Leukemia adalah penyakit neoplastik yang ditandai dengan diferensiasi dan proliferasi sel induk hematopoietik yang mengalami transformasi dan ganas, menyebabkan supresi dan penggantian elemen sumsum normal (Baldy, (Baldy, 2006). Leukemia dibagi menjadi menjadi 2 tipe umum: leukemia limfositik dan leukemia mielogenosa (Guyton and Hall, 2007). Berikut ini adalah permasalahan dalam skenario 1: Ny. Kassian DL, 42 tahun, tahun, datang ke poliklinik dengan keluhan lemas , pucat, mudah capai , capai kadang panas, yang sudah dirasakan sejak 6 bul . Akhir-akhir ini sering disertai bul an terakh terakh ir . Pada pemeriksaan fisik didapatkan: pucat, gizi . perdarah perdarah an l ewat hidun g gizi kes kesan k ur ang Suhu aksiler 38,5° , nadi 108 kali /meni mmHg, C /meni , t irama teratur, tekanan darah 124/78 mmHg, anemis papil l idah atrofi atrofi frekuensi nafas 18 kali/menit. Konj ungti va anemis , sklera tidak ikterik, papil , . Terdapat li mf adenopati , pada pemeriksaan ti dak ditemukan pembe pembengkakan ngkakan gusi adenopati leher leher abdomen didapatkan hepatomegali dan splenomegali. Hasil pemeriksaan laboratorium: H b 3 3 3 7,5 g/dL ; jumlah l euk osit osit 24.500/mm 24.500/mm ; jumlah tr ombosit ombosit 67 x 10 /mm . Penderita dianjurkan dirujuk ke rumah sakit. B. RUMUSAN MASALAH
1. Apakah penyakit yang diderita oleh pasien? 2. Mengapa pasien mengalami gejala-gejala klinis seperti dalam kasus? 3. Bagaimanakah penatalaksanaan penyakit yang diderita pasien? C. TUJUAN PENULISAN
1. Mengetahui penyakit yang diderita oleh pasien. 2. Mengetahui penyebab pasien mengalami gejala-gejala klinis seperti dalam kasus. 3. Mengetahui penatalaksanaan penyakit yang diderita pasien. D. MANFAAT PENULISAN
Mahasiswa mampu menjelaskan konsep patogenesis dan patofisiologi penyakit hematologi. Mahasiswa mampu menentukan pemeriksaan penunjang diagnosis penyakit hematologi. Mahasiswa mampu menyusun data dari gejala, pemeriksaan fisik, prosedur klinis, dan pemeriksaan laboratorium untuk mengambil kesimpulan suatu diagnosis penyakit hematologi. Mahasiswa mampu merancang manajemen penyakit hematologi secaraa komprehensif.
F. HIPOTESIS
Pasien dalam kasus mengalami leukemia. Hal ini ditandai dengan adanya gejala trias leukemia yang berupa 1) anemia; 2) leukositosis; dan 3) trombositopenia. BAB II TINJAUAN PUSTAKA
1. A. Etiologi Leukemia Walaupun penyebab dari leukemia tidak diketahui, predisposisi genetik maupun faktor-faktor lingkungan kelihatannya memainkan peranan (Baldy, 2006). Diduga hal ini dapat disebabkan oleh interaksi sejumlah faktor, diantaranya 1) Neoplasia; 2) Infeksi; 3) Radiasi; 4) Keturunan; 5) Zat kimia; dan 6) Perubahan kromosom (Hoffbrand and Petit, 1996). 1. B. Klasifikasi Leukemia t: translokasi *sel null: limfosit yang kekurangan sel B (immunoglobulin membrane) atau penanda sel T (pembentukan rosette-E) Badan auer: badan berwarna merah yang terlihat dalam sitoplasma mieloblas yang khas pada leukemia mielogenosa akut ‡CD10: dahulu cALLa (antigen LLA yang lazim)— kompleks glikoprotein membran permukaan yang jelas dibawa oleh 70% limfoblas leukemia sel bukan-T (Baldy, 2006) Klasifikasi besar adalah leukemia akut dan kronis. Leukemia akut, dimana terdapat lebih 50% mieloblas atau limfoblas dalam sumsum tulang pada gambaran klinis, lebih lanjut dibagi dalam leukemia mieloid (mieloblastik) akut (AML) dan leukemia limfoblastik akut (ALL). Leukemia kronis mencakup dua tipe utama, leukemia granulositik (mieloid) kronis (CGL/CML) dan leukemia limfositik kronis (CLL). Tipe kronis lain termasuk leukemia sel berambut, leukemia prolimfositik, dan berbagai sindroma mielodisplastik, yang sebagian dianggap sebagai bentuk leukemia kronis dan lainnya sebagai ―pre-leukemia‖ (Hoffbrand and Petit, 1996). Leukemia limfositik disebabkan oleh produksi sel limfoid yang bersifat kanker, biasanya dimulai di nodus limfe atau jaringan limfositik lain dan menyebar ke daerah tubuh lainnya. Leukimia mielogenosa dimulai dengan produksi sel mielogenosa muda yang bersifat kanker di sumsum tulang dan kemudian menyebar ke seluruh tubuh, sehingga leukosit diproduksi di banyak organ ekstramedular, terutama di nodus limfe, limpa, dan hati (Guyton and Hall, 2007). 1. C. Pemeriksaan dan Diagnosis Leukemia
Hematologi rutin dan Hitung darah lengkap digunakan untuk mengetahui kadar Hberitrosit, leukosit, dan trombosit. Apus darah tepi digunakan untuk mengetahui morfologi sel darah, berupa bentuk, ukuran, maupun warna sel-sel darah, yang dapat menunjukkan kelainan hematologi. Aspirasi dan biopsi sumsum tulang digunakan untuk mengetahui kondisi sumsum tulang, apakah terdapat kelainan atau tidak. Karyotipik digunakan untuk mengetahui keadaan kromosom dengan metode FISH ( Flurosescent In Situ Hybridization).
Immunophenotyping mengidentifikasi jenis sel dan tingkat maturitasnya dengan antibodi yang spesifik terhadap antigen yang terdapat pada permukaan membran sel. Sitokimia merupakan metode pewarnaan tertentu sehingga hasilnya lebih spesifik daripada hanya menggunakan morfologi sel blas pada apus darah tepi atau sumsum tulang. Analisis sitogenetik digunakan untuk mengetahui kelainan sitogenetik tertentu, yang pada leukemia dibagi menjadi 2: kelainan yang menyebabkan hilang atau bertambahnya materi kromosom dan kelainan yang menyebabkan perubahan yang seimbang tanpa menyebabkan hilang atau bertambahnya materi kromosom. Biologi molekuler mengetahui kelainan genetik, dan digunakan untuk menggantikan analisis sitogenetik rutin apabila gagal.
(Sudoyo et.al, 2007). 1. D. Patogenesis dan Patofisiologi Leukemia Populasi sel leukemik ALL dan banyak AML mungkin diakibatkan proliferasi klonal dengan pembelahan berturut-turut dari sel blas tunggal yang abnormal. Sel-sel ini gagal berdiferensiasi normal tetapi sanggup membelah lebih lanjut. Penimbunannya mengakibatkan pertukaran sel prekursor hemopoietik normal pada sumsum tulang, dan akhirnya mengakibatkan kegagalan sumsum tulang. Keadaan klinis pasien dapat berkaitan dengan jumlah total sel leukemik abnormal di dalam tubuh. Gambaran klinis dan mortalitas pada leukemia akut berasal terutama dari neutropenia, trombositopenia, dan anemia karena kegagalan sumsum tulang (Hoffbrand and Petit, 1996). Blokade maturitas pada AML menyebabkan terhentinya diferensiasi sel-s el mieloid pada sel muda (blast ) dengan akibat terjadi akumulasi blast di sumsum tulang. Akumulasi blast di dalam sumsum tulang akan mengakibatkan gangguan hematopoiesis normal dan pada gilirannya akan mengakibatkan sindrom kegagalan sumsum tulang (bone marrow failure syndrome) yang ditandai dengan adanya sitopenia (anemia, leukopenia, dan trombositopenia). Selain itu, infiltrasi sel-sel blast akan menyebabkan tanda/gejala yang bervariasi tergantung organ yang diinfiltrasi, misalnya kulit, tulang, gusi, dan menings (Kurnianda, 2007). Pada umumnya gejala klinis ALL menggambarkan kegagalan sumsum tulang atau keterlibatan ekstramedular oleh sel leukemia. Akumulasi sel-sel limfoblas ganas di sumsum tulang menyebabkan kurangnya sel-sel normal di darah perifer dan gejala klinis dapat berhubungan dengan anemia, infeksi, dan perdarahan. Demam atau infeksi yang jelas dapat ditemukan pada separuh pasien ALL, sedangkan gejala perdarahan pada sepertiga pasien yang baru didiagnosis ALL (Fianza, 2007). CGL/CML adalah penyakit gangguan mieloproliferatif, yang ditandai oleh seri grabulosit tanpa gangguan diferensiasi, sehingga pada apusan darah tepi kita dapat dengan mudah melihat tingkatan diferensiasi seri granulosit, mulai dari promielosit (bahkan mieloblas), meta mielosit, mielosit, sampai granulosit. Pada awalnya, pasien seri ng mengeluh pembesaran limpa, atau keluhan lain yang tidak spesifik, seperti rasa cepat lelah, lemah badan, demam yang tidak terlalu tinggi, keringat malam, dan penurunan berat badan yang berlangsung lama. Semua keluhan tersebut merupakan gambaran hipermetabolisme akibat proliferasi sel-sel leukemia. Anemia dan trombositopenia terjadi pada tahap akhir penyakit (Fadjari, 2007).
CLL pada awal diagnosis, kebanyakan pasien C LL tidak menunjukkan gejala (asimptomatik). Gejala yang paling sering ditemukan pada pasien adalah limfadenopati generalisata, penurunan berat badan, dan kelelahan. Gejala lain meliputi hilangnya nafsu makan dan penurunan kemampuan latihan/olahraga. Demam, keringat malam, dan infeksi jarang terjadi pada awalnya, tetapi semakin menyolok sejalan dengan penyakitnya. Akibat penuumpukan sel B neoplastik, pasien mengalami limfadenopati, splenomegali, dan hepatomegali. Kegagalan sumsum tulang yang progresif pada CLL ditandai dengan memburuknya anemia dan atau trombositopenia (Rotty, 2007). 1. E. Penatalaksanaan Leukemia Pengobatan utama untuk keganasan hematologi selama beberapa dekade adalah pembedahan, kemoterapi, dan terapi radiasi (Baldy, 2006). Saat ini, pengobatan yang lain tersedia ter batas tetapi penggunaannya meningkat, dengan kemajuan dalam uji klinis, yang dikenal sebagai Biological. Kelompok obat ini adalah zat alami yang diambil dari sumber a lami atau disintesis dalam laboratorium untuk menyerang target biologi tertentu (Finley, 2000). Biological dianggap menjaga sel induk hematopoietik dan oleh karena itu kurang toksik dan bersifat kuratif (Baldy, 2006). Kemoterapi atau Terapi Obat Sitotoksik . Obat sitotoksik merusak kapasitas sel untuk reproduksi. Tujuan terapi sitotoksik mula-mula menginduksi remisi dan selanjutnya mengurangi populasi sel leukemik yang tersembunyi, dan memulihkan sumsum tulang dengan kombinasi siklik dua, tiga atau empat obat. Pemulihan ini tergantung pada pola pertumbuhan kembali (differential regrowth pattern) sel hemopoietik normal dan sel leukemik. Transplantasi Sumsum Tulang. Transplantasi sumsum tulang dilakukan untuk memulihkan sistem hemopoietik pasien setelah penyinaran seluruh tubuh dan kemoterapi intensif diberikan dalam usaha membunuh semua leukemmik yang tinggal (Hoffbrand and Petit, 1996).
Terapi ALL dibagi menjadi:
Induksi remisi
Terapi ini biasanya terdiri dari prednisone, vinkristin, antrasiklin dan L-asparaginase.
Intensifikasi atau konsolidasi
Berbagai dosis mielosupresi dari obat yang berbeda diberikan tergantung protocol yang dipakai.
Profilaksis SSP
Terdiri dari kombinasi kemoterapi intratekal, radiasi cranial, dan pemberian sistemik obat yang mempunyai bioavailabilitas yang tinggi seperti metotreksat dosis tinggi dan sitarabin dosis tinggi.
Pemeliharaan jangka panjang
Terapi ini terdiri dari 6-merkaptopurin tiap hari dan metotreksa t seminggu sekali selama 2 tahun (Fianza, 2007). BAB III PEMBAHASAN
Apakah penyakit yang diderita oleh pasien? Berdasarkan gejala-gejala klinis dan hasil pemeriksaan fisik serta pemeriksaan laboratorium yang ada, pasien menderita leukemia. Namun jenis leukemia yang diderita belum dapat dipastikan lebih lanjut, karena masih membutuhkan beberapa pemeriksaan lain seperti morfologi sel darah melalui pemeriksaan apusan darah, aspirasi dan biopsi sumsum tulang, analisis sitogenetik, serta immunophenotyping . Untuk diagnosis sementara sebelum dilakukan pemeriksaan penunjang seperti diatas, manifestasi klinis yang ada lebih merujuk ke arah leukemia limfoblastik. Perkembangan penyakit, yaitu dalam 6 bulan telah menimbulkan gejala hepatomegali dan splenomegali merujuk ke arah leukemia akut. Selain itu anemia dan trombositopenia pada leukemia kronis timbul pada stadium akhir penyakit. Padahal, stadium akhir leukemia kronik dicapai setelah penyakit berjalan selama bertahun-tahun. Sementara, dalam kasus, anemia dan trombositopenia terjadi dalam rentang waktu yang relatif singkat, hanya 6 bulan. Kemudian tidak adanya pembengkakan gusi mungkin dapat menjadi salah satu petunjuk bahwa pasien tidak mengalami leukemia limfoblastik akut (AML). Jadi, kesimpulan yang didapatkan dari kasus, pasien mengalami leukemia limfoblastik akut (ALL). Mengapa pasien mengalami gejala-gejala klinis seperti terdapat dalam kasus? Lemas, mudah lelah, demam yang tidak terlalu tinggi (aksiler 38,5°C), dan gizi kesan kurang. Disebabkan oleh hipermetabolisme yang terjadi karena aktivitas proliferasi sel-sel leukemia. Semua cadangan energi tubuh dipergunakan oleh aktivitas sel-sel l eukemik yang ganas, sehingga semakin lama cadangan lemak dalam jaringan adiposa semakin berkurang, akibatnya gizi pasien terkesan kurang, lemas, dan mudah lelah. Kemungkinan lain penyebab penurunan status gizi pasien adalah anemia dan gangguan oksigenasi jaringan. Peningkatan aktivitas seluler yang terjadi mengakibatkan peningkatan suhu inti, akibatnya tubuh menjalankan mekanisme pengaturan suhu sehingga terjadi demam. Kemungkinan lain akibat terjadinya demam adalah adanya infeksi. Walaupun sel-sel l eukosit yang berperan dalam sistem imunitas meningkat, tetapi sel yang terbentuk tidak berdiferensiasi dengan sel imun jenis apapun, sehingga tidak fungsional dalam menjaga kekebalan tubuh. Fenomena ini disebut dengan leukopenia fungsional. 3
3
Perdarahan lewat hidung dan trombositopenia (trombosit 67 x 10 /mm [normal 1,5-3 x 5 3 10 /mm ]). Akibat dari terjadinya penekanan hematopoiesis lainnya di sumsum tulang, maka produksi trombosit menurun. Padahal, trombosit berperan penting dalam sistem hemostasis primer. Jika trombosit berkurang, maka akan terjadi perdarahan yang waktunya lebih panjang daripada jika kondisi dan jumlah trombositnya normal. Kapiler pada keadaan normal memang sering mengalami ruptur, tetapi hal ini dapat cepat diatasi oleh sistem hemostasis primer, yaitu trombosit. Jika terjadi trombositopenia maka salah satu gejala yang timbul adalah perdarahan hidung akibat pecahnya dinding kapiler.
Takikardi (108x/menit [normal 60-100/menit]), konjungtiva anemis, papil lidah atrofi, dan anemia (Hb 7,5 g/dl [normal 12-16 g/dl]). Serupa dengan trombositopenia, anemia yang timbul terjadi akibat penekanan hematopoietik oleh sel-sel leukemik pada sumsum tulang. Akibatnya timbul manifestasi klinis khas anemia seperti di atas. Takikardi timbul akibat kerja keras jantung dalam memenuhi kebutuhan oksigen jaringan karena kuantitas hemoglobin (Hb) yang rendah dengan mekanisme mempercepat jalannya aliran darah. Kuantitas Hb yang rendah mengakibatkan central pallor eritrosit berwarna pucat. Hal inilah yang kemudian direpresentasikan oleh berbagai jaringan tubuh, misalnya konjungtiva, bantalan kuku, telapak tangan, serta membran mukosa mulut. Atrofi papil lidah mungkin saja terjadi akibat cedera sel papila akibat kekurangan oksigen yang terjadi akibat anemia yang diderita oleh pasien. Limfadenopati leher. Hiperplasia terjadi akibat kerja limfonodus yang berlebihan dalam memproduksi limfosit. Sehingga sel-sel limfonodus yang berlebihan menyebabkan timbulnya rasa sakit ( pathy). Hepatomegali. Terjadi dapat disebabkan karena tiga hal terkait: 1) infeksi; 2) akibat anemia hemolitik; atau 3) akibat infiltrasi. Namun, dalam kasus ini, kaitan yang paling mungkin adalah hepatomegali terjadi akibat infiltrasi sel-sel leukemik ke dalam jaringan hepar. Splenomegali. Splenomegali yang terjadi dapat disebabkan karena tiga hal terkait: 1) infiltrasi; 2) infeksi; atau 3) sumbatan/gangguan aliran darah. Namun, dalam kasus ini, kemungkinan yang paling besar splenomegali terjadi akibat infiltrasi sel -sel leukemia ke dalam limpa/splen.
Bagaimanakah penatalaksanaan pasien dalam kasus? Berdasarkan kesimpulan, pasien dalam kasus menderita leukemia limfositik akut (ALL). Sehingga penatalaksanaan pasien dalam kasus lebih difokuskan pada terapi untuk ALL. Terapi ALL itu sendiri meliputi induksi remisi, intensifikasi atau konsolidasi, profilaksis SSP, dan pemeliharaan jangka panjang. BAB IV PENUTUP A. KESIMPULAN
Berdasarkan hasil pemeriksaan yang didapatkan sementara dan manifestasi klinis yang ada, pasien dalam kasus mengalami leukemia limfoblastik akut (ALL). B. SARAN
1. Sebaiknya pasien menjalani pemeriksaan lanjutan untuk menentukan jenis leukemia yang diderita, agar rencana penatalaksanaan dapat ditentukan sesegera mungkin. 2. Pemeriksaan lanjutan minimal yang dilaksanakan sebaiknya pemeriksaan morfologi sel darah dan aspirasi sumsum tulang. DAFTAR PUSTAKA
Baldy, Catherine M. Gangguan Sel Darah Putih dalam Price, Sylvia A. Wilson, Lorraine M. 2006. Patofisiologi, Konsep Klinis Proses-Proses Penyakit edisi 6 . Jakarta: EGC. Fadjari, Heri. Leukemia Granulositik Kronis dalam Sudoyo, Aru W. Setiyohadi, Bambang. Alwi, Idrus. Simadibrata K, Marcellus. Setiati, Sit i. 2007. Buku Ajar Ilmu Penyakit Dalam. Jakarta: Pusat Penerbitan Departemen Ilmu Penyakit Dalam FKUI. Fianza, Panji Irani. Leukemia Limfoblastik Akut. ————————————— Greer JP et.al, Acute myelogenous leukemia. In Lee RG et. al, editors: hematology, ed 10, Baltimore, 1999, Williams & Wilkins.
Wintrobe’s clinical
Guyton, Arthur C. Hall, John E. 2007. Buku Ajar Fisiologi Kedokteran Edisi 11. Jakarta: EGC. Hoffbrand, A.V. Petit, J.E. 1996. Kapita Selekta Haematologi. Jakarta: EGC. Kurnianda, Johan. Leukemia Mieloblastik Akut dalam Sudoyo, Aru W. Setiyohadi, Bambang. Alwi, Idrus. Simadibrata K, Marcellus. Setiati, Siti.et.al. 2007. Buku Ajar Ilmu Penyakit Dalam. Jakarta: Pusat Penerbitan Departemen Ilmu Penyakit Dalam FKUI. Rotty, Linda W.A. Leukemia Limfositik Kronis . ——
Sel-sel leukemik berinfiltrasi ke dalam sumsum tulang, mengganti unsur-unsur sel yang normal. Akibatnya, timbul anemia, dan dihasilkan sel darah merah dalam jumlah yang tidak mencukupi. Timbul perdarahan akibat menurunnya jumlah trombosit yang bersirkulasi. Infeksi juga terjadi lebih sering karena berkurangnya jumlah leukosit normal. I nvasi sel-sel leukemik ke dalam organ-organ vital menimbulkan hepatomegali, splenomegali, dan limfadenopati. http://fkunhas.com/topic/penyebab+hepatomegali+dan+splenomegali.html
After completing this article, readers should be able to: 1. 2. 3. 4.
Identify the possible causes of simultaneous hepatomegaly and splenomegaly. List the important diagnostic considerations in patients who have hepatomegaly. Delineate the most helpful initial radiographic test. Describe what clinical findings occurring concomitantly in a patient who has hepatomegaly suggest metabolic or storage disease. 5. List the risk factors for infectious hepatitis.
Top OBJECTIVES Introduction Pathogenesis History Physical Examination Laboratory Studies Imaging Studies Pathology Diagnostic Evaluation of the... Diagnostic Evaluation of the... Conclusion Suggested Reading
Introduction Hepatomegaly can represent intrinsic liver disease or may be the presenting physical finding of a generalized disorder. Early diagnosis and treatment of children who have liver disease is important because specific treatments are available for some diseases that can prevent disease progression or hepatic failure. The presence of a palpable liver does not always indicate hepatomegaly. Normal liver size is based on normative values of liver span by percussion, degree of extension below the right costal margin, or length of the vertical axis estimated from imaging techniques. In general, a liver edge greater than 3.5 cm in newborns and greater than 2 cm in children below the right costal margin suggests enlargement. Liver span is determined by measuring the distance between the upper edge, determined by percussion, and the lower edge, determined by palpation, in the midclavicular line. The lower border also may be determined by auscultation. With the stethoscope placed below the xiphoid, the examiner should gently scratch superiorly, starting in from the right lower quadrant, and listen for sound enhancement as the finger passes over the liver edge. Liver span increases linearly with body weight and age in both genders and correlates more with weight than with height. The normal range for liver span by percussion at 1 week of age is 4.5 to 5 cm. At 12 years, the normal value for boys is 7 to 8 cm and for girls is 6 to 6.5 cm. The liver can be displaced inferiorly by the diaphragm or thoracic organs, giving the impression of hepatomegaly. Accumulation of fluid or air in the thorax (eg, pneumothorax) also may displace the liver inferiorly. A retroperitoneal mass, choledochal cyst, or perihepatic abscess also may be mistaken for hepatomegaly. Children who have orthopedic abnormalities such as narrow chest walls or pectus excavatum can erroneously appear to have hepatomegaly. A normal variant of the right lobe of the liver, called a Riedel lobe, may extend far below the right costal margin and be confused as pat hologic hepatic enlargement. However, patients who have a Riedel lobe will have no signs, symptoms, or laboratory evidence of liver disease.
Pathogenesis
Hepatomegaly generally occurs via five mechanisms: inflammation, excessive storage, infiltration, congestion, and obstruction (Table 1 ). Infections from viruses, bacteria, fungi, and parasites promote inflammation-induced hepatomegaly. Toxins, radiation, autoimmune disease, and Kupffer cell hyperplasia also may cause hepatomegaly by this mechanism.
Top OBJECTIVES Introduction Pathogenesis History Physical Examination Laboratory Studies Imaging Studies Pathology Diagnostic Evaluation of the... Diagnostic Evaluation of the... Conclusion Suggested Reading
View this table: Table 1. Mechanisms of Hepatomegaly and Representative [in this window] Diseases [in a new window]
Storage products that accumulate in the enlarged liver include glycogen, fats, metals, and abnormal proteins. Glycogen storage occurs in glycogen storage disease and diabetes mellitus and in some patients receiving parenteral nutrition. Steatosis, the accumulation of fat in the liver, occurs most commonly in overweight children and less commonly in the presence of certain metabolic diseases and diabetes. Metals and abnormal proteins can be stored inappropriately in the liver. For example, hepatomegaly is caused by the accumulation of copper in Wilson disease and the accumulation of abnormal protein in alpha-1-antitrypsin deficiency. Cellular infiltration can occur from primary tumors of the liver or metastatic disease. Primary tumors can be malignant or benign. Malignant tumors include hepatoblastoma or hepatocellular carcinoma. Benign tumors include hemangiomas, teratomas, and focal nodular hyperplasia. Metastatic infiltration occurs in leukemia, lymphoma, neuroblastoma, and histiocytosis. Parasitic cysts, although uncommon in North America, are a common cause of liver enlargement worldwide. Extramedullary hematopoiesis and hemophagocytic syndrome cause hepatomegaly due to infiltration by blood cells. Congestive blood flow in the liver causes hepatomegaly. Suprahepatic obstruction from congestive heart failure, restrictive pericardial disease, hepatic vein thrombosis (BuddChiari), or suprahepatic vascular webs are examples. Veno-occlusive disease causes hepatomegaly by obstructing intrahepatic blood flow. This problem occurs mainly in bone marrow transplant patients. Lastly, obstruction of biliary flow causes hepatic enlargement. This may be due to tumors outside the liver or congenital and acquired problems of the biliary system. Biliary atresia, choledochal cysts, and cholelithiasis are examples of diseases in which bile flow is obstructed.
Top OBJECTIVES Introduction Pathogenesis History Physical Examination Laboratory Studies Imaging Studies Pathology Diagnostic Evaluation of the... Diagnostic Evaluation of the... Conclusion Suggested Reading
History A thorough evaluation of hepatomegaly should begin with a complete history. In the neonate, a history of hyperbilirubinemia after 2 weeks of age requires rapid assessment of the underlying disorder to rule out extrahepatic biliary atresia. A family history of early infant death or hepatic, neurodegenerative, or psychiatric disease suggests a metabolic etiology. Eliciting a careful birth history may uncover risk factors for perinatally acquired infections, such as maternal intravenous drug use, maternal infections, or previous blood transfusions. Prenatal history of Rh or ABO incompatibility suggests isoimmunization and hemolysis as the cause of hepatomegaly. Maternal infections that can be transmitted to the fetus or neonate include hepatitis B, toxoplasmosis, syphilis, cytomegalovirus, rubella, herpes simplex, enterovirus, rubella, and human immunodeficiency virus. A history of an umbilical catheter increases the risk for hepatic abscess. A history of prolonged hyperbilirubinemia in infancy may point to cystic fibrosis or alpha-1-antitrypsin deficiency. Delayed passage of meconium also suggests cystic fibrosis. In the child and adolescent, careful questioning about foreign travel, ingestion of shellfish or drugs, and environmental toxins may reveal risk factors for acute hepatitis or parasitic disease. A history of poor weight gain, vomiting, diarrhea, distinctive odors, loss of developmental milestones, complex seizure disorder, or hypotonia suggests a metabolic disease. A history of hyperbilirubinemia with or without acholic stools and dark urine indicates hepatic dysfunction. Acholic stool usually suggests obstruction of the biliary tract, but it also can be seen in severe hepatocellular injury. Acute onset of hepatomegaly associated with hyperbilirubinemia in an older child raises the suspicion of infection with hepatitis A. Exposure to blood products, having a tattoo, and illicit intravenous drug use are risk factors for hepatitis C and B infection. Commonly used medications that may cause hepatic enlargement include nonsteroidal anti-inflammatory agents, isoniazid, propylthiouracil, and sulfonamides. Systemic symptoms related to chronic inflammatory diseases should be sought in the older child who has hepatomegaly. A history of inflammatory bowel disease or immunodeficiency increases the likelihood for primary sclerosing cholangitis.
Top OBJECTIVES Introduction Pathogenesis History Physical Examination Laboratory Studies Imaging Studies Pathology Diagnostic Evaluation of the... Diagnostic Evaluation of the... Conclusion Suggested Reading
Physical Examination A careful physical examination often can narrow the diagnostic considerations (Table 2 ). In addition to size, liver nodularity and firmness should be assessed. Auscultation over the liver may detect bruits or increased flow to the liver. The stigmata of generalized disease processes should be sought. Jaundice (yellowing of the skin and sclera) usually becomes apparent when the serum bilirubin concentration reaches 34.2 to 51.3 mcmol/L (2 to 3 mg/dL). Other nonspecific signs and symptoms of hepatic disease include fatigue, anorexia, weight loss, blood in the stool, and abdominal distention. Signs of chronic liver disease, such as spider angiomas, xanthomas, and palmar erythema, are more common among adults. Fever suggests a systemic illness or infection. A neonatal history of intrauterine growth retardation, microcephaly, chorioretinitis, and purpura accompanied by hepatomegaly strongly suggests congenital infection, which will allow the clinician to tailor the diagnostic evaluation accordingly.
View this table: Table 2. Useful Signs and Symptoms in the Diagnosis of [in this window] Hepatomegaly [in a new window]
Portal hypertension, hepatic infiltration by malignant cells, or storage disease cause splenomegaly as well as hepatomegaly. Other signs of portal hypertension include ascites or a prominent abdominal venous pattern. Massive splenomegaly is more common with storage diseases and malignancies than with portal hypertension. An altered sensorium may be due to a metabolic disease. Failure to thrive and hepatomegaly in infancy result from a metabolic disease such as glycogen storage, hereditary fructose intolerance, galactosemia, or cystic fibrosis. If the patient has a distinctive breath or urine odor, consider organic acidemias. Cutaneous hemangiomas or a hepatic bruit suggests hemangiomatosis. Patients who exhibit progressive neurologic deterioration may have glycogen or lipid storage disease or Wilson disease. The constellation of mongoloid facies, hypotonia, and neurologic deterioration suggests Zellweger syndrome, a disorder of peroxisomal function. Coarse facial features are
seen with the mucopolysaccharidoses. Ocular findings of Kayser-Fleischer rings or cataracts occur in Wilson disease. Papular acrodermatitis (or Gianotti-Crosti syndrome) is a selflimiting dermatosis that may be seen in patients who have viral hepatiti s. //pedsinreview.aappublications.org/cgi/content/full/21/9/303
SPLENOMEGALI
Splenomegaly is defined as spleen size >12 cm, a s measured by ultrasound along its longer dimension.[citation needed ] Poulain et al. classify splenomegaly as:
Moderate splenomegaly, if the largest dimension is between 11 – 20 cm Severe splenomegaly, if the largest dimension is greater than 20 cm
Splenomegaly should not be confused with hypersplenism. The former is a statement about the size of the spleen, and the latter about the spleen's function: these may coexist, or they may not. Symptm n sign
Symptoms may include abdominal pain, chest pain, chest pain similar to pleuritic pain when stomach, bladder or bowels are full, back pain, ear ly satiety due to splenic encroachment, or the symptoms of anemia due to accompanying cytopenia. Signs of splenomegaly may include a palpable left upper quadrant abdominal mass or splenic rub. It can be detected on physical examination by using Castell's sign or Traube's space, but an ultrasound can be used to confirm diagnosis.[1]
[edit] Causes The most common causes of splenomegaly in developed countries are infectious mononucleosis, splenic infiltration with cancer cells from a hematological malignancy and portal hypertension (most commonly secondary to liver disease) Also by Bacterial infections, such as syphilis or an infection of the heart's inner lining (endocarditis) .[2] Splenomegaly grouped on the basis of the pathogenic mechanism Increased function Removal of defective RB Cs
spherocytosis thalassemia hemoglobinopathies nutritional anemias
Abnormal blood flow Organ Failu re
cirrhosis
Infiltration M etaboli c diseases
Vascular
Gauchers disease Niemann – Pick disease alpha-mannosidosis Hurler syndrome and other
early sickle cell anemia
I mmune hyperpl asia
Response to infection (viral, bacterial, fungal, parasitic)
mononucleosis, AIDS, viral hepatitis Infections subacute bacterial endocarditis, bacterial hepatic septicemia schistosomias splenic abscess, typhoid is fever hepatic brucellosis, leptospirosis, echinococcosi tuberculosis s histoplasmosis malaria, leishmaniasis, trypanosomiasis ehrlichiosis
hepatic vein obstruction portal vein obstruction Budd – Chiari syndrome splenic vein obstruction
mucopolysaccharidoses amyloidosis Tangier disease
Benign and mali gnant infiltrations
leukemias (acute, chronic, lymphoid, and myeloid) lymphomas (Hodgkins and non-Hodgkins) myeloproliferative disorders metastatic tumors (commonly melanoma) histiocytosis X hemangioma, lymphangioma splenic cysts hamartomas eosinophilic granuloma
Disordered immunoregulation
rheumatoid arthritis SLE serum sickness autoimmune hemolytic anemia sarcoidosis drug reactions
Ex tr amedul l ary hematopoiesi s
myelofibrosis marrow infiltration by tumors, leukemias marrow damage by radiation, toxins
The causes of massive splenomegaly (>1000 g) are much fewer and include:
thalassemia visceral leishmaniasis (kala-azar) schistosomiasis chronic myelogenous leukemia chronic lymphocytic leukemia lymphomas hairy cell leukemia myelofibrosis
polycythemia vera Gauchers disease Niemann – Pick disease sarcoidosis autoimmune hemolytic anemia malaria
Abnormal hepatic function and splenomegaly on the newly diagnosed acute leukemia patients. Sharma Poudel B, Karki L.
Source
Department of Medicine, NAMS, Bir Hospital, Kathmandu, Nepal.
[email protected] Abstract
To evaluate the liver function, splenomegaly and related factors in the newly diagnosed acute leukemia patients. One hundred of fifty eight acute leukemia patients a dmitted in our hospital from March 2003 to April 2006 were studied. The related factors such as peripheral WBC count, bone marrow blasts, peripheral blasts, sex, age, AML, ALL affecting the liver function and splenomegaly were evaluated. Sixty two (39.24%) patients presented with splenomegaly. Twelve (7.59%) patients presented with hepatomegaly. Serum ALT was elevated in 54 (34.17%) patients. Similarly, serum AST, GGT, ALP, and Direct bilirubin were elevated in 26 (16.45%), 32 (20.25%), 20 (12.65%), and 22 (13.92%) patients, respectivel y. Low serum albumin was found in 40 (25.31%) patients. PT was prolonged in 62 (39.24%) patients. Statistical study shows that there is a relation between high WBC counts and elevated serum ALT (P<0.05) and high WBC counts and splenomegaly (P<0.05). Acute l eukemia patients with leukocytosis are more prone to develop abnormal liver function and splenomegaly. http://www.ncbi.nlm.nih.gov/pubmed/18340367
SPLENOMEGALY
Most occurrences of splenomegaly result from one of seven basic mechanisms.
One of the most common of these mechanisms is hyperplasia of cells of the RES system or lymphoid lines. This occurs in many acute systemic infections, in autoimmune disease, viz. Felty's Syndrome and SLE, and in thyrotoxicosis. Common infectious causes of splenomegaly include infectious endocarditis, tuberculosis, infectious mononucleosis, and histoplasmosis. Passive congestive splenomegaly: most often this results f rom hepatic disease, especially cirrhosis (Banti's Syndrome), with portal hypertension. However, thrombosis of the splenic or portal veins and cor pulmonale can have the same effect. Reactive hyperplasia of the RES cells of the red pulp often occurs in congestive splenomegaly, adding further to the size of the spleen. Splenomegaly due to this mechanism is usually asymptomatic. Abnormal RBC morphology (especially hereditary spherocytosis, thalassemias, and early SSA), autoimmune hemolytic anemia, and polycythemia vera can cause trapping of erythrocytes in red pulp sinusoids. This produces congestive splenomegaly, and anemia as well. The finding of anemia alone does not make this diagnosis, however, since splenomegaly from most other causes is accompanied by increased splenic sequestration of RBCs (as well as other formed blood elements); further analysis is required. Splenic hematopoiesis occurs in states of bone marrow insufficiency, most commonly resulting from myeloid metaplasia and the myelophthisic syndromes. In such situations, anemia is generally found in addition to splenomegaly. Malignancies, either metastatic or primar y to the spleen, constitute another major mechanism of splenomegaly. The most common primary splenic cancers are lymphomas (Hodgkin's and non-Hodgkin's), chronic l ymphocytic and granulocytic leukemias, and the acute leukemias. Splenomegaly accompanied by generalized lymphadenopathy suggests lymphoma or CLL. Infiltration of the spleen with abnormal material occurs in a number of diseases, including amyloidosis and various "storage diseases" (e.g. Gaucher's, NeimannPick's). Splenomegaly from this causes is often complicated by reactive hyperplasia of red-pulp macrophages. Various non-neoplastic space-occupying lesions: Hemangiomas, cysts, and hematomas are the most common entities in this category. Others include infectious granulomas (in mycobacterial and fungal disease), non-infectious granulomas (e.g. in sarcoidosis), and infarcts. Ischemic infarcts occur often in SSA, resulting from blockage of splenic sinusoids with deformed RBCs. They also result from cardioemboli, usually from valvular vegetations in SBE or from mural thrombi. 99Tcradionuclide scanning of the spleen is useful in identi fying areas of infarct.
Clinical evaluation:
In the setting of acute illness, splenomegaly is likely to be due to reactive hyperplasia or space-occupying lesions. The spleen tends to be soft on palpation, with blunt edges In chronic illness, the mechanisms of congestion, splenic hematopoiesis, mali gnancy, or infiltrative processes are more probabl. S hard, sharp-edged spleen is often felt. Presentation of splenomegaly with left-upper quadrant pain and splenic tenderness suggests infarction, subcapsular hematoma, or rupture due to trauma or infection (infectious mononucleosis, typhoid fever, and malaria are known to cause splenic rupture). Asymptomatic splenomegaly is commonly due to passive congestion.
Fever accompanying splenomegaly points to an infectious etiology; fever, rash, and arthralgias, however, suggest autoimmune disease.
http://faculty.washington.edu/momus/PB/splenome.htm
Leukemia (with splenomegaly) Introduction: In many lymphoproliferative disorders such as
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leukemia, lymphomas and severe infections such as Epstein Barr virus (= mononucleosis) the spleen can be enlarged to several times the normal size. This enlargement of the spleen is medically c alled " splenomegaly ". The spleen removes red blood cells that are older than 120 days and also old platelets.
The balance can tip and a condition of " hypersplenism" can develop, where one or more of the blood cell types are filtered out by the spleen: red blood cells (causing anemia), white blood cells (causing leukopenia) or platelets (causing thrombocytopenia). This condition calls for a referral to a hematologist to sort out the cause behind this condition and to treat it. Symptoms:
The symptoms can be quite varied depending on the underlying cause of the hypersplenism. If there is a leukemia as the underlying cause, then there would be weight loss and weakness with a high blood cell count, but missing platelets and red blood cells in the blood tests. With a connective tissue disease such as lupus(=systemic lupus erythematosus) there would be joint involvement and possible skin lesions as well as typical blood titres (positive ANA titre). In all of the diseases with an enlarged spleen there would be left upper abdominal pain and breathing with the left lung may be labored due to the diaphragm finding it hard to move against the massive spleen. With thrombocytopenia pin point bleeding of the skin is common(=petechial bleeding). With low white blood cell counts (leukopenia) there is a danger of infections. Anemia presents as tiredness, lack of energy, increased infection rates and delayed wound healing. With cirrhosis of the liver, where the spleen ca n get congested (=congested splenomegaly), there is an increased risk for bleeding from esophageal varices. www.nethealthbook.com/articles/leukemiawithsplenomegaly.php
