This document discusses gout (monosodium urate arthropathy). It begins by defining gout as a disorder of purine metabolism seen in middle-aged males and post-menopausal women that results from hyperuricemia and deposition of monosodium urate crystals in joints. It then covers the pathophysiology of purine metabolism and uric acid production, classification of primary and secondary gout, clinical features including podagra, and diagnostic tests including synovial fluid analysis. It concludes by outlining treatment approaches for acute gout attacks and chronic gout prevention including NSAIDs, colchicine, corticosteroids, allopurinol, febuxostat, probenecid,

1. MONOSODIUM
URATE
ARTHROPATHY
(GOUT)
By: Dr. Nirav Prajapati

2. Introduction
 Disorder of purine metabolism
 Seen in middle aged male and post
menopausal women
 Hyperuricemia and deposition of monosodium
urate crystal in joints.

3. aetiology
- Over production of uric acid(10%)
Primary idiopathic hyperuricemia
- Hypoxanthine-guanine phosporibosyl-transferase
deficeincy.
 Inability to excrete uric acid (90%)
PCKD, renal insufficency, Diabetes.

4. Pathophysiology
 uric acid is the end product of the degradation
of purines. Uric acid has no known
physiologic purpose and therefore is regarded
as a waste product.
 the enzyme uricase breaks down uric acid to
the more soluble allantoin, and thus uric acid
does not accumulate.

5. Pathophysiology
 The purines from which uric acid is produced originate
from three sources:
1. Dietary purine
2. Conversion of tissue nucleic acid to purine nucleotides.
3. Synthesis of purine bases
 The purines derived from these three sources enter a
common metabolic pathway leading to the production of
either nucleic acid or uric acid.

6. Pathophysiology
Purine metabolism

7. In kidneys
• 100% of urate undergoes glomerular filtration.
• 98% is reabsorbed by the PCT.
• 50% is secreted by the distal tubule.
• 40% of it undergoes post secretary resorbtion.
• 10% of filtered urate is excreted in urine.

8. Clinical features
 pain, swelling, tenderness and increased temperature of the
first metatarsophalangeal joint ( classically called podagra)
 Skin over affected joint is Red-purplish, tight and shiny.
 Patient may have systemic signs like fever, chills, malaise,
tachycardia.
Note: Podagra or pain in the first metatarsophalangeal joint
is the classic presentation.

9. CLASSIFICATIONOF
GOUT:
1. Primary gout: basic metabolic defect is unknown. Elevated
serum uric acid levels may be due to following:
a) Increased production of uric acid due to excessive dietary
purines or due to rare enzyme mutation defects (Lesch-
Nyhan syndrome due to deficiency of hypoxanthine
guanine phosphoribosyl tranferase (HGPRT); variants in
enzyme phosphoribosyl- 1- pyrophosphate (PRPP) have
increased de novo purine production).
b) Undersecretion of uric acid results from a defect in renal
excretion.

10. CLASSIFICATIONOF
GOUT:
2. Secondary gout: It is associated with
increased nucleic acid turnover, decreased renal
function, increased purine production or drugs.

11. Gout generally
passes through four stages:
1. Asymptomatic hyperuricemia
2. Acute gouty arthritis (the gout flare) lasting few days to
weeks.
3. Interval gout is the period when the symptoms resolve
fully.
This freedom from symptoms during the intercritical period
is an important feature in the diagnosis of an episode of
acute arthritis as a crystal induced process, potentially
gout,

12. Gout generally
passes through four stages:
 4. chronic tophaceous gout
- characterized by the identifiable deposition of solid urate
(tophi) in connective tissues, including articular structures,
with ultimate development of a destructive arthropathy,
often with secondary degenerative changes.

13. STAGESOFGOUT:

15. Diagnosis
 Investigation
- Laboratory investigations show leucocytosis and
ESR is increased.
- Synovial fluid study (presence of mono sodium
urate crystals). most important diagnostic method.
- creatinine
- Raised uric acid level (4.0-8.5 mg/dl).
- 24 hour urine uric acid excretion (>800 mg/day)

16. Diagnosis
 Radiological
Xrays
The common joints affected
are:
First metatarsophalangeal
joint
Feet
Tarsal joints
Ankles
Fingers
Wrist
Elbow

17. TREATME
NT:
Treatment aims in gout:
• Rapid alleviation of the acute attack.
• Prevention of future attacks.
• Lower serum uric acid levels to below
saturation point.
• Reduce risk of co-morbidities.
• Lifestyle modification.

18. MANAGEMENTOFACUTEGOUT:
Drugs used in the management of an acute
attack include:
1. First line: NSAIDs (use maximum dose)
2. Second line: Colchicine
3. Third line: Corticosteroids like
prednisolone, methylprednisolone,
triamcinolone

19. 1.NSAIDs:
MOA: NSAIDs (Non steroidal anti-inflammatory
drugs) act by direct inhibition of cyclooxygenase-1
(COX-1) and cyclooxygenase-2 (COX-2) via
blockade of the cyclooxygenase enzyme site. The
subsequent inhibition of prostaglandin production
reduces inflammation, but also results in additional
activities on platelet aggregation, renal
homeostasis and mucosal injury.
ADRs: Upper GI effects, acute tubular
necrosis, hepatotoxicity, vasculitis etc.
Dose: Indomethacin-25mg TID, Diclofenac-25-
50mg TID.

20. 2. COLCHICINE:
MOA: It is an alkaloid used to relieve acute attack of gouty
arthritis. It is not an analgesic and uricosuric agent,
although it relieves pain in acute attack. Colchicine inhibits
migration of neutrophils to the affected area.
ADRs: Abdominal cramps, nausea, vomiting, diarrhoea
and rarely bone marrow supression, neuropathy and
myopathy.
Dose: Tablets-0.5mg (0.5-1mg PO followed by 0.5-1.2mg
every 1- 2 hours). Injection-1mg/2ml (1mg initially, followed
by 500mcg every 2- 3hrs).
Maintenance dose of 0.5-1mg/day may be given for 4-8
weeks.

21. 3. CORTICOSTEROIDS:
MOA: Corticosteroids act by inhibiting cytokine
release and give rapid relief of symptoms and
decrease inflammation. They can be given oral,
intravenous or intraarticular routes.
ADRs: Diabetes, increased risk of infection,
hypertension, weight gain, insomnia, menstrual
irregulations, osteoporosis,etc.
Dose: Methyl prednisolone-80mg or 40mg,
Triamcinolone-40mg, Oral prednisolone-30mg.

22. Algorithm for managing acute gout

23. MANAGEMENTOFCHRONICGOUT:
patients may only experience a single episode
and a change in lifestyle, diet or concurrent
medication may be sufficient to prevent further
attacks.
Classification of prophylactic agents used to
lower serum urate:
1. Uricostatic agents: allopurinol, febuxostat
2. Uricosuric agents: Benzbromarone,
probenecid, sulphinpyrazone
3. Uricolytic agents: rasburicase, polyethylene
glycol-uricase

24. Contd
...
The criteria for starting prophylactic treatment
for gout:
1. One or more acute attacks within 12 months of
the first attack.
2. Tophi present at the first presentation of an acute
attack.
3. Presence of uric acid stones.
4. Need to continue medication associated with
raised uric acid levels. e.g.
Diuretics.
5. Young patients with a family history of renal or
cardiac disease.

25. 1. URICOSTATICAGENTS:
MOA: They inhibit the enzyme xanthine oxidase, which is essential for
the conversion of hypoxanthine to xanthine and then to uric acid.
Thereby they prevent the synthesis of uric acid by inhibiting
the enzyme xanthine oxidase and the plasma concentration
of uric acid is reduced.
ADRs: Rashes, itching, erythema, GI disturbances like nausea, vomiting,
diarrhoea, hepatotoxicity, fever, headache.
Dose:
Allopurinol-100mg/day
Febuxostat-80mg or
120mg/day

26. 2. URICOSURICAGENTS:
MOA: They inhibit active tubular reabsorption of uric acid
in proximal tubules and thereby increase excretion of uric
acid.
ADRs: GI disturbances like nausea, vomiting, skin
rashes, ulceration, blood disorders.
Dose: Benzbromarone-
50-200mg/day
Probenecid-0.5-
2gm/day
Sulphinpyrazone-200-800mg/day

27. 3. URICOLYTICAGENTS:
 MOA: They convert the uric acid to more soluble allantoin
and increase its excretion through urine.
 ADRs: Haemolysis, GI disturbances, hypersensitivity
reactions like skin rashes may occur.
 Dose: Rasburicase-
0.2mg/day for 5-7days
Poly ethylene glycol-
uricase-3.5gm/day

28. Algorithm for managing chronic gout