Acidemia

This complex consists of at least 25 separate polypeptides, seven of which are encoded by mtDNA. Its catalytic action is to transfer electrons from NADH to ubiquinone, thus replenishing NAD concentrations. Complex I deficiency has been described in myopathic syndromes, characterized by exercise intolerance and lactic acidemia. In at least some patients it has been demonstrated that the defect is tissue specific and a defect in nuclear DNA is assumed. Muscle biopsy findings in these patients are typical of those in many respiratory chain abnormalities. Instead of the even distribution of mitochondria seen in normal muscle fibers, mitochondria are seen in dense clusters, especially at the fiber periphery, giving rise to the ragged-red fiber (Figure 10). This appearance is a hallmark of many mitochondrial myopathies. 

Fatal infantile cytochrome c oxidase (CCO) deficiency is characterized by total absence of catalytic activity in skeletal muscle. This often occurs within the context of the Fanconi syndrome, or less commonly in association with a cardiomyopathy. Although the deficiency is global in skeletal muscle, with all fibers affected, only isolated scattered fibers show abnormal aggregations of mitochondria (ragged-red fibers). Multiple affected siblings within one family are frequently encountered and suggest autosomal recessive inheritance. The condition normally proves fatal before the age of six months and is characterized by worsening intractable lactic acidemia. 

Type 1 Von Gierke s disease Deficiency of glucose-6-phosphatase Liver cells and renal tubule cells loaded with glycogen. Hypoglycemia, lactic-acidemia, ketosis, hyperlipemia. 

Reaction 3 is analogous to the dehydrogenation of fatty acyl-CoA thioesters (see Figure 22—3). In isovaleric acidemia, ingestion of protein-rich foods elevates isovalerate, the deacylation product of isovaleryl-CoA. Figures 30-20, 30-21, and 30-22 illustrate the subsequent reactions unique to each amino acid skeleton. 

Mutation of the dihydrolipoate reductase component impairs decarboxylation of branched-chain a-keto acids, of pyruvate, and of a-ketoglutarate. In intermittent branched-chain ketonuria, the a-keto acid decarboxylase retains some activity, and symptoms occur later in life. The impaired enzyme in isovaleric acidemia is isovaleryl-CoA dehydrogenase (reaction 3, Figure 30-19). Vomiting, acidosis, and coma follow ingestion of excess protein. Accumulated... 

The catabolism of leucine, valine, and isoleucine presents many analogies to fatty acid catabolism. Metabolic disorders of branched-chain amino acid catabolism include hypervalinemia, maple syrup urine disease, intermittent branched-chain ketonuria, isovaleric acidemia, and methylmalonic aciduria. 

Under normal circumstances the arterial pH is tightly regulated between 7.35 and 7.45. Acidemia is an abnormally low arterial blood pH (less than 7.35) while acidosis is a pathologic process that acidifies body fluids. Similarly, alkalemia is an abnormally high arterial blood pH (less than 7.45) while alkalosis is a pathologic process that alkalinizes body fluids. As such, although a patient can simultaneously have acidosis and alkalosis, the end result will be acidemia or alkalemia. 

Another option for patients with severe acidemia is tromethamine (THAM). This inert amino alcohol buffers acids and C02 through its amine (—NH2) moiety ... 

As with the treatment of metabolic acidosis, the role of NaHC03 therapy is not well defined for respiratory acidosis. Realize that administration of NaHC03 can paradoxically result in increased C02 generation (HC03 + H+ —> H2C03 —> H20 + C02) and worsened acidemia. Careful monitoring of the pH is required if NaHC03 therapy is started for this indication. The use of THAM in respiratory acidosis (see metabolic acidosis, above) has unproven safety and benefit. 

Hyperventilation and vomiting result in early alkalosis, which changes to acidosis and lactic acidemia. 

Acidemia An increase in the hydrogen ion concentration of the blood or a fall below normal in blood pH. 

Acidosis A pathologic state that leads to acidemia. 

Uremia is characterized by retention in the blood of urea, phosphates, proteins, amines and a number of poorly defined low-molecular-weight compounds. Despite acidemia, the pH of brain, muscle and CSF are normal in humans with renal failure. Whereas brain water, K+ and Mg2+ content are normal, Al3+ and Ca2+ concentrations are significantly increased [14]. 

OH-butyryl-CoA 3-OH-butyryl-CoA deacylase deficiency deacylase Propionic acidemia Propionyl-CoA carboxylase... 

Low protein diet to restrict intake of leucine (precursor to isovaleric acidemia)... 

Arterial blood gases are measured to determine oxygenation and acid-base status (Fig. 74-1). Low pH values (less than 7.35) indicate acidemia, whereas high values (greater than 7.45) indicate alkalemia. The PaC02 value helps to determine if there is a primary respiratory abnormality, whereas the I IC( )3 concentration helps to determine if there is a primary metabolic abnormality. Steps in acid-base interpretation are described in Table 74-2. 

The manifestations of acute severe metabolic acidemia (pH less than 7.15 to 7.20) involve the cardiovascular, respiratory, and central nervous systems. Hyperventilation is often the first sign of metabolic acidosis. Respiratory compensation may occur as Kussmaul s respirations (i.e., deep, rapid respirations characteristic of diabetic ketoacidosis). 

Asymptomatic patients with mild to moderate acidemia (HCO3-, 12 to 20 mEq/L pH, 7.2 to 7.4) can usually be managed with gradual correction of the acidemia over days to weeks using oral sodium bicarbonate or other alkali preparations (Table 74-4). The dose of bicarbonate can be calculated as follows ... 

Organic Acidemia Association http //www.oaanews.or icbd.htm... 

Extremely low insulin levels In a person with uncontrolled type 1 diabetes mellltus produce acidemia and aciduria due to high concentrations of ketone bodies, which are acids and contribute to the decreased pH. 

Intravenous L-camitine and acetyl-L-camitine in medium-chain acyl-coenzyme A dehydrogenase deficiency and isovaleric acidemia. 

Vorperian VR, Wisialowski , Deegan R, Roden DM Effect of hypercapnic acidemia on anisotropic propagation in the canine ventricle. Circulation 1994 90 456-461. 

Lysine Urea cycle defects Organic acidemias Hyperornithinemia... 

Proline Prolinemia type 1 and 2 Lactic acidemias P-5-C synthase deficiency... 

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