Functional Anatomy of the Respiratory System & Diffusion of Gases😊

Functional Anatomy of the Respiratory System

Weibel's classification system:

• Divides the lower respiratory tract.
• 0 - 23

Resistance to Airflow

• Maximum resistance to airflow:
• Divisions 4-5.
• Lobar and segmental bronchi.
• Medium to large-sized bronchi.

• Airway resistance changes with lung volume:

Diffusion of Gases

• Transit time of blood in alveolar capillaries: 0.75 sec.

• Simple diffusion:
• Does not require ATP (Passive process).
• Should take place in ≤ 0.75 sec.

Factors Affecting Diffusion (Fick's Law)

Directly Proportional	Inversely Proportional
Concentration gradient (High → low)	Thickness respiratory membrane
Surface area of respiratory membrane	Size of particle
Lipid solubility of gas	ㅤ

Applied Aspects

Emphysema

• α1 antitrypsin deficiency → ↑ trypsin activity (Protease) → ↑ destruction of Rm → ↓ membrane surface area → ↓ diffusion of gases

Pulmonary Fibrosis

• Fibrosis → ↑ thickness of Rm → ↓ diffusion of gases

DLCO (Diffusion Lung Capacity of Carbon Monoxide)

• Test purpose:
• Assess diffusion capacity of lung using carbon monoxide (CO).

• CO: 
• ↑ affinity to Hb (210 x O₂ affinity).
• Diffusion of CO₂ → 20 times the solubility of O₂.

• Normal value: 
• 25 ml/min/mmHg

Conditions Affecting DLCO

Mechanics of the Respiratory System: Pressures

• Pleural Layers & Fluid:
• Alveolus → Visceral pleura → Intrapleural fluid → Parietal pleura → Chest wall.
• Intrapleural fluid amount: Approx. 10 to 20 ml.

Intrapleural pressure:

• Normally negative

• Value: Approx. 2.5 mm of mercury or 5 cm of water 
• measured at end of normal expiration

• Negative due to opposite elastic recoiling:
• Lung: Inward recoil.
• Chest wall: Outward recoil.

Transmural pressures (pressure differences):

• Measurement timing:
• Pressures typically taken at end of normal expiration.

Functional Residual Capacity (FRC):

• Air volume in lung at end of normal expiration.

• FRC = Expiratory Reserve Volume (ERV) + Residual Volume (RV).

• Aka Relaxation lung volume or Resting lung volume.

Lung and Chest Wall Compliance/Mechanics
(Pressure-Volume Curves)

Image-based questions (identify curves by y-axis intercept):

• Hysteresis

Ventilation Perfusion (VQ) Ratio

Ventilation-Perfusion (VQ) Ratio

Normal Values

• Alveolar ventilation: 4.2 L/min

• Perfusion (cardiac output to lungs): 5.4 L/min

• Average VQ ratio: 0.8

VQ Ratio in Upright Posture (due to gravity)

• Apex of lung: 3.3

• Middle of lung: 0.8

• Base of lung: 0.6

Note:

• Ventilation & Perfusion is maximum at the base

• Normal point:
• PO₂ ~ 100 mmHg
• PCO₂ ~ 40 mmHg

VQ Ratio → 0

• Cause: Bronchial obstruction (Ventilation = 0, Perfusion = intact)

• Alveolar gas composition:
• PO₂ ~ 40 mmHg
• PCO₂ ~ 46 mmHg
• Similar to venous blood gas

VQ Ratio → ∞

• Cause: Pulmonary embolism (Perfusion = 0, Ventilation = intact)

• Alveolar gas composition:
• PO₂ ~ 150 mmHg
• PCO₂ ~ 0.3 mmHg
• Similar to inspiratory air

• Represents alveolar dead space

• Vapour pressure at body temp = 47

• P for P → Perfusion limited → Plateau

• CO → diffusion limited

Respiratory Formulas

Factors Affecting Diffusion (Fick's Law)

Directly Proportional	Inversely Proportional
Concentration gradient (High → low)	Thickness respiratory membrane
Surface area of respiratory membrane	Size of particle
Lipid solubility of gas	ㅤ

Static Lung Volumes and Capacities

Volumes/Capacities not measurable by standard spirometry

• RV, FRC, TLC (any containing RV)

Dynamic Lung Volumes and Capacities
(Flow-Volume Loop)

Maneuver Sequence

• Normal breathing → Deep inspiration → Pause → Forceful expiration

Flow-Volume Loop in Diseases:

Differentiation of Lung Diseases using Spirometry

Stepwise Chain for Diagnosis Based on PFT

• Step 1: Check FEV1/FVC Ratio
• ↓ Reduced → Obstructive pattern
• ↑ Increased / Normal → Restrictive pattern

• Step 2: If Obstructive (↓ FEV1/FVC) → Check TLC
• ↑ Increased TLC → Suggests Emphysema
• Normal TLC → Suggests Asthma

• Step 3: If Restrictive (↑ FEV1/FVC or Normal) → Check RV
• ↓ RV → Parenchymal Restriction (Fibrosis)
• ↑ RV → Extra-Parenchymal Restriction (e.g. Myasthenia Gravis)

• Step 4: Check DLCO (Diffusion Capacity)
• ↑ DLCO → Asthma (increased pulmonary blood volume)
• ↓↓ DLCO → Emphysema (diffusion defect due to alveolar wall destruction)
• ↓ DLCO → Fibrosis
• ↓ DLCO → Also seen in Extra-Parenchymal but less specific

Upper airway obstructions:

• BOX → Look like car(scar) , thyroid, FB

• Mala → mukalil poi Kuuuuu kuuki → Vocal cord poi (paralysis), Pharyngeal muscles paralysed ayi → pani vann (LN)

• Paranna pradesham → tumor () varumbo truck (Tracheomalacia) odikkum

Compliance of the Lung

• Compliance (C): 
• C = ΔV / ΔP

Compliance	Interpretation	Disease
High compliance curve	Lung expands easily	Emphysema
Low compliance curve	Lung stiff, hard to expand	Lung fibrosis, Restrictive lung disease

Surfactant:

• More surfactant → More compliance

Oxygen Transport and Oxygen-Hemoglobin Dissociation Curve (ODC)

Positive co-operativity

• Shape: Sigmoid curve
• Due to Cooperative binding of O₂ to hemoglobin

• P₅₀ value:
• PO₂ at which Hb is 50% saturated with O₂
• Normal: 23–26 mmHg

• At Normal arterial PO₂:
• 98–100 mmHg ⇒ Hb saturation ~97%

2,3-DPG and Hemoglobin Oxygen Affinity

• 2,3-DPG binds β-chains of Hb
• Decreases O₂ affinity
• Promotes O₂ release to tissues
• 2,3 BPG / DPG = Currency for O2 excahnge

Right shift of ODC:

• Means: Increased P50 value

• Indicates: Decreased oxygen affinity of hemoglobin.

• Effect: Increased release (unloading) of oxygen to tissues.

Causes:

• Increased 2,3-DPG.

• Increased temperature.

• Increased carbon dioxide.

• Increased acidosis
• Bohr effect: Right shift due to increased H+ or CO2.
• Haldane effect: ↑ O2 → ↑ CO2 released by Hb → ↓↓ CO2 content

Physiological Significance of 2,3-BPG / 2,3 DPG

• Maintains taut state of haemoglobin.

• Binds to β-chains of globin of HbA → facilitates O₂ release at tissues.

• Shifts the ODC to the right.

• HbF has α and γ chains
• unaffected
• favor O₂ absorption from maternal blood.

• Factors increasing
• Anemia, hypoxia, high altitude,
• exercise, hyperthyroidism, ↑↑ growth hormone/androgen,
• Inosine, pyruvate, phosphate.

Left shift of ODC:

• Means: Decreased P50 value.

• Indicates: Increased oxygen affinity of hemoglobin.

• Effect: Decreased release (unloading) of oxygen to tissues.

Causes:

• Decreased 2,3-DPG.

• Decreased temperature.

• Decreased carbon dioxide.

• Decreased acidosis

Other causes:

• Fetal hemoglobin (HbF) 
• Gamma chains (instead of Beta chains)
• bind 2,3-DPG less effectively

• Storage of blood
• Normally → ↓ 2,3 DPG
• CPDA (Citrate Phosphate Dextrose Adenine)
• Superior for blood storage bcz
• A/w less fall in 2,3 DPG
• Improved Viability of Red Blood Cells
• It is less acidic

• Carbon Monoxide (CO) Poisoning
• CO binds Hb with 250× higher affinity than O₂
• Causes left shift of ODC
• Increases O₂ affinity of remaining sites → impairs O₂ release to tissues

• Methemoglobinemia
• Hb iron oxidized to Fe³⁺ → can't bind O₂
• Remaining sites bind O₂ more tightly → left shift
• Result: impaired O₂ delivery

• Thalassemia
• Abnormal or reduced globin chains
• Alters Hb function

Anemia and Oxygen Curves

• Anemia:
• Curve similar shape to normal
• but lower oxygen content.

• Anaemia:
• Does not change Saturation curve
• Saturation depends on PO2, which is normal

O₂-Myoglobin Dissociation Curve

• Rectangular hyperbola

• Function: O₂ storage in muscles.

• 1 myoglobin
• binds to 1 O₂ molecule (1:1 ratio).

• No cooperativity.

CO₂ Dissociation Mechanism

Transport Steps

• PCO₂:
• Tissue: 45 mm Hg → Plasma: 40 mm Hg.
• CO₂ diffuses from Tissue → Interstitial fluid → Plasma → RBC.

Reactions in RBC (Venous Blood)

• CO₂ + H₂O → Carbonic anhydrase → H₂CO₃ (Carbonic acid).

• H₂CO₃ → H⁺ + HCO₃⁻.

• H⁺ 
• Buffered by Hb ⇒ Forms carbamino Hb.

• HCO₃⁻:
• Leaves RBC for plasma via Anion exchanger.
• In Plasma → Accounts for 70% of CO₂ transport

Cl⁻ Shift (Hamburger Phenomenon)

• Cl⁻ moves into RBC
• To maintain electroneutrality as HCO₃⁻ exits
• Cl⁻ is osmotically active
• RBC swells
• Consequence: ↑ Hematocrit/PCV of venous blood by 3%.

CO₂ Dissociation Curve

• Transport capacity: 
• 4 ml CO₂ transported per 100ml of blood
• from arteries to veins.

• Pressure difference:
• Between arterial (PaCO₂ = 40 mm Hg) and venous blood (PvCO₂ = 45 mm Hg).