Updated: 5/13/2019

Mycobacterium Tuberculosis

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Snapshot
  • A 33-year-old man presents to his primary care physician for a cough and generalized malaise. His symptoms are associated with 2 episodes of mild hemoptysis and night sweats. He denies any sick contacts or recent travels; however, he states he was released from prison 4 months ago. Physical examination is unremarkable. A chest radiograph is obtained, which demonstrates pulmonary infiltrates and cavitations in the upper lobe.
Introduction
  • Classification
    • acid-fast, rod-shaped, obligate aerobic, intracellular bacteria 
  • Epidemiology
    • risk factors
      • traveling to endemic areas (e.g., Angola and the Central African Republic)
      • close contact (e.g., prisons, nursing homes, homeless shelters, and hospitals)
      • immunocompromised (e.g., HIV, immunosuppressive medications, and diabetes)
  • Transmission
    • airborne spread of droplet nuclei from patients with infectious tuberculosis (TB)
  • Microbiology
    • acid-fast on Ziehl-Neelsen staining 
    • immune system itself causes damage
      • TB contains no endotoxins or exotoxins
    • cord factor
      • inhibits leukocyte migration
      • causes characteristic serpentine growth pattern
      • induces TNF-α release
    • tuberculin
      • triggers cell-mediated immunity → caseation and granulomas
      • triggers delayed hypersensitivity reaction
      • a surface protein
    • sulfatides
      • prevent phagosome-lysosome fusion
  • Pathogenesis
    • the infected person coughs up small droplets containing the bacteria that reaches the terminal alveoli of the uninfected person
      • alveolar macrophages are recruited, which eventually become infected, transporting the microbe to deeper tissues 
      • more alveolar macrophages are recruited, leading to granuloma formation 
        • granulomas are formed to "wall off" TB, where it lies dormant  
    • secondary TB occurs when the patient's immune system is weakened (e.g., newly acquired HIV infection, being on immunosuppressant medications, malignancy, and poor nutrition)
      • TB infection typically manifests in the apical/posterior segments of the lung due to its increased oxygen tension
Presentation
  • TB can lead to pulmonary and extrapulmonary manifestations
    • lymph nodes (tuberculous lymphadenitis)
    • pleura
    • genitourinary
    • skeleton (can lead to Pott disease with spinal involvement)
    • meninges
    • gastrointestinal system
    • pericardium (tuberculous pericarditis)
  • Symptoms
    • typically asymptomatic in primary TB
    • cough
    • hemoptysis
    • fever
    • night sweats
    • malaise
  • Physical exam
    • weight loss
    • lymphadenopathy
    • dullness to percussion or decreased/absent breath sounds if there is a pleural effusion
    • back pain in spinal TB (Pott disease)
Imaging
  • Chest radiograph
    • indication
      • initial imaging study in the evaluation of TB
    • findings
      • middle or lower lung infiltrate (suggestive of primary infection)
      • upper lobe infiltrate (suggestive of latent TB reactivation)
      • cavitary lesions 
      • Ghon complex (lobar or perihilar lymph node involvement) 
Studies
  • Sputum acid-fast testing
    • demonstrates acid-fast bacilli
  • Real-time nucleic acid amplification
    • rapidly confirms TB and is considered the first-line diagnostic study
  • Tuberculin skin test (TST)
    • most widely used to screen for latent TB infection
    • a delayed-type hypersensitivity reaction against purified protein derivative (PPD) is induced
      • the size of the induration is assessed after 48-72 hours
      • note, patients who received the Bacille Calmette-Guerin (BCG) vaccination will have false positive results
      • a false negative result can be seen in immunocompromised patients
    • interpretation (positive results)
      • ≥ 15 mm in patients with no risk factors
      • ≥ 10 mm in patients with risk factors (e.g., healthcare worker, traveling to endemic areas, and being in prison)
      • ≥ 5 mm in immunocompromised patients (e.g., HIV, on immunosuppressants, and organ transplant recipients)
      • positive tests require a chest radiograph
  • Interferon-γ release assay
    • measures interferon levels released by the patient's immune system in response to TB antigens
      • the results are not affected by previous BCG vaccination
Differential
  • Lung cancer
    • differentiating factor
      • patients will not have positive TB studies
Treatment
  • Medical
    • rifampin, isoniazid, pyrazinamide, and ethambutol therapy
      • indication
        • first-line treatment for active pulmonary TB infection for 4 months
          • after 4 months, treatment involves isoniazid and rifampin
      • comments
        • isoniazid can cause peripheral neuropathy as well as sideroblastic anemia due to vitamin B6 deficiency, thus warranting pyridoxine in hopes to prevent this development from occurring  
          • can also cause hepatitis
        • ethambutol can cause optic neuropathy 
        • mutations in RNA polymerase lead to rifampin resistance 
    • isoniazid monotherapy
      • indication
        • prophylactic treatment for latent primary TB after active TB has been excluded 
Complications
  • Pott disease
  • Miliary or disseminated TB
  • Meningitis
  • Pericarditis
  • Lymphadenitis
  • Adrenal insufficiency
 

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Questions (10)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.MC.75) A 38-year-old woman presents to her primary care provider after a 3-month trip to China. She complains of chills and a cough for the past 2 weeks. Vital signs are notable for a body temperature of 101°F, and the patient’s weight has decreased by 4 kg since her last visit 3 months ago. A chest radiograph is obtained and shown in Figure A. The patient’s whole blood is incubated with a peptide, and ELISA assay reveals high amounts of IFN-gamma. What is the primary mechanism for the pulmonary tissue destruction evident on the patient’s chest radiograph? Review Topic

QID: 106769
FIGURES:
1

Proteolytic enzymes released by bacteria

3%

(1/39)

2

Invagination of the lysosomal membrane with uptake of cytoplasmic material

3%

(1/39)

3

Macrophages ingested with microbes are activated by CD4+ effector T cells

69%

(27/39)

4

Deposition of immune complexes with resulting inflammatory response

15%

(6/39)

5

Excessive presence of peroxides and free radicals

3%

(1/39)

M1

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PREFERRED RESPONSE 3

(M1.MC.29) A 44-year-old Caucasian male presents with a fever, recent weight loss, and a cough productive of bloody sputum. A chest X-ray and CT scan were performed, revealing cavities near the apex of his lungs. The patient is started on rifampin, isoniazid, ethambutol and pyrazinamide. Formation of the cavities in the patient's lungs is mainly mediated by: Review Topic

QID: 100832
1

TH1 cells

71%

(148/208)

2

Toxin secretion by the bacterium

9%

(19/208)

3

B-cells

3%

(6/208)

4

NK cells

8%

(16/208)

5

Apoptosis

8%

(16/208)

M1

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PREFERRED RESPONSE 1

(M1.MC.129) A 78-year-old man presented to his primary physician with a 3-month history of weight loss, fever, fatigue, night sweats, and cough. He is a former smoker. A recent HIV test was negative. A CT scan of the chest reveals a 3 cm lesion in the lower lobe of the left lung and calcification around the left lung hilus. A sputum smear was positive for acid fast organisms. These findings are most consistent with which of the following: Review Topic

QID: 100932
1

Primary tuberculosis

69%

(175/254)

2

Adenocarcinoma

3%

(7/254)

3

Miliary tuberculosis

2%

(6/254)

4

Coccidioidomycosis infection

1%

(2/254)

5

Secondary tuberculosis

24%

(62/254)

M1

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PREFERRED RESPONSE 1
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(M1.MC.11) The lung of a 45-year-old Caucasian male who died from Mycobacterium tuberculosis infection reveals the following at autopsy (Image A). Of the steps leading to the formation of this structure, which occurs first? Review Topic

QID: 100814
FIGURES:
1

Activation of macrophages by T-lymphocytes

17%

(25/148)

2

Th1 cell activation

30%

(44/148)

3

Bacterium-mediated inhibition of phagosome-lysosome fusion

50%

(74/148)

4

Formation of epithelioid cells

1%

(1/148)

5

Formation of giant cells

1%

(2/148)

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PREFERRED RESPONSE 3
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