Renal sodium retention in cirrhosis: Tubular site and relation to hepatic dysfunction

Wood, Laurence J.; Massie, Denise; McLean, Allan J.; Dudley, F. J.

doi:10.1002/hep.1840080422

Cited by 63 publications

(22 citation statements)

References 24 publications

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“…It has been shown that chronic aldosterone-receptor blockade prevents sodium retention in rats with cirrhosis induced by CCl 4 22 or common bile duct ligation. 8 However, the present study, as well as studies by others [4][5][6][7][8]23,24 shows that plasma levels of aldosterone are normal during early sodium retention in cirrhosis. This argues against hyperaldosteronism and increased collecting-duct sodium reabsorption as a major factor in early sodium retention.…”

Section: Renal Function During Early Sodium Retention In Cirrhosissupporting

confidence: 40%

Increased natriuretic efficiency of furosemide in rats with carbon tetrachloride-induced cirrhosis

et al. 2000

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The authors examined the natriuretic efficiency of furosemide in rats with cirrhosis induced by carbon tetrachloride (CCl 4 ). Rats were treated for 17 weeks with intraperitoneal injections of CCl 4 in groundnut oil twice a week throughout the study. Control rats were treated with vehicle (groundnut oil). Studies in metabolic cages showed that sodium retention was present from week 14. Renal clearance experiments were performed in chronically, instrumented conscious rats at the end of week 14 and at the termination of the study (end week 16) when ascites and hyponatremia were present. After 14 weeks, cirrhotic rats had sodium retention along with increased renal plasma flow, normal GFR, normal renal lithium handling, and a significantly increased diuretic (؉41% vs. control) and natriuretic (؉56% vs. control) response to a test dose furosemide (7.5 mg/kg b.w., intravenously). The natriuretic efficiency of furosemide, i.e., the natriuresis expressed relative to the furosemide excretion rate (⌬U Na V/U FUR V) was increased by 51% versus control. After 17 weeks, ascites and hyponatremia had developed, and significant decreases in renal plasma flow (؊33%), GFR (؊30%), and fractional lithium excretion (؊44%) were observed. At this stage urinary recovery of furosemide was significantly decreased and the diuretic (؊27% vs. Control) and natriuretic (؊38% vs. control) responses to furosemide were significantly impaired. However, the increased natriuretic efficiency of furosemide was still present (؉34% vs. control). Together these results suggest that increased sodium reabsoprtion in the thick ascending limb of Henle's loop is involved in the renal sodium retention in cirrhosis in rats that eventually results in decompensation with the

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Section: Renal Function During Early Sodium Retention In Cirrhosissupporting

confidence: 40%

Increased natriuretic efficiency of furosemide in rats with carbon tetrachloride-induced cirrhosis

et al. 2000

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“…36 Whereas all authors agree that increased renal sodium retention occurs in cirrhosis, the opinions differ with respect to temporal relationship, mechanism, and quantitative relevance of aldosterone. 1,[37][38][39][40][41][42][43] Aldosterone receptors are transcription factors that can be activated not only by the mineralocorticosteroid aldosterone, but also by the endogenous glucocorticosteroids, cortisol and corticosterone. 6 Under normal conditions, however, only aldosterone, but not cortisol or corticosterone, has access to the MR, because a gate-keeper enzyme, the 11␤-HSD2, converts cortisol and corticosterone into glucocorticosteroids devoid of affinity for the MR, namely cortisone and dehydrocorticosterone, respectively.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of 11?-hydroxysteroid dehydrogenase by bile acids in rats with cirrhosis

et al. 1999

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Renal sodium retention and potassium loss occur early, in many instances in the preascitic state of cirrhosis, an observation that cannot be fully explained by increased aldosterone concentrations. We therefore hypothesize that 11␤-hydroxysteroid dehydrogenase 2 (11␤-HSD2), which protects mineralocorticoid receptors (MR) from glucocorticosteroids, is down-regulated in cirrhosis. Cirrhosis was induced by bile duct ligation in rats. The urinary ratio of (tetrahydrocorticosterone ؉ 5␣-tetrahydrocorticosterone)/ 11-dehydro-tetrahydrocorticosterone [(THB؉5␣-THB)/ THA] was measured by gas chromatography. Cortical collecting tubules (CCT) were isolated by microdissection and used for measurements of the activity of 11␤-HSD2 by assessing the conversion of corticosterone to dehydrocorticosterone. The mRNA content of 11␤-HSD2 was determined by reverse-transcription polymerase chain reaction (RT-PCR) in CCTs. The urinary ratio of (THB؉5␣-THB)/ THA increased concomitantly with the urinary excretion of bile acids following bile duct ligation. Chenodeoxycholic acid (CDCA) dose-dependently inhibited 11␤-HSD2 in CCT with a Ki of 19.9 mol/L. Four weeks after bile duct ligation, 11␤-HSD2 activity was decreased in CCT, an observation preceded by a reduced mRNA content at weeks 2 and 3. In cirrhosis, the MR-protecting effect by 11␤-HSD2 is diminished, and therefore, endogenous glucocorticoids can induce MR-mediated sodium retention and potassium loss. (HEPATOLOGY 1999;30:623-629.)Renal sodium retention and potassium loss are observed in patients suffering from cirrhosis. Traditionally, this abnormality was attributed to secondary hyperaldosteronism as a consequence of renal hypoperfusion related to intraabdominal fluid sequestration.

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“…55 The elevated renal venous noradrenaline concentration in cirrhotic patients [56][57][58] suggests that augmented renal sympathetic nerve activity is a mechanism underlying the abnormal body fluid regulation in liver cirrhosis. This increase has the capacity to alter renal function by altering tubular reabsorption, renin release and renal hemodynamics, in a manner consistent with the phenomena observed in cirrhosis.…”

Section: Liver Cirrhosismentioning

confidence: 99%

Negative feedforward control of body fluid homeostasis by hepatorenal reflex

Morita

Abe

2011

Hypertens Res

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The liver, well known for its role in metabolism, clearance and storage can also be regarded as a sensory organ. The liver is an ideal place to monitor the quality and quantity of absorbed substances, because portal blood delivers substances absorbed from the intestine to the liver and these substances circulate in the hepatic vasculature before substances enter the systemic circulation. Sodium (Na + )-sensitive mechanism exists in the liver; it is stimulated by the increase in Na + concentration in the portal vein, and then hepatorenal reflex is triggered. Renal sympathetic nerve activity is reflexively decreased and urinary Na + excretion is increased. This Na + -sensitive hepatorenal reflex has a significant role in post-prandial natriuresis. However, the long-term role of this reflex in Na + homeostasis may be less important, probably because of the desensitization of Na + -sensitive mechanisms. Na + -K + -2Cl -cotransporter (NKCC1) is involved in the hepatoportal Na + -sensitive mechanism, and NKCC1 expression is reduced if the hepatoportal region is exposed to high Na + concentrations for a long time. This situation occurs when animals intake a high-sodium chloride diet for a long time. Liver cirrhosis also impairs the Na + -sensitive hepatorenal reflex. Hepatoportal baroreceptor-induced renal sympathetic excitation and the impaired Na + -sensitive hepatorenal reflex may partially explain the Na + retention in liver cirrhosis. Keywords: hepatorenal reflex; hepatic afferent nerve; liver cirrhosis; post-prandial natriuresis; renal sympathetic nerve It is well documented that the mammalian liver is not only a metabolic, clearance and storage organ but also contains many receptors, including osmoreceptors, 1,2 baroreceptors 3,4 and ionic receptors. [5][6][7] Given the roles that these receptors have in the systemic circulation, it is possible that they are also involved in the regulation of body fluid homeostasis. A growing body of evidence suggests that the osmoreceptors and ionic receptors in the liver and its vasculature detect a variety of physiological events and are responsible for the activation of a number of physiological responses, which may have important roles in the regulation of body fluid homeostasis. The important features of the hepatic sensor mechanism are: (1) substances consumed orally are absorbed from the intestine into the blood, circulate in the hepatic vasculature and then enter the systemic circulation; and (2) the portal venous blood flow is 20-25% of the cardiac output. Because of these features, the hepatic osmoreceptors and ionic receptors have advantages over those receptors located in the systemic circulation. First, the hepatic receptors are triggered by changes in portal venous osmolality and ionic concentration before any changes occur in the systemic blood, and then reflexively regulate renal excretion and intestinal absorption. 7-10 Second, the concentrations of the absorbed substances in the hepatoportal region and the changes in them are 4-5 times greater than those in th...

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Renal sodium retention in cirrhosis: Tubular site and relation to hepatic dysfunction

Cited by 63 publications

References 24 publications

Increased natriuretic efficiency of furosemide in rats with carbon tetrachloride-induced cirrhosis

Increased natriuretic efficiency of furosemide in rats with carbon tetrachloride-induced cirrhosis

Inhibition of 11?-hydroxysteroid dehydrogenase by bile acids in rats with cirrhosis

Negative feedforward control of body fluid homeostasis by hepatorenal reflex

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