Hepatopulmonary, Portopulmonary and Hepatoadrenal Syndromes

Hepatopulmonary Portopulmonary and Hepatoadrenal Syndromes

Chad Hatfield MD

April 22 2010

Questions

1 38 year old female with cirrhosis due to AIH presents for an evaluation of a 6-month history of slowly progressive exertional dyspnea Physical exam reveals multiple spider angioimas clubbing and acrocyanosis Cardiopulmonary exams are unremarkable and CXR and PFTs are normal Testing of ABG reveals a PaO2 of 69mmHg

Questions

Which of the following tests is the best screening test to define the diagnosisndash A Pulmonary angiographyndash B Contrast echocardiography with bubble studyndash C Abdominal ultrasound with Doppler exam of

hepatic vasculaturendash D Bronchoscopyndash E Right heart catheterization to assess

pulmonary arterial pressure

Question

2 47 year white male with history of ETOH cirrhosis presents with 4 months of dyspnea on exertion and one episode of syncope On cardiopulmonary exam there is systolic murmur and RBBB on EKG PaO2 on room air is 78mm Hg Right heart catheterization reveals a mPAP of 55 with a 20 decrease in his mPAP with inhaled NO

What is the next step in the management of this patientA Evaluate the patient of urgent transplantationB Place central access and administer Epoprostenol C TIPS to decrease portal hypertensionD Add non-selective beta blockerE Bronchoscopy

Outline

HepatopulmonaryPortopulmonary (Portopulmonary Hypertension)Hepatoadrenal

ndash Definitionndash Epidemiologyndash Natural Historyndash Pathophysiologyndash Clinical Manifestationsndash Diagnosisndash Management

Happenings in 1977

Star Wars Episode IV A New Hope opens was the highest grossing movie to dateLast execution by Guillotine in FranceSnow falls for the first time in Miami FloridaPlane carrying Lynard Skynyrd crashes in Mississippi killing lead singer Ronnie Van Zant and othersHepatorenal syndrome was first used to identify the altered pulmonary gas exchange that occurs in liver disease

HepatopulmonarySyndrome

Definitionndash Is characterized by decreased systemic arterial oxygenation

induced by pulmonary vascular dilation associated with liver disease

ndash Clinical Triad (all must be present to establish the diagnosis)1 PaO2 less than 80mm Hg or widened age-corrected A-a gradient

more than 15 mm Hg while on room air2 Evidence of intrapulmonary vascular dilation positive finding on

contrast enhanced echocardiography or abnormal uptake in the brain with radioactive lung perfusion scan

3 Portal hypertension with or without cirrhosis

ndash May coexist with intrinsic cardiopulmonary disease


Epidemiologyndash Prevalence of HPS ranges from 5 to 32 various ranges of

abnormal A-a gradient and partial pressure of oxygen (Po2) used to define gas exchange accounts for such a wide range

ndash Is not associated with any specific etiology of liver disease nor is there any relationship between HPS and degree of liver dysfunction

ndash Can be seen in non-cirrhotic portal hypertension (extrahepatic portal vein thrombosis Budd-Chiari)

ndash Also in instances where portal hypertension is not a significantfactor (acute and chronic viral hepatitis without cirrhosis)


Natural Historyndash Progressive deterioration of arterial oxygenation occurs in most

cases (mean PaO2 decline of 52 mm Hg per year has been estimated)

ndash Mean survival without liver transplantation is 2 years with a five year mortality of 23

ndash Worse survival is evident if presenting PaO2 is less than 50mm Hg

ndash Death typically comes from complications of liver disease and not from hypoxic respiratory failure


PathophysiologyPathology

ndash Alterations in the pulmonary vascular tree within a lung with normal parenchyma is the distinctive pathological feature of HPS

ndash Situations that allow poorly oxygenated blood to pass directly into the pulmonary veins

Ventilationperfusion mismatchDiffusion impairmentAnatomical AV shuntsExtrapulomary factors


PathophysiologyVentilationPerfusion Mismatch

ndash Normally blood flow to poorly oxygenated regions of the lung are diverted via arteriolar vasoconstriction to areas with better ventilation

ndash This diversion does not occur in HPS due to Intra-pulmonary vasodilation (IPVD)

Diffusion Impairmentndash Oxygen pressure within the alveoli is not sufficient to oxygenate the RBCs that pass

through the center of the capillaries

Anatomical AV Shuntsndash AV fistulas have been seen bw pulmonary artery and veins as well as vascular

plexuses bw bronchial arteries and veins along the pleural surface

Extrapulmonary Factorsndash Increased cardiac output decreases the RBC transit time through the dilated alveolar

capillaries


Pathophysiology VentilationPerfusion MismatchThere are two postulated mechanisms of IPVD1 Failure of the liver to clear pulmonary vasodilator

substances (intestinal endotoxemia- gut bacterial translocation resulting in higher TNF-α)

-treating with norfloxacin (decreasing gram bacteria) andor pentoxifylline is thought to decrease the occurrence of HPS

2 Production of vasodilator substances by the diseased liver


Pathophysiology VentilationPerfusion MismatchVasodilators substances produced from the Liver

ndash Prostaglandins prostacyclin prostaglandin E1 and prostaglandinI2

ndash NO vasoactive intestinal peptide calcitonin glucagonndash Substance-P atrial natriuretic peptide and platelet activating

factor

These findings are strengthened by the presence of increased NO in exhaled air in patients with HPS and oxygenation is improved by giving an NO inhibitor (methylene blue)

Nitric Oxide stimulates guanylyl cyclase in vascular smooth muscle resulting in relaxation

methylene blue is a guanylyl cyclase inhibitor


Pathophysiology Vascular Shunting

ndash Diffusion-perfusion impairment exists due to vasodilation of precapillary and capillary vessels

This diffusion defect can be partially overcome with the drivingforce of supplemental oxygen

ndash Oxygenation is further compromised by the increased cardiac output associated with liver disease

This limits the time of oxygen exchange in the alveolus


Clinical Manifestations

ndash Symptoms of HPS can often be attributed to worsening of the underlying liver disease or other common conditions in such patients (anemia malnutrition ascites or intrinsic lung disease)

ndash Insidious onset of dyspnea upon exertion and subsequently at rest is the most common finding (57-78)

ndash Spider angiomas cyanosis digital clubbing are signs associatedwith HPS

Spider nevi are found in gt80 of patients with HPS and predict a more severe disease also found in 40-70 of cirrhotics without HPS


Clinical Manifestationsndash Platypnea

Dyspnea in the upright position that resolves in the recumbent positionIs more specific for HPS but is present in only a few

ndash OrthodeoxiaArterial deoxygenation in the upright position and relieved by reclining

ndash Fall in PaO2 ge5 or ge4mm Hg from supinendash Caused by gravity-induced heterogeneous redistribution of blood flow in

lung bases that increases intrapulmonary shut and VP imbalance

ndash These findings are not pathognomonic for HPS in the presence of portal hypertension they are strongly suggestive of HPS


Clinical ManifestationsABG

ndash HPS can be diagnosed if the age-corrected alveolar-arterial oxygen pressure gradient is higher than normal

(age-corrected upper limit of normal= 10+[026 x age-043]) with or without severe hypoxia (PaO2lt70mm Hg)Age correction is necessary due to Paco2 increases with age

ndash ERS Task Force on Pylomary-Hepatic Vascular Disorders has staged the severity of HPS based on the PaO2 on room air and has prognostic significance

Mild (ge80mm Hg) moderate (ge60 and lt80mm Hg) severe (ge50 and lt60mm Hg) and very severe (lt50mm Hg lt300 mm Hg if on 100 oxygen)


Clinical Manifestationsndash Chest radiograph

One third of HPS patients have coexisting COPD often is nonspecific with increased basilar markings consistent with pulmonary vascular dilation

ndash PFTsDiffusion capacity for CO is consistently abnormal and may not improve with liver transplantation


Diagnosis-Requires the presence of intrapulmonary vascular dilations

ndash Preferred diagnostic test Transthoracic Contrast Enhanced Echocardiography (TT-CEE)

ndash Performed by injecting 10mL of agitated saline iv which produces echogenic microbubbles 24-180 microm in diameter

ndash Microbubble opacification of the Left Atrium after 3 heart beats of their detection in the right chambers indicates passage of microbubbles through a dilated pulmonary vascular bed (microbubbles do not pass through normal diameter vascular bed because normal lung capillaries are 7-15 microm)

ndash Could also indicate intracardiac communication if microbubbles are seen before 3 cardiac cycles

ndash Cannot determine the degree of intrapulmonary shunt or determine the typendash TE-CEE is used in patients with a high suspecicion of HPS and negative TT-CEE Note 20 of cirrhotics will have a positive TT-CEE without alterations in arterial

oxygenation


Diagnosisndash Nuclear Lung Scanning

Uses Technetium-labeled macroaggregated albumin (20-90 microm in diameter) combined with whole body scintigraphy showing uptake of radionucleotide in the brain and kidney suggesting Right to Left shunt with transit through the intrapulmonary vessels

ndash Disadvantages compared to TT-CEE may be negative in less severe disease (PaO2gt60mm Hg) cannot distinguish intracardiac from intrapulmonary shunt cannot estimate pulmonary artery presure

ndash Pulmonary AngiographyIndicated only with severe hypoxemia (Po2lt60mm Hg) to attempt to visualize AVM which would be amendable to percutaneous embolization

ndash Two patterns on angiography for HPS-Type I (diffuse) Lower lobe diffuse dilation of small peripheral branches of the pulmonary artery

good response to 100inspired oxygen-Type II (Focal) Discrete AV communications poor response to inspired O2

ndash High-Resolution Chest Computed TomographyNot yet an acceptable method of diagnosing HPSTo some degree can identify greater peripheral pulmonary artery diameter compared to controls


ScreeningAll liver transplant candidates should be screened for HPSAdditional MELD points are given to those with sever HPS (PaO2lt60mm Hg but gt50mm Hg on room air)

ndash Post operative mortality is unacceptable once PaO2 falls below 50mm Hg

History Physical Exam CXR PFTs ABGs

Right-to-Left Shunt

+ -

No Right-to-Left Shunt

lt3 heart beats gt 3 heart beats

Intracardiac

Shunt

IPVD

Abn ABG Abn ABG NL ABG

RVSPgt40-50mm Hg RVSPlt40-50mm Hg

RHC

TT contrast-enhanced echocardiography

uarrMPAPNL MPAP

Initial HPS

NL PCWP (Abn TPG) uarrPVR

Abn PCWP (NL TPG)

NL PVR

POPHVol Overload or LHD

Observe

Abn ECHO

Yes No

Valvulopathyetc

Cont Eval

+ +NL CP Eval Abn CP Eval

Tc-MAA Scan

HPS+ -HPS

+Intrinsic CP Dz

Intrinsic CP Dz


TreatmentOxygen Therapy

ndash Mortality in HPS is due to liver-related complications suggesting that hypoxia may accelerate the progression of liver disease (fibrosis)

ndash Therefore oxygen is used in patients with significant hypoxemiandash No studies have assessed the effects of supplemental oxygen on the

progression of HPS

Pharmacological Therapyndash Currently there are no promising medical managementndash Treatment with antibiotics Somatostatin analogues indometacin and

inhaled NO inhibitors (methylene blue) have shown promise in small uncontrolled trials

ndash Improved arterial oxygenation has been noted in (49 16 of 33) with HPS treated with garlic powder


TreatmentInterventional Radiology

ndash Coil embolotherapy for discrete pulmonary AV fistulaendash TIPS could theoretically improve HPS by relieving portal hypertension but case series

have demonstrated a persistent IPVD in HPS patients following TIPS suggesting that oxygenation improved because of redistribution of blood flow to regions with normal VP ratios rather than true reversal of HPS

TIPS should not be considered a therapy for HPS until more evidence is available

Transplantationndash HPS can reverse following transplantation despite hypoxemia

Recovery may be slow (gt1 year) indicating important structural alterations in the pulmonary vasculature

ndash Postoperatively having prior HPS increases the mortalityndash Strongest predictor of postoperative death is Po2 lt50mm Hg and lung scan with brain

uptake of 20 or more

Portopulmonary Syndrome

Definitionaka Portopulmonary Hypertension (POPH)

By definition pulmonary artery hypertension associated with portal hypertension

Before a diagnosis of POPH is given all criteria must be fulfilledndash Presence of portal hypertension with or without cirrhosisndash Mean pulmonary arterial pressure (MPAP)gt25mm Hg at restndash Pulmonary vascular resistance (PVR)gt240 dynscm^5

Right heart catheterization with complete hemodynamic study is required to make the diagnosis correctly

Is classified as a subset of pulmonary hypertensionndash According to the 2004 classification

Mild 24-34mm HgModerate 35-44mm HgSevere gt44mm Hg


Epidemiology

ndash Can be seen in patients with portal hypertension without cirrhosisNodular regenerative hyperplasiaPortal vein thrombosis

ndash Portal hypertension typically precedes the onset of POPH by 4 years

ndash Is a rare complication or portal hypertension with a prevalence between 2 to 10

ndash Mean age of onset is 55 mf is 111

ndash No clear correlations between severity of liver disease degree of portal hypertension or hyperdynamic circulation

ndash In patients with refractory ascites an unusually high prevalence of POPH of 16 has been reported


Natural History

ndash Overall 3 to 5 year survival (irrespective of the medical management including liver transplantation) is 30 to 50

ndash No cases of spontaneous resolution of POPH have been reported

ndash Complications of liver disease and those related to POPH (right sided heart failure sudden death) account for a similar proportion of deaths

ndash Low cardiac index is a strong predictor of cardiopulmonary related death

ndash The extent to which vasodilator therapy and liver transplantation reverse this condition or improve survival is unknown


Pathogenesisndash Several mechanisms are believed to occur

Hyperdynamic circulatory state ndash increased cardiac output leads to increased shear stress on pulmonary circulationndash The medial smooth muscle hypertrophies in the small pulmonary arteries and arteriolesndash pulmonary vascular resistance (vasoconstriction pulmonary remodeling and

thrombosis)

Portosystemic shunting and defective hepatic metabolismndash Imbalance of VasodilationVasoconstriction promoting mediators in the pulmonary

vasculaturendash Splanchnic volume overload and bowel wall congestion release of endotoxins and

cytokines (NO cytokines prostacyclin) producing vasodilation ndash ET-1 and thromboxane vasoconstriction

Coagulopathy found in cirrhotics may influence in situ thrombosis in the affected vessels and lead to further blood flow resistance


Clinical findingsndash Early stages patients are asymptomatic

ndash More common is progressive dyspnea on exertion

ndash Syncope dyspnea at rest chest pain are less common

ndash Typical cirrhotic exam with the addition of rightndashsided heart dysfunction (accentuated and split S2 systolic murmur (tricuspid regurg) right ventricular heave right-sided S3 gallop lower extremity edema)


Clinical findingsndash ABG usually reveal an increased A-a gradient hypocapnia and less

frequently a mild degree of hypoxemia even in the setting of moderate-to-severe POPH

ndash CXR in moderately disease may show prominent main pulmonary artery and cardiomegaly without parenchymal alterations

ndash EKG demonstrates typical Right sided failure findings right atrial enlargement right ventricular hypertrophy right bundle branch block

ndash Pulmonary angiography shows dilation of proximal pulmonary arteries with tapering of peripheral arteries


Diagnosisndash Transthoracic echocardiogram is a useful non-invasive exam to estimate

pulmonary artery systolic pressurePPV of detecting clinically significant pulmonary artery hypertension 37 but NPV is 92Therefore is a good way to exclude pulmonary artery hypertension when the pressure is lt15mm HgIdentifies tricuspid regurgitant jet (present in 80-90 of POPH patients) pulmonic valve insufficiency RVH and dilation right atrial hypertrophy paradoxical septal motionEffective screening method for HPS

ndash Gold standard is right heart catheterizationAllows the direct measurement of MPAP PCWP and cardiac output and the calculation of PVR and SVRIf POPH is found acute vasodilator testing should be performed during the right heart catherization using epoprostenol iv or inhaled NO

ndash A 20 decrease in MPAP and PVR without a decline in cardiac output indicates a significant response

ndash Reflects to what extent the vasoconstriction is reversible and identifies therapeutic expectations

Should be obtained in anyone with PA pressures greater than 50mm Hg on TTE


Diagnostic Criteriandash Portal hypertension and

An increased mPAP of 25 mm Hg at rest or greater than 30 mm Hg with exertionElevated PVR greater than 240 dynescmNormal or decreased pulmonary wedge pressure less than 15 mm Hg


Managementndash Avoiding circumstances that may worsen portal hypertension pulmonary

vasoconstriction or stress to the heart

ndash TIPS is not recommended due to increased cardiac output may worsen pulmonary hypertension and precipitate right-sided heart failure

ndash Oxygen therapy to avoid hypoxic pulmonary vasoconstriction

ndash Withdrawal of beta-blockers is associated with improvements in exercise capacity with the use of alternative variceal bleeding prevention


Managementndash Vasodilator therapy

Improves symptoms pulmonary hemodynamics and survival in large studies of idiopathic PAH

ndash In POPH no large studies conducted only small uncontrolled

Patients with moderate to severe POPH (MPAPgt35mm Hg) and a significant vasodilatory response may benefit from therapy

ndash Duration of effects are unknown



Prostacyclin analoguesndash Epoprostenol (Flolan)-is best studied

is a potent pulmonary and vascular vasodilatorHas antiproliferative and anti-platelet aggregating propertiesShort half-life (3-5 min) requires long-term continuous administration through central vein Significantly darrMPAP and PVR uarr Cardiac OutputSE headaches flushing diarrhea nausea muscle pain hypotension splenomegaly with leukothrombocytopenia life threatening sudden pulmonary vasoconstriction with abrupt interruption of perfusion

ndash More stable prostacylin analogues (iloprost and treprostinil) have only anecdotal reports



Endothelin Receptor Antagonistndash Bosentan (Tracleer)

Dual ETA and ETB receptor antagonist that is given orallyOnly studied in low-to-medium doses in well-compensated cirrhosis and at 1 year demonstrated improved pulmonary hemodynamics

Phosphodiesterase Inhibitorsndash Sildenafil (Viagra)

oral medication that inhibits phosphodiesterase-5 which then allows NO not be broken down promoting vasodilationIn advanced cirrhosis and severe POPH when used alone or in combination has shown variable improvements in pulmonary hemodynamicsSide effects exacerbation of portal hypertension and hyperdynamic circulation variceal bleeding


Managementndash Liver Transplantation

Unclear how OLT affects the natural history of POPH as normalization improvement no change and worsening of POPH havebeen reported

In favorable cases POPH may take months to years to resolve

De novo development of POPH transition from HPS to POPH and recurrence of POPH following graft failure have all been noted after OLT

Unlike HPS POPH is not an indication for OLT


Managementndash Liver Transplant

POPH is associated with increased morbidity and mortality in those undergoing OLT

ndash Transplant hospitalization mortality of 36 with 40 of intraoperative deaths

ndash Rate of mortality in POPH patients undergoing OLT0 for MPAP lt35mm Hg (additional MELD pts is controversial)50 for MPAP 35 to 50mm Hg and PVR ge 250 dynscm^5100 for MPAP ge 50mm Hg

Most recent data from the Mayo Clinic (2008) showed that there is a 28 five year survival without liver transplantation (n=60) and 56 with a transplanted organ (n=28)

Risk of complications are the greatest during induction of anesthesia before and after graft reperfusion and immediate postoperative period

ndash Increase MPAP during reperfusion of graft may cause right sided heart failure (Dobutamine stress echo with volume challenge may help predict this complication)

ndash Anesthesia with isofluorane and intraoperative vasodilators may help control MPAP in these patients


Managementndash Vasodilator therapy for rescuing liver transplant candidates

Moderate-to-severe POPH (MPAPgt35mm Hg) are the most likely to benefit from this therapyUp to 75 of them may achieve reductions of MPAP below 35mm Hg and be successfully bridged to OLTThis combination provides a survival advantage to these patientsVasodilator therapy should be continued during and after OLT with withdrawal safely achieved within one year

Intrinsic cardiopulmonary conditionsObstructive lung diseaseChronic obstructive pulmonary diseaseAsthmaOthers including emphysema

Disease of lung parenchymaPneumoniaInterstitial lung diseaseOther including atelectasis

Pulmonary vascular diseasesPulmonary embolismSecondary pulmonary hypertension (due to heartlung disease or others)

Disorders of the heart and circulatory systemCongestive heart failureValvular heart diseaseCardiomyopathyOthers (including arrhythmias coronary artery disease)

Conditions related to liver disease and portal hypertensionAssociated with specific liver diseasealpha-1-Antitrypsin deficiency emphysemaPrimary biliary cirrhosis fibrosing alveolitis pulmonary granulomasSarcoidosis lung restrictive disease nonnecrotizing granulomas cardiomyopathyHemochromatosis cardiomyopathy pneumoniaCystic fibrosis bronchiectasis pneumonia

General complications of liver disease and portal hypertensionAscitesHepatic hydrothoraxMuscular wasting

Pulmonary vascular abnormalitiesHepatopulmonary syndromePortopulmonary hypertension

Differential diagnosis of cardiopulmonary dysfunction in liver disease

HPS POPH

Symptomatology Progressive dyspnea Progressive dyspneaChest painSyncope

Clinical examination CyanosisFinger clubbingSpider angiomas ()

No cyanosisRV heavePronounced P2 component

ECG findings None RBBBRightward axisRV hypertrophy

Arterial blood gas levels Moderate to severe hypoxemia Nomild hypoxemia

Chest radiography Normal CardiomegalyHilar enlargement

CEE Always positive left atrial opacification for gt3ndash6 cardiac cycles after right atrial opacification

Usually negative however positive for lt3 cardiac cycles (if atrial septal defect or patent foramen ovale exists)

99mTcMAA shunting index ge6 lt6

Pulmonary hemodynamics Normallow PVR Elevated PVRNormal mPAP

Pulmonary angiography Normalldquospongyrdquo appearance (type I)Discrete AV communications (type II)

Large main pulmonary arteriesDistal arterial pruning

OLT Always indicated in severe stages Only indicated in mild to moderate stages

Hepatoadrenal Syndrome

DefinitionAssociationsndash The vascular and inflammatory changes seen in acute liver

injury or decompensation of chronic liver disease can be likened to septic shock

Hyperdynamic circulatory failure with low MAPDecreased SVRIncreased Cardiac OutputElevated IL-6 and TNF-αDecreased monocyte function and immunoparalysis

ndash Cortisol combats the above by inhibiting inflammatory mediators such as neutrophil recruitment and cytokine release increases vascular tone and cardiac output


DefinitionAssociationsndash 70 of circulating cortisol exists bound to

corticosteroid binding globulin (CBG) 20 bound to albumin and 10 exists as biologically free cortisol

ndash In liver disease CBG and albumin are low (which is reflected in a low total cortisol) whereas free cortisol may be normal or elevated


History of Cortisol and Sepsis

ndash Corticosteroids were first shown to be effective in decreasing mortality in sepsis if given at high doses

ndash Lower doses of corticosteroids were later proved to be more physiologic with lower adverse events lessened the time that vasopressors were needed and maintained a lower mortality rate

ndash Clinical adrenal insufficiency is based on basal cortisol lt15 mcgdL orRelative Adrenal Insufficiency (RAI) is an inadequate response to ACTH stimulation (250microg) lt9 mcgdL rise from baseline


Adrenal Insufficiency in liver diseasendash Three studies have shown that adrenal insufficiency is common in

critically ill patients with liver disease in the absence of clinical sepsis

Prospective study by Harry et al examined cortisol level in acute Tylenol induced fulminate hepatic failure

ndash Found that the degree of adrenal insufficiency was directly related to the severity of liver injury

Same group evaluated corticosteroid therapy (hydrocortisone 300mg daily) in 20 vasopressor-dependent patients with acute or acute on chronic liver failure

ndash Showed that corticosteroids decreased the dose of vasopressor but no survival benefit actually had a higher rate of infection with resistant organisms


Adrenal Insufficiency in liver diseaseMarik et al reported on a prospective study on 340 patients with varying degree of liver disease (including post OLT) who had low cortisol baseline level (lt20 mcgdL) or low stem (1microg stem (lt15mcgdL))

ndash Identified 92 of post OLT patients on a steroid free immunosuppressive regimen had adrenal insufficiency

ndash Low HDL cholesterol was found to be the only predictor of adrenal insufficiency

ndash This is a plausible hypothesis however other mechanisms are likely to play a role


Adrenal Insufficiency in liver disease + sepsisTwo studies focused on chronic liver disease complicated by sepsis

101 patients enrolled 51 had baseline cortisol less than 9mcgdL or an increase in cortisol lt9mcgdL following 250 microg ACTH

bull Degree of adrenal dysfunction correlated with disease severity as measured by Childs Pugh MELD and Apache III scores

25 patients enrolled 68 found to have RAI and were treated with hydrocortisone

bull Group was compared to chronic liver disease patients with sepsis without adrenal testing and found that the hydrocortisone group had a survival benefit


Adrenal Insufficiency in liver diseasendash Patients with acute or chronic liver injury especially in the presence of

sepsis have a high incidence of relative adrenal insufficiencyndash RAI can also be found in the absence of sepsisndash It is proposed that the same process that leads to low cortisol in sepsis too

occurs in hepatoadrenal syndrome-elevated pro-inflammatory cytokines reducesCRH and ACTH release-increased conversion of cortisol to inactive cortisone and peripheral cortisol resistance-also the presence of adrenal hemorrhage

ndash The degree of adrenal dysfunction is correlated with the severity of liver disease


Managementndash Accurate diagnosis of RAI in liver disease is crucialndash If diagnosed in the setting of critical illness or sepsis most experts would

recommend treatment with IV Hydrocortisone (200-300 mgday)This is supported by studies that show an improved survival benefit

-Currently there is no controlled trial data to recommend this approach in liver failure alone

In the study by Harry et al the use of hydrocortisone was not associated with survival benefit and the incidence of sepsis was increasedOne explanation is that the hydrocortisone treated patients survived for longer leading to an increased risk of inpatient acquisition of resistant organisms


Futurendash Whether RAI in liver disease is an entity specific to liver failure or occurs by

the same mechanism as in sepsis is unknown and represents an exciting area of clinical research

ndash It too is unknown if the adrenal insufficiency is primary or secondary in liver disease

ndash The effect of corticosteroid therapy on mortality in patients with liver disease and RAI has never been examined in controlled studies

ndash How RAI is defined in the context of liver failure will require studies using different doses of ACTH (1 vs 250 microg) to determine the optimal performance of this test

ndash Patients with liver disease are also prone to sepsis which is frequently culture negative

Therefore to identify adrenal dysfunction as secondary to sepsis or a component of liver disease more sensitive tests for infections such as bacterial DNA screens should be used

Answers


Answers

Which of the following tests is the best screening test to define the diagnosis

ndash A Pulmonary angiographyndash B Contrast echocardiography with bubble studyndash C Abdominal ultrasound with Doppler exam of hepatic

vasculaturendash D Bronchoscopyndash E Right heart catheterization to assess pulmonary arterial

pressure

Answers


Answers

What is the next step in the management of this patientA Evaluate the patient of urgent transplantationB Place central access and administer EpoprostenolC TIPS to decrease portal hypertensionD Add non-selective beta blockerE Bronchoscopy

Take Home Points

HPSndash Decreased arterial oxygenation induced by pulmonary

vasculature dilation in liver diseasendash Gold standard testing is with Transthoracic Contrast

Enhanced Echocardiography (TT-CEE)ndash PaO2 less than 80mm Hg or A-a gradient more than 15

mm Hg while on room airndash No effective management option other than OLT which is

promising despite an increased postoperative mortality rate

Take Home Points

POPHndash Presence of portal hypertension and Mean pulmonary

arterial pressure (MPAP)gt25mm Hg at restndash Right heart catheterization is required to make the diagnosis

correctlyndash Hyperdynamic circulatory state and imbalance between

intrapulmonary vasodilationvasoconstriction are the major causes

ndash Right sided heart dysfunction of cardiac exam and EKGndash Mild degree of hypoxia on ABGndash Treated with prostacyclins

Take Home Points

Hepatoadrenal Syndromendash Monitoring for adrenal insufficiency in liver

disease and sepsis abnormalities basal cortisol (peaks at 8am) lt15 mcgdL or lt9mcgdL rise with 250 microg of cosyntropin injection

ndash Unclear as to if adrenal insufficiency should be treated in liver disease alone more prospective studies are needed


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Right-to-Left Shunt

+ -



Intracardiac

Shunt

IPVD



RHC


uarrMPAPNL MPAP

Initial HPS


Abn PCWP (NL TPG)

NL PVR


Observe

Abn ECHO

Yes No

Valvulopathyetc

Cont Eval


Tc-MAA Scan

HPS+ -HPS

+Intrinsic CP Dz

Intrinsic CP Dz





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Right-to-Left Shunt

+ -



Intracardiac

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RHC


uarrMPAPNL MPAP

Initial HPS


Abn PCWP (NL TPG)

NL PVR


Observe

Abn ECHO

Yes No

Valvulopathyetc

Cont Eval


Tc-MAA Scan

HPS+ -HPS

+Intrinsic CP Dz

Intrinsic CP Dz





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+ -



Intracardiac

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IPVD



RHC


uarrMPAPNL MPAP

Initial HPS


Abn PCWP (NL TPG)

NL PVR


Observe

Abn ECHO

Yes No

Valvulopathyetc

Cont Eval


Tc-MAA Scan

HPS+ -HPS

+Intrinsic CP Dz

Intrinsic CP Dz





progression of HPS





















Epidemiology








Natural History









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Right-to-Left Shunt

+ -



Intracardiac

Shunt

IPVD



RHC


uarrMPAPNL MPAP

Initial HPS


Abn PCWP (NL TPG)

NL PVR


Observe

Abn ECHO

Yes No

Valvulopathyetc

Cont Eval


Tc-MAA Scan

HPS+ -HPS

+Intrinsic CP Dz

Intrinsic CP Dz





progression of HPS





















Epidemiology








Natural History









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Intracardiac

Shunt

IPVD



RHC


uarrMPAPNL MPAP

Initial HPS


Abn PCWP (NL TPG)

NL PVR


Observe

Abn ECHO

Yes No

Valvulopathyetc

Cont Eval


Tc-MAA Scan

HPS+ -HPS

+Intrinsic CP Dz

Intrinsic CP Dz





progression of HPS





















Epidemiology








Natural History









thrombosis)











































































HPS POPH
































































Answers


Answers




pressure

Answers


Answers


Take Home Points






Take Home Points






Take Home Points





Questions

Questions

Question

Outline

Happenings in 1977










































Answers

Answers

Answers

Answers

Take Home Points

Take Home Points

Take Home Points



































capillaries










factor








































oxygenation













Right-to-Left Shunt

+ -



Intracardiac

Shunt

IPVD



RHC


uarrMPAPNL MPAP

Initial HPS


Abn PCWP (NL TPG)

NL PVR


Observe

Abn ECHO

Yes No

Valvulopathyetc

Cont Eval


Tc-MAA Scan

HPS+ -HPS

+Intrinsic CP Dz

Intrinsic CP Dz





progression of HPS





















Epidemiology








Natural History









thrombosis)











































































HPS POPH
































































Answers


Answers




pressure

Answers


Answers


Take Home Points






Take Home Points






Take Home Points





Questions

Questions

Question

Outline

Happenings in 1977










































Answers

Answers

Answers

Answers

Take Home Points

Take Home Points

Take Home Points










factor








































oxygenation













Right-to-Left Shunt

+ -



Intracardiac

Shunt

IPVD



RHC


uarrMPAPNL MPAP

Initial HPS


Abn PCWP (NL TPG)

NL PVR


Observe

Abn ECHO

Yes No

Valvulopathyetc

Cont Eval


Tc-MAA Scan

HPS+ -HPS

+Intrinsic CP Dz

Intrinsic CP Dz





progression of HPS





















Epidemiology








Natural History









thrombosis)











































































HPS POPH
































































Answers


Answers




pressure

Answers


Answers


Take Home Points






Take Home Points






Take Home Points





Questions

Questions

Question

Outline

Happenings in 1977










































Answers

Answers

Answers

Answers

Take Home Points

Take Home Points

Take Home Points





































oxygenation













Right-to-Left Shunt

+ -



Intracardiac

Shunt

IPVD



RHC


uarrMPAPNL MPAP

Initial HPS


Abn PCWP (NL TPG)

NL PVR


Observe

Abn ECHO

Yes No

Valvulopathyetc

Cont Eval


Tc-MAA Scan

HPS+ -HPS

+Intrinsic CP Dz

Intrinsic CP Dz





progression of HPS





















Epidemiology








Natural History









thrombosis)











































































HPS POPH
































































Answers


Answers




pressure

Answers


Answers


Take Home Points






Take Home Points






Take Home Points





Questions

Questions

Question

Outline

Happenings in 1977










































Answers

Answers

Answers

Answers

Take Home Points

Take Home Points

Take Home Points













Right-to-Left Shunt

+ -



Intracardiac

Shunt

IPVD



RHC


uarrMPAPNL MPAP

Initial HPS


Abn PCWP (NL TPG)

NL PVR


Observe

Abn ECHO

Yes No

Valvulopathyetc

Cont Eval


Tc-MAA Scan

HPS+ -HPS

+Intrinsic CP Dz

Intrinsic CP Dz





progression of HPS





















Epidemiology








Natural History









thrombosis)











































































HPS POPH
































































Answers


Answers




pressure

Answers


Answers


Take Home Points






Take Home Points






Take Home Points





Questions

Questions

Question

Outline

Happenings in 1977










































Answers

Answers

Answers

Answers

Take Home Points

Take Home Points

Take Home Points





progression of HPS





















Epidemiology








Natural History









thrombosis)











































































HPS POPH
































































Answers


Answers




pressure

Answers


Answers


Take Home Points






Take Home Points






Take Home Points





Questions

Questions

Question

Outline

Happenings in 1977










































Answers

Answers

Answers

Answers

Take Home Points

Take Home Points

Take Home Points


















Epidemiology








Natural History









thrombosis)











































































HPS POPH
































































Answers


Answers




pressure

Answers


Answers


Take Home Points






Take Home Points






Take Home Points





Questions

Questions

Question

Outline

Happenings in 1977










































Answers

Answers

Answers

Answers

Take Home Points

Take Home Points

Take Home Points


Natural History









thrombosis)











































































HPS POPH
































































Answers


Answers




pressure

Answers


Answers


Take Home Points






Take Home Points






Take Home Points





Questions

Questions

Question

Outline

Happenings in 1977










































Answers

Answers

Answers

Answers

Take Home Points

Take Home Points

Take Home Points




thrombosis)











































































HPS POPH
































































Answers


Answers




pressure

Answers


Answers


Take Home Points






Take Home Points






Take Home Points





Questions

Questions

Question

Outline

Happenings in 1977










































Answers

Answers

Answers

Answers

Take Home Points

Take Home Points

Take Home Points







































































HPS POPH
































































Answers


Answers




pressure

Answers


Answers


Take Home Points






Take Home Points






Take Home Points





Questions

Questions

Question

Outline

Happenings in 1977










































Answers

Answers

Answers

Answers

Take Home Points

Take Home Points

Take Home Points



















































Answers


Answers




pressure

Answers


Answers


Take Home Points






Take Home Points






Take Home Points





Questions

Questions

Question

Outline

Happenings in 1977










































Answers

Answers

Answers

Answers

Take Home Points

Take Home Points

Take Home Points

Answers




pressure

Answers


Answers


Take Home Points






Take Home Points






Take Home Points





Questions

Questions

Question

Outline

Happenings in 1977










































Answers

Answers

Answers

Answers

Take Home Points

Take Home Points

Take Home Points

Answers


Answers


Take Home Points






Take Home Points






Take Home Points





Questions

Questions

Question

Outline

Happenings in 1977










































Answers

Answers

Answers

Answers

Take Home Points

Take Home Points

Take Home Points

Answers


Take Home Points






Take Home Points






Take Home Points





Questions

Questions

Question

Outline

Happenings in 1977










































Answers

Answers

Answers

Answers

Take Home Points

Take Home Points

Take Home Points

Take Home Points






Take Home Points






Take Home Points





Questions

Questions

Question

Outline

Happenings in 1977










































Answers

Answers

Answers

Answers

Take Home Points

Take Home Points

Take Home Points

Take Home Points






Take Home Points





Questions

Questions

Question

Outline

Happenings in 1977










































Answers

Answers

Answers

Answers

Take Home Points

Take Home Points

Take Home Points

Take Home Points





Questions

Questions

Question

Outline

Happenings in 1977










































Answers

Answers

Answers

Answers

Take Home Points

Take Home Points

Take Home Points

Hepatopulmonary, Portopulmonary and Hepatoadrenal Syndromes

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Transcript of Hepatopulmonary, Portopulmonary and Hepatoadrenal Syndromes