Biochemistry seminar for mbbs first year students

1. GOUT
GROUP 4 – CAROLIN, CAROLINE, CHELLO AND CHETHAN

2. PRESENTATION
TITLE
2
CASE 1
A 49- YEAR-OLD MALE PRESENTS WITH THE HISTORY OF EPISODIC PAIN AND
SWELLING IN THE 1ST METATARSOPHALANGEAL JOINTS. HE GIVES THE HISTORY
OF EXACERBATION OF THESE SYMPTOMS UPON CONSUMPTION OF ALCOHOL.
PHYSICAL EXAMINATION SHOWED ROCK-HARD LUMP ON THE RIGHT PINNA AND
HOT, TENDER PURPLISH-BLUE SWELLING IN THE KNEE AND LEFT MIDFOOT. SERUM
URIC ACID CONCENTRATION WAS 9.9 MG/DL. SYNOVIAL FLUID ASPIRATE
CONTAINED INTRACELLULAR NEEDLE-SHAPED CRYSTALS WITH STRONG
NEGATIVE BIREFRINGENCE.

3. DIAGNOSIS

4. 4
PRESENTATION
TITLE
CLINICAL FEATURES
o Acute Recurrent Gout flare of metatarsophalangeal joint of the first toe is seen in 70-90% of the cases.
o Affected joints become warm, red or purplish, tender and swollen with a appearance that mimics
cellulitis.
o Triggers of gout flares include purine-rich food, alcohol, diuretic use etc.
o Chronic gouty arthritis is associated with ongoing synovitis, subcutaneous tophi, deformity and bony
deformity.

5. PRESENTATION
TITLE
5
LABORATORY
DIAGNOSIS
o Synovial Fluid aspiration is the method used
o In acute gout flares – Needle shaped MSU (
monosodium urate) crystals typically are present
both intracellulary and extracellularly
o Under compensated polarized light, they show
bright, negative birefringence

6. HOW GOUT OCCURS
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PRESENTATION
TITLE

7. URIC ACID METABOLISM
• Uric Acid is the final breakdown product of purine degradation in humans
• Urate is the ionized form of uric acid are predominant in extracellular fluid, plasma and
synovial fluid in the form of MSU (98%)
• Plasma is saturated with MSU at a concentration of 6.8 mg/dl
• Other ionized forms are disodium, potassium, ammonium and calcium urates
• Urate is produces in liver and small intestine primarily and varies with purine content
• Three fourths of urate is excreted by kidney and the rest by intestines
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PRESENTATION
TITLE

8. 8
TOTAL BODY URATE POOL
PRESENTATION
TITLE

9. 9
PURINE
METABOLISM

10. TYPES OF
HYPERURICEMIAS

11. TYPES OF HYPERURICEMAS
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PRESENTATION
TITLE
PRIMARY
HYPERURICEMIAS
SECONDARY
HYPERURICEMIAS

12. PRIMARY HYPERURICEMIAS
• About 10% of cases of primary gout are idiopathic. Primary gout may show a
familial incidence
• Causes of primary gout are :
i. Abnormal PRPP Synthetase
ii. Deficiency of Enzymes of Salvage Pathway : Reactions which consume
PRPP and produce more nucleotides will inhibit the enzyme
iii. Glucose-6-phosphatase Deficiency: Von Gierke’s Disease.
iv. Glutathione reductase variant: Increased production of ribulose-5-
phosphate thereby increasing levels of PRPP
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PRESENTATION
TITLE

13. SECONDARY HYPERURICEMIAS
• Increased Production of Uric Acid
i. Hyperuricemia is also seen in cancer patients on radio- therapy or
chemotherapy (tumor lysis syndrome) due to increased cellular turnover.
Hence these patients are given allopurinol also, to decrease uric acid levels.
ii. Increased tissue damage due to trauma and raised rate of catabolism as in
starvation.
• Reduced Excretion Rate
i. Renal failure
ii. Lactose acidosis and Ketoacidosis due to interference with tubular secretion.
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PRESENTATION
TITLE

14. INVESTIGATION,
TREATMENT AND
MANAGEMENT
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PRESENTATION
TITLE

15. INVESTIGATION
1. Serum Uric Acid (Normal : Male = 3 – 7 mg/dl, Female = 2-5 mg/dl)
2. ESR and CRP Level (Increased due to inflammation produced by liver)
3. Hypoxanthine and Xanthine Levels
4. RFT (Done to check creatinine, BUN, uric acid level)
5. Aspiration and Examination of Synovial Fluid mostly in 1st
metacarpophalangeal joint

16. MANAGEMENT
OF GOUT
1. Decrease alcohol intake (Since, alcohol
is rich in purines which is metabolized
to uric acid as the end product)
2. Decrease meat intake (Since, meat
(especially red meat) is rich in purines
which is metabolized to uric acid as the
end product)
3. Decrease fructose rich diet
4. Decrease junk food
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PRESENTATION
TITLE

17. TREATMENT
PROBENECID
Increase excretion of uric
acid by using uricosuric
drugs
i
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PRESENTATION
TITLE

18. TREATMENT
ALLOPURINOL
Reduce uric acid
production by allopurinol
which is a competitive
inhibitor of xanthine
oxidase
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PRESENTATION
TITLE

19. OTHER TREATMENT OPTIONS
1. Aim to decrease uric acid level below saturation point
(6.5mg/dl)
2. Maintain high fluid diet
3. Alkalization of urine
4. NSAIDs and Colchicine are useful to arrest arthritis in gout
5. Uricase is an enzyme which can convert uric acid to more
soluble allantoin which is easily excreted
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PRESENTATION
TITLE

20. THANK YOU