1、王婧婧王婧婧山东大学医学院病理生理学教研室山东大学医学院病理生理学教研室氧气的获得和利用氧气的获得和利用:ventilationgas exchangeinternal respirationexternal respirationairalveoliAlveolar capillaryGas transportTissue cells运送氧运送氧或或利用氧利用氧发生障碍时,机体发生发生障碍时,机体发生功能功能、代谢代谢、形态结构改变形态结构改变的病理过程的病理过程.Tissue cells cant obtain enough oxygen or cant fully utilize oxy
2、gen metabolic,functional and structural changesO2 capacityO2 content(CO2)O2 saturationO2O2O2 in a blood sampleO2 content动静脉血氧差动静脉血氧差:动脉血氧含量动脉血氧含量-静脉血氧含量静脉血氧含量19ml/dl14ml/dl5ml/dlO2O2O2O2O2AVCaOCaO2 2-CvO-CvO2 2Reflect the oxygen consumption rate of Reflect the oxygen consumption rate of the tissue.t
3、he tissue.O2 saturation指指Hb结合氧的百分数结合氧的百分数Amount of oxygen actually combined with Hb,expressed as a percentage of oxygen capacity.CO2 O2 of physical solutionCO2 max100%=2,3-DPG2,3-DPGlIntroductionlClassification,etiology and pathogenesislFunctional and metabolic changeslFactors involved in tolerance
4、to hypoxialOxygen treatment and oxygen toxicityAirGas transport+Hb circulationTissue cellsExternal respirationClassification血液性缺氧血液性缺氧Hemic Hemic hypoxiahypoxia循环性缺氧循环性缺氧Circulatory Circulatory hypoxiahypoxia低张性缺氧低张性缺氧Hypotonic Hypotonic hypoxiahypoxia组织性缺氧组织性缺氧HistogenousHistogenoushypoxiahypoxia低张
5、性缺氧低张性缺氧Hypotonic Hypotonic hypoxiahypoxia血液性缺氧血液性缺氧Hemic Hemic hypoxiahypoxia循环性缺氧循环性缺氧Circulatory Circulatory hypoxiahypoxia组织性缺氧组织性缺氧HistogenousHistogenoushypoxiahypoxia Causes:1)PiO2:high altitude(30004000m)海拔高度海拔高度 大气压大气压 PiO2 PAO2 SO2 (m)(mmHg)(mmHg)(mmHg)%海平面海平面 760 159 105 951000 680 140 90
6、942000 600 125 70 923000 530 110 62 905000 405 85 45 756000 366 74 40 708000 270 56 30 50 2040608010020406080100氧氧饱饱和和度度%氧分压氧分压(mmHg)pH2,3-DPGTemp NO 3000 m呼吸中枢抑制脊髓高位损伤脊髓前角细胞受损运动神经受损呼吸肌 无力弹性阻力增加 胸壁损伤气道狭窄 或阻塞2)Dysfunction of external respirationNormal lung bronchial asthma Bronchioles normalPAO2 norm
7、alPaO2 normalBronchioles constrictedPAO2 lowPaO2 low表面活性物质肺泡血液内皮细胞上皮细胞基膜O2CO2Normal lung pulmonary edema Bronchioles normalPAO2 normalPaO2 normalPAO2 normalIncreased diffusion distancePaO2 low3)Shunt HbO2HHb2.6g/dl正常正常5g/dl缺氧缺氧发绀发绀 (cyanosis)毛细血管中脱氧血红蛋白毛细血管中脱氧血红蛋白5 g/dl,使皮肤、粘,使皮肤、粘膜呈青紫色膜呈青紫色.发绀发绀 (c
8、yanosis)缺氧不一定有发绀,发绀不一定有缺氧。缺氧不一定有发绀,发绀不一定有缺氧。当血红蛋白过多或过少 时,发绀与缺氧常不一致。例如重度贫血患者,血红蛋白可降至50 g/L(5 g/dl)以下,出现严重缺氧,但不会发生紫绀。红细胞增多病患者,血中还原血红蛋白超过50 g/L(5 g/dl),出现发绀,但可无缺氧症状。紫绀紫绀 与与 缺氧缺氧的关系的关系Types ofhypoxiaPaO2SaO2CO2(a-v)Hypotonic hypoxiaN(or)(or N)Hb量量,质质改变改变血液携带氧的能力血液携带氧的能力或或Hb结合的氧不结合的氧不易释出易释出组织缺氧组织缺氧Causes
9、:anemia anemic hypoxiacarboxyhemoglobinemiab.CO抑制抑制RBC内糖酵解内糖酵解2,3-DPG生成生成氧解离曲线左移氧解离曲线左移Hb和和O2的亲和力的亲和力释放释放O2COO2O2O2Hb:2 2樱桃红色樱桃红色高铁血红蛋白血症(高铁血红蛋白血症(methemoglobinemia)methemoglobinemia)Hb-Fe2+HbFe3+OH氧化氧化还原还原 肠源性紫绀肠源性紫绀(enterogenous cyanosis)(enterogenous cyanosis)咖啡色咖啡色 P50:HbHb与与O2O2的亲和力异常的亲和力异常tran
10、sfusion of depot bloodTypes ofhypoxiaPaO2CO2maxCaO2SaO2CO2A-VHypotonic hypoxiaN or or NHemic hypoxiaN N NN P50P50 肠源性紫绀肠源性紫绀(enterogenous cyanosis)(enterogenous cyanosis)血液循环发生障碍,组织供血量血液循环发生障碍,组织供血量 引起的缺氧引起的缺氧.缺血缺血:ischemic hypoxia 淤血淤血:hypoxia动脉动脉静脉静脉毛细血管毛细血管内压内压动脉动脉静脉静脉毛细血管毛细血管内压内压19ml/dl12ml/dl7m
11、l/dlO2O2O2O2O2AVO2O2O2缺血,淤血缺血,淤血血流缓慢血流缓慢血液流经血液流经capcap的时间的时间细胞摄氧细胞摄氧COCO2 2a-va-v单位时间流经组织的总血量单位时间流经组织的总血量 弥散入细胞的总弥散入细胞的总氧量氧量 氧供氧供 CirculatoryhypoxiaNNNNTypes ofhypoxiaPaO2CO2maxCaO2SaO2CO2A-VHypotonic hypoxiaN or or NHemic hypoxiaN N NN Inability of the cells to utilize the oxygen 组织细胞利用氧障碍组织细胞利用氧障碍
12、(1)“Histotoxic hypoxia”抑制细胞氧化磷酸化抑制细胞氧化磷酸化:CN-与线粒体中氧化型细胞色素氧化酶上Fe3+结合,使其不能还原,失去传递电子的功能,呼吸链中断砷化物抑制细胞色素氧化酶、呼吸链酶复合物、丙酮酸氧化酶甲醇通过其氧化产物甲醛与细胞色素氧化酶结合,导致呼吸链中断 Result:CvO2 CO2a-vCirculatoryhypoxiaNNNNTypes ofhypoxiaPaO2CO2maxCO2SaO2CO2A-VHypotonic hypoxiaN or or NHemic hypoxiaN N NN HistogenoushypoxiaNNNN失血性休克失血
13、性休克HbHb 肺淤血、水肿肺淤血、水肿循环障碍循环障碍Hemic hypoxiaHypotonic hypoxiaCirculatory hypoxialIntroductionlClassification,etiology and pathogenesislFunctional and metabolic changeslFactors involved in tolerance to hypoxialOxygen treatment and oxygen toxicityHypotonic hypoxia(1)Compensatory response PaO2 60mmHg peri
14、pheral chemoreceptor H+central chemoreceptor alveolar ventilation PaO2 PaCO2(limit)Respiratory rate and depth 静脉回流静脉回流 心输出量和肺血流量心输出量和肺血流量 有利于氧的摄取和运输有利于氧的摄取和运输低张性缺氧引起的肺通气变化与缺氧持续的时间有关4000m高原:当天:通气量仅增加65%(低碳酸血症,呼碱限制)2-3天:通气量增加5-7倍(呼碱肾代偿)久居:通气量增加15%(外周化学感受器的敏感性)肺通气量增加是急性缺氧最重要的代偿性反应但:肺通气 耗氧量(2 2)Injured
15、Manifestations)急性低张性缺氧高原性肺水肿 快速登上4000米以上的高原,可在14天发生肺水肿,表现为呼吸困难、咳嗽、血性泡沫痰、肺部有湿罗音、皮肤粘膜发绀、头痛等。男性发病率明显高于女性。缺氧、寒冷和劳累是主要诱因。轻微高原病症状如头疼、恶心及睡眠障碍等多在到达高原后的第二天至第四天出现。干咳是较早的表现,其发生可先于肺部罗音的出现。其它常见的临床表现有心动过速、低热、胸痛及白色泡沫痰甚至咯血。部分患者病情进行性恶化,出现严重的呼吸困难、精神淡漠等HAPE表现,严重者在数小时内即出现呼吸窘迫,发生急性呼吸衰竭甚至死亡。“肺动脉高压肺动脉高压”:缺氧缺氧呼吸运动呼吸运动 胸内负压
16、胸内负压缺氧缺氧外周血管收缩外周血管收缩回心血量,肺血流量回心血量,肺血流量缺氧性肺血管收缩缺氧性肺血管收缩肺循环阻力肺循环阻力 局部收缩较轻或不收缩局部收缩较轻或不收缩非炎性漏出非炎性漏出炎性因子炎性因子肺泡毛细血管膜炎性渗出肺泡毛细血管膜炎性渗出肺动脉高压肺动脉高压cap内压内压)中枢性呼吸衰竭)中枢性呼吸衰竭PaO2 30mmHg 可直接抑制呼吸中枢 呼吸抑制,呼吸的节律和频率不规则。2.circulatory system(1)Compensatory response CO 氧的运输a.心率(肺牵张SN兴奋)b.心肌收缩性(缺氧 SN兴奋)c.静脉回流量(呼吸、心脏)pulmonar
17、y vasoconstriction “缺氧性肺血管收缩缺氧性肺血管收缩”以调整肺内不同区域通气/血流比 氧的摄取 a.缺氧直接对VSMC作用:KV,KCa,KATPu缺氧 KV K+外流 细胞膜去极化电压依赖性Ca2+开放Ca2+内流 VSMC收缩血管收缩:肺小动脉u胞浆游离Ca2+Kca开放uATP KATP开放 b.体液因素:缩血管物质(Ang,ET,TXA2)占优势。c.交感神经作用:肺血管-肾上腺受体密度较高,交感神经兴奋时肺小动脉收缩。血管舒张:心、脑 blood redistribution blood redistribution 保证重要器官的氧供保证重要器官的氧供a.皮肤、
18、腹腔脏器血流(交感兴奋,受体密度高)b.心、脑血流(局部代谢产物,扩血管)c.心脑血管平滑肌细胞膜的KCa和KATP开放,钾外向电流增加,细胞膜超极化,Ca2+内流。cajpillary proliferation cajpillary proliferation 长期缺氧 缺氧诱导因子-1(HIF-1)血管内皮生长因子(VEGF)基因表达,尤其是心、脑、骨骼肌毛细血管增生 氧弥散距离,供氧量(2)Injured Manifestations Pulmonary arterial hypertension a.慢性缺氧 肺血管收缩 肺循环阻力 肺动脉高压:抑制肺动脉Kv通道mRNA和蛋白质的表
19、达 Kv通道 钙内流 b.钙内流 肺血管重塑:血管平滑肌细胞和成纤维细胞肥大、增 生 血管硬化 持续的肺动脉高压右心肥大、右心衰 Decreased myocardial contractility and extensibility a.缺氧 ATP b.缺氧 ATP 心肌细胞膜和肌浆网钙转运功能障碍c.慢性缺氧 RBC,血粘度d.严重缺氧心肌收缩蛋白破坏,心肌挛缩或断裂 Arrhythmia Arrhythmia 严重缺氧 细胞内外离子分布异常心动过缓、期前收缩、室颤等 decreased venous return a.严重缺氧 呼吸中枢受抑制 胸廓运动减弱 b.严重而持久的缺氧乳酸、腺
20、苷等扩血管产物积累 Hypertension OSAHS睡眠呼吸暂停综合征引起的高血压可达 45%48%儿茶酚胺,呼吸暂停,睡眠紊乱血压升高与 打鼾的严重程度和呼吸暂停时间呈正比关系;血压失去正常的昼夜节律性变化规律,出现夜间血压比白天高,早晨血压比入睡前高,优以舒张压升高为著,脉压差减小,白天活动后改善了缺氧状态,血压反而降低了;白天伴有嗜睡、头痛头晕、乏力、记忆力减退,夜尿增多等;多见于中老年肥胖男性和更年期妇女;单纯降压药物治疗很难奏效,必须有效治疗 鼾症后血压才可能降低或恢复正常。3.Hemic system(1)Compensatory response(1)Increase of
21、RBC and Hb 急性缺氧:急性缺氧:交感神经兴奋,血液重分布肝、脾储血释放 慢性缺氧慢性缺氧 肾脏分泌促红细胞生成素 RBC、Hb 血液的CO2 max和CaO2 组织的供氧量(2)Rightward shift of oxyhemoglobin dissociation curve 缺氧 糖无氧酵解 2,3-DPG 氧离曲线右移RBC向组织释放O2的能力 组织的供氧量 (2)Injured ManifestationsPO2 0.5 atm 1.肺型氧中毒肺型氧中毒(puImonary type of oxygen intoxication)7I9KbMePgRiUlWnYp!s%u*
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31、w)z0B2D5G7I9LcNePgSjUlWoZq!s%v(x-z1C3E5H8JaLcOfQhSkVmXoZr$t&v)y+A1DiTkVnYp#r$u*w)gRjUlWnYq!s%u(x-z0C3E5G7JaLcNfQhSjVmXoZq$t&v(y+A1C3F6H8JbMdOfRiTkVmYp#r$u*w)y0B2D4F7I9KbNePgRiUlWnYq!s%u(x-z0B3E5G7JaLcNfQhSjUmXoZq$t&v(x+A1C3FmXoZr$t&v)y+A1D4F6H8KbMdOgRiTkWnYp#r%u*w)z0B2D4G7I9KcNePgSjUlWnZq!s%v(x-z1C3
32、E5G8JaLcOfQhSjVmXoZr$t&v)y+A1C4F6H8KbMdOgRiTkVnYp#r%u*w)y0B2D4nZq!s%u(x-z0C3E5G8JaLcNfQhSjVmXoZq$t&vbMdOfQiTkVmYp#r$t*w)y+B2D4F7I9KbMePgRiUlWnYq!s%u*x-z0B3E5G7Zq!s%v(x-z1C3E5G8JaLcOfQhSjVmXoZr$t&v)y+A1C4F6H8KbMdOfRiTkVnYp#r%u*w)y0B2D4G7I9KcNePgRjUlWnZq!s%u(x-z0C3E5G8JaLcNfQhSjVmXoZr$t&v(y+A1C4F6H8Jb
33、M*w)y0B2D4F7I9KbNePgRjUlWnYq!s%u(x-z0C3E5G7JaLcNfQhSjUmXoZq$t&v(y+A1C3F6H8JbMdOfRiTkVmYp#r$u*w)y+B2D4FlWnYp!s%u*x-z0B2E5G7IaLcNeQhSjUlXoZq!t&v(x-A1CjVmXoZr$t&v(y+A1C4F6H8JbMdOfRiTkVnYp#r$u*w)y0B2D4G7I9KbNePgRjUlWnYq!s%u(x-z0C3E5G7JaLcNfQhSjUmXoZq$t&v(y+A1C3F6H8JbMdOfRiTkVmYp#r$u*w)yRiUlWnYq!s%u*x-z0
34、B3E5G7JaLcNeQhSjUmXoZq$t&v(x+A1C3F6H8JaMdOfQiTkVmYp#r$t*w)y+B2D4F7I9KbMePgRiUlWn2E5G7IaLcNePhSjUlXoZq!s&v(x-A1C3E6H8JaLdOfQhTkVmXo#r$t&w)y+A2D4F6H9K%u*w-z0B2D5G7I9LcNePhSjUlWoZq!s&v(x-z1C3E5H8JaLdOfQhSkVmXo#r$t&w)y+A1D4F6H9KbMdOgRiTkWnYp#s%u*w)z0B2D5G7I9LcNePgSjUlWoZq!s%v(x-z1SjUlXoZq!t&v(x+A1C3E6H8
35、JaMdOfQiTkVmXp#r$t*w)y+A2D4F6I9KbMePgRi-z0B2D5G7I9LcNePhSjUlWoZq!s&v(x-A1C3E5H8JaLdOfQhSkVmXo#r$t&w)y+A1D4F6H9KbMdPgRiTkWnYp#s%u*w)z0B2lWoZq!s%v(x-z1C3E5H8JaLcOfQhSkVmXoZr$t&v)y+A1D4F6H8KbMdOgRiTkWnYp#r%u*w)z0B2D4G7I9KcNePgSjUlWnZq!s%v(x-zhSjUlXoZq!t&v(x-A1C3E6H8JaMdOfQhTkVmXp#r$t9KbMdOgRiTkWnYp#s%u
36、*w)z0B2D5G7I9LcNePgSjUlWoZq!s%v(x-z1C3E5H8JaLcOfQhSkVmXo#r$t&v)gRiTkWnYp#r%u*w)z0B2D4G7I9KcNePgSjUlWnZq!s%v(x-z1C3E5G8JaLcOfQhSjVmXoZr$t&v)y+A1C4F6H8KbMdOgRiTkVnYp#r%u*w)y0B2D4GnYp#s%u*w-z0B2E5G7I9LcNePhSjUlXoZqZq$JaLcOfQhSkVmXo#r$t&v)y+A1D4F6H8KbMdOgRiTkWnYp#r%u*w)z0B2D5G7I9KcNePgSjUlWnZq!s%v(x-z1C
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