Tumor Lysis Syndrome - Symptoms and Pathogenesis

Symptoms and Pathogenesis

Hyperkalemia. Potassium is mainly an intracellular ion. High turnover of tumor cells leads to spill of potassium into the blood. Symptoms usually do not manifest until levels are high (> 7 mmol/L) and they include

• cardiac conduction abnormalities (can be fatal)
• severe muscle weakness or paralysis

Hyperphosphatemia. Like potassium, phosphates are also predominantly intracellular. Hyperphosphatemia causes acute renal failure in tumor lysis syndrome, because of deposition of calcium phosphate crystals in the renal parenchyma.

Hypocalcemia. Because of the hyperphosphatemia, calcium is precipitated to form calcium phosphate, leading to hypocalcemia. Symptoms of hypocalcemia include (but are not limited to):

• tetany
• seizures
• sudden mental incapacity, including emotional lability
• parkinsonian (extrapyramidal) movement disorders
• papilledema
• myopathy

Hyperuricemia and hyperuricosuria. Acute uric acid nephropathy (AUAN) due to hyperuricosuria has been a dominant cause of acute renal failure but with the advent of effective treatments for hyperuricosuria, AUAN has become a less common cause than hyperphosphatemia. Two common conditions related to excess uric acid, gout and uric acid nephrolithiasis, are not features of tumor lysis syndrome.

Lactic acidosis.

Pretreatment spontaneous tumor lysis syndrome. This entity is associated with acute renal failure due to uric acid nephropathy prior to the institution of chemotherapy and is largely associated with lymphomas and leukemias. The important distinction between this syndrome and the post-chemotherapy syndrome is that spontaneous TLS is not associated with hyperphosphatemia. One suggestion for the reason of this is that the high cell turnover rate leads to high uric acid levels through nucleobase turnover but the tumor reuses the released phosphate for growth of new tumor cells. In post-chemotherapy TLS, tumor cells are destroyed and no new tumor cells are being synthesized.