1. Hypoxia Hypoxia

2. Concept Oxgen supply = CaO 2 × Q Oxygen consumption = （ CaO 2 － CvO 2 ） × Q Tissue cells can’t obtain enough oxygen or can’t fully utilize oxygen metabolic, functional and structural changes

3. CO 2 － dissolved O 2 CO 2 max O 2 saturation （ SO 2 ） = × 100% SaO 2 95%, SvO 2 70% Parameters of blood gas Partial pressure of O 2 （ PO 2 ） PaO 2 100mmHg, PvO 2 40 mmHg O 2 content （ CO 2 ） = CO 2 max×SO 2 + dissolved O 2 CaO 2 19ml/dl, CvO 2 14ml/dl O 2 capacity （ CO 2 max ） = 1.34 ml/g × Hb g/dl

4. Dissociation curve of oxyhemoglobin Dissociation curve of oxyhemoglobin

6. Classification, etiology and pathogenesis 1. Hypotonic hypoxia — PaO 2 ↓ 1. Hypotonic hypoxia — PaO 2 ↓ Causes : 1) PiO 2 ↓ 2) pulmonary dysfunction 3) shunt Results : PaO 2 ↓→ SaO 2 ↓→ CaO 2 ↓ hypotonic hypoxemia, cyanosis （ PaO 2 － P M O 2 ） ↓ → （ CaO 2 － CvO 2 ） ↓ PaO 2 ＜ 60mmHg → VO 2 ↓ ？

7. Results : CO 2 max↓↓  CaO 2 ↓↓  （ CaO 2 － CvO 2 ） ↓ P 50 ↓  （ CaO 2 － CvO 2 ） ↓ 2. Hemic hypoxia — CO 2 max 2. Hemic hypoxia — CO 2 max ↓ Causes : 1) anemia 2) carboxyhemoglobinemia 3) methemoglobinemia enterogenous cyanosis 4) P 50 ↓ ： transfusion of depot blood

8. Result : Q↓↓→ CvO 2 ↓ → （ CaO 2 － CvO 2 ） ↑ Causes : general circulatory failure local circulatory disorder 3. Circulatory H — Q↓ 3. Circulatory H — Q↓ ·

9. 4. Histogenous hypoxia Causes: 1) histotoxic H cyanide poisoning 2) cell injured by biological or physical factor 3) vitamin deficiency --- B 1 Result : CvO 2 ↑ → （ CaO 2 － CvO 2 ） ↓

10. What kind of hypoxia might occur in septic shock ？

11. Hypotonic hypoxia PaO 2 ＜ 60mmHg → compensation ＜ 30mmHg → severe disturbances Functional and metabolic alterations Functional and metabolic alterations

12. 1. Respiratory system 1. Respiratory system Respiratory rate and depth ↑ arrive at 4000m high →ventilation ↑ 65% few days later → ventilation ↑ 5 – 7 times long residents → 15 % more than at sea level Hyperventilation→PaO 2 ↑→CaO 2 ↑ ↘ O 2 consumption ↑ occur in any type of hypoxia? Severe hypoxia→pulmonary edma ↘ Inhibition of respiratory center

13. 2. Circularory system 2. Circularory system Cardiac output↑ due to: 1. cardiac contractility↑ 2. heart rate↑ 3. venous return↑ Redistribution of blood flow α-Adrenoceptor vasoconstriction Local metabolites vasodilation

14.  Pulmonary vasoconstriction (HPV)→PaO 2 ↑ Sympathetic nerve Humoral factors — AT 、 ET 、 LTs 、 TxA 2 PGI 2 、 NO 、 histamine Direct effect of O 2 on SMC — Kv How to prove?  Capillary proliferation --- VEGF

15. Severe hypoxia  Myocardiac systolic and diastolic dysfunction Cardiac arrhythmia --- Hypoxia  acidosis  hyperkalemia  Arrhythmia Venous return↓  Pulmonary hypertention right ventricle

16. 3. Hemic system 3. Hemic system RBC↑--- erythropoitin  P 50  ---- 2.3 - DPG↑

17. 4.Central nervous system 4.Central nervous system Acute H → headache 、 impaired attention Chronic H → sleepiness, depression Severe H → confusion, coma, convulsion due to : energy deficiency and acidosis decreased RMP abnormal neurotransmitter synthesis cell damage vasodilation and cerebral edema

18. 5. Cellular alterations 5. Cellular alterations Adaptation Adaptation Ability to use O 2 ↑--- number of mitochondia, it’s enzymes Anaerobic glycolysis↑ ATP/ADP↓ → phosphofructokinase activity Low metabolic state --- caused by acidosis Myoglobin↑

19. Dissociation curve of oxymyoglobin and oxyhemoglobin

20. Cell membrane decreased permeability + ion pump dysfunction [ Na + ] i  → Cellular swelling [ K + ] i ↓ → Synthetic metabolism↓ [ Ca 2+ ] i  → Mitochondria damage ROS  Lysosome damage Severe H → Cellular damage

21. Mitochondria Respiratory function ↑ (PmO 2 < 1mmHg) PmO 2 < 1mmHg dehydrogenase activity Lysosome Acidosis  phospholipase activity hydrolases release

22. Factors influencing the tolerance to hypoxia Oxygen consumption rate Compensatory ability to hypoxia

23. Oxygen therapy and oxygen intoxication Oxygen intoxication --- PO 2 > 0.5 atm Cerebral type --- visual and auditory dysfunction, nausea, convulsion and coma How to differentiate it from hypoxic encephalopathy? Pulmonary type --- cough, dyspnea vital capacity , PaO2 