Respiratory System: Gas Exchange and Gas Laws

Gas Exchange

• Gas exchange in the respiratory system involves the diffusion of O₂ and CO₂ in the lungs and peripheral tissues.
• O₂ moves from alveolar gas into pulmonary capillary blood, then to tissues, diffusing from systemic capillary blood into cells.
• CO₂ moves from tissues to venous blood, then to pulmonary capillary blood, and finally to alveolar gas for expiration.

Gas Laws

• Gas exchange relies on the fundamental properties of gases, including their behavior in solution.

General Gas Law

• The general gas law states that PV = nRT, where P is pressure, V is volume, n is the number of moles, R is the gas constant, and T is temperature.
• Pressure is measured in mm Hg.
• Volume is measured in Liters.
• Moles denoted in measurement as mol.
• Temperature is measured in Kelvins.
• Respiratory physiology uses BTPS (body temperature, ambient pressure, saturated with water vapor) for gas phase and STPD (standard temperature, standard pressure, dry gas) for liquid phase.
• BTPS entails a body temperature of 37°C (310 K) and ambient pressure, saturated with water vapor.
• Standard temperature is 0°C (273 K), standard pressure is 760 mm Hg, using dry gas.
• Conversion from BTPS to STPD volume: Volume(BTPS) x (273/310) x ((Pb - 47)/760), where Pb is barometric pressure and 47 mm Hg is water vapor pressure at 37°C

Boyle's Law

• Boyle's Law, a special case of the general gas law, says that pressure times volume remains constant at a given temperature: P1V1 = P2V2.
• During inspiration, the diaphragm contracts, increasing lung volume, which decreases gas pressure in the lungs, driving airflow.

Dalton's Law of Partial Pressures

• It says that the partial pressure of a gas in a mixture is the pressure the gas would exert if it occupied the total volume alone.
• Partial pressure = total pressure times the fractional concentration of dry gas: Px = PB × F

Pressure of Humidified Gas

• The pressure of humidified gas is determined by correcting the barometric pressure for water vapor pressure.

Dalton's Law Applied

• The sum of partial pressures of all gases in a mixture equals the total pressure of the mixture; barometric pressure (PB) is the sum of partial pressures of O₂, CO₂, N₂, and H₂O.
• Percentages of gases in dry air at 760 mm Hg: O₂ is 21% (0.21), N₂ is 79% (0.79), and CO₂ is 0% (0.0004).
• Water vapor pressure is 47 mm Hg at 37°C in humidified airways and considered a negligible error.
• CX = PX × Solubility, where CX is the concentration of dissolved gas (ml gas per 100 ml blood), PX is the partial pressure of the gas (mm Hg), and Solubility is the gas's solubility in blood (ml gas/100 ml blood per mm Hg).
• This equation calculates the volume percent of free dissolved gas in blood, excluding gas bound to hemoglobin or plasma proteins.

Fick's Law of Diffusion

• Fick’s Law states that gas transfer across cell membranes is directly proportional to driving force, diffusion coefficient, and surface area, but inversely proportional to membrane thickness.

Lung Diffusing Capacity

• Lung diffusing capacity (Dl) combines diffusion coefficient, membrane surface area (A), and membrane thickness (Δx).
• Dl also accounts for the time it takes gas to combine with pulmonary capillary blood proteins, can be measured using carbon monoxide (CO).
• CO transfer across the alveolar/pulmonary capillary barrier is diffusion-limited.
• Dl CO is measured by having a subject breathe a gas mixture with a low CO concentration where the rate of CO disappearance is proportional to Dl.
• Emphysema decreases surface area for gas exchange and reduces Dl.
• Fibrosis or pulmonary edema increases diffusion distance, reducing Dl.
• Anemia reduces hemoglobin in red blood cells, decreasing Dl
• Exercise increases perfused capillaries, increasing surface area for gas exchange and Dl.

Forms of Gases in Solution

• In alveolar air, gases exist as partial pressure, while in blood, gases can be dissolved, bound to proteins, or chemically modified.
• Total gas concentration in solution equals dissolved gas plus bound gas plus chemically modified gas.

Dissolved Gases and Henry's Law

• All gases in solution exist, to some degree, in the dissolved form, described via Henry's law.
• For a given partial pressure, higher gas solubility leads to higher gas concentration in solution.
• Only dissolved gas molecules contribute to partial pressure.
• N₂ is unique as it is only carried in dissolved form, never bound or chemically modified and for this reason, it is used for certain respiratory measurements.

Bound and Chemically Modified Gases

• O₂, CO₂, and CO bind to blood proteins.
• O₂ and CO bind to hemoglobin inside red blood cells.
• CO₂ binds to hemoglobin in red blood cells and to plasma proteins.
• Most CO₂ in blood is carried as bicarbonate (HCO₃⁻), created from CO₂ by carbonic anhydrase, rather than as dissolved or bound CO₂.

Gas Transport Overview

• Pulmonary capillaries are perfused with blood from the right heart, which undergoes gas exchange with alveolar gas.
• O₂ diffuses from alveolar gas into pulmonary capillary blood, while CO₂ diffuses from pulmonary capillary blood into alveolar gas.
• The blood leaving the pulmonary capillary then goes to the left heart, becoming systemic arterial blood.

Partial Pressures in Inspired Air

• In dry inspired air, P_O₂ (partial pressure of oxygen) is about 160 mm Hg and P_CO₂ (partial pressure of carbon dioxide) is essentially zero
• This calculation multiplies the barometric pressure by the fractional concentration of oxygen (21% of 760 mm Hg= 160 mm Hg approximately).

Inspired Air and Alveoli

• When inhaled air is fully saturated with water vapor at 37°C, oxygen is slightly diluted.
• To calculate partial pressures in humidified air, subtract water vapor pressure from barometric pressure, then multiply by the gas fractional concentration.
• The partial pressure of oxygen in humidified air is approximately 150 mm Hg (760 mm Hg – 47 mm Hg water vapor pressure = 713 mm Hg; 713 mm Hg x 0.21 = 150mm Hg approximately)
• Alveolar air has a lower P_O₂ (approximately 100 mm Hg) and a higher P_CO₂ (approximately 40 mm Hg) compared to inspired air.
• These changes are due to O₂ transferring to the blood/CO₂ being expelled from the blood into the alveoli to balance O₂ needs/CO₂ production.

Blood Entering Pulmonary Capillaries

• Blood entering the pulmonary capillaries is mixed venous blood containing waste products with lower O₂ and higher CO₂ levels (P_O₂ ≈ 40 mm Hg, P_CO₂ ≈ 46 mm Hg).
• This blood is pumped from the right ventricle into the pulmonary artery and to the lungs for gas exchange.

Oxygenated Blood Leaving Pulmonary Capillaries

• Oxygenated blood leaves pulmonary capillaries as arterial blood with higher O₂ levels (P_O₂ ≈ 100 mm Hg).
• The arterial blood returns to the left heart to be pumped throughout the body.
• Arterial blood and alveolar air typically have similar oxygen and carbon dioxide levels.

Physiologic Shunt and A-a Difference

• A physiologic shunt, or small fraction of blood that bypasses the alveoli, creates a slight difference between oxygen levels in alveolar air and systemic arterial blood; bronchial and coronary venous blood can contribute to shunts.
• Increased shunts due to conditions/lung diseases result in a disparity in gas exchange and blood that is less oxygenated than normal.
• The difference in oxygen levels between alveolar air and arterial blood, or A – a difference, shows the inefficiency extent.
• An increased A – a difference shows a reduced oxygen transfer efficacy.

Gas Partial Pressures

• Gas exchanges occur between systemic arterial blood (rich in oxygen) and mixed venous blood (rich in carbon dioxide).
• Oxygen, delivered from the systemic arterial blood into the systemic tissues, is consumed by the tissues/producing carbon dioxide, which diffuses back into the capillaries.
• This back-and-forth conversion of gases from systemic arterial blood to mixed venous blood is recirculated to the lungs.

Types of Gas Exchange

• The types of gas exchange across the alveolar/pulmonary capillary barrier are classified into diffusion limitation or perfusion limitation

Diffusion-Limited Gas Exchange

• Gas exchange is restricted by the diffusion rate.
• Diffusion persists throughout the capillary if a partial pressure gradient exits.

Perfusion-Limited Gas Exchange

• Gas exchange is restricted by blood flow or perfusion rate.
• Increased blood flow is the only method of enhancing gas transport if the partial pressure gradient vanishes.

Gas Exchange Dynamics

• Diffusion-limited gas exchange involves carbon monoxide (CO) transport across the alveolar/pulmonary capillary barrier, oxygen (O₂) during intense exercise/conditions such as emphysema and fibrosis.
• Alveolar air has a constant partial pressure of CO (P a CO) at a pulmonary capillary beginning creating a partial pressure gradient.
• As CO is transported into the blood, the capillary blood partial pressure of CO (Pa CO) rises; the rise in Pa CO is limited by the binding strength of CO to hemoglobin in red blood cells keeping free CO concentration and diffusion gradient constant.
• CO does not reach equilibrium by the capillary end and would continue to diffuse if the capillary was longer.
• Perfusion-limited gas exchange is illustrated by nitrous oxide (N2O) in addition to oxygen (O₂) and carbon dioxide (CO₂) under normal conditions.
• The constant alveolar partial pressure of N2O (P a N2O) and an assumed zero initial Pa N2O at the capillary onset create a significant initial partial pressure gradient.
• N2O, which doesn't bind in the blood and remains entirely free, has a capillary blood partial pressure that swiftly equates with the alveolar gas, achieving equilibrium in the first ⅕ of the capillary length.
• Enhanced blood flow is the only means of diffusion for N2O.

O2 Transport

• Oxygen transport to pulmonary capillaries is perfusion-limited under normal conditions (and diffusion-limited under fibrosis or strenuous exercise.)
• Arterial partial pressure of oxygen is contant at 100 mm Hg
• Partial pressure of the capillary beginning is at 40 mm Hg.
• Large partial pressure gradient for oxygen exists.
• Diffusion is maintained since oxygen binds to hemoglobin.
• Equilibrium of oxygen occurs about ⅓ of the distance along the capillary.
• Increases in pulmonary blood flow will increase the total amount of O2 transported, and decreases in pulmonary blood flow will decrease the total amount transported.
• Diffusion is distance slows equilibration between alveoli and the capillary blood.
• Gradient for O2 is maintained along the entire length.

O2 Transport at High Altitudes

• Decreased pressure in alveolar gas.
• Mixed venous Po2 is 25 mm Hg (as opposed to the normal value of 40 mm Hg).
• Gradient is greatly reduced.
• Reduced diffusion means equilibration occurs more slowly Final equilibrium value for Pa O2 is only mm Hg because Pa O2 is only 50 mm Hg. Pulmonary blood does not equilibrate by the cap and results in values for Pa O2 as low as 30 mm Hg which will impair delivary to tissues.

Dissolved Oxygen Transport

• 2% total oxygen in blood.
• Form of oxegen that produces a partial pressure that drives oxygen diffusion.
• 0.003 ml O2/100mL blood per mmHG concentration of dissolved oxygen: 0.3 mL O2/100mL.
• Not enough for tissue demands Requires oxygen bound to hemoglobin instead

Oxygen Bound to Hemoglobin

• 98% Reversibly bound to hemoglobin in red blood cells.
• Each subunit consists of heme (iron-binding porphyrin)
• Polypeptide Chain
• Adult hemoglobin consists of 2Alpha and 2Beta chains. Each subunit can bind one molecule of oxygen.

Hemoglobin Variants

• Methemoglobin: heme moieties has ferric state and can not bind oxygen. Due to oxidation, nitrates and a deficiency
• Fetal Hemoglobin: Two beta chains and a higher affinity for oxygen than adult hemoglobin, replaced in the first year.
• Hemoglobin S: For sickle cell, contains normal alpha and abnormal beta, this creates issues for oxygenated hemoglobin.

Oxygen Binding vs Content

• Volume Blood per concentration/Oxygenbinding.
• Exposing to Air
• Compmuting Oxygen capacity means gram can bind and contencentration is gram per 100mL.
• Oxygen amount over volume.
• From biding capacity is at a percent saturation.
• Capacity time saturation and dissolved is delivery
• Rapid combining and heme binding.
• For every hemoglobin has capacity to bind molecules.
• configuration saturation.

Hemoglobin Saturation

PO2 Function of Blood

Sigmoidal Shape of Curve

• change on O 2 volume.
• O2 increasing efficiency and occurring at Po.
• Occurs at molecules hemoglobin, phenomenon cooperation
• Po where hem is 50 with a affinity change. Increases means decrease and vice versa
• Sig loading and unloading of O₂

Erythropoietin

• Glycoprotein
• Primary produced, for red blood production
• EPO stimulation to transforms.
• Hypoxia triggers EPO production
• Hypoxia alpha sub unit

Renal System Role in Erythropoietin Synthesis

Chronic Renal Failure and Erythropoietin

• Decline in kidney function causes decreased EPO synthesis.
• Anemia treatment recombinant EPO.
• Carbon Dioxide Transport involves dissolved carbaminohemoglobin and bicarbonate
• Carbonic important, Bicarbonate is chemical modified
• Henry says concentration is mulitplied and solubility is mol blood
• Dissoled 2% O content

Carbaminohemoglobin and Hemoglobin

• Binds to terminal protein groups.
• bound to hemoglobin.
• Bonds the proteins in the Plasma
• Bins at a different location than O.
• Hemoglobin affinity for oxygen is reduced.
• Causes shift between o curve and BOHR Affect
• Affiniity is increase for binding: Haldane Effect
• In lungs HOC reconverts from a volume.
• CO2 is produced by metabolism.
• By partial pressure and simple diffusion.
• Reactions are to the right.
• Bicarbonate dissaocates.
• H will buffer from deoxyhemglobin
• Bicarb volume is exchanged.
• H is buffered to keep the levels correct
• In capillaries and Deoxy, Hemoglobin and Oxy, Hemoglobin
• Chloride preservers electrircal neutrality
• Chloride shifts protein