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Query: UMLS:C0085584 (encephalopathy)
 18,178 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cyclotron-produced radionuclide, 13N, was used to label ammonia and to study its metabolism in a group of 5 normal subjects and 17 patients with liver disease, including 5 with portacaval shunts and 11 with encephalopathy. Arterial ammonia levels were 52-264 micron. The rate of ammonia clearance from the vascular compartment (metabolism) was a linear function of its arterial concentration: mumol/min = 4.71 [NH3]a + 3.76, r = +0.85, P less than 0.005. Quantitative body scans showed that 7.4 +/- 0.3% of the isotope was metabolized by the brain. The brain ammonia utilization rate, calculated from brain and blood activities, was a function of the arterial ammonia concentration: mumol/min per whole brain = 0.375 [NH3]a - 3.6, r = +0.93, P less than 0.005. Assuming that cerebral blood flow and brain weights were normal, 47 +/- 3% of the ammonia was extracted from arterial blood during a single pass through the normal brains. Ammonia uptake was greatest in gray matter. The ammonia utilization reaction(s) appears to take place in a compartment, perhaps in astrocytes, that includes less than 20% of all brain ammonia. In the 11 nonencephalopathic subjects the [NH3]a was 100 +/- 8 micron and the brain ammonia utilization rate was 32 +/- 3 mumol/min per whole brain; in the 11 encephalopathic subjects these were respectively elevated to 149 +/- 18 micron (P less than 0.01), and 53 +/- 7 mumol/min per whole brain (P less than 0.01). In normal subjects, approximately equal to 50% of the arterial ammonia was metabolized by skeletal muscle. In patients with portal-systemic shunting, muscle may become the most important organ for ammonia detoxification. Muscle atrophy may thereby contribute to the development of hyperammonemic encephalopathy with an associated increase in the brain ammonia utilization rate.
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PMID:The dynamics of ammonia metabolism in man. Effects of liver disease and hyperammonemia. 42 64

The method of Pattern Flash elicited P300 (PFP300) has been applied to evaluate the dynamic alterations in cognitive function of a 58 year old woman (H. C.) presenting with hepatic failure due to fulminant hepatitis Non-A-Non-B. At the time of the first investigation she complained about slight memory deficits and revealed signs of hepatic encephalopathy grade I according to Parson-Smith et al. (bilirubin 26.0 mg/dl, NH3 102 micrograms/dl, electrolytes and blood sugar normal). Psychometric tests: Number connection test (NCT): 54 s (28-53 s, greater than 2sd); Syndrom-Kurz-Test (SKT): total score = 9 (0-4), compatible with a slight "organic brain syndrome". PFP300: N250 latency 343.5 ms (276.4 +/- 14.7 ms, greater than 4sd); PFP300-latency: 442.5 ms (326.9 +/- 14.7, greater than 7sd); PFP300 amplitudes: 16.0 microV (14.4 +/- 8.4, +/- 1sd), indicating severe disturbance in visual discrimination without visual attention deficits. Due to progressive deterioration of liver function the patient had to undergo orthotopic liver transplantation. The patient was reinvestigated four weeks later. The clinical and laboratory status were normal and no signs of hepatic encephalopathy could be detected clinically or by means of the psychometric tests. The parameters of the PFP300 complex had also completely returned to normal: N250-latency: 273.0 ms (less than 1sd); PFP300-latency: 348.0 ms (less than 1sd). This observation suggests that the analysis of P300 can help to detect and follow minor cognitive deficits in cases of acute hepatic encephalopathy. It further underscores the hepatic etiology as well as the potential reversibility of this type of encephalopathy.
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PMID:[Visual P300 in acute hepatic encephalopathy resulting from non-A-non-B fulminant hepatitis: analysis of the course before and after orthotopic liver transplantation]. 178 89

Cerebral blood flow (CBF), measured by the non-invasive 133-Xenon inhalation method, plasma levels of ammonia (NH3) and free tryptophan (fTRP) were determined in 30 cirrhotic patients without overt encephalopathy. Psychometric evaluation detected subclinical hepatic encephalopathy (SHE) in 20 of them, and was normal in the other 10. A significant CBF difference (p less than 0.05) was found between the SHE and the non-SHE patients. fTRP levels were significantly (p less than 0.05) higher in patients with SHE than in those without SHE, and a significant negative correlation (p = 0.003) was found between CBF values and fTRP in the whole group of patients. NH3 did not differ in the two subgroups and did not correlate with CBF values. It is concluded that CBF could have some implications in SHE, although its relevance is still unclear. The negative correlation between CBF and fTRP prompts further investigation concerning the relationships between plasma fTRP, brain serotonin, cerebral metabolism and blood flow in the development of brain derangement during cirrhosis.
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PMID:Cerebral blood flow and plasma free tryptophan in cirrhotics with and without hepatic encephalopathy. 279 14

To obtain a more precise pathophysiological evaluation of the role of ammonia in acute hepatic encephalopathy, we compared the plasma ammonia concentrations and electroencephalographic recordings (EEGs) of rabbits with surgically induced acute hepatic failure (AHF, n = 10) and normal rabbits administered an infusion of ammonium acetate (NH4-Ac, n = 7) over a 10-hr period. AHF was surgically induced by portocaval shunting followed by hepatic artery ligation 48 hr later. In the infusion group the dose of NH4-Ac, initially 0.78 mmol/kg/hr, was increased every 2 hr by 0.13 mmole/kg/hr during a 10-hour period to simulate the arterial NH3 concentrations observed in AHF. Ammonia levels in rabbits administered the NH4-Ac infusion were identical to those observed in AHF, with the exception of the higher initial value in the AHF group. Moreover, the mean rates of increase in grade of encephalopathy in the two groups were similar, although the EEG grades in the infusion group were significantly less at all time points. In conclusion, this study demonstrates that a more pathophysiological approach to identification of the putative toxins in hepatic encephalopathy is feasible. Some of the EEG abnormalities of acute hepatic encephalopathy in rabbits are presumably due to hyperammonemia; the encephalopathy observed in AHF at zero time is probably caused by the previously constructed portocaval shunt via an undefined, but possibly also ammonia-related, mechanism.
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PMID:Continuous intravenous ammonia infusion as a model for the study of hepatic encephalopathy in rabbits. 292 62

Despite greater than 23 years of study, an incomplete understanding of the etiology, epidemiology and pathogenesis of Reye's syndrome persists. Better understanding of the disease has been hampered by the lack of a good animal model on which hypotheses of its pathogenesis could be tested. Human studies indicate that a primary mitochondrial injury may lead to complex metabolic disturbances that produce the observed pathophysiology. Specific directions regarding avenues for future research should pursue two lines: a good animal model still needs to be developed in which the biochemical and morphologic alterations identified in Reye's syndrome are duplicated. This model should include an antecedent viral illness but may not require aspirin exposure as an essential ingredient. With the identification of a satisfactory model, specific questions about the roles of environmental toxins or medications may be answered. Study of noncomatose cases of Reye's syndrome should continue. The specific emphasis should be to delineate what factors (NH3, free fatty acids and dicarboxylic acids) may be implicated in the pathogenesis of the CNS disease with the hopes of devising strategies for more effective treatment of encephalopathy and its attendant morbidity and mortality.
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PMID:Reye's syndrome: current concepts. 354 76

The Number Connection Test (NCT) by Harold O. Conn was tested for its usefulness for diagnosis and treatment control of portasystemic encephalopathy in out-patients. For this purpose in 30 patients with liver cirrhosis the time in the NCT was determined and the serum ammonia level (NH3) was measured before the treatment with lactulose and neomycin was started. Moreover, 12 clinical symptoms and 10 laboratory parameters were tested for correlation with the NCT-time. We found a positive correlation between the NCT-time and NH3 serum level. For the prediction of the NCT-time the multiple linear regression yielded the combination of NH3 with the proof of ascites and palmar erythema as the best subset of predictor variables. By means of the NCT the effectiveness of the treatment with lactulose and neomycin was demonstrated. We recommend the NCT for the clinical routine in particular for the early diagnosis and for treatment control of portasystemic encephalopathy in patients with liver cirrhosis.
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PMID:[Ambulatory diagnosis and therapy control of portasystemic encephalopathy in patients with liver cirrhosis]. 409 54

Although total diversion of portal blood flow has been considered to be the main factor leading to encephalopathy following nonselective shunt (NSS), increased intestinal absorption of cerebral toxins secondary to mesenteric venous decompression could also play a role. Conversely, the low frequency of encephalopathy after the distal splenorenal shunt (DSRS) may be due to preservation of both hepatic portal perfusion and mesenteric venous hypertension. Portal hemodynamics, intestinal absorption of D-xylose, ammonia metabolism, and clinical encephalopathy were assessed preoperatively and in the early and late postoperative periods in cirrhotic patients selected for the DSRS (n = 12) and NSS (n = 10). Preoperatively, NSS patients had significantly less hepatopetal portal blood flow (P = 0.03) and lower D-xylose absorption (P = 0.004) than DSRS patients. DSRS resulted in no significant alterations in hepatic portal perfusion, portal pressure, D-xylose absorption, fasting blood ammonia (NH3), or tolerance to an oral dose of ammonium chloride. In contrast, NSS resulted in complete portal diversion and decompression and significant enhancement of D-xylose absorption on both the early (P = 0.02) and late (P = 0.03) postoperative evaluations. Early and late postoperative levels of MH3 were significantly higher in NSS patients. Encephalopathy was more frequent after NSS (80%) than after DSRS (17%, P = 0.003). When all patients were considered, preoperative to early DSRS (17%, P = 0.003). When all patients were considered, preoperative to early postoperative change in NH3 correlated with change in D-xylose absorption (r = 0.52, p = 0.02), and there were significantly more individuals with a greater than 2 gm increase in D-xylose absorption who developed encephalopathy (83%) than patients with no or minimal increase in D-xylose absorption (33%, P = 0.04). The results of this study suggest that altered intestinal absorption may be one of many factors determining postshunt cerebral function.
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PMID:Portal hemodynamics, intestinal absorption, and postshunt encephalopathy. 687 34

Femoral arterio-venous (A-V) differences of blood free amino acids and plasma ammonia (NH3) were simultaneously determined after an overnight fast in 16 patients with decompensated liver cirrhosis in the absence and presence of encephalopathy, as compared with those in 8 control subjects. In spite of increased releases of phenylalanine (Phe) and tyrosine (Tyr) from the peripheral tissue, releases of isoleucine (Ile) and leucine (Leu) as well as alanine (Ala) were found to be significantly reduced in decompensated liver cirrhosis, particularly in the presence of hepatic encephalopathy. Furthermore, NH3 was found to be significantly taken up by the skeletal muscle of these patients, and a positive correlation was observed between arterial NH3 level and the A-V differences of Leu, of Ile and of Ala. These findings strongly suggest that net degradation (or utilization) of branched-chain amino acids (in particular, Leu and Ile) is enhanced in the muscle for detoxication of ammonia (i.e., glutamine synthesis) by supplying the carbon skeleton and energy in cirrhosis of the liver.
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PMID:Augmented utilization of branched-chain amino acids by skeletal muscle in decompensated liver cirrhosis in special relation to ammonia detoxication. 722 60

Hepatic encephalopathy (HE) is associated with elevated arterial ammonia levels. The relationship is variable, in part due to ammonia methodology. One method, based on the indophenol reaction (IPh), is interfered with a number of amino acids including all aromatic amino acids. We have determined arterial ammonia simultaneously with the Blood Ammonia Checker II (BAC) as reference method and with the IPh method. The difference BAC-IPh, mumol/l, was assumed to express the interference in the indophenol method (IFI) by amino acids. It may be positive or negative. The aim was to establish the value of BAC in comparison with IPh in the diagnosis of liver disease and overt HE and to assess any added value of IFI. Of two reference groups without disturbances, A (n = 39) had not and B (n = 13) had encephalopathy. Group C consisted of 125 liver patients (34 no cirrhosis, 91 cirrhosis) of which 55 had no manifest HE (C:HE-) and 70 had HE (C:HE+). Median BAC ammonia nitrogen (NH3-N), mumol/l: A 21, B 35, C 80, C:HE - 57 and C:HE+ 98 (A < B < C and A < B < C:HE - < C:HE +, P < 0.001). Median IPh NH3-N, mumol/l: A 27, B 30, C 30, C:HE - 25 and C:HE + 35 mumol/l (A = B = C and C:HE - < C:HE+, P < 0.01). IFI medians: A -6, B 3, C 40, C:HE - 29 and C:HE + 58 mumol/l (A < B (P < 0.05) < C (P < 0.0001); A, B < C:HE - and C:HE+; C:HE- < C:HE + (all P < 0.0001)). While BAC correlated weakly with IPh in the (sub)groups C, C:HE-, C:HE+ (r = 0.3, 0.3, 0.4, P < 0.05), it correlated strongly with IFI (r = 0.9, 0.9, 0.8, P < 0.0001). There was no correlation between IPh and IFI. BAC, as well as IFI, could discriminate all liver patients (C) from both reference groups A and B with 100% positive likelihoods. BAC, IPh and IFI could discriminate between HE- and HE+. To differentiate cirrhosis from non-cirrhosis the specificity of IPh was uniformly high and the sensitivity satisfactory, whereas BAC had a high sensitivity but an insufficient specificity. In conclusion, in blood, BAC is the ammonia determination of choice. It differentiates between reference groups (encephalopathic or not) and liver disease and the more so HE. The combination of BAC and IPh (indicating IFI) may eventually be shown useful to rapidly assess the severity of underlying liver disease in HE patients. In other biological fluids, IPh is excellent when the inhibiting influence of non-protein nitrogen substances is absent or can be eliminated.
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PMID:Arterial ammonia with Blood Ammonia Checker II and with indophenol reaction to assess presence of hepatic encephalopathy. 881 63

Although gaseous ammonia (NH3) can freely enter cells through the plasma membrane where NH3 is cyto(neuro)toxic, NH3 and ionic ammonia (NH4+) contents have not been studied in biological materials. We developed a new method for measurement of expiratory NH3 concentration, which may reflect blood NH3 concentrations. The method is a sensor tube type-gas assay system. Expiratory NH3 concentration in patients with chronic liver diseases increased when their blood ammonia (NH4(+)+NH3) concentrations increased above 90 micrograms/dl (normal range; 12-66 micrograms/dl). However, cirrhotic patients, who had relatively higher expiratory NH3 concentration compared to blood NH3 concentrations (calculated from Henderson-Hasselbalch formula), were found to have subclinical encephalopathy. Measurement of expiratory NH3 concentration may be of clinical significance for the diagnosis of encephalopathy associated with hyperammonemia.
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PMID:Measurement of the expiratory ammonia concentration and its clinical significance. 920 60


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