Review Article
Clinical implications of the hyperdynamic syndrome in cirrhosis

https://doi.org/10.1016/j.ejim.2014.09.004Get rights and content

Highlights

  • HS is secondary to hemodynamic changes in patients with cirrhosis and PH.

  • Esophageal varices, ascites, encephalopathy and HRS are common in HS.

  • Pulmonary involvement occurring during cirrhosis includes HPS, POPH and HH.

  • CC is a chronic cardiac dysfunction in patients without cardiovascular disease.

Abstract

The hyperdynamic syndrome is a late consequence of portal hypertension in cirrhosis. The principal hemodynamic manifestations of the hyperdynamic syndrome are high cardiac output, and increased heart rate and total blood volume, accompanied by reduced total systemic vascular resistance. Pathophysiology involves a complex of humoral and neural mechanisms that can determine hemodynamic changes, and lead to hyperdynamic circulation.

In this review we focus our attention on the manifestations of the hyperdynamic syndrome. Some of these are well described and directly related to portal hypertension (varices, ascites, hepatic encephalopathy, and hepatorenal syndrome), while others, such as hepatopulmonary syndrome, portopulmonary hypertension, and cirrhotic cardiomyopathy, are less known as clinical manifestations related to cirrhosis and, therefore, merit further investigation.

Introduction

Patients with advanced chronic liver disease show varying degrees of portal hypertension (PH) and splanchnic vasodilatation, which are often associated with a hyperdynamic circulatory state. The hyperdynamic syndrome (HS) is a consequence of cirrhosis of varying etiologies [1], [2]. This syndrome has been defined by high cardiac output, increased heart rate and total blood volume, reduced total systemic vascular resistance, and low, normal or decreased arterial pressure [1], [2], [3]. In this review, we will attempt to describe and explain the pathophysiological and clinical manifestations related to HS.

Among all hemodymanic alterations typical of advanced phases of cirrhosis, vasodilatation is the first of vascular changes that finally lead to multi-organ involvement. However, the mechanisms of vasodilation are still not entirely understood [2].

Development of PH due to architectural changes typical of cirrhosis plays a fundamental role in the genesis of HS. In fact, PH consists of an increase in portal pressure gradient (HVPG), defined by the difference between the portal vein and the inferior vena cava pressures [4]. It is caused by an increased resistance to portal outflow and inflow, with an abnormal distribution of the blood volume, which increases mostly in the splanchnic district. This alteration of blood volume distribution with underfilling of arterial circulation triggers baroreceptor activation to release vasoconstrictor factors to restore integrity of the circulation [5]. Usually, the HVPG ranges from 1 to 5 mmHg, becoming clinically significant when it reaches 10 mmHg [6]. In clinical practice, an increase in HPVG values of at least 12 mmHg is usually associated with the presence of esophageal varices [2], [6]. Progressing through the stages of cirrhosis, there is a wide development of a network of collateral vessels, which bypassing the liver, creates communication between the portal vein and the systemic circulation. The main collateral network is the gastro-epiploic system, responsible for the formation of gastro-esophageal varices, which together with the reduction in circulating platelets and hypersplenism are the clinical hallmark of PH [5], [6], [7].

Splanchnic circulation is responsible for the reduction of vascular resistance in the portal hypertensive state. The increase in splanchnic blood flow is related to: 1.) an increase in vasodilatator factors (nitric oxide (NO), prostacyclines, carbon monoxide (CO), endo-cannabinoides); 2.) reduced response to vasoconstrictor factors; and 3.) mesenteric neoangiogenesis [8], [9], [10], [11]. The increase in NO, maintained in pre-sinusoidal areas, is due to endothelial nitric oxide synthase activation by pro-inflammatory cytokines released by bacterial translocation and shear stress. Moreover, the splanchnic vasodilatation is caused by reduced response to vasoconstrictor factors, which, instead, are increased in other organs, such as the kidney and brain. The reduced response to local vasoconstrictors is likely related to increased levels of vasodilatator factors (NO, CO), and functional alterations of smooth muscular and endothelial cells.

At early compensated stages of cirrhosis, hyperdynamic circulation is not clinically manifest, but becomes more evident during the evolution of the disease. Any modification in peripheral resistance is rapidly compensated by variations in cardiac output. Though the reduction in peripheral resistance is slow, compensatory mechanisms play a pivotal role in maintaining and further worsening the hyperdynamic circulation (Fig. 1) [12], [13], [14], [15], [16]. Plasma volume expansion is relevant in these cirrhotic patients, even if distribution between the central and peripheral vascular areas is often not balanced [6], [17]. The splanchnic vasodilation in cirrhosis precedes the increase in cardiac output and heart rate [18]. However, when the splanchnic vasodilatation becomes more pronounced, the hyperdynamic circulation may no longer be sufficient for correcting hypovolemia [12], [17] (Fig. 2). Central arterial blood volume (heart, lungs, and central arterial tree blood volume) is more often decreased, while the non-central blood volume (splanchnic) is usually increased in cirrhotics.

Section snippets

Clinical manifestations

The first described clinical signs of the HS were arterial hypotension, wide pulse pressure, tachycardia, warm extremities and palmar erythema. Splanchnic vasodilatation is the first pathophysiological stage of clinical complications of cirrhosis, while PH and its sequelae are a cause of admission to the hospital, worsening of clinical conditions, and death. In fact, esophageal or gastric variceal bleeding, ascites with consequent spontaneous bacterial peritonitis (SBP), hepatic encephalopathy

Conclusions

The HS is a complex of hemodynamic alterations involving patients with cirrhosis and PH. The pathophysiological mechanisms that characterize the HS are complex and only partially known.

Multi-organ involvement is crucial, and is characterized by a set of more or less explored complications of cirrhosis. Clinical manifestations of PH such as ascites, esophageal varices, and HRS have been described in numerous studies, while the HPS and CC remain among the least explored and understood

Learning points

  • In clinical practice, portal hypertension has been defined as an increase in the hepatic venous pressure gradient (HPVG), and PPG values of at least 12 mmHg are usually associated with the presence of esophageal varices.

  • Arteriolar vasodilatation, low systemic vascular resistance, expanded blood volume, and raised sympathetic nervous activity contribute to increased cardiac output, and to configuring the hemodynamic changes typical of hyperdynamic circulation.

  • Esophageal varices are present in

Conflict of interest

None.

References (86)

  • H.A. Kontos et al.

    General and regional circulatory alterations in cirrhosis of the liver

    Am J Med

    (1964)
  • A. Luca et al.

    Noninvasive measurement of femoral blood flow and portal pressure response to propranolol in patients with cirrhosis

    Hepatology

    (1995)
  • R. De Franchis et al.

    Revising consensus in portal hypertension: report of the Baveno V consensus workshop on methodology of diagnosis and therapy in portal hypertension

    J Hepatol

    (2010)
  • S. Madonia et al.

    Prognostic indicators of successful endoscopic sclerotherapy for prevention of rebleeding from oesophageal varices in cirrhosis: a long-term cohort study

    Dig Liver Dis

    (Dec 2000)
  • C. Ripoll et al.

    Hepatic venous gradient predicts clinical decompensation in patients with compensated cirrhosis

    Gastroenterology

    (2007)
  • A. Rimola et al.

    Diagnosis, treatment and prophylaxis of spontaneous bacterial peritonitis: a consensus document. International Ascites Club

    J Hepatol

    (2000)
  • P. Ginés et al.

    Comparison of paracentesis and diuretics in the treatment of cirrhotics with tense ascites. Results of a randomized study

    Gastroenterology

    (1987)
  • A. Ginès et al.

    Randomized controlled trial comparing albumin, dextran-70 and polygelin in cirrhotic patients with ascites treated by paracentesis

    Gastroenterology

    (1996)
  • W.R. Caly et al.

    A prospective study of bacterial infections in patients with cirrhosis

    J Hepatol

    (1993)
  • V. Arroyo et al.

    Advances in the pathogenesis and treatment of type-1 and type-2 hepatorenal syndrome

    J Hepatol

    (2007)
  • A.J. Sanyal et al.

    A randomized, prospective, double-blind, placebo-controlled trial of terlipressin for type 1 hepatorenal syndrome

    Gastroenterology

    (2008)
  • M. Martin-Llahi et al.

    Terlipressin and albumin vs albumin in patients with cirrhosis and hepatorenal syndrome: a randomized study

    Gastroenterology

    (2008)
  • S. Piano et al.

    Continuous recurrence of type 1 hepatorenal syndrome and long-term treatment with terlipressin and albumin: a new exception to MELD score in the allocation system to liver transplantation?

    J Hepatol

    (2011)
  • E.F. Wijdicks et al.

    Propofol to control intracranial pressure in fulminant hepatic failure

    Transplant Proc

    (2002)
  • M.R. Arguedas et al.

    Prospective evaluation of outcomes and predictors of mortality in patients with hepatopulmonary syndrome undergoing liver transplantation

    Hepatology

    (2003)
  • G.A. Abrams et al.

    Diagnostic utility of contrast echocardiography and lung perfusion scan in patients with hepatopulmonary syndrome

    Gastroenterology

    (1995)
  • G. Simonneau et al.

    Updated clinical classification of pulmonary hypertension

    J Am Coll Cardiol

    (2009)
  • N. Sussman et al.

    Successful liver transplantation following medical management of portopulmonaryhypertension: a single-center series

    Am J Transplant

    (2006)
  • M. Ashfaq et al.

    The impact of treatment of portopulmonary hypertension on survival following liver transplantation

    Am J Transplant

    (2007)
  • X. Xiol et al.

    Spontaneous bacterial empyema in cirrhosis patients: a prospective study

    Hepatology

    (1996)
  • E.M. Zardi et al.

    Cirrhotic cardiomyopathy

    J Am Coll Cardiol

    (Aug 10 2010)
  • M. Torregrosa et al.

    Cardiac alterations in cirrhosis: reversibility after liver transplantation

    J Hepatol

    (2005)
  • A. Milani et al.

    Cirrhotic cardiomyopathy

    Dig Liver Dis

    (Jun 2007)
  • Y. Iwakiri et al.

    The hyperdynamic circulation of chronic liver diseases: from the patient to the molecule

    Hepatology

    (2006)
  • H.J. Kowalski et al.

    The cardiac output at rest in Laennec's cirrhosis

    J Clin Invest

    (1953)
  • J. Bosch et al.

    The clinical use of HVPG measurements in chronic liver disease

    Nat Rev Gastroenterol Hepatol

    (2009)
  • R.J. Groszmann et al.

    Portal Hypertension Collaborative Group. β-blockers to prevent gastroesophageal varices in patients with cirrhosis

    N Engl J Med

    (2005)
  • G. Hamilton et al.

    The relationship between prostacyclin activity and pressure in the portal vein

    Hepatology

    (1982)
  • Y. Iwakiri

    The molecules: mechanisms of arterial vasodilation observed in the splanchinc and systemic circulation in portal hypertension

    J Clin Gastroenterol

    (2007)
  • A.M. Geerts et al.

    Increased angiogenesis and permeability in the mesenteric microvasculature of rats with cirrhosis and portal hypertension: an in vivo study

    Liver Int

    (2006)
  • J.G. Abraldes et al.

    Mild increases in portal pressure upregulate vascular endothelial growth factor and endothelial nitric oxide synthase in the intestinal microcirculatory bed, leading to a hyperdynamic state

    Am J Physiol Gastrointest Liver Physiol

    (2006)
  • A. Maroto et al.

    Brachial and femoral artery blood flow in cirrhosis: relationship to kidney dysfunction

    Hepatology

    (1993)
  • M. Carrella et al.

    Capillary blood flow to the skin of forearm in cirrhosis

    Angiology

    (1992)
  • Cited by (0)

    View full text