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BLOOD【血液】 Qiang XIA (夏强), PhD Department of Physiology

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Presentation on theme: "BLOOD【血液】 Qiang XIA (夏强), PhD Department of Physiology"— Presentation transcript:

1 BLOOD【血液】 Qiang XIA (夏强), PhD Department of Physiology
Zhejiang University School of Medicine Tel:

2 Objectives After studying this part, you should be able to:
describe the components of blood, their origins, and the role of hemoglobin in transporting oxygen in red blood cells. understand the molecular basis of blood groups and the reasons for transfusion reactions. delineate the process of hemostasis that restricts blood loss when vessels are damaged, and the adverse consequences of intravascular thrombosis. understand the basis of disease states where components of the blood are abnormal, dysregulated, or both.

3 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)

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5 Plasma The fluid portion of the blood, the plasma, is a remarkable solution containing an immense number of ions, inorganic molecules, and organic molecules 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 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

6 System for Naming Blood-Clotting Factors
Names I Fibrinogen II Prothrombin III Thromboplastin IV Calcium V Proaccelerin, labile factor, accelerator globulin VII Proconvertin, SPCA, stable factor VIII Antihemophilic factor (AHF), antihemophilic factor A, antihemophilic globulin (AHG) IX Plasma thromboplastic component (PTC), Christmas factor, antihemophilic factor B X Stuart–Prower factor XI Plasma thromboplastin antecedent (PTA), antihemophilic factor C XII Hageman factor, glass factor XIII Fibrin-stabilizing factor, Laki–Lorand factor HMW-K High-molecular-weight kininogen, Fitzgerald factor Pre-Ka Prekallikrein, Fletcher factor Ka Kallikrein PL Platelet phospholipid

7 Some of the Proteins Synthesized by the Liver: Physiologic Functions and Properties
Name Principal Function Binding Characteristics Serum or Plasma Concentration Albumin Binding and carrier protein; osmotic regulator Hormones, amino acids, steroids, vitamins, fatty acids 4500–5000 mg/dL Orosomucoid Uncertain; may have a role in inflammation Trace; rises in inflammation α1-Antiprotease Trypsin and general protease inhibitor Proteases in serum and tissue secretions 1.3–1.4 mg/dL α-Fetoprotein Osmotic regulation; binding and carrier proteina Hormones, amino acids Found normally in fetal blood α2-Macroglobulin Inhibitor of serum endoproteases Proteases 150–420 mg/dL Antithrombin-III Protease inhibitor of intrinsic coagulation system 1:1 binding to proteases 17–30 mg/dL Ceruloplasmin Transport of copper Six atoms copper/mol 15–60 mg/dL C-reactive protein Uncertain; has role in tissue inflammation Complement C1q < 1 mg/dL; rises in inflammation Fibrinogen Precursor to fibrin in hemostasis 200–450 mg/dL Haptoglobin Binding, transport of cell-free hemoglobin Hemoglobin 1:1 binding 40–180 mg/dL Hemopexin Binds to porphyrins, particularly heme for heme recycling 1:1 with heme 50–100 mg/dL Transferrin Transport of iron Two atoms iron/mol 3.0–6.5 mg/dL Apolipoprotein B Assembly of lipoprotein particles Lipid carrier Angiotensinogen Precursor to pressor peptide angiotensin II Proteins, coagulation factors II, VII, IX, X Blood clotting 20 mg/dL Antithrombin C, protein C Inhibition of blood clotting Insulinlike growth factor I Mediator of anabolic effects of growth hormone IGF-I receptor Steroid hormone-binding globulin Carrier protein for steroids in bloodstream Steroid hormones 3.3 mg/dL Thyroxine-binding globulin Carrier protein for thyroid hormone in bloodstream Thyroid hormones 1.5 mg/dL Transthyretin (thyroid-binding prealbumin) 25 mg/dL

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11 Plasma includes water, ions, proteins, nutrients, hormones, wastes, etc. 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).

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

13 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

14 Normal Values for the Cellular Elements in Human Blood
Cells/μL (average) Approximate Normal Range Percentage of Total White Cells Total white blood cells 9000 4000–11,000 Granulocytes    Neutrophils 5400 3000–6000 50–70    Eosinophils 275 150–300 1–4    Basophils 35 0–100 0.4 Lymphocytes 2750 1500–4000 20–40 Monocytes 540 300–600 2–8 Erythrocytes    Females 4.8 × 106    Males 5.4 × 106 Platelets 300,000 200,000–500,000

15 Development of various formed elements of the blood from bone marrow cells

16 White blood cells (Leucocytes) (白细胞)

17 Platelets (Thrombocytes) 血小板
Platelets are small, granulated bodies that aggregate at sites of vascular injury They lack nuclei and are 2–4 μm in diameter There are about 300,000/μL of circulating blood, and they normally have a half-life of about 4 days The megakaryocytes, giant cells in the bone marrow, form platelets by pinching off bits of cytoplasm and extruding them into the circulation Between 60 and 75% of the platelets that have been extruded from the bone marrow are in the circulating blood, and the remainder are mostly in the spleen Splenectomy causes an increase in the platelet count (thrombocytosis)

18 Physiological properties of platelets
Adhesion

19 Physiological properties of platelets
Aggregation

20 Physiological properties of platelets
Release or secretion

21 Physiological properties of platelets
Contraction

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 Red cell formation and destruction

25 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

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

27 Reactions of Hemoglobin

28 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

29 Blood Types The membranes of human red cells contain a variety of blood group antigens, which are also called agglutinogens (凝集原) The most important and best known of these are the A and B antigens, but there are many more

30 Antigens of the ABO system on the surface of red blood cells

31 Summary of ABO System Blood Type Agglutinins in Plasma
Frequency in United States % Plasma Agglutinates Red Cells of Type: O Anti-A, anti-B 45 A, B, AB A Anti-B 41 B, AB B Anti-A 10 A, AB AB None 4

32 The Rh Group Aside from the antigens of the ABO system, those of the Rh system are of the greatest clinical importance The Rh factor, named for the rhesus monkey because it was first studied using the blood of this animal, is a system composed primarily of the C, D, and E antigens, although it actually contains many more Unlike the ABO antigens, the system has not been detected in tissues other than red cells D is by far the most antigenic component, and the term Rh-positive as it is generally used means that the individual has agglutinogen D The D protein is not glycosylated, and its function is unknown The Rh-negative individual has no D antigen and forms the anti-D agglutinin when injected with D-positive cells The Rh typing serum used in routine blood typing is anti-D serum Eighty-five per cent of Caucasians are D-positive and 15% are D-negative; over 99% of Asians are D-positive Unlike the antibodies of the ABO system, anti-D antibodies do not develop without exposure of a D-negative individual to D-positive red cells by transfusion or entrance of fetal blood into the maternal circulation D-negative individuals who have received a transfusion of D-positive blood (even years previously) can have appreciable anti-D titers and thus may develop transfusion reactions when transfused again with D-positive blood

33 Hemolytic Disease of the Newborn

34 Hemostasis Hemostasis is the process of forming clots in the walls of damaged blood vessels and preventing blood loss while maintaining blood in a fluid state within the vascular system A collection of complex interrelated systemic mechanisms operates to maintain a balance between coagulation and anticoagulation

35 Summary of reactions involved in hemostasis

36 The Clotting Mechanism

37 Anticlotting Mechanisms
The tendency of blood to clot is balanced in vivo by reactions that prevent clotting inside the blood vessels, break down any clots that do form, or both These reactions include the interaction between the platelet-aggregating effect of thromboxane A2 and the antiaggregating effect of prostacyclin, which causes clots to form at the site when a blood vessel is injured but keeps the vessel lumen free of clot

38 Examples of Diseases Due to Deficiency of Clotting Factors
Deficiency of Factor: Clinical Syndrome Cause I Afibrinogenemia 无纤维蛋白原血症 Depletion during pregnancy with premature separation of placenta; also congenital (rare) II Hypoprothrombinemia (hemorrhagic tendency in liver disease)低凝血酶原血症 Decreased hepatic synthesis, usually secondary to vitamin K deficiency V Parahemophilia 副血友病 Congenital VII Hypoconvertinemia VIII Hemophilia A (classic hemophilia)甲型血友病 Congenital defect due to various abnormalities of the gene on X chromosome that codes for factor VIII; disease is therefore inherited as a sex-linked characteristic IX Hemophilia B (Christmas disease) X Stuart–Prower factor deficiency XI PTA deficiency XII Hageman trait

39 Anticlotting Mechanisms
Antithrombin III is a circulating protease inhibitor that binds to serine proteases in the coagulation system, blocking their activity as clotting factors. This binding is facilitated by heparin, a naturally occurring anticoagulant that is a mixture of sulfated polysaccharides. The clotting factors that are inhibited are the active forms of factors IX, X, XI, and XII The endothelium of the blood vessels also plays an active role in preventing the extension of clots. All endothelial cells except those in the cerebral microcirculation produce thrombomodulin, a thrombin-binding protein, on their surfaces. In circulating blood, thrombin is a procoagulant that activates factors V and VIII, but when it binds to thrombomodulin, it becomes an anticoagulant in that the thrombomodulin–thrombin complex activates protein C. Activated protein C (APC), along with its cofactor protein S, inactivates factors V and VIII and inactivates an inhibitor of tissue plasminogen activator, increasing the formation of plasmin Plasmin (fibrinolysin) is the active component of the plasminogen (fibrinolytic) system

40 The fibrinolytic system and its regulation by protein C

41 Anticoagulants Heparin is a naturally occurring anticoagulant that facilitates the action of antithrombin III. Low-molecular-weight fragments have been produced from unfractionated heparin, and these are seeing increased clinical use because they have a longer half-life and produce a more predictable anticoagulant response than unfractionated heparin. The highly basic protein protamine forms an irreversible complex with heparin and is used clinically to neutralize heparin In vivo, a plasma Ca2+ level low enough to interfere with blood clotting is incompatible with life, but clotting can be prevented in vitro if Ca2+ is removed from the blood by the addition of substances such as oxalates, which form insoluble salts with Ca2+, or chelating agents, which bind Ca2+ Coumarin derivatives (香豆素类) such as dicumarol and warfarin are also effective anticoagulants. They inhibit the action of vitamin K, which is a necessary cofactor for the enzyme that catalyzes the conversion of glutamic acid residues to γ-carboxyglutamic acid residues. Six of the proteins involved in clotting require conversion of a number of glutamic acid residues to γ-carboxyglutamic acid residues before being released into the circulation, and hence all six are vitamin K-dependent. These proteins are factors II (prothrombin), VII, IX, and X, protein C, and protein S

42 Summary Blood cells; plasma
Blood cells arise in the bone marrow and are subject to regular renewal; the majority of plasma proteins are synthesized by the liver Hemoglobin; fetal hemoglobin; mutated forms of hemoglobin lead to red cell abnormalities and anemia Blood group systems Hemostasis Clotting mechasnism Anticlotting mechanisms Anticoagulants

43 Thank you for your attention!


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