How oxygen is carried in blood — hemoglobin does almost all the work
Oxygen is transported in two ways: 98% bound to hemoglobin (oxyhemoglobin) and 2% dissolved in plasma. Each hemoglobin molecule carries 4 O2 molecules (one per heme group). Oxygen content = (Hgb × 1.34 × SaO2) + (0.003 × PaO2). Normal = ~20 mL O2/100 mL blood. SpO2 (pulse ox) measures saturation, not content — anemia patient can have 100% saturation but low O2 content (not enough Hgb). This is why Hgb level matters for oxygen delivery, not just SpO2.
Hgb binding
1.34 mL O2 per gram of Hgb at full saturation. 4 O2 per Hgb molecule.
Dissolved O2
0.003 mL per mmHg PaO2 — tiny contribution but measured by ABG.
Anemia trap
SpO2 100% but low Hgb → low O2 delivery. Content not saturation is what matters.
CO poisoning
CO binds Hgb 240× stronger than O2 → SpO2 reads normal → patient hypoxic. Give 100% O2.
Oxyhemoglobin Dissociation Curve
CADET face RIGHT — CO2, Acid, DPG, Exercise, Temp shift RIGHT
Right shift = decreased O2 affinity = O2 released to tissues
What shifts the oxygen-hemoglobin curve — and what each shift means
The S-shaped oxyhemoglobin dissociation curve shows hemoglobin saturation vs PO2. Right shift: hemoglobin releases O2 more easily (good for exercising muscle). Causes: increased CO2 (Bohr effect), decreased pH (acidosis), increased 2,3-DPG, increased temperature, exercise. Left shift: hemoglobin holds O2 more tightly (Hgb grabs O2 at lungs). Causes: low CO2, alkalosis, fetal hemoglobin (HbF), CO poisoning, decreased temperature. P50 = PO2 at which Hgb is 50% saturated. Normal P50 = 27 mmHg. Increased P50 = right shift.
CO2↓, pH↑, HbF, CO, Temp↓ → O2 held tightly. Good for placenta (HbF grabs O2 from mother).
Bohr effect
CO2 and H+ reduce Hgb-O2 affinity → right shift → O2 delivered to active tissues.
2,3-DPG
Increases in chronic hypoxia, anemia → right shift → more O2 released to tissues.
CO2 Transport
70-23-7 — Bicarbonate · Hgb · Dissolved
70% as HCO3- · 23% on hemoglobin · 7% dissolved
Three ways CO2 is carried in blood — bicarbonate dominates
CO2 is transported in three forms. 70% as bicarbonate (HCO3-): CO2 + H2O → H2CO3 → H+ + HCO3- (catalyzed by carbonic anhydrase in RBCs). HCO3- exits RBC via chloride shift (Cl- enters). 23% as carbaminohemoglobin: CO2 binds amino groups of Hgb (not heme — different site from O2). 7% dissolved in plasma. Haldane effect: deoxygenated Hgb carries more CO2 — at tissues where O2 is released, Hgb picks up CO2 more efficiently.
Bicarbonate (70%)
CO2 + H2O → HCO3- + H+. Carbonic anhydrase in RBCs. Chloride shift.
Carbamino (23%)
CO2 binds amino groups of Hgb. Deoxy-Hgb carries more (Haldane effect).
Dissolved (7%)
In plasma. PaCO2 measures this — drives the other two forms.
Chloride shift
HCO3- exits RBC → Cl- enters to maintain electrical neutrality.
Ventilation-Perfusion Matching
V/Q = 1 is perfect · Dead space V/Q = ∞ · Shunt V/Q = 0
Ventilation/Perfusion ratio — matching air to blood flow
V/Q ratio — the key concept behind respiratory failure and lung disease
Optimal gas exchange requires matching ventilation (V) to perfusion (Q). V/Q = 1 is ideal. Dead space: alveoli ventilated but not perfused (V/Q = ∞) — no gas exchange possible. Pulmonary embolism creates dead space. Shunt: alveoli perfused but not ventilated (V/Q = 0) — deoxygenated blood bypasses gas exchange. Pneumonia, atelectasis, pulmonary edema create shunt. Gravity: apex of lung has highest V/Q (least perfusion), base has lowest V/Q (most perfusion). V/Q mismatch is the most common cause of hypoxemia.
Dead space
V/Q = ∞. Ventilated, not perfused. PE, emphysema. Raises PaCO2.
High V/Q — well ventilated, poorly perfused. TB favors apex (high O2).
Base
Low V/Q — less ventilated, well perfused. Aspiration pneumonia favors base.
Acid-Base Interpretation
ROME — Respiratory Opposite · Metabolic Equal
In respiratory disorders pH and CO2 move opposite · In metabolic pH and HCO3 move together
How to interpret any acid-base disorder using ROME
ROME is the fastest way to identify acid-base disorders. Respiratory: pH and CO2 move in OPPOSITE directions. pH down + CO2 up = respiratory acidosis. pH up + CO2 down = respiratory alkalosis. Metabolic: pH and HCO3 move in the SAME (Equal) direction. pH down + HCO3 down = metabolic acidosis. pH up + HCO3 up = metabolic alkalosis. Then check for compensation — the body always compensates in the same direction as the primary disorder to minimize pH change. Compensation never fully corrects pH to normal.
Dipalmitoylphosphatidylcholine (DPPC) produced by type II pneumocytes
What surfactant does — and why premature infants can't breathe without it
Surface tension in alveoli would cause them to collapse (smaller alveoli have higher pressure — LaPlace's Law). Surfactant (DPPC) is produced by type II alveolar cells — it reduces surface tension, preventing collapse. Without surfactant, the work of breathing increases dramatically. Premature infants (born before 34–36 weeks) lack surfactant → respiratory distress syndrome (RDS/hyaline membrane disease) → blue baby who grunts with each breath. Treatment: synthetic surfactant down the endotracheal tube and antenatal corticosteroids to accelerate surfactant production.
Type II cells
Produce surfactant. Also regenerate type I cells (gas exchange) after injury.
LaPlace's Law
P = 2T/r. Smaller alveoli have higher collapse pressure — surfactant equalizes this.
Exogenous surfactant ET tube + antenatal corticosteroids (betamethasone) to mature lungs.
Control of Breathing
CO2 drives breathing normally · O2 drives in COPD
Central chemoreceptors detect CO2/H+ · Peripheral detect O2, CO2, pH
What controls breathing rate — and the critical COPD exception
Breathing is controlled by the respiratory center in the medulla (pre-Bötzinger complex). Normal drive: central chemoreceptors in the medulla detect rising CO2 (as H+ in CSF) → increased ventilation. CO2 is the primary driver of breathing in healthy people. COPD exception: chronic CO2 retention → central chemoreceptors adapt and become insensitive to CO2 → the patient's ONLY drive to breathe is hypoxia (low O2) detected by peripheral chemoreceptors (carotid and aortic bodies). Giving high-flow O2 to a COPD patient may eliminate their hypoxic drive → apnea (the "hypoxic drive" phenomenon — controversial but clinically important to know).
Central receptors
Medulla — detect CO2/H+ in CSF. Primary drive. Adapt in chronic hypercapnia.
Peripheral receptors
Carotid + aortic bodies — detect O2↓, CO2↑, pH↓. Respond to severe hypoxia.
COPD drive
Chronic CO2 retainer — hypoxic drive may be primary. Cautious O2 therapy.
Four basic lung volumes and how they combine into capacities
TV (tidal volume) = ~500 mL normal breath. IRV (inspiratory reserve) = extra air you can inhale. ERV (expiratory reserve) = extra air you can exhale. RV (residual volume) = air always remaining in lungs (~1200 mL, can't be exhaled). TLC = TV + IRV + ERV + RV. VC = TLC - RV.
TTidal Volume = ~500 mL/breath
VVital Capacity = TV + IRV + ERV
IIRV = inspiratory reserve volume
RRV = residual volume (never exhaled)
Oxygen-Hemoglobin Curve Shifts
CADET — CO2 · Acid · DPG · Exercise · Temp → Right shift
📌 Gas Transport
Right shift = O2 unloads easier (good for tissues); left shift = hemoglobin holds O2 tighter
Right shift (↓ affinity, ↑ O2 delivery to tissues): ↑ CO2, ↑ H+ (acidosis), ↑ 2,3-DPG, ↑ temperature. Left shift (↑ affinity, ↓ O2 release): ↓ CO2, alkalosis, ↓ temp, fetal Hb. Bohr effect: acidosis shifts curve right → more O2 delivered to active tissues.
CCO2 increase → right shift
AAcidosis (↑H+) → right shift
DDPG increase → right shift
EExercise → right shift
TTemperature increase → right shift
Ventilation-Perfusion (V/Q)
Match = gas exchange · Mismatch = dead space or shunt
📌 V/Q Ratio
V/Q matching is essential for gas exchange — mismatches cause hypoxemia
Normal V/Q = ~0.8. V/Q = 0 (shunt): perfusion but no ventilation (pneumonia, atelectasis) → deoxygenated blood passes through. V/Q = ∞ (dead space): ventilation but no perfusion (pulmonary embolism) → wasted ventilation. Lung apices have higher V/Q; bases have lower V/Q.
VVentilation = air reaching alveoli
QPerfusion = blood reaching alveoli
0V/Q = 0 = shunt (no air)
∞V/Q = ∞ = dead space (no blood)
Respiratory Control
CO2 drives breathing — O2 is backup
📌 Neural Control
The primary drive to breathe is CO2/pH, not oxygen — except in COPD patients
Central chemoreceptors (medulla): respond to CO2/H+ → primary breathing drive. Peripheral chemoreceptors (carotid + aortic bodies): respond to O2, CO2, pH. In healthy people, CO2 drives breathing. In COPD with chronic hypercapnia: body resets CO2 threshold → hypoxic drive takes over → giving high O2 can suppress breathing!
CCO2 = primary breathing stimulus
OO2 = backup (peripheral receptors)
PCOPD = hypoxic drive (danger with O2)
🎓 Common Exam Questions
Q: What is the difference between obstructive and restrictive lung disease on spirometry?
A: Obstructive (COPD, asthma, bronchiectasis): airflow limited on expiration → ↓ FEV1, normal or ↓ FVC → FEV1/FVC < 0.70 (diagnostic). Air trapping → ↑ RV, ↑ TLC. COPD: irreversible (emphysema destroys alveolar walls → ↓ elastic recoil + chronic bronchitis → mucus obstruction). Asthma: reversible with bronchodilators. Restrictive (pulmonary fibrosis, obesity, neuromuscular, pleural disease): all volumes reduced → ↓ TLC, ↓ FVC, ↓ FEV1, but FEV1/FVC normal or ↑. Intrinsic restrictive (fibrosis, sarcoid): ↓ compliance. Extrinsic (obesity, kyphoscoliosis, neuromuscular): normal compliance. DLCO: ↓ in emphysema and fibrosis; normal in asthma.
Q: How is oxygen transported in the blood and what happens in CO poisoning?
A: Oxygen transport: 98% bound to hemoglobin (each Hb carries 4 O2; 1 g Hb carries 1.34 mL O2 when fully saturated). 2% dissolved in plasma (Henry's law). O2 content = (Hb × 1.34 × SaO2) + (0.003 × PaO2). Anemia: ↓ Hb → ↓ O2 content despite normal PaO2 and SaO2. CO poisoning: CO binds Hb 250× more tightly than O2 → forms carboxyhemoglobin → ↓ O2 carrying capacity + left-shift of curve (remaining Hb holds O2 tighter) → tissue hypoxia. Pulse ox reads HbCO as oxyHb — falsely normal! SaO2 appears normal but patient is hypoxic. Treat with 100% O2 (competes with CO) or hyperbaric O2.
Q: What is the physiologic basis of hypoxemia and how do you distinguish the causes?
A: Five mechanisms: (1) Low FiO2 (high altitude) — ↓ PaO2, responds to O2. (2) Hypoventilation (↑ PaCO2 → ↓ PaO2 by alveolar gas equation) — normal A-a gradient, responds to O2. (3) V/Q mismatch (most common) — ↑ A-a gradient, partially responds to O2. (4) Shunt — ↑ A-a gradient, does NOT respond to 100% O2 (blood bypasses alveoli). (5) Diffusion impairment (fibrosis) — ↑ A-a gradient, responds to O2. A-a gradient = PAO2 − PaO2 (normal ≤10–15 mmHg in young). Elevated A-a gradient = problem is in the lung (V/Q mismatch, shunt, diffusion). Normal A-a = problem is upstream (hypoventilation, low FiO2).
Q: How does the body regulate respiration at rest and during exercise?
A: At rest: central chemoreceptors in medulla respond to CO2/H+ in CSF — primary drive. Peripheral chemoreceptors (carotid and aortic bodies) respond to ↓ PaO2 (<60 mmHg), ↑ PaCO2, ↓ pH. In COPD: chronic CO2 retention → central receptors reset → hypoxic drive (peripheral O2 sensing) becomes primary — danger of giving high O2. During exercise: ventilation increases dramatically. Not primarily driven by ↑ CO2 or ↓ O2 (both remain near normal) — primarily driven by neural signals from motor cortex (central command) and proprioceptors in muscles/joints. CO2 production ↑ in proportion to O2 consumption → ventilation matches precisely → no hypoxemia or hypercapnia in healthy exercising person.
Q: What are the major complications of mechanical ventilation and how are they prevented?
A: Ventilator-associated pneumonia (VAP): most common infectious complication. Prevention: head of bed elevation 30–45°, oral decontamination, minimize sedation, daily spontaneous breathing trials. Barotrauma/volutrauma: high airway pressures or tidal volumes → alveolar rupture → pneumothorax, pneumomediastinum, subcutaneous emphysema. Prevention: lung-protective ventilation (tidal volume 6 mL/kg ideal body weight, plateau pressure <30 cmH2O) — proven to reduce mortality in ARDS. Oxygen toxicity: FiO2 >0.6 for prolonged periods → free radical injury → worsening ARDS. Goal: lowest FiO2 to maintain SpO2 88–95%. Hemodynamic compromise: positive pressure reduces venous return → ↓ CO → hypotension — especially with PEEP.