06 hypoxia

patholophysiology of hypoxia
Pathophysiology（病理生理学）
Pathology
uploaded by prabesh 杰诗

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, and Classification, Etiology, and
MechanismMechanism
d.d.Alterations of Metabolism and Alterations of Metabolism and
Function in the BodyFunction in the Body
e.e.Pathophysiological Basis of Pathophysiological 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 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

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

7. Parameters for Evaluation of
Hypoxia
PO
2
: Partial pressure of O
2
C-O
2max
: O
2
binding capacity
C-O
2
: Blood O
2
content
SO
2
: O
2
saturation
Da-vO
2
: Difference in arterio-venous O
2

8. PO
2
: Partial Pressure of O
2
Tension produced by the O
2
molecules
physically dissolved in plasma.
Normal PaO
2
: 80-110 mmHg (100 mmHg, 13.3 kPa)
PvO
2
: 37-40 mmHg (40 mmHg, 5.32 kPa)
1 kPa = 7.5 mmHg

9. Factors Affecting PO
2
FiOFiO
22: Fraction (percentage) of inspired oxygen: Fraction (percentage) of inspired oxygen
Normal FiONormal FiO
22: 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)

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

11. C-O
2
max:
Oxygen Oxygen binding capacitybinding capacity of hemoglobin of hemoglobin
when fully oxygenated.when fully oxygenated.
- Maximal amount of - Maximal amount of O
2 that could be bound by that could be bound by
Hb. (Ability of Hb to carry Hb. (Ability of Hb to carry O
2.).)
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.

12. C-O
2
: O
2
Content
Oxygen that is Oxygen that is actually bound to actually bound to
hemoglobinhemoglobin plus free O plus free O
2 2 (0.3 ml/dl).(0.3 ml/dl).
- Sealed off from air. - Sealed off from air.
Normal value: Ca-ONormal value: Ca-O
22: 19 ml/dl: 19 ml/dl
Cv-OCv-O
22: 14 ml/dl: 14 ml/dl
Determined by PODetermined by PO
22 and C-O and C-O
22max.max.
Little but
important

13. SO
2
: O
2
Saturation
Percentage of Hb present as oxygenated
Hb.
Normal value: SaO
2
: 93～98％
SvO
2
: 70～75％
Determined by: PO
2
. (SO
2
vs. PO
2
: Oxygen Dissociation Curve)
Affected by: pH, Temp, PCO
2
, 2,3-DPG.
C-O
2

C-O
2
max
SO
2
= 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
P
O
2
(
%
)
PO
2
(mmHg)
Oxygen Dissociation Curve
2,3-DPG ↑
[H+]↑ (pH ↓)
CO
2
↑
Temp ↑
2,3-DPG↓
[H+] ↓ (pH↑)
CO
2
↓
Temp ↓
Hb-O
2
affinity?
Hb-O
2
affinity?

16. 20
40
60
80
100
0 20 40 60 80 100
[H+] ↓ (pH↑)
[H+]↑ (pH ↓)
O
x
y
g
e
n

s
a
t
u
r
a
t
i
o
n

(
%
)
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 O
2.
Effect of 2,3-DPG on O
2
Binding
Glycerate
2,3-Diphosphoglycerate

18. Da-vO
2
:
Normal Value: Da-vO
2
=CaO
2
-CvO
2
=19-14=5 ml/dl
Difference in arterio-venous oxygen content.
- reflecting tissue oxygen usage (function
of internal respiration).

19. Factors affecting Da-vO
2
:
PO
2
Speed of blood flow
Metabolic rate
Hb-O
2
affinity

20. 2323
HypoxiaHypoxia
a.a.IntroductionIntroduction
b.b.Parameters of HypoxiaParameters of Hypoxia
c.c.Classification, Etiology, and Classification, Etiology, and
MechanismMechanism
d.d.Alterations of Metabolism and Alterations of Metabolism and
Function in the BodyFunction in the Body
e.e.Pathophysiological Basis of Pathophysiological 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 Hemic③ Circulatory
④ Histogenous

23. 3.1 Hypotonic Hypoxia
Hypotonic hypoxia is characterized by the
decrease of PaO
2
(< 60 mmHg).
Also called Hypoxic Hypoxia.

24. Etiology and Mechanism
Decreased O
2
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 O
2
(mmHg)
PaO
2
(mmHg)
SaO
2
Symptom
8
5
3
0
58
85
110
158
30
45
62
100
58%
75%
90%
95% -
±
++
Mostly dead

26. 29
Defect in Defect in
interventricular interventricular
septumseptum
Shunt from right
to left
PaOPaO
22 ¯¯
Venous-to-arterial Shunt
(Tetralogy of Fallot)

27. Changes of Blood Oxygen Parameters
During Hypotonic Hypoxia
Type PaO
2
C-O
2
max Ca-O
2
SaO
2
Da-vO
2
Hypotonic ↓ N ↓ ↓ ↓

28. 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.

29. 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 O
22
 Carbon monoxide (CO) poisoningCarbon monoxide (CO) poisoning
form Carboxyhemoglobin (HbCO)form Carboxyhemoglobin (HbCO)
 FeFe
3+3+
poisoning poisoning
form Methemoglobin (HbFeform Methemoglobin (HbFe
3+3+
) )

30. 34
Carbon Monoxide PoisoningCarbon Monoxide Poisoning
Hb+COHb+CO HbCOHbCO
↓ ↓ 2,3-DPG2,3-DPG ↓ ↓ OO
22 release release
↓ ↓ Ability to carry OAbility to carry O
22

31. Methemoglobinemia
The ferrous state of iron (Fe
2+
) in Hb may be
oxidized to the ferric state (Fe
3+
) under the
action of oxidizers, e.g. nitrite and
nitrobenzene.
HbFe
3+
loses the ability to carry oxygen.
HbFeHbFe
2+2+
HbFeHbFe
3+3+
NitriteNitrite

32. Type PaO
2
C-O
2
max Ca-O
2
SaO
2
Da-vO
2
Anemia N ↓ ↓ N ↓
Changes of blood oxygen parameters

33. 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.

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 PaO
2
C-O
2
max Ca-O
2
SaO
2
Da-vO
2
Circ. Hyp. N N N N ↑

36. 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.

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 (B
2 2 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 PaO
2
C-O
2
max Ca-O
2
SaO
2
Da-vO
2
Histo. Hyp.N N N N ↓

39. Characteristic Changes of Different
Types of Hypoxia

40. Type PaO
2
C-O
2
max Ca-O
2
SaO
2
Da-vO
2
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, and Classification, Etiology, and
MechanismMechanism
d.d.Alterations of Metabolism and Alterations of Metabolism and
Function in the BodyFunction in the Body
e.e.Pathophysiological Basis of Pathophysiological 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 (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

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
•Arrhythmia Arrhythmia
- Vagus Nerve- Vagus Nerve
- K- K
++
/Ca/Ca
2+2+
disturbance disturbance
•Decreased myocardial function Decreased myocardial function
•Decreased venous return to heart Decreased venous return to heart
•Hypertension Hypertension

47. 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 O
22 release in the tissue; release in the tissue;
•badbad for O for O
22 binding in the lungs binding in the lungs

48. 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

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
↑ ↑ Glycolysis Glycolysis
↑ ↑ Capillary density Capillary density
↓ ↓ Metabolic state Metabolic state
↑ ↑ Myoglobin (OMyoglobin (O
22 reservoir) reservoir)
4.5 Tissues and Cells

51. Enhanced Myoglobin
20 40
60
80
SO
2
20
40
60
80
(mmHg)
(%)

52. Injury Manifestations
Mitochondria injuryMitochondria injury
↓ ↓ ATPATP
Cell membrane injuryCell membrane injury
↑↑ NaNa
++
and Ca and Ca
2+2+
inflow inflow
↑↑ KK
++
outflow outflow
Lysosome injury Lysosome injury
Autocytosis (necrosis)Autocytosis (necrosis)

53. 6262
HypoxiaHypoxia
a.a.IntroductionIntroduction
b.b.Parameters of HypoxiaParameters of Hypoxia
c.c.Classification, Etiology, and Classification, Etiology, and
MechanismMechanism
d.d.Alterations of Metabolism and Alterations of Metabolism and
Function in the BodyFunction in the Body
e.e.Pathophysiological Basis of Pathophysiological 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 O
22. .
- Usually not exceeding 60% O- Usually not exceeding 60% O
22 (FiO (FiO
22 0.6). 0.6).
Increase the pressure of OIncrease the pressure of O
2.2.
- Not exceeding 3 atmosphere. - Not exceeding 3 atmosphere.

55. O
2
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 O
22 Therapy: Therapy:
The best — Hypotonic hypoxia The 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 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)