Diabetes Lecture 5

HYPERURICEMIA

Overview

• Hyperuricemia is defined as an elevated serum uric acid greater than 7 mg/dl.

• Asymptomatic hyperuricemia refers to elevated serum urate without any urate crystal deposition disease.

• Associated disease: Gout

  • Types: Acute gouty arthritis, intercritical gout, chronic tophaceous gout.

  • Uric acid renal diseases: acute hyperuricemic nephropathy, chronic hyperuricemic nephropathy, and uric acid nephrolithiasis.

DEFINITION

• Hyperuricemia: Elevated uric acid levels in the blood (>7 mg/dl).

• Asymptomatic Hyperuricemia: High urate levels without symptoms.

• Urate Crystal Deposition Disease:

  • Gout (with variations)

  • Uric Acid Renal Diseases:

    • Acute hyperuricemic nephropathy

    • Chronic hyperuricemic nephropathy

    • Uric acid nephrolithiasis

PATHOGENY

• Divided into three main categories:

  • Overproduction: Increased uric acid by endogenous synthesis or dietary intake.

  • Underexcretion: Decreased uric acid elimination from the body.

  • Combined Causes: Both overproduction and underexcretion.

• Key mechanisms:

  • Production: Tissue nucleic acids, endogenous purines, and dietary intake.

  • Excretion: Renal processes including filtration, reabsorption, secretion, and excretion.

PATHOPHYSIOLOGY

Uric Acid Production

• Utilizes glucose and the pentose phosphate pathway.

• PRPP synthetase facilitates nucleotide pathways leading to uric acid formation.

Uric Acid Excretion

• Influenced by:

  • Transporters: SLC22A12 and GLUT9 for urate homeostasis, OATs for urate transport, ABCG2 and others for secretion into renal tubules.

• Impaired function can lead to increased uric acid levels.

CLASSIFICATION OF HYPERURICEMIA

Underexcretion Causes

• Factors include:

  • Decreased glomerular filtration (renal insufficiency).

  • Increased tubular reabsorption from medications (diuretics, nicotinic acid).

Overproduction Causes

• Exogenous Factors: Rich purine diets or fructose intake.

• Endogenous Factors: Rapid cell proliferation, enzymatic defects (e.g., Lesch-Nyhan syndrome).

Combined Mechanisms

• Alcohol, obesity, and fructose effects on uric acid levels.

ACUTE GOUTY ARTHRITIS

• Results from urate crystal deposition in joints due to hyperuricemia.

• Symptoms include sudden joint pain, typically starting in the first metatarsophalangeal joint.

• Risk factors include trauma, alcohol consumption, and certain medications.

• Diagnosis: Presence of MSU crystals in joint fluid is the gold standard.

CHRONIC TOPHACEOUS GOUT

• Occurs in patients with prolonged hyperuricemia.

• Characterized by low-intensity pain and gouty tophi appearing years after the first gout attack.

• Tophi can appear on various bodily locations, indicating severe urate deposits.

RADIOGRAPHIC FEATURES

• Key imaging findings include bone erosions, joint space narrowing, and soft tissue masses indicative of tophi.

MANAGEMENT OF HYPERURICEMIA

Medical Nutrition Therapy

• Emphasizes dietary restrictions on purines, inadequate caloric intake, and fluid consumption.

• Specific recommendations include:

  • Low-calorie, low-protein diet to manage uric acid levels

  • Avoidance of specific high-purine foods and excessive alcohol intake.

Pharmacological Treatments

• Acute Gout Management: NSAIDs, colchicine, and corticosteroids.

• Hypouricemic Therapy: Initiated based on patient uric acid levels and frequency of gout attacks.

• Treatment options include xanthine oxidase inhibitors (e.g., Allopurinol) and uricosurics (e.g., Probenecid).

SUMMARY

• The continuum of hyperuricemia involves risk factors like dietary habits and comorbid conditions.

• Understanding pathophysiology and mechanisms aids in the diagnosis and treatment of gout and associated conditions.