GOUT

Gusti Putu AB 405090119

 Gout
 a disorder caused by the tissue accumulation of excessive amounts
of URIC ACID.

 recurrent episodes of acute arthritis, sometimes accompanied by

the formation of tophi and chronic joint deformity.

 Results from the precipitation of Monosodium Urate crystals from

supersaturated body fluids into the tissues especially the joints.

 Big toe is the most common site of an acute gout attack of

arthritis.
An acute attack of gouty arthritis at the base of the big toe is
medically referred to as podagra.

 Gout is divided into Primary Gout (90% of cases) and Secondary

Gout (10% of cases)
 Chronic tophaceous gout,
with subcutaneous tophi
causing bony deformity of the
hands of the patient
 Gout causes + Risk factors
1) Genetics (If your parents have gout, then you
have a 20% chance of developing it.)
2) Gender (Men have higher uric acid levels in
their blood than women.)
3) Overindulgence in alcohol and foods rich
in purines
4) Trauma
5) Starvation and dehydration
6) Intravenous contrast dyes
7) Chemotherapy
8) Medications (aspirin etc.)
 PATHOGENESIS
Elevation of the level of
serum uric acid may result
from overproduction or
reduced excretion of uric
acid, or from both.

To understand the

mechanisms underlying
disturbances in uric acid
production or excretion, a
brief review of normal uric
acid synthesis and excretion
is warranted.
 Pathogenesis
Hyperuricaemia

May be asymptomatic

Deposition of monosodium urate crystals in synovial tissue
(contain various Ig’s, complement, fibrinogen, fibronectin)

Complement activated

Neutrophils phagocytose & lyse crystals

Release chemical mediators (e.g. TNF-α; IL-1)

ACUTE GOUTY ARTHRITIS

May resolve & become asymptomatic
(INTERCRITICAL GOUT)
Robbins , p:1375
• Uric acid is the end product of purine
metabolism.

• Increased synthesis of uric acid, a common

feature of primary gout, results from some
abnormality in the production of purine
nucleotides.

• The synthesis of purine nucleotides occurs

along two pathways, referred to as the de
novo and salvage pathways.
 Clinical features
• Acute gouty arthritis
– Painful
– Involves one joint initially, then polyarticular
– Podagra (painful, red metatarsophalangeal joint)
• Tophaceous gout
– Development of tophi
• Chalky, cheesy, yellow-white, pasty deposits of
monosodium urate crystals
– Helix and antihelix of ear
– Achilles tendon
 Diagnosis
• More than one attack • Tophus
• Maximum inflammation • Hyperuricemia
in one day • Asymmetric swelling
• Monoarthritis • Subcortical cysts
• Redness • MSU crystals in joint
• First MTP involved fluid
• Unilateral first MTP • Joint fluid culture
• Unilateral tarsal attack negative
 Symptoms and signs
• Severe pain in your joint (most commonly
the big toe, but it can occur in your feet,
ankles, knees, hands and wrists.);
• Swelling and warmth around your joint;
• Red and shiny skin around your joint;
• Mild fever;
• Firm, white lumps beneath your skin – these
are urate crystals called tophi.
 Diagnosis
• Based on history and physical examination
• Confirmed by arthrocentesis
• Urate crystals: needle-shaped negatively birefringent
either free floating or within neutrophils &
macrophages.
• Uric acid level non specific.
• 30% may show normal level
• Urine collection:
– <800 mg underexcertor(<600 purine-free diet)
Synovial fluid

Spiked rods of uric acid (MSU) crystals photographed under a microscope

withpolarized light from a synovial fluid sample. Formation of uric acid crystals
in the joints are associated with gout.

A definitive diagnosis of gout is based upon the identification of monosodium

urate (MSU) crystals in synovial fluid or a tophus.[3] All synovial fluid samples
obtained from an undiagnosed inflamed joints should be examined for these
crystals.®

Under polarized light microscopy they have a needle-like morphology and

strong negative birefringence. This test is difficult to perform and often requires
a trained observer.[20]

The fluid must also be examined relatively quickly after aspiration as

temperature and PH affect their solubility
Blood tests

Hyperuricemia is a classic feature of gout, however gout occurs nearly half of

the time without hyperuricemia and most people with raised uric acid levels
never develop gout.[3][21] Thus the diagnostic utility of measuring a uric acid
level is limited.[3]

Hyperuricemia is defined as a plasma urate level greater than 420 ^mol/L (7.0
mg/dL) in males and 360 ^mol/L (6.0 mg/dL) in females.[22] Other blood tests
commonly performed are white blood cell count, electrolytes,renal function, and
erythrocyte sedimentation rate (ESR).

However both the white blood cells and ESR may be elevated due to gout in
the absence of infection.[23][24] A white blood cell count as high as 40*109/L
(40,000/mm3) has been documented.[1]
Differential diagnosis

The most important differential diagnosis in gout is septic arthritis.[3][6]

This should be considered in those with signs of infection or those who do not
improve with treatment.[3]

To help with diagnosis a synovial fluid gram stain and culture may be
performed.[3]

Other conditions which present similarly includepseudogout and rheumatoid

arthritis.[3]

Gouty tophi, in particular when not located in a joint, can be mistaken for basal
cell carcinoma,[25] or other neoplasms
 Complications
1) Emergence of tophi under the skin can
damage the nerves, bones, and cartilage.
(tophi is only associated with chronic gout,
and can be prevented with regular gout
medication).
2) Kidney stones (if urate crystals collect in
your urinary tract)
3) Kidney damage (if urate crystals collect in
your kidney tissue)
 CLASSIFICATION OF GOUT
Clinical Category Metabolic Defect
PRIMARY GOUT (90% of cases)

Enzyme defect unknown 85-90% of primary gout Overproduction of uric acid

Normal excretion (majority)
Increased excretion (minority)
Under excretion of uric acid with normal production

Known enzyme defects (e.g., partial HGPRT Overproduction of uric acid

deficiency)

SECONDARY GOUT (10% of cases) SECONDARY GOUT (10% of cases)

Associated with increased Overproduction of uric acid with increased urinary

nucleic acid turnover (e.g., excretion
Leukemias)

Chronic Renal Disease Reduced excretion of uric acid with normal production

Overproduction of uric acid with increased urinary

Inborn errors of metabolism (e.g., complete excretion
HGPRT deficiency [ Lesch-Nyhan syndrome])
 CLINICAL STAGES OF GOUT

• FOUR STAGES:

• 1. Asymptomatic (without symptoms)

hyperuricemia-

In this stage, a person has elevated levels of

uric acid in the blood but no other symptoms.
A person in this stage does not usually
require treatment.
2. Acute gout, or acute gouty arthritis
 In this stage, hyperuricemia has caused the deposit of uric
acid crystals in joint spaces.

 This leads to a sudden onset of intense pain and swelling in

the joints, which also may be warm and very tender.

 An acute attack commonly occurs at night and can be

triggered by stressful events, alcohol or drugs, or the
presence of another illness.

 Early attacks usually subside within 3 to 10 days, even

without treatment, and the next attack may not occur for
months or even years.

 Over time, however, attacks can last longer and occur more
frequently.
3. Interval or Intercritical Gout
This is the period between acute attacks. In this stage,
a person does not have any symptoms and has
normal joint function.

4. Chronic tophaceous gout

This is the most disabling stage of gout and usually
develops over a long period, such as 10 years.

In this stage, the disease has caused permanent

damage to the affected joints and sometimes to the
kidneys.

With proper treatment, most people with gout do not

progress to this advanced stage.
 Compare Gout from Pseudo-gout

 Gout and pseudo-gout are the 2 most common

crystal-induced arthropathies. They are debilitating
illnesses in which pain and joint inflammation are
caused by the formation of crystals within the joint
space.
• What differentiates between gout and
pseudo-gout is the type of crystal
deposits.
• Gout is inflammation caused by
monosodium urate monohydrate (MSU)
crystals
• Pseudo-gout is inflammation caused by
calcium pyrophosphate (CPP) crystals and
is sometimes referred to as calcium
pyrophosphate disease (CPPD)
 Gout or pseudogout?
Gout
• >40
• small joints esp 1st MTP
• Severe joint pain swelling
• Uric acid crystals neg
bifringent
• Rest nsiad prohylaxis
• hyperuricaemia
Pseudogout
• Elderly
• Large joints esp knee
• Mod pain and swelling
• Calcium pyrophosphate positively
bifringent
• Rest nsaid joint aspiration
Gout initially affects the joints in the big
toe.

 It also can affect the instep, ankles,

heels, knees, wrists, fingers, and
elbows.
 Mechanism of Action of the ff pharmacologic
agents used in the tx of hyperuricemia & gout:

• Colchicine
• Probenecid
• Allopurinol
• Celecoxib
NSAIDs

NSAIDs are the usual first-line treatment for gout, and no specific agent is
significantly more or less effective than any other.[2] Improvement may be seen
within 4 hours and treatment is recommended for 1-2 weeks.™

They however are not recommended in those with certain other health
problems such as gastrointestinal bleeding, renal failure, or heart failure.[32]

While indomethacin has historically been the most commonly used NSAID, an
alternative like ibuprofen may be preferred due to its better side-effect profile in
the absence of superior effectiveness.[15]
For those at risk of gastric side effects from NSAIDs, an additional proton
pump inhibitor may be given
 Drug Mechanism of Action Indication

Colchicine It is known to bind to free tubulin For the termination of

(anti- causing depolymerization of acute attacks of gouty
inflammatory microtubules; this may prevent the arthritis; prophylaxis of
agent) movement of neutrophils into an recurrent acute episodes
area containing crystals of MSU. of gouty arthritis.
 Drug Mechanism of Action Indication
Probenecid Interferes with the kidney’s • For “underexcretors”
(uricosuric agent) organic anion transporter (OAT). Lower serum urate levels

Urine Uric acid Plasma (Hyperuricemia)

Probenecid:
Urine Uric acid Plasma

Excrete
 Drug Mechanism of Action
Allopurinol Inhibits xanthine oxidase leading
to prevention of synthesis of
urate from hypoxanthine and
xanthine.
Indication
• For “overproducers”
Lowers serum urate levels to
prevent further deposition of
MSU
 Drug Mechanism of Action Indication
Celecoxib COX-2 selective For patients who need
(NSAID) inhibitors → inhibition regular and long term
of prostaglandin pain relief.
production

Nonselective NSAID (aspirin) – inhibit COX1 & COX 2 – inhibit synthesis of

prostaglandin & thromboxane

Selective NSAID (celecoxib)– inhibit COX2 w/o affecting COX1 – inhibit

synthesis of prostaglandin only