HELP ME - Alcoholic Ketoacidosis?

[Unregistered111]

I have fried my brain today trying to figure out this concept and have had no luck. I am hoping to get some clarity from anyone here on the forum.

In alcoholics, there is an increase in NADH (metabolism of ethanol puts out NADH), causing the following:

- inhibition of pyruvate hydrogenase thus an increase in lactate
- inhibition of gluconeogenis (OAA gets converted to malate)
- increase in Glycerol – 3 phosphate from DHAP

This combination results in hypoglycemia

A high NADH state also favors an increase in glycerol 3 – phosphate. This can therefore cause inappropriate fatty acids to be stored in the liver. Also, when ethanol is metabolized from acetate it turns into Acetyl Co causing it to favor more fatty acid synthesis – resulting in fatty liver over time.

Finally, high NADH states will also inhibit fatty acid B-oxidation via various mechanisms that we do not need to be concerned about.

Up until here I am able to understand this. However, the part that confuses me is what causes alcoholic ketoacidosis? Here is my problem that I can’t seem to wrap my head about.

In a non-alcoholic person, low levels of energy will trigger Ketone bodies synthesis by the break down of fatty acids via B-oxidation. The acetyl- CoA has two pathways it can travel…either make ketone bodies or enter into the TCA cycle. Both yielding energy that the body can use during periods of fasting.

But in an alcoholic, the B-oxidation of fatty acids is inhibited. So how do alcoholics get ketoacidosis? Or do they?

How is it possible to have ketoacidosis when the B-oxidation of Fatty acids is inhibited?

I don’t know if I’m confusing myself….or if I made any sense. I have searched online and all I get is that alcoholic ketoacidosis is due to the low energy state (hypoglycemia) and then on other websites it says that the increase in NADH will inhibit B-oxidation.

Please help me before I drive myself mad.

Thanks!

[Dr. X]

alcoholic ketoacidosis vs diabetic ketoacidosis. Main difference is that in AKA there will be "hypoglycemia" and DKA, "hyperglycemia". both will be dehydrated... big time.

The acetyl- CoA has two pathways it can travel…either make ketone bodies or enter into the TCA cycle. Both yielding energy that the body can use during periods of fasting.

But in an alcoholic, the B-oxidation of fatty acids is inhibited

Beta-oxidation is the process where acetly-coA gets converted into energy by going through TCA cycle. since that gets inhibited.. the other one.. is the "ketogenesis" (increased availability of FA and acetyl coa). so more ketones can be found in (lil) urine and blood. Alas, ketoacids are excreted by the kidney usually but due to dehyrdation kidney does its thing and tries to retain water and along with it, the ketoacids. Also know that the process of making ketones from acetyl-coA depletes acid buffers (bicarbonate) in ecf and icf.. which causes the acidosis. keep in mind that build of lactate will also cause "lactic" acidosis.. so you get severe metabolic acidosis.

dont forget to rehydrate em. why the dehyrdation: vomitting, inhibition of ADH.

bridge to micro --> did you know that DKA is associated with UTI's infections (1st) more commonly than diabetes mellitus type1 (2nd). DKA is also associated with mucormycosis (by mucor or rhizopus). jus got that latter point from doing uw this morning. ;)