6 ch 19 Human Physiology: Gas Exchange and Transport Study Exchange and Transport Notes

Introduction to Gas Exchange and Homeostasis

• The human body requires a constant supply of oxygen ($O_2$) and must effectively remove excess carbon dioxide ($CO_2$) to maintain homeostasis.
• Hypoxia: This condition occurs when there is insufficient $O_2$ available to maintain homeostasis.
  • It can be caused by various factors, including:
  • Low $O_2$ levels in the ambient air.
  • Low hemoglobin levels in red blood cells.
  • Blocked blood flow to tissues.
  • Toxins that interfere with the process of cellular respiration.
• Hypercapnia: This occurs when $CO_2$ concentrations in the body become too high, negatively impacting homeostasis.
• Hypoxia and hypercapnia often, though not always, occur simultaneously.

Classification of Hypoxias

• Hypoxic hypoxia: Defined by low arterial $P_{O_2}$.
  • Typical Causes: High altitude; alveolar hypoventilation; decreased lung diffusion capacity; abnormal ventilation-perfusion ratio.
• Anemic hypoxia: Defined by a decreased total amount of $O_2$ bound to hemoglobin.
  • Typical Causes: Blood loss; anemia (due to low hemoglobin concentration [Hb] or altered Hb-$O_2$ binding); carbon monoxide poisoning.
• Ischemic hypoxia: Defined by reduced blood flow.
  • Typical Causes: Heart failure (leading to whole-body hypoxia); shock (leading to peripheral hypoxia); thrombosis (leading to hypoxia in a single specific organ).
• Histotoxic hypoxia: Defined by the failure of cells to use $O_2$ because they have been poisoned.
  • Typical Causes: Cyanide and other metabolic poisons that prevent aerobic metabolism.

Normal Blood Values in Pulmonary Gas Exchange

• Arterial Blood Values:
  • $P_{O_2}$: $95 mm Hg$ (Range: $85-100$)
  • $P_{CO_2}$: $40 mm Hg$ (Range: $35-45$)
  • $pH$: $7.4$ (Range: $7.38-7.42$)
• Venous Blood Values:
  • $P_{O_2}$: $40 mm Hg$
  • $P_{CO_2}$: $46 mm Hg$
  • $pH$: $7.37$

Principles of Gas Exchange in Lungs and Tissues

• Gas exchange and transport involve taking in $O_2$ and removing $CO_2$ via the respiratory system.
• Both gases are transported through the blood between the lungs and the tissues.
• Diffusion Gradients: Gases follow both pressure and concentration gradients, moving from areas of high pressure/concentration to low pressure/concentration.
• Partial Pressure in Blood: Gas particles moving within the blood still exert a partial pressure and will follow pressure gradients.
  • In the Lungs: Alveolar partial pressure of oxygen ($P_{O_2}$) is higher than the $P_{O_2}$ in the blood; thus, $O_2$ moves down the gradient into the bloodstream.
  • In the Tissues: Tissue $P_{O_2}$ is lower than blood $P_{O_2}$; thus, $O_2$ moves out of the blood and into the tissues.
  • Carbon Dioxide: $CO_2$ behaves in the opposite manner to $O_2$, diffusing into the blood at the tissues and into the alveoli at the lungs.

Factors Affecting Alveolar $P_{O_2}$ and Oxygen Uptake

• The degree of $O_2$ diffusion into the blood is determined by the partial pressure of oxygen inside the alveoli.
• At equilibrium, blood $P_{O_2}$ can only reach the level of the alveolar $P_{O_2}$.
• Factors Decreasing Alveolar $P_{O_2}$:
  • High Altitude: Lower partial pressure of oxygen in the ambient air.
  • Hypoventilation: Insufficient fresh air entering the lungs.
  • Causes of hypoventilation include: decreased lung compliance, increased airway resistance, and Central Nervous System (CNS) depression (e.g., caused by alcohol or drug overdose).

Diffusion and Hypoxia

• To prevent hypoxia, $O_2$ must diffuse into the blood fast enough to fully oxygenate it.
• Rate of Diffusion Factors:
  • Proportional to: Surface area available for exchange, the size of the partial pressure gradient, and the permeability of the barrier.
  • Inversely proportional to: Diffusion distance.
• Disease States and Diffusion Problems:
  • Decreased Surface Area: Damage to alveoli (e.g., emphysema).
  • Decreased Permeability: Thickening of the alveolar membrane due to scarred (fibrotic) lung tissue.
  • Increased Diffusion Distance: Conditions like pulmonary edema (accumulation of interstitial fluid).
  • Low Alveolar $P_{O_2}$: Slows the overall rate of diffusion.

Gas Solubility and Henry’s Law

• When gas contacts a liquid, partial pressure pushes gas molecules into the liquid until they become solutes.
• Movement into/out of liquid is proportional to:
  1. The partial pressure gradient.
  2. The solubility of the gas in the specific liquid.
  3. The temperature of the gas (note: temperature remains relatively constant in the human body, making pressure and solubility the primary drivers).
• Equilibrium: Gas molecules move until the partial pressure in the air equals the partial pressure in the liquid.
• Solubility Differences:
  • Higher solubility means more molecules enter the liquid at a given pressure.
  • At equilibrium ($100 mm Hg$), $[CO_2]$ in solution is approximately $3.00 mmol/L$, while $[O_2]$ in solution is only approximately $0.15 mmol/L$ due to oxygen's lower solubility.
  • Because the liquid is "crowded," a small number of molecules in a liquid can exert the same pressure as a large number of molecules in the air.

Oxygen Transport in the Blood

• Dissolved Oxygen: Accounts for less than $2\%$ of total oxygen in the blood because $O_2$ has very low solubility in plasma.
• Hemoglobin ($Hb$) Bound Oxygen: Accounts for more than $98\%$ of oxygen in the blood.
  • Only free (dissolved) $O_2$ molecules contribute to the partial pressure ($P_{O_2}$).
  • Binding to hemoglobin removes $O_2$ from the dissolved pool, lowering $P_{O_2}$ and allowing more oxygen to diffuse into the blood.
• Hemoglobin Structure: Each hemoglobin molecule contains four heme groups, providing four binding sites for $O_2$.
• Reversible Binding: The association of $O_2$ and $Hb$ is reversible ($Hb + O_2 \rightleftharpoons HbO_2$).
  • High $P_{O_2}$ (e.g., in lungs) promotes binding.
  • Low $P_{O_2}$ (e.g., in tissues) promotes unbinding, creating a constant stream of oxygen for tissues.

Hemoglobin Saturation and Oxygen Content

• Saturation: The percentage of available hemoglobin binding sites filled with $O_2$.
  • $100\%$ saturation = all sites full; $50\%$ saturation = half of the sites full.
• Factors controlling the amount of $O_2$ bound to $Hb$:
  • Plasma $P_{O_2}$: Determines the percent saturation of $Hb$.
  • Total number of $Hb$ binding sites: This is calculated by the hemoglobin content (amount of $Hb$ per RBC multiplied by the number of RBCs).
• Oxygen Content at Different Pressures:
  • At a normal $P_{O_2}$ of $100 mm Hg$, total $O_2$ content is approximately $200 mL O_2/L$ of blood ($3 mL$ dissolved, $197 mL$ bound).
  • At a reduced $P_{O_2}$ of $28 mm Hg$, total $O_2$ content drops to approximately $100.3 mL O_2/L$ (approx. $50\%$ saturation).

Factors Affecting Hemoglobin Affinity

• Hemoglobin saturation is influenced by several physiological factors:
  • ${P_{CO_2}}$, pH, and Temperature: Increased metabolic activity in tissues produces more $CO_2$ and heat, and lowers $pH$.
  • The Bohr Effect: High $P_{CO_2}$ and low $pH$ cause $O_2$ to unbind from hemoglobin more readily, shifting the saturation curve and delivering more oxygen to active tissues.
  • Example: At $P_{O_2} = 40 mm Hg$ and $P_{CO_2} = 40 mm Hg$, $Hb$ is approx. $70\%$ saturated. If $P_{CO_2}$ rises to $80 mm Hg$, saturation drops to approx. $55\%$.
  • 2,3-BPG: A chemical that also affects binding affinity.
• Fetal Hemoglobin: Fetal $Hb$ has a higher affinity for $O_2$ than adult $Hb$.
  • Example: At $P_{O_2} = 40 mm Hg$, maternal $Hb$ is approx. $75\%$ saturated, while fetal $Hb$ is approx. $90\%$ saturated, allowing the fetus to extract oxygen from the mother's blood.

Carbon Dioxide Transport Mechanisms

• Carbon dioxide is transported in the blood in three ways:
  1. Dissolved in Plasma ($7\%$): Despite higher solubility than $O_2$, only a small fraction is dissolved.
  2. Bound to Hemoglobin ($23\%$): Forms carbaminohemoglobin ($HbCO_2$). $CO_2$ binds to different sites on the hemoglobin molecule than oxygen.
  3. Converted to Bicarbonate ($70\%$): The majority of $CO_2$ is converted into bicarbonate ions ($HCO_3^-$).

The Bicarbonate Buffer System and Chloride Shift

• Enzymatic Reaction: Red blood cells contain the enzyme carbonic anhydrase (CA), which facilitates the reversible reaction:
  • $H_2O + CO_2 \rightleftharpoons H^+ + HCO_3^-$
• In Systemic Capillaries (Tissues):
  • $CO_2$ diffuses from cells into RBCs.
  • CA converts $CO_2$ and water into $H^+$ and $HCO_3^-$.
  • Hemoglobin buffers the $H^+$ ($H^+ + Hb \rightarrow HbH$).
  • Chloride Shift: To maintain electrical neutrality, $HCO_3^-$ is transported out of the RBC into the plasma in exchange for chloride ions ($Cl^-$).
  • This removal of product keeps internal $P_{CO_2}$ low, allowing more $CO_2$ to diffuse in from tissues.
• In Pulmonary Capillaries (Lungs):
  • The process reverses due to the law of mass action.
  • $HCO_3^-$ moves back into the RBC, and $Cl^-$ moves out.
  • $HCO_3^-$ binds with $H^+$ to form $CO_2$ and $H_2O$.
  • Dissolved $CO_2$ and $CO_2$ released from hemoglobin diffuse into the alveoli to be exhaled.