Chapter 5 Hypoxia or AnoxiaObjective 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 functionsUtilized disturbance of oxygen metabolisms damage structures

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(CO2dissolved 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

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 oxygen dissociation curve : The relationship curve between PO2 and SO2

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 .

Hypotonic hypoxia (hypoxic hypoxia) PO22. Hemic hypoxia (isotonic hypoxemia) CO2 maxor(disorders of oxygen release)3.Circulatory hypoxia (hypokinetic hypoxia) Blood flow4.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. 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 orbut affinity O2 released disorder afford O2 to tissue

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 perfusiona. 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 poisoninghistotoxic 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-CvO2Hypotonic hypoxia N or NHemic 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 (

2.circulatory system 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.

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