Diabetic Ketoacidosis

1. Diabetic Ketoacidosis

2. An anion gap acidosis due to severe insulin deficiency and excess of counterregulatory hormones Diabetic Ketoacidosis

3. Insulin is required for efficient transport of glucose into muscle, adipose, and liver cells Proper utilization of glucose within liver cells is also dependent on insulin In the absence of insulin glucose cannot be effectively transported into cells and it accumulates in the blood The liver begins to manufacture glucose from amino acids (gluconeogenesis) Additional glucose is thus secreted into the bloodstream Insulin Deficiency

4. When the degree of hyperglycemia exceeds the kidney’s capacity for tubular reabsorption glucose appears in the urine Osmotic diuresis ensues and the patient develops polyuria Severe dehydration may result Insulin Deficiency: Effects on the Kidney

5. Under normal circumstances insulin inhibits lipolysis In the absense of insulin adipose cells degrade their stores of triglycerides into fatty acids Fatty acids are converted by the liver into ketone bodies (acetoacetate and b-hydroxybutyrate) A metabolic acidosis develops Insulin Deficiency: Effects on Lipolysis

6. Glucagon when unopposed by normal insulin is responsible for the hepatic components of diabetic decompensation Increased glycogenolysis Increased gluconeogenesis Increased ketogenesis Actions of Glucagon

7. Insulin deficiency causes augmented delivery to the liver of substrates for glucose and ketone production Glucagon is the switch that activates the hepatic production machinery for glucose and ketones

8. Failure to take insulin Failure to increase insulin during acute illness, infection Other intercurrent illness such as myocardial infarction, pancreatitis, stroke, trauma or severe emotional stress The counterregulatory hormones released during medical stress oppose insulin and stimulate glucagon release Hypovolemia increases the secretion of glucagon, catecholamines by decreasing renal blood flow and this further reduces glucagon degradation by the kidney Precipitating Factors in DKA

9. Polyuria and polydipsia Kussmaul hyperventiation Vomiting and abdominal pain An acetone odor to breath Dehydration Stupor and coma Signs and Symptoms of DKA

10. Hyperglycemia Anion gap acidosis Positive urine and serum ketones Hyperosmolarity Initial Lab Findings

11. Anion gap acidosis: (Na + K) - (Cl +Bicarb) >16 Alcoholic ketoacidosis Lactic acidosis Renal failure Ethylene glycol or methyl alcohol poisoning Starvation in late pregnancy or lactation (rare) Differential Diagnosis

12. Initial Lab Findings in DKA

13. Replacement of fluid and electrolytes Insulin therapy Glucose administration Treatment of DKA

14. Restores perfusion of tissues to normal and lowers levels of counterregulatory hormones Average fluid deficit is 3-5 liters 1-2 liters of normal saline administered rapidly in the first 2 hours If hypernatremia develops 1/2 NS can be substituted Hyperkalemia usually present on admission recedes when insulin action begins; potassium replacement is then required Phosphate deficit becomes apparent after insulin administration but is usually clinically silent Bicarbonate is usually not given unless pH is below 7 or bicarb less than 5 mmol/l Replacement of Fluid and Electrolytes

15. IV bolus of 10-20 units regular insulin Follow by hourly insulin infusion Insulin should be given intravenously until the urine is free of ketones Insulin Therapy

16. Once insulin has restored glucose uptake and suppressed hyperglucagonemia, hypoglycemia will occur unless exogenous glucose is provided Glucose levels always fall before ketone levels decrease therefore exogenous glucose must be provided to cover the insulin needed to reverse ketosis Glucose is usually started when plasma glucose reaches 250-300 mg/dl Glucose Administration

17. Insulin-Glucose Infusion for DKA

18. Most patients require 0.5-0.6 units of insulin per kg body weight 1/2 - 2/3 requirement is given as long-acting insulin - NPH, Lente, Ultralente or Lantus 1/3-1/2 is given as short-acting meal time insulin - regular, Humalog or Novolog Give both long and short acting insulin subcutaneously about 2 hours prior to tapering insulin infusion Patient education key to avoiding future episodes Following Resolution of DKA

19. Administration of hypertonic glucose solutions at the outset Giving insulin in patients with severe volume deficit without sufficient fluids can cause fluid shift into cells can precipitate shock Premature administration of potassium before insulin has begun to act can cause fatal hyperkalemia Failure to administer potassium after insulin has begun to act can lead to fatal hypokalemia Recurrent ketoacidosis caused by failure to maintain IV insulin and glucose until ketones have cleared or by failure to administer subcutaneous insulin before stopping IV infusion Hypoglycemia caused by insufficient glucose administration Clinical Errors

20. Pregnancy is a state of relative insulin resistance marked by enhanced lipolysis and ketogenesis High serum ketones may be teratogenic DKA represents a substantial risk for the fetal compromise DKA and Pregnancy

21. Death is usually due to precipitating or complicating illness such as MI, pancreatitis or sepsis Infection Vascular thrombosis Cerebral edema Respiratory distress syndrome Complications of DKA

22. Extreme hyperglycemia and dehydration which results when the ability to excrete glucose as rapidly as it enters the extracellular space Maximum hepatic glucose output results in a plateau of plasma glucose no higher than 300-500 mg/dl When sum of glucose excretion plus metabolism is less than the rate at which glucose enters extracellular space Hyperosmolar Nonketotic Coma

23. Older patients with intercurrent illness with impaired ability to ingest fluids When urine volume falls the ability to excrete glucose falls As glucose rises CNS dysfunction occurs and water intake is additionally impaired The result is extreme hyperglycemia and hyperosmolarity with high mortality Either enough insulin is present to prevent ketosis or the extreme hyperglycemia inhibits lipolysis Hyperosmolar Nonketotic Coma

24. Extreme dehydration Supine or orthostatic hypotension Confusion to coma Seizures or other neurological findings Admission Findings: Hyperosmolar Nonketotic Coma

25. Average glucose 1200 Na 144 K 5 Bicarb 17 Osm 384 Admission Findings: Hyperosmolar Nonketotic Coma

26. Fluid repletion: give first 2-3 liters rapidly Total deficit may be 10 liters: replete 1/2 the deficit in the first 6 hours Insulin 10 unit bolus followed by sliding scale hourly Treat underlying precipitating illness Treatment of HONK