Oxygen Transport and
Asphyxia
AnS 536
Spring 2016
Goals
 To transport oxygen from maternal blood across the placenta to
fetal blood, and after birth from the lungs to the blood stream
 To move oxygen from blood to tissues to allow aerobic
metabolism (efficient production of ATP)
 To move carbon dioxide in the reverse direction
Erythrocytes
 After maturation from stem cells in bone marrow,
erythrocytes have a circulating life of ~120d
 Highly specialized cells:
 Cytoplasm contains ~35% solution of hemoglobin, but
is devoid of subcellular organelles
 Cannot synthesize nucleic acids or proteins, limited lipid
metabolism
 Carbohydrate metabolism devoted to maintaining
functional pumps on cell membrane
Erythrocytes
 After cell death, hemoglobin degraded and iron
recycled to bone marrow
 As they pass through capillaries, cells deform into
ellipsoidal, hemispheric, or teardrop shapes
 Cell fragility increased during newborn period
 Increased risk and incidence of hemolytic diseases
Transport of Gases in Blood
 PO2 not only determines the dissolved oxygen
content of blood, but also affects the amount of
oxygen in reversible chemical combination with
hemoglobin
 Chemical and physiological actions of gases
depend on the partial pressures they exert in the
gas phase and in solution in various body fluids
Hemoglobin
 The binding of one molecule of O2 to Fe2+ increases the affinity of
the other sites for oxygen binding (4 total)
 Carbon dioxide binds to the globulin portions of the molecule rather
than to the iron molecules
 Accounts for about 10% of CO2 transport
 The sigmoidal shape of the oxygen dissociation curve is physiologically
important
 Permits blood to deliver much more oxygen to tissues than a hyperbolic
curve
Hemoglobin
Video Break
OXYGEN BINDING VIDEO:
http://www.dnatube.com/video/274/Hemoglobin-Oxygen-Binding
OXYGEN TRANSPORT VIDEO:
http://www.youtube.com/watch?feature=player_detailpage&v=WXOBJE
XxNEo
O2-Hb Dissociation Curve
Illustrates a relationship between the partial pressure of
oxygen (PO2) and percent saturated hemoglobin (Hb)
Hemoglobin
 Increasing pH in RBC will increase the affinity of
Hb for oxygen (in the lungs)
 When Hb binds to oxygen, it undergoes a
conformational change that releases H ions from
globin chains, decreasing pH in the cell
 In capillaries H+ generated by carbonic anhydrase
activity in RBC decreases pH and facilitates oxygen
delivery to tissues as well (high CO2
concentrations)
Oxygen Loading and Unloading
Bohr and Haldane Effects
 Bohr Effect
 Describes the influence of CO2 and pH on the release of O2
 ↓ in pH (↑ in acidity) due to CO2 and hydrogen ions can combine reversibly with Hb
at the sites other than the O2 binding sites (allosteric binding)
 Results in a structural change of Hb, reducing its affinity for O2
 Haldane Effect
 Displacement of O2 from Hb increases affinity for CO2 and hydrogen ions
Bohr and Haldane Effects
 Work together facilitating O2 liberation and the uptake of
CO2 and hydrogen ions at the tissue level
 A Bohr or Haldane shift reduces Hb affinity for O2
 Important in placental O2 transport
 pH is highest in veins where O2 is picked up (umbilical and
placental arterioles)
 pH is lowest at arteries after CO2 and hydrogen ions have
been picked up
 Changes in pH and CO2 on both maternal and fetal side of
placenta regulate the rate of O2 transfer to a great extent
Bohr and Haldane Effects
 Fetal pH is lower (more acidic) than maternal pH
 Fetal acidosis is metabolic and not related to the high PCO2
 Primarily due to placentally produced lactate and pyruvate
 The effect of low pH on O2 delivery to tissues is often
overlooked, but may be important in maintaining O2 delivery to
tissues at an appropriate rate
2,3-Bisphosphoglycerate
(2,3-BPG)
 Binds with greater affinity to Maternal deoxyhemoglobin
 Once it binds to first binding site, it allosterically affects other sites
in hemoglobin to effectively increase the rate of release of oxygen at
tissue level
 Right-shift of curve
Fetal Hemoglobin (HbF)
 HbF has a higher affinity for O2
than HbA
 Two alpha-gamma dimers rather
than two alpha-beta dimers
 Creates a LEFT shift in the
dissociation curve much like the
effect of
↑ pH, ↓ temperature,
or ↓ 2,3 BPG
 ↑ affinity for O2 by Hb in the fetal blood
enhances O2 transport across the
placenta
 After birth HbF declines as neonates
begin to manufacture new erythrocytes
and HbA
 HbF binds 2,3-BPG poorly
Hemoglobin Transitions
Fetal Hemoglobin
Fetal Hemoglobin
Cytochrome P450
 O2 is MUCH more soluble in lipids (like membranes)
than in water (as in plasma or cytoplasm)
 Cytochrome P450 enhances transport processes due
to its high affinity for O2 and accumulates along the
endoplasmic reticulum (ER) of placental cells
 Many different varieties
 Most involve drug metabolism
 All incorporate oxygen into metabolic processes
 Tissues can up- or down-regulate the levels of this
molecule to enhance O2 transport into cell
Cytochrome P450
 ER forms channels from the cell membrane to the mitochondria allowing
O2 to move more freely throughout or across the cell
 Alignment of P450 along the ER channels creates a high affinity, O2
soluble freeway for O2 to travel
 P450 enhances transplacental O2 transport
 Studies have shown blocking P450 will decrease transplacental O2 flux by
over 75%
Fetal Gas Exchange
 CO2 diffuses across placenta primarily in molecular form - not as
bicarbonate ion
 Fetal PCO2 is higher than maternal
 Fetal oxygen consumption is equivalent to adult values
 Placenta is designed to protect the fetus from inadequate or
excessive oxygen availability
Fetal Gas Exchange Cont…
 Fetal mechanisms for protection against oxygen radicals are
poorly developed prior to birth
 Increased oxygen in fetal blood may have more adverse effects
than beneficial effects
 Induction of superoxide dismutase is due to increased exposure to
oxygen postnatally
Questions?