Gout pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Shivam Singla, M.D.[2]

Overview

In terms of pathophysiological classification, we can categorize gout into 2 main types

1) Primary gout: Mainly hereditary or related to enzymatic abnormalities

2) Secondary Gout: Secondary to other reasons like drugs, renal insufficiency, dietary or related to malignancy

The pathophysiology of Gout mainly relates to hyperuricemia. Greater is the degree of hyperuricemia greater is the likelihood of developing Gout.

Numerous reasons can lead to the development of an increase in the level of uric acids:

Increased intake

The increased uptake is mainly related to

Increases intake of purine-rich food substances by the patient such as
- Asparagus, meat broths, mushrooms, liver, kidney, sweetbreads.
- The increased intake of all of these substances can increase the risk of accumulation of more and more purines ultimately resulting in the excess of uric acid.

Increased production

The increased production is mainly

Increase in turn over of cells like in various hematological conditions such as Hemolytic anemia, leukemia, and lymphoma.
Conditions associated with an increased rate of cell proliferation and cell death.
- Cytotoxic therapy
- Radiation
- Psoriasis
Obesity - As the urate production is directly proportional to the body surface area

Hereditary conditions
Enzymatic Pathway resulting in hyperuricemia- De novo synthesis pathway and HGPRT pathway http://themedicalbiochemistrypage.org/nucleotides-biosynthesis-catabolism/
Enzyme abnormalities
- Overactivity of Phosphoribosyltransferase
- Deficiency of HGPRT
- Absence of HGPRT ( Lesch-Nyhan syndrome)

Decreased/Reduced renal excretion

This is the most common cause of hyperuricemia. Various factors responsible for its reduced elimination are:

Hereditary
Compromised renal function ( Reduced GFR)
On Diuretics
Alcohol intake
- The lactic acid blocks the excretion of urate from the renal tubules. Alcohol induces the purine metabolism in the liver and increases the formation of lactic acid and
- Alcohol also directly stimulates the synthesis of urate by the liver

Drugs like cyclosporine that are toxic to the renal tubules leads to the decreased elimination of uric acid and ultimately resulting in the urate retention.