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

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

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!