GOUT

Dr. Suhaemi, SpPD, FINASIM

Asam Urat,
Hiperurisemia
Asam urat (urat) adalah produk
akhir dari metabolisme protein
(purin)
Hiperurisemia : konsentrasi
asam urat yang larut dalam
darah berlebih ( > 6.8 mg/dl)
Akibat overproduksi asam urat
atau ekskresi (pengeluaran) yang
berkurang
Kelainan konsentrasi zat dalam
Distribusi kadar
asam urat
Kaskade
Hiperurisemia
Produksi dan
Eliminasi A.Urat
Sebab Hiperurisemia
Overproduksi
Primer / idiopatik
Sekunder
Intake tinggi
Peningkatan turnover purin
Peningkatan degradasi protein

Hipoekskresi
Primer / idiopatik
Sekunder
Gangguan fungsi ginjal
Hipertensi, hiperparatiroid
Silent Tissue
Deposition
Akibat kadar yang tinggi di
cairan ekstraseluler terbentuk
kristal urat monosodium
Sendi dan jaringan lunak
Kristal Urat
Monosodium
Dipengaruhi oleh
Turunnya kelarutan asam urat
Suhu, pH rendah
Gangguan pada sendi dan jar.
ikat
Trauma / injury
Reabsorpsi air supersaturasi
Kurang gerak sendi (mis. saat
tidur)
Gout
Kondisi yang diakibatkan
pengendapan kristal asam urat
pada sendi
Ditandai peningkatan asam
urat dalam darah &
peradangan sendi berulang
(artritis)
Terbanyak menyerang usia
dekadi 4-6 (Pria : 9x dibanding
Faktor Resiko
Usia & Jenis kelamin
Obesitas
Alkohol
Hipertensi
Gangguan Fungsi Ginjal
Penyakit-penyakit metabolik
Pola diet
Obat: Aspirin dosis rendah, Diuretik, obat-
obat TBC
Faktor Pencetus
Dehidrasi
Alkohol
Overeating
Trauma / injury pada sendi
Demam
Tindakan pembedahan
Diagnosis
Gejala
Inflamasi dan nyeri sendi yang
mendadak, biasanya timbul pada
malam hari
Nyeri hebat, bengkak, kemerahan,
panas
Demam, menggigil, nyeri badan

Hilang dalam 3-10 hari walau

tanpa pengobatan
90% serangan pertama
Diagnosa
Laboratorium
Kadar asam urat bisa normal /
tinggi
Pemeriksaan cairan sendi Gold
Standard
Ditemukan kristal yang mengendap
pada sendi
Terapi
Mengatasi serangan akut dengan segera
Obat: analgetik, colcichine, kortikosteroid
Program pengobatan untuk mencegah
serangan berulang
Obat: analgetik, colcichine dosis rendah
Mengelola hiperurisemia (menurunkan
kadar as.urat) & mencegah komplikasi
lain
Obat-obat penurun asam urat
Lifestyle
Gout kronis
Sendi bengkak, kaku, tidak
nyaman persisten
Intensitas nyeri lebih kurang
daripada serangan awal
Kadang-kadang diselingi
serangan akut
Perubahan bentuk sendi
Timbul benjolan berisi endapan
asam urat pada jaringat ikat
Why Worry About Gout
?
Prevalence increasing
May be signal for
unrecognized
comorbidities : ( Not to
point of searching)

Obesity (Duh!)
Metabolic syndrome
DM
HTN
CV disease
Renal disease
URATE,
HYPERURICEMIA &
GOUT
Urate: end product of purine
metabolism

Hyperuricemia: serum urate > urate

solubility (> 6.8 mg/dl)

Gout: deposition of monosodium urate

crystals in tissues
GOUT: A Chronic
Disease of 4 stages

Asymptomatic hyperuricemia

Acute Flares of crystallization

Intervals between flares

Advanced Gout & Complications

ACUTE GOUTY FLARES
Abrupt onset of severe joint
inflammation, often nocturnal;
Warmth, swelling, erythema, &
pain;
Possibly fever
Untreated? Resolves in 3-10 days
90% 1st attacks are monoarticular
50% are podagra
SITES OF ACUTE
FLARES
90% of gout
patients
eventually have
podagra : 1st
MTP joint
Sites
Can occur in
other joints,
bursa & tendons
INTERVALS SANS
FLARES
Asymptomatic

If untreated, may advance

Intervals may shorten

Crystals in asx joints
Body urate stores increase
FLARE INTERVALS
Silent tissue
deposition &
Hidden Damage
ADVANCED GOUT
Chronic Arthritis

X-ray Changes

Tophi Develop

Acute Flares continue

ADVANCED GOUT
Chronic Arthritis
Polyarticular
acute flares with
upper extremities
more involved
TOPHI
Solid urate
deposits in
tissues
TOPHI
Irregular &
destructive
TOPHI RISK FACTORS

Long duration of hyperuricemia

Higher serum urate

Long periods of active, untreated

gout
RADIOLOGIC SIGNS
X-RAYS
X-RAYS
DIAGNOSING GOUT

Hx & P.E.

Synovial fluid analysis

Not Serum Urate

SERUM URATE LEVELS
Not reliable

May be normal with flares

May be high with joint Sx from

other causes
GOUT RISK FACTORS
Male
Postmenopausal
female
Older
Hypertension
Pharmaceuticals:
Diuretics, ASA,
cyclosporine
GOUT RISK FACTORS
Transplant
Alcohol intake
Highest with beer
Not increased with wine
High BMI (obesity)
Diet high in meat & seafood
SYNOVIAL FLUID
ANALYSIS (Polarized
Light Microscopy)
The Gold standard

Crystals intracellular during

attacks

Needle & rod shapes

Strong negative birefringence

SYNOVIAL FLUID
DIFFERENTIAL
DIAGNOSIS

Pseudogout: Chondrocalcinosis,
CPPD
Psoriatic Arthritis
Osteoarthritis
Rheumatoid arthritis
Septic arthritis
Cellulitis
Gout vs. CPPD

Similar Acute attacks

Different crystals under Micro;

Rhomboid, irregular in CPPD
Gout vs CPPD
 RA vs Gout

Both have polyarticular,

symmetric arthritis

Tophi can be mistaken for RA

nodules
RA vs Gout
REDNECK MEDICAL
TERMS

BENIGN: WHAT YOU

BE AFTER YOU BE EIGHT
TREATMENT GOALS

Rapidly end acute flares

Protect against future flares
Reduce chance of crystal inflammation

Prevent disease progression

Lower serum urate to deplete total body
urate pool
Correct metabolic cause
ENDING ACUTE FLARES
Control inflammation & pain &
resolve the flare
Not a cure
Crystals remain in joints
Dont try to lower serum urate
during a flare
Choice of med not as critical as
alacrity & duration EBM
Acute Flare Med
Choices

NSAIDS

Colchicine

Corticosteroids
MED Considerations
NSAIDS :
Interaction with
warfarin
Contraindicated
in:
Renal disease
PUD
GI bleeders
ASA-induced RAD
MED Considerations
Colchicine :
Not as effective late in flare
Drug interaction : Statins,
Macrolides, Cyclosporine
Contraindicated in dialysis pt.s
Cautious use in : renal or liver
dysfunction; active infection, age
> 70
MED Considerations

Corticosteroids :
Worse glycemic control
May need to use mod-high doses
TREATMENT GOALS
Rapidly end acute flares
Protect against future flares
Reduce chance of crystal inflammation

Prevent disease progression

Lower serum urate to deplete total
body urate pool
Correct metabolic cause
PROTECTION VS.
FUTURE FLARES
Colchicine : 0.5-1.0 mg/day
Low-dose NSAIDS

Both decrease freq & severity of flares

Prevent flares with start of urate-lowering RX
Best with 6 mos of concommitant RX
EBM
Wont stop destructive aspects of gout
TREATMENT GOALS
Rapidly end acute flares
Protect against future flares
Reduce chance of crystal inflammation

Prevent disease progression

Lower serum urate to deplete total
body urate pool
Correct metabolic cause
PREVENT DISEASE
PROGRESSION
Lower urate to < 6 mg/dl : Depletes
Total body urate pool
Deposited crystals EBM
RX is lifelong & continuous
MED choices :
Uricosuric agents
Xanthine oxidase inhibitor
PREVENT THIS
URICOSURIC AGENTS
Probenecid, (Losartan &
fenofibrate for mild disease)

Increased secretion of urate into

urine

Reverses most common

physiologic abnormality in gout
( 90% pt.s are underexcretors)
XANTHINE OXIDASE
INHIBITOR
Allopurinol :
Blocks conversion of
hypoxanthine to uric acid
Effective in overproducers
May be effective in
underexcretors
Can work in pt.s with renal
insufficiency
WHICH AGENT ?

Allopurinol Uricosuric
Issue in renal disease X X
Drug interactions X X
Potentially fatal hypersen-
sitivity syndrome X
Risk of nephrolithiasis X
Mutiple daily dosing X
WHICH AGENT
Base choice on above
considerations & whether pt is an
overproducer or underexcretor :
Need to get a 24-hr. urine for
urate excretion:
< 700 --- underexcretor
(uricosuric)
> 700 --- overproducer
(allopurinol)
NEW AGENTS
RX gaps :
Cant always get urate < 6
Allergies
Drug interactions
Allopurinol intolerance
Worse Renal disease
URICASE ENZYMES
(Stay Tuned)

Catabolize urate to allantoin:

More soluble, excretable form

Currently approved for hypoeruricemia

in tumor lysis syndrome

Some concerns: fatal immunogenicity

& unknown long-term effects
 DIET PENDERITA
GOUT(ASAM URAT)
.
1.Pembatasan purin
Maka yang harus dilakukan adalah
membatasi asupan purin menjadi 100-
150 mg purin per hari (diet normal
biasanya mengandung 600-1.000 mg
purin per hari).

2.Kalori sesuai kebutuhan

Jumlah asupan kalori harus benar
disesuaikan dengan kebutuhan tubuh
berdasarkan pada tinggi dan berat
 3.Tinggi karbohidrat
Karbohidrat kompleks seperti
nasi, singkong, roti dan ubi
sangat baik dikonsumsi oleh
penderita gangguan asam urat
karena akan meningkatkan
pengeluaran asam urat melalui
urin. Konsumsi karbohidrat
kompleks ini sebaiknya tidak
kurang dari 100 gram per hari.
 4.Rendah protein
Asupan protein yang dianjurkan adalah sebesar 50-70
gram/hari atau 0,8-1 gram/kg berat badan/hari. Sumber
protein yang disarankan adalah protein nabati yang
berasal dari susu, keju dan telur.
5.Rendah lemak
Lemak dapat menghambat ekskresi asam urat melalui
urin. Konsumsi lemak sebaiknya sebanyak 15 persen
dari total kalori.
6.Tinggi cairan
Konsumsi cairan yang tinggi dapat membantu
membuang asam urat melalui urin. disarankan untuk
menghabiskan minum minimal sebanyak 2,5 liter atau
10 gelas sehari.
7.kurangi alkohol
alkohol akan meningkatkan asam laktat plasma. Asam
Colchicine
Produces its anti-inflammatory
effects by binding to the
intracellular protein tubulin,
preventing its polymerization
leading to the inhibition of
leukocyte migration into affected
area.
Inhibits the synthesis & release of
leukotrienes.
Pharmacokinetics
Given orally , rapidly absorbed
from GIT.
Partially metabolized and
excreted in urine & part of the
drug is recycled in the bile and is
excreted unchanged in feces.
Clinical uses
Selective for an acute attack of
gouty arthritis ,alleviating the
pain within 12 hours.
Prophylaxis of recurrent attacks of
acute gout.
In preventing attacks of acute
Mediterranean fever.
Hepatic cirrhosis.
Adverse effects
Diarrhea is a common adverse
effect. May cause
nausea,vomiting ,abdominal pain.
Chronic use may cause,
alopecia,bone marrow
depression,peripheral neuritis,
myopathy.
Acute intoxication
Burning throat pain.
Bloody diarrhea.
Shock.
Hematuria.
Fatal ascending C.N.S.depression.
Contraindication &
Precaution
Contraindicated in pregnancy
Should be used with caution in
hepatic , renal or cardiovascular
diseases.
Allopurinol
Inhibits synthesis of uric acid by
inhibiting xanthine oxidase
enzyme
 Purine nucleotides

hypoxanthine Allopurinol
Xanthine
xanthine
oxidase
Oxypurinol
Uric acid

Urinary Alimentary Tissue deposition

excretion excretion in excess

Urate crystal microtophi

uricosurics
Phagocytosis
colchicine with acute
NSAID
inflammation 82

and arthritis
Pharmacokinetics
80% absorbed after oral
administration.
Metabolized to active metabolite
alloxanthine.
Given once daily.
Drug & its metabolite are
excreted in the feces & urine.
Serious Adverse Effects-
Allupurinol
Agranulocytosis
Anemia
Hepatotoxicity
Myelosuppression
Stevens-Johnson syndrome

84
QUESTIONS