Kjeld Winkler

Quantification of liver fat using magnetic resonance spectroscopy.

Localized proton MR spectroscopy using stimulated echoes was used to quantify the liver fat concentration in patients with various degrees of fatty liver due to alcohol abuse. Ten patients underwent a liver biopsy followed by chemical triglyceride estimation of the fatty content. A statistically significant correlation was found between the fat concentration measured in the liver biopsies, and the concentration calculated from the spectroscopic experiments (r = 0.9, p < .001). Quantitative assessment of liver fat concentrations using localized spectroscopy is superior to methods based on differences in relaxation times, and can be used to estimate the fat concentration over the full range of fat content in contrast to the spectroscopic imaging methods. Localized spectroscopy may replace liver biopsy in the diagnosis of diffuse fatty infiltrations, and can be used for follow-up, due to its noninvasive nature.

DETERMINATION OF THE HEPATIC ARTERIAL BLOOD FLOW AND OXYGEN SUPPLY IN MAN BY CLAMPING THE HEPATIC ARTERY DURING SURGERY

The function of the hepatic artery has been extensively studied in animals (1-5). Great differences have been found from one species to another (6, 7), and our knowledge of the significance of the arterial blood supply to the human liver is limited mainly to observations of the late effect of occlusion of the hepatic artery (8) or of the portal vein (9, 10). As these events are followed by compensatory changes in the hepatic circulation (11, 12), no definite conclusions regarding the physiological role of the hepatic artery can be made on this basis. It might be expected that acute, transitory interruption of the blood flow through the hepatic artery minimizes this compensation and thus gives a clearer picture of the function of the artery.

Hepatic blood flow determination: A comparison of 99mTc-diethyl-IDA and indocyanine green as hepatic blood flow indicators in man*

99mTc-diethyl-acetanilide-iminodiacetic acid (IDA) was compared with indocyanine green (ICG) as an indicator of hepatic blood flow (HBF). Twelve subjects (8 with cirrhosis, 2 with fatty liver, one with pancreatitis, and one with intestinal angina) were studied during hepatic vein catheterization. In 9 subjects the HBF measurements (indirect Fick-principle) were within 0.8-1.9 l/min, and no significant difference was observed between the values obtained by ICG and 99mTc-diethyl-IDA (mean 1.24 vs 1.26 l/min, P greater than 0.4). In 2 subjects with cirrhosis very high but almost identical values were found with the two indicators. In one subject ICG could not be measured in plasma because of hyperlipidaemia, but HBF was easily determined by 99mTc-diethyl-IDA. The results indicate that 99mTc-diethyl-IDA can be used as an indicator of HBF. This indicator is not superior to ICG in patients with decreased liver function, but offers advantages in that it can be used with small plasma samples and permits the determination of HBF in the presence of hyperlipidaemia.

The Intraductal Pancreatic Pressure in Chronic Obstructive Pancreatitis

During operations for chronic obstructive pancreatitis in seven men the intraductal pressure was measured after puncture of the dilated pancreatic duct. The median pressure was 26 mm Hg (range, 20–42 mm Hg). The increased pressures indicate that the dilatation is secondary to the obstruction of the pancreatic duct, demonstrated by pancreatography.

SOURCES OF VENOARTERIAL ADMIXTURE IN PORTAL HYPERTENSION

It has been shown that cirrhosis of the liver is often accompanied by admixture of venous blood to the arterial blood, sometimes to a degree producing cyanosis (1-8). Two possible routes have been demonstrated morphologically: intrapulmonary arteriovenous shunts (2, 9), and channels connecting the portal circulation through esophageal and mediastinal veins with pulmonary veins (10, 11). The aim of the present study was to evaluate the physiological significance of these communications.

Glycerol Metabolism in the Human Liver: Inhibition by Ethanol

Glycerol is metabolized predominantly in the liver, the first step presumably being phosphorylation to α-glycerophosphate. When ethanol is present in the blood the rate of glycerol uptake by the splanchnic organs is reduced to about one-third of the control value. At the same time glycerophosphate accumulates in the liver. Hepatic blood flow and oxygen consumption are not influenced by the combined infusion of glycerol and ethanol. The phenomenon may be connected with the increased concentration of the reduced form of diphosphopyridine nucleotide present in the liver during ethanol metabolism.

Filtration as the main transport mechanism of protein exchange between plasma and the peritoneal cavity in hepatic cirrhosis

Fractional peritoneal reabsorption rates (FPRR) were determined from the plasma activity after simultaneous intraperitoneal injection of 131I-labelled serum albumin (a) and 125I-labelled immunoglobulin G-IgG (g) in eight patients with cirrhosis (+ ascites 6, -ascites 2) and in one patient with carcinomatous ascites. Trans-vascular escape rates of albumin (TERa) and IgG (TERg) were determined in the cirrhotic patients from the disappearance of simultaneously intravenously injected 131I-labelled serum albumin and 124I-labelled IgG. Peritoneal space to plasma appearance times ranged 0.1-3.3 h, and the appearance times of albumin and IgG were almost identical. In patients with cirrhosis FPRRa and FPRRg were on average 1.27 and 1.21% of intraperitoneal protein masses returning to plasma per hour, respectively. Mean FPRRg/FPRRa ratio was 0.95 and this value was not significantly different from unity, but significantly higher (P < 0.001) than the ratio between the free diffusion coefficients of IgG and albumin (0.06). The calculated ascitic fluid flow rate was on average 61 ml/h. TERa and TERg were on average 9.6 and 8.6% of intravascular protein masses per hour, mean TERg/TERa ratio was 0.95. Peritoneal space to plasma protein flux averaged 0.4% of the intravascular protein mass per hour. The results point to filtration (convective flux) as the main transport mechanism responsible for protein passage into the peritoneal cavity as well as for the protein passage (lymphatic drainage) back into the plasma. Pressure measurements during catheterization confirmed pressure differences essential for convective flux.

The Hepatic Metabolism of Ethanol in Patients with Cirrhosis of the Liver

Splanchnic ethanol uptake was lower in cirrhosis compared to normals. The accelerating effect of fructose on ethanol metabolism was smaller in cirrhosis. From studies of portocaval shunts, it appeared that acetate, formed from ethanol, was not metabolized in the liver. The peripheral metabolism of acetate, glucose and lactate was diminished in cirrhosis.

Filtration as the main mechanism of increased protein extravasation in liver cirrhosis

Transvascular escape rates of albumin and immunoglobulin-G, IgG (TERalb and TERIgG, i.e, the fractions of intravascular mass of albumin and IgG passing to the extravascular space per unit time) were determined simultaneously from the disappearance of intravenously injected 131I-labelled human serum albumin and 125I-labelled human IgG in eight patients with cirrhosis of the liver. The mean wedged hepatic venous pressure was 22 mmHg (range 13-34). TERalb and and TERIgG/TERalb ratio was on average 8.4 +/- 0.8%/h (SD), and 7.4 +/- 1.9%/h (SD), respectively and these values are significantly increased compared to normal subjects [TERalb = 5.2 +/- 1.0 %/h (SD) and TERIgG = 3.0 +/- 0.7 %/h (SD), P less than 0.001]. The TERIgG/TERalb ratio was on average 0.88 +/- 0.20 (SD), which is significantly higher than that of normals [0.58 +/- 0.08 (SD), P less than 0.005]. The results indicated that increased filtration (bulk flow) is the dominant process of the increase microvascular protein escape in cirrhosis, due most likely to increased hepatic, but also to increased extrahepatic splanchnic transcapillary protein flux.

Increased transvascular escape rate of albumin during experimental portal and hepatic venous hypertension in the pig. Relation to findings in patients with cirrhosis of the liver

Transvascular escape rate of albumin [TERalb, i.e. the fraction of the intravascular mass of albumin (IVMalb) passing to the extravascular space per unit time] was determined from the disappearance of i.v. injected radioiodinated serum albumin in anaesthetized pigs during control conditions and during regional venous congestion in the infradiaphragmatic area. Balloon catheters were placed in the portal vein (infrahepatic portal congestion) and in the inferior vena cava above (suprahepatic caval congestion) and below (infrahepatic caval congestion) the outlets of the hepatic veins. TERalb was on the average 13% IVMalb.h-1 under basal pressure conditions. TERalb rose significantly (p less than 0.01) during suprahepatic caval and infrahepatic portal congestion to an average of 29 and 19% IVMalb.h-1, respectively. TERalb was positively correlated to the portal pressure (r = 0.75, P less than 0.001). Only a minor increment in TERalb was found during infrahepatic caval congestion. The hepatic share of the increased TERalb during stasis above the hepatic veins was estimated to be threefold that of the extrahepatic splanchnic area. Our results point to filtration of protein, predominantely through the lining of the sinusoids and perisinusoidal space of the liver into the interstitial space around the portal vessels and further into the lymphatics, as the main mechanism of the previously demonstrated marked increase in TERalb in patients with portal venous hypertension due to cirrhosis of the liver.