Author: Vasudevan A Raghavan, MBBS, MD, MRCP(UK); Chief Editor: George T Griffing, MD more... Updated: Apr 13, 2011
Diabetic ketoacidosis (DKA) is an acute, major, life-threatening complication of diabetes. DKA mainly occurs in patients with type 1 diabetes, but it is not uncommon in some patients with type 2diabetes. DKA is a state of absolute or relative insulin deficiency aggravated by ensuing hyperglycemia, dehydration, and acidosisproducing derangements in intermediary metabolism. The most common causes are underlying infection, disruption of insulin treatment, and new onset of diabetes. (See Etiology.) DKA is defined clinically as an acute state of severe uncontrolled diabetes associated withketoacidosis that requires emergency treatment with insulin and intravenous fluids. (See Treatment and Management and Medications.) Biochemically, DKA is defined as an increase in the serum concentration of ketones greater than 5 mEq/L, a blood glucose level greater than 250 mg/dL (although it is usually much higher), and a blood (usually arterial) pH less than 7.3. Ketonemia and ketonuria arecharacteristic, as is a serum bicarbonate level of 18 mEq/L or less (< 5 mEq/L is indicative of severe DKA). (See Clinical Presentation.) Mental status changes can be seen with mild-to-moderate DKA; more severe deterioration in mental status is typical with moderate-to-severe DKA. See Diabetes Mellitus, Type 1 and Diabetes Mellitus, Type 2 for more complete information on these topics.
PathophysiologyDiabetic ketoacidosis (DKA) is a complex disordered metabolic state characterized by hyperglycemia, ketoacidosis, and ketonuria. DKA usually occurs as a consequence of absolute or relative insulin deficiency that is accompanied by an increase in counter-regulatory hormones (ie, glucagon, cortisol, growth hormone, epinephrine). This type of hormonal imbalance enhances hepatic gluconeogenesis,glycogenolysis, and lipolysis. Hepatic gluconeogenesis, glycogenolysis secondary to insulin deficiency, and counter-regulatory hormone excess result in severe hyperglycemia, while lipolysis increases serum free fatty acids. Hepatic metabolism of free fatty acids as an alternative energy source (ie, ketogenesis) results in accumulation of acidic intermediate and end metabolites (ie, ketones, ketoacids).Ketones include acetone, beta-hydroxybutyrate, and acetoacetate. Hepatic gluconeogenesis, glycogenolysis secondary to insulin deficiency, and counter-regulatory hormone excess result in severe hyperglycemia, while lipolysis increases serum free fatty acids. Ketone bodies are produced from acetyl coenzyme A mainly in the mitochondria within hepatocytes when carbohydrate utilization is impaired becauseof relative or absolute insulin deficiency, such that energy must be obtained from fatty acid metabolism. High levels of acetyl coenzyme A present in the cell inhibit the pyruvate dehydrogenase complex, but pyruvate carboxylase is activated. Thus, the oxaloacetate generated enters gluconeogenesis rather than the citric acid cycle, as the latter is also inhibited by the elevated level ofnicotinamide adenine dinucleotide (NADH) resulting from excessive beta-oxidation of fatty acids, another consequence of insulin resistance/insulin deficiency. The excess acetyl coenzyme A is therefore rerouted to ketogenesis. Ketones include acetone, beta-hydroxybutyrate, and acetoacetate. Progressive rise of blood concentration of these acidic organic substances initially leads to a state of ketonemia,although extracellular and intracellular body buffers can limit ketonemia in its early stages, as reflected by a normal arterial pH associated with a base deficit and a mild anion gap. When the accumulated ketones exceed the body's capacity to extract them, they overflow into urine (ie, ketonuria). If the situation is not treated promptly, a greater accumulation of organic acids leads to frank...