The Effect of Hypotension in Obstructive Jaundice

Williams, Roger D.; Elliott, Dan W.; Zollinger, Robert M.

doi:10.1001/archsurg.1960.01300020162022

Cited by 100 publications

(35 citation statements)

References 3 publications

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“…CRH expression is decreased in the hypothalamus, which, in turn, has an inhibitory effect on ACTH (POMC) expression in the pituitary, leading to a decreased expression of the key steroidogenic enzymes HSD-3␤ and Cyp11b1 in the adrenal glands, which results in decreased circulating glucocorticoids. As mentioned above, the link between cholestasis and the HPA axis has been demonstrated clinically, with cholestatic patients often exhibiting clinical features suggestive of adrenal insufficiency, such as hypovolemia, hypotension, and renal failure (55,57). Furthermore, patients with congenital hypopituitarism or glucocorticoid deficiency often exhibit cholestatic hepatitis (5,20,28).…”

Section: Discussionmentioning

confidence: 96%

“…The hippocampus, which is the major controlling organ of the HPA axis, is the initial location in which the HPA axis can be suppressed. However, every region involved in the HPA axis has a negative-feedback mechanism, all leading to reduced circulating corticosteroid levels (6,8,24,26,27,29).Cholestatic patients exhibit clinical features suggestive of adrenal insufficiency, such as hypovolemia, hypotension, and renal failure (55,57). Furthermore, patients with congenital hypopituitarism or glucocorticoid deficiency often exhibit cholestatic hepatitis (5,20,28).…”

mentioning

confidence: 99%

“…Cholestatic patients exhibit clinical features suggestive of adrenal insufficiency, such as hypovolemia, hypotension, and renal failure (55,57). Furthermore, patients with congenital hypopituitarism or glucocorticoid deficiency often exhibit cholestatic hepatitis (5,20,28).…”

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confidence: 99%

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Suppression of the HPA axis during extrahepatic biliary obstruction induces cholangiocyte proliferation in the rat

Quinn¹,

Ueno

Pae

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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Cholestatic patients often present with clinical features suggestive of adrenal insufficiency. In the bile duct-ligated (BDL) model of cholestasis, the hypothalamic-pituitaryadrenal (HPA) axis is suppressed. The consequences of this suppression on cholangiocyte proliferation are unknown. We evaluated 1) HPA axis activity in various rat models of cholestasis and 2) effects of HPA axis modulation on cholangiocyte proliferation. Expression of regulatory molecules of the HPA axis was determined after BDL, partial BDL, and ␣-naphthylisothiocyanate (ANIT) intoxication. The HPA axis was suppressed by inhibition of hypothalamic corticotropinreleasing hormone (CRH) expression by central administration of CRH-specific Vivo-morpholinos or by adrenalectomy. After BDL, the HPA axis was reactivated by 1) central administration of CRH, 2) systemic ACTH treatment, or 3) treatment with cortisol or corticosterone for 7 days postsurgery. There was decreased expression of 1) hypothalamic CRH, 2) pituitary ACTH, and 3) key glucocorticoid synthesis enzymes in the adrenal glands. Serum corticosterone and cortisol remained low after BDL (but not partial BDL) compared with sham surgery and after 2 wk of ANIT feeding. Experimental suppression of the HPA axis increased cholangiocyte proliferation, shown by increased cytokeratin-19-and proliferating cell nuclear antigen-positive cholangiocytes. Conversely, restoration of HPA axis activity inhibited BDL-induced cholangiocyte proliferation. Suppression of the HPA axis is an early event following BDL and induces cholangiocyte proliferation. Knowledge of the role of the HPA axis during cholestasis may lead to development of innovative treatment paradigms for chronic liver disease.corticotropin-releasing hormone; glucocorticoids; biliary epithelium; adrenocorticotropic hormone CHOLANGIOCYTES ARE EPITHELIAL cells that line the intra-and extrahepatic bile ducts. They are constitutively mitotically dormant but possess marked proliferative capacity (2), which is apparent during experimental conditions, such as cholestasis induced by bile duct ligation (BDL) or ␣-naphthylisothiocyanate (ANIT) intoxication (1), as well as in human cholangiopathies (2). In humans, cholangiocyte proliferation occurs in extrahepatic biliary obstruction, in the course of chronic cholestatic liver diseases (e.g., primary sclerosing cholangitis, primary biliary cirrhosis, liver allograft rejection, and graft-vs.-host disease) (2), and in many forms of liver injury (e.g., in response to alcohol, toxin, or drugs) (2, 43).The hypothalamic-pituitary-adrenal (HPA) axis describes a complex set of positive-and negative-feedback influences between the hypothalamus, pituitary gland, and adrenal gland (25). These feedforward and feedback mechanisms work in a neuroendocrine manner to modulate a number of physiological processes, such as immunity (32), digestion (30), and the body's response to stress (30). In addition, the HPA axis has been shown to have an influence on human psychology (7, 53).The mechanism by which the HPA axis rem...

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Section: Discussionmentioning

confidence: 96%

mentioning

confidence: 99%

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Suppression of the HPA axis during extrahepatic biliary obstruction induces cholangiocyte proliferation in the rat

Quinn¹,

Ueno

Pae

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Increased perioperative morbidity and mortality are well recognized in patients with cholestasis, and are associated with hypovolemia, hypotension, and renal failure (1)(2)(3). These complications of cholestasis resemble the clinical features of adrenal insufficiency (4).…”

Section: Introductionmentioning

confidence: 99%

Suppression of hypothalamic-pituitary-adrenal axis responsiveness to stress in a rat model of acute cholestasis.

Swain¹,

Patchev²,

Vergalla³

et al. 1993

J. Clin. Invest.

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Cholestatic patients undergoing surgery have increased mortality and demonstrate clinical features suggestive of adrenal insufficiency. To examine whether cholestasis influences the status of the hypothalamic-pituitary-adrenal axis, we evaluated rats with acute cholestasis caused by bile duct resection (BDR) and sham-operated and unoperated controls. Basal unstressed plasma concentrations of AC`TH and corticosterone were similar in BDR and sham-operated and unoperated control rats. However, exposure of BDR rats to saturated ether vapor resulted in significantly less ACTH and corticosterone release in plasma than in the control animals. To understand the mechanism(s) of decreased HPA axis responsiveness to ether stress in cholestasis, we administered corticotropin-releasing factor (CRF) and measured hypothalamic content, mRNA levels and in vitro secretion of CRF and arginine vasopressin (AVP), the two principal secretagogues of ACTH. In BDR animals, ACTH responses to CRF were decreased and hypothalamic content of CRF and CRF mRNA expression in the paraventricular nucleus were decreased by 25 and 37%, respectively. Furthermore, CRF release from hypothalamic explants of BDR rats was 23% less than that ofcontrols. In contrast to CRF, hypothalamic content of AVP was 35% higher, AVP mRNA in the paraventricular nucleus was increased by 6.6-fold, and hypothalamic explant release of AVP was 24% higher in BDR rats than in control animals. Pituitary ACTH contents were similar in BDR and sham resected rats, but higher than unoperated controls. These findings demonstrate that acute cholestasis in the rat is associated with suppression of hypothalamic-pituitaryadrenal axis responsiveness to stress and demonstrate a dissociation between mechanisms of ACTH regulation mediated by

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“…Evidence also exists suggesting that obstructive jaundice may increase the risk of postoperative acute renal failure in humans (11), and it may predispose the kidney to ischemic damage in rodents (1,2). In these studies, however, the various parameters of renal function during obstructive jaundice were not evaluated.…”

Section: Introductionmentioning

confidence: 99%

Effect of Chronic Bile Duct Obstruction on Renal Handling of Salt and Water

Better¹,

Massry²

1972

J. Clin. Invest.

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A B S T R A C T Renal sodium reabsorption and the concentrating and diluting abilities of the kidney were evaluated in the same trained mongrel dogs before and after chronic common bile duct ligation (BDL). Glomerular filtration rate (GFR) and CPAH were not altered by BDL. The natriuretic response to a standardized infusion of 0.45% solution of NaCl was markedly blunted by BDL (P < 0.01); calculated distal sodium delivery was significantly less in experiments after BDL than in control studies. Furthermore, the fractional reabsorption of sodium at the diluting segment for any given rate of distal delivery was enhanced by BDL. Similarly, CH2o/ 100 ml GFR for a given sodium delivery was higher after BDL than control values. Maximal urinary concentration (Uosm-max) was lower after BDL, and the mean Uosm-max for the whole group of animals was 60% of the control value (P<0.001). Mean maximal TCH-o/100 ml GFR after BDL was not different from control values; however, TCH2o/100 ml GFR for a given Cosm/100 ml GFR was lower after BDL in three dogs only. The sodium content of the inner part of renal medulla after BDL was significantly lower than the values obtained in control animals. The excretion of an oral water load in the conscious state was impaired after BDL; although all animals excreted hypotonic urine, urinary osmolality was usually higher after BDL than in control studies. Maximal urinary concentration and the excretion of an oral water load were not affected by sham operation.These studies demonstrate that chronic, common bile duct ligation is associated with (a) enhanced sodium Dr.

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The Effect of Hypotension in Obstructive Jaundice

Cited by 100 publications

References 3 publications

Suppression of the HPA axis during extrahepatic biliary obstruction induces cholangiocyte proliferation in the rat

Suppression of the HPA axis during extrahepatic biliary obstruction induces cholangiocyte proliferation in the rat

Suppression of hypothalamic-pituitary-adrenal axis responsiveness to stress in a rat model of acute cholestasis.

Effect of Chronic Bile Duct Obstruction on Renal Handling of Salt and Water

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