HypoxiaHypoxia

ConceptConcept

Oxgen supply = CaO2× Q

Oxygen consumption = （ CaO2 － CvO2 ） × Q

Tissue cells can’t obtain enough oxygen

or can’t fully utilize oxygen

metabolic, functional and structural changes

CO2 － dissolved O2

CO2maxO2 saturation （ SO2 ） = ×100%

SaO2 95%, SvO2 70%

Parameters of blood gasParameters of blood gasPartial pressure of O2 （ PO2 ） PaO2 100mmHg , PvO2 40 mmHg O2 content （ CO2 ） = CO2max×SO2 + dissolved O2

CaO2 19ml/dl , CvO2 14ml/dl

O2 capacity （ CO2max ） = 1.34 ml/g × Hb g/dl

Dissociation curve of oxyhemoglobinDissociation curve of oxyhemoglobin

Classification, etiology and pathogenesisClassification, etiology and pathogenesis 1. 1. Hypotonic hypoxiaHypotonic hypoxia — — PaOPaO22↓ ↓

Causes : 1) PiO2↓

2) pulmonary dysfunction

3) shunt

Results : PaO2↓→ SaO2↓→ CaO2↓ hypotonic hypoxemia, cyanosis （ PaO2 － PMO2 ）↓ →（ CaO2 － CvO

2 ）↓

PaO2 ＜ 60mmHg → VO2↓ ？

Results : CO2max↓↓ CaO2 ↓↓

（ CaO2 － CvO2 ） ↓ P50 ↓ （ CaO2 － CvO2 ） ↓

2.2. Hemic hypoxia — COHemic hypoxia — CO22maxmax ↓

Causes : 1) anemia

2) carboxyhemoglobinemia

3) methemoglobinemia

enterogenous cyanosis

4) P50↓ ： transfusion of depot blood

Result : Q↓↓→ CvO2↓

→ （ CaO2 － CvO2 ）↑

Causes : general circulatory failure

local circulatory disorder

3. 3. Circulatory H — Q↓Circulatory H — Q↓

··

4. Histogenous hypoxia

Causes: 1) histotoxic H

cyanide poisoning

2) cell injured by biological or p

hysical factor

3) vitamin deficiency --- B1

Result : CvO2↑ → （ CaO2 － CvO2 ）↓

What kind of hypoxia might occur in

septic shock ？

Hypotonic hypoxia

PaO2 ＜ 60mmHg → compensation ＜ 30mmHg → severe disturbances

Functional and metabolic alterationsFunctional and metabolic alterations

1. 1. Respiratory systemRespiratory system

• Respiratory rate and depth ↑

arrive at 4000m high →ventilation ↑ 65%

few days later → ventilation ↑ 5 – 7 times

long residents → 15 % more than at sea level

•

• Hyperventilation→PaO2↑→CaO2 ↑

↘O2 consumption ↑

occur in any type of hypoxia?

Severe hypoxia→pulmonary edma

↘Inhibition of respiratory center

2. 2. Circularory systemCircularory system

• Cardiac output↑ due to: 1. cardiac contractility↑ 2. heart rate↑ 3. venous return↑

• Redistribution of blood flow α-Adrenoceptor vasoconstriction Local metabolites vasodilation

Pulmonary vasoconstriction (HPV)→PaO2 ↑

Sympathetic nerve

Humoral factors — AT 、 ET 、 LTs 、 TxA2

PGI2 、 NO 、 histamine

Direct effect of O2 on SMC — Kv

How to prove?

Capillary proliferation --- VEGF

Severe hypoxia

• Myocardiac systolic and diastolic dysfunction

• Cardiac arrhythmia ---

Hypoxia acidosis hyperkalemia

Arrhythmia

• Venous return↓

• Pulmonary hypertention right ventricle

3. 3. Hemic systemHemic system

• RBC↑--- erythropoitin • P50 ---- 2.3 - DPG↑

4.4.Central nervous systemCentral nervous system

• Acute H → headache 、 impaired attention • Chronic H → sleepiness, depression

• Severe H → confusion, coma, convulsion

due to : energy deficiency and acidosis

decreased RMP

abnormal neurotransmitter synthesis

cell damage

vasodilation and cerebral edema

5. 5. Cellular alterationsCellular alterations

AdaptationAdaptation

• Ability to use O2↑---

number of mitochondia , it’s enzymes

• Anaerobic glycolysis↑

ATP/ADP↓ → phosphofructokinase

activity

• Low metabolic state --- caused by acidosis

• Myoglobin↑

Dissociation curve of oxymyoglobin and oxyhemoglobin

• Cell membrane

decreased permeability + ion pump dysfunction

[ Na+ ]i → Cellular swelling

[ K+ ]i ↓ → Synthetic metabolism↓

[ Ca2+ ]i → Mitochondria damage

ROS

Lysosome damage

Severe H → Cellular damage

• Mitochondria Respiratory function ↑ (PmO2< 1mmHg)

PmO2< 1mmHg dehydrogenase activity

• Lysosome Acidosis phospholipase activity

hydrolases release

Factors influencing the tolerance to hypoxiaFactors influencing the tolerance to hypoxia

• Oxygen consumption rate

• Compensatory ability to hypoxia

Oxygen therapy and oxygen intoxication

Oxygen intoxication --- PO2> 0.5 atm

• Cerebral type --- visual and auditory

dysfunction , nausea, convulsion and coma

How to differentiate it from hypoxic encephalopathy?

• Pulmonary type --- cough, dyspnea

vital capacity , PaO2