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
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
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:
5) Loss of function.
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.
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.
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 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
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
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)
3] Prostaglandin E1, and I2
4] Leukotriene B4
5] C5 fragment of complement
B. Vasopermeability - the mediators that alter the permeability of the microvasculature include the following mediators:
5] Platelet Aggregating Factor
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
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.
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
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:
 it will rupture at a surface
following a tract called a SINUS or FISTULOUS TRACT
 It will spread along fascial plane between healthy tissues
 It will become encapsulated and contained within fibrous tissue
 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, multi-focal, 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.
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
Fascia - Fasciitis
Fat - steatitis
Gallbladder - cholecystitis
Glans penis - balanitis
Heart - carditis
Intestine - enteritis
Iris - iritis
Joints - arthritis
Kidney - nephritis
Lacrimal gland - dacryoadenitis
Ligaments - desmitis
Lip - cheilitis
Liver - hepatitis
Lung - pneumonitis
Lymph nodes - lymphadenitis
Lymph vessels - lymphangitis
|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
Trachea - tracheitis
Tympanum - tympanitis
Uterus - metritis
Vagina - vaginitis
Vas deferens - vasitis
Vein - phlebitis
Vertebra - spondylitis
Vessels - vasculitis