Metabolic acidosis clinical presentation

Renal Effects. The patient described by Letz et al. (1984) (see Section 2.2.3.1) who lived for 64 hours after exposure to toxic levels of 1,2-dibromoethane had acute renal failure as evidenced by severe oliguria 24 hours after exposure and abnormal clinical chemistry values (blood urea nitrogen, creatinine, and serum uric acid). Severe metabolic acidosis was present despite two hemodialysis procedures. 

This chapter deals with disorders of galactose, fructose and glycogen metabolism. The clinical presentations of these disorders can be mild or severe and life-threatening. The clinical features include failure to thrive, hepatomegaly, hypoglycemia, jaundice, metabolic acidosis, and myopathy including muscle pain and weakness. 

GSH-S deficiency is a more frequent cause of GSH deficiency (HI7), and more than 20 families with this enzyme deficiency have been reported since the first report by Oort et al. (05). There are two distinct types of GSH-S deficiency with different clinical pictures. In the red blood cell type, the enzyme defect is limited to red blood cells and the only clinical presentation is mild hemolysis. In the generalized type, the deficiency is also found in tissues other than red blood cells, and the patients show not only chronic hemolytic anemia but also metabolic acidosis with marked 5-oxoprolinuria and neurologic manifestations including mental retardation. The precise mechanism of these two different phenotypes remains to be elucidated, because the existence of tissue-specific isozymes is not clear. Seven mutations at the GSH-S locus on six alleles—four missense mutations, two deletions, and one splice site mutation—have been identified (S14). 

In another case of acute systemic allergy to quinine, which mimicked septic shock, with little hemolysis or renal involvement, the patient presented twice with a virtually identical clinical picture sudden fever, rigors, and back pain, followed by hypotension, metabolic acidosis, granulocytopenia, and disseminated intravascular coagulation. On each occasion chnical and laboratory indices recovered spontaneously within 36 hours. A retrospective analysis of the patient s serum showed the presence of neutrophil-specific, quinine-dependent antibodies. 

There are two distinct types of GSH-S deficiency, both associated with mild chronic hemolysis in one type, hemolysis is the only clinical manifestation. In the other, the major clinical features are mental retardation, severe generalized muscle weakness, tremors, incoordination, hemolytic anemia, and metabolic acidosis. This second and much more severe type of GSH-S deficiency is also known as 5-oxopro-linurta or pyroglutamic aciduria. The difference in severity of these disorders reflects the fact that in the mild form, GSH-S deficiency is confined to the RBCs because in this disorder the GSH-S is unstable. GSH-S activity is present in adequate quantity in young RBCs, but it rapidly declines as the cells age, because the cells are unable to synthesize new molecules of GHS-S. Other cells of the body that have nuclei and ribosomes can compensate for accelerated denaturation of GSH-S by synthesizing more. On the other hand, in the severe systemic form of GSH-S deficiency, aE cells of the body have low activities of GSH-S because they cannot form this enzyme in adequate amounts. In both types of GSH-S deficiency, RBCs exhibit notable reduction in GSH concentration. 

Benzyl alcohol is a preservative that may be present in multidose vials of bacteriostatic sodium chloride and bacteriostatic water for injection and pharmaceuticals available in multidose vials for parenteral use. An association between the presence of benzyl alcohol in solutions used for flushing intravascular catheters and to reconstitute medications and a gasping syndrome and deaths in neonates was first reported in the early 1980s.The neonates also displayed clinical findings such as an elevated anion gap, metabolic acidosis, CNS depression, seizures, respiratory failure, renal and hepatic failures, cardiovascular collapse, and death. Those at highest risk were premature infants who weighted less... 

The presence of mild elevations in the SAG caimot be antomat-ically attribnted to the presence of a high SAG metabolic acidosis. Elevations in the SAG are commonly seen in hospitalized patients, especially those who are critically iU. A variety of factors may con-tribnte to this nonspecific elevation in the SAG, inclnding the presence of alkalemia, which increases the anionic charge of albnmin and other plasma proteins. The nsefnlness of the SAG as a marker of acid-base status is dependent on proper interpretation of a patient s clinical status. Despite these limitations, when the SAG exceeds 20 to 25 mEq/L a significant organic acidosis is likely to be present. 

II. Toxic dose. Inhalation or ingestion of as little as 1 mg of fluoroacetate is sufficient to cause serious toxicity. Death is likely after ingestion of mote than 5 mg/kg. Clinical presentation. After a delay of minutes to several hours (in one report coma was delayed 36 hours), manifestations of diffuse cellular poisoning become apparent nausea, vomiting, diarrhea, metabolic acidosis, renal failure, agitation, confusion, seizures, coma, respiratory arrest, pulmonary edema, and ventricular arrhythmias may occur. One case series reported a high incidence of hypocalcemia and hypokalemia. 

Chi CH et al Clinical presentation and prognostic factors in sodium monofluoroacetate intoxication. J Toxicol Clin Toxicol 1996 34(6) 707-712. [PMID 8941201] (Rotrospectiv review of 38 cases found 18% mortality. H otension, metabolic acidosis, and increased creatinine were important predictors of mortality.)... 

In acute severe systemic intoxication abnormalities of routine clinical chemistry are usually present such as metabolic acidosis, increased anion gap, cytopenia, hypoglycemia, hyperammonemia (which can mask acidosis), lactic acidemia, elevations of triglycerides and free fatty acids, and ketosis. Testing for ketonuria is an especially simple and useful first line investigation. In most newborns as well as in older children with organic acid disorders, including some patients with fatty acid oxidation defects, there is pronounced ketonuria. Ketonuria is only rarely observed even in very sick newborns without metabolic disease. 

A further development in the description of the disease was reported by Robinson et al. (1979), who reported a patient, a female child of unrelated French-Canadian parents, who presented with metabolic acidosis, acetonuria and coma after a fever at 30 months of age. Her clinical condition deteriorated and she died with features of salicylism, including a serum salicylate of 20 mg dl A second child (female) born several years later to the same family subsequently presented at 1 year with fever, metabolic acidosis, vomiting and persistent tachypnoea. She had ketonuria, and an apparent serum salicylate of 11.2 mg dl despite having received no salicylates during the previous 6 days. GC-MS of urinary organic acids extracted using solvents revealed the presence of increased concentrations of lactate (510 mg per g of creatinine), 3-hydroxy-butyrate (2310 mg per g of creatinine), acetoacetate (2080 mg per g of creatinine), 2-methyl-3-hydroxybutyrate (480 mg per g of creatinine), 2-methylacetoacetate (572 mg per g of creatinine), 3-hydroxyisovalerate (470 mg per g of creatinine) and tiglylglycine (152 mg per g of creatinine). The apparent salicylate in serum was found to be due to acetoacetate. 

Lactic acidosis occurs in two clinical settings (1) type A (hypoxic), associated with decreased tissue oxygenation, such as shock, hypovolemia, and left ventricular failure and (2) type B (metabolic), associated with disease (e.g., diabetes melUtus, neoplasia, liver disease), drugs and/or toxins (e.g., ethanol, methanol, and salicylates), or inborn errors of metabolism (e.g., methylmalonic aciduria, propionic acidemia, and fatty acid oxidation defects). Lactic acidosis is not uncommon and occurs in approximately 1% of hospital admissions. It has a mortality rate greater than 60%, which approaches 100% if hypotension is also present. Type A is much more common. 

At present, the important clinical indication areas for therapy with thiamine are the beriberi of alcoholics and Wernicke s encephalopathy (Korner and Vollm 1976). In both cases, therapy is started with daily doses of at least 50-100 mg (in severe cases up to 200 mg) thiamine administered parenterally. Therapy is then continued with oral doses of 100-300 mg daily. Neuritis accompanying pregnancy responds particularly well to vitamin therapy. In some severe disorders of the intermediate metabolism (e.g., diabetic acidosis, severe hepatic malfunction), the necessary phosphorylation of thiamine in the organism is no longer ensured. Thiamine has, therefore, to be administered directly in its active form, thiamine pyrophosphate (TPP, cocarboxylase). Instances of toxicity of thiamine have been reported, primarily showing effects on the cardiovascular and nervous systems (Un-NA 1972 DiPalma and Ritchie 1977). 

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