[Systemic circulation in portal hypertension].
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Biomedical subjects
Publications and source records attributed to M Grün.
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Investigations were performed in rats with portacaval anastomosis (PCA) in order to measure hepatic hemodynamics and cardiac output (CO) 3, 6, 14 and 28 days after operation under pentobarbitone anesthesia using the flow fraction distribution method (131I-MAA) of CO. The latter was calculated using Vierordt's principle from blood volume (BV) (125RIHSA-dilution method) and ICG-appearance time (ICG-AT) (ear-densitometry). Even 3 days after PCA CO was increased to 38.7 +/- 5.0 (SD) ml/min/100 g b.w. (normal 23.8), due to an increase of BV from 6.3 +/- 1.4 to 7.5 +/- 0.6 ml/100 g b.w. and a decrease of ICG-AT from 3.6 +/- 0.4 to 2.8 +/- 0.5 s. Arterial hepatic flow fraction of CO increased to 8.7 +/- 2.8% (control: 5.5 +/- 2.4%). Changes could be observed up to day 28. Hepatic blood flow per g liver tended to stabilize but was still decreased at day 28: 1.5 +/- 0.6 ml/min/g liver (control: 2.0 +/- 0.3). The typical hemodynamic changes in human liver cirrhosis can be reproduced by PCA alone. They are considered to be compensatory mechanisms for a reduced portal liver blood flow, which are not found to compensate completely.
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Renal dysfunction in patients with cirrhosis of the liver is frequent especially in connection with endotoxaemia. Renal and intrarenal haemodynamics were investigated, therefore, in normal rats with or without portacaval anastomosis (PCA) by means of the cardiac output (CO) fractionation technique using microspheres. The intrarenal blood distribution was estimated after anatomical separation of renal cortex and medulla. In normal rats the total renal fraction of CO was 22.5 +/- 7.2%, and the renal medulla fraction 0.8 +/- 0.4% of CO. After a single injection of E. coli-endotoxin (1.5 mg/kg b.w.) the animals developed a high-cardiac-output state, the mean arterial pressure decreased from 110 +/- 15 mm Hg to 81 +/- 6 mm Hg. Renal fraction of CO was unaltered but the blood flow through the kidney was increased due to the high CO. The blood flow of the medulla increased five to tenfold of control values whereas renal cortical blood flow decreased. During the first eight hours after endotoxin administration the animals developed polyuria with a decrease of urine osmolality. Comparable systemic and renal haemodynamics were present in untreated PCA-rats, in which endotoxaemia was present spontaneously (Limulus Gelation Test). Additional endotoxin administration in these animals caused severe shock syndrome with a decrease in total renal perfusion and a further decrease in renal cortical blood flow. Endotoxin administration in normal rats caused minimal morphological alterations in the kidneys which were comparable with those found in PCA-rats. Endotoxin administration in PCA-rats however leads to severe damage of the kidney with fibrin deposits in the glomerula and acute tubular necroses. The haemodynamic, functional and morphological changes caused by endotoxin in the experiments are observed in principle in patients with cirrhosis of the liver too. This indicates that endotoxin should be taken into considerations concerning the pathogenesis of renal failure in patients with cirrhosis of the liver.
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Endotoxins of gram-negative bacteria and of intestinal origin, insufficiently cleared by the hepatic reticulo-endothelial system are of an increasing interest within the pathogenesis of liver diseases. With purpose to obtain data concerning incidence and course of endotoxaemia in patients with liver cirrhosis an unselected group of these patients, sequentially admitted, was investigated by means of the Limulus-gelation test, regarded as most sensitive to endotoxins. At the admittance, 65% of the patients had endotoxaemia, further 14% developed endotoxaemia later. In total 79% of the patients investigated had endotoxaemia.---Bleeding from oesophageal varices was associated with endotoxaemia in 78%, functional renal impairment in 75%, consumption coagulopathy in 81%, encephalopathy in 77% and a pyrogen reaction in 82% of the patients. Regarding the Limulus assay, the dilution technique was more sensitive in detection of free endotoxaemia as opposed to the chloroform extract. It is concluded from the results that endotoxaemia in patients with liver cirrhosis is frequent and has to be viewed as relevant within the pathogeneses of chronic liver diseases.
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The supply of copper to ruminants as influenced by and depending on the geological origin of soils was investigated in different parts of the GDR by using the hair test. Red clovers (meadow clover and field clover) were used as indicator plants. The following results were obtained: Data on the Cu content of clovers grown on soils of the same geological origin were found to correlate with r = 0,81. After eliminating the effects of Cu antagonists resulting from industrial pollution it was possible to establish numerical relations (B = 0.39 and B = 0.89) between the relative values (specific for the particular location) for the Cu content of the indicator plants and the percentage of cows suffering from Cu deficiencies (6.0 and 5.0 ppm Cu in hair). The lowest percentages of Cu supply to the ruminants (established on the basis of the Cu content of red clovers) were found on diluvial sandy soils, glacial loams and peat and bog soils whereas the highest percentages of Cu were found on weathered soils (of phyllite, gneiss, shell limestone, red marl soils and porphyry). Secondary Cu deficiencies in ruminants may arise, independent of the geological origin of the soil material, in places exposed to the main direction of the winds from major industrial areas (emission of SO2, Cd and Mo). Due to primary and/or secondary deficiencies the supply of Cu to ruminants in various locations (syenite, granite, red sandstone, gneiss, loess; peat soils, diluvial sandy soils) may be insufficient. A detailed description is given of areas where Cu deficiency is likely to occur and recommendations are given on how to use mineral mixtures containing a high proportion of Cu (1.00 g Cu per kg).
The supply of zinc to ruminants as influenced by and depending upon the geological origin of soils was investigated using the hair test and the technique of indicator plants. A total of 1276 samples of red meadow clover and 3022 samples of red field clover and 4184 hair specimens from cows were analyzed. The following statistically well-established results were obtained which appear to be generalizable: Red meadow clover contained significantly more Zn than red field clover (48 ppm/38 ppm). Red meadow clover and field clover grown on loamy soils (59%), weathered soils of less (59%), red sandstone (57%) basalt (53%), shell limestone (47%) and Keuper (41%) contained only 59%-41% of the amount of Zn found in indicator plants that were grown in locations were the highest Zn level (weathered soils of porphyry). Zn concentrations in red meadow and field clover grown on soils of the same geological origin correlated with r = 0.87. A positive correlation (B = 0.53) was found to exit between the relative proportions of Zn contained in indicator plants grown on a particular soil and the proportions of Zn contained in hair specimens from Zn-deficient cows (less than 100 ppm of Zn). The largest number of hair specimens containing less than 100 ppm of Zn were found in cows from areas with soils of basalt (17%), and loess (18%), areas with loamy soils (24%), and sandy diluvial soils (25%), or with alluvial pastures (23%), or with soils of Keuper (27%), shell limestone (22%) or red sandstone (29%). Ruminants in these areas are liable to suffer from Zn deficiencies.
The effects of intravenously administered endotoxin on the hepatic and systemic circulation as well as on the coagulation system were evaluated in normal rats (n = 26), in rats with experimental portal hypertension (n = 15), and in rats with portacaval anastomosis (n = 22). Endotoxin (1-5 mg/kg) in the normal rat leads to a prompt increase of transaminase activity and to a hyperdynamic circulation with a consequent increase in the total hepatic blood flow. In a later phase (6 h postoperatively) the hepatic artery dilated with a consequent hepatic arterial hyperperfusion. The coagulation system was affected with signs of consumption coagulopathy. In the rats with portal hypertension and portacaval collaterals as well as in those with portacaval anastomosis, the endotoxin injection resulted in acute liver necrosis within 12 to 15 hours. The hepatic artery became overdilated with a cardiac output fraction of 25% (normal 5-5%). Blood extravasates and thrombi, rich in fibrin, were detected in the liver. It is suggested that this exaggeration of the endotoxin effect was due to an impaired clearance function of the reticuloendothelial system, probably as consequence of portacaval collateral circulation. It is concluded that endotoxins (1) damage the liver even in a normal organism; (2) are potent to induce acute liver necrosis, if the reticuloendothelial system is altered; (3) have to be taken into consideration as contribution to the pathogenesis of acute as well as chronic liver diseases.
Morphological investigations by lightmicroscopy were performed to evaluate the influence of an altered liver RES-function state on the course of Gal-N-hepatitis. There was a good correlation between the biochemical data and the morphological alterations. The simultaneous infusion of Gal-N 1 g/kg b.w. and carbon particles (2.6 mg/100 g b.w) into the portal vein was followed by subtotal necrosis of the liver and Sanarelli-Shwartzmann-phenomenon. Signs of RES-activity were nearly absent. 8 days after pretreatment with carbon, Gal-N application did not produce Gal-N hepatitis; 21 days after carbon infusion the morphological changes normally found after Gal-N application were present. The morphological studies confirm the concept that an altered RES-function state is a very important factor for the development of liver cell necrosis.
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