Tuberculosis

Tuberculosis

1. Affect the lungs

   • Normal structure
     • The right lung consists of three lobes: the superior, middle, and inferior lobes
     • Blood Supply
       • Pulmonary artery that arises from the pulmonary trunk and carries deoxygenated, arterial blood to the alveoli
       • Once the blood is oxygenated, it drains from the alveoli by way of multiple pulmonary veins, which exit the lungs through the hilum
     • The left lung consists of two lobes: the superior and inferior lobes
     • Pyramid-shaped, paired organs that are connected to the trachea by the right and left bronchi
     • Nervous Innervation
       • The parasympathetic system causes bronchoconstriction, whereas the sympathetic nervous system stimulates bronchodilation
       • Sensory nerve fibers arise from the vagus nerve, and from the second to fifth thoracic ganglia
       • The pulmonary plexus is a region on the lung root formed by the entrance of the nerves at the hilum

2. Caused by

   • Mycobacterium tuberculosis
     • Types of Mycobacteria

3. Epidemiology

   • In 2017, 10 million people fell ill with TB, and 1.6 million died from the disease (including 0.3 million among people with HIV)
   • Globally, TB incidence is falling at about 2% per year. This needs to accelerate to a 4–5% annual decline to reach the 2020 milestones of the End TB Strategy
   • An estimated 54 million lives were saved through TB diagnosis and treatment between 2000 and 2017

4. Transmission

   • Airborne, ingestion, touch

5. Risk factors

   • Recently infected with TB
   • Medical conditions that weaken the immune system
     • HIV infection / Substance abuse / Silicosis / Diabetes mellitus / Severe kidney disease / Low body weight / Organ transplants / Head and neck cancer / Corticosteroids or organ transplant / Crohn’s disease

6. Signs and symptoms

   • Cough
     • Causes of productive cough
   • Fever
     • Mechanism of fever
       • Pyrogen > Macrophages and immune cells are activated > IL-1, IL-6, IL-8, TNF-a, interferon gamma > Laminae terminalis > Pre-optic region > Posterior hypothalamic region > Activate phospholipase > Induce the production of prostaglandins E2 > Prostaglandins E2 will change the temperature set point > Peripheral vasoconstriction > Norepinephirne increases thermogenesis in adipose tissue > Shivering
   • Weight loss
   • Blood stained sputum
   • Night sweats

7. Investigations

   • History and physical examinations
   • CBC
   • Kidney and liver function tests
   • Inflammatory markers and (ESR)
   • CSF
   • Biopsies or mediastinoscopy
   • Histological examinations
   • Chest X-rays, CT scan, MRI
     • X-ray
       • Typical Post-Primary)
       • Atypical (Primary)
   • Laboratory diagnosis
     • Starts with the collection of a specimen
       • Early morning sputum / Bronchoalveolar lavage / Gastric aspirate / CSF / Lymph node biopsy or aspirates / Other tissue biopsies
     • Microscopy
       • Ziehl Neelsen Staining / Acid Fast Staining (Specificity of 98% / Low sensitivity < 50% / Qualitative and quantitative)
       • Fluorescent staining (Auramine-Rhodamine Fluorochrome) (Rapid and more sensitive / Expensive / Dye toxicity)
     • Culture (The Gold Standard)
       • Solid Media: Agar based (Middlebrook 7H10) / Egg based (Löwenstein-Jensen medium) / Culture is incubated at 35 C, 5-10%, CO2 and in high humidity. It takes 4-8 weeks / can be reported negative after 8 weeks / Rough, tough and buff colonies
       • Liquid Media: BACTEC 460 / Mycobacteria Growth Indicator Tube (MGIT) / Positive in 2-3 weeks / can be reported negative after 6 weeks
       • Radiometric culture has faster results (3-4 days)
     • Molecular Methods
       • PCR / Molecular Line Probe Assays (LPA): DNA-based diagnostic test that identifies multidrug-resistant TB (MDR TB) / Xpert MTB/RIF Assays: new NAAT that quickly identifies possible rifampicin resistance
     • Tuberculin Test (Mantoux tuberculin skin test)
       • Injecting tuberculin intradermally, which contains purified protein derivative from mycobacteria tuberculosis (PPD tuberculin) / Induration measured after 48-72 hours
         • A positive test indicates the exposer to a mycobacterium / It can be positive in case of active TB (disease), people with latent infections, and people who had received BCG vaccination / A positive test in people with normal immune system will be a 10 mm induration after 48-72 hours
     • Serology
       • Interferon-Gamma Release Assays (IGRAs)
         • Measures the person’s immune reactivity to mycobacteria tuberculosis / Test that detects IFN-g that is released by WBC when mixed with antigens derived from M. tuberculosis / The results within 24 hours / BCG vaccination does not cause a false positive IGRA test result
   • Of TB Contacts
     • Assessment of the person's health / skin test / Contacts with skin test reaction of an induration diameter of >5 mm or with any symptoms of TB disease > diagnostic tests > chest radiograph / Specimen collection from sputum depends on the case and not recommended for healthy contacts with normal chest radiographs / Contacts with susceptibility to TB > examination and diagnostic testing > regardless of whether they have a positive skin test result or are ill

8. A Notifiable disease

   • Other notifiable diseases (UAE)

9. Pathogenesis

   • Histology

10. Management

    • Approach Considerations
      • Isolate / Negative pressure / Masks / Continue isolation until sputum smears are negative for 3 consecutive determinations
        • Airborne precautions
          • Masks and Respirators
            • N95 Respirator / Powered Air-Purifying Respirator (PAPR)
    • Drugs
      • Isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months ( Initial phase) / Isoniazid and rifampin for 4 more months (Continuation phase)
        • Pyrazinamide > Serum uric acid assessments / Ethambutol > Visual acuity and red-green color perception testing (Ishihara test) for color blindness
    • Evaluating response to treatment
      • Clinical evaluation / Bacteriological examination / Chest radiograph

11. BCG vaccine

    • Bacille Calmette-Guerin vaccine contains a live but very weakened form of a bacteria called Mycobacterium bovis
      • Not given to immunocompromised people and pregnant

12. Complications

    • Extra pulmonary TB
      • CNS (Meningitis) / Lymphatics (Scrofula / Pleura (Tuberculosis pleurisy) / Disseminated (Miliary TB) / Bones and joints of spine (Pott’s disease) / Genitourinary ( Urogenital TB)

13. Prognosis

    • If treated (Excellent prognosis) / If not treated (Mortality rate > 50%)

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