Inflammation & Repair PDF

INFLAMMATION & REPAIR INFLAMMATION *Definition: inflammation means local changes which occur in living tissues when exposed to injury, provided that the injury is not severe enough to produce immediate death of tissues. It is indicated by adding the suffix "itis" to...

INFLAMMATION & REPAIR INFLAMMATION *Definition: inflammation means local changes which occur in living tissues when exposed to injury, provided that the injury is not severe enough to produce immediate death of tissues. It is indicated by adding the suffix "itis" to the Latin name of the affected organ or tissue. * Examples: Glossitis, Gastritis, Hepatitis, Cholecystitis, Cystitis. Few exceptions are present as:  Pneumonia = inflammation of the lung.  Pleurisy = inflammation of the pleura. *Causes of inflammation: 1- Physical agents: as trauma, heat, cold, electricity and irradiation. 2-Chemical agents: as acids, alkalies and irritant oils. 3- Living agents (infections): viruses, bacteria, fungi and parasites. 4- Immunological disturbances. * Types of inflammation: According to the onset and duration of inflammation, it is divided into: - Acute: sudden onset and short duration: hours to days Characterized by polymorphnuclearleucocytes (PMNL)  Types - Subacute : grades in between the acute and chronic - Chronic: gradual onset and long duration: months to years Characterized by lymphocytes, plasma cells& histiocytes. ACUTE INFLAMMATION Phenomena of acute inflammation: A – Vascular changes: - Momentary vasoconstriction followed by vasodilatation of arterioles and capillaries resulting in increased quantity of blood flow to the affected area i.e. hyperaemia (which explains the classical signs of redness and hotness). B – Margination and emigration of leucocytes:  Margination of leucocytes: Increased vascular permeability results in extravasation of protein-rich fluid. This causes the RBCs to become more concentrated - 27 -  INFLAMMATION & REPAIR increased viscosity and slowing of blood flow (stasis). This helps the leucocytes to leave the axial stream and to arrange themselves at the periphery. Margination affected by adhesive molecules.  Emigration of leucocytes: at the same time: * The vascular endothelial cells become swollen and gaps are formed between them. * Leucocytes (polymorphs and monocytes) send pseudopodia and escape outside the blood vessels through these gaps. * After penetration of the vessel wall, the subsequent movement of the leucocytes is controlled by chemotaxis. C – Formation of inflammatory exudate: It is a protein rich fluid passing through the vessel wall into the interstitial tissue and explains the swelling sign of acute inflammation. ITEM EXUDATE TRANSUDATE - Spec. gravity >1018 3 gm% < 3 gm% - Fibrin rich no fibrin - Coagulation present absent - Cells rich in inflammatory cells minimal or absent. * Mechanism: Due to increased filtration pressure resulting from: 1-Increased capillary blood pressure due to vasodilatation of arterioles and capillaries. 2-Increased capillary permeability and passage of protein from capillaries. 3-Increased tissue osmotic pressure. * Composition of the inflammatory exudate:  It is formed of a haematogenous part (plasma = serum +fibrin+leucocytes) and a histogenous part (histiocytes, plasma cells, lymphocytes and mast cells).  Its protein content is more than 3 gm %.  Its specific gravity is more than 1018. - 28 -  INFLAMMATION & REPAIR * Functions: 1. Dilution and neutralization of bacterial toxins. 2. Bring antibodies from the blood to the site of inflammation. 3. It helps in localization of infection by formation of fibrin threads around the area of injury. 4. The cells in the inflammatory exudates engulf microorganisms and secrete proteolytic enzymes which liquefy dead tissues and prepare the area for healing. *Chemotaxis: It means attraction of cells towards a chemical -substance (chemotactic agent) as:  Chemical substances released from damaged tissues.  Factors derived from pathogenic organisms.  Factors derived from sensitized lymphocytes (lymphokines).  Factors derived from neutrophils (leukotrienes).  Fraction of the complement in the blood (e.g. C5a).  It is a selective mechanism, thus: 1. Cocci attract PMNL. 2. Bacilli attract monocytes. 3. Viruses attract lymphocytes. 4. Parasites attract eosinophils. *Phagocytosis: It is an active process by which phagocytic cells are capable of engulfing and destroying:- 1-Microorganisms. 2- Dead tissues. 3- Foreign substances. Phagocytosis consist of three steps: 1. Recognition and attachment of the particle to the ingesting leukocyte. 2. Engulfment, with subsequent formation of a phagocytic vacuole. 3. Killing and degradation of the ingested material. NB: It is an important defense mechanism particularly in bacterial infections. It is helped by antibodies known as opsonins. - Examples of phagocytic cells are:  Polymorphs (microphages).  Histiocytes and blood monocytes (macrophages). - 29 -  INFLAMMATION & REPAIR Chemical mediators of acute inflammation *Definition: these are chemical substances that may be circulating in plasma and require activation or they may be secreted by inflammatory cells. *Functions: they are concerned with the various inflammatory processes such as vasodilatation, increased permeability of blood vessels, margination and emigration of leucocytes and chemotaxis. *Examples: 1- Polypeptides as kallikrein and bradykinin from plasma. 2- Vasoactive amines as histamine from mast cells and serotonin (5HT)from platelets. 3- Prostaglandins as PGE2 secreted by polymorphs and other tissues. 4- Lysosomal enzymes. 5- Bacterial toxins. 6- Activated complement fractions as C3a and C5a. - 30 -  INFLAMMATION & REPAIR Manifestations of acute inflammation: I) Local: 5 cardinal changes: 1- Redness 2- Hotness 2- Swelling 3- Pain 5- Disturbance of function. II) General: 1. Fever: caused by bacterial toxins and products of leucocytes (interleukin) release of PGE2 by the hypothalamus. Aspirin reduce fever by suppression of release of PGE2. 2. Other toxic manifestations: as headache, malaise, loss of appetite and rapid pulse. 3. Leucocytosis: It is caused by leucocyte promoting factor produced by necrotic tissues and by products of T lymphocytes. * Cells of inflammation: 1. Polymorphonuclear leucocytes(PML):  It is the most characteristic cell of acute inflammation.  Its main function is phagocytosis of microorganisms (microphage).  When it is dead, it becomes changed into pus cells. 2. Lymphocytes:  They are seen in chronic inflammation.  There are two types of lymphocytes:  B-lymphocytes, which form immunoglobulins.  T-lymphocytes, which produce lymphokines. 3. Plasma cells:  They are the most characteristic cells of chronic inflammation.  They secrete and store immunoglobulins  They are formed by B lymphocytes. - 31 -  INFLAMMATION & REPAIR 4. Macrophage- in the tissue named histiocytes - in the blood named monocytes  They are large cells with abundant cytoplasm and vesicular nuclei.  They are capable of phagocytosing microorganisms, foreign bodies and debris of dead tissues including dead polymorphs. Thus they act as scavengers and prepare the damaged tissues for repair.  They also play an important role in immune response and produce many substances such as complement.  Monocytes are capable of crossing the capillaries to different organs by  different names e.g.: - in the liver called kupffer cells - in the lung called alveolar macrophages - in the bone called osteoclasts - in the nervous system called microglial cells 5. Eosinophils: - They are particularly seen in allergic and parasitic inflammation. - The function of eosinophils is a matter of discussion.  At one hand it is believed that: - They release substances which antagonize histamine, serotonin and bradykinin. - They release enzymes  killing parasites (e.g. schistosomulae).  On the other hand, it is believed that they release substances which exaggerate some allergic conditions as bronchial asthma. 6. Mast cells and blood basophils: - They contain heparin, histamine and serotonin. - They play an important role in allergic reactions. 7. Giant cells:  Formation of multinucleated giant cells is a special feature of some chronic inflammations as tuberculosis. They are formed by fusion of histiocytes and monocytes or by nuclear division without cytoplasmic division.  They are phagocytic cells.  There are many types of giant cells: 1. Langhans giant cells 5. tumour giant cells 2. megakaryocytes 6. Hodgkin giant cells 3. osteoclasts 7. Aschoff giant cells 4. foreign body giant cells Langhans giant cells - 32 -  INFLAMMATION & REPAIR * Types of acute inflammation: 1- Abscess. Localized 2- Furuncle (boil). Suppurative 3- Carbuncle. Diffuse Cellulitis( Phlegmonous ) Types Non-suppurative  Catarrhal  Pseudo-membranous  Serous inflammation  Fibrinous inflammation  Serofibrinous inflammation  Hemorrhagic  Allergic I – Non suppurative inflammation: 1. Catarrhal inflammation: *Affect the mucous membranes (mild type). *The best example is common cold or coryza. *characterized by formation of abundant exudates rich in mucous. *Microscopically: The mucous lining cells are swollen, some cells are ruptured. The submucosa shows hyperaemia, oedema and cellular infiltration with leucocytes. 2. Pseudo-membranous inflammation :  This is a severe type of acute inflammation characterized by formation of a membrane like structure on the affected area.  Examples: Diphtheria and bacillary dysentery.The causative bacteria remain on the mucosal surface and produce powerful exotoxin which causes patchy mucosal necrosis. *Grossly: the mucosa is congested and shows a yellowish pseudo-membrane which is adherent to the underlying structures and if it is removed it leaves a bleeding surface. *Microscopically:  The pseudomembrane is formed of fibrin threads, causative microorganisms, necrotic mucosal cells, acute inflammatory cells and some RBCs.  The submucosa is hyperaemic, oedematous and infiltrated by polymorphs. - 33 -  INFLAMMATION & REPAIR 3. Serous inflammation :  Characterized by the formation of abundant fluid exudate in serous sacs.  Examples: Pleural effusion and epidermal blisters following burns. 4. Fibrinous inflammation :  In this type the exudate is rich in fibrin.  Examples: acute pleurisy and lobar pneumonia. 5. Serofibrinous inflammation: Exudate is rich in serous fluid and fibrin. It also occurs in serous sacs. 6. Haemorrhagic inflammation: The exudate is rich in blood and is caused by virulent organisms that cause damage of blood vessels as in cases of small pox. 7. Allergic inflammation : It is characterized by exudation of abundant fluid containing eosinophils e.g. urticaria. It is caused by antigen antibody reaction. II -Suppurative inflammation: *Definition: it is a severe type of acute inflammation which is characterized by formation of pus. It may be primary or complicate any other type of inflammation. *Causative organism: staphylococci, streptococci, gonococci and meningococci. *Pathogenesis of pus formation:  Bacterial toxins necrosis of the tissue particularly in the center.  The causative bacteria strongly chemotactic, they attract a large number of polymorphs.  Some polymorphs will be killed in the battle against the microorganism  pus cells (Pus cell is a dead polymorph).  The dead polymorphs and bacteria release proteolytic enzymes which liquefy necrotic tissues and result in the formation of pus. Pus is composed of: 1. Living and dead microorganisms 2. Living and dead polymorphs. 3. Liquefied Necrotic tissues. 4. Some blood cells and globules of fat. 5. Inflammatory exudate. - 34 -  INFLAMMATION & REPAIR Types of suppurative inflammation: A- Localized suppurative inflammation: 1- Abscess: *Definition: localized area of suppurative inflammation. *Causative organism: pyogenic microorganisms particularly: staphylococciproduce coagulase enzymes  fibrin threads  surround and localize the area of inflammation. *Pathology: An abscess is formed of three zones: a- A central core of necrotic tissue, which gradually undergoes liquefaction by the action of proteolytic enzymes liberated from dead polymorphs. b- Abscess cavity containing pus in the middle. c- The cavity is surrounded by devitalized tissue known as pyogenic membrane and it is infiltrated by a large number of polymorphs. *Fate of abscess:  If the abscess is not evacuated it will rupture at the point of least mechanical resistance.  If the abscess is evacuated the swelling subsides, cavity collapses  healing by granulation tissue. *Complications of abscess: 1- Complications of healing: a- Ulcer: Which is an area of epithelial discontinuity. b- Sinus: Which is blind ended tract opening to the surface and discharging pus. c- Fistula: which is a tract with two openings e.g. one to the surface and the second to a mucous membrane. 2- Chronicity: If the abscess is not completely drained. 3- Spread of infection by: a- Lymphatics causing lymphangitis and lymphadenitis. b- Blood causing toxaemia, or septicaemia. c- Septic thrombophlebitis causing pyaemia. Epidermis Dermis Cavity containing pus Pyogenic membrane ABSCESS - 35 -  INFLAMMATION & REPAIR 2 - Boil or Furuncle: It is a localized suppuration in hair follicle or sebaceous gland. 3 - Carbuncle:  It is a type of localized suppuration in the subcutaneous tissue, particularly in the region of the back.  It is characterized by formation of multiple loculi containing pus which open on the surface by multiple openings (sinuses).  It is a serious condition and it occurs in diabetic patients. Epidermis Dermis Cavities containing pus Carbuncle B- Diffuse suppurative inflammation: Phlegmonous inflammation:  It is a diffuse form of acute inflammation which occurs in the subcutaneous tissues (cellulitis) and mucous membranes e.g. the appendix.  It is caused by streptococcal infection  spreading factor (hyaluronidase enzyme and fibrinolysin) dissolve fibrin, thus helping the spread of infection. * Sequels of acute inflammation: 1- Resolution: It occurs if the inflammation is mild and the resistance of the individual is good. 2- Healing: by regeneration or organization 3- Spread of infection: by  Direct spread.  Lymphatics causing lymphangitis and lymphadenitis.  Blood causing, toxaemia, or septicaemia.  Septic thrombophlebitis causing pyaemia. 4- Suppuration: if the infection is not suppurative from the beginning. 5-Chronicity: due to persistence of the causative agent. - 36 -  INFLAMMATION & REPAIR CHRONIC INFLAMMATION It may follow acute inflammation which fails to subside or it may start as chronic inflammation from the beginning. Comparison between acute and chronic inflammation Acute inflammation Chronic inflammation  Acute onset  Gradual onset  Short duration  Long duration  Vasodilatation and hyperaemia  Not present  Marked inflammatory exudate  minimal amount  Inflammatory cells are mainly  Lymphocytes, plasma cells and polymorphs macrophages.  No fibrosis  Fibrosis is present and arterioles show (end arteritis obliterans).  Local redness, hotness and swelling.  Absent  Fever and leucocytosis  Low grade fever * TYPES AND CAUSES: 1- Granulomatous chronic inflammation (Specific inflammation): see later It is characterized by focal accumulation of macrophages and it includes: A- Infective granulomas: as tuberculosis, syphilis, leprosy. B- Foreign body granuloma: as talc granuloma. C- Granuloma of unknown origin: as sarcoidosis and Crohn’s disease. 2- Non-granulomatouschronic inflammation (Non-specific): It is characterized by diffuse infiltration by lymphocytes, plasma cells and macrophages. - 37 -  INFLAMMATION & REPAIR GENERAL COMPLICATIONS OF BACTERIAL INFECTIONS I- Toxaemia: *Definition: means the circulation of bacterial toxins in the blood. A) Acute toxaemia:  As in diphtheria, bacillary dysentery, Clostridium perfringens and Clostridium tetanuspowerful exotoxins which pass in the circulation and produces toxic manifestations as:  Fever, rigor , tachycardia and headache  The parenchymatous organs (heart, liver and kidney)  cloudy swelling, fatty degeneration.  In severe cases it causes: 1-toxic myocarditis and acute heart failure. 2-Necrosis and hemorrhage of the adrenal cortex. B) Chronic toxaemia: It is seen in cases of tuberculosis loss of weight, anemia, fever and leucopenia, Amyloid degeneration of the liver. II- Bacteraemia *Definition: It is the presence of bacteria in the circulating blood without causing toxic manifestations. It is a temporary condition seen after: 1- Extraction of a septic tooth. 2- Septic wound or focus of infection in the tonsils, nasal sinuses and gall bladder. III- Septicaemia: *Definition: the circulation of large number of virulent multiplying bacteria in the blood producing severe clinical manifestations such as fever, rigor, rapid pulse, petechial haemorrhage and leucocytosis.  The responsible organisms are Streptococcus haemolyticus, Staphylococcus aureus pneumococci and gonococci.  The condition is seen in cases of osteomyelitis, puerperal sepsis, meningitis and cellulitis.  The picture of septicemia includes the following: 1. Fever, rigor, tachycardia and leucocytosis. 2. The parenchymatous organs (heart, liver and kidney)  cloudy swelling, fatty degeneration. - 38 -  INFLAMMATION & REPAIR 3. The spleen is swollen, soft and friable. The capsule is tense (acute splenic swelling). 4. The bone marrow may show leucoplastic reaction. 5. Petechial hemorrhage in the skin. 6. Hemorrhage in the suprarenal gland. 7. Tinge of jaundice. IV- Pyaemia: *Definition: It is the circulation of septic emboli in the blood and their impaction in different organs producing multiple abscesses.  The causative organisms are staphylococci and streptococci. Gonococci and pneumococci may be also responsible. *Pathogenesis:  Septic focus or an area of suppuration in the body inflammation of a vein with formation of a thrombus (septic thrombophlebitis).  The thrombus becomes invaded by bacteria, and then becomes fragmented (septic emboli) which circulate in blood, and then become impacted in some organs producing septic infarcts which change into abscesses. *Types and causes: A - Systemic pyaemia: Multiple abscesses in organs supplied by systemic circulation as lungs, brain and kidney. It is caused by: Pyaemic abscesses in kidney 1. Acute suppurative osteomyelitis. 2. Puerperal sepsis. 3. Acute bacterial endocarditis. 4. Suppurative otitis media. 5. Septic thrombosis of the cavernous sinuses. 6. As a complication of portal pyaemia. B - Portal pyaemia: Multiple abscesses in the liver. Due to suppurative foci from organs drained by portal vein as in cases of: 1. Acute suppurative appendicitis. 2. Suppuration in gall bladder. 3. Infected thrombosed piles. 4. Septic ulceration in the intestine. - 39 -  INFLAMMATION & REPAIR *Characters of pyaemic abscesses: 1. Multiple. 2. Small in size. 3. Nearly equal in size and similar in shape. 4. They are surrounded by a zone of congestion and haemorrhage. 5. Because the condition is rapidly fatal, there is no fibrous tissue around the wall of the abscesses. REPAIR (Healing and regeneration) *Definition: an active process by which the living tissue repair the damaged area. *Types of repair: I- Regeneration. II- Healing by granulation tissue and scar formation. I- REGENERATION *Definition: means replacement of the destroyed cells by new similar cells by division nearby living cells. *Regeneration depends on: 1. The regenerative capacity of the involved cells. 2. The presence of connective tissue framework for restoration of normal structure. 3-Before regeneration necrotic cells must be removed by the activity of liquefactive enzymes of neutrophils and phagocytic power of macrophages. *The cells of the body vary in their capacity for regeneration and they are divided into three types of cells: 1-Labile cells:  They undergo continuous removal and replacement under normal conditions.  Examples: Basal cells of all epithelial lining, haemopoietic stem cells in the bone marrow and endometrium. 2-Stable cells:  Characterized by low rate of division, but they can divide rapidly if some of them are damaged.  Examples: Parenchymal cells of the liver, renal tubules, osteoblasts and fibroblasts. - 40 -  INFLAMMATION & REPAIR  For regeneration by stable cells to occur, enough viable tissue and intact connective tissue framework otherwise fibrosis will occur. 3-Permenant cells:  They have no capacity for mitotic division in postnatal life.  Examples of permanent cells include: Neurons of central and peripheral nervous system, cardiac muscle fibers and renal glomeruli.  Once they are lost fibrosis. II- HEALING BY GRANULATION TISSUE OR SCAR FORMATION *Definition: replacement of injured or dead tissues by granulation tissue, followed by collagen deposition and scar formation. *Factors which affects the rate of healing: 1. General: 1. Age: healing is more rapid in young than in old. 2. General condition: diabetes, anaemia, kidney disease and liver cirrhosis delay the rate of healing. 3. Cortisone: inhibit the rate of healing. 4. Vitamin C: helps formation of ground substance. 5. Zinc is necessary for collagen formation. 6. irradiation: diminish the rate of healing. 2. Local: 1-Proper vascularization of the affected part is essential for healing. 2-Presence of foreign bodies inhibits healing process. 3-Infection interferes with healing. 4-Immobilization (rest) promotes healing particularly in bone fracture. *Types of healing: 1- Healing by primary (first) intention: It occurs in clean surgical wounds with minimal destruction of tissues and good opposition of edges of the wound (no gap formation). 1- At first extravasated blood fills the cleft together with appearance of polymorphs followed by macrophages. 2- Granulation tissue formation which is formed of (Newly formed capillaries, and proliferating fibroblasts lay down collagen) in the damaged area. At the same time, the surface epithelium grows from both sides and covers the wound. - 41 -  INFLAMMATION & REPAIR 3- After few weeks, more and more collagen is formed with gradual closure of capillaries white fibrous scar is formed under the surface epithelium. NB: No hair follicles or sebaceous glands are found in the scar. Healing by primary (first) intention 2- Healing by second intention (secondary union): Occurs in open wounds with significant loss of tissues and infection. 1-At first, the cavity is filled with extravasated blood and blood clot and becomes surrounded by acute inflammatory cells at the edges of the cavity. 2-Few days later, Granulation tissue formation which is formed of (Newly formed capillaries, and proliferating fibroblasts lay down collagen) and fill the gap. At the same time, the surface epithelium at the edges undergoes mitotic activity and there is gradual narrowing of the gap until there is complete bridging by the surface epithelium. - 42 -  INFLAMMATION & REPAIR 3-In the second week and later on, there is gradual deposition of collagen and gradual narrowing of the capillaries until thick collagenous avascular ugly scar is formed under the surface epithelium. This process takes few months to be completed. NB: Granulation tissue: is pink in colour, not sensitive and bleeds on touch. It is composed of newly formed capillaries, fibroblasts and inflammatory cells. Healing by secondary intention *Complications of wound healing: 1. Contracture: shortening of collagen bundles leading to cosmetic disturbances. e.g. following healing of burns. 2. Keloid: excessive formation of collagen. 3. Delayed healing. 4. Secondary infection. 5. Chronic ulcer. - 43 -  INFLAMMATION & REPAIR 6. Sinus. 7. Fistula. 8. Inclusion epidermoid cyst formation. *Healing of an abscess (healed by secondary intention): 1. After evacuation of pus, the cavity becomes filled with exudate. 2. Formation of (granulation tissue). 3. Regeneration of the epidermis. 4. Formation of scar tissue. *Healing of serofibrinous exudate: 1. The fluid is slowly absorbed. 2. Granulation tissue is formed.It becomes transformed into fibrous tissue. 3. The mesothelial cells proliferate and cover the fibrous tissue. 4. Sometimes the fibrous tissue from the surfaces of serous sac unites together resulting in formation of fibrous adhesions, covered by mesothelial cells. - 44 -