Granulomatous Inflammation PDF

Granulomatous inflammation By Dr. Shaimaa Dawa  learning Objectives Define granuloma List causes and types of granuloma Define tuberculosis List predisposing factors of TB Enumerate routes of infection of TB Illustrate pathogenesis of TB Identify morph...

Granulomatous inflammation By Dr. Shaimaa Dawa  learning Objectives Define granuloma List causes and types of granuloma Define tuberculosis List predisposing factors of TB Enumerate routes of infection of TB Illustrate pathogenesis of TB Identify morphology of TB Identify pathological features of pulmonary TB List fate of pulmonary TB list pathological features of intestinal TB  Granulomatous Inflammation A granuloma : Is a focus of chronic specific inflammation consisting of focal accumulations of activated macrophages (epithelioid cells) surrounded by collar of lymphocytes and occasionally plasma cells, with a rim of fibroblasts, and granulation tissue.  Types of granulomas 1- Infective granulomas are caused by microbes that are capable of inducing a cell - mediated immune response. a. Bacterial b. Parasitic c. Fungal 2- Foreign body granulomas: Silicosis ,Suture, breast prosthesis, vascular graft 3- Granuloma of unknown cause: e.g. sarcoidosis and Crohn's disease  Bacterial Parasitic Tuberculosis (Mycobacterium – Schistosomiasis (Schistosoma mansoni, tuberculosis) S. haemotobium, S. japonicum) Leprosy (Mycobacterium leprae) Fungal Syphilitic gumma (Treponema pallidum) Histoplasma capsulatum Cat-scratch disease Blastomycosis (Bartonella henselae) Cryptococcus neoformans Coccidioides immitis Inorganic Metals or Dusts Foreign Body :Suture, breast prosthesis, Silicosis vascular graft Berylliosis Unknown Sarcoidosis Crohn's disease  Pathogenesis of granuloma: Two types of granulomas, differ in their pathogenesis I-Foreign body granulomas: II-Immune granulomas  Pathogenesis of granuloma I- Foreign body granulomas: Caused by inert foreign bodies as sutures, silica Macrophages engulf the foreign material and present some of it to appropriate T-lymphocytes resulting in their activation to produce cytokines and IFN-γ These mediators activate macrophages and transform them into epithelioid cells and multinucleate giant cells.  2-Immune granulomas by agent's poorly degradable → delayed type hypersensitivity (DTH, type IV): Proliferation and Differentiation of CD4+ T Cells. 1] Macrophages engulf foreign protein antigen, process it, and present peptides to AG-specific Naive CD4+ T cells, and produce IL-12, which induces differentiation of CD4+ T cells to the TH1 subset 2] Some of the differentiated activated TH1 cells enter the circulation and may remain in the memory pool of T cells for long periods, sometimes years.  Responses of Differentiated Effector T Cells. Repeated exposure to an antigen → activated TH1 secrete cytokines: The released cytokines (lymphokines) have the following actions: 1. Attract leucocytes to the area of inflammation. 2. Inhibit macrophages migration. 3. Stimulate lymphocytes proliferation. 4. Trigger inflammation and Causes tissue necrosis  TUBERCULOSIS chronic infective granuloma caused by Mycobacterium Tuberculosis. In tuberculosis the granuloma is referred to as a TUBERCLE. Aetiology: Mycobacterium tuberculosis (human & bovine types). Mycobacterium tuberculosis is – Non-motile, – Not proteolytic – Non toxic – Acid and alcohol fast, – very resistant organism, but easily killed by sunlight.  Route of infection Inhalation: is the commonest method. The inhaled bacilli infect the tonsils or lungs. Ingestion: of raw milk contaminated with bovine (mycobacterium bovis) or human bacilli, infect the tonsils or the intestine. Skin inoculation: by handling infected materials as infected meat. This method is not common.  Predisposing factors : Poverty, Malnourishment, Poor living conditions, Lack of medical care or any debilitating or immunosuppressive conditions.  The pathological changes depend upon the chemical structure a) A lipid fraction: the capsule. Attract histiocytes Responsible for resistance of organism. Type IV hypersensitivity reaction b) A protein fraction: the body of the organism called tuberculoprotein. – The pathogenicity of the organism depends mainly upon the antigenic nature of the tuberculoprotein. – Attract T lymphocytes. – Responsible for the allergic reaction (caseation necrosis) c) A small polysaccharide fraction (CHO). Attract neutrophils  Pathogenesis Mycobacterium tuberculosis Non motile NOT produce any exotoxin, endotoxin or any histolytic enzyme. Pathogenesis depends on ------- its ability to escape killing by macrophages and induce delayed type hypersensitivity through the reaction with its cell wall content  Tubercle formation: Polysaccharide fraction -------- attracts the neutrophil within few hours - ----- phagocytose the bacteria but are unable to destroy them as the bacteria are protected by the lipid capsule and the neutrophils do not contain the enzyme lipase. The lipid fraction -------- attracts the macrophages (tissue histiocytes & blood monocytes) after the first day. – Mac.------- collect and phagocytose the free bacilli and those inside the neutrophils and are now called EPITHELIOID CELLS. – The bacilli are partially digested with the release of tuberculoprotein. The tuberculoprotein stimulates a cell mediated immune response (delayed hypersensitivity) within a period of about 10 days. Sensitized T- lymphocytes appear and surround the epithelioid cells.  Tubercle formation The sensitized lymphocytes release various lymphokines which have the following actions: – Macrophage Chemotactic factor – Macrophage activating factor – Migration inhibition factor (MIF) – Mitogenic factor – Skin reactive factor – Cytotoxic factor In this manner more tubercles are formed in the infected area.  Macroscopic picture The tubercle is of microscopic size. Tubercles fuse with one another to form small rounded grossly visible gray follicles 1-2 millimeters in diameter. When caseation occurs the lesion appears pale yellow and cheesy in consistency.  Microscopically: The tubercle consists of collection of many epithelioid cells, langhan's giant cells and lymphocytes. 1 Epithelioid cells 2 Langhan's giant cells 3 Lymphocytes  epithelioid cell granuloma epithelioid cell langhans-type giant cell There are two types of T.B. infection  Fate of tubercle: Depends on immunity High immunity: Small foci are completely fibrosed. Large foci are capsulated by fibrous tissue and its central caseating part shows dystrophic calcification. Living bacteria may remain in the lesion.  Low immunity: The lesion spreads by: Direct spread: tubercle bacilli are non-motile organisms. Macrophages and tissue fluids carry the bacilli to the surrounding tissues. Lymphatic spread: free bacilli or macrophages carrying the bacilli pass via lymphatic vessels to the regional lymph nodes, causing tuberculous lymphadenitis. Blood spread: A caseous focus may involve a blood vessel and the bacilli pass to the blood stream. Intracanalicular spread: spread through the lumen of a natural tube, e.g. spread through the bronchi or the ureter Intracanalicular spread  Intracanalicular spread In tuberculosis ,the granuloma is referred to as a) Fruncle b) Tubercle c) Carbuncle d) Sarcoidosis  Intracanalicular spread In tuberculosis ,the granuloma is referred to as a) Fruncle b) Tubercle c) Carbuncle d) Sarcoidosis  Intracanalicular spread A 53-year-old man develops weakness, malaise, cough with bloody sputum, and night sweats. A chest X-ray reveals numerous apical densities bilaterally. Exposure to Mycobacterium tuberculosis was documented 20 years ago, and M. tuberculosisis identified in the sputum. The patient subsequently dies of respiratory insufficiency. Which of the following best characterizes this pulmonary lesion? A) Acute suppurative inflammation (B) Chronic inflammation (C) Fat necrosis (D) Fibrinoid necrosis (E) Granulomatous inflammation  Intracanalicular spread A 53-year-old man develops weakness, malaise, cough with bloody sputum, and night sweats. A chest X-ray reveals numerous apical densities bilaterally. Exposure to Mycobacterium tuberculosis was documented 20 years ago, and M. tuberculosisis identified in the sputum. The patient subsequently dies of respiratory insufficiency. Which of the following best characterizes this pulmonary lesion? A) Acute suppurative inflammation (B) Chronic inflammation (C) Fat necrosis (D) Fibrinoid necrosis (E) Granulomatous inflammation  Intracanalicular spread Primary sites of TB infection include the following except : a) Lung b) Liver c) Tonsils d) Intestine e) Skin  Intracanalicular spread Primary sites of TB infection include the following except : a) Lung b) Liver c) Tonsils d) Intestine e) Skin  PULMONARY TUBERCULOSIS I. Primary pulmonary tuberculosis:- First infection of the lung with tubercle bacilli Frequent in children. Infection is by inhalation of the human bacilli. Pathological features: The primary pulmonary complex: triad of: 1) Ghon's focus, 2) Tuberculous lymphangitis. 3) Tuberculous lymphadenitis of the regional lymph nodes.  The primary pulmonary complex I- Ghon's focus: Is an initial tuberculous lung lesion. Grossly: – It is a yellowish lesion – 1-1.5 cm in diameter. – It is commonly subpleural. – It occurs anywhere in the lung, but the most frequently involved sites are the lower aspect of the upper lobes or the upper aspect of the lower lobes Microscopically: It consists of several adjacent caseating tubercles  The primary pulmonary complex II. Tuberculous lymphangitis: A chain of tubercles along the course of lymphatic vessels III.Tuberculous lymphadenitis The hilar lymph nodes are enlarged and show caseating tubercles. Caseation may be marked and the nodes may become matted forming a "cold abscess"  Fate of primary pulmonary complex Depends on infection and body resistance Healing: Spread: low body resistance. – Direct spread – Haematogenous spread (miliary) –  Fate of primary pulmonary complex Healing: If infection is mild and the resistance is good. * small lesion heals by complete fibrosis. * bigger one heals by dystrophic calcification.  Spread: low body resistance. Direct spread: in the lung tissue causing tuberculous pneumonia to the pleura causing tuberculous pleurisy. Healing occurs by organization leaving adhesion  Haematogenous spread Small number of bacilli: Destroyed by the cells of the reticulo-endothelial system. Moderate number of bacilli: settle in one of the favorable sites may be arrested or progress causing isolated organ tuberculosis. Large number of bacilli: usually results from opening of a caseous focus through a large vessel. The bacilli reach different organs at the same time (lung, liver, kidney, adrenal, bones, serous membranes.. etc) forming small uniform tuberculous lesions about 1-2 millimeters. The condition is known as MILIARY TUBERCULOSIS and is rapidly fatal. Miliary tuberculosis of the spleen. The cut surface shows numerous gray- white tubercles  II-Secondary pulmonary tuberculosis Tuberculous infection that arises in :A previously sensitized individuals“ whenever defenses are lowered". Infection: is either: – Exogenous: inhalation of human bacilli. – Endogenous: Reactivation of a capsulated primary focus.  Course: depends on: The dose and virulence of bacteria State of immunity and hypersensitivity. Regression: occurs with small number of bacilli and high immunity. The lesion heals by fibrosis and is called fibrotic tuberculosis. Progression: Chronic fibrocaseous pulmonary tuberculosis – Occurs in patients with moderate levels of immunity and hypersensitivity – Slow chronic course Bronchopneumonia – Acute caseous pneumonia – One or more of the following factors are present: 1 Large dose of virulent bacteria. 2 High hypersensitivity. 3 Low immunity Acute fatal course  Complications: 1 Hemoptysis: due to erosion of vessels. 2 Rupture of the cavity: into the pleural sac result in pneumothorax. 3 Spread of infection: (less common than primary T.B.) a) Direct leading --- tuberculous pleurisy or tuberculous empyema b) Blood spread ---- isolated organ tuberculosis or miliary tuberculosis. c) Bronchial spread: coughing of infected sputum ------- tuberculosis of larynx, tonsils, tongue. Swallowing of this sputum causes secondary intestinal tuberculosis. d) Lymphatic spread. 4 Right-sided heart failure :due to bilateral lung fibrosis (in bilateral cases). 5 Secondary amyloidosis (reactive systemic amyloidosis:) due to continuous breakdown of the lung tissue.  INTESTINAL TUBERCULOSIS Primary intestinal tuberculosis: Aetiology: ingestion of infected milk ( bovine bacilli). Pathology: A primary intestinal complex : – 1- Intestinal lesions: tubercles in the payer's patches (where macrophages carry the bacilli to this area) at the terminal ileum. The covering mucosa -------- minimal ulceration. – 2- Tuberculous lymphangitis. – 3- Tuberculous lymphadenitis: (tabes mesentaris).  Fate: 1) Localization. 2) Spread: a) Direct and lymphatic: this leads to tuberculous peritonitis b) Hematogenous spread leading to isolated organ or miliary tuberculosis.  Secondary intestinal tuberculosis: Aetiology: Due to swallowing infected sputum in patients with chronic fibrocaseous tuberculosis. Pathological features: – The lesions develop mainly in the terminal ileum and adjacent caecum. – The bacilli reach the payer's patches. – Caseous necrosis and erosion of the covering mucosa results in tuberculous ulcers. – The mesenteric lymph nodes show minimal lesions.  Tuberculous ulcers Multiple. Ragged and undermined edges Yellowish, caseous and soft floors Transversely arranged (girdle ulcers). Heal by fibrosis Tuberculous ulcers  Complications: Fibrosis leads to intestinal obstruction Perforation of the ulcers leads to – septic peritonitis. – Intestinal hemorrhage – Intestinal fistula. Spread of infection: Secondary amyloidosis.  Tuberculous ulcers of intestine : a) Sharp edge b) undermined edges c) raised edge d) Everted edge  Tuberculous ulcers of intestine : a) Sharp edge b) undermined edges c) raised edge d) Everted edge A granuloma : Is a focus of chronic specific inflammation consisting of focal accumulations of activated macrophages surrounded by collar of lymphocytes and occasionally plasma cells, with a rim of fibroblasts, and granulation tissue. Tuberculosis is a chronic infective granuloma caused by Mycobacterium Tuberculosis. In tuberculosis the granuloma is referred to as a tubercle.