Biochemistry seminar for mbbs students first year

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

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

6. HoW gout occurs 6 presentation title URIC ACID METABOLISM

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 o f urate is excreted by kidney and the rest by intestines 7 presentation title

8. 8 Total body urate pool presentation title

9. 9 PURIne metabolism

10. TYPES OF HYPERURICEMIAS

11. Types of hyperuricemas 11 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 : Abnormal PRPP Synthetase Deficiency of Enzymes of Salvage Pathway : Reactions which consume PRPP and produce more nucleotides will inhibit the enzyme Glucose-6-phosphatase Deficiency: Von Gierke’s Disease. Glutathione reductase variant: Increased production of ribulose-5-phosphate thereby increasing levels of PRPP 12 presentation title

13. Secondary hyperuricemias I ncreased Production of Uric Acid 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. Increased tissue damage due to trauma and raised rate of catabolism as in starvation. Reduced Excretion Rate Renal failu re Lactose acidosis and Ketoacidosis due to interference with tubular secretion. 13 presentation title

14. Investigation, treatment and management 14 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 1 st metacarpophalangeal joint

16. management of gout Decrease alcohol intake (Since, alcohol is rich in purines which is metabolized to uric acid as the end product) Decrease meat intake (Since, meat (especially red meat) is rich in purines which is metabolized to uric acid as the end product) Decrease fructose rich diet Decrease junk food 16 presentation title

17. Treatment Probenecid Increase excretion of uric acid by using uricosuric drugs i 17 presentation title

18. Treatment Allopurinol Reduce uric acid production by allopurinol which is a competitive inhibitor of xanthine oxidase 18 presentation title

19. Other treatment options Aim to decrease uric acid level below saturation point (6.5mg/dl) Maintain high fluid diet Alkalization of urine NSAIDs and Colchicine are useful to arrest arthritis in gout Uricase is an enzyme which can convert uric acid to more soluble allantoin which is easily excreted 19 presentation title

20. Thank you