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Hypoxia

Hypoxia. Zhihua Gao Zhejiang University. Overview. Review of respiration Measurements of O 2 Hypoxia definition classification, etiology, mechanism resultant changes in the body prevention and treatment. Respiration-a process of gas exchange. 1. O2 intake. External respiration.

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Hypoxia

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  1. Hypoxia Zhihua Gao Zhejiang University

  2. Overview Review of respiration Measurements of O2 Hypoxia definition classification, etiology, mechanism resultant changes in the body prevention and treatment

  3. Respiration-a process of gas exchange 1. O2 intake External respiration 2. Hb carrying O2 3. O2 transport in circulation 4. O2 utilization in the tissue

  4. O2 dependence Large amount of O2 consumption ----250ml/min (360L/day) Small amount of O2 storage ----1.5L (sustain life only six minutes) Continuous hypoxia >6 min--life-threatening

  5. Measurements of O2 (1) • PO2 (partial pressure of oxygen) 血氧分压 • Oxygen tension 血氧张力 • the tension produced by oxygen molecules physically dissolved in the blood • Arterial (PaO2): 100 mmHg (13.3kPa)， 取决于吸入气体的氧分压和外呼吸功能 • Venous (PvO2): 40 mmHg (5.33kPa) ，取决于组织摄氧和用氧的能力 • Influence factors (IFs): • Pressure of O2 in the air （空气氧分压） • External respiratory function （外呼吸功能） • Shunt of blood (血液分流)

  6. Measurements of O2 (2) • CO2max (oxygen binding capacity)，最大血氧容量 • Maximal amount of oxygen that can be potentially bound by the haemoglobin (Hb), reflecting the ability of Hb carrying O2. • Under ideal condition, the binding capacity is ~1.34 ml/g Hb • CO2max 反映血液携氧能力的强弱 • IFs: • Quantity of Hb (血红蛋白的量) • Quality of Hb or affinity of Hb (血红蛋白的质与亲和力)

  7. Measurements of O2 (3) • CO2: (oxygen content), 实际血氧含量 • theactual O2 content in the blood, including the oxygen bound to the Hb and O2 dissolved in the blood. • Arterial CO2 (CaO2): 19 ml/dl • Venous CO2 (CvO2): 14 ml/dl • Differences of CO2 between arterial and venous (Da-vCO2): 动-静脉血氧含量差：5 ml/dl • IFs: • PaO2 • CO2 max--Hb quantity and quality

  8. Measurements of O2 (4) • SO2 (oxygen saturation)， 血氧饱和度 • the percentage of oxygen-bound form (oxyhemoglobin) in total Hb. • SO2=(血氧含量-溶解氧量)、血氧容量X100% • Arterial (SaO2): 97-99% • Venous (SvO2): 75% • IFs: • PO2 • pH, temperature • CO2, DPG

  9. O2 saturation dissociation curve (SDC) Left shift Right shift A curve reflecting the relationship between the PO2 and SO2 S (sigmoid) shape SO2 , SDC left shift Hb affinity SO2 , SDC right shift Hb affinity

  10. P50-a value indicating the flexibility of Hb P50: the PO2 @ 50% SO2 Reflecting the flexibility of Hb carrying O2 SDC right shift , P50↑ SDC left shift, P50↓

  11. Hypoxia Inadequate supply of O2 (氧供不足) Insufficient utilization of O2 （用氧障碍） Defintion: A pathological process in which O2 supply to tissues is inadequate to meet the demand of cells, or utilization of O2 is insufficient in cells despite adequate O2 supply, leading to changes in functions, metabolisms and structures of cells and tissues in the body.

  12. Classification of hypoxia 1. O2 intake 1. Hypotonic hypoxia 2. Hb carrying O2 2. Hemic hypoxia 3. O2 transport in circulation 3. Circulatory hypoxia 4. O2 utilization in the tissue 4. Histogenous hypoxia

  13. Hypotonic/hypoxic hypoxia(低张性缺氧) The most common type of hypoxia • Causes: • O2 supply • Tibetan Plateau, mineral wells • Dysfunction in external respiration, a.k.a respiratory hypoxia • Bronchial obstruction • Respiratory muscle paralysis • Venous-to-arterial shunts • Congenital cardiac defects

  14. Hypotonic/hypoxic hypoxia Features: minor: PaO2↓;CO2 N Severe: PaO2↓; CO2max N, CaO2↓; SaO2↓ D(a-v)O2↓or N Central cyanosis (紫绀) Respiratory compensation

  15. Cyanosis (发绀或紫绀)

  16. Cyanosis (发绀或紫绀) Deoxyhemoglobin >5g/dl(central cyanosis) Patients with hypoxia can show cyanosis, but cynosis does not mean hypoxia. Patients with severe anemia (贫血)， with total amount of hemoglobin <5g/dl, will not show cyanosis when they are hypoxic. Hypoxia patients may not have cyanosis. Enterogenous cyanosis (肠源性紫绀):

  17. Hemic/isotonic hypoxia（血液性缺氧） • Hypoxia caused by abnormalities in hemoglobin (Hb) • Amount of Hb ↓ • Altered binding capacity of Hb • Causes: • Anemia • CO poisoning • Methemoglobinemia • Higher affinity of Hb to O2

  18. Hb concentration &CaO2 relationship 300 100 polycythemia Hb = 20 100 200 normal Hb = 15 CaO2, ml/l 150 SaO2, % 100 anemia Hb = 10 20 60 100 120 PaO2 , mmHg

  19. CO poisoning（一氧化碳中毒） CO binds to Hb to form COHb (碳氧血红蛋白), which cannot take up O2. Affinity of Hb to CO is ~210 times higher than O2, dissociation of CO from Hb is much slower than O2.

  20. Methemoglobinemia (高铁血红蛋白血症) • 正常血红蛋白的铁主要以二价形式存在，亚硝酸盐，过氧酸盐、磺胺衍生物等氧化剂可使血红蛋白中的二价铁氧化成三价铁，形成高铁血红蛋白血症 （Methemoglobinemia，HbFe3+OH）。 • Central cyanosis (紫绀) v.s. Enterogenous cyanosis (肠源性紫绀): • 食用大量含亚硝酸盐的腌菜后，硝酸盐颈肠道细菌还原为亚硝酸盐，吸收入血后，使血红蛋白的二价铁氧化为三价铁，导致高铁血红蛋白血症。 • 当血液中HbFe3+OH>1.5g/dl, 皮肤，粘膜可出现青紫，为肠源性紫绀。

  21. Hemic/isotonic hypoxia Features: Normal PaO2 CO2 max ↓and CaO2↓→O2 delivery to tissue ↓ CO2 max normal but affinity ↑→ O2 release to tissue ↓

  22. Circulatory/hypokinetic hypoxia（循环性缺氧） • Inadequate blood flow resulting in insufficient oxygenation of the tissue • Causes: • General circulatory dysfunction-shock, heart failure • Local circulatory dysfunction-stenosis, occlusion, thrombosis • Mechanisms---tissue perfusion ↓ • ischemia hypoxia （缺血性缺氧） • congestive hypoxia （充血性缺氧）

  23. Circulatory/hypokinetic hypoxia（循环性缺氧） Features: a. PaO2: N PvO2↓ b. CaO2: N CvO2↓ c. CO2max: N d. SaO2: N e. (Da-vCO2)↑ f. Peripheral cyanosis (外周性紫绀) g. Respiratory compensation 由于全身性或局部循环障碍使血液流经组织毛细血管的时间延长， 细胞从单位容量血液中摄取的氧量增加，使静脉血氧含量降低，动-静脉血氧分差增加

  24. Histogenous/dysoxidative hypoxia (组织性缺氧) • Causes: • Cell/tissue poisoningcyanide (氰化物) poisoning→histotoxic hypoxia • Arsenic poisoning (砒霜) • Mitochondria injury radiation ; ROS • Inadequate synthesis of biological oxidation coenzyme deficiency of vitamin B2 or PP

  25. Mechanisms: Aberrant biological oxidation or oxidative phosphorylation → deficiency in oxygen consumption →ATP↓.

  26. Features: a. PaO2 = N, PvO2↑ b. CaO2 = N, CvO2↑ c. CO2max = N d. SaO2 = N e. (CaO2-CvO2)↓ f. No cyanosis g. No respiratory compensation

  27. Features of different types of hypoxia Type PaO2 SaO2 CO2 max CaO2 D(a-v)CO2 Hypotonic hypoxia ↓↓ N ↓↓ or N Hemic hypoxia N ↓ or N↓ or N↓ or N ↓ Circulatory hypoxia N N N N ↑ Histogenic hypoxia N N N N ↓ Notes: ↓— decrease; ↑ — increase; N — normal.

  28. Features of different types of hypoxia Hypotonic hypoxia: PaO2 Hemic hypoxia: Normal PaO2, altered Hb quantity and quality, CO2max or Circulatory hypoxia: Normal PaO2, Hb quantity and quality, blood flow Histogenous hypoxia: normal O2 supply to the tissue, O2 utilization

  29. Impact of hypoxia on the body Slight hypoxia: stimulation Compensatory responses Severe hypoxia: impairment dysfunction and failure of cells and tissues Acute hypoxia: mainly damage Chronic hypoxia: both damage and compensation Respiratory system Circulatory system Hematologic system Central nervous system Tissues and cells

  30. Respiratory system Compensatory reaction-hyperventilation (过度通气) PaO2 <8Kpa or 60 mmHg → chemoreceptors↑→respiratory rate and depth↑→ hypoxic ventilation reaction (HVR). Consequences:respiratory surface↑, O2 diffusion↑, PaO2&SaO2↑ More fresh air into the lung, PaO2 ↑，PCO2↓ blood volume returning to the heart↑

  31. 缺氧引起的过度通气其意义在于： • 增加肺泡通气量和肺泡气的PO2(PAO2)，从而增加动脉血氧分压PO2(PaO2) • 胸廓运动增强，增大胸内负压，促进静脉回流、增加回心血量，继而增加心输出量和肺血流量， 有利于血液摄取和运输更多的氧 肺通气量增加是急性低张性缺氧的最重要代偿方式。

  32. Injury manifestation High-altitude pulmonary edema Respiratory failure Severe hypoxia (PaO2 <30 mmHg)→ inhibition of respiratory center → slow and periodic or irregular breathing → stop of breathing.

  33. Circulatory system Compensatory responses Cardiac output ↑ : tachycardia （心动过速） → arrhythmia → myocardial contractility↑ Pulmonary vasoconstriction → pulmonary arterial hypertension → right heart failure Redistribution of blood → ensure enough blood to heart and brain Capillary hyperplasia

  34. Injury manifestation Pulmonary hypertension Decreased diastolic and systolic myocardial function Arrhythmia Decrease in Venous blood return to the heart

  35. Hemic system Compensatory responses Rightward shift of oxyhemoglobin dissociation curve Increase of red blood cell and erythropoietin(EPO) Injury manifestation Blood viscosity ↑

  36. Central nervous system Brain is highly sensitive to hypoxia. Blood redistribution to the brain PaO<28 mmHg， mental disorder Cerebral edema

  37. Cell • Compensation: • increased ability to use O2 • anaerobic glycolysis ↑ • increase of myoglobin • Injury manifestation • cellular membrane injury • mitochondria impairment • lysosome breakage

  38. Factors involved in tolerance to hypoxia Oxygen consumption rate Brain → oxygen consumption rate↑→ tolerance↓ Skin → oxygen consumption rate↓→ tolerance↑ Compensatory ability of the body

  39. Prevention and treatment Inhalation of oxygen (氧吸入) Efficiency: Hypotonic hypoxia — the best Histogenous hypoxia —the worst When the patient inhaled high pressure of oxygen(PO2 is 2-3 times atmosphere), a series of toxic signs and symptoms was appeared, this condition is termed as oxygen toxication （氧中毒）.

  40. Oxygen toxication:1. Pulmonary oxygen toxication 2. Cerebral oxygen toxication The mechanisms of oxygen toxicity: Reactive oxygen species (氧自由基) or oxygen free radicals .

  41. 学 习 目 标 与 内 容 掌握各项血氧检测指标的意义。 掌握缺氧概念，分类与特征。 掌握紫绀，肠源性紫绀的概念。 熟悉呼吸的基本过程。 熟悉机体对缺氧的代偿反应。 熟悉缺氧治疗的原则。 了解氧中毒概念。

  42. Thank you !

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