Lecture 10 Hypoxia and CO2 Transport

Zuheir A Hasan

Professor of physiology

College of Medicine

HU

Objectives • Define hypoxia and hypoxemia

• List main cause of hypoxia and hypoxemia

• State the relationship between the partial pressure of carbon dioxide in the blood and the amount of carbon dioxide physically dissolved in the blood.

• Review the transport of CO2 in the lung and tissue capillarie

• List the forms by which Co2 id transported in the blood

• Describe the transport of carbon dioxide as carbamino compounds with blood proteins.

• Explain how most of the carbon dioxide in the blood is transported as bicarbonate.

• Describe the carbon dioxide dissociation curve for whole blood.

• Describe Haldane effect.

• Know common clinically used terms in respiratory physiology

Pulse Oximetry

• measures % saturation of arterial blood (e.g., of the finger) using dual-wavelength spectrophotometry.

• Because oxyhemoglobin and deoxyhemoglobin have different absorbance characteristics, the machine calculates % saturation from absorbance at two different wavelengths.

• Pulse oximetry measures arterial % saturation because arterial blood “pulses,” whereas venous and capillary blood do not

• Pulse oximetry does not directly measure PaO2. However, knowing % saturation, one can estimate PaO2 from the O2-hemoglobin dissociation curve.

Hypoxia and hypoxemia

• Hypoxemia is defined as a decrease in arterial PO2.

• Hypoxia is defined as a decrease in O2 delivery to, or utilization by, the tissues.

• Hypoxemia is one cause of tissue hypoxia, although it is not the only cause.

• One useful tool for comparing the various causes of hypoxemia is the AO2 − aO2 gradient, or A − a difference

Causes of hypoxemia

Hypoxia

• Hypoxia is decreased O2 delivery to the tissues. or O2 utilization by the tissues

• Because O2 delivery is the product of cardiac output and O2 content of blood, hypoxia is caused by decreased cardiac output (blood flow) or decreased O2 content of blood.

A Classification of the Causes of HypoxiaIncreased

FIo2

helpful?Classification PAo2 Pao2 Cao2 Cvo2Pvo2

Hypoxic hypoxia

Low alveolar Po2

Diffusion impairment

Right to left shunts

V/Q mismatch

Anemic hypoxia

CO poisoning

Hypoperfusion hypoxia

Histotoxic hypoxia

Low

Norm

Norm

Norm

Norm

Norm

Norm

Norm

Low

Low

Low

Low

Norm

Norm

Norm

Norm

Low

Low

Low

Low

Low

Low

Norm

Norm

Low

Low

Low

Low

Low

Low

Low

High

Low

Low

Low

Low

Low

Low

Low

High

Yes

Yes

No

Yes

No

Possibly

No

No

Causes of hypoxia

• Inadequate oxygenation of the blood in the lungs because of extrinsic reasons

• a. Deficiency of O2 in the atmosphere

• b. Hypoventilation (neuromuscular disorders)

• 2. Pulmonary disease

• a. Hypoventilation caused by increased airway resistance or decreased pulmonary compliance

• b. Abnormal alveolar ventilation-perfusion ratio (including either increased physiological dead space or increased physiological shunt)

• Diminished respiratory membrane diffusion

• Venous-to-arterial shunts (“right-to-left” cardiac shunts

Causes of hypoxia

• 4. Inadequate O2 transport to the tissues by the blood• a. Anemia or abnormal hemoglobin

• b. General circulatory deficiency

• c. Localized circulatory deficiency (peripheral, cerebral, coronary vessels)

• d. Tissue edema

• 5. Inadequate tissue capability of using O2• a. Poisoning of cellular oxidation enzymes

• b. Diminished cellular metabolic capacity for using due oxygen toxicity, vitamin deficiency

CO2 Exchange pulmonary capillary and systemic capillary

Diffusion of carbon dioxide from the pulmonary blood into the alveolus.

Uptake of carbon dioxide by the blood in the tissue capillaries. (PCO2 in tissue cells = 46 mm Hg, and in interstitial fluid= 45 mm Hg.)

Methods of CO2 transport

• Once leaving the tissue and enters tissue capillary , Carbon dioxide is carried in the blood in the following forms :

• Dissolved in plasma 7 % Range( 5-10 % )• Chemically combined to amino acids in blood to

Hb and other plasma proteins as carbamino compound 23 %

• bicarbonate ions 70 % • Please note that the percent varies in different

resources

Carbamino Compound

Transport of CO2 in combination with hemoglobin and plasma proteins:

• Carbon dioxide can combine chemically with the terminal amine groups in blood proteins, forming carbamino compounds (arbaminohemoglobin (CO2Hb)).

• Deoxyhemoglobin can bind more carbon dioxide as carbamino groups than can oxyhemoglobin. Therefore, as the hemoglobin in the venous blood enters the lung and combines with oxygen, it releases carbon dioxide from its terminal amine groups

• A small amount of CO2 also reacts in the same way with the plasma

proteins in the tissue capillaries. However, this reaction is less

significant than Hb transport of CO2.

• The contribution of the carbaminohemoglobin and plasma proteins in

the transport of CO2 to the lungs is just above 20% of the total

quantity transported

TRANSPORT OF CARBON DIOXIDE BY THE BLOOD

Dissolved CO2

• About 200–250 mL of carbon dioxide is produced by the tissue metabolism each minute in a resting 70-kg person and must be carried by the venous blood to the lung for removal from the body.

• At a cardiac output of 5 L/min, each 100 mL of blood passing through the lungs must therefore unload 4–5 mL of carbon dioxide.

• Carbon dioxide is about 20 times more soluble in the plasma (and inside the erythrocytes) compared to oxygen.

• As a result, about 5–10% of the total carbon dioxide transported by the blood is carried in physical solution.

Dissolved CO2 (5-10 %)

• Solubility of CO2 is equal About 0.0006mL CO2/(mm Hg Pco2 ) will dissolve in 1 mL of plasma at 37C.

• Or it is equal to 0.06 ml/100 ml of blood

• According To Henry law Henry’s Law relates partial pressure of CO2 to concentration of dissolved CO2 in plasma as follows:

[CO2] = 0.0006 x PCO2

• CO2 Dissolves in arterial blood = 0.0006 X 40 = 0.024 ml CO2 /ml are dissolved in 1 ml of blood of blood

• One hundred milliliters of plasma or whole blood at a Pco2 of 40 mm Hg, therefore, contains about 2.4 mL CO2 in physical solution

• Total CO2 content of whole blood is about 48 mL CO2/100 mL of blood at 40 mm Hg, so approximately 5% of the carbon dioxide carried in the arterial blood is in physical solution

• Similarly, multiplying 0.0006 mL CO2/ml multiplied by PCO2 of mixed venous blood

• CO2 dissolved /ml = 0.0006 x 45 = 0.027 ml CO2 dissolved in 1 ml of blood

• CO2 dissolved in 100mL of mixed venous blood = about 2.7 mL CO2 is physically dissolved in the mixed venous

• . The total carbon dioxide content of venous blood is about 52.5 mL CO2/100 mL of blood; a little more than 5% of the total carbon dioxide content of venous blood is in physical solution

Carbon dioxide dissociation curve:

:

1. The normal blood PCO2 ranges between

a narrow range of 40 mmHg in arterial

blood and 45 mmHg in venous blood.

2. The concentration of CO2 rises to about

52 volumes percent as the blood passes

through the tissues and falls to about 48

volumes percent as it passes through the

lungs.

3. Only 4 volumes percent of the CO2

concentration is exchanged during

normal transport of CO2 from the

tissues to the lungs.

Carbon dioxide dissociation curves for whole blood (37C) at different oxyhemoglobin saturations.

Note that the ordinate is whole blood CO2 content in milliliters of CO2 per 100 mL of blood. a, arterial point; v–, mixed venous point

Total CO2 content of whole arterial blood is about 48 mL CO2/100 mL

The total carbon dioxide content of venous blood is about 52.5 mL CO2/100 mL of blood;

A little more than 5% of the total carbon dioxide content of venous blood is in physical solution

Carbon Dioxide Dissociation Curve

Haldane effect

The carbon dioxide dissociation curve for whole blood is shifted to the right at greater levels of oxyhemoglobinand shifted to the left at greater levels of deoxyhemoglobin.

The Haldane effect allows the blood to load more carbon dioxide at thetissues, where there is more deoxyhemoglobin, and unloadmore carbon dioxide in the lungs, where there is more oxyhemoglobin.

The Haldane Effect

• Binding of oxygen with hemoglobin tends to displace CO2

from the blood.

• The combination of O2 with hemoglobin in the lungs

causes the hemoglobin to become a stronger acid.

• The more highly acidic hemoglobin has less tendency to

combine with CO2 to form carbaminohemoglobin, thus

displacing much of the CO2 that is present in the

carbamino form from the blood.

• Also the increased acidity of the hemoglobin →

↑release of H+ ions → ↑binding of H+ with

bicarbonate ions to form H2CO3 → dissociation of

H2CO3 into water and CO2 → ↑release of CO2 from the

blood into the alveoli.

• The Haldane effect approximately doubles the amount ofCO2 released from the blood in the lungs and approximately doubles the pickup of CO2 in the tissues.

➢ Bicarbonate 70 % Other sources (80-90%)

CO2 + H2O H2CO3 H+ + HCO3

CarbonicAnhydrase

-

CO2 (Gas phase)

(Dissolved in the aqueous phase)

Transport of CO2 by the blood as bicarbonate

Schematic representation of uptake and release of carbon dioxide and oxygen at the tissues (A) and in the lung (B).Note that small amounts of carbon dioxide can form carbamino compounds with blood proteins other than hemoglobin and may also be hydrated in little amounts in the plasma to form carbonic acid and then bicarbonate

Glossary of Clinically Important Respiratory States

• Apnea Transient cessation of breathing

• Asphyxia O2 starvation of tissues, caused by a lack of O2 in the air, respiratory impairment, or inability of the tissues to use O2

• Cyanosis Blueness of the skin resulting from insufficiently oxygenated blood in the arteries

• Dyspnea Difficult or labored breathing

• Eupnea Normal breathing

• Hypercapnia Excess CO2 in the arterial blood

Glossary of Clinically Important Respiratory States

• Hyperpnea Increased pulmonary ventilation that matches increased metabolic demands, as in exercise

• Hyperventilation Increased pulmonary ventilation in excess of metabolic requirements, resulting in decreased PCO2 and respiratory alkalosis

• Hypocapnia Below-normal CO2 in the arterial blood

• Hypoventilation Underventilation in relation to metabolic requirements, resulting in increased PCO2 and respiratory acidosis

Glossary of Clinically Important Respiratory States

• Hypoxia Insufficient O2 at the cellular level

• Anemic hypoxia Reduced O2-carrying capacity of the blood

• Circulatory hypoxia Too little oxygenated blood delivered to the tissues; also known as stagnant hypoxia

• Histotoxic hypoxia Inability of the cells to use available O2

• Hypoxic hypoxia Low arterial blood PO2 accompanied by inadequate Hb saturation

• Respiratory arrest Permanent cessation of breath

• Acute respiratory failure is impairment of oxygenation, carbon dioxide elimination, or both. Respiratory failure may occur because of impaired gas exchange, decreased ventilation, or both