Physiology-Diabetic Ketoacidosis Flashcards
What is responsible for the profound hyperglycemia and glycosuria in DKA?
Tons of gluconeogenesis from high levels of glucagon and failure of glucose uptake by insulin dependent cells.
What is responsible for the high rate of ketoacid delivery to the blood in DKA?
Normally hormone sensitive lipase is inhibited by insulin. In absence of insulin, it goes crazy and sends a ton of free fatty acids and acetyl CoA to liver to either form triglycerides or be oxidized. In low insulin states, malonyl-CoA levels are low because lipogenesis is inhibited. Low levels of malonyl-CoA and high levels of glucagon -> disinhibition of CPT-1. CPT-1 takes all of the excess fatty acids into the mitochondria and the vast majority become ketoacids in the liver. Additionally there is limited utilization of the ketoacids once they are released into the blood.
What is responsible for extra and intracellular fluid volume depletion with serum hypertonicity in diabetic ketoacidosis?
Hyperglycemia -> osmotically active in blood vessels -> intracellular dehydration. Glucosuria -> osmotic diuresis -> intravascular volume depletion. Ketonuria + charge and osmotic activity -> loss of electrolytes (K+ & PO4) -> Hypernatremia.
How do you treat diabetic ketoacidosis?
1) Immediate isotonic saline to drop blood glucose levels via renal filtration and excretion 2) Infuse insulin and K+ slowly and carefully to move K+ back into cells 3) After DKA hyperglycemia is corrected, glucose infusion 4) Maybe PO4 replacement
What enzymes in fat metabolism are activated and inhibited by insulin?
LPL is activated and hormone sensitive lipase is inactivated
Why do we not go into hypoglycemic shock every time we eat a high protein meal?
Insulin rises to take amino acids into the cells despite no elevation in blood glucose. Luckily, glucagon also rises in response to amino acids after a meal and increases blood glucose levels so they don’t drop in response to insulin
A 5 year old girl is brought to the ED with vomiting and abdominal pain since last evening. The mom says her daughter has had increased fatigue and appetite for 2-3 weeks, weight loss and new night time enuresis. She has no other GI symptoms. Physical exam reveals sunken eyes, dry mucous membranes, HR 144, capillary refill 3s, and 2kg weight loss. Labs are shown below. What is your diagnosis?
Since blood glucose > 200, pH 12 and + ketonemia she meets criteria for diabetic ketoacidosis.
Diagnostic criteria for patients with diabetes
1) Symptoms + random glue > 200 mg/dL 2) Fasting glucose > 126 mg/dL 3) 2-hr glucose > 200 mg/dL during oral glucose tolerance test 4) HbA1C > 6.5%
Hypothesis for the cause of diabetes
2 hit hypothesis: association with HLA DR3/4 and DQ2/8 alleles. Environmental: viral (rubella) or nutritional (cow’s milk, vitamin D deficiency) triggers
Below is an image of the pathophysiology of DKA. How do you navigate treating this patient?
1) Replace fluids (corrects hyperglycemia by dilution) 2) Give insulin (stops production of ketones by stopping lipolysis and protein breakdown) 3) Replace electrolytes (insulin will drive K+ into the cells, so you will become hypokalemic if you don’t replace K+)
Why aren’t you aggressive with fluids in patients with DKA?
Giving fluids too quickly can result in cerebral edema. This is because suddenly the neurons in the brain become hyperosmolar compared to the rest of the body and will begin to swell. You should give 10cc/kg boluses over the first 1-2 hours.
A child comes in with DKA, you get her blood sugar down to 100mg/dL, but blood pH is still 7.25. What do you do?
Do not stop the insulin drip (0.05 - 0.1 U/kg/hr)! Start her on a dextrose infusion to keep blood sugars up until the acidosis corrects.
How do you diagnose cerebral edema? How do you treat?
Treat prior to imaging with mannitol 1-2g/kg over 30-60 minutes
