Tuberculosis: Pathology review

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Questions

USMLE® Step 1 style questions USMLE

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A 37-year-old male with a past medical history of Crohn disease treated with infliximab is admitted to the hospital after initiation of therapy for active tuberculosis. On day four of hospitalization, the patient reports worsening pain in the left great toe. Temperature is 37.0°C (98.6°F), pulse is 80/min, respirations are 16/min, blood pressure is 120/64 mmHg, and O2 saturation is 93% on room air.  Physical exam and laboratory findings are demonstrated below:  


Image reproduced from Wikimedia Commons  

 Laboratory Value  Result 
 Alanine aminotransferase (ALT, GPT)  150 U/L 
 Aspartate aminotransferase (AST, GOT)  175 U/L 
 Alkaline phosphatase   205 U/L 
 
Which of the following describes the mechanism of action of the medication likely causing this observed side effect?

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While doing your rounds, you meet Josh, an HIV-positive 25-year-old man who presents with a 2-month history of non-productive cough. He also describes poor appetite and significant weight loss, fever, night sweats, and excessive tiredness. He denies dyspnea or hemoptysis. Physical examination is unremarkable. A PPD intradermal test was performed and it was negative. His chest X-ray showed a peri-hilar lesion with central necrosis and calcification as well as lymphadenopathy of nearby nodes.

Now, this person seems to suffer from tuberculosis, or TB for short. But first, a bit of microbiology. Mycobacteria tuberculosis are slender, rod-shaped, Gram positive bacteria that need oxygen to survive, in other words, they’re “strict aerobes”. One piece of high-yield information is that although they are classified as Gram positive - meaning they have an outer cell wall, it is the same wall that makes the bacteria special. This is because Mycobacterium have an unusually waxy cell wall made of mycolic acid, which is composed of long chains of branched lipids, which won't stain with Gram. This makes them “acid-fast” so the Ziehl-Neelsen stain has to be applied, a dye that will not be washed away by acids, giving the bacteria a bright red color. The wall also makes the bacteria incredibly hardy, and allows them to resist weak disinfectants, antibiotics, and allow them to survive on dry surfaces for months at a time.

Okay, so Tuberculosis is a type of pulmonary infection caused by Mycobacterium tuberculosis, sometimes just called TB bacteria. Before we start, you need to know that there are a few high-yield risk factors for TB. These include immunosuppression, like in people with HIV; iatrogenic immunosuppression, like in people who undergo treatment with corticosteroids; systemic diseases such as COPD, diabetes, and end-stage renal disease; extremes of age; substance abuse; and populations with an increased risk of exposure, like the prison populations, homeless people, those born in an endemic country, and health care workers.

Summary

Tuberculosis (TB) is a chronic infectious disease caused by the bacterium Mycobacterium tuberculosis. The pathophysiology of TB involves a complex interplay between the bacterium and the immune system of the host. When a person inhales air contaminated with M. tuberculosis, the bacteria can enter the lungs and infect the alveolar macrophages, which are the immune cells responsible for clearing foreign particles from the lungs. In most cases, the immune system can contain the infection and prevent the development of active TB disease.

However, in some cases, the bacteria can evade the immune system and establish a latent infection, in which the bacteria remain dormant in the body for years or even decades. Latent TB infection is not contagious and does not cause symptoms, but it can progress to active TB disease if the immune system becomes weakened, such as in people with HIV/AIDS, malnutrition, or other conditions that compromise the immune system.

In active TB disease, the bacteria can multiply and spread throughout the body, causing symptoms such as cough, fever, weight loss, and night sweats. The infection can also damage the lungs and other organs, leading to complications such as pleural effusion, pneumonia, and meningitis.

Sources

  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
  4. "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
  5. "Fishman's Pulmonary Diseases and Disorders, 2-Volume Set, 5th edition" McGraw-Hill Education / Medical (2015)
  6. "Dyspnea" CRC Press (2014)
  7. "Extrapulmonary tuberculosis: an overview" Am Fam Physician (2005)
  8. "Tuberculosis" The Lancet (2011)
  9. "Acute Forms of Tuberculosis in Adults" The American Journal of Medicine (2009)
  10. "Les tuberculoses extrapulmonaires" Revue de Pneumologie Clinique (2015)
  11. "Patogénesis de la tuberculosis y otras micobacteriosis" Enfermedades Infecciosas y Microbiología Clínica (2018)
  12. "Perspectives on Advances in Tuberculosis Diagnostics, Drugs, and Vaccines" Clinical Infectious Diseases (2015)
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