Anhui Medical university Hypoxia Department of pathophysiology Basic Medical Science college
Dec 23, 2015
Anhui Medical university
Hypoxia
Department of pathophysiology
Basic Medical Science college
Anhui Medical university
Respiration and oxygen Respiration and oxygen exchangeexchange
Air
Alveoli
Alveolarcapillary
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 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.
Anhui Medical university
【【 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.
Anhui Medical university
【【 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 。。
【【 Normal valueNormal value 】】
CaOCaO22≈≈8.47mmol/L(19.3ml%)8.47mmol/L(19.3ml%) ;; CvOCvO2 2 ≈≈5.35mmol/L(14ml%)5.35mmol/L(14ml%) 。。
Anhui Medical university
【【 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
【【 Normal valueNormal value 】 】
A-VdOA-VdO2 2 ≈ ≈ 2. 232. 23 ~~ 3.57mmol/L(5ml%3.57mmol/L(5ml% ~~ 8ml%)8ml%) 。。
Anhui Medical university
【 Oxygen saturation, SO2 】
The percentage of hemoglobin present as oxyhemoglobin
【 Meaning 】
The degree of connected Hb to oxygenThe degree of connected Hb to oxygen
【【 Normal valueNormal value 】】
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
Anhui Medical university
【【 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.
【【 Normal valueNormal value 】】
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
Anhui Medical university
Classification and Etiology
Anhui Medical university
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)
Anhui Medical university
【【 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
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: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
Anhui Medical university
High affinity of Hb for O2
Alkaline solution
Depot blood
AnemiaAnemia
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 HbFe2+ to form HbFe3+. The skin appears to coffee color. This phenomenon is called enterogenous cyanosis.
HbFeHbFe2+2+ HbFeHbFe3+3+OHOHoxidizersoxidizers
nitritenitrite
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
hypotonichypotonic
COCO2max2maxPaOPaO22 CaOCaO22 SaOSaO22
CO2
(A-V)
hemichemic
circulatorycirculatory
histogenoushistogenous
Changes of Blood GasChanges of Blood GasBrief
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
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
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 Ca2+ 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