Anhui Medical university Hypoxia Department of pathophysiology Basic Medical Science college

Anhui Medical university Respiration and oxygen exchange Air Alveoli Alveolar capillary Gas transport Tissue cells Ventilation Gas exchange External respiration Internal respiration Bound to haemoglobin

Anhui Medical university Tables of content Concept Parameters of blood oxygen Classification and Etiology Changes of function and metabolism Treatment

Anhui Medical university 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.

Anhui Medical university Partial pressure of oxygen, PO2 Oxygen binding capacity, CO2max Oxygen content, CO2 A-VdO2 Oxygen saturation, SO2 P50 Parameters of blood oxygen

Anhui Medical university 【 Partial pressure of oxygen, PO2 】 PO2 is the pressure or tension caused by oxygen physically dissolved in the blood. 【 Normal value 】 PaO 2 : 13.3kPa(100mmHg) ； PvO 2 : 5.32kPa(40mmHg) 。 PaO 2 : PaO 2 : The partial pressure of oxygen in the plasma phase of arterial blood. The PaO2 gives us valuable information about adequacy of gas exchange within the lungs, when it is subtracted from the calculated alveolar PO2. PvO 2 : PvO 2 : The partial pressure of oxygen in the plasma phase of venous blood. The PvO2 is determined by whole body oxygen demand, and the capacity of the tissues to extract oxygen.

Anhui Medical university 【 Oxygen binding capacity, CO2max 】 CO 2 max Is the maximum amount of oxygen combined by Hb in 100ml blood under fully saturated condition in which the PO 2 is 150mmHg, PCO 2 40mmHg, and the temperature is 38 ℃. 【 Normal value 】 CO2max: 8.92mmol/L (1.34ml/g×15gHb% =20ml%) 。 【 Meaning 】 The ability of Hb to carry O2.

Anhui Medical university 【 Oxygen content, CO2 】 The total amount of oxygen contained actually in 100 ml blood sample, including the part combined with Hb and the part physically dissolved in plasma. CO2 = PaO 2 + CO 2 max 。 【 Normal value 】 【 Normal value 】 CaO 2 ≈ 8.47mmol/L(19.3ml%) ； CvO 2 ≈ 5.35mmol/L(14ml%) 。 CaO 2 ≈ 8.47mmol/L(19.3ml%) ； CvO 2 ≈ 5.35mmol/L(14ml%) 。

Anhui Medical university 【 A-VdO2 】 The difference value is between arterial and venous blood oxygen content. 【 Meaning 】 A-VdO2 = volume of O2 tissue uptake = CaO2-CvO2 【 Normal value 】 A-VdO 2 ≈ ～ 3.57mmol/L(5ml% ～ 8ml%) 。

Anhui Medical university 【 Oxygen saturation, SO2 】 The percentage of hemoglobin present as oxyhemoglobin 【 Meaning 】 The degree of connected Hb to oxygen 【 Normal value 】 SaO 2 ： 93% ～ 98% ； SvO 2 ： 70% ～ 75% 。 SaO 2 ： 93% ～ 98% ； SvO 2 ： 70% ～ 75% 。 SO2% = CO2 – O2 dissolved physically in plasma/ CO2max 【 Influence 】 PaO 2

Anhui Medical university 【 p50 】 One measure of the position of the curve is the PO2 at the 50% SO2. 【 Normal value 】 3.47 ～ 3.6 kPa (26 ～ 27mmHg) 。 【 Significance 】 The P50 indicates affinity of hemoglobin for oxygen 【 Influence 】 H+, CO2, temperature, 2 、 3-DPG

Anhui Medical university Classification and Etiology

Anhui Medical university Hypotonic Hypoxia (Hypoxic Hypoxia) Classification and Etiology Hemic Hypoxia (Isotonic Hypoxia) Circulatory Hypoxia(Hypokinetic Hypoxia) Histogenous Hypoxia(Histotoxic Hypoxia)

Anhui Medical university 【 Hypoxic hypoxia 】 oxygen tension in arterial blood is lower than normal, which resulted in lack of oxygen from blood to tissues. Causes : 1) Decreased PO2 of inspired air 2) External respiratory dysfunction 3) Venous-to-arterial shunt Characteristics of blood oxygen PaO2↓, SaO2↓, CaO2 ↓, CO2max N, CaO2-CvO2 ↓/N

Anhui Medical university 【 Cyanosis 】 The bluish color of skin, nails, lips and mucous membranes when the deoxyhemoglobin concentration of the blood in the capillaries is more than 5g/dl 。

Anhui Medical university 【 Hemic hypoxia, isotonic hypoxia 】 Hemic hypoxia refers to the altered affinity of Hb for oxygen or decrease in amount of Hb in the blood Causes: （ 1 ） Anemia （ 2 ） Higher affinity of Hb to oxygen （ 3 ） Carbon monoxide poisoning （ 4 ） Methemoglobinemia, MHb

Anhui Medical university High affinity of Hb for O 2 Alkaline solution Depot blood Anemia

Anhui Medical university Carbon monoxide poisoning CO can react with Hb to form carboxyhemoglobin which can not take up oxygen. So there is a deficiency of Hb that can carry oxygen. CO can inhibit glycolysis in RBC, which reduces the production of 2,3-DPG and shifts the ODC to the left, decreasing the amount of oxygen released. Methemoglobinemia

Anhui Medical university 【 Enterogenous cyanosis 】 When a lot of pickled vegetables containing nitrate are taken, the reabsorbed nitrite reacts with HbFe 2+ to form HbFe 3+. The skin appears to coffee color. This phenomenon is called enterogenous cyanosis. HbFe 2+ HbFe 3+ OH HbFe 3+ OH oxidizers nitrite

Anhui Medical university Characteristics of blood oxygen PaO2 N, SaO2 N, CaO2 ↓/N, CO2max ↓/N, CaO2-CvO2 ↓ Skin colour Severe anemia : pallor CO poisoning : cherry red Methemoglobinemia: coffee color

Anhui Medical university 【 Circulatory hypoxia ， hypokinetic hypoxia 】 Circulatory hypoxia refers to inadequate blood flow leading to inadequate oxygenation of the tissues, which is also called hypokinetic hypoxia. Etiology and mechanism Ischemic hypoxia: shock, left heart failure, thrombosis, arterial stenosis Congestive hypoxia ： right heart failure Characteristics of blood oxygen ： PaO2 N, SaO2 N, CaO2 N, CO2max N, CaO2-CvO2 ↑

Anhui Medical university 【 Histogenous hypoxia 】 Histogenous hypoxia refers to the tissue cells can not make use of the oxygen supplied to them, though the amount of oxygen delivered to them is adequate. Etiology and mechanism Inhibition of oxidative phosphorylation - tissue intoxicity cyanides, sulphuret, rotenone, ( cytochrome oxidase) Mitochondria injury bacteriotoxin, radiation, free radical Absence of Vitamin Vit B1, Vit B2, Vit PP ， co-enzyme

Anhui Medical university Characteristics of blood oxygen ： PaO2 N, SaO2 N, CaO2 N, CO2max N, CaO2-CvO2 ↓ The mitochondrial respiratory chain and its inhibitors

Anhui Medical university hypotonic CO 2max CO 2max PaO 2 CaO 2 SaO 2 SaO 2 CO 2 (A-V) hemic circulatory histogenous Changes of Blood Gas Brief

Anhui Medical university Changes of function and metabolism Respiratory system Circulatory system Hematologic system Central nervous system Tissues and cells

Anhui Medical university 【 Respiratory system 】 1. Compensatory response ： Low PaO2 stimulates the chemoreceptor in carotid and aortic body, which reflexly causes ventilation to increase. PO2 → ventilation 2. Decompensatory effects: 1 ） High altitude pulmonary edema 2 ） Central respiratory failure respiratory inhibition, irregular respiratory rhythm and frequency, hypoventilation, e.g. periodic breathing, Cheyne-Stoke respiration, Biot’s breathing

Anhui Medical university 【 Circulatory system 】 1. Compensatory response ： Cardiac output↑ due to: 1)cardiac contractility↑ 2) heart rate↑ 3) venous return↑ Redistribution of blood flow α-Adrenoceptor vasoconstriction Local metabolites vasodilation

Anhui Medical university Hypoxic Pulmonary vasoconstriction (HPV)→PaO2 ↑ Sympathetic nerve Humoral factors — AT 、 ET PGI2 、 NO 、 histamine Direct effect of O2 on SMC Capillary proliferation --- VEGF

Anhui Medical university 2. Decompesatory effect: Pulmonary hypertension Decreased diastolic and systolicmyocardial function Arrhythmia Decrease in venous return to the heart

Anhui Medical university 【 Hematologic system 】 1.Compensatory response Increase in the amount of RBCs and Hb More EPO produced and released by kidney Improved RBC oxygen release capability （ Rightward shift of O2Hb dissociation curve ） More 2,3-DPG produced from glycolysis process

Anhui Medical university 1111 1111 2222 2222 HbO 2 1111 1111 2222 2222 HHb 2,3-DPG unable to bind to bind 2,3-DPG binding site 2,3-DPG binds to HHb at the central cavity

Anhui Medical university 2. Decompesatory effect: Plasma viscosity↑, blood flow resistance ↑, afterload of heart ↑ When PO2 is low markedly, 2,3-DPG will cause CaO2 to decrease.

Anhui Medical university 【 Central nervous system 】 1.Acute hypoxia: headache, agitation, poor faculty of memory, inability to make judgment, depress or loss of coordination 2. Chronic hypoxia: impaired concentration, fatigue, drowsiness 3. Cerebral edema and neuron injury

Anhui Medical university 【 Tissue and cellular alteration 】 1.Compensatory response Enhanced cell capacity for use of oxygen number and membrane surface of mitochondria↑ activity of succinic dehydrogenase and cyt-oxidase ↑ Enhanced anaerobic glycolysis ATP↓ and ATP/ADP ↓→phosphofructokinase ↑ Enhanced myoglobin Low metabolic state

Anhui Medical university 2. Decompesatory effect: 1)Cell membrane injury Na+ influx cell swelling K+ efflux synthetic disorder Ca 2+ influx phospholipase Ca2+-dependent protein kinase 2. Mitochondria injury severe hypoxia 3. Lysosome injury

Anhui Medical university 【 Pathophysiological basis of prevention and treatment 】 Eliminating causes Oxygen therapy Hyperbaric oxygen therapy

Anhui Medical university