anhui medical university hypoxia department of pathophysiology basic medical science college

Anhui Medical university

Hypoxia

Department of pathophysiology

Basic Medical Science college


Respiration and oxygen Respiration and oxygen exchangeexchange

Air

Alveoli

Alveolarcapillary

Gas transport Tissue

cells

Ventilation

Gas exchange

External respiration

Internal respiration

Bound to haemoglobin


Tables of content

• Concept

• Parameters of blood oxygen

• Classification and Etiology

• Changes of function and metabolism

• Treatment


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.


• Partial pressure of oxygen, PO2

• Oxygen binding capacity, CO2max

• Oxygen content, CO2

• A-VdO2

• Oxygen saturation, SO2

• P50

Parameters of blood oxygen


【 Partial pressure of oxygen, PO2 】 PO2 is the pressure or tension caused by oxygen

physically dissolved in the blood.

【【 Normal valueNormal value 】】

PaPaOO22: 13.3kPa(100mmHg): 13.3kPa(100mmHg) ；； PvPvOO22: 5.32kPa(40mmHg): 5.32kPa(40mmHg) 。。

PaPaOO22: : 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.

PvOPvO22: : 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.


【【 Oxygen binding capacity, CO2maxOxygen binding capacity, CO2max 】】

COCO22max Is the maximum amount of oxygen combined by max Is the maximum amount of oxygen combined by

Hb in 100ml blood under fully saturated condition in Hb in 100ml blood under fully saturated condition in which the POwhich the PO22 is 150mmHg, is 150mmHg, PPCOCO2 2 40mmHg, and the 40mmHg, and the

temperature is 38 .℃temperature is 38 .℃

【 Normal value 】

CO2max: 8.92mmol/L (1.34ml/g×15gHb% =20ml%) 。

【 Meaning 】

The ability of Hb to carry O2.


【【 Oxygen content , CO2 Oxygen content , CO2 】】 The total amount of oxygen contained actually in 100 ml bloodThe total amount of oxygen contained actually in 100 ml blood

sample, including the part combined with Hb and the part sample, including the part combined with Hb and the part

physically dissolved in plasma. physically dissolved in plasma.

CO2 = PaOCO2 = PaO2 2 + CO+ CO22maxmax 。。


CaOCaO22≈≈8.47mmol/L(19.3ml%)8.47mmol/L(19.3ml%) ；； CvOCvO2 2 ≈≈5.35mmol/L(14ml%)5.35mmol/L(14ml%) 。。


【【 A-VdO2A-VdO2 】】The difference value is between arterial and venous blood oxygen The difference value is between arterial and venous blood oxygen

content.content.

【【 MeaningMeaning 】】

A-VdO2 = volume of O2 tissue uptake = CaO2-CvO2A-VdO2 = volume of O2 tissue uptake = CaO2-CvO2


A-VdOA-VdO2 2 ≈ ≈ 2. 232. 23 ～～ 3.57mmol/L(5ml%3.57mmol/L(5ml% ～～ 8ml%)8ml%) 。。


【 Oxygen saturation, SO2 】

The percentage of hemoglobin present as oxyhemoglobin

【 Meaning 】

The degree of connected Hb to oxygenThe degree of connected Hb to oxygen


SaOSaO22 ：： 93%93% ～～ 98%98% ；； SvOSvO22 ：： 70%70% ～～ 75%75% 。。

SO2% = CO2 – O2 dissolved physically in plasma/ CO2maxSO2% = CO2 – O2 dissolved physically in plasma/ CO2max

【【 InfluenceInfluence 】】 PaOPaO22


【【 p50p50 】】One measure of the position of the curve is the PO2 at One measure of the position of the curve is the PO2 at

the 50% SO2.the 50% SO2.


3.473.47 ～～ 3.6 kPa3.6 kPa

(26(26 ～～ 27mmHg)27mmHg) 。。

【【 SignificanceSignificance 】】The P50 indicates affinity of The P50 indicates affinity of hemoglobin for oxygenhemoglobin for oxygen

【【 InfluenceInfluence 】】H+, CO2, temperature, H+, CO2, temperature, 22 、、 3-DPG3-DPG


Classification and Etiology


Hypotonic Hypoxia (Hypoxic Hypoxia)Hypotonic Hypoxia (Hypoxic Hypoxia)

Classification and EtiologyClassification and Etiology

Hemic Hypoxia (Isotonic Hypoxia)Hemic Hypoxia (Isotonic Hypoxia)

Circulatory Hypoxia(Hypokinetic Hypoxia)Circulatory Hypoxia(Hypokinetic Hypoxia)

Histogenous Hypoxia(Histotoxic Hypoxia)Histogenous Hypoxia(Histotoxic Hypoxia)


【【 Hypoxic hypoxiaHypoxic hypoxia 】】

oxygen tension in arterial blood is lower than normal, oxygen tension in arterial blood is lower than normal,

which resulted in lack of oxygen from blood to tissues.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


【 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。


【 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:Causes:

（（ 11 ）） AnemiaAnemia

（（ 22 ）） Higher affinity of Hb to Higher affinity of Hb to oxygenoxygen

（（ 33 ）） Carbon monoxide poisoningCarbon monoxide poisoning

（（ 44 ）） Methemoglobinemia, MHbMethemoglobinemia, MHb


High affinity of Hb for O2

Alkaline solution

Depot blood

AnemiaAnemia


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


【 Enterogenous cyanosis 】

When a lot of pickled vegetables containing nitrate are taken, the reabsorbed nitrite reacts with HbFe2+ to form HbFe3+. The skin appears to coffee color. This phenomenon is called enterogenous cyanosis.

HbFeHbFe2+2+ HbFeHbFe3+3+OHOHoxidizersoxidizers

nitritenitrite


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


【 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 ↑


【 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


Characteristics of blood oxygen：PaO2 N, SaO2 N, CaO2 N, CO2max N, CaO2-CvO2 ↓

The mitochondrial respiratory chain and its inhibitors


hypotonichypotonic

COCO2max2maxPaOPaO22 CaOCaO22 SaOSaO22

CO2

(A-V)

hemichemic

circulatorycirculatory

histogenoushistogenous

Changes of Blood GasChanges of Blood GasBrief


Changes of function and metabolism

Respiratory system

Circulatory system

Hematologic system

Central nervous system

Tissues and cells


【 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


【 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


Hypoxic Pulmonary vasoconstriction (HPV)→PaO2 ↑

Sympathetic nerve

Humoral factors — AT 、 ET PGI2 、 NO 、 histamine

Direct effect of O2 on SMC

Capillary proliferation --- VEGF


2. Decompesatory effect:

Pulmonary hypertension

Decreased diastolic and systolicmyocardial function

Arrhythmia

Decrease in venous return to the heart


【 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


11

1122

22

HbOHbO22

11

1122

22

HHbHHb

2,3-DPG unable2,3-DPG unable to bindto bind

2,3-DPG binding site2,3-DPG binding site

2,3-DPG binds to HHb at the 2,3-DPG binds to HHb at the central cavitycentral cavity



Plasma viscosity↑,

blood flow resistance ↑,

afterload of heart ↑

When PO2 is low markedly, 2,3-DPG will cause CaO2 to decrease.


【 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


【 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



1)Cell membrane injury Na+ influx cell swelling K+ efflux synthetic disorder Ca2+ influx phospholipase Ca2+-dependent protein kinase

2. Mitochondria injury severe hypoxia

3. Lysosome injury


【 Pathophysiological basis of prevention and treatment 】

Eliminating causes

Oxygen therapy

Hyperbaric oxygen therapy

anhui medical university hypoxia department of pathophysiology basic medical science college

Documents

oxygen supply

use of oxygen

anhui medical university

co2max oxygen content

oxygen normal value

vdo2 oxygen saturation

venous blood oxygen

body oxygen demand