RT 127
Oxygen Transport

Normal Blood Gas Values

Arterial blood gas analysis looks at two major components: ventilation and oxygenation. Adequacy of ventilation is reflected in the pH, PCO2 and HCO3 measurements. Adequacy of oxygenation of the blood is reflected by the PaO2. Respiratory Care Practitioners know the normal values for each of these parameters, and are able to identify abnormalities, and classify the severity of those abnormalities. This week we will look at the oxygenation component of the blood gas analysis. It is important to remember that when giving an interpretation of the blood gas results you will need to not only indicate the acid-base disturbance but also the severity of the oxygenation abnormality. The table below gives the normal values for a patient breathing room air. Remember that a normal PaO2 of 80 - 100 mm Hg when a patient is breathing supplemental oxygen is not normal.

 

abg values.jpg

Adequacy of tissue oxygenation is reflected in the venous blood values.

Oxygen Transport

Dissolved

means that the gas maintains its precise molecular structure

About 0.003 mL of O2 will dissolve in 100 mL of blood for every 1 mm Hg of PO2

Thus, a PaO2 of 100 mm Hg = 0.3 mL of Oxygen physically dissolved in the plasma of the blood

100 mm Hg X 0.003 ml/ mmHg/ 100 ml of blood = 0.3 ml/100 ml of blood

Written as 0.3 volumes percent (Vol%)

Vol% represents amount of O2 (in mL) that is in 100 mL of blood

Key Concept: A very small portion of the total amount of oxygen carried in the blood is transported as dissolved

A key component of a blood gas result is the partial pressure of oxygen in the artery. This gives us a good indication of how well oxygen is getting into the blood stream. However, this measurement reflects the plasma or dissolved component and does not give a good picture of total oxygen available to the tissues. The majority of oxygen is carried combined to the hemoglobin molecule, therefore a arterial PO2 without any idea of the patient's hemoglobin level, is of limited usefulness.

Combined

means that the molecule chemically binds to another, oxygen forms a reversible bond with the hemoglobin binding sites

Each RBC contains about 280 million hemoglobin (Hb) molecules

Normal adult Hb molecule (Hb A) consists of:

4 heme groups (iron portion of the Hb) - the sites to which oxygen binds

100% Saturation occurs when all four heme sites of each molecule are combined with oxygen

4 amino acid chains: 2 alpha and 2 beta (affect hemoglobins affinity for oxygen, alterations in these chains result in abnormal hemoglobin

heme.jpg

Oxyhemoglobin is hemoglobin bound with oxygen

The partial pressure of oxygen influences the amoung of oxygen carried by the hemoglobin molecule. In the pulmonary capillaries the partial pressure is high and the pressure gradient facilitates the diffusion of oxygen into the RBC where it binds with hemoglobin. In the capillaries of the tissues, the pressure gradient reverses - and oxygen diffuses out of the blood stream into the tissues.

Reduced hemoglobin or deoxyhemoglobin is hemoglobin not bound with oxygen

Hemoglobin becomes reduced when it releases oxygen at the tissues. That is also where the carbon dioxide is released from the tissues into the blood. Carbon dioxide is carried in the RBC back to the lung, and participates in the reaction with intracellur water to create carbonic acid which causes a change in the RBC pH. Reduced hemoglobin is a weak acid and can buffer pH changes in the RBC.

 

 

O2 binding to hemoglobin.jpg

Normal adult male Hb value: 14-16 g/100 mL

Normal adult female Hb value:12-15 g/100 mL

Clinically, the weight measurement of hemoglobin, in reference to 100 mL of blood, is referred to as either:

Gram percent of hemoglobin (g% Hb) or

Grams per deciliter (g/dL)

remember the % sign indicates per 100 which in this case is per 100 ml of blood

dL is a decaliter - one tenth of a liter, which is also 100 ml

Each g% Hb can carry 1.34 mL of oxygen

Thus, if Hb level is 15 g%, and if Hb is fully saturated, about 20.1 vol% of O2 will be bound to the Hb

combined formula.jpg

This is also referred to the hemoglobin's capacity to carry oxygen. In other words each heme site on the hemoglobin molecule is combined with oxygen - or 100% saturated.

At a normal PaO2 of 100 mm Hg, however, the Hb saturation (SaO2) is only about 97% due to the following three normal physiologic shunts

•Thebesian venous drainage into the left atrium

•Bronchial venous drainage into pulmonary veins

•Alveoli that are under ventilated, also referred to as dead space ventilation

Thus, the amount of arterial oxygen in the preceding equation must be adjusted to 97 percent:

combined content.jpg

Total Oxygen Content

To determine the total amount of oxygen in 100 mL of blood, the following must be added together:

Dissolved oxygen

Oxygen bound to hemoglobin

The following case study summarizes the calculations required to compute an individual's total oxygen content

27-year-old woman

Long history of anemia (decreased hemoglobin concentration)

Showing signs of respiratory distress 

Respiratory rate 36 breaths/min

Heart rate 130 beats/min

Blood pressure 155/90 mm Hg 

Hemoglobin concentration is 6 g%

PaO2 is 100 mm Hg (SaO2 97%)

Based on this information, the patient's total oxygen content is computed as follows:

1. Dissolved O2:

PaO2 100 mm Hg x 0.003 ml/100 ml blood/mmHg = 0.3 ml O2/100 ml of blood (written as 0.24 vol% O2)

*Notice that the mm Hg units cancel

2.  Oxygen Bound to Hemoglobin:

      6 g% Hb x 1.34 (O2 bound to Hb factor) = 8.04 vol% O2 (capacity at SaO2 of 100%)

Since her measured SaO2 is 97% not 100% we have to calculate 97% of the capacity:

      8.04 vol% O2 x 0.97 SaO2 = 7.80 vol% O2

3.  Total oxygen content:

7.80 vol% O2 (bound to hemoglobin) + 0.3 vol% O2 (dissolved O2) = 8.1 vol% O2 (total amount of O2/100 ml of blood)

*Note:

Patient's total arterial oxygen content is less than 50 percent of normal even though she has a normal PaO2

Her hemoglobin concentration, which is the primary mechanism for transporting oxygen, is very low.

Once problem is corrected, respiratory distress should no longer be present

Giving more oxygen will not correct the problem since 97% is as fully saturated as we can get it taking the physiologic shunts into consideration.

Treatment: Treat the anemia with a transfusion of packed RBC's which will increase the amount of hemoglobin (think of them as boxcars that are loaded at the lungs and unloaded at the tissue level) that can carry oxygen.

Total Oxygen Contents can be calculated for the following

CaO2 = Oxygen content of arterial blood - reflects the amount of oxygen available to the tissues.

(Hb x 1.34)SaO2 + (PaO2 x 0.003)

CvO2 = Oxygen content of mixed venous blood - reflects the amount of oxygen remaining in the blood after it has passed through the tissues. An indicator of adequacy of tissue oxygenation, tissue perfusion, and the tissues ability to utilize oxygen.

(Hb x 1.34)SvO2 + (PvO2 x 0.003)

* Note that both the partial pressure of oxygen and the saturation must be measured from a mixed venous blood sample.

CcO2 = Oxygen content of pulmonary capillary blood - eliminates component of physiologic shunts, looks at function at the a-c membrane.

(Hb x 1.34) + (PaO2 x 0.003)

Various mathematical manipulations of the CaO2, CvO2, and CcO2 values are used in different oxygen transport studies to reflect important factors concerning the patient's cardiac (perfusion and cardiac output) and ventilatory status.

Oxygen Dissociation Curve

The oxygen dissociation curve plots the % saturation against the partial pressure of oxygen, and its contribution to the total oxygen content. This is an S shaped curve due to the alterations in hemoglobin's affinity for oxygen in response to other physiologic factors. Please note the dotted line at the bottom of the graph. This represents the dissolved O2. Dissolved O2 is a linear relationship to its partial pressure and results in a straight line.

 

o2_dissoc _curve.jpg

PO2 can fall from 100 to 60 mm Hg and the hemoglobin will still be 90 percent saturated with oxygen

Excellent safety zone, this corresponds to the flat upper portion of the curve. Also indicates that the hemoglobin can load a fair amount of oxygen at the lungs even if there is a diffusion problem.

As the Hb moves through the A-C system, a significant partial pressure difference continues to exist between the alveolar gas and blood, even after most O2 has transferred.

Oxygen that diffuses from the alveolus into the capillary plasma passes into the RBC to bind with hemoglobin where it no longer exerts a partial pressure. This process facilitates and enhances the diffusion of oxygen by maintaining the pressure gradient between the alveolus and the plasma.

However, once the hemoglobin molecules are saturated, increasing PO2 beyond 100 mm Hg adds very little O2 to the blood

Effects dissolved O2 only (PO2 x 0.003 = dissolved O2)

A reduction of PO2 below 60 mm Hg causes a rapid decrease in amount of O2 bound to hemoglobin.

However, diffusion of oxygen from hemoglobin to tissue cells is enhanced by this process. This corresponds to the steep portion of the curve.

P50

The P50 represents the partial pressure at which hemoglobin is 50 percent saturated with oxygen.

Normal P50 is 27 mm Hg

P50 provides a means of quantifying the hemoglobin's affinity (willingness to bond) with oxygen. Reflects what are called shifts of the dissociation curve.

Right shift – hemoglobin has decreased affinity, increased P50 – takes more oxygen to reach 50% (higher partial pressure to get 50% saturated)

Left shift – increased affinity, decreased P50 – less oxygen to reach 50% (less partial pressure to get 50% saturated)

p50.jpg

Factors that influence hemoglobin's affinity for oxygen include

changes in

• pH

• Temperature

• Carbon Dioxide

• 2,3-DPG

and the presence of hemoglobin variants

• Fetal Hemoglobin

• Carbon Monoxide Hemoglobin

• Hemoglobin S (sickle cell)

• Methemoglobin

shifts.jpg

Bohr Effect – effect of changes in pH and PCO2 on oxygen binding to hemoglobin

Enhances unloading @ cells - pH 7.40 to pH 7.37 results in a right shift, decreased affininity and release of oxygen

Enhances uptake @ lungs – pH 7.37 to 7.40 results in a shift back to normal, normal affinity

Temperature is related to metabolism

Increased temperature causes increased metabolism and results in

An increased cellular need for O2

Decreases hemoglobin's affinity and helps unload O2

Hypothermia results in a decrease metabolic rate

Decreased Oxygen need

Increases affinity and decreases unloading

2,3 diphosphoglycerate (organic phospate) – stabilizes the Hb molecule in its deoxygenated state and decreases affinity for O2

Increase 2,3 DPG results in a R shift of the curve

Causes of increased 2,3 DPG include anemia, alkalosis, chronic hypoxemia

Decrease 2,3 DPG results in a L shift of the curve

Causes by acidosis, administration of stored blood

Blood stored one week loses 2/3rds of DPG. So even though we give blood to increase hemoglobin levels and improve oxygen content the O2 is not released easily @ the cellular level until the body restores the DPG levels

HbS causes a R shift : decreases affinity

Methemoglobinemia (pronounced as Met Hemoglobinemia not Meth) is the change of the iron molecule from Ferrous 2+ to Ferric 3+

Ferric ion is unable to combine with O2 therefore greatly decreases hemoglobin's affinity – R shift of curve

Seen in nitrate poisoning, shellfish toxins and algae blooms

A good first indicator is BROWN (chocolate syrup) blood – treated with methylene blue or ascorbic acid

Like rusted blood!

Carboxyhemoglobin

Hb affinity for CO is 200 times that of O2!

Strong bond with site prevents O2 from bonding

Also increases hemoglobin affinity for the oxygen that is present and prevents the release of O2 from those sites it has bonded to

Results in the bright red color of the blood and tissues (cherry red appearance to lips) which may be misidentified as good oxygenation when in fact the tissues are severely compromised. PaO2 will be normal!

L shift of curve

Treatment is removal from the environment where CO is present and 100% oxygen to create a large pressure gradient to compete for binding sites in an attempt to drive off the CO which will be released back into the lungs for exhalation.

CLINICAL SIGNIFICANCE OF SHIFTS IN THE O2 DISSOCIATION CURVE

When an individual's blood PaO2 is within normal limits (80-100 mm Hg):

Shift of oxygen dissociation curve to the right or left does not significantly affect hemoglobin's ability to transport oxygen to the peripheral tissues.

However, when an individual's blood PaO2 falls below the normal range:

A shift to the right or left can have a remarkable effect on the hemoglobin's ability to pick up and release oxygen.  

This is because shifts below the normal range occur on the steep portion of the curve.

For example, consider the loading and unloading of oxygen during the following clinical conditions:

Picture the loading of oxygen onto hemoglobin as blood passes through the alveolar-capillary system at a time when the alveolar oxygen tension (PAO2) is moderately low, around 60 mm Hg.

Normally, when the PAO2 is 60 mm Hg, the plasma PaO2 is about 60 mm Hg, and Hb is about 90% saturated.

right_shift.jpg

If, however, the oxygen dissociation curve shifts to the right, the hemoglobin will be only about 75 percent saturated with oxygen as it leaves the alveoli.

 

R_Shift_loading.jpg

In view of this gas transport phenomenon, it should be stressed that:

Total oxygen delivery may be much lower than indicated by a particular PaO2 value when a disease process is present that causes the oxygen dissociation curve to shift to the right.

Although total oxygen delivery may be decreased in the above situation plasma PO2 at the tissue sites does not have to fall as much to unload oxygen.

For example, if tissue cells metabolize 5 vol% oxygen at a time when the oxygen dissociation is in the normal position:

When the plasma PO2 is 60 mm Hg, the PO2 must fall to about 35 mm Hg to free 5 vol% oxygen for metabolism (PO2 falls 25 mmHg)

R_Shift_unloading.jpg

If, however, the curve shifts to the right in response to a pH of 7.1:

Plasma PO2 at tissue sites would only have to fall from 60 mm Hg to about 40 mm Hg to unload 5 vol% oxygen from the hemoglobin (a decrease of 20 mm Hg)

RShiftunloading2.jpg

If the oxygen dissociation curve shifts to left in response to a pH of 7.6:

Hemoglobin will be about 95 percent saturated with oxygen leaving the lungs

left_shift_loading.jpg

Although total oxygen increases in the previously mentioned situation, plasma PO2 at the tissue sites must decrease more than normal in order for oxygen to dissociate from the hemoglobin (remember left shift increases the affinity or the strength of the bond between hemoglobin and oxygen, so the pressure gradient must be greater to cause it to release the oxygen) 

If the curve shifts to the left because of a pH of 7.6:

Plasma PO2 at the tissue sites would have to fall from 60 mm Hg to about 30 mm Hg to unload 5 vol% oxygen from the hemoglobin (a decrease of 30 mm Hg)

 

Left_shift_unloading.jpg

The illustration from Cardiopulmonary Anatomy and Physiology summarizes the important values that you should know
Normal SaO2

Normal SvO2

Normal CaO2

Normal PvO2

Normal A-V Oxygen Content Difference (CaO2 - CvO2)

important_values.jpg

Oxygen Transport Values

 

Total Oxygen Delivery: DO2 = QT x (CaO2 x 10)

The total amount of oxygen delivered or transported to the peripheral tissues is dependent on

  1. The body's ability to oxygenate blood
  2. The hemoglobin concentration
  3. The cardiac output (QT) which should have a dot over the Q to indicate the time period which in this case is per minute.

For example:

If a patient has a cardiac output of 5 L/min and a CaO2 of 20 vol%

DO2 will be about 1000 mL of oxygen per minute:

total_oxygen_delivery.jpg

*Since O2 content is given as ml/100 ml blood, we need to convert it to ml per 1000 ml of blood

DO2 decreases in response to:

Low blood oxygenation that can be caused by

Low PaO2

Low SaO2

Low hemoglobin concentration

Low cardiac output

DO2 increases in response to:

Increased blood oxygenation caused by

Increased PaO2

Increased SaO2

Increased hemoglobin concentration

Increased cardiac output

Arterial-Venous Oxygen Content Difference

av_difference_formula.jpg

(Remember in all these equations the 'v' refers to mixed venous and should be written with a line over the v to designate it as a mixed venous value)

The C(a-v)O2 is the difference between the CaO2 and the CvO2

Normally, the CaO2 is about 20 vol% and the CvO2 is 15 vol%.

Thus, the C(a-v)O2 is about 5 vol%:

av_difference_example.jpg

Factors that Increase the C(a-v)O2

Decreased cardiac output

Periods of increased oxygen consumption as a result of

Exercise

Seizures

Shivering

Hyperthermia

Factors that Decrease the C(a-v)O2

Increased cardiac output

Skeletal relaxation 

Induced by drugs

Peripheral shunting

Sepsis, trauma

Certain poisons

Cyanide - prevents tissues from using oxygen

Hypothermia

Oxygen Consumption

Amount of oxygen extracted by the peripheral tissues during the period of one minute

Also called oxygen uptake (VO2) which would be written with a dot over the V to indicate a period of time (in this case per minute)

Calculated as follows:

If a patient has a cardiac output of 5 L/min and a C(a-v)O2 of 5 vol%:

What is the total amount of oxygen consumed by the tissue cells in one minute?

O2_consumption_formula.jpg

Normal_O2_consumption.jpg

Factors that Increase VO2

Exercise

Seizures

Shivering

Hyperthermia

Body Size

Factors that Decrease VO2

Skeletal Muscle Relaxation

Induced by drugs

Peripheral shunting

Sepsis, trauma

Certain poisons

Cyanide

Hypothermia

Oxygen Extraction Ratio

Oxygen extraction ratio (O2ER) is the amount of oxygen extracted by the peripheral tissues (Ca-vO2) divided by the amount of oxygen delivered to (CaO2) the peripheral cells

Also called:

Oxygen coefficient ratio

Oxygen utilization ratio

Can also be expressed as a percentage

 

In considering the normal CaO2 of 20 vol% and the normal CvO2 of 15 vol%:

O2ER is about 0.25, or 25%

O2ERnormal.jpg

O2ER provides an important view of the oxygen transport status when O2 consumption remains the same

For example, consider the following two cases with the same C(a-v)O2 (5 vol%), but with different CaO2 (reduced by half)

O2ERex1.jpg

 

o2ERex2.jpg

Factors that Increase O2ER

Decreased cardiac output

Periods of increased O2 consumption

Exercise

Seizures

Shivering

Hyperthermia

Anemia

Factors that Decrease O2ER

Increased cardiac output

Skeletal muscle relaxation

Drug induced

Peripheral shunting (e.g., sepsis)

Certain poisons

Cyanide

Hypothermia

Increased Hb

Increased arterial oxygenation (PaO2)

Mixed Venous Oxygen Saturation (SvO2)

Changes in the SvO2 can be used to detect changes in the:

C(a-v)O2

VO2

O2ER

Factors that Decrease the SvO2

Decreased cardiac output

Exercise

Seizures

Shivering

Hyperthermia

Factors that Increase the SvO2

Increased cardiac output

Skeletal muscle relaxation

Drug induced

Peripheral shunting

Sepsis

Certain poisons

Cyanide

Hypothermia

Pulmonary Shunting

The portion of the cardiac output that moves from the right side to the left side of the heart without being exposed to alveolar oxygen (PAO2).

Clinically, pulmonary shunting can be subdivided into absolute and relative shunts:

Absolute Shunt, also called True Shunt  (Anatomic Shunt)

anatomic_Shunt.jpg

 

Relative Shunt, also called shunt-like effects

shunt_like_effects.jpg

Common Causes of Absolute Shunting

Congenital heart disease

Intrapulmonary fistula

Vascular lung tumors

Capillary shunting is commonly caused by:

Alveolar collapse or atelectasis

Alveolar fluid accumulation

Alveolar consolidation

Key Concept: True shunts are refractory to supplemental oxygen

Refractory means that it does not respond to increased oxygen delivery.

Common Causes of Relative Shunt

When pulmonary capillary perfusion is in excess of alveolar ventilation, a relative or shunt-like effect is said to exist

Hypoventilation

Ventilation/perfusion mismatches

Chronic emphysema, bronchitis, asthma

Alveolar-capillary diffusion defects

Alveolar fibrosis or alveolar edema

Key Concept: Relative or Shunt-Like effects can be corrected by supplemental oxygen

Venous Admixture

Venous mixture is the mixing of shunted, non-reoxygenated blood with reoxygenated blood distal to the alveoli

Occurs downstream in the pulmonary venous system after the blood leaves the pulmonary capillary

venous_admixture.jpg

Pulmonary Shunt Equation

shunt_equa.jpg

Data that you would need in order to calculate the pulmonary shunt:

PB

PaO2

PaCO2

PvO2

Hb

PAO2

FIO2

SaO2

SvO2

Clinical Significance of  Pulmonary Shunting

<10%

Normal status

10 to 20%

Indicates intrapulmonary abnormality

20 to 30%

Significant intrapulmonary diseases

> 30%

Potentially life-threatening

HYPOXEMIA VERSUS HYPOXIA

Hypoxemia: abnormally low arterial oxygen tension (PaO2) in the blood (hence the -emia ending)

Hypoxia a condition of underoxygenation, which is an inadequate level of tissue oxygenation for cellular metabolism

Hypoxemia frequently results in hypoxia - but not always! When you look at the PaO2 on a blood gas you are only looking at the amount of oxygen dissolved in the blood which can reflect hypoxemia. You cannot infer a condition of hypoxia unless you evaluate total oxygen content and delivery to the tissues. Thus we use the following terminology to classify the amount of oxygen in the blood, and to describe the severity of the deficiency.

hypoxemia.jpg

There are four main types of hypoxia

Hypoxic hypoxia: inadequate oxygen at the tissue cells caused by low arterial oxygen tension (PaO2)

Common Causes

Low PAO2 caused by

Hypoventilation - increased CO2 in alveolus displaces oxygen

High altitude - low barometric pressure decreases partial pressure of oxygen in the alveolus

Diffusion defects

Ventilation-perfusion mismatch (most common cause)

Pulmonary shunting (R to L shunts)

Hypoxemic Hypoxia – decreased O2 content (CaO2)

Anemic hypoxia PaO2 is normal, but the oxygen carrying capacity of the hemoglobin is inadequate

Common Causes

Decreased hemoglobin

Anemia

Hemorrhage

Abnormal hemoglobin

Carboxyhemoglobinemia

Methemoglobinemia

Circulatory hypoxia

Stagnant hypoxia or hypoperfusion where blood flow to the tissue cells is inadequate.Thus, oxygen delivery is not adequate to meet tissue needs.

systemic = shock

ischemia = local lack of perfusion

Common causes

Slow or stagnant (pooling) peripheral blood flow

Arterial-venous shunts

Decreased cardiac output

Histotoxic hypoxia - impaired ability of the tissue cells to metabolize oxygen 

Common causes

Cyanide poisoning

Dysoxia - sepsis alters tissues ability to utilize oxygen

Cyanosis

Blue-gray or purplish discoloration seen on the mucous membranes, fingertips, and toes

Blood in these areas contain at least 5 g% of reduced hemoglobin

Subjective observation

Exceptions

Anemia - patient can be deficient in total content but not show signs of cyanosis. Usually look pale but not cyanotic. If a person with a hemoglobin of 7 where showing cyanosis their oxygen content would be incapatable with life!

Polycythemia - patient has an abundance of hemoglobin (greater than 17 g%). Common in patient's with chronic lung diseases that have hypoxemia. Body compensates by increasing the number of RBC (boxcars) to carry more oxygen. These patients can appear cyanotic yet have adequate oxygen contents.

Look at the complete picture when assessing oxygenation

PaO2 by itself will not tell you all you need to know. You must be able to utilize the transport calculations to adequately assess the condition of the patient. This will assist you in determining the proper course of treatment.