Platelets & Hemostasis 血小板及止血
The total volume of blood in a normal healthy adult is about 5.5 liters (8% of body weight)
Hematocrit 血比容
A high hematocrit indicates a higher than normal concentration of erythrocytes in the blood, called polycythemia.
Albumin 白蛋白：調控oncotic osmotic pressure 膠體滲透壓
Fibrinogen 纖維蛋白原
— is synthesized by the liver
— is a key substance in the formation of blood clots
Serum 血清 is plasma from which fibrinogen and other clotting proteins have been removed.
Among cells of the blood, RBCs are unique in that they lack nuclei 細胞核,mitochondria 粒腺體, and other organelles, such as ribosomes.
無粒線體核糖體
RBCs are shaped like biconcave disks雙凹型的盤子 → is due to the presence of a cytosolic protein called spectrin(flexible易彎曲的)
The HGF that stimulates RBC production is erythropoietin 紅血球生成素 →it is released from certain cells in the kidney in response to low oxygen levels in blood
reticulocytes 網狀細胞：紅血球前驅細胞，還有細胞核
bone marrow製造erythrocyte ，送到spleen，拆成Heme, Globin，Heme被拆成Iron+bilirubin，Iron透過T-iron運送回bone marrow， bilirubin運到肝臟變bile(膽汁)
Iron-deficiency anemia 缺鐵性貧血—a lack of iron in the diet → the RBCs are smaller than normal due to a decrease in the amount of Hb per RBC
Pernicious anemia 惡性貧血—a lack of vitamin B12 → the RBCs are larger than normal RBC size but a decrease in the number of RBC
Folic acid 葉酸 → necessary for DNA replication, thus cell proliferation
Vitamin B12 維他命B12 → necessary for DNA replication, thus cell proliferation
Hemoglobin 血紅素 catabolized
– After iron removed, heme 血基質 →bilirubin 膽紅素
Bilirubin, a yellow compound, released into bloodstream → travels to liver for further metabolism
– Products of bilirubin catabolism secreted in bile to intestinal tract or released into bloodstream and excreted in urine
Iron transported in blood bound to transferrin 運鐵蛋白 → from GI tract or liver to bone marrow
Iron stored bound to ferritin 鐵蛋白 in the liver, spleen, or small intestine
Neutrophilis 嗜中性白血球，最多
Eosinophils 嗜酸性白血球Defend against parasitic invaders 寄生蟲的入侵 (e.g. worms 蠕蟲)
Basophils 嗜鹼性白血球Contribute to allergic reactions 過敏反應
– Histamine 組織胺
– Heparin 肝素
Monocytes 單核球Fixed 固定的 macrophages →Kupffer cells in the liver
Lymphocytes 淋巴球
Platelets 血小板 are colorless cell fragments 無色的細胞碎片 →they are smaller than RBCs and contain mitochondria, smooth endoplasmic reticulum, and cytoplasmic granules, but no nucleus
沒有細胞核
1. Vascular spasm 血管筋攣
2. Formation of platelet plug 形成血小板塞
3. Blood coagulation 血液凝集
Platelets possess granules 顆粒 containing a variety of substances that can be secreted into the plasma, including ADP, serotonin, epinephrine,and a variety of chemicals that participate in the formation of a blood clot 血液凝塊
Platelet Plug Formation 血小板塞的形成
1. Blood Vessel Damage
2. Exposure of Subendothelium
3. vWf(凝血因子) Binds to Collagen Fibers
4. Platelets Bind to vWf，Platelet Adhesion, Sticky, Secretions:ADP, serotonin, epinephrine
Integral to the formation of a blood clot 血栓 is a plasma protein called fibrin 纖維蛋白 → blood clots are also called fibrin clots纖維凝塊
intrinsic pathway 內在路徑everything in plasma trigger = collagen
extrinsic pathway 外在路徑requires Factor III from damaged tissue
The intrinsic pathway starts when circulating factor XII is activated by contact with substances in the
subendothelium, including collagen and phospholipids.內在路徑從12開始
The extrinsic pathway starts when tissue damage allows tissue factor 組織因子
(factor III) to contact the plasma and react with inactive factor VII. 外在路徑從3, 7開始
Even though the intrinsic and extrinsic pathways start from separate places, they eventually
merge at activation of factor X to form a common pathway.外在或內在均最後活化10
Hemophilia 血友病 = genetic disorder, deficiency in clotting factor, usually Factor VIII
Anticoagulants 抗凝血劑 ：tissue factor pathway inhibitor, thrombomodulin
1. Binds to thrombin, forming complex that activates protein C
2. Activated protein C inhibits both the intrinsic and extrinsic pathways
所以protein C才是主角
溶血
Once formed, fibrin clots are eventually dissolved by plasmin 胞漿素, a protein derived from the plasma protein plasminogen 胞漿素原
Plasminogen is converted to plasmin by plasminogen activators 胞漿素原活化物 secreted by a variety of cell types
最終把fibrin及fibrinogen 分解
Role of Coagulation Factors in Clot Formation Disorders 血液凝集因子在血塊形成疾病上的角色
1. Hemophilia 血友病
2. Von Willebrand’s disease
3. Vitamin K deficiencies
Aspirin as an Anticoagulant 阿斯匹靈當作抗凝血劑
Low doses – anticoagulant → inhibits formation of thromboxane A2
(TXA2)
High doses → inhibits formation of prostacyclin (PGI2)
(左)ventricle 的收縮最強
atrium 的收縮因為很弱，在基礎上常常被忽略，但是在臨床上，年紀大的人ventricle 的功能愈來
愈差，所以atrium 的收縮就愈來愈顯得重要
Cardiovascular system = closed system
Pulmonary circulation 屬於low pressure area，resistance 較低；systemic circulation 則屬high pressure area，resistance 較高
coronary artery 的開口在aortic valve 上方，所以心臟要得到氧氣和nutrients 是在diastole(心室舒張) 的時候
主動脈瓣膜關閉即舒張期的時候，血才會進入冠狀動脈
Three layers of the heart wall
Epicardium (outer)
• External membrane
Myocardium (middle)
• Cardiac muscle
Endothelium (inner)
• Layer of endothelial cells
心包膜分兩層
纖維性心包膜(Fibrous pericardium)
• 漿膜性心包膜(Serosal pericardium)壁層(外面)
• 心包腔：充滿心包液
• 漿膜性心包膜臟層=心外膜
（由外至內）
• 纖維性心包膜(Fibrous pericardium)
• 漿膜性心包膜(Serosal pericardium)壁層
• 心包腔：充滿心包液
• 漿膜性心包膜臟層=心外膜 ─┐
• 心肌層：最厚 ├—心臟壁
• 心內膜：單層鱗狀上皮 ─┘
Right AV valve = tricuspid valve
Left AV valve = bicuspid valve = mitral valve
左心房室瓣二，右心房室瓣三
Atrioventricular valves(AV valve) 被chordae tendineae(腱索 ) 固定在心室中的papillary muscles 上
first heart sound: lub
• When the atrioventricular valves close
second heart sound: dup
• When the pulmonary and aortic valves close
Sinoatrial node 簡稱 SA node
Atrioventricular node 簡稱 AV node
SA node→ AV node→ bundle of His→ left/right bundle branches→ Purkinje fibers
最初的depolarization 是在位於right atrium 的SA node 發出，其位置接近SVC(superior vena cava上腔靜脈) 的入口。它會使action potential 往整個心臟散佈，因此被稱為pacemaker
Ionic Basis of Electrical Activity in the cardiac
contractile cells 收縮快
Phase 0快: increased permeability to Na+
Phase1早期再極化: decreased permeability to Na+
Phase2平原期Plateau: increased permeability to Ca2+, decreased permeability to K+
Phase3再極化: increased permeability to K+, decreased permeability to Ca2+
Phase4恢復期: resting membrane potential
Ionic Basis of Electrical Activity in automaticity (Ionic Basis of The Slow Response) 自發慢
Phase 4緩慢去極化：Na+、K+、Ca2+(T-type)通道皆開
Phase 0去極化：Ca2+ (L-type)通道打開流入
Phase 3再極化： L-type Ca2+通道關閉， K+通道打開流出
心電圖，PQRST波
AV node傳導速度最慢，PR interval 代表的是AV node傳導速度的快慢。
AV node 最易受autonomic system 影響，
• sympathetic 興奮時，PR 會縮短，心跳加快
• parasympathetic 興奮時，PR 則延長
cardiac contractile cells起始膜電位：－80～－90mV(K+的平衡電位)
automaticity起始膜電位：－40～－60mV
靜止膜電位要記
P波：心房收縮
QRS波：心室收縮
T波：心室再極化
P wave: atrial depolarization
QRS complex: ventricular depolarization and atrial repolarization
T wave: ventricular repolarization
Q2:為何心室仍有動作電位？
其實心臟的傳導系統，各個部位均可自己放電；是因為SA node放電最快，因此在各部位放電前，就已經傳導到各處。所以，一旦去除了SA node的傳導，各部位仍會放電，但是速度較慢。
電力的refractory period和張力曲線的時間長，幾乎相同，因此不會有在「機械性活動下的」張力累積（summation），換言之，也不會有骨骼肌會有的tetanus（強直）現象
循環路徑：
Ventricular filling心室充盈期 → atrial contraction → Isovolumetric ventricular contraction(valve都關閉)同時第一心音 → Ventricular ejection射血期 → Isovolumetric ventricular relaxation(valve都關閉)第二心音
心音是valve關閉的聲音
第一：房室瓣
第二：半月瓣
Diastole舒張 Lowest point = diastolic pressure
Systole收縮 Highest point = systolic pressure
•SV (stroke volume)心搏量
•CO (cardiac output)心輸出量
兩個baroreceptor位置，分別
在aortic arch主動脈弓 和carotid sinus頸動脈竇
Norepinephrine 接在beta receptor
Acetylcholine 接在 Muscarinic receptor2
epinephrine 和norepinephrine 使用同樣的受器，在心臟中主要是β1 adrenergic receptor （ADRB1）
※α receptor 主要在blood vessels 中，而β2 主要是在呼吸系統中
副交感主要會降低SA node的節律速率
交感對心肌收縮影響較明顯
副交感只減少心率，不影響心室收縮
瘦肉精ractopamine 是種β-adrenergic receptor agonist，也就是β stimulator
Sympathetic preganglionic fibers – Acetylcholine
• exception : adrenal gland – Epinephrine
Sympathetic postganglionic fibers – Norepinephrine
• exception : sweat glands – Acetylcholine
交感Glucagon: increases heart rate
影響心搏量的因素大致可分為三點：
(1)心室收縮力的大小
(2)心室舒張末期容積的變化；
(3)動脈周邊阻力Afterload
→心室收縮所需要抵抗的阻力→SVR
→可以受到arterial tone的影響
前負荷(preload)當心室開始收縮時, 心室肌肉所承受的張力，主要由舒張末期容積(end diastolic volume, EDV)來決定
進一步, 會影響"舒張末期容積"的生理因素和疾病主要包括：由靜脈回流心房的血液容量, 是否有二尖瓣/三尖瓣狹窄,是否有大動脈瓣/肺動脈瓣關閉不全, 心室肌肉疾病等.
Hormones
• Epinephrine binds to β1 adrenergic receptors
• Thyroid hormones, insulin, and glucagon increase force of contraction
中心靜脈壓指的是右心房和胸腔內大靜脈的血壓。正常值為5至10厘米水柱。
中心靜脈壓的大小取決於心臟射血能力和靜脈回心血量之間的相互關係。若心臟射血能力強，能將回心的血液及時射到動脈內，中心靜脈壓則低。反之由於心力衰竭等原因造成的射血能力下降則會導致中心靜脈壓變高。
測得的central venous pressure其實就是right atrium的壓力，中心靜脈壓可作為臨床上作為補液速度和補液量的指標(ex：車禍人士補充液體時的參考)
Factors affecting resistance to flow
• Radius of vessel(arterioles )(最主要)必考
• Length of vessel
• Viscosity of fluid = η
Arterioles provide greatest resistance to blood flow
The effect of arteriole radius on blood flow
• Regulation of radius of arterioles (and small arteries)最主要
Vasoconstriction
• Decreased radius → increased resistance
Vasodilation
• Increased radius → decreased resistance
Changes associated with increased metabolic activity generally cause vasodilation
• Carbon dioxide
• Potassium
• Hydrogen ions
Changes associated with decreased metabolic activity generally cause vasoconstriction
• Oxygen
主動性充血 : 指器官或局部組織細動脈血輸入量增多。
Active hyperemia: increased blood flow in response to increased metabolic activity
被動性充血:靜脈血液回流受阻
Reactive hyperemia: increased blood flow in response to a previous reduction in blood flow
Effects of epinephrine on arteriole radius
• Higher concentrations—binds α and β2
• Dominant effect is usually vasoconstriction
高濃度Epinephrine 最後是使血管收縮
• Filtration = movement out of capillary into interstitial space
• Absorption = movement into capillary from interstitial space
hydrostatic靜水壓：液體壓力差(XX的靜水壓代表流出去)
and
osmotic pressures(XX的滲透壓代表流進來)
Net filtration pressure = filtration pressure出去 –absorption pressure進來
MAP = CO × TPR
• CO = HR × SV
• Therefore: MAP平均動脈壓 = HR × SV × TPR(Total peripheral resistance)
Regulation of Mean Arterial Pressure
Short-term regulation: seconds to minutes
• Regulates cardiac output and total peripheral resistance
• Involves the heart and blood vessels
• Primarily neural control
Long-term regulation: minutes to days
• Regulates blood volume
• Involves the kidneys
• Primarily hormonal control
Arterial baroreceptors = sinoaortic receptors
• Aortic arch主動脈弓
• Carotid sinuses頸動脈竇
Parasympathetic input to
• SA node (decreases HR)
• AV node
Sympathetic input to
• SA node (increases HR)
• AV node
• Ventricular myocardium (increases contractility)
• Arterioles (increases resistance)
• Veins (increases venomotor tone)
副交感只調控心率
Regulation of Mean Arterial Pressure
• Epinephrine
• Vasopressin
• Angiotensin II
Vasopressin，Angiotensin II只作用在小動脈平滑肌
During inspiration
• ↑ sympathetic activity → ↑ HR
During expiration
• ↑ parasympathetic activity → ↓ HR
週邊化學受納器主要位於
（1）內、外頸動脈交叉處的頸動脈體（carotid body）和
（2）主動脈弓的主動脈體（aortic body）
跟baroreceptors 不一樣
發生缺氧時，週邊化學受納器（主要是頸動脈體）會被活化：
• 首要作用（primary effect）是活化延腦的迷走神經中樞，增加心臟迷走神經的活性，使得心跳變慢；
• 續發作用（secondary effect）則是透過深化呼吸的活動，產生低碳酸血症（hypocapnia）和增加肺臟的伸展（stretch），進而抑制迷走神經中樞，降低心臟迷走神的活性，使得心跳增快。首要作用與續發作用相互拮抗結果，造成心跳些微的下降
小小結論：中樞化學反射所造成心跳的加速，可克服週邉化學反射所造成心跳的減速，最終體循環的缺氧將造成心跳的増快。
更多量的一氧化氮（nitric oxide, NO），造成血管平滑肌的舒張而降低血管阻力。
• 體循環缺氧對穩態血行力學的影響為：（1）心跳加速、（2）血流增加、（3）總的週邊血管阻力下降；但對血壓的作用並不顯著。
• 然而應注意的是：心跳太快會增加心臟氧的需求量，導致心臟氧的需求與供給失衡，使得心肌有缺氧的
現象。心肌缺氧容易造成心肌病變，導致心臟收縮功能與舒張功能的損害。
• 因此攀登高山時，應留意身體缺氧所導致心跳的過度增加，以免發生危險
