Week 3- Gout Flashcards
what is gout?
its a group of diseases of increased levels of uric acid in the blood- HYPERURICAEMIA
what is gout caused by?
increase production or decreased excretion or both
what is happeneing during gout?
- Deposition of monosodium urate
monohydrate crystals in joints & soft tissues
➔ acute inflammation & eventually tissue damage
what is the epidemilogy of gout?
- more common in men 30-60yrs and in older ppl
- more likely if there is family history of it
what is the physiology of gout?
-normally for synthesis Uric acid is end product of purine (adenine & guanine) metabolism.
-last 2 steps controlled by xanthine oxidase
-nomrally for uric acid excertion
- Completely filtered by glomerulus
-90-100% reabsorbed in proximal tubule
(URAT-1 specific anion transporter)
-50% actively secreted in distal tubule
-40-45% post secretary reabsorption
➔ ~ 5-10% of original glomerular load is
excreted
what is the aetiology of gout?
-icnreased rate of synthesis of purine precursors of
uric acid (10%)
- decreased elimination of uric acid by kidney (90%)
what are the 2 types of gout?
-Primary:
– Due to rare inborn errors of metabolism or renal
excretion (not covered here)
- Secondary:
– Occur due to drugs or consequence of other
disorder
what is the explantation of gout due to over consumption of uric aicd?
-Offal (liver, kidney, heart, sweetbreads), game,
oily fish (anchovies, herring, mackerel, sardines,
sprats, trout), seafood, yeast or meat extracts.
what is the explantation of gout due to over production of uric acid?
⚫ Excessive cell turnover (E.g: neoplastic
disease, psoriasis, haemolytic anaemias)
⚫ Cell lysis caused by cancer chemotherapy &
radiotherapy
⚫ Excessive synthesis of uric acid due to rare
enzyme mutation defects
what is the explantation of gout due to under excretion of uric acid?
Hyperuricaemia ➔ large urate loads filtered
through glomerulus ➔ increased urate reabsorption
to avoid dumping of insoluble urate into
urinary tract
-Also reduction tubular secretion
what type of situation would you get under excretion of uric acid?
-renal failure, kidney cant excrete it
-alcohol (beer, red wine) have high levels of purine, when its breaks down produced uric acid and excretion in kidney
-Drugs:
– Diuretics - Especially thiazides, furosemide
– aspirin, ciclosporin,, omeprazole, ethambutol,
pyrazinamide, niacin, didanosine, levodopa,
cytotoxics
what are other causes for gout and risk factors?
⚫ Physical Stress
– Tight shoes, hill walking, hiking, history of joint
trauma
⚫ Other independent risk factors: hypertension,
obesity & hypertriglyceridaemia
what is the gout pathophysiology?
– Formation and deposition of monosodium urate crystals is more likely to occur when levels
are persistently > 380 micromol/mL (solubility limit)
⚫ HIGHER plasma urate level ➔ increased incidence of gout
⚫ PROLONGED DURATION of increase urate levels ➔ increased likelihood of developing gout.
when is uric acid a probelm?
-when its supersaturation withn join and formation crystals
-Solubility is influenced by:
– Temperature, pH, cation concentration, articular
dehydration and presence of nucleating agents (nonaggregated proteoglycans, insoluble collagens and
chondroitin)
when may a patient have symptoms of gout?
-crystal are shed in the bursa triggering inflammatory reaction (small sacs of synovial fluid surrounding
joint)
-Crystal deposition may continue for many
months or years without causing symptoms
what are some symptoms that a patient might experience?
Shedding can be triggered by e.g:
– Trauma, dehydration, rapid weight loss, illness &
surgery
what do the urate crystals do once they are in the bursa?
Urate crystals are directly able to initiate, amplify
and sustain inflammatory responses, through:
⚫ Humoral and cellular inflammatory mediators
⚫ Complement system
⚫ Overall this causes:
⚫ a proinflammatory cascade of cytokines, chemotactic factors,
TNF
⚫ Inflammatory cell accumulation (monocytes and mast cells in
the early phase and neutrophils in the later phase)
⚫ IL-1beta has been shown to be critically related to
the inflammatory response in gout
what are the 5 stages clinical presentation of gout?
– Asymptomatic hyperuricaemia (long period before gout manifests) – Acute gouty arthritis – Interval gout/Intercritical gout – Chronic tophaceous gout – Gouty nephropathy
what is acute gouty arthritis?
-first acute attack of gout, 90% monoarticular
⚫ 80% first metatarsophalangeal joint of great
toe (podagra)
⚫ Others: small joints of feet/ankles, hands
(distal interphalangeal), elbows & knees
⚫ Caused by deposition of urate crystals in
joints
what are some signs and symptoms of gout?
⚫ Severe pain with hot, red, swollen and extremely painful joints ⚫ Begin abruptly – max intensity 8-12hrs ⚫ Weight bearing impossible ⚫ Erythema(redness) ⚫ Synovitis(inflammation) ⚫ Leucocytosis(increase in wbc) ⚫ Confusion in elderly
when do attacks of gout happen?
⚫ Attack at anytime but can be caused by trigger factors (E.g: food, alcohol, dehydration, starting diuretic) ⚫ Left untreated last around 7 days ➔ desquamation(shredding of outer layer of skin) of overlying skin
what is intercritical gout?
⚫ Time between acute attacks of gout
⚫ Variable intervals of months to years when
there are no symptoms
what is chronic tophaceous gout?
⚫ Presence of tophi: – White deposits of monosodium urate – Nodule formation affecting joints – Subcutaneous and periarticular areas – Ear lobes, Achilles tendon, fingers -paitent who have this had probs had gout for 10-15 years
what is Gouty nephropathy/ Hyperuricaemia
induced renal disease?
⚫ Crystals of urate deposited around renal tubules ➔ inflammatory response (interstitial nephritis) ⚫ Proteinuria & renal impairment ⚫ Renal stone formation