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Pulmonary Physiology

Usually weeks 12-13 of a medical physiology course, right after the cardiovascular unit

Pulmonary physiology is a short unit with a long reach: every blood gas, every pulmonary function test, and every hypoxic patient you will ever manage is read with the rules built here. The course moves from mechanics (volumes, pressures, compliance, resistance) to gas exchange (partial pressures, the alveolar gas equation, diffusion) to transport (the oxyhemoglobin curve and the bicarbonate system) and finally to V/Q matching and the control of breathing. The exam lives in four places: reading spirometry and flow-volume loops as obstructive or restrictive, calculating PAO2 and the A–a gradient, predicting which way the oxyhemoglobin curve shifts, and sorting a hypoxemic patient into one of the five mechanisms. Learn the equations well enough to use them, not just recite them.

On the PANCE this unit feeds:Pulmonary · 9%Cardiovascular · 11%Hematology · 5%

This guide is the frame. The exams are written from your lectures— drop this unit's slides on the dashboard to get flashcards and board-style questions from your own course, and quiz them all semester (a course whose exams re-test earlier units rewards nothing more than early, repeated self-testing). The physiology playbook has the weekly loop.

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AI-authored study notes, not faculty-reviewed and not medical advice. Verify every mechanism against your course materials and faculty; programs differ in emphasis.

High-Yield Pearl

Before you name a lung disease, calculate the A–a gradient and read the FEV1/FVC ratio — those two numbers sort nearly every hypoxemia and every spirometry question into the right box.

What the exam asks
Mechanisms, curves, and what happens when each one fails.
  • Lung volumes and capacities. Four non-overlapping VOLUMES: tidal volume (TV, ~500 mL at rest), inspiratory reserve volume (IRV, the extra air inhaled beyond a normal breath, ~3 L), expiratory reserve volume (ERV, the extra air forced out after a normal exhalation, ~1.2 L), and residual volume (RV, ~1.2 L, the air that can never be exhaled). CAPACITIES are sums of two or more: inspiratory capacity = TV + IRV; functional residual capacity (FRC) = ERV + RV; vital capacity (VC) = IRV + TV + ERV; total lung capacity (TLC) = all four (~6 L). A spirometer only measures air that moves in and out of the mouth, so RV — and therefore FRC and TLC — cannot be measured by simple spirometry; they require helium dilution, nitrogen washout, or body plethysmography (the only method that also counts gas trapped behind closed airways). FRC is the resting volume of the respiratory system, where the lung's inward elastic recoil exactly balances the chest wall's outward spring.
  • Dead space and alveolar ventilation. Anatomic dead space is the volume of the conducting airways (nose to terminal bronchioles), about 150 mL (roughly 1 mL per pound of ideal body weight) — air that is moved but never exchanged. Alveolar dead space is ventilated alveoli with no perfusion; anatomic plus alveolar dead space is PHYSIOLOGIC dead space, which equals anatomic in a healthy lung. The Bohr equation measures it: VD/VT = (PaCO2 − PECO2) / PaCO2, where PECO2 is mixed expired CO2 (normal VD/VT ≈ 0.2–0.35). Minute ventilation = VT × RR; alveolar ventilation = (VT − VD) × RR — at 500 mL, 150 mL, and 12 breaths/min, 4.2 L/min. PaCO2 is inversely proportional to alveolar ventilation (PaCO2 ∝ VCO2 / VA), so halving VA doubles PaCO2. That is why rapid shallow breathing is inefficient: the fixed dead space eats a larger share of each small breath.
  • The pressures of breathing. Quiet inspiration is active: the diaphragm (phrenic nerve, C3–C5) contracts, the thorax enlarges, intrapleural pressure falls from about −5 cmH2O at FRC to about −8 cmH2O, and alveolar pressure dips slightly below atmospheric (about −1 cmH2O) so air flows in. At end-inspiration flow stops and alveolar pressure returns to zero. Quiet expiration is PASSIVE — elastic recoil raises alveolar pressure above atmospheric; forced expiration recruits the abdominal and internal intercostal muscles and can drive intrapleural pressure positive. Transpulmonary pressure (alveolar minus intrapleural) is the distending pressure that holds the lung open; it is positive throughout normal breathing. A pneumothorax lets air into the pleural space, intrapleural pressure rises to atmospheric, transpulmonary pressure vanishes, and the lung recoils inward while the chest wall springs outward.
  • Compliance, elastic recoil, and surfactant. Compliance is ΔV/ΔP — the slope of the pressure-volume curve — and is the inverse of elastance. It is highest in the mid range near FRC and falls near TLC as the lung reaches its elastic limit. Elastic recoil comes from two sources: elastin and collagen in the tissue, and — the larger share — surface tension at the air-liquid interface of the alveoli. Emphysema destroys elastin: compliance RISES, recoil falls, and the lung hyperinflates (barrel chest, high FRC). Fibrosis stiffens the lung: compliance FALLS, recoil rises, and volumes shrink. The law of Laplace (P = 2T/r) predicts that at equal surface tension a small alveolus has a higher collapsing pressure and would empty into a large one. Surfactant — mainly dipalmitoylphosphatidylcholine made by type II pneumocytes — lowers surface tension, and lowers it MORE as the alveolus shrinks and the surfactant film concentrates, which stabilizes small alveoli, increases compliance, reduces the work of breathing, and keeps the alveoli dry. Fetal production begins in the second trimester and becomes adequate late in the third; a lecithin:sphingomyelin ratio above 2 signals maturity.
  • Airway resistance and dynamic compression. By Poiseuille's law, resistance varies with 1/r⁴, so halving an airway's radius raises its resistance 16-fold. Yet the greatest total resistance sits in the MEDIUM-SIZED bronchi, not the smallest airways — the small airways are so numerous and arranged in parallel that their summed cross-section is enormous (the 'quiet zone' where early disease hides). Resistance falls at high lung volumes (radial traction pulls airways open) and with sympathetic β2 stimulation; it rises with parasympathetic (muscarinic) tone, histamine, leukotrienes, and irritants. During forced expiration intrapleural pressure turns positive; pressure inside the airway falls along its length, and at the EQUAL PRESSURE POINT it equals the surrounding pleural pressure — downstream of that point the airway is compressed. Pushing harder raises both alveolar and pleural pressure equally, so flow over most of the expiratory limb is EFFORT-INDEPENDENT. In emphysema, lost recoil moves the equal pressure point upstream into small, unsupported airways, which collapse and trap air; pursed-lip breathing adds back-pressure and moves it toward the mouth.
  • Obstructive vs restrictive patterns. Obstruction (COPD, asthma, bronchiectasis, cystic fibrosis) narrows airways, so air gets out slowly: FEV1 falls much more than FVC and the FEV1/FVC ratio drops below 0.70. Air trapping raises RV, FRC, and often TLC; the flow-volume loop shows a scooped, concave expiratory limb shifted toward high volumes. Reversibility after a bronchodilator (≥12% and ≥200 mL rise in FEV1) points to asthma. Restriction (interstitial lung disease, chest wall deformity, neuromuscular weakness, obesity) shrinks volumes: FEV1 and FVC fall TOGETHER, so the ratio is normal or HIGH (recoil in a fibrotic lung pulls air out fast), and TLC is reduced — the finding that confirms restriction, since a low FVC alone can be trapped air. DLCO separates the causes: low in parenchymal disease (fibrosis) and emphysema, normal in pure chest wall or neuromuscular restriction and usually in asthma.
  • Gas laws and the alveolar gas equation. Dalton's law: each gas's partial pressure = total pressure × its fraction. Inspired air is humidified in the airways, and water vapor (47 mmHg at body temperature) takes its share first: PIO2 = FiO2 × (PB − 47) = 0.21 × 713 ≈ 150 mmHg at sea level. In the alveolus CO2 dilutes O2, giving the alveolar gas equation: PAO2 = FiO2(PB − 47) − PaCO2/R, with the respiratory quotient R ≈ 0.8 — so PAO2 ≈ 150 − 40/0.8 = 100 mmHg. Henry's law: dissolved gas = solubility × partial pressure (dissolved O2 = 0.003 mL/dL per mmHg). The A–a gradient (PAO2 − PaO2) is normally about 5–15 mmHg and rises with age (a rough upper limit is age/4 + 4). A normal gradient in a hypoxemic patient means the lung itself is working — the problem is hypoventilation or low inspired O2; a WIDE gradient means V/Q mismatch, shunt, or diffusion limitation.
  • Diffusion and DLCO. Fick's law: gas transfer across the alveolar-capillary membrane = (area × solubility × ΔP) / thickness. Emphysema reduces AREA; fibrosis and edema increase THICKNESS; both slow diffusion. CO2 is about 20 times more soluble than O2, so it diffuses far more readily despite a smaller gradient — CO2 retention is almost never a diffusion problem. PERFUSION-LIMITED gases (N2O, and O2 and CO2 in a healthy lung at rest) equilibrate with capillary blood within the first third of the capillary, so more uptake needs more blood flow. DIFFUSION-LIMITED gases never equilibrate — carbon monoxide is the textbook example, because hemoglobin soaks it up and its partial pressure in plasma stays near zero. O2 becomes diffusion-limited during strenuous exercise, at high altitude, and in fibrosis. That property makes CO the probe gas for DLCO (diffusing capacity), which falls in emphysema, interstitial lung disease, pulmonary vascular disease, and anemia, and rises in polycythemia and alveolar hemorrhage (extra hemoglobin to bind CO).
  • Oxygen transport and the oxyhemoglobin curve. O2 content (CaO2) = (1.34 × Hb × SaO2) + (0.003 × PaO2) ≈ 20 mL/dL — nearly all of it bound to hemoglobin. Oxygen delivery = cardiac output × CaO2. The oxyhemoglobin curve is SIGMOID because binding is cooperative: each O2 that binds raises the affinity of the remaining heme sites. The flat upper PLATEAU (PO2 above ~60 mmHg, saturation ~90%) protects loading — PaO2 can fall from 100 to 60 with little loss of content. The STEEP portion (PO2 10–40) is where tissues unload: a small drop in PO2 releases a large amount of O2. Arterial blood sits near 100 mmHg/97%, mixed venous near 40 mmHg/75%. P50, the PO2 at 50% saturation, is ~26–27 mmHg. A RIGHT shift (higher P50, lower affinity) comes from ↑PCO2, ↑H+ (the Bohr effect), ↑temperature, and ↑2,3-BPG — the conditions of working tissue — and favors unloading. A LEFT shift comes from the opposites plus fetal hemoglobin (γ chains bind 2,3-BPG poorly, P50 ~19), carbon monoxide, and methemoglobin. Carbon monoxide is a double hit — it occupies heme sites (lowering content) and left-shifts the rest — while PaO2 and a standard pulse oximeter read normal; anemia lowers content with PaO2 and SaO2 both normal; methemoglobin (Fe3+) cannot carry O2 and pins SpO2 near 85%. The peripheral chemoreceptors sense PaO2, not content, so none of these drives ventilation much.
  • Carbon dioxide transport. CO2 travels three ways: about 70% as bicarbonate, about 20% bound to hemoglobin as carbamino compounds, and about 10% dissolved. In the tissues CO2 enters the red cell, carbonic anhydrase converts it to H2CO3, which splits into H+ (buffered by deoxyhemoglobin) and HCO3−; bicarbonate exits to the plasma in exchange for Cl− — the CHLORIDE SHIFT (the band 3 exchanger), which is why venous red cells hold more chloride. In the lungs every step runs backward. The HALDANE EFFECT is the CO2 side of the coin: deoxygenated hemoglobin binds more CO2 and H+, so unloading O2 in tissues helps pick up CO2, and oxygenating hemoglobin in the lungs drives CO2 off. The BOHR EFFECT is the O2 side: CO2 and H+ lower hemoglobin's O2 affinity, helping release O2 where metabolism is high. The CO2 dissociation curve is nearly linear across the physiologic range — no plateau — which is why hyperventilating normal alveoli can blow off extra CO2 but cannot load extra O2.
  • V/Q matching, the zones, hypoxemia, and hypoxic vasoconstriction. Ideal V/Q is about 1; the whole-lung average is about 0.8. In an upright lung both ventilation and perfusion are greater at the BASE, but perfusion rises more steeply, so V/Q is highest at the apex (~3: high PAO2, low PACO2 — the reason reactivation tuberculosis favors the apex) and lowest at the base (~0.6). West's zones: zone 1, alveolar > arterial > venous pressure, no flow — alveolar dead space, which appears only when arterial pressure falls (hemorrhage) or alveolar pressure rises (positive-pressure ventilation); zone 2, arterial > alveolar > venous, flow set by the arterial-alveolar difference; zone 3, arterial > venous > alveolar, continuous flow at the base. At the extremes, V/Q = 0 is SHUNT (perfusion without ventilation: pneumonia, atelectasis, ARDS, intracardiac right-to-left) and V/Q = ∞ is DEAD SPACE (ventilation without perfusion: pulmonary embolism). Five causes of hypoxemia: low inspired PO2 (altitude) and hypoventilation keep a NORMAL A–a gradient; V/Q mismatch (the most common), diffusion limitation, and shunt WIDEN it. Supplemental O2 corrects all but true shunt — refractory hypoxemia on 100% O2 is the signature of a shunt. Hypoxic pulmonary vasoconstriction, unique to the lung, constricts arterioles supplying poorly ventilated alveoli and redirects blood to well-ventilated ones; when hypoxia is global (altitude, chronic lung disease) it raises pulmonary artery pressure and can produce cor pulmonale, and in the fetus it keeps pulmonary vascular resistance high until the first breath.
  • Control of breathing, altitude, and exercise. The rhythm is generated in the medulla — the pre-Bötzinger complex in the ventral respiratory group drives it; the dorsal respiratory group (nucleus tractus solitarius) handles inspiration and receives vagal and glossopharyngeal input; the ventral group adds active expiration during forced breathing; pontine centers shape the pattern. CENTRAL chemoreceptors on the ventral medulla respond to H+ in the CSF: CO2 crosses the blood-brain barrier freely and is hydrated there, while H+ and HCO3− cross poorly — so PaCO2 is the dominant minute-to-minute driver of ventilation. PERIPHERAL chemoreceptors (carotid bodies via CN IX, aortic bodies via CN X) are the only sensors of hypoxemia, firing sharply once PaO2 falls below ~60 mmHg; the carotid bodies also answer to H+ (the Kussmaul breathing of metabolic acidosis). Stretch receptors terminate inspiration (Hering-Breuer reflex). In chronic CO2 retention the central response blunts as CSF bicarbonate rises, and hypoxemia contributes more of the drive — but oxygen-induced hypercapnia is driven mainly by worsened V/Q matching (release of hypoxic vasoconstriction) and the Haldane effect, so the fix is titrated O2 (SpO2 88–92%), never withholding it. At HIGH ALTITUDE the low PIO2 triggers peripheral-chemoreceptor hyperventilation → respiratory alkalosis → renal bicarbonate excretion over days (acetazolamide speeds it), plus ↑2,3-BPG, ↑erythropoietin and hematocrit, and hypoxic pulmonary vasoconstriction (pulmonary hypertension, HAPE risk). In moderate EXERCISE ventilation rises in step with CO2 production, so arterial PO2, PCO2, and pH stay essentially normal; venous PO2 falls, O2 extraction rises, apical perfusion improves V/Q matching, and the muscle curve shifts right. Only past the lactate threshold does pH fall and ventilation climb out of proportion.
Worth drilling · 45 concepts
Each with the one fact that identifies it. Your course's slides are the authority; use this to check your list against.
  1. 1Tidal volume — air moved in one quiet breath, about 500 mL
  2. 2Inspiratory reserve volume — the extra air inhaled with maximal effort after a normal inspiration
  3. 3Expiratory reserve volume — the extra air forced out after a normal, passive expiration
  4. 4Residual volume — air left after maximal expiration; invisible to simple spirometry
  5. 5Functional residual capacity — ERV plus RV; resting volume where lung and chest wall recoil balance
  6. 6Vital capacity — IRV plus TV plus ERV; the largest breath exhaled after maximal inspiration
  7. 7Total lung capacity — all four lung volumes; reduced in every true restrictive disease
  8. 8Inspiratory capacity — tidal volume plus inspiratory reserve volume
  9. 9Anatomic dead space — conducting-airway volume, about 150 mL, that never exchanges gas
  10. 10Physiologic dead space — anatomic plus alveolar dead space; measured with the Bohr equation
  11. 11Alveolar dead space — ventilated alveoli with no perfusion, as in pulmonary embolism
  12. 12Bohr equation — VD/VT equals (PaCO2 minus mixed expired PCO2) divided by PaCO2
  13. 13Alveolar ventilation — (VT minus VD) × respiratory rate; inversely sets PaCO2
  14. 14Intrapleural pressure — about −5 cmH2O at FRC, more negative during inspiration
  15. 15Transpulmonary pressure — alveolar minus intrapleural pressure; the pressure that holds the lung open
  16. 16Lung compliance — change in volume per change in pressure; high in emphysema, low in fibrosis
  17. 17Surfactant — dipalmitoylphosphatidylcholine that lowers surface tension most in small alveoli
  18. 18Law of Laplace — collapsing pressure equals 2T/r, so small alveoli collapse without surfactant
  19. 19Medium-sized bronchi — site of the greatest total airway resistance
  20. 20Equal pressure point — where airway pressure equals pleural pressure during forced expiration
  21. 21Dynamic airway compression — squeezes airways in forced expiration and makes late flow effort-independent
  22. 22FEV1/FVC ratio — below 0.70 defines obstruction; normal or high in restriction
  23. 23Alveolar gas equation — PAO2 equals FiO2(PB − 47) − PaCO2/0.8
  24. 24A–a gradient — alveolar minus arterial PO2; normal in hypoventilation, wide in shunt
  25. 25Fick's law of diffusion — gas transfer rises with area and gradient, falls with membrane thickness
  26. 26DLCO — carbon monoxide diffusing capacity; low in emphysema and fibrosis, normal in asthma
  27. 27Perfusion-limited exchange — gas equilibrates early in the capillary, so uptake needs more blood flow
  28. 28Diffusion-limited exchange — gas never equilibrates along the capillary; carbon monoxide is the model
  29. 29P50 — PO2 at 50% hemoglobin saturation, about 26–27 mmHg
  30. 30Rightward curve shift — higher P50 from more CO2, acid, heat, or 2,3-BPG; favors unloading
  31. 312,3-BPG — red cell glycolytic byproduct that lowers hemoglobin's O2 affinity; rises at altitude
  32. 32Fetal hemoglobin — gamma chains bind 2,3-BPG poorly, so its curve sits left of adult blood
  33. 33Carboxyhemoglobin — lowers O2 content and left-shifts the curve while PaO2 stays normal
  34. 34Chloride shift — bicarbonate leaves the red cell in exchange for Cl− through band 3
  35. 35Haldane effect — oxygenating hemoglobin in the lung releases its CO2
  36. 36Bohr effect — CO2 and H+ lower hemoglobin's O2 affinity where tissues work
  37. 37Apical ventilation-perfusion ratio — about 3; highest PAO2 in the upright lung
  38. 38Basal ventilation-perfusion ratio — about 0.6; most blood flow and most ventilation
  39. 39West zone 1 — alveolar pressure exceeds arterial, so no flow; seen with hemorrhage or positive pressure
  40. 40Right-to-left shunt — perfusion without ventilation; hypoxemia that 100% O2 does not correct
  41. 41Hypoxic pulmonary vasoconstriction — arterioles to poorly ventilated alveoli constrict to rematch V/Q
  42. 42Pre-Bötzinger complex — medullary rhythm generator for breathing
  43. 43Central chemoreceptors — ventral medullary sensors of CSF H+ generated from PaCO2
  44. 44Peripheral chemoreceptors — carotid and aortic bodies; the only sensors of PaO2 below 60 mmHg
  45. 45High-altitude acclimatization — hyperventilation, renal bicarbonate loss, more 2,3-BPG and red cells
Practice it
Active recall over the drill list — flip and claim, match the pairs, produce the answers cold, fill in the diagram, or read the curves like the exam does.

Every concept on the drill list, one card at a time — the name up front, the fact that identifies it on the flip. Claim each card honestly and the deck learns what to lead with next time. Progress lives in this browser only.

What everyone misses
The distinctions that lose points on this material, year after year.
  • Spirometry cannot see residual volume. Anything that contains RV — FRC and TLC — is invisible to a spirometer, because RV never leaves the lung. Questions that ask how to measure FRC or TLC want helium dilution, nitrogen washout, or body plethysmography, and only plethysmography counts gas trapped behind closed airways. A low FVC therefore does not prove restriction; a reduced TLC does.
  • Restriction does NOT lower the FEV1/FVC ratio. Both numbers fall in restrictive disease, usually in proportion, and the stiff, high-recoil lung empties quickly — so the ratio is normal or even increased. A low ratio means obstruction. Students who see 'FEV1 is low' and stop reading pick obstruction every time.
  • A normal A–a gradient narrows the list to two. Hypoxemia with a normal gradient is hypoventilation (opioids, neuromuscular weakness — look for a high PaCO2) or low inspired O2 (altitude). Everything that damages the lung itself — V/Q mismatch, shunt, diffusion limitation — widens it. Calculate PAO2 before you guess.
  • PaO2, SaO2, and O2 content are three different numbers. Anemia lowers content but leaves PaO2 and SaO2 normal. Carbon monoxide lowers content and true saturation while PaO2 stays normal and a standard pulse oximeter reads falsely normal. PaO2 reflects only dissolved O2 and the lung's exchange; content is what the tissues get. The peripheral chemoreceptors sense PaO2, which is why these patients are not dyspneic in proportion to their hypoxia.
  • Greatest resistance is in the medium bronchi, not the smallest airways. Poiseuille's r⁴ rule tempts students to pick the bronchioles, but those airways are arranged in enormous parallel numbers, so their combined resistance is small. The medium-sized bronchi carry the most total resistance — and early small-airway disease can progress silently before spirometry changes.
  • The apex has the highest V/Q, but the base gets more of everything. Both ventilation and perfusion are greater at the base of the upright lung; perfusion simply increases more steeply with gravity. So V/Q is high at the apex (little blood) and low at the base. Saying 'the apex is better ventilated' is the wrong reason for the right ratio.
  • O2 in chronic CO2 retainers: titrate, don't withhold. The classic teaching blames loss of hypoxic drive, but the larger contributors to oxygen-induced hypercapnia are release of hypoxic pulmonary vasoconstriction (worse V/Q matching) and the Haldane effect. The board answer is controlled O2 targeting SpO2 88–92% — never denying oxygen to a hypoxemic patient.
Clinical correlations
Where this unit shows up again — in clinic, on rotations, and on the boards.
  • COPD — emphysema pattern. A long-time smoker with dyspnea, a barrel chest, and pursed-lip breathing: FEV1/FVC below 0.70 that does not normalize after bronchodilator, high RV, FRC, and TLC, low DLCO, and a scooped flow-volume loop. Elastin destruction raises compliance and lowers recoil, so the equal pressure point moves into unsupported small airways and air is trapped. Alpha-1 antitrypsin deficiency gives the same picture earlier, at the lung bases, in a young nonsmoker.
  • Asthma. Episodic wheeze, cough, and chest tightness with an obstructive pattern that reverses with a β2 agonist (≥12% and ≥200 mL FEV1 improvement), a positive methacholine challenge when spirometry is normal, and a normal or elevated DLCO. In an acute attack a NORMAL or rising PaCO2 in a tachypneic patient is ominous — it means the patient is tiring and can no longer hyperventilate.
  • Idiopathic pulmonary fibrosis. An older adult with progressive dyspnea, dry cough, fine 'velcro' crackles, and clubbing: restrictive spirometry (low FVC, normal or high FEV1/FVC), reduced TLC, low DLCO, and a lung so stiff that breathing becomes rapid and shallow. Hypoxemia worsens with exertion because O2 transfer becomes diffusion-limited when capillary transit time shortens.
  • Neonatal respiratory distress syndrome. A premature infant with grunting, retractions, and cyanosis within hours of birth; ground-glass lungs with air bronchograms. Too little surfactant leaves surface tension unopposed, so alveoli collapse at end-expiration (Laplace) — low compliance, atelectasis, and intrapulmonary shunt. Antenatal corticosteroids accelerate surfactant production; treatment is exogenous surfactant and CPAP. Maternal diabetes delays maturation (fetal insulin suppresses surfactant synthesis).
  • Pulmonary embolism. Sudden dyspnea and pleuritic pain after immobility or surgery, with tachycardia and hypoxemia. The occluded vessel creates alveolar dead space, blood is diverted to other regions (V/Q mismatch), the A–a gradient widens, and hyperventilation usually produces respiratory alkalosis with a low PaCO2. A large embolus strains the right ventricle.
  • Carbon monoxide poisoning. A family with headache, nausea, and confusion in a house with a faulty heater in cold weather: SpO2 reads normal, PaO2 is normal, and co-oximetry shows elevated carboxyhemoglobin. Treat with 100% O2 by non-rebreather, which shortens CO's half-life from several hours to about an hour; hyperbaric oxygen for severe cases, pregnancy, or neurologic signs.
  • Opioid overdose — pure hypoventilation. Pinpoint pupils, a respiratory rate of 6, and a PaCO2 of 70: blunted central chemoreceptor drive lowers alveolar ventilation, PAO2 falls by the alveolar gas equation, and the A–a gradient stays NORMAL because the lung is healthy. Naloxone restores the drive; oxygen alone treats the number but not the hypercapnia.
  • High-altitude illness. A lowlander on a rapid ascent develops headache, nausea, and poor sleep (acute mountain sickness); worse cases progress to high-altitude pulmonary edema (patchy hypoxic vasoconstriction overperfuses the remaining capillaries) or cerebral edema. Descent is the definitive treatment; acetazolamide speeds acclimatization by inducing a bicarbonate diuresis that offsets the respiratory alkalosis, and nifedipine is used for HAPE.

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