Tumor lysis syndrome pathophysiology: Difference between revisions
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__NOTOC__ | __NOTOC__ | ||
{{Tumor lysis syndrome}} | {{Tumor lysis syndrome}} | ||
{{CMG}} {{AE}} {{MJK}} | {{CMG}} {{AE}} {{MJK}} {{N.F}} | ||
==Overview== | ==Overview== | ||
'''Tumor lysis syndrome''' ('''TLS''') is cosidered to be an oncologic emergency that develops after chemotherapy or radiotherapy. Tumor lysis syndrome is more common in highly proliferative [[Lymphoma|lymphomas]]<nowiki/>and [[Leukemia|leukemias]], and sometimes even without treatment. As evident by its name, tumor cells breakdown with chemotherapy releases potassium, nucleic acids, and phosphorus into the circulation, resulting in [[hyperkalemia]], [[hyperphosphatemia]], [[hyperuricemia]], [[hypocalcemia]], and [[acute renal failure]]. Hyperuricaemia results from rapid release and catabolism of intracellular nucleic acids. Hyperphosphataemia results from the rapid release of intracellular phosphorous from malignant cells. The malignant cells contain as much as four times the amount of organic and inorganic phosphorous as compared to normal cells. Hyperkalaemia results from breakdown of tumor cells and then becomes exacerbated by the development of renal failure. Hypocalcaemia results from hyperphosphataemia and the precipitation of calcium phosphate crystals in the renal tubules. When the calcium phosphorus levels rises up there is a significant risk of calcium phosphate deposition in the kidney and other tissues. This secondarily leads to systemic hypocalcaemia. | |||
==Pathogenesis== | |||
*Tumor lysis syndroms develops after [[chemotherapy]] or [[Radiation therapy|radiotherapy]] usually [[lymphoma]]s and [[leukemia]]s, and sometimes even without treatment.<ref name="DarmonThiery2007">{{cite journal|last1=Darmon|first1=Michael|last2=Thiery|first2=Guillaume|last3=Azoulay|first3=Elie|title=Preventing acute renal failure is crucial during acute tumor lysis syndrome|journal=Indian Journal of Critical Care Medicine|volume=11|issue=1|year=2007|pages=29|issn=0972-5229|doi=10.4103/0972-5229.32434}}</ref><ref name="pmid15384972">{{cite journal |vauthors=Cairo MS, Bishop M |title=Tumour lysis syndrome: new therapeutic strategies and classification |journal=Br. J. Haematol. |volume=127 |issue=1 |pages=3–11 |date=October 2004 |pmid=15384972 |doi=10.1111/j.1365-2141.2004.05094.x |url=}}</ref> | |||
*Massive cells destruction will lead to a rapid release of intracellular [[anions]], [[cations]] and metabolic products of [[proteins]] and [[nucleic acids]] into the bloodstream. As consequences of their high intracellular concentration, [[potassium]], [[calcium]], [[Phosphate|phosphates]] and [[uric acid]] will be released in the [[extracellular space]]. | |||
*'''[[Hyperuricemia|Hyperuricaemia]]''' results from rapid release and [[catabolism]] of [[intracellular]] [[Nucleic acid|nucleic acids]]. | |||
*Purine nucleic acids are catabolized to→ [[hypoxanthine]]→ [[xanthine]] → uric acid by [[xanthine oxidase]]. | |||
*Uric acid excretes through the [[kidney]], and approximately 500 mg of uric acid is excreted through the kidneys each day. | |||
*'''[[Hyperphosphatemia|Hyperphosphataemia]]''' results from the rapid release of intracellular phosphorous from [[malignant]] cells. | |||
*The malignant cells contain as much as four times the amount of organic and inorganic phosphorous as compared to normal cells. | |||
*Initially, the kidneys are able to respond to the increased concentration of phosphorous from tumour lysis by increased urinary excretion and decreased tubular re‐absorption of phosphorous. | |||
*Later on the tubular transport mechanism becomes saturated and serum phosphorous levels rise. | |||
*The development of hyperphosphataemia may be further exacerbated by acute renal insufficiency associated with uric acid precipitation or other complications of tumour therapy, | |||
*Hyperphosphataemia can lead to the development of acute renal failure after the precipitation of calcium phosphate in renal tubules during TLS. | |||
*'''[[Hyperkalemia|Hyperkalaemia]]''' may also be a life‐threatening consequence of TLS and is partly because of the kidneys inability to clear the large quantities of potassium released after breakdown of tumor cells | |||
*Hyperkalaemia results from breakdown of tumor cells and then becomes exacerbated by the development of renal failure | |||
*The rapid rise in serum potassium may result in severe [[arrhythmias]] and [[sudden death]]. | |||
*'''[[Hypocalcemia|Hypocalcaemia]]''' may be asymptomatic or symptomatic. | |||
*Hypocalcaemia results from hyperphosphataemia and the precipitation of calcium-phosphate crystals in the renal tubules. | |||
*When the calcium phosphorus levels rises up there is a significant risk of calcium phosphate deposition in the kidney and other tissues. | |||
*This secondarily leads to systemic hypocalcaemia. | |||
*'''[[Uremia|Uraemia]]''' is another common manifestation of TLS | |||
*The most common cause of uraemia during TLS is uric acid crystal formation in the renal tubules secondary to hyperuricaemia. | |||
*Other mechanisms of uremia during TLS include calcium phosphate deposition, tumor infiltration in the kidney, tumor‐associated obstructive uropathy, drug associated‐nephrotoxicity and/or acute sepsis.. | |||
*Pretreatment spontaneous tumor lysis syndrome is associated with [[acute renal failure]] due to uric acid [[nephropathy]] prior to the institution of chemotherapy and is largely associated with [[Lymphoma|lymphomas]] and [[Leukemia|leukemias]]. | |||
*The important distinction between this syndrome and the post-chemotherapy syndrome is that spontaneous tumor lysis syndroms 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 [[nucleoprotein]] turnover but the tumor reuses the released phosphate for resynthesis of new tumor cells. In post-chemotherapy tumor lysis syndroms, tumor cells are destroyed and no new tumor cells are being synthesized.<ref>{{Cite web | title = Tumor lysis syndrome | url =https://en.wikipedia.org/wiki/Tumor_lysis_syndrome }}</ref> | |||
==References== | ==References== | ||
{{reflist|2}} | {{reflist|2}} | ||
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[[Category:Blood]] | [[Category:Blood]] | ||
[[Category:Hematology]] | [[Category:Hematology]] | ||
[[Category:Up-To-Date]] | |||
[[Category:Oncology]] | |||
[[Category:Medicine]] | |||
Latest revision as of 19:55, 17 December 2018
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mohamad Alkateb, MBBCh [2] Nazia Fuad M.D.
Overview
Tumor lysis syndrome (TLS) is cosidered to be an oncologic emergency that develops after chemotherapy or radiotherapy. Tumor lysis syndrome is more common in highly proliferative lymphomasand leukemias, and sometimes even without treatment. As evident by its name, tumor cells breakdown with chemotherapy releases potassium, nucleic acids, and phosphorus into the circulation, resulting in hyperkalemia, hyperphosphatemia, hyperuricemia, hypocalcemia, and acute renal failure. Hyperuricaemia results from rapid release and catabolism of intracellular nucleic acids. Hyperphosphataemia results from the rapid release of intracellular phosphorous from malignant cells. The malignant cells contain as much as four times the amount of organic and inorganic phosphorous as compared to normal cells. Hyperkalaemia results from breakdown of tumor cells and then becomes exacerbated by the development of renal failure. Hypocalcaemia results from hyperphosphataemia and the precipitation of calcium phosphate crystals in the renal tubules. When the calcium phosphorus levels rises up there is a significant risk of calcium phosphate deposition in the kidney and other tissues. This secondarily leads to systemic hypocalcaemia.
Pathogenesis
- Tumor lysis syndroms develops after chemotherapy or radiotherapy usually lymphomas and leukemias, and sometimes even without treatment.[1][2]
- Massive cells destruction will lead to a rapid release of intracellular anions, cations and metabolic products of proteins and nucleic acids into the bloodstream. As consequences of their high intracellular concentration, potassium, calcium, phosphates and uric acid will be released in the extracellular space.
- Hyperuricaemia results from rapid release and catabolism of intracellular nucleic acids.
- Purine nucleic acids are catabolized to→ hypoxanthine→ xanthine → uric acid by xanthine oxidase.
- Uric acid excretes through the kidney, and approximately 500 mg of uric acid is excreted through the kidneys each day.
- Hyperphosphataemia results from the rapid release of intracellular phosphorous from malignant cells.
- The malignant cells contain as much as four times the amount of organic and inorganic phosphorous as compared to normal cells.
- Initially, the kidneys are able to respond to the increased concentration of phosphorous from tumour lysis by increased urinary excretion and decreased tubular re‐absorption of phosphorous.
- Later on the tubular transport mechanism becomes saturated and serum phosphorous levels rise.
- The development of hyperphosphataemia may be further exacerbated by acute renal insufficiency associated with uric acid precipitation or other complications of tumour therapy,
- Hyperphosphataemia can lead to the development of acute renal failure after the precipitation of calcium phosphate in renal tubules during TLS.
- Hyperkalaemia may also be a life‐threatening consequence of TLS and is partly because of the kidneys inability to clear the large quantities of potassium released after breakdown of tumor cells
- Hyperkalaemia results from breakdown of tumor cells and then becomes exacerbated by the development of renal failure
- The rapid rise in serum potassium may result in severe arrhythmias and sudden death.
- Hypocalcaemia may be asymptomatic or symptomatic.
- Hypocalcaemia results from hyperphosphataemia and the precipitation of calcium-phosphate crystals in the renal tubules.
- When the calcium phosphorus levels rises up there is a significant risk of calcium phosphate deposition in the kidney and other tissues.
- This secondarily leads to systemic hypocalcaemia.
- Uraemia is another common manifestation of TLS
- The most common cause of uraemia during TLS is uric acid crystal formation in the renal tubules secondary to hyperuricaemia.
- Other mechanisms of uremia during TLS include calcium phosphate deposition, tumor infiltration in the kidney, tumor‐associated obstructive uropathy, drug associated‐nephrotoxicity and/or acute sepsis..
- Pretreatment spontaneous tumor lysis syndrome 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 tumor lysis syndroms 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 nucleoprotein turnover but the tumor reuses the released phosphate for resynthesis of new tumor cells. In post-chemotherapy tumor lysis syndroms, tumor cells are destroyed and no new tumor cells are being synthesized.[3]
References
- ↑ Darmon, Michael; Thiery, Guillaume; Azoulay, Elie (2007). "Preventing acute renal failure is crucial during acute tumor lysis syndrome". Indian Journal of Critical Care Medicine. 11 (1): 29. doi:10.4103/0972-5229.32434. ISSN 0972-5229.
- ↑ Cairo MS, Bishop M (October 2004). "Tumour lysis syndrome: new therapeutic strategies and classification". Br. J. Haematol. 127 (1): 3–11. doi:10.1111/j.1365-2141.2004.05094.x. PMID 15384972.
- ↑ "Tumor lysis syndrome".