gout is a inflammation in the articular and peri articulars tissues of bones here in this ppt their is a brief view on gout

1. BY
NAKKA VARSHITHA
1

2. CONTENTS
 Definition
 Epidemiology
 Etiology
 Risk factor
 classification
 Pathogenesis
 Clinical manifestations
 Diagnosis
 Treatment
 Prevention
2

3. DEFINITION
The term gout is the most common inflammatory disease caused due to
deposition of mono sodium urate crystals in articular and peri articular
tisssues.
3
Fig-1:comparison of normal joint and the joint with gout

4. EPIDEMIOLOGY
• Historically gout has been referred to as the “Disease of King” since it was
often associated with the affluent societies and life styles of over
indulgence, gluttony and intemperance.
• Gout affects men about 7-9 times often than women's.
• The lowest rate of gout are observed in young women ,approximately 0.8
cases per 1000 patients in a year.
• The incidence of gout increases with age, peaking at 30 to 50 years of age
with an annual incidence ranging from 1 in 1000 and 1.8 in 1000 for those
55 to 60 years.
• Gout affects around 1–2% of the Western population at some point . 5.8
million people were affected in 2013.
4
Fig-2

5. ETIOLOGY
• Gout is mainly associated with the disorder in the purine metabolism
uric acid
excretion
uric acid
production
5

6. RISK FACTORS
 Genetics
A polymorphism of SLC22A12 gene, GLU9, SLC2A9 has been associated with
under excretion of uric acid and hyperuricaemia.
 Renal disease
The likelihood of stones increases with serum urate concentration, extent of
urinary acid secretion and low urine pH.
 Alcohol
metabolism of ethanol to acetyl coenzyme A leads to
increased formation of adenosine mono phosphate,
a precursor of uric acid.
 Diet
Consumption of large quantities of red meat, sea food,
Sweteened drinks cause an increases uric acid levels.
 Co-morbidities
Metabolic syndrome is a multiplex risk factor for atherosclerotic cardiovascular
disease that consists of atherogenic dyslipidaemia , hypertension, diabetes
 Medication
Loop and thiazide diuretics, Aspirin (bimodal effect) 6
Fig-3

7. CLASSIFICATION:
• Hypoxanthine-guanine
phosphoribosyl transferase deficiency
• Phosphoribosyl pyrophosphate
synthetase super-activity
• Ribose-5-phosphate deficiency
• AMP-deaminase deficiency
PRIMARY GOUT
Idiopathic ,Rare enzyme
deficiencies
• Increased uric acid
production(Glucose-6 phosphate
deficiency,High purine dietSecondary
polycythemia,Severe exfoliative
psoriasis)
• Reduced uric acid secretion(Renal
failure,Hypertension,alcohol)
SECONDARY
GOUT
Increased uric acid
production/decreased uric
acid excretion
7

8. PATHOGENESIS
1.FORMATION OF URIC ACID:
Ribose-5-phosphate PRPPS
(denovo purine synthesis) phospho ribosyl pyrophosphate
GMP and AMP HGPRT+APRT
(derived from cellular Inosine Mono Phosphate
Breakdown of nucleicacid)
Inosine
HGPRT
Hypoxanthine
Xanthine oxidase Xanthine oxidase
Uric acid Xanthine
2.CONVERSION OF URIC ACID
TO M.S.U CRYSTALS:
urate Ionisation
Na +
Mono sodium urate
solubility concentration
exceeds 380µmol/lit
mono sodium urate crystals 8

9. 3.DEPOSITION OF MONO SODIUM URATE CRYSTAL:
 Mono sodium urate crystals preferentially form in cartilage and fibrous tissues
where they are protected from contact with the inflammatory mediators.
4.EXCRETION OF URIC ACID:
The kidney excretes about two-thirds of the uric acid produced daily with the remainder
being eliminated via the biliary tract with subsequent conversion to soluble allantoin by
colonic bacterial uricase. 9
Fig-4:process of gouty arthritis.

10. CLINICALMANIFESTATIONS
ASYMPTOMATIC HYPERURICEMIA:
No symptoms
ACUTE GOUTY ARITHIRITIS:
 At first it will effect
metatarsophalangeal joint(big toe)
followed by mid tarsi,ankles ,knee and
arms.
 Patient may also have
fever,leucocytosis,anorexia,nausea
change in mood.
CHRONIC GOUT:
 Acute episodes with an increase in
frequency leading to tophous
formation and permenant joint
damage.
10Fig-5

11. DIAGNOSIS
Gout can be primarily diagnosed by its symptoms
Diagnosis can be done through the following:
 Synovial fluid analysis
 Blood test
 Differential diagnosis
Fig-9Needle is
inserted in to the
joints and the fluid
is collected
11
Fig-10:urate crystals under
polarised microscopeFig-8:x ray comparison
Fig-7 signs of gout

12. TREATMENT
treatment
aims in Gout
life style modification
reduce risk of
co morbidities
rapid alleviation of the
acute attack
lower serum uric acid levels
to below saturation point
prevention of future
attacks
12

13. PHARMACOLOGICAL TREATMENT
MANAGEMENT OF ACUTE ATTACK:
Non Steroidal Anti Inflammatory Drugs:
Mechanism of action:
• NSAIDs act by direct inhibition of cyclo-oxygenase-1 (COX-1) and cyclo-
oxygenase-2 (COX-2) via blockade of the cyclo-oxgenase enzyme site. The
subsequent inhibition of prostaglandin production reduces inflammation.
Side effects:Gastric ulceration,GIT disturbances,Gastric erosion,Internal
bleeding,CVS problems
DRUG BRAND NAME DOSE FREQUENCY
Azapropazone PROLIXAN® 12001800mg OD
Etoricoxib COXIA® 120mg per day OD
Indometacin- INDOCIN® 25/50mg TID
Diclofenac VOLTAREN® 35,50,75mg BID
Ibuprofen ADVIL® 800mg TID
13

14. TREATMENT
COLCHICINE: (COLJOY®)
Mechanism of action:
 It arrest microtubule assembly in
neutrophils and inhibit many
cellular functions.
 It suppressesmonosodium urate
crystal-induced NALP3
inflammasomedriven caspase-1
activation, IL-1β processing and
release, and L-selectin expression
on neutrophils.
Dose:
Initially 1 mg followed by 500µcg for
every 2-3 hours until relief of pain is
obtained
Side effects:
Abdominalpain,Nausea,Vomiting,Diarr
hoea,Bone marrow supression.
CORTICOSTEROIDS:
Drugs:
 Triamcinolone acetonide
60mg40mg(AZMACORT®)
 Methyl prednisolone 8040mg
(DEPO-MEDROL®)
Mechanism of action:
They have immunosuppressant and
anti inflammatory properties
Side effects:
GITdisturbances,Weightgain,Acne,Dia
betes,Headaches
INTERLEUKIN-1 INHIBITORS:
Drug: Anakinra 100mg S.C (3 doses)
It inhibit interleukin-1 associated
inflammatory response
14

15. TREATMENT
MANAGEMENT OF CHRONIC GOUT:
CLASS DRUGS MOA DOSE SIDE EFFECTS
Uricostatic
agents
Allopurinol
(ALOPRIM®)
Febuxostat
(FABULAS®)
Inhibition of xanthine
oxidase enzyme
Decreased production of
uric acid
100mgday
80mg120mg
•Rashes
•GIT disturbances
•Hepatotoxicity
•Fever
Uricosuric
agents
Benzbromarone
(BENZRONE®)
Sulphinpyrazone
(ANTURANE®)
Probenecid
(BENEMID®)
inhibits post-secretary
tubular absorption of uric
acid from filtered urate in
the kidney.
increase uric acid
excretion
50-200mg
200-800mg
per day
0.5 -2 gmday
•GIT disturbance
•Ulceration
•Blood disorders
Uricolytic
agents
Rasburicase
(ELITEK®)
Poly ethylene
glycol
(MIRALAX®)
They convert the uric acid
to more soluble allontoin
and increased its excretion
through kidneys
0.2mgday for
5-7 days
3500mg
•GIT disturbances
•Rashes
•Headache
15

16. NON PHARMACOLOGICAL TREATMENT
16
Fig-11

17. PREVENTION
By medication:
xanthine oxidase inhibitors/uricosuric agents+ NSAID or colchicines for
first 3-6 months
By life style modifications:
17
Fig-12
Fig-13

18.  Gout is a painful disease that can effect any one
 Medications and life changes are the only way to control it
18
Fig-14

19. 19