Urea-Increting Function of the Liver and Urea-Secreting Function of the Kidneys After Liver Resection and Hyperbaric Oxygenation
P.N. Savilov*, D.V. Molchanov
Department of Normal Physiology, N. N. Burdenko Voronezh State Medical Academy, Voronezh, Russia
*Corresponding author
P.N. Savilov, Department of Normal Physiology, N. N. Burdenko Voronezh State Medical Academy, Voronezh, Russia
DOI: 10.55920/JCRMHS.2025.11.001469
Abstract
In experiments on 30 white female rats weighing 180-220 g, the effect of hyperbaric oxygenation (HBO, 3 ata (303.6 kPa), 50 min. on the urea-increting function of the liver and the urea-excreting function of the kidneys during liver resection (LR, 15-20% of the organ mass) was studied. HBO was used 4-8, 24 and 48 hours after LR. The studies were conducted on the 3rd day of the postoperative period. RP reduced the incretion of urea from the operated organ into the bloodstream, which was accompanied by a decrease in its excretion of urea from the body with urine. As a result, the concentration of urea in arterial blood remained within the normal range. At the same time, an increase in the concentration of urea in the blood of the portal vein was noted. The use of HBO eliminated the violation of the urea-increting function of the operated liver. Stimulated the incretion of urea into the bile capillaries and its hepatic-intestinal circulation in the operated organism. Under HBO conditions, the excretion of urea with urine by the kidneys in the operated organism increased while maintaining its increased entry into the bloodstream from the renal tissue.
Key words: Hyperoxia, Liver Resection, Urea, Metabolism
Introduction
It is generally accepted that an increase in the concentration of urea in the blood (along with creatinine) may indicate both a violation of the filtration capacity of the kidneys and an increase in catabolic processes in the body. Therefore, depending on the cause that caused the increase in these metabolites in the blood, a distinction is made between retention and production hyperazotemia. In the process of discussing the role of the kidneys in the excretion of urea from the body, most researchers point to the liver, where the formation of urea is associated with the neutralization of ammonia in the ornithine cycle. At the same time, the fact that the formation of urea may not be accompanied by the neutralization of ammonia is ignored. For this, the presence of arginase in the cell is sufficient, which is found in many organs and tissues of mammals, including the kidneys [1]. As studies have shown [2], the disruption of the urea-forming function of hepatocytes reduces the concentration of urea in the blood of the hepatic veins. However, in arterial blood it remains within the normal range or increases.
This is achieved by activating compensatory-adaptive mechanisms that prevent a decrease in the concentration of urea in arterial blood [2]. Consequently, urea in the body of mammals and humans is not only one of the final products of protein breakdown, but also a substance involved in the adaptation of the body to the action of pathogenic factors [2]. Currently, the role of urea as a participant in pathological processes in the nervous system [3,4,5], in the lungs during the development of ventilator-associated pneumonia [4], and in hepatorenal toxicity of pharmacological drugs [6] is being discussed. The role of urea as an endogenous antioxidant in the adaptation of the body to the therapeutic regimens of hyperbaric oxygenation (HBO) has been established [7,8]. At the same time, the question of the state of the urea-increting function of the liver and the urea-excreting function of the kidneys during liver resection and hyperbaric oxygenation (HBO) remains open.
Objective
To study the effect of liver resection and its combination with hyperbaric oxygenation (HBO) on the kinetics of urea in the liver and kidneys of rats.
Methodology
Experimental studies were conducted on 30 female white rats weighing 180-220 g. Liver resection (LR) was performed under ether anesthesia, removing part of the left lobe of the liver (15-20% of the organ mass). HBO was performed with medical oxygen in an experimental pressure chamber 4-8, 24 and 48 hours after LR in the 3 ata (303.6 kPa) mode. Compression time was 5 min, isopressure time was 50 min, decompression time was 5 min. Work with experimental animals was carried out in accordance with the regulations of the EU declaration of September 22, 2005 on the use of laboratory animals for scientific purposes. The study was approved by the Ethics Committee of the Voronezh State Medical Academy.
The objects of the study were the left and middle lobes of the liver (LLL and MLL, respectively), kidneys, common bile duct, urine, and blood: a. femoralis, v. porta, v. hepatica, v. renalis. Blood from the v. hepatica was obtained from the interlobar sinus (between the left and middle lobes of the liver) after its isolation from the posterior vena cava in situ. The operated animals were withdrawn from the experiment under ethaminal anesthesia on the 3rd day after liver resection; oxygenated animals - immediately after the end of the third session of HBO. The content of urea in tissue and biological fluids was determined by the diacetyl monoxime method [9]. The research results were statistically processed using the parametric Student t-test and the nonparametric Mann-Whitney test after preliminary testing of the hypothesis of normality of the sample distribution. The results were considered reliable at a value of p < 0.05. Statistical analysis was performed using the packages “Microsoft Excel”, Statistica 5.0 Statsoft” and “Biostat”.
Results
Normally, the urea content in the blood of v.hepatica significantly exceeded the same indicator in the arterial blood and the blood of v.porta, which made the hepatic arteriovenous (hAVDm) and portovenous (PVDm) differences in urea negative (Table). This indicates the incretion of urea from the intact liver into the central bloodstream. The arterioportal (APDm) and renal arteriovenous (rAVDm) differences in urea were positive (Table). This indicates the excretion of "arterial" urea into the lumen of the gastrointestinal tract (GIT) and renal tubules, respectively. The concentrations of urea in the LLL and MLL did not differ significantly (Table). On the 3rd day after LR, the urea content in the LLL, bile and arterial blood did not differ from the norm. In the unoperated MLL and blood, v. hepatica decreased by 16% and 28%, respectively. In the blood of v. porta, it increased by 45% (table). hAVDm was unreliable, PVDm was positive, APDm was negative. In the kidneys, the urea concentration remained within the normal range, decreased by 30% in urine and increased by 29% in the blood of v. renalis, as a result, rAVDm became unreliable (table).
In oxygenated rats with LR, on the 3rd day of the postoperative period, a reliable increase in the concentration of urea in the LLL and MLL was found both in comparison with the norm and with non-oxygenated animals with LR (table). In the blood of v.hepatica, its content was within the normal range, exceeding the similar indicator of animals of the 2nd series by 54% (table). Compared with the norm, the urea content in arterial blood, v. porta blood and bile was increased by 70%, 167% and 91%, respectively; whereas compared with the 2nd series of experiments - by 84%, 63% and 82%, respectively (Table). Negative hAVDm was restored, but was 48% below the norm, PVDРm and APDm were unreliable (Table). In the kidneys, the urea content did not change, but was increased in the blood of v. renalis relative to the norm and the 2nd series by 122% and 78%, respectively. This was accompanied by an increase in the concentration of urea in the urine relative to the norm and the 2nd series by 34% and 92%, respectively. rAVDm was reliable (Table).
Table 1: Urea content in the liver, kidneys (mmol/kg wet tissue) and biological fluids (mmol/l) on the 3rd day after liver resection and a three-day course of hyperbaric oxygenation (M ±m)
Discussion
The decrease in urea incretion from the operated liver into the central bloodstream on the 3rd day after LR did not lead to a similar change in the arterial blood. This was accompanied by retention of urea in the liver, which was supplied in excess with the blood v.porta. As indicated by the positive PVDm. However, this was not enough to prevent a decrease in the urea concentration in the MLL. One of the reasons for this should be considered a decrease in its formation by hepatocytes of the operated organ [10]. At the same time, the excretion of urea from the operated liver with bile did not change. In turn, a negative APDm indicated a decrease in the secretion of "arterial" urea" into the lumen of the gastrointestinal tract, which led to an increase in its content in the blood of v. porta. At the same time, there was a decrease in the excretion of urea with urine as a result of an increase in its reabsorption in the renal tubules. This is indicated by an increase in its concentration in the blood of v. renalis, while in arterial blood it was within normal limits.
(p<0,05) – достоверность различий по сравнению с LR (2 серия), nsd – not significant difference,
Comparison of the degree of increase in urea concentration in the operated liver of oxygenated rats, as well as in the blood flowing into and swells from it (table) allows us to draw the following conclusions. Firstly, about hyperoxic stimulation of urea formation in the operated liver with its subsequent preferential incretion into the bile capillaries and activation of the hepatointestinal circulation of urea. This is indicated by the positive correlation between the urea content in the bile and blood v. porta (r=0.89).
Secondly, under the conditions of using HBO, the reduced excretion of "arterial" urea into the lumen of the gastrointestinal tract was maintained in the operated organism. Thirdly, under the conditions of HBO, the increased reabsorption of urea in the kidneys caused by LR was eliminated. This was accompanied by an increase in its concentration in the urine. Fourthly, HBO stimulated the formation of urea by cells of the renal tubules with its subsequent incretion into the renal blood flow. This is indicated by the discrepancy between the degree of increase in the urea content in the arterial blood and the blood of the v. renalis compared to the norm
Conclusion
Liver resection reduces the incretion of urea from the operated organ into the bloodstream, which does not lead to the development of urea deficiency in arterial blood. At the same time, the excretion of urea in the urine decreases as a result of increased reabsorption in the kidneys and its content in the blood of the portal vein increases as a result of decreased secretion of the metabolite into the lumen of the gastrointestinal tract. A three-day course of HBO in the 3 ata, 50 min mode, applied after LR, eliminates the disturbance of the urea-increting function of the operated liver. This is accompanied by the normalization of the urea content in the blood flowing from the liver against the background of hyperoxic stimulation of its entry into the bile capillaries. Under HBO conditions, the excretion of urea with urine by the kidneys of the operated organism increases while maintaining its increased entry into the bloodstream from the renal tissue.
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