Mechanism of Respiration

Functional Anatomy of the Respiratory Tract

The respiratory system is structurally divided into two main components: the conducting zone (airways) and the respiratory zone (gas exchange area).

A. Conducting Zone (Airways)

This zone includes a series of interconnected passages that function to deliver air to the respiratory zone, while simultaneously filtering, warming, and moistening the inspired air. Gaseous exchange does not occur in this region.

• Components: Structures include the nose, pharynx, larynx, trachea (zeroth generation), bronchi, bronchioles, and terminal bronchioles.

• Musculature: The walls of the conducting airways contain smooth muscle.

• Lining: Airways are lined with mucus-secreting and ciliated cells. The mucus traps inhaled particles, which are then swept upward by the rhythmic beating of the cilia.

• Regulation (Airway Diameter): The smooth muscle is controlled by both sympathetic and parasympathetic innervation.

    ◦ Sympathetic/Adrenergic: Stimulates β2 receptors on bronchial smooth muscle, leading to relaxation and dilation of the airways (e.g., using drugs like isoproterenol or epinephrine).

    ◦ Parasympathetic/Cholinergic: Activates muscarinic receptors, leading to contraction and constriction of the airways.

B. Respiratory Zone

This is the region where gaseous exchange (external respiration) occurs.

• Components: Includes the respiratory bronchioles, alveolar ducts, and alveolar sacs, all of which are lined with alveoli.

• Alveoli: These are cup-shaped pouches surrounded by a dense network of pulmonary capillaries.

• Respiratory Membrane: This membrane is formed by the thin walls of the alveoli and pulmonary capillaries. It is extremely thin to allow rapid diffusion of gases.

• Alveolar Cells (Pneumocytes):

    ◦ Type I pneumocytes: Line the alveoli (epithelial cells).

    ◦ Type II pneumocytes: Synthesize pulmonary surfactant, which is essential for reducing surface tension and maintaining alveolar opening.

• Alveolar Macrophages: These phagocytic cells migrate to the bronchioles to clear the alveoli of dust and debris.

C. Pulmonary Circulation (Blood Supply)

The lungs have a complex double blood supply.

1. Pulmonary Arteries: These carry deoxygenated blood from the right ventricle into the lungs for oxygenation (Pulmonary Circulation).

    ◦ The pulmonary vasculature is a low-resistance network of highly distensible vessels characterized by much lower pressures and resistances than the systemic circulation.

2. Bronchial Arteries: These bring oxygenated blood to the lung tissue, specifically supplying the conducting airways and connective tissues.

    ◦ Most bronchial blood is returned via pulmonary veins, but some drains into the superior vena cava via bronchial veins.

Non-Respiratory Functions of Lungs

The lungs perform several vital non-respiratory functions, including physical protection, metabolic and endocrine roles, and fluid regulation.

A. Protection and Clearance

1. Mucociliary Clearance: The ciliated epithelial cells lining the respiratory passages move a layer of mucus upward toward the throat, trapping particles and pathogens.

2. Phagocytosis: Alveolar macrophages patrol the alveoli, consuming dust and cellular debris, thereby maintaining tissue sterility.

3. Physical/Mechanical Protection: The pleural membrane covers the lungs and lines the thoracic cavity, providing protection and lubrication.

4. Blood Filtration: The lungs serve to filter the entire cardiac output of the right heart and participate in the clearance of microthrombi and emboli.

B. Metabolic and Endocrine Roles

1. Surfactant Production: Type II alveolar cells synthesize and secrete pulmonary surfactant (primarily dipalmitoyl phosphatidylcholine), which reduces the surface tension in the alveoli.

2. Angiotensin Activation: Pulmonary endothelial cells rapidly convert angiotensin I to angiotensin II by the action of Angiotensin-Converting Enzyme (ACE).

3. Hormone/Neurotransmitter Processing: Lungs are involved in the partial removal or inactivation of substances from the circulation, including serotonin, acetylcholine, bradykinin, and prostaglandins E and F.

4. Vasoactive Substance Synthesis: The lungs synthesize certain vasoactive substances, such as prostaglandins.

C. Regulation and Fluid Dynamics

1. Fluid and Heat Exchange: Lungs contribute to heat loss and aid in fluid distribution. They excrete water vapor in the expired air.

2. Acid-Base Balance: The lungs eliminate volatile acid, primarily carbon dioxide (CO2). This is the body's fastest mechanism for adjusting pH, and breathing is regulated primarily by the production of CO2  in the tissues.

3. Auxiliary Pump for Venous Return: The rhythmic changes in intrathoracic pressure caused by respiratory movements act as an auxiliary pump to accelerate venous return to the heart.

4. Absorption: The lungs are a major site for the absorption of general anesthetics and drugs.

5. Vocalization: The respiratory system functions in sound production (phonation)

Mechanics of Normal Respiration and Chest Movements

The movement of air into and out of the lungs, known as pulmonary ventilation or breathing, is a mechanical process dependent on the existence of a pressure gradient. Energy transformation in the body produces movement on a macroscopic scale, which is required for the intake of oxygen and the expulsion of carbon dioxide.

I. Mechanics and Muscles of Normal Respiration

Normal, quiet respiration is primarily achieved through muscle contraction during inspiration, while expiration is typically a passive process.

A. Inspiration (Active Process)

Inspiration requires muscle contraction to increase the volume of the thoracic cavity, thus generating the necessary pressure gradient.

1. Primary Muscle: The diaphragm is the most important muscle for inspiration.

2. Movement: When the diaphragm contracts, it pushes the abdominal contents downward, simultaneously lifting the ribs upward and outward.

3. Thoracic Volume: This action produces an increase in intrathoracic volume, which initiates the flow of air into the lungs.

4. Accessory Muscles: The external intercostal muscles and accessory muscles are not used for inspiration during normal quiet breathing. These are typically engaged during exercise or vigorous inspiration.

B. Expiration (Passive Process)

Normal expiration requires no muscle contraction and relies entirely on elastic forces.

1. Mechanism: Expiration is normally a passive process. Air is driven out of the lungs by the reverse pressure gradient as the lung–chest wall system is elastic and returns to its resting position after inspiration.

2. Muscles of Forced Expiration: Expiratory muscles, such as the abdominal muscles and internal intercostal muscles, are only used during exercise or when airway resistance is increased (e.g., in disease like asthma).

II. Pressures and Movements During the Breathing Cycle

The mechanics of breathing are governed by the relationship between intrapulmonary (alveolar) pressure, intrapleural pressure, and atmospheric pressure (referred to as zero).

A. Rest (Between Breaths)

The respiratory system is at its equilibrium volume, known as the Functional Residual Capacity (FRC).

1. Alveolar Pressure (PA): Alveolar pressure equals atmospheric pressure, and therefore it is zero. There is no air flow because there is no pressure difference between the atmosphere and the alveoli.

2. Intrapleural Pressure (PIP): Intrapleural pressure is negative (e.g., approximately −5 cm H2O). This negative pressure is created by the elastic forces of the lungs tending to collapse and the chest wall tending to expand. The negative intrapleural pressure opposes the natural tendency of the lungs to collapse.

B. Inspiration

The chest moves to create a favorable pressure gradient for air entry.

1. Movement and Volume: The inspiratory muscles contract, causing the volume of the thorax to increase. The lung volume increases by the tidal volume (VT).

2. Alveolar Pressure (PA): As lung volume increases, alveolar pressure decreases to a value less than atmospheric pressure (e.g., −1 cm H2O halfway through). This negative pressure establishes a gradient that drives air flow into the lungs.

3. Intrapleural Pressure (PIP): Intrapleural pressure becomes even more negative (e.g., approximately −8 cm H2O at the end of inspiration). This increase in negativity is due to the increased elastic recoil of the expanded lungs pulling more forcefully on the intrapleural space.

C. Expiration

Normal expiration is passive, allowing pressures to return to the resting state.

1. Movement and Volume: The chest and lungs recoil. Air flows out of the lungs, and lung volume returns to FRC.

2. Alveolar Pressure (PA): Alveolar pressure becomes greater than atmospheric pressure (i.e., becomes positive, e.g., +1 cm H2O). This positive pressure drives air flow out of the lungs down the reversed pressure gradient.

3. Intrapleural Pressure (PIP): Intrapleural pressure returns to its resting negative value (e.g., −5 cm H2O).

Parameter - At Rest (End of Normal Expiration) - During Normal Inspiration

1. Air Flow - Zero (No gradient) - Inward (Driven by negative PA)

2. Alveolar PA(cm H2O) - 0 (Equal to atmospheric) - Negative (e.g., −1 cm H2​O)

3. Intrapleural PIP(cm H2O) - Negative (e.g., −5 cm H2O) - More Negative (e.g., −8 cm H2O)

4. Mechanism - Equilibrium between opposing forces - Diaphragm contracts, expanding thorax

Analogy: The mechanics of breathing are much like inflating a balloon inside a rigid jar where the air inlet is sealed. To inflate the balloon (lungs), you must create a vacuum (negative intrapleural pressure) inside the jar (thorax) by pulling the jar walls outward (contracting the diaphragm), causing the air outside to rush into the balloon through its open neck

Pressure and Volume Changes During Normal Respiration

Breathing (pulmonary ventilation) is a mechanical process driven by the pressure difference (ΔP) between the atmosphere and the alveoli. Airflow (Q) is directly proportional to this pressure gradient and inversely proportional to airway resistance (R) (Q=ΔP/R).

I. Key Pressure Definitions

1. Alveolar Pressure (PA) / Intrapulmonary Pressure: The pressure inside the alveoli. This pressure must be compared to atmospheric pressure (which is conventionally set to zero).

2. Intrapleural Pressure (PIP): The pressure in the intrapleural space (between the lung and chest wall). This pressure is always negative during normal respiration because the elastic lungs tend to collapse, and the elastic chest wall tends to spring out.

3. Transpulmonary Pressure (PL): The difference between alveolar pressure (PA) and intrapleural pressure (PIP). This is the expanding pressure that keeps the airways and lungs open (PL=PA−PIP).

II. The Breathing Cycle (Quiet Respiration)

Normal quiet breathing involves active inspiration followed by passive expiration.

A. Resting State (Between Breaths)

This phase occurs at the end of a normal expiration when the muscles are relaxed. The respiratory system is at its equilibrium volume, the Functional Residual Capacity (FRC).

Parameter - Value (Relative to Atmosphere) - Mechanism/Significance

Alveolar Pressure (PA) - 0 cm H2O -  Equal to atmospheric pressure; thus, there is no airflow.

Intrapleural Pressure (PIP) - Negative (e.g., −5 cm H2O) - Results from the opposing forces of the lungs trying to collapse and the chest wall trying to expand.

Lung Volume - FRC (e.g., 2.4 L) - The volume remaining after a normal expiration; FRC is the equilibrium volume where the opposing elastic forces are balanced.

B. Inspiration (Active Phase)

Inspiration requires the contraction of the diaphragm and other inspiratory muscles, increasing the volume of the thoracic cavity.

Parameter - Change/Value - Consequence/Mechanism

Thoracic Volume - Increases - Diaphragm contraction pushes contents downward and lifts ribs upward.

Alveolar Pressure (PA) - Decreases (e.g., to −1 cm H2O) - Due to the increase in lung volume (Boyle’s law). This negative pressure creates the gradient needed to drive air into the lungs.

Intrapleural Pressure (PIP) - Becomes More Negative (e.g., −8 cm H2O) - Due to the increased elastic recoil of the stretched lungs pulling more forcefully on the intrapleural space.

Lung Volume - Increases by the Tidal Volume (VT) - VT is typically 500 mL during quiet breathing.

C. Expiration (Passive Phase)

Normal expiration is passive, requiring no muscle action, relying instead on the elastic recoil of the lung-chest wall system.

Parameter - Change/Value - Consequence/Mechanism

Alveolar Pressure (PA ) - Increases (e.g., to +1 cm H2O) - Due to the elastic recoil compressing the air in the alveoli. This positive pressure reverses the gradient and drives air out of the lungs.

Intrapleural Pressure (PIP) - Returns to resting negative value (e.g., −5 cm H2O) - The opposing elastic forces of the relaxed lung and chest wall return to equilibrium.

Lung Volume - Returns to FRC - Volume decreases by the VT

Clinical Applications of Pressure and Volume Changes

Abnormal pressure dynamics or volume capacities are essential indicators of disease.

A. Obstructive Lung Diseases (Airway Resistance)

These conditions (e.g., asthma, COPD) are characterized by increased resistance to airflow.

• FEV1/FVC Ratio: The fraction of the forced vital capacity (FVC) that can be expired in the first second (FEV1) is decreased because FEV1 is decreased disproportionately due to increased airway resistance.

• Expiration Becomes Active: Because of the high resistance, accessory expiratory muscles may be used, converting expiration from a passive process to an active one.

• Increased FRC: In diseases like emphysema (a type of COPD), the loss of elastic tissue increases the compliance of the lungs (decreased elastic recoil force). This causes the opposing elastic forces to balance at a new, higher lung volume, thus increasing FRC.

• Airway Collapse: During a forceful expiration (as in COPD), the use of expiratory muscles raises intrapleural pressure to a positive value. In severe disease, this positive PIP can compress the weakened airways, causing them to collapse and impeding airflow.

B. Restrictive Lung Diseases (Decreased Compliance)

These conditions (e.g., fibrosis) are characterized by reduced lung volumes and decreased compliance (increased stiffness/elastance).

• FEV1/FVC Ratio: This ratio may be normal or increased because the decrease in FEV1 is less than the decrease in FVC.

• Decreased FRC: Due to the increased elastic recoil force of the stiffened lungs (fibrosis), the equilibrium volume (FRC) of the lung-chest wall system is decreased.

• Auscultatory Gap: Severe pulmonary edema (fluid in the alveoli/interstitium, often due to heart failure) increases lung stiffness, reducing lung compliance.

C. Pressures and Pathology

• Pneumothorax (Air in the Chest): If air enters the intrapleural space, the natural negative pressure is eliminated, and intrapleural pressure becomes equal to atmospheric pressure (zero). As a result, the unopposed elastic recoil causes the lung to collapse.

• Pulmonary Hypertension (Right Heart Afterload): The right ventricle pumps blood into the pulmonary circulation at much lower pressures (∼15 mm Hg mean) compared to the systemic circulation (∼100 mm Hg mean). If pulmonary vascular resistance increases chronically, the right ventricle must pump against increased afterload, which can lead to right ventricular hypertrophy.

Analogy: The breathing cycle acts like a syringe attached to a flexible bellows (the lung). To draw air in (inspiration), you actively pull the plunger out (muscle contraction), lowering the internal pressure (negative PA). To push air out (normal expiration), you simply let go of the plunger, and the spring inside (elastic recoil) does the work, forcing the internal pressure slightly positive (positive PA). In emphysema, the spring weakens, making it easy to pull the plunger out but hard to push air back in. In fibrosis, the bellows material stiffens, making it difficult to pull the plunger out at all (low volume, low compliance).