O2 & CO2 Transport in Blood

Henry’s Law

Concentration of dissolved oxygen in blood (C_O2) is directly proportional to the partial pressure of oxygen (P_O2) in the surrounding gas.

Partial Pressure of O2

100 mmHg

0.3 mL O2/100 mL

Concentration of dissolved oxygen in the blood

Hemoglobin

Required to allow for O2 to meet tissue demand as free O2 is not enough. 

Forms of O2 in Blood

Dissolved O2

O2 Bound to Hemoglobin (Hb)

Hemoglobin (Hb)

Globular protein made up of 4 subunits. Each subunit has a heme moiety and polypeptide chain (2 alpha and 2 beta). 

Heme Moiety

Gives Hb ability to bind O2 due to presence of Fe²⁺

Pigment Molecule

Found in hemoglobin RBC giving RBCs their red color found in myoglobin giving red color.

Adult Hemoglobin (HbA)

4 subunits with each subunit binding to one O2 molecules (4 O2 per Hb). 

Oxyhemoglobin

Oxygenated Hb w/ O2

Deoxyhemoglobin

deO2 Hb

% Saturation

% of heme groups bound to O2

Ferrous State

Fe²⁺

Ferric State

Fe³⁺

Methemoglobin

Heme ferrous Fe²⁺ iron is oxidized to the ferric state - cannot bind O2 in this state

Methemoglobinemia

Less oxygen is delivered to the tissues, leading to hypoxia (reduced O2 supply), even if the blood O2 levels appear normal 

Causes of Methemoglobinemia

Acquired due to drugs or exposure of benzocaine, and lidocaine

Lack of enzymes

G6PD Deficiency 

Fetal Hemoglobin (HbF)

2 alpha and 2 gamma subunits with increased affinity to O2, aiding in transport from mother to fetus. 

Fetal Blood

Enters placenta through the umbilical arteries, flowing into chorionic villi surrounded by maternal blood in the intervillous spaces. O2 and nutrients diffuse across the placental barrier from maternal blood to fetal blood. HbF binds O2 strongly, allowing for efficient O2 transfer from maternal blood. 

Umbilical Vein

O2 blood returns to the fetus

Umbilical Artery

Fetal blood entering placenta

Sickle Cell Disease

Abnormal variant of Hb (HbS) where 2 beta chains are abnormal, causing a different shape, reduced O2 transport, and shortened RBC lifespan.

Abnormal Hemoglobin Shape

HbS forms abnormal hemoglobin molecules that polymerize when O2 is low, causing RBC to assume a rigid shape.

Reduced O2 Transport

Sickle-shaped cells have reduced ability to carry O2 and can block blood flow in small vessels, leading to tissue damage and pain. 

Shortened Red Cell Lifespan

Sickle cells are fragile and break down more easily, leading to hemolysis and chronic anemia.

HbS Polymerization

Causes long hydrophobic chain (polymer) distorting RBC in sickle shape

Hemoglobin C (HbC)

Structural variant of normal HbA caused by AA substitution. 

Hemoglobin C Trait (HbAC)

Phenotypically normal

Hemoglobin C Disease (Hb CC)

Mild degree of hemolytic anemia, possibly protecting against malaria in homozygous state.

Blood O2 Determined By

Hb concentration [Hb]

O2-Binding Capacity to Hb

O₂ Delivery

CO (O₂ content in blood)

CO (dissolved O2 + O2 bound to Hb)

Fick Equation

Provides O2 consumption

O2 Consumption = CO (Arterial _O2 - Venous _O2 )

O2-Hemoglobin Dissociation Curve

Explains how hemoglobin efficiently loads O2 in the lungs (high pO2) and releases it in tissues (pO2 is lower), supporting O2 delivery to meet metabolic demands.₂

High pO₂

100% saturation, where affinity is highest due to (+) cooperatively 

Low pO₂

The affinity of Hb for O2 is lower (30% not bound to O2) 

2,3-Diphosphoglycerate (2,3-DPG)

Byproduct of glyoclysis in RBC, binding to deO2 hemoglobin (beta chains).

2,3 - DPG Function

Stabilizes the T (tense) state of Hb → Low O2 affinity

Facilitates O2 unloading to tissues 

Shift to Right

Less O2 affinity for Hb; Higher PO₂ needed to reach 50% saturation

Increase PCO2

Decrease pH

More temperature

Increased 2,3 - DPG

Shift to Left

High O2 affinity for Hb; Less PO₂ needed to reach 50% saturation

Low PCO2

High pH

Low temperature

Less 2,3 - DPG

High Altitudes

The body produced more 2,3-DPG as an adaptive mechanism to facilitate O2 release from Hb to tissues.

Carbon Monoxide (CO)

Binds to Hb much more tightly than O2, having a higher affinity (shifts the graph to the left)

Pulse Oximeter

Hb that is O2 has higher absorbance (red due to moiety)

Hb that is deO2 has lower absorbance (blue light)

Pitfalls of Pulse Oximeter

Overestimate O2 levels in darker skin due to interference in light absorption. Leads to hypoxemia that is not detected.

Erythropoietin (EPO)

Glycoprotein growth factor that regulates RBC production, primarily synthesized in the kidneys. 

Major stimulus for RBC production is by promoting differentiation of pro-erthroblasts into RBCs

Synthesis induced in response to hypoxia

Hypoxia Induced EPO

Less O2 delivery to the kidneys from less Hb or less P_aO2

Induces increased production of alpha subunit of hypoxia-inducible factor

Factor acts on fibroblasts in the renal cortex and medulla to synthesizes EPO mRNA, which generates EPO

EPO stimulates differentiates of pro-fibroblasts into EPO 

Hypoxia

1. Hypoxia inducible factor 1 alpha

2. Renal fibroblasts increase EPO mRNA

3. EPO synthesis

4. Proerythroblasts

5. Erythrocytes

CO2 Transport Forms

Dissolved Gas

Bound to Hb as carboaminohemoglobin

HCO3^- 

Bicarbonate Formation

1. Tissue CO2 moved into RBC

2. Carbonic anhydrase turns CO2 to cabronic acid, then bicarbonate

3. Bicarbonate is transported out of the cell with Cl- antiport into blood and moved to lungs

4. HCO3 in lungs is reconverted to CO2 & H2O 

CO2 Transport

1. CO2 diffuses out of cell into the capillaries

2. 5% of CO2 dissolved in plasma

3. 25% of CO2 binds to hemoglobin, forming carboaminohemoglobin

4. 60% of CC2 load is converted to bicarbonate and H+ (hemoglobin buffers H+)

5. HCO3 enters plasma in exchange for Cl-

6. At lungs CO2 diffuses out of the plasma

7. CO2 unbinds from Hb and diffuses out of RBC

8. Carbonic acid reverses, pulling HCO3 back into the RBC and converting it back to CO2

PO2

High in lungs and low in tissues, allowing for the inspiration of this molecule.

PCO2

Low in lungs and high in tissues, allowing for the expiration of this molecule.