Dept. of PathologyDept. of Pathology
Medical CollegeMedical College
Hunan Normal UniversityHunan Normal University
(( 湖南师范大学医学院病理学教研室湖南师范大学医学院病理学教研室 )) 1
Chapter 6Chapter 6
HypoxiaHypoxia(缺氧)(缺氧)
22
HypoxiaHypoxia
①① IntroductionIntroduction
②② Parameters of HypoxiaParameters of Hypoxia
③③ Classification, Etiology, and Classification, Etiology, and
MechanismMechanism
④④ Alterations of Metabolism and Alterations of Metabolism and
Function in the BodyFunction in the Body
⑤⑤ Pathophysiological Basis of Pathophysiological Basis of
TreatmentTreatment
Oxygen is one of the most important necessities in our life!
Important necessities of life①Oxygen②Water③Food④Vitamins
Normal Process of Oxygen Acquiring and Utilization
Air Lungs Blood Tissue utilization Ventilation Diffusion Transportation
Internal respirationExternal respiration
Oxygen usageOxygen supply
Deficiency in either the delivery or the Deficiency in either the delivery or the
utilization of oxygenutilization of oxygen at the tissue level, at the tissue level,
leading to leading to changes in functions, metabolisms changes in functions, metabolisms
and structuresand structures of cells and tissues of the body. of cells and tissues of the body.
Hypoxia: Definition
88
HypoxiaHypoxia
①① IntroductionIntroduction
②② Parameters of HypoxiaParameters of Hypoxia
③③ Classification, Etiology, and Classification, Etiology, and
MechanismMechanism
④④ Alterations of Metabolism and Alterations of Metabolism and
Function in the BodyFunction in the Body
⑤⑤ Pathophysiological Basis of Pathophysiological Basis of
TreatmentTreatment
Parameters for Evaluation of Hypoxia
PO2: Partial pressure of O2
C-O2max: O2 binding capacity
C-O2: Blood O2 content
SO2: O2 saturation
Da-vO2: Difference in arterio-venous O2
PO2: Partial Pressure of O2
Tension produced by the O2 molecules physically dissolved in plasma.
Normal PaO2: 80-110 mmHg (100 mmHg, 13.3 kPa)
PvO2: 37-40 mmHg (40 mmHg, 5.32 kPa)
1 kPa = 7.5 mmHg
Factors Affecting PO2
FiOFiO22: Fraction (percentage) of inspired oxygen: Fraction (percentage) of inspired oxygen
Normal FiONormal FiO22: 21% (0.21) : 21% (0.21)
Pulmonary functionPulmonary function•Ventilation problem Ventilation problem
Obstruction of airwayObstruction of airway
•Exchange (diffusion) problemExchange (diffusion) problem
Edema (inflammation)Edema (inflammation)
Venous-to-arterial shunt (shortcut)Venous-to-arterial shunt (shortcut)Venous-to-arterial shunt (shortcut)Venous-to-arterial shunt (shortcut)
Sketch Map of Normal Oxygen Pressure GradientSketch Map of Normal Oxygen Pressure Gradient
AlveolusAirAlveolar
capillaryArterial blood
Body
capillary
Venous
blood
mm
Hg
C-O2max:
Oxygen Oxygen binding capacitybinding capacity of hemoglobin of hemoglobin when fully oxygenated.when fully oxygenated. - Maximal amount of - Maximal amount of O2 that could be bound by that could be bound by Hb. (Ability of Hb to carry Hb. (Ability of Hb to carry O2.).)
Normal value: 20 ml/dl Normal value: 20 ml/dl (1.34 x 15)(1.34 x 15)
Affected by quantity and quality of Hb.Affected by quantity and quality of Hb.
C-O2: O2 Content
Oxygen that is Oxygen that is actually bound to actually bound to hemoglobinhemoglobin plus free O plus free O2 2 (0.3 ml/dl).(0.3 ml/dl).
- Sealed off from air. - Sealed off from air.
Normal value: Ca-ONormal value: Ca-O22: 19 ml/dl: 19 ml/dl
Cv-OCv-O22: 14 ml/dl: 14 ml/dl
Determined by PODetermined by PO22 and C-O and C-O22max.max.
Little but important
SO2: O2 Saturation
Percentage of Hb present as oxygenated Hb.
Normal value: SaO2: 93 ~ 98% SvO2: 70 ~ 75 %
Determined by: PO2. (SO2 vs. PO2: Oxygen Dissociation Curve)
Affected by: pH, Temp, PCO2, 2,3-DPG.
C-O2
C-O2max
SO2 = x 100%
20
40
60
80
100
0 20 40 60 80 100
PO
2 (%
)
PO2 (mmHg)
Oxygen Dissociation Curve
2,3-DPG ↑
[H+]↑ (pH ↓)
CO2 ↑
Temp ↑
2,3-DPG↓
[H+] ↓ (pH↑)
CO2↓
Temp ↓
Hb-O2 affinity?
Hb-O2 affinity?
20
40
60
80
100
0 20 40 60 80 100
[H+] ↓ (pH↑)
[H+]↑ (pH ↓)
Ox
yg
en s
atu
rati
on
(%
)
Oxygen pressure (mmHg)
Bohr effect:
When [H+]↑, ODC will right shift (the affinity ↓) ; When [H+] ↓, ODC will left shift (the affinity ↑).
Bohr effect:
When [H+]↑, ODC will right shift (the affinity ↓) ; When [H+] ↓, ODC will left shift (the affinity ↑).
Bohr effectBohr effect
The binding of 2,3-DPG prevents binding of O2. The binding of 2,3-DPG prevents binding of O2.
Effect of 2,3-DPG on O2 Binding
Glycerate
2,3-Diphosphoglycerate
Da-vO2:
Normal Value: Da-vO2=CaO2-CvO2=19-14=5 ml/dlNormal Value: Da-vO2=CaO2-CvO2=19-14=5 ml/dl
Difference in arterio-venous oxygen content.
- reflecting tissue oxygen usage (function of internal respiration).
2323
HypoxiaHypoxia
①① IntroductionIntroduction
②② Parameters of HypoxiaParameters of Hypoxia
③③ Classification, Etiology, and Classification, Etiology, and
MechanismMechanism
④④ Alterations of Metabolism and Alterations of Metabolism and
Function in the BodyFunction in the Body
⑤⑤ Pathophysiological Basis of Pathophysiological Basis of
TreatmentTreatment
Classification of Hypoxia
①Hypotonic (Hypoxic)
②Hemic (Hematogenous)
③Circulatory
④Histogenous (Dysoxidative)
④Histogenous (Dysoxidative)
Oxygen SupplyOxygen Supply
Oxygen UsageOxygen Usage
3.1 Hypotonic Hypoxia
Hypotonic hypoxia is characterized by the decrease of PaO2 (< 60 mmHg).
Also called Hypoxic Hypoxia.
Etiology and Mechanism
Decreased O2 level of inspired air
Hypoventilation
Diffusion abnormality
Venous-to-arterial shunt (tetralogy of Fallot)
O2
Diffusion abnormality
Venous-to-arterial
shunt
Hypo-ventilation
Relationship Between Altitude and Hypoxia
Altitude(km)
Air O2
(mmHg)PaO2
(mmHg)SaO2 Symptom
8
5
3
0
58
85
110
158
30
45
62
100
58%
75%
90%
95% -
±
++
Mostly dead
29
Defect in Defect in interventricular interventricular
septumseptum
Shunt from right to left
PaOPaO22
Venous-to-arterial Shunt (Tetralogy of Fallot)
Changes of Blood Oxygen Parameters
During Hypotonic Hypoxia
Changes of Blood Oxygen Parameters
During Hypotonic Hypoxia
Type PaO2 C-O2max Ca-O2 SaO2 Da-vO2Type PaO2 C-O2max Ca-O2 SaO2 Da-vO2
Hypotonic ↓ N ↓ ↓ ↓Hypotonic ↓ N ↓ ↓ ↓
3.2 Hemic Hypoxia
Refers to decreased Refers to decreased quantity of Hb in the blood quantity of Hb in the blood or altered affinity of Hb for or altered affinity of Hb for oxygen.oxygen.
Also called Also called HematogenousHematogenous or or IsotonicIsotonic Hypoxia. Hypoxia.
Etiology and Mechanism
Quantity of Hb changed (Anemia)Quantity of Hb changed (Anemia)
Quality of Hb changed Quality of Hb changed
→ ↓→ ↓ ability of Hb to bind Oability of Hb to bind O22
Carbon monoxide (CO) poisoningCarbon monoxide (CO) poisoning
form Carboxyhemoglobin (HbCO)form Carboxyhemoglobin (HbCO)
FeFe3+3+ poisoning poisoning
form Methemoglobin (HbFeform Methemoglobin (HbFe3+3+) )
34
Carbon Monoxide Carbon Monoxide PoisoningPoisoning
Hb+COHb+CO HbCOHbCO
↓ ↓ 2,3-DPG2,3-DPG ↓ ↓ OO22 releaserelease
↓ ↓ Ability to carry OAbility to carry O22
Methemoglobinemia
The ferrous state of iron (Fe2+) in Hb may be oxidized to the ferric state (Fe3+) under the action of oxidizers, e.g. nitrite and nitrobenzene.
HbFe3+ loses the ability to carry oxygen.
HbFeHbFe2+2+ HbFeHbFe3+3+
NitriteNitrite
Type PaO2 C-O2max Ca-O2 SaO2 Da-vO2Type PaO2 C-O2max Ca-O2 SaO2 Da-vO2
Anemia N ↓ ↓ N ↓Anemia N ↓ ↓ N ↓
Changes of blood oxygen parametersChanges of blood oxygen parameters
3.3 Circulatory Hypoxia
Circulatory hypoxia refers to inadequate Circulatory hypoxia refers to inadequate
blood flow leading to inadequate blood flow leading to inadequate
oxygenation of the tissues.oxygenation of the tissues.
Also called Hypokinetic Hypoxia.Also called Hypokinetic Hypoxia.
Etiology and mechanism
Systemic circulation obstacleShock
Local circulation obstacleLeft heart failure
Thrombosis
Arterial stenosis (narrowing)
Tissue congestion, tissue ischemia
Changes of Blood Oxygen Parameters During Circulatory
Hypoxia
Changes of Blood Oxygen Parameters During Circulatory
Hypoxia
Type PaO2 C-O2max Ca-O2 SaO2 Da-vO2Type PaO2 C-O2max Ca-O2 SaO2 Da-vO2
Circ. Hyp. N N N N ↑Circ. Hyp. N N N N ↑
3.4 Histogenous hypoxia
Even though the amount of oxygen Even though the amount of oxygen delivered to tissue is adequate, the tissue delivered to tissue is adequate, the tissue cells can not make use of the oxygen cells can not make use of the oxygen supplied to them.supplied to them.
Also called Dysoxidative Hypoxia.Also called Dysoxidative Hypoxia.
Mitochondrial injuryMitochondrial injuryCyanide poisoningCyanide poisoningArsenideArsenideRadiationRadiationBacterial toxinsBacterial toxinsOxygen free radicalOxygen free radical
inhibit the function of the mitochondriainhibit the function of the mitochondria
Deficiency of B group vitamins (BDeficiency of B group vitamins (B2 2 or PP)or PP)
Coenzymes required for oxidative phosphorylation.Coenzymes required for oxidative phosphorylation.
Causes of Histogenous Hypoxia
Changes of Blood Oxygen Parameters During Histogenous
Hypoxia
Changes of Blood Oxygen Parameters During Histogenous
Hypoxia
Type PaO2 C-O2max Ca-O2 SaO2 Da-vO2Type PaO2 C-O2max Ca-O2 SaO2 Da-vO2
Histo. Hyp. N N N N ↓Histo. Hyp. N N N N ↓
Characteristic Changes of Different Types of Hypoxia
Characteristic Changes of Different Types of Hypoxia
Type PaO2 C-O2max Ca-O2 SaO2 Da-vO2
Hypotonic ↓ N ↓ ↓ ↓
Hemic N ↓ ↓ N ↓
Circulatory N N N N ↑
Histogenous N N N N ↓
Changes of Blood Oxygen Parameters in Different Types of
Hypoxia
4949
HypoxiaHypoxia
①① IntroductionIntroduction
②② Parameters of HypoxiaParameters of Hypoxia
③③ Classification, Etiology, and Classification, Etiology, and
MechanismMechanism
④④ Alterations of Metabolism and Alterations of Metabolism and
Function in the BodyFunction in the Body
⑤⑤ Pathophysiological Basis of Pathophysiological Basis of
TreatmentTreatment
Section 4. Alterations of Metabolism and Function
Respiratory system
Circulatory system
Hematologic system
Central nervous system
Tissues and cells
Central respiratory failureCentral respiratory failure
- Periodic breathing- Periodic breathing
Cheyne-Stoke respirationCheyne-Stoke respiration
Biot’s breathingBiot’s breathing
High altitude pulmonary edema (HAPE)High altitude pulmonary edema (HAPE)
Clinical Manifestations
Biot’s breathingBiot’s breathing
Cheyne-StokeCheyne-Stoke
4.1 Respiratory system
High Altitude Pulmonary Edema (HAPE)
A life-threatening form of pulmonary edema (fluid A life-threatening form of pulmonary edema (fluid accumulation in the lungs) that occurs at altitudes accumulation in the lungs) that occurs at altitudes typically above 2.5 km.typically above 2.5 km.
The major cause of death related to high-altitude The major cause of death related to high-altitude exposure.exposure.
Mechanisms of HAPE:Mechanisms of HAPE:Excitement of the sympathetic nerveExcitement of the sympathetic nerve↑ ↑ lung artery pressure lung artery pressure (due to (due to Hypoxic Pulmonary Hypoxic Pulmonary Vasoconstriction (Vasoconstriction (HPV)) HPV)) → Exudation of fluid→ Exudation of fluid↑↑ permeability of the vascular endotheliumpermeability of the vascular endothelium
4.2 Circulatory systemIncreased cardiac output (CO) and heart rate (HR)Increased cardiac output (CO) and heart rate (HR)
Redistribution of blood flowRedistribution of blood flow
Dilation of heart and brain vesselsDilation of heart and brain vessels
Hypoxic Pulmonary Vasoconstriction (Hypoxic Pulmonary Vasoconstriction (HPV)HPV)
Capillary proliferationCapillary proliferation
Hypoxia → HIF (hypoxia-inducible factor) → Hypoxia → HIF (hypoxia-inducible factor) → VEGF → Capillary growthVEGF → Capillary growth
Injury Manifestations
•Pulmonary hypertensionPulmonary hypertension
•Arrhythmia Arrhythmia
- Vagus Nerve- Vagus Nerve- K- K++/Ca/Ca2+2+ disturbance disturbance
•Decreased myocardial function Decreased myocardial function
•Decreased venous return to heart Decreased venous return to heart
•Hypertension Hypertension
4.3 Hematologic System
Increase in RBCs and HbIncrease in RBCs and Hb
Hypoxia → HIF → EPOHypoxia → HIF → EPO
↑ ↑ 2,3-DPG 2,3-DPG (produced from glycolysis)(produced from glycolysis)
→→ ODC shift (left or right?)ODC shift (left or right?)
• goodgood for O for O22 release in the tissue; release in the tissue;
• badbad for O for O22 binding in the lungs binding in the lungs
Plasma viscosity↑ Plasma viscosity↑ → → blood flow resistance ↑ blood flow resistance ↑ → → afterload of heart ↑afterload of heart ↑
Affinity between Hb and oxygen Affinity between Hb and oxygen ↓↓- Due to - Due to ↑ ↑ 2,3-DPG2,3-DPG
Injury Manifestations
4.4 Central nervous systemAcute hypoxiaAcute hypoxia
HeadacheHeadachePoor memoryPoor memoryInability to make judgmentInability to make judgmentDepressionDepression
Chronic hypoxiaChronic hypoxiaUnable to concentrateUnable to concentrateFatigueFatigueDrowsinessDrowsinessCerebral edema and neuron injury → Cerebral edema and neuron injury → worsen hypoxia → deathworsen hypoxia → death
↑ ↑ Ability to use of oxygenAbility to use of oxygen
(All types except histogenous hypoxia)(All types except histogenous hypoxia)
↑ ↑ Number and density of mitochondriaNumber and density of mitochondria
↑ ↑ Activity of mitochondrial enzymesActivity of mitochondrial enzymes
↑ ↑ Glycolysis Glycolysis
↑ ↑ Capillary density Capillary density
↓ ↓ Metabolic state Metabolic state
↑ ↑ Myoglobin (OMyoglobin (O22 reservoir) reservoir)
4.5 Tissues and Cells
Enhanced MyoglobinEnhanced Myoglobin
2020 4040 6060 8080
SO2SO2
2020
4040
6060
8080
(mmHg)(mmHg)
(%)(%)
Injury Manifestations
Mitochondria injuryMitochondria injury↓ ↓ ATPATP
Cell membrane injuryCell membrane injury↑↑ NaNa++ and Ca and Ca2+2+ inflow inflow↑↑ KK++ outflow outflow
Lysosome injury Lysosome injury Autocytosis (necrosis)Autocytosis (necrosis)
6262
HypoxiaHypoxia
①① IntroductionIntroduction
②② Parameters of HypoxiaParameters of Hypoxia
③③ Classification, Etiology, and Classification, Etiology, and
MechanismMechanism
④④ Alterations of Metabolism and Alterations of Metabolism and
Function in the BodyFunction in the Body
⑤⑤ Pathophysiological Basis of Pathophysiological Basis of
TreatmentTreatment
5.Pathophysiological Basis of Prevention and Treatment
Eliminating causesEliminating causes
Oxygen therapy: Oxygen therapy:
Increase the concentration of OIncrease the concentration of O22. .
- Usually not exceeding 60% O- Usually not exceeding 60% O22 (FiO (FiO22 0.6).0.6).
Increase the pressure of OIncrease the pressure of O2.2.
- Not exceeding 3 atmosphere. - Not exceeding 3 atmosphere.
O2 Therapy
All patients with hypoxia can be treated All patients with hypoxia can be treated with inhalation of oxygen, but the efficiency with inhalation of oxygen, but the efficiency is quite different to every type of hypoxia.is quite different to every type of hypoxia.
Effectiveness of OEffectiveness of O22 Therapy: Therapy: The best — Hypotonic hypoxia The best — Hypotonic hypoxia The worst — Histogenous hypoxiaThe worst — Histogenous hypoxia
When the patient inhales high pressure of oxygen, When the patient inhales high pressure of oxygen, a series of toxic signs and symptoms will appear, a series of toxic signs and symptoms will appear, this condition is termed as this condition is termed as oxygen toxicationoxygen toxication..
Cerebral oxygen toxication (Acute)Cerebral oxygen toxication (Acute)
Pulmonary oxygen toxication (Chronic)Pulmonary oxygen toxication (Chronic)
The mechanisms of oxygen toxicity.The mechanisms of oxygen toxicity.
Reactive oxygen species or oxygen free radicals.Reactive oxygen species or oxygen free radicals.
Oxygen Toxication (OT)
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