Blood Physiology Blood 의구성 1) cellular component (45%) (1) RBC (erythrocyte) (2) WBC (leukocyte) 1 granulocyte : neutrophil eosinophil basophil 2 lymphocyte 3 monocyte (3) platelet (thrombocyte) 2) plasma (55%) (1) plasma protein (7%) 1 albumin 2 globulin - α-globulin β-globulin γ-globulin (immunoglobulin) (2) water (91.5%) (3) others(1.5%) : electrolyte, lipid, enzyme, hormone, vitamin Functions of blood 1) transport of oxygen and carbon dioxide 2) transport of nutrient and metabolite 3) transport of hormone, vitamin, enzyme 4) regulation of body temperature 5) regulation of ph 6) prevention of bleeding 7) body defence blood volume : adult) 6-8% of BW - 정상성인은약 4-6l child) 8-9% of BW
RBC (Red Blood Cell) 1. major function 1 gas 운반 : transport of oxygen - RBC내의 hemoglobin에산소가결합되어 lung에서 tissue로운반 : transport of carbon dioxide - RBC내에많이존재하는 carbonic anhydrase의촉매작용으로 tissue에서 lung으로이산화탄소가운반 2 Acid-base buffer로의기능 : ph 7.4 유지 2. shape and size of the RBC : biconcave disk (1-2um 7.5um) : 핵이없다. 3. concentration of RBC (Normal value of RBC count) : male - 5,200,000 (±300,000) 개 / mm3 (ul) of blood : female - 4,700,000 (±300,000) 개 / mm3 (ul) of blood 4. Hematocrit ratio (=PCV, packed cell volume) : blood volume에서 RBC가차지하는비율 : adult male) 44-46% adult female) 41-43% newborn) 20% higher than female adult child) 10% lower than female adult 5. Quantity of hemoglobin in the cells : RBC 의 Hb 최대농축능력은 34g/100ml of RBC volume - 정상인은최대의농축상태를유지 6. RBC production (=erythropoiesis) : 출생전 : 출생후 - bone marrow - red BM - yellow BM 1) blood cell's genesis : BM 내에 PHSC (pluripotent hematopoietic stem cell) 이분화 ---> commited stem cell - CFU-E CFU-GM CFU-M CFU-L
* growth inducer : stem cell 의 growth and reproduction 을조절하는 protein 으로 4 가지 type - interleukin-3 대표적 * differentiation inducer : stem cell 의분화를촉진 inducer의생산은 bone marrow 외부자극에의해조절 : PHSC --->CFU-E ---> proerythroblast ---> basophilic erythroblast ---> polychromatophil erythroblast ---> orthochromatic erythroblast ---> reticulocyte ---> RBC 2) regulation of RBC production : tissue의 oxygen demand에대한 RBC의 oxygen supply 부족에의해조절 : indication - anemia high altitude cardiac failure lung disease : erythropoietin - 일종의 hormone으로 hypoxia 시에생산증가 - kidney에서생산 ( 약 90%) 3) Maturation of RBC - vit B 12 and folic acid :Vit B 12 - 세포성장의조효소 - DNA 합성에필요한 thymidine triphospastase의생산에필요 - 부족시 1 DNA 생산감소, 2 abnormal DNA : macrocyte : membrane fragility 증가 : cytoskeleton 구성요소에이상 - ileum에서흡수그러나위장관을통할때위산과소화액에의해파괴 - stomach's parietal cell - HCl and intrinsic factor 분비 - Vit B 12 deficiency anemia (pernicious anemia) : atrophic mucosal gastritis, 위절제술환자 8. Hemoglobin 1) Synthesis of hemoglobin : Hb 합성은 mitochondria에서일어남. acetic acid가 Kreb's cycle을거쳐 succinyl CoA가됨. ---> 2 succinyl CoA + 2 glycine ---> pyrrole compound ---> 4 pyrrole ---> protoporphyrin Ⅸ ---> protoporphyrin Ⅸ + Fe ---> Heme ---> Heme + globin ---> Hb chain (subunit)
: 4 of Hb subunit -α, β, γ, δ chain (globin 의 amino 구성에따라 ) 2) Type of hemoglobin : HbA : HbF : HbA1C : HbS 9. Fe 의대사인체내철은약 4g정도있다 - 60% Hb에존재 - 4% myoglobin - 15-30% ferritin or hemosiderin의형태로저장 : Fe - Fe 3+ (Ferric iron) Fe 2+ (Ferrous iron) : Fe 3+ (ferric iron) ------> Fe 2+ (ferrous iron) in stomach : ferrous iron + gastroferritin ---> 소장세포내로이동 --> ferrous iron + transferrin (apotf) 혈액내로이동하여 plasma apotf와결합 ---> BM 으로이동 ---> BM : mitochondria로들어가 Hb 합성에이용 Muscle : myoglobin 합성에이용 mitochondria : cytochrome 합성에이용 : 남는 plasma TF는 liver or tissue macrophage system에저장 ---> liver내의 ferrous iron은 apoferritin과결합하여 ferritin으로저장초과양은 hemosiderin의형태가되어저장. * hemosiderin : 조직에침착된상태로존재하기때문에다시이용할수없다. 10. Bilirubin 대사 : RBC 수명 - 120 일 : RBC 파괴 - spleen's sinusoid (diameter 3 μm )
* conjugated bilirubin unconjugated bilirubin * Van den Bergh test - direct - indirect * Unconjugated bilirubin vs Conjugated bilirubin * Jaundice (=icterus) : hyperbilirubinemia - blood level 2mg/100ml 이상 : kernicterus ( 핵황달 ) - 정상적신생아황달과구분 - RBC 파괴증가 ---> unconjugated bilirubin 증가 : 종류 1) hemolytic jaundice 2) hepatic jaundice 3) posthepatic jaundice Anemia ( 빈혈 ) * Definition : RBC 수 - 4,000,000 개 / mm3이하 or Hb - 10g/100ml 이하 * 종류 1) normocytic anemia - 급성실혈, 용혈성빈혈, 재생불량성빈혈 2) macrocytic anemia - pernicious anemia 3) microcytic anemia - 철분결핍빈혈, hereditary spherocytosis * compensation mechanism 1) Hb-O 2 해리곡선이우측으로이동 2) erythropoietin 증가 3) cardiac output 증가 4) 피부, 근육의혈관수축 적혈구과다증 (Polycythemia) : physiologic polycythemia : polycythemia vera
Blood Groups(Types) ; Transfusion 1. ABO 혈액형 1) A & B antigen - agglutinogen( 응집원 ) : RBC 표면에 A와 B antigen이있고, 그존재여부에따라 4가지 ABO blood types이결정. 이 antigen에대해서 plasma에는 A, B antibody가존재. : A & B antigen은혈액이외에 salivary gland, saliva, pancreas, kidney, liver, lung, testis, semen, amnionic fluid등의조직에존재. 2) Antibody - agglutinin : 대부분 γ- globulin 으로구성 : agglutinin 의역가는나이에따라달라짐. - 출생직후 0 출생후 2-8 개월부터 agglutinin 생산이시작 8-10 세에역가가최고에이름. : titer of agglutinin - agglutinogen 과반응해응집반응을일으킬수있는최대의 serum 희석정도를말한다. Genotype Blood type (phenotype) agglutinogen agglutinin ratio OO O - anti-a & anti-b 45-47% OA or AA A A anti-b (β) 41% OB or BB B B anti-a (α) 9-10% AB AB A & B - 3-4% 2. Rh blood types : Rh antigen 은 C, D, E 가있고, D 가가장 antigenicity 가강하다. D antigen 이있으면 Rh(+), 없으면 Rh(-). : Rh antigen 은 RBC 막에만존재 : ABO의경우는 agglutinin이자연적으로생기나, Rh의경우 antigen에심하게노출되어야 agglutinin이생김. --- by transfusion or pregnancy : Rh 부적합에의한임신시의문제 ( Erythroblastosis fetalis = Hemolytic disease of newborn) - 기전 - 증상
- 유병율 : 1st Rh(+) baby pregnancy - 반응없다. 2nd " - 17% 3rd " - 더높아짐 * 예방법 : 1st Rh(+) baby 를낳은직후인산욕기때 anti-rh antibody (Rh Immune globulin) 을 single 로 mother 에 injuct 해 mother 의 antibody 형성을억제하여예방. 백혈구 ( leukocyte, White Blood Cell ) : 핵이있고, 크기가적혈구보다크다. : 골수와림프절에서생성 : 5,000-10,000 개 /mm3 1) 종류 - granulocyte : neutrophill (62%) : eosinophill (2.3%) : basophill (0.4%) - lymphocyte (30%) : T cell : B cell - monocyte (5.3%)
Plasma - 구성 : 90-91% water 6.5-8% plasma protein (Normal value : 6.5-8g/dl of serum) 2% small molecule (electrolyte 등 ) 1. Electrolyte : 혈액의삼투압중 96% 는 inorganic electrolyte ( 특히 NaCl) 에의한것이며이를 crystalloid osmotic pressure 라고함. 2. Plasma protein : 기능 1 nutrition 2 transport 3 cation 운반 4 colloid osmotic pressure (=oncotic pressure) - albumin이중요 5 buffer 로서의기능 6 bleeding 방지 Hemostasis and Blood Coagulation 1. Event of Hemostasis : Blood loss를막는과정을말하며 4 단계의 mechanism. 1. vascular constriction 2. formation of platelet plug 3. blood coagulation = blood clotting 4. growth of fibrous tissue into the blood clot
1) vascular constriction : 강력한수축이일어나 blood flow를감소 - ateriole 이나 small artery에서강함. mechanism - nervous reflex local myogenic spasm local humoral factor 2) formation of platelet plug : mechanism - platelet adhesion platelet activation platelet aggregation and plug formation : 약하나중요한기전 3) blood coagulation = blood clotting : 손상이심할경우에는 15-20초내에시작하고약할경우 1-2분내에시작 : 손상된혈관벽이나주위조직또는혈소판에서나온 activator substance들과혈액내 clotting protein들이결합하여시작 : basic theory of blood coagulation - procoagulant 와 anticoagulant가균형을이루며인체에존재 : clotting factor Factor I - fibrinogen Factor II - prothrombin Factor III - tissue thromboplastin Factor IV - 칼슘이온 Factor V - proaccelerin Factor VII - proconvertin Factor VIII - antihemophillic factor Factor IX - plasma thromboplastin component (=Christmas factor) Factor X - Stuart-Prower factor Factor XI - plasma thromboplastin antecedent Factor XII - Hageman factor Factor XIII - fibrin-stabilizing factor prekallikrein and kallikrein High molecular weight kininogen (HMWK) platelet phospholipid
4) growth of fibrous tissue into the blood clot 2. Lysis of blood clot (Fibrinolysis) plasmin (plasminogen activated) 3. Prevention of blood clotting in the normal vascular system ( = intravascular anticoagulant) 1) endothelial surface factor 2) thrombin의작용을억제해발생된 clotting의 spread를막는것 3) heparin 4. Bleeding tendency 를초래하는상황들 1) Vit K deficiency : factor II, VII, IX, X 은 liver 에서생산 2) Hemophillia 3) Thrombocytopenia