Chapter 02. RBC ( 적혈구 ) RBC/red blood cell/erythrocyte O 전체혈액량의 42-47% (hematocrit) O 6-8 um O biconcave shape O anucleated cell O color; red (hemoglobin) O gas exchange (oxygen, carbon dioxide) O disease: 빈혈 (anemia), 적혈구증가증 (erythrocytosis)

01. Differentiation of erythrocyte Step of differentiation O Pluripotential (pluripotent, multipotential) stem cell O Myeloid stem cell (common myeloid progenitor cell) O BFU (burst forming unit)-E O CFU (colony forming unit)-E O Erythroblast ( 적혈모구 : 이때부터 형태학적으로 구별가능 ) - Pronormoblast ( 풋정상적혈모구 ): - Basophilic normoblast ( 호염기적혈모구 ): - Polychromatic normoblast ( 다염적혈모구 ): - Orthochromatic normoblast ( 정염적혈모구 ): O Reticulocte ( 그물적혈구, 망상적혈구, 어린적혈구 ): O Mature RBC:

Erythropoietin ( 조혈소 ) O 적혈구생성 촉진인자 O 분자량 : 35,000 dalton O alpha2-globulin, glycoprotin O in plasma; 3-8 mU/ml (1-4mU/ml in urine) O synthesis: kidney – proximal tubular cell 근위뇨세관 세포, peritubular interstitial cell 관주위간질세포 liver – Kupffer cell (20%) O 합성증가 : 동맥혈 산소분압 감소, 내분비자극 ( 산, 염기평형변화, 출혈증가 )

O 적아구 성숙에 따른 특징 - Pronormoblast -> mature RBC : 4-6 days - chromatin: fine -> coarse -> condensation (clumping) - nucleolus: O -> X - cytoplasm: blue -> red - cell size 대 -> 소 - nucleus/cytoplasm ratio: 대 -> 소 - Proliferation O -> X ( 감소 ) - hemoglobin X -> O ( 증가 ) - RNA O -> X ( 감소 ) - 비중 소 -> 대

02. Maturation of normoblast 풋정상적혈모구 (pronormoblast, rubriblast) O size: um, 적혈모구중 가장 큼 O cytoplasm: 진한청색 (dark blue), 무과립 (peroxidase negative) O Chromatin: fine O nucleolus: 1-3 개 O N/C ratio: 8:1 O 정상골수 : 1% 호염기적혈모구 (basophilic normoblast, prorubricyte) O size: um O cytoplasm: 옅은청색 (pale blue) O Chromatin: 과립상 (granular), 차륜상 (cartwheel) O nucleolus: X O N/C ratio: 4-6:1 O 정상골수 : 1-4%

다염적혈모구 (polychromatic normoblast, rubricyte) O size: 9-12 um O cytoplasm: 적청색 (reddish blue), 다염성 (RNA+Hb) O Chromatin: 결절상 (nodular mass) O N/C ratio: 1:1 O mitochondria: 가장 많다 정염적혈모구 (orthochromatic normoblast, metarubricyte) O size: 8-10 um, 가장 성숙한 적아구 O cytoplasm: 정상적혈구와 같음 O Chromatin: 농축된 모습 (pyknotic: 핵농축, condensed) O DNA 합성 X, 세포분열 X O 정상골수 : 5-10%

그물적혈구 (reticulocyte, polychromatophilic erythrocyte) O size: 8-9 um, anucleated O cytoplasm: polychromatophilia (residual RNA) O Nucleus: X O 초생체염색 (supravital staining): reticular filaments (rRNA) O Wright stain: bluish gray O 말초혈액에서 %, 1-2 일 후면 성숙 O 급성출혈, 용혈성빈혈, 철결핍성빈혈, 악성빈혈 회복기 : 수치증가 조혈기능저하, 재생불량성빈혈 : 수치감소 적혈구 (erythrocyte) O size: 6-8 um, anucleated O cytoplasm: pink-orange, central pallor O ribosome, mitochondria: X,

O pronormoblast ( 풋정상적혈모구 ) 핵 O, 분열 O, RNA O, Hb 합성 / 존재 O, O nucleolus O, mitochondria O, O Basophilic normoblast ( 호염기적혈모구 ): 핵 O, 분열 O, RNA O, Hb 합성 O, O nucleolus X, mitochondria O O Polychromatic normoblast ( 다염적혈모구 ): 핵 O, 분열 O, RNA O, Hb 합성 O, O mitochondria O (peak) O Orthochromatic normoblast ( 정염적혈모구 ): 핵 O, 분열 X, RNA O, Hb 합성 O, O mitochondria O O Reticulocte ( 그물적혈구, 망상적혈구, 어린적혈구 ): 핵 X, 분열 X RNA O, Hb 합성 O, O mitochondria O O Mature RBC ( 성숙적혈구 ): 핵 X, 분열 X, RNA X, Hb 합성 X, O mitochondria X, ribosome X,

03. Megaloblastic series ( 거대적혈모구계 ) O deficiency of vitamin B 12 or folic acid ( 엽산 ) O Defect of DNA synthesis O Division stop O enlargement of cytoplasm O formation of megaloblast - chromatin; fine - 핵과 세포질의 성숙도가 정상과 다름 - 핵성숙 늦음, 세포질 증가 - 골수 내 합성에서 쉽게 파괴 : megaloblastic anemia O promegaloblast O basophilic megaloblast O polychromatic megaloblast O orthochromtic megaloblast O megalocyte - cell size; larger (9-12 um)

04. Morphology of erythrocyte ( 적혈구 형태 ) O biconcave disk shape O compared with spherocyte ( 공모양적혈구 ) - 혈구 표면적 증가 : 가스교환효율 증가 - 저항력 증가 : 삼투압의 변화, 외부충격 - 유연성 증가 (deformability): 모세혈관 통과용이 O hemoglobin 이 적혈구 내부의 1/3 차지

05. Function of erythrocyte ( 적혈구 기능 ) oxygen transport O Hemoglobin (Hb): reduced(deoxy) Hb, oxy Hb O 산소분압차에 의한 확산 (diffusion) O Effectors associated with oxygen binding - O 2 partial pressure: 산소분압 high, affinity high - blood pH: CO 2 partial pressure high, pH low, affinity low - 2,3-diphosphoglycerate (DPG): 2,3-DPG high, affinity low carbon dioxide transport (1) Indirect erythrocyte mechanism (3/4) CO 2 + H 2 O = H 2 CO 3 (carbonic acid) by carbonic anhydrase H 2 CO 3 = HCO 3 - (bicarbonate) + H + chloride shift: HCO3 - out of the cell, chloride (Cl - ) into the cell (2) Direct transport system (1/4) CO 2 + deoxyHb = carbamino-Hb stabilize deoxy form, decrease oxygen affinity (3) Solution in plasma

07. Structure and function of RBC membrane O Lipid (42%), protein (50%), carbohydrate (8%) 로 구성됨

(1) Membrane lipid O Phospholipid, Glycolipid, Free cholesterol O Inner leaflet: PE, PS Outer leaflet: PC, SM (2) Membrane protein O Membrane skeleton - Band 3 (Anion exchanger protein) Chloride shift function - Band Ankyrin - Spectrin (alpha, beta subunit) - Glycophorin : - Band Actin - Spectrin CB: Coomassie blue staining PAS: Periodic acid schiff’s staining (Glycophorin)

(3) Membrane carbohydrate O 당지질 - Ganglioside: sugar-containing lipid - Sialic acid (N-acetylneuraminic acid, NANA): negative charged carbohydrate (COO - ) - Outer leaflet (negative charge) - G M1, G M3 O ABO 형 결정당기 A : N-acetylgalactosamine B : D-galactose O : L-fucose O 당단백질 - Glycophorin: stained by PAS (periodic acid schiff’s stain) * Lipid O Fatty acid O nonpolar lipid: Triacylglycerol (fat, oil) (glycerol backbone) O polar lipid: Glycerophospholipid (glycerol backbone) Sphingolipid (sphingosine backbone) - ceramide - sphingomyelin - glycosphingolipid cerebroside ganglioside

7.5 glycoproteins Proteins that have covalently bonded carbohydrate units attached to them Glycoprotein structure

8.1 Fatty acids * Fatty acid structure - Biomolecules containing a carboxyl functional group connected to an unbranched aliphatic chain, amphiphilic - metabolic fuel; complete metabolism of fatty acids produce twice as much energy per gram as for carbohydrates - rarely found in a free form in cells and tissues - 12 to 24 carbon atoms

8.3 Polar lipid - amphiphilic; they have both nonpolar and polar structural features - construction of biological membranes

* Glycerophospholipids - phosphatidic acid; 1,2-diacylglycerol-3-phosphate - 16, 18 carbon fatty acids are prevalent - a preference for saturated fatty acids at C1 and for unsaturated at C2 - phosphate group at C3 - amphiphilic; polar head and nonpolar tail

* Sphingolipids - Sphingosine 18-carbon amino alcohol - ceramides; linked via an amide bond with a fatty acids at C2 hydroxyl group at C1 - Sphingomyelin phosphocoline unit at C1 myelin sheath, insulation - glycosphingolipids 1. cerebrosides; ceramide and monosaccharide unit at C1 brain and nervous system 2. gangliosides; ceramide and several carbohydrate unit * recognition, tissue specificity