Ketoacidosis

1. Ketoacidosis SaroshTamboliMichael BrigantiJolina Botman Tarun Mehta PHM142 Fall 2013 Coordinator: Dr. Jeffrey Henderson Instructor: Dr. David Hampson

2. What is ketoacidosis? • A metabolic status caused by formation of “ketone bodies” • By-products are produced by metabolism of fatty acids for energy. This is usually due to inability to use glucose • Acetoacetic acid and Beta-hydroxybutyrate are commonly produced • They are acids which lead to drop in blood pH  potentially fatal • Ketones can also form during deamination of amino acids

3. General Signs and Symptoms • Commonly noticed by a “fruity” breath smell similar to nail polish (acetone) • Lowered blood pH, possibly altered state of consciousness • Deeper and more labored breathing (Kussmaul breath) • Seen often in diabetics or during ketogenic dieting

4. Diabetic Ketoacidosis (DKA) • Patients with diabetes mellitus have a high incidence of ketoacidosis. • DKA arises because of a lack of insulin in the body. • Insulin stops the use of fat as an energy source by inhibiting the peptide hormone glucagon. • Without insulin, glucagon levels rise resulting in the release of free fatty acids from adipose tissue as well as amino acids from muscle cells.

6. Type 1 and Type 2 Diabetes • Type 1 diabetes (insulin-dependent) diabetes, is due to low insulin production as a consequence of autoimmune destruction of pancreatic beta cells. • Severe insulin deficiency causes marked increases in the use of fats as a source of energy. Ketones, are produced in excess, and diabetic ketoacidosis may develop with potentially dire consequences. • Type 2 diabetes (DM 2) is a consequence of insulin resistance by the tissues, despite very high levels of serum insulin, initially (insulin levels typically fall as the disease progresses). • Therefore…Ketoacidosis is highly unusual in DM 2, since insulin is present.

7. DKA: Effects on the Body • A decrease in blood pH can have severe negative effects on the human body. • Symptoms of DKA include dry skin, blurred vision, feeling weak, loss of appetite and vomiting. • When DKA is severe enough breathing becomes difficult and the brain can swell. • This can lead to a coma and even death.

8. Mechanism of DKA • Compensates for the starvation as a result of insufficient insulin to utilize glucose • Counter-regulatory hormones activate lipase which breaks down triglycerides to glycerol and fatty acids • Beta-oxidaztion breaks down fatty acids in the mitochondria producing acetyl CoA to enter the TCA cycle • Increased concentrations of acetyl Co A forms ketone bodies: acetoacetate, beta-hydroxybutyric acid and acetone • Ketone bodies are released into circulation where peripheral tissue converts them to acetyl CoA • In DKA the production of ketone bodies exceeds the demands at peripheral tissues • Ketonemia is elevation of ketone bodies in blood • Ketonuria is elevation of ketone bodies in urine

10. Mechanisms of DKA • At physiological pH beta-hydroxybutyric acid and acetoacetic acid dissociate completely causing acidosis • Excess hydrogen ions bind to bicarbonate decreasing serum levels • The ketone bodies in anionic form leads to the anion gap • Calculated by: Na+-(Cl- -HCO3-) • Hyperventilation occurs through stimulation of chemoreceptors and respiratory centers due to buildup of CO2

11. Diagnosis of DKA • DKA is confirmed via laboratory investigation • Blood tests including glucose, ketone, and pH levels • Urine dipstick analysis of glucose and ketones • Ketones are tested with the nitroprusside reaction • Acetoacetic acid reacts with sodium nitroferricyanide and glycine in alkaline medium

13. Diabetic Ketoacidosis Treatment • Insulin, regular insulin is given in a dose of 0.1—0.2 U/kg i.v. hourly. If glucose levels do not fall ≤ 3 mmol/L in first hour continue doubling insulin dose hourly until glucose falls steadily 3-4 mmol/l hourly. When the plasma glucose level reaches 12–14 mmol/L, the insulin infusion rate may be decreased and adjusted to maintain ( check every 4-6 hours). Subcutaneous insulin therapy is then initiated. • Intravenous fluids, it is vital to correct dehydration. Normal saline is infused i.v. initially at the rate of 1L/hr, reducing progressively 0.5 L/4 hrs depending on the volume status. Once BP & heart rate has stabilized and adequate renal perfusion is assured change over to ½ N saline. After blood sugar has reached 300 mg/dl, 5% glucose in ½ N saline is the most appropriate solution.

14. DKA Treatment Continued • KCL: rehydration and insulin is typically associated with a rapid decline in the plasma potassium concentration, particularly during the first few hours of therapy. This is due several factors: most significant being the insulin-mediated re-entry of potassium into the intracellular compartment, extracellular fluid volume expansion, correction of acidosis and continued potassium loss owing to osmotic diuresis and ketonuria. Potassium replacement must be initiated as soon as levels fall below 5.0 mmol/L. It is recommended that 20–30 mmol of potassium be added to each litre of infusion fluid to maintain the serum potassium concentration between 4 and 5 mmol/L. • Sodium bicarbonate: Controversial, however if arterial pH is < 7.0 after 1 hour of hydration bicarbonate therapy is recommended. Sodium bicarbonate should then be administered in hypotonic fluid (44.6 mmol/L) every 2 hours until the pH is at least 7.0.

16. Summary • Ketoacidosis is a metabolic status caused by formation of “ketone bodies” • They are by-products produced by metabolism of fatty acids for energy. This is usually due to inability to use glucose • Patients with diabetes mellitus have a high incidence of ketoacidosis due to low insulin levels. • Ketoacidosis is more common in type 1 diabetes than type 2 • In DKA the production of ketone bodies exceeds the demands at peripheral tissues leading to elevated levels of ketones in blood (ketonemia) and urine (ketonuria) • Acidosis is a result of dissociation of ketone bodies and increases the anion gap as hydrogen binds to carbonate • Diagnosis of DKA: high glucose levels, presence of ketone bodies and decreased pH and bicarbonate levels via blood and urinalysis • In order to treat the elevated glucose levels and dehydration of DKA insulin and fluid therapy are used respectively. • In addition, these two therapies cause a lowering of plasma potassium which is administered via IV to maintain levels. • Severe acidisos can cause organ damage, it is recommended that if pH is below 7 that sodium bicarbonate be given

17. References • http://www.anaesthetist.com/icu/organs/endocr/dm/Findex.htm#dka.htmhttp://web.campbell.edu/faculty/nemecz/308_lect/lect7/fig07.jp • http://endoemergencies.org/sample-chapter.html • http://www.mayoclinic.com/health/diabetic-ketoacidosis/DS00674/DSECTION=tests-and-diagnosis • http://health.nytimes.com/health/guides/disease/diabetic-ketoacidosis/overview.html • http://www.medialabinc.net/spg506350/testing_for_ketones_in_the_urine.aspx • Chiasson, Jean-Louis, et al. "Diagnosis and treatment of diabetic ketoacidosis and the hyperglycemic hyperosmolar state." Canadian Medical Association Journal 168.7 (2003): 859-866. • http://www.ncbi.nlm.nih.gov/pmc/articles/PMC151994/