General Pathology-2 Lecture Notes 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. -com...

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 Secondary Tuberculosis Reinfection tyype •This is tuberculous infection for the first time. •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