Hypoxia
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Hypoxia. Department of pathophysiology Basic Medical Science college. Air. Alveoli. Alveolar capillary. Gas transport. Tissue cells. Bound to haemoglobin. Internal respiration. Respiration and oxygen exchange. Ventilation. External respiration. Gas exchange. T ables of content.

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Hypoxia

Hypoxia

Department of pathophysiology

Basic Medical Science college


Hypoxia

Air

Alveoli

Alveolar

capillary

Gas

transport

Tissue

cells

Bound to haemoglobin

Internal respiration

Respiration and oxygen exchange

Ventilation

External respiration

Gas exchange


T ables of content

Tables of content

  • Concept

  • Parameters of blood oxygen

  • Classificationand Etiology

  • Changes of function and metabolism

  • Treatment


Concept

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.


Parameters of blood oxygen

Parameters of blood oxygen

  • Partial pressure of oxygen, PO2

  • Oxygen binding capacity, CO2max

  • Oxygen content, CO2

  • A-VdO2

  • Oxygen saturation, SO2

  • P50


Hypoxia

【 Partial pressure of oxygen, PO2 】

PO2 is the pressure or tension caused by oxygen physically dissolved in the blood.

PaO2: The partial pressure of oxygen in the plasma phase of arterial blood.

The PaO2 gives us valuable information about adequacy of gas exchange within the lungs, when it is subtracted from the calculated alveolar PO2.

PvO2: The partial pressure of oxygen in the plasma phase of venous blood.

The PvO2 is determined by whole body oxygen demand, and the capacity of the tissues to extract oxygen.

【Normal value】

PaO2: 13.3kPa(100mmHg);PvO2: 5.32kPa(40mmHg)。


Hypoxia

【Oxygen binding capacity, CO2max】

CO2max Is the maximum amount of oxygen combined by Hb in 100ml blood under fully saturated condition in which the PO2 is 150mmHg, PCO2 40mmHg, and the temperature is 38℃.

【Normal value】

CO2max: 8.92mmol/L (1.34ml/g×15gHb% =20ml%)。

【Meaning】

The ability of Hb to carry O2.


Hypoxia

【Oxygen content , CO2 】

The total amount of oxygen contained actually in 100 ml blood

sample, including the part combined with Hb and the part

physically dissolved in plasma.

CO2 = PaO2 + CO2max。

【Normal value】

CaO2≈8.47mmol/L(19.3ml%);CvO2 ≈5.35mmol/L(14ml%)。


Hypoxia

【A-VdO2】

The difference value is between arterial and venous blood oxygen

content.

【Normal value】

A-VdO2 ≈ 2. 23~3.57mmol/L(5ml%~8ml%)。

【Meaning】

A-VdO2 = volume of O2 tissue uptake = CaO2-CvO2


Hypoxia

【 Oxygen saturation, SO2 】

The percentage of hemoglobin present as oxyhemoglobin

【Normal value】

SaO2:93%~98%; SvO2:70%~75%。

SO2% = CO2 – O2 dissolved physically in plasma/ CO2max

【Influence】 PaO2

【Meaning】

The degree of connected Hb to oxygen


Hypoxia

【p50】

One measure of the position of the curve is the PO2 at the 50% SO2.

【Normal value】

3.47~3.6 kPa

(26~27mmHg)。

【Significance】

The P50 indicates affinity of hemoglobin for oxygen

【Influence】

H+, CO2, temperature,

2、3-DPG


Classification and etiology

Classification and Etiology


Hypoxia

Hypotonic Hypoxia (Hypoxic Hypoxia)

Classification and Etiology

Hemic Hypoxia (Isotonic Hypoxia)

Circulatory Hypoxia(Hypokinetic Hypoxia)

Histogenous Hypoxia(Histotoxic Hypoxia)


Hypoxia

【Hypoxic hypoxia】

oxygen tension in arterial blood is lower than normal,

which resulted in lack of oxygen from blood to tissues.

Causes : 1) Decreased PO2 of inspired air

2) External respiratory dysfunction

3) Venous-to-arterial shunt

Characteristics of blood oxygen

PaO2↓, SaO2↓, CaO2 ↓, CO2max N, CaO2-CvO2 ↓/N


Hypoxia

【Cyanosis】

The bluish color of skin, nails, lips and mucous membranes when the deoxyhemoglobin concentration of the blood in the capillaries is more than 5g/dl。


Hypoxia

【Hemic hypoxia, isotonic hypoxia】

Hemic hypoxia refers to the altered affinity of Hb for oxygen or

decrease in amount of Hb in the blood

Causes:

(1)Anemia

(2)Higher affinity of Hb to oxygen

(3)Carbon monoxide poisoning

(4)Methemoglobinemia, MHb


Hypoxia

Anemia

High affinity of Hb for O2

Alkaline solution

Depot blood


Hypoxia

Carbon monoxide poisoning

CO can react with Hb to form carboxyhemoglobin which can not take up oxygen. So there is a deficiency of Hb that can carry oxygen.

CO can inhibit glycolysis in RBC, which reduces the production of 2,3-DPG and shifts the ODC to the left, decreasing the amount of oxygen released.

Methemoglobinemia


Hypoxia

【Enterogenous cyanosis】

When a lot of pickled vegetables containing nitrate are taken, the reabsorbed nitrite reacts with HbFe2+ to form HbFe3+. The skin appears to coffee color. This phenomenon is called enterogenous cyanosis.

oxidizers

HbFe2+

HbFe3+OH

nitrite


Hypoxia

Characteristics of blood oxygen

PaO2 N, SaO2 N, CaO2 ↓/N, CO2max ↓/N, CaO2-CvO2 ↓

Skin colour

Severe anemia : pallor

CO poisoning : cherry red

Methemoglobinemia: coffee color


Hypoxia

【Circulatory hypoxia,hypokinetic hypoxia】

Circulatory hypoxia refers to inadequate blood flow leading to inadequate oxygenation of the tissues, which is also called hypokinetic hypoxia.

Etiology and mechanism

Ischemic hypoxia:

shock, left heart failure, thrombosis, arterial stenosis

Congestive hypoxia:

right heart failure

Characteristics of blood oxygen:

PaO2 N, SaO2 N, CaO2 N, CO2max N, CaO2-CvO2 ↑


Hypoxia

【Histogenous hypoxia】

Histogenous hypoxia refers to the tissue cells can not make use of the oxygen supplied to them, though the amount of oxygen delivered to them is adequate.

Etiology and mechanism

Inhibition of oxidative phosphorylation - tissue intoxicity

cyanides, sulphuret, rotenone, ( cytochrome oxidase)

Mitochondria injury

bacteriotoxin, radiation, free radical

Absence of Vitamin

Vit B1, Vit B2, Vit PP ,co-enzyme


Hypoxia

The mitochondrial respiratory chain and its inhibitors

Characteristics of blood oxygen:

PaO2 N, SaO2 N, CaO2 N, CO2max N, CaO2-CvO2 ↓


Hypoxia

Brief

Changes of Blood Gas

CO2

(A-V)

CO2max

PaO2

CaO2

SaO2

hypotonic

hemic

circulatory

histogenous


Changes of function and metabolism

Changes of function and metabolism

Respiratory system

Circulatory system

Hematologic system

Central nervous system

Tissues and cells


Hypoxia

【Respiratory system】

1. Compensatory response:

Low PaO2 stimulates the chemoreceptor in carotid and aortic body, which reflexly causes ventilation to increase.

PO2 → ventilation

2. Decompensatory effects:

1)High altitude pulmonary edema

2)Central respiratory failure

respiratory inhibition, irregular respiratory rhythm and frequency, hypoventilation, e.g. periodic breathing, Cheyne-Stoke respiration, Biot’s breathing


Hypoxia

【Circulatory system】

  • 1. Compensatory response:

  • Cardiac output↑

  • due to:

  • cardiac contractility↑ 2) heart rate↑ 3) venous return↑

  • Redistribution of blood flow

  • α-Adrenoceptor vasoconstriction

  • Local metabolites vasodilation


Hypoxia

Hypoxic Pulmonary vasoconstriction (HPV)→PaO2 ↑

Sympathetic nerve

Humoral factors — AT、ET

PGI2、NO、histamine

Direct effect of O2 on SMC

Capillary proliferation --- VEGF


Hypoxia

  • 2. Decompesatory effect:

    • Pulmonary hypertension

    • Decreased diastolic and systolicmyocardial function

    • Arrhythmia

    • Decrease in venous return to the heart


Hypoxia

【Hematologic system】

  • Compensatory response

  • Increase in the amount of RBCs and Hb

  • More EPO produced and released by kidney

  • Improved RBC oxygen release capability

  • (Rightward shift of O2Hb dissociation curve)

  • More 2,3-DPG produced from glycolysis process


Hypoxia

2,3-DPG binds to HHb at the central cavity

HHb

HbO2

1

1

2

1

1

2

2

2

2,3-DPG unable

to bind

2,3-DPG binding site


Hypoxia

2. Decompesatory effect:

Plasma viscosity↑,

blood flow resistance ↑,

afterload of heart ↑

When PO2 is low markedly, 2,3-DPG will cause CaO2 to decrease.


Hypoxia

【Central nervous system】

1.Acute hypoxia:

headache, agitation, poor faculty of memory, inability to make judgment, depress or loss of coordination

2. Chronic hypoxia:

impaired concentration, fatigue, drowsiness

3. Cerebral edema and neuron injury


Hypoxia

【Tissue and cellular alteration】

  • Compensatory response

  • Enhanced cell capacity for use of oxygen

  • number and membrane surface of mitochondria↑

  • activity of succinic dehydrogenase and cyt-oxidase ↑

  • Enhanced anaerobic glycolysis

  • ATP↓ and ATP/ADP ↓→phosphofructokinase ↑

  • Enhanced myoglobin

  • Low metabolic state


Hypoxia

2. Decompesatory effect:

1)Cell membrane injury

Na+ influx cell swelling

K+ efflux synthetic disorder

Ca2+ influx

phospholipase

Ca2+-dependent protein kinase

2. Mitochondria injury severe hypoxia

3. Lysosome injury


Hypoxia

【Pathophysiological basis of prevention and treatment】

Eliminating causes

Oxygen therapy

Hyperbaric oxygen therapy


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