Lactate acidosis

Metformin, a biguanide derivative, can lower excessive blood glucose levels, provided that insulin is present Metformin does not stimulate insulin release. Glucose release from the liver is decreased, while peripheral uptake is enhanced. The danger of hypoglycemia apparently is not increased. Frequent adverse effects include anorexia, nausea, and diarrhea Overproduction of lactic acid (lactate acidosis, lethality 50%) is a rare, potentially fatal reactioa Metformin is used in combination with sulfony-lureas or by itself. It is contraindicated in renal insufficiency and should therefore be avoided in elderly patients. 

High levels of lactate (acidosis) and acetyl-CoA (ketosis) lead to ketoacidosis. 

The liver plays an essential part in the metabolism of amino acids, (s. p. 38) (s. tab. 3.6) For this reason, a shift of the amino acid profile in the plasma has to be reckoned with in severe liver diseases. There is clear evidence of an increase in aromatic amino acids as well as a reduction in branched-chain amino acids, (s. tab. 15.1) Extrahepatic mechanisms (glucagon, insulin, lactate acidosis, etc.) can also effect significant changes to the amino acid spectrum. Multiple biochemical repercussions may result from this, affecting the development of HE. (8, 13, 45, 48, 53, 61, 68, 71)... 

Fructose, xylitol and sorbitol should not be used in view of the danger of lactate acidosis. Restraint is hkewise called for with the application of medium-chain triglycerides, since substances such as octanoate are only metabohzed slowly and also deemed to be potentially neurotoxic. 

Acid-base disorders Initial metabolic alkalosis (resulting from decreased urea synthesis with reduced bicarbonate consumption) may be superimposed by respiratory alkalosis as an outcome of disorders in lung function. During the further course, metabolic acidosis (with renal insufficiency) and respiratory acidosis (with pulmonary insufficiency) can be expected. In advanced or severe stages of the disease, lactate acidosis may develop in some 50% of all comatose patients owing to restricted gluconeogenesis. 

Side effects of ribavirin can appear in the form of nausea, pruritus, insomnia, irritability, haemolysis (224) and aggravation of IFNa-induced thrombopenia or leucopenia. In combination with other nucleoside analogues, there is a risk of lactate acidosis. Side effects of Peg INFa are similar to those of IFNa. (229, 233) The latter usually necessitates a reduction in dosage in about 20% and termination of therapy in 5—10% of cases. Side effects of combined IFNa + ribavirin include pancreatitis (215), pulmonary toxicity (226), manifestation of sarcoidosis (220, 240) and mental disorders (235). It should be noted that even in combination with ribavirin IFNa may show its own customary side effects. 

A limited quantity of D-lactate is converted to pyruvate by a mitochondrial flavoprotein enzyme D-2-hydroxy acid dehydrogenase. Thus, the development of D-lactate acidosis requires excessive production of D-lactate and an impairment in its metabolism. The clinical manifestations of D-lactic acidosis are characterized by episodes of encephalopathy after ingestion of foods containing carbohydrates. 

The inhibition of cytochrome c oxidase, and resultant disturbance of electron transport, results in decreased mitochondrial O2 utilization and decreased ATP (Olsen and Klein, 1947). Anaerobic metabolism leads to an accumulation of lactic acid and lactate acidosis, and the combination of lactate acidosis and cytotoxic hypoxia causes severe metabolic disturbances, particularly in the central nervous system (CNS), resulting in disturbances of perception and consciousness. 

It is important to reverse the acid-base imbalance of lactate acidosis by the i.v. infusion of bicarbonate. 

D-Fructose is the sweetest natural sugar. Its use as a natural sweetener is, therefore, increasing rapidly. It is absorbed slowly from the intestine, and thus does not cause abrupt changes in the serum levels of carbohydrates. It has little, if any, effect on insulin secretion. Thus, it exerts beneficial effects as a component of diets for mild and well-balanced diabetes, but should be taken within caloric restriction,445 as obesity impairs D-glucose tolerance and increases the insulin resistance of peripheral tissue.446 Use of D-fructose in the direct treatment of diabetic ketoacidosis does not offer advantages over routine, fluid therapy, and may even be dangerous on the basis that rapid infusion of large amounts of D-fructose may cause lactate acidosis. 

The early development of tachypnoea, usually accompanied by hyperpnoea, and resulting in an increased tidal volume, is frequently ascribed to stimulation of the carotid and aortic chemore-ceptors as a result of local accumulation of acid metabolites following cytochrome c oxidase inhibition. However, the general blood acid-base balance changes, notably lactate acidosis, may also be an important factor in breathing changes. 

C3HJO3, Mr 90.08. The racemate and the enantiomers occur in nature. (/f)-Form, mp. 53 °C, [0] -2.6° (HjO), pK 3.83. Prismatic platelets, soluble in water, ethanol, and ether, insoluble in chloroform. (/ )-(-)-L. is formed in the fermentation of glucose by Lactobacillus leichmannii and L. delbrueckii with 1 - and 2-valent metal ions it forms dextrorotatory salts and laevorotatory salts with 3-valent metal ions, e.g., zinc D-(+)-lactate 2H2O, [alo" -i-8.18° (HjO). (5)-form (sarcolactic acid, paralactic acid), mp. 53 °C, [ajp l 3.82° (H2O), pKg 3.79 (25 °C), is highly hygroscopic, occurs in blo, muscles serum, bile, kidneys, and other organs. The content of L. increases after strenuous muscle activity (lactate acidosis). The racemate, oil.mp. 17°C,bp. 122 °C(1.86 kPa), steam distillable, is widely distributed in nature, e. g., in sour milk products, in molasses as a result of partial fermentation of the sugars from apples and other fruits. For biochemistry and preparation, see Ut.. ... 

A 50-year-old man was treated for acute asthma with repeated doses of nebulized salbutamol, and as a result of this treatment he developed marked lactate acidosis [50 ]. 

Lauritsen L, Sahl C, Thorsen S. Nebulized salbutamol as a possible cause of lactate acidosis in a patient with acute asthma. Ugeskr Laeger 2013 175(3) lll-2. 

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