HepatoPulmonary Syndrome

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Hepato-Pulmonary Syndrome

• Prof. Dr. Mohamed El-Khashab Prof. of Hepatology
  Gastro-Entrology Zagazig University

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Definition

• HPS is a disease process with a triad of
• 1- Liver disease
• 2- Widespread intrapulmonary vasodilatation
• 3- Gas exchange abnormality results in Hypoxemia.

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The Liver diseases responsible for HPS are

• 1- Liver Cirrhosis.
• 2- Non-Cirrhotic portal hypertension
• 3- Non-Cirrhotic portal fibrosis
• 4- Extra-hepatic portal vein obstruction
• 5- Chronic Active Hepatitis
• 6- Fulminate hepatic failure

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Prevalence

• It is reported to be between 9-29 of patients
  with Liver Diseases.

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Pathophysiology

• 1- Hypoxemia due to
• a- Widespread pulmonary vasodilatation.
• b- AV communications results in direct right to
  left shunt of de-oxygenated blood
• c- Pleural spider angiomae
• N.B. Pulmonary capillary diameter is about 8-12
  um normally, which could rise up to 500um in HPS.

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Pathophysiology

• Intra-pulmonary vasodilatation is widespread but
  occurs mostly in the base of lungs thus,
  explaining orthodeoxia and platypnea. Where O2
  molecules can not reach the center of dilated
  capillaries

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Pathophysiology

• Response to breathing 100 O2 its significance
• In response to breathing 100 oxygen if PO2 rose
  to levels gt600mmHg. shunting of blood is
  unlikely, but if it failed to exceed 500ummHg.
  shunt is most probably the main mechanism of
  hypoxemia. The significance of above mentioned
  test in HPS is that if shunt is the responsible
  pathogenic factor, hypoxemia may not be resolved
  after orthotopic liver transplantation.

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Pathophysiology

• 2- Vasodilatation
• The most probable mechanism explaining persistent
  pulmonary and systemic vasodilatation is the
  imbalance of vasodilator and vasoconstrictor
  agents favoring vasodilators which could be due
  to production of the vasodilators from injured
  hepatobiliary system, or a decrease in their
  clearance by the liver, or production of a
  vasoconstrictor inhibitor.

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Pathophysiology

• 2- Vasodilatation
• Normally pulmonary vasoconstriction in response
  to hypoxemia is blunted in HPS. Numerous
  vasodilators are suspected but nitric oxide is
  the most important one. Other mediator include
  calcitonin related peptide, glucagon and platelet
  activating factor.

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Clinical Manifestations

• More than 80 of patients present with signs and
  symptoms of liver disease (e.g. ascites,
  jaundice, GI bleeding, ) but in about 18 the
  presenting symptoms and signs are related to lung
  disease.
• Respiratory signs and symptoms include dyspnea,
  cyanosis and clubbing. Platypnea and orthodeoxia.
  This picture present in 5 of cirrhotic patients
  and 88-100 of HPS patients.

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Clinical Manifestations

• There is controversy on a correlation of severity
  and liver disease (as Childs Classification) and
  HPS. Some studies have shown that severer liver
  disease accompanied by severer HPS, but others
  have failed.
• Mortality is high and is reported in 41 of
  patients with 2.5 years after presentation.

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Diagnostic Procedures

• 1- Arterial blood gas analysis PO2lt70mmg
• 2- Chest X-ray is normal in HPS or represents
  minor reticulonodular changes in the base of
  lungs.
• 3- Pulmonary functions test is normal or may
  show mild restrictive pattern due to pleural
  effusion or ascites. - Diffusion ability of
  lungs may be decrease due to intrapulmonary
  vasodilatation.

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Diagnostic Procedures

• 4- Two dimensional contrast enhanced
  echocardiography (CEEC) a contrast agent which
  produces micro-bubbles after injection into a
  peripheral vein is introduced to systemic
  circulation and is traced in heart chambers by
  trans-thoracic echocardiography. According to
  size of bubbles which are larger than normal
  diameter of pulmonary capillary bed, they are
  trapped in lungs after visualization in the right
  chamber of heart and thus could not be seen in
  left heart normally.

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Diagnostic Procedures

• However, if intrapulmonary vasodilatation or
  discrete A-V communication or intra-cardiac
  shunts exists, micro-bubbles appear in left
  ventricle and timing of their appearance
  determines whether cardiac shunt is present or
  intrapulmonary vasodilatation is responsible. If
  these micro-bubbles appear soon after their
  visualization in right heart chambers (within 3
  heart beats) it is in favor of cardiac shunts and
  if this process is delayed to after 4-6 hearts
  beats intrapulmonary vasodilatations or A-V
  communication are responsible. Contrast agents
  used commonly are air, indocyanin green ,
  agitated saline or agitated modified fluid
  gelatin solutions.

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Diagnostic Procedures

• 5- Macro aggregated albumin scanning Technetium
  99m- labeled macro-aggregated albumin is injected
  into a peripheral vein and then scanning is done
  from lungs and another viscera which receives a
  large proportion of cardiac output such as brain,
  kidney, liver or spleen. Aggregated albumin has a
  diameter about 20-50um and is trapped in normal
  capillary bed with a diameter of 8-15um but can
  pass through dilated pulmonary capillaries.

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Diagnostic Procedures

• 6- Angiography
• Type I Minimal changes with diffuse spider like
  branches due to vascular dilatations.
• Type II Patients with this type show lesions
  cause direct right to left shunt of desaturated
  blood.
• 7- CT- Scan In HPS, CT scanning of lungs may
  shows dilatation of peripheral pulmonary
  vasculature.

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Treatment

• 1- Medical therapy
• a- Indomethacin is used with the logic of
  inhibition of prostaglandin production which has
  a role of vasodilatation.

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Treatment

• b- Methylene blue is a potent inhibitor of NO
  and its intracellular mediator. It had several
  effects increase of PO2, decrease of shunt
  fraction and increase of mean pulmonary artery
  pressure, increase of pulmonary vascular
  resistance and lowered cardiac output. Beneficial
  effects on gas exchanged continued up to 10
  hours. So it might be used in the post-operative
  period of liver transplantation in cases who have
  transient hypoxemia.

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Treatment

• c- Garlic extract induced improved oxygenation
  and alveolo-arterial oxygen gradient but more
  data are needed.

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Treatment

• 2- Interventions other than liver
  transplantation
• a- Embolotherapy it is recommended for those HPS
  patients who respond poorly to breathing 100
  oxygen i.e. PO2lt150-200mmHg.

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Treatment

• b- Portal decompression with transjugular
  intrahepatic portosystemic shunt (TIPS) Portal
  decompression is suggested as a potential way for
  improving HPS. Some studies confirmed and others
  ruled out usefulness of TIPS. Overall, TIPS could
  be considered as a palliative treatment and/or as
  a bridge to orthotopic liver transplantation in
  severe hypoxemic HPS.

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Treatment

• 3- Liver transplantation Orthotopic Liver
  transplantation (OLT) is the most important and
  effective therapeutic modality of HPS. The rate
  of improvement of HPS patients undergoing OLT is
  about 80. OLT is not only indicated for
  improvement of liver function and portal
  decompression but also for treatment of HPS and
  resultant hypoxemia.

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Treatment

• 3- Liver transplantation It is observed that the
  more the hypoxemia, the more mortality rate in
  the perioperative period. In severe hypoxemia OLT
  was considered as absolute contraindication.

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Thank You