臨床藥理學(xué) 血液系統(tǒng)

血液系統(tǒng)由血液與造血器官組成。血液由血漿及懸浮其中的血細(xì)胞(紅細(xì)胞、白細(xì)胞及血小板)組成。出生后，主要的造血器官是骨髓、胸腺、脾和淋巴結(jié)。血細(xì)胞是體內(nèi)更新最快的細(xì)胞。血細(xì)胞的更新有賴于正常的骨髓造血功能。

血液系統(tǒng)疾病指原發(fā)或主要累及血液和造血器官的疾病。紅細(xì)胞的不足和功能障礙導(dǎo)致貧血。白細(xì)胞或血小板過(guò)少也將產(chǎn)生白細(xì)胞減少癥或出血性紫癜。血漿中有大量的由肝臟產(chǎn)生的凝血因子，它們和血小板功能的異常將導(dǎo)致出凝血疾病。 血液系統(tǒng)最常見(jiàn)的疾病是貧血和白血病。血液系統(tǒng)疾病貧血 貧血與發(fā)熱、高血壓一樣，為一種病癥或綜合征，而非為單一的疾病。各種原因造成的血細(xì)胞總數(shù)或血紅蛋白量不足為貧血。貧血的原因很多，可由遺傳因素造成的各種血紅蛋白病，可由各種造血原料缺乏，可由慢性疾病、感染、放射線和中毒等造成骨髓抑制，可由外傷、鉤蟲病、痔瘡等致慢性出血也可由藥物、免疫等各種因素產(chǎn)生溶血所致。 最常見(jiàn)的貧血為缺鐵性貧血和慢性病(如慢性腎炎)所致的造血機(jī)能抑制的貧血。造血物質(zhì)缺乏性貧血造血原料缺乏(主要為鐵、葉酸和維生素B12)鐵缺乏——缺鐵性貧血葉酸、維生素B12缺乏——巨幼細(xì)胞貧血內(nèi)因子、維生素B12缺乏——惡性貧血Hematopoiesisrequiresanadequatesupplyofminerals(e.g.,iron,cobalt,andcopper)andvitamins(e.g.,

folicacid,vitaminB12,pyridoxine,ascorbicacid,andriboflavin).缺鐵性貧血是最常見(jiàn)的貧血病中的—種，其病因大致有：鐵的供應(yīng)不足，例如營(yíng)養(yǎng)缺乏等；機(jī)體吸收不良，例如消化道疾病，胃癌等；利用太多，如妊娠期、哺乳期等；丟失過(guò)多，例如鉤蟲病、痔瘡、月經(jīng)過(guò)多等一、缺鐵性貧血體內(nèi)鐵含量mg/kgofBODYWEIGHTMaleFemaleEssentialiron

Hemoglobin3128Myoglobinandenzymes65Storageiron

134Total5037體內(nèi)鐵的動(dòng)態(tài)平衡。腸上皮的鐵循環(huán)。Systemicironhomeostasis.Hepcidinregulatescellularironexportintoplasma.缺鐵性貧血的連續(xù)改變(REmarrowFe,reticuloendothelialhemosiderin)特點(diǎn)：小細(xì)胞、低色素網(wǎng)織紅細(xì)胞增多血清鐵降低總鐵結(jié)合力升高轉(zhuǎn)鐵蛋白飽和度降低。治療補(bǔ)充鐵劑：口服硫酸亞鐵、葡萄糖酸鐵等。同服維生素C。一次攝入過(guò)多可致鐵中毒，一般不注射鐵劑。增加營(yíng)養(yǎng)：缺鐵患者，常有蛋白質(zhì)等營(yíng)養(yǎng)缺乏，故同時(shí)應(yīng)注意改善飲食，增加蛋白質(zhì)及水果等攝入，因維生素C可促進(jìn)鐵的吸收。去除病因：將可以引致病人發(fā)生缺鐵的原因設(shè)法去除，如治療胃腸道疾病，終止慢性失血，合理安排飲食等。Thepatient'sabilitytotolerateandabsorbmedicinalironisakeyfactorindeterminingtherateofresponsetotherapy.Normalironabsorptionisabout1mgperdayinadultmenand1.4mgperdayinadultwomen;3to4mgofdietaryironisthemostthatnormallycanbeabsorbed.Thisprovidesanaturalceilingonhowmuchironcanbesuppliedbyoraltherapy.Inthepatientwithamoderatelysevereiron-deficiencyanemia,tolerabledosesoforalironwilldeliver,atmost,40to60mgofironperdaytotheerythroidmarrow.不良反應(yīng)Sideeffectsincludeheartburn,nausea,uppergastricdiscomfort,anddiarrheaorconstipation.Agoodpolicyistoinitiatetherapyatasmalldosage,todemonstratefreedomfromsymptomsatthatlevel,andthengraduallytoincreasethedosagetothatdesired.Largeamountsofferroussaltsaretoxic,butfatalitiesarerareinadults.Mostdeathsoccurinchildren,particularlybetweentheagesof12and24months.Aslittleas1to2gofironmaycausedeath.二、營(yíng)養(yǎng)性巨幼細(xì)胞貧血 巨幼細(xì)胞貧血，簡(jiǎn)稱巨幼貧，為細(xì)胞DNA合成障礙，骨髓及外周圍細(xì)胞呈特殊巨型改變的大細(xì)胞性貧血，主要原因是葉酸和／或維生素B12缺乏，故稱之為營(yíng)養(yǎng)性巨幼細(xì)胞貧血。惡性貧血也是一種維生素B12缺乏的巨幼貧、但有其自身特點(diǎn)，是由于胃粘膜分泌內(nèi)因子缺陷所致，與其他巨幼貧有區(qū)別。還有少數(shù)與葉酸或維生素B12無(wú)關(guān)。惡性貧血：內(nèi)因子和維生素B12。治療：補(bǔ)充葉酸補(bǔ)充維生素B12(注射給藥)內(nèi)因子(口服保健品)藥效?血細(xì)胞生長(zhǎng)因子發(fā)生障礙再生障礙性貧血慢性腎臟疾病引起的貧血腫瘤化療引起的貧血慢性炎癥引起的貧血血細(xì)胞的發(fā)生多能造血干細(xì)胞紅細(xì)胞系粒細(xì)胞系淋巴細(xì)胞系單核細(xì)胞系巨核細(xì)胞（血小板）系HematopoiesisandhematopoieticgrowthfactorsHematopoieticstemcellsareraremarrowcellsthatmanifestself-renewalandlineagecommitment,resultingincellsdestinedtodifferentiateintotheninedistinctblood-celllineages.Forthemostpart,thisprocessoccursinthemarrowcavitiesoftheskull,vertebralbodies,pelvis,andproximallongbones;itinvolvesinteractionsamonghematopoieticstemandprogenitorcellsandthecellsandcomplexmacromoleculesofthemarrowstroma,andisinfluencedbyanumberofsolubleandmembrane-boundhematopoieticgrowthfactors.血細(xì)胞的發(fā)生和相關(guān)造血生長(zhǎng)因子造血生長(zhǎng)因子產(chǎn)量的變化和調(diào)節(jié)Redbloodcellproductioncanincreasemorethantwentyfoldinresponsetoanemiaorhypoxemia,缺氧、貧血whitebloodcellproductionincreasesdramaticallyinresponsetoasystemicinfection,感染plateletproductioncanincreaseten-totwentyfoldwhenplateletconsumptionresultsinthrombocytopenia.血小板減少促紅細(xì)胞生成素ErythropoietinErythropoietinisencodedbyageneonhumanchromosome7thatisexpressedprimarilyinperitubularinterstitialcellsofthekidney.Erythropoietincontains193aminoacids,ofwhichthefirst27arecleavedduringsecretion.Thefinalhormoneisheavilyglycosylatedandhasamolecularmassofapproximately30,000daltons.促紅細(xì)胞生成素生成的調(diào)節(jié)Erythropoiesisiscontrolledbyahighlyresponsivefeedbacksysteminwhichasensorinthekidneydetectschangesinoxygendeliverytomodulatetheerythropoietinsecretion.Thesensormechanismisnowunderstoodatthemolecularlevel.Hypoxia-induciblefactor(HIF-1)Hypoxia-induciblefactor(HIF-1)Hypoxia-induciblefactor(HIF-1)isaheterodimeric(HIF-1aandHIF-1b)transcriptionfactorthatenhancesexpressionofmultiplehypoxia-induciblegenes,suchasvascularendothelialgrowthfactoranderythropoietin.HIF-1aislabileduetoitsprolylhydroxylationandsubsequentpolyubiquitinationanddegradation,aidedbythevonHippel-Lindau(VHL)protein.Duringstatesofhypoxia,theprolylhydroxylaseisinactive,allowingtheaccumulationofHIF-1aandactivatingerythropoietinexpression,whichinturnstimulatesarapidexpansionoferythroidprogenitors.再生障礙性貧血(aplasticanemia) 是一種骨髓造血的功能過(guò)度抑制性疾病，表現(xiàn)為全血細(xì)胞的減少。其病理機(jī)制呈高度異質(zhì)性，不同的患者有不同的發(fā)病機(jī)制。近年來(lái)大量的研究資料表明，免疫功能障礙及細(xì)胞因子分泌紊亂參與再障發(fā)病。骨髓造血微環(huán)境受到破壞。治療：雄激素特異性免疫抑制劑，環(huán)孢毒素A、抗胸腺球蛋白骨髓移植集落刺激因子、促紅細(xì)胞生成素等造血生長(zhǎng)因子的長(zhǎng)期療效不明顯。AplasticAnemia:AGeneralOverviewAplasticanemiahasbeensuccessfullytreatedinmodernpracticeswithsibling-matchedHLAallogeneicbonemarrow/stemcelltransplantation.Long-termsurvivalforpatientswhosuccessfullyundergoallogeneictransplantationhasbeenreportedtobeashighas92%,comparedwithanequallyimpressivesu