Gas Exchange & Transport – Comprehensive Study Notes

Learning Objectives

• How O2 and CO2 move between atmosphere

• tissues

  • Bulk flow

  lungs; diffusion

  across A/C membrane; perfusion

  to tissues.

• Determinants of alveolar O2 (P{AO2}) & CO2 (P{ACO2})

  • Calculation of P_{AO2} via Alveolar-Air Equation.

• Normal regional (gravity-dependent) \frac{V}{Q} variations & their effects on gas exchange.

• Computing total arterial O2 content C{aO2}.

• Factors altering the arteriovenous O2 content difference \Delta C{(a-v)O_2} \approx 5\;\text{mL·dL}^{-1}.

• Variables that shift the HbO_2 dissociation curve and thus control loading/unloading.

• Three blood transport forms for CO_2; role of Haldane effect.

• Inter-relationship between O2 & CO2 carriage.

• Causes & recognition of impaired O2 delivery or CO2 removal.

Introduction to Respiration

• Definition: sequential movement of O2 to tissues for aerobic metabolism + removal of metabolic CO2.

• Two exchange sites

  • Lungs: atmosphere

blood.

• Peripheral tissues: blood

cells.

Diffusion Basics

• Whole-body gradients drive passive diffusion.

• O2 cascade: P{O2}:\;159\;\text{mmHg (air)} \to \sim5\;\text{mmHg (mitochondria)}.

• CO2 gradient reversed: P{CO2}:\;\sim60\;\text{mmHg (cell)} \to 1\;\text{mmHg (air)}.

Determinants of Alveolar Gas Tensions

Alveolar CO_2

• P{ACO2} varies directly with metabolic CO2 production and inversely with alveolar ventilation (\dot V_A).

• \uparrow physiologic dead space (V_D) (e.g., pulmonary embolus)

\uparrow P_{ACO2}.

• Normal range: 35–45\;\text{mmHg}.

Alveolar O_2

• Primary driver: inspired partial pressure P_{IO2}.

• Dilution by H2O vapor (47 mmHg at 37 °C) + alveolar CO2.

• Alveolar-Air Equation:
  P{AO2}=F{IO2}(PB-47)-\frac{P{ACO2}}{0.8}

• When F{IO2}>0.60, the CO2 term can be omitted.

Alveolar N_2

• By Dalton’s law:
  P{AN2}=PB-(P{AO2}+P{ACO2}+P_{H2O}).

• With constant F{IO2}, P{AO2} varies inversely with P{ACO2} because PB & P_{H2O} are fixed.

Mechanisms & Limits of Diffusion across A/C Membrane

• Barriers: alveolar epithelium

interstitial space

capillary endothelium

RBC membrane.

• Fick’s Law: \dot V{gas}=\frac{A\,D\,(P1-P_2)}{T} (A = area, D = diffusing constant, T = thickness).

• Transit time

  • Rest: blood in pulmonary capillary

  0.75\;s.

  • Heavy exercise: \downarrow to 0.25\;s.

  • Equilibration normally complete by 0.25\;s

diffusion reserve.

• Any diffusion limitation or further \downarrow transit (e.g., tachycardia, fibrosis) threatens equilibration.

Variations from Ideal Gas Exchange

Anatomic Shunts

• Bronchial & Thebesian veins drain de-oxygenated blood directly into left heart

PaO2 5–10 mmHg below P{AO2}.

Dead Space Definitions

• Anatomic dead space: conducting airways to terminal bronchioles (\approx150\;\text{mL}).

• Alveolar dead space: ventilated alveoli lacking perfusion.

Regional \frac{V}{Q} Inequality (Gravity Effects)

• Ideal \frac{V}{Q} =1.

• Apices: \frac{V}{Q}\approx3.3

  • \uparrow P{AO2}\,(\sim132\;\text{mmHg}); \downarrow P{ACO2}\,(\sim32\;\text{mmHg}).

• Bases: \frac{V}{Q}\approx0.66

  • Ventilation \uparrow but perfusion
    cancel{} \uparrow\uparrow (\times20)

\downarrow P{AO2}\,(\sim89\;\text{mmHg}); \uparrow P{ACO2}\,(\sim42\;\text{mmHg}).

Oxygen Transport

Forms

1. Physically dissolved

   • Henry’s Law: \text{mL O}2\,/\,\text{dL}=0.003\times P{O2}(\text{mmHg}).

2. Chemically bound to Hb

   • Capacity: 1.34\;\text{mL O}_2\,\text{·g}^{-1}\;Hb.

   • Approximately 70
     \times more O_2 carried bound vs dissolved.

Hemoglobin Saturation & Dissociation Curve

• S{aO2}=\frac{HbO2}{Hb_{total}}\times100; normal 95–100 %.

• Sigmoid curve

  • Flat plateau (>90 % S{aO2}) safeguards loading at lungs even if P{aO2} drops.

  • Steep limb (<90 %) aids unloading in tissues.

Total Arterial O_2 Content

• C{aO2}=(0.003\,P{aO2})+(1.34\,Hb\,S_{aO2})

• Normal: 16–20 {\text{mL·dL}}^{-1}.

• Arterio-venous difference: \sim5\;\text{mL·dL}^{-1}.

Factors Shifting the HbO_2 Curve

• pH (Bohr effect)

  • \downarrowpH (\uparrow H^+)

right shift

\downarrow affinity

\uparrow unloading.

• Tissue pH

  7.37; lung pH

  7.40.

  • Temperature

• \uparrowT

right shift (meets \uparrow metabolic need).

• \downarrowT

left shift (\downarrow demand).

• 2,3-DPG

  • \uparrow2,3-DPG (e.g., chronic hypoxemia)

right shift.

• Stored banked blood loses 2,3-DPG

risk impaired unloading.

• Abnormal Hemoglobins

  • HbS: sickling, hemolysis; ACS major mortality.

  • HbCO: CO binds 200
    \times > O2; displaces O2 + left shift; Tx = hyperbaric O_2.

  • MetHb (Fe^{3+}): cannot bind O_2; drugs (NO, NTG, lidocaine) induce; monitor metHb%.

Carbon Dioxide Transport

• Total carriage: 45–55 {\text{mL·dL}}^{-1}

1. Dissolved (\approx8\;\%): high solubility.

2. Carbamino compounds (\approx12\;\%): binds terminal amino groups on proteins/Hb.

3. Bicarbonate (\approx80\;\%): via hydrolysis (CO2+H2O \leftrightarrow H2CO3 \leftrightarrow H^+ + HCO_3^-).

   • Reaction accelerated by carbonic anhydrase inside RBCs.

   • HCO_3^- exits RBC in exchange for Cl^- (chloride shift / Hamburger phenomenon).

CO_2 Dissociation Curve & Haldane Effect

• As Hb is oxygenated in lungs, capacity for CO_2 falls

facilitates unloading.

• In tissues, deoxygenated Hb binds more CO_2 (carbamino) and buffers H^+.

Abnormalities of Gas Exchange & Transport

Inadequate O_2 Delivery

• \dot D{O2}=C{aO2}\times CO

• Hypoxemia etiologies

  • Low \frac{V}{Q} (most common)

  high \frac{V}{Q} areas cannot fully compensate due to plateau of HbO_2 curve.

  • Hypoventilation, diffusion limitation, anatomic/physiologic shunt, low (P_{IO2}) (altitude).

• Hemoglobin Deficiency

  • Absolute: true anemia

\downarrow[Hb].

• Relative: O_2 displacement (CO), abnormal Hb variants (MetHb, HbS).

  • Low Blood Flow

• Shock

global hypoxia; ischemia

localized (may progress to infarction, metabolic acidosis).

• Dysoxia (Cytopathic hypoxia)

  • Normal \dot D{O2} yet cells cannot utilize O2 (e.g., cyanide poisoning, severe sepsis/ARDS).

  • Low extraction ratio (\frac{\dot V{O2}}{\dot D{O2}}).

Impaired CO_2 Removal

• \downarrow \dot V_A relative to metabolic rate.

  • Hypoventilation: \downarrow V_T (opioids), rarely \downarrow f.

  • \uparrowDead-space fraction (\frac{VD}{VT}): rapid shallow breathing or \uparrowphysiologic dead space (PE).

• If compensatory \uparrow\dot V_E fails

hypercapnia & respiratory acidosis.

• In chronic severe disease (e.g., COPD) \uparrow \frac{V}{Q} mismatch with limited ventilatory reserve leads to chronic hypercarbia