Respiratory Function and Alterations in Gas Exchange Notes

Pulmonary System: Anatomy

• The pulmonary system is anatomically divided into the upper and lower airway structures.

• Upper airway structures include:

  • Nasopharynx

  • Oropharynx

  • Laryngopharynx

  • These structures constitute the CONDUCTING PORTION.

• Lower airway structures include:

  • Larynx

  • Trachea

  • Bronchi

  • Bronchopulmonary segments

  • Terminal bronchioles

  • Alveoli

  • These structures constitute the RESPIRATORY PORTION.

Pulmonary System: Trachea and Bronchi

• Blood supply comes from:

  • Bronchial artery system

  • Pulmonary artery system

• Partial pressures (denoted as PA for alveolar and Pa for arterial):

  • PAO_2: partial pressure of oxygen in alveoli

  • PACO_2: partial pressure of carbon dioxide in alveoli

  • PaO_2: partial pressure of oxygen in blood

  • PaCO_2: partial pressure of carbon dioxide in blood

Pulmonary System: Alveoli

• Alveolar cells:

  • Type I alveolar cells: epithelial structural cells.

  • Type II alveolar cells:

    • Produce surfactant, a phospholipid.

    • Lowers surface tension.

    • Facilitates gas exchange.

  • Alveolar macrophages:

    • Phagocytize foreign particles.

    • Can be damaged by smoking and inhalation of silica.

Pulmonary System: Nervous System Control

• Autonomic nervous system controls bronchi and bronchiole musculature.

  • Parasympathetic stimulation:

    • Mediated by acetylcholine.

    • Via the vagus nerve (cranial nerve X).

    • Leads to constriction of muscle.

  • Sympathetic stimulation:

    • Mediated by β2-adrenergic receptors.

    • Leads to relaxation of the smooth muscle.

The Breathing Process

• Inhalation/inspiration

• Exhalation/expiration: Normally a passive process.

• The diaphragm is shaped like a parachute.

Mechanisms of Breathing

• Inspiration:

  • Lungs expand.

  • Chest wall moves out.

  • Diaphragm moves down.

• Expiration:

  • Lungs recoil.

  • Chest wall moves in.

  • Diaphragm moves up.

Inhalation

• Inhalation involves the diaphragm and external intercostals.

  • Diaphragm contracts leading to increased lung volume.

• Ribs elevate as the diaphragm moves downward, creating a negative intrapleural pressure.

• The lungs have a natural recoil tendency; the chest wall favors the expanded state.

Exhalation

• Resting exhalation is due to muscle relaxation and is a passive process.

  • Diaphragm rises and ribs fall, leading to decreased lung volume.

• Forceful breathing involves active use of internal intercostals and abdominal muscles.

  • Push diaphragm up & pull ribs in, resulting in more decreased lung volume.

• At the end of normal expiration, alveoli still have some gas remaining, known as functional residual capacity.

• Surfactant decreases surface tension, allowing the alveoli to open easily with each breath.

Pressure Changes During Ventilation

• Atmospheric pressure = 760 mmHg

  • At rest (diaphragm relaxed): Alveolar pressure = 760 mmHg

  • During inhalation (diaphragm contracting): Alveolar pressure = 758 mmHg

  • During exhalation (diaphragm relaxing): Alveolar pressure = 762 mmHg

Factors Affecting Breathing

• Airway Resistance

• Lung Compliance

• Distribution of Ventilation

• Neurological control of ventilation

Airway Resistance

• Relationship between pressure and flow = airway resistance

• Airway resistance is influenced by:

  • Airway radius: Resistance increases as the airway diameter decreases.

    • Factors that decrease airway radius:

      • Mucus

      • Bronchospasm

      • Stress

      • Pulmonary deconditioning

      • Age

  • Pattern of gas flow

• Highest airway resistance is at the nose because of turbulent flow and high velocity.

• Lowest airway resistance is in the small bronchioles, where turbulent flow is small.

• Airway resistance is higher in the neonate than the adult.

• Bronchospasm increases airway resistance.

Lung Compliance

• Lung compliance represents lung expandability and ease of lung inflation.

• Compliance = change in volume ÷ change in pressure

• Compliance provides an estimate of airway resistance and elasticity of the lung.

• Lung compliance:

  • Increased in neonates and young children < 3.5 years due to their chest wall flexibility.

  • Decreased in elderly due to:

    • Increased chest wall rigidity

    • Reduced mobility of the ribs

    • Partial contraction of inspiratory muscles

    • Loss of elastic fibers in the lung

Distribution of Ventilation

• In the upright individual (vertical),

  • Alveoli at the apices of the lung are much larger than those at the base.

  • Ventilation is greatest at the bottom of the lung and decreases towards the apices.

• Regional differences in ventilation are less in the supine position.

Neurological Control of Ventilation

• Neural control center for respiration is located in the pons and medulla oblongata.

• Efferent fibers travel from the brainstem to the diaphragm via the phrenic nerve to stimulate inspiratory muscles.

• Medullary dorsal neurons stimulate inspiratory muscles (intercostals, diaphragm).

• Abrupt cessation of neurostimulation allows for expiration.

Diffusion and Transport of Respiratory Gases

• Diffusion: movement of gas from high concentration to low concentration areas

• Barriers to diffusion:

  1. Surfactant

  2. Alveolar membrane

  3. Interstitial fluid

  4. Capillary membrane

  5. Plasma

  6. Red blood cells

Alterations in Pulmonary Function: Hypoventilation

• HYPOVENTILATION: air delivered to alveoli is insufficient to provide O2 and remove CO2.

• Hypoventilation results in increased PaCO_2.

• Causes of hypoventilation:

  • Morphine

  • Barbiturates

  • Obesity

  • Myasthenia gravis

  • Obstructive sleep apnea

  • Chest wall damage

  • Paralysis of respiratory muscles

  • Surgery of the thorax or abdomen

Alterations in Pulmonary Function: Hyperventilation

• HYPERVENTILATION: increase of air entering the alveoli leads to hypocapnia (PaCO_2 <35 mm Hg)

• Causes: pain, fever, anxiety, obstructive and restrictive lung diseases, sepsis, high altitude, and brainstem injury

• Low PaCO_2 leads to greater binding of oxygen to the hemoglobin molecule

• Hypoxemia/Hypoxia: deficient blood oxygen

OBSTRUCTION v. RESTRICTION

• Obstruction

  • Air trapping

  • SMALL AIRWAY

  • RESISTANCE TO EXPIRATION – Just can’t get out!

  • Obstruction, i.e., wheezing

  • HYPEREXPANSION on CXR

• Restriction

  • “Compliance”

  • “Infiltrative”

  • REDUCED lung VOLUME, DYSPNEA, CYANOSIS

  • REDUCED GAS TRANSFER

  • RESISTANCE TO INSPIRATION – Just can’t get in!

  • REDUCED COMPLIANCE, i.e., less sponginess!

  • “GROUND GLASS” on CXR

General Pulmonary Disorders

• When you think of pulmonary disorders think:

  • Inflammation

  • Edema

  • Excess mucous production

Obstructive Pulmonary Disorders: Classifications

• Obstruction from conditions in the wall of the lumen

  • Asthma

  • Acute Bronchitis

  • Chronic Bronchitis

• Obstruction related to loss of lung parenchyma

  • Emphysema

• Obstruction of the airway lumen

  • Bronchiectasis

  • Bronchiolitis

  • Cystic Fibrosis

  • Acute Tracheobronchial Obstruction

  • Epiglottitis

  • Croup Syndrome

• Obstructive Pulmonary Disorders are manifested by increased resistance to airflow.

Asthma

• Characterized by:

  • Airway obstruction that is reversible (not completely in some patients)

  • Airway inflammation

  • Increased airway responsiveness to a variety of stimuli

• Common symptoms

  • Wheezing

  • Feeling of tightness of chest

  • Dyspnea

  • Cough (dry or productive)

  • Increased sputum production (thick, tenacious, scant, and viscid)

Asthma: Epidemiology and Predisposing Factors

• Who has asthma?

  • Occurs in 5% to 12% of U.S. population

  • Most common chronic disease of children

  • High-risk populations

    • African Americans

    • Inner-city residents

    • Premature/low-birth-weight children

• Predisposing factors

  • Genetic for atopy and structural (smaller airways)

  • Chromosomes 5, 11, 14

  • History of hay fever, eczema

  • Family history

  • Positive skin test reactions to allergens

Asthma: Intrinsic vs. Extrinsic

• Intrinsic Asthma

  • Non-allergic

  • ADULT ONSET

  • Antigen-antibody reactions are not directly involved

  • IgE levels may be elevated

• Extrinsic Asthma

  • Allergic

  • PEDIATRIC ONSET

  • 1/3 to ½ of asthma cases

  • An IgE-mediated response is common

Asthma: EXTRINSIC (ALLERGIC)

• Clinical Manifestations:

  • Elevated IgE levels

  • Allergic rhinitis

  • Eczema

  • Positive family history of allergy

  • Attacks associated with seasonal, environmental or occupational exposure

• Mechanism of Action:

  1. Immediate phase

  2. Chemical mediators released

  3. Normal respiratory epithelium is denuded (loss of outside layer) and replaced by goblet cells

  4. Alterations in epithelial integrity

  5. Increased microvascular permeability

  6. Late phase

  7. Epithelial damage

Asthma: EXTRINSIC (ALLERGIC) Mechanism of Action

• 1- Immediate phase

  • Initiated by exposure to specific antigen that has previously sensitized mast cells in airway mucosa

  • Antigen reacts with antibody on surface of mast cell

  • Mast cell releases packets of chemical mediator substances

• 2- Chemical mediators released

  • Histamine

  • Slow-reacting substances of anaphylaxis (leukotrienes)

  • Prostaglandins

  • Bradykinins

  • Eosinophilic chemotactic factor

  • Serotonin

• 3- Normal respiratory epithelium is denuded (loss of outside layer) and replaced by goblet cells

• 4- Alterations in epithelial integrity

• 5- Increased microvascular permeability

  • Mucosal edema

  • Inflammatory exudates

  • Bronchoconstriction

  • Leakage

• 6- Late phase

  • Arrival of recruited leukocytes signals initiation

  • More mediator release causes damage to epithelium

• 7- Epithelial damage

  • Hypertrophied smooth muscle

  • Edema

  • Mucous gland hypertrophy

  • Mucus in lumen

Bronchial Asthma: Histologic Findings

• What are the 4 classical histologic findings in bronchial asthma?

  1. Inflammation

  2. Bronchial (luminal) narrowing

  3. Increased Mucous

  4. Smooth muscle hyperplasia

• What is the 5th finding if the etiology is allergy?

  • Increased eosinophils

Asthma: Diagnosis

• Physical findings

  • Cough

  • Wheezing

  • Hyperinflated chest

  • Decreased breath sounds

• Radiographic finding

  • Hyperinflation with flattening of the diaphragm

• Sputum examination

  • Charcot-Leyden crystals (formed from crystallized enzymes from eosinophilic membranes)

  • Eosinophils

  • Curschmann spirals (mucous casts of bronchioles)

• Pulmonary function tests

  • Forced expiratory volumes decrease

  • Peak expiratory flow rate (PEFR)

REMEMBER (Nervous System)

• Parasympathetic stimulation (mediated by acetylcholine) via the vagus nerve (cranial nerve X) leads to constriction of muscle

• Sympathetic stimulation (mediated by β2-adrenergic receptors); leads to relaxation of the smooth muscle

Asthma: Treatment

• Antigenic and nonantigenic stimuli cause mast cell degranulation

• Parasympathetic nervous system stimulation via acetylcholine

• Blocked by ipratropium

• Chemotaxis of neutrophils and eosinophils

• Blocked by corticosteroids

• Histamine

• Leukotrienes

• Prostaglandins

• Mast cell migration inhibited by corticosteroids

• Blocked by mast cell stabilizers (e.g., corticosteroids, cromolyn, nedocromil)

• Blocked by receptor antagonist; (e.g., zafirlukast)

• Blocked by leukotriene inhibitors

• Blocked by histamine receptor blockers (e.g.. diphenhydramine)

• Bronchial smooth muscle cell contraction

• Mucus secretion

• Mucosal edema

• Inhibited by β2 agonists, theophylline, muscarinic antagonists

• Inhibited by corticosteroids

• Target tissue

Asthma: Treatment Strategies

• Avoid triggers

• Environmental control

  • Removal of allergens

  • Air purifiers

  • Air conditioners

• Preventive therapy

• Desensitization (allergen specific immunotherapy)

• Medications

  • O_2 therapy

  • Small-volume nebulizers

  • B2 agonists

  • Corticosteroids

  • Leukotriene modifiers

  • Mast cell inhibitors