Respiratory Physiology

Figure 4.1 Branches of the respiratory tree. (Reproduced, with permission, from Kibble JD, Halsey CR: Medical Physiology: The Big Picture. New York, NY: McGraw-Hill; 2009.)

RESPIRATORY ANATOMY

What is the purpose of the branching pattern shown above?

To allow for dramatic increase in cross-sectional area.

What is the approximate cross-sectional area of the trachea?

2.5 cm²

How many alveoli are there present in a normal adult?

About 300 million

How many branches are there in the respiratory tree?

23

How many generations until alveoli are present; that is, how many branch generations in the conducting zone?

16 (trachea to the terminal bronchioles)

What type of epithelium lines the conducting zone?

Ciliated, pseudostratified columnar (also known as respiratory epithelium)

At what point in the respiratory tree does gas exchange begin?

Respiratory bronchioles (branch point 17)

What is the surface area of alveolar-capillary interface available for gas exchange?

50 to 100 m²; approximately the size of a tennis court

What are the barriers to gas exchange at the alveolar-capillary interface?

Surfactant

Alveolar epithelium

Interstitial space

Capillary endothelium

What types of cells compose the alveolar surface?

Type I pneumocytes: thin cells that constitute 90% of the surface area, even though less abundant than type II cells in numbers

Type II pneumocytes: most abundant, but only constitute 10% of surface, and produce surfactant

Phagocytic alveolar macrophages: ingests and clears foreign, inhaled particles

What are the two types of dead space?

1. Anatomic dead space (respiratory tree with no alveoli present)
   
2. Alveolar dead space (alveoli with no perfusion)

How is anatomic dead space approximated?

Ideal body weight in pounds is roughly equivalent to anatomic dead space in milliliters.

What is the function of anatomic dead space?

Warm and humidity inspired air Removal of foreign particles

In which locations and by what mechanisms is air filtered?

1. In vibrissae (aka nasal hairs)
   
2. By mucus in bronchi and bronchioles
   
3. Alveolar macrophages remove particles that make it to alveoli

What is the mucociliary escalator?

As foreign particles are trapped in the mucus that lines the epithelium of the respiratory tract, the cilia on the epithelium beat upwards, away from alveoli and lower respiratory structures.

What common inhalant inhibits the mucociliary escalator?

Cigarette smoke

Why do particles in venous blood not reach the arterial circulation?

They are filtered out by the pulmonary circulation (these particles can vary, but can be clots, agglutinated red blood cells, gas bubbles, etc).

What does this “filter” prevent?

Thrombotic or occlusive events on the left side of circulation (such as stroke, MI, etc)

LUNG VOLUMES AND CAPACITIES

Define the following lung volumes:

Tidal volume (V_T)

Volume of a normal breath at rest (average 500 mL)

Inspiratory reserve volume (IRV)

Additional volume of gas that can be inspired above the V_T (average 3 L)

Expiratory reserve volume (ERV)

Volume of gas that can be forcefully expired after a normal passive expiration (average 1.3 L)

Residual volume (RV)

Volume of gas that remains after maximal expiration (average 1.5 L)

How are lung volumes and capacities related?

A capacity is the sum of two or more volumes

Define the following lung capacities:

Total lung capacity (TLC)

Volume of gas present after a maximal inspiration (average 6 L)

Vital capacity (VC)

Maximal volume that can be expelled after a maximal inspiration (average 4.5 L). This is the maximal volume that can be exchanged in a single breath

Functional residual capacity (FRC)

Volume remaining at the end of a normal breath at rest (average 3 L)

Identify the labeled lung volumes on the spirogram below.

Figure 4.2 Lung volumes.

1. Tidal volume (V_T)
   
2. Inspiratory reserve volume (IRV)
   
3. Expiratory reserve volume (ERV)
   
4. Residual volume (RV)
   
5. Vital capacity (VC)
   
6. Functional reserve capacity (FRC)
   
7. Total lung capacity (TLC)

What are the volumes that make up the following capacities?

Inspiratory capacity (IC)

IC = V_T + IRV

FRC

FRC = RV + ERV

VC

VC = ERV + V_T + IRV

TLC

TLC = RV + ERV + V_T + IRV

Which lung volumes and capacities cannot be measured using spirometry?

RV, FRC, and TLC

How can the above capacities be measured?

Nitrogen washout

Helium dilution

Body plethysmography

How does FRC change with position?

FRC increases when standing/sitting and decreases when supine

How does age affect the following parameters of pulmonary function tests (PFTs)?

TLC

Decreased

RV

Increased

VC

Decreased

FRC

Does not change

Define minute ventilation (V_E):

Volume of air inspired or expired per minute:

V_E = V_T × frequency

What are:

Forced vital capacity (FVC)

Volume exhaled with maximal expiratory effort

Forced expiratory volume in 1 second (FEV₁)

Volume that can be forcefully expired in 1 second

What is the normal ratio of FEV₁ per FVC?

80% (FEV₁/FVC = 0.8)

What is alveolar ventilation?

The volume of air reaching the alveoli per minute

Why is alveolar ventilation less than minute ventilation?

Last part of inspired air only reaches the conducting zone and never reaches the respiratory zone

How does shallow versus deep breathing affect alveolar ventilation?

Rapid shallow breathing produces much less alveolar ventilation; most of each breath ventilates the conducting zone

How is dead space calculated?

V_d = V_t × ([PaCO₂ × PeCO₂]/PaCO₂)

V_d: Dead space volume

V_t: Total lung volume

PaCO₂: Partial pressure of arterial CO₂

PeCO₂: Partial pressure of expired CO₂

RESPIRATORY MECHANICS

What are the muscles of inspiration?

1. Diaphragm (majority of work at rest)
   
2. External intercostals (increase thoracic size and prevent retraction)
   
3. Accessory muscles of inspiration (not used during quiet breathing)

What are the accessory muscles of inspiration?

Sternocleidomastoid, scalenes, strap muscles of neck

What is the innervation of the diaphragm?

Phrenic nerve (C3,4,5 keep the diaphragm alive)

Where does referred diaphragmatic pain occur?

Ipsilateral shoulder (remember the dermatomes of the nerve roots!)

Does the diaphragm contribute more to inspiration while supine or standing?

Supine; when standing, external intercostals contribute significantly

What action does the diaphragm perform?

As it contracts it flattens into the abdominal cavity, increasing the volume of the thoracic cavity

Which muscles are involved in normal, quiet expiration?

None. It is a passive process due to the elastic recoil by the lungs.

Which muscles are active in active expiration (e.g., exercise)?

Abdominal muscles and internal intercostals

During quiet breathing, which is longer, inspiration or expiration?

Expiration, in about a 2:1 ratio

Where is the intrapleural space?

It is between the lung and the chest wall. It is actually only a “potential space” under normal conditions because the visceral and parietal pleural layers are usually closely apposed.

What is the normal intrapleural pressure at rest?

Slightly subatmospheric (−3 to −5 cm H₂O)

How can the intrapleural pressure be measured?

A swallowed balloon can measure the intrathoracic pressure, which approximates the intrapleural pressure.

What is the normal series of events during inspiration?

Respiration initiated by central
nervous system
↓
Diaphragm contracts, along with
other external intercostals↓Thoracic volume increases
Decrease in intrapleural pressure
↓
Alveoli expand
↓
Alveolar pressure becomes
subatmospheric
↓
Air flows into alveoli to equilibrate
with atmospheric pressure

Figure 4.3 Volume, pressure, and airflow during a respiratory cycle.

Define compliance (C):

An indication of how easily the lungs and chest wall can be stretched or inflated. In general terms, it refers to the lungs ability to accommodate incoming volume.

What is the equation for compliance?

C= ΔV/ΔP

ΔV = change in volume

ΔP = change in pressure

What physiologic elements influence compliance?

Most widely discussed are things like intrinsic recoil of pulmonary tissues, but remember that lung volume and alveolar surface tension also contribute

What processes can cause a decrease in compliance?

Pulmonary congestion and various restrictive lung diseases

What causes an increase in compliance?

Destruction of lung tissue with concomitant loss of elastic tissues (e.g., emphysema)

Figure 4.4 Comparison of spirograms between normal and diseased lungs.

Compare the FEV1: FVC ratio of a normal lung to a lung with emphysema or chronic bronchitis (COPD)

Normal lung has an FEV1: FVC ratio of 80%, emphysematous lung has an FEV1: FVC ratio of <80% (usually 60%-70% or less).

What other obstructive lung disease cause this pattern?

Asthma, bronchiectasis

What physical examination findings correlate with obstructive lung disease?

Increased anteroposterior diameter of the chest (barrel chested), and prolonged expiratory phase

How does the FVC compare between a normal lung and one with restrictive disease?

Total FVC is lower due to decreased lung compliance

How does compliance change with lung volumes?

Increases at low volumes, decreases at high volumes

Define elasticity:

The recoil force generated by distension of a structure

How is compliance related to elasticity?

Inversely (C= 1/E)

What contributes to the lungs’ recoil properties?

Lung parenchyma (elastin, collagen, etc)

Surface tension at air-liquid interface in alveoli

How does Laplace law relate to surface tension, and how does that affect the collapsibility of alveoli?

P = collapsing pressure (dyne/cm²)

T = surface tension (dyne/cm)

r= alveolar radius (cm)

Which is easier to keep open, a large alveoli or a small one?

Large alveoli (alveolar radius is inversely proportional to collapsing pressure, see above equation)

Which cells produce surfactant?

Type II alveolar epithelial cells

What are the functions of pulmonary surfactant?

1. Reduce surface tension at low lung volumes (prevent atelectasis)
   
2. Increase surface tension at high lung volumes (contribute to lung recoil)
   
3. Increase alveolar radius
   
4. Reduce pulmonary capillary infiltration

What is the effect of surfactant on compliance and elasticity?

Surfactant increases compliance, and decreases elasticity

What is surfactant composed of?

1. Dipalmitoyl phosphatidylcholine (aka lecithin)-major
   
2. Phosphatidylglycerol
   
3. Other lipids
   
4. Neutral lipids
   
5. Proteins

How may surfactant synthesis be reduced?

Developmental deficiency (e.g., prematurity)

Hypovolemia

Hypothermia

Acidosis

Hypoxemia

Rare genetic disorders of surfactant synthesis

What is the significance of surfactant in infant respiratory distress syndrome (IRDS)?

In this condition a surfactant deficiency results in high surface tension in the alveoli of the lungs, leading to alveolar collapse and atelectasis. Because of this, there is decreased FRC with subsequent arterial hypoxemia.

What does the therapy for IRDS include?

1. Positive end-expiratory pressure (PEEP)
   
2. Steroids
   
3. Exogenous surfactant

By what week do the fetal lungs make surfactant?

Week 34 to 36

What may indicate fetal pulmonary maturity?

The ratio of lecithin to sphingomyelin or L/S ratio in the amniotic fluid. Over the course of gestation, lecithin gradually increases with pulmonary maturity while the sphingomyelin remains constant, so it serves as a useful meter.

The presence of minor phospholipids (e.g., phosphatidylglycerol) is also indicative in cases where the L/S ratio is borderline.

What L/S ratio usually indicates pulmonary maturity?

2:1

What can be used to help accelerate the maturation of surfactant in the lungs of a fetus?

Glucocorticoid hormones

Under normal conditions, what structural feature of individual alveoli helps to prevent them from collapsing?

Alveolar walls and airway walls are structurally connected so that tension on alveolar walls created by one collapsing alveolus helps to hold adjacent alveoli open.

What is the above theory called?

Alveolar interdependence

What two types of resistance make up pulmonary resistance?

1. Airway resistance (~80%)
   
2. Pulmonary tissue resistance (~20%)

In what pathologic states is pulmonary tissue resistance increased?

Fibrosis from any cause, examples include amyloidosis and sarcoidosis

What factors determine airway resistance?

Gas viscosity

Diameter of the airway

Length of the airway

What law describes airway resistance?

Poiseuille law:

R = resistance

η = viscosity of inspired gas

l = length of airway

r= radius of airway

How are airway resistance and airflow related?

Much like flow through the cardiovascular system, they are inversely related:

Q = airflow (L/min)

Δ P= pressure gradient (cm H₂O)

R = airway resistance (cm/H₂O/L/min)

Which part of the respiratory system is the major site of airway resistance?

Medium-sized bronchi

Which part of the respiratory system has the highest individual resistance?

Small terminal airways; they are not the major site of airway resistance because they are far more numerous and are arranged in parallel

What factors can change airway resistance?

Altering the radius of the airways
Changes in lung volume
Viscosity/density of the inspired gas

What is bronchoconstriction/dilation?

Changes in the diameter of conducting airways

What causes bronchoconstriction?

Parasympathetic discharge

Substance P

Adenosine

Hypersensitivity response (e.g., histamines)

Arachidonic acid metabolites (e.g., prostaglandins and leukotrienes)

How does bronchoconstriction affect airways?

1. Reduces airway radius
   
2. Increases resistance
   
3. Via the above two changes, limits airflow during inspiration or expiration

What causes bronchodilation?

Sympathetic discharge and sympathetic agonists via β2 receptors

How do obstructive diseases affect respiratory mechanics?

Increase airway resistance; it creates air trapping which increases lung volumes

How do restrictive diseases affect respiratory mechanics?

Decrease compliance, affecting inspiration mechanics; more on this later

GAS EXCHANGE

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