Hepatopulmonary syndrome (HPS) is characterized by liver disease, intrapulmonary vasodilation, and impaired oxygenation. It is caused by an imbalance of vasodilator and vasoconstrictor agents produced by the damaged liver that cause widespread pulmonary vasodilation. This leads to ventilation-perfusion mismatching and hypoxemia. While no medical treatments are effective, liver transplantation can completely resolve HPS.

1. HEPATOPULMONARY
SYNDROME
DR.BHARAT

2. DEFINITION
HPS is a disease process with a triad of
• 1- cirrhosis or portal hypertension.
• 2- widespread intrapulmonary vasodilation on CE-Transthoracic Echo
• 3- A widened age-corrected alveolar-arterial oxygen gradient (>15mmHg)

3. • The most common liver disease responsible for HPS is liver cirrhosis.
• Other liver diseases may contribute ;
- Non cirrhotic portal hypertension.
- Extrahepatic portal vein obstruction.
- Chronic active hepatitis.
- Fulminant hepatic failure

4. PATHOPHYSIOLOGY
I) Vasodilatation: Persistent pulmonary and systemic vasodilatation is mostly
explained by the imbalance of vasodilator and vasoconstrictor agents favoring
vasodilators. This could be due to:
a- Overproduction of the vasodilators from injured hepatobiliary system.
b- Decrease in their clearance by the liver.
c- Production of a vasoconstrictor inhibitor.
D- Some degree of inhibition of hypoxic pulmonary vasoconstriction.

5. POSSIBLE MEDIATORS OF VASCULAR DILATATION IN
HPS
• #Increased Pulmonary Vasodilators # Decreased vasoconstrictors
• Glucagon - Prostaglandin F2a
• Atrial natriuretic peptide -Angiotensin I
• Substance P
• Platelet-activating factor
• Prostaglandin I2 or E1
• Nitric oxide

6. II) HYPOXEMIA:
The main pathophysiologic event underlying hypoxemia is
widespread pulmonary precapillary and capillary vasodilatation.
- Pulmonary capillary diameter is normally about 8-15
micrometer and this could rise up to 100 micrometer in HPS.
- In addition, there is distinct arterio-venous (AV)
malformations and direct AV communications.
- Pleural spider angiomas may also form.

7. VENTILATION PERFUSION ( V/Q) MISMATCH: -
-Results from widespread pulmonary vasodilatation and decreased V/Q ratio in
alveolar-capillary units leading to low pressure of oxygen in arterial blood
( PaO2) and low oxygen (O2) content of the blood leaving these units.
-This hypoxemia is correctable by breathing 100% oxygen.

9. DIFFUSION IMPAIRMENT
• Excessive vasodilatation causes O2 molecules not to reach the center of
dilated capillaries readily.
• Increased cardiac out put and decreased transition time of blood through
pulmonary vascular bed on the other hand impairs diffusion, this is called
diffusion-perfusion defect or alveolar capillary oxygen disequilibrium.

10. RIGHT TO LEFT SHUNTING OF THE BLOOD
• This results from direct arterio-venous communications that have no contact
with breathed air.
• If numerous, they can give rise to severe hypoxemia unresponsive to
breathing 100% oxygen.

12. CLINICAL FEATURES
• More than 80% of patients present with symptoms and signs of liver disease.
• In less than 20%, the presenting symptoms and signs are related to lung
disease.
• These include dyspnea, platypnea and orthodeoxia.

13. ON PHYSICAL EXAMINATION
• Patient with HPS may present with spider angioma, digital clubbing and
peripheral cyanosis.
• most persons will present with the signs and symptoms of liver disease,
including gastrointestinal bleeding, esophageal varices, ascites, palmar
erythema, and splenomegaly

14. DISORDERS ASSOCIATED WITH HPS
• Primary biliary cirrhosis • Chronic active hepatitis
• Fulminant hepatic failure • Chronic hepatic allograft rejection
• Nodular regenerative hyperplasia • Congenital hepatic fibrosis
• Biliary atresia • Budd-Chiari syndrome
• a1-antitrypsin deficiency • Atrial septal defect
• Post pneumonectomy • Post pulmonary emboli

15. • Dyspnea (18%); may be accompanied by platypnea and orthodeoxia.
• – Platypnea: an increase in dyspnea in the upright position which improves in
the recumbent position.
• – Orthodeoxia: a decrease of > 10 mmHg in PaO2 or 5% Spo2 when changing
from the recumbent to the seated position.
• Platypnea and orthodeoxia occur because the pulmonary AVMs occur
predominantly in the bases of the lungs
• Therefore, when sitting up or standing, blood pools at the bases of the lung
with resultant increased AV shunting
• Portal hypertension + spider nevi + clubbing + hypoxemia -highly suggestive of
HPS.

17. DIAGNOSIS:
• Arterial blood gas analysis : Performed in the supine and sitting positions.
• Chest X-ray and chest CT: Are normal or show non-specific minor
reticulonodular changes in the base of the lungs and /or dilatation of the
peripheral pulmonary vasculature.

18. • Pulmonary function tests: commonly show decreased diffusion ability of the
lungs pointing to intrapulmonary vasodilatation.
• Two dimensional contrast enhanced echocardiography (CEEC): Is the method
of choice for diagnosing intrapulmonary vasodilatation and is the most
sensitive procedure designed for this purpose.

19. • CEEC , however, lacks specificity in that in chronic liver disease the prevalence
of pulmonary vasodilatation is about 20% by this method despite normal gas
exchange status.
• Hence, Contrast enhanced trans-esophageal echocardiography is more
sensitive than trans-thoracic echocardiography, and correlates more with gas
exchange abnormality.

20. MACRO AGGREGATED ALBUMIN SCANNING:
• Technetium 99m- labeled macroaggregated albumin is used.
• 99mTcMAA is injected IV and uptake detected in lungs and brain.
• Advantage: Specific for HPS even in the presence of intrinsic lung
diseases. Hence it helps to distinguish hypoxemia from HPSfrom that
due to parenchymal disease if both are present.
• The estimated sensitivity of this method for diagnosing intrapulmonary
vasodilatation is about 84% and its specificity is 100%.
• In addition, it allows quantification of shunt, but cannot differentiate
from intracardiac and intrapulmonary shunt.

21. • Pulmonary angiography:
• Two types: Type 1 and type 2
• Advanced type of type 1 and type 2 responds poorly to oxygen.

22. TYPE I
• minimal type - with
diffuse spider like
branches
• advanced type - with a
blotchy, spongy
appearance
• (more common)
• -Responds to breathing
100% oxygen.
• Liver transplant is helpful

23. TYPE II:
-vascular lesions as vascular
dilatations representing A-V
communications
-(less common)
-Responds poorly to
breathing oxygen and liver
transplantation is not as
suitable as for type I
vascular lesions.
- Embolisation is treatment
of choice.

24. • TypeⅡpatients:
embolization, since
these lesions fail to
regress with liver
transplant.

26. TREATMENT
• No medical therapy has been shown to improve patients with HPS.
• Many agents have been tried unsuccessfully,
• • Norfloxacin • Glucocorticoids
• Indomethacin • Plasma exchange
• Chronic ambulatory oxygen therapy • Somatostatin analog
• Pulmonary embolization • Sympathomimetic drugs
• Liver transplantation • b-blockers
• Methylene blue ( Nitric oxide inhibitors )

27. • Pentoxifylline, a PDE4 inhibitor that interferes with tumour necrosis factor
(TNFa) synthesis.
• In a pilot study of 10 children, 3 months of treatment was associated with a
significant increase in Pao2 (>10mmHg in all patients)
• However the treatment effect disappeared 3 months after discontinuation.
• Drug discontinuation was due to side effects.
• A pilot study of pentoxifylline in adults showed no significant change in Pao2.
• The drug was poorly tolerated due to gastrointestinal toxicity.

28. • Adrenergic blocking agents and direct pulmonary vasoconstrictors
– Directly influence pulmonary vascular tone
– No significant improvement in arterial oxygenation
• Somatostatin
– Inhibits the secretion of vasodilating neuropeptides.
– Subsequent investigations failed to confirm a positive response

29. • Indomethacin
– Inhibiting the production of vasodilating prostaglandins
– Enhance hypoxic pulmonary vasoconstriction and improve oxygenation.
• Methylene blue
– Inhibits the activation of soluble guanylate cyclase by NO.

30. • LIVER TRANSPLANTATION - complete resolution of HPS.
• The time required for improvement in oxygenation may take up to 1 year or
longer.
• Hypoxemia due to HPS may complicate the postoperative course in liver
transplantation.
• In one prospective study, the finding of a preoperative Pao2<50 and a MAA
shunt fraction >20% was associated with increased mortality.
• Other studies suggests that liver transplantation may be safely performed in
patients with severe hypoxemia.

31. SUMMARY
• HPS is a liver induced pulmonary vascular disorder characterized by
intrapulmonary vascular dilatation resulting in ventilation perfusion mismatch
and diffusion limitation for oxygen.
• No known medical treatment for HPS exists, and patients with HPS have a
poorer prognosis than for patients with liver disease without HPS.
• HPS is an indication for, and is curable by liver transplantation.