V/Q Ratio & Mismatch
V = ventilation. Q = perfusion. Whole-lung average = 0.8. Both extremes are bad.
The upright lung gradient
ApexV/Q ≈ 3
Wasted ventilation. Alveoli open big, gravity pulls blood down, less Q. High O2, low CO2. TB loves the apex (obligate aerobe).
Whole lungV/Q = 0.8
V (~4 L/min) divided by Q (~5 L/min) equals 0.8.
BaseV/Q ≈ 0.6
Wasted perfusion. Compressed alveoli, large vessels. Both V and Q are higher than apex but Q rises more.
When V/Q breaks
↓ V/Q · airway problem
Shunt
V/Q = 0
VentilationBlocked
PerfusionNormal
ResultBlood bypasses gas exchange
100% O2 does NOT correct hypoxia
Causes: atelectasis, lobar pneumonia (pus-filled alveoli), pulmonary edema, ARDS, foreign body, mucus plug.
↑ V/Q · vessel problem
Dead Space
V/Q = ∞
VentilationNormal
PerfusionBlocked
ResultAir ventilates nothing
100% O2 DOES correct hypoxia
Causes: pulmonary embolism (classic), low cardiac output / shock, excess PEEP compressing vessels.
V/Q scan to PE diagnosis
Suspect PE
→
V/Q scan
→
V normal, Q absent in segment
→
PE confirmed
Q is the abnormal one. The clot blocks blood flow but air still gets in. CT angiography is now first-line in most cases. V/Q scan reserved for pregnancy, contrast allergy, or renal failure.
100% O2 split
Hypoxia that does NOT correct with 100% O2 = shunt (atelectasis, pneumonia, ARDS).
Hypoxia that DOES correct with 100% O2 = V/Q mismatch / dead space (PE, COPD).
"TB reactivates in upper lobes" because V/Q is highest at apex = highest O2 tension. M. tuberculosis is an obligate aerobe.
Hypoxia that DOES correct with 100% O2 = V/Q mismatch / dead space (PE, COPD).
"TB reactivates in upper lobes" because V/Q is highest at apex = highest O2 tension. M. tuberculosis is an obligate aerobe.
Alveolar Cells & ARDS
Three cells, each with one job. Lose Type II to lose the lung.
Most surface area
Type I Pneumocyte
ShapeSquamous, flat
JobGas diffusion
Coverage~95% area
Divide?No
Thin = short diffusion path. Cannot regenerate itself. Replaced by Type II.
The workhorse
Type II Pneumocyte
ShapeCuboidal
Job 1Make surfactant
Job 2Stem cell
MarkerLamellar bodies
Two hats: surfactant factory + replacement source for damaged Type I.
The cleaner
Alveolar Macrophage
OriginMonocyte
JobEats dust + bugs
CHF markerHemosiderin
"Dust cells" normally. In CHF they eat RBCs from edema = "heart failure cells" (hemosiderin-laden).
Regeneration loop
Type I damaged
→
Type II divides
→
Differentiates
→
New Type I
Type II is the stem cell. If Type II survives the lung heals. If Type II is wiped out, nothing rebuilds.
When it goes wrong: ARDS
Insult (sepsis, trauma, aspiration)
→
Type II destroyed
→
↓ Surfactant
→
Alveoli collapse
→
No Type I regen
→
Diffuse alveolar damage
Berlin criteria: acute onset · bilateral infiltrates · not from heart failure · PaO2/FiO2 ratio ≤ 300.
Path finding: hyaline membranes (protein-rich exudate lining alveoli).
Vent strategy: low tidal volume (6 mL/kg ideal body weight) + plateau pressure ≤ 30 cm H2O. Permissive hypercapnia. Prone positioning for severe.
Path finding: hyaline membranes (protein-rich exudate lining alveoli).
Vent strategy: low tidal volume (6 mL/kg ideal body weight) + plateau pressure ≤ 30 cm H2O. Permissive hypercapnia. Prone positioning for severe.
Anthracosis vs CWP
Anthracosis (benign). Coal dust cleared by airway cilia + macrophages. Asymptomatic. Common in city dwellers, smokers, ANY long-term urban exposure. Black-pigmented macrophages but no fibrosis.
Coal Worker's Pneumoconiosis. Macrophages overwhelmed by occupational coal dust. Coal macules → progressive massive fibrosis. Restrictive disease. Caplan syndrome = CWP + rheumatoid arthritis = pulmonary nodules.
Cell-level lung killers
Premature baby + grunting + ground-glass on CXR = neonatal RDS (Type II not mature, no surfactant). Tx: betamethasone before delivery, exogenous surfactant after.
Adult + sepsis or aspiration + bilateral infiltrates + refractory hypoxia = ARDS. Hyaline membranes on path.
"Heart failure cells" on sputum = hemosiderin-laden macrophages = chronic pulmonary edema.
Adult + sepsis or aspiration + bilateral infiltrates + refractory hypoxia = ARDS. Hyaline membranes on path.
"Heart failure cells" on sputum = hemosiderin-laden macrophages = chronic pulmonary edema.
Airway Obstruction: Where vs When
Location decides which phase of breathing makes it worse.
Air flow needs the airway open. Pressure changes during breathing either help or squeeze it shut, depending on whether the obstruction sits above or below the thoracic inlet.
Inspiration generates negative pleural pressure.
Expiration generates positive pleural pressure.
Expiration generates positive pleural pressure.
Above thoracic inlet
Extrathoracic
Larynx · upper trachea
Worse phaseInspiration
SoundSTRIDOR
WhyNegative airway pressure sucks walls in
Causes: croup (barking cough), epiglottitis (thumbprint sign), upper foreign body, laryngeal mass, anaphylaxis.
Below thoracic inlet
Intrathoracic
Bronchi · lower trachea
Worse phaseExpiration
SoundWHEEZE
WhyPositive pleural pressure squeezes airway
Causes: asthma, COPD, bronchiolitis (RSV), lower foreign body (right mainstem in adults), bronchial tumor.
Restrictive vs Obstructive
Restrictive: cannot get air IN. Stiff lungs (interstitial fibrosis, pneumoconioses, IPF, sarcoid) or chest wall problem (kyphoscoliosis, obesity). PFTs: ↓ FVC, ↓ FEV1, NORMAL or ↑ FEV1/FVC ratio.
Obstructive: cannot get air OUT. Airway blocked, air trapped (asthma, COPD, bronchiolitis). PFTs: ↓↓ FEV1, normal or ↑ FVC, ↓ FEV1/FVC ratio (under 0.7).
Stridor vs wheeze in 3 stems
Kid + barking cough + stridor on inspiration = croup (extrathoracic, parainfluenza).
Kid choked on a peanut, now wheezing = foreign body lodged in right mainstem (intrathoracic, right mainstem is the wider straighter take-off).
Sudden dyspnea + hypoxia + low CO2 post-op or post-flight = PE until proven otherwise (dead space, V/Q mismatch).
Kid choked on a peanut, now wheezing = foreign body lodged in right mainstem (intrathoracic, right mainstem is the wider straighter take-off).
Sudden dyspnea + hypoxia + low CO2 post-op or post-flight = PE until proven otherwise (dead space, V/Q mismatch).
Pneumoconioses by Exposure
The job tells you the disease. The path finding seals it.
Worked in shipyards, roofing, pipe insulation, brake pads, old buildings.
Asbestosis
Shipyard · roofing · brake pads
Affects ↓ LOWER lobes (heavy fibers settle).
Path findings. Ferruginous bodies (asbestos fiber + iron-coated macrophage, dumbbell shape on iron stain, pathognomonic). Pleural plaques (calcified, the imaging giveaway). Interstitial fibrosis.
Cancer risk. #1 = bronchogenic adenocarcinoma (most common cancer overall in asbestos). #2 = mesothelioma (pathognomonic but less common). Smoking + asbestos = MULTIPLICATIVE risk, not additive.
Sandblaster, quarry worker, glass maker, foundry, mining.
Silicosis
Sandblasting · mining · foundry · glass
Affects ↑ UPPER lobes.
Path findings. Eggshell calcification of hilar nodes (imaging buzzword). Silicotic nodules (collagen whorls). Birefringent particles under polarized light.
Why dangerous. Silica DESTROYS macrophages (toxic to phagolysosomes) → no macrophages, no TB containment, sky-high TB risk. Anyone with silicosis gets active TB screening.
Coal miner, decades of exposure.
Coal Worker's Pneumoconiosis
Coal mining
Affects ↑ UPPER lobes.
Path findings. Black-pigmented macrophages. Coal macules (small) progress to progressive massive fibrosis (PMF, big black scars).
Caplan syndrome. CWP + rheumatoid arthritis = pulmonary nodules. Boards loves this combo.
Aerospace, nuclear, electronics, ceramics worker.
Berylliosis
Aerospace · nuclear · electronics
Affects ↑ UPPER lobes.
Path findings. Non-caseating granulomas, identical to sarcoidosis. Hilar lymphadenopathy.
Boards trap. Histologically IDENTICAL to sarcoidosis. The exposure history is the ONLY thing that splits them. Aerospace worker + non-caseating granuloma = berylliosis, not sarcoid. Increased risk of lung cancer too.
Cotton mill, textile worker, worse on Mondays.
Byssinosis
Cotton · textile · flax · hemp
Reactive airway pattern, not really fibrotic.
Pattern. Endotoxin from cotton dust triggers bronchoconstriction. Symptoms worst Monday, improve through the week. "Monday fever."
Disease type. OBSTRUCTIVE (the odd one out among pneumoconioses, which are otherwise restrictive). Tolerance develops as the work week goes on, then resets over the weekend.
Asbestos is the heavy outlier
Asbestos = LOWER lobes. Everything else (silica, coal, beryllium) = UPPER lobes. Asbestos fibers are heavy and settle by gravity.
Asbestos exposure: lung cancer is more common than mesothelioma. Mesothelioma is pathognomonic, but #1 risk is bronchogenic adenocarcinoma. Boards loves to trick you here.
"Aerospace worker + non-caseating granuloma" = berylliosis, NOT sarcoidosis. Exposure splits them.
Asbestos exposure: lung cancer is more common than mesothelioma. Mesothelioma is pathognomonic, but #1 risk is bronchogenic adenocarcinoma. Boards loves to trick you here.
"Aerospace worker + non-caseating granuloma" = berylliosis, NOT sarcoidosis. Exposure splits them.
V/Q Villains
Six patterns. Tap each to see how boards will test it.
V/Q = 0
Shunt
Airway blocked. Blood flows past alveoli that cannot ventilate.
O2 test: NO response to 100% O2
tap to flip →
SHUNT · V/Q = 0
Trace ItAlveoli flooded or collapsed. Blood passes through with no gas exchange.
CausesARDS, lobar pneumonia, atelectasis, pulmonary edema, mucus plug
ABGLow PaO2, normal or low PaCO2. A-a gradient elevated.
O2 test100% FiO2 does NOT correct hypoxia. Blood bypasses the alveolus entirely.
SHUNT does NOT respond to O2. If it corrects, it is not a shunt.
V/Q = ∞
Dead Space
Vessel blocked. Air ventilates alveoli that have no blood flow.
O2 test: DOES respond to 100% O2
tap to flip →
DEAD SPACE · V/Q = ∞
Trace ItPerfusion blocked. Well-ventilated alveoli waste their effort.
CausesPulmonary embolism (classic), low cardiac output, excess PEEP
ABGLow PaO2, low PaCO2 (tachypnea). A-a gradient elevated.
O2 test100% FiO2 DOES correct hypoxia. The small amount of blood that flows past picks up O2 from the enriched gas.
Dead space responds to O2. PE until proven otherwise.
Membrane
Diffusion Impairment
Gas exchange membrane too thick or surface area too small.
Worsens with exercise (faster RBC transit)
tap to flip →
DIFFUSION IMPAIRMENT
Trace ItThickened alveolar-capillary membrane slows O2 diffusion. At rest, RBCs linger long enough. During exercise, transit shortens and diffusion fails.
CausesIPF, sarcoidosis, emphysema (loss of surface area)
Key testDLCO is the specific PFT. Reduced in all diffusion disorders. Normal in pure obstruction (asthma) unless emphysema coexists.
IPF + exercise hypoxia + reduced DLCO = diffusion impairment. Boards loves DLCO.
Protective
Hypoxic Vasoconstriction
The lung's auto-redirect. Shunts blood away from hypoxic alveoli.
Keeps overall V/Q ratio stable
tap to flip →
HYPOXIC VASOCONSTRICTION
Trace ItLow alveolar PO2 triggers pulmonary arteriole constriction. Blood diverts to better-ventilated zones. Automatic and protective.
Clinical useSingle-lung anesthesia: collapsed lung vasoconstricts, blood flows to the ventilated lung.
COPD trapHigh-flow O2 relieves hypoxic vasoconstriction in bad V/Q units, blood floods back, CO2 rises (Haldane effect). Target SpO2 88-92%.
Helpful locally. Harmful globally when every unit is hypoxic → cor pulmonale.
Apex → Base
West Zones I / II / III
Gravity sets up three different pressure regimes from top to bottom.
Zone I = dead space / Zone III = shunt tendency
tap to flip →
WEST ZONES I / II / III
Zone I (Apex)Alveolar pressure exceeds capillary. Dead space tendency. Exists only in positive-pressure ventilation or massive hemorrhage.
Zone II (Mid)Intermittent flow. V/Q closest to normal (0.8).
Zone III (Base)Both arterial and venous pressure exceed alveolar. Continuous flow. Higher perfusion. Lower V/Q. Shunt tendency.
TB lives hereApex has highest PO2 (V/Q ~3). M. tuberculosis is an obligate aerobe. Reactivates where oxygen is richest.
Apex = dead space, TB. Base = perfusion dominant. Gravity runs the show.
Most Common
V/Q Mismatch
#1 cause of hypoxemia. Imperfect match between airflow and blood flow.
Responds to supplemental O2
tap to flip →
V/Q MISMATCH
Trace ItDifferent lung units have different V/Q ratios. Low-V/Q units add deoxygenated blood to the circulation, pulling down overall PaO2.
CausesCOPD, asthma, pneumonia, interstitial lung disease
O2 responseResponds to supplemental O2 because some ventilation reaches the low-V/Q units.
A-a gradientAlways elevated. Normal A-a rules out V/Q mismatch and diffusion impairment.
V/Q mismatch = #1 cause of hypoxemia. Elevated A-a gradient. Responds to O2.
Hypoxemia Decision Tree
Step through the logic. Every branch is boards-testable.
Patient has hypoxemia. What does the A-a gradient look like?
A-a gradient is elevated
A-a gradient is normal
A-a gradient is elevated. Does 100% O2 improve PaO2?
Yes, PaO2 rises with 100% O2
No, PaO2 does NOT improve on 100% O2
Responds to O2 + elevated A-a. What does imaging show?
Focal perfusion defect: V/Q scan mismatch or CT angio filling defect
Diffuse interstitial changes, reduced DLCO on PFTs, exercise-induced
Patchy changes, known COPD or asthma
Segmental perfusion defect. Clinical context?
Post-op, long flight, hypercoagulable, immobilized
Severe hypotension, cardiogenic shock
A-a gradient is NORMAL. Check PaCO2.
PaCO2 is HIGH (above 45 mmHg)
PaCO2 normal or low, patient at altitude or breathing low FiO2
Diagnosis
Memory Hooks
Tap the key icon to unlock the mnemonic. Each one is a boards anchor.
Shunt (V/Q = 0) does not respond to 100% O2. The blood never touches the alveolus. 🔑Shunt = Stupid to give more O2. The blood bypasses the alveolus entirely. ARDS, lobar pneumonia, atelectasis. More FiO2 cannot save blood that never passes ventilated tissue.
Dead space (V/Q = infinity) responds to 100% O2. PE is the prototype. 🔑Dead space Does respond to O2. Think: movie theater with bricked-up front doors (blocked perfusion) but working side entrances. Flood the air supply, the side-entrance crowd benefits. PE = dead space.
The A-a gradient splits "lung problem" from "not the lung." 🔑A-a elevated = lung problem (shunt, V/Q mismatch, diffusion). A-a NORMAL = lung is fine (hypoventilation, altitude). This is the FIRST branch of every hypoxemia workup. Calculate it: [FiO2 x 713 - PaCO2/0.8] - PaO2.
The apex has V/Q ~3, the base has V/Q ~0.6. TB reactivates at the apex. 🔑TB loves the Top. Obligate aerobe + high PO2 at the apex = perfect reactivation spot. Base has more blood, more CO2, less O2. TB cannot survive down there.
Hypoxic pulmonary vasoconstriction redirects blood from bad alveoli to good ones. When global, it causes cor pulmonale. 🔑Local = protective (blocks shunt flow). Global = dangerous (raises PAP, dilates RV, causes cor pulmonale). High-altitude climbers and severe COPD patients get global hypoxic vasoconstriction. O2 is the treatment.
ARDS = shunt physiology + diffuse alveolar damage. Bilateral infiltrates. PaO2/FiO2 under 300. 🔑ARDS + flooded alveoli = shunt (V/Q = 0). High FiO2 does nothing. Management: low tidal volume 6 mL/kg + PEEP + prone for severe. Hyaline membranes on path. Protect the lung, not rescue the O2 number.
Type II pneumocytes are the stem cells. They make surfactant and rebuild Type I. 🔑Type II = Twin jobs: surfactant factory + stem cell. Lamellar bodies = the surfactant storage organelle. Lose Type II in ARDS, lose the ability to regenerate. Neonatal RDS: Type II not mature yet, no surfactant, alveoli collapse every breath.
Asbestos hits lower lobes. Everything else (silica, coal, beryllium) hits upper lobes. 🔑Asbestos is Anchor-heavy. Heavy fibers sink by gravity to the lower lobes. Other pneumoconioses (silica, coal, beryllium) are lighter and lodge in the upper lobes. Lower lobe fibrosis + shipyard worker = asbestos.
Berylliosis and sarcoidosis have identical biopsies. Occupation is the only split. 🔑Berylliosis = Big aerospace job. Same non-caseating granuloma, same hilar lymphadenopathy. Aerospace/nuclear/electronics worker = berylliosis. Black woman or Scandinavian without occupational exposure = sarcoid. Same biopsy, totally different answer based on who shows up.
The 100% O2 test is the single most important bedside physiology split on boards. 🔑Give 100% FiO2 for 15 minutes. PaO2 rises significantly → NOT a shunt (V/Q mismatch or dead space). PaO2 stays low despite 100% FiO2 → shunt (blood bypasses ventilated tissue). This split appears on every shelf exam and Step 1.
COPD + high-flow O2 raises CO2 via Haldane effect plus V/Q redistribution. Target SpO2 88-92%. 🔑The old "COPD breathes on hypoxic drive" story is mostly wrong. Real mechanism: O2 relieves hypoxic vasoconstriction in the worst V/Q units, blood floods back into alveoli that still cannot ventilate, and oxygenated Hb carries CO2 less efficiently (Haldane). Titrate O2 to 88-92%, never 100%.
Byssinosis is the odd pneumoconiosis: obstructive, not restrictive. Monday fever. Cotton mills. 🔑Byssinosis on Bad Mondays. Cotton endotoxin triggers bronchoconstriction. Worst on Monday after the weekend away, improves as the week goes on. Tolerance resets over the weekend. Only obstructive pneumoconiosis. Textile, cotton, flax workers.
Clinical Images
Real pathology. Tap any image to expand.
📷 V/Q Scan
📷 Alveoli Diagram
📷 Alveolus
📷 Gas Exchange
Diagnostic Algorithm
Pick a branch. Each path walks the boards logic for that physiology concept.
Which pulmonary physiology concept do you want to work through?
Low V/Q (below 0.8): Blood flow exceeds ventilation. Alveolus is underventilated relative to its perfusion. Deoxygenated blood escapes into circulation. Classic causes: pneumonia, atelectasis, mucus plug. A-a gradient elevated. Responds to supplemental O2 because some ventilation still reaches the unit.
High V/Q (above 0.8, approaching infinity): Ventilation exceeds blood flow. Alveolus is wasted on gas exchange that has no blood to pick it up. Classic cause: pulmonary embolism blocking perfusion, or low cardiac output. A-a gradient elevated. Responds to O2. CO2 rises (wasted ventilation cannot blow off CO2 from the blocked segment).
Board rule: V/Q = 0 is shunt. V/Q = infinity is dead space. Both elevate the A-a gradient. The O2 response is the split: shunt does NOT respond, dead space DOES.
High V/Q (above 0.8, approaching infinity): Ventilation exceeds blood flow. Alveolus is wasted on gas exchange that has no blood to pick it up. Classic cause: pulmonary embolism blocking perfusion, or low cardiac output. A-a gradient elevated. Responds to O2. CO2 rises (wasted ventilation cannot blow off CO2 from the blocked segment).
Board rule: V/Q = 0 is shunt. V/Q = infinity is dead space. Both elevate the A-a gradient. The O2 response is the split: shunt does NOT respond, dead space DOES.
Shunt (V/Q = 0): Alveoli flooded or collapsed. Blood bypasses gas exchange entirely. 100% O2 does NOT correct PaO2 because blood never contacts enriched air. ARDS, lobar pneumonia, pulmonary edema, atelectasis. A-a gradient elevated.
Dead Space (V/Q = infinity): Vessels blocked. Ventilated alveoli have no blood. 100% O2 DOES correct PaO2 because the small remaining perfused fraction picks up enriched gas. Pulmonary embolism, low cardiac output, excess PEEP. A-a gradient elevated.
The bedside test: Place the patient on 100% non-rebreather. If PaO2 rises above 300, it is not shunt. If PaO2 stays below 150, shunt physiology is present. This is the single most useful discriminator at the bedside.
Dead Space (V/Q = infinity): Vessels blocked. Ventilated alveoli have no blood. 100% O2 DOES correct PaO2 because the small remaining perfused fraction picks up enriched gas. Pulmonary embolism, low cardiac output, excess PEEP. A-a gradient elevated.
The bedside test: Place the patient on 100% non-rebreather. If PaO2 rises above 300, it is not shunt. If PaO2 stays below 150, shunt physiology is present. This is the single most useful discriminator at the bedside.
At rest: RBCs spend about 0.75 seconds in the pulmonary capillary. Even with a thickened membrane, O2 equilibration is usually complete by the 0.25 second mark. Hypoxemia at rest only occurs with severe membrane thickening (advanced IPF, sarcoidosis).
With exercise: Cardiac output rises and RBC transit time shortens to 0.25 seconds. The membrane does not have time to equilibrate. Hypoxemia appears only during exertion. This is the hallmark of early diffusion impairment.
Key test: DLCO (diffusing capacity for carbon monoxide). Reduced in all diffusion disorders, emphysema (loss of surface area), and pulmonary fibrosis. Normal DLCO in pure asthma and obesity hypoventilation. Boards loves DLCO as the discriminating PFT.
With exercise: Cardiac output rises and RBC transit time shortens to 0.25 seconds. The membrane does not have time to equilibrate. Hypoxemia appears only during exertion. This is the hallmark of early diffusion impairment.
Key test: DLCO (diffusing capacity for carbon monoxide). Reduced in all diffusion disorders, emphysema (loss of surface area), and pulmonary fibrosis. Normal DLCO in pure asthma and obesity hypoventilation. Boards loves DLCO as the discriminating PFT.
Zone 1 (Apex) - PA greater than Pa greater than Pv: Alveolar pressure exceeds both arterial and venous. Capillaries are compressed. Dead space tendency. Only exists during positive-pressure ventilation or severe hemorrhage. Normal breathing does not generate Zone 1 in healthy people.
Zone 2 (Middle) - Pa greater than PA greater than Pv: Arterial pressure exceeds alveolar, but venous does not. Intermittent flow. V/Q closest to the ideal ratio of 0.8.
Zone 3 (Base) - Pa greater than Pv greater than PA: Both arterial and venous exceed alveolar. Continuous perfusion. High blood flow relative to ventilation. V/Q falls toward zero. Shunt tendency. Also where dependent atelectasis forms.
Board pearl: TB reactivates at the apex because V/Q is highest there (up to 3), so PO2 is highest and M. tuberculosis, an obligate aerobe, thrives.
Zone 2 (Middle) - Pa greater than PA greater than Pv: Arterial pressure exceeds alveolar, but venous does not. Intermittent flow. V/Q closest to the ideal ratio of 0.8.
Zone 3 (Base) - Pa greater than Pv greater than PA: Both arterial and venous exceed alveolar. Continuous perfusion. High blood flow relative to ventilation. V/Q falls toward zero. Shunt tendency. Also where dependent atelectasis forms.
Board pearl: TB reactivates at the apex because V/Q is highest there (up to 3), so PO2 is highest and M. tuberculosis, an obligate aerobe, thrives.
Boards Quiz
Eight board-style questions on pulm physiology.