BLOOD【 血液 】

1. BLOOD【血液】 Qiang XIA (夏强), PhD Department of Physiology Room C518, Block C, Research Building, School of Medicine Tel: 88208252 Email: xiaqiang@zju.edu.cn

2. Body Fluid = 60% of Body Weight (BW) Plasma 5% of BW Extracellular Fluid 1/3, 20% of BW Interstitial Fluid 15% of BW 70 kg Male, 42 L Intracellular Fluid 2/3, 40% of BW Internal environment （内环境）

3. Plasma 5% of BW Extracellular Fluid 1/3, 20% of BW Interstitial Fluid 15% of BW Internal Environment

5. Homeostasis（稳态） Homeostasis(from the Greek words for “same” and “steady”): maintenance of static or constant conditions in the internal environment Walter B. Cannon http://www.harvardsquarelibrary.org/unitarians/cannon_walter.html

6. Components of Homeostasis: • Concentration of O2 and CO2 • pH of the internal environment • Concentration of nutrients and waste products • Concentration of salt and other electrolytes • Volume and pressure of extracellular fluid

7. How is homeostasis achieved? ----Regulation Body's systems operate together to maintain homeostasis: Skin system Skeletal and muscular system Circulatory system Respiratory system Digestive system Urinary system Nervous system Endocrine system Lymphatic system Reproductive system

8. Components of blood • Plasma（血浆） • Blood Cells • Red Blood Cells (RBC) or Erythrocytes（红细胞） • White Blood Cells (WBC) or Leucocytes（白细胞） • Platelets (PLT) or Thrombocytes（血小板）

14. The hematocrit（血细胞比容） is a rapid assessment of blood composition.It is the percent of the blood volume that is composed of RBCs (red blood cells). Plasma includes water, ions, proteins, nutrients, hormones, wastes, etc.

15. the volume of red blood cells as a percentage of centrifuged whole blood M: 40~50% F: 37~48% Hematocrit（packed cell volume, 血细胞比容） International Council for Standardization in Haematology (ICSH) Recommendations for "Surrogate Reference" Method for the Packed Cell Volume

16. Physical & chemical properties of blood 1. Specific Gravity（比重） Depending on hematocrit & protein composition Whole blood： 1.050~1.060 Plasma： 1.025~1.035 Red blood cells： 1.090

17. 2. Viscosity（粘度） • relative viscosity of whole blood 4~5 depending on hematocrit • relative viscosity of plasma 1.6~2.4 related to the protein composition of  the plasma

18. 3. Osmotic Pressure（渗透压） • The osmotic pressure of a solution depends on the number of solute particles in the solution, NOT on their chemical composition and size

19. Plasma osmotic pressure (~300 mOsm/L） • Crystalloid Osmotic Pressure（晶体渗透压） • Pressure generated by all crystal substances, particularly electrolytes • Important in maintaining fluid balance across cell membranes • Colloid Osmotic Pressure（胶体渗透压） • Osmotic pressure generated by plasma proteins, particularly albumin. • Approximately 25 mmHg, but important in fluid transfer across capillaries

20. 4. Plasma pH • Normal range: 7.35~7.45 • Buffer systems（缓冲系统）: NaHCO3/H2CO3, Pro-Na/Pro, Na2HPO4/NaH2PO4 Hb-K/Hb, HbO2-K/HbO2, K2HPO4/KH2PO4, KHCO3/H2CO3

21. Functions of blood • Transportation • O2 and CO2 • Nutrients (glucose, lipids, amino acids) • Waste products (e.g., metabolites) • Hormones • Regulation • pH • Body temperature • Protection • Blood coagulation • Immunity

22. Body Fluid = 60% of Body Weight (BW) Plasma 5% of BW Extracellular Fluid 1/3, 20% of BW Interstitial Fluid 15% of BW 70 kg Male, 42 L Intracellular Fluid 2/3, 40% of BW Plasma

23. Composition Water (92% of plasma) serves as transport medium; carries heat Proteins (6~8% of plasma) Inorganic constituents (1% of plasma) e.g., Na+, Cl-, K+, Ca2+… Nutrients glucose, amino acids, lipids & vitamins Waste products e.g., nitrogenous wastes like urea Dissolved gases O2 & CO2 Hormones

24. Plasma proteins

25. Albumins （白蛋白）(60-80% of plasma proteins) • most important in maintenance of osmotic balance • produced by liver • Globulins （球蛋白）(1-, 2-, -, -) • important for transport of materials through the blood (e.g., thyroid hormone & iron) • clotting factors • produced by liver except -globulins which are immunoglobulins (antibodies) produced by lymphocytes • Fibrinogen（纤维蛋白原） • important in clotting • produced by liver

26. Red blood cells (Erythrocytes)（红细胞）

27. Structure • Biconcave • No nucleus • Few organelles • Small • Hemoglobin molecules

28. Count RBC count M: 4.0~5.5×1012/L F: 3.5~5.0×1012/L Hemoglobin（血红蛋白） M: 120~160 g/L F: 110~150 g/L

29. Physiological properties Plastic deformability （可塑变形性）

30. d Suspension stability（悬浮稳定性） Erythrocyte Sedimentation Rate (ESR)（红细胞沉降率） • The distance that red blood cells settle in a tube of blood in one hour • Normal value [Westergren method（魏氏法，国际血液学标准化委员会推荐魏氏法为标准法）]: M: 0~15 mm/h，F: 0~20 mm/h • An indication of inflammation which increases in many diseases, such as tuberculosis & rheumatoid arthritis… International Council for Standardization in Haematology (ICSH)

31. 红细胞叠连（rouleaux formation）

32. Osmotic fragility （渗透脆性） the susceptibility of a red blood cell to break apart when exposed to saline solutions of a lower osmotic pressure than that of the human cellular fluid

33. Notice that hemolysis begins in the 0.45% tube and is complete in the 0.35% tube.

34. Only substances which act as impermeant molecules can be used to make isotonic solutions （等张溶液）. E.g. cells placed in an isosmotic solution （等渗溶液） of urea (1.9%), a permeant molecule, will swell and bust. Solutions which have the same calculated osmotic pressure are said to be ISOSMOTIC but are not necessarily ISOTONIC

35. Function of RBCs 1. Transport of O2 and CO2 2. Buffering

36. Production of RBC (Erythropoiesis)

37. Hemocytoblast stem cell • Stem cell becomes committed • Early erythroblasts have ribosomes • Erythroblasts accumulate iron and hemoglobin • Normoblasts eject organelles • Released as erythrocyte

38. Nutritional Requirements for Erythropoiesis 1. Many vitamins, minerals, and proteins are necessary for normal RBC production 2. Clinically, folic acid（叶酸）, VitB12, and iron（铁） are the most important. Deficiencies of these factors lead to characteristic anemias（贫血）

40. Diagram of iron kinetics from iron stores to developing red blood cell (RBC). Iron stores include the bone marrow, reticuloendothelial system (liver and spleen) and RBCs. Transferrin (total iron-binding capacity [TIBC]) transports iron (Fe) to developing erythrocytes. Iron is deposited in the RBC, and transferrin returns to storage sites to bind more Fe for transport. Lactoferrin is a competitor of transferrin; it takes Fe that is free and returns it to storage sites. Lactoferrin levels are elevated in anemia of chronic disease. Increases in interleukin-1 increase the sequestration of Fe in storage sites. (Hb=hemoglobin)

41. Regulation of Erythropoiesis 1. Erythropoietin（促红细胞生成素） 2. Hormones: Androgen（雄激素） Others Hypoxia-inducible factor-1, HIF-1

42. Erythropoiesis is hormonally regulated: decreased oxygen delivery to the kidney causes the secretion of erythropoietin, which activates receptors in bone marrow, leading to an increase in the rate of erythropoiesis.

43. Destruction of RBC average lifespan = about 120 days • Macrophages engulf old RBCs • Iron is salvaged • Heme degrades into bilirubin

44. Anemia（贫血） • Anemia is defined as a qualitative or quantitative deficiency of hemoglobin, a protein found inside red blood cells (RBCs) • The three main classes of anemia： • excessive blood loss (acutely such as a hemorrhage or chronically through low-volume loss) • excessive blood cell destruction (hemolysis) • deficient red blood cell production (ineffective hematopoiesis)

45. Iron deficiency anemia （缺铁性贫血）

46. 巨幼红细胞性贫血（megaloblastic anemia）

48. Hemolysis（溶血） Red blood cells without (left and middle) and with (right) hemolysis. Note that the hemolyzed sample is transparent, because there are no cells to scatter light.

49. White blood cells (Leucocytes) （白细胞） • Types of WBC

50. WBC count WBC Count (109/L) % Granulocytes Neutrophils 2.0~7.0 50~70 Eosinophils 0.02~0.5 0.5~5 Basophils 0~0.1 0~1 Monocytes 0.12~0.8 3~8 Lymphocytes 0.8~4.0 20~40 Total 4~10