Chapter 5 Hypoxia or Anoxia
Objective Contradiction:
large amount O2 consumption ---250ml/min (360L/day)
Small amount O2 storage ---1.5L (sustain life only six minutes)
Hypoxia is a fundamental pathologic process.
Hypoxia is always direct causes of death.
§1. 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.
Supply inadequate of oxygen
functions
Utilized disturbance of oxygen metabolisms damage
structures
§2. Parameters of blood oxygen
1.partial pressure of oxygen (PO2):
normal value : NPaO2= 13.3kpa (100mmHg)
NPvO2 = 5.3kpa (40mmHg)
influence factor: (1) PO2 of inhalation air
(2) extrarespiratory function
(3) shunting of blood
2. Oxygen binding capacity (CO2 max):
N.V: NCaO2 max =NCvO2max=20ml/dl
I . F: Hb---- (1) quantity
(2) quality or affinity with O2
3. Oxygen content (CO2):
N.V: NCaO2 = 19ml/dl
NCvO2 = 14ml/dl
N(CaO2 – CvO2) = 5ml/dl
I . F: (1) PO2
(2) CO2max : Hb — quantity
quality
4. Oxygen saturation (SO2):
SO2＝(CO2－dissolved O2/CO2max)×100%
N.V: NSaO2 = 95%
NSvO2 = 70%
I . F: (1) ability of oxygen combined with Hb
(2) SO2 is determined by PO2 at normal
affinity
oxygen dissociation curve :
The relationship curve between PO2 and SO2
Fig. S ( sigmoid shaped )
I . F: [H+]↑
pCO2↑
temperature↑
2,3- DPG↑
[H+] ↓
pCO2↓
temperature↓
2,3- DPG↓
a. right shift
b. affinity↓
a. left shift
b. affinity↑
5. P50:
P50 is the PO2 at the 50% SO2
N. V: N P50 = 26 – 27 mmHg
I . F: right shift → P50↑
left shift → P50↓
§3. Types/Causes/Mechanisms/Features
of hypoxia
The processes of oxygen supplied and
utilization contains:
a. lung intake oxygen
b. Hb carring O2
c. circulation transporting O2
d. cell utilizing O2
Therefore, hypoxia can be divided into four
types .
1. Hypotonic hypoxia (hypoxic hypoxia)：
PO2↓
2. Hemic hypoxia (isotonic hypoxemia)：
CO2 max↓or↑(disorders of oxygen release)
3.Circulatory hypoxia (hypokinetic hypoxia)：
Blood flow↓
4.Histogenous hypoxia (dysoxidative hypoxia)：
Failure to utilize the oxygen
1. Hypotonic hypoxia (hypoxic hypoxia)
Causes:
a. Decreased PO2 of inhaled air – atmospheric
hypoxia
b. disturbance of extrarespiration – respiratory
hypoxia
c. shunting of blood
mechanisms:
PaO2↓→ CO2 ↓→ SaO2 ↓→ inadequate supply O2 to
tissue
Features:
a. PaO2↓ PvO2↓
b. CaO2↓ CaO2↓
c. CO2max = N
d. SaO2↓
e. (CaO2 - CvO2)↓or N
f. central cyanosis
g. Respiratory compensation
2. Hemic hypoxia (isotonic hypoxemia)
causes:
a. Anemia → anemic hypoxia
b. carbon monoxide poisoning
c. Methemoglobinemia
d. higher affinity of Hb to oxygen
Mechanisms :
a. CO2max↓→ CO2↓→ afford O2 to tissue↓
b. CO2max N or↑but affinity↑→ O2 released
disorder → afford O2 to tissue ↓
Features: a. PaO2 =N, PvO2 =N
b. CaO2↓ CvO2↓
c. CO2max ↓ ( except higher
affinity )
d. SaO2: anemia = N
intoxication →↓
higher affinity →↑
e. (CaO2 - CvO2)↓
f. no cyanosis
g. no respiratory compensation
3.Circulatory hypoxia (hypokinetic hypoxia)
Causes:
a.General circulatory dysfunction —e.g. shock; heart failure.
b.Local circulatory deficiency —e.g. stenosis; occlusion; thrombosis.
Mechanisms:
Reduced tissue perfusion—a. ischemia hypoxia
b. congestive hypoxia
Features:
a. PaO2 = N
PvO2↓
b. CaO2 = N CvO2↓
c. CO2max = N
d. SaO2 = N
e. (CaO2-CvO2)↑
f. peripheral cyanosis
g. Respiratory compensation or not
4.Histogenous hypoxia (dysoxidative hypoxia)
Causes:
a.Cell poisoning:
cyanide poisoning→histotoxic hypoxia
b.Mitochondria injury:
radiation ; oxygen free radical
c. Inadequate synthesis of biological oxidation
coenzyme :
deficiency of vitamin B2 or PP
Mechanisms:
Disorder of biological oxidation or
oxidative phosphorylation → failure to
utilization of oxygen →ATP↓.
Features:
a. PaO2 = N, PvO2↑
b. CaO2 = N, CvO2↑
c. CO2max = N
d. SaO2 = N
e. (CaO2-CvO2)↓
f. No cyanosis
g. No respiratory compensation
The changes of blood oxygen parameters
in four types of hypoxia
Type
Hypotonic hypoxia
PaO2
↓
SaO2
O2 capacity
↓
N
CaO2
↓
↓ or N
CaO2-CvO2
↓ or N
↓ or N
↓
Hemic hypoxia
N
N
Circulatory hypoxia
N
N
N
N
↑
Histogenic hypoxia
N
N
N
N
↓
Note: ↓— decrease;
↑ — increase;
N — normal.
§4.Functional and metabolic changes of
the body in hypoxia
1. Respiratory system
PaO2 ( <8Kpa ) → chemoreceptors↑→
respiratory rate and depth↑→ hyperventilation.
Severe hypoxia → depressing respiratory
center → slow and periodic or irregular breathing
→ stop of breathing.
2.circulatory system
a.Cardiac output↑ : tachycardia → arrhythmia
myocardial contractility↑
b.Redistribution of blood → To afford blood to
heart and brain
c.Pulmonary vasoconstriction → pulmonary
arterial hypertension → right heart failure
3.Hemic system
a. Rightward shift of oxyhemoglobin dissociation
curve
b. Increase of red blood cell: erythropoietin(EPO)
4.Central nervous system:
Dysfunction.
5.Cell
Compensation: a. increased ability to use O2
b. anaerobic glycolysis ↑
c. increase of myoglobin
Damage: a. cellular membrane injury
b. mitochondria impairment
c. lysosome break
§5. Factors involved in tolerance to
hypoxia
a. Oxygen consumption rate
Brain → oxygen consumption rate↑→ tolerance↓
Skin → oxygen consumption rate↓→ tolerance↑
b. Compensatory ability of the body
§6. Oxygen treatment and oxygen
toxicity
All patients with hypoxia can be treated with
inhalation of oxygen , but the efficiency is quite different to
every type of hypoxia.
Efficiency:
Hypotonic hypoxia — the best
Histogenous hypoxia —the worst
When the patient inhaled high pressure of oxygen(PO2
higher than a half atm) ,a series of toxic signs and
symptoms was appeared, this condition is termed as
oxygen toxication.
Oxygen toxication:
1. Pulmonary oxygen toxication
2. Cerebral oxygen toxication
The mechanisms of oxygen toxicity:
Reactive oxygen species or oxygen free radicals .