Gout
How a raised uric acid level leads to urate crystals in cool, peripheral joints, why those crystals set off one of the most intense inflammatory responses in medicine, and how repeated attacks lead to tophi and joint damage.
By the end, you can
- Describe how uric acid is made from purines and excreted, mainly by the kidneys.
- Explain why under-excretion is the commonest cause of hyperuricaemia.
- Explain why urate crystals form preferentially in the big toe and other cool, peripheral joints.
- Explain how crystals trigger acute inflammation through the inflammasome and interleukin-1.
- Describe chronic gout, tophi and the kidney and cardiovascular associations.
- Recognise the classic appearances, stages, key numbers and tests of gout, tell it apart from pseudogout and septic arthritis, and explain how each main drug class acts on its mechanism.
What it is
Gout is inflammatory arthritis caused by deposition of monosodium urate crystals in and around joints when urate in the body fluids stays above its solubility limit (hyperuricaemia). It causes sudden, very painful attacks that settle, and, if hyperuricaemia continues, chronic arthritis and urate deposits called tophi.
2 types to tell apart
- Acute gout
- An attack of intense inflammation, usually in one joint, settling over one to two weeks.
- Chronic tophaceous gout
- Years of untreated hyperuricaemia: frequent attacks, tophi, persistent joint pain and erosions.
US spelling: hyperuricaemia → hyperuricemia.
Normal function
Making and excreting uric acid
Purines, from the breakdown of the body’s own nucleic acids and from food, are converted to uric acid by the enzyme xanthine oxidase. Humans lack the enzyme uricase that most mammals use to break uric acid down further, so our urate levels are relatively high.
About two-thirds of urate is excreted by the kidneys and a third by the gut. The kidney filters urate at the , then the reabsorbs most of it and secretes some back, through transporter proteins. The net result is that only about a tenth of filtered urate leaves in the urine.
In body fluids at 37 °C, urate stays dissolved up to about 0.40 mmol/L (6.8 mg/dL). Above that level, solutions are supersaturated and crystals can form.
Underlying change · Step 1 of 4
Urate rises above its solubility
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 2 of 4
Crystals form in cool, peripheral joints
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 3 of 4
Crystals trigger intense inflammation
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Consequences · Step 4 of 4
Chronic gout and tophi
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Symptoms and signs
Symptoms, signs and findings
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Exam detail
Exam detail
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Treatment
How treatment works
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Recap
Recap
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Self-check
Check your understanding
The full lesson is part of Student Pro
It takes you through all 4 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .