View source for WBR0275

 {{WBRQuestion
|QuestionAuthor= {{Ochuko}} (Reviewed by  {{YD}} and  {{AJL}})
|ExamType=USMLE Step 1
|MainCategory=Pathology
|SubCategory=Pulmonology
|MainCategory=Pathology
|SubCategory=Pulmonology
|MainCategory=Pathology
|SubCategory=Pulmonology
|MainCategory=Pathology
|MainCategory=Pathology
|MainCategory=Pathology
|SubCategory=Pulmonology
|MainCategory=Pathology
|SubCategory=Pulmonology
|MainCategory=Pathology
|SubCategory=Pulmonology
|MainCategory=Pathology
|SubCategory=Pulmonology
|MainCategory=Pathology
|MainCategory=Pathology
|SubCategory=Pulmonology
|Prompt=A 36-year-old man presents to the physician’s office with complaints of a 5-week history of non-productive cough and fever. He recently moved back to the United States from sub-Saharan Africa, where he lived in a densely populated city for 5 years. Upon review of systems, the patient also reports night sweats and weight loss. Chest X ray demonstrates a right upper lobe infiltrate with several right perihilar lesions. Sputum smear returns positively when stained with carbol fuchsin and phenol (shown below). Which type of necrosis is associated with this patient's condition?

[[Image:WBR0275.jpg|500px]]
|Explanation=Pulmonary tuberculosis (TB) is a global pandemic that commonly affects individuals living in or recently immigrated from developing countries, homeless individuals, healthcare workers, elderly patients, immunocompromised patients, and patients who are administered TNF-alpha inhibitors. Pulmonary TB manifests as a subacute process with worsening, non-productive cough that lasts for more than 3 weeks along with constitutional symptoms, such as fever, gradual weight loss, night sweats, and malaise. In advanced cases, patients develop gradual dyspnea and hemoptysis; but these 2 features are less likely to be initially present. The diagnosis of pulmonary TB is often suspected upon history-taking and physical examination. Chest radiograph typically shows upper lobe zones of infiltration that may be associated with cavitation. Nonetheless, these radiographic findings may not be present in cases of primary TB infection or in immunocompromised patients, as they are more typical of TB reactivation. The diagnosis is then confirmed by direct smear examination of sputum samples, which demonstrate positivity upon acid-fast-bacilli staining (eg. Ziehl-Neelson stain that uses carbol fuchsin and phenol). Other diagnostic modalities include sputum culture, which requires special techniques (ie. Lowenstein-Jensen agar and might take 1-8 weeks before results return). Novel molecular diagnostic techniques, such as PCR, are also available. Unfortunately,  not all patients have sputum samples that yield positive results. In these cases, physicians use the combination of clinical features, radiographic findings, and tuberculin-skin testing/interferon-gamma release assay (IGRA) to make the diagnosis. 

''M. tuberculosis'' is a unique organism that multiplies within macrophages in pulmonary alveoli. As the organism invades the macrophages, the immune system is activated (coordinated by cell-mediated immunity, which are T-cell lymphocytes that release interferons and lymphokines, and executed by macrophages). When engulfed in macrophages, ''M tuberculosis'' is able to grow intracellularly and evade the phagosome-lysosome complex. Eventually cell lysis occurs, and the organism moves another macrophage. As it grows, ''M. tuberculosis'' is transported into lymph nodes, which become inflamed (primary complexes). Approximately 6 weeks following initial infection, the tuberculin growth stops and caseous necrosis occurs at the time the immunocompetent host develops cell-mediated immunity and delayed-type hypersensitivity. Caseous (cheese) necrosis is a necrosis of the exudative alveolar lesions due to alveolar injury. It develops by the action of the cytotoxic T-cells that kill macrophages infected with ''M. tuberculosis'', resulting in collateral destruction of the surrounding tissue. The destructive process results in a acellular, cheese-like debris in the center of the granuloma which contains dead tubercle bacilli, activated macrophages, CD4 helper T cells and multinucleated giant cells. The cheese-like appearance of caseous necrosis is due to the presence of lipids from the tubercle bacilli within the necrosis. The majority of immunocompetent patients infected with ''M. tuberculosis'' are capable of containing the infection with the help of the host cell-mediated immunity. In these individuals, TB fails to progress and remains latent. Caseous necrosis is also observed with other infections, such as systemic fungal infections (''Histoplasma capsulatum'', ''Coccidioides immitis'', and ''Blastomyces dermatitidis'').
|AnswerA=Caseous necrosis
|AnswerAExp=Caseous (cheese) necrosis is a necrosis of the exudative alveolar lesions due to alveolar injury. It develops by the action of the cytotoxic T-cells that kill macrophages infected with ''M. tuberculosis'', resulting in collateral destruction of the surrounding tissue. The destructive process results in a acellular, cheese-like material in the center of the granuloma which contains activated macrophages, CD4 helper T cells and multinucleated giant cells. The cheese-like appearance of caseous necrosis is due to the presence of lipids from the tubercle bacilli within the necrosis
|AnswerB=Coagulative necrosis
|AnswerBExp=[[Coagulative necrosis]] involves the denaturation of enzymes and structural proteins. Microscopically, indistinct outlines of cells are observed within dead tissues. Coagulative necrosis occurs mostly in the heart, liver, and kidneys.
|AnswerC=Liquefactive necrosis
|AnswerCExp=[[Liquefactive necrosis]] is often observed in the brain from the autocatalytic effect of hydrolytic/lysosomal enzymes released by neutrophils or necrotic cells. Liquefactive necrosis occurs in the central nervous system (CNS), most frequently in localized bacterial infections (abscesses).
|AnswerD=Fat necrosis
|AnswerDExp=[[Fat necrosis]] occurs in fatty tissue as a result of trauma or adipose tissue inflammation. Fat necrosis may be observed in breast tissue (trauma) and pancreatic tissue (leaked pancreatic lipases cause fat necrosis necrosis in acute pancreatitis).
|AnswerE=Fibrinoid necrosis
|AnswerEExp=[[Fibrinoid necrosis]] frequently occurs in blood vessels, such as small arteries, arterioles, venules, and glomerular capillaries.
|EducationalObjectives=Caseous (cheese) necrosis is a necrosis of the exudative alveolar lesions due to alveolar injury. It develops by the action of the cytotoxic T-cells that kill macrophages infected with ''M. tuberculosis'', resulting in collateral destruction of the surrounding tissue. The destructive process results in a acellular, cheese-like debris in the center of the granuloma which contains dead tubercle bacilli, activated macrophages, CD4 helper T cells and multinucleated giant cells.
|References=Campbell IA, Bah-Sow O. Pulmonary tuberculosis: diagnosis and treatment. BMJ. 2006;332:1194-7.<br>
Grosset J. ''Mycobacterium tuberculosis'' in the extracellular compartment: an underestimated adversary. Antimicrob Agents Chemother. 2003;47(3):833-6.<br>
First Aid 2014 page 134
|RightAnswer=A
|WBRKeyword=Pulmonary tuberculosis, Tuberculosis, TB, Cough, Fever, Night sweats, Weight loss, Caseating necrosis, Caseous necrosis, Necrosis, Types of necrosis
|Approved=Yes
}}