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Changes of portal hemodynamics with the progression of chronic liver disease and changes caused by body posture and physical exercise were investigated using an ultrasonic pulsed Doppler flowmeter in healthy adults and in patients with chronic persistent hepatitis, chronic active hepatitis, and cirrhosis. Portal venous velocity was significantly reduced in patients with chronic active hepatitis, cirrhosis without a large splenorenal shunt, and cirrhosis with a large splenorenal shunt, compared with normal subjects and patients with chronic persistent hepatitis. Portal venous flow, by contrast, was significantly reduced only in patients with cirrhosis and a large splenorenal shunt compared with normal subjects and with the other three groups; there was no significant difference in portal venous flow among the latter four groups. Both portal venous velocity and flow showed a tendency toward further reduction in patients with cirrhosis who had hepatofugal flow of part of the superior mesenteric venous blood into the splenic vein and a large splenorenal shunt. Both exercise and posture change from supine to sitting significantly reduced portal venous velocity and portal venous flow in normal subjects, as well as in the patients with chronic liver disease.

Basophilic hepatic foci, nodules, and trabecular hepatocellular carcinomas, collectively referred to as focal hepatic lesions, were induced by single injections of 5.0 micrograms of diethylnitrosamine (DEN) per gram body weight in 15-day-old C57BL/6J X C3HeB/FeJ F1 (B6C3 F1) mice. Groups of eight experimental and eight control mice were killed at 3 days and at 1, 2, 4, 10, 20, 28, 36 and 41 weeks after injection. The only observable acute hepatic toxic effect of DEN, a mild steatosis, was noted at 3 days, but this had disappeared by 7 days following injection. Basophilic foci, composed entirely of altered hepatocytes, were first noted, when very small, at 10 weeks. At later times, some of the foci also contained small collections of proliferated ductules, apparently a result of secondary ingrowth from nearby interlobular bile ducts. The hepatocytes within basophilic foci were characterized by their abundant cytoplasmic RNA, a high nuclear to cytoplasmic ratio (two times greater than normal), which gave them a "crowded appearance," and decreased glucose-6-phosphatase activity. During the course of the study, basophilic foci appeared to increase in size and number. Cytologic anaplasia also became more evident, ultimately culminating in the development of typical trabecular hepatocellular carcinomas by 44 weeks. Invasion of hepatic veins by basophilic foci, first noted at 10 weeks, was prominent by 20 weeks and indicated that many of the lesions manifested this characteristic of malignancy well in advance of the anaplastic features that are also diagnostic of hepatocellular carcinoma. The high growth rates of basophilic foci were confirmed by their greatly increased 3H-thymidine labeling indices, which were 20 times greater than background hepatocytes at 20 weeks following DEN injection. Tumor progression during the course of the study was also suggested by a doubling of labeling indices of hepatocytes in the basophilic foci between 20 to 28 weeks. (The term tumor progression is used in a broad biological sense to encompass any or all of the qualitative and quantitative changes describing the stepwise development of initiated cells to highly malignant neoplasms. This definition differs from the more clinical usage which restricts the process to qualitative changes during the late stages in the development of fully autonomous neoplasms.) An analysis of the number and size of transections through basophilic foci and in some cases, actual reconstructions of the foci from serial sections, indicated that, in aggregate, they grew exponentially between 10 to 36 weeks, with a volume doubling time of 2.5 weeks. The combined morphologic and kinetic data support the view that trabecular hepatocellular carcinomas develop from basophilic foci. Because of their ease of quantitation on conventional H&E stained sections, their rather uniformly spherical shapes, and the high probability of their clonal origin, the induced focal hepatic lesions should provide a useful model for studying tumor growth kinetics during carcinogenesis.Ima...

An ultrasonic sector scanner and pulsed Doppler flowmeter were combined to measure portal venous velocity in 19 patients with portal hypertension and compared with cineangiographic mapping of a droplet of oil released into the portal vein. In 12 patients, measurements were made before and after pitressin [7] or ranitidine [5]. With the Doppler method, maximum basal portal venous velocity was 17.0 +/- 3.9 cm/sec., while average cineangiographic velocity was 8.5 +/- 2.7 cm/sec., a significant difference (p less than 0.001). After pitressin, velocity decreased to 8.3 +/- 2.7 cm/sec. with the Doppler method and 3.6 +/- 1.0 cm/sec. with cineangiography. Ranitidine did not produce an appreciable change. Doppler and cineangiographic velocity measurements exhibited significant correlation over a wide range of values (r = 0.960). Thus the pulsed Doppler method may give accurate values of portal venous velocity if they are corrected to cineangiographic values. Flow can be calculated from velocity and the cross-sectional area of the portal vein as measured on the sonogram. The Doppler method is simple and noninvasive and is particularly useful in studying changes in portal hemodynamics.

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