Source: Lectures 33–34
Tags: gas exchange, diffusion, Fick's law, partial pressure, Henry's law, Graham's law, ventilation, tidal, countercurrent, crosscurrent, gills, bird lung, mammalian lung, alveoli, hemoglobin, Bohr effect, Haldane effect, CO2 transport, chloride shift
Difficulty: Intermediate Prerequisites: Diffusion concepts, circulatory systems (Lectures 30 to 32), basic chemistry (partial pressures, solubility).
This material covers how animals get oxygen in and carbon dioxide out. It builds on the circulatory system content by showing how respiratory surfaces interface with the blood to exchange gases via diffusion. You will learn the physics of gas diffusion (Fick's law, Henry's law, Graham's law), compare how different animals ventilate their respiratory surfaces (tidal, unidirectional, countercurrent), and then follow O2 and CO2 as they are transported in the blood (hemoglobin binding, the Bohr and Haldane effects, bicarbonate chemistry). If you are shaky on partial pressures or diffusion, revisit those concepts before starting.
Gas exchange ultimately relies on diffusion down partial pressure gradients, and organisms maximise it by increasing surface area, decreasing diffusion distance, and maintaining steep gradients through ventilation and perfusion. Hemoglobin is the key O2 carrier, with its sigmoidal binding curve tuned by pH (Bohr effect) and CO2 (Haldane effect) to load O2 in the lungs and unload it in metabolically active tissues. CO2 is transported primarily as bicarbonate, with carbonic anhydrase catalysing the conversion inside red blood cells.
Fick's law of diffusion
Rate of diffusion across a tissue sheet: dQ/dt = D x A x (dC/dx). Rate increases with diffusion coefficient (D), surface area (A), and concentration gradient (dC/dx). This is the master equation for gas exchange. In simple terms: more surface, thinner barrier, steeper gradient = faster gas transfer.
Henry's law
Describes how gas dissolves in liquid: [G] = P_gas x S_gas, where [G] is concentration of dissolved gas, P_gas is the partial pressure above the liquid, and S_gas is the solubility of that gas. Think of it as: higher pressure above the liquid pushes more gas molecules into solution.
Partial pressure
The pressure exerted by a single gas in a mixture. The driving force for gas dissolution and diffusion. At equilibrium, partial pressure in the gas phase equals partial pressure in the liquid, though concentrations may differ because of solubility differences.
Graham's law
Diffusion rate of a gas in a liquid is proportional to its solubility and inversely proportional to the square root of its molecular weight.
Boyle's law
At constant temperature, pressure and volume are inversely related (P1V1 = P2V2). Governs how ventilation creates pressure gradients that move air or water.
Tidal ventilation
Air moves in and out of the same pathway. Fresh air mixes with residual air, so blood PO2 can only approach the PO2 of exhaled air, not inhaled air. Used by mammals.
Countercurrent flow
Medium and blood flow in opposite directions. Maintains a PO2 gradient across the entire exchange surface, allowing blood PO2 to approach that of the incoming medium. The most efficient arrangement.
Crosscurrent flow
Blood flows perpendicular to the medium. Maintains a gradient better than concurrent but not as well as countercurrent. Used in bird lungs.
Concurrent flow
Medium and blood flow in the same direction. Gradient diminishes quickly; blood PO2 can only reach about 50% of the medium PO2.
Hemoglobin
Metalloprotein in red blood cells; a tetramer of 2 alpha and 2 beta subunits, each with a haeme group containing Fe2+ that reversibly binds one O2 molecule (4 O2 per hemoglobin).
O2 equilibrium curve (O2-hemoglobin dissociation curve)
Sigmoidal curve showing the relationship between PO2 and hemoglobin saturation. The sigmoidal shape results from cooperative binding. P50 is the PO2 at 50% saturation and indicates O2 affinity.
Bohr effect
Decrease in pH (increased CO2 and H+) reduces hemoglobin's O2 affinity, shifting the dissociation curve to the right (increased P50), promoting O2 release in metabolically active tissues. Increase in pH shifts it left.
Haldane effect
Oxygenation of hemoglobin decreases its ability to carry CO2. In tissues (low O2), hemoglobin releases O2 and picks up more CO2. In lungs (high O2), hemoglobin binds O2 and releases CO2.
Carbonic anhydrase
Enzyme in red blood cells that rapidly catalyses CO2 + H2O to H2CO3 (and back), speeding up bicarbonate formation and breakdown.
Chloride shift
In tissues, HCO3- leaves the RBC into plasma while Cl- enters, maintaining electrical neutrality. Reversed in the lungs.
Diffusion time scales with the square of distance: t = x squared / 4D. This makes diffusion efficient only over very short distances (fractions of a millimetre). Larger organisms need ventilation (bulk flow) to bring the respiratory medium close to exchange surfaces, and a circulatory system to carry gases the rest of the way.
Gas exchange occurs at two interfaces: between the respiratory medium (air or water) and the blood, and between the blood and the interstitial fluid around tissues. Both rely on diffusion down partial pressure gradients.
O2 partial pressures along the pathway: approximately 150 mmHg in the respiratory medium, then a gradient through blood, down to approximately 2 mmHg in tissues.
Surface area to volume ratio: as radius (r) increases, SA/V decreases (SA/V = 3/r for a sphere). Larger cells and organisms face longer diffusion distances and relatively less surface area, making specialised respiratory systems necessary.
Air vs water as respiratory media:
O2 diffusion coefficient is approximately 10,000 times higher in air than in water
O2 solubility is approximately 30 times lower in water than in air
O2 concentration is approximately 30 times higher in air than in water
Water is approximately 800 times denser and approximately 50 times more viscous than air
CO2 solubility is similar in both media
Consequence: water breathers must work much harder to extract the same amount of O2
Nondirectional ventilation (well-mixed medium, thin surface): maintains a strong, constant PO2 gradient across the surface. Blood PO2 can approach medium PO2. Efficient.
Nondirectional ventilation (poorly mixed or thick surface): PO2 gradient diminishes quickly. Blood PO2 rises only slightly and plateaus well below medium PO2. Inefficient.
Tidal ventilation (mammals): air moves in and out along the same pathway, so fresh air mixes with residual stale air. Blood PO2 can only approach the PO2 of exhaled air. Limited efficiency because the lungs can never be completely emptied.
Concurrent flow: medium and blood move in the same direction. Initial steep gradient, but it diminishes quickly as both equilibrate. Blood PO2 reaches only about 50% of medium PO2.
Countercurrent flow (fish gills): medium and blood flow in opposite directions. Maintains a PO2 gradient across the entire exchange surface. Blood PO2 can approach the PO2 of the incoming medium. Highest efficiency.
Crosscurrent flow (bird lungs): blood flows perpendicular to the medium in stages. Better than concurrent, less than countercurrent.
Unidirectional ventilation: medium flows in one direction only across the respiratory surface (no mixing with exhaled air). Combined with countercurrent blood flow, this achieves the highest possible gas exchange efficiency.
Cutaneous respiration: diffusion of gases directly across the skin into the blood. Requires a thin, moist surface and short diffusion distance. Limited to small or thin organisms.
Teleost fish gills:
Use a buccal-opercular pump to generate unidirectional water flow across the gills
Water enters the mouth, passes over gill arches and lamellae, exits via the operculum
Blood in gill capillaries flows opposite to the water (countercurrent exchange)
Primary and secondary lamellae increase surface area enormously
The combination of unidirectional ventilation and countercurrent blood flow maximises O2 uptake by maintaining a partial pressure gradient across the entire gill surface
The ventilatory cycle uses Boyle's law (P1V1 = P2V2) to create pressure changes that drive water flow
Bird lungs:
Lungs are stiff and non-expanding, organised into hexagonal units with parabronchi (the actual gas exchange sites)
Air capillaries run through parabronchi; blood flows through capillaries in a crosscurrent arrangement
Anterior and posterior air sacs act as bellows to move air but do not perform gas exchange themselves
Airflow is unidirectional and continuous through the lungs
Requires two full breathing cycles to move one bolus of air through the system: (1) first inhalation pushes fresh air into posterior air sacs, (2) first exhalation pushes that air through the parabronchi, (3) second inhalation moves it into anterior air sacs, (4) second exhalation pushes it out the trachea
This unidirectional flow plus crosscurrent blood flow maintains a high PO2 gradient continuously
Mammalian lungs:
Tidal (bidirectional) ventilation driven by the diaphragm
Inhalation: diaphragm contracts and flattens, chest expands, thoracic volume increases, pressure decreases, air flows in
Exhalation: diaphragm relaxes and domes upward, chest recoils, thoracic volume decreases, pressure increases, air flows out
Because air moves in and out along the same pathway, fresh and stale air mix, and blood PO2 can only approach the PO2 of exhaled air
Highly branched (fractal-like) airway geometry: nares/mouth, nasal cavity, trachea, bronchi, bronchioles, terminal bronchioles (conducting zone), respiratory bronchioles, alveolar ducts, alveolar sacs, alveoli (respiratory zone)
The branching greatly increases total surface area while decreasing individual airway diameter, maximising A and minimising x in Fick's law
Alveoli: tiny thin-walled sacs providing enormous surface area for gas exchange with surrounding capillaries
Type I cells: thin squamous cells forming most of the alveolar surface, specialised for gas exchange
Type II cells: secrete surfactant to reduce surface tension and prevent alveolar collapse
Alveolar macrophages: immune cells that engulf debris and pathogens
Alveolar pores: small openings between adjacent alveoli allowing air movement and pressure equalisation
Hemoglobin structure: a tetramer of 2 alpha and 2 beta subunits, each with a haeme group containing Fe2+. Each haeme binds one O2, so one hemoglobin carries up to 4 O2 molecules.
The O2-hemoglobin dissociation curve is sigmoidal because of cooperative binding: once the first O2 binds, subsequent binding becomes easier (conformational change). P50 is the PO2 at which hemoglobin is 50% saturated and serves as a measure of O2 affinity.
Bohr effect (pH down, rightward shift): in metabolically active tissues, CO2 and H+ accumulate. Decreased pH reduces hemoglobin's O2 affinity (increased P50), promoting O2 release where it is needed most. In the lungs, higher pH favours O2 loading (leftward shift, decreased P50).
Hypoxia responses:
Short term: increased ventilation, spleen contraction releasing stored red blood cells
Long term: sustained low O2 activates HIF-1, increasing erythropoietin (EPO) production, which stimulates more red blood cell production
CO2 produced in tissues enters the blood and is carried in three forms:
Dissolved in plasma (approximately 7%)
Bound to hemoglobin as carbaminohemoglobin (approximately 23%)
Converted to bicarbonate inside red blood cells (approximately 70%), the dominant form
Bicarbonate formation: CO2 + H2O is converted to H2CO3 (carbonic acid) by carbonic anhydrase, which rapidly dissociates to HCO3- + H+. The bicarbonate exits the RBC into plasma via the Cl-/HCO3- exchanger (chloride shift: Cl- enters the RBC to maintain charge balance).
In the lungs, the reactions reverse: bicarbonate re-enters the RBC (reversed chloride shift), is converted back to CO2 by carbonic anhydrase, and CO2 diffuses into alveoli to be exhaled.
Haldane effect: oxygenation of hemoglobin reduces its capacity to carry CO2. In tissues (low O2), hemoglobin releases O2 and binds more CO2. In lungs (high O2), hemoglobin binds O2 and releases CO2. This reciprocal relationship links O2 and CO2 transport.
Tissue conditions favour O2 unloading: high CO2 and H+ reduce O2 affinity (Bohr effect). CO2 also binds hemoglobin directly (carbaminohemoglobin) and H+ binds hemoglobin (Hb-H), further reducing O2 affinity.
Lung conditions favour O2 loading: high O2 drives O2 binding, which causes H+ release from hemoglobin. H+ combines with bicarbonate, carbonic anhydrase converts this back to CO2 + H2O, and CO2 diffuses out to be exhaled.
Formula | Equation | Variables |
|---|---|---|
Diffusion time | t = x^2 / 4D | t = time, x = distance, D = diffusion coefficient |
Fick's law | dQ/dt = D x A x (dC/dx) | dQ/dt = rate of diffusion, D = diffusion coefficient, A = surface area, dC/dx = concentration gradient |
Fick's law (gas in liquid, expanded) | Rate proportional to (D x A x delta-P_gas x S_gas) / (x x sqrt MW) | delta-P_gas = partial pressure gradient, S_gas = solubility, MW = molecular weight |
Henry's law | [G] = P_gas x S_gas | [G] = dissolved gas concentration, P_gas = partial pressure, S_gas = solubility |
Graham's law | Diffusion rate proportional to S_gas / sqrt MW | S_gas = solubility, MW = molecular weight |
Boyle's law | P1 x V1 = P2 x V2 | P = pressure, V = volume (at constant temperature) |
SA:V ratio (sphere) | SA/V = 3/r | r = radius |
The countercurrent exchange principle in fish gills is the same principle used in industrial heat exchangers, dialysis machines, and radiator designs. Engineers run fluids in opposite directions to maximise transfer efficiency, exactly as evolution arrived at in gill capillaries.
Surfactant deficiency in premature infants (respiratory distress syndrome) illustrates why Type II cells matter: without surfactant, alveoli collapse and gas exchange fails.
Students often think CO2 is carried primarily as dissolved gas in plasma. It is not. Approximately 70% travels as bicarbonate inside and outside red blood cells.
Students confuse the Bohr and Haldane effects. Bohr effect: pH affects O2 binding. Haldane effect: O2 affects CO2 binding. They work in the same direction (both promote O2 release and CO2 pickup in tissues) but describe different molecular mechanisms.
Students assume tidal ventilation is inherently inefficient compared to countercurrent. While tidal ventilation is less efficient at extracting O2 from the medium, mammals compensate with enormous alveolar surface area and the much higher O2 concentration available in air compared to water.
Students forget that bird lungs require two full breathing cycles to move one bolus of air through the system. A single inhalation does not complete the journey.
Know Fick's law and be able to identify which variables an organism can change biologically (A, delta-P, x) versus which are properties of the gas and medium (D, S_gas, sqrt MW).
Be able to rank ventilation/flow patterns by efficiency: countercurrent > crosscurrent > tidal > concurrent, and explain why.
Understand the bird lung two-cycle breathing sequence and why unidirectional airflow is more efficient than tidal.
Be able to explain how the Bohr effect promotes O2 delivery to active tissues and O2 loading in the lungs.
Know all three forms of CO2 transport and the role of carbonic anhydrase and the chloride shift.
Be comfortable with the O2-hemoglobin dissociation curve: what P50 means, what shifts the curve left or right, and the physiological significance of each shift.
True or false: O2 diffuses approximately 10,000 times faster in air than in water.
True.
Fill in the blank: The enzyme that catalyses CO2 + H2O to H2CO3 inside red blood cells is ___.
Carbonic anhydrase.
True or false: In countercurrent exchange, blood PO2 can approach the PO2 of exhaled medium.
False. Blood PO2 can approach the PO2 of the incoming (inhaled) medium, which is the highest available.
Fill in the blank: A decrease in blood pH shifts the O2-hemoglobin dissociation curve to the ___, promoting O2 ___.
Right; release (unloading).
Q: Explain why fish gills are more efficient at extracting O2 from water than mammalian lungs would be if submerged. Reference both the ventilation pattern and the blood flow arrangement.
A: Fish gills use unidirectional ventilation (water flows in one direction across the gill surface, never mixing with "used" water) combined with countercurrent blood flow (blood in gill capillaries flows opposite to the water). This maintains a partial pressure gradient across the entire gill surface. In contrast, mammalian lungs use tidal ventilation, where the medium reverses direction with each breath and mixes stale air with fresh air. Even if submerged, the tidal pattern would equilibrate blood PO2 only to the PO2 of the "exhaled" medium, not the incoming medium.
Q: A patient presents with respiratory distress syndrome due to surfactant deficiency. Using Fick's law, explain how the loss of functional alveoli affects gas exchange.
A: Surfactant reduces surface tension and keeps alveoli open. Without it, alveoli collapse, dramatically reducing the functional surface area (A) available for gas exchange. Fick's law (dQ/dt = D x A x dC/dx) shows that if A drops, the rate of diffusion drops proportionally, even if the partial pressure gradient remains unchanged. Collapsed alveoli may also increase effective diffusion distance (x) at remaining surfaces due to fluid accumulation, further reducing gas exchange.
Q: Describe the journey of a CO2 molecule from a metabolically active muscle cell to its exhalation from the lungs. Include the chemical reactions and transport mechanisms involved.
A: CO2 diffuses out of the muscle cell and into the blood. Most enters red blood cells, where carbonic anhydrase catalyses CO2 + H2O to H2CO3, which dissociates to HCO3- + H+. HCO3- exits the RBC via the Cl-/HCO3- exchanger (chloride shift: Cl- enters to maintain charge balance). H+ binds to deoxygenated hemoglobin. Some CO2 also binds hemoglobin directly as carbaminohemoglobin. In the lungs, the reactions reverse: HCO3- re-enters the RBC (reversed chloride shift), recombines with H+ to form H2CO3, carbonic anhydrase converts this to CO2 + H2O, and CO2 diffuses across the alveolar membrane into the alveolar air to be exhaled.
This material builds directly on the circulatory system (Lectures 30 to 32): the blood vessels and cardiac output studied there are the delivery system that makes gas exchange at distant tissues possible.
The physics of diffusion and partial pressures will reappear in renal physiology (gas exchange in the kidneys) and in any discussion of membrane transport.
The Bohr and Haldane effects connect to acid-base chemistry and buffering, relevant to renal and metabolic physiology.
gas exchange, diffusion, Fick's law, partial pressure, Henry's law, Graham's law, Boyle's law, ventilation, tidal ventilation, countercurrent, crosscurrent, concurrent, unidirectional, nondirectional, respiratory surface, gills, gill arches, lamellae, operculum, buccal pump, bird lung, parabronchi, air sacs, mammalian lung, alveoli, alveolar sac, bronchi, bronchiole, trachea, diaphragm, surfactant, Type I cell, Type II cell, alveolar macrophage, hemoglobin, haemoglobin, O2-hemoglobin dissociation curve, P50, cooperative binding, Bohr effect, Haldane effect, CO2 transport, bicarbonate, carbonic anhydrase, chloride shift, carbaminohemoglobin, hypoxia, EPO, erythropoietin, cutaneous respiration