What causes shock in disseminated tuberculosis (TB)?

Causes of Shock in Disseminated Tuberculosis

Shock in disseminated tuberculosis is primarily caused by sepsis with systemic inflammatory response syndrome, adrenal insufficiency, and immune dysregulation leading to vasodilation and vascular permeability.

Pathophysiological Mechanisms

1. Septic Shock

• Mycobacterium tuberculosis can cause septic shock through several mechanisms:
  • Lipoarabinomannan (LAM) on the mycobacterial cell wall interacts with antigen-presenting cells, triggering inflammatory cascades 1
  • Systemic inflammatory response with hypercytokinemia leads to vasodilation and increased vascular permeability 2
  • Endothelial dysfunction results in impaired tissue perfusion and organ dysfunction
  • Disseminated infection with high mycobacterial load overwhelms host defenses

2. Adrenal Insufficiency

• Bilateral adrenal involvement is common in disseminated TB:
  • Direct infiltration of adrenal glands by M. tuberculosis 3
  • Destruction of adrenal tissue leads to primary adrenal failure (Addison's disease)
  • Resulting glucocorticoid deficiency impairs vascular tone maintenance and stress response
  • Mineralocorticoid deficiency causes refractory hyponatremia and hypotension

3. Immune Dysregulation

• Disseminated TB causes profound immune system alterations:
  • T-cell dysfunction with impaired IFN-γ production 2
  • Excessive inflammatory cytokine production (TNF-α, IL-6)
  • Complement consumption and activation 2
  • Defective neutrophil function and bacterial killing

Clinical Presentation and Diagnosis

• Patients with disseminated TB and shock typically present with:

  • Persistent hypotension despite fluid resuscitation
  • Elevated lactate levels and metabolic acidosis
  • Multi-organ dysfunction (respiratory, renal, hepatic)
  • Evidence of disseminated TB (miliary pattern on chest imaging, extrapulmonary involvement)

• Diagnostic approach:

  • Blood cultures and sputum examination with molecular testing
  • Adrenal function assessment (cortisol levels, ACTH stimulation test)
  • Imaging to identify extent of dissemination
  • Tissue sampling from accessible sites for mycobacterial culture

Management Considerations

1. Antimicrobial Therapy

• Early initiation of anti-TB therapy is critical for survival in TB-related septic shock 4
• Patients receiving appropriate anti-TB therapy within 24 hours of hypotension onset have significantly higher survival rates (54.5%) compared to those with delayed treatment (4.8%) 4
• Standard regimen includes isoniazid, rifampin, pyrazinamide, and ethambutol 2

2. Hemodynamic Support

• Norepinephrine is the first-line vasopressor for TB-related septic shock 2
• Fluid resuscitation with crystalloids (20-30 ml/kg) to maintain mean arterial pressure >65 mmHg 5
• Continuous monitoring of hemodynamic parameters and tissue perfusion

3. Adrenal Support

• Hydrocortisone supplementation for suspected adrenal insufficiency 5
• Mineralocorticoid replacement may be necessary for electrolyte management
• Monitor for and correct electrolyte abnormalities, particularly hyponatremia

4. Additional Considerations

• Evaluate for paradoxical reactions, especially in HIV-infected patients 2
• Consider adjunctive corticosteroids for severe inflammatory responses
• Address potential immune reconstitution inflammatory syndrome (IRIS) in HIV co-infection

Prognosis and Pitfalls

• Mortality in MTB septic shock is significantly higher (79.2%) compared to other bacterial septic shock (49.7%) 4

• Common pitfalls:

  • Delayed recognition of TB as the cause of septic shock
  • Failure to initiate anti-TB therapy promptly
  • Overlooking adrenal insufficiency
  • Inadequate source control of disseminated infection

• Keys to improved outcomes:

  • High index of suspicion in at-risk populations
  • Early appropriate antimicrobial therapy
  • Comprehensive supportive care
  • Monitoring for and managing complications

Understanding these mechanisms is crucial for early recognition and appropriate management of this life-threatening condition.