Oxygen and Carbon Dioxide Transport

External Respiration: This is defined as the exchange of gases that occurs between the alveoli and the pulmonary capillaries.
Internal Respiration: This is defined as the exchange of gases that occurs between the systemic capillaries and the tissues of the body.

Mechanisms of Oxygen Transport:
- Approximately $98\%$ of oxygen ( $O_{2}$ ) in the blood is transported as oxyhemoglobin.
- Approximately $2\%$ of oxygen is dissolved directly in the blood. Oxygen is characterized by low water solubility, which accounts for the small percentage transported in this manner.

Quaternary Structure: Hemoglobin is a protein with a quaternary structure consisting of several components:
- $4$ globin chains.
- $4$ heme groups.
- $4$ $Fe^{2+}$ (iron ions), with one situated at the center of each heme group.
Oxygen Binding:
- Oxygen specifically binds to the $Fe^{2+}$ ions within the heme groups.
- Hemoglobin is considered fully saturated when it has bound $4$ oxygen molecules.
Carbon Dioxide Binding:
- Hemoglobin can also bind carbon dioxide ( $CO_{2}$ ), but this binding occurs on the globin chains rather than the iron-containing heme groups.
- There is a reciprocal relationship between the binding sites: the binding of carbon dioxide affects the binding affinity for oxygen, and the binding of oxygen conversely affects the binding of carbon dioxide.

Graph Parameters:
- The y-axis represents the saturation of hemoglobin with oxygen expressed as a percentage ( $\%$ ).
- The x-axis represents the partial pressure of oxygen ( $pO_{2}$ ).
General Relationship:
- It is expected that as the $pO_{2}$ increases, the saturation of hemoglobin with oxygen also increases.
- Conversely, the lower the $pO_{2}$ , the lower the oxygen saturation of hemoglobin.
Specific Saturation Benchmarks:
- At a $pO_{2}$ of $105\,mmHg$ , hemoglobin is $98.5\%$ saturated. This occurs as a red blood cell moves past the alveolus and picks up $4$ oxygen molecules, becoming fully saturated.
- At a $pO_{2}$ of $40\,mmHg$ (the level found in the tissues), hemoglobin is $75\%$ saturated. This implies that hemoglobin typically releases only one of its four oxygen molecules as it passes through the tissues, retaining $3$ oxygen molecules attached.

Shape: The hemoglobin-oxygen saturation curve is sigmoid (S-shaped).
The Flat Upper Portion: The top part of the curve is relatively flat. This means that the $pO_{2}$ can decrease slightly without causing a significant drop in hemoglobin saturation. Consequently, hemoglobin remains nearly $100\%$ saturated as it passes through the lungs, even if the partial pressure of oxygen drops a little.
The Steep Left Portion: The left part of the curve is steep. In this range, even a slight decrease in $pO_{2}$ results in a large change in hemoglobin saturation. This physiological design ensures that hemoglobin can give up more oxygen to the specific tissues that require it.

Right Shift Conditions: A right shift in the hemoglobin-oxygen saturation curve occurs under conditions of high temperature, high concentration of hydrogen ions ( $H^{+}$ ), or high partial pressure of carbon dioxide ( $pCO_{2}$ ).
- Result: Hemoglobin is more loosely bound to oxygen and delivers its oxygen more easily to the tissues.
Left Shift Conditions: A left shift occurs when there is low temperature, low concentration of $H^{+}$ ions, or low $pCO_{2}$ .
- Result: Hemoglobin binds its oxygen more tightly.

Mechanism: Pulse oximetry measures the color of hemoglobin to determine oxygen status.
Output: It provides a reading of the saturation of hemoglobin with oxygen based on that color.
Interpretations:
- A reading of $98.5\%$ saturation reflects a $pO_{2}$ of approximately $100\,mmHg$ .
- A reading of $75\%$ saturation reflects a $pO_{2}$ of approximately $40\,mmHg$ .

Distribution: Carbon dioxide is transported in the blood in three main ways:
- Approximately $7\%$ is dissolved in the plasma. Carbon dioxide is more water-soluble than oxygen, allowing for a higher percentage to be dissolved.
- Approximately $23\%$ is bound directly to hemoglobin.
- Approximately $70\%$ is transported as bicarbonate ( $HCO_{3}^{-}$ ).

Formation in the Tissues:
- Chemical Reaction: $CO_{2} + H_{2}O \rightarrow H_{2}CO_{3} \rightarrow H^{+} + HCO_{3}^{-}$
- Process: Carbon dioxide moves from the tissues into the red blood cell. The enzyme carbonic anhydrase converts the carbon dioxide into carbonic acid ( $H_{2}CO_{3}$ ), which then dissociates into $H^{+}$ and $HCO_{3}^{-}$ .
- Movement: Bicarbonate leaves the red blood cell to be transported in the plasma. To maintain electrical neutrality (even out the charge), chloride ions ( $Cl^{-}$ ) enter the cell. The resulting hydrogen ions ( $H^{+}$ ) are buffered by hemoglobin.
Reversion in the Lungs:
- Chemical Reaction: $CO_{2} + H_{2}O \leftarrow H_{2}CO_{3} \leftarrow H^{+} + HCO_{3}^{-}$
- Process: Upon reaching the pulmonary capillaries, bicarbonate moves from the plasma back into the red blood cell. To even out the charge, $Cl^{-}$ ions move out of the red blood cell into the plasma. Carbonic anhydrase then converts the bicarbonate back into carbon dioxide.

Bohr Effect: In tissues where carbon dioxide and hydrogen ion levels are high, hemoglobin binding to oxygen becomes looser. This facilitates the release of oxygen and the uptake of $CO_{2}$ .
Haldane Effect: In the lungs where oxygen levels are high, hemoglobin binding to carbon dioxide becomes looser. This allows hemoglobin to give up $CO_{2}$ to the alveolus for exhalation while oxygen is being picked up.