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BLOOD【 血液 】

BLOOD【 血液 】. XIA Qiang ( 夏强 ), PhD Department of Physiology School of Medicine Tel: 88206417, 88208252 Email: xiaqiang@zju.edu.cn. 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.

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BLOOD【 血液 】

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  1. BLOOD【血液】 XIA Qiang (夏强), PhD Department of Physiology School of Medicine Tel: 88206417, 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） Internal Environment

  3. 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

  4. 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

  5. How is homeostasis achieved? 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

  6. 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）

  7. Normal Values for the Cellular Elements in Human Blood

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. Bone Marrow • In the adult, red blood cells, many white blood cells, and platelets are formed in the bone marrow • In the fetus, blood cells are also formed in the liver and spleen, and in adults such extramedullary hematopoiesis may occur in diseases in which the bone marrow becomes destroyed or fibrosed Changes in red bone marrow cellularity in various bones with age

  17. Development of various formed elements of the blood from bone marrow cells

  18. Plasma • The fluid portion of the blood, the plasma, is a remarkable solution containing an immense number of ions, inorganic molecules, and organicmolecules that are in transit to various parts of the body or aid in the transport of other substances • Normal plasma volume is about 5% of body weight, or roughly 3500 mL in a 70-kg man • Plasma clots on standing, remaining fluid only if an anticoagulant is added • If whole blood is allowed to clot and the clot is removed, the remaining fluid is called serum • Serum has essentially the same composition as plasma, except that its fibrinogen and clotting factors II, V, and VIII have been removed and it has a higher serotonin content because of the breakdown of platelets during clotting

  19. 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

  20. Plasma proteins • 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

  21. Some of the Proteins Synthesized by the Liver: Physiologic Functions and Properties

  22. Red blood cells (Erythrocytes)（红细胞） • The red blood cells (erythrocytes) carry hemoglobin in the circulation • They are biconcave disks that are manufactured in the bone marrow • In mammals, they lose their nuclei before entering the circulation • In humans, they survive in the circulation for an average of 120 days • The average normal red blood cell count is 5.4 million/μL in men and 4.8 million/μL in women • The number of red cells is also conveniently expressed as the hematocrit, or the percentage of the blood, by volume, that is occupied by erythrocytes. • Each human red blood cell is about 7.5 μm in diameter and 2 μm thick, and each contains approximately 29 pg of hemoglobin • There are thus about 3 × 1013 red blood cells and about 900 g of hemoglobin in the circulating blood of an adult man

  23. Human red blood cells and fibrin fibrils

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

  25. Hemoglobin • The red, oxygen-carrying pigment in the red blood cells of vertebrates is hemoglobin, a protein with a molecular weight of 64,450

  26. Reactions of Hemoglobin

  27. Hemoglobin in the Fetus • The blood of the human fetus normally contains fetal hemoglobin (hemoglobin F) • Its structure is similar to that of hemoglobin A except that the β chains are replaced by γ chains; that is, hemoglobin F is α2γ2 • Fetal hemoglobin is normally replaced by adult hemoglobin soon after birth

  28. Physiological properties Plastic deformability a) Illustration showing structural modifications inside a sickle RBC. Modified, with permission, from (Barabino, Platt et al.,2010). (b-d) Typical morphologies of sickle RBCs measured by DPM; (b) echinocyte, (c) discocyte, and (d) crescent-shaped irreversibly sickled cell.

  29. 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… Suspension stability （悬浮稳定性） International Council for Standardization in Haematology (ICSH)

  30. 红细胞叠连（rouleaux formation）

  31. 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

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

  33. 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

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

  35. Production of RBC (Erythropoiesis)

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

  37. 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）

  38. 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

  39. 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.

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

  41. Red cell formation and destruction

  42. Role of the Spleen • The spleen is an important blood filter that removes aged or abnormal red cells • It also contains many platelets and plays a significant role in the immune system • Abnormal red cells are removed if they are not as flexible as normal red cells and consequently are unable to squeeze through the slits between the endothelial cells that line the splenic sinuses

  43. 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)

  44. Iron deficiency anemia （缺铁性贫血）

  45. 巨幼红细胞性贫血（megaloblastic anemia）

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