5-hypoxia 23_2

Zhao Mingyao BMC.ZZU. 2004-3-8

Why does our body need O2? What we alter can lead to change the need of body for O2? O2 consumption

O2 supply

Equilibrium : normal life

Concept of hypoxia O2 supply ↓ and/or O2 consumption↓

cell

tissue organ

?

O2 metabolism pathway disorder O2 in air

O2 Hb Hb

Lung Hb- O2 Circulation

O2 Hb- O2 ?

Cell (mitochondria)

body

energy

energy

Section 1

Parameters of blood oxygen

① PO2— ② CO2 –— ③ CaO2 - CvO2 ④ CO2 max — ⑤ SO2 — ⑥ P50 ( OxyHb dissociation curve ) —

1. PO2—dissolved physically The normal value

PaO2

100mmHg

PvO2

O2 O2

O2

O2

Mt PmO2 0mmHg

40mmHg

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

3.CaO2 - CvO2 — O2 consumption total mixed blood coronary blood

19 － 14=5 ml% 19 － 7=12 ml%

19ml/dl A

O2 O2 O2

14ml/dl O2 O2

5ml/dl

O2

V

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

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

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

P50

27mmHg

80

60

Section 2 Classification, etiology & pathogenesis of hypoxia ① ② ③ ④

hypotonic ~ hemic ~ circulatory ~ histogenous ~

O2 →Lung→Hb→Circulation→Cell(mitochondria)

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

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

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

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

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.

(1) Cause of Hemic hypoxia *Anemia: Hb *CO poisoning: HbCO *Oxidant poisoning: HbFe3+ (MHb) * Higher affinity of Hb to O2: Hb mol disease, pH↑ skin color : ? parameter: Hb relative ~

(1) Cause of Hemic hypoxia The decreased amount of Hb ①Anemia: Hb anemic hypoxia

* Changes of ability of Hb ① Carboxyhemoglobinemia CO+Hb

HbCO

O2+Hb

HbO2

Effect: O2 carrying Curve

24

②Methemoglobinemia • HbFe2+ + NaNO2(oxidant) = HbFe3+ ferrous

Reductant Methylene Blue Urolene Blue

ferric

Effect: O2 carrying Curve

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

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

27

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

28

Skin Color ???

anemia: CO poisoning: HbFe3+(MHb-nemia): higher affinity of Hb to O2:

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

(2) Alterations of blood oxygen

parameters CaO2 - CvO2 ↑ PaO2 , SaO2, CaO2max and CaO2 are ordinary

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 ↓

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

Cyanide poisoning CN- +Ctyaa3Fe3+ ----→ Ctyaa3Fe3+ -CN Na2S2O3 + CN- ----→ SCN ----→ urinary excretion HbFe3+ + CN- > Ctyaa3Fe3+ + CN - --→ HbFe3+ - CN oxidant

HbFe2+ ----→ HbFe3+

(2)Alterations of blood oxygen parameters CaO2-CvO2 ↓

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

1. Respiratory system response to hypotonic hypoxia PaO2 < 60mmHg (30~60) < 30mmHg —→ carotid and aortic body chemoreceptors depression —→ respiratory center + + + —→ hyperventilation

(2) High altitude pulmonary edema

When someone gets HAPE, his lungs fill up with fluid.

2.Circulatory system Heart: CO↑ Blood redistribution: Pulmonary vasoconstriction: nervous, humoral, direct effect Capillary proliferation: Collateral circulation: Circulatory failure: heart failure, arrhythmia, venous return

3. Hemic system Bone marrow: EPO, polycythemia Right shift of curve(P50):

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

5.Cellular responses Mitochondria↑ Enzyme activity↑ Anaerobic glycolysis ↑ Hypometabolism Myoglomin ↑ ?? store O2 ↑ Membrane permearbility ↑ Mitochondria damage Lysosome damage

Hypoxia and cerebral function

PO2 (mmHg)

Affection

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

Body tolerance to hypoxia O2 total storage: 1250ml

Section 4

(lung 400 ,Hb 850 ml) 200~300ml O2 consumption /min , 5min apnea

O2 supply

O2 consumption

Equilibrium : normal life Tolerance ↑: O2 consumption rate↓: hypothermia, hibernation, CNS (-) Compensatory ability↑: lung, heart ,bone marrow

 

Brain-Cooling to Reduce Brain Injury at Birth

Section 5 oxygen therapy prevent O2 intoxication:

80~100% O2, 8 hr

Lung

Hyperbaric O2, 4atm, dozens of min

Brain

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

2006-02-23