Gout pathophysiology

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

Overview

Hyperuricemia is considered a multifactorial metabolic disorder in the general population. The levels of uric acid are influenced by the use of drugs, medications, renal impairment, and Alcohol also. The excess of uric acid levels gets deposited in the joints, kidneys, and a lot of tissue leading to clinical manifestations such as tophi, nephrolithiasis along the presence of urate nephropathy. Decreased excretion of uric acid contributes the maximum towards the development of Hyperuricemia. Along with the minimal contribution from other factors like increased production and increased consumption of foods rich in uric acid. The deposits in the joints, skin, and other tissues compromise the function of organs and resulting in the abnormal configuration of joint with funv=ctional limitation along with the presence of clinical signs in the form of pain and swelling.

Pathophysiology

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

Pathophysiological factors for the development of Gout https://www.pinterest.com/pin/129971139223442993/?nic_v2=1a30H8fPo

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:

• Enhanced or increased purine uptake.
• Decreased excretion of uric acid
• Increased production of uric acid
• Etiology in a lot of cases with rising uric acid levels is still unknown.
  

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.

• Beer is also particularly rich in guanosine which is a purine nucleotide.

Pathophysiology of Gout https://www.researchgate.net/figure/Key-checkpoints-in-gout-pathogenesis_fig1_44601699

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.

Gross and Microscopic Pathology

Kidney: Uric Acid Deposition: Gross, an excellent example of gouty nephropathy with deposits and excavation in pyramids

Kidney: Papillary Necrosis: Gross, yellow foci in pyramids, a gout kidney

Gout (Needles, no birefringence, monosodium urate)

Skin: Tophus: Micro med mag H&E uric acid deposits with giant cells. Easily recognizable as gout or uric acid tophus

Sources

Copyleft images obtained courtesy of Charlie Goldberg, M.D., UCSD School of Medicine and VA Medical Center, San Diego, CA) Images courtesy of Professor Peter Anderson DVM Ph.D. and published with permission © PEIR, the University of Alabama at Birmingham, Department of Pathology