1. GOUT
Disease caused by tissue deposition of Monosodium urate crystals as a result of supersatuaration of extra cellular fluid with MSU.

2. Hyperuricemia Serum uric acid above normal level for age and sex.
>7mg for adult men and > 6mg for adult women.
Only 15-20% of all patient with hyperuricemia develop gout.
Why we produce uric acid :End product of purine metabolism but human do not have enzyme uricase to convert it to allantoin (highly soluble)

3. Mechanism of Hyperuricemia
PURINES DEGREDATION PRODUCT
OVERPRODUCTION OF URATE
ENDOGENOUS OR EXOGENOUS
UNDEREXCRETION OF URATE (RENAL)
90% OF GOUT PATIENT
COMBINATION OF THE ABOVE TWO

4. EPIDEMIOLOGY Disease of adult men with peak in 5th decade.
Very rare before puberty and in premenopausal women.
Less than 25% of hyperuricemic develop GOUT
Duration and serum uric acid directly correlate with Gout development
20% family history

5. Primary Under excretion:
Idiopathic 90% of patients with hyperuricemia.
Normal excretion of uric acid only when serum uric acid high
Over production :rare
Idiopathic
Hypoxanthine-guanine phosphoribosyltransferase deficiency
Phosphoribosyl-1-pyrophosphate synthetase super activity.

6. ACQUIRED CAUSES OF HYEPERURICEMIA
URATE OVERPRODUCTION
Excess dietary purine consumption
Accelerated ATP degradation : alcohol abuse,glycogen storage disease,
Myeloproliferative and Lymphoproliferative disorders both causing increased nucleotide turnover.

7. ACQUIRED CAUSES OF HYEPERURICEMIA
Urate under excretion
Renal disease
Poly cystic kidney disease
Hyperparathyroidism
Hypothyroidism
Hypertension

8. DRUGS CAUSE HYPERURICEMIA DERCREASED RENAL EXCRETION
Decreased renal excretion
Cyclosporine
Alcohol
Nicotinic acid
Thiazide
Lasix(furosemide)
Ethambutol
Aspirin (low dose)
Pyrazinamdie
Unknown mechanism
Levodopa
Theophylline
Didanosine

9. ALCOHOL MECHANISM OF HYPERURICEMIA
Increases lactic acid production which reduces renal excretion of urate.
Increases Urate synthesis because of increased ATP degradation.
Beer also contain purine guanosine.

10. Stages of Gout Prolonged a symptomatic hyperuricemia(years)
Acute intermittent Gout
Chronic tophaceous Gout

11. GOUT: CLINICAL MANIFESATATION
Recurrent Gouty Arthritis( articular and periarticular.
Tophi
Uric acid urinary calculi
Interstitial nephropathy with renal function impairment

12. Gout involving DIPs

13. Podegra (gout of 1st MTP) Gout of ankle joint
Acute onset
Gout affect 1st MTP 75%
Severe pain
Erythema
Very tender
May be febrile
Resolve 3-10 days

14. Tophacous Gout

15. Tophi hands and olecranon bursa

16. Olecranon bursitis

19. Gout crystals Needle like Can be Intra or extra cellular
Negatively birefringent

21. Gout Soft tissue swelling because of Tophi Large erosions involving
DIPs,with hanging edges

22. Gout Soft tissue swelling around 1st MTP Erosion around 1st MTP
This takes time to develop
(YEARS)

23. Deferential Diagnosis
Pseudo Gout (CPPD)
Septic arthritis
Reactive arthritis
Other inflammatory arthritis

24. MANAGEMENT OF ACUTE GOUT
NSAID:indomethacin used more than other NSAIDs my use any other NSAIDs at full dose like ibuprofen 800mg TID or Naprosyn 500mg bid expect to as effective as indomethacin and my be less toxic
Know NSAID toxicities
Know NSAIDs contraindications,

25. CONTINUE ACUTE GOUT MANAGMENT
Colchicine: 0.6-1mg bid oral
Limited because of toxicity
Main side effects GI :abdominal pain/diarrhea/nausea
Need adjustment in renal impairment
May cause myelosuppression
May be linked to azospermia and infertility
IV Colchicine very toxic to bone marrow

26. CONTINUE ACUTE GOUT MANAGEMENT
Steroids safe for acute management with fast results,and when NSAID and Colchicine use not warranted
Intra-articular injection of triamcinolone is fastest way to get relief ,at the same time can get synovial fluid for analysis
Oral or parentral steroids e.g.:prednisolone oral mg daily for 5-7 days ,equivalent doses of IV steroids may be used if unable to take oral
Always make sure no infection coexist.

27. Prophylaxis Till hyperuricemia controlled
May use Colchicine
NSAID

28. Prevention and control of hyperuricemia indications
1-recurrent attacks of Gout
2-renal stones
3-tophaceous Gout
4-chronic gout with joint damage and erosions
5-hyperuricemia uric acid > 12mg/dl
6-24 hr urine excretion of >1100 mg uric acid

29. Uricosuric agents Probencid,sulfinprazone
Who is good candidate
1-age <60
2-Creatinine clearance >50ml/min
3-24 hr urine of uric acid < 700mg(under excretion)
4-No history of renal stone

30. Xanthine oxidase inhibitor Allopurinol
Hyperuricemia with :
Urinary uric acid >1000mg
Uric acid nephropathy
Nephrolithiasis
Before chemotherapy
Renal insufficiency GFR<50
Allergy to Uricosuric agents

31. Allopurinol Average dose 300mg Renal impairment use lower dose
May precipitate acute gout when first used
Side effects can be very serious range from dyspepsia,headache,diarrhea,rash,to more severe including fever,esosinophilia,interstitial nephritis,hepatitis,vasculitis,acute renal failure,toxic epidermal necrolysis,and hypersensitivity syndrome.

32. Gout in transplnat
Patient usually on Steroids,azathioprine,cyclosporine
Colchicine and NSAID use potentially toxic
Allopurinol increase level of azathioprine and toxicity
Steroids intra-articular ,oral or parentral can be used
May need adjust or change transplant medications

39. Chondrocalcinosis