Pathogenesis ,symptom & Diagnosis of Tumour lysis Syndrome

[အာကာလြင္]

Symptoms and pathogenesis & Diagnosis of Tumour lysis Syndrome
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/dL) [normal
3.5-5.0 mmol/dL] 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
• mental retardation / dementia
• parkinsonian (extrapyramidal) movement disorders
• papilledema
• emotional instability / agitation / anxiety
• myopathy
Hyperuricemia[2] 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.
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.
Diagnosis
TLS should be suspected in patients with large tumor burden who
develop acute renal failure along with hyperuricemia (> 15 mg/dL) or
hyperphosphatemia (> 8 mg/dL). (Most other acute renal failure occurs
with uric acid < 12 mg/dL and phosphate < 6 mg/dL). Acute uric acid
nephropathy is associated with little or no urine output. The
urinalysis may show uric acid crystals or amorphous urates. The
hypersecretion of uric acid can be detected with a high urine uric
acid - creatinine ratio > 1.0, compared to a value of 0.6-0.7 for most
other causes of acute renal failure.
Cairo-Bishop Definition
In 2004, Cairo and Bishop defined a classification system for tumor
lysis syndrome.[3]
• Laboratory tumor lysis syndrome: abnormalitiy in two or more of the
following and occurs within 3 days before or 7 days after
chemotherapy.
o uric acid > 8 mg/dL or 25% increase
o potassium > 6 meq/L or 25% increase
o phosphate > 4.5 mg/dL or 25% increase
o calcium < 7 mg/dL or 25% decrease
• Clinical tumor lysis syndrome: laboratory tumor lysis syndrome plus
one or more of the following:
o increase serum creatinine (1.5 times upper limit of normal)
o cardiac arrhythmia or sudden death
o seizure
A grading scale (0-5) is used depending on the presence of lab TLS,
serum creatinine, arrhythmias, or seizures.