Saturday, February 28, 2015

Study group discussion: Hyperuricemia

Why does pyrazinamide cause hyperuricemia?

I guess it competes with uric acid for excretion because it is a weak acid.

Ohh.. Didn't know this.

There's an interesting concept I heard learnt while studying the uric acid thingy - Why does alcohol ingestion have attacks of gout? Anyone wants to guess?

Consumption of alcohol produces gout because when alcohol is coverted to acetaldehyde, NAD is converted to NADH. More NADH causes conversion of pyruvic acid to lactic acid. Lactate is not metabolised and excreted to kidney... Increased lactic acid excreation causes decreased uric acid excretion and hence gout occurs.

Alcohol produces lactic acid which competes with uric acid.
Loop and thiazide diuretics also cause hyperuricemia through this mechanism.

Correct! We have a brilliant mind in the group! B)

A random review question from top of my head since its the topic of uric acid: Which ARB drug is a uricosuric?

Angiotensin receptor blocker, right?

Losartan.

Yup.

Low dose aspirin also competes with uric acid. High dose aspirin uricosuric by inhibiting absorption.

Wow..nice info!

Any condition causing inorganic phosphate depletion also causes hyperuricemia.

Why does phosphate depletion cause hyperuricemia though?

Hypophosphatemia leads to accumulation of AMP which is then converted into uric acid. Galactosemia fructose intolerance cause hyperurecemia through this mechanism.

Amazing concept!

I feel so jealous if you.. Biochemistry is like my biggest threat!

Updated later:
Recently, we had a discussion on hyperuricemia caused by diuretics. It was mentioned it is due to the resultant acidosis that causes hyperuricemia. I read something on those lines. Diuretics do cause acidosis cause of slight CA ase inhibitory action on the PT. Thus acidosis even caused is not very marked. They cause hyperuricemia primarily by competiting with uric acid to get secreted via the organic anion transporter in the PT. Plus as the E.C.F volume is depleted due to diuretics, there is also increased absorption of the secreted uric acid. That's what I read.

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