34.PULMONARY STRUCTURE & MECHANICS

REGIONS OF RESPIRATORY TRACT

1. The 3 regions of the respiratory tract (must-know)

Just memorize this ladder:

1. Upper airway
• Nose → nasal cavity → mouth → pharynx → larynx
2. Conducting airway
• From larynx down through trachea, bronchi, bronchioles (air pipes only, no gas exchange).
3. Alveolar airway (lung parenchyma / acinar tissue)
• Alveoli = gas exchange region.

👉 Exam trigger:

If you see “acinar tissue / parenchyma” → think alveoli + gas exchange.

If you see “conducting airway” → think pipes, no exchange.

2. Jobs of the nose & upper airway (super important)

The nose is the main entry point for air, so its lining gets hit by the highest dose of:

• Allergens
• Toxic chemicals
• Dust/particulate matter

Core functions (this is gold):

1. Filter big particles
2. Warm the air
3. Humidify (moisten) the air

👉 So by the time air reaches the delicate lower airways and alveoli, it’s:

• Cleaner
• Warm
• Moist

That protects the lungs.

3. Particle sizes – what gets stuck where?

Very exammable idea: different sizes stop at different levels.

• > 30–50 µm
• Too big → usually don’t get inhaled through the nose at all.
• ≈ 5–10 µm
• Can enter the nose and pharynx
• Impact on nasopharynx and upper conducting airway
• They don’t follow the curve of the airstream going down into lungs → instead they slam into the wall (especially near tonsils/adenoids).

Where do they stick?

• They settle on mucous membranes of:
• Nose
• Pharynx
• Around tonsils & adenoids (lymphoid tissue).

4. Immune angle (why tonsils & adenoids are sitting there)

• Tonsils and adenoids = big lymphoid (immune) organs in the back of the pharynx.
• Particles + microbes hit and stick there → the immune system samples them.

So the logic:

Air comes in dirty → nose & upper airway trap particles in mucus → deliver them to lymphoid tissue (tonsils/adenoids) sitting in the “traffic path” to handle invaders.

CONDUCTING AIRWAY

1. What is the conducting airway exactly?

• Starts at the trachea.
• Branches ~16 generations → bronchi → bronchioles → terminal bronchioles.
• Function: conduct air, not gas exchange (that’s the respiratory/acinus zone).

If the question says:

“Conducting zone”

You should think:

Trachea → bronchi → bronchioles → terminal bronchioles (first 16 generations).

2. Wall structure – the “airway mucosa” & supporting layers

Core layers to remember:

• Mucosal epithelium
• Basement membrane
• Lamina propria

👉 These together = airway mucosa

Below that:

• Smooth muscle layer
• Connective tissue + cartilage
• More cartilage in larger bronchi
• Cartilage disappears as you go to small bronchioles/terminal bronchioles
• Smooth muscle becomes more prominent in bronchioles

Very exam-type line:

Glands & cartilage are absent in bronchioles and terminal bronchioles; smooth muscle is important here.

3. Key cell types – who does what?

Proximal conducting airway (bronchi)

Epithelium is:

• Pseudostratified ciliated epithelium

Main cells:

• Ciliated cells → beat mucus upwards.
• Goblet cells + submucosal glands (glandular acini)
• Make mucus and other secretions.
• Basal cells
• Stem / progenitor cells → replace damaged epithelium.

Distal conducting airway (bronchioles & terminal bronchioles)

Changes you MUST know:

• No secretory glands in bronchioles/terminal bronchioles.
• Cartilage largely absent.
• Smooth muscle more important (hence bronchiolar constriction in asthma etc.).
• Club cells (Clara cells)
• Non-ciliated cuboidal cells
• Secrete defence molecules
• Act as progenitor cells after injury

If an MCQ says “non-ciliated cuboidal cells in terminal bronchioles acting as progenitors” → Club cells.

4. Defence chemicals from airway epithelium (innate immunity)

Airway epithelial cells secrete a lot of defence molecules:

• IgA (secretory immunoglobulin A)
• Collectins: esp. Surfactant proteins A & D (SP-A, SP-D)
• Defensins & other antimicrobial peptides/proteases
• Reactive oxygen species (ROS)
• Reactive nitrogen species (RNS)
• Chemokines and cytokines

What do they do?

• Direct antimicrobial action → kill/inhibit microbes.
• Recruit immune cells → through chemokines/cytokines (neutrophils, macrophages, etc.).

The big idea:

The airway lining is not passive tubing; it’s an active immune organ.

5. Mucociliary escalator – the cleaning conveyor belt

Where?

• From anterior third of the nose → up to the start of respiratory bronchioles = ciliated epithelium.

How it works:

• Cilia:
• Sit in a periciliary fluid layer
• Beat at ~10–15 Hz
• On top of cilia: a mucus layer
• Made of proteins + polysaccharides from goblet cells & glands
• Traps foreign particles

Cilia beat → move mucus away from the lungs:

• Clearance rate: ≥ 16 mm/min (just remember: it’s fast enough to continuously clear).

Name for this system:

Mucociliary escalator = mucus (trap) + cilia (transport).

If this fails?

• In smokers
• In genetic ciliary defects
• In diseases like cystic fibrosis (thick sticky mucus + poor clearance)

→ Mucus transport nearly absent →

• Chronic sinusitis
• Recurrent lung infections
• Bronchiectasis

6. Particle size + reflexes

Smaller particles:

• Size ~2–5 µm
• Can go past upper airway and reach bronchi
• As airflow slows in smaller tubes, they fall on bronchial walls

What can happen:

• Reflex bronchoconstriction
• Cough
• Or they are cleared upwards by mucociliary escalator

7. Autonomic & sensory innervation – control of airway calibre & secretions

Sensory nerves

• Nerve endings in airway walls detect:
• Dust, cold air, toxic gases, cigarette smoke etc.
• Send signals to respiratory centers → trigger:
• Cough reflex
• Sneeze reflex (upper airway)
• Receptors show rapid adaptation → they stop firing continuously, so you don’t cough non-stop.

Autonomic receptors

• β₂-adrenergic receptors:
• Cause bronchodilation
• Increase mucus/bronchial secretions
• α₁-adrenergic receptors:
• Inhibit secretions

So:

• β₂ = open airway + more secretions
• α₁ = less secretions

ALVEOLAR AIRWAY

1. Big picture: What is the alveolar airway?

• From trachea → alveolar sacs, the airways divide 23 times.
• The last 7 generations = transitional + respiratory zone =
• Respiratory bronchioles
• Alveolar ducts
• Alveoli
• These are the gas exchange regions (not just conducting).

Key geometry ideas:

• Cross-sectional area:
• Trachea ≈ 2.5 cm²
• Alveoli total ≈ 11,800 cm²
• Because area ↑ huge → airflow velocity in small airways becomes very low → allows time for gas exchange.
• Humans have about 300 million alveoli, giving ~70 m² of surface area (like a tennis court) for gas exchange.

👉 Exam thought:

“Large total area + slow airflow + thin barrier = efficient gas exchange.”

2. Alveolar cell types – Type I vs Type II

Type I pneumocytes

• Flat, thin cells with wide cytoplasmic spread.
• Cover ~95% of the alveolar surface area.
• Main job: form the thin gas-exchange surface.

Type II pneumocytes

• Thicker, more cuboidal (“granular” cells).
• Only ~5% of surface area, but ~60% of epithelial cells numerically.
• Two big roles:
1. Produce surfactant
2. Act as progenitor cells for repair (can divide and replace damaged Type I and II cells).

3. Surfactant – what it is and how it behaves

Made by Type II cells:

• They produce lamellar bodies = phospholipid-packed organelles.
• These are secreted into alveolar lumen → form tubular myelin → then a phospholipid film lining the alveolar surface.

Orientation:

• Hydrophobic fatty acid tails face the alveolar air (lumen).

Main function:

Reduce surface tension → prevents alveoli from collapsing and helps them stay open.

Important relationship:

• Surface tension ∝ 1 / (surfactant concentration per unit area).

So:

• During inspiration → alveoli enlarge → surfactant molecules spread apart → surface tension increases.
• During expiration → alveoli shrink → surfactant molecules come closer together → surface tension decreases → helps prevent collapse.

Recycling:

• Some surfactant protein-lipid complexes are taken back into Type II cells by endocytosis and recycled.

4. Blood–gas barrier – why gas exchange is so efficient

• Alveoli are surrounded by a dense network of pulmonary capillaries.
• In most regions, air and blood are separated only by:
• Alveolar epithelium
• Capillary endothelium
• Distance between air and blood ≈ 0.5 µm.

This extremely thin barrier + huge surface area + slow airflow = very efficient gas exchange.

5. Alveolar macrophages (PAMs) – the “cleaners” of the alveoli

Also inside the alveoli:

• Pulmonary alveolar macrophages (PAMs / AMs)
• Also some lymphocytes, plasma cells, neuroendocrine cells, mast cells, but for marks: focus on macrophages.

Key points on PAMs:

• Derived from bone marrow (like other macrophages).
• Actively phagocytic → eat small particles that escaped the mucociliary escalator.
• Functions:
• Ingest dust/particles/microbes in alveoli.
• Process inhaled antigens for immune attack (antigen presentation).
• Secrete substances that:
• Attract granulocytes to lungs.
• Stimulate granulocyte & monocyte production in bone marrow.

Double-edged sword:

• When they swallow large amounts of cigarette smoke particles or irritants, they can:
• Release lysosomal enzymes and other products outside the cell.
• This causes inflammation and damage → contributes to chronic lung disease.

CYSTIC FIBROSIS

1. Core identity of Cystic Fibrosis (CF)

• Very common genetic disease in whites
• 3% are carriers.
• Inheritance: Autosomal recessive.
• Gene: CFTR (Cystic Fibrosis Transmembrane Conductance Regulator)
• Location: Chromosome 7 long arm.
• Function: Regulated Cl⁻ channel on apical membrane of many secretory/absorptive epithelia (airways, sweat glands, pancreas, etc.).

👉 If you see: CF = CFTR Cl⁻ channel defect on chromosome 7, autosomal recessive.

2. CFTR mutation classes – only the idea you really need

There are >1000 mutations, grouped into 5 classes (I–V):

• Class I – No protein made.
• Class II – Misprocessed protein (trafficking problem).
• Class III – Channel regulation defect (gate doesn’t open properly).
• Class IV – Channel conducts poorly (reduced conductance).
• Class V – Reduced synthesis (less protein made).

💡 Big picture:

Lower class number = more severe functional loss (I–III usually more severe than IV–V).

Most common mutation:

• ΔF508 = loss of phenylalanine at position 508
• Class: Class II
• Defect: protein misfolded, doesn’t reach membrane properly → less CFTR at apical surface.

3. Lung pathophysiology – why lungs get destroyed

Key points in the lungs:

1. ↓ Cl⁻ secretion across airway epithelium.
2. In lungs (unlike sweat glands):
• Na⁺ reabsorption is ↑ (enhanced)
• → water follows Na⁺ out of the airway lumen.
3. Result:
• Airway secretions become “inspissated” = very thick & sticky.
• Periciliary layer is reduced → cilia can’t beat properly.
• Mucociliary escalator function is impaired.
• Antimicrobial secretions are less effective.

Clinical consequences:

• Recurrent lung infections, especially Pseudomonas aeruginosa.
• Chronic inflammation and obstruction → progressive, eventually fatal lung destruction.

👉 Key sentence to remember:

CF → thick sticky mucus + poor clearance → chronic infection (Pseudomonas) → lung destruction.

4. Sweat glands vs lungs – opposite Na⁺ behavior (very exammy)

• In sweat glands:
• Cl⁻ secretion is reduced.
• Na⁺ reabsorption is also depressed → salty sweat (clinical test, even though this box only hints at Na⁺).
• In lungs:
• Cl⁻ secretion depressed, but
• Na⁺ reabsorption is increased → lumen dries out (Na⁺ + water leave airway).

So:

5. Treatment – old vs new approach

Traditional (symptom-based) treatments

• Chest physiotherapy + mucolytics
• Loosen thick mucus → help clearance.
• Antibiotics
• Control chronic infection and prevent new infections.
• Bronchodilators + anti-inflammatory drugs
• Open airways and reduce inflammation → better airflow and clearance.
• Pancreatic enzymes + nutritional supplements
• Help digestion and nutrient absorption, support weight gain.

Attempts at “curative” / mechanism-based therapy

• Gene therapy
• Logical because it’s a “single-gene” disease,
• But so far: not successful in practice.
• Newer drugs: CFTR modulators
• Directly target molecular defects in CFTR.
• In clinical trials and practice, they’re showing very promising improvement in outcomes.

👉 Exam idea:

Historically: symptom control (mucus clearance, antibiotics, enzymes).

Modern era: CFTR-targeted drugs (modulators) now transforming care.

RESPIRATORY MUSCLES

1. Who does MOST of the work in quiet breathing?

• Lungs sit inside the thoracic cage (ribs + spine).
• Main muscle of quiet inspiration = diaphragm
• Does about 75% of the intrathoracic volume change in quiet inspiration.
• When diaphragm contracts:
• It moves downward like a piston over the liver.
• Moves ~1.5 cm in quiet inspiration, up to 7 cm in deep inspiration.
• Downward movement → thoracic volume ↑ → intrathoracic pressure ↓ → air flows in.

👉 If you remember only one line:

Diaphragm = primary inspiratory muscle (75% of quiet inspiration).

2. Structure of the diaphragm – 3 parts & a key clinical twist

Three main parts:

1. Costal portion
• Muscle fibres attached to the ribs around the lower thoracic cage.
2. Crural portion
• Fibres attached to ligaments along vertebrae.
• Pass on either side of the esophagus → can compress esophagus when they contract.
3. Central tendon
• Where costal + crural fibres insert.
• Forms the inferior part of the pericardium (heart sits on it).

Important functional detail:

• Costal & crural parts are innervated by different parts of the phrenic nerve → they can contract separately.
• Example: vomiting & eructation (belching)
• Costal fibres contract → ↑ intra-abdominal pressure.
• Crural fibres remain relaxed → esophagus not closed → stomach contents can move into esophagus.

👉 Exam trigger:

Different functional behavior of costal vs crural diaphragm in vomiting.

3. External intercostals – the other key inspiratory muscle

• External intercostal muscles run:
• Obliquely downward and forward from rib to rib.
• When they contract:
• Lower ribs are elevated (ribs hinge at the back).
• Sternum moves outward.
• Anteroposterior diameter of chest ↑ (and transverse diameter ↑ somewhat).

Key idea:

• Either diaphragm alone or external intercostals alone can maintain adequate ventilation at rest.

4. Spinal cord lesions & phrenic nerve – life or death

• Phrenic nerve roots: C3–C5 (“C3–5 keeps the diaphragm alive”).
• Transection above C3 → all phrenic output gone → fatal without ventilatory support.
• Transection below C5 → phrenic nerve intact → diaphragm still works → respiration possible.

Clinical contrast:

• Bilateral phrenic nerve palsy (diaphragm out, but intercostals OK)
• Respiration is laboured but adequate for life.

So you should link:

• C3–5 → phrenic → diaphragm → survival.

5. Accessory inspiratory muscles

Used in deep, laboured breathing:

• Scalene muscles
• Sternocleidomastoid (SCM)

They help elevate the upper ribs and thoracic cage in respiratory distress.

6. Expiratory muscles – when breathing out becomes active

Normal quiet expiration = passive recoil of lungs & chest wall.

But forced expiration uses muscles:

1. Internal intercostals
• Run obliquely downward and backward from rib to rib (opposite to external intercostals).
• When they contract → pull ribs down → decrease thoracic volume.
2. Anterior abdominal wall muscles
• Pull rib cage downward and inward.
• Increase intra-abdominal pressure → push diaphragm upward.
• Net effect: decrease intrathoracic volume → forced expiration.

7. Glottis & laryngeal muscles – the gate for air and food

• Glottis = area including and between the vocal folds in the larynx.
• For air to enter the airway → it must pass through the glottis.

During inspiration

• Abductor muscles of the larynx contract early in inspiration.
• They pull the vocal cords apart → open the glottis → air can pass.

During swallowing / gagging

• Adductor muscles reflexly contract → close the glottis →
• Prevent aspiration of food, fluid, vomitus into the lungs.

Clinical danger:

• In unconscious or anesthetized patients:
• Glottic closure may be incomplete.
• Vomitus can enter trachea → causes aspiration pneumonia (chemical + infectious insult).

👉 Mental hook:

Open glottis to breathe, close glottis to protect; failure to close → aspiration.

PLEURA

1. Pleura – two layers + one key function

• Parietal pleura
• Lines the inside of the chest wall (thoracic cavity).
• Visceral pleura
• Closely covers the surface of the lung.
• Pleural cavity
• Potential space between the two pleurae.
• Contains about 15–20 mL of pleural fluid.

🔑 Main function:

Pleural fluid acts as a lubricant → reduces friction and allows smooth lung movement against the chest wall during inspiration & expiration.

If an exam stem says “lubricating space allowing lung movement” → think pleural cavity + pleural fluid (15–20 mL).

2. Lung support framework – why it doesn’t collapse like a plastic bag

• Lung is ~80% air → great for gas exchange surface, but structurally fragile.
• Needs connective tissue framework inside the visceral pleura to maintain shape.

Three key layers of support:

1. Superficial elastic fibres under mesothelium
• Wrap around the lobes (3 on right, 2 on left).
2. Deep fine fibre sheet
• Follows the outline of individual alveoli → supports each air sac.
3. Connective tissue between these two layers
• Contains cells that maintain and support lung structure & function.

You don’t need every micro-detail, just the idea:

Elastic + fine connective tissue layers in visceral pleura form a scaffold to keep the air-filled lung structurally stable.

3. Dual blood supply – pulmonary vs bronchial (very exammy)

Pulmonary circulation (gas exchange)

• Pulmonary artery
• Carries deoxygenated blood from the right ventricle → lungs.
• Follows the branching of bronchi all the way to respiratory bronchioles.
• Pulmonary capillary bed
• Site of gas exchange.
• Pulmonary veins
• Carry oxygenated blood back to left atrium.
• They do NOT strictly follow bronchi → they run between bronchial structures on their way back.

Main job:

Pulmonary circulation = gas exchange circuit.

Bronchial circulation (nutritive/systemic)

• Bronchial arteries
• Come from systemic arteries (high-pressure side).
• Supply:
• Trachea → terminal bronchioles
• Pleura
• Hilar lymph nodes
• Bronchial arteries → capillaries → drain via:
• Bronchial veins → azygos vein

and/or

• Anastomose with pulmonary capillaries/veins.

Main job:

Bronchial circulation = nutrition for airway and supporting structures (not main gas exchange).

Compare:

4. Lymphatics – massively developed in the lung

• Lymphatic channels are more abundant in the lungs than in any other organ.

→ Very important in infection, tumor spread, and edema control.

• Lymph nodes:
• Arranged along the bronchial tree.
• Present until bronchi are about 5 mm in diameter.
• Size range:
• ~1 mm at bronchial periphery.
• Up to ~10 mm along the trachea (big hilar/mediastinal nodes).
• Flow pattern:
• Nodes are connected by lymph vessels.
• Lymph flows uni-directionally towards the subclavian veins (where it enters venous circulation).

Key idea:

Lungs have rich lymphatic drainage → explains why infections and cancers often show hilar/mediastinal lymphadenopathy.

INSPIRATION & EXPIRATION

1. Why intrapleural pressure is negative

• Lungs: elastic → want to recoil inward (collapse)
• Chest wall: elastic → wants to spring outward
• Between them = intrapleural space with a thin fluid layer
• Like two wet glass plates → easy to slide, hard to separate
• Because each is pulling in opposite directions →

→ Intrapleural pressure is subatmospheric (negative)

At end of quiet expiration:

• Inward recoil (lungs) = outward recoil (chest wall) → balanced
• This is the resting position of the respiratory system

Clinical points:

• Open the chest (trauma/surgery) → air enters pleural space → lungs collapse
• If lungs lose elasticity (e.g. emphysema) → chest wall wins → barrel-shaped chest

2. What happens during quiet inspiration

Inspiration = active (muscles contract).

1. Inspiratory muscles contract (main: diaphragm, external intercostals)

→ Intrathoracic volume ↑

2. Intrapleural pressure at lung bases:
• Start of inspiration: about –2.5 mmHg
• During inspiration: falls to about –6 mmHg
3. More negative intrapleural pressure → lungs pulled into a more expanded position
4. As lungs expand:
• Airway/alveolar pressure becomes slightly negative (just below atmospheric)
• Air flows into lungs (air moves from high → low pressure)

At the end of inspiration:

• Lungs are stretched → their recoil starts pulling chest back toward expiration.

3. What happens during quiet expiration

Quiet expiration = mostly passive.

1. Inspiratory muscles relax (except a slight “braking” activity early on)
2. Elastic recoil of lungs → thoracic volume decreases
3. This makes airway pressure slightly positive
4. Air flows out of lungs

Important subtle point:

• In early expiration, inspiratory muscles don’t fully switch off:
• They contract a bit, giving a “braking action”
• This slows expiration and prevents lungs from suddenly snapping back

4. Forced breathing – when things get exaggerated

• Strong inspiratory effort:
• Intrapleural pressure can go down to about –30 mmHg
• → Much greater lung inflation
• When ventilation increases (exercise, distress):
• Expiration becomes active
• Expiratory muscles (abdominal wall, internal intercostals) contract
• → Intrathoracic volume decreases further

→ More complete deflation of lungs

5. One-line summary to keep in your head

Lungs pull in, chest pulls out → negative intrapleural pressure. Inspiration = active, intrapleural pressure more negative → air in. Quiet expiration = passive recoil, airway pressure slightly positive → air out. Forced breathing = both inspiration and expiration become muscular.

QUANTITATING RESPIRATORY PHENOMENA

1. How do we measure breathing?

• Spirometer
• Measures how much air goes in and out of the lungs.
• Corrects for temperature, pressure, and water vapour so we get standardised volumes.
• Used for diagnostic spirometry (compare patient vs normal / vs their own previous values).
• Gas analysis
• O₂ and CO₂ electrodes can be placed in airways or blood → continuously record PO₂ and PCO₂.
• Pulse oximeter
• Non-invasive clip (e.g. finger) that continuously measures arterial oxygen saturation (SpO₂).
• Standard tool for chronic assessment of oxygenation.

👉 Key idea:

Spirometry = volume; electrodes + pulse ox = gas content / oxygenation.

2. Static lung volumes & capacities — definitions + key numbers

Think of volumes = single boxes, capacities = sums of boxes.

Basic volumes

• Tidal Volume (TV)
• Air in or out in quiet breath.
• ≈ 500–750 mL.
• Inspiratory Reserve Volume (IRV)
• Extra air you can breathe in above TV with a maximal effort.
• ≈ 2 L.
• Expiratory Reserve Volume (ERV)
• Extra air you can force out after a normal expiration.
• ≈ 1 L.
• Residual Volume (RV)
• Air left in lungs after maximal forced expiration.
• ≈ 1.3 L.
• Cannot be exhaled; keeps alveoli open.

Capacities (combinations)

1. Total Lung Capacity (TLC)
• All air in the lungs after a maximal inspiration.
• TLC = TV + IRV + ERV + RV ≈ 5 L.
2. Vital Capacity (VC)
• Max air you can exhale after a maximal inspiration.
• VC = TV + IRV + ERV ≈ 3.5 L.
• What you can “use” in active breathing.
3. Inspiratory Capacity (IC)
• Max air you can inhale from end of a normal expiration.
• IC = TV + IRV ≈ 2.5 L.
4. Functional Residual Capacity (FRC)
• Air remaining in lungs after a normal expiration.
• FRC = ERV + RV ≈ 2.5 L.
• This is the resting volume where lung inward recoil = chest wall outward recoil.

👉 If you can write these 4 formulas + rough numbers, you’ve basically covered the static lung volumes part.

3. Dynamic measurements – how we detect lung disease

These involve time + effort.

Forced Vital Capacity (FVC)

• FVC = largest amount of air forcibly exhaled after a maximal inspiration.
• Reflects:
• Strength of respiratory muscles
• Lung and chest wall mechanics

FEV₁ & FEV₁/FVC

• FEV₁ = volume exhaled during the first second of a forced expiration.
• FEV₁/FVC ratio:
• Key index to classify airway disease:
• Obstruction → FEV₁ ↓ more than FVC (ratio ↓)
• Restriction → both ↓ but ratio can be normal or ↑ (concept, your text hints at its use).

Respiratory Minute Volume (RMV)

• RMV = TV × respiratory rate.
• Normal example given:
• TV ≈ 500 mL, RR ≈ 12/min → RMV ≈ 6 L/min.

Maximal Voluntary Ventilation (MVV)

• MVV = largest volume of gas that can be moved in and out in 1 min by voluntary effort.
• Actually measured over 15 seconds and scaled up to 1 min.
• Normal values:
• ≈ 140–180 L/min (healthy adult men).
• Changes in RMV and MVV can indicate lung dysfunction.

👉 One-liner:

FVC + FEV₁ + FEV₁/FVC = pattern of disease; RMV + MVV = how much air you can move per minute at rest vs max effort.

COMPLIANCE

1. What is compliance?

• Definition:

👉 Compliance = ΔV / ΔP

= Change in lung volume per unit change in pressure (airway/alveolar pressure).

• In words:

How easily the lungs + chest wall expand when you apply pressure.

1. High compliance → easy to inflate (little pressure → big volume change).
2. Low compliance → stiff → need more pressure to get same volume.
• Normal combined lung + chest wall compliance ≈ 0.2 L/cm H₂O in a healthy adult man (in the steep part of the curve).

That single formula + number gives you a lot of marks.

2. Balance of forces at FRC (functional residual capacity)

After a normal quiet expiration (at FRC / relaxation volume):

• Lungs:
• Tend to collapse inward (recoil in).
• This generates a slightly positive pressure from lungs (Pᴸ).
• Chest wall:
• Tends to spring outward (recoil out).
• This generates a slightly negative pressure from the chest wall (Pʷ).

At FRC:

Lung inward recoil = Chest wall outward recoil

→ Their pressures cancel → total airway pressure = 0 (atmospheric)

→ No net airflow.

That’s why FRC is called the relaxation volume of the respiratory system.

3. How do we actually measure the pressure–volume (P–V) curve?

Method (conceptual, don’t need deep detail in viva, just idea):

1. Person inhales or exhales to a certain volume.
2. A valve at the mouth is closed → airway is now a sealed space.
3. Person relaxes respiratory muscles → system is at equilibrium.
4. Airway pressure is recorded (this reflects the recoil of lungs + chest wall).
5. Repeat at different lung volumes.

Plot airway pressure vs lung volume → you get the P–V curve for the total respiratory system (P_TR).

• At FRC → airway pressure is 0.
• Above FRC → P_TR becomes positive (system wants to recoil inward).
• Below FRC → P_TR becomes negative (system wants to expand).

Compliance = slope of this P–V curve (ΔV/ΔP).

• Measured where the curve is steepest → that’s where small pressure changes give the biggest volume change.

4. Key properties of compliance

• Compliance depends on lung volume
• It is not constant across the entire curve.
• Example: a person with only one lung has about half the ΔV for the same ΔP → overall compliance of lung system roughly halves.
• Compliance is slightly greater during deflation than inflation
• This is called hysteresis.
• Clinically: remember that the deflation limb of the P–V curve is a bit steeper.

For exams, just remember:

Compliance varies with volume and is a bit higher on deflation than inflation.

5. Disease patterns (super high-yield)

Think of how “stiff” or “floppy” the lungs are:

1️⃣ Decreased compliance → curve shifts down & right

• Causes:
• Pulmonary edema
• Interstitial pulmonary fibrosis
• Progressive restrictive disease with stiff, scarred lungs.

Effect:

• Lungs are stiffer → need more pressure to get same volume.
• On P–V curve:
• For a given pressure, volume is less → curve downwards & to the right.

Clinically: “restrictive = stiff = ↓ compliance”.

2️⃣ Increased compliance → curve shifts up & left

• Classic example: emphysema.

Effect:

• Lungs are floppy, easy to inflate but hard to recoil.
• For a given pressure, volume is higher → curve upwards & to the left.

Clinically:

• Emphysematous lungs: ↑ compliance, but poor recoil → air trapping → barrel chest (from previous section).

6. One compact “memory paragraph”

Compliance is ΔV/ΔP, about 0.2 L/cm H₂O for lung + chest wall in a healthy adult, measured near FRC where the P–V curve is steepest. At FRC, inward lung recoil and outward chest wall recoil balance, so airway pressure is 0. Fibrosis/edema make lungs stiff → ↓ compliance, P–V curve shifts down-right. Emphysema makes lungs floppy → ↑ compliance, curve shifts up-left.

CLINICAL BOX

1. Core spirometry patterns – normal vs obstructive vs restrictive

Memorise this table + logic, and you’re safe for most questions.

Normal

• FVC ≈ 4.0 L
• FEV₁ ≈ 3.3 L
• FEV₁/FVC ≈ 80%

👉 Means: person can blow out most of their vital capacity in the first second.

Obstructive disease (e.g. asthma, COPD pattern)

• Example in text:
• FVC ≈ 2.0 L (↓)
• FEV₁ ≈ 1.0 L (↓↓)
• FEV₁/FVC ≈ 50%

Pattern:

• Expiration curve: slow, shallow slope → it takes long time to empty lungs.
• FEV₁ falls more than FVC → ratio ↓ markedly.

Hallmark for obstructive disease:

✅ Low FEV₁

✅ Low FEV₁/FVC ratio

FVC may also be reduced, but the ratio is the key.

Restrictive disease

• Example:
• FVC ≈ 2.0 L (↓)
• FEV₁ ≈ 1.8 L (also ↓ but not as much)
• FEV₁/FVC ≈ 90%

Pattern:

• Airflow is fast initially, then quickly plateaus at the small FVC.
• Both FEV₁ and FVC reduced, but the FEV₁/FVC ratio is normal or even ↑.

Hallmark for restrictive disease:

✅ Low FVC

✅ FEV₁/FVC normal or high (≈ 80–90%)

So the super-core:

• Obstructive → ↓ FVC + big ↓ FEV₁/FVC
• Restrictive → ↓ FVC but preserved / ↑ FEV₁/FVC

Real patients can show mixed patterns, but this is the exam “pure pattern.”

2. Asthma – key pathophysiology (the exam triad)

Asthma is an obstructive disease with:

1. Airway obstruction that is at least partially reversible
2. Airway inflammation
3. Airway hyperresponsiveness to various triggers

Symptoms:

• Episodic or chronic:
• Wheezing
• Cough
• Chest tightness
• Due to bronchoconstriction.

Immunology / mediators (key points):

• Often linked to allergy → ↑ IgE.
• Eosinophils important:
• Release proteins that damage airway epithelium → increases hyperresponsiveness.
• Leukotrienes (from eosinophils and mast cells):
• Strongly enhance bronchoconstriction.
• Many amines, neuropeptides, chemokines, interleukins:
• Contribute to smooth muscle contraction and inflammation.

Big takeaway:

Asthma = reversible obstruction driven by inflammation + hyperreactive airways, with a strong allergic/IgE + eosinophil + leukotriene component.

3. Asthma treatment – what the box really wants you to know

Main “rescue” treatment

• β₂-adrenergic agonists (inhaled)
• Mechanism: stimulate β₂ receptors on bronchial smooth muscle → bronchodilation.
• Used as rescue therapy in mild–moderate attacks.

Anti-inflammatory backbone

• Inhaled corticosteroids
• Used even in mild–moderate cases.
• Very effective at reducing airway inflammation.
• Side effects are an issue, but they are standard in long-term control.

Leukotriene pathway blockers

• Drugs that:
• Block leukotriene synthesis, or
• Block CysLT₁ receptors (for cysteinyl leukotrienes).
• Useful in some patients to:
• Reduce bronchoconstriction
• Reduce inflammation.

So the exam pill:

Rescue → inhaled β₂ agonists (bronchodilation).

Control → inhaled steroids ± leukotriene modifiers (inflammation + mediators).

4. One compact memory paragraph

In a normal person, FVC ≈ 4 L, FEV₁ ≈ 3.3 L, so FEV₁/FVC ≈ 80%. In obstructive disease, both FEV₁ and FVC fall but FEV₁ falls much more, so FEV₁/FVC is low (~50%). In restrictive disease, FVC falls but FEV₁/FVC is normal/high (~90%). Asthma is an obstructive, often allergic disease with reversible airway obstruction, inflammation, and hyperresponsiveness, driven by IgE, eosinophils, and leukotrienes. Treatment centres on β₂ agonists for bronchodilation, inhaled steroids for inflammation, and leukotriene blockers as add-ons.

AIRWAY RESISTANCE

1. What is airway resistance?

Definition (for your formula brain):

Airway resistance (Rᴀw) = ΔP / V̇

• ΔP = pressure difference from alveoli → mouth
• V̇ = flow rate of air (how fast the air is moving)

So:

• For a given flow, if you need more pressure → resistance is higher.
• If the same pressure gives you more flow → resistance is lower.

2. Where does most of the resistance come from?

Because of the branching bronchial tree, it’s complicated mathematically, but practically:

• Bronchi + bronchioles are the main contributors to airway resistance.
• This is where small changes in radius (via smooth muscle) make a huge difference.

Key point:

Contraction of bronchial smooth muscle → airway narrowing → ↑ resistance → breathing becomes harder.

This is exactly what happens in asthma, for example.

3. Effect of lung volume on airway resistance

• As lung volume decreases, airway resistance increases significantly.

Why (conceptually)?

• At low lung volume, airways are narrower / less stretched, so:
• Resistance ↑ (Poiseuille-like logic: small radius → big resistance).

So:

Low lung volume = narrower airways = ↑ resistance = harder to move air.

This is why in obstruction, patients often breathe at higher lung volumes (air trapping) to keep airways more open.

4. One-sentence summary for your notes

Airway resistance = ΔP / V̇ (pressure from alveoli to mouth divided by flow). It mainly comes from bronchi and bronchioles, increases a lot when lung volume is low, and goes up further when bronchial smooth muscle contracts, making breathing more difficult.

Role of Surfactant in Alveolar Surface Tension

1. Why surface tension matters for lung compliance

• Alveoli are lined by a thin fluid layer → this fluid–air interface has surface tension.
• Surface tension tends to make alveoli collapse and makes lungs stiffer (↓ compliance).

How do we know?

• In experiments, lungs are taken out and inflated:
• Once with air
• Once with saline
• Saline removes the air–fluid interface → surface tension ≈ 0

→ So the saline P–V curve = pure tissue elasticity only.

• Air P–V curve = tissue elasticity + surface tension.

Key observations:

• With air, lungs are less compliant (stiffer) than with saline.
• The difference between air and saline curves is smaller at low volumes (where surfactant is most effective).
• With air, the inflation and deflation curves are not the same → this difference is called hysteresis.
• With saline, there’s no hysteresis.

So:

Surfactant + surface tension effects = hysteresis + variable compliance.

2. Role of surfactant: keep small alveoli from collapsing (Laplace)

At small alveolar volumes, surface tension is kept low because of surfactant.

• Surfactant = mostly DPPC (dipalmitoylphosphatidylcholine) + other lipids + proteins.

The key physics:

• For a spherical structure (like an alveolus):

👉 Law of Laplace:

[

P = \frac{2T}{r}

]

1. P = distending pressure
2. T = surface tension
3. r = radius

If r decreases (small alveolus):

• Without surfactant:
• T stays high, r ↓ → P needed to keep it open ↑ a lot

→ alveolus collapses.

• With surfactant:
• When alveoli get smaller during expiration, surfactant molecules become more concentrated → T falls

→ P doesn’t need to rise as much → small alveoli stay open.

So, main roles:

1. Prevents alveolar collapse (atelectasis), especially during expiration.
2. Improves compliance by lowering surface tension → lungs easier to inflate.

3. Surfactant helps prevent pulmonary edema

• If surfactant were absent, surface tension would generate about a 20 mmHg inward force.
• This strong inward pull would:
• Favor movement of fluid from capillaries into alveoli (transudation).
• → Leads to pulmonary edema (fluid-filled alveoli).

So:

Surfactant not only stabilizes alveoli, it also reduces the tendency for fluid to leak into alveoli.

4. Surfactant proteins – who does what?

Surfactant contains 4 special proteins: SP-A, SP-B, SP-C, SP-D.

SP-A

• Large glycoprotein, has a collagen-like domain.
• Functions:
• Helps regulate feedback uptake of surfactant by Type II alveolar cells (the cells that secrete it).
• Involved in organization and recycling of surfactant.

SP-B & SP-C

• Small hydrophobic proteins.
• Key for forming the monomolecular surfactant film:
• Help phospholipids (like DPPC) spread and form a stable surface film at the air–liquid interface.

SP-D

• Also a glycoprotein.
• Important in organizing SP-B and SP-C in the surfactant layer.
• Full function not completely understood, but clearly part of surfactant structure + defence.

SP-A & SP-D as collectins / innate immunity

• Both SP-A and SP-D are collectins:
• Pattern-recognition molecules involved in innate immunity.
• Present in conducting airways and alveoli.
• Help bind pathogens, opsonize them, and modulate immune responses.

So:

Surfactant is not just mechanics; it is also a defence system via SP-A & SP-D.

5. One compact memory paragraph

Lung compliance is strongly influenced by alveolar surface tension. Experiments with saline vs air show that surface tension + surfactant create hysteresis in the lung P–V curve. Surfactant, mainly DPPC + SP-B and SP-C, lowers surface tension, especially at small volumes, preventing alveolar collapse (Laplace: (P = 2T/r)) and helping prevent pulmonary edema. SP-A and SP-D, both collectins, participate in innate immunity and in organizing the surfactant layer.

SURFACTANT

1. Role of surfactant at birth – why it’s critical

• In utero:
• Fetus makes respiratory movements, but lungs stay collapsed and filled with fluid.
• At birth:
• Baby makes strong inspiratory efforts → lungs expand for the first time.
• Surfactant keeps the alveoli from collapsing again after each breath.

👉 Core idea:

Surfactant is essential to keep newborn alveoli open after the first breaths.

2. Surfactant deficiency → Infant Respiratory Distress Syndrome (IRDS)

• IRDS = hyaline membrane disease.
• Occurs in preterm infants whose surfactant system is not yet functional.

Main pathophysiology:

• High surface tension in alveoli (because of low/no surfactant).
• Many alveoli collapse → atelectasis.
• This causes severe respiratory distress shortly after birth.

So, simple core:

Premature baby + immature surfactant → high surface tension → alveolar collapse → IRDS.

3. Fluid clearance at birth – role of ENaC

During fetal life:

• Pulmonary epithelium secretes Cl⁻ and fluid into the airways → lungs are fluid-filled.

At birth:

• There is a switch from Cl⁻ secretion → Na⁺ absorption via epithelial Na⁺ channels (ENaCs).
• Na⁺ absorption pulls water with it → lung fluid is absorbed, helping clear the air spaces.

In IRDS:

• There is prolonged immaturity of ENaC function → poor Na⁺ absorption →
• More fluid retained in lungs → worsens respiratory problems on top of surfactant deficiency.

👉 So in IRDS you have:

• Collapsed alveoli (atelectasis) from high surface tension
• Excess lung fluid from immature ENaC-mediated Na⁺ absorption

Both together = bad gas exchange.

4. Too much / abnormal surfactant → Pulmonary Alveolar Proteinosis (PAP)

• Not only deficiency, but also overproduction or dysregulation of surfactant proteins is harmful.
• PAP = disease where abnormal surfactant accumulates in alveoli →
• Impairs gas exchange
• Causes respiratory distress.

So surfactant must be just right: not too little, not too dysfunctional.

5. Therapy – where surfactant replacement works (and where it doesn’t)

In IRDS (neonates)

• Surfactant replacement therapy is standard and effective.
• Given to preterm infants with IRDS (often via endotracheal tube).
• Helps reduce surface tension, open alveoli, and improve survival.

In adults with respiratory distress

• Surfactant problems can occur in adults (e.g. ARDS, severe lung injury).
• But surfactant replacement therapy in adults has not shown the same success in clinical trials.
• The pathology is more complex (inflammation, edema, damage, etc.), not just “missing surfactant.”

👉 Exam line:

Surfactant replacement works well in neonatal IRDS, but has been disappointing in adult respiratory distress.

6. One compact paragraph for recall

At birth, surfactant is crucial to keep newly expanded alveoli from collapsing. Premature infants with inadequate surfactant develop IRDS (hyaline membrane disease) with high surface tension, atelectasis, and additional fluid retention due to immature ENaC-dependent Na⁺ absorption. Surfactant overproduction/dysregulation can cause pulmonary alveolar proteinosis (PAP). Surfactant replacement therapy is effective in IRDS but has not shown comparable success in adults with surfactant-related respiratory distress.

WORK OF BREATHING

1. What is the work of breathing?

Your respiratory muscles do work to:

1. Stretch elastic tissues (lungs + chest wall) → elastic work
• ~65% of total work
2. Move inelastic tissues (viscous resistance of tissues)
• ~7%
3. Move air through the airways (airway resistance)
• ~28%

So main idea:

Most work is to stretch elastic structures (≈ 2/3), then overcome airway resistance, then a small part for tissue viscosity.

2. How is work of breathing measured?

• Work = pressure × volume.
• Units:
• Pressure (g/cm²) × Volume (cm³) = g·cm = force × distance → same dimension as work.
• So we can calculate work from the pressure–volume (P–V) curve of the respiratory system.

Important point:

• The relaxation pressure curve of the total system (P_TR) is not the same as the curve for lungs alone (P_L).
• Elastic work to inflate lungs alone would be more.
• Inflating the whole system (lungs + chest wall) requires less work because:
• When lungs expand, the chest wall is also moving toward its equilibrium position and stores some elastic energy.

👉 Short version:

Thorax helps share the elastic work, so total elastic work < lung-only elastic work.

3. How much work is done in real life?

• Quiet breathing: total work of breathing ≈ 0.3–0.8 kg·m/min.
• During exercise:
• Work of breathing rises a lot, but still usually < 3% of total energy expenditure in healthy people.
• Most exercise energy is still in limbs, not breathing.

4. Work of breathing in disease + muscle fatigue

Work of breathing becomes very high in:

• Emphysema
• Asthma
• Heart failure with dyspnea and orthopnea

Why?

• Increased airway resistance
• Altered compliance
• Often abnormal lung volumes and mechanics → muscles working at a disadvantage.

Respiratory muscles:

• Have length–tension relationships like skeletal and cardiac muscle:
• If overstretched → weaker contraction.
• They can fatigue:
• If demand is too high for too long → pump failure
• Result = inadequate ventilation → rising CO₂, falling O₂.

👉 Key clinical idea:

Increased work of breathing + muscle fatigue → respiratory failure risk.

5. One exam-ready summary line

The work of breathing (mostly elastic work ≈ 65%, then airway resistance ≈ 28%, tissue viscosity ≈ 7%) is calculated from the P–V curve as pressure × volume. Quiet breathing costs little energy (0.3–0.8 kg·m/min, <3% of exercise energy), but rises sharply in diseases like emphysema, asthma, and heart failure. If respiratory muscles are overstretched and fatigued, they can fail as a pump, leading to inadequate ventilation.

DIFFERENCES IN VENTILATION & BLOOD FLOW IN DIFFERENT PARTS OF THE LUNG

1. Ventilation: base vs apex – who gets more air?

Key fact:

In an upright person, ventilation per unit lung volume is greater at the base than at the apex.

Why?

At the start of inspiration (around FRC):

• Intrapleural pressure is:
• More negative at the apex
• Less negative at the base

So:

• Apex alveoli
• Have higher transpulmonary pressure → are more expanded already (closer to their “max volume”).
• On the pressure–volume curve, they are on the flatter (stiffer) part.
• So for a given change in pressure (during inspiration) → small change in volume → less ventilation.
• Base alveoli
• Less negative intrapleural pressure → less expanded at rest (smaller starting volume).
• They sit on the steeper part of the compliance curve.
• Same pressure change → larger change in volume → more ventilation.

👉 Short version:

Base alveoli start smaller but are more compliant → they expand more with each breath → more ventilation. Apex alveoli start big and stiff → less extra expansion → less ventilation.

2. Blood flow: base vs apex – who gets more blood?

Key fact:

Blood flow is also greater at the base than at the apex.

• Gravity pulls blood downwards → perfusion at the base is much higher than at the apex in upright posture.
• Important detail from the text:

The relative change in blood flow from apex → base is greater than the relative change in ventilation.

So:

• Both ventilation (V) and perfusion (Q) ↑ from apex → base,

but Q increases more steeply than V.

Result:

• Base → V/Q low (more blood relative to air).
• Apex → V/Q high (more air relative to blood).

This is the classic V/Q gradient in the upright lung.

3. Gravity… but not only gravity

Traditional teaching:

• Differences in V and Q from apex to base are due to gravity:
• In supine position → these gradients tend to disappear.
• The weight of the lung tissue would increase pressure at the base in upright posture.

But:

• Studies in weightlessness (space) showed:
• Inequalities in ventilation and blood flow still persist to a remarkable degree.

So:

Gravity is important, but not the only factor – structural and mechanical differences in the lung also contribute.

4. One exam-ready summary paragraph

In the upright lung, ventilation and perfusion are both greater at the base than at the apex, because basal alveoli are less expanded but more compliant and pulmonary blood is gravity-dependent. However, perfusion increases more than ventilation from apex to base, so V/Q is low at the base and high at the apex. These gradients are classically attributed to gravity and reduce in the supine position, but studies in weightlessness show that non-gravitational factors also contribute to V/Q inequality.

If you want, I can next give you a tiny table “Apex vs Base” (volume, compliance, V, Q, V/Q, PO₂, PCO₂) – that’s a favourite exam integration.

DEAD SPACE & UNEVEN VENTILATION

1. What is dead space?

a) Anatomic dead space

• Definition: Volume of the conducting airways where no gas exchange occurs

(nose → terminal bronchioles; excludes alveoli).

• Rule of thumb:

Anatomic dead space (mL) ≈ body weight in pounds

1. 150 lb man → ~150 mL anatomic dead space.

Example with a TV of 500 mL:

• First 150 mL inspired → fills dead space only.
• Only the next 350 mL → reaches alveoli and can do gas exchange.
• On expiration:
• First 150 mL out = air that was in dead space (no gas exchange).
• Last 350 mL = alveolar gas.

So:

Alveolar ventilation (VA) < minute ventilation (RMV) because of dead space.

Important consequence:

At the same minute ventilation (RMV),

• Rapid shallow breathing = LOT of each breath wasted in dead space → very poor alveolar ventilation.
• Slow deep breathing = proportionally less wasted → much better alveolar ventilation.

That comparison is a classic MCQ.

2. Anatomic vs physiologic (total) dead space

• Anatomic dead space
• “Plumbing volume” = conducting airways, no alveoli.
• Physiologic (total) dead space
• All gas that does NOT equilibrate with blood (i.e. wasted ventilation).
• = Anatomic dead space
• Non-perfused or under-perfused alveoli
• Overventilated alveoli beyond what is needed to arterialize blood.

In a healthy person:

• Physiologic dead space ≈ anatomic dead space (because almost all alveoli are well perfused).

In disease:

• Some alveoli may be:
• Not perfused at all (true alveolar dead space)
• Very poorly perfused → ventilated but not effectively exchanging.
• So physiologic dead space > anatomic dead space.

👉 Exam sentence:

Healthy: anatomic ≈ physiologic dead space.

Disease: physiologic dead space increases due to V/Q mismatch / non-perfused alveoli.

3. Single-breath N₂ test – how anatomic dead space is measured

Method:

1. From mid-inspiration, patient takes a deep breath of 100% O₂.
2. Then they exhale slowly and steadily, while we continuously measure N₂ in expired gas.

N₂ curve has 4 phases:

• Phase I
• First expired gas = pure dead space gas.
• No N₂ (because it’s just the O₂ that filled the conducting airways).
• Phase II
• Rapid rise in N₂ as mix of dead space + alveolar gas comes out.
• Phase III
• Alveolar plateau: mostly alveolar gas.
• Usually has a slight positive slope even in normals → means later gas is coming more from upper (N₂-richer) regions of lungs.
• Phase IV
• Starts at closing volume (CV).
• Airways in dependent (lower) lung regions start closing → expired gas disproportionately comes from upper regions, which are more N₂-rich → N₂% suddenly rises.

Key definitions:

• Dead space volume = volume expired from peak inspiration to midpoint of phase II.
• Closing volume (CV):
• Lung volume above RV at which dependent airways begin to close.

Why upper lung gas is more N₂-rich:

• At start of O₂ inspiration, upper alveoli are more distended, so incoming O₂ dilutes N₂ less there than in lower, less-filled alveoli.
• Hence, gas from upper regions has higher N₂.

4. Bohr equation – calculating total (physiologic) dead space

We use CO₂ to compute VD because:

• Inspired PCO₂ ≈ 0, so any CO₂ in expired gas has come from perfused alveoli.

Bohr equation (conceptual form):

[

P_{ECO₂} \times V_T = P_{aCO₂} \times (V_T - V_D) + P_{ICO₂} \times V_D

]

Because PICO₂ ≈ 0, we ignore that last term and rearrange:

[

V_D = V_T - \frac{P_{ECO₂} \times V_T}{P_{aCO₂}}

]

Where:

• VT = tidal volume
• VD = dead space volume
• PECO₂ = mean PCO₂ of expired gas
• PaCO₂ = arterial PCO₂

Example (from text):

• PECO₂ = 28 mmHg, PaCO₂ = 40 mmHg, VT = 500 mL

→

[

V_D = 500 - \frac{28 \times 500}{40} = 500 - 350 = 150 \text{ mL}

]

So dead space = 150 mL.

Difference between PaCO₂ and PACO₂ (alveolar)

• PaCO₂ = arterial PCO₂ → reflects perfused alveoli only.
• PACO₂ (alveolar) = from last 10 mL of expired gas → average of all ventilated alveoli, regardless of perfusion.

Use:

• To compute physiologic dead space, use PaCO₂.
• To compute anatomic dead space, you replace PaCO₂ with PACO₂ (alveolar PCO₂).

In disease with underperfused alveoli:

• PACO₂ (alveolar) < PaCO₂, because non-perfused or poorly perfused areas blow off CO₂ but don’t reflect arterial equilibrium.

5. One compact paragraph for memory

Dead space is the part of tidal volume that does not participate in gas exchange. Anatomic dead space ≈ body weight in pounds and sits in the conducting airways. Physiologic dead space includes anatomic dead space plus non-perfused or underperfused alveoli (wasted ventilation) and increases in disease. Anatomic dead space can be measured using the single-breath N₂ test (Phase I–IV, with closing volume at the start of Phase IV). Bohr’s equation uses CO₂ (PaCO₂, PECO₂, VT) to calculate VD and shows that in a 500 mL breath with PaCO₂ 40 and PECO₂ 28, dead space is 150 mL.

Partial pressures

1. What is partial pressure?

Key rule (Dalton’s law):

In a gas mixture, total pressure = sum of partial pressures of each gas.

Partial pressure of a gas = (fraction of that gas) × (total pressure)

So if:

• Total pressure (P_B) = 760 mmHg (sea level)
• O₂ fraction = 0.21

Then:

[

P_{O_2} = 0.21 \times 760 \approx 160 \text{ mmHg}

]

That’s it. Same idea for N₂, CO₂, etc.

2. Composition of dry air at sea level (PB = 760 mmHg)

Given:

• O₂ ~ 20.98% ≈ 21%
• CO₂ ~ 0.04%
• N₂ ~ 78.06%
• Others (Ar, He) ~ 0.92%

Approximate partial pressures in dry air:

• P_O₂ ≈ 0.21 × 760 ≈ 160 mmHg
• P_CO₂ ≈ 0.0004 × 760 ≈ 0.3 mmHg
• P_N₂ + inert ≈ 0.79 × 760 ≈ 600 mmHg

These “160, 0.3, 600” numbers are classic.

3. Effect of water vapour in inspired air

By the time air reaches the lungs:

• It is fully saturated with water vapour at body temp (37°C).
• P_H₂O at 37°C = 47 mmHg.

This water vapour “uses up” part of the total 760 mmHg:

[

P_{\text{dry gases}} = 760 - 47 = 713 \text{ mmHg}

]

Now O₂ etc are fractions of 713, not 760.

So inspired air at sea level reaching the lungs:

• P_O₂ ≈ 0.21 × 713 ≈ 150 mmHg
• P_CO₂ ≈ 0.0004 × 713 ≈ 0.3 mmHg
• P_N₂ + inert ≈ rest ≈ 563 mmHg

Important: 150 mmHg is the standard textbook value for inspired O₂ at the trachea (before gas exchange).

4. How gases move and dissolve – key concept

• Gases diffuse from higher partial pressure → lower partial pressure.
• Rate depends on:
• Pressure (concentration) gradient
• Barrier properties (thickness, area, etc.)

When a gas mixture contacts a liquid (e.g. air in alveoli, blood in capillaries):

• Each gas dissolves according to:
• Its partial pressure
• Its solubility in that liquid.

Definition:

Partial pressure of a gas in a liquid = the pressure that the gas phase would need to have, at equilibrium, to produce that same dissolved concentration.

This is basically the idea behind Henry’s law:

• Higher partial pressure in gas phase → more dissolved in liquid until equilibrium is reached.

SAMPLING ALVEOLAR AIR

1. How do we sample alveolar air?

Idea: you want the gas that was actually sitting in the alveoli, not the gas in the dead space.

• In a 150 lb man, ~150 mL of each breath = anatomic dead space.
• TV at rest ≈ 500 mL:
• First 150 mL expired = dead-space gas (no gas exchange).
• Last ≈ 350 mL = mostly alveolar gas.

Because there is mixing at the interface, we don’t trust the early part:

• Using modern equipment, we collect only the last ~10 mL of expiration during quiet breathing.
• This end-tidal sample is taken as representative of alveolar gas.

👉 Take-home:

Alveolar gas ≈ composition of the last part of expired air, not the first part.

2. Alveolar gas equation – what it really means

The text gives the alveolar gas equation for PAO₂ (alveolar PO₂).

Conceptual form (high-yield version):

[

P_{AO₂} \approx P_{IO₂} - \frac{P_{ACO₂}}{R}

]

Where:

• PAO₂ = alveolar O₂ partial pressure
• PIO₂ = inspired O₂ partial pressure (after humidification, ~150 mmHg at sea level on room air)
• PACO₂ ≈ PaCO₂ (arterial CO₂)
• R = respiratory exchange ratio
• ( R = \frac{\text{V̇CO₂}}{\text{V̇O₂}} )
• At rest usually ≈ 0.8

Meaning:

• O₂ in alveoli = what comes in (PIO₂) minus what is “used up” in exchange for CO₂ (PACO₂/R).
• It gives you the ideal alveolar PO₂, assuming good matching of ventilation and perfusion.

That’s the key idea:

The alveolar gas equation links inspired PO₂, CO₂ production, and alveolar PO₂.

3. Why alveolar gas composition is so stable

At FRC, alveolar gas volume ≈ 2 L.

Each quiet breath:

• Only ~350 mL fresh air actually reaches alveoli.
• So each breath changes alveolar gas only a small fraction.

Meanwhile:

• O₂ is continuously diffusing out of alveolar gas into blood.
• CO₂ is continuously diffusing in from blood to alveoli.
• During inspiration:
• Incoming fresh air replaces the O₂ removed and dilutes the CO₂.
• During expiration (between breaths):
• PO₂ falls slightly, PCO₂ rises slightly → until the next inspiration.

Because the alveolar volume is large compared to each breath:

Alveolar PO₂ and PCO₂ remain remarkably constant

– not just at rest, but even across many conditions (up to certain limits).

This “large reservoir + mixing” concept is why we can talk about fairly stable, meaningful values like PAO₂ ~100 mmHg, PACO₂ ~40 mmHg in normal physiology.

4. One compact memory paragraph

The last part of expiration (end-tidal gas) best reflects alveolar air, because the first 150 mL is dead-space gas. The alveolar gas equation (PAO₂ ≈ PIO₂ – PACO₂/R) relates alveolar PO₂ to inspired PO₂, CO₂ production, and the respiratory exchange ratio, and is the key to understanding PAO₂. Because the alveoli contain a relatively large volume of gas (~2 L at FRC) and each breath only replaces ~350 mL, the composition of alveolar gas (PO₂ and PCO₂) changes very little from breath to breath and thus remains fairly constant in steady-state conditions.

DIFFUSION ACROSS CAPILLARY MEMBRANE

1. The barrier: what is the alveolocapillary membrane?

Gas has to cross a very thin “sandwich”:

• Alveolar epithelium
• Fused basement membranes
• Capillary endothelium

Blood spends about 0.75 s in a pulmonary capillary at rest. Whether a gas reaches equilibrium in that time depends on what happens to it inside the blood.

2. Flow-limited vs diffusion-limited gases

Think:

• Flow-limited → membrane is fine, blood supply is the limiter.
• Diffusion-limited → blood is fine, membrane/transfer is the limiter.

a) Nitrous oxide (N₂O) – flow-limited

• N₂O does not bind to Hb – it just dissolves.
• It reaches equilibrium between alveolar gas and capillary blood in about 0.1 s (very fast).
• After that, further uptake is limited only by how much blood flows past.

👉 So N₂O uptake is flow-limited.

b) Carbon monoxide (CO) – diffusion-limited

• CO binds to Hb extremely avidly.
• So its capillary partial pressure stays very low (because as soon as it diffuses in, it’s “hidden” on Hb).
• Equilibrium is not reached in the 0.75 s capillary transit time.
• So CO uptake is limited by how fast it can diffuse across the membrane, not by blood flow.

👉 CO uptake is diffusion-limited → that’s why DLCO uses CO.

c) Oxygen (O₂) – in between, but perfusion-limited in normal lungs

• O₂ does bind to Hb, but less avidly than CO.
• O₂ reaches equilibrium (between alveolar gas and capillary blood) in about 0.3 s (well before 0.75 s is over).
• That means under normal resting conditions, O₂ uptake is perfusion-limited (like N₂O):
• More blood flow → more total O₂ uptake.

3. Diffusing capacity (DL) and DLCO – what it really means

Diffusing capacity (DL) of the lung for a gas:

How much gas crosses the alveolocapillary membrane per minute per mmHg of pressure gradient.

It is:

• Directly proportional to:
• Surface area of membrane
• Inversely proportional to:
• Thickness of membrane

Why use CO for DL?

• Because CO is diffusion-limited, its uptake reflects membrane properties, not blood flow.

Equation:

Diffusing capacity for CO (DLCO)

= Amount of CO taken up by the lungs per minute/Alveolar partial pressure of CO

So you can write it as:

DLCO = (CO uptake per minute) / (alveolar CO partial pressure)

Meaning of each term

• DLCO

= Diffusing capacity of the lung for carbon monoxide

= How good the lung is at transferring CO from alveoli into blood,

measured as mL of CO per minute per mmHg.

• CO uptake per minute (V̇CO)

= The volume of CO that moves from alveoli into blood each minute.

• Alveolar CO partial pressure (PACO)

= The partial pressure of CO in alveolar gas during the test.

1. In non-smokers, CO in capillary blood is almost zero, so we ignore capillary PCO

Normal DLCO at rest ≈ 25 mL/min/mmHg.

• In exercise: DLCO can increase up to 3× due to:
• Capillary dilation
• More capillaries recruited → more surface area.

4. O₂ and CO₂ diffusion – numbers and key concept

Oxygen

• Alveolar PO₂ (PAO₂) ≈ 100 mmHg
• Mixed venous PO₂ ≈ 40 mmHg
• Diffusing capacity for O₂ at rest is similar to DLCO, ~25 mL/min/mmHg.
• Blood leaving lungs reaches PaO₂ ≈ 97 mmHg (just under alveolar PO₂).

So: normal lungs easily equilibrate O₂ with blood under resting conditions.

Carbon dioxide (CO₂)

• Venous PCO₂ ≈ 46 mmHg
• Alveolar PCO₂ ≈ 40 mmHg
• Blood leaving lungs has PCO₂ ≈ 40 mmHg.

Important:

• CO₂ crosses membranes much more easily than O₂ → its diffusing capacity is higher than for O₂.

Clinical pearl:

In diseases like pulmonary fibrosis, the diffusing capacity for O₂ can drop a lot, causing hypoxemia, but CO₂ retention is usually not a big problem early on, because CO₂ diffuses so easily.

PULMONARY CIRCULATION

1. Structure of the pulmonary vessels – what’s special?

• Pulmonary vascular tree looks like systemic but with key differences:
• Pulmonary artery + branches: walls are only ~30% as thick as the aorta → low-pressure, low-resistance system.
• Small pulmonary arteries/arterioles: mostly endothelial tubes with little smooth muscle, unlike systemic arterioles.
• Postcapillary venules: do have some smooth muscle.
• Pulmonary capillaries: large, dense network; each alveolus sits in a capillary basket → huge surface area for gas exchange.

👉 Exam idea: pulmonary circulation = thin-walled, compliant, low-pressure, designed for gas exchange, not high-resistance control like systemic arterioles.

2. Flow and the two small “shunts”

Almost all the blood from the left ventricle returns to the right atrium and is then pumped by the right ventricle through the lungs.

But there are two small physiologic shunts:

1. Bronchial circulation:
• Some bronchial capillary blood drains:
• Into bronchial veins (→ right heart), and
• Some into pulmonary veins/capillaries, bypassing the right ventricle.
2. Coronary circulation:
• Some blood from coronary arteries drains directly into the left-sided heart chambers (Thebesian veins–type inflow).

Result:

• This small “venous admixture” makes systemic arterial blood:
• PaO₂ ~ 2 mmHg lower than ideal end-capillary blood
• Hemoglobin saturation ~0.5% lower than that of blood perfectly equilibrated with alveolar gas.

👉 Key phrase: normal physiologic shunt → PaO₂ slightly lower than PAO₂.

3. Pressures and edema risk – the core numbers

• Pressure gradient in pulmonary circulation ≈ 7 mmHg
• Compare: ~90 mmHg in systemic circulation.
• Pulmonary capillary hydrostatic pressure ≈ 10 mmHg
• Plasma oncotic pressure ≈ 25 mmHg
• So net inward (reabsorption) force ≈ 15 mmHg → keeps alveoli dry, except for a thin fluid film.

Critical threshold:

• When pulmonary capillary pressure > 25 mmHg:
• Net inward force is lost → pulmonary congestion and edema occur.

👉 Remember:

Pulmonary capillaries are normally low pressure (~10 mmHg).

>25 mmHg → big risk of pulmonary edema.

4. Blood volume and transit time in pulmonary circulation

• Total blood in pulmonary vessels at any moment ≈ 1 L
• <100 mL of this is actually in the capillaries at one time.
• Mean blood velocity:
• In root of pulmonary artery ≈ same as aorta (~40 cm/s).
• Slows in smaller vessels, then rises slightly in large pulmonary veins.
• Capillary transit time:
• At rest: about 0.75 seconds
• During exercise: can fall to 0.3 seconds or less
• Still usually enough time for O₂ and CO₂ to equilibrate in healthy lungs.

👉 Ties back to previous topic:

Normal O₂ uptake is perfusion-limited because even at 0.3 seconds, blood has enough time to fully equilibrate with alveolar gas in a healthy lung.

Effect of gravity on pulmonary blood flow

Alright, this one is really two things mixed together:

1. Effect of gravity on pulmonary blood flow (zones / waterfall idea)
2. Pulmonary hypertension – causes, consequence, treatment

I’ll pull out just what you need for exams + clinical sense.

1. Effect of gravity on pulmonary blood flow (upright lung)

Think apex → middle → base and compare alveolar pressure (PA) vs arterial (Pa) vs venous (Pv).

A. General gravity effects

In the upright position:

• Top (apex):
• Less blood flow (far above heart level)
• Alveoli larger (more stretched by negative intrapleural pressure)
• Ventilation less than at the base
• Base:
• More blood flow
• Smaller but more compliant alveoli
• Ventilation greater

Now add pressures and capillary compression.

B. Apex: capillaries close easily → physiologic dead space

At the top of the lungs:

• Capillary pressure is low, close to alveolar pressure.
• Under normal conditions, pulmonary arterial pressure just manages to keep them open.
• If:
• Pulmonary arterial pressure falls, or
• Alveolar pressure rises (e.g. high PEEP, positive-pressure ventilation)
• Then:
• Capillaries collapse
• Those alveoli are ventilated but not perfused → physiologic dead space.

👉 Key idea:

Apex: gravity + low Pa → vessels easily compressed by alveolar pressure → dead-space-like units if Pa too low or PA too high.

This is what textbooks call Zone 1 when it occurs (PA > Pa ≥ Pv).

C. Middle lung: “waterfall effect” (Zone 2)

In the middle lung regions:

• Pulmonary arterial & capillary pressures > alveolar pressure

but:

• Pulmonary venous pressure (Pv) may be < alveolar pressure, especially during normal expiration.

So:

• Venules can be partially collapsed.
• Blood flow is now determined by:

Pulmonary artery pressure − alveolar pressure,

rather than artery − vein difference.

This is the “waterfall effect”:

• Think of a constriction at the venous end:
• Blood flows until it “falls” beyond the compressed segment into compliant pulmonary veins

which simply receive whatever flow comes through.

This is classic Zone 2 physiology:

Pa > PA > Pv, flow ∝ (Pa − PA).

As you go towards the base, arterial pressure rises (gravity), so:

• Compression by PA decreases
• Flow increases.

D. Base of the lung: normal artery–vein gradient (Zone 3)

At the bottom:

• Alveolar pressure is lower than pressures in all parts of the pulmonary circulation:
• Pa > Pv > PA
• Vessels are fully open.
• Blood flow is now determined by the usual:

Arterial–venous pressure difference (Pa − Pv)

This is Zone 3: maximum flow.

Exam picture for gravity effect

• Apex: low Pa, PA can compress capillaries → risk of dead space if Pa ↓ or PA ↑.
• Middle: waterfall effect → flow depends on (Pa − PA).
• Base: PA < Pa and Pv, flow depends on (Pa − Pv), highest flow.

2. Pulmonary hypertension (Clinical Box 34–4)

A. What it is

• Sustained elevation of pulmonary arterial pressure.
• Can occur at any age.
• Like systemic HTN, it’s a syndrome with multiple causes, but different causes from systemic HTN.

B. Causes listed in the text

Key causes to remember:

• Hypoxia (chronic low O₂ → pulmonary vasoconstriction)
• Inhalation of cocaine
• Appetite-suppressant drugs like dexfenfluramine
• These increase extracellular serotonin.
• Systemic lupus erythematosus (SLE)
• Familial forms:
• Related to mutations that:
• Increase pulmonary vessel sensitivity to growth factors, or
• Cause structural abnormalities / deformations of the pulmonary vascular tree.

All these → increased pulmonary vascular resistance (PVR).

C. What happens if untreated?

• ↑ PVR → ↑ right ventricular afterload.
• RV has to pump against a stiffer, high-pressure pulmonary bed.
• Eventually → right heart failure and death if not treated.

👉 Core clinical line:

Chronic pulmonary HTN loads the right ventricle → cor pulmonale.

D. Treatment – what the box emphasises

• Vasodilators are the key:
• Especially prostacyclin and prostacyclin analogues.
• Older limitation:
• Traditionally had to be given as continuous IV infusion.
• Newer development:
• Aerosolized prostacyclin preparations are now available and appear effective → easier to give, more practical.

So for exam:

Pulmonary HTN: multiple causes (hypoxia, cocaine, dexfenfluramine/serotonin, SLE, familial mutations → ↑ PVR), leading to ↑ RV afterload and right heart failure; treated with pulmonary vasodilators such as prostacyclin and its analogs (IV or newer aerosol forms).

One combined memory paragraph

Gravity causes marked regional differences in pulmonary blood flow: at the apex, low vascular pressures allow alveolar pressure to collapse capillaries and convert units into physiologic dead space if Pa falls or PA rises (Zone 1). In the mid-lung (Zone 2), flow shows a “waterfall effect” and depends on the pulmonary artery–alveolar pressure difference, whereas at the base (Zone 3), alveolar pressure is lower than Pa and Pv and flow is determined by the usual artery–vein gradient, giving maximal perfusion. Pulmonary hypertension arises from causes such as hypoxia, cocaine, appetite suppressants like dexfenfluramine (via serotonin), SLE, and familial mutations that increase pulmonary vascular resistance, thereby increasing right ventricular afterload and eventually causing right heart failure if untreated. Vasodilators, especially prostacyclin and its analogs (now also in aerosol form), are key therapies.

V/Q RATIOS

1. What is the V/Q ratio?

• Ventilation (V) = air reaching alveoli per minute.
• Perfusion (Q) = blood reaching alveoli per minute.

For the whole lung at rest:

• V ≈ 4.2 L/min
• Q ≈ 5.5 L/min

So:

Overall V/Q ≈ 0.8

That “0.8” is the normal global V/Q ratio you must remember.

2. What happens if V/Q is low or high?

Think per alveolus:

A. Low V/Q (ventilation ↓ relative to blood flow)

• Ventilation is too little for the blood flow.
• Consequences in that alveolus:
• PO₂ falls → less O₂ delivered to that alveolus, but blood keeps taking O₂ away.
• PCO₂ rises → CO₂ comes from blood but isn’t blown off properly.

This behaves like a “shunt-like” unit (blood leaving under-oxygenated).

B. High V/Q (perfusion ↓ relative to ventilation)

• Blood flow is too little for the ventilation.
• Consequences:
• PCO₂ falls → less CO₂ delivered, so alveolar CO₂ drops.
• PO₂ rises → fresh air keeps adding O₂, but little blood is taking it away.

This behaves like “dead-space-like” ventilation (plenty of air, little blood).

3. Regional differences in the upright lung

In the upright position:

• Both ventilation and perfusion decrease from base → apex.
• But perfusion falls more steeply than ventilation as you go up.

So:

• Base → V and Q both high, but Q relatively higher → V/Q low.
• Apex → V and Q both low, but Q very low → V/Q high.

👉 So even in a normal lung, different regions have different V/Q ratios.

4. Why V/Q mismatch is clinically important

“When widespread, nonuniformity of ventilation and perfusion in the lungs can cause CO₂ retention and lowers systemic arterial PO₂.”

Meaning:

• Small regional differences = normal.
• But if many lung units have very low or very high V/Q (e.g. disease):
• O₂ falls in arterial blood (PaO₂ ↓) → hypoxemia.
• CO₂ can rise (PaCO₂ ↑) → CO₂ retention, especially if compensation fails.

This is one of the main mechanisms of hypoxemia in lung disease:

V/Q mismatch, not just diffusion problem.

5. One exam-ready summary paragraph

The normal overall V/Q ratio for the lung at rest is about 0.8 (4.2 L/min ventilation ÷ 5.5 L/min blood flow). In individual alveoli, if ventilation is low relative to perfusion (low V/Q), alveolar PO₂ falls and PCO₂ rises; if perfusion is low relative to ventilation (high V/Q), alveolar PO₂ rises and PCO₂ falls. In the upright lung, both ventilation and perfusion decrease from base to apex, but perfusion falls more steeply, so V/Q is low at the base and high at the apex. When V/Q non-uniformity is widespread in disease, it causes low arterial PO₂ and can lead to CO₂ retention.

METABOLIC & ENDOCRINE FUNCTIONS OF THE LUNGS

1. Big picture: lungs are also a metabolic/endocrine organ

Beyond gas exchange, lungs:

• Make surfactant
• Help lyse clots in pulmonary vessels (fibrinolytic system)
• Activate and inactivate hormones and peptides as blood passes through
• Remove some vasoactive substances from venous blood
• Release others into systemic arterial blood

So: every time blood crosses the lung, it is not only oxygenated but also chemically “edited.”

2. The most high-yield pathway: ACE and angiotensin

This is the single most important exam point.

• Lungs have large amounts of angiotensin-converting enzyme (ACE) on pulmonary capillary endothelial cells.
• In the pulmonary circulation:
• Angiotensin I (inactive decapeptide)

is converted to

• Angiotensin II (active octapeptide):
• Potent pressor (raises blood pressure)
• Stimulates aldosterone release.

Key facts:

• About 70% of angiotensin I is converted to angiotensin II in a single pass through the lungs.
• ACE also inactivates bradykinin (a vasodilator).

So:

Lungs are the main ACE factory → they activate angiotensin I to II and destroy bradykinin in under 1 second.

That’s the classical RAAS physiology and also why ACE inhibitors have effects on BP and bradykinin (cough, angioedema).

3. What the lungs synthesize or store and release

From the table:

1. Synthesized and used locally in lungs
• Surfactant
• Made by type II pneumocytes
• Essential for lowering alveolar surface tension and preventing collapse.
2. Synthesized or stored and released into blood
• Prostaglandins
• Histamine
• Kallikrein

And additionally from the text:

• Prostaglandins are both:
• Removed from circulation
• Synthesized and released when lung tissue is stretched.

So lungs can both make and clear some mediators.

4. What the lungs partially remove from blood

Substances partially removed as venous blood passes through pulmonary capillaries:

• Prostaglandins
• Bradykinin
• Adenine nucleotides
• Serotonin
• Norepinephrine
• Acetylcholine

Key concept:

Removal of serotonin and norepinephrine reduces how much of these strong vasoactive amines reach systemic circulation.

So lungs act like a filter for certain vasoactive substances.

5. Which vasoactive hormones pass through unchanged

Important contrast:

• Many hormones are not significantly metabolized by lungs and pass through as they are:
• Epinephrine
• Dopamine
• Oxytocin
• Vasopressin (ADH)
• Angiotensin II (already active form)

Also, lungs have neuroendocrine cells that secrete various amines and polypeptides locally.

6. Mini-summary table for memory

You can drop this straight into XMind/notes:

• Synthesized and used in lungs
• Surfactant
• Synthesized or stored and released into blood
• Prostaglandins
• Histamine
• Kallikrein
• Partially removed from blood (inactivated/cleared)
• Prostaglandins
• Bradykinin
• Adenine nucleotides
• Serotonin
• Norepinephrine
• Acetylcholine
• Activated in lungs
• Angiotensin I → Angiotensin II (via ACE)
• ACE also inactivates bradykinin
• Largely pass through unchanged
• Epinephrine
• Dopamine
• Oxytocin
• Vasopressin
• Angiotensin II

7. One exam-ready paragraph

In addition to gas exchange, the lungs have important metabolic roles: they make surfactant, have a fibrinolytic system that lyses clots, and act as a major endocrine “filter” for blood. Pulmonary capillary endothelial cells express large amounts of ACE, which converts inactive angiotensin I to active angiotensin II and inactivates bradykinin; about 70% of angiotensin I is converted in a single pulmonary passage. The lungs synthesize and use surfactant locally, and synthesize or store and release prostaglandins, histamine, and kallikrein. They partially remove prostaglandins, bradykinin, adenine nucleotides, serotonin, norepinephrine, and acetylcholine from blood, while many hormones such as epinephrine, dopamine, oxytocin, vasopressin, and angiotensin II pass through unaltered. Various neuroendocrine cells in the lungs also secrete amines and peptides.