血液的主要功能
Function of Blood
夏 强，MD & PhD
浙江大学医学院生理学系
医学院科研楼C座518室
电话：88208252
Email：xiaqiang@zju.edu.cn
血液的成分
• 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）
Hematocrit（packed cell volume, 血细胞比容）
Plasma includes
water, ions, proteins,
nutrients, hormones,
wastes, etc.
The hematocrit is a rapid
assessment of blood
composition.
It is the percent of the
blood volume that is
composed of RBCs
(red blood cells).
血量
• 是指全身血液的总量
• 占体重的7-8%
休克种类的图示。
没有休克 (左), 血管扩张，分布性休克
(中), 低血容量休克，失血引起 (右)
血液的功能
• 运输
–
–
–
–
O2 and CO2
Nutrients (glucose, lipids, amino acids)
Waste products (e.g., metabolites)
Hormones
• 调节
– pH
– Body temperature
• 保护
– Blood coagulation
– Immunity
红细胞
Red blood cells (Erythrocytes)
• 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
• 功能：
– 运输O2和CO2
– 缓冲
d
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)
Iron deficiency anemia
（缺铁性贫血）
巨幼红细胞性贫血（megaloblastic anemia）
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.
白细胞
White blood cells (Leucocytes)
WBC count
WBC
Count (109/L)
Granulocytes粒细胞
Neutrophils中性粒细胞
2.0~7.0
Eosinophils嗜酸性粒细胞
0.02~0.5
Basophils嗜碱性粒细胞
0~0.1
Monocytes单核细胞
0.12~0.8
Lymphocytes淋巴细胞
0.8~4.0
Total
4~10
%
50~70
0.5~5
0~1
3~8
20~40
Overview table
Type
Microscopic
Appearance
Diagram
Approx. %
in adults
Diameter
(μm)
Main targets
Nucleus
Granules
Lifetime
Neutrophil
54-62%
10-12
bacteria
fungi
multilobed
fine, faintly
pink
6 hours-few
days
(days in
spleen and
other tissue)
Eosinophil
1-6%
10-12
parasites
in allergic
reactions
bi-lobed
full of pinkorange (when
stained)
8-12 days
(circulate for
4-5 hours)
Basophil
<1%
12-15
in allergic
reactions
bi- or tri-lobed
large blue
?
Type
Microscopic
Appearance
Diagram
Approx. %
in adults
Diameter
(μm)
Lymphocyte
25-33%
7-8
Monocyte
2-8%
14-17
Macrophage
Dendritic cells
21 (human)
13 (rat)
Main targets
B cells: various
pathogens
T cells:
oCD4+ (helper):
extracellular bacteria
broken down into
peptides presented by
MHC class 2 molecule.
oCD8+ cytotoxic T cells:
virus-infected and
tumor cells.
o T cells:
Natural killer cells: virusinfected and tumor cells.
Monocytes migrate from
the bloodstream to other
tissues and differentiate
into tissue resident
macrophages or dendritic
cells.
Phagocytosis
(engulfment and
digestion) of cellular
debris and pathogens,
and stimulation of
lymphocytes and other
immune cells that
respond to the pathogen.
Main function is as an
antigen-presenting cell
(APC) that activates T
lymphocytes.
Nucleus
Granules
Lifetime
deeply
staining,
eccentric
NK-cells
and
Cytotoxic
(CD8+) Tcells
weeks to years
kidney
shaped
none
hours-days
activated=days
immature=mont
hs-years
similar to
macrophages
血小板
Platelets (Thrombocytes)
• 正常值：
– (100~300) x 109/L
• 主要参与止血
血小板的生理特性
1. 黏附Adhesion
Platelets adhere to the vessel wall at the site of injury
von Willebrand factor, vWF
Unifying model of platelet adhesion to collagen at arterial shear. Two different pathways by which human and mouse platelets firmly adhere to collagen at
arterial shear are illustrated. In both, the majority of platelets are initially tethered to collagen via GP Ib/IX/V interacting with collagen-bound VWF (left),
although a minority of platelets interact directly with collagen independently of VWF/GP Ib/IX/V. In the first pathway (upper), signaling from GP VI first
leads to activation of integrins α2β1 (GP Ia/IIa) and αIIbβ3 (GP IIb/IIIa). Activated integrins then firmly attach the platelet to collagen, either directly (α2β1)
or via collagen-bound VWF (αIIbβ3) (right). In the second pathway (lower), platelets first adhere to collagen via integrin α2β1, before GP VI engages
collagen and induces activation. These two pathways are likely to reinforce each other and the events of thrombus formation. Release of secondary
mediators (ADP and TxA2) would further potentiate these events (right). (Redrawn from Auger JM, Kuijpers MJ, Senis YA: Adhesion of human and mouse
platelets to collagen under shear: a unifying model. FASEB J 2005;19:825-827.)
2. 聚集Aggregation
Platelets adhere to one another
Platelet Aggregation Pathway
Platelet activation and coagulation normally do not occur within an intact blood
vessel. After vessel wall injury, platelet-plug formation is initiated by the
adherence of platelets to subendothelial collagen. In high shear arterial blood,
platelets are first slowed down from their blood flow velocity by interacting with
the collagen-bound von Willebrand factor (VWF) and subsequently stopped by
binding directly to collagen via their glycoprotein receptor complex. The
activation of these collagen receptors on platelets following their binding to
collagen activates phospholipase C (PLC)-mediated cascades. This results in
a mobilization of calcium from the dense tubula system. An increase in
intracellular calcium is associated with activation of several kinases necessary
for morphological change, the presentation of the procoagulant surface, the
secretion of platelet granular content, the activation of glycoproteins, and the
activation of Phospholipase A2 (PLA2). Activation of PLA2 releases
arachidonic acid (AA), which is a precursor for TBXA2 synthesis. PTGS1
catalyzes the first step in the formation of TBXA2 from AA. This reaction is
irreversibly blocked by aspirin, which also leads to the blockage of platelet
aggregation
These processes result in the local accumulation of molecules like thrombin,
TBXA2, and ADP, which are important for the further recruitment of platelets
as well as the amplification of activation signals as described above. The
secreted agonists activate their respective G protein coupled receptors:
thrombin receptor (F2R), thomboxane A2 receptor (TBXA2R), and ADP
receptors (P2RY1 and P2RY12). The P2RY12 receptor couples to Gi, and
when activated by ADP, inhibits adenylate cyclase. This interaction
counteracts the stimulation of cAMP formation by endothelial-derived
prostaglandins, which alleviates the inhibitory effect of cAMP on IP3-mediated
calcium release. Thienopyridines, a class of oral antiplatelet agents,
permanently inhibit P2RY12 signaling, which is sufficient to block platelet
activation.
F2R, TBXA2R and P2RY1 couple to the Gq-PLC-IP3-Ca2+ pathway, inducing
shape change and platelet aggregation. In addition, receptor signaling through
G12/13 (F2R; TBXA2R) contributes to morphological changes through
activation of kinases.
Platelet adhesion, cyotoskeletal reorganization, secretion, and amplification
loops are all different steps towards the formation of a platelet-plug. These
cascades result in the activation of the Fibrinogen Receptor expressed on
platelet cells. This activation develops binding sites for fibrinogen, which are
not available in inactive platelets. The binding of fibrinogen results in the
linkage of activated platelets through fibrinogen bridges, thereby mediating
aggregation. Inhibition of this receptor through Glycoprotein IIb/IIIa inhibitors
blocks platelet aggregation induced by any agonist.
• Inducers of platelet aggregation
– ADP
• Low dose 1st reversible phase
• High dose 2nd irreversible phase
– Thromboxane A2 (TXA2)
– Collagen
– Thrombin
Phospholipid
Phospholipase A2
Arachidonic Acid
Cyclo-oxygenase
PGG2 & PGH2
Thromboxane synthase
Prostacyclin synthase
(Platelets)
(Vascular endothelium)
TXA2
PGI2
Aggregation
Anti-aggregation
Contraction
Relaxation
Platelet interactions with agonists and antagonists of platelet aggregation, the vessel wall, other
platelets, and adhesive macromolecules. Agents in parentheses prevent the formation or inhibit
the function of the adjacent agonists of platelet aggregation. ADP = adenosine diphosphate, VWF
= von Willebrand factor, cAMP = cyclic adenosine monophosphate, GP = glycoprotein.
• 3. 释放或分泌Release or secretion:
Platelets contain alpha and dense granules
– Dense granules: containing ADP or ATP, calcium,
and serotonin
– α-granules: containing platelet factor 4, PDGF,
fibronectin, B-thromboglobulin, vWF, fibrinogen,
and coagulation factors V and XIII
Schematic drawing of the
platelet (top figure), showing its
alpha and dense granules and
canalicular system. The bottom
figure illustrates the platelet's
major functions, including
secretion of stored products,
as well as its attachment, via
specific surface glycoproteins
(GP), to denuded epithelium
(bottom) and other platelets
(left).
VWF: von Willebrand factor;
TSP: thrombospondin; PF4:
platelet factor 4; PDGF:
platelet derived growth factor;
b-TG: beta thromboglobulin;
ADP: adenosine diphosphate;
ATP: adenosine triphosphate.
A schematic representation of selected platelet responses to activation and the congenital disorders of platelet function. AC = adenylyl cyclase; BSS =
Bernard–Soulier syndrome; CO = cyclooxygenase; DG = diacylglycerol; G = GTP-binding protein; IP3 = inositol trisphosphate; MLC = myosin light chain; MLCK
= myosin light chain kinase; P2Y1, P2Y12 = G-protein-coupled ADP receptors; PAF = platelet activating factor; PGG2/PGH2 = prostaglandin arachidonic
pathway intermediates; PIP2 = phosphatidylinositol bisphosphate; PKC = protein kinase C; PLA2 = phospholipase A2; TK = tyrosine kinase; PLC =
phospholipase C; TS = thromboxane synthase; TxA2 = thromboxane A 2; vWD = von Willebrand disease; vWF = von Willebrand factor. The Roman numerals
in the circles represent coagulation factors and yellow Ps indicate phosphorylation. (Modified with permission from Rao AK: Congenital disorders of platelet
function: disorders of signal transduction and secretion. Am J Med Sci 1998; 316:69-76.)
• 4. 收缩Contraction
Clot retraction (血块回缩)
• 5. 吸附Adsorption
Clotting factors: I, V, XI, XIII
止血
Hemostasis
• 正常情况下，小血管受损后引起的出血，
在几分钟内就会自行停止
• 三个机制：
– Vascular spasm（血管收缩）
– Formation of a platelet plug（血小板血栓形成）
– Blood coagulation (clotting)（血液凝固）
血液凝固
Blood coagulation
Clotting factors
Clotting factor
Synonyms
I
II
III
IV
V
VII
VIII
IX
X
XI
XII
XIII
fibrinogen纤维蛋白原
prothrombin凝血酶原
tissue thromboplastin组织因子
Ca2+
proaccelerin前加速素易变因子
proconvertin前转变素稳定因子
antihemophilic factor抗血友病因子
plasma thromboplastin component血浆凝血活酶
Stuart-Prower factor
plasma thromboplastin antecedent血浆凝血活酶前质
contact factor接触因子
fibrin-stabilizing factor纤维蛋白稳定因子
Coagulation factors and related substances
Number and/or name
I (fibrinogen)
II (prothrombin)
Tissue factor
Calcium
Function
Forms clot (fibrin)
Its active form (IIa) activates I, V, VII, VIII, XI, XIII, protein C, platelets
V (proaccelerin, labile factor)
Co-factor of VIIa (formerly known as factor III)
Required for coagulation factors to bind to phospholipid (formerly known as
factor IV)
Co-factor of X with which it forms the prothrombinase complex
VI
VII (stable factor)
VIII (antihemophilic factor)
IX (Christmas factor)
X (Stuart-Prower factor)
XI (plasma thromboplastin antecedent)
XII (Hageman factor)
XIII (fibrin-stabilizing factor)
von Willebrand factor
prekallikrein
high-molecular-weight kininogen (HMWK)
fibronectin
antithrombin III
heparin cofactor II
Unassigned – old name of Factor Va
Activates IX, X
Co-factor of IX with which it forms the tenase complex
Activates X: forms tenase complex with factor VIII
Activates II: forms prothrombinase complex with factor V
Activates IX
Activates factor XI and prekallikrein
Crosslinks fibrin
Binds to VIII, mediates platelet adhesion
Activates XII and prekallikrein; cleaves HMWK
Supports reciprocal activation of XII, XI, and prekallikrein
Mediates cell adhesion
Inhibits IIa, Xa, and other proteases;
Inhibits IIa, cofactor for heparin and dermatan sulfate ("minor antithrombin")
protein C
protein S
Protein Z-related protease inhibitor (ZPI)
Inactivates Va and VIIIa
Cofactor for activated protein C (APC, inactive when bound to C4b-binding
protein)
Mediates thrombin adhesion to phospholipids and stimulates degradation
of factor X by ZPI
Degrades factors X (in presence of protein Z) and XI (independently)
plasminogen
alpha 2-antiplasmin
tissue plasminogen activator (tPA)
urokinase
plasminogen activator inhibitor-1 (PAI1)
plasminogen activator inhibitor-2 (PAI2)
cancer procoagulant
Converts to plasmin, lyses fibrin and other proteins
Inhibits plasmin
Activates plasminogen
Activates plasminogen
Inactivates tPA & urokinase (endothelial PAI)
Inactivates tPA & urokinase (placental PAI)
Pathological factor X activator linked to thrombosis in cancer
protein Z
Coagulation cascade
3 processes
2 pathways
Structure of
Fibrinogen
Fibrin
Polymerization
A deficiency of a clotting factor can lead to
uncontrolled bleeding.
Vitamin K is a cofactor needed for the synthesis of
factors II, VII, IX, & X in the liver. So a deficiency of
Vitamin K predisposes to bleeding.
内源性抗凝物质
Anticoagulants
• 丝氨酸蛋白酶抑制物Serine Protease Inhibitors：
主要有抗凝血酶、肝素辅因子II、C1抑制物等
• 蛋白质C系统Protein C system
• 组织因子途径抑制物Tissue factor pathway
inhibitor (TFPI)
• 肝素Heparin
纤维蛋白溶解
Fibrinolysis
小结
•
•
•
•
•
•
•
血管内皮
凝血系统
抗凝物质
纤溶系统
单核-巨噬细胞的吞噬
血流的稀释
纤维蛋白的吸附