow of water and ions
into the extravascular tissues.
Fluid accumulation in extravascular spaces is
called oedema, the fluid may be a transudate
or exudate.
Whereas exudates are typical of inflammation,
transudates accumulate in various
noninflammatory conditions.
 Exudation
The increase of protein-rich fluid from vessels to the
interstitial space due to increased vascular permeability
during an inflammatory condition.
Components of exudates
- Water
Proteins (immunoglobulins), albumin and fibrinogen in severe
cases
Hormones
Natural antibacterial opsonin
Cells-White blood cells (WBCs)

Advantages of exudation
-Dilute toxins in the area of inflammation
- Globulins are protective antibodies
Fibrin helps in limiting the spread of factors causing
inflammation and also assists wound healing
 Mechanisms for Increased Endothelial Permeability
Endothelial cell contraction leading to intercellular gaps
in post capillary venules is the most common cause of
increased vascular permeability.
It is a reversible process elicited by histamine, bradykinin,
leukotrienes, and many other chemical mediators.
Endothelial cell contraction is usually short-lived (15-30
minutes) it is also known as the immediate transient
response.
Endothelial injury results in vascular leakage by causing
endothelial cell necrosis and detachment.
Direct injury to endothelial cells is usually seen after
severe injuries (e.g. burns and some infections).
In most cases leakage begins immediately after the injury
and persists for several hours (or days) until the damaged
vessels are thrombosed or repaired.
Therefore, this reaction is known as the immediate
sustained response
 Direct injury to endothelial cells may also induce a
delayed prolonged leakage that begins after a delay of
2 to 12 hours, lasts for several hours or even days, and
involves venules and capillaries.
Examples include mild to moderate thermal injury, certain
bacterial toxins, and X-rays or ultraviolet irradiation (i.e.
the sunburn that appears in the evening after a day in the
sun).
Leukocyte-mediated endothelial injury may occur as a
consequence of leukocyte accumulation along the
vessel wall.
Activated leukocytes release many toxic mediators that
may cause endothelial injury or detachment.
Leakage from new blood vessels
Tissue repair involving new blood vessels formation
(angiogenesis) which remain leaky until proliferating
endothelial cells mature sufficiently to form
intercellular junctions.

 Changes/Events During Acute

Inflammation
An important function of the inflammatory response is
to deliver leukocytes to the site of injury and to
activate them.
Leukocytes ingest offending agents, kill bacteria and
other microbes, and eliminate necrotic tissue and
foreign substances.
Once activated, leucocytes may induce tissue damage
and prolong inflammation, because leukocyte products
that destroy microbes can also injure normal host
tissues.
Key to the normal function of leukocytes in host
defence is to ensure that they are recruited and
activated only when needed (i.e. in response to foreign
invaders and dead tissues).
 Leukocytes Recruitment
The sequence of events in the recruitment of
leukocytes from the vascular lumen to the
extravascular space consists of the following:
Margination: this is the adhesion of leucocytes to
endothelium, and rolling along the vessel wall.
Transmigration: this is the movement of leucocytes
between endothelial cells o Migration: this is the
entrance of the leucocytes in the interstitial tissues
toward a chemotactic stimulus.
Chemical mediators or chemo attractants and
certain cytokines affect these processes by
stimulating directional movement of the
leukocytes.
 Leukocytes Activation
Once leukocytes have been recruited to the
site of infection or tissue necrosis, they must
be activated to perform their functions.
Stimuli for activation include microbes,
products of necrotic cells, and several
mediators.
Engagement of these receptors by microbial
products or by various mediators of
inflammation induces a number of responses
in leukocytes that are part of their normal
defensive functions and are grouped under
the generic term leukocyte activation.
 Phagocytosis
It consists of three distinct but interrelated steps.
Recognition and attachment of the particle to the ingesting
leukocyte.
Engulfment, with subsequent formation of a phagocytic
vacuole; and.
Killing and degradation of the ingested material.
Leukocytes bind and ingest most microorganisms and
dead cells via specific surface receptors, which
recognize either components of the microbes and dead
cells, or host proteins, called opsonins, that coat
microbes and target them for phagocytosis (a process
called opsonization).
The most important opsonins are antibodies of the
immunoglobulin G (IgG) class that bind to microbial
surface antigens.
 Morphologic Patterns of Acute
Inflammation
Serous Inflammation
It is characterized by the outpouring of a watery,
relatively protein-poor fluid that, depending on
the site of injury, derives either from the serum
or from the secretions of mesothelial cells lining
the peritoneal, pleural, and pericardial cavities.
The skin blister resulting from a burn or viral
infection is a good example of a serous effusion
accumulated either within or immediately
beneath the epidermis of the skin
Fluid in a serous cavity is called an effusion.
 Fibrinous Inflammation
This occurs as a consequence of more severe injuries,
resulting in greater vascular permeability that allows large
molecules (such as fibrinogen) to pass the endothelial
barrier.
Histologically, the accumulated extravascular fibrin appears
as an eosinophilic meshwork of threads or sometimes as an
amorphous coagulum.
A fibrinous exudate is characteristic of inflammation in the
lining of body cavities, such as the meninges, pericardium,
and pleura.
Such exudates may be degraded by fibrinolysis, and the
accumulated debris may be removed by macrophages, resulting
in restoration of the normal tissue structure (resolution).
Failure to completely remove the fibrin results in the in growth
of fibroblasts and blood vessels (organization), leading
ultimately to scarring that may have significant clinical
consequences.
For example, organization of a fibrinous pericardial exudate forms
dense fibrous scar tissue that bridges or obliterates the pericardial
space and restricts myocardial function.
 Suppurative (Purulent) Inflammation
This is manifested by the presence of large amounts of
purulent exudate or pus consisting of neutrophils,
necrotic cells, and oedema fluid
Certain organisms (e.g. staphylococci) are more likely
to induce such localized suppuration and are therefore
referred to as pyogenic
Local accumulation of pus is known as abscess
Ulceration o An ulcer is a local defect or excavation of
the surface of an organ or tissue which is produced by
necrosis of cells and sloughing of inflammatory
necrotic tissue.
Ulceration can occur only when tissue necrosis and
resultant inflammation exist on or near a surface. It is most
commonly encountered in inflammatory necrosis of the
mucosa of the mouth, stomach, intestines, or
genitourinary tract.
 Chemical Mediators and Fate of
Inflammation
Mediators of inflammation can be defined as
any soluble substance that act on the blood
vessel, inflammatory cells or any other cell to
contribute to an inflammatory response.
Mediators of inflammation can be classified
according to their source as follows:
Cellular derived mediators
Plasma derived mediators
 Cellular Derived Mediators
The main/principal cell derived mediators include
Histamine o From basophils, mast cells and platelets
Their principal actions are vasodilation, increase vascular
permeability and endothelia activation
Serotonin o From platelets
Their principal actions are vasodilatation and increase
vessel permeability
Prostaglandins o Derived from mast cells and
leucocytes
Their principal actions are vasodilatation, induction of pain
and fever
Platelet activating factor o Derived from leucocytes
and endothelial cells
Their principal actions are vasodilation, increase vascular
permeability, leucocyte adhesion and chemotaxis
 Plasma Protein-Derived Mediators
Complement proteins o Produced by the liver
Their principal actions are chemotaxis, opsonisation
and stimulation of mast cells
Coagulation proteins o Produced by the liver
Activated factor XII triggers the clotting, kinin and
complement cascades, and activates the fibrinolytic
system
Kinins
Produced by the liver
Their principal actions are to increase vascular
permeability, smooth muscle contraction, induce
pain and vasodilation
 Outcomes of Acute Inflammation
Resolution
o Complete healing when tissue damage is minimal or process is
short lived and the tissue has the ability of regeneration.
Progression
o The acute inflammation can progress to chronic inflammation
when the tissue damage is extensive or when the exudates is not
completely eliminated or cleared.
Fibrosis
o This occurs when there is extensive tissue damage, exudates are
not timely cleared and tissue involved has no capacity to
regenerate.
Spread
Direct e.g.cellulitis
Lymphatic-lymphangitis progressing to acute lymphadenitis
Blood vessels
Pyaemia-spread of pyogenic organisms in infected micro-thrombi via the blood
stream possibly giving rise to secondary (metastatic) abscesses.
Septicaemia-multiplication of organisms in the blood stream in the absence of
adequate host defences.

 Death resulting from
o Septicaemia, e.g. endotoxic shock and its
complications
o Involvement of vital organs, e.g.
encephalitis, myocarditis

Figure1: Outcomes of Acute Inflammation

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 Key Points
Inflammation is one of the bodys defence
mechanisms.
There are vascular changes which cause increased
vessel permeability and cellular changes which cause
leucocytes recruitment and activation.
Cardinal feature of inflammation include, swelling,
pain, redness, hotness, and loss of function.
Chemical mediators released by damaged cells (cellular
derived) and the liver (plasma protein derived) trigger
the inflammatory response.
The inflamed tissue may heal completely (resolution),
or the process may progress to become chronic
(progressive), or may heal through scarification if the
tissue does not have the power of regeneration-
(fibrosis).
 Evaluation
What is inflammation?
What are the types of inflammation?
What are the cardinal features of acute
inflammation?
What is the importance of inflammation?