INFLAMMATION AND HEALING

EM Cabana, DVM (CLSU, Phil '84), MVSt (UQ, Aus '91)

Asst Professor - Veterinary Pathology
College of Veterinary Science and Medicine
Central Luzon State University
Nueva Ecija 3120, Philippines
http://www2.mozcom.com/~emcdvm

INTRODUCTION
Inflammation is a local complicated vascular and cellular reaction of an individual to
an injury/irritant. The purposes of the inflammatory reaction are as follows:
a) Minimise the effect of the irritant or injury
b) Heal the damaged tissue and restore the affected animal to normal health.
It is a protective mechanism, in that protective factors such as antibodies,
complement, and phagocytic cell normally confined to the bloodstream can gain
access at localised tissue sites, to destroy foreign invaders.
An understanding of inflammation and subsequent repair and regeneration of injured
tissue is necessary for understanding many diseases and surgical processes. Most
of these will induce tissue damage (necrosis) and will involve inflammation.
Inflammation is a dynamic sequential process. While vascular and cellular responses
that make up inflammatory reaction are similar irrespective of the aetiology, these
can be modified by nature, severity and longevity of the irritant and/or by host
factors. These include the location and the type of tissue affected. The result in host
tissue therefore may not always be the same. If inflammatory reaction is successful,
healing occurs. If not successful, further tissue reaction that is harmful to the host
may occur. The initial or acute stage of inflammation is characterised by certain
clinical or cardinal signs. These are:
1) Redness
2) Swelling
3) Heat
4) Pain
5) Loss of function.
AETIOLOGY
The aetiologies of inflammation vary and include both living and non-living agents as:
Bacteria, Fungi, Viruses, Parasites, Protozoa, Immunologic injury, Trauma, Heat,
Cold, Toxins or poisons, and Irradiation.
SUMMARY OF EVENTS IN ACUTE INFLAMMATION
1. Transient vasoconstriction of arteriole (few seconds to about five minutes)
followed by an increased rate of blood flow through the terminal vascular bed. The

latter are due to dilation of all the blood vessels in the area. This includes the
opening of new capillary and venular beds.
2. Increase in the permeability of the terminal vascular bed with consequent
exudation of plasma factors into the tissues. This results in tissue swelling and
retardation of blood flow with haemoconcentration in the vascular bed.
3. The attraction to and adherence of leucocytes to the walls of the terminal vascular
bed (Margination) and subsequent migration of leucocytes and exudation of
erythrocytes into the tissue. The process that attracts cells into the tissues is
Chemotaxis.
4. Removal of any aetiological agent by leucocytes (phagocytosis). Breakdown of
necrotic tissue by phagocytes and removal by reabsorption through the lymph
vessels or into venules.
5. Repair and regeneration:
a) Replacement of dead cells by division of similar cells that escaped necrosis
(regeneration)
b) Replacement fibrosis (repair) if regeneration is not possible
c) a mixture of repair and regeneration.
VASCULAR AND CELLULAR CHANGES
The main components of the inflammatory response are fluids, plasma proteins and
cells. Together they are called EXUDATE that means they have entered the tissue
from the blood as part of an active process. This allows mechanisms of host defence
such as antibodies, complement, and phagocytic cells into the tissues to destroy
antigens.
VASCULAR CHANGES
The initial events in response to injury involve the endothelium of the small vessels,
i.e. arterioles, venules, the direct inter-communication vessels and the true
capillaries. Many true capillaries arise from the direct channels that have occasional
smooth muscle fibres in their walls. It is probable that neurogenic adjustments of the
flow of blood through the shunts help govern the flow through capillaries. The only
control that capillaries themselves have on blood flow is to respond passively to the
pressure gradient between their two ends. Apart from being a tube of endothelial
cells, these small vessels have scattered along and closely applied to them,
pericytes. The function of pericytes is not clear, but it may be supportive to the
endothelial cells.
In the first stage of the acute inflammatory response, there is:
1) Dilation of these small vessels leading to an increased blood flow (hyperaemia) in
the arterioles and capillaries. The overload of venous drainage leads to passive
congestion that also contributes to the vasodilatation.

2) Increase permeability of the small vessels compared with that operating in health.
Apart from direct damage the endothelial cells loosen their attachments to each
other. This process commences in small venules and later involves true capillaries.
The increase in permeability coupled with an increase in hydrostatic pressure due to
increased blood flow, leads to exudation of fluid and plasma factors into the tissue
spaces. This leads to swelling in the inflamed area.
There are two phases of vascular permeability. An immediate transient phase lasting
less than one hour is followed by a prolonged phase which last 3-4 hours or longer if
the stimulus persists. A third phase which is delayed in onset, but last for several
days has also been described. Sunburn is an example of this phase.
CELLULAR RESPONSE
An early manifestation of inflammation is the phenomenon by which platelets and
leucocytes adhere to endothelium (Margination). Many cells may eventually line the
endothelium (Pavementing). There is a slowing of the blood flow and sludging of red
cells in the terminal vascular bed. This is due to:
1] Haemoconcentration consequent to loss of fluid to extravascular tissues.
2] Increased resistance to flow associated with adherence of cells to each other and
to the endothelium.
Migration of leucocytes into the tissues is accomplished by a pseudopodia into the
intercellular junction of the endothelial cells, enlarging the opening and squeezing
through. This allows the passive extravasation of red cells. All leucocytes have
similar migration capacity. Chemotaxis is the process by which leucocytes are
attracted to sites in injured tissue.
Neutrophils and eosinophils are usually first and move through fibrin and past tissue
cells to their destination. Accumulation may reach a peak in about four hours,
although this will vary as to the stimulus. They have been called microphages but
pathologist does not commonly use the term. They are more frequently called
polymorphs or granulocytes. Monocytes become macrophages in the tissues.
Red cells have no amoeboid capabilities, but may take advantage of the holes
created. Leakage of blood (haemorrhage) from the damaged small vessels into the
extravascular tissue spaces gives the appearance of a bruise. A large extravascular
clot is called haematoma or haematocyst.
PHAGOCYTOSIS
Phagocytosis is the process by which particulate matter in taken into the cell, usually
by invagination of the cell membrane to form a vacuole containing the particle
(Phagosome). It is probably the most important defence system available to animals,
and while it does occur without antibody it is enhanced by opsonin. Opsonins are
mainly antibodies, and complement components (C3b fragment), but other serum
components such as polypeptides and basic poly-amino acids have been described
as playing a role. Opsonin improved the efficiency of phagocytosis. Factors favoring

phagocytosis apart from opsonin include higher body temperature, and enmeshment
of the antigen (e.g., bacteria) within the inflammatory exudate.
The phagosome merges with lysosomes to form a phagolysosome, in which the
particle is exposed to the digestive enzymes of the lysosomes and the normally
dormant oxygen consuming pathways. The enzymes break down carbohydrates and
proteins but not fat. Undigested material is called a residual body (Figure 14). In
phagocytosis, contact of neutrophils with the stimuli results to the activation of an
oxygen consuming pathway. This "Respiratory Burst" is characterised by a two- to
three- fold increase in oxygen consumption, the production of hydrogen peroxide
(H2O2), an increase in the activity of the hexose monophosphate shunt, and the
generation of superoxide anion (O2-). The reaction between O2- and H2O2
produces a bactericidal hydroxyl radical. The oxygen dependent mechanism is a
major cause of microbial death. This is due to the activities of the H2O2 acting either
alone or with myeloperoxidase, the hydroxyl radical, the superoxide anion and
singlet oxygen (O2). Oxygen-independent agents include lysozyme, lactoferrin,
phospholipase, and granule-associated cationic proteins.

Figure 13. Schematic diagram of phagocytosis

Some agents are resistant to digestion and remain inside the phagocytic cells for
prolonged period and are protected from other defence mechanisms, and from the
action of antibacterial drugs. Infection may spread because of migration via the
lymphatics of the phagocytes containing the organism. The release of lysosomal
enzymes from the cells apart from having a chemotactic effect may influence clotting
mechanisms and act as pyrogens (fever-inducing agent).
MEDIATORS OF INFLAMMATION
The alterations in blood flow, vascular permeability and the cellular response at the
site of injury are controlled and influenced by chemical mediators of both tissue and

plasma origin, acting singly or in combination. In addition there are humoral

amplification systems which expand the contribution of many mediators. Thus, a
complex interaction of various mediators exists to the point that a single event in
inflammatory reaction is mediated by a host of mediators.
In simplest term, mediators of inflammation are chemical messengers that will act on
blood vessels and/or cells to contribute to an inflammatory response. Recent
literatures suggest the term AUTACOIDS to distinguish such chemical messengers
from hormones and neurotransmitter substances. The mediators of inflammation can
be classified in several ways. One way is the subdivision of mediators based on
source as:
1] Exogenous mediator - coming from the outside
2] Endogenous mediator - those synthesised by the body.
Bacterial products and toxins exemplify exogenous mediators. Endogenous
mediators are classified based on source or origin as:
1] Plasma derived
2] Cell or tissue derived
In the plasma, there are three major mediator-producing systems:
1] Coagulation-Fibrinolytic system
2] Kinin system
3] Complement system
Other mediators may be cells or tissue derived and may be
1] Preformed and stored in granules (e.g. histamine and cationic proteins)
2] Newly synthesised by cells (e.g. interleukin, leukotrienes and platelet activating
factor).
Some mediators may be classified based on the biochemical synthetic pathways for
its production as:
1] Peptide mediators - generated consequently of multiple enzymic steps involving
the sequential activation of molecules by limited proteolysis (e.g. complement, and
coagulation-fibrinolytic system)
2] Lipid mediators - mediators derived from arachidonic acid following the action of
phospholipase to membrane phospholipid, and mediators generated by this process
are collectively called Eicosanoids.
Most of the biologically active mediators of inflammation are derived either from the
systems in the plasma (Kinin, Coagulation-Fibrinolytic, and Complement systems),
or because of cell membrane damage leading to catalysis of membrane phospholipid
producing eicosanoids.
EFFECTS OF MEDIATORS

A. Vasodilatation and hyperaemia - there are several mediators that effect

vasodilatation and hyperaemia at the onset of inflammatory response. Of which, the
most potent mediators that influence the microvasculature include:
1] Histamine (released from mast cells and basophils)
2] Bradykinin
3] Prostaglandin E1, and I2
4] Leukotriene B4
5] C5 fragment of complement
6] Thromboxane.
B. Vasopermeability - the mediators that alter the permeability of the
microvasculature include the following mediators:
1] Histamine
2] Serotonin
3] Bradykinin
4] Kallikrein
5] Platelet Aggregating Factor
6] Lymphokines
7] Anaphylatoxin (C3 and C5 Fragment of Complement)
8] Leukotriene B4, C4, and D4
9] 5-HPETES (5 hydroperoxy- eicosatetranoic acid)
10) Fibrin degradation products.
C. Leucocyte emigration and chemotaxis - the mediators attracting neutrophils in an
inflammatory response include the following:
1] C5a fragment of Complement
2] Leukotriene B4
3] Bacterial toxins
4] Platelet aggregating factor
The chemotactic agents acting on monocytes and macrophages include
1] C5a fragment of Complement
2] Leukotriene B4
3] Bacterial toxins
4] Cationic protein fractions of neutrophils
5] Lymphokines
6] Fibrin degradation products.
Lymphocytes are attracted mainly by Lymphokines, while eosinophils are attracted
by eosinophil chemotactic factor of anaphylaxis (ECF-A) derived from mast cells,
and prostaglandin D2.
INFLAMMATORY EXUDATES

Exudates are fluids and cells that have accumulated in tissue spaces during
inflammation. Accordingly, the exudate has certain characteristics. It will contain
protein, have inflammatory cells, may have bacteria, and depending on the degree of
damage, erythrocytes and globulins. The latter usually includes fibrinogen, and lead
to clotting. The fluid portions of the exudate will:
[a] Dilute the toxic substances at the site of injury and neutralise toxins
[b] Provide a suitable nutrient environment for sustaining the leucocytes that quickly
invade the area
[c] Form a fibrin net from the fibrinogen released. This will help opposing surfaces
of the wound to adhere together, and localise the bacteria (if present) by
enveloping them in a fibrillar meshwork.
Fibrin acts as a physical barrier to confine and prevent the spread of the irritant. It
also provides a scaffold that enables the leucocytes to move towards and
phagocytose the bacteria or other foreign material that may be present.
Subsequently, it allows capillary loops and fibroblast to invade during the process of
healing and repair.
TYPES OF INFLAMMATORY EXUDATES
1.SEROUS EXUDATE - primarily a clear fluid, low in protein (mainly albumin) which
exudes from serosal or mucosal surfaces because of mild irritation. Such an exudate
can also be located within body organs. Neutrophils can be present in considerable
number, in which case there will be whitish appearance to the exudate. The initial
exudate in many inflammatory reactions is serous.
2.FIBRINOUS EXUDATE - exudation of a fluid rich in fibrinogen which will clot to
form a yellowish gel. Usually occurs with severe vascular injury and is seen more
commonly on mucosal and serosal surfaces such as intestine, pleura, peritoneum,
and synovial membranes. Fibrinous pneumonia is also an example.
Because fibrin is chemotactic large number of neutrophils are usually present.
Where two opposing surfaces have a fibrinous exudate between them, the
organisation of the fibrin leads to adhesion. Viewed microscopically the fibrin may
appear as solid clumps or long delicate strands. In severe mucosal damage where
the epithelium is lost the fibrin that accumulates may become adhered to the
remaining mucosa. A diphtheritic membrane or pseudomembrane is formed. The
term diphtheritic applies to fibrous organisation of any fibrinous or necrotic exudate
on a mucosal surface.
3.HAEMORRHAGIC EXUDATE - haemorrhage is prominent and therefore such an
exudate occurs where the blood supply is abundant, and there is severe damage to
the terminal vascular bed. The term must not be confused with haemorrhage alone,
which can occur without any inflammatory reaction.
4.CATARRHAL OR MUCUPURULENT EXUDATE - occur on mucous membranes
and mucosal surfaces of the alimentary, respiratory, and reproductive tracts.
Characterised by the outpouring of large amounts of mucous that is accompanied by
neutrophils, tissue debris, fibrin and sometimes red blood cells. Other signs of
inflammation are present in the underlying mucosa.

5.PURULENT OR SUPPURATIVE EXUDATE - characterised by the production of

pus (suppuration) which may be defined as a thick creamy fluid composed of large
numbers of viable and necrotic polymorphs, which is partially liquefied by hydrolytic
enzymes released from dead leucocytes. It is a characteristic response to certain
types of bacteria that are "pyogenic" (pus forming). A mucopurulent or catarrhal
exudate may be seen on a mucosal surface, and similarly the term fibrinopurulent
may be appropriate with some exudates.
The morphology of purulent exudate may be significantly altered by its position. A
PUSTULE is a visible collection of pus within or beneath the epidermis. An
ABSCESS is a localised collection of pus caused by suppuration in a tissue or
confined space, usually in response to a pyogenic bacteria. As the island of necrotic
tissue and neutrophils grows, a wall of fibrinous tissue is formed around it in an
endeavor to confine it. A good blood supply in the tissue ensures a nutrient supply for
the neutrophils which cross the barrier. This tissue wall with an active blood supply
that surrounds an abscess is called a PYOGENIC MEMBRANE. An abscess is
classified as "hot" when the reaction is still acute and characterised by the cardinal
signs of inflammation. A "cold" abscess is well encapsulated and not showing the
cardinal signs. It may still be active but more often or not it is "sterile". Sometimes,
dystrophic calcification may occur in a cold abscess. The likely fates of an abscess
include:
[1] it will rupture at a surface following a tract called a SINUS or FISTULOUS
TRACT
[2] It will spread along fascial plane between healthy tissues
[3] It will become encapsulated and contained within fibrous tissue
[4] It will branch sending out a tract to nearby surface to release pressure.
Pus within a body cavity is called EMPYEMA. CELLULITIS or PHLEGMONOUS
INFLAMMATION refers to spreading diffuse inflammation often suppurative, present
in the subcutaneous tissues. Its margins are poorly defined. This is often seen in
cats because of infected deep bite wound following a fight.
CELLS IN THE INFLAMMATORY EXUDATE
1.NEUTROPHILS - first cells to migrate in large number to the tissue and are
aggressively phagocytic. Attracted to the site of injury by chemotactic factors. Where
a bacterial infection is the cause of inflammation, neutrophils migrate to the tissues in
very large number. They will endeavor to limit the spread of infection. Neutrophils
have a very short life span irrespectively of cytotoxic factors (24-48 hours in tissues
following a half-life blood circulation time of about six hours). Large numbers of dead
and dying neutrophils are the chief constituents of pus. The fluid nature of pus is due
to the liquefactive effect of lysosomal enzymes. Neutrophils phagocytose particulate
matters and they can degranulate releasing enzyme-laden granules into the tissues
at local sites of inflammation with the formation of chemotactic factors. In dying all
their lysosomal enzymes are released, and this helps liquefy cellular debris and fibrin
as a prelude to repair. Enzymes released include alkaline phosphatase, lysozyme,
myeloperoxidase, beta-glucoronidase, alpha-mannosidase and proteinase.
2.EOSINOPHILS - react to stimuli similar to those for neutrophils. Granules contain
with a few exceptions an assortment of enzymes similar to neutrophils. They are

phagocytic like neutrophils but are more prominent in certain inflammatory reactions
such as in parasitic infections and in allergic reactions. Antigen-antibody complexes
attract eosinophils when arrested in the tissues. The antigens of parasites because
of their bulk persist longer and attract eosinophils. Apart from parasitic disease, the
presence of eosinophils in an inflammatory reaction in great number is not
consistent. They are found in some granulomas (e.g., eosinophilic granulomas in
cats), in eosinophilic myositis, and in the meninges of pigs with salt poisoning. They
also have some neutralising effect against histamine, but it is probably not a major
role.
3.BASOPHILS - similar in form and function to the tissue mast cells. Circulatory
numbers in the blood are very low. Basophils play a role in hypersensitivity reactions.
4.LYMPHOCYTES - they are not phagocytic, and do not ordinarily migrate during the
acute phase of inflammation, but may be many in the more chronic phase
particularly where there is mucous membrane involvement. Lymphocytes are
associated with the host's immune response and are often present in lesions around
small blood vessels where they form a cuff.
5.PLASMA CELLS - tend to be found in areas of more chronic inflammation and are
usually present along with lymphocytes, macrophages and fibroblast. The formation
of mature plasma cells from lymphocytes (B-cells) requires 4-5 days. The nucleus is
displaced to one side and the cytoplasm has a clear halo on one side of the nucleus.
It produces antibodies and their presence in an inflammatory reaction usually reflects
a subacute or chronic process. Plasma cells are also found in high number in lymph
tissue that is producing antibody to any antigen.
6.MONOCYTES (MACROPHAGES) - less common in blood than neutrophils.
Although they arrive at the site of inflammation later than the polymorphs
(granulocytes), they start to emigrate simultaneously. Their movement is slower but
they are responsive to chemotactic influences. They are much longer-lived than the
polymorphs. Their numbers are augmented by local mitotic proliferation of histiocytes
(a histiocyte is a macrophage present in tissues which is derived from blood
monocytes made in the bone marrow). The macrophages are more efficient than the
polymorph at phagocytizing fibrin and cellular debris from the site of inflammation in
preparation for repair. They process many antigens before transferring them to
lymphocytes for antibody production. If antigens are readily broken down the
macrophages do not persist. If difficulty in this process is encountered then the
macrophages will persist in the lesion. They respond to a variety of stimuli, such as
antigen-antibody complexes, complement, and bacterial and neutrophil products also
immune and non-immune stimuli. Macrophages may divide in tissue to form other
macrophages or may form epithelioid or giant cells.
7.EPITHELIOID CELLS - formed from macrophages with similar appearance, but lie
closer together and take the shape and arrangements similar to prickle cells in the
epidermis. The cytoplasm is eosinophilic and the cell membrane is indistinct. They
do not appear to phagocytize but probably work at destruction of the irritant by
secretion. It is common in many granulomatous types of inflammatory reactions (see
later).

8.GIANT CELLS - formed by the cytoplasmic fusion of macrophages found in

reactions to certain organism such as the tubercle bacillus. Thought to be poorly
phagocytic and probably have a life span of only a few days.
9.FIBROBLAST - fibroblasts are found during the repair phase and will produce new
fibrous tissue. They arise from undifferentiated mesenchymal cells mostly about
blood vessels. Fibroblast multiplies rapidly in situ and secretes globular proteins that
precipitate as macromolecular collagen fibres in the interstitium. Tissue lost through
necrosis can only be replaced by proliferation of remaining viable epithelial cells or
by fibrous repair. Fibrous proliferation will also occur in many chronic inflammatory
processes particularly where there are large defects in tissue, due to the persistence
of an irritant.
CLASSIFICATION OF INFLAMMATION
The inflammatory response can be classified on a time basis as acute, subacute or
chronic. However, this is arbitrary because an acute response can last from a few to
several days, and a chronic process can vary from weeks, months and up to years.
There is no ideal system of classification. The clinical assessment also the gross and
microscopic appearance of inflammation serves as a better guide for classification.
ACUTE INFLAMMATION is characterised by the appearance of the cardinal signs
mentioned earlier. It is sometimes called Exudative Inflammation. Microscopically the
acute lesion has some classic features such as hyperaemia and fluid exudation.
There is usually cellular exudation, particularly neutrophils that will appear in large
number if there is bacterial involvement. The presence of fluid and neutrophils
(exudation) microscopically is consistent with an acute lesion whereas mononuclear
cells and fibrosis suggest a chronic lesion. However, while this is a basic assumption
it may not always occur. For example lymphocytes and macrophages may be very
prominent in a lesion two days after its initiation, i.e. the lesion may appear chronic in
the microscopic context, but is acute in the clinical context.
CHRONIC INFLAMMATION occurs when there is persistent irritation or injury over a
long period. It is often called Proliferative Inflammation because it is characterised by
a proliferation of cells than exudation of cells and fluids. There is usually evidence of
host attempt at repair, namely FIBROSIS.
In many chronic inflammatory lesions, there may be "acute foci" by which focal
accumulations of neutrophils may be present within a lesion consisting mainly of
macrophages and fibrous tissue. In chronic inflammation the proliferating cells may
be macrophages, lymphocytes, plasma cells and fibroblasts. New tissue made up of
fibroblast and capillary loop is known as GRANULATION TISSUE. Such tissue fills n
gaps caused by necrosis and removal of debris. Chronic inflammation may take
several forms:
1] Chronic ulceration - where an ulcer is not repaired
2] Chronic abscessation - where there is fibrous encapsulation of pus

3] Chronic granulomatous inflammation - characterised by the formation of

granulation tissue that is heavily infiltrated with macrophages, polymorphs,
lymphocytes, and possibly plasma cells. Signs of exudation may be considerable in
granulation tissue if the causative agent is still operative.
A GRANULOMA is a term used to describe small nodular lesions of chronic
inflammation with some special features. They are usually found within a larger area
of granulomatous inflammation but occasionally they may be of a solitary nature.
Granulomas are associated with certain aetiological gents such as foreign bodies,
fungi, and bacteria (e.g., tubercle bacilli). The main features of granulomas are that
they sometimes have a caseous centre consists predominantly of epithelioid cells
which at the periphery of the nodule may have fibroblast, other macrophages and
sometimes other inflammatory cells inter-mingled with them. It is also not uncommon
to see mulinucleate giant cells associated with granulomas.
ORGAN SITE AND DISTRIBUTION
When an organ is inflamed it is described by adding the suffix "-itis", e.g., kidney
inflammation - nephritis. Within an organ, an inflammatory lesion can be focal, multifocal, locally extensive or diffuse. Focal lesions are usually small and surrounded by
normal tissue. If it is well demarcated, the lesion is discrete. If it merges into the
surrounding tissue, it is diffuse focal lesion. Multi-focal lesions represent several
scattered foci of inflammation. Locally extensive lesions involve a considerable area
of tissue within an organ. Diffuse lesions involve all of the tissues or organs and
should not be confused with diffuse focal lesions.
BODY REACTIONS AND TISSUE DAMAGE
Tissue damage invariably occurs in sites of inflammation. Two prominent reasons for
tissue injury are: 1] Release of enzymes from the granules and lysosomes of
infiltrating cells, and 2] Production of oxygen radicals by these cells.
The infiltrating cells carry with them lysosomes and many potentially damaging
enzymes. The release of these substances following death of infiltrating cells will
injure the tissue. This may be considered damaging to the individual, or may be
beneficial in the sense that tissue damage will lead to a more intense reaction
leading to its resolution. Oxygen radicals are derived from the reduction of molecular
oxygen by inflammatory cells or damage to cellular membranes and are extremely
toxic to cells. Tissue damage following the liberation of oxygen radicals could be
traced back to formation of cytotoxic products following cell membrane lipid
peroxidation, and damage to hyaluronic acid and collagen. Thus damage to
basement membranes, cell membranes, and intercellular cement substances will
result to epithelial or endothelial cell separation, and eventually cell death. Body
reactions to localised inflammation can include the following:
1] Altered leucocyte counts in the blood. The most common change is an increase in
the circulating number of neutrophils because of stimulation of the bone marrow to
produce more cells by as yet ill-defined leucocyte promoting factors.

2] Breakdown products cause pyrexia (fever).

3] Circulating enzyme levels may alter because of tissue damage. These can be a
useful diagnostic aid in locating the site of inflammation where internal organs are
involved.
4] Lymph drainage from the inflammatory site often results in an inflammatory
reaction in the regional lymph node. This will be swollen, tender on palpation, and if
sectioned may appear reddened (hyperaemic).
HEALING: REGENERATION AND REPAIR
The reparative process begins while the inflammatory reaction is still in full swing,
but cannot be completed until the injurious agent has been destroyed or neutralised.
The healing of a local injury calls into play two sets of biological process. Depending
on the tissue involved, one or the other prevails: 1] Regeneration, and 2] Repair.
REGENERATION implies that cells of the same kind replace lost cells. Not all tissues
are capable of this feat and some are capable of regeneration only under specific
conditions. In the evolutionary process, mammalian species lost their capacity to
regenerate total body structures unlike the simpler aquatic, amphibian and reptilian
species. When regeneration is not possible, the replacement of tissue occurs
through a process called REPAIR. This is the replacement of lost tissue of any kind
by a mass of connective tissue and ultimately by a fibrous mass called SCAR
TISSUE. However, the process of regeneration and/or repair is not mutually
exclusive. Regeneration of tissues may also require a temporary filling of connective
tissue which later will be slowly resorbed and replaced by tissues of the same kind.
REGENERATIVE CAPACITY OF TISSUES
The cells of the body have been divided into three groups based on their
regenerative capacity:
1]LABILE CELLS - continue to multiply throughout life to replace those shed or
destroyed by normal physiological processes (apoptosis and necrobiosis). These
include the cells of the epithelial surfaces, the lymphoid and haematopoietic cells.
Included among the epithelial surfaces are the epidermis, lining of buccal cavity,
gastrointestinal tract, respiratory tract, genital tract, and lining of ducts. In all these
sites, the surface cells exfoliate throughout life and are being replaced every few
days.
2]STABLE CELLS - retain the latent capacity to regenerate, but under normal
circumstances do not actively replicate because they have a survival time measured
in terms of years and possibly equal to the life span of the individual. It includes the
parenchymal cells of all glands in the body including the liver, the pancreas, salivary
gland, endocrine glands, kidney tubular epithelia, glands of the skin, the
mesenchymal cells of the body and their derivatives (e.g. fibroblast, chondroblast,
osteoblast, and adipose tissue), endothelial cells, and smooth muscle cells.

3]PERMANENT CELLS - cannot regenerate and damage to these tissues

represents permanent loss. It includes neurons, skeletal and cardiac muscle cells.
However, in neuronal damage, the nerve cells are capable of replacing severed
axonal processes but they must follow the pre-existing pathway of degenerated
axon. If not the re-growth may give rise to a mass of tangled fibres sometimes
termed "amputation or traumatic neuroma" and is nonfunctional. Skeletal muscle and
cardiac muscles are always replaced by scar tissue.
PARENCHYMAL REGENERATION
The replacement of destroyed parenchymal cells by proliferation of reserved cells
can only occur in those cells capable of replication. The perfection of parenchymal
repair of an injury depends on more than the ability of cells to regenerate.
Preservation of the stromal (connective tissue framework) architecture of the injured
tissue is often necessary. For example, in injury to the liver, if the supporting reticular
framework is preserved, there is orderly regeneration of the hepatocytes and the
normal acinar architecture and functions are restored. If the stromal support is not
preserved or destroyed, regeneration is disorderly, and may lead to scar formation.
Thus, the preservation of stromal framework decides in considerable extent the
success of regeneration and restoration of function. When this is lost, regeneration
may restore the mass of injured tissue but not complete function.
REPAIR BY CONNECTIVE TISSUE
The usual consequence of most tissue damage is proliferation of fibroblast and
capillary buds and the subsequent laying down of collagen to produce a scar.
Connective tissue scarring is ubiquitous and efficient method of repair, but it
demands a loss of specialised parenchymal function. Repair by connective tissue is
traditionally considered as either primary union (or first intention healing) or
secondary union (or second intention healing). In the former, connective tissue repair
takes place when the injured sites are in close apposition as in surgical wound
coapted by sutures. In such an instance, there is little or no loss of substance,
exudate and necrotic debris are minimal, and the repair occurs quite promptly. In the
latter instance, there is significant loss of tissue as in open wound. Considerable
amount of debris and exudates must be removed and healing takes place more
slowly.
In either case, the tissue defect is initially filled with highly vascularized connective
tissue called GRANULATION TISSUE. The term granulation tissue is derived from its
gross appearance that is pink, soft and granular. Microscopically, it consists of newly
formed small blood vessels embedded in loose ground substance containing
fibroblast and inflammatory cells (consisting largely of macrophages, lymphocytes,
eosinophils, mast cells, plasma cells, and some persisting neutrophils). As
granulation tissue matures, inflammatory cells decrease in number, fibroblast lay
down collagen, and the capillaries become less prominent and blood supply in the
area restored.
Two aberrations may occur in wound healing whether the process is by first or
second intention healing. The accumulation of excessive amounts of collagen may
give rise to a protruding tumour-like scar known as KELOID. The exact mechanism

involved in keloid formation and the predisposing factors remain unknown. The other
deviation in wound healing is the formation of excessive amount of granulation tissue
that protrudes above the levels of the injury. This has been called EXUBERANT
GRANULATION or PROUD FLESH.
Scarring is an inevitable consequence of all repair except in the ideal situation in
which an entire parenchymal injury permits perfection of regenerative activity and
reconstitution of the original architecture. Fibroblasts are the workhorses of scar
formation, and the collagen is their essential product that ultimately provides the
tensile strength in the healing of soft tissue wound.
The acquisition of tensile strength follows a sigmoid curve. The first phase has been
described as the catabolic phase when there may be destruction of collagen. The
second phase (also called anabolic, proliferative or collagen phase) involves
deposition of collagen and stabilisation. As the collagen matures, polymerisation of
collagen results, and contraction of the scar tissue follows. The strength of the scar
tissue formed thus depends on the degree of maturation of collagen laid down during
repair.

ANATOMICAL TERMINOLOGY OF INFLAMMATION

Artery - arteritis
Bile Ducts - cholangitis
Bladder - cystitis
Blood Vessel - vasculitis
Bone - osteitis
Bone marrow - osteomyelitis
Brain - encephalitis
Bursa - bursitis
Caecum - typhlitis
Colon - colitis
Cornea - keratitis
Dura mater- pachymeningitis
Ear - otitis
Endocardium - endocarditis
Eustachian tube - eustachitis
Eye - ophthalmitis
Eyelid blepharitis
Fascia - Fasciitis
Fat - steatitis
Gallbladder - cholecystitis
Glans penis - balanitis
Heart - carditis
Intestine - enteritis
Iris - iritis

Meninges - meningitis
Mouth - stomatitis
Muscle (skeletal) - myositis
Myocardium - myocarditis
Nasal cavity rhinitis
Nerve - neuritis
Ovary - oophoritis
Oviduct - salpingitis
Pancreas - pancreatitis
Pericardium - pericarditis
Peritoneum - peritonitis
Pleura - pleuritis
Prepuce - posthitis
Renal glomeruli - glomerulitis
Renal pelvis - pyelitis
Salivary gland - sialadenitis
Sinus - sinusitis
Skin - dermatitis
Spermatic cord - funiculitis
Spinal nerve root - radiculitis
Spleen - splenitis
Stomach - gastritis
Testicle - orchitis
Tongue - glossitis

Joints - arthritis
Kidney - nephritis
Lacrimal gland - dacryoadenitis
Ligaments - desmitis
Lip - cheilitis
Liver - hepatitis
Lung - pneumonitis
Lymph nodes - lymphadenitis
Lymph vessels - lymphangitis

Trachea - tracheitis
Tympanum - tympanitis
Uterus - metritis
Vagina - vaginitis
Vas deferens - vasitis
Vein - phlebitis
Vertebra - spondylitis
Vessels - vasculitis