Hypoxia Zhao Mingyao BMC ZZU Why does our

Hypoxia Zhao Mingyao BMC. ZZU.

Why does our body need O 2? O 2 consumption O 2 supply Equilibrium : normal life

body energy

O 2 in air 150 O 2 Hb PV O 2 40 Hb Lung 105 Hb- O 2 Circulation Pa. O 2100 O 2 Hb- O 2 ? Cell (mitochondria) O 2 metabolism pathway ?

Concept of hypoxia O 2 supply ↓ and/or O 2 consumption↓ cell tissue organ ?

Section 1 Parameters of blood oxygen ① PO 2— ② CO 2 –— ③ Ca. O 2 - Cv. O 2 ④ CO 2 max — ⑤ SO 2 — ⑥ P 50 ( Oxy. Hb dissociation curve ) —

1. PO 2—dissolved physically The normal value Pa. O 2 100 mm. Hg Pv. O 2 O 2 Mt O 2 Pm. O 2 0 mm. Hg 40 mm. Hg

2. CO 2 –— Hb carrying O 2 actually CO 2 max Ca. O 2 Cv. O 2 20 ml% 19 ml% 14 ml%

3. Ca. O 2 - Cv. O 2 — O 2 consumption total mixed blood 19 － 14 = 5 ml% coronary blood 19 － 7 = 12 ml% 19 ml/dl A O 2 O 2 14 ml/dl O 2 5 ml/dl O 2 V

4. CO 2 max — O 2 -carrying Hb, standard condition CO 2 max=1. 34 ml/g × 15 g%=20 ml%

5. SO 2 —Hb carrying O 2 ratio Sa. O 2 19/20 = 95% Sv. O 2 14/20 = 70%

6. P 50 ( Oxy. Hb dissociation curve ) — relationship between PO 2 and SO 2 27 mm. Hg P 50

80% NO DPG ↑ CO 2 ↑ H+ ↑ T↑ 60 DPG: 2, 3 -diphosphoglycerate

Section 2 Classification, etiology & pathogenesis of hypoxia ① hypotonic ~ ② hemic ~ ③ circulatory ~ ④ histogenous ~ O 2 →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 • ↓PO 2 in the inspired air • Disorder of external respiration • Admixture of venous blood into arterial blood

(2) Affect of hypotonic hypoxia Pa. O 2 ↓— Ca. O 2 ↓ Ca. O 2 - Cv. O 2 ↓ Sa. O 2 ↓ CO 2 max — acute ~ normal chronic ~ ↑ P 50 — according [H+ ], CO 2, 3 -DPG

sign — cyanosis It occurs when the deoxyhemoglobin in capillaries increases to more than 5 g/dl bluish skin [deoxy. Hb] 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 The decreased amount of Hb ①Anemia: Hb anemic hypoxia

Changes of ability of Hb ① Carboxyhemoglobinemia Hb. CO O 2+Hb Hb. O 2 Effect: O 2 carrying Curve

②Methemoglobinemia Hb. Fe 2+ + Na. NO 2(oxidant) = Hb. Fe 3+ ferrous Reductant Methylene Blue Urolene Blue ferric Effect: ①O 2 carrying↓ for Hb ②Curve leftshift

Enterogenous cyanosis • Hb. Fe 2+ + Na. NO 2(oxidant) = Hb. Fe 3+ Nitrite Enteron bacteria Nitrate in intestine

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

2. Alterations of blood O 2 parameters Hb ↓ or its ability to combine O 2 * Ca. O 2 max↓ Ca. O 2↓ * Ca-v. O 2 ↓ * Sa. O 2 & Pa. O 2 normal

Skin Color ? ? ? Anemia: CO poisoning: Hb. Fe 3+(MHb-nemia): higher affinity of Hb to O 2:

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 O 2 parameters Ca. O 2 - Cv. O 2 ↑ Pa. O 2 , Sa. O 2, Ca. O 2 max and Ca. O 2 are ordinary

4. Histogenous hypoxia Oxidative-reductive process disorder (O 2 consumption ↓) *toxic substance poisoning *cell (mitochondria) injury *respiratory chain formation deficiency: Vit B 1 ↓ skin color: ? parameter: Ca. O 2 - Cv. O 2 ↓

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

Cyanide poisoning CN- +Ctyaa 3 Fe 3+ ----→ Ctyaa 3 Fe 3+ -CN Na 2 S 2 O 3 + CN- ----→ SCN ----→ urinary excretion Hb. Fe 3+ + CN- > Ctyaa 3 Fe 3++ CN - --→ Hb. Fe 3+ - CN oxidant Hb. Fe 2+ ----→ Hb. Fe 3+ hyposulphite thiocyanate radical

(2)Alterations of blood O 2 parameters Ca. O 2 -Cv. O 2 ↓

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

1. Respiratory system response to hypotonic hypoxia Pa. O 2 < 60 mm. Hg (30~60) —→ peripheral chemoreceptors —→ respiratory center + + + —→ hyperventilation < 30 mm. Hg Depression of respiratory center

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

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

3. Hemic system Bone marrow: EPO, polycythemia Right shift of curve(P 50): pɔli: sai'θi: mi: ə]

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

Hypoxia and cerebral function PO 2 (mm. Hg) Affection 65 (Sa. O 291%) night vision ↓ 50 (Sa. O 285%) 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

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

HIF and adaptation effects of hypoxia

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

Section 4 Body tolerance to hypoxia O 2 total storage: 1250 ml(lung 400, Hb 850 ml) 200~300 ml O 2 consumption /min, 5 min apnea

O 2 consumption O 2 supply Equilibrium : normal life Hypoxia tolerance ↑: O 2 consumption rate↓: hypothermia, hibernation, CNS (-) Compensatory ability↑: lung, heart, bone marrow

Brain-Cooling to Reduce Brain Injury at Birth

Section 5 Oxygen therapy prevent O 2 intoxication: 80~100% O 2, 8 hr Lung Hyperbaric O 2, 4 atm, dozens of min Brain

Pathogenesis of O 2 Intoxication OFR : O 2 pressure and concentration O 2 physical damage: washing out of N 2