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LEARNINGOBJECTIVES

After studying this chapter, the student is expected to:


1. Explain the role of normal defences in preventing disease.
2. Describe how changes in capillary exchange affect the tissues and the blood.
3. Compare normal capillary exchange with exchange during the inflammatory response.
4. Describe the local and systemic effects of inflammation.
5. Explain the effects of chronic inflammation.
6. Discuss the modes of treatment of inflammation.
7. Describe the types of healing and complications of healing.
8. List the factors , including a specific example for each, that hasten healing.
9. Identify the classifications of burns and describe the effects of burns.
10. Describe the possible complication occurring in the first few days after a burn.
11. Explain the reasons why the healing of a burn may be difficult.
Chapter 2: Inflammation & Healing
inflammation is a protective non-specific
response intended to eliminate the initial cause
of cell injury as well as the necrotic cells and
tissues resulting from the original insult.
Inflammations are named using the ending -itis.
For example, pancreatitis, appendicitis,
laryngitis or ileitis.
Inflammation is interwoven with repair
processes.
Inflammation may be classified into two types:
Acute inflammation is of relatively short
duration, lasting from a few minutes up to a few
days, and is characterized by fluid and plasma
protein exudation and a predominantly
neutrophilic leukocyte accumulation.
Chronic inflammation is of longer duration
(days to years) and is typified by influx of
lymphocytes and macrophages with
associated vascular proliferation and
scarring.
Acute inflammation
Major phenomena (events):
1- Vascular changes: After transient (seconds)
vasoconstriction, arteriolar vasodilation
occurs > redness (erythema) and warmth.
the microvasculature becomes more
permeable, resulting in the movement of
protein-rich fluid into the extravascular
tissues. increasing blood viscosity and
slowing the circulation. These changes are
reflected microscopically by numerous dilated
small vessels packed with erythrocytes
(stasis).
N.B. .Inflammatory fluid exudate is protein-rich
fluid that contain inflammatory cells, while
transudation is filtration of plasma with low
protein content.

2- Cellular events: emigration of the leukocytes
(neutrophils) from the microcirculation and
accumulation in the focus of injury (cellular
recruitment and activation). It involves
leukocyte margination, rolling, adhesion to the
endothelial surface and then transmigration
(diapedesis).

Inflammatory Mediators:
ECs = endothelial cells
Local Effects

The cardinal signs of inflammation are redness
(rubor or erythema), heat, swelling, pain and
loss of function.

Redness and warmth are caused by increased
blood flow into the damaged area.
Swelling or edema is caused by the shift of
protein and fluid into the interstitial space.
Pain results from the increased pressure of
fluid on the nerves, especially in enclosed
areas, and by the local irritation of nerves by
chemical mediators.
Loss of function may develop if the cells lack
nutrients, for example, liver cells, or if
swelling interferes mechanically with an
action, for example, joint movement.
SYSTEMIC EFFECTS
(acute-phase reaction)

Fever, increased somnolence, malaise,
anorexia, accelerated degradation of
skeletal muscle proteins, hypotension,
hepatic synthesis of a variety of
proteins (e.g., complement and
coagulation proteins), and alterations
in the circulating white blood cell pool.

Fever results from the release of
pyrogens, or fever-producing
substances (e.g., interleukin-l), from white
blood cells (WBCs) or macrophages.
Pyrogens circulate in the blood and cause
the body temperature control system
(the thermostat) in the hypothalamus to
be reset at a higher level.
Leukocytosis (increased white blood cell count). The leukocyte count typically increases to 15,000
or 20,000 cells per L (normal = 4000 to 10,000 cells per L) but may climb as high as 40,000 to
100,000 cells per L, a so-called leukemoid reaction. Leukocytosis initially results from the release
of cells from the bone marrow and is associated with an increased number of relatively immature
neutrophils in the blood ("left-shift").
Most bacterial infections induce a relatively selective increase in polymorphonuclear cells
(neutrophilia)
Parasitic infections (as well as allergic responses) characteristically induce eosinophilia.
Certain viruses, such as infectious mononucleosis, mumps, and rubella, engender selective
increases in lymphocytes (lymphocytosis).
However, most viral infections, as well as rickettsial, protozoal, and certain types of bacterial
infections (typhoid fever), are associated with a decreased number of circulating white cells
(leukopenia). Leukopenia is also encountered in infections that overwhelm patients debilitated by,
for example, disseminated cancer.
Elevated serum C-reactive protein (CRP), an elevated erythrocyte sedimentation rate or
ESR, and increased plasma proteins and cell enzymes in the serum are nonspecific Changes
Increased circulating plasma proteins (fibrinogen, prothrombin, and alpha-antitrypsin).
Cell enzymes and isoenzymes (more specific forms) may be elevated in the blood in the presence
of severe inflammation and necrosis. For example, aspartate aminotransferase (AST, formerly
serum glutamicoxaloacetic transaminase [SGOT]) is elevated in liver disease and in the acute stage
of a myocardial infarction (heart attack). However, the isoenzyme CK-MB (isoenzyme of creatine
kinase with myocardial component) is specific for myocardial infarction. The enzyme alanine
aminotransferase (ALT) is specific for the liver.

Laboratory Findings / Diagnostic tests

Outcomes of Acute Inflammation

Resolution. When the injury is limited or short-lived, when there has been no or minimal
tissue damage, and when the tissue is capable of replacing any irreversibly injured cells, the
usual outcome is restoration to histologic and functional normalcy. lymphatic drainage and
macrophage ingestion of necrotic debris lead to the clearance

Scarring or fibrosis results after substantial tissue destruction or when inflammation occurs
in tissues that do not regenerate.. Abscess formation may occur in the setting of extensive
neutrophilic infiltrates (see later) or in certain bacterial or fungal infections (these organisms
are then said to be pyogenic, or "pus forming"). Due to the extensive underlying tissue
destruction (including the extracellular matrix), the only outcome of abscess formation is
scarring.

Progression to chronic inflammation may follow acute inflammation, Depending on the
extent of the initial and ongoing tissue injury, as well as the capacity of the affected tissues to
regrow, chronic inflammation may be followed by regeneration of normal structure and
function (regeneration) or may lead to scarring.

Chronic Inflammation
Chronic inflammation is characterized by the following:
prolonged duration (weeks to months to years) .
Infiltration with mononuclear ("chronic inflammatory") cells, including macrophages,
lymphocytes, and plasma cells..
Tissue destruction, largely directed by the inflammatory cells.
Granuloma formation. A mass of inflammatory cells with necrotic center and surrounded by
fibroblasts and collagen.
Repair, involving new vessel proliferation (angiogenesis) and fibrosis.


MORPHOLOGIC PATTERNS OF ACUTE AND CHRONIC INFLAMMATION
1- SEROUS INFLAMMATION. This is
characterized by watery, relatively protein-
poor fluid (effusion).
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.
2- FIBRINOUS INFLAMMATION.
severe injuries > vascular permeability allowing
fibrinogen to pass the endothelial barrier >
eosinophilic meshwork of threads or amorphous
coagulum
Fate: 1- Resolution. Fibrinous exudates may be
degraded by fibrinolysis, and the accumulated
debris may be removed by macrophages,
resulting in restoration of the normal tissue
structure.
2- Organization. failure to completely remove the
fibrin results in the ingrowth of fibroblasts and
blood vessels > scarring > interfere with function.
3- SUPPURATIVE (PURULENT) INFLAMMATION.
Purulent exudate (pus) consisting of neutrophils,
necrotic cells, and edema fluid. Certain organisms (e.g.,
staphylococci) are more likely to induce this localized
suppuration and are therefore referred to as pyogenic.
Abscesses are localized collections of pus that may be
caused by deep seeding of pyogenic organisms into a
tissue or by secondary infections of necrotic foci.
Abscesses typically have a central, largely necrotic
region rimmed by a layer of preserved neutrophils with
a surrounding zone of dilated vessels and fibroblastic
proliferation indicative of early repair.
Cellulitis is a diffuse form of suppurative inflammation.
4- ULCERATION.
site of inflammation where an epithelial surface has
become necrotic and eroded (lost), with associated
subepithelial acute and chronic inflammation.
TREATMENT OF INFLAMMATION
1- Drugs
TREATMENT OF INFLAMMATION
2- Other Therapies

First-aid directives for injury-related inflammation frequently recommend Rest, Ice,
Compression, Elevation (RICE).

Cold applications are useful in the early stage of acute inflammation. Application of cold
causes local vasoconstriction, thereby decreasing edema and pain. The use of hot or cold
applications during long-term therapy and recovery periods depends on the particular
situation. In some instances, for example, acute rheumatoid arthritis, heat, and moderate
activity may improve the circulation in the affected area, thereby removing excess fluid, pain-
causing chemical mediators, and waste metabolites as well as promoting healing.

Mild-to-moderate exercise is useful in cases of many chronic inflammatory conditions
where improved blood and fluid flow is beneficial and mobility could be improved.

Other treatment measures, including physiotherapy, may be necessary to maintain joint
mobility, although splints may be required during acute episodes to prevent contractures,
fixed abnormal joint positions.

Rest and adequate nutrition and hydration are important.
Healing
Repair begins very early in the process of inflammation and involves two processes:
1- Regeneration: Replacement of injured tissue by parenchymal cells of the same type.
2- Fibrosis: Replacement of injured tissue by connective tissue resulting in a scar.

Healing BY FIBROSIS

Repair begins within 24 hours of injury by the migration of
fibroblasts and the induction of fibroblast and
endothelial cell proliferation. By 3 to 5 days,
granulation tissue, is apparent. It is characterized by
proliferation of fibroblasts and new thin-walled,
delicate capillaries, in a loose extracellular matrix.
Granulation tissue then progressively accumulates
connective tissue matrix, eventually resulting in dense
fibrosis (scarring), which may further remodel over
time.
WOUND HEALING involves the following steps:
Induction of an acute inflammatory response by the
initial injury
Parenchymal cell regeneration (where possible)
Migration and proliferation of both parenchymal and
connective tissue cells
Synthesis of ECM proteins
Remodeling of parenchymal elements to restore tissue
function
Remodeling of connective tissue to achieve wound
strength
Healing by First Intention
(primary union)

Healing of a clean, uninfected surgical incision approximated by surgical sutures so epithelial
regeneration predominates over fibrosis. The narrow incisional space rapidly fills with fibrin-
clotted blood; dehydration at the surface produces a scab to cover and protect the healing
repair site.
Within 24 hours, neutrophils are seen at the incision margin, migrating toward the fibrin
clot. Within 24 to 48 hours, epithelial cells from both edges have begun to migrate and
proliferate along the dermis to meet in the midline.
By day 3, neutrophils have been largely replaced by macrophages, and granulation tissue
progressively invades the incision space.
By day 5, neovascularization reaches its peak as granulation tissue fills the incisional space.
Collagen fibrils become more abundant and begin to bridge the incision. The epidermis
recovers its normal thickness
During the second week, there is continued collagen accumulation and fibroblast
proliferation. The leukocyte infiltrate, edema, and increased vascularity are substantially
diminished. The long process of "blanching" begins.
By the end of the first month, the scar comprises a cellular connective tissue largely devoid
of inflammatory cells and covered by an essentially normal epidermis. However, the dermal
appendages destroyed in the line of the incision are permanently lost.
Secondary union, (healing by second intention)
Secondary healing differs from
primary healing by:
1- Greater volume of necrotic
debris, exudate, and fibrin that must
be removed. Inflammatory reaction
is more intense, with greater
potential for secondary,
inflammation-mediated injury.
2- A greater volume of granulation
tissue results in a greater mass of
scar tissue.
3- Secondary healing exhibits the
phenomenon of wound
contraction due to the presence of
myofibroblasts (modified
fibroblasts with contractile
function).

Causes of delayed Healing:

1- Infection is the single most important cause of delay in healing.

2- Nutrition has profound effects on wound healing; protein deficiency, and vitamin C deficiency, inhibit
collagen synthesis.

3- Glucocorticoids (steroids) have anti-inflammatory effects, and their administration may result in poor
wound strength owing to diminished fibrosis. Chemotherapy also delays healing.

4- Mechanical factors such as increased local pressure or torsion may cause wounds to pull apart.

5- Poor perfusion, due to arteriosclerosis, or obstructed venous drainage.

6- Foreign bodies: fragments of steel, glass, or even bone.

7- The type (and volume) of tissue and The location of the injury, For example, inflammations arising in
tissue spaces (e.g., pleural) develop extensive exudates > resolution or organization.

9- Advanced age, anemia, diabetes, cancer.
Complications of wound healing:
1- Loss of Function: results from the loss of normal cells and the lack of specialized structures or
normal organization in scar tissue. For example, skin, organized organ such as the kidney

2- Contractures and Obstructions: Scar tissue is non elastic and tends to shrink over time. This
process may restrict the range of movement of a joint and eventually may result in fixation and
deformity of the joint, a condition known as contracture. Fibrous tissue may also limit movement of
the mouth or eyelids. Physiotherapy or surgery may be necessary to break down the fibrous tissue
and improve mobility. If the esophagus is shortened, malposition of the stomach (hiatal hernia) or a
narrowed esophagus (stenosis) causing obstruction during swallowing.

3- Adhesions: are bands of scar tissue joining two surfaces that are normally separated. Common
examples are adhesions between loops of intestine (see Fig. 2-88) or between the pleural
membranes.


4- Hypertrophic scar tissue. An overgrowth of fibrous tissue consisting of excessive collagen
deposits may develop, leading to hard ridges of scar tissue or keloid formation. These masses
are disfiguring and frequently cause more severe contractures.
Keloid. This is accumulation of exuberant amounts of collagen that gives rise to prominent, raised scars.
There appears to be a heritable predisposition to keloid formation, and the condition is more common in
blacks.

5- Ulceration. Blood supply may be impaired around the scar, resulting in further tissue breakdown and
ulceration at a future time. This may occur when scar tissue develops in the stomach following surgery
or healing of an ulcer.
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Acute Inflammation http://www.youtube.com/watch?v=suCKm97yvyk&feature=related
Wound Healing http://www.youtube.com/watch?v=FraKUUetOpc&feature=related