gout Flashcards
gout definition
Imbalance in purine metabolism (production > excretion)
Deposits of monosodium urate (MSU) crystals in articular & periarticular tissues
* Leads to inflamm: pain & swelling
gout syndrome
- Recurrent acute gouty arthritis
○ Assoc w/ urate crystals in synovial fluid - Tophi
○ Deposits of MSU crystals in tissue & surrounding joint - Interstitial renal disease
○ Gouty nephropathy - Uric acid nephrolithiasis
○ Uric acid kidney stones
risk factors
- dietary and lifestyle factors
- obese pts
Asx hyperuricemia (uric acid) assoc w/ HTN, CKD, insulin resistant, CVD
purine metabolism
- Glutamine + PRPP –> nucleic acids in body tissues (RNA, DNA)
- Break down —> Guanine & Adenine
○ Recycled to form nucleic acids (HGPRT + PRPP) - Break down —> hypoxanthine
○ Recycled to form nucleic acids - XANTHINE (XO)
- URIC ACID (XO)
uric acid properties
○ Weak organic acid (Pka 5.75 in blood)
○ Soluble in normal arterial pH of 7.4
○ Solubility limit at 6.8mg/dL
○ Less soluble at lower temp = Peripheral joints
uric acid animal vs human
- Excreted in humans
○ 65% in urine (reabsorbed by urate transporter 1, URAT1 & GLUT9)
○ 35% in GI (degrade by intestinal flora) - animals (uric acid –> allantoin) by uricase
gout patho
- High uric acids –> crystallised and hidden in joints
- TRAUMA Releases crystals into blood plasma
- Immune cells activated, recognise and attack crystals
○ Proliferation of immune cells (neutrophils, macrophage)
○ Cytokine production
○ Adhesion and trafficking - Inflammation as leukocytes attack urate crystals
+ve feedback that incr inflammation
- Incr inflammation as neutrophils try unsuccessfully to phagocytize urate crystals
○ Crystals lyse neutrophils (released out)
○ Release lysosomal enzymes too
○ More damage to joint & tissues
+ve feedback loop
2 main pathways
1) Over production of uric acids (excrete > 600mg)
2) Underexcretion of uric acid (<600mg/24h)
Incr uric acid > solubility = deposition of urate crystals
- Periarticular fibrous tissue of synovial joints
- Renal tubules
overprod
> 600mg excrete
* PRIMARY: inborn error in metabolism
* Secondary: conditions that incr cell turnover & purine generation
* Diet (purine rich foods)
* Incr Guanine & Adenine
underexcretion
<600mg excrete
* Incr uric acid conc (reabsorbed by urate transporter 1, URAT1 & GLUT9)
* 90% of gout cases
measure uric acid excretion
not commonly done as diet is difficult
- Serum uric acid & 24h urine
- purine free diet
> 600mg excrete: OVER-production
<600mg excrete: UNDER-excretion
gout presentation
- Usually monoarticular (MTP of great toe)
- Most common at periphery (lower temp = incr ppt)
- Occur one joint at a time
- Sleep disrupted by pain
- Severe pain x hrs
- Pain resolves but swelling and discomfort continues days~wks
- Joint red, hot, swollen, tender
- Chronic gout
- Tophaceous/ tophi formation
○ Pus (urate crystals + inflamm cells, no microog) - Joint damage
- Tophaceous/ tophi formation
dx of gout
Monosodium urate crystals Microscopy (birefringent 2 sharp points)
* Synovial fluid (joint aspirate)
* May look diff: turbid, pus (infection), blood
* Yellow, cloudy, low viscosity
* High WBC, neut
* -ve microbial (not septic)
* Tophaceous deposits (tissue secretions)
Asx hyperURICemia =/= gout
hyperuricemia levels
- W: > 6mg/dL (450umol/L)
- M: > 7 mg/dL (360umol/L)
stages of gout
- Asx hyperuricemia = no tx
- Acute attack = colchicine, NSAID, CS
- Acute arthritis
- 1st MTP
- Excruciating pain
- Intercritical phase = no tx (10% not have another acute attack)
- Chronic gout = ULT
- Clinical or imaging findings of gouty arthropathy damage
- Hx of urolithiasis (kidney stone)
- Tophi formation
- freq acute gout attack (≥2/yr)
Consider: diuretic therapy, CKD stage 3-5
goals of gout tx
- Provide rapid, safe, effective pain relief
- Reduce future attacks
- Reduce SU conc (taken at baseline + monitored)
- Treat to target conc
- Address assoc comorbidities (kidney, medication use)
- Prevent complications
- joint destruction and tophi formation
- Incr QOL
- joint destruction and tophi formation
tx acute inflamm
- Colchicine
○ Reduce leukocyte migration into joints - Non-selective NSAIDs (naproxen, indomethacin)
○ Anti-inflamm and analgesic
Indomethacin: older NSAID (wider MOA = inhibit phospholipase A2 + COX) - COX2 selective NSAIDs (celecoxib)
- Glucocorticoids (prednisolone PO or intra-articular inj)
consideration of acute gout tx
- Combi therapy (reduce inflamm asap)
- Colchicine + NSAID/ COXIBS
- Colchicine + prednisolone
- X NSAID + CS
- Non-pharm: topical ice
- Start ULT (if indicated)
- 2-4wks later after acute, sx resolved
- Start even when on flare if
* Pt non-adherence, not return
*Pt highly motivated for tx
chronic gout prevention tx
- Xanthine oxidase inhibitors [allopurinol, febuxostat]
○ Decr production of uric acid
○ Incr migration of crystals from joint to plasma - Uricosuric agents [Probenecid]
○ Incr excretion of urate through kidneys
○ Push uric acids from blood to kidney - incr uric acid metabolism [pegioticase]
○ recombinant PEGylated uricase, incr uric acid metabolism
monitor
- SU level (tx to target: base, mnthly – until reach target)
- Annual if continue tx
○ Non-tophaceous: <360umol/L (6mg/dL)
○ Tophaceous: <300umol/L (5mg/dL) - Assess lifestyle and comorbidities
○ Obesity, HTN, CKD - Review meds (int?)
- Non-pharm
○ Diet, weight, alcohol - Need for ULT? (freq attack)