Gout and pseudogout: Pathology review

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Gout and pseudogout: Pathology review



Gout and pseudogout: Pathology review

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A 64-year-old woman comes to the physician complaining of pain in the right knee for the past day. The patient reports associated joint swelling, warmth, and redness. She says this has happened before in her knees and hips, but those episodes lasted for only a few hours and resolved spontaneously. She also reports feeling fatigued during the past several months, but attributes this to frequently waking up at night to urinate. The patient has also had to strain more than usual when having a bowel movement and frequently takes laxatives to help. Vital signs are within normal limits. Physical examination reveals swelling, erythema, and warmth of the right knee joint. It is tender to palpation with decreased active and passive range of motion. Laboratory studies show the following:

Arthrocentesis of the right knee is performed. Gram stain is negative. Polarized light microscopy shows rhomboid-shaped, weakly positively birefringent crystals. Further evaluation of this patient is most likely to show which of the following?


On your rounds, you see Ashvir, a 50-year-old man who complains of severe pain and swelling in his first toe on the right foot.

This is the first time he has experienced this and the symptoms developed in the last 5 hours.

He described the pain as very severe and that it’s causing him to limp.

On examination, he is obese and the toe is swollen, red, warm, and painful to the touch.

Then you see Bianca, a 22-year old who also came in with a pain and swelling of the left big toe and left knee, which developed yesterday.

However, unlike Ashvir, she is not overweight and has a history of hemochromatosis.

Synovial fluid analysis was performed in both, detecting negatively bi-refringent crystals in Ashvir, and weakly positively birefringent crystals in Bianca.

Now, both seem to have some type of crystalline arthropathy.

But let’s talk about physiology first.

Purines, together with pyrimidines, are key components of nucleic acids like DNA and RNA.

Purines are first broken down into adenosine monophosphate or AMP and guanosine monophosphate or GMP.

AMP is converted to inosine via two different mechanisms; either by removing an amino group to form inosine monophosphate or IMP, which is quickly converted to inosine, or by removing a phosphate group to form adenosine, which is also converted to inosine.

Inosine is then converted to hypoxanthine, and hypoxanthine to xanthine, which is finally metabolized to uric acid.

These last two steps are catalyzed by the enzyme xanthine oxidase.

GMP is converted to guanosine, which is then converted to guanine.

Guanine is deaminated to form xanthine, which is oxidized by xanthine oxidase to form the final product, uric acid.

Now, under normal physiologic conditions, uric acid circulates in plasma and synovial fluid as urate an-ions.

However, human tissues have a limited ability to metabolize urate; thus, it is quickly eliminated by the kidney and the gut to maintain urate homeostasis.

Another way the body can avoid excess uric acid is by recycling purines via the purine salvage pathway.

This is when organs convert hypoxanthine back to IMP via hypoxanthine-guanine phospho-ribo-syl-transferase or HGPRT, which then gets converted to AMP to make new purines; conversely, we can take guanine and convert it to GMP by HGPRT to make new purines;

Now, gout is a monoarticular inflammatory disease where monosodium urate crystals cause joint damage.

When plasma becomes saturated with urate acid molecules, these bind sodium to form monosodium urate crystals, especially in areas with slow blood flow, like the joints and the kidney tubules.


  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "The British Society for Rheumatology Guideline for the Management of Gout" Rheumatology (2017)
  4. "Diagnosing and Treating Gout: A Review to Aid Primary Care Physicians" Postgraduate Medicine (2010)
  5. "The British Society for Rheumatology Guideline for the Management of Gout" Rheumatology (Oxford) (2017)
  6. "Gout" The Lancet (2010)
  7. "Management of Gout: A Systematic Review in Support of an American College of Physicians Clinical Practice Guideline" Annals of Internal Medicine (2016)
  8. "Diagnosis of Acute Gout: A Clinical Practice Guideline From the American College of Physicians" Ann Intern Med (2017)
  9. "Genetics and Mechanisms of Crystal Deposition in Calcium Pyrophosphate Deposition Disease" Current Rheumatology Reports (2011)
  10. "European League Against Rheumatism recommendations for calcium pyrophosphate deposition. Part I: terminology and diagnosis" Annals of the Rheumatic Diseases (2011)

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