A 67 year old man with history of cirrhosis secondary to Hepatitis C and alcohol, hepatocellular carcinoma with recent TACE, presented with worsening dyspnea on exertion and positional shortness of breath. His breathing was worse when he sat upright, and better when he was supine. What’s going on?

Just to go over some terms:

• Orthodoxia: Drop in PaO2 by 5mmHg or O2sat by 5% when moving from supine to upright.
• Platypnea: Dyspnea that is induced by moving to an upright position, relieves when supine.

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Hepatopulmonary syndrome

Triad

• Chronic liver disease or portal hypertension
• Intrapulmonary vascular dilations (IPVD)
• Impaired oxygenation

Epidemiology:

Up to 25% of patients with chronic liver disease will have some degree of shunting, can occur at any stage (mild or severe)

Pathophysiology

• Not well understood but the theory is due to increased nitric oxide production and reduced NO clearance, resulting in pulmonary vasodilation (IPVDs) mostly concentrated at the lung bases.
• When upright, blood preferentially perfuse the lower lung  zones due to gravity.
• Vasodilation leads to poor gas exchange.

• This leads to a VQ mismatch

Diagnosis:

• CXR: Not helpful, might show e/o interstitial lung markings.
• CT: Can reveal IPVDs
  • Dilated peripheral pulmonary vessels
  • Inc pulmonary artery to bronchus ratios
• PFT: Not helpful
• Transthoracic contrast echo (TTCE): Can be used to demonstrate presence of intrapulmonary shunts supportive of presences of IPVDs
  • Concept of bubble study: Shooting agitated saline (with bubbles into the vasculature
  • Bubbles visible in the R heart chambers, should not be visible in the left heart chambers.
  • If presence of bubbles in the left: This is indicative of a shunt:
    • Intracardiac shunt: bubbles seen within 1 beat
    • Intrapulmonary shunts: bubbles seen after 3-8 beats.

 

Normal Echo: Notice how the agitated saline bubbles remain on the right side of circulation and do not cross over. The bubbles were filtered out by the pulmonary vasculature.

 

Echo demonstrating intrapulmonary shunting (see bubbles crossing over from the right to the left)

 

Management

• Supplemental O2 indicated if O2 sats < 88%, PaO2 < 55mmHg
• Mild to moderate: Monitor Q6-12 months
• Severe to very severe: Referral for liver transplant
• Insufficient data on other treatment options (garlic, pentoxifylline, NO synthase inhibitors, IPVD embolization, plasma exchange, oxtreotide).

Image adapted from Uptodate

Check out this article if you’re interested in the data behind pentoxifylline!