Granulomatous inflammation. A granuloma is a microscopic aggregation of macrophages that are transformed into epithelium-like cells surrounded by a collar

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  • Granulomatous inflammation

  • Granulomatous inflammation A granuloma is a microscopic aggregation of macrophages that are transformed into epithelium-like cells surrounded by a collar of mononuclear leukocytes, principally lymphocytes and occasionally plasma cells.

  • Granulomatous InflammationGranuloma = Nodular collection of epithelioid macrophages surrounded by a rim of lymphocytes

    Epitheloid macrophages: squamous cell-like appearance

  • Why is it important?Granulomas are encountered in certain specific pathologic states; consequently, recognition of the granulomatous pattern is important because of the limited number of conditions (some life-threatening) that cause it

  • Granulomatous inflammation Epithelioid cells fuse to form giant cells containing 20 or more nuclei.The nuclei arranged either peripherally (Langhans-type giant cell) or haphazardly (foreign body-type giant cell).These giant cells can be found either at the periphery or the center of the granuloma.

  • Langhans Giant CellLymphocytic Rim

  • CAUSES OF GRANULOMATOUS DISEASES

  • Granulomatous Inflammation CausesImmune granuloma:BacteriaTuberculosisLeprosy Actinomycosis Cat-scratch diseaseParasitesSchistosomiasis -Leishmaniasis

    FungiHistoplasmosisBlastomycosisMetal/DustBerylliosisSilicosis

    Non-immune granulomaForeign bodySplinterSutureGraft material

    unknownSarcoidosis

  • Granulomatous inflammation Foreign body Granulomas:endogenous ( keratin, necrotic bone or adipose tissue, uric acid crystals)

    Exogenous(wood, silica, asbestos, silicone,suture)Specific chemicals:

    Beryllium

  • Mechanism Of granulomaformation

  • Granulomatous InflammationmechanismWhat is the initiating event in granuloma formation?

    deposition of a indigestible antigenic material

    IFN- released by the CD4+ T cells of the TH1 subset is crucial in activating macrophages.

  • Granuloma: bacilli are inhaled by droplets

    Bacteria are phagocytosed by alveolar macrophagesAfter amassing substances that they cannot digest, macrophages lose their motility, accumulate at the site of injury and transform themselves into nodular collections; the Granuloma

    A localized inflammatory response recruits more mononuclear cells

    The granuloma consists of a kernel of infected macrophages surrounded by foamy macrophages and a ring of lymphocytes and a fibrous cuff (containment phase)

    Containment usually fails when the immune status of the patient changes; the granuloma caseates, ruptures and spills into the airway

  • Granuloma

  • Tuberculosis

  • Etiology Mycobacterum tuberculosis Mycobacteria fungus like.. slender rods acid fast bacilli [AFB] (i.e., they have a high content of complex lipids that readily bind the Ziehl-Neelsen [carbol fuchsin] stain and subsequently resist decolorization).

    Mycobacterium bovis ..intestinal TB , milk injection

    Other types M. leprae (Hansen bacillus) ..LeprosyM. kansasii, M. avium, M. intracellulare ..Atypical mycobacterial infectionsM. ulcerans .Buruli ulcer

  • AFB - Ziehl-Nielson stain

  • Infection - ImmunityPathogenesis of TB:

  • If the bacilli enter the body

  • If the bacilli enter the body The bacilli have 4 potential fates:

    (1) They may be killed by the immune system,

    (2) they may multiply and cause primary TB, (3) they may become dormant and remain asymptomatic,

    (4) they may proliferate after a latency period (reactivation disease). Reactivation TB may occur following either (2) or (3) above.

    (5 ) if immunosuppressed ---- Primary Progressive TB Miliary TB

  • TBPrimary tuberculosis [initial infection]

    secondary tuberculosis [ re-activation or re-infection ]

  • Primary tuberculosisNon immunized individual [initial infection] children

    Subpleural zone of lung can be at other sites

    Brief acute inflammation neutrophils.

    5-6 days invoke granuloma formation.

    2 to 8 weeks healing Ghon focus (+ lymph node Ghon complex)

    Develop immunity Mantoux positive ( tuberculin test , PPD )

  • Primary or Ghons ComplexCharacteristics

    initial infection

    non immunized individual

    5-6 days granuloma

    2 to 8 weeks healing

    subpleural zone. Ghon focus

    + lymph node Ghon complex

    Develop immunity Mantoux positive [ PPD ]

  • Secondary Tuberculosis:Post Primary in immunized individuals.

    Reactivation or Reinfection

    Cavitary Granulomatous response.

    Apical lobes or upper part of lower lobes O2

    Caseation, cavity - soft granuloma

    Pulmonary or extra-pulmonary

    Local or systemic spread / MiliaryVein via left ventricle to whole bodyArtery miliary spread within the lung

  • Secondary Tuberculosis:

    Cough, sputum, Low grade fever, night sweats, fatigue and weight loss.Hemoptysis or pleuritic pain = severe disease

  • Miliary TBMillet like grain.

    Low immunity

    blood or bronchial spread

    Pulmonary or Systemic types.

  • TB OF DIFFERENT ORGANS

  • Adrenal TB - Addison Disease

  • Testes TB Orchitis.

  • TB Peritonitis + liver Miliary TB

  • TB Brain Caudate n.

  • TB Intestineany part can be affectedileum

  • Prostate TB

  • Spinal TB - Potts Disease

  • Diagnosis of TBClinical features Depend on organ involved.Pulmonary tuberculosis (TB): productive cough, fever, and weight loss, night sweats.

  • Investigations Patients suspected of having tuberculosis (TB)

    Tuberculin skin testing (Mantoux test, PPD) Intradermal injection of purified protein derivative ( PPD). The response is measured as the amount of induration at 48-72 hours. The size of induration, rather than erythema, is diagnostic.BCG gives + result

    Sputum, bronchial wash or biopsyAcid fast smear ( ZN stain )cultures require weeks for growth and identificationNewer technologies, including ribosomal RNA probes or DNA polymerase chain reaction, allow identification within 24 hours.

    Chest radiographs patchy or nodular infiltrate. may be found in any part of the lung, but upper-lobe involvement is most common

  • PPD result after 72 hours

  • What will be your action after diagnosis?

    Patients with TB should remain in isolation until sputum becomes negative;

  • 1 TB usually involves the middle or lower lung zones and is associated with hilar adenopathy (Gohn complex).

    2 TB represents reactivation and typically involves the upper lungs and cavitation.

    regimen RIPERifampin, Isoniazid (INH), Pyrazinamide, and Ethambutol daily for eight weeks, followed by INH and rifampin for an additional 16 weeks. Give vitamin B6 to prevent INH-associated neuropathy.

  • Leprosy

  • LeprosyLeprosy is a chronic infection caused by the acid-fast, rod-shaped bacillus Mycobacterium leprae.

    skin peripheral nerves

  • Leprosy Symptoms

    skin Painless skin patchperipheral nervesLoss of sensationWasting and muscle weakness Foot drop or clawed handsUlcerations on hands or feet

  • AetiologyMycobacterium lepraeAcid fast gram-positive bacillus cannot be culturedThe mode of transmission is unknown, probably inhalation of bacilli incubation period is several years.The classical method for demonstrating leprosy bacilli in lesions is a modified Ziehl-Neelsen stain. The Fite methods are the most commonly used

  • Classification Depends on the strength of the delayed (type IV) hypersensitivity response in the infected individual.Lepromatous leprosypoor Cell-mediated immunitybacilli are plentiful large numbers of macrophagesSensation is not impairedTuberculoid leprosystrong cell-mediated immunityFew or no acid-fast bacilli.granulomatous reaction in the nerves and dermis anaesthesiaIndeterminate leprosy

  • The lepromin skin testIntradermal injection of a preparation of M. leprae

    A positive reaction consists of the formation of a nodule measuring 5 mm or more in diameter after 2 to 4 weeks. On histologic examination, the nodule shows an epithelioid cell granuloma.

    Tuberculoid ..lepromatous ..

  • DIAGNOSISSKIN BIOPSYTuberculoid leprosy granulomatous dermatitisFew acid-fast bacilli in nervesintraneural granuloma

    Lepromatous leprosy a mass of macrophages in the dermis (no granuloma formation), leaving a clear grenz zone under the epidermis

  • Schistosomiasis

  • SchistosomiasisAlso known as bilharziasis

    Parasite The main forms of human schistosomiasis : Schistosoma hematobium, Schistosoma mansoni, Schistosoma japonicum, Schistosoma intercalatum, Schistosoma mekongi.

  • Life cycle

  • Life cyclepathophysiologyCercariaInfective stageCercarial dermatitis..itching Adult worm:In the venous blood lays eggs 4-6 weeks after cercarial penetration. rarely pathogenic. EggsPathogenicDiagnostic

  • Acute schistosomiasismost clinical manifestations are benign Cercarial dermatitis: Individuals who have been exposed to fresh or salt water may develop a pruritic rash due to cercarial dermatitis (also called swimmer's itch). some are severe and may require hospitalization.

  • Chronic schistosomiasisMost patients are asymptomatic or mildly symptomatic and do not require medical attention. Only a small proportion of the endemic population harbors a heavy worm burden that later leads to clinical complications.