Current concepts of the pathogenesis and management of diabetic ketoacidosis (DKA).
Diabetic ketoacidosis (DKA) is the commonest endocrine emergency encountered in clinical practice. Although in the last 3 decades the average worldwide immediate mortality has decreased from 10% to 5%, survival has not improved strikingly. The pathogenesis of DKA is currently attributed to a combination of two hormonal abnormalities--a relative insulin insufficiency and stress hormone excess (glucagon, catecholamines, cortisol and growth hormone). Withdrawal of exogenous insulin, pancreatic beta cell failure and insulin resistance are factors leading to relative insulin insufficiency. Factors leading to stress hormone excess include fasting, stress and dehydration. The combination of these two hormonal abnormalities leads to impaired carbohydrate utilization and ketonaemia which in turn results in metabolic acidosis with loss of water through acidotic breaths, rise in plasma lipids, hyperglycaemia and glycosuria leading to osmotic diuresis and further loss of water, excretion of partly neutralised ketoacids via the kidney with loss of cations (Na+ and K+). A net increase in protein catabolism which leads to an increased amino acid flux from muscle and an enhanced load of gluconeogenic precursor to the liver and a rise in blood pyruvate and lactate concentration. The prevention of either of these hormonal abnormalities will prevent the development of DKA. The successful outcome in the treatment of DKA is clearly related to the prompt recognition of the diagnosis and the precipitation factors, the severity of the initial metabolic derangements, the judicious use of fluid and electrolyte replacement, the choice, route and dosage of the insulin therapy and above all the close monitoring and meticulous clinical care of the patient throughout the entire course of the treatment. Current acceptable treatment of DKA include the following: adequate fluid replacement: low dose insulin therapy at frequent intervals; adequate potassium replacement from time of first insulin therapy with ECG monitoring; bicarbonate replacement if pH less than 7.1; broad spectrum antibiotics if infections is suspected and other supportive measures. The role of phosphate and magnesium replacement is still controversial. An awareness of the complications during the treatment of DKA including cerebral edema (paradoxical acidosis), altered central nervous system oxygenation, vascular thrombosis, shock, myocardial infarction, pancreatitis, infection, inhalation of vomitus , overhydration, underhydration , hypoglycaemia, hyperkalemia and hypokalemia all certainly help improve the morbidity and mortality of DKA.
D000368:Aged; D001639:Bicarbonates / Q000627:therapeutic use; D002648:Child; D016883:Diabetic Ketoacidosis / Q000150:complications / Q000209:etiology / Q000378:metabolism / Q000628:therapy*; D004573:Electrolytes / Q000008:administration & dosage / Q000627:therapeutic use*; D005440:Fluid Therapy / Q000009:adverse effects; D006801:Humans; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D007651:Keto Acids / Q000096:biosynthesis; D007657:Ketone Bodies / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008274:Magnesium / Q000627:therapeutic use; D010710:Phosphates / Q000627:therapeutic use; D011188:Potassium / Q000627:therapeutic use; D012964:Sodium / Q000627:therapeutic use; D017693:Sodium Bicarbonate
D001639:Bicarbonates; D004573:Electrolytes; D007328:Insulin; D007651:Keto Acids; D007657:Ketone Bodies; D010710:Phosphates; D017693:Sodium Bicarbonate; D012964:Sodium; D008274:Magnesium; D011188:Potassium