HV Gout and Tumor lysis

• Uric acid is produced by the breakdown of purine nucleotides in the liver and is one of the body's nitrogen-containing waste products
• Plasma uric acid shows daily and seasonal variation, with normal levels in adults being:

  • Males: 0.21 - 0.43 mmol/L
  • Females: 0.16 - 0.36 mmol/L
• Uric acid is a weak acid with a pKa of 5.75, existing as urate anion in blood and undissociated uric acid in urine
• Solubility of sodium urate in blood is 15x more soluble than uric acid, but once serum urate level rises above about 0.42 mmol/L, precipitation can occur, leading to gout
• Uric acid is excreted mainly (75%) in the kidney and the rest via the intestine, with renal excretion involving glomerular filtration, active reabsorption in the proximal tubule, and simultaneous secretion
• Humans have higher blood uric acid levels and risk of precipitation due to the absence of uricase, renal reabsorption mechanisms, and potential antioxidant and immune-enhancing functions of uric acid
• Purine metabolism involves nucleic acids DNA and RNA, with purine bases degraded to uric acid if not salvaged, requiring a basic understanding to comprehend uric acid overproduction
• Causes of hyperuricaemia include under-excretion, overproduction, and over-consumption, with complications like tumour lysis syndrome characterized by metabolic abnormalities like hyperkalaemia, hyperuricaemia, hyperphosphataemia, and hypocalcaemia
• Tumour lysis syndrome is a group of metabolic complications caused by rapid lysis of malignant cells, leading to acute kidney injury and characterized by hyperkalaemia, hyperuricaemia, hyperphosphataemia, and hypocalcaemia
• The pathophysiology of tumour lysis syndrome involves the release of potassium, phosphorus, and nucleic acids from lysed cancer cells, leading to increased uric acid levels in the blood and acute kidney injury
• When cancer cells lyse, they release potassium, phosphorus, and nucleic acids which are metabolized to uric acid in the liver
• Uric acid induces acute kidney injury by intrarenal crystallization or by other crystal-independent mechanisms such as renal vasoconstriction, impaired autoregulation, decreased renal blood flow, oxidation, and inflammation
• Hyperkalaemia can cause serious, and occasionally fatal, cardiac dysrhythmias
• Hyperphosphataemia can cause secondary hypocalcaemia and deposition of calcium and phosphorus salts in the kidney and soft tissues
• Hypocalcaemia leads to neuromuscular irritability (tetany), dysrhythmia, and seizure
• Prevention strategies for uric acid-induced complications:

  • Suspect and anticipate
  • Adequate IV hydration to maintain high urine output (> 2.5 L/day)
  • Reduce uric acid load prophylactically with Allopurinol or Rasburicase
• Gout is characterized by acute painful arthritis in a single joint due to deposition of monosodium urate crystals
• Diagnosis of gout:

  • Clinical features
  • Definitive diagnosis: Uric acid crystals in joint fluid aspirate
  • Elevated serum uric acid levels are suggestive (normal levels don’t exclude the diagnosis)
• Treatment of gout:

  • Colchicine to reduce acute pain
  • Allopurinol to reduce uric acid formation
  • Uricosurics (e.g., probenecid) to reduce renal reabsorption of uric acid
  • General measures: lose weight, decrease alcohol consumption, decrease purine intake
• Multiple Myeloma is a malignant proliferation of a clone of plasma cells in the bone marrow, often caused by genetic alterations
• Plasma cells produce immunoglobulins (antibodies) consisting of a pair of identical heavy chains and a pair of identical light chains
• Multiple Myeloma leads to uncontrolled proliferation of plasma cells and the secretion of high levels of abnormal and non-functional immunoglobulins
• Clinical presentation of Multiple Myeloma includes bone pain, fatigue (anaemia), pathological fractures, weight loss, paresthesias, and fever
• Diagnostic criteria for Multiple Myeloma:

  • Clonal bone marrow plasma cells >10% or biopsy-proven plasmacytoma
  • CRAB features: Hypercalcemia, Renal dysfunction, Anemia, Bone lesions
  • Myeloma-defining events (MDEs): 60% or greater clonal plasma cells on bone marrow examination, SFLC ratio > 100, more than one focal lesion on MRI ≥ 5mm
• Laboratory features of Multiple Myeloma:

  • High total protein due to increased immunoglobulins
  • Monoclonal antibody on serum protein electrophoresis
  • Suppression of other immunoglobulins "immunoparesis"
  • Bence Jones proteinuria may be present