The liver has a dual circulation, 75% of the bloodstream provided by the portal vein, and 25% by the hepatic artery, each of them supplying about half of the oxygen required by the liver metabolic processes.¹

Liver pathologies, whether inflammatory or tumoral, generate changes in hepatic circulation through mediators or metabolic factors released locally, so that early detection of these changes may indicate the presence of pathologies difficult to evidentiate by routine analyses.

Considering the formation of the portal vein, factors that induce changes in the flow of the superior mesenteric vein and/or splenic vein can influence the parameters quantified for the portal vein; in this perspective an assessment of portal vein automatically involves also the evaluation of its tributaries.

The scientific data are currently inconsistent in terms of normal range of flow parameters, factors which influence the hepatic blood flow and the quantum of changes induced by them. Normal portal flow is regulated by multiple factors, such as hormonal secretion and splanchnic blood flow, which are themselves regulated by metabolic products, tissue osmolarity, local pO₂, hydrogen ions, CO, adenosine and nitric oxide.^2-5 Considering that the flow parameters are influenced also by race, geographical area and geographical genome^6-11and that in our country there are no relevant studies published at the moment which address this issue, our paper brings an important contribution to the characterization of hepatic circulation.

In this paper we evaluate the hepatic vascularization in order to define the range of normality, and to identify the physiological factors which influence the vascular parameters (dimension and flow velocity) and how they change the recorded baseline values.

We conducted a prospective observational study between January and April 2015, at the National Institute for Infectious Diseases "Prof.Dr. Matei Balş” (Romania), evaluating 50 healthy subjects.

The inclusion criteria were: age over 18 years, asymptomatic subjects.

The exclusion criteria were: inflammatory bowel pathologies, abdominal tumors, surgical procedures within 6 months prior to examination, inadequate ultrasound window, heart or antihypertensive medication, acute or chronic hepatobiliary pathologies

All examinations were performed by the same examiner, on an Aloka α7 device (Hitachi, Tokyo, Japan), using a convex multi-frequency probe, with B mode for evaluation of parenchymal structures, and color Doppler and pulsed Doppler for assessment of vascular elements.

We quantified the dimensions and the flow velocities for the portal vein, superior mesenteric vein and splenic vein (in fasting and postprandial state, and in supine position, left lateral decubitus, inspiratory and expiratory apnea).

The fasting values were considered baseline values in calculating the changes in size and velocity induced by diet, respiration and position.

Postprandial measurement was performed 30 minutes after ingestion of a standard meal consisting in 250 mL of fluid with a caloric value of approximately 320 kcal (containing 15 g proteins, 12 g lipids and 38 g glucids).

All measurements were performed three times, registering the average size.

The measurements of the portal vein were performed at its intersection with the inferior vena cava. The measurements of the splenic vein were performed at its intersection with the abdominal aorta. The measurements of the superior mesenteric vein were performed at its intersection with the lower edge of the pancreas.

For the measurements of the flow velocity, we used angular adjustments under 60 degrees, and a sampler approximately half of the vessel caliber.

Considering the fact that we analyzed the impact of various physiological factors on the same study group, the statistical analysis was performed using the z-test: two samples for means.

Duplex ultrasonography is considered a noninvasive method which allows both qualitative and quantitative assessment of portal blood flow, providing accurate data similar to the information rendered by angiography, thus representing a valuable alternative to this invasive technique for the characterization of portal flow parameters.¹²

Breathing plays an important role in the variations of morphological and functional vascular parameters by modifying intra-abdominal pressure; the inspiration process increases intra-abdominal pressure, thus emptying the abdominal veins and increasing the vein-flow towards the heart. In case of the portal venous system, the venous return presents a number of particularities: the increase in the abdominal pressure during inspiration is also accompanied by a compression of the liver by the right hemidiaphragm; in conditions of a normal liver, without fibrotic changes, we will have an increased venous return from the spleno-mesenteric territory and at the same time an increase in resistance of the hepatic veins. These elements will determine an increased intravascular hydrostatic pressure leading to increased vessel dimensions: portal vein, splenic vein (SV), and superior mesenteric vein (SMV). The increased intrahepatic flow resistance and vein dimension will determine a lower flow velocity in the portal vein and its tributaries.

The modifications induced by expiratory apnea are opposed to those discussed in case of inspiratory apnea: increased degree of "blood sequestration" in spleno-mesenteric territory and lower intrahepatic flow-resistance, leading to decreased vein dimensions and higher flow velocities in the portal venous system. Sugano et al.¹³ have shown that in normal patients, portal blood flow can decrease during maximal inspiration compared to flow during normal respiration (-24.6±8.3%) and can increase after maximal expiration (+11.8±9.4%). The variation induced by respiration in portal blood flow was less in cirrhotics showing the utility of the dynamic evaluation in reflecting also the pathological conditions.

Inaba et al. demonstrated also the existence of portal venous flow changes according to respiratory phase, registering a mean velocity and flow rate into the right portal vein during maximal expiration, 14.3±4.4 cm/sec and 457±218 mL/min, showing a significantly greater value than the parameters registered during maximal inspiration: 11.8±3.8 cm/sec (mean±SD) and 364±191 mL/min.¹⁴

The changes registered in postprandial conditions in the portal vein, superior mesenteric vein and splenic vein indicated increased dimensions and flow velocities – which could be explained by the increased blood flow into the intestinal vessels induced by the release of local vascular factors, a higher cholinergic activity during digestion process and absorbed alimentary factors.^15-18 Sadke et al. showed a significant increase of the portal rate after a meal for Doppler measurements, with a range of mean of 24 to 74%.¹⁹

In normal conditions an increased vessel diameter will determine a lower flow velocity, but in postprandial conditions the increased diameter is associated with a higher flow velocity in the portal system due to the increased intestinal blood flow.

Changes in postprandial blood flow within the portal vein are also dependent on the amount and type of food ingested, and the time interval between diet and time of measurement. Lipid- and protein-rich meals are generally more potent than carbohydrate-rich meals in inducing hyperemia.²⁰ Postprandial portal hyperemia is mainly due to mesenteric arterial vasodilation; a reduced postprandial portal hyperemia could be interpreted as a portal decompensation – in patients with cirrhosis it is attributable to portocollateral runoff.²¹

Miyake et al. also demonstrated an increase by about 77% in postprandial portal flow velocity in healthy volunteers with no significant difference related to age,²²data similar to those communicated by Dauzat et al.²³

Hoost et al. investigated the effect of fractional meal stimulation on postprandial hemodynamic changes before and after ingestion of isocaloric, isovolumetric high-protein, carbohydrate or fat meals obtaining an increased portal vein flow after all meals, especially after fat, but also after the control meal (consisting in plain water).²⁴

The meal test with postmeal portal flow volume (PFV) measurements is generally accepted as a reproducible noninvasive test to evaluate the severity of portal hypertension.^25-29 Studies confirm that PFV increases not only in normal subjects but also in patients with chronic hepatitis while in cirrhotic patients no significant changes occur, demonstrating the relevance and utility of postmeal flow measurement.

An important aspect in postmeal evaluation of hepatic circulation is also represented by an important increase in the liver stiffness (independent of the food-type) not only for normal patients but also in patients with cirrhosis, severely altering the results of the portal flow parameters; therefore in order to obtain accurate results the ultrasound evaluation should be performed in fasting conditions.³⁰

The variation of vascular parameters determined by left lateral decubitus of the patient can be explained by the gravitational effect, which causes a reduction in blood flow from the spleen towards the liver, increasing the amount of mesenteric blood into the portal vein when the patient is positioned in this incidence. This represents an important aspect for several reasons – in current practice, most liver ultrasound examinations are performed with the patient positioned in left lateral decubitus, especially if the lower edge of the liver does not exceed costal margin or if the colon has a higher position, limiting the examination window.

The blood in the portal vein is a mixture of splenic and mesenteric blood; each vein (SV and SMV) has different viscosity, proportional to the blood cell count: less elements in the splenic vein because of cell blood destruction in the spleen (with an increased destruction in case of hypersplenism and splenomegaly), while mesenteric blood has a higher number of blood cells and is also loaded with absorbed food elements. Considering these aspects and also the relatively short length of the portal vein, the portal blood is not homogenous (the miscibility is not complete). Apart from this aspect, another important factor is also the Coanda-effect: a fluid flowing through a tube (in our case through SV and SMV), keeps the initial flow direction. All these cumulated aspects define a different blood flow in the portal vein compared to the peripheral veins. In normal conditions, in a vein there is a laminar flow pattern with the maximum velocity in the center of vessel and close to zero in the proximity of the vascular wall. In case of the portal vein, the flow pattern is "spiral", the blood flows originating from SV and SMV circulate around each other and simulate a bidirectional flow during Doppler evaluation if the velocity difference between SV and SMV is important (if the patient associated hypersplenism or if the patient has eaten shortly before examination).

The concomitant influence of more physiological factors on portal flow is very common, so measurement of the dimensions and the flow velocity may tend to overestimate (evaluation conducted during inspiratory apnea and in postprandial condition) or underestimate (evaluation conducted during inspiratory apnea and left lateral decubitus of the patient) the actual value of portal parameters. Based on these factors a patient could be wrongly diagnosed with portal hypertension (left lateral decubitus and inspiratory apnea could decrease portal velocity with over 30%) or a patient with portal hypertension could be considered as normal under the influence of physiological factors.

To avoid such errors, we recommend that in case that recorded values are outside the normal range or if there is an inconsistency between the clinical and ultrasound findings, measurements should be repeated with the patient positioned in dorsal decubitus and while shallow breathing, thus eliminating eventual error factors. If by eliminating the potential interfering factors the resulted parameters are still outside the normal range, the patient requires further investigation to exclude or confirm a liver pathology.

Considering that the evaluated physiological factors (inspiratory apnea, expiratory apnea, alimentation and the position of the patient) influence in the same way both the portal vein and its tributaries, we do not consider that flow parameter measurements for the splenic vein and the superior mesenteric vein would bring new information besides those provided by the evaluation of the portal vein in characterizing the hepatic circulation.

However if alterations of the flow parameters in the SV or SMV are registered – a reduction or an increase of the induced variation (outside the standard deviation) – we can consider this as indirect pathology indicator.

Usual physiological factors (breathing, eating, and patient position) can significantly interfere with the morphological and functional vascular parameters inducing important variations which can lead to underestimation or overestimation of the performed measurements, a very important aspect to consider, in order not to wrongly interpret them as markers of chronic hepatitis or even elements of portal circulation decompensation.

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