What causes a low Systemic Vascular Resistance (SVR) state in patients with cirrhosis?

Pathophysiology of Low Systemic Vascular Resistance in Cirrhosis

The primary mechanism of low systemic vascular resistance (SVR) in cirrhosis is splanchnic arterial vasodilation, which results from excessive production of vasodilatory substances, particularly nitric oxide, in response to portal hypertension. 1

Pathophysiological Cascade Leading to Low SVR

1. Initial Portal Hypertension Development

• Portal pressure initially increases due to:
  • Structural changes: Architectural distortion from fibrosis and regenerative nodules (70% of increased resistance)
  • Functional component: Increased intrahepatic vascular tone due to endothelial dysfunction and reduced nitric oxide bioavailability within the liver (30% of increased resistance) 1

2. Splanchnic Vasodilation

• Portal hypertension triggers splanchnic arterial vasodilation through:
  • Increased production of vasodilatory substances:
    • Nitric oxide (NO)
    • Carbon monoxide
    • Prostacyclin
    • Endocannabinoids 1
  • Shear stress in vascular endothelial cells upregulates endothelial nitric oxide synthase (eNOS) 2
  • Portosystemic collaterals develop, allowing vasodilators to bypass liver metabolism 2

3. Systemic Hemodynamic Consequences

• Splanchnic vasodilation leads to:
  • Decreased effective circulating volume ("effective hypovolemia")
  • Reduced SVR
  • Increased cardiac output
  • Hyperdynamic circulation 1, 2

4. Compensatory Mechanisms

• Activation of vasoconstrictor systems:
  • Renin-angiotensin-aldosterone system (RAAS)
  • Sympathetic nervous system
  • Arginine-vasopressin secretion 1
• These compensatory mechanisms contribute to:
  • Sodium and water retention
  • Ascites formation
  • Hepatorenal syndrome 1, 3

5. Vascular Hyporesponsiveness to Vasoconstrictors

• Reduced alpha-adrenergic responsiveness in cirrhosis:
  • Decreased sensitivity to vasoconstrictors like phenylephrine 4
  • Maintained beta-adrenergic responsiveness 4
• This vascular hyporesponsiveness further contributes to persistent vasodilation despite activated vasoconstrictor systems 2

Progression with Disease Severity

• The hyperdynamic circulation worsens with:
  • Advanced cirrhosis (Child-Pugh class B and C)
  • Increased inflammation in acute-on-chronic liver failure 1
  • Decreased ability to increase effective blood volume in response to volume expansion 5

Clinical Implications

• Patients with pre-existing hypertension may become normotensive as cirrhosis develops 6
• Low SVR contributes to complications:
  • Ascites formation
  • Hepatorenal syndrome
  • Hepatopulmonary syndrome 7
  • Increased susceptibility to shock 1

Therapeutic Considerations

• Treatments targeting portal hypertension may indirectly affect SVR:
  • Non-selective beta-blockers reduce portal venous inflow by causing splanchnic vasoconstriction 1
  • Transjugular intrahepatic portosystemic shunt (TIPS) bypasses the increased resistance 1, 3
  • Albumin infusion addresses arterial underfilling 1, 3

Monitoring Considerations

• Assessment of volume status and cardiac function is essential in critically ill cirrhotic patients 1
• Bedside transthoracic echocardiography helps evaluate fluid status and cardiac function 1
• Careful monitoring during fluid resuscitation is crucial to avoid overresuscitation 1

Understanding this pathophysiology is essential for managing complications of cirrhosis and developing targeted therapies to address the hyperdynamic circulation that characterizes advanced liver disease.