Transport of Oxygen in the Blood

 Although oxygen dissolves in blood, only a small amount of oxygen, 1.5% is transported in the blood
and is dissolved directly into the blood itself.
 Most oxygen—98.5 percent—is bound to a protein called hemoglobin and carried to the tissues.
Hemoglobin
 Hemoglobin, or Hg/Hb, is a protein molecule found in red blood cells (erythrocytes) made of four
subunits: two alpha subunits and two beta subunits (Figure 1).
 Carries oxygen from the lungs to the body's tissues and returns carbon dioxide from the tissues back to
the lungs.
 Each subunit surrounds a central heme group that contains iron and binds one oxygen molecule,
allowing each hemoglobin molecule to bind four oxygen molecules.
 Molecules with more oxygen bound to the heme groups are brighter red. As a result, oxygenated
arterial blood where the Hb is carrying four oxygen molecules is bright red, while venous blood that is
deoxygenated is darker red.
 It is easier to bind a second and third oxygen molecule to Hb than the first molecule. This is because
the hemoglobin molecule changes its shape, or conformation, as oxygen binds.
 The fourth oxygen is then more difficult to bind

Figure 3
Key Terms:
 Diseases like sickle cell anemia and thalassemia decrease
the blood’s ability to deliver oxygen to tissues and its oxygen-carrying capacity.
 In sickle cell anemia, the shape of the red blood cell is crescent-shaped, elongated, and stiffened,
reducing its ability to deliver oxygen (Figure 3).
 In this form, red blood cells cannot pass through the capillaries. This is painful when it occurs.
 Thalassemia is a rare genetic disease caused by a defect in either the alpha or the beta subunit of Hb.
Patients with thalassemia produce a high number of red blood cells, but these cells have lower-than-
normal levels of hemoglobin. Therefore, the oxygen-carrying capacity is diminished.
 heme:
 the component of hemoglobin responsible for binding oxygen; consists of an iron that binds to
oxygen in the lungs and carries it to the tissues

SUMMARY: TRANSPORT OF OXYGEN IN THE BLOOD

 Hemoglobin is a protein found in red blood cells that is comprised of two alpha and two beta subunits
that surround an iron-containing heme group
 Oxygen readily binds this heme group. The ability of oxygen to bind increases as more oxygen
molecules are bound to heme
 Disease states and altered conditions in the body can affect the binding ability of oxygen, and increase
or decrease its ability to dissociate from hemoglobin.
  The majority of oxygen in the body is transported by hemoglobin, which is found inside red blood cells.

Key Points
 Hemoglobin is made up of four subunits and can bind up to four oxygen molecules.
 Carbon dioxide levels, blood pH, body temperature, environmental factors, and diseases can all affect
oxygen’s carrying capacity and delivery.
 A decrease in the oxygen-carrying ability of hemoglobin is observed with an increase in carbon dioxide
and temperature, as well as a decrease in pH within the body.
 Sickle cell anemia and thalassemia are two hereditary diseases that decrease the blood’s oxygen-
carrying capacity.

Figure 39.4A.139.4A.1: Hemoglobin: The protein inside red blood cells (a) that carries oxygen to cells and
carbon dioxide to the lungs is hemoglobin (b). Hemoglobin is made up of four symmetrical subunits and four
heme groups. Iron associated with the heme binds oxygen. It is the iron in hemoglobin that gives blood its red
color.

 Not all of the oxygen transported in the blood is transferred to the tissue cells.
 The amount of oxygen extracted by the cells depends on their rate of energy expenditure.
 At rest, venous blood returning to the lungs still contains 70 to 75 percent of the oxygen that was
present in arterial blood; this reserve is available to meet increased oxygen demands.
 During extreme exercise the quantity of oxygen remaining in venous blood decreases to 10 to 25
percent.
 Hemoglobin binds not only to oxygen but to other substances such as hydrogen ions (which determine
the acidity, or pH, of the blood), carbon dioxide, and 2,3-diphosphoglycerate (2,3-DPG; a salt in red
blood cells that plays a role in liberating oxygen from hemoglobin in the peripheral circulation).
 These substances do not bind to hemoglobin at the oxygen-binding sites.
 However, with the binding of oxygen, changes in the structure of the hemoglobin molecule occur that
affect its ability to bind other gases or substances.
 Conversely, binding of these substances to hemoglobin affects the affinity of hemoglobin for oxygen.
(Affinity denotes the tendency of molecules of different species to bind to one another.)
 Increases in hydrogen ions, carbon dioxide, or 2,3-DPG decrease the affinity of hemoglobin for oxygen,
and the oxygen-dissociation curve shifts to the right.
 Because of this decreased affinity, an increased partial pressure of oxygen is required to bind a given
amount of oxygen to hemoglobin.
 A rightward shift of the curve is thought to be of benefit in releasing oxygen to the tissues when needs
are great in relation to oxygen delivery, as occurs with anemia or extreme exercise.
 Reductions in normal concentrations of hydrogen ions, carbon dioxide, and 2,3-DPG result in an
increased affinity of hemoglobin for oxygen, and the curve is shifted to the left. This displacement
increases oxygen binding to hemoglobin at any given partial pressure of oxygen and is thought to
be beneficial if the availability of oxygen is reduced, as occurs at extreme altitude.
  Temperature changes affect the oxygen-dissociation curve similarly.
 An increase in temperature shifts the curve to the right (decreased affinity; enhanced release of
oxygen); a decrease in temperature shifts the curve to the left (increased affinity).
 The range of body temperature usually encountered in humans is relatively narrow, so that
temperature-associated changes in oxygen affinity have little physiological importance.

Transport of carbon dioxide

 Transport of carbon dioxide in the blood is considerably more complex.
 A small portion of carbon dioxide, about 5 percent, remains unchanged and is transported dissolved in
blood.
 The remainder is found in reversible chemical combinations in red blood cells or plasma.
 Some carbon dioxide binds to blood proteins, principally hemoglobin, to form a compound known as
carbamate.
 About 88 percent of carbon dioxide in the blood is in the form of bicarbonate ion.
 The distribution of these chemical species between the interior of the red blood cell and the
surrounding plasma varies greatly, with the red blood cells containing considerably less bicarbonate
and more carbamate than the plasma.
 Less than 10 percent of the total quantity of carbon dioxide carried in the blood is eliminated during
passage through the lungs.
 Complete elimination would lead to large changes in acidity between arterial and venous blood.
 Furthermore, blood normally remains in the pulmonary capillaries less than a second, an insufficient
time to eliminate all carbon dioxide.
 Carbon dioxide enters blood in the tissues because its local partial pressure is greater than its partial
pressure in blood flowing through the tissues.
 As carbon dioxide enters the blood, it combines with water to form carbonic acid (H2CO3), a relatively
weak acid, which dissociates into hydrogen ions (H+) and bicarbonate ions (HCO3-).
 Blood acidity is minimally affected by the released hydrogen ions because blood proteins, especially
hemoglobin, are effective buffering agents. (A buffer solution resists change in acidity by combining
with added hydrogen ions and, essentially, inactivating them.)
 The natural conversion of carbon dioxide to carbonic acid is a relatively slow process;
however, carbonic anhydrase, a protein enzyme present inside the red blood cell, catalyzes this
reaction with sufficient rapidity that it is accomplished in only a fraction of a second.
 Because the enzyme is present only inside the red blood cell, bicarbonate accumulates to a much
greater extent within the red cell than in the plasma.
 The capacity of blood to carry carbon dioxide as bicarbonate is enhanced by an ion transport system
inside the red blood cell membrane that simultaneously moves a bicarbonate ion out of the cell and
into the plasma in exchange for a chloride ion.
 The simultaneous exchange of these two ions, known as the chloride shift, permits the plasma to be
used as a storage site for bicarbonate without changing the electrical charge of either the plasma or
the red blood cell. Only 26 percent of the total carbon dioxide content of blood exists as bicarbonate
inside the red blood cell, while 62 percent exists as bicarbonate in plasma; however, the bulk of
bicarbonate ions is first produced inside the cell, then transported to the plasma.
 A reverse sequence of reactions occurs when blood reaches the lung, where the partial pressure of
carbon dioxide is lower than in the blood.
 Hemoglobin acts in another way to facilitate the transport of carbon dioxide.
 Amino groups of the hemoglobin molecule react reversibly with carbon dioxide in solution to yield
carbamates.
  A few amino sites on hemoglobin are oxylabile, that is, their ability to bind carbon dioxide depends on
the state of oxygenation of the hemoglobin molecule.
 The change in molecular configuration of hemoglobin that accompanies the release of oxygen leads to
increased binding of carbon dioxide to oxylabile amino groups.
 Thus, release of oxygen in body tissues enhances binding of carbon dioxide as carbamate.
 Oxygenation of hemoglobin in the lungs has the reverse effect and leads to carbon dioxide elimination.
 Only 5 percent of carbon dioxide in the blood is transported free in physical solution without chemical
change or binding, yet this pool is important, because only free carbon dioxide easily crosses biologic
membranes. Virtually every molecule of carbon dioxide produced by metabolism must exist in the free
form as it enters blood in the tissues and leaves capillaries in the lung.
 Between these two events, most carbon dioxide is transported as bicarbonate or carbamate.

Gas exchange in the lung

 The introduction of air into the alveoli allows the removal of carbon dioxide and the addition of oxygen
to venous blood.
 Because ventilation is a cyclic phenomenon that occurs through a system of conducting airways, not all
inspired air participates in gas exchange.
 A portion of the inspired breath remains in the conducting airways and does not reach the alveoli
where gas exchange occurs.
 This portion is approximately one-third of each breath at rest but decreases to as little as 10 percent
during exercise, due to the increased size of inspired breaths.
 In contrast to the cyclic nature of ventilation, blood flow through the lung is continuous, and almost all
blood entering the lungs participates in gas exchange.
 The efficiency of gas exchange is critically dependent on the uniform distribution of blood flow and
inspired air throughout the lungs.
 In health, ventilation and blood flow are extremely well matched in each exchange unit throughout the
lungs.
 The lower parts of the lung receive slightly more blood flow than ventilation because gravity has a
greater effect on the distribution of blood than on the distribution of inspired air.
 Under ideal circumstances, partial pressures of oxygen and carbon dioxide in alveolar gas and arterial
blood are identical.
 Normally there is a small difference between oxygen tensions in alveolar gas and arterial blood
because of the effect of gravity on matching and the addition of a small amount of venous drainage to
the bloodstream after it has left the lungs.
 These events have no measurable effect on carbon dioxide partial pressures because the difference
between arterial and venous blood is so small.

Abnormal gas exchange:

 Lung disease can lead to severe abnormalities in blood gas composition
 Because of the differences in oxygen and carbon dioxide transport, impaired oxygen exchange is far
more common than impaired carbon dioxide exchange

Mechanisms of abnormal gas exchange are grouped into four categories:

 Hypoventilation
 Shunting,
 Ventilation and Blood flow imbalance
 Limitations of diffusion
Hypoventilation
 This happens If the quantity of inspired air entering the lungs is less than is needed to maintain normal
exchange, the alveolar partial pressure of carbon dioxide rises and the partial pressure of oxygen falls
almost reciprocally.
 Similar changes occur in arterial blood partial pressures because the composition of alveolar gas
determines gas partial pressures in blood perfusing the lungs.
 This abnormality leads to parallel changes in both gas and blood and is the only abnormality in gas
exchange that does not cause an increase in the normally small difference between arterial and
alveolar partial pressures of oxygen

In shunting:
 Venous blood enters the bloodstream without passing through functioning lung tissue.
 Shunting of blood may result from abnormal vascular (blood vessel) communications or from blood
flowing through unventilated portions of the lung (e.g., alveoli filled with fluid or inflammatory
material).
 A reduction in arterial blood oxygenation is seen with shunting, but the level of carbon dioxide in
arterial blood is not elevated even though the shunted blood contains more carbon dioxide than
arterial blood.
 The differing effects of shunting on oxygen and carbon dioxide partial pressures are the result of the
different configurations of the blood-dissociation curves of the two gases.
 When blood perfusing the collapsed, unventilated area of the lung leaves the lung without exchanging
oxygen or carbon dioxide, the content of carbon dioxide is greater than the normal carbon dioxide
content.
 The remaining healthy portion of the lung receives both its usual ventilation and the ventilation that
normally would be directed to the abnormal lung. This lowers the partial pressure of carbon dioxide in
the alveoli of the normal area of the lung.
 As a result, blood leaving the healthy portion of the lung has a lower carbon dioxide content than
normal.
 The lower carbon dioxide content in this blood counteracts the addition of blood with a higher carbon
dioxide content from the abnormal area, and the composite arterial blood carbon dioxide content
remains normal. This compensatory mechanism is less efficient than normal carbon dioxide exchange
and requires a modest increase in overall ventilation, which is usually achieved without difficulty.
Because the carbon dioxide-dissociation curve is steep and relatively linear, compensation for
decreased carbon dioxide exchange in one portion of the lung can be counterbalanced by increased
excretion of carbon dioxide in another area of the lung.
 In contrast, shunting of venous blood has a substantial effect on arterial blood oxygen content and
partial pressure.
 Blood leaving an unventilated area of the lung has an oxygen content that is less than the normal
content
 In the healthy area of the lung, the increase in ventilation above normal raises the partial pressure of
oxygen in the alveolar gas and, therefore, in the arterial blood.
 The oxygen-dissociation curve, however, reaches a plateau at the normal alveolar partial pressure, and
an increase in blood partial pressure results in a negligible increase in oxygen content.
 Mixture of blood from this healthy portion of the lung (with normal oxygen content) and blood from
the abnormal area of the lung (with decreased oxygen content) produces a composite arterial oxygen
content that is less than the normal level.
 Thus, an area of healthy lung cannot counterbalance the effect of an abnormal portion of the lung on
blood oxygenation because the oxygen-dissociation curve reaches a plateau at a normal alveolar
partial pressure of oxygen
  This effect on blood oxygenation is seen not only in shunting but in any abnormality that results in a
localized reduction in blood oxygen content.
Mismatching of ventilation and blood flow is by far the most common cause of a decrease in partial
pressure of oxygen in blood.
 There are minimal changes in blood carbon dioxide content unless the degree of mismatch is
extremely severe.
 Inspired air and blood flow normally are distributed uniformly, and each alveolus receives
approximately equal quantities of both.
 As matching of inspired air and blood flow deviates from the normal ratio of 1 to 1, alveoli become
either overventilated or underventilated in relation to their blood flow.
 In alveoli that are overventilated, the amount of carbon dioxide eliminated is increased, which
counteracts the fact that there is less carbon dioxide eliminated in the alveoli that are relatively
underventilated. Overventilated alveoli, however, cannot compensate in terms of greater oxygenation
for underventilated alveoli because, as is shown in the oxygen-dissociation curve, a plateau is reached
at the alveolar partial pressure of oxygen, and increased ventilation will not increase blood oxygen
content. In healthy lungs there is a narrow distribution of the ratio of ventilation to blood flow
throughout the lung that is centred around a ratio of 1 to 1.
 In disease, this distribution can broaden substantially so that individual alveoli can have ratios that
markedly deviate from the ratio of 1 to 1.
 Any deviation from the usual clustering around the ratio of 1 to 1 leads to decreased blood
oxygenation—the more disparate the deviation, the greater the reduction in blood oxygenation.
 Carbon dioxide exchange, on the other hand, is not affected by an abnormal ratio of ventilation and
blood flow as long as the increase in ventilation that is required to maintain carbon dioxide excretion in
overventilated alveoli can be achieved.

Limitation of diffusion (of gases across the thin membrane separating the alveoli from the pulmonary
capillaries)
 A variety of processes can interfere with this orderly exchange; for oxygen, these include increased
thickness of the alveolar–capillary membrane, loss of surface area available for diffusion of oxygen, a
reduction in the alveolar partial pressure of oxygen required for diffusion, and decreased time
available for exchange due to increased velocity of flow
 These factors are usually grouped under the broad description of “diffusion limitation,” and any can
cause incomplete transfer of oxygen with a resultant reduction in blood oxygen content.
 There is no diffusion limitation of the exchange of carbon dioxide because this gas is more soluble than
oxygen in the alveolar–capillary membrane, which facilitates carbon dioxide exchange.
 The complex reactions involved in carbon dioxide transport proceed with sufficient rapidity to avoid
being a significant limiting factor in exchange.

Heme
 The part of certain molecules that contains iron
 The heme part of hemoglobin is the substance inside red blood cells that binds to oxygen in the
lungs and carries it to the tissues.