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
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. 1 2 3 4 5 6 7 8 Acute Inflammation http://www.youtube.com/watch?v=suCKm97yvyk&feature=related Wound Healing http://www.youtube.com/watch?v=FraKUUetOpc&feature=related