RESPIRATORY SYSTEM

CONDUCTING ZONE

Nose → pharynx → larynx → trachea → bronchi → bronchioles

• move air in/out

• traps debris and pathogens in mucus

• warms and humidifies air

• no gas exchange

RESPIRATORY ZONE

Terminal bronchioles → alveolar ducts → alveolar sacs → alveoli

• gas exchange between blood and air

• via passive diffusion

• across 0.5 um membrane

TERMINAL BRONCHIOLES

The last of the conducting zone

RESPIRATORY BRONCHIOLES

First part of gas-exchanging zone

WHY SURFACE AREA MATTERS

As airways branch:

• individual airway diameter decreases, then plateaus

• airway numbers increase exponentially

• cross-sectional area near alveoli increases greatly

This matters because gas exchange is passive diffusion and relies on:

• surface area

• diffusion distance

RESPIRATORY ENDOTHELIUM

Conducting portion:

• nasal cavity + trachea + bronchus + bronchi

• pseudostratified columnar epithelial cells

Gas-exchange portion:

• alveoli

• simple squamous

GAS-EXCHANGE PORTION

Type I alveolar cells

• simple squamous epi

• thin diffusion barrier

• tight junctions

Type II alveolar cells

• cuboidal epi

• surfactant secreting

• replace damaged Type I cells

FLICK’S LAW OF DIFFUSION

Shorter distance = greater rate of diffusion

Greater surface area = greater rate of diffusion

SCARRING AND GAS EXCHANGE

If the alveolar wall is replaced by scar tissue:

• diffusion distance becomes greater than the normal 0.5um

• scar tissue is stiff so lungs are harder to inflate

This occurs in Idiopathic Pulmonary Fibrosis and once advanced, lifespan is reduced to a few years.

LUNG PLEURA

Each lung is wrapped in a thin, two-layered, fluid-filled membrane containing:

• inner visceral pleura (on the lung)

• outer parietal pleura (on the chest wall)

• pleural cavity filled with pleural fluid

PLEURA FUNCTIONS

1. Lubrication

• reduces friction during breathing

2. Surface tension

• helps position lungs against thoracic wall

3. Division

• Isolates respiratory system from other major organs

PLEURA CRITICAL POINTS

It is a closed system and air should never be inside.

If pleura is compromised, the lung cannot follow the rib cage and you cannot breathe effectively.

BOYLE’S LAW

For a fixed amount of gas at a constant temperature, pressure and volume are inversely related.

P1V1 = P2V2

INSPIRATION STEPS

1. Inspiratory muscles contract (diaphram descends, ribcage raises)

2. Thoracic cavity volume increases

3. Lungs are stretched - intrapulmonary volume increases

4. Intrapulmonary pressure drops (-1mmHg relative to atmosphere)

5. Air flows down pressure gradient until intrapulmonary pressure returns to zero.

EXPIRATION STEPS

1. Inspiration muscles relax (elastic recoil of lungs)

2. Thoracic volume decreases

3. Intrapulmonary pressure rises to +1mmHg relative to atmosphere

4. Air flows out down pressure gradient until intrapulmonary pressure equals zero

LUNG VOLUME AND TIME

• Rising is slowest at the end of inspiration because the lung is resisting further inflation

• Rising is fastest at the start of expiration because recoil is strongest when the lung is most inflated

PRESSURE GRADIENTS

Intra-alveolar pressure:

• most negative mid-inspiration

Intrapleural pressure:

• keeps falling throughout inspiration and only rises once inspiratory muscles fully relax

• never fully equalises with atmosphere because pleural space is sealed

TRANSPULMONARY PRESSURE

• the net distending pressure that keeps the lung open

• should always be positive

• alveolar pressure > intrapleural pressure always

• tidal volume approx. 400-500mL per breath

Ptp = Palveolar - Pintrapleural

PNEUMOTHORAX

If pleural seal is breached, air enters pleural space and it is no longer sealed →

Intrapleural pressure rises to equal atmosphere →

Transpulmonary pressure collapses to zero →

Lungs collapse

LUNG PRESSURES

Key factors influencing negative intrapleural pressure:

1. Surface tension

• pleural fluid provides surface tension between pleural layers

2. Elastic force by lungs

• elastic tissue in lungs recoils and pulls lungs inward

3. Elastic force by thoracic cage

• thoracic wall naturally pulls away from lungs

• parietal pleura pulled outward

MODES OF BREATHING

Quiet breathing:

• At rest without conscious thought

• Inspiration = diaphragm or external intercostals

• Expiration = passive - relaxation only, no muscle contraction

Forced breathing:

• Requires extra muscle contraction both phases

• Inspiration = diaphragm, external intercostals + accessory muscles

• Expiration = internal intercostal + thoracic transversus compress abdomen and push diaphragm upward.

THE MASTER EQUATION

Airflow rate (F) = Pressure gradient (P) / Airway resistance (R)

Three factors govern how easily air moves and how easily the lung inflates:

1. Airway resistance

2. Lung compliance and elastic recoil

3. Alveolar surface tension

AIRWAY RESISTANCE

Resistance is friction from air moving against airway walls and depends mostly on airway diameter. Increases with:

• bronchoconstriction

• mucus/secretions

• fluid/oedema

Large airways have low resistance because of large diameter.

Small airways have low resistance because of large cross-sectional area.

Therefore, medium airways have the greatest resistance.

ASTHMA

Uncontrolled bronchospasms narrow the airway, raising resistance and work of breathing,

LARGE VS SMALL AIRWAY STRUCTURE

Large airways are held open by cartilage and cannot collapse.

Small airways have no cartilage support, they are floppy and can be squeezed shut from outside.

DYNAMIC AIRWAY CLOSURE

At the point in the small airway where airway pressure drops below the surrounding intrapleural pressure, the higher external pressure physically pinches it shut.

This traps remaining air proximal to the closure point, and that trapped air becomes part of the residual volume.

• This is a normal, healthy mechanism

• no one can fully empty their lungs

EARLY AIRWAY CLOSURE IN ASTHMA

Overstimulated small airways →

Increased small airway resistance →

Critical closure point reached earlier →

Decreased Forced Vital Capacity (FVC) + increased Residual Volume (RV)

EARLY AIRWAY CLOSURE IN EMPHYSEMA

Loss of lung tissue →

Decreased lung elastic recoil →

Small airways collapse earlier during expiration →

Decreased Forced Vital Capacity (FVC) + increased Residual Volume (RV)

LUNG COMPLIANCE

• how easily lung can be stretched

• measure of elastic resistance

• increased compliance = easy to inflate

C = change in V / change in P

LUNG ELASTIC RECOIL

• the tendency of the lung to rebound back

• compliance and elastic recoil are inversely related

FIBROSIS COMPLIANCE

• decreased compliance

• scar tissue is inelastic

• harder to inflate, increased breathing work rate

EMPHYSEMA COMPLIANCE

• increased compliance

• loss of lung tissue = less to stretch and recoil

• easier to inflate but fewer functional alveoli for gas exchange

ALVEOLI SURFACE TENSION

• Alveolar surface coated in water film

• water molecules are charged and attract to each other

• creates surface tension that tends to collapse the alveolus and resists inflation

LAW OF LAPLACE

Magnitude of inward-directed pressure in a bubble (alveoli) = 2 x Surface tension / radius of bubble (alveoli)

PULMONARY SURFACTANT

Pulmonary surfactant is produced in roughly equal quantities by the Type II cells of each alveolus, regardless of alveolus size.

In smaller alvelous:

• the same amount of surfactant is more concentrated

• surface tension lowered more

In larger alveolus:

• the same amount of surfactant is more dilate

• surface tension lowered less

SURFACTANT EQUILISATION

The different concentrations equilises collapsing pressure across alveoli of different sizes.

Overall, more concentrated surfactant = increased lung compliance + decreased work of breathing

INFANTORY RESPIRATORY DISTRESS SYNDROME

• Premature infants (before 28 weeks) or newborns who have inadequate surfactant production

• Alveoli collapse during expiration

Treatment:

• surfactant spray

• mechanical ventilation

ALVEOLI AND FORCES

Keep alveoli OPEN

• transpulmonary pressure gradient

• pulmonary surfactant

• alveolar indpendence

Promote alveoli COLLAPSE

• elastic recoil of pulmonary connective tissue

• Alveolar surface tension

PRESSURE TERMINOLOGY

P (capital) followed by gas = partial pressure

Ex. PO2 = partial pressure of oxygen

Subscript a = arterial partial pressure

Ex. PaO2 = partial arterial pressure of oxygen

Subscript v = venous partial pressure

Ex. PvO2 = venous partial pressure of oxygen

FiO2 = fraction of inspired oxygen

Ex. %of O2 patient breathes in

VENTILATION - PERFUSION MATCHING

Three factors govern external respiration

1. V/Q Matching

• alveolar ventilation vs pulmonary blood perfusion

2. Structural characteristics

• of respiratory membrane (surface area, distance)

3. Partial Pressure gradients

• And gas solubility

WHY V/Q MATCHING MATTERS

Alveoli are not uniformly inflated therefore, body automatically diverts more blood flow to better ventilated alveoli.

Matching perfusion to ventilation maximises gas exchange efficiency.

Ideal is V/Q = 1.

V/Q < 1 (SHUNTING)

• alveolus poorly ventilated but still perfused

• blood passes without gas exchange

• high CO2, low O2 in mixed blood

• = local hypoxia as airway attempts to dilate

V/Q > 1 (DEADSPACE)

• alveolus is well ventilated but no blood flow reaches it (no perfusion)

• low CO2, high O2 overall

• Airway constricts to divert fresh air to alveoli that are perfused

PRONING

Turning someone on their belly for 6+ hours to improve V/Q Matching in unhealthy patients.

RESPIRATORY MEMBRANE

Alveolar walls

• thin squamous epi cells

Capillaries

• tightly encase external alveolar surface

Type II pneumocytes

• secrete pulmonary surfactant

Interstitial fluid

• very thin layer (0.5um)

DALTON’S LAW

In a mixture of gases, the partial pressure exerted by any one gas is proportional to its percentage amount in the mixture.

HENRY’S LAW

The amount of gas that dissolves a liquid is directly proportional to the partial pressure of that gas above the liquid.

DALTON + HENRY

Partial pressure of a gas can be used a surrogate marker for the amount of that gas dissolved in blood.

FOUR PROCESS OF RESPIRATION

1. Pulmonary ventilation (breathing)

2. External respiration

3. Transport of respiratory gases

4. Internal respiration

2 + 4 = gas exchange

3 = gas transport

PARTIAL PRESSURE THROUGH SYSTEM

Atmospheric air (dry)

• 159 PO2

• 0.3 PCO2

Alveoli air (humidified + mixed)

• 104 PO2

• 40 PCO2

Mixed venous blood

• 40 PO2

• 46 PCO2

Arterial blood

• 97 PO2

• 40 PCO2

FACTORS AFFECTING GAS EXCHANGE

1. Partial pressure gradient

2. Surface area of membrane

3. Thickness of membrane

4. Diffusion coefficient

5. V/Q matching

DIFFUSION COEFFICIENT

• related to gas solubility and molecular weight

• D for CO2 is x20 D for O2 (CO2 diffuses more easily)

• BUT O2 has bigger partial pressure gradient than CO2

• therefore, CO2 and O2 are exchanged equally despite different solubilities

EMPHYSEMA

Decreased surface area and increased membrane thickness.

Causes:

• pulmonary oedema

• pneumonia

• pulmonary fibrosis

ACUTE RESPIRATORY DISTRESS SYNDROME

• Affects 1 in 10 mechanically ventilated ICU patients

• 30-50% mortality rates

• fast onset, <2 weeks

• no specific treatment exists

PNEUMONIA

1. Community acquired

2. Hospital/ventilator acquired

Inflammation → fluid/oedema → respiratory membrane becomes leaky → membrane thickness increases → diffusion rate decreases → arterial PaO2 drops

PNEUMONIA SEVERITY

Measured using ratio:

P/F ratio = PaO2 / FiO2

P/F ratio > 300 = Good/normal

P/F ratio = 200-300 = 30% mortality

P/F ratio = 100-200 = 40% mortality

P/F ratio <100 = 40-60% mortality