LIU Chuan Yong 刘传勇 Institute of Physiology Medical School of SDU Tel 88381175 (lab)

1. LIU Chuan Yong 刘传勇 Institute of Physiology Medical School of SDU Tel 88381175 (lab) 88382098 (office) Email: liucy@sdu.edu.cn Website: www.physiology.sdu.edu.cn

2. Chapter 3 BLOOD Section 1 Composition and Properties of the Blood

3. Blood • a suspension solution of blood cells in plasma • circulating through the cardiovascular system.

4. Composition • cellular portion (formed elements) • fluid portion (plasma).

5. I Plasma • Straw-colored liquid consisting of water and dissolved solutes. • Sodium ion is the major solute of the plasma in terms of its concentration. • In addition to Na+, plasma contains • many other salts and ions, • as well as organic molecules such as metabolites, hormones, enzymes, antibodies, and other proteins.

6. Plasma Proteins– constitute 7-9% of the plasma • Albumins (60% - 80%) • Produced by the liver • Provide the osmotic pressure and necessary to maintain blood volume and pressure. • Effective Filtration Pressure = (capillary pressure + interstitial osmotic pressure) – (plasma colloid osmotic pressure + interstitial hydrostatic pressure) • Globulins, divided into three types: • Alpha and beta globulin, produced by the liver and function to transport lipids and fat soluble vitamins in the blood. • Gamma globulins are antibodies produced by lymphocytes and function in immunity.

7. Plasma pH: 7.35 – 7.45 • Maintained in a very narrow range through numerous mechanisms. • Acids in the blood are buffered by bicarbonate in the plasma, and blood pH is maintained by the actions of the lungs and kidneys. • The lungs aid acid –base balance through elimination of carbon dioxide, which regulates the amount of carbonic acid in the blood. • The kidneys participate in acid – base balance by excreting H+ and retaining plasma bicarbonate.

8. II. Blood Cells • red blood cells (erythrocytes) • white blood cells (leucocytes) • platelets (thrombocytes).

11. Red cells (Erythrocytes) • Number: 5.1 to 5.8 million in males and 4.3 to 5.2 million in females per milliliter blood. • Shape: flat, biconcave discs, about 7 um in diameter and 2.2 um thick. • Importance of the unique shape: provides an increased surface area through which gas can diffuse.

13. Lift Span of Red Cells • Erythrocytes lack a nucleus and mitochondria • (they get energy from anaerobic (but not aerobic) respiration). • Life span: about 120 days • destroyed by phagocytic cells in the liver, spleen and bone marrow.

14. Physical and Chemical Properties of the Red Cells • Hematocrit • Function • Material for the production • Erythropoiesis

15. Hematocrit • Concept: The percentage of blood volume occupied by the packed red blood cell volume • Normal range: man, 40% - 50%, Women 37% - 48%

17. The arterial and venous red cell Function: • To transport oxygen from the lungs to the tissue (function of hemoglobin) • To transport carbon dioxide in blood.

18. Material for the production. • The protein and iron are used for hemoglobin synthesis. • Both vitamin B12 and folic acid are necessary co-factors for DNA synthesis, which is essential for maturation of the red cells

19. Erythropoiesis • Concept: The production of new red blood cells to replace the old and died ones • In the adult, all the red cells are produced in bone marrow

20. Erythropoiesis- Pluripotent stem cells • in the bone marrow • can produce any type of blood cells. • is capable of both self-replication and differentiation to committed precursors-cells that can produce only a specific cell line. CPU：colony-forming unit

21. Early Intermediate Late Proerythroblast (Pronormoblast) Polychromatophilic Normoblast Reticulocyte Basophilic Normoblast Orthochromatophilic Normoblast Erythrocyte Erythropoiesis-CPU-E • the committed red cell precursor undergoes several divisions. • The daughter cells becomes progressively smaller, • the cytoplasm changes color from blue to pink as hemoglobin is synthesized, • the nucleus becomes small and dense and then extrude.

22. Early Intermediate Late Proerythroblast (Pronormoblast) Polychromatophilic Normoblast Reticulocyte Basophilic Normoblast Orthochromatophilic Normoblast Erythrocyte Erythropoiesis-CPU-E • The resulting non-nucleated cells is termed a reticulocyte since it still contains RNA. • Within a few days of entering the circulation, the reticulocytes lose their RNA and becomes mature red cells

23. Importance of the Erythropoiesis • Maintain the number of the red cells remarkable constant • Anemia • Decrease rate of erythropoiesis or increased rate of red cells destruction • decreased number of red cells and weight of hemoglobin

24. Regulation of Erythropoiesis • A. Erythropoietin, • a glycoprotein released predominantly from the kidneys in response to tissue hypoxia. • also produced by reticuloendothelial system of the liver and spleen. • Effect: • a, Stimulates the proliferation and differentiation of the committed red cell precursor • b, Accelerates hemoglobin synthesis • c, Shortens the period of red development in the bone marrow.

25. Regulation of Erythropoiesis • B. Other hormones stimulate erythropoiesis • Adrenal cortical steroids, • Pituitary growth hormone, • Parathyroid hormone • Androgen • C. Estrogen – inhibit erythropoiesis

26. White blood cells (leucocytes) • Leukocytes contain nuclei and mitochondria and can move in an amoeboid fashion, • so they can squeeze through pores in capillary and get to a site of infection. • Number, 5000 to 10000/µl • Classification: • Granular leukocytes, having granules in the cytoplasm; • Agranular (or nongranular) leukocytes: without granules in the cytoplasm.

28. Granular Leukocytes-Eosinophils • 0.5-5%. • Function: • Limit the action of basophils in the rapid allergic reactions (through release of prostaglandin E and histamine oxidase) • Participate in the immune response to parasites

29. Granular Leukocytes- Basophils • less than 1%, • release heparin and histamine that are responsible for the allergic reaction.

30. Granular Leukocytes- Neutrophils • 50 % - 70%. • nonspecific cellular immunity : • After attracted by chemical substances (chemotaxis) released by bacteria, • They engulf and digest the bacteria or other foreign substances by means of phagocytosis (噬菌作用）.

31. Agranular Leukocytes- Monocytes • 3% - 8%. • Wander into the tissue and become fixed in the tissue and swell to become fixed tissue macrophages. • During the inflammation, they can divide in situ and form more macrophages • - “wall process” for preventing spread of infection focus.

32. Agranular Leukocytes- Lymphocytes • 20% - 40% • T (thymus dependent) lymphocytes, responsible for the cellular immunity • B lymphocytes, responsible for the humoral immunity.

33. Platelets (thrombocyte) • 0.13 to 0.36 million / µl • Non-nucleated • irregularly shaped • minute round cells • 2-4 µm in diameter.

35. Platelets (thrombocyte) • Produced in the bone marrow and • Budded off from the cytoplasm of the megakaryocytes （巨核细胞）

36. Platelets (thrombocyte) • have an average life span of 7 to 14 days and • are removed and destroyed by reticuloendothelial cells in the liver and spleen.

37. Function fo Platelets (thrombocyte) • Play a key role in hemostasis （止血）. • Assist in maintaining the integrity of vascular endothelium • by quickly repairing the minor breaks in the endothelium. • When too few platelets are circulating in the blood, red cells leak more easily through blood vessel walls. (spontaneous bleeding)

38. III. Physical and Chemical Properties of the Blood • Gravity • Suspension Stability of the Red Cells and Erythrocyte sedimentation rate (ESR). • Viscosity • Plasma Osmotic Pressure

39. Gravity • Blood: 1.05-1.60 • Plasma: 1.025-1.030

40. Suspension Stability of the Red Cells • The erythrocytes are very stable in suspension due to the repelling force by the same (negative) charge of the red cells. • When the blood is anticoagulated （抗凝）and added in a narrow tube, rouleaux（叠连）of the red cells are formed and then its sediment gradually takes place. • The length of sedimentation of the red cells within one hour is termed erythrocyte sedimentation rate (ESR).

41. erythrocyte sedimentation rate (ESR). • The normal range • 0-3 mm per hour in men, • 0 – 10 mm per hour in women. • depends mainly on the relative concentration of the plasma protein (Albumins and Globulins). • Globulin and fibrinogen enhances the formation of the rouleaux. • Almost all the infections (especially the tuberculosis 结核and rheumatism风湿) that are accompanied by a rise of globulin can accelerate ESR.

42. Viscosity • The frictional force between the elements in the blood. • The relative viscosity of the blood is 4-5, which is greater than that in plasma (1.6 – 2.4) and water (1). • The higher the red cell concentration and the amount of plasma protein, the greater the viscosity of the blood. • Increase of the viscosity can enhance the peripheral blood resistance, decreasing the blood supply to tissue.

43. Plasma Osmotic Pressure • Osmosis: Net diffusion of the water across a semipermeable membrane to a region in which there is a higher concentration of solute

44. Effects of Osmosis H20 moves by osmosis into the lower [H20] until equilibrium is reached.

45. osmotic pressure. • The osmosis of the water molecules can be opposed by applying a pressure in direction opposite that of the osmosis. • The precise amount of pressure required to prevent the osmosis is called the osmotic pressure

46. osmotic pressure. • The total plasma osmotic pressure : • 313 mOsm/L or 708.9 kPa (5330 mmHg). • It consists of two parts. • The plasma crystal osmotic pressure • The plasma colloid osmotic

47. plasma crystal osmotic pressure • 5305 mmHg (99.5%). • formed from the crystal substances and in the plasma • plays an important role in maintaining water equilibrium between the plasma and the intracellular fluid.

48. plasma colloid osmotic pressure • 25 mmHg (0.5%). • formed from the colloid substances and plasma proteins in the plasma • important to maintain the water equilibrium between the plasma and the interstitial fluid.

49. osmotic pressure. • In clinical practice, it is common to substitute the term tonicity for osmolarity when referring to solutions. • A solution is isotonic (isosmotic) if a normal cell does not change its volume when exposed to it. • This solution has a same osmotic pressure as that of the plasma.

50. A solution that causes the cell to swell is termed hypotonic (hypoosmotic) solution. 0.9% Na solution 99.1% H2O 0.5% Na 99.5% H2O