Hyperuricemia and Gout: etiology, types, pathogenesis, sign and symptoms

1. GOUT
PATHOPHYSIOLOGY
Nem Kumar Jain
MS (Pharm.) Pharmacology & Toxicology
Assistant Professor, School of Pharmacy
ITM University Gwalior

2. GOUT
• Metabolic disease characterized by Monosodium urate crystal deposition within or
around joints which results in inflammation in joints and surrounding tissue.
• Clinical appearance:
• Acute inflammatory arthritis
• Hyperuricemea
• Uric acid nephrolithiasis
• Commonly mono-articular (primarily affects metatarso-phalangeal joint (MTP) of
big toe)
• Other locations for urate crystal deposition
• Elbows
• Knees
• Feets
• Ear pinna (helix of the ear)
• Etiology: Hyperuricemia (blood uric acid level > 6.8 mg/dl)
• Hyperuricemia is a condition when blood serum uric acid level gets increased
• Normal plasma uric acid level
• male: 3-7 mg/dl, Female: 2-6 mg/dl

3. • Uric acid is product of purine metabolism
• Gout is of two types –
1. Primary gout
2. Secondary gout
Primary gout : it is an inborn error of metabolism of purine due to over production of
uric acid. This is mostly related to increased synthesis of purine nucleotides.
Secondary gout :
secondary hyperuricemia is due to various disease causing increased synthesis or
decreased excretion of uric acid.
• Factors: Diseases because of defects of purine metabolism
• Lesch-Nyhan syndrome: partial or complete deficiency of HGPRT enzyme
• Severe combined immunodeficiency disease (SCID): deficiency of Adenosin
deaminase
• Superactivity of Phosphoribosyl pyrophosphate synthetase activity
• Other Factors: cancer therapy, Dehydration, Lactic acidosis, starvation , Diuretic
therapy Renal failure, Excessive purine intake , Alcohol intake, Carbohydrate
ingestion

4. • Diet rich in purines:
• Red meat and organ meats (eg. liver) Yeasts and yeast extracts (eg. beer and alcoholic
beverages) Asparagus, spinach, beans, peas, lentils, oatmeal, cauliflower and mushrooms
• Coffee, tea etc.

5. PATHOGENESIS
• The inflammation in gout is triggered by precipitation of urate crystals in the joints,
stimulating the production of cytokines that recruit leukocytes.

6. MORPHOLOGY
• Acute arthritis is characterized by a dense inflammatory infiltrate
that permeates the synovium and synovial fluid
• crystals are frequently found in the cytoplasm of the neutrophils
and are arranged in small clusters in the synovium
• They are long, slender, and needle-shaped, and are negatively
birefringent
• synovium is edematous and congested, and it also contains scattered
lymphocytes, plasma cells, and macrophages
• Chronic tophaceous arthritis: evolves from the repetitive precipitation of
urate crystals during acute attacks. The crystals encrust the articular
surface and form visible chalky deposits in the synovium
• The synovium becomes hyperplastic, fibrotic, and thickened by
inflammatory cells and forms a pannus that destroys the underlying
cartilage.
• Tophi in the articular cartilage, ligaments, tendons, and bursae are
pathognomonic of gout .They are formed by large aggregations of
urate crystals surrounded by an intense foreign body giant cell
reaction
• Gouty nephropathy refers to the renal complications caused by

7. Tophi

8. SIGN AND SYMPTOMS
• Sudden onset of excruciating pain, localized hyperemia, warmth.
• Most first attacks are monoarticular; 50% occur in the first metatarsophalangeal joint.
• May become polyarticular if left untreated

9. SUMMARY
Food intake Cell breakdown
Purines
Uric acid
HYPERURICAEMIA
Kidney Soft tissue of
the joints
Other tissue
Ear
Overproduction Under excretion