netherlandsjournalofcriticalcare
180 nethjcritcare•volume11•no4•august2007
review
Copyright©2007,NederlandseVerenigingvoorIntensiveCare.AllRightsReserved. ReceivedNovember2006;acceptedinrevisedformJuly2007
B van der Hoven
Department of Intensive Care, Erasmus University Medical Center, Room H-602, PO Box 2040, 3000 CA Rotterdam, The Netherlands
Abstract. A substantial number of patients admitted to the ICU with a major infection develop sepsis or septic shock. The role
of the liver and hepatic microcirculation in subsequent events, including organ failure, has been established but continues to be a
topic of intensive research. Combined effects on contractile sinusoidal cells i.e. endothelial cells and stellate or Ito cells, regulate the
hepatic arterial and venous portal parts of the perfusion in the liver sinusoids with consecutive effects on hepatocyte function and
metabolism. However, improving inadequate liver function, based on defcient tissue perfusion and oxygenation, and assessing
therapeutic interventions by monitoring the liver microcirculation is diffcult. Current monitoring techniques include liver-specifc
clearance of substances and intravital microscopic visualization of the microcirculation combined with computer-aided video analy-
sis. Simple and minimally invasive bedside monitoring of the microcirculation would be a great advantage in the future.
Introduction
One of the most important goals of therapy in critically ill patients is
to restore and maintain adequate perfusion and oxygenation of vital
organs during recovery from circulatory failure, such as in sepsis
and trauma.
Microvascular dysfunction early in sepsis represents the frst
critical stage in tissue hypoxia and organ failure [1]. The gastro-
intestinal tract plays a key role in the development of shock and
multiple organ failure. The impaired integrity of the mucosal layer
when rendered hypoxic disrupts the barrier function against luminal
bacteria and bacterial products like endotoxins [2, 3]. Transloca-
tion of bacteria and endotoxins to the lymphatic and portal systems
occurs initially and leads ultimately to distant organ damage. The
gut and liver macrophages (Kupfer cells) are important as a frst line
of defence against further spread to the general circulation. Mes-
enteric perfusion and autoregulation of the microcirculatory blood
fow distribution in the splanchnic area is impaired during systemic
bacteraemia and in endotoxaemia. Regional blood fow distribution
is fawed and changes under normal circumstances are not refected
in conditions of sepsis and septic shock. The fow distribution to
the mucosa is decreased in sepsis while the general splanchnic fow
remains largely intact [2, 4].
Blood fow distribution and regional perfusion have to adapt to
local metabolic demand. Because the diffusion of oxygen in tissues
is limited, the nutritional delivery has to depend on a dense, fnely
distributed network of capillaries [1, 5].
The microcirculatory blood fow in the splanchnic organs is
heterogeneous both in early hypodynamic shock as well as later in
hyperdynamic shock, and can therefore not be predicted by general
changes in systemic or even regional blood fow [6]. Consequently,
monitoring the microcirculation seems to be important in our aim
to identify patients at risk of developing organ system failure, and to
evaluate our therapeutic interventions [1, 7-9]. Although hepatic dys-
function is known to independently infuence outcome and recovery
of critically ill patients and seems especially warranted in daily
practice, due to the anatomical particulars, measuring the hepatic
circulation poses a unique challenge [10, 11]. Unlike any other organ,
the liver receives blood from two types of afferent vessel i.e. the por-
tal system and the hepatic artery, and monitoring of this system at
bedside is diffcult at present, except perhaps at laparotomy.
This article presents an overview of some physiological aspects of
the hepatic microcirculation and oxygenation, the different methods
used to monitor hepatic perfusion and oxygenation, and their rel-
evance in the research and the clinical setting.
Specificsofhepaticanatomy
Together with the small bile ductuli culminating in the common bile
duct, the terminal portal venules and the terminal hepatic arterioles
form a triad which forms the basis of the microscopic structure of
the liver . The hepatocytes are organized in the Kiernan’s or clas-
sic lobules around central hepatic venules, which form the hepatic
vein (in a hexagonal outline), the boundaries of which are defned
in humans by imaginary interlobular septal lines. The portal tracts
(composed of terminal portal venules, terminal hepatic arterioles
and the smallest branches of the bile duct) are situated in the ‘cor-
ners’ of the hepatic lobules [12, 13]. Functionally, a further refne-
ment is the ‘simple liver acinus’, consisting of the smallest portal
tract at the centre and the terminal hepatic venule in the periphery.
The zone closest to the afferent vessel is referred to as ‘zone 1’ and
the area surrounding the peripheral efferent hepatic venule as ‘zone
3’. ‘Zone 2’ is located between these two areas (Fig. 1).
This morphological and functional structure provides a rational
approach to study the hepatic metabolism in each zone because, for
instance, an oxygen gradient exists from zones 1 to 3, making zone
3 hepatocytes vulnerable to oxygen deprivation as in sepsis [14]. The
cytochrome P-450 3A4 system (e.g. essential for drug metabolism)
is located predominantly in zone 3 hepatocytes and is oxygen depen-
dent or even hypoxic, as was shown in mice [15]. Compromised
fow will reduce its function and lead to accumulation of the primary
drug.
Exploring the hepatic microcirculation
in critical illness: a challenge
Correspondence:
BvanderHoven
E-mail:b.vanderhoven.1@erasmusmc.nl