3. Diabetic Ketoacidosis

Question 1

very generally, what is the function of insulin?

Answer 1

to allow storage of calories in the form of glycogen, proteins, TAGs

Question 2

carbohydrates: circulating form? storage form?

Answer 2

circ: glucose.
storage: glycogen

Question 3

fats: circulating form? storage form?

Answer 3

circ forms: triglycerides, lipoapoproteins

storage forms: triglyceride fat droplets, membranes

Question 4

proteins: circulating form? storage form?

Answer 4

circ: amino acids.
storage: cellular proteins

Question 5

what are the first few events that lead towards diabetic ketoacidosis?

Answer 5

insulin stops for some reason (usually pt stops taking it). glucose rises, and leads to osmotic diuresis.

Question 6

at what serum level can kidney no longer recapture all glucose? what is the result?

Answer 6

at a BG of about 200, kidney cannot recapture glucose. result = osmotic diuresis and hypovolemia

Question 7

when circ volume falls as a result of osmotic diuresis, what is response of arteries?

Answer 7

sympathetic response = release of epinephrine, cortisol, growth hormone. effect is vasoconstriction and attempt to maintain pressure, also lessened response to insulin

Question 8

what is the balance of insulin and glucagon once someone stops taking insulin? what is the effect?

Answer 8

relatively greater glucagon. effect is overall a catabolic state (as opposed to anabolic)

Question 9

what is the effect of low insulin on the liver? what enzymes incr and which decr?

Answer 9

liver:
- reduced storage of glucose via decr activity of glycogen synthase, incr activity of PFK, incr activity of pyruvate kinase
- increased glucose production via decr activity of glucose-6P

Question 10

what is the effect of low insulin on the fat? what enzymes incr and which decr?

Answer 10

release of free fatty acids into circulation

increased hormone sensitive lipase activity -> lipolysis & release of FFA

Question 11

what is the effect of low insulin on muscle?

Answer 11

protein breakdown, release of alanine into circulation. less uptake of glucose because GLUT4 transporter requires insulin to import

Question 12

very generally: what do the liver, fat, and muscle tissues do in the absence of insulin? (what processes/what do they release)

Answer 12

Liver: gluconeogenesis, releases glucose
Fat: lipolysis, releases FFA, glycerol
Muscle: proteolysis, releases alanine

Question 13

if you see a patient in a state of DKA, you can be 99% sure he has what type of DM? why?

Answer 13

T1DM. because T2DM pts make a tiny amount of insulin, which is sufficient to prevent acidosis

Question 14

T1DM patient: is there ever reason to withhold insulin? what about T2DM?

Answer 14

T1DM: never stop giving insulin. they need enough to replete their basal level of glucose, even if they are not eating/going for a surg procedure
T2DM: may hold insulin (or cut in half) if not eating or going for surg.

Question 15

why does someone start making ketones?

Answer 15

if the pathway from FFA –> Acetyl-CoA –> krebs cycle is saturated (requires NAD, which can be used up), then the other option is for the Acetyl-CoA to turn into ketones.

Question 16

under what scenarios will someone create ketone bodies?

Answer 16

• complete lack of insulin (DKA)

- complete lack of glucose (starvation)

Question 17

what will be the fate of FFA in the liver if insulin > glucagon? what if glucagon > insulin?

Answer 17

more insulin: triglyceride synthesis, TCA

more glucagon: keton bodies

Question 18

what are the names of the two ketone bodies?

Answer 18

Beta-hydroxybutyrate, Acetoacetate

Question 19

someone in DKA will have what kind of breathing?

Answer 19

deep and rapid: Kussmaul. breath will be fruity because he is trying to blow off acid via beta-hydroxybutyrate

Question 20

what is the first line of treatment for someone in DKA?

Answer 20

volume repletion.

Question 21

what is the status of potassium levels in DKA?

Answer 21

high serum K levels, but low intracellular levels. reason: acidic blood has been buffered by cell trading K+ for H+. Potassium has been drawn out of cells

Question 22

what will happen if you re-hydrate someone in DKA without replacing their potassium?

Answer 22

once the acidosis corrects, they will become dangerously low in serum K and may have a heart attack.

Question 23

which electrolytes are low in someone with DKA? what processes cause them to be low?

Answer 23

potassium (due to acid buffering), sodium (due to osmotic diuresis) and phosphate (also due to diuresis)

Question 24

what is the reason why we replete volume in DKA before we give insulin?

Answer 24

since pt is so hypovolemic, sympathetic system has tried to vasoconstrict. Lots of epinephrine/cortisol in system which will antagonize insulin if insulin is given before sympathetic system calms down.

Question 25

what happens to the alanine and FFA that have been released by muscle and fat?

Answer 25

they go to the liver and converted to circulating glucose and triglycerides. some are metabolised in mitochondria to ATP. however this requires NAD. once NAD is repleted, the only other option is production of ketones.

Question 26

overall what are treatment goals of reversing DKA?

Answer 26

1. Replete volume with IV saline: restore blood pressure, lower osmolarity, lower epinephrine levels
2. IV insulin for metabolic control: control nutrient flux from muscle/fat, control gluconeogenesis, promote glucose uptake, control ketoacid production

Question 27

what does glycogen synthase do?

Answer 27

final step to create glycogen from its precursor (UDP glucose) in glycogen synthesis pathway

Question 28

what does phosphofructokinase do?

Answer 28

enzyme in intermediate step for pathway from glycogen to pyruvate (for use in TCA)

Question 29

what does pyruvate kinase do?

Answer 29

enzyme in final step from glycogen to pyruvate

Question 30

what does glucose 6P do?

Answer 30

phosphorylates glucose intracellularly so it is trapped

Question 31

what does hormone sensitive lipase do?

Answer 31

breakdown of TAG into FFA in fat cells

Question 32

what is HONK? what typically brings it on?

Answer 32

hyperosmolar non ketotic coma. typically brought on by precipitating illness

Question 33

what patients usually develop HONK?

Answer 33

T2DM, elderly, under care of someone else, become very dehydrated and hyperglycemic.

Question 34

what are the biggest differences between DKA and HONK?

Answer 34

DKA: younger, glucose 200-800, severe acidosis and anion gap. lose 2-4 L fluid in under 1 day
HONK: usually elderly, glucose over 1000, no acidosis, no anion gap. lose 10-15L fluid in 3-5 days