Hypoxia
Department of pathophysiology
Basic Medical Science college
Anhui Medical university
Respiration and oxygen exchange
Air
Ventilation
External respiration
Alveoli
Gas exchange
Alveolar
capillary
Gas
transport
Bound to haemoglobin
Tissue
cells
Internal respiration
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Tables of content
• Concept
• Parameters of blood oxygen
• Classification and Etiology
• Changes of function and metabolism
• Treatment
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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.
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Parameters of blood oxygen
• Partial pressure of oxygen, PO2
• Oxygen binding capacity, CO2max
• Oxygen content, CO2
• A-VdO2
• Oxygen saturation, SO2
• P50
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【 Partial pressure of oxygen, PO2 】
PO2 is the pressure or tension caused by oxygen
physically dissolved in the blood.
PaO2: 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.
PvO2: 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.
【Normal value】
PaO2: 13.3kPa(100mmHg)；PvO2: 5.32kPa(40mmHg)。
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【Oxygen binding capacity, CO2max】
CO2max Is the maximum amount of oxygen combined by
Hb in 100ml blood under fully saturated condition in
which the PO2 is 150mmHg, PCO2 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.
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【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 = PaO2 + CO2max。
【Normal value】
CaO2≈8.47mmol/L(19.3ml%)；CvO2 ≈5.35mmol/L(14ml%)。
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【A-VdO2】
The difference value is between arterial and venous blood oxygen
content.
【Normal value】
A-VdO2 ≈ 2. 23～3.57mmol/L(5ml%～8ml%)。
【Meaning】
A-VdO2 = volume of O2 tissue uptake = CaO2-CvO2
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【 Oxygen saturation, SO2 】
The percentage of hemoglobin present as oxyhemoglobin
【Normal value】
SaO2：93%～98%； SvO2：70%～75%。
SO2% = CO2 – O2 dissolved physically in plasma/ CO2max
【Influence】 PaO2
【Meaning】
The degree of connected Hb to oxygen
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【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
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Classification and Etiology
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Classification and Etiology
Hypotonic Hypoxia (Hypoxic Hypoxia)
Hemic Hypoxia (Isotonic Hypoxia)
Circulatory Hypoxia(Hypokinetic Hypoxia)
Histogenous Hypoxia(Histotoxic Hypoxia)
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【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
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【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。
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【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
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Anemia
High affinity of Hb for O2
Alkaline solution
Depot blood
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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
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【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.
oxidizers
HbFe2+
HbFe3+OH
nitrite
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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
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【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 ↑
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【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
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The mitochondrial respiratory chain and its inhibitors
Characteristics of blood oxygen：
PaO2 N, SaO2 N, CaO2 N, CO2max N, CaO2-CvO2 ↓
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Brief
Changes of Blood Gas
PaO2
CO2max CaO2 SaO2
CO2
(A-V)
hypotonic
hemic
circulatory
histogenous
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Changes of function and metabolism
Respiratory system
Circulatory system
Hematologic system
Central nervous system
Tissues and cells
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【Respiratory system】
1. Compensatory response：PO2 → ventilation
Low PaO2 stimulates the chemoreceptor in carotid and aortic body,
which reflexly causes ventilation to increase.
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
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【Circulatory system】
1. Compensatory response：
Cardiac output↑
due to:
1) cardiac contractility↑
2) heart rate↑
3) venous return↑
Redistribution of blood flow
α-Adrenoceptor
Local metabolites
vasoconstriction
vasodilation
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Hypoxic Pulmonary vasoconstriction
(HPV)→PaO2 ↑
Sympathetic nerve
Humoral factors — AT、ET
PGI2、NO、histamine
Direct effect of O2 on SMC
Capillary proliferation --- VEGF
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2. Decompesatory effect:
Pulmonary hypertension
Decreased diastolic and systolicmyocardial
function
Arrhythmia
Decrease in venous return to the heart
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【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
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2,3-DPG binds to HHb at the
central cavity
HbO2
1
1
2
HHb
1
2
2,3-DPG unable
to bind
1
2
2
2,3-DPG binding site
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2. Decompesatory effect:
Plasma viscosity↑,
blood flow resistance ↑,
afterload of heart ↑
When PO2 is low markedly, 2,3-DPG will cause CaO2 to
decrease.
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【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
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【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
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2. Decompesatory effect:
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
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【Pathophysiological basis of
prevention and treatment】
Eliminating causes
Oxygen therapy
Hyperbaric oxygen therapy
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