Diabetic Ketoacidosis

Diabetic Ketoacidosis


Return to The Medical Biochemistry Page

© 1996–2014 themedicalbiochemistrypage.org, LLC | info @ themedicalbiochemistrypage.org

Definition of Diabetic Ketoacidosis

The most severe and life threatening complication of poorly controlled type 1 diabetes is diabetic ketoacidosis (DKA). DKA is characterized by metabolic acidosis, hyperglycemia and hyperketonemia. Diagnosis of DKA is accomplished by detection of hyperketonemia and metabolic acidosis (as measured by the anion gap) in the presence of hyperglycemia.

The anion gap refers to the difference between the concentration of cations other than sodium and the concentration of anions other than chloride and bicarbonate. The anion gap therefore, represents an artificial assessment of the unmeasured ions in plasma. Calculation of the anion gap involves sodium (Na+), chloride (Cl) and bicarbonate (HCO3) measurements and it is defined as [Na+ – (Cl + HCO3)] where the sodium and chloride concentrations are measured as mEq/L and the bicarbonate concentration is mmol/L. The anion gap will increase when the concentration of plasma K+, Ca2+, or Mg2+ is decreased, when organic ions such as lactate are increased (or foreign anions accumulate), or when the concentration or charge of plasma proteins increases. Normal anion gap is between 8mEq/L and 12mEq/L and a higher number is diagnostic of metabolic acidosis. Rapid and aggressive treatment is necessary as the metabolic acidosis will result in cerebral edema and coma eventually leading to death.

The hyperketonemia in DKA is the result of insulin deficiency and unregulated glucagon secretion from α-cells of the pancreas. Circulating glucagon stimulates the adipose tissue to release fatty acids stored in triglycerides. The free fatty acids enter the circulation and are taken up primarily by the liver where they undergo fatty acid oxidation to acetylCoA. Normally, acetyl CoA is completely oxidized to CO2 and water in the TCA cycle. However, the level of fatty acid oxidation is in excess of the livers' ability to fully oxidize the excess acetyl CoA and, thus, the compound is diverted into the ketogenesis pathway. The ketones (ketone bodies) are β-hydroxybutyrate and acetoacetate with β-hydroxybutyrate being the most abundant. Acetoacetate will spontaneously (non-enzymatic) decarboxylate to acetone. Acetone is volatile and is released from the lungs giving the characteristic sweet smell to the breath of someone with hyperketonemia. The ketones are released into the circulation and because they are acidic lower the pH of the blood resulting in metabolic acidosis.

Insulin deficiency also causes increased triglyceride and protein metabolism in skeletal muscle. This leads to increased release of glycerol (from triglyceride metabolism) and alanine (from protein metabolism) to the circulation. These substances then enter the liver where they are used as substrates for gluconeogenesis which is enhanced in the absence of insulin and the elevated glucagon. The increased rate of glucose production in the liver, coupled with the glucagon-mediated inhibition of glucose storage into glycogen results in the increased glucose release from the liver and consequent hyperglycemia. The resultant hyperglycemia produces an osmotic diuresis that leads to loss of water and electrolytes in the urine. The ketones are also excreted in the urine and this results in an obligatory loss of Na+ and K+. The loss in K+ is large, sometimes exceeding 300 mEq/L/24 h. Initial serum K+ is typically normal or elevated because of the extracellular migration of K+ in response to the metabolic acidosis. The level of K+ will fall further during treatment as insulin therapy drives K+ into cells. If serum K+ is not monitored and replaced as needed (see below), life-threatening hypokalemia may develop.

Treatment of Diabetic Ketoacidosis

 

 

 

 

 

 

 

 

 

 

The following is not intended to be considered as routine orders for the diagnosis and treatment of all cases of DKA but is presented only as one possible treatment regimen. Each case of DKA must be treated on an individual basis.

Initial Assessment of DKA

blood glucose > 250mg/dL

arterial pH <7.3

serum bicarbonate <15mEq/L

urinary ketones ≥ 3+ and/or serum ketones are positive

Monitoring

vital signs every hour

serum glucose every hour and as needed

blood gas pH every 2 hrs (use arterial for 1st measurement then can use venous)

electrolytes every 1–2 hrs

urine ketones on each void

fluid input and output continuously

magnesium and phopshorous immediately and then every 1–2 hrs

Fluid Management

start normal saline at 1L/hr or 15–20ml/kg/hr initially

determine hydration status, goal being to replace 50% of estimated volume loss in the 1st 4hrs then remainder over next 8–12 hrs

infuse normal saline 125–500 ml/hr, rate dependent on hydration status

once serum Na+ is corrected infuse ½ normal saline at 4–14ml/kg/hr

when serum glucose reaches 250mg/dL change fluid to D5W ½ normal saline at same rate

Insulin Management

discontinue all oral diabetic medications and previous insulin orders

give regular insulin iv bolus of 10 units

start insulin infusion usually at a rate of 0.15units/kg

insulin administration goal is to reduce serum glucose 50–70mg/dL/hr

when serum glucose is ≤ 150mg/dL then can switch to adult sq insulin with basal insulin

Potassium Management

if serum K+ is <3.3 give 40mEq/hr until it is >3.3

if serum K+ is >3.3 but <5.0 give 20–30mEq/L of iv fluids to keep serum K+ between 4–5mEq/L

if serum K+ is ≥5.0 do not give K+ but check serum levels every 2hrs

when replacing K+ both potassium chloride and potassium phosphate can be used

hold K+ replacement if patient urine output is <30ml/hr

Bicarbonate Management

assess need for bicarbonate by arterial pH measurement

if pH <6.9 give 100mEq sodium bicarbonate in 1L D5W and infuse at 200ml/hr

if pH is 6.9 – 7.0 give 50mEq sodium bicarbonate in 1L D5W and infuse at 200ml/hr

if pH >7.0 do not give bicarbonate

continue sodium bicarbonate administration until pH is >7.0

monitor serum K+


return to the Diabetes page
return to Fatty Acid Oxidation Page
Return to The Medical Biochemistry Page
Michael W King, PhD | © 1996–2014 themedicalbiochemistrypage.org, LLC | info @ themedicalbiochemistrypage.org

Last modified: February 8, 2013