Understanding Hypoxia: Why Does Our Body Need Oxygen?

1. Hypoxia Zhao Mingyao BMC.ZZU.

2. Why does our body need O2? O2 supply O2 con- sumption Equilibrium : normal life

3. body energy energy

5. O2 in air 150 O2 Lung 105 Hb O2 Hb- O2 PV O2 40 Hb Circulation PaO2100 Hb- O2 Cell (mitochondria) ? ? O2 metabolism pathway

6. Concept of hypoxia O2 supply ↓ and/or O2 consumption↓ organ tissue cell ?

7. Section 1 Parameters of blood oxygen ① PO2— ② CO2 –— ③ CaO2 -CvO2 ④ CO2 max — ⑤ SO2— ⑥ P50 ( OxyHb dissociation curve ) —

8. 1. PO2—dissolved physically The normal value PaO2 100mmHg PvO2 40mmHg O2 O2 O2 O2 Mt PmO2 0mmHg

9. 2.CO2 –— Hb carrying O2 actually CO2 max20ml% CaO2 19ml% CvO2 14ml%

10. 3.CaO2 -CvO2— O2 consumption total mixed blood 19 － 14 = 5 ml% coronary blood 19 － 7 = 12 ml% O2 O2 O2 O2 O2 19ml/dl 14ml/dl A V O2 5ml/dl

11. 4. CO2 max — O2-carrying Hb, standard condition CO2 max=1.34ml/g × 15g%=20ml%

12. 5. SO2—Hb carrying O2 ratio SaO2 19/20 = 95% SvO2 14/20 = 70%

13. 6. P50 ( OxyHb dissociation curve ) —relationship between PO2 and SO2 27mmHg P50

14. 80% NO DPG DPG ↑ CO2 ↑ H+ ↑ T ↑ 60 DPG: 2,3-diphosphoglycerate

15. Section 2 Classification, etiology & pathogenesis of hypoxia ① hypotonic ~ ② hemic ~ ③ circulatory ~ ④ histogenous ~ O2 →Lung→Hb→Circulation→Cell(mitochondria)

16. Hypotonic hypoxia The primary character of the type is the decreased arterial partial pressure of oxygen

17. (1) Cause of hypotonic hypoxia ↓PO2 in the inspired air Disorder of external respiration Admixture of venous blood into arterial blood

18. (2) Affect of hypotonic hypoxia PaO2 ↓— CaO2 ↓ CaO2 -CvO2 ↓ SaO2 ↓ CO2 max — acute ~ normal chronic ~ ↑ P50 — according [H+ ], CO2, 2,3-DPG

19. sign — cyanosis It occurs when the deoxyhemoglobin in capillaries increases to more than 5g/dl bluish skin [deoxyHb] b> 5 g%

20. 2. Hemic hypoxia ------- caused by the low oxygen capacity of blood owing to the reduction of the amount of Hb or its ability to combine oxygen.

21. Cause of Hemic hypoxia The decreased amount of Hb ①Anemia: Hb anemic hypoxia

22. Changes of ability of Hb ① Carboxyhemoglobinemia HbCO O2+Hb HbO2 Effect: O2 carrying Curve

23. ②Methemoglobinemia HbFe2+ + NaNO2(oxidant) = HbFe3+ ferrous ferric Reductant Methylene Blue Urolene Blue Effect: ①O2 carrying↓ for Hb ②Curve leftshift

24. Enterogenous cyanosis HbFe2+ + NaNO2(oxidant) = HbFe3+ Nitrite Enteron bacteria Nitrate in intestine

25. ③Higher affinity of Hb to O2 ①bank blood transfusion ②alkaline solution infusion ③Hb molecular diseases

26. 2. Alterations of blood O2 parameters Hb ↓ or its ability to combine O2 * CaO2max↓ CaO2↓ * Ca-vO2 ↓ * SaO2 & PaO2 normal

27. Skin Color ??? Anemia: CO poisoning: HbFe3+(MHb-nemia): higher affinity of Hb to O2:

28. 3. Circulatory hypoxia the decreased blood flow (1)causes tissue perfusion ↓ (ischemia) blood flow velocity↓(stagnation) general or local skin color: ?

29. (2) Alterations of blood O2 parameters CaO2 -CvO2 ↑ PaO2 , SaO2, CaO2max and CaO2 are ordinary

30. 4. Histogenous hypoxia Oxidative-reductive process disorder (O2 consumption ↓) *toxic substance poisoning *cell (mitochondria) injury *respiratory chain formation deficiency: Vit B1 ↓ skin color: ? parameter: CaO2 -CvO2 ↓

31. (1) Causes ①histotoxication ②mitochrondria injury ③ decreased synthesis of respiratory enzymes

32. Cyanide poisoning CN- +Ctyaa3Fe3+ ----→ Ctyaa3Fe3+ -CN Na2S2O3 + CN- ----→ SCN ----→ urinary excretion HbFe3+ + CN- > Ctyaa3Fe3++ CN - --→ HbFe3+ -CN oxidant HbFe2+ ----→ HbFe3+ hyposulphite thiocyanate radical

33. (2)Alterations of blood O2 parameters CaO2-CvO2 ↓

34. Section 3 Effects of hypoxia on body Adaptation and compensation Damage and injury

35. 1. Respiratory system response to hypotonic hypoxia PaO2 < 60mmHg (30~60) —→ peripheral chemoreceptors —→ respiratory center + + + —→ hyperventilation < 30mmHg Depression of respiratory center

36. (2) High altitude pulmonary edema When someone gets HAPE, his lungs fill up with fluid

37. 2.Circulatory system Cardiovascular: ①CO↑ ②Blood redistribution: ③Pulmonary vasoconstriction: nervous, humoral, direct effect (Kv(-)) ④Capillary proliferation: ⑤Collateral circulation: Circulatory failure: heart failure, arrhythmia, venous return

38. 3.Hemic system Bone marrow: EPO, polycythemia Right shift of curve(P50): pɔli:sai'θi:mi:ə]

39. 4.CNS responses ①hypermetabolism ②high energy consumption from aerobic oxidation with G + O2 ③no O2 storage, quickly consume O2 as soon as O2 supply ④ it can`t regenerate

40. 65 (SaO291%) night vision ↓ 50 (SaO285%) visual field ↓ blind spot↑ color discrimination ↓ 35~50 serious but reversible deterioration <30 loss of consciousness <20 few min irreversible damage Anoxia 10~15 sec unconsciousness Hypoxia and cerebral function PO2 (mmHg) Affection

42. 5.Cellular responses (1)Adaptation effects ① Utililization↑of O2:Mt and Enzyme activity↑ ② Anaerobic glycolysis ↑ ③ synthetic metabolism↓ ④ Myoglobin ↑ , store O2 ↑ ??

43. HIF and adaptation effects of hypoxia

44. (2)Damage effects Membrane permearbility ↑ Mitochondria damage Lysosome damage

45. Section 4 Body tolerance to hypoxia O2 total storage: 1250ml(lung 400, Hb 850 ml) 200~300ml O2 consumption /min, 5min apnea

46. O2 supply O2 con- sumption Equilibrium : normal life Hypoxia tolerance ↑: O2 consumption rate↓: hypothermia, hibernation, CNS (-) Compensatory ability↑: lung, heart, bone marrow

47. Brain-Cooling to Reduce Brain Injury at Birth

48. Section 5 Oxygen therapy prevent O2 intoxication: Hyperbaric O2, 4atm, dozens of min 80~100% O2, 8 hr Brain Lung

50. Pathogenesis of O2 Intoxication OFR : O2 pressure and concentration O2 physical damage: washing out of N2