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
Non-immune granulomaForeign bodySplinterSutureGraft material
Granulomatous inflammation Foreign body Granulomas:endogenous ( keratin, necrotic bone or adipose tissue, uric acid crystals)
Exogenous(wood, silica, asbestos, silicone,suture)Specific chemicals:
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
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
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
Cough, sputum, Low grade fever, night sweats, fatigue and weight loss.Hemoptysis or pleuritic pain = severe disease
Miliary TBMillet like grain.
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
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.
LeprosyLeprosy is a chronic infection caused by the acid-fast, rod-shaped bacillus Mycobacterium leprae.
skin peripheral nerves
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
SchistosomiasisAlso known as bilharziasis
Parasite The main forms of human schistosomiasis : Schistosoma hematobium, Schistosoma mansoni, Schistosoma japonicum, Schistosoma intercalatum, Schistosoma mekongi.
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.