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Hyperdynamic circulation in liver cirrhosis: Not peripheral vasodilatation

but 'splanchnic steal'

Article  in  QJM: monthly journal of the Association of Physicians · January 2003

DOI: 10.1093/qjmed/95.12.827 · Source: PubMed

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Q J Med 2002; 95:827–830
Commentary
Hyperdynamic circulation in liver cirrhosis: not peripheral
vasodilatation but ‘splanchnic steal’
D.E. NEWBY and P.C. HAYES 1
From the Departments of Cardiology and 1Medicine, University of Edinburgh, Royal Infirmary,
Edinburgh, UK
Introduction
It is generally accepted that liver cirrhosis is
associated with a hyperdynamic circulation and
peripheral vasodilatation. The Oxford Textbook of
Medicine describes the clinical features of ‘flushed
extremities, bounding pulses and capillary pulsa-
tions’ in cirrhosis,1 and a resting tachycardia and
systemic hypotension, with experimental evidence
of elevated cardiac output and reduced total
systemic vascular resistance, confirm the existence
of a hyperdynamic circulation. In 1988, Schrier
and colleagues2 proposed the ‘peripheral arterial
vasodilatation hypothesis’ to account for this hyper-
dynamic circulation as well as the initiation of
sodium and water retention in cirrhosis. Many sub-
sequent theories have been expounded to explain
the underlying mechanism of this peripheral arterial
vasodilatation. Most suggest the production of,
or failure to metabolize, a circulating vasodilator
substance that causes decreased vascular tone,
recruitment of arteriovenous anastamoses and sys-
temic hypotension. Various candidate vasodilators
have been proposed, including nitric oxide, eico-
sanoids, bile salts, adenosine and tachykinins,
such as substance P, and calcitonin-gene-related
peptide.3 This unidentified vasodilator substance
has been held responsible for the sodium and
water retention associated with ascites, due to the
consequent activation of the sympathetic nervous,
renin-angiotensin-aldosterone and vasopressin sys-
tems. Nitric oxide has gained the most attention,4
although it is interesting to note that there is little
Address correspondence to Dr D.E. Newby, Department of Cardiology, Royal Infirmary, Lauriston Place, Edinburgh
EH3 9YW. e-mail: d.e.newby@ed.ac.uk
ß Association of Physicians 2002
QJM
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evidence of elevated basal nitric oxide release in
the peripheral circulation of patients with early or
advanced cirrhosis.5–7
Although there is a marked reduction in total
systemic vascular resistance, we contest the belief
that liver cirrhosis is associated with peripheral
vasodilatation, and that this is due to the effects
of a systemic circulating vasodilator substance.
This is not consistent with clinical observations or
experimental evidence, which have shown little
evidence of peripheral vasodilatation. In our experi-
ence, patients with advanced cirrhosis rarely have
‘flushed peripheries and capillary pulsations’.
Although arteriolar vasodilatation in the form of
spider naevi and palmar erythema may be pre-
sent, their occurrence is unpredictable and does
not correlate with disease severity. Thermography
demonstrates that patients with advanced liver
cirrhosis have cool peripheries, with skin pallor
and poor capillary perfusion.8 Indeed, in clinical
questionnaires, patients with cirrhosis are more
likely to complain of cold hands.9 Haemodynamic
measurements show that, while splanchnic blood
flow is markedly increased,10 blood flow is sig-
nificantly reduced in the upper and lower limbs11,12
as well as the extra-splanchnic viscera13 including
the brain.14
How then do we account for the findings of
peripheral vasoconstriction in the face of a hyper-
dynamic circulation? We propose that the high
cardiac output and systemic hypotension relate to
828 D.E. Newby and P.C. Hayes

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Figure 1. Schematic representation of the splanchnic steal phenomenon.

 Splanchnic steal in liver cirrhosis
the marked and dysregulated splanchnic vasodila-
tation consequent on the development of liver
cirrhosis, and as a result of portal hypertension.
Hepatic fibrosis causes a marked impairment of
portal blood flow into the liver, and maladaptive
splanchnic vasodilatation attempts to rectify the
associated reduction in hepatic perfusion by
increasing blood flow and pressure in the portal
venous system. However, rather than increasing
perfusion of the liver, this hyperaemia and hyper-
tension results in incremental shunting of portal
blood into the systemic circulation via porto
systemic collateral anastamoses. Progressive colla-
teral shunting exacerbates the reduction in portal
blood flow to the liver, creating a true ‘steal’
phenomenon (Figure 1). Both arterial and venous
steals take place in this model: arterial steal occurs
from the systemic circulation into the splanchnic
arterial system, while venous steal occurs from the
portal vein inflow of the liver into the porto-
systemic collaterals. This latter steal becomes
extreme in advanced liver disease, where blood
flow in the portal vein may even become reversed.
This is supported by the correlation of worsening
liver function with increases in cardiac output and
azygous (collateral) blood flow,15 and decreases in
hepatic perfusion.16
The fundamental cardiovascular consequences
of liver cirrhosis would, therefore, appear to be
due to a ‘splanchnic steal’ where progressive and
inexorable vasodilatation of the splanchnic bed
occurs. Homeostatic mechanisms, including activa-
tion of neurohumoral reflexes, attempt to correct
these derangements and lead not to peripheral
vasodilatation, but peripheral vasoconstriction with
reduced tissue perfusion. Plasma concentrations of
vasoconstrictor mediators such as catecholamines,
angiotensin II, and endothelin are elevated, and
lead to increases in peripheral vascular tone.7,12
Indeed, systemic blockade of the sympathetic
nervous or renin-angiotensin systems causes pro-
found hypotension in patients with cirrhosis.17,18
This again indicates that the peripheral circula-
tion is under increased vasoconstrictor tone, despite
systemic hypotension and a reduction in total sys-
temic vascular resistance: homeostatic mechanisms
attempting to sustain blood pressure despite resis-
tant and persistent splanchnic vasodilatation. This
also explains the impaired pressor responses to
exogenously administered vasoconstrictor agents,
such as noradrenaline and angiotensin II,19,20 since
the basal vascular tone of the extra-splanchnic
circulations is already increased, and additional
stimulation will be unable to produce the same
incremental response as that observed in normal
healthy volunteers.
829
This ‘splanchnic steal’ is consistent with, and
assists in the explanation of, the observed haemo-
dynamic responses to two therapeutic manoeuvres
used in patients with cirrhosis. A transjugular intra-
hepatic portosystemic shunt (TIPSS) is inserted to
reduce the risk of variceal bleeding by alleviating
portal hypertension through increased collateral
shunting. This exacerbates the haemodynamic
derangements of cirrhosis,21 leading to increases
in cardiac output, reductions in hepatic sinusoidal
perfusion and progressive peripheral vasoconstric-
tion. In contrast, terlipressin, a long-acting analogue
of vasopressin, causes selective splanchnic vaso-
constriction and is used in the treatment of hepa-
torenal syndrome.22 Administration of terlipressin
improves blood pressure and renal function by
reducing the steal into the splanchnic circulation,
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and diverting blood to the systemic and renal
circulations.
We would, therefore, suggest that, although liver
cirrhosis is associated with a hyperdynamic circula-
tion and low total systemic vascular resistance,
marked peripheral arterial vasoconstriction is the
dominant clinical picture. We hypothesize that
these apparently contradictory phenomena reflect
a ‘splanchnic steal’ effect where dysregulated splan-
chnic vasodilatation and porto-systemic shunting
induce a high cardiac output state associated with
peripheral extra-splanchnic vasoconstriction.
References
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