SF

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.