Gas Transport

I. Oxygen Transport

1. Dissolved Oxygen in Plasma

   • Only approximately $1.5\%$ of inspired oxygen is dissolved directly in blood plasma due to its low solubility coefficient in aqueous solutions (Henry's law).

   • Although small, this dissolved fraction establishes the arterial partial pressure of oxygen ($P_{O_2}$) and directly drives diffusion across capillary and cellular membranes.

   • external respiration : drawing oxygen and CO2 from the outside into the lungs

   • internal respiration : trading of O2 and CO2 between tissues and blood

2. Hemoglobin-Mediated Transport

   • The remaining $98.5\%$ of oxygen is transported chemically bound to hemoglobin ($Hb$) within erythrocytes.

   • Structure of Hemoglobin:

   • Quaternary protein consisting of four globin subunits (two alpha and two beta chains in adult hemoglobin, $HbA$).

   • Each subunit contains an iron-containing heme prosthetic group with iron in the ferrous state ($Fe^{2+}$).

   • Each ferrous iron reversibly binds one molecule of $O_2$, meaning one fully saturated hemoglobin molecule carries four $O_2$ molecules as oxyhemoglobin ($HbO_2$).

3. Loading and Unloading Dynamics

   • Loading in Pulmonary Capillaries:

   • High alveolar $P_{O_2}$ ($\approx 100\,\text{mmHg}$) drives diffusion of oxygen into blood plasma and erythrocytes.

   • Deoxyhemoglobin rapidly binds oxygen to form oxyhemoglobin:     $Hb + 4O_2 \rightleftharpoons Hb(O_2)_4$

   • Systemic Circulation: Oxygen-rich blood travels from pulmonary veins through the left heart into the systemic arterial circulation.

   • Unloading in Systemic Capillaries:

   • Metabolically active tissues consume oxygen, maintaining a lower tissue $P_{O_2}$ ($\approx 40\,\text{mmHg}$ or lower).

   • This concentration gradient drives oxyhemoglobin to dissociate and release $O_2$ into plasma and surrounding tissue cells.

   • Venous Return: Deoxygenated blood returns through systemic veins to the right heart and pulmonary circulation for re-oxygenation.

4. Hemoglobin Saturation and Factors Affecting Affinity

   • Percent saturation reflects the percentage of heme binding sites bound to oxygen, characterized by a sigmoidal (S-shaped) oxygen-hemoglobin dissociation curve due to positive cooperativity.

   • Modulating Factors:

   • Partial Pressure of Oxygen: Primary factor determining saturation; elevated $P_{O_2}$ promotes loading, whereas reduced $P_{O_2}$ promotes dissociation.

   • Bohr Effect ($\text{pH}$ and $P_{CO_2}$): Increased metabolic activity lowers local $\text{pH}$ (higher $[H^+]$) and increases $P_{CO_2}$, shifting the curve to the right, lowering affinity, and facilitating oxygen release at tissues.

   • Temperature: Elevated temperature shifts the curve to the right, decreasing affinity and facilitating oxygen delivery to warm, metabolically active tissues.

   • 2,3-Bisphosphoglycerate (2,3-BPG): Produced by erythrocytes during glycolysis; binds deoxyhemoglobin and stabilizes the low-affinity state, promoting unloading under hypoxic conditions.

II. Carbon Dioxide Transport

1. Mechanisms of Transport

   • Carbon dioxide is continuously generated as a metabolic byproduct of cellular respiration and transported from tissues to the lungs through three distinct mechanisms:

   • Dissolved in Plasma: Approximately $7\%$ to $10\%$ is carried physically dissolved in plasma; this fraction determines arterial $P_{CO_2}$.

   • Carbaminohemoglobin: Approximately $20\%$ binds directly to the terminal amine groups of globin polypeptide chains on hemoglobin (not the heme group):     $Hb + CO_2 \rightleftharpoons HbCO_2$

     • Haldane Effect: Deoxygenation of hemoglobin increases its capacity to carry $CO_2$, facilitating carbon dioxide uptake in peripheral tissues.

   • Bicarbonate Ions ($HCO_3^-$): Approximately $70\%$ of carbon dioxide is converted into bicarbonate ions, representing the principal transport mechanism in blood.

2. Formation of Bicarbonate and the Chloride Shift

   • $CO_2$ rapidly diffuses from metabolizing tissues into erythrocytes, where the enzyme carbonic anhydrase (CA) catalyzes its hydration:   $CO_2 + H_2O \rightleftharpoons H_2CO_3 \rightleftharpoons HCO_3^- + H^+$

   • Carbonic acid ($H_2CO_3$) spontaneously dissociates into bicarbonate ($HCO_3^-$) and hydrogen ions ($H^+$).

   • Buffering by Hemoglobin: Deoxyhemoglobin buffers free $H^+$ ions, preventing extreme acidification of erythrocytes and blood plasma.

   • Chloride Shift (Hamburger Phenomenon): An anion exchanger protein transports accumulated $HCO_3^-$ out of erythrocytes into plasma in exchange for chloride ions ($Cl^-$) moving in, preserving electrical neutrality across the membrane.

3. Elimination of Carbon Dioxide in Pulmonary Capillaries

   • In the pulmonary capillaries, the low alveolar $P_{CO_2}$ ($\approx 40\,\text{mmHg}$) reverses the chemical equilibrium:

   • Bicarbonate ($HCO_3^-$) moves back into erythrocytes as chloride ($Cl^-$) exits (reverse chloride shift).

   • $HCO_3^-$ recombines with $H^+$ released from oxygenating hemoglobin to regenerate carbonic acid ($H_2CO_3$).

   • Carbonic anhydrase converts $H_2CO_3$ back into $CO_2$ and $H_2O$.

   • Dissolved $CO_2$ diffuses down its partial pressure gradient across the respiratory membrane into the alveoli and is exhaled.

III. Control Mechanisms for Ventilation

1. Chemical Stimuli for Ventilation

   • Ventilation rate and depth are continually adjusted by respiratory centers in response to arterial levels of $P_{CO_2}$, $[H^+]$ ($\text{pH}$), and $P_{O_2}$.

   • Under normal conditions, arterial $P_{CO_2}$ is the primary and most sensitive chemical regulator of respiratory drive.

2. Chemoreceptor Systems

   • Central Chemoreceptors:

   • Located on the ventrolateral surface of the medulla oblongata.

   • Respond to changes in $[H^+]$ within cerebrospinal fluid (CSF).

   • Because $CO_2$ readily crosses the blood-brain barrier whereas charged $H^+$ cannot, arterial hypercapnia causes rapid diffusion of $CO_2$ into CSF, where it hydrates and dissociates into $H^+$, stimulating central chemoreceptors to elevate ventilation.

   • Peripheral Chemoreceptors:

   • Located in the carotid bodies (conveyed by cranial nerve IX) and aortic bodies (conveyed by cranial nerve X).

   • Primarily sensitive to significant drops in arterial $P_{O_2}$ ($P_{O_2} < 60\,\text{mmHg}$), as well as increases in arterial $[H^+]$ and $P_{CO_2}$.

3. Ventilatory Regulation of Acid-Base Balance

   • Arterial $P_{CO_2}$ is determined by the balance between metabolic $CO_2$ production and alveolar ventilation rate.

   • Alterations in ventilation directly modify blood hydrogen ion concentration:

   • Hypoventilation: Reduced alveolar ventilation allows $CO_2$ retention (hypercapnia), shifting the equilibrium toward increased $[H^+]$ and causing respiratory acidosis ($\text{pH} < 7.35$).

   • Hyperventilation: Excess ventilation expels $CO_2$ faster than metabolic generation (hypocapnia), shifting the equilibrium toward decreased $[H^+]$ and causing respiratory alkalosis ($\text{pH} > 7.45$).