Diabetic Ketoacidosis and Hyperosmolar Nonketotic Diabetes Mellitus

Diabetic ketoacidosis (DKA) is the culmination of diabetes mellitus that results in unrestrained ketone body formation in the liver, metabolic acidosis, severe dehydration, shock and possibly death. Hepatic lipid metabolism becomes deranged with insulin deficiency and nonesterified fatty acids are converted to acetyl-co-enzyme A (acetyl-CoA) rather than being incorporated into triglycerides. AcetylCoA accumulates in the liver and is converted into acetoacetyl-CoA and then ultimately to ketones including acetoacetic acid, beta-hydroxybutyrate (primary ketone in dogs and cats) and acetone. As insulin deficiency culminates in DKA, accumulation of ketones and lactic acid in the blood and loss of electrolytes and water in the urine results in profound dehydration, hypovolemia, metabolic acidosis and shock. Ketonuria and osmotic diuresis caused by glycosuria causes sodium and potassium loss in the urine exacerbating hypovolemia and dehydration. Nausea, anorexia and vomiting, caused by stimulation of the chemoreceptor trigger zone via ketonemia and hyperglycemia, contribute to the dehydration caused by osmotic diuresis. Dehydration leads to further accumulation of glucose and ketones in the blood. Stress hormones such as cortisol and epinephrine contribute to the hyperglycemia in a vicious cycle. Eventually severe dehydration may result in hyperviscosity, thromboembolism, severe metabolic acidosis, renal failure, and finally death.