Chronic liver failure

Ammonia concentrations in arterial blood of patients with liver failure rise to 0.5-1 mmol/1, in contrast to the normal range of 0.01-0.02 mmol/1. Using positron emission tomography (PET see Ch. 58), increases of the cerebral metabolic rate for ammonia (CMRA), i.e. the rate at which ammonia is taken up and metabolized by the brain, have been reported in chronic liver failure [9]. Increased CMRA in chronic liver failure is accompanied... 

Lactitol 40 is a disaccharide that has been used in the management of hepatic encephalopathy, a major neuropsychiatric complication of both acute and chronic liver failure. It has mild laxative properties and is used to reduce the production and absorption of gut-derived neurotoxic substances symptomatic of hepatic encephalopathy. Although long considered a first-line pharmacological treatment, there is a lack of sufficient evidence to support lactitol s efficacy and continued use when weighed against other suitable therapeutic alternatives such as oral antibiotics <2006MI94>. 

Graziadei IW Joseph JJ, Wiesner RH, et al. Increased risk of chronic liver failure in adults with heterozygous oq-antitrypsin deficiency. Hepatology 28 1058-1063,1998. 

Heidelbaugh JJ and Sherbondy M (2006) Cirrhosis and chronic liver failure Part II. 

Insufficient digestive agents Biliary obstruction Chronic liver failure Chronic pancreatitis Cystic fibrosis Lactase deficiency Pancreatic cancer Pancreatic resection Sucrase-isomaltase deficiency... 

Sen, S., Williams, R., Jalan, R. The pathophysiological basis of acute-on-chronic liver failure. Liver 2002 22 (Suppl. 2) 5-13... 

The use of potentially nephrotoxic drugs requires close monitoring of renal function. The serum creatinine concentration is the most common method utilized to assess renal function but suffers from its lack of sensitivity. In patients with normal baseline renal function substantial renal injury can occur before there is a demonstrable rise in the serum creatinine concentration. A rise in the serum creatinine concentration that just exceeds the normal range may reflect as much as a 50% dechne in the GFR. The failure of the serum creatinine to accurately reflect the degree of renal injury is particularly evident in patients with decreased muscle mass or those with chronic liver failure. Creatinine is produced from the metabolism of creatine in skeletal muscle. In turn, creatine is derived from the liver. In the setting of chronic liver disease or malnourished patients with decreased muscle mass creatinine synthesis becomes impaired. As a result... 

The acquired causes of hyperammonemia are advanced liver disease and renal failure. Severe or chronic liver failure (as occurs in fiilminant hepatitis and cirrhosis, respectively) leads to a significant impairment of normal ammonia metabolism. Reye s syndrome, which is primarily a central nervous system disorder with minor hepatic dysfunction, is also associated with hyperammonemia. Hepatic en-... 

Acute liver failure Aseptic meningoencephalitis Cholestatic liver injury Chronic liver failure Liver carcinoma Liver cirrhosis... 

The clinical manifestations of HE can range from subtle mental status abnormalities, detectable only with psychological testing, to deep coma. Additionally, different classifications or patterns of HE can also be described. HE is seen in two broad clinical settings, acute fulminant liver failure and chronic liver failure. In patients with chronic liver failure, HE occurs in three patterns, acute, chronic, and subclinical. ... 

Hepatorenal syndrome, functional renal failure in the setting of cirrhosis in the absence of intrinsic renal disease, occurs in patients with cirrhosis as a result of intense vasoconstriction within the renal cortical vasculature. It is common and develops in approximately 40% of patients with cirrhosis and ascites within 5 years. The resultant reduction in blood supply to the kidneys causes avid sodium retention and oliguria. The vasoconstriction that occurs in the kidneys is in stark contrast to the state of systemic vasodilation that is characteristic of chronic liver failure. The pathophysiologic mechanism responsible for these effects is unknown, but is linked to the systemic vasodilation, hypovolemia, and hyperkinetic circulation seen in chronic liver failure. ... 

Hepatic Encephalopathy (HE) is a serious neuropsychiatric complication of both acute and chronic liver failure. A study group concluded in 2002 that HE is a spectrum of neuropsychiatric abnormalities seen in patients with liver dysfunction after exclusion of other known brain diseases (Ferenci et al., 2002). A multiaxial definition of HE was proposed that defines both the type of hepatic abnormality and the characteristics of the neurological manifestations. Three types of hepatic abnormalities were defined, namely ... 

Fig. 9.1 Alzheimer Type II astrocytosis in HE (chronic liver failure) (a) light micrograph of cerebral cortex from a cirrhotic patient who died in hepatic coma. Note prominence of pale, enlarged astroglial nuclei frequently occurring in pairs (anvw) suggestive of hyperplasia. A normal astrocyte nucleus is shown for comparison purposes (arrowhead). Bar = 20 pM. (b) Similar section showing intranuclear glycogen inclusions (arrow). Inset irregular lobular astrocyte in pallidum. Reproduced from Norenbeig (1987), with permission from Humana Press...

Fig. 9.2 Early changes in astrocytic morphology in experimental HE (chronic liver failure) Electron micrograph of an astrocyte process showing mitochondrial proliferation from a portacaval-shunted rat with mild HE resulting from feeding of ammonia resins. N nucleus. Bar = 1 pM Reproduced from Norenberg (1987), with permission from Humana Press...

Butterworth, 2001) and the loss of transporter capacity resnlts in increased extracellular brain concentrations of glntamate in the frontal cortex of these animals (Michalak et al., 1996). Increased extracellular brain glntamate has been confirmed in a wide range of models of ALF (Felipo and Bntterworlh, 2002). In contrast to ALF, chronic liver failure does not consistently resnlt in a loss of glutamate transport capacity (Raghavendra Rao et al., 1995). 

There is evidence to suggest that changes in expression of the PTBR are an integral part of the Alzheimer type II changes that are characteristic of astrocytes in chronic liver failure (Fig. 9.1). Expression of the PTBR IBP is significantly correlated with the presence of Alzheimer type II changes in autopsied brain tissue from cirrhotic patients who died in hepatic coma (Belanger et al., 2004). 

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome associated with severe, acute and chronic liver failure. According to the recommendations of a working party (Ferenci et al 2002) held at the d"" World Congress of Gastroenterology in Vienna in 1998, 3 types of HE should be differentiated, on principle ... 

The liver is usualy not enlarged or pa taMe, and it may become smaller and fibrotic. True cirrhosis (i.e., the destruction of normai hepatic architecture by fibrous sepia tiiat encompasses the regenerative nodules of hepatocytes) is rare in domestic animals with chronic hepatotoxicosis. Most chronic liver failure tram acute or chronic bndcosis in animals is characterized by marked fibrosis, but does not involve regenerative trodules. 

Metabolomic fingerprints Acute-on-chronic liver failure in humans with alcoholic cirrhosis, requiring intensive care 173... 

Khuroo, M. S., Khuroo, M. S., and Farahat, K. L. (2004). Molecular adsorbent recirculating system for acute and acute-on-chronic liver failure A meta-anal5rsis. Liver Transplant. 10,1099 [see comment]. Koda, Y., Nishi, S., Miyazaki, S., Haginoshita, S., Sakurabayashi, T., Suzuki, M., Sakai, S., Yuasa, Y., Hirasawa, Y., and Nishi, T. (1997). Switch from conventional to high-flux membrane reduces the risk of carpal tunnel syndrome and mortality of hemodialysis patients. Kidney Int. 52, 1096. Kolff, W. J., Jacobsen, S. C., Stephen, R. L., and Ron, D. (1976). Towards a wearable artificial kidney. Kidney Int. 10, S300. 

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