病理生理学缺氧课件

1、Hypoxia缺 氧Shimin Chen, P Department of PathophysiologyHainan Medical CollegeSeptember 1, 2016(3x40min)绝食14天绝水7天绝O2数分钟O2是人体的第一生命物质。一、概述国外教材Do you know “the Rule of Threes”?You can live 3 minutes without air, 3 days without water, 3 weeks without food. Why?Glucose葡萄糖Krebss cycleO2H2O32 ATPGlucose 葡萄糖P

2、yruvate丙酮酸Lactate乳酸2 ATPCO2Hypoxia缺氧Anaerobic无氧 Aerobic oxidation of glucose 葡萄糖有氧氧化O2(tricarboxylic acid(TCA)cycle)三羧酸循环Glycolysis糖酵解 32 ATP有氧代谢2 ATP无氧酵解1分子葡萄糖为什么说O2是人体的第一生命物质?Na +K+若有ATP和 Na + -K + ATPase, 细胞可维持膜电位若细胞缺乏 ATPK+Na +H2ONa+H2OAirAlveoliAlveolarcapillaryGas binds to HbVentilationGas exc

3、hangeExternal respiration外呼吸Internal respiration内呼吸Tissue cellsCirculation Gas transport气体运输空气肺泡肺泡毛细血管氧气和Hb 结合组织细胞循环系统 呼吸的基本过程Exchange of oxygen and carbon dioxide氧气及二氧化碳的交换Extrapulmonary肺外intrapulmonary肺内Concept of Hypoxia缺氧的概念1. Concept of HypoxiaHypoxia is a pathological process. It is defined as

4、 a deficiency in either the delivery or the utilization of oxygen at the tissue level, which can lead to changes in function, metabolism and even structure of the body.O2 DeliveryO2 UtilizationDeficiencyCellular ATPDecreaseFunctionMetabolism Structure Changes 因组织供氧减少或用氧障碍引起细胞代谢、功能和形态结构异常变化的病理过程称为缺氧。

5、Hypoxia is a pathological process, not a disease. 缺氧是一种病理过程，不是独立的疾病。Hypoxia is always direct causes of death. 缺氧常常是死亡的直接原因。常用血氧指标Partial pressure of oxygen, PO2 血氧分压Oxygen binding capacity, C-O2max 血氧容量Oxygen content, C-O2 血氧含量Da-vO2 动-静脉氧含量差Oxygen saturation, SO2 血氧饱和度P50 血氧饱和度为50%时的血氧分压组织的供氧量=？组织耗

6、氧量=？血氧是反映组织的供氧量与耗氧量的重要指标。组织的供氧量= 动脉血氧含量组织血流量组织的耗氧量=（动脉血氧含量-静脉血氧含量）组织血流量。【Normal value】正常值PaO2: 13.3kPa(100mmHg)；PvO2: 5.32kPa(40mmHg)。PaO2: The partial pressure of oxygen in the plasma phase of arterial blood.动脉血氧分压PvO2: The partial pressure of oxygen in the plasma phase of venous blood.静脉血氧分压【Influ

7、ence factors】影响因素 (1) Partial pressure of inspired oxygen （吸入气氧分压， PiO2 ） (2) external respiratory function 外呼吸功能 (3) shunting of blood 静脉血分流入动脉【Influence factors】影响因素(1) PaO2动脉血氧分压(2) Function of internal respiratory 内呼吸功能(细胞利用氧能力) 血氧分压 (Partial pressure of oxygen，PO2 ）CO2max is the maximum amount

8、of oxygen combined by Hb in 100ml blood under fully saturated condition in which the PO2 is 150mmHg, PCO2 40mmHg, and the temperature is 38.100ml血液中Hb所能结合氧的最大毫升数2. 血氧容量 （Oxygen binding capacity，C-O2max）【Normal value】正常值CO2max: 8.92mmol/L (1.34ml/g15gHb% =20ml%)。【Meaning】意义 The ability of Hb to carry

9、 O2. 反映血红蛋白携带氧的能力 【Influence factors】 影响因素 Hb quantity, Hb quality or affinity with O2血红蛋白数量, 血红蛋白质量或与氧的亲和力 The total oxygen content of blood 100ml includes oxygen that is bound to haemoglobin an physically dissolved in plasma. 100ml血液实际所含的氧量，含与 Hb化学结合及物理溶解两部分。3. 血氧含量 （Oxygen content，C-O2） 【Meaning】

10、意义 CaO2: oxygen supplement 氧供CvO2: oxygen consumption 氧耗 【Normal value】正常值 CaO28.47mmol/L(19.3ml%)； CvO2 5.35mmol/L(14ml%)。【Influence factors】影响因素 C-O2max , PaO2 A.V. 4. 动-静脉氧含量差 (arteriovenous blood oxygen difference , Da-v O2 ，CaO2-CvO2)19ml/dl14ml/dl5ml/dlO2O2O2O2O2【Normal value】正常值 5ml%【Influenc

11、e factors】影响因素 utilization of oxygen in the tissue 组织对氧的利用5.血氧饱和度( Oxygen saturation, SO2 )The percentage of hemoglobin present as oxyhemoglobin. 氧合血红蛋白(HbO2) 占总血红蛋白百分数.【Meaning】意义Influence oxygen content 影响血氧含量【Normal value】正常值 SaO2：93%98%； SvO2：70%75%。 【Influence factors】影响因素 (1) PO2 , 氧分压; (2) ab

12、ility of oxygen combined with Hb 氧和血红蛋白结合的能力 (SO2 is determined by PO2 at normal affinity)血氧饱和度血氧含量-物理溶解氧量血氧容量 100PiO2（氧分压）CO2max (氧容量)CO2 (氧含量)PaO2 （氧分压）SO2 (氧饱和度)6. p50 P50 is the PO2 at the 50% SO2 P50 指血红蛋白氧合饱和度为50%时的血氧分压.【Normal value】正常值3.473.6 kPa(2627mmHg)。 【Significance】意义The P50 indicates

13、affinity of hemoglobin for oxygen血红蛋白与氧的亲和力【Influence factors】影响因素 H+, CO2, temperature, 2、3-DPG吸入气体氧分压外呼吸功能血氧分压（PaO2） 血液中Hb的质血液中Hb的量 血氧容量（CO2max）血氧含量（CO2）血氧饱和度各种血氧指标间的相互关系发生缺氧的基本环节空气肺泡肺泡毛细血管氧气和Hb 结合内呼吸组织细胞循环系统 外呼吸肺通气肺换气气体运输Hb携带氧运输氧Hemic Hypoxia血液性缺氧 Hypoxic Hypoxia乏氧性缺氧Circulatory Hypoxia循环性缺氧 Hist

14、ogenous Hypoxia组织性缺氧 缺氧类型Hemic Hypoxia 血液性缺氧 Hypoxic Hypoxia 乏氧性缺氧Circulatory Hypoxia 循环性缺氧 Histogenous Hypoxia 组织性缺氧 病因 (etiology) : (1)吸入气氧分压低Decreased PO2 of inspired airAtmospheric hypoxia（大气性缺氧）Plateau （高原性缺氧) (2) 外呼吸功能障碍 External respiratory dysfunction (3) 静脉血分流入动脉 Venous-to-arterial shunt 乏氧

15、性缺氧 (Hypoxic Hypoxia ) （低张性缺氧, Hypotonic hypoxia）Oxygen tension in arterial blood is lower than normal, which resulted in lack of oxygen from blood to tissues.各种原因使PaO2，以致血氧含量 ，组织供氧不足而引起的缺氧。AltitudemAtmospheremmHgPiO2mmHgPAO2mmHgSaO2%076015910595100068014090942000600125709230005301106290400046098508

16、55000405854575600036674407070003106535608000270563050(1) 吸入气氧分压降低( Decreased PO2 of inspired air)Altitude 3700 m (Tibet Lhasa Potala Palace) 布达拉宫Altitude 1532 m (yellow mountain) 黄山 Altitude 8848 m (The Himalayas ) 喜马拉雅山 法洛氏四联症（tetralogy of Fallot ） (2) 外呼吸功能障碍： respiratory hypoxia （呼吸性缺氧）(3) 静脉血分流入

17、动脉： tetralogy of Fallot (法洛氏四联症)心室间隔缺损，肺动脉狭窄，右心室向心性肥厚。升主动脉开口向右侧偏移Mechanisms:PaO2 CO2 SaO2 inadequate supply O2 to tissue 机制: 动脉血氧分压 血氧含量 血氧饱和度 对组织供氧不足血氧指标变化PaO2 Quality of Hb Quantity of HbOxygen binding capacity （CO2max）Oxygen content （CO2）Oxygen saturation, SO2PiO2Function of external respirationI

18、fNNa. PaO2 PvO2b. CaO2 CvO2 c. CO2max = Nd. SaO2 e. (CaO2 - CvO2)or N 血氧变化特征 Characteristics of blood oxygen:特征性变化PaO2注: N=normal =正常其它变化：1. central cyanosis 中枢性紫绀2. Respiratory compensation 呼吸代偿明显紫绀 【Cyanosis】 The bluish color of skin, nails, lips and mucous membranes when the deoxyhemoglobin (脱氧血红

19、蛋白, 还原型血红蛋白 ) concentration of the blood in the capillaries is more than 5g/dl。5g/dl2.6g/dlHHb5g时，皮肤粘膜呈青紫色的现象.紫绀缺氧Hb 5g/dlSevere anemia严重贫血Hb20g/dlpolycythemia红细胞增多症紫绀 【Cyanosis】 ?+(2) 血液性缺氧 Hemic hypoxia 等张性缺氧 ( isotonic hypoxia)Hemic hypoxia refers to the altered affinity of Hb for oxygen or decre

20、ase in amount of Hb in the bloodHb数量减少Hb性质改变血液携带氧能力下降或不易释放氧缺氧 血液性缺氧病因 :（1）贫血 （Anemia） 最常见的血液性缺氧（2）一氧化碳中毒 （Carbon monoxide poisoning）（3）高铁血红蛋白血症 （Methemoglobinemia, MHb）（4）血红蛋白和氧亲和力过高 （Higher affinity of Hb to oxygen）Mechanisms : a. CO2max CO2 afford O2 to tissue b. CO2max N or but affinity O2 releas

21、ed disorder afford O2 to tissue 机制:血氧容量 血氧含量 对组织供氧不足。或血氧容量正常，但血红蛋白与氧亲和力增加，对组织释放氧减少。血氧指标变化PaO2 Quality of Hb Quantity of HbOxygen binding capacity （CO2max）Oxygen content （CO2）Oxygen saturation, SO2PiO2Function of external respirationIfNNNa. PaO2 =N, PvO2 =Nb. CaO2 CvO2 c. CO2max ( except higher affin

22、ity ) d. SaO2:贫血anemia = N 中毒intoxication 高亲和力 higher affinity e. (CaO2 - CvO2)血氧变化特征Characteristics of blood oxygen:特征性变化 CO2max 其它变化：1 . 无紫绀 no cyanosis（肠源性紫绀除外 except enterogenous cyanosis） 2. 无呼吸代偿 no respiratory compensation血红蛋白与氧亲和力增加 High affinity of Hb for O2 输入碱性液体 (Alkaline solution shifts

23、 the ODC to the left) 输入大量库存血 (Depot blood)1) 贫血 AnemiaSkin colour (Severe anemia) pallor 苍白 Normal 2)一氧化碳中毒 Carbon monoxide poisoning CO与Hb的亲和力比O2大210倍，当吸入的气体内含有0.1%CO时，血液中的血红蛋白可能有50%转为HbCO。机制 (Possible mechanisms of toxicity include)：血红蛋白携带氧能力降低减少2,3-DPG 产生，使氧离曲线左移抑制细胞呼吸结合肌红蛋白，影响心肌和骨骼肌功能Skin color

24、 : 樱桃红 cherry redTable . COHb Levels and Symptomatology 10% Asymptomatic or may have headaches 无症状或有头痛20% Dizzyness, nausea, and syncope 头晕、恶心及晕厥30% Visual disturbances 视觉障碍40% Confusion and syncope 思维混乱、晕厥50% Seizures and coma 痉挛，昏迷60% Cardiopulmonary dysfunction and death 心肺功能不全，死亡3) 肠源性紫绀 Enterog

25、enous cyanosisWhen a lot of pickled vegetables （咸菜，泡菜） containing nitrate（硝酸盐） are taken, the reabsorbed nitrite(亚硝酸盐) reacts with HbFe2+ to form HbFe3+. HbFe2+ HbFe3+OH氧化剂oxidizers亚硝酸盐 nitriteMethemoglobin高铁血红蛋白The skin appears to coffee or chocolate color（皮肤呈咖啡色、巧克力色或石板色） while HbFe3+ OH 1.5g/dl.

26、This phenomenon is called enterogenous cyanosis（肠源性紫绀）.Coffee bean Enterogenous cyanosis肠源性紫绀chocolate(3) 循环性缺氧 Circulatory hypoxia (低动力性缺氧, hypokinetic hypoxia) Circulatory hypoxia refers to inadequate blood flow leading to inadequate oxygenation of the tissues, which is also called hypokinetic hyp

27、oxia.由于组织血流量减少,使组织供氧量减少所引起的缺氧。病因: a. 全身性循环障碍 （General circulatory dysfunction） - 如休克、心衰 （e.g. shock; heart failure.） b.局部性循环障碍（Local circulatory deficiency） - 如血管狭窄、闭塞、血栓形成（e.g. stenosis; occlusion; thrombosis.） 机制 Mechanisms: 组织血液灌流减少 （Reduced tissue perfusion）： a. 缺血性缺氧 （ischemia hypoxia） b. 淤血（充血

28、）性缺氧 （congestive hypoxia）血氧指标变化PaO2 Quality of Hb Quantity of HbOxygen binding capacity （CO2max）Oxygen content （CO2）Oxygen saturation, SO2PiO2Function of external respirationIfNNNNNN a. PaO2 = N PvO2 b. CaO2 = N CvO2 c. CO2max = N d. SaO2 = N e. Da-v O2 (CaO2-CvO2) 血氧变化特征 Characteristics of blood ox

29、ygen:特征性变化 Da-v O2 (CaO2-CvO2) 其它变化：1. 外周性紫绀 （peripheral cyanosis）2. 有或无呼吸代偿 （Respiratory compensation or not）(4) 组织性缺氧 Histogenous Hypoxia (用氧障碍性缺氧 dysoxidative hypoxia)Histogenous hypoxia refers to the tissue cells can not make use of the oxygen supplied to them, though the amount of oxygen delive

30、red to them is adequate.组织细胞利用氧的能力下降所致的缺氧，即氧利用障碍.病因: a. 细胞中毒 线粒体功能受损 Cell poisoning dysfunction of Mitochondria : cyanide poisoninghistotoxic hypoxia b. 线粒体损伤 Mitochondria injury: radiation ; oxygen free radical c. 维生素缺乏呼吸酶不足 deficiency of vitamin B2 or PP机制 Mechanisms: Disorder of biological oxidat

31、ion or oxidative phosphorylation failure to utilization of oxygen ATP.生物氧化和氧化磷酸化发生障碍，细胞不能利用氧ATP.The mitochondrial respiratory chain and its inhibitors线粒体呼吸链及其抑制物鱼藤酮抗霉素氰化物还原型辅酶黄素单核甘酸黄素腺嘌呤二核甘酸琥珀酸盐三氟乙酸铊铁硫蛋白细胞色素体系辅酶Q血氧指标变化PaO2 Quality of Hb Quantity of HbOxygen binding capacity （CO2max）Oxygen content （C

32、O2）Oxygen saturation, SO2PiO2Function of external respirationIfNNNNNN a. PaO2 = N, PvO2 b. CaO2 = N, CvO2 c. CO2max = N d. SaO2 = N e. (CaO2-CvO2)血氧变化特征Characteristics of blood oxygen:特征性变化 Da-v O2 (CaO2-CvO2) 其它变化：1. 无紫绀 （No cyanosis）2.无呼吸代偿 （No respiratory compensation） CO2maxPaO2CaO2 SaO2CO2(A-V)

33、各型缺氧的原因和血氧特点BriefTypesMeans normal value 正常 乏氧性缺氧血液性缺氧循环性缺氧组织性缺氧小鼠缺氧时肝脏颜色变化Liver color changes in mice hypoxia 正常Normal control一氧化碳中毒CO poisoning乏氧性缺氧Hypoxic hypoxia肠源性紫绀Enterogenous cyanosisBrief混合性缺氧临床所见缺氧的原因往往不是单一的，常为混合性缺氧。例如感染性休克时主要是循环性缺氧，内毒素还可引起组织利用氧的功能障碍而发生组织性缺氧，并发休克肺时可有呼吸性缺氧（低张性缺氧）。 四. 缺氧体征Si

34、gns of hypoxia Signs of hypoxiaMild to moderateSevereTachypnea呼吸急促Paleness苍白Tachycardia心动过速Mild hypertension轻度高血压 Restlessness烦躁不安Headache头痛Lassitude 疲乏Tachypnea 呼吸急促Cyanosis 紫绀Bradycardia 心动过缓Arrhythmias 心律失常Hypotension 低血压Confusion 思维混乱Impaired judgement 判断力减退五、缺氧时机体的功能代谢变化Functional and metabolic

35、 changes of the body in hypoxia提问：缺氧对机体的影响范围？全身性？局部性？ 急性严重缺氧时机体变化以失代偿和损伤为主； 轻度缺氧时机体或细胞以代偿性调节为主。 慢性缺氧时机体的代偿反应和缺氧性损伤并存。缺氧时机体的功能代谢变化Changes of function and metabolism呼吸系统的变化 Respiratory system循环系统的变化 Circulatory system血液系统的变化 Hematologic system中枢神经系统的变化 Central nervous system 组织和细胞变化 Tissues and cells呼

36、吸系统的变化【Respiratory system】1. 代偿反应 Compensatory response：PaO2 ( 8Kpa , 60mmHg) chemoreceptorsrespiratory rate and depth hyperventilation.PaO2 ventilation Severe hypoxia(PaO230mmHg) depressing respiratory center slow and periodic or irregular breathing stop of breathing.Kussmauls respirationNormal res

37、piration【Respiratory system】 2. 失代偿反应 Decompensatory effects: 1）高原肺水肿 High altitude pulmonary edema 2）中枢性呼吸衰竭 Central respiratory failure 1）高原肺水肿（high altitude pulmonary edema, HAPE）进入4000m高原后14d内出现发病率：5.717.7临床表现：胸闷，咳嗽，发绀，呼吸困难，血性泡沫痰体征：肺部湿罗音高原肺水肿发病机制 外周血管收缩，回心血量增加；缺氧性肺血管收缩，肺动脉高压；肺动脉收缩不均一引起超灌注非炎性漏出；肺

38、毛细血管壁通透性增加。2）中枢性呼吸衰竭 （Central respiratory failure） Respiratory inhibition, irregular respiratory rhythm and frequency, hypoventilation, e.g. periodic breathing, Cheyne-Stoke respiration (陈-施呼吸，又称潮式呼吸), Biots breathing.spinal meningitisapneaapneaheart failure, strokes, traumatic brain injuries and br

39、ain tumorsbreathing is absent for a period and then rapid for a period循环系统的变化【Circulatory system】心输出量增加Cardiac output -Adrenoceptor vasoconstrictionLocal metabolites vasodilation保证心脑血液供应To afford blood to heart and brain(1) 代偿反应 Compensatory effect: 心肌收缩性增加 Myocardial contractility 心动过速Tachycardia D

40、ecreasing blood flow in guts and skin Increasing blood flow in heart and brain 血液重分布Redistribution of blood2. 失代偿反应 Decompensatory effect: 肺动脉高压 （Pulmonary hypertension ）：使得右室后负荷增加，引起右心室肥大代偿、失代偿、心力衰竭。心肌的收缩与舒张功能降低（Decreased diastolic and systolicmyocardial function）：心肌缺氧和酸中毒心律失常 （Arrhythmia）：窦性心动过缓、引

41、起期前收缩和各种心律失常，包括引起心室纤维颤动致死。静脉回流减少（Decrease in venous return to the heart）：严重、持久的缺氧使得外周血管扩张，血液淤滞。血液系统的变化【Hematologic system】代偿反应 Compensatory response增加红细胞数和血红蛋白数 （Increase in the amount of RBCs and Hb）More erythropoietin(EPO) produced and released by kidney改善红细胞释放氧能力 （Improved RBC oxygen release capa

42、bility）（Rightward shift of oxyhemoglobin dissociation curve ） More 2,3-DPG produced from glycolysis process1122HbO21122HHb2,3-DPG unable to bind2,3-DPG binding site2,3-DPG binds to HHb at the central cavity2. 失代偿反应 Decompensatory effect: 血浆粘滞度增高 Plasma viscosity, 外周阻力（血流阻力）增大 blood flow resistance ,

43、 心脏后负荷增高 afterload of heart 当氧分压过低， 2,3-DPG 会引起动脉血氧含量降低。 When PO2 is low markedly, 2,3-DPG will cause CaO2 to decrease.中枢神经系统的变化【Central nervous system】2 % of a humans body weight is brain.15-20% of the blood in the body is used by the brain.20% of all the oxygen breathed in is used by the brain.6%

44、of cerebral oxygen consumption by white.94% of cerebral oxygen consumption by gray matter.Brain cells are extremely sensitive to hypoxia. 脑细胞对缺氧非常敏感。 脑重仅为体重的2%左右，而脑血流量约占心输出量之15%，脑耗氧量约为总耗氧量的23%，所以脑对缺氧十分敏感。脑灰质比白质的耗氧量多5倍，对缺氧的耐受性更差。中枢神经系统【Central nervous system】(1) 急性缺氧 Acute hypoxia: headache, agitatio

45、n, poor ability of memory, inability to make judgment, depress or loss of coordination(2) 慢性缺氧 Chronic hypoxia: impaired concentration, fatigue, drowsiness(3) 脑水肿和神经元损伤 Cerebral edema and neuron injury脑功能障碍 Dysfunction急性缺氧、慢性缺氧、严重缺氧（PaO228mmHg)可以产生严重程度不同的CNS功能障碍缺氧时CNS功能障碍的主要原因和机制：神经细胞膜电位降低神经介质合成减少ATP生成不足酸中毒细胞水肿细胞内游离Ca2+增多溶酶体酶释放神经细胞的结构破坏等机制 ： 脑细胞水肿 血脑屏障功能受损 脑静脉内血栓形成高原性脑水肿：重度高原反应并发症，CNS受损，颅内高压组织、细胞的变化【Tissue and cellular alteration】(1) 代偿反应 Comp