DKA occurs in: 20–40% of children with new-onset diabetes Children with known diabetes who omit insulin doses or Who do not successfully manage an intercurrent illness.
PATHOPHYSIOLOGY Insulin performs a critical role in the storage and retrieval of cellular fuel.
Functions of insulin: In liver: Glucose uptake, Glycogen synthesis, absence of gluconeogenesis, absence of ketogenesis In mescle: Glucose uptake, glycogen synthesis, protein synthesis In adipose tissue: Glucose uptake, triglyceride uptake, lipid synthesis
PATHOPHYSIOLOGY Moderate insulinopenia: glucose utilization by muscle and fat decreases, postprandial hyperglycemia appears. Lower insulin levels: liver produces excessive glucose via glycogenolysis and gluconeogenesis, fasting hyperglycemia begins. Hyperglycemia produces an osmotic diuresis (glycosuria) when the renal threshold is exceeded (180 mg/dL)
PATHOPHYSIOLOGY This entire progression happens much more quickly (over a few weeks) in younger children, probably owing to more aggressive autoimmune destruction of β cells. In infants, most of the weight loss is acute water loss because they will not have had prolonged caloriuria at diagnosis, and there will be an increased incidence of DKA at diagnosis.
PATHOPHYSIOLOGY In adolescents, the course is usually more prolonged (over months), and most of the weight loss represents fat loss due to prolonged starvation
PATHOPHYSIOLOGY The resulting loss of calories and electrolytes, as well as the persistent dehydration, produce a physiologic stress with hypersecretion of stress hormones (epinephrine, cortisol, growth hormone, and glucagon). Stress of an intercurrent illness or trauma can also produce hypersecretion of stress hormones.
PATHOPHYSIOLOGY These stress hormones impair insulin secretion or antagonize its action and promote glycogenolysis, gluconeogenesis, lipolysis, and ketogenesis.
PATHOPHYSIOLOGY Insulin deficiency and glucagon excess shunts the free fatty acids into ketone body formation. Accumulation of these keto acids results in metabolic acidosis (diabetic ketoacidosis, DKA) and compensatory rapid deep breathing in an attempt to excrete excess CO 2 (Kussmaul respiration).
PATHOPHYSIOLOGY Acetone is responsible for the characteristic fruity odor of the breath. As in any hyperosmotic state, the degree of dehydration may be clinically underestimated because intravascular volume is conserved at the expense of intracellular volume.
PATHOPHYSIOLOGY Keto acids produce abdominal discomfort, nausea, and emesis, preventing oral replacement of urinary water losses. Dehydration accelerates, causing weakness, but polyuria persists.
PATHOPHYSIOLOGY With progressive dehydration, acidosis and hyperosmolality, consciousness becomes impaired.
PATHOPHYSIOLOGY Osmotic diuresis, the kaliuretic effect of the hyperaldosteronism, and the ketonuria accelerate renal losses of potassium and phosphate. Acidosis move potassium and phosphate from the cell to the serum. Although patients with DKA have a total body potassium deficit, the initial serum level is often normal or elevated.
PATHOPHYSIOLOGY Improved hydration increases renal blood flow, allowing for increased excretion of potassium in the elevated aldosterone state. The net effect is often a dramatic decline in serum potassium levels, especially in severe DKA.
PRECIPITATING CAUSES OF DKA Omission or reduction of insulin Undiagnosed diabetes Infection Respiratory UTI Gastroenteritis Septicemia Pancreatitis Unknown
MANAGEMENT Resuscitation Monitoring Fluid and electrolyte Insulin Bicarbonate Treatment of any precipitating cause
Lab tests a. Urinalysis: Glucose, Ketone. b. Blood Glucose, BUN, Creatinine, Electrolytes, CBC, Blood Gas, ketone bodies d. Cultures, ESR, CRP e. Lead II EKG.
MANAGEMENT 1. Resuscitation: 10% of the Cases are Comatose.
MANAGEMENT Monitoring: Frequent neurologic checks for any signs of increasing intracranial pressure, such as a change of consciousness, depressed respiration, worsening headache, bradycardia, apnea, pupillary changes, papilledema, posturing, and seizures. Mannitol must be readily available for use at the earliest sign of cerebral edema. Monitoring laboratory changes; hypokalemia or hypoglycemia can occur rapidly.
MANAGEMENT FLUID AND ELECTROLYTE THERAPHY Maintenance Deficit Ongoing abnormal loss
MANAGEMENT First 12 hours Half of the maintenance Half the deficit Ongoing abnormal Next 24 hours Remainder of deficit Maintenance for 24 hours
MANAGEMENT TYPE OF FLUID: Initial fluid normal saline D/W %5 + 30 meq/l sodium when The blood glucose approach 300 mg/dl
MANAGEMENT POTASSIUM THERAPY Is a crucial aspect of therapy 1-2 hour after initial fluid therapy 40 meq/l of fluid
MANAGEMENT Insulin infusion is begun without a bolus at a rate of 0.1 U/kg/h.
Bicarbonate buffers, regenerated by the distal renal tubule and by metabolism of ketone bodies, steadily repair the acidosis once keto acid production is controlled. Bicarbonate therapy is rarely necessary and may even increase the risk of hypokalemia and cerebral edema.
Persistent acidosis may indicate inadequate insulin or fluid therapy, infection, or rarely lactic acidosis. Urine ketones may be positive long after ketoacidosis has resolved because the nitroprusside reaction routinely used to measure urine ketones by dipstick measures only acetoacetate.
During DKA, most excess ketones are β- hydroxybutyrate, which increases the normal ratio to acetoacetate from 3 : 1 to as high as 8 : 1. With resolution of the acidosis, β- hydroxybutyrate converts to acetoacetate, which is excreted into the urine and detected by the dipstick test.