Granulomatous inflammation tuberculosis syphillis

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<ul><li><p>GRANULOMATOUS INFLAMMATION : </p><p>Tuberculosis, SyphilisTuberculosis, Syphilis</p><p>Dr. Deepak K Gupta</p></li><li><p>Syllabus</p><p> Granulomations inflammation. Tuberculosis</p><p> Epidemiology Pathogenesis (Formation of tubercle) Pathological features of Primary and secondary TB Complications and Fate Complications and Fate</p><p> Syphilis Epidemiology Types and stages of syphilis Pathological features Diagnostic criterias Oral lesions</p></li><li><p>Introduction</p><p> It is a distinctive pattern of chronic inflammation characterized by aggregates of activated macrophages that assume an epithelioidappearance.appearance.</p><p> Certain specific pathologic states</p><p> Walls off- offending agent Tuberculosis is the </p><p>prototype of a granulomatous disease.</p></li><li><p>Granulomatous Disease</p><p>Disease Cause</p><p>Tuberculosis Mycobacterium tuberculosis</p><p>Leprosy Mycobacterium leprae</p><p>Syphilis Treponema pallidumSyphilis Treponema pallidum</p><p>Cat Scratch Disease Gram () bacillus</p><p>Sarcoidosis Unknown etiology</p><p>Crohn Disease Immune reaction against intestinal bacterial, self antigen</p></li><li><p>PATHOGENESIS OF GRANULOMA</p><p>Engulfment by </p><p>Macrophages</p><p> Unable to eat MCO like M. tubercle</p><p> Undergo morphologic changes to epithelioid cells.</p><p> When macrophage fails to kill MCO</p><p>CD4+ T cells</p><p> When macrophage fails to kill MCO</p><p> It presents it to CD4+ cells.</p><p>Cytokines</p><p> IL-1 and IL-2, Interferon-, TNF-</p><p> Fibroblast proliferation</p></li><li><p>Histological features The following three layer structure of the inflammatory </p><p>granulation tissue is common Resorption zone</p><p> Innermost borders directly on the necrotic material and primarily consists </p><p>of phagocytic histiocytes. store the poorly soluble fat in lysosomal vacuoles - foam cells store the poorly soluble fat in lysosomal vacuoles - foam cells</p><p> Granulation zone granulation tissue rich in capillaries and fibroblasts. Resorptive and reparative function</p><p> Mature connective tissue zone oldest and outermost layer of tissue - highly fibrous connective </p><p>tissue</p></li><li><p>Histological features</p></li><li><p>Histological features</p></li><li><p>COMPOSITION OF GRANULOMA</p><p> Following structural components</p><p> Epitheloid cells</p><p> Multinucleate giant Multinucleate giant cells</p><p> Lymphoid cells - cell mediated immune reaction</p><p> Necrosis &amp; Fibrosis.</p></li><li><p>Epithelioid cells</p><p> epithelial cell-like appearance</p><p> modified macrophages/histiocytes</p><p> abundant cytoplasm with hazy outlines</p><p> cell membrane of adjacent epithelioid cells is cell membrane of adjacent epithelioid cells is closely apposed</p><p> Epithelioid cells are weakly phagocytic</p></li><li><p>Multinucleate giant cells</p><p> fusion of adjacent epithelioidcells</p><p> 20 or more nuclei Langhans giant cells - nuclei </p><p>may be arranged may be arranged Periphery Horseshoe Ring Clustered at the two poles.</p><p> Foreign body giant cells centrally placed nuclei</p><p> Weakly phagocytic</p></li><li><p>Multinucleate giant cells</p></li><li><p>Necrosis &amp; Fibrosis</p><p> Necrosis may be a feature of some granulomatousconditions Central caseation Central caseation</p><p>necrosis of tuberculosis</p><p> Fibrosis - healing by proliferating fibroblasts at the periphery of granuloma. Ex: Rheumatoid Arthritis</p></li><li><p>Mycobacteria</p><p> Slender rods with lipid-rich cell walls Cell walls are unusual</p><p> 60 percent lipid Longchain (75 to 90 carbons), -hydroxylated fatty </p><p>acids (mycolic acids)acids (mycolic acids) This complexes with variety of polysaccharides and </p><p>peptides waxy cell surface - strongly hydrophobic, impervious </p><p>and acid fast staining</p><p> Resistant to drying but not to heat or ultraviolet irradiation</p></li><li><p>Mycobacteria They are grouped in </p><p>three groups</p><p> Tuberculosis causing Mycobacterium. </p><p> Atypical Bacteria. </p><p> Lepra group.</p></li><li><p>Tubercle bacillus</p><p> Robert Koch in 1882 Organism is a strict aerobe Grows best in tissues with high oxygen tension </p><p>such as in the apex of the lung M. tuberculosis hominis (human strain) most M. tuberculosis hominis (human strain) most </p><p>commonly found M. tuberculosis bovis (bovine strain) - unpasteurised</p><p>milk M. africanum - isolated from patients from parts of </p><p>Africa) M. microti, M. pinnipedii and M. canettii</p></li><li><p>M. tuberculosis hominis</p><p> neutral on Gram staining</p><p> demonstrated by the following methods Acid fast (Ziehl-Neelsen) staining</p><p> Fluorescent dye methods Fluorescent dye methods</p><p> Culture of the organism from sputum in Lowenstein Jensen (L.J.) medium for 6 weeks</p><p> Guinea pig inoculation -subcutaneous injection</p><p> Molecular methods - PCR</p></li><li><p>Atypical Mycobacterium</p><p> Other than M. tuberculosis complex and M. leprae.</p><p> Environmental mycobacteria widely distributed in the environment </p><p> Occasionally cause human tuberculosis - atypical Occasionally cause human tuberculosis - atypical mycobacteriosis</p><p> Resistant to usual antitubercular drugs.</p><p> Classified on the basis of colour of colony produced in culture and the speed of growth in media (solid)</p></li><li><p>Atypical Mycobacterium</p><p> Speed of growth</p><p> Rapid growers - within 7 days</p><p> Ex: M. abscessus, M.fortuitum, M. chelonae</p><p> Slow growers - 2-3 weeks</p><p> Ex: M. avium-intracellulare, M. kansasii, M. ulcerans Ex: M. avium-intracellulare, M. kansasii, M. ulcerans</p><p> Color of colony formed</p><p> Photochromogens - yellow pigment in the presence of light</p><p> Scotochromogens produces pigments in the absence of light</p><p> Non-chromogen - no pigmentation</p></li><li><p>Atypical Mycobacterium</p><p> Acquired directly from the environment</p><p> lesions - granulomas, nodular collection of foamy cells, or acute inflammation</p><p> Less virulent Less virulent</p></li><li><p>Mycobacterium leprae</p><p> damage to the skin and the peripheral nervous system.</p><p> Hansens disease</p><p> transmitted from human to human - through prolonged human - through prolonged contact</p><p> exudates of a leprosy patients skin lesions and the abraded skin of another individual</p><p> Low virulence</p></li><li><p>Mycobacterium leprae</p><p> Long incubation period -develop years or even decades after initial contact with the with the organism.</p><p> Two clinical extremes: tuberculoid and lepromatous leprosy</p></li><li><p>Mycobacterium leprae : tuberculoidleprosy</p><p> lesions occur as large maculae (spots) in cooler body tissues, such as </p><p> skin (especially the nose, outer ears, and testicles), superficial nerve endings. </p><p> Neuritis - patches of anesthesia in the skin. Neuritis - patches of anesthesia in the skin. Lesions are heavily infiltrated by lymphocytes and </p><p>giant and epithelioid cells, but caseation does not occur. </p><p> a strong cell-mediated immune response and develops delayed hypersensitivitY - skin test with lepromin, a tuberculin-like extract of lepromatoustissue. </p><p> There are few bacteria in the lesions (paucibacillary). </p></li><li><p>Initial lesion of Leprosy</p></li><li><p>Mycobacterium leprae : lepromatousleprosy</p><p> slow but progressive </p><p> Large numbers of organisms - present in the lesions and the lesions and reticuloendothelialsystem (multibacillary), </p><p> Severely depressed immune system.</p><p> No well-formed granulomas emerge</p></li><li><p>Tuberculosis</p></li><li><p>Introduction</p><p> Communicable chronic granulomatous disease caused by Mycobacterium tuberculosis</p><p> It usually involves the lungs but may affect any organ or tissue in the body.organ or tissue in the body.</p><p> Typically, the centers of tubercular granulomasundergo caseous necrosis</p></li><li><p>Epidemiology</p><p> one of the oldest diseases known to affect humans</p><p> major cause of death worldwide</p><p> one third of the worlds population is infected with M. tuberculosis</p><p> one third of the worlds population is infected with M. tuberculosis</p><p> If untreated, the disease may be fatal within 5 years in 5065% of cases</p><p> 50 percent of the HIV-infected population is coinfected with M. tuberculosis.</p></li><li><p>Etiology</p><p> M. tuberculosis hominis is responsible for most cases of tuberculosis</p><p> reservoir of infection is usually found in humans with active pulmonary disease</p><p> Transmission is usually direct Transmission is usually direct Inhalation : fresh cough droplets or in dried sputum from </p><p>infected person Ingestion : tonsillar or intestinal tuberculosis, self-</p><p>swallowing of infected sputum Inoculation infected postmortem tissue Transplacental route congenital tuberculosis in foetus</p><p>from infected mother and is a rare mode</p></li><li><p>Pathogenesis No demonstrable toxins Virulence mycobacteria reach the </p><p>alveoli Macrophage initiates </p><p>phagocytosis, but unable to do so bacterial sulfolipids inhibit the fusion </p><p>of phagocytic vesicles with of phagocytic vesicles with lysosomes</p><p> multiply in the pulmonary epithelium or macrophages</p><p> 2 to 4 weeks - destroyed by the immune system, but some survive and are spread by the blood to extrapulmonary sites</p><p> Ability to survive and grow within host cells</p></li><li><p>Types of Tuberculosis</p><p> Tubercle bacilli is of 2 main types</p><p> Primary tuberculosis</p><p> Secondary tuberculosis.</p></li><li><p>Primary tuberculosis</p><p> Individual - not been previously infected or immunised. </p><p> Ghons complex or childhood tuberculosis.</p><p> begins with a primary subpleural focus (Ghon begins with a primary subpleural focus (Ghoncomplex) in the central parenchyma of the lung.</p><p> Incidence of primary infection is high in immuno-compromised patients</p></li><li><p>Lung Anatomy</p></li><li><p>Ghons complex</p><p> lungs consists of 3 components Pulmonary component</p><p> 1-2 cm solitary area located peripherally under a patch of </p><p>pleurisy in any part of the lung but more often in </p><p>subpleural focus in the upper part of lower lobe.subpleural focus in the upper part of lower lobe.</p><p> Lymphatic vessel component lymphatics draining the lung lesion </p><p>contain phagocytes containing bacilli</p><p> Lymph node component enlarged hilar and tracheo-bronchial </p><p>lymph nodes in the area drained by lymph</p><p> lymph nodes are matted and show caseation necrosis</p></li><li><p>Ghons complex</p></li><li><p>Tuberculous peritonitis Small primary focus in intestine</p><p> Enlarged mesenteric lymph nodes producing tabes mesenterica. </p><p> When it enlarges - rupture into peritoneal cavity and cause tuberculous peritonitiscavity and cause tuberculous peritonitis</p></li><li><p>FATE OF PRIMARY TUBERCULOSIS</p><p>1. Heals by fibrosis or calcification and even ossification</p><p>2. Progressive primary tuberculosis : Spreads to other parts of Lungs</p><p>3. Primary miliary tuberculosis : bacilli may enter 3. Primary miliary tuberculosis : bacilli may enter the circulation through erosion in a blood vessel and spread to various tissues and organs. Ex: liver, spleen, kidney, brain and bone marrow</p><p>4. Progressive secondary tuberculosis : bacilli lying dormant in acellular caseous material gets activated</p></li><li><p>Secondary Tuberculosis</p></li><li><p>Secondary Tuberculosis</p><p> The infection of an individual who has been previously infected or sensitised is called secondary, or post-primary or reinfection, or chronic tuberculosis</p><p> The infection may be acquired from Endogenous source : reactivation of dormant primary Endogenous source : reactivation of dormant primary </p><p>complex</p><p> Exogenous source : fresh dose of reinfection by the tubercle bacilli</p><p> Most commonly in lungs in the region of apex</p><p> Other sites like tonsils, pharynx, larynx, small intestine and skin</p></li><li><p>Secondary Tuberculosis</p></li><li><p>Secondary Pulmonary Tuberculosis</p><p> begin as 1-2 cm apical area of consolidation of the lung</p><p> With time develop a small area of central caseation necrosis and peripheral fibrosiscaseation necrosis and peripheral fibrosis</p><p> This occurs by haematogenous spread from the site of primary complex</p><p> oxygen tension is high and favourable forgrowth of aerobic tubercle bacilli</p></li><li><p>Secondary Pulmonary Tuberculosis</p><p> Microscopically, it represents tuberculousgranulomas with caseationnecrosis</p><p> HIV patientsIf previously exposed will If previously exposed will have more incidence of reactivation</p><p> involvement of hilar lymph nodes rather than cavitaryand apical lesions in the lung</p><p> M. avium-intracellulare more common</p></li><li><p>FATE OF SECONDARY PULMONARY TUBERCULOSIS</p><p> Either of the following lesions may heal with fibrous scarring and</p><p>calcification.</p><p> lesions may coalesce together to form larger area of tuberculous pneumoniaof tuberculous pneumonia</p><p> Or produce progressive secondary pulmonary tuberculosis Fibrocaseous tuberculosis</p><p> Tuberculous caseous pneumonia</p><p> Miliary tuberculosis</p></li><li><p>FIBROCASEOUS TUBERCULOSIS</p><p> Massive central caseation necrosis, which may either form</p><p> Cavitary lesion : break into a bronchus from a cavity. Also known as open tuberculosis may cause cavity. Also known as open tuberculosis may cause endobronchial, endotracheal, laryngeal andintestinal tuberculosis</p><p> Non-cavitary : Remain as a soft caseous lesion without drainage into a bronchus or bronchiole</p></li><li><p>FIBROCASEOUS TUBERCULOSIS</p><p>1. The external surface shows thickened pleura </p><p>3. The cavity is lined by yellowish caseous necrotic yellowish caseous necrotic material. The lung tissue around the cavity is consolidated. The hilumshows a few enlarged and matted lymph nodes </p></li><li><p>FIBROCASEOUS TUBERCULOSIS</p><p>Sectioned surface of the lung shows a cavity in the apex of the lung</p></li><li><p>Morphological Features</p><p> Gross cavity is spherical with thick fibrous wall lined by yellowish, caseous, necrotic material lumen is traversed by thrombosed blood vessels consolidation are seen around the wall of cavity consolidation are seen around the wall of cavity The overlying pleura may also be thickened </p><p> Microscopic shows eosinophilic, granular, caseous material foci of dystrophic calcification Coalesced tuberculous granulomas composed of epithelioid</p><p>cells, Langhans giant cells and peripheral mantle of lymphocytes</p><p> outer wall of cavity shows fibrosis</p></li><li><p>Morphological Features</p></li><li><p>Complications of cavitary secondary tuberculosis</p><p> Aneurysms of patent arteries crossing the cavity haemoptysis</p><p> Extension to pleura producing bronchopleuralfistulafistula</p><p> Tuberculous empyema - deposition of caseous material on the pleural surface</p><p> Thickened pleura - adhesions of parietal pleura</p></li><li><p>TUBERCULOUS CASEOUS PNEUMONIA</p><p> high degree of hypersensitivity -spreadto rest of the lung producing caseouspneumoniaproducing caseouspneumonia</p><p> Microscopically it shows exudative formations </p><p>containing tubercle bacilli</p><p> oedema, fibrin, polymorphs and monocytes</p></li><li><p>MILIARY TUBERCULOSIS Lymphohaematogenous</p><p>spread of tuberculousinfection from primary focus or later stages of tuberculosis - systemic organs or isolated organorgans or isolated organ</p><p> Infection into Pulmonary vein : </p><p>disseminated or isolated organ lesion</p><p> Pulmonary artery : restricting the development of lesions within the lung</p></li><li><p>MILIARY TUBERCULOSIS</p><p>The pleural (1) as well as sectioned surface as sectioned surface shows presence of minute (about pin-head sized) yellowish nodules with central necrosis called miliarytubercles (2)</p></li><li><p>MILIARY TUBERCULOSIS</p><p> Lesions are millet seed-sized (1 mm diameter)</p><p> Yellowish, firm areas Yellowish, firm areas without grossly visible caseation necrosis</p><p> Structure of tubercles with minute areas of caseation necrosis</p></li><li><p>MILIARY TUBERCULOSIS</p><p>Milliary TB of Spleen</p></li><li><p>References</p><p> Robbinson's basic pathology 8 ed</p><p> Harsh Mohan - Textbook of Pathology 6th Ed.</p><p> Color atlas of pathology</p><p></p></li></ul>


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