Tumour lysis syndrome: pattern, kidney injury and rasburicase
Tumour lysis syndrome is a medical emergency of rapid tumour cell breakdown: uric acid (made from purines, building blocks of DNA and RNA), potassium and phosphate rise, and calcium falls.
Remember
In tumour lysis syndrome, uric acid, potassium and phosphate rise and calcium falls: three up, one down.
Memory aid
allopurinol turns off the factory, whereas rasburicase clears the stock already made
Allopurinol stops new uric acid forming, whereas rasburicase breaks down uric acid that is already present.
Tumour lysis syndrome (TLS) follows the rapid breakdown of tumour cells, particularly in acute leukaemia and high-grade lymphoma (a fast-growing cancer of the lymph tissue), often after chemotherapy (the drug treatment that kills cancer cells). Their contents reach the blood faster than the body can clear them, giving the typical pattern of high uric acid, potassium and phosphate with low calcium.
Nucleic acids (DNA and RNA) from the dying cells contain purines, which are converted to uric acid. That gives hyperuricaemia (a high blood uric acid level). The dying cells also release potassium (hyperkalaemia, meaning high potassium) and phosphate (hyperphosphataemia, meaning high phosphate). Calcium is then bound by the extra phosphate, so it falls: hypocalcaemia (low calcium).
Match each abnormality to its organ.
- Kidney: uric acid forms crystals in the renal tubules (the narrow tubes that carry urine through the kidney) and blocks them, causing acute kidney injury. Calcium phosphate crystals can add to the damage.
- Heart: hyperkalaemia causes arrhythmias (dangerous heart rhythm disturbances).
- Nerves and muscle: low calcium, following the phosphate rise, causes tetany (painful muscle spasms) and seizures.
Prevention is more effective than treatment. Patients at risk of tumour lysis syndrome are given intravenous fluids before chemotherapy, together with either allopurinol (a drug that stops uric acid forming by blocking xanthine oxidase, the enzyme that makes uric acid) or, in high-risk patients, rasburicase. Rasburicase is an enzyme that breaks down uric acid already present into allantoin, which the kidneys excrete easily. It is avoided in G6PD deficiency (an inherited red cell enzyme deficiency) because of the risk of haemolysis (breakdown of red blood cells).
Key facts
- Pattern
- uric acid, potassium and phosphate rise and calcium falls, usually soon after effective treatment starts.
- Where the rise comes from
- the dying cells release purines, which are converted to uric acid, together with potassium and phosphate.
- Why calcium falls
- the extra phosphate binds it.
- Kidney injury
- uric acid crystals block the renal tubules, and calcium phosphate crystals can add to the damage.
- Heart and nerves
- hyperkalaemia causes arrhythmias, while low calcium causes tetany and seizures.
- Rasburicase
- an enzyme that converts existing uric acid to allantoin, whereas allopurinol only prevents new uric acid forming.
- Safety
- rasburicase is avoided in G6PD deficiency because of the risk of haemolysis.
Exam traps
- Hypokalaemia (low potassium) points the wrong way for tumour lysis syndrome, because dying cells release potassium into the blood, so it rises and can cause arrhythmias.
- Hypophosphataemia (low phosphate) also points the wrong way: dying cells release their phosphate, so phosphate rises, and the high phosphate is the reason calcium falls.
- Hypercalcaemia (high calcium) belongs to a separate emergency in cancer, not to tumour lysis syndrome, where calcium falls because the released phosphate binds it.
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