Respiratory System
Structure & Gas Exchange
Master the anatomy of the airways, the mechanics of ventilation, and the physics of gas exchange at the alveolar-capillary interface: from \( P_{O_2} \) gradients to the oxygen-hemoglobin dissociation curve.
MCAT Biology
Section 3B
The Respiratory System at a Glance
The respiratory system delivers oxygen to tissues and removes carbon dioxide. It is divided into two functional zones:
Conducting Zone
Nose, pharynx, larynx, trachea, bronchi, and bronchioles down to the terminal bronchioles. Warms, humidifies, and filters air. No gas exchange occurs here (anatomical dead space).
Respiratory Zone
Respiratory bronchioles, alveolar ducts, and alveoli. This is the only region where gas exchange occurs across an enormous surface area (\( \approx 70 \) m²).
Airway Anatomy: From Trachea to Alveoli
Key Terminology
Ventilation
The mechanical process of moving air in (inspiration) and out (expiration) of the lungs.
Perfusion
Blood flow through the pulmonary capillaries surrounding the alveoli.
Diffusion
The net movement of gas molecules from high to low partial pressure across the respiratory membrane.
Mechanics of Breathing
Ventilation is driven by pressure gradients created by the diaphragm and intercostal muscles. Boyle's Law governs this relationship:
Inspiration
Diaphragm contracts (flattens), thoracic volume increases, \( P_{\text{alv}} \) drops below \( P_{\text{atm}} \), air rushes in. Active process.
Expiration
Diaphragm relaxes (domes up), thoracic volume decreases, \( P_{\text{alv}} \) rises above \( P_{\text{atm}} \), air pushed out. Passive at rest.
Dalton's Law & Partial Pressures
The total atmospheric pressure is the sum of the partial pressures of each gas. At sea level \( P_{\text{atm}} = 760 \) mmHg:
1
Dry inspired air: \( P_{O_2} = 0.21 \times 760 \approx 160 \) mmHg
2
Humidified tracheal air: \( P_{O_2} = 0.21 \times (760 - 47) \approx 150 \) mmHg (water vapor \( P_{H_2O} = 47 \) mmHg at 37°C)
3
Alveolar air: \( P_{A_{O_2}} \approx 104 \) mmHg (diluted by \( CO_2 \) and residual volume)
Fick's Law of Diffusion
The rate of gas transfer across the alveolar membrane depends on several factors captured by Fick's Law:
Increases Rate
Larger surface area (A), greater pressure gradient \( \Delta P \), higher diffusion coefficient (D)
Decreases Rate
Greater membrane thickness (T): seen in pulmonary edema or fibrosis
Alveolar-Capillary Gas Exchange
Oxygen-Hemoglobin Dissociation Curve
The Bohr Effect: Shifting the Curve
Right Shift (Unloads \( O_2 \))
Increased: temperature, \( P_{CO_2} \), \( H^+ \) (lower pH), 2,3-BPG. Hb has decreased affinity for \( O_2 \), facilitating delivery to active tissues.
Left Shift (Holds \( O_2 \))
Decreased: temperature, \( P_{CO_2} \), \( H^+ \) (higher pH), 2,3-BPG. Also: fetal hemoglobin (HbF) and CO poisoning. Hb holds \( O_2 \) more tightly.
\( CO_2 \) Transport in the Blood
Carbon dioxide is transported from tissues to the lungs in three forms:
1
Bicarbonate ion (~70%): \( CO_2 + H_2O \xrightarrow{\text{carbonic anhydrase}} H_2CO_3 \rightarrow HCO_3^- + H^+ \). The dominant form. Chloride shift maintains electrical neutrality.
2
Carbaminohemoglobin (~23%): \( CO_2 \) binds directly to amino groups on hemoglobin (not the heme iron).
3
Dissolved \( CO_2 \) (~7%): A small fraction remains dissolved in plasma.
Lung Volumes & Capacities
Tidal Volume (TV)
~500 mL: normal breath at rest
IRV
~3000 mL: extra air you can inhale beyond TV
ERV
~1200 mL: extra air you can exhale beyond TV
RV
~1200 mL: air remaining after maximal exhalation (keeps alveoli open)
Ventilation vs Perfusion Matching
| High V/Q | Normal V/Q | Low V/Q | |
|---|---|---|---|
| Condition | Dead space (ventilation without perfusion) | ~0.8 | Shunt (perfusion without ventilation) |
| Example | Pulmonary embolism | Healthy lung | Pneumonia, atelectasis |
| Effect | Wasted ventilation | Optimal exchange | Deoxygenated blood bypasses alveoli |
| Compensation | Bronchoconstriction | None needed | Hypoxic vasoconstriction |
How to Solve Gas Exchange Problems
1
Identify the gas and location: Are you looking at \( O_2 \) or \( CO_2 \)? Alveolus, blood, or tissue?
2
Determine partial pressures: Use Dalton's Law or the alveolar gas equation: \( P_{A_{O_2}} = F_{IO_2}(P_{\text{atm}} - P_{H_2O}) - \frac{P_{A_{CO_2}}}{R} \)
3
Apply the pressure gradient: Gas always moves from high to low partial pressure. Compare the two compartments.
4
Consider Fick's Law factors: Is the membrane thickened (fibrosis)? Is surface area reduced (emphysema)? These slow diffusion.
5
Check the Hb curve: At the given \( P_{O_2} \), what is Hb saturation? Has the curve shifted?
Example 1: Alveolar Gas Equation
A patient breathes room air (\( F_{IO_2} = 0.21 \)) at sea level. Their arterial \( P_{CO_2} = 40 \) mmHg. What is their alveolar \( P_{O_2} \)? Assume respiratory quotient \( R = 0.8 \).
1
Write the equation: \( P_{A_{O_2}} = F_{IO_2}(P_{\text{atm}} - P_{H_2O}) - \frac{P_{A_{CO_2}}}{R} \)
2
Substitute values: \( P_{A_{O_2}} = 0.21(760 - 47) - \frac{40}{0.8} \)
3
Calculate: \( P_{A_{O_2}} = 0.21 \times 713 - 50 = 149.7 - 50 \approx 100 \) mmHg
Example 2: Fick's Law in Disease
A patient with pulmonary fibrosis has a thickened alveolar membrane. How does this affect gas exchange?
\( O_2 \) Affected First
\( O_2 \) is diffusion-limited in diseased lungs. At rest, equilibrium may not be reached in the shortened available time along the capillary.
\( CO_2 \) Spared Initially
\( CO_2 \) has ~20x higher solubility, so even with thickened membranes, it diffuses adequately until disease is severe.
Example 3: Bohr Effect in Exercise
During intense exercise, skeletal muscle tissue has elevated temperature, \( P_{CO_2} \), and \( H^+ \). How does this affect \( O_2 \) delivery?
1
Identify the shifts: High temp, high \( P_{CO_2} \), low pH all cause a right shift of the O₂-Hb curve.
2
Effect on P50: P50 increases (Hb needs a higher \( P_{O_2} \) to be 50% saturated), meaning \( O_2 \) is released more easily.
3
Result: At the tissue \( P_{O_2} \) of ~20-30 mmHg, Hb unloads a much greater percentage of \( O_2 \) than at rest: more \( O_2 \) delivered to working muscles.
Common Mistakes
✕ Confusing \( O_2 \) and \( CO_2 \) Transport
\( O_2 \) is mainly carried by hemoglobin (~98.5%), while \( CO_2 \) is mainly carried as bicarbonate (~70%). Do not mix them up.
✕ Mixing Up Shifts
Right shift = decreased affinity = \( O_2 \) unloading. Left shift = increased affinity = \( O_2 \) holding. CO poisoning shifts left, not right.
✕ Pulmonary vs Systemic Response
Hypoxia causes vasoconstriction in the lungs but vasodilation systemically. Students often apply the systemic rule to the lungs.
Summary: Key Values to Know
| Parameter | Value | Clinical Relevance |
|---|---|---|
| Alveolar \( P_{O_2} \) | ~100-104 mmHg | Drives \( O_2 \) into blood |
| Venous \( P_{O_2} \) | ~40 mmHg | Deoxygenated blood returning |
| Arterial \( P_{CO_2} \) | ~40 mmHg | Reflects ventilation adequacy |
| Venous \( P_{CO_2} \) | ~46 mmHg | \( CO_2 \) picked up from tissues |
| Hb P50 | ~26.6 mmHg | 50% saturation point |
| Tidal Volume | ~500 mL | Normal resting breath |
| Dead Space | ~150 mL | Conducting zone only |
Question 1 of 5
According to Fick's Law of diffusion, which change would most increase the rate of gas transfer across the alveolar membrane?
Fick's Law: \( \dot{V} = \frac{D \cdot A \cdot \Delta P}{T} \). Increasing \( \Delta P \) (the partial pressure gradient) directly increases the rate. Increasing T or decreasing A or D would all decrease the rate.
Question 2 of 5
A right shift of the oxygen-hemoglobin dissociation curve is caused by all of the following EXCEPT:
Increased pH means the blood is more alkaline (lower \( H^+ \) concentration), which causes a left shift (increased Hb affinity for \( O_2 \)). All other options cause a right shift by decreasing Hb's affinity for \( O_2 \).
Question 3 of 5
The majority (~70%) of \( CO_2 \) is transported in the blood as:
About 70% of \( CO_2 \) is converted to \( HCO_3^- \) by carbonic anhydrase inside RBCs. ~23% is carried as carbaminohemoglobin (bound to amino groups, not the heme iron), and ~7% is dissolved in plasma.
Question 4 of 5
A patient with emphysema has destruction of alveolar walls. According to Fick's Law, which variable is primarily affected?
Emphysema destroys alveolar walls, reducing surface area (A) for gas exchange. This is distinct from fibrosis, which increases membrane thickness (T). Both decrease the rate of diffusion, but through different mechanisms.
Question 5 of 5
In the pulmonary circulation, localized hypoxia causes:
Hypoxic pulmonary vasoconstriction is unique to the lungs. When alveolar \( P_{O_2} \) is low, local arterioles constrict, redirecting blood to better-ventilated regions. This is the opposite of systemic circulation, where hypoxia causes vasodilation.