Chemical Pathology Concepts Flashcards
What catabolism underlines gout?
Purine Catabolism
Why does gout affect the first metatarsophalangeal joint?
Because monosodium urate has a slower solubility in colder temp. which occurs in the extremities
How much urate is reabsorbed in the kidney?
90% reabsorbed - only 10% filtered (FEUA)
What does FEUA mean
Fractional excretion of uric acid - which accounts for the 10% of urate
What are the two ways to make purines?
De novo purine metabolism
Salvage Pathways
What is the De Novo purine metabolism?
Produces purine from scratch, and is very energy consuming and only occurs in Bone Marrow
What is the salvage pathway in purine metabolism
A form of recycling to make purines, and is highly energy efficient
This process predominates in the body mostly
What is the main enzyme involved in the salvage pathway
HPRT - Hypoxanthine-guanine phosphoribosyltransferase
What is Lesch-Nyhan Syndome
A deficiency in HPRT, which makes the de novo pathway go into overdrive
And IMP is being catabolised without being recycled => leads to build up of urate
Typical clinical features of Lesch-Nyhan Syndrome
o Normal at birth
o Developmental delay at 6 months
o Hyperuricaemia (very rare in children) – significant feature
o Choreiform movements (at 1 year)
o Spasticity and mental retardation
o KEY FEATURE: Self-mutilation in 85% of patients at ages 1-16 (e.g. biting lips very hard, biting digits)
Key difference between acute and chronic gout?
Acute - Podagra
Chronic - Tophi (found on fingers and ear lobe) - which may lead to periosteal erosion
What steps are involved in diagnosis Gout?
• Usually history, examination and uric acid levels is enough to diagnose gout
• However, if there is any doubt, you should tap the effusion and view under polarised (aligned in one axis) light using a red filter (red compensator)
- Needle-shaped and negatively birefringence (90 degree to axis)
Managing Gout in terms of reducing inflammation
1st - NSAIDs
2nd - Cochine (which inhbits the manufacture of tubulin to reduce mitosis and motility of neutrophils)
3rd-Glucocorticoids
Managing Gout in terms of Hyperuricaemia
Life style:
Drink water
Allopurinol (Xanthine oxidase inhibitor)
Provenecid to increase urate excretion in kidney
Important contra-indications for allopurinol
Never give to someone with Azathioprine
