Chapter 5 Hypoxia or Anoxia Objective Contradiction: large amount O2 consumption ---- 250ml/min (360L/day) Small amount O2 storage ---- 1.5L (sustain life only six minutes) Hypoxia is a fundamental pathologic process. Hypoxia is always direct causes of death.

§1. Concept Hypoxia: Hypoxia is referred to a pathological process in which oxygen supply to tissues or organs is inadequate to meet the demand of cells, or there is adequate delivery to tissue but the tissue cells cannot make use of oxygen, leading to changes in functions, metabolisms and structures of cells and tissues of the body. Supply inadequate of oxygen functions Utilized disturbance of oxygen metabolisms damage structures

§2. Parameters of blood oxygen 1 §2. Parameters of blood oxygen 1.partial pressure of oxygen (PO2): normal value : NPaO2= 13.3kpa (100mmHg) NPvO2 = 5.3kpa (40mmHg) influence factor: (1) PO2 of inhalation air (2) extrarespiratory function (3) shunting of blood

2. Oxygen binding capacity (CO2 max): N.V: NCaO2 max =NCvO2max=20ml/dl I . F: Hb---- (1) quantity (2) quality or affinity with O2

3. Oxygen content (CO2): N.V: NCaO2 = 19ml/dl NCvO2 = 14ml/dl N(CaO2 – CvO2) = 5ml/dl I . F: (1) PO2 (2) CO2max : Hb — quantity quality

4. Oxygen saturation (SO2): SO2＝(CO2－dissolved O2/CO2max)×100% N.V: NSaO2 = 95% NSvO2 = 70% I . F: (1) ability of oxygen combined with Hb (2) SO2 is determined by PO2 at normal affinity

oxygen dissociation curve : The relationship curve between PO2 and SO2 Fig. S ( sigmoid shaped ) I . F: [H+]↑ pCO2↑ a. right shift temperature↑ b. affinity↓ 2,3- DPG↑ [H+] ↓ pCO2↓ a. left shift temperature↓ b. affinity↑ 2,3- DPG↓

5. P50: P50 is the PO2 at the 50% SO2 N. V: N P50 = 26 – 27 mmHg I 5. P50: P50 is the PO2 at the 50% SO2 N. V: N P50 = 26 – 27 mmHg I . F: right shift → P50↑ left shift → P50↓

§3. Types/Causes/Mechanisms/Features of hypoxia The processes of oxygen supplied and utilization contains: a. lung intake oxygen b. Hb carring O2 c. circulation transporting O2 d. cell utilizing O2 Therefore, hypoxia can be divided into four types .

Failure to utilize the oxygen Hypotonic hypoxia (hypoxic hypoxia)： PO2↓ 2. Hemic hypoxia (isotonic hypoxemia)： CO2 max↓or↑(disorders of oxygen release) 3.Circulatory hypoxia (hypokinetic hypoxia)： Blood flow↓ 4.Histogenous hypoxia (dysoxidative hypoxia)： Failure to utilize the oxygen

1. Hypotonic hypoxia (hypoxic hypoxia) Causes: a. Decreased PO2 of inhaled air – atmospheric hypoxia b. disturbance of extrarespiration – respiratory hypoxia c. shunting of blood

mechanisms: PaO2↓→ CO2 ↓→ SaO2 ↓→ inadequate supply O2 to tissue

Features: a. PaO2↓ PvO2↓ b. CaO2↓ CaO2↓ c. CO2max = N d. SaO2↓ e. (CaO2 - CvO2)↓or N f. central cyanosis g. Respiratory compensation

2. Hemic hypoxia (isotonic hypoxemia) causes: a 2. Hemic hypoxia (isotonic hypoxemia) causes: a. Anemia → anemic hypoxia b. carbon monoxide poisoning c. Methemoglobinemia d. higher affinity of Hb to oxygen

Mechanisms : a. CO2max↓→ CO2↓→ afford O2 to tissue↓ b. CO2max N or↑but affinity↑→ O2 released disorder → afford O2 to tissue ↓

Features: a. PaO2 =N, PvO2 =N b. CaO2↓ CvO2↓ c Features: a. PaO2 =N, PvO2 =N b. CaO2↓ CvO2↓ c. CO2max ↓ ( except higher affinity ) d. SaO2: anemia = N intoxication →↓ higher affinity →↑ e. (CaO2 - CvO2)↓ f. no cyanosis g. no respiratory compensation

3.Circulatory hypoxia (hypokinetic hypoxia) Causes: a.General circulatory dysfunction —- 　　e.g. shock; heart failure. b.Local circulatory deficiency —- 　　e.g. stenosis; occlusion; thrombosis.

Mechanisms: Reduced tissue perfusion—a. ischemia hypoxia b. congestive hypoxia

Features: a. PaO2 = N PvO2↓ b. CaO2 = N CvO2↓ c. CO2max = N d. SaO2 = N e. (CaO2-CvO2)↑ f. peripheral cyanosis g. Respiratory compensation or not

4.Histogenous hypoxia (dysoxidative hypoxia) Causes: a.Cell poisoning: cyanide poisoning→histotoxic hypoxia b.Mitochondria injury: radiation ; oxygen free radical c. Inadequate synthesis of biological oxidation coenzyme : deficiency of vitamin B2 or PP

Mechanisms: Disorder of biological oxidation or oxidative phosphorylation → failure to utilization of oxygen →ATP↓.

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

The changes of blood oxygen parameters in four types of hypoxia Type PaO2 SaO2 O2 capacity CaO2 CaO2-CvO2 Hypotonic hypoxia ↓ ↓ N ↓ ↓ or N Hemic hypoxia N N ↓ or N ↓ or N ↓ Circulatory hypoxia N N N N ↑ Histogenic hypoxia N N N N ↓ Note: ↓— decrease; ↑ — increase; N — normal.

§4.Functional and metabolic changes of the body in hypoxia 1. Respiratory system PaO2 ( <8Kpa ) → chemoreceptors↑→ respiratory rate and depth↑→ hyperventilation. Severe hypoxia → depressing respiratory center → slow and periodic or irregular breathing → stop of breathing.

2.circulatory system myocardial contractility↑ a.Cardiac output↑ : tachycardia → arrhythmia myocardial contractility↑ b.Redistribution of blood → To afford blood to heart and brain c.Pulmonary vasoconstriction → pulmonary arterial hypertension → right heart failure

3.Hemic system a. Rightward shift of oxyhemoglobin dissociation curve b. Increase of red blood cell: erythropoietin(EPO)

4.Central nervous system: Dysfunction.

5.Cell Compensation: a. increased ability to use O2 b. anaerobic glycolysis ↑ c. increase of myoglobin Damage: a. cellular membrane injury b. mitochondria impairment c. lysosome break

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

§6. Oxygen treatment and oxygen toxicity All patients with hypoxia can be treated with inhalation of oxygen , but the efficiency is quite different to every type of hypoxia. Efficiency: Hypotonic hypoxia — the best Histogenous hypoxia —the worst When the patient inhaled high pressure of oxygen(PO2 higher than a half atm) ,a series of toxic signs and symptoms was appeared, this condition is termed as oxygen toxication.

The mechanisms of oxygen toxicity: Oxygen toxication: 1. Pulmonary oxygen toxication 2. Cerebral oxygen toxication The mechanisms of oxygen toxicity: Reactive oxygen species or oxygen free radicals .