Pathophysiology: DKA and HHS Fisher Flashcards
What is the diagnostic difference between DKA and HHS? (emphasized)
HHS:
>600gluc.
>7.3 pH
>15 bicarb
DKA:
>250gluc.
<10 bicarb
What is DKA seen in?
Type I DM
What is HHS seen in?
Type II DM
What is DKA?
High sugar
High Acid
High Ketones
What are metabolic acid states?
Lactic acidosis
Hyperchloremic acidosis
Drug-induced acidosis
Uremia
What are other ketotic states?
Alcoholic KA
Starvation KA
Ketotic Hypoglycemia
What are other hyperglycemic states?
DM
HHS
Impaired glucose tolerance
Stress
What hormones or factors go up with insulin stimulation? (*very important)
Basically everything but glucose and C peptide: Glucagon Epi Growth Hormone Cortisol NE ACTH Prolactin
What is the MAIN cause of DKA and HHS in DM?
Infection!
Usually pneumonia!
What is the second most cause of DKA and HHS?
New onset DM
What causes use of ketones in normal body? (remember that…)
Stress: any type
Epi–> Fat cells make free fatty acids
Glucagon–>Alanine/AA from muscle
–> liver gluconeogenosis/glycogenolysis
What are the main effects of acute insulin deficiency on glucose?
more glycogen breakdoen less glucose use, glucose buildup in blood polyuria polyphagia loss of fluid and electrolytes circulatory collapse (shock)
What are the main effects of acute insulin deficiency on protein?
increased protein breakdown
increase plasma AA
BUN increase
liver gluconeogenesis–>circulatory collapse
What is the main effect of acute insulin deficiency on pH?
Epi-->lipocyte-->FFA FFA become VLDL-->Hyperlipidemia FFA liver oxidation-->ketone formation ketone acids suck up alkali reserves Acidosis
What is the endpoint of ABSOLUTE insulin deficiency?
DKA:
High glucose
Hyperlipidemia
Ketoacidosis
What is the endpoint of RELATIVE insulin deficiency
HHS: NO KETONES!!!! no hyperlipidemia
Hyperglycemia–>dehydration–>hyperosmolarity
What is the summary of DKA?
Metabolic acidosis
and
Volume depletion
What enzyme releases FFA from fat?
Lipase
What enzyme in blood stimulates FFA release in fat?
Protein kinase (activates lipase)
What does FFA become?
Fatty acid CoA
and
Triacylglycerol (hyperlipidemia!)
What does Fatty acid CoA become?
Malonyl CoA
CAT1 (catecholamine1)
Fatty acid carnitine (which enters the mitochondria)
What does Fatty acid carnitine become?
Ketones (FFA–>FACoA–>FAC–>K)
What molecule causes hyperlipidemia in DKA?
Triacylglycerol
Fatty acyl CoA inhibits what enzyme in mitochondria?
Citrate synthetase, shunting Fatty acid carnitine into mitochondria for ketogenesis
What 4 enzymes complete the gluconeogenesis in the mitochondria?
PC: Pyruvate carboxylase
PEP CK
F1.6 Carboxylase
What enxyme allows glucose into the cell?
G-6-phosphatase
What is blocked in the mitochondria during DKA, and how?
the TCA cycle (it does ketogenesis instead)
Fatty acyl CoA blocking Citrate synthase makes Fatty acid carnitine the only thing that can come in
What are the enzymes of gluconeogenesis?
PC
PEP CK
F1,6BP
G6Phosphatase
What enzymes are blocked by FFA in the biochemistry of insulin deficiency? (emphacized twice)
Fatty acid blocks:
HK: hexokinase
PFK: phosphofructokinase
PK: pyruvate kinase
What happens to body compartments size during DKA?
All are shrunk!
How do you fix the dehydration of all body compartments in DKA? (his research!)
1 L of normal isotonic saline
then
1 L of HYPOtonic saline
