Uremic encephalopathy renal failure

Uremic and dialysis encephalopathies. Patients with renal failure continue to manifest neuropsychiatric symptoms despite significant advances in therapeutics and management. Patients with renal failure who are not yet on dialysis develop an array of symptoms, including clouding of consciousness, disturbed sleep patterns, tremor and asterixis that may progress to coma and death. 

The major population at risk for aluminum loading and toxicity consists of individuals with renal failure. In a study by Alfrey (1980), 82% of nondialyzed uremic patients and 100% of dialyzed uremic patients had an increased body burden of aluminum. The decreased renal function and loss of the ability to excrete aluminum, ingestion of aluminum compounds to lessen gastrointestinal absorption of phosphate, the aluminum present in the water used for dialysate, and the possible increase in gastrointestinal absorption of aluminum in uremic patients can result in elevated aluminum body burdens. The increased body burdens in uremic patients has been associated with dialysis encephalopathy (also referred to as dialysis dementia), skeletal toxicity (osteomalacia, bone pain, pathological fractures, and proximal myopathy), and hematopoietic toxicity (microcytic, hypochromic anemia). Pre-term infants may also be particularly sensitive to the toxicity of aluminum due to reduced renal capacity (Tsou et al. 1991)... 

Thrombotic thrombocytopenic purpura is a rare acute or subacute disease in adults, rather similar to the hemolytic uremic syndrome in children, in which there is systemic malaise, fever, skin purpura, renal failure, hematuria and proteinuria. Hemorrhagic infarcts caused by platelet microthrombi occur in many organs in the brain they may cause stroke-like episodes (Matijevic and Wu 2006) although more commonly there is global encephalopathy. The blood film shows thrombocytopenia, hemolytic anemia and fragmented red cells. The differential diagnosis includes infective endocarditis, idiopathic thrombocytopenia, heparin-induced thrombocytopenia with thrombosis, systemic lupus erythematosus, non-bacterial thrombotic endocarditis and disseminated intravascular coagulation. 

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 presenting symptoms of uremia are similar to many other encephalopathic states. The differential diagnosis is even more complex, since patients with renal failure are subjected to other intercurrent illnesses that may also induce other encephalopathic effects. In patients with renal failure, treatment with dialysis will restore more normal body fluid composition. Despite the possibility that multiple causes of encephalopathy might occur simultaneously, uremic encephalopathy may be successfully differentiated in most instances by means of the usual clinical methods. 

In patients who have other medical problems such as advanced liver disease with hepatic insufficiency, it is often difficult to differentiate whether the encephalopathy is due to hepatic or renal causes. In patients with renal failure, the major route for elimination of urea is not available thus, there is an ino-ease in blood urea. The amount of urea that enters the colon is ino-eased because of the elevated plasma urea. Urea is then acted on by colonic bacteria and mucosal enzymes in a manner similar to that of protein and amino acids. This leads to inCTeased ammonia production in uremic subjects that may either increase plasma ammonia levels or lead to misinterpretation of this test. 

If the patient with kidney failure also has cirrhosis or some other form of hver failure, this additional ammonia load may present a stress that cannot be adequately handled by the diseased liver. The result may be increased blood and central nervous system ammonia levels with development of encephalopathy (Fraser Arieff, 1985). Thus, patients with cirrhosis and end-stage kidney disease are at particular risk for developing encephalopathy since both conditions act synergistically to increase both blood and central nervous system ammonia. It should also be noted that plasma urea and serum creatinine do not always adequately reflect renal function in patients with severe liver disease. Recent studies suggest that many patients who have cirrhosis, ascites, and normal plasma urea and creatinine may in fact have severe renal functional impairment (Gines et al., 1988 Papadakis Arieff, 1987 Takabatake et al., 1988). In such individuals, differentiation of hepatic from uremic encephalopathy on clinical grounds may be difficult. 

Although there are many factors that contribute to uremic encephalopathy, most investigations have shown no correlation between encephalopathy and any of the commonly measured indicators of renal failure. In recent years, there has been considerable discussion of the possible role of PTH as a uremic toxin. There is a substantial amount of evidence to suggest that PTH may exert an adverse effect on the central nervous system (Cogan et al., 1978 Cooper et al., 1978 Guisado et al., 1975 Mahoney Arieff, 1982). 

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