Metabolic encephalopathy symptoms

A. Assessment. Agitation, delirium, or psychosis may be caused by a variety of drugs and toxins (Table 1-14). In addition, such symptoms may result from a functional thought disorder or metabolic encephalopathy caused by medical... 

One example of reversible metabohc encephalopathy is that seen in thiamine deficiency. Both animal models and humans with pure thiamine deficiency develop highly specific neurological symptoms. These symptoms can be reversed completely, or dramatically improved, often within hours, by the administration of thiamine. These results are instrumental in leading to the concept of metabolic encephalopathy , a disorder without structural brain changes. From a historical standpoint, there are increasing numbers of such disorders, which are amenable to successful treatment. Sadly, for example, in the case of kemicterus, managed health care has led to an increase in the number of cases due to the early release from hospitals of newborn infants after birth, even before the onset of jaundice. 

The area of metabolic encephalopathies is unique in that animal models of disease closely mimic the symptoms seen in human disorders, allowing excellent correlative studies. Seizures are an example of this feature. Many animal models of experimentally induced seizures are available for study in mice and rats, and the neurochemical alterations before and after anticonvulsive therapy can be carefully studied. These more or less direct comparisons permit a more rapid application of results from animal studies to humans. 

Hawkins, R.A., Jessy, J., Mans, A.M., De Joseph, M.R. (1993). Effect of reducing brain glutamine synthesis on metabolic symptoms of hepatic encephalopathy. J. Neurochem. 60, 1000-1006. Henderson, R.M., Graf, J., Boyer, J.L. (1989). Inward-rectifying potassium channels in rat hepatocytes. Am. J. Physiol. 256, G1028-G1035. 

Hawkins, R.A., J.Jessy, A.M.Mans, and M.R.De Joseph. 1993. Effect of reducing brain glutamine synthesis on metabolic symptoms of hepatic encephalopathy. J. Neurochem. 60(3) 1000-1006. 

Encephalopathy can occur in a number of extrahepatic diseases, such as toxic, metabolic or circulatory disorders, intracranial space-occupying lesions, hypothyroidism (35) and neurological/psychiatric diseases, (s. tab. 15.2) Identification of neuropsychiatric symptoms always calls for careful differential diagnosis. 

The dose of ammonium chloride can be calculated on the basis of the chloride deficit using the same method as for HCl, using the conversion of 20 g ammonium chloride providing 374 mEq of H . However, only half of the calculated dose of ammonium chloride should be administered so as to avoid ammonia toxicity. Ammonium chloride is available as a 26.75% solution containing 100 mEq in 20 mL, which should be further diluted prior to administration. A dilute solution may be prepared by adding 100 mEq of ammonium chloride to 500 mL of normal saline and infusing the solution at a rate of no more than 1 mEq/min. Improvement in metabolic stams is usually seen within 24 hours. CNS toxicity, marked by confusion, irritability, seizures, and coma, has been associated with more rapid rates of administration. Ammonium chloride must be administered cautiously to patients with renal or hepatic impairment. In patients with hepatic dysfunction, impaired conversion of ammonia to urea may result in increased ammonia levels and worsened encephalopathy. In patients with renal failure, the increased urea synthesis may exacerbate uremic symptoms. ... 

The precise pathogenesis of the central nervous system (CNS) signs and symptoms that accompany liver failure (hepatic encephalopathy) in patients such as Percy Veere is not completely understood. These changes are, however, attributable in part to toxic materials that are derived from the metabolism of nitrogenous substrates by bacteria in the gut that circulate to the liver in the portal vein. These materials "bypass" their normal metabolism by the liver cells, however, because the acute inflammatory process of viral hepatitis severely limits the ability of liver cells to degrade these compounds to harmless metabolites. As a result, these toxins are "shunted" into the hepatic veins unaltered and eventually reach the brain through the systemic circulation ("portal-systemic encephalopathy"). 

The absolute level of ammonia and its metabolites, such as glutamine, in the blood or cerebrospinal fluid in patients with hepatic encephalopathy correlates only roughly with the presence or severity of the neurologic signs and symptoms. y-Aminobutyric acid (GABA), an important inhibitory neurotransmitter in the brain, is also produced in the gut lumen and is shunted into the systemic circulation in increased amounts in patients with hepatic failure. In addition, other compounds (such as aromatic amino acids, false neurotransmitters, and certain short-chain fatty acids) bypass liver metabolism and accumulate in the systemic circulation, adversely affecting central nervous system function. Their relative importance in the pathogenesis of hepatic encephalopathy remains to be determined. 

Tn recent years there has been a great deal of interest in understanding the mechanisms involved in ammonia metabolism in brain. The reasons for this interest are twofold ammonia is thought to be a major toxin contributing to the symptoms of encephalopathy associated with liver disease (1,2) and of Reye s disease (3) and earlier experiments with N-labeled ammonia suggested the existence of at least two distinct metabolic pools in brain (4). 

Type A encephalopathy and type B and C encephalopathy share many clinical symptoms. However, there are also a considerable number of clinical features which are significantly different. Generally the brain s reaction to a distinct metabohc disturbance differs depending on the rate at which the metabolic alteration occurs, since there is little scope for adaptation to acute severe metabohc alterations. 

Total parenteral nutrition (TPN) can produce trace metal deficiency associated with different clinical symptoms. Therefore trace metal supplementation (Fe, Cu, Zn, Se, Cr, Mo, Mn) in TPN solutions is necessary to disclose complications [59]. In addition, hemodialysis treatment influences trace metal metabolism and may derange trace metal balance (Zn, Cu, Se, and Mg). Complications in hemodialysis caused by aluminum treatment to prevent hyperphosphatemia include dialysis encephalopathy, osteomalacia, and anemia. Aluminum determination in blood serum is one of most important tests in therapy monitoring [60]. 

Erythrocyte transketolase activity was found to be lowered in different groups of TD patients (Herve et al. 1995 Khounnorath et al. 2011) (Table 33.2). However, post mortem brains of alcoholics who died without symptoms of Wernicke s encephalopathy (WE) revealed 20-35% reductions in the activities of all TDP-dependent enzymes in various brain regions (Lavoie and Butterworth 1995). This means that some degree of TD-induced reductions in oxidative metabolism may be tolerated. In fact, individual sensitivity to TDP deficits may be modified by coexisting clinical conditions such as alcoholism, renal insufficiency, dialysis programmes, aging, diabetes, cardiovascular complications, and voluntary or socio-economically dependent dietary habits (Tables 33.1 and 33.2). 

Biochemical disease involves a departure from the normal in some body component, e.g. an enzyme, a structural protein or a membrane transport mechanism. Some biochemical diseases are almost entirely environmental in origin, e.g. lead encephalopathy, but at present attention is largely directed to genetically determined conditions—the inborn errors of metabolism and other molecular diseases. In some cases it is the interaction between genotype and external environment which brings about the signs and symptoms, in others, such as the gangliosidoses, no modification of the external environment can appreciably alter the course of the disease. 

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