Transcript 조혈과 조혈기관
조혈과 조혈기관 Hematopoietic Organs • • • • • • Yolk sac (2m) Liver & Spleen (2-7m) BM (pelvis, sternum, vertebra) LN & Thymus Red marrow vs Yellow marrow Extramedullary hematopoiesis Bone Marrow Structure • Hemopoietic area (stem cell & hemopoietic cell) • Microenvironment(stroma) • Vessel(arteriol, sinus, venule) • Trabecular bone • Paratrabecular area • Fat Aging Process of BM BM RBC release 골수의 혈구 분포 (%) Myeloblast 0.1- 3.5 Promyelocyte 0.5- 5.0 Myelocyte 5.0-20.0 Metamyelocyte 10.0-30.0 Band N 5.0-20.0 Segmented N 7.0-25.0 Lymphocyte Monocyte Eosinophils Basophils Megakaryocyte 0.1-0.5 Reticulum cell 0.1-2.0 0.3- 6.0 0 –1.0 5.0-20 0-0.2 Proerythroblast 0.5-5.0 Erythroblast 4.0-30 Plasma cell 0.1-3.5 조혈 능력 1일 적혈구 혈소판 과립구 : : : 20억/kg 20억/kg 8.5억/kg 소요기간 ( 조혈모세포혈구) 적혈구 : 5일 혈소판 : 7일 과립구 : 10일 Stem Cell Sources • BM • PB • • • • Umbilical cord Fetal liver Placenta Yolk sac 조혈모세포 (Stem Cell) CD34+, c-kit+, Sca-1+, Thy-1.1+, CFU-S, CFU-C CFU-GEMM, CFU-GM, CFU-E, CFU-Meg CD34+(CD13+ or -19+) : 5.66% of BM MNC, 1.9% of PB MNC, 1.7% of CB MNC Self-renewal, asymetric division 20 cell divisions produce 106 cells 조혈모세포 분화 단계 Pleuripotent stem cell--------CFUGEMM ---- (repopulating cell) -----BFUE-CFUE---------------normoblast ---------RBC ---- CFU-GMEo--CFUGM--CFU-G --myeloblast--neutrophil CFUM--monoblast ---monocyte CFUEo --myeloblast---eosinophil CFUbaso--myeloblast-----basophil ---- CFUMEG----------------------megakaryoblast---platelet ------Lymphoid stem cell---pre-B lympho--B lymphocyte--plasma cell pre-T lymphocyte---T lymphocyte Bone Marrow Microenvironment • Stromal cells • Extracellular matrix • Hemopoietic growth factor, Stromal Cells • Macrophage, fibroblast, endothelial cell, fat cell, dentritic cell • Characters : type IV collagen+, laminin+, vimentin+, CD10+, muscle actin+, Stro-1+ Extracellular Matrix Fibronectin Hemonectin Laminin Collagen Proteoglycan(haparan etc) Hemopoietic Growth Factors Multipotent stem cells: IL-3, SCF, IL-1, LIF Myeloid progenitors: GM-CSF, G-CSF, M-CSF, Epo, LIF, SCF, IL-3,-4,-5,-6,-9,-11, TPO T-Lymphoid progenitors : IL-2,-4,-6,-7, B-Lymphoid progenitors:IL-2,-3,-5,-6,-7,-11 Stem Cell and Microenvironment Stem Cell and Adhesion Molecules Sources of Hemopoietic Growth Factors Recombinant CSFs Produced by stromal cells, endothelial cells, lymphocytes, fibroblasts, macrophages and epithelial cells. Growth factor receptors and Action Receptors: M-CSFR(c-fms), SCFR(c-kit), IL-R, GM-CSFR, G-CSFR, Epo-R Action: cell division, differentiation commitment , maturation induction , functional activity of mature granulocytes and macrophages, maintaining membrane transport integrity and preventing cell death by apoptosis. Clinical Application of the CSFs • • • • • • • Anemia of chronic renal failure, Neutropenia Thrombocytopenia Following cancer chemotherapy PBSC collection ex vivo BM expansion Stem cell transplantation 조혈능 저하 원인 방사선 조사, 독성 물질: 항암 치료제, 항생제, 항히스타민제, 벤진, 한약제 - 영지, 반하 바이러스 질환 : B형 간염, Parvovirus B19 면역학적 억제 : 재생불량성 빈혈, 혈액 질환 : 백혈병, 암 전이, 골수섬유증 골수 상해(Myeloablation )의 소견 • • • • • • -Serous atrophy -Eosinophilic granular stroma (fibrinoid necrosis) -Increased phagocytic macrophages and fat cells -Dyspoiesis (dyserythropoiesis) -Dilated sinuses -Transient reticulin fibrosis Ablazed BM BM Regeneration, day 14 조혈능력의 판단 CBC : complete blood count RBC, Hb, Hct, WBC, Platelet, Neutrophil, Reticulocyte, Immature reticulocyte Immature granulocyte 골수 재생을 알 수 있는 방법 • Absolute neutrophil count (ANC) • Immature reticulocyte fraction (IRF) • Hemopoietic precusor cells (HPC) Immature Reticulocyte Fraction • • • • Earlier indicator of BM reconstitution High, Middle, Low fluorescence ratio IRF = HFR + MFR =5 - 23% HFR : < 3.3% Immature Granulocyte Scattergram Chemotherapy후 CD34+, HMFR,Neutrophil 증가 • Neutrophil >500 : auto:17d/ allo :20.5d • HFR >2% : 10d/14d • Ret. >20,000 : 13/18.5 조혈세포가 재생되는 순서 시기 • Granulo/Erythroid recovery :1-2 w • Megakaryocyte :2 w Spleen Splenic Sinusoid • RBC transit • RBC phagocytosis