Portosystemic shunt

BUN, blood urea nitrogen IV, intravenous Na, sodium PMN polymorphonuclear leukocyte TIPS, transjugular intrahepatic portosystemic shunt. (From Chung RT, Podolsky DK. Cirrhosis and its complications. In Kasper DL, Braunwald E, Fauci AS, et a I, (eds.) Harrison s Principles of Internal Medicine. 16th ed. New York McGraw-Hill, 2005 1858-1869, with permission.)... 

FIGURE 21-2. Management of acute variceal hemorrhage. (ABCs, airway, breathing, and circulation TIPS, transjugular intrahepatic portosystemic shunt.)... 

If standard therapy fails to control bleeding, a salvage procedure such as balloon tamponade (with a Sengstaken-Blakemore tube), transjugular intrahepatic portosystemic shunt, or surgical shunting is necessary. 

CBC, complete blood cell count EEG, electroencephalogram NSAIDs, nonsteroidal antiinflammatory drugs O2, oxygen PPF, plasma protein fraction PT, prothrombin time TIPS, transjugular intrahepatic portosystemic shunt. 

Acetyls alley lie acid was shown to prevent cirrhosis under certain experimental conditions [125]. Naproxen and indomethacin partially protected against LPS and D-galactosamine-in-duced hepatotoxicity [126] Acetylsalicylic acid and ibuprofen were also protective in endo-toxic shock [127]. Endotoxaemia is one of the complications in cirrhotic patients [128] and is probably caused by an impaired ability of the liver to take up and detoxify gut-derived LPS [116]. The presence of portosystemic shunts in cirrhotic patients may also contribute to this spill-over of LPS into the systemic circulation [129]. NSAIDs, however, are also reported to provoke deleterious effects on renal function in cirrhosis [130], and can therefore not be used in cirrhotic patients. Cell-specific delivery of NSAIDs to SECs and/or KCs may make application of these drugs in cirrhosis feasible by circumventing the renal side-effects. 

Since the structure of the liver is completely changed during fibrosis, distribution of a liver targeting compound has to be tested in the pathological state as well. Parts of the liver may become inaccessible by portosystemic shunts and individual cells may be hampered in the uptake of compounds by the excess extracellular matrix deposited around them. Uptake processes themselves may also be impaired. The phagocytic activity of KCs has been reported to be depressed in some forms of fibrosis [153,154] and some receptors, such as the... 

Khan S, Tudur Smith C, WUhamson P, Sutton R. Portosystemic shunts versus endoscopic therapy for variceal rebleeding in patients with cirrhosis. Cochrane Database Syst Rev 2006. 

Cirrhosis Hyperglycaem i a Portosystemic shunting of insulin and decreased hepatic insulin breakdown leads to inhibition of muscle glucose utilisation and peripheral insulin resistance, leading to elevated glucose levels Hyperglycaemia, acidosis, osmotic diuresis... 

There are several theories behind the cause of hepatic encephalopathy. One of these is that the accumulation of toxins in the brain, particularly ammonia, is the cause. Ammonia is produced in the intestine and is usually metabolised in the liver to urea via the urea cycle. As a result of portosystemic shunting and reduced metabolism in the liver, ammonia serum levels rise as the transformation to urea is reduced. However, the validity of this theory is questionable as not all patients with signs of hepatic encephalopathy have raised serum ammonia levels. Another theory is that patients with hepatic encephalopathy have increased permeability of the blood-brain barrier, and hence the increased toxin levels permeate the brain more than usual, leading to altered neuropsychiatric function. There are also theories relating to increased levels of neurotransmitters, short-chain fatty acids, manganese and increased GABA-ergic transmission. 

Transjugular intrahepatic portosystemic shunt (TIPS) is a side-to-side non-selective portosystemic shunt that is frequently performed in cirrhosis to manage the complications of portal hypertension, such as variceal bleeding. The observation that the bioavailability of oral midazolam was significantly higher in cirrhotic patients with TIPS than in cirrhotic controls and healthy volunteers [57] may be due to reduced intestinal CYP3A activity or reduced contact with CYP3A in the entero-cyte due to increased splanchnic blood flow [57, 92]. 

Chalasani N, Gorski JC, Patel NH, et al. (2001) Hepatic and intestinal cytochrome P450 3A activity in cirrhosis effects of transjugular intrahepatic portosystemic shunts. Hepatology 34 1103-1108. 

When portosystemic shunting is present total hepatic blood flow (Q) equals the sum of perfusion flow (Q ) and shunt flow (Qs). Portocaval shunting will impair the efficiency of hepatic extraction and reduce the extraction ratio as indicated by the following modification of Equation 7.5 (23). 

There can be a pronounced increase in methionine and its derivatives in acute liver failure or in serious cases of cirrhosis. From these substances, mercaptans are formed in the colon (e. g. methandiol, ethandiol, dimethyldisul-phide). The cause of the sweetish aromatic smell of the expiratory air ( fresh-raw liver ) known as hepatic foetor (F. Umber, 1926 L. Schiff, 1946) is deemed to be volatile dimethylsulphide. (38) Its concentration does not correlate with the degree of encephalopathy or hepatic insufficiency, but with the intensity of the portosystemic shunts. Trimethylamine is also suspected of being a causative factor. (22) (s.pp 267, 379)... 

Urata, J., Yamashlta, Y., Tsnchigame, T., Hatanaka, Y., Matsukawa, T., Snml, S., Matsuno, Y., Takahashi, M. The effects of transjugular intrahepatic portosystemic shunt on portal hypertensive gastropathy. J. Gastroenterol. Hepatol. 1998 13 1061-1067... 

While hepatic encephalopathy is nearly always found in acute liver failure, it can only be expected in some 25-40% of patients with a portosystemic shunt. When these two preconditions coincide, as in the case of liver cirrhosis, manifest hepatic encephalopathy is witnessed in 30-50% of patients and a subclinical course of disease in 50-70%. In other words, the frequency, the degree of severity and the course taken by HE depend on the underlying conditions. 

Sanyal, A.J., Freedman, A.M., Shiffman, M.L., Purdum, PR, Luketic, V.A., Cheatham, A.K. Portosystemic encephalopathy after transjugular intrahepatic portosystemic shunt results of a prospective controlled study. Hepatology 1994 20 46-55... 

Sarin, S.K., Nundy, S. Subclinical encephalopathy after portosystemic shunts in patients with non-cirrhotic portal fibrosis. Liver 1985 5 142-146... 

Gines, E, Uriz, J., Calahorra, B., Garcia-Tsao, G., Kamath, P.S., Rnlz-del-Arbol, L., Planas, R., Bosch, J., Arroyo, V., Rodes, J. Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis. Gastroenterology 2002 123 ... 

Degawa, M., Hamasaki, K., Yano, K., Kanao, K., Kato, Y., Sakamoto, I., Nakata, K., Eguchi, K. Refractory hepatic hydrothorax treated with transjugular intrahepatic portosystemic shunt. J. Gastroenterol. 1999 34 128-131... 

Refractory ascites early experience in treatment with transjugular intrahepatic portosystemic shunt. Radiology 1993 189 795-801... 

Gerbes, A.L., Giilberg, V., Waggershauser, T., Holl, J., Reiser, M. Renal effects of transjugular intrahepatic portosystemic shunt in cirrhosis comparison of patients with ascites, with refractory ascites, or without ascites. Hepatology 1998 28 683-688... 

Trotter, J.F., Suhocki, P.W., Rockey, D.C. Transjugular intrahepatic portosystemic shunt (TIPS) in patients with refractory ascites effect on body weight and Child-Pugh score. Amer. J. Gastroenterol. 1998 93 1891-1894... 

Younossi, Z.M., McHutchlson, J.G., Broussard, C., Cloutier, D., Sedghi-Vaziri, A. Portal decompression by transjugular intrahepatic portosystemic shunt and changes in serum-ascites albumin gradient. J. CUn. Gastroenterol. 1998 27 149-151... 

Lasch, H.M., Fried, M.W., Zacks, S.L., Odell, R, Johnson, M.W., Gerber, D.A., Sandhu, F.S., Fair, J.H., Shrestha, R. Use of transjugular intrahepatic portosystemic shunt as a bridge to liver transplantation in a patient with severe hepatopulmonary syndrome. Liver Transplant. 2001 7 147-149... 

Ri er, J.L., Lang, KA., Johnson, S.P., Westerman, J.H. Transjugular intrahepatic portosystemic shunt improves oxygenation in hepatopulmonary syndrome. Gastroenterology 1995 109 978-983... 

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