The document discusses hypoxia, including its parameters, classification, etiology, mechanisms, effects on metabolism and body functions, and pathophysiological basis of treatment. It covers topics such as the types of hypoxia (hypotonic, hemic, circulatory, histogenous), their characteristics and causes. It also examines the alterations caused by hypoxia in various body systems like respiration, circulation, hematology and tissues. These include changes in breathing patterns, blood flow redistribution, increased erythropoiesis, and impacts on organ functions.

1. Dept. of PathologyDept. of Pathology
Medical CollegeMedical College
Hunan Normal UniversityHunan Normal University
(( 湖南 范大学医学院病理学教研室师湖南 范大学医学院病理学教研室师 )) 1
Chapter 6Chapter 6
HypoxiaHypoxia
（缺 ）氧（缺 ）氧

2. 22
HypoxiaHypoxia
a.a. IntroductionIntroduction
b.b. Parameters of HypoxiaParameters of Hypoxia
c.c. Classification, Etiology, andClassification, Etiology, and
MechanismMechanism
d.d. Alterations of Metabolism andAlterations of Metabolism and
Function in the BodyFunction in the Body
e.e. Pathophysiological Basis ofPathophysiological Basis of
TreatmentTreatment

3. Oxygen is one of the most important
necessities in our life!
Important necessities of life
a. Oxygen
b. Water
c. Food
d. Vitamins

4. Normal Process of Oxygen
Acquiring and Utilization
Air Lungs Blood Tissue utilization
Ventilation Diffusion Transportation
Internal respirationExternal respiration
Oxygen usageOxygen supply

5. Deficiency in either the delivery or theDeficiency in either the delivery or the
utilization of oxygenutilization of oxygen at the tissue level,at the tissue level,
leading toleading to changes in functions, metabolismschanges in functions, metabolisms
and structuresand structures of cells and tissues of the body.of cells and tissues of the body.
Hypoxia: Definition

6. 88
HypoxiaHypoxia
a.a. IntroductionIntroduction
b.b. Parameters of HypoxiaParameters of Hypoxia
c.c. Classification, Etiology, andClassification, Etiology, and
MechanismMechanism
d.d. Alterations of Metabolism andAlterations of Metabolism and
Function in the BodyFunction in the Body
e.e. Pathophysiological Basis ofPathophysiological Basis of
TreatmentTreatment

7. Parameters for Evaluation of
Hypoxia
PO2: Partial pressure of O2
C-O2max: O2 binding capacity
C-O2: Blood O2 content
SO2: O2 saturation
Da-vO : Difference in arterio-venous O

8. 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

9. 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 problemVentilation 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)

10. Sketch Map of Normal Oxygen Pressure Gradient
AlveolusAir
Alveolar
capillary
Arterial
blood
Body
capillary
Venous
blood
mmHg

11. C-O2max:
OxygenOxygen binding capacitybinding capacity of hemoglobinof hemoglobin
when fully oxygenated.when fully oxygenated.
- Maximal amount of- Maximal amount of O2 that could be bound bythat could be bound by
Hb. (Ability of Hb to carryHb. (Ability of Hb to carry O2.).)
Normal value: 20 ml/dlNormal 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.

12. C-O2: O2 Content
Oxygen that isOxygen that is actually bound toactually bound to
hemoglobinhemoglobin plus free Oplus free O22 (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-Oand C-O22max.max.
Little but
important

13. 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%

14. Oxygen Dissociation Curve (ODC)
2,3-DPG: 2,3-diphosphoglycerate

15. 20
40
60
80
100
0 20 40 60 80 100
PO2(%)
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?

16. 20
40
60
80
100
0 20 40 60 80 100
[H+] ↓ (pH↑)
[H+]↑ (pH ↓)
Oxygensaturation(%)
Oxygen pressure (mmHg)
Bohr effect:
When [H+]↑, ODC will right shift (the affinity ↓) ;
When [H+] ↓, ODC will left shift (the affinity ↑).
Bohr effect

17. The binding of 2,3-DPG prevents binding of O2.
Effect of 2,3-DPG on O2 Binding
Glycerate
2,3-Diphosphoglycerate

18. Da-vO2:
Normal Value: Da-vO2=CaO2-CvO2=19-14=5 ml/dl
Difference in arterio-venous oxygen content.
- reflecting tissue oxygen usage (function
of internal respiration).

19. Factors affecting Da-vO2:
 PO2
 Speed of blood flow
 Metabolic rate
 Hb-O2 affinity

20. 2323
HypoxiaHypoxia
a.a. IntroductionIntroduction
b.b. Parameters of HypoxiaParameters of Hypoxia
c.c. Classification, Etiology, andClassification, Etiology, and
MechanismMechanism
d.d. Alterations of Metabolism andAlterations of Metabolism and
Function in the BodyFunction in the Body
e.e. Pathophysiological Basis ofPathophysiological Basis of
TreatmentTreatment

21. Classification of Hypoxia
a. Hypotonic
(Hypoxic)
b. Hemic
(Hematogenous)
c. Circulatory
d. Histogenous
(Dysoxidative)
Oxygen Supply
Oxygen Usage

22. Types of Hypoxia
Air Lungs
① Hypotonic
Blood
Tissue
utilization
② Hemic ③ Circulatory
④ Histogenous

23. 3.1 Hypotonic Hypoxia
Hypotonic hypoxia is characterized by the
decrease of PaO2 (< 60 mmHg).
Also called Hypoxic Hypoxia.

24. 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

25. 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

26. 29
Defect inDefect in
interventricularinterventricular
septumseptum
Shunt from right
to left
PaOPaO22 ↓↓
Venous-to-arterial Shunt
(Tetralogy of Fallot)

27. Changes of Blood Oxygen Parameters
During Hypotonic Hypoxia
Type PaO2 C-O2max Ca-O2 SaO2 Da-vO2
Hypotonic ↓ N ↓ ↓ ↓

28. 3.2 Hemic Hypoxia
Refers to decreasedRefers to decreased
quantity of Hb in the bloodquantity of Hb in the blood
or altered affinity of Hb foror altered affinity of Hb for
oxygen.oxygen.
Also calledAlso called HematogenousHematogenous
oror IsotonicIsotonic Hypoxia.Hypoxia.

29. Etiology and Mechanism
 Quantity of Hb changed (Anemia)Quantity of Hb changed (Anemia)
 Quality of Hb changedQuality 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+
poisoningpoisoning
 form Methemoglobin (HbFeform Methemoglobin (HbFe3+3+
))

30. 34
Carbon Monoxide PoisoningCarbon Monoxide Poisoning
Hb+COHb+CO HbCOHbCO
↓↓ 2,3-DPG2,3-DPG ↓↓ OO22 releaserelease
↓↓ Ability to carry OAbility to carry O22

31. 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

32. Type PaO2 C-O2max Ca-O2 SaO2 Da-vO2
Anemia N ↓ ↓ N ↓
Changes of blood oxygen parameters

33. 3.3 Circulatory Hypoxia
Circulatory hypoxia refers to inadequateCirculatory hypoxia refers to inadequate
blood flow leading to inadequateblood flow leading to inadequate
oxygenation of the tissues.oxygenation of the tissues.
Also called Hypokinetic Hypoxia.Also called Hypokinetic Hypoxia.

34. Etiology and mechanism
Systemic circulation obstacle
Shock
Local circulation obstacle
Left heart failure
Thrombosis
Arterial stenosis (narrowing)
Tissue congestion, tissue ischemia

35. Changes of Blood Oxygen Parameters
During Circulatory Hypoxia
Type PaO2 C-O2max Ca-O2 SaO2 Da-vO2
Circ. Hyp. N N N N ↑

36. 3.4 Histogenous hypoxia
Even though the amount of oxygenEven though the amount of oxygen
delivered to tissue is adequate, the tissuedelivered to tissue is adequate, the tissue
cells can not make use of the oxygencells can not make use of the oxygen
supplied to them.supplied to them.
Also called Dysoxidative Hypoxia.Also called Dysoxidative Hypoxia.

37. Mitochondrial injuryMitochondrial injury
Cyanide poisoningCyanide poisoning
ArsenideArsenide
RadiationRadiation
Bacterial toxinsBacterial toxins
Oxygen 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 (B22 or PP)or PP)
Coenzymes required for oxidative phosphorylation.Coenzymes required for oxidative phosphorylation.
Causes of Histogenous Hypoxia

38. Changes of Blood Oxygen Parameters
During Histogenous Hypoxia
Type PaO2 C-O2max Ca-O2 SaO2 Da-vO2
Histo. Hyp. N N N N ↓

39. Characteristic Changes of Different
Types of Hypoxia

40. 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

41. 4949
HypoxiaHypoxia
a.a. IntroductionIntroduction
b.b. Parameters of HypoxiaParameters of Hypoxia
c.c. Classification, Etiology, andClassification, Etiology, and
MechanismMechanism
d.d. Alterations of Metabolism andAlterations of Metabolism and
Function in the BodyFunction in the Body
e.e. Pathophysiological Basis ofPathophysiological Basis of
TreatmentTreatment

42. Section 4. Alterations of
Metabolism and Function
Respiratory system
Circulatory system
Hematologic system
Central nervous system
Tissues and cells

43. 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 breathing
Cheyne-StokeCheyne-Stoke
4.1 Respiratory system

44. High Altitude Pulmonary Edema (HAPE)
A life-threatening form of pulmonary edema (fluidA life-threatening form of pulmonary edema (fluid
accumulation in the lungs) that occurs at altitudesaccumulation 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-altitudeThe 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 pressurelung artery pressure (due to(due to Hypoxic PulmonaryHypoxic Pulmonary
Vasoconstriction (Vasoconstriction (HPV))HPV)) → Exudation of fluid→ Exudation of fluid
↑↑ permeability of the vascular endotheliumpermeability of the vascular endothelium

45. 4.2 Circulatory system
Increased 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

46. Injury Manifestations
•Pulmonary hypertensionPulmonary hypertension
•ArrhythmiaArrhythmia
- Vagus Nerve- Vagus Nerve
- K- K++
/Ca/Ca2+2+
disturbancedisturbance
•Decreased myocardial functionDecreased myocardial function
•Decreased venous return to heartDecreased venous return to heart
•HypertensionHypertension

47. 4.3 Hematologic System
Increase in RBCs and HbIncrease in RBCs and Hb
Hypoxia → HIF → EPOHypoxia → HIF → EPO
↑↑ 2,3-DPG2,3-DPG (produced from glycolysis)(produced from glycolysis)
→→ ODC shift (left or right?)ODC shift (left or right?)
• goodgood for Ofor O22 release in the tissue;release in the tissue;
• badbad for Ofor O22 binding in the lungsbinding in the lungs

48. Plasma viscosity↑Plasma viscosity↑ →→ blood flow resistance ↑blood flow resistance ↑
→→ afterload of heart ↑afterload of heart ↑
Affinity between Hb and oxygenAffinity between Hb and oxygen ↓↓
- Due to- Due to ↑↑ 2,3-DPG2,3-DPG
Injury Manifestations

49. 4.4 Central nervous system
Acute hypoxiaAcute hypoxia
HeadacheHeadache
Poor memoryPoor memory
Inability to make judgmentInability to make judgment
DepressionDepression
Chronic hypoxiaChronic hypoxia
Unable to concentrateUnable to concentrate
FatigueFatigue
DrowsinessDrowsiness
Cerebral edema and neuron injury →Cerebral edema and neuron injury →
worsen hypoxia → deathworsen hypoxia → death

50. ↑↑ 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
↑↑ GlycolysisGlycolysis
↑↑ Capillary densityCapillary density
↓↓ Metabolic stateMetabolic state
↑↑ Myoglobin (OMyoglobin (O22 reservoir)reservoir)
4.5 Tissues and Cells

51. Enhanced Myoglobin
20 40 60 80
SO2
20
40
60
80
(mmHg)
(%)

52. Injury Manifestations
Mitochondria injuryMitochondria injury
↓↓ ATPATP
Cell membrane injuryCell membrane injury
↑↑ NaNa++
and Caand Ca2+2+
inflowinflow
↑↑ KK++
outflowoutflow
Lysosome injuryLysosome injury
Autocytosis (necrosis)Autocytosis (necrosis)

53. 6262
HypoxiaHypoxia
a.a. IntroductionIntroduction
b.b. Parameters of HypoxiaParameters of Hypoxia
c.c. Classification, Etiology, andClassification, Etiology, and
MechanismMechanism
d.d. Alterations of Metabolism andAlterations of Metabolism and
Function in the BodyFunction in the Body
e.e. Pathophysiological Basis ofPathophysiological Basis of
TreatmentTreatment

54. 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.

55. O2 Therapy
All patients with hypoxia can be treatedAll patients with hypoxia can be treated
with inhalation of oxygen, but the efficiencywith 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 hypoxiaThe best — Hypotonic hypoxia
The worst — Histogenous hypoxiaThe worst — Histogenous hypoxia

56. 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 asthis 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)