GOUT

GOUT

z Common

medical problem,
z Male: female ratio 7:1 to 9:1.

GOUT
z

Humans do not express the enzyme uricase,

uricase
which degrades uric acid, an end product of
purine nucleotide catabolism.

Consequently, statistically normal uric acid

levels in men and premenopausal women are
close to the limits of urate solubility in vitro,
imposing a delicate physiologic urate balance.

Uric Acid Production

Uric Acid Overproduction

Primary causes
z
z
z

Idiopathic
HGPRT deficiency
Increased PRPP activity

Secondary causes
z

Excessive dietary purine

intake
z Increased nucleotide turnover
z
z
z
z

Myeloproliferative disease
Lymphoproliferative disease
Hemolytic anemia
Psoriasis

Accelerated ATP degradation

z
z
z
z

Hereditary fructose
intolerance
Glycogen storage disease
Severe muscle exertion
Ethanol abuse

Uric Acid underexcretion

z

Renal insufficiency

Inhibition of tubular
urate secretion:

Keto- and lactoacidosis

Undefined
mechanism:
z

Enhanced tubular
urate reabsorption:
z
z
z

Diuretics,
Insulin resistance,
Dehydration

z
z

Hypertension,
Hyperparathyroidis
Low-dose salicylates,
Pyrazinamide,
Ethambutol
Lead nephropathy

GOUT
Clinical & Laboratory Features

Stages of classical gout

1. Asymptomatic Hyperuricemia:
Very common biochemical abnormality
Epidemiological definition:
Serum urate level above the mean.
The upper normal value is 8.0-8.5mg/dl

Stages - Asymptomatic Hyperuricemia

z In

physiological terms any level above 6.8

mg/dl is hyperuricemia, since it exceeds
the soluble concentration of MSU in body
fluids.
z Vast majority of people with hyperuricemia
will never develop symptoms.

Stages - Acute intermittent gout

z Characteristic
z

gout attack:

rapid development of warmth, swelling,

erythema and pain in the affected joint.

z The

initial attack

is monoarticular and
z in 50% of cases involves the 1st metatarsal
joint, which will finally be affected in 90% of
patients.
z

Acute Podagra

Stages - Acute intermittent gout

z Other

joints: MT, ankle, heels and knees.

z Systemic symptoms: Fever, chills and
malaise.
z Early in the disease the episodes are
infrequent
z Between the attacks the previously
affected joints are free of pain,
z

despite this, MSU crystals can be identified

in the synovial fluid.

Stages Chronic Tophaceous Gout

z Usually

develops after 10 years of acute

intermittent gout.

z In

this stage the affected joints become

persistently uncomfortable and swollen.

z The

intensity of these symptoms is much

less than the acute attacks.

Stages Chronic Tophaceous Gout

Characterized by:
tophi formation and
polyarticular involvement, including the
small joints of the hands .

Subcutaneous gouty tophi can be found

in the fingers, wrists, ears, knees,
olecranon bursa and pressure points

Tophi

Tophi

GOUTY TOPHUS FORMATION

z

Macrophage acinus is the first structure,

it has a core of noncrystalline material surrounded
by mononuclear phagocyte.

MSU crystals start forming in the core.

Macrophages proliferate forming a corona

which will be replaced by fibrous material.

Finally nearby structures will coalesce to form

multilobulated tophi

Provocative factors
z

The degree of decrease or increase in the

concentration of synovial-fluid urate is more
related to acute attack than the degree of
hyperuricemia .

Trauma is frequently reported as an initiating

event for an acute gouty attack:
z
z

the attack sometimes occurs when the joint is

allowed to rest,
there is a rapid efflux of water from the joint fluid
and the result is sudden increase in urate
concentration.

Provocative factors
z Alcohol ingestion:
ingestion

By accelerating the breakdown of intracellular

ATP
z Alcohol contains large quantities of guanosine.
z

z Drugs:
Drugs
z

thiazides

Clinical association Renal involvement

z

Chronic urate nephropathy:

nephropathy
z
z

Deposition of MSU in the renal medulla

Associated with mild microalbuminuria.

Acute uric acid nephropathy:

nephropathy
z

ARF caused by hyperuricemia

in tumor lysis syndrome or post chemotherapy.

Uric acid renal stones:

stones
z
z

10-25% of all people with gout,

the incidence correlate with the serum urate levels.

Radiological features
z In early stages :

Soft tissue swelling around the affected

joints
z Preserved joint space
z

z Later:

Bony erosions that are both atrophic and

hypertrophic,
z Erosions with overhanging edges
z

Radiological features

Radiological features

Laboratory Features and Diagnosis

z Uric

acid level in serum is of limited

value in establishing the diagnosis:
z The majority of hyperuricemic subjects
will not develop gout.
z Normal level of uric acid during gouty
attack is frequent.

Diagnosis
z

Definitive diagnosis is possible only by

aspiration and inspection of the synovial fluid
or tophaceous material.
material

Crystals are needle or rod-shaped.

z On polarized microscopy, they appear as a
bright, birefringent crystals (usually
intracellular) that are yellow in color

Crystals

Diagnosis

z The

synovial fluid finding consistent with

moderate to severe inflammation.

Treatment

The management of gout involves

z treating acute arthritic inflammation and
urolithiasis
z lowering urate levels with the goal of
preventing recurrent disease and
progression.

Treatment of Acute Gouty Arthritis

NSAIDs are considered first-line therapy.

z Selective Cox-2 inhibitors are an alternative
in patients with GI contraindications.

Corticosteroids or subcutaneous injections of

corticotropin are additional alternatives.

Because colchicine adverse effects can be

serious, IV colchicine should not be used.

Long-Term or Prophylactic Therapy

z

z
z

NSAIDs and colchicine are frequently used

as prophylaxis against recurrent acute gout,
since such episodes are common during the
initiation of uric acidlowering treatment.
Allopurinol and
Probenecid - a potent uricosuric agents
equally acceptable as first-line drug in the
absence of documented urate overproduction
or renal failure.

Thank you