AssessmentsGout and pseudogout: Pathology review
USMLE® Step 1 style questions USMLE
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?
Content Reviewers:Yifan Xiao, MD
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.
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.
Ok, so the main risk factor for gout is excess uric acid, or hyperuricemia, and it can be caused by many things.
First is underexcretion of uric acid by the kidney, which can be idiopathic, when the cause is not known; due to renal failure; or it can be exacerbated by medication, like thiazide diuretics and aspirin.
Second is overproduction of purines.
This can occur with increased consumption of purine-rich foods such as shellfish, anchovies, and red meat.
High-fructose corn syrup containing beverages can contribute to hyperuricemia too, usually by increasing purine synthesis.
Others might have a genetic predisposition to overproduction of uric acid, or it can develop as a result of chemotherapy or radiation treatment, where a lot of tumor cells die, causing what is known as tumor lysis syndrome.