General Pathology2.pdf

Dr. Mohammed Abdellah General Pathology-2 sinaiuniversity.net Chronic Inflammation Tuberculosis By the end of lecture you should be able to understand: -Definition of tuberculosis. -aetiology of TB. -Mode of inection of tuberculosis Mechanism of caseation. -mechanism and routes of spread. -compl...

Dr. Mohammed Abdellah General Pathology-2 sinaiuniversity.net Chronic Inflammation Tuberculosis By the end of lecture you should be able to understand: -Definition of tuberculosis. -aetiology of TB. -Mode of inection of tuberculosis Mechanism of caseation. -mechanism and routes of spread. -complications and types of TB. -Primary tuberculosis . TUBERCULOSIS DEFINITION: Tuberculosis is a chronic infectious granulomatous disease caused by Mycobecterium tuberculosis . Causes of cell injury (Causes of Disease): 1. Living Irritants: Bacteria and their toxins, viruses, parasites and fungi. 2. Non Living Irritants: Include:  Physical irritants: e.g. excess heat, excess cold and radiation.  Chemical irritants: e.g. acids, alkalis, poisons.  Mechanical irritants: e.g. trauma, friction. 3. Hypoxia (Decrease in Oxygen supply) as in anemia. 4. Ischemia (Decrease in blood supply): as in arterial occlusion. 5. Immunological reactions. 6. Nutritional disturbances. 7. Genetic disorders. AETIOLOGY: Predisposing factors: . Tuberculosis is common in communities with low Standards of nutrition and housing. The causative bacteria: 1) Human tubercle bacilli. 2) Bovine tubercle bacilli . Tubercle bacilli are Gram-positive, acid-fast bacilli. ,best stained with Ziehl-Neelsen stain. The structure: the bacteria consists of an outer lipid capsule covering a body composed of a polysaccharide fraction and a protein component (tuberculoprotein). Bacterial effect on tissues (pathogenesis): tuberculoprotein is strongly antigenic and the destructive lesions are mainly attributed to hypersensitivity reactions. Mode of infection: 1-Human Tubercle Bacilli: Bacteria are expectorated in sputum of patients having pulmonary tuberculosis .Bacteria can contaminate dust & survive for long periods. a) Inhalation of contaminated dust leads to lung tuberculosis. b)Swallowing of contaminated dust leads to tuberculosis of tonsils or intestine. c)Inoculation through skin is extremely rare. 2-Bovine Tubercle Bacilli: These bacteria exist in milk of tuberculous cows and are transmitted to man by swallowing of infected milk causing tuberculosis of tonsils or intestine. TISSUE REACTION IN T.B: I) THE PROLIFERATIVE TISSUE REACTION (THE TUBERCLE) It is the basic lesion of tuberculosis. It develops around the tubercle bacilli. Several tubercles are formed and as they enlarge, they fuse together. Mode of Formation of Tubercles 1-Neutrophils are attracted within few hours to the polysaccharide fraction of the bacilli. They may engulf the bacilli but cannot digest them. 2-Macrophages are attracted to the lipid part of the bacilli & accumulate gradually. They engulf the bacteria they digest the lipid capsule of these bacteria liberation of tuberculoprotein in the cytoplasm of macrophages alteration of macrophages which become epithelioid cells. 3-Some epithelioid cells fuse together forming giant cells called Langhan's giant cells 4-T-lymphocytes interact with macrophages that carry the bacterial antigenic material (tuberculoprotein). This leads top sensitization of T lymphocytes. Sensitized T lymphocytes accumulated around the epithelioid cells in 10-14 days and release lymphokines acquired immunity and hypersensitivity… Mechanism of caseation: 1-Hypersensitivity (cytotoxic lymphokines). 2-Ischemic necrosis Fate of Tubercles: 1-Localization: a)Small lesions are totally replaced by fibrosis. b)Larger caseous may be only surrounded by fibrosis (encapsulation. Later on the body resistance is lowered, these dormant bacilli lead to reactivation of tuberculosis. 2-Spread of tuberculosis due to failure of localization. II) THE EXUDATIVE TISSUE REACTION It has been found that tuberculous reaction in serous membranes it is commonly exudative ,while in lungs it is proliferative, exudative or combined. The typical exudative tissue reaction occurs in sensitized persons (having sensitized T lymphocytes) characterized by: 1-Outpouring of fluid exudate containing fibrinogen. 2-Numerous lymphocytes (and often neutrophils), but few epithelioid cells & giant cells. 3-Caseation is usually marked & undergoes rapid liquefaction by enzymes derived from neutrophils. Spread of TB. Mechanism 1. Macrophages carry bacilli 2. Free bacilli (non-motile) carried by tissue fluids, lymph, blood. Routes 1-Direct spread to the surroundings. 2-Lymphatic spread to the draining lymph nodes. 3-Blood spread: a) No effects. b) Isolated organ tuberculosis: c) Miliary tuberculosis: A large number of bacteria reach the blood. The lungs, liver, kidneys, adrenals, serous membranes and other organs will show huge numbers of small adjacent tuberculous lesions; 1-2 mm each. The condition is rapidly fatal. 4-Intracanalicular spread FACTORS INFLUENCING THE COURSE OF TB 1-Dose Of Infection and Virulence of the organism. 2-Immunity & Hypersensitivity: a) Natural Innate Immunity and general health. b) Degree of acquired immunity and delayed hypersensitivity. Both mediated by sensitized T lymphocytes (cell mediated immunity). Hypersensitivity in 10 to 14 d (delayed hypersensitivity typeIV COMPLICATIONS OF TUBERCULOSIS: 1-Spread 2-Hemorrhage 3-Organ destruction and severe fibrosis 4-Amyloidosis (in chronic cases) 5-Recurrence (re-activation) Types of TB.: Primary Tuberculosis This is tuberculous infection for the first time. Secondary Tuberculosis Reinfection tyype This is tuberculous infection of sensitized individuals In Egypt it mainly affects children. In Egypt it mainly affects adults. Spread of infection is more common. Spread of infection is less common Tissue destruction is less marked. Tissue destruction is more marked . Tissue reaction is slow. Tissue reaction is accelerated. Course of infection is mainly affected by innate immunity. Course of infection is determined by degrees of innate immunity, acquired immunity & hypersensitivity. PRIMARY TUBERCULOSIS (CHILDHOOD TYPE) Primary tuberculosis may develop in the lungs , in tonsils or intestine or rarely in the skin. Tubercle bacilli will exist in three sites: 1-Somewhere in the infected organ (primary tuberculous focus) 2-In the draining lymphatics (tuberculous lymphangitis). 3-In the draining lymph nodes (tuberculous lymphadenitis). .Fate of primary tuberculosis: a)Localization (with possible later reactivation) b)Spread. PRIMARY PULMONARY TUBERCULOSIS Aetiology: Inhalation of human tubercle bacilli. Pathology: Primary Complex: 1-Ghon's Focus: It is the initial tuberculous lung lesion: Small tan yellow subpleural granuloma in mid lung field on the Rt. In the hilum is a small yellow tan granuloma in a hilar lymph node next to a bronchus. 2-Tuberculous Lymphangitis 3-Tuberculous Lymphadenitis Fate of primary pulmonary TB.: 1-Localization and healing (fibrous replacement or capsulation), but living bacilli may persist within healed lesions. 2-Spread: a)Direct spread to: - Adjacent lung tissue: tuberculous pneumonia. - Pleura: tuberculous pleurisy. -Pericardium :tuberculous pericarditis b)Lymphatic spread. c)Hematogenous : - Small number No effect - Moderate number  Isolated organ tuberculosis - Large number  Miliary tuberculosis, commonly fatal. d)Bronchial spread: Caseous erosion of a bronchus from Ghon's focus or hilar lymph nodes  bronchial spread  distal bronchi and adjacent lung tissue  tuberculous bronchopneumonia. Coughing of infected sputum  affection of larynx, tonsils...etc 3-Reactivation of capsulated or healed lesions (with persistent tubercle bacilli) may occur few years later if immunity is lowered, leading to secondary pulmonary tuberculosis and spread of infection. The small millet seed sized granulomas in this lung are typical for miliary Tuberculosis Microscopic examination of TB granuloma: Thanks Dr. Mohammed Abdellah General Pathology-2 sinaiuniversity.net Chronic Inflammation Tuberculosis By the end of lecture you should be able to understand: . -Primary tuberculosis of intestine . PRIMARY TUBERCULOSIS OF INTESTINE Swallowing of human or bovine tubercle bacilli with dust or infected milk. Pathology: Primary complex: 1-The initial lesion usually appears in the terminal ileum and consists of a group of tubercles in the region of the Payer’s patches (where macrophages carry the bacilli to this area). The covering mucosa may undergo minimal ulceration. 2-Tuberculous Lymphangitis. 3-Tuberculous Lymphadenitis (tabes mesenterica): The mesenteric lymph nodes are enlarged and show caseating tubercles. They may become matted (cold abscess).. Fate: 1-Localization. 2-Spread: a)Direct and lymphatic: This leads to tuberculous peritonitis b)Hematogenous spread leading to isolated organ or miliary tuberculosis PRIMARY TUBERCULOSIS OF TONSILS Swallowing of human or bovine tubercle bacilli. Pathology: Primary complex 1-The initial lesion is a small focus composed of tubercles.The covering mucosa of tonsil may ulcerate. 2-Tuberculous lymphangitis. 3-Tuberculous lymphadenitis of the cervical lymph nodes which become enlarged & show caseating tubercles. Matting may occur & a cold abscess may develop. The overlying skin may develop tuberculous sinuses. Fate: 1-Localization. 2-Spread PRIMARY TUBERCULOSIS OF SKIN Tubercle bacilli inoculated through a skin abrasion lead to a primary complex, which may localize or spread. TUBERCULOUS LYMPHADENITIS Tuberclous lymphadenitis occurs as a part of primary complex. The hilar lymph nodes are affected in case of primary pulmonary T.B, the cervical nodes in case of primary T.B of tonsils & the mesenteric nodes in case of primary intestinal T.B. Gross Features: The affected nodes are enlarged , first discrete, then may become matted and soft due to marked caseation (Cold Abscess). Microscopy: Tubercles… Fate & Complications: 1-Localization 2-Spread: a)Direct from cervical lymph nodes cervical skin sinus formation, from hilar nodes tuberculous pericarditis and from mesenteric nodes tuberculous peritonitis. b)Lymphatic spread to other lymph nodes. c)Blood spread causing isolated organ or miliary tuberculosis. d)Bronchial spread due to bronchial erosion from hilar nodes in case of pulmonary tuberculosis. 3-Reactivation (if immunity is lowered). Thanks Dr. Mohammed Abdellah General Pathology-2 sinaiuniversity.net •Chronic Inflammation •Tuberculosis By the end of lecture you should be able to understand: . -secondary Tb in different organs . SECONDARY TB SECONDARY (REINFECTION) TUBERCULOSIS (ADULTHOOD TYPE) -This is tuberculosis in persons that have had a previous primary exposure to tuberculosis. -It may be due to one of two possibilities: 1-New exogenous infection (inhalation, ingestion). 2-Reactivation of dormant living tubercle bacilli within a healed primary tuberculous lesion. I) SECONDARY PULMONARY TUBERCULOSIS Aetiology: 1-Inhalation of human tubercle bacilli (exogenous route) 2-Reactivation of healed or capsulated Ghon’s focus Course of infection: Disease severity depends on dose and virulence of bacteria, degree of immunity & hypersensitivity. The lesions may be a) Minimal and undergo fibrosis (regressive lesion) b) Progressive disease of two main forms. CHRONIC FIBROCASEOUS TUBERCULOSISB (CAVITARY TUBERCULOSIS) Gross Features: cavity (or more than one cavity) , mostly in one or both lung apices 1-Apical Lesion: In most cases, the lesions start in apex of one or both lungs (more in right lung which has a wider bronchus). 2-Basal Lesions (acinar lesions): Small caseous foci occurring in the base of lung . 3-Insignificant Lesions within the hilar lymph nodes. Microscopic Features: 1-Large areas of caseous necrosis, surrounded by: 2- Fibrosis & scattered tubercles 3-Adjacent vessels show endarteritis. Clinical Features (signs & symptoms): Due to tissue destruction & accompanying toxemia: 1-Weight loss, anemia, pallor, fever and sweating. 2-Chest pain & dyspnea 3-Hemoptysis 4-Pleural effusion Complications: 1-Hemoptysis, due to erosion of vessels. 2-Rupture of the cavity into the pleural sac results in pneumothorax. 3-Spread of infection (relatively less common than primary T.B): a)Direct leading to: i) tuberculous pleurisy or tuberculous empyema ii) tuberculous pericarditis and mediastinitis. b)Blood spread leading to isolated organ tuberculosis or miliary tuberculosis. c)Bronchial spread: i) Coughing of infected sputum may lead to tuberculosis of larynx, tonsils, tongue. ii) Swallowing of this sputum causes secondary intestinal tuberculosis. d)Lymphatic spread : Uncommon. 4-Right-sided heart failure 5-Secondary amyloidosis II) SECONDARY TUBERCULOSIS OF INTESTIN Ingestion of infected sputum in patients with chronic fibrocaseous pulmonary tuberculosis. Pathological Features: 1-The lesions develop mainly in the terminal ileum and adjacent caecum. Tuberculous ulcers which are characterize by: Multiple, edges are ragged and undermined, ulcer floor is yellowish, caseous. In the terminal ileum they are transversely arranged (girdle ulcers). 2-The mesenteric lymph nodes show minimal lesions. II) SECONDARY TUBERCULOSIS OF INTESTIN Complications: 1-Intestinal Hemorrhage, Intestinal fistulae. 3-Perforation of the ulcers leads to septic peritonitis. 4-Spread of infection: a)Direct and Lymphatic  tuberculous peritonitis. b)Blood spread  isolated organ or miliary tuberculosis. 5-Fibrosis  intestinal obstruction. 6-Secondary amyloidosis ORGAN TUBERCULOSIS DUE TO SPREAD OF INFECTION: Pulmonary , intestinal, tonsillar & skin tuberculosis can occur as primary or secondary disease . However spread in either primary or secondary tuberculosis can lead to affection of any organ. TUBERCULOSIS OF BONE (Tuberculous Osteomyelitis) Source of infection: Usually blood-borne Pathological features: 1- Caseous necrosis & bone destruction (tuberculous caries) 2- Inadequate callus formation (poor healing). Sites: 1- Ends of long bones: Tuberculous lesions start in the metaphysis then spread leading to subperiosteal cold abscess .. 2- Flat bones as ribs & pelvis. This is rare. A subperiosteal cold abscess develops. 3-Short bones of hands or feet (tuberculous dactylitis) 4-Vertebrae (Pott’s disease). TUBERCULOSIS OF VERTEBRAE (POTT'S DISEASE) Aetiology: Blood borne infection. Pathological Features The lower thoracic &upper lumbar vertebrae are the most common sites followed by cervical vertebrae. Two or more adjacent vertebrae as well as the intervening discs are destroyed. Thanks Dr. Mohammed Abdellah General Pathology-2 sinaiuniversity.net •Chronic Inflammation •Bilharziasis &SYPHILIS By the end of lecture you should be able to understand: . -BILHARZIASIS AND SYPHILISdefinition; aetiology and types. . SYPHILIS What is Syphilis ? Chronic specific infective granulomatous disease by Treponema pallidum.  Methods of infection • Direct (STD) sexually transmitted disease • Transplacental • Blood transfusion (accidentally) Tissue Reaction    Thick walled blood vessels Fibrosis Perivascular chronic inflamm. cells infiltrate esp. plasma cells. Syphilis is a chronic specific, infective, venereal, granulomatous disease caused by Treponema pallidum. -Primary Syphilis; chancre -Secondary Syphilis: Skin rash, mucous patches, condyloma lata, generalized lymphadenopathy. -Tertiary Syphilis: Syphilitc gumma and diffuse lesions of tertiary syphilis. Bilharziasis Endemic disease in Egypt caused by schistosoma haematobium and mansoni. Pathogenesis: 1. Cercariae: maculopapular rash at site of penetration 2. Worms:  Living: nothing  Dead: allergic necrotizing reaction in the vessel walls. 3. Ova:  local granulomatous reaction resulting in fibrosis. Caused by:  components of the shell  Antigenic substances from miracidia.  T- lymphocytes Bilharziasis of the urinary bladder  Caused by schistosoma hematobium Effect of Ova deposition:  Deposited in the submucosa leading to granulomatous reaction.  Pierce the mucosa at end of micturation leading to terminal hematuria.  Site:  Dome  Ureteric orifices  Bladder neck Bilharziasis of the urinary bladder Gross: 1. Granular mucosa. 2. Sandy patches: pale irregular sanded areas due to heavy deposition of ova 3. Bilharzial polypi sessile or pedunculated, simple or branched May slough causing bilharizial ulcer more common in intestinal Bilharziasis 4. Bilharzial ulcers: due to piercing by ova or stretching of mucosa over sandy patches 5. Cystitis cystica: They appear as mucosal vesicles few mm in diameter. 6. Fibrosis: in bladder neck or ureter Bilharziasis of the urinary bladder -Hyperplastic transitional epithelium with dipping to form Brunn's nests. -Cystic degeneration of the central cells form Cystitis cystica. -Others are lined by columnar epithelium to form Cystitis glandularis. Bilharziasis of the urinary bladder Microscopic: A. Mucosa: 1- Hyperplasia. 2- Brunn's nests: epithelial dipping to form subepithelial solid nests 3- Cystitis cystica: Hydropic degeneration of brunn's nests 4- Cystitis glandularis: d.t metaplasia in cystitis cystica Precancerous → Adenocarcinoma 5- Squamous metaplasia precancerous→ Squamous cell carcinoma 6- Dysplasia : Carcinoma in situ, invasive transitional cell carcinoma. B. Submucosa: bilharzial reaction : formed of collection of Eosinophils, Lymphocytes ,Plasma cells ,Macrophages , Fibroblasts +/-Giant cells. Bilharziasis of the large intestine caused by schistosoma mansoni Pathological Lesions: Site: mostly in rectum. Gross: Early: hyperemia, edema & hemorrhage. Later: Bilharzial polypi. Sandy patches Bilharzial ulcers. Fibrosis Microscopic : Submucosa: bilharzial reaction : Granuloma: formed of collection of Eosinophils, Lymphocytes ,Plasma cells ,Macrophages , Fibroblasts +/-Giant cells. Thanks Dr. Mohammed Abdellah General Pathology-2 sinaiuniversity.net •Chronic Inflammation •Granulomas By the end of lecture you should be able to understand: . -Other granulomas: as sarcoidosis. . Granulomas Definition: This is a particular form of chronic inflammation characterized by nodular collections of modified macrophages, as well as lymphocytes, plasma cells and sometimes neutrophils. The modified macrophages often acquire pink cytoplasm and are called epithelioid cells. These epithelioid cells commonly coalesce forming multinucleate giant cells. Some granulomas may exhibit central necrosis. Sarcoidosis Definition: Granulomatous disease of unknown cause Age: 20-40y – no sex predilection Sarcoidosis Microscopic: Small non-caseating granulomas… May show: *Schaumann bodies: rounded calcified laminated bodies *Asteroid bodies: star –shaped inclusions. Sarcoidosis Diagnosis: Clinical and radiographic features. Lymph node or lung biopsy: non-caseating granulomas Laboratory findings: calcuim in blood calcuim in urine ACE level. (Angiotensin converting enzyme) FUNGAL INFECTIONS (Mycotic Infections) Fungi are plant-like organisms, morphologically classified into moulds, yeasts, yeast-like & dimorphic fungi. Fungi are best demonstrated by PAS stain . Tissue reaction is very variable; there may be no reaction at all, there may be suppurative, tuberculoid or nonspecific reactions. Fungal diseases may be clinically classified into: 1-Superficial (Skin) Fungal Infections (dermatophytes). Examples: 1)Tinea 2)Mycetoma. 3)Some cases of Candidiasis 2-Deep Fungal Infections: These fungi can invade widely and can cause systemic disease. Examples of deep fungal infections include some cases of candidiasis , histoplasmaosis , MYCETOMA PEDIS (MADURA FOOT, NOCARDIASIS) Definition & aetiology: Fugal mycetoma is chronic suppurative granuloma caused by a group of mycetoma fungi (also called Nocardia fungi). It live in soil & can be inoculated in the skin of the bare-footed individuals, through skin abrasions. The disease is famous in India (in Madura district) and hence the name “Madura Foot’. It also occurs in Egypt. MYCETOMA PEDIS (MADURA FOOT, NOCARDIASIS) Gross: Foot is swollen, indurated and there is widespread destruction of tissues resulting in multiple suppurative foci that open onto the skin by multiple sinuses discharging pus and fungal colonies which often appear as black granules (but may be red, white, yellow). Bone destruction is not accompanied by adequate repair. MYCETOMA PEDIS (MADURA FOOT, NOCARDIASIS) Gross: MYCETOMA PEDIS (MADURA FOOT, NOCARDIASIS) Microscopic: 1-Fungal colonies: Grow as hyphae and largely resemble the bacterial colonies of actinomycosis. 2-Inflammatory cells: Neutrophils, pus cells, macrophages, lymphocytes and plasma cells. 3-Granulation tissue and fibrosis. No spread. ) Microscopic: Section in skin shows: Many abscesses Each abscess consists of fungal colonies surrounded by neutrophils and macrophages The fungal colonies consist of dark blue hyphae attached to pink stained club shaped peripheral structures. DIAGNOSIS: Mycetoma (Madura foot) CANDIDIASIS (MONILIASIS ) =Definition & aetiology: This is infections with the fungus "Candida albicans" . This fungus is a normal commensal of oral cavity, GIT, vagina and skin. It is a yeast-like fungus. It becomes pathogenic in the following conditions: 1-Prolonged broad spectrum antibiotic therapy. 2-Low immunity as in cases of a) Immunosuppressive therapy. b)Others states of immunocompromization as diabetes and AIDS CANDIDIASIS (MONILIASIS ) There are several patterns: 1-Superficial Candidiasis: Most common .Usually due to prolonged antibiotic use . Manifestations: a)Thrush: White oral mucosal patches composed of fungal colonies, necrotic debris & inflammatory cells b)Vaginal lesions: similar to oral thrush. c)Paronychia (lesions under the nails) and macerations 2-GIT Candidiasis: Most common in oesophagus; particularly in AIDS. 3-Invasive (disseminated) Candidiasis: It is due to blood spread. It is often fatal. The manifestations include: a)Microabscesses affecting lungs, liver, kidneys, brain, myocardium… etc. b)Endocarditis. c) Meningitis. d)Endophthalmitis =A 4o year old male came with enlarged hilar lymph nodes. Biopsy showed a non caseating granuloma with asteroid and schaumann bodies the most likely diagnosis a) Late tuberculosis b) Sarcoidosis c) Tuberculoid Leprosy d) Syphilis e) Talc powder granuloma This lesion represents an example of: a)Acute suppurative Inflammation b)Acute non suppurative inflammation c) Chronic specific inflammation d) Chronic non specific inflammation - Ova are mostly identified within : a) mucosa b) submucosa c) muscle layer - Granuloma around ova is rich in………………… d) serosa Thanks Dr. Mohammed Abdellah General Pathology-2 sinaiuniversit y.net •DISORDERS OF IMMUNE REACTION By the end of lecture you should be able to understand: . -DISORDERS OF IMMUNE REACTION. Definitions Antigen: a foreign protein that can evoke an immune response mediated by B (plasma cells) or T lymphocytes. When a tissue is antigenic = auto-antigen and leads to an autoimmune disease. Hapten: (incomplete antigen) a non-protein foreign substance (e.g. drug) that can evoke an immune response by combining with one of the body proteins (this combination acts as an antigen) . Antibodies: proteins secreted by plasma cells called immunoglobulins e.g. IgA, IgG, IgM ,IgE & IgD. -Secretions of T lymphocytes are called lymphokines. IMMUNITY: body defense mechanisms aiming at disposal of living irritants. Nonspecific immunity : including phagocytosis (macrophages and neutrophils), natural killer cells (nonspecific cytotoxic cells), opsonins (antibodies that help phagocytosis) and lysozyme (in saliva and other body secretions). Specific (acquired) immunity 1-Humoral immunity: Serum antibodies (immunoglobulins IgG , IgM, IgA, IgD & IgE) are secreted by plasma cells. Plasma cells develop from stimulated B lymphocytes. Examples of useful antibodies include bacteriolysins, agglutinins & others . 2-Cell- mediated immunity: Lymphokines (cellular antibodies) are secreted by stimulated T lymphocytes. These lymphokines have several functions e.g. specific activation of macrophages to engulf an organism. IMMUNOPATHOLOGY I- Hypersensitivity or allergy II- Autoimmunity III- Immunodeficiency IMMUNOPATHOLOGY I- Hypersensitivity or allergy -This is Exaggerated immune response. -It represents a harmful reaction against living irritants (bacteria, virus. etc) or non living irritants (such as food proteins, dust, pollens, drugs…etc) leading to tissue destruction. -There are 4 main types -Type I, II & III are mediated by immunoglobulins and develop rapidly (immediate hypersensitivity), -Type IV is mediated by sensitized T cells (cellmediated) and the reaction develops in a longer time, up to several days (delayed hypersensitivity). TYPE I HYPERSENSITIVITY (Immediate Hypersensitivity) Mechanism: Introduction antigen for the first time stimulates IgE formation, which becomes fixed to surface of mast cells. Re-exposure to same antigen produces reaction with IgE fixed on mast cell leading to liberation of histamine and other chemical mediators leading to: #Tissue necrosis. #Vasodilatation (which in systemic reactions leads to hypotension) #Allergic inflammation characterized by excess fluid exudate (oedema) and eosinophils #Bronchospasm #Increased mucus secretion by mucous glands TYPE I HYPERSENSITIVITY Examples: 1-Anaphylactic Shock: May follow rupture of hydatid cyst, injection of penicillin or antitoxic sera.... Manifestations develop within minutes and include: #Urticaria #Bronchospasm #Generalized oedema #Hypotension, shock and sometimes death. 2-Atopy (Atopic Diseases): Atopy means strange. This type of hypersensitivity has genetic predisposition. It differs from anaphylaxis in that IgE production is localized within a certain tissue or organ in contrast to the systemic production of IgE in case of anaphylaxis. Examples : #bronchial asthma, allergic rhinitis & allergic conjunctivitis. Thanks Dr. Mohammed Abdellah General Pathology-2 sinaiuniversity.net •DISORDERS OF IMMUNE REACTION (2) By the end of lecture you should be able to understand: . -DISORDERS OF IMMUNE REACTION. TYPE II HYPERSENSITIVITY (Cytotoxic Hypersensitivity):. Mechanism: The antigen is a component of a cell membrane. The antibodies are of the IgG and IgM classes. The reaction requires complement activation. The target cells undergo lysis. Examples: Incompatible blood transfusion. Rh incompatibility (erythroblastosis foetalis). Some types of rejection of transplanted organs. Autoimmune hemolytic anaemias. TYPE III HYPERSENSITIVITY (Immune Complex Reaction): Mechanism: The antibodies (IgG and IgM) combine with the antigen producing immune complex. The immune complexes are trapped within the vascular basement membranes. Complement activation leads to lysis and destruction of the basement membrane. Examples: -Acute proliferative post-streptococcal glomerulonephritis. -Arthus reaction: Repeated subcutaneous injection of antigens(e.g. insulin) producing local vasculitis, necrosis and oedema. Serum sickness: - The antigen is serum- injected for the first time in large amounts. - Part of the antigen will, still be present by the time the antibodies are formed (about 10 days after injection of the antigen). - Immune complexes are formed producing systemic manifestations including: Urticaria, fever, joint pains, generalized lymph node enlargement and glomerulonephritis. Some autoimmune diseases as SLE. TYPE IV HYPERSENSITIVITY (Delayed Hypersensitivity) Mechanism: The antigen is a part of a microorganism: bacteria as tuberculosis ,virus , fungus or parasite The antigen stimulates T lymphocytes Sensitized T lymphocytes lymphokines of several types, of which some cell mediated immunity (e.g. by attracting macrophages & inhibiting their migration from the area) & other lymphokines cause necrosis. TYPE IV HYPERSENSITIVITY (Delayed Hypersensitivity) Examples: Caseous necrosis in tuberculosis and tuberculin skin test. Cell-mediated graft rejection. Contact dermatitis. Some autoimmune diseases. Allergic contact dermatitis Autoimmunity -Loss of tolerance , where some of the normal tissue components are considered antigenic (autoantigens) autoantibodies tissue destruction & development of disease. Immunodeficency -Deficient response (immunodeficiency) involving B or T lymphocytes, macrophages , complement. -Congenital: as: X-linked agammaglobulinemia of Bruton, congenital thymic hypoplasia (DiGeorge syndrome), isolated IgA deficiency . -Acquired: AIDS, drug-induced immunodeficiency (e.g. immuran) & diabetes mellitus. II)AUTOIMMUNE DISEASES DEFINITION: These are hypersensitivity diseases resulting from destruction of one or more of the body tissues or organs by autoantibodies. due to a defect in the immune mechanism of self recognition; thus one of the body proteins is erroneously considered as "non-self" . MECHANISM: Altered tissue antigenicity may be drug-induced, or produced by actions of microorganisms. Cross reactions: This may occur between some human structures and certain microbes Mutations of immunocompetent cells. Release of isolated proteins e.g. thyroglobulin. Imbalance of suppressor-helper T cell function. Genetic factors play a role in some autoimmune diseases. Autoimmunity EXAMPLES : -Endocrine Diseases as Hashimoto's thyroiditis, 1ry myxoedema & 1ry Addison’s disease. -Some types of male infertility. -Autoimmune hemolytic anemia. -Gastrointestinal diseases as ulcerative colitis & Crohn’s disease. -Liver diseases as autoimmune hepatitis, 1ry biliary cirrhosis & primary sclerosing cholangitis. COLLAGEN DISEASES (Connective Tissue Diseases) Definition: A group of autoimmune diseases characterized by injury of collagen within & around vessels. Pathology: The fragmented collagen fibers resemble a mass of fibrin= fibrinoid necrosis or fibrinoid degeneration, accompanied by inflammation associated with increase of mucopolysaccharides within ground substance. Finally Fibrosis =the hallmark of disease state. COLLAGEN DISEASES (Connective Tissue Diseases) Collagen diseases include: -Rheumatic fever . -Rheumatoid arthritis. -Polyarteritis nodosa. -Systemic lupus erythematosus (SLE). -Scleroderma: characterized by systemic fibrosis affecting skin, GIT, lung, myocardium & kidneys. -Dermatomyositis: characterized by systemic muscle weakness (proximal > distal), eventually progressing to motor disability. In 50% of cases the disease is associated with skin rash . Thanks Dr. Mohammed Abdellah General Pathology-2 sinaiuniversity.net •Circulatory disturbances By the end of lecture you should be able to understand: . - Thrombosis; definition; mechanism, types, sites and classification. - Embolism; definition; and types. Ischaemia;infarction definition, types and effects. - Gangrene, definition; causes and types. Thrombosis A thrombus is a compact mass formed of blood elements, inside blood vessel or heart during life. Causes : 1. Damage to the vascular endothelium : (Endothelial injury). 2. Slowing of blood stream (Stasis). 3. Disorders of blood stream : (Turbulence). 4. Changes in blood composition : (Hypercoagulability of blood). Classification and Types of Thrombi: I. According to the colour: # Pale: Formed mainly of platelets and fibrin. It is small, greyish white, firm and adherent to the intima e.g. cardiac vegetations. # Red: Formed mainly of red cells and fibrin. It is dark red, soft, and loosely attached to the vessel wall. It is very rare. # Mixed: Most thrombi has pale and red components. II. According to whether occlusive or not: # Mural # Occlusive # Propagating: If the formed thrombus occludes a vein completely, → proximal to occlusion the blood will be stagnant and it clots. III. Presence or absence of bacteria: # Infected thrombus (septic) # Non infected (aseptic) - Fate and complications of thrombosis : A- Septic thrombus : may be fragmented by the proteolytic enzymes into septic emboli pyaemic abscesses . B- Aseptic thrombus : 1- Lysis, fragmentation & embolization. 2- Fibrosis, or fibrosis & canalization. 3- Dystrophic clacification. 4-Propagation. 5- Arterial occlusion (ischaemia) or venous occlusion (congestion) 6- Incorporation of arterial thrombi into atheroma. Embolism Embolus is an insoluble material circulating in the blood. Embolism is the impaction of an embolus in a blood vessel. Types of emboli : 1. Emboli of thrombotic origin (thrombo -embolism): * Course and site of impaction of emboli: From systemic vein or right side of heart, the emboli pass to the pulmonary artery and impact in the lung causing Pulmonary embolism. From systemic artery or left side of the heart, the emboli impact in any organ (spleen, brain, kidney) causing Systemic embolism. From portal veins, the emboli impact in the liver causing Portal embolism 2. Air embolim : (Gas embolism): due to : a. Injury of large neck veins . b. Faulty techniques of atrificial pneumothorax or blood transfusion under pressure. c. Caisson's disease in divers (decompression sickness): In deep dives compressed gases are inhaled. The high pressure increases the amount of gases dissolved in the blood. If decompression is done rapidly gases specially nitrogen form emboli in the blood vessels.; Small amount of air is harmless, but 50-100 cc. interfere with cardiac contraction and cause acute heart failure. 3. Fat embolism : due to : 1- Fractures of long bones. 2- Burns or inflammation of fatty areas. The fat globules enter through the ruptured veins and produce Pulmonary or systemic embolism. 4. Amniotic fluid embolism : Rare condition in which strong uterine contractions cause a tear in the foetal membranes and the amniotic fluid is pushed in an opened vein. 5.Tumour embolism. Iscaemia Decrease blood supply to tissue or organ due to occlusion of its arterial supply. Types : 1- Sudden or Acute (Complete) Ischaemia: Causes : Thrombosis or embolism. Ligature of an artery. Torsion or twisting of movable vessels in intestine or ovary. Arterial spasm as in ergot poisoning. Effects: (a) Sudden occlusion of end arteries or arteries with inefficientcollaterals causes infarction or gangrene. (b) Sudden occlusion of arteries with efficient collaterals may not Cause tissue damage. 2- Gradual or Chronic (Incomplete) Ischaemia: Causes : Atherosclerosis. Endarteritis obliterans as in syphilis. Pressure from outside by enlarged lymph nodes, tumour mass. Effects: The gradual occlusion gives chance for the collaterals to open up so: (a) With inefficient collaterals, cellular degeneration, atrophy and replacement fibrosis occur e.g. atherosclerosis of the coronary branches causes myocardial fibrosis. (b) With efficient collaterals no tissue damage occurs. Infarction An area of coagulative necrosis caused by sudden ischaemia. It is liquifactive in the brain. Aetiology: Mainly thrombosis or embolism causing arterial occlusion. Rarely surgical ligature, arterial spasm or twisting of vessels. General features of infarction : 1. Gross : Size : depends upon size of occluded vessel. Site : always subcapsular, and peripheral Shape : pyramidal or triangular in shape. Surface: raised when recent & depressed when healed Surrounded : by a red zone of hyperaemia. Types : Pale (white) infart Red (Haemorrhagic) infarct 2-Micro: Early : Cells show post necrotic changes after 12h. Next : loss of cellular details & preservation of general architecture (ghosts of original structure) after 36h. 3- Fate : Fibrosis with dystrophic calcification Gangrene Definition: Gangrene is massive tissue necrosis followed by putrefaction. Causes: (1) Necrosis: Is caused by Sudden ischaemia or bacterial toxins. (2) Putrefaction: Is caused by saprophytic bacteria which breaks down the protein of the necrotic tissue liberating hydrogen Sulphide →that gives the tissue a foul odour. →Hydrogen sulphide unites with the iron of haemoglobin forming iron sulphide→ that stains the gangrenous tissue black. Types of Gangrene: (l) Dry gangrene. (2) Moist gangrene. (3) Infective gangrene. (4) Gas gangrene. I. DRY GANGRENE: Dry gangrene of a limb results when the main arterial supply of a limb is Cut off and the collateral circulation is poor as in: (1) Thrombosis (2) Embolus. (3) Thromboangitis obliterans. (4) Ergot poisoning and Raynaud's disease which cause spastic occlusion. (5) Surgical ligature. N.B.:- As the arterial supply is only occluded venous and lymphatic drainage and surface evaporation occur, so the gangrene will be of the dry type. The commonest example of dry gangrene is senile gangrene of the lower limb. Senile Gangrene: Usually affects old males. Predisposing factors: (1) Atherosclerosis common in old age, predisposes to arterial thrombosis and poor collateral circulation. (2) Weak heart action and low blood pressure causes vascular stasis. (3) Low body resistance due to nutritional disturbances, nephritis, anaemia ... etc. II. MOIST GANGRENE Caused by: Sudden arterial and venous occlusion. Site: It Occurs mainly in internal organs as the intestine from which no evaporation of fluids can Occur. The presence of tissue fluids aid rapid putrefaction. Gangrene spreads rapidly. The line of demarcation is Poor and the line of separation is absent. The toxaemia is sever. Comparison between Dry and Moist Gangrene: Dry Gangrene Moist Gangrene (1) Gradual arterial occlusion Sudden arterial and venous occlusion (2) Exposed parts (limbs) Internal organs (intestine). (3) slow putrefaction Rapid putrefaction (4) Tissue mummification Tissue oedema (5) Slow spread Rapid spread. (6) Marked line of demarcation Poor line of demarcation (7) Self separation may occur Self-separation absent. 8) Severe toxaemia More severe toxaemia Thanks NUTRITIONAL DISORDERS UNDERNUTRITION: Types of undernutrition: 1-Total (starvation) 2-Selective as: • vitamin deficiency. • protein deficiency (protein calorie undernutrition). VITAMIN DEFICIENCIES VITAMIN D DEFICIENCY I) RICKETS DEFINITION: Rickets is a disease of infants characterized by defective bone mineralization (calcium & phosphate) resulting in bone softening and abnormalities of bone growth. AETIOLOGY: 1-Vitamin D deficiency ;commonly due to lack of exposure to sun. 2-Chronic renal disease (renal rickets). 3-Deficiency of calcium & phosphorus 4-Hereditary (X-linked dominant) vitamin D resistant rickets. Rare. PATHOLOGY: 1-Skeletal Lesions: • Skull: Delayed closure of fontanelles, delayed eruption of teeth, craniotabes, bossing of frontal and parietal bones. • Vertebrae: Dorsal kyphosis, lumbar lordosis, scoliosis. • Chest: Rosary Chest, Harrison’s sulcus, Pigeon Chest. • Long bones: Bowing of weight-bearing bones and pathological fractures, rachitic metaphysis. • Pelvis: Narrowed contracted trifoil pelvis. COMPLICATIONS OF RICKETS: 1-Bone deformities. 2-Pathological fracture. 3-Infections due to low immunity. 4-Future labour problems in female patients (narrow pelvis). VITAMIN A DEFICIENCY Vitamin A deficiency results in: 1-Skin & mucous membranes: a)Hyperkeratosis of skin (appears dry & scaly). b)Squamous metaplasia. 2-Eye: a)Night blindness. b)Xerophthalmia (dry eyes due to keratinization of lacrimal glands). c) Keratomalacia (softening of the cornea). 3-Retarded growth in children This woman had a dry oral mucosa, a beefy red tongue, an erythematous throat without exudates, angular stomatitis bilaterally. The skin displayed a blanching maculopapular scaling rash on the extremities with some punctate erythematous lesions MICROSCOPIC DESCRIPTION: There is focal, patchy parakeratosis with follicular plugging, a focally thickened granular cell layer, and a hyperplastic epidermis. There was a minimal perivascular dermal chronic infiltrate. VITAMIN K DEFICIENCY Aetiology: 1-Prolonged use of broad spectrum antibiotics. 2-Obstructive jaundice. 3-Temporarry deficiency in newly born infants. Pathological effects: Vitamin K deficiency leads to defective formation of prothrombin which leads to: 1-Hemorrhagic tendency e.g. interstitial hemorrhage due to minimal trauma. 2-Prolonged bleeding e.g. prolonged post operative hemorrhage VITAMIN C DEFICIENCY( SCURVY). Vitamin C deficiency is rare. It leads to defective formation of ground substance and collagen resulting in: 1-Bone : Bone weakening, fractures and defective bone healing. 2-Teeth: Defective formation of teeth in children associated with teeth loosening 3-Wound healing : Defective wound healing 4-Hemorrhage: hemorrhages are common which may be mild ( petechial) , mostly in the gums , but may be severe hemorrhage from node, GIT or subcutaneous tissue. Repeated hemorrhages lead to anemia.. VITAMIN B DEFICIENCY I)PELLAGRA Definition : Pellagra (which means rough skin) is a disease caused mainly by nicotinic acid deficiency. Aetiology: Nicotinic acid deficiency mainly occurs in people who depend on maize as the main source of starch, since maize is deficient in tryptophane from which nicotinic acid is synthesized. Pathology: 3Ds 1-Skin: Dermatitis. 2-GIT lesions: Painful inflamed tongue and Diarrhea due to colonic inflammation. 3-CNS: a)Demyelination of lateral and posterior columns (subacute combined degeneration). b)Degeneration of nerve cell leads to dementia. II) BERI BERI Defintion & Aetiology: A disease caused by deficiency of vitamin B1. Pathology: 1-Dry beri-beri: Peripheral neuritis affect the cranial and spinal sensory and motor nerves due to degeneration of myelin and axis cylinders. 2-Wet beri-beri:. The heart, mainly the right side is affected and shows fatty change and dilatation. Congestive heart failure may occur leading to generalized oedema (& hence the name wet beriberi) III)VITAMIN B12 AND/OR FOLIC ACID DEFICIENCY Causing macrocytic anemia.