Granulomatous inflammation tuberculosis syphillis

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    Tuberculosis, SyphilisTuberculosis, Syphilis

    Dr. Deepak K Gupta

  • Syllabus

    Granulomations inflammation. Tuberculosis

    Epidemiology Pathogenesis (Formation of tubercle) Pathological features of Primary and secondary TB Complications and Fate Complications and Fate

    Syphilis Epidemiology Types and stages of syphilis Pathological features Diagnostic criterias Oral lesions

  • Introduction

    It is a distinctive pattern of chronic inflammation characterized by aggregates of activated macrophages that assume an epithelioidappearance.appearance.

    Certain specific pathologic states

    Walls off- offending agent Tuberculosis is the

    prototype of a granulomatous disease.

  • Granulomatous Disease

    Disease Cause

    Tuberculosis Mycobacterium tuberculosis

    Leprosy Mycobacterium leprae

    Syphilis Treponema pallidumSyphilis Treponema pallidum

    Cat Scratch Disease Gram () bacillus

    Sarcoidosis Unknown etiology

    Crohn Disease Immune reaction against intestinal bacterial, self antigen


    Engulfment by


    Unable to eat MCO like M. tubercle

    Undergo morphologic changes to epithelioid cells.

    When macrophage fails to kill MCO

    CD4+ T cells

    When macrophage fails to kill MCO

    It presents it to CD4+ cells.


    IL-1 and IL-2, Interferon-, TNF-

    Fibroblast proliferation

  • Histological features The following three layer structure of the inflammatory

    granulation tissue is common Resorption zone

    Innermost borders directly on the necrotic material and primarily consists

    of phagocytic histiocytes. store the poorly soluble fat in lysosomal vacuoles - foam cells store the poorly soluble fat in lysosomal vacuoles - foam cells

    Granulation zone granulation tissue rich in capillaries and fibroblasts. Resorptive and reparative function

    Mature connective tissue zone oldest and outermost layer of tissue - highly fibrous connective


  • Histological features

  • Histological features


    Following structural components

    Epitheloid cells

    Multinucleate giant Multinucleate giant cells

    Lymphoid cells - cell mediated immune reaction

    Necrosis & Fibrosis.

  • Epithelioid cells

    epithelial cell-like appearance

    modified macrophages/histiocytes

    abundant cytoplasm with hazy outlines

    cell membrane of adjacent epithelioid cells is cell membrane of adjacent epithelioid cells is closely apposed

    Epithelioid cells are weakly phagocytic

  • Multinucleate giant cells

    fusion of adjacent epithelioidcells

    20 or more nuclei Langhans giant cells - nuclei

    may be arranged may be arranged Periphery Horseshoe Ring Clustered at the two poles.

    Foreign body giant cells centrally placed nuclei

    Weakly phagocytic

  • Multinucleate giant cells

  • Necrosis & Fibrosis

    Necrosis may be a feature of some granulomatousconditions Central caseation Central caseation

    necrosis of tuberculosis

    Fibrosis - healing by proliferating fibroblasts at the periphery of granuloma. Ex: Rheumatoid Arthritis

  • Mycobacteria

    Slender rods with lipid-rich cell walls Cell walls are unusual

    60 percent lipid Longchain (75 to 90 carbons), -hydroxylated fatty

    acids (mycolic acids)acids (mycolic acids) This complexes with variety of polysaccharides and

    peptides waxy cell surface - strongly hydrophobic, impervious

    and acid fast staining

    Resistant to drying but not to heat or ultraviolet irradiation

  • Mycobacteria They are grouped in

    three groups

    Tuberculosis causing Mycobacterium.

    Atypical Bacteria.

    Lepra group.

  • Tubercle bacillus

    Robert Koch in 1882 Organism is a strict aerobe Grows best in tissues with high oxygen tension

    such as in the apex of the lung M. tuberculosis hominis (human strain) most M. tuberculosis hominis (human strain) most

    commonly found M. tuberculosis bovis (bovine strain) - unpasteurised

    milk M. africanum - isolated from patients from parts of

    Africa) M. microti, M. pinnipedii and M. canettii

  • M. tuberculosis hominis

    neutral on Gram staining

    demonstrated by the following methods Acid fast (Ziehl-Neelsen) staining

    Fluorescent dye methods Fluorescent dye methods

    Culture of the organism from sputum in Lowenstein Jensen (L.J.) medium for 6 weeks

    Guinea pig inoculation -subcutaneous injection

    Molecular methods - PCR

  • Atypical Mycobacterium

    Other than M. tuberculosis complex and M. leprae.

    Environmental mycobacteria widely distributed in the environment

    Occasionally cause human tuberculosis - atypical Occasionally cause human tuberculosis - atypical mycobacteriosis

    Resistant to usual antitubercular drugs.

    Classified on the basis of colour of colony produced in culture and the speed of growth in media (solid)

  • Atypical Mycobacterium

    Speed of growth

    Rapid growers - within 7 days

    Ex: M. abscessus, M.fortuitum, M. chelonae

    Slow growers - 2-3 weeks

    Ex: M. avium-intracellulare, M. kansasii, M. ulcerans Ex: M. avium-intracellulare, M. kansasii, M. ulcerans

    Color of colony formed

    Photochromogens - yellow pigment in the presence of light

    Scotochromogens produces pigments in the absence of light

    Non-chromogen - no pigmentation

  • Atypical Mycobacterium

    Acquired directly from the environment

    lesions - granulomas, nodular collection of foamy cells, or acute inflammation

    Less virulent Less virulent

  • Mycobacterium leprae

    damage to the skin and the peripheral nervous system.

    Hansens disease

    transmitted from human to human - through prolonged human - through prolonged contact

    exudates of a leprosy patients skin lesions and the abraded skin of another individual

    Low virulence

  • Mycobacterium leprae

    Long incubation period -develop years or even decades after initial contact with the with the organism.

    Two clinical extremes: tuberculoid and lepromatous leprosy

  • Mycobacterium leprae : tuberculoidleprosy

    lesions occur as large maculae (spots) in cooler body tissues, such as

    skin (especially the nose, outer ears, and testicles), superficial nerve endings.

    Neuritis - patches of anesthesia in the skin. Neuritis - patches of anesthesia in the skin. Lesions are heavily infiltrated by lymphocytes and

    giant and epithelioid cells, but caseation does not occur.

    a strong cell-mediated immune response and develops delayed hypersensitivitY - skin test with lepromin, a tuberculin-like extract of lepromatoustissue.

    There are few bacteria in the lesions (paucibacillary).

  • Initial lesion of Leprosy

  • Mycobacterium leprae : lepromatousleprosy

    slow but progressive

    Large numbers of organisms - present in the lesions and the lesions and reticuloendothelialsystem (multibacillary),

    Severely depressed immune system.

    No well-formed granulomas emerge

  • Tuberculosis

  • Introduction

    Communicable chronic granulomatous disease caused by Mycobacterium tuberculosis

    It usually involves the lungs but may affect any organ or tissue in the body.organ or tissue in the body.

    Typically, the centers of tubercular granulomasundergo caseous necrosis

  • Epidemiology

    one of the oldest diseases known to affect humans

    major cause of death worldwide

    one third of the worlds population is infected with M. tuberculosis

    one third of the worlds population is infected with M. tuberculosis

    If untreated, the disease may be fatal within 5 years in 5065% of cases

    50 percent of the HIV-infected population is coinfected with M. tuberculosis.

  • Etiology

    M. tuberculosis hominis is responsible for most cases of tuberculosis

    reservoir of infection is usually found in humans with active pulmonary disease

    Transmission is usually direct Transmission is usually direct Inhalation : fresh cough droplets or in dried sputum from

    infected person Ingestion : tonsillar or intestinal tuberculosis, self-

    swallowing of infected sputum Inoculation infected postmortem tissue Transplacental route congenital tuberculosis in foetus

    from infected mother and is a rare mode

  • Pathogenesis No demonstrable toxins Virulence mycobacteria reach the

    alveoli Macrophage initiates

    phagocytosis, but unable to do so bacterial sulfolipids inhibit the fusion

    of phagocytic vesicles with of phagocytic vesicles with lysosomes

    multiply in the pulmonary epithelium or macrophages

    2 to 4 weeks - destroyed by the immune system, but some survive and are spread by the blood to extrapulmonary sites

    Ability to survive and grow within host cells

  • Types of Tuberculosis

    Tubercle bacilli is of 2 main types

    Primary tuberculosis

    Secondary tuberculosis.

  • Primary tuberculosis

    Individual - not been previously infected or immunised.

    Ghons complex or childhood tuberculosis.

    begins with a primary subpleural focus (Ghon begins with a primary subpleural focus (Ghoncomplex) in the central parenchyma of the lung.

    Incidence of primary infection is high in immuno-compromised patients

  • Lung Anatomy