《红细胞与贫血课件.pptx》由会员分享，可在线阅读，更多相关《红细胞与贫血课件.pptx（108页珍藏版）》请在三一文库上搜索。
1、基础血 液 学红细胞与贫血Erythrocyte 带3阴离子运转蛋白 （高丰度跨膜糖蛋白，转运Cl- 水通道蛋白 KCC1, 氯化物-阳离子协同转运蛋白家族KCl协同转运系统 NKCC2, Na-K-Cl协同转运蛋白基底侧分子形式 SK, small conductance potassium channel.小电导钾通道,2. Cell Membrane,红细胞与贫血,Membrane Function membrane antigenicity and immunologic function, Blood group antigens are associated with the re
2、d cell membrane and are either integral to its structure or are adsorbed onto it from the plasma. They are made of proteins or carbohydrates. senescent cell antigen, SCA（老化抗原）,2. Cell Membrane,红细胞与贫血,ANTIGENS ON RBC MEMBRANE,Membrane Function membrane antigenicity and immunologic function,2. Cell Me
3、mbrane,红细胞与贫血,Membrane Function receptors,hormone receptors：insulin，glucagon Neurotransmitter receptors：noradrenaline Virus receptors：flu. receptor others：TfR，EPO receptor,2. Cell Membrane,红细胞与贫血,2. Cell Membrane (disease),Hereditary Spherocytosis, Elliptocytosis （遗传性球形红细胞增多症，椭圆形红细胞增多症）,abnormal spe
4、ctrin gene reduced spectrin synthesis or dysfunctional spectrin spherocytes or elliptocytes,遗传性球形红细胞增多症是一种以外周血涂片成熟红细胞呈球形、网织红细胞增多和脾脏肿大为特征的先天性溶血性贫血。红细胞在通过脾脏微循环时，由于细胞膜丢失和膜面积缩小而呈球形样改变并伴有变形可塑性降低。失去变形能力的红细胞在脾脏被破坏最终导致贫血。,红细胞与贫血,Hereditary Spherocytosis, Elliptocytosis （遗传性球形红细胞增多症，椭圆形红细胞增多症）,遗传性球形红细胞增多症病理生
5、理学。 HS主要缺陷为细胞膜丢失，膜面积减少，表面积减少， 导致细胞球形变，变形能力减弱。,2. Cell Membrane (disease),红细胞与贫血,the process of spherocytosis in hereditary spherocytosis,Hereditary Spherocytosis, Elliptocytosis,2. Cell Membrane (disease),红细胞与贫血,The Congenital Dyserythropoietic Anemias（CDA） 先天性红细胞生成异常性贫血,先天性红细胞生成异常性贫血（CDA）是指一类罕见的，以红
6、系无效造血，多核红细胞和组织内铁蓄积为特征的遗传性难治性贫血。可分为、型。,先天性红细胞生成异常性贫血（CDA）型中 带3蛋白-N-乙酰乳糖聚糖链合成不足， 而鞘磷脂表现为过度糖基化。,2. Cell Membrane (disease),红细胞与贫血,Lipids,PS exposure 磷脂酰丝氨酸外翻,磷脂酰丝氨酸外翻可启动凝血活化途径 PS exposure to trigger thrombosis,磷脂酰丝氨酸外翻可被巨噬细胞识别并吞噬 PS exposure to be recognizedandphagocytized by macrophage,2. Cell Membran
7、e (disease),红细胞与贫血,Alteration in lipid composition can produce target cells or acanthocytes.,靶形红细胞,棘形红细胞,Lipids,2. Cell Membrane (disease),红细胞与贫血,3. Cell Metabolism,红细胞与贫血,metabolic changes in erythropoiesis,3. Cell Metabolism,红细胞与贫血,3. Cell Metabolism,HAEMOGLOBIN 血红蛋白,Haemoglobin, MW 68,000Da 96% o
8、f the red blood cells dry weight 65% of haemoglobin synthesis occurs during the nucleated stages of RBC maturation and 35% occurs during the reticulocyte stage,红细胞与贫血,HAEMOGLOBIN Structure,3. Cell Metabolism,红细胞与贫血,HAEMOGLOBIN Function,3. Cell Metabolism,Iron atom in each heme can bind to one O2 mol
9、ecule Each Hb molecule can transport four O2 Hemoglobin binds reversibly with oxygen O2 loading in the lungs Produces oxyhemoglobin（氧合血红蛋白） (ruby red) O2 unloading in the tissues Produces deoxyhemoglobin（脱氧血红蛋白） or reduced hemoglobin (dark red) CO2 loading in the tissues Produces carbaminohemoglobin
10、 （氨基甲酰血红蛋白）(carries 20% of CO2 in the blood),红细胞与贫血,HAEMOGLOBIN Globin（珠蛋白）,3. Cell Metabolism,Hemoglobin Genes and Gene Products 、,红细胞与贫血,Mehta, A. B., and A. V. Hoffbrand. 2000. Haematology at a glance, Blackwell Science, Malden, Mass.,3. Cell Metabolism,Hemoglobin Genes and Gene Products,HAEMOGLO
11、BIN Globin（珠蛋白）,红细胞与贫血,Embryonic haemoglobins include Gower 1, Gower 2 and Hb Portland. HbF is the predominant haemoglobin of fetal life (65-95%). Adults have only trace amounts of HbF (95%) and HbA2 (2.5-3.5%) are the main adult haemoglobins.,3. Cell Metabolism,Six Hb variants are normally formed.,
12、HAEMOGLOBIN Globin（珠蛋白）,红细胞与贫血,3. Cell Metabolism,Hemin can accelerate the synthesis 珠蛋白的合成受血红素调节,HRI，Heme-regulated eIF2 kinase； eIF，eukaryote Initiation factor； eIF-2B ，eIF-2B GDP-GTP exchange factor,HAEMOGLOBIN Globin（珠蛋白）,红细胞与贫血,HAEMOGLOBIN HEME（血红素）,3. Cell Metabolism,红细胞与贫血,HAEMOGLOBIN HEME（血红
13、素）,3. Cell Metabolism,HEME consists of four pyrrole rings （吡咯环）with a central iron atom linked to the four nitrogen atoms. The iron atom has two further binding sites, one of which is bound to a globin histidine residue and the other binds reversibly to oxygen.,红细胞与贫血,3. Cell Metabolism,HAEMOGLOBIN
14、HEME（血红素）,血红素合成的限速酶： ALA synthase， aminolevulinic acid合酶 (-氨基-酮基戊酸合酶) 辅酶： 磷酸吡哆醛（Vit B6）,红细胞与贫血,3. Cell Metabolism,Regulation of ALA Synthase （ALA合酶的调节） Level of enzyme synthesis （ALA合酶的表达水平） Enzyme synthesis, as well as its transport to the mitochondria, is inhibited by elevated levels of heme and h
15、emin (the Fe3+ oxidation product of heme) （过量的血红素高铁血红素抑制酶合成） Enzyme synthesis is upregulated by a large number of drugs including barbiturates, steroids (e.g. testosterone) and some oral contraceptives. （巴比妥类药物，类固醇，睾丸素，口服避孕药） Level of enzyme activity （ALA合酶的酶活性） Heme （血红素）and hemin（高铁血红素） inhibit AL
16、A synthase activity Requires pyridoxal phosphate (Vitamin B6，磷酸吡哆醛) as a coenzyme,HAEMOGLOBIN HEME（血红素）,红细胞与贫血,3. Cell Metabolism (disease),PORPHYRIAS 卟啉症,卟啉病是由于血红素生物合成途径中酶缺陷导致反应过程中间代谢产物过量生成与蓄积，并引发神经系统症状和（或）关照性皮肤症状等疾患,血红素生物合成途径中各种酶与中间代谢产物，以及与酶缺乏相对应的卟啉病类型。,红细胞与贫血,Chronic infections and inflammatory d
17、isorders cause chronic anaemia as a result of; 1. slightly shortened red blood cell life span 2. sequestration of iron in inflammatory cells called macrophages Both procedures result in a decrease in the amount of iron available to make red blood cells.,3. Cell Metabolism (disease),红细胞与贫血,HEMOGLOBIN
18、OPATHY 血红蛋白病,血红蛋白病是全球最常见的遗传性红细胞疾病。 是指珠蛋白生成障碍贫血（珠蛋白合成不足）和 异常血红蛋白病（珠蛋白一级结构中氨基酸突变）， 以地中海贫血和镰状细胞综合征为主。 可导致中度到重度贫血。,3. Cell Metabolism (disease),红细胞与贫血,地中海贫血以一条或多条珠蛋白链合成缺陷的遗传性疾病。包括和-地中海贫血。由于珠蛋白链合成的不平衡，导致无效红细胞生成，溶血和不同程度的贫血。,HEMOGLOBINOPATHY-Thalassemias （地中海贫血）,3. Cell Metabolism (disease),红细胞与贫血,HEMOGLOB
19、INOPATHY-Thalassemias （地中海贫血）,地中海贫血，过多的 链形成 4分子（HBH）（可溶）,-地中海贫血，过多的链（不可溶）致红细胞损伤，造成重度贫血。,3. Cell Metabolism (disease),红细胞与贫血,HEMOGLOBINOPATHY-Thalassemias （地中海贫血）,3. Cell Metabolism (disease),红细胞与贫血,HEMOGLOBINOPATHY-Sickle cell anemia (镰状细胞贫血),3. Cell Metabolism (disease),红细胞与贫血,镰状细胞综合征是-珠蛋白链第6位氨基酸谷氨
20、酸被缬氨酸所替代，导致血红蛋白分子脱氧时变得不可溶，形成HBS多聚体，改变了红细胞的正常结构，使红细胞呈僵硬，并由双凹圆盘状变为镰刀形。这类红细胞变形能力差，易破损溶血，导致血管阻塞、组织缺氧、损伤、坏死。,Genetics of Sickle Cell Anemia,HEMOGLOBINOPATHY-Sickle cell anemia (镰状细胞贫血),3. Cell Metabolism (disease),红细胞与贫血,Hemoglobin Electrophoresis,Relative protein charge,Start (samples applied here),Anod
21、e (+),Cathode (-),HEMOGLOBINOPATHY-Sickle cell anemia,3. Cell Metabolism (disease),红细胞与贫血,HEMOGLOBINOPATHY-Sickle cell anemia,3. Cell Metabolism (disease),红细胞与贫血,Schema summarizing the pathophysiology of sickle cell anemia. K+, potassium; NO, nitric oxide; PS, phosphatidylserine; RBC, red blood cell
22、; ROS, reactive oxygen species; TF, tissue factor; WBC, white blood cell; XO, xanthine oxidase.,HEMOGLOBINOPATHY-Sickle cell anemia,3. Cell Metabolism (disease),红细胞与贫血,metabolic changes in erythropoiesis,3. Cell Metabolism,红细胞与贫血,3. Cell Metabolism,Glycometabolism,Mature red cells no mitochondrial a
23、pparatus for oxidative metabolism-Red cells deliver oxygen, not consume it Limited Glucose as a source of energy Glycolysis generates ATP and 2,3-bisphosphoglycerate （2,3-二膦酸甘油酸，2,3-DPG） The pentose phosphate pathway produces NADPH Glutathione synthesis (谷胱甘肽合成) the antioxidant defense system,红细胞与贫血
24、,Energy required for: Maintenance of cation pumps Maintenance of RBC integrity and deformability Reduce oxidants in the system Maintenance of HB in reduced state Maintenance of reduced sulfhydryl groups in HB and other proteins,3. Cell Metabolism,Glycometabolism,红细胞与贫血,Key Metabolic Pathways for the
25、 Erythrocyte,Glycolysis or Embden-Meyerhof pathway （糖酵解，恩-迈氏途径） Rapaport-Luebering Shunt（2,3-DPG支路，2，3二膦酸甘油酸支路） Hexose Monophosphate Shunt（磷酸戊糖途径，磷酸己糖支路） Methemoglobin reductase pathway （高铁血红蛋白还原酶途径）,3. Cell Metabolism,红细胞与贫血,Key Metabolic Pathways for the Erythrocyte,Glycolysis or Embden-Meyerhof p
26、athway 糖酵解（恩-迈氏途径）,3. Cell Metabolism,红细胞与贫血,Key Metabolic Pathways for the Erythrocyte,Glycolysis or Embden-Meyerhof pathway （糖酵解，恩-迈氏途径） Generates 90- 95% of energy needed by RBCs Glucose is metabolized and generates two molecules of ATP (energy). Functions in the maintenance of RBC shape, flexibi
27、lity and the cation pumps,3. Cell Metabolism,红细胞与贫血,Key Metabolic Pathways for the Erythrocyte,Rapaport-Luebering Shunt （2,3-DPG支路，2，3二膦酸甘油酸支路）,3. Cell Metabolism,1,3-二膦酸甘油酸,二膦酸甘油酸变位酶,3膦酸甘油酸,2，3-二膦酸甘油酸,红细胞与贫血,Key Metabolic Pathways for the Erythrocyte,3. Cell Metabolism,Rapaport-Luebering Shunt （2,3
28、-DPG支路，2，3二膦酸甘油酸支路）,红细胞与贫血,Key Metabolic Pathways for the Erythrocyte,3. Cell Metabolism,Rapaport-Luebering Shunt （2,3-DPG支路，2，3二膦酸甘油酸支路）,红细胞与贫血,Key Metabolic Pathways for the Erythrocyte,Rapoport- Luebering Shunt （ 2,3-DPG支路，2，3二膦酸甘油酸支路） Allows the RBC to regulate oxygen transport during conditions
29、 of hypoxia or acid-base imbalance. Permits the accumulation of 2,3-DPG which is essential for maintaining normal oxygen tension, regulating hemoglobin affinity,3. Cell Metabolism,红细胞与贫血,Key Metabolic Pathways for the Erythrocyte,3. Cell Metabolism,Hexose Monophosphate Shunt （磷酸戊糖途径，磷酸己糖支路）,红细胞与贫血,K
30、ey Metabolic Pathways for the Erythrocyte,3. Cell Metabolism,Hexose Monophosphate Shunt （磷酸戊糖途径，磷酸己糖支路）,红细胞与贫血,Key Metabolic Pathways for the Erythrocyte,3. Cell Metabolism,Hexose Monophosphate Shunt （磷酸戊糖途径，磷酸己糖支路）,红细胞与贫血,Key Metabolic Pathways for the Erythrocyte,Metabolizes 5-10% of glucose. NADP
31、H is end product Protects the RBC from oxidative injury. If the pathway is deficient, intracellular oxidants cant be neutralized , and then globin denatures and precipitates. The precipitates are referred to as Heinz bodies. Most common defect is deficiency of the enzyme glucose-6-phosphate dehydrog
32、enase (G-6PD，葡萄糖-6-磷酸脱氢酶).,3. Cell Metabolism,Hexose Monophosphate Shunt （磷酸戊糖途径，磷酸己糖支路）,红细胞与贫血,In red cells, there is a Met Hb reductase (高铁血红蛋白还原酶) which can use NADH to regenerate Hb,Key Metabolic Pathways for the Erythrocyte,Methemoglobin reductase pathway （高铁血红蛋白还原酶途径）,3. Cell Metabolism,红细胞与贫血
33、,Key Metabolic Pathways for the Erythrocyte,Maintains iron in the ferrous (Fe+) state. In the absence of the enzyme (methemoglobin reductase), methemoglobin accumulates and it cannot carry oxygen.,3. Cell Metabolism,Methemoglobin reductase pathway （高铁血红蛋白还原酶途径）,红细胞与贫血,Key Metabolic Pathways for the
34、Erythrocyte,3. Cell Metabolism,红细胞与贫血,3. Cell Metabolism (Disease),Disorders of Red Cells Resulting from Enzyme Abnormalities酶异常导致的红细胞疾病,Glucose-6-phosphate dehydrogenase (G6PD) deficiency 6-磷酸葡萄糖脱氢酶缺乏是最常见的红细胞酶缺陷，溶血发作只有在感染或应用“氧化性”药物，以及某些进食蚕豆等应激时才发生。临床上最严重的并发症是新生儿黄疸。,红细胞与贫血,Disorders of Red Cells Res
35、ulting from Enzyme Abnormalities,3. Cell Metabolism (Disease),红细胞与贫血,Disorders of Red Cells Resulting from Enzyme Abnormalities,Pyruvate kinase deficiency 丙酮酸激酶缺陷是引起非球形红细胞溶血性贫血的常见原因。,3. Cell Metabolism (Disease),红细胞与贫血,3. Cell Metabolism,iron metabolism,铁分布,红细胞与贫血,iron metabolism,3. Cell Metabolism,
36、铁的出入平衡,红细胞与贫血,iron metabolism,3. Cell Metabolism,人体铁循环 铁在一个几乎完全封闭的系统内紧密保存。,红细胞与贫血,3. Cell Metabolism,iron metabolism,铁的吸收,肠绒毛细胞从肠道摄入铁并转运到血浆 DMT-1，二价金属离子运转蛋白 Ferritin，铁蛋白 Ferroportin，膜铁运转蛋白 Hephaestin，膜铁转运辅助蛋白,红细胞与贫血,iron metabolism,红细胞与贫血,3. Cell Metabolism (disease),Disorders of Iron Metabolism 铁代谢
37、异常,铁缺乏和缺铁性贫血是常见的营养性和血液学疾病。 铁缺乏是体内铁含量低于正常的一种状态。 铁缺乏的原因： 慢性失血 饮食中铁摄入不足（婴幼儿铁缺乏） 妊娠和哺乳（铁转移至胎儿和婴儿的红系造血） 铁吸收不良 血管内溶血伴血红蛋白尿 铁向非造血组织转移 遗传因素 铁减少储存铁减少血清铁浓度和转铁蛋白饱和度降低缺铁性贫血,红细胞与贫血,Disorders of Iron Metabolism 铁代谢异常,成人缺铁性贫血红细胞指标。 虚线为平均血红蛋白浓度（MCHC）的下限值。 静脉血红蛋白浓度和MCHC之间的相关性（50%）。,成人缺铁性贫血红细胞指标。 静脉血红蛋白浓度和平均红细胞体积（MCV
38、）之间的相关性（70%）。 对于缺铁状态改变，MCV比MCHC更敏感。,50%,70%,3. Cell Metabolism (disease),红细胞与贫血,Disorders of Iron Metabolism 铁代谢异常,凹甲，手指甲的成嵴、变薄和勺状凹陷。,3. Cell Metabolism (disease),红细胞与贫血,Disorders of Iron Metabolism 铁代谢异常,血涂片 A 正常血涂片 形态正常正细胞色素性红细胞 B 轻度铁缺乏 少量中心淡然区扩大的红细胞，少量呈卵圆或椭圆形 C 重度铁缺乏 显著低色素的细胞明显增加且小细胞更多见,3. Cell M
39、etabolism (disease),红细胞与贫血,3. Cell Metabolism,Nucleotide Metabolism（核苷酸代谢DNA合成）,Pathways of deoxynucleoside and DNA synthesis 脱氧核苷酸和DNA合成途径,胸腺嘧啶,叶酸的活性形式四氢叶酸作为一碳单位的载体参与DNA合成,红细胞与贫血,3. Cell Metabolism,Nucleotide Metabolism,高半胱氨酸,胸腺嘧啶核苷酸合酶,亚甲基四氢叶酸,甲基四氢叶酸,二氢叶酸还原酶,叶酸,红细胞与贫血,folic acid (叶酸) vitamin B12, 钴
40、胺素),蝶呤啶,对氨基苯甲酸,谷氨酸,人体不能合成叶酸，必须由食物供给。主要在绿色蔬菜、香蕉等水果。,Vit B12 只存在于动物食品中。,红细胞与贫血,3. Cell Metabolism,Nucleotide Metabolism,内因子,红细胞与贫血,叶酸，钴胺素和巨幼红细胞贫血 FOLATE, COBALAMIN, AND MEGALOBLASTIC ANEMIAS,deficiency of vitamin B12 or folic acid anemia or pancytopenia caused by impaired DNA synthesis affects all mar
41、row elements,血涂片 恶性贫血 卵圆形大红细胞，并有异形细胞,骨髓片 恶性贫血 幼红细胞体积变大及核质发育不平衡,3. Cell Metabolism (disease),红细胞与贫血,Fate and Destruction of Erythrocytes,4. Cell Aging,Macrophages engulf dying RBCs in the spleen Old RBCs become fragile, and Hb begins to degenerate heme bilirubin secreted in bile by liver iron recycle
42、d globulin amino acids,Life span: 100120 days cellular function ability to deform in capillaries risk of rupture,Bilirubin indirect: unconjugated, not water soluble formed during initial destruction binds with albumin for transport to liver direct: conjugated, water soluble formed in liver and excre
43、ted in bile,红细胞与贫血,5. RBC Diseases,Polycythemia excess of RBCs that increase blood viscosity Polycythemia verabone marrow cancer Secondary polycythemiawhen less O2 is available (high altitude) or when EPO production increases Blood doping,红细胞与贫血,5. RBC Diseases,Anemia blood has abnormally low O2-car
44、rying capacity a symptom of a pathologic process (not a specific disease) Blood O2 levels cannot support normal metabolism Accompanied by fatigue, paleness, shortness of breath, and chills,红细胞与贫血,5. RBC Diseases,Anemia,physiologic definition: decrease in oxygen carrying capacity and thus oxygen avai
45、lability to tissues is a lab term that indicates low RBC count decreased hemoglobin decreased hematocrit,Laboratory Diagnosis,红细胞与贫血,WHOs Hemoglobin thresholds used to define anemia(1g/dL=0.6206mmol/L),5. RBC Diseases,Anemia,红细胞与贫血,Anemia Scale（Hb level in g/L）,grade scale 1(mild) 91g/Llower limit o
46、f normal 2(moderate) 61g/L90g/L 3(severe) 31g/L60g/L 4(life-threatening) 30g/L,5. RBC Diseases,Anemia,红细胞与贫血,5. RBC Diseases,Anemia,Causes of Anemia BLOOD LOSS ACUTE CHRONIC IN-creased destruction (HEMOLYTIC) DE-creased production,红细胞与贫血,5. RBC Diseases,Anemia Classification,Depends on: 1- Aetiology
47、 decreased production/increased destruction/ Inappropriate loss of RBCs 2- morphology of RBCs microcytic/normocytic/macrocytic 3- Bone marrow evaluation hyperplastic/hypoplastic,红细胞与贫血,Hemolysis (Hemolytic Anemia),5. RBC Diseases,红细胞与贫血,Hemolysis (Hemolytic Anemia),Anemia of increased destruction an
48、y situation resulting in accelerated destruction of RBCs the erythropoiesis in bone marrow in a decompensated status normochromic anemia shortened RBC survival reticulocytosis - Response to increased RBC destruction increased indirect bilirubin increased LDH,5. RBC Diseases,红细胞与贫血,clinical features
49、of anaemiaGeneral symptoms and signs,General Signs Pallor of mucous membranes (most common sign). This is a general sign.,Nail bed; demonstrating koilonychia (spoon-shaped nails). This is specific to iron deficiency.,Atrophic glossitis; red large swollen tongue. This is seen in both vitamin B12 and folate deficiency.,Angular stomitis; fissuring at corners of mouth. This is seen in both vitamin B12 and folate deficiency.,Dysphagia: pharyngeal web (Paterson-Kelly syndrome). This occurs in iron deficiency.,Peri