Chapter 2 Inflammation & Healing PDF

:Chapter 2 INFLAMMATION & HEALING  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 no...

:Chapter 2 INFLAMMATION & HEALING  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.  Review of Body Defenses First line of defense – Nonspecific defense /General defense mechanism *Mechanical barrier like : Unbroken skin and mucous membranes. Associated with it are : Secretions such as saliva or tears and gastric juices  Review of Body Defenses Second line of defense – Nonspecific defense *Phagocytosis – Vulture cells …Neutrophils (leukocyte) & macrophages engulf & destroy bacteria ,cell debris /foreign matter *Inflammation-limits effects of injury /dangerous agents *Interferon protect uninfected cells from virus.  Review of Body Defenses Third line of defense Specific defense-- - : Provide protection by* Production of unique antibodies / sensitized lymphocytes Cell-mediated immunity -  PATHOGENS OR INJURIOUS AGENTS Or General  Normal Capillary Exchange Generally not all capillaries in a particular capillary bed are open unless cells metabolic needs are not met /accumulation of metabolic waste occur. Movement of fluid, electrolytes, oxygen, and nutrients on arterial end based on net hydrostatic pressure Venous end—osmotic pressure is high & hydrostatic pressure is decreased this will facilitate movement of fluid, carbon dioxide, and other wastes return to blood.  Definition Inflammation is a protective non-specific response to tissue injury.It is intended to localize and remove an injurious agent. Inflammations are named using the ending -itis. For example, pancreatitis, appendicitis, laryngitis, ileitis, blepharitis. Inflammation is interwoven with repair processes.  Causes of Inflammation Direct physical damage Foreign bodies – Examples: cut, sprain – Examples: splinter, glass Caustic chemicals Infection – Examples: acid, drain Insect bite cleaner Small burn Ischemia or infarction Allergic reactions Extremes of heat or cold Severity of inflammation depends on cause & duration of exposure  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 Pathophysiology of Inflammation  Steps of Inflammation Injury to capillaries and tissue cells result in : Release of bradykinin ( biochemical mediator) from injured cells Bradykinin stimulates pain receptors. Pain stimulate mast cells & basophils to release chemicalmediators eg: histamine. Bradykinin and histamine cause capillary dilation - it increase of blood flow & increased capillary permeability Break in skin allows bacteria to enter tissue – This result in migration of neutrophils & monocytes to the site of injury. Neutrophils phagocytize bacteria. Macrophages (mature monocytes) leave the bloodstream and phagocytose microbes.  Inflammation Inflammation may develop -Immediately & last only short time OR -Be of delayed onset (sunburn) OR - Be severe and prolonged Severity – based on cause & duration Acute inflammation - Acute inflammation Major phenomena (events): Pathophysiology 1- Vascular response: Nerve reflex at site of injury cause When Tissue injury transient vasoconstriction,but the rapid release of occur- chemical mediators cause arteriolar vasodilation > redness /hyperemia and warmth. the capillary Damaged Mast cells & platelets membrane becomes more permeable, resulting in the >release chemical mediators movement of plasma protein & fluid into the eg: Histamine ,serotonin , interstitial space which dilute toxic material > prostaglandin & leukotrienes increasing blood viscosity and slowing the into interstitial fluid & blood. circulation. These changes are reflected microscopically by numerous dilated small vessels packed with > These Chemicals effect blood erythrocytes (stasis). Globulin serve as antibodies & vessels & nerves in damaged fibrinogen form a Fibrin mesh around the area.to area. localize injurious agent. 2. Cytokines(small secreted N.B.. Inflammatory fluid exudate is protein-rich fluid that proteins released by cells) contain inflammatory cells. serve as communicator in 2- During Cellular response: Leukocytes are attracted by tissue fluid send message to Chemotaxis to area of inflammation as damaged cells lymphocytes & macrophages release chemical mediators that attract leukocytes - /immune system / 1st neutrophils later monocyte & macrophage migrate hypothalamus to induce fever. through capillary wall into interstitial area towards area of inflammation.This movement of cell is called diapedesis. Local Effects SYSTEMIC EFFECTS (acute-phase reaction) The 5 cardinal signs of inflammation are redness (RUBOR or erythema), heat Fever, increased somnolence, malaise, (CALOR), swelling (TUMOR), pain anorexia, accelerated degradation of (DOLOR) and loss of function (FUNCTIO skeletal muscle proteins, hypotension, LAESA ). hepatic synthesis of a variety of · Redness and warmth are caused by increased proteins (e.g., complement and blood flow into the damaged area. coagulation proteins), and alterations in the circulating white blood cell pool. · Swelling or edema is caused by the shift of protein and fluid into the interstitial space. Fever results from the release of · Pain results from the increased pressure of pyrogens , or fever-producing fluid on the nerves, especially in enclosed substances (e.g., interleukin-l), from white areas, and by the local irritation of nerves by blood cells (WBCs) or macrophages. chemical mediators. Pyrogens circulate in the blood and cause the body temperature control system Loss of function may develop if the cells lack (the thermostat) in the hypothalamus to nutrients, for example, liver cells, or if be reset at a higher level. swelling interferes mechanically with function, for Following removal of cause ,body example, joint movement. temperature return to normal by reversing Exudate- collection of interstitial fluid in the the mechanism. inflamed area.( Next slide )  LOCAL EFFECT Exudate – refer to collection of interstitial fluid in inflamed area Characteristics of exudate 2- FIBRINOUS. Exudate is thick & sticky & have high 1- SEROUS Exudate /watery exudate. cell & fibrin content. Consist primarily of fluid with small amount of protein & WBC (effusion). This type of exudate increases risk of scar tissue in the area. The skin blister resulting from a burn or Fate: 1- Resolution. Fibrinous exudates may be viral infection is a good example of a serous effusion accumulated either within degraded by fibrinolysis, and the accumulated or immediately beneath the epidermis of debris may be removed by macrophages, resulting the skin. 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. 4- ULCERATION. Purulent exudate (pus) are thick ,yellow green “site of inflammation where an in colour and contain more leukocytes &cell epithelial surface has become debris as well as microorganisms. Exudate necrotic and eroded (lost)”, with indicates bacterial infection and is refered as “pus” / pyogenic. associated subepithelial acute and Abscesses are localized collections of pus / chronic inflammation. pocket of purulent exudate in a solid tissue (eg : around a tooth / in the brain ) Cellulitis is a diffuse form of suppurative inflammation. Hemorrhagic exudate may be.5 present if blood vessels have been. damaged Course of Inflammation and Healing  Healing Types of Healing: a. Resolution-When there is minimal tissue damage. The damaged cells recover & tissue return to normal. Eg: mild sunburn. b. Regeneration – – Damaged tissue replaced with cells that are functional Replacement – Functional tissue replaced by scar tissue – Loss of function  Inflammation vedio https://www.youtube.com/watch? v=suCKm97yvyk  Laboratory Findings / Diagnostic tests Leukocytosis (increased white blood cell count). The leukocyte count typically increases to 15,000 or 20,000 cells per μL (normal = 4000 to 10,000 cells per μL) but may climb as high as 40,000 to 100,000 cells per μL, 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.  Potential complication 1. Local complication – eg: inflammation of lung & decreased oxygenation / Joint inflammation & ROM 2. Infection – microorganisms penetrate through skin & mucous damage & blood supply. 3. Skeletal muscle spasm – due to pressure on nerve.  Chronic Inflammation Chronic inflammation is characterized by the following: Prolonged duration (weeks to months to years). There is less swelling and exudate but presence of lymphocytes, macrophages & fibroblast (connective tissue cells ) than in acute inflammation More tissue destruction, largely directed by the inflammatory cells. More collagen is produced in the area > fibrous scar tissue formation. Granuloma formation. A small mass of cells with necrotic center and covered by connective tissue develop around foreign object eg: splinter or as part of immune response in some infection (TB) Repair, involving new vessel proliferation (angiogenesis) and fibrosis. COMPLICATION : 1. Deep ulcers 2. Perforation (erosion through the wall) 3. Extensive scar tissue 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 Process Healing process starts following injury when a blood As well Fibroblast & macrophages produce clot form and seal the area. growth factor (cytokines)in the area for Inflammation develop in surrounding area attracting more fibroblast that act as mitogen, After 3-4days foreign material & cell debris are for epithelial cell proliferation, migration & removed by Phagocytes, monocytes,& macrophages promote development of new blood vessel Then granulation tissue grows into the gap from (angiogenesis ) nearby connective tissue. Granulation tissue is highly vascular, moist, pink/red. It contain many new Collagen fiber shorten>tighten & become capillary buds. This tissue is fragile & easily break strong scar. down. As the wound cavity fills in with granulation Capillary in the area decrease ,color of tissue > nearby epithelial cells undergo mitosis. scar fades. Shortly Fibroblast , connective tissue cells enter the area and produce collagen ,a protein - basic Scar tissue is not normal/functional & component of scar tissue & provide strength for new does not have functional tissue.Eg: Hair repair. follicle.  Healing by first intention 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.  Healing by first intention By day 5, neovascularization reaches its peak as granulation tissue fills the incisional space. Collagen fibrin 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 remains  Secondary union, (healing by second intention) Secondary healing differs from :primary healing by Greater volume of necrotic debris, -1 exudate, and fibrin that must be removed. Inflammatory reaction is more intense, with greater potential for secondary, inflammation-mediated.injury A greater volume of granulation tissue -2 results in a greater mass of scar.tissue Secondary healing exhibits the -3 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. 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.  Reference Gould’s Pathophysiology for the Health Professions, Robert J.Hebert &Karin C.VanMeter, 6th Edition 2018, Elsevier. Chapter 5 page 66-78 Acute Inflammation http://www.youtube.com/watch?v=suCKm97yvyk&feature=related Wound Healing http://www.youtube.com/watch?v=FraKUUetOpc&feature=related