Contents

1. 1 Definition
2. 2 Pathophysiology
3. 3 Treatment
4. 4 References

Definition

• Liver disease --> excessive pulmonary microvascular dilation +/- AVMs --> altered gas exchange --> hypoxemia
• No relationship b/w severity of HPS and severity of liver disease

• Diagnostic criteria:
• PaO2 <80 mmHg or Aa gradient >15 mmHg on room air
• Positive contrast echocardiography or abnormal uptake in the brain with radioactive lung-perfusion scanning (see below for explanations)
• Liver disease

Pathophysiology

Increased pulmonary vasodilatation caused by:

• Increased nitric oxide production in the lungs (no clear explanation)

• Increased lung angiogenesis factors (no clear explanation)

Mechanism of Hypoxemia

• Diffusion-perfusion limitation
• Capillaries dilated too much --> O2 can't traverse to bind to RBC in the core of the vessel
• If pt has elevated cardiac output --> decreased transit time in capillary bed --> even less O2 binding
• Can be corrected w/ supplemental O2

• Ventilation-perfusion mismatch
• Vascular dilation --> increased perfusion relative to preserved ventilation
• If pt has atelectasis/edema/PNA --> localized hypoxic alveoli --> impaired hypoxia induced vasoconstriction due to HPS --> even more V/Q mismatch
  
• Can be corrected w/ supplemental O2

• Shunts
• HPS associated w/ pulmonary and extrathoracic AVMs --> blood flow that bypasses pulmonary capillary beds and never gets oxygenated
  
• CanNOT be corrected w/ supplemental O2

Symptoms of HPS

• Dyspnea, cyanosis, clubbing

• Platypnea
• Dyspnea in upright position that is alleviated when supine (likely due to orthodeoxia)

• Orthodeoxia
  • Hypoxemia in upright position that is alleviated when supine
  • Vascular tone remains fixed in all parts of the lung in HPS --> when upright, you decrease the surface area of gravity dependent alveolar units with better ventilation capabilities --> worse V/Q matching

Diagnosis of HPS

• Best test = transthoracic echo w/ agitated saline injected in peripheral vein
• Bubbles are suppose to get trapped in pulmonary capillary bed because they are too big to pass through
  
• In HPS, capillaries dilate --> bubbles can now pass through
• If bubbles seen in left atrium 3 or more cardiac cycles after bubbles seen in right atrium --> intrapulmonary vascular dilation (if less than 3, could be due to intracardiac shunt)

• Pts w/ liver disease may have other lung disease that impairs gas exchange, somake sure to evaluate for:
  • Hepatic encephalopathy --> aspiration PNA
  • Emphysema from a1-AT deficiency
  • Hepatic hydrothorax (pleural effusion)
  • Atelectasis from massive ascites
  • Muscle wasting --> restrictive lung disease
  • Pulmonary HTN (entity called portopulmonary HTN)
  • Hepatic synthetic dysfunction --> PE
  • Chronic medical illness unrelated to liver disease (RAD, asthma, COPD, ILD, sarcoid, cancer, etc)

Prognosis of HPS

• Higher mortality compared to liver pts w/o HPS
  • Severe hypoxemic resp. failure is usually NOT the cause of death
  • Death from complication of liver disease (GIB, coagulopathy, sepsis, heptagonal syndrome, etc)
• Worse functional class and quality of life compared to liver pts w/o HPS

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Treatment

• Supplemental O2
  • No data to confirm clinical benefit (but makes sense...)
    
• Pentoxifylline
  • Reduces nitric oxide synthesis
  • Clinical trials have resulted in conflicting conclusions of its benefit in HPS
    
• Embolization if AVM exists
• Vasodilator therapy (iNO, sildenafil) usually not used but could potentially be useful in the setting of other pulmonary disease causing VQ mismatch
• Liver transplant
  • Only proven successful treatment
  • Improves 5 year survival rate compared to no transplant
  • Hypoxia may persist or even worsen after transplant
  • Normalization of gas exchange may take 6-12 months
    • More severe pre-op hypoxia = longer time to resolution of hypoxia

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