Structure and Function of Respiratory System - Chapter 29

Learning Objectives

• Identify all anatomical structures and organs involved in the respiratory system.

• Distinguish between the different physiological components of respiration.

• Describe the precise mechanisms of pulmonary ventilation and alveolar gas exchange.

• Explain acid-base balance mechanisms and interpret Arterial Blood Gas ($\text{ABG}$) parameters.

• Analyze the oxygen-hemoglobin dissociation curve ($\text{ODC}$) and factors causing curve shifts.

Respiratory System Anatomy and Structural Organization

• Upper and Lower Respiratory Tract Structures:

  • Frontal sinus and Sphenoidal sinus: Air-filled cavities lined with mucous membrane that warm, humidify, and filter inhaled air while providing resonance to speech.

  • Nasal cavity: Primary entrance for air, lined with ciliated mucosa that traps debris and humidifies air.

  • Pharynx: Muscular passageway divided into three distinct regions:

  • Nasopharynx: Posterior to the nasal cavity; functions exclusively as an airway.

  • Oropharynx: Posterior to the oral cavity; serves as a shared passage for both air and food.

  • Laryngeal pharynx (Laryngopharynx): Inferior region opening into both the esophagus and larynx.

  • Epiglottis: Leaf-shaped elastic cartilage flap that folds over the laryngeal inlet during swallowing to prevent food and liquids from entering the lower airway.

  • Larynx and vocal cords: Voice box composed of cartilaginous structures housing the vocal cords, responsible for phonation and protecting the trachea.

  • Esophagus: Muscular tube running posterior to the trachea, conducting food to the stomach.

  • Trachea: Windpipe reinforced with C-shaped hyaline cartilage rings that maintain airway patency leading down to the primary bronchi.

  • Right bronchus and Left bronchus: Primary branches off the trachea entering the hilum of each lung.

  • Terminal bronchiole: Final conducting structures before reaching the respiratory zone.

  • Mediastinum: Central thoracic compartment containing the heart, esophagus, trachea, and major blood vessels, separating the two pleural cavities.

  • Diaphragm: Primary muscle of respiration separating the thoracic and abdominal cavities.

• Microscopic Gas Exchange Structures (Alveolar-Capillary Unit):

  • Alveolar duct: Small conduits connecting respiratory bronchioles to clusters of alveoli.

  • Alveoli: Primary microscopic sac-like structures where gas exchange occurs.

  • Capillaries: Dense pulmonary network encircling alveoli to minimize diffusion distance.

  • Pulmonary artery branch: Delivers deoxygenated blood from the right ventricle into the alveolar capillary beds.

  • Pulmonary vein branch: Carries oxygenated blood away from the alveolar capillaries to the left atrium.

• Thoracic Cross-Sectional and Pleural Cavity Organization:

  • Thoracic vertebra and Sternum: Posterior and anterior bony boundaries of the thoracic cage protecting the lungs.

  • Wall of thorax: Ribs and intercostal muscles enclosing the thoracic cavity.

  • Parietal pleura: Outer serous membrane lining the inner surface of the thoracic cavity wall.

  • Visceral pleura: Inner serous membrane tightly adhering to the outer surface of each lung.

  • Pleural space (Pleural cavity): Potential space between the parietal and visceral pleurae containing lubricating pleural fluid that reduces friction during breathing and maintains negative intrapleural pressure.

Functional Classification of Airway Structures

• Conducting Airway Structures:

  • Function: Form the anatomical conduits that transport, warm, humidify, and filter air before reaching the gas-exchange zones, without participating directly in gas exchange.

  • Nasal passages: Primary portal for warming and humidifying ambient air.

  • Mouth and pharynx: Secondary entrance route and shared passageway.

  • Larynx: Protects the lower airway and enables vocalization.

  • Trachea: Main airway trunk conducting air into the chest cavity.

  • Bronchi: Primary, secondary, and tertiary branching conduits.

  • Bronchioles: Smaller cartilaginous and non-cartilaginous branches controlling resistance.

  • Mucociliary blanket: Continuous layer of mucus produced by goblet cells and submucosal glands, moved continuously upward toward the pharynx by the rhythmic beating of ciliated epithelial cells to trap and remove inhaled particulates and pathogens.

• Respiratory Tissues (Gas Exchange Zone):

  • Function: Structures containing functional alveoli where rapid gas exchange between air and blood takes place.

  • Alveolar bundle: Clusters of alveoli arising from alveolar ducts.

  • Respiratory membrane: Thin composite barrier across which gas diffusion occurs, composed of the alveolar epithelium, basement membrane, and capillary endothelium.

Cellular Composition of Alveolar Structures

• Type I Alveolar Cells (Type I Pneumocytes):

  • Thin, flat squamous epithelial cells covering approximately $95\%$ of the total alveolar surface area.

  • Primary structural component of the alveolar wall designed to facilitate rapid gas diffusion due to their minimal cytoplasm and extreme thinness.

• Type II Alveolar Cells (Type II Pneumocytes):

  • Cuboidal cells interspersed among Type I pneumocytes.

  • Synthesize and secrete pulmonary surfactant, a complex surface-active mixture of phospholipids and proteins.

  • Function of Surfactant: Lowers alveolar surface tension at the air-water interface, preventing alveolar collapse (atelectasis) during expiration, improving lung compliance, and reducing the work of breathing.

Dual Pulmonary Circulation

• Pulmonary Circulation:

  • Origin: Arises directly from the pulmonary artery receiving deoxygenated blood pumped from the right ventricle.

  • Functional Role: Provides the blood flow required for the primary gas exchange function of the lungs, delivering carbon dioxide to be exhaled and picking up oxygen for systemic distribution.

  • Path: Low-pressure, low-resistance system terminating in alveolar capillaries and draining via pulmonary veins into the left atrium.

• Bronchial Circulation:

  • Origin: Arises directly from the thoracic aorta as part of the systemic arterial circulation.

  • Functional Role:

  • Supplies oxygenated blood to meet the metabolic needs of the lung tissues, including the parenchyma, adventitia, large blood vessels, and nervous tissue.

  • Distributes blood to nourish the structural components of the conducting airways.

  • Warms and humidifies incoming air as it passes through the upper and conducting airways.

Mechanics of Ventilation and Gas Exchange

• Overview of Ventilation:

  • Defined as the physical process of moving air into and out of the lungs to maintain adequate alveolar gas levels.

• Phases of Ventilation:

  • Inspiration (Inhalation):

  • Active process where air is drawn into the lungs.

  • Contraction of the diaphragm (moving downward) and external intercostal muscles (elevating ribs) expands thoracic volume.

  • Increased thoracic volume creates a negative intrapulmonary pressure relative to atmospheric pressure, pulling air inward.

  • Expiration (Exhalation):

  • Passive process during quiet breathing where air moves out of the lungs.

  • Relaxation of inspiratory muscles allows passive elastic recoil of the lungs and chest wall.

  • Decreased thoracic volume raises intrapulmonary pressure above atmospheric pressure, pushing air outward.

Physical Properties and Pressures of Gases

• Atmospheric or Barometric Pressure:

  • The force exerted by the weight of air in the atmosphere surrounding the earth (standard at sea level is $760\,\text{mm Hg}$).

• Partial Pressure:

  • The individual pressure exerted by a single gas within a mixture of gases, directly proportional to its fractional concentration (e.g., $PO_2$, $PCO_2$).

• Respiratory Pressure:

  • Pressures measured within the respiratory system expressed relative to atmospheric pressure (assigned a relative value of 0\,\text{cm H_2O} or $0\,\text{mm Hg}$).

• Intrapulmonary Pressure (Intra-alveolar Pressure):

  • The pressure inside the alveoli of the lungs, which fluctuates between negative (during inspiration) and positive (during expiration) relative to atmospheric pressure.

Lung Volumes and Capacities

• Dynamic Air Exchange Metrics:

  • Represents the quantified amounts of air moved during various phases of the respiratory cycle.

• Primary Lung Volume Components:

  • Tidal Volume ($TV$): The volume of air inhaled or exhaled with each normal, quiet, resting breath.

  • Inspiratory Reserve Volume ($IRV$): The maximal volume of air that can be forcibly inhaled beyond a normal tidal inspiration.

  • Expiratory Reserve Volume ($ERV$): The maximal volume of air that can be forcibly exhaled beyond a normal tidal expiration.

• Integrated Volumetric Measures:

  • Minute Volume ($\dot{V}_E$): The total volume of gas entering or leaving the lungs per minute, calculated as tidal volume multiplied by respiratory rate ($\dot{V}_E = TV \times \text{Respiratory Rate}$).

Integrated Processes of Respiration

• Ventilation:

  • The physical movement of gas from the external atmosphere into the alveolar spaces of the lungs and back out.

• Perfusion ($Q$):

  • The continuous flow of blood through the pulmonary capillary bed surrounding the alveoli.

• Diffusion:

  • The passive molecular transfer of gases ($O_2$ and $CO_2$) across the respiratory membrane down their respective partial pressure concentration gradients.

Oxygen and Carbon Dioxide Transport Mechanisms

• Dual Modes of Oxygen Transport in Blood:

  • Dissolved State (Physical Solution):

  • A very small fraction of oxygen dissolves directly in blood plasma, determined by Henry's law and $PO_2$.

  • Chemical Combination with Hemoglobin:

  • Overwhelming majority ($98\%$ to $99\%$) of oxygen is transported bound reversibly to iron atoms in hemoglobin molecules within red blood cells.

• Arterial Oxygen Partial Pressure:

  • Normal $PO_2$ in systemic arterial blood is maintained above $80\,\text{mm Hg}$ (typically $80\text{--}100\,\text{mm Hg}$).

• Oxyhemoglobin Dynamics:

  • Formed when oxygen molecules reversibly bind to hemoglobin ($\text{Hb} + 4O_2 \rightleftharpoons \text{Hb}(O_2)_4$).

  • Binding Affinity: The biochemical attraction between hemoglobin and oxygen molecules, which varies dynamically based on local metabolic and chemical conditions.

Arterial Blood Gas (ABG) Parameters and Clinical Reference Ranges

• Arterial Blood Gas Parameters:

  • $\text{pH}$ Range: $7.35\text{--}7.45$

  • Indicates systemic acid-base status; values below $7.35$ represent acidemia, while values above $7.45$ represent alkalemia.

  • $PCO_2$ Range: $35\text{--}45\,\text{mm Hg}$

  • Represents the partial pressure of carbon dioxide in arterial blood; controlled primarily by alveolar ventilation rate (respiratory component of acid-base balance).

  • $HCO_3^-$ Range: $22\text{--}26\,\text{mEq/L}$

  • Represents the concentration of bicarbonate ions in arterial blood; regulated primarily by renal excretion and reabsorption (metabolic component of acid-base balance).

  • $PO_2$ Range: $80\text{--}100\,\text{mm Hg}$

  • Represents the partial pressure of oxygen dissolved in arterial blood; serves as a primary index of pulmonary oxygenation efficiency.

• Clinical Rationale for Arterial Sampling over Venous Sampling:

  • Arterial blood provides a uniform, baseline measurement of oxygenation and acid-base status immediately after blood has been processed by the lungs and before it enters systemic tissue beds.

  • Venous blood reflects variable tissue-specific oxygen consumption and metabolic waste accumulation from local organ beds, making it unreliable for evaluating overall pulmonary gas exchange performance.

Oxygen-Hemoglobin Dissociation Curve (ODC) Physiology

• Structural Features of the Sigmoidal Curve:

  • Plateau Region (High $PO_2$ Range: $60\text{--}100+\,\text{mm Hg}$):

  • Located at the top of the curve corresponding to pulmonary capillary conditions.

  • Ensures that hemoglobin remains highly saturated ($>90\%$) even if alveolar $PO_2$ drops significantly due to high altitude or mild respiratory disease, acting as a critical physiological safety margin.

  • Steep Region (Low $PO_2$ Range: $20\text{--}40\,\text{mm Hg}$):

  • Located in the middle and lower portion of the curve corresponding to systemic tissue capillaries.

  • Allows large amounts of oxygen to be rapidly released (unloaded) from hemoglobin to tissues in response to small decrements in local tissue $PO_2$

• Physiological Significance of Curve Shifts:

  • Normal $P_{50}$: The partial pressure of oxygen at which hemoglobin is $50\%$ saturated with oxygen (normally approximately $26.6\,\text{mm Hg}$).

  • Shift to Right (Decreased Affinity):

  • Facilitates oxygen unloading to metabolically active tissues.

  • Triggered by:

    • Increased partial pressure of carbon dioxide ($PCO_2$)

    • Decreased $\text{pH}$ / Increased hydrogen ion concentration ($H^+$) — the Bohr effect

    • Increased body temperature

    • Increased levels of $2,3\text{-diphosphoglycerate}$ ($2,3\text{-DPG}$)

  • Shift to Left (Increased Affinity):

  • Increases affinity of hemoglobin for oxygen, causing tighter binding and reduced tissue unloading.

  • Triggered by:

    • Decreased partial pressure of carbon dioxide ($PCO_2$)

    • Increased $\text{pH}$ / Decreased hydrogen ion concentration ($H^+$)

    • Decreased body temperature

    • Decreased levels of $2,3\text{-DPG}$

• Impact of Hemoglobin Concentration (Normal vs. Anemia):

  • Percent saturation ($\% \text{ Hb saturation}$) curve shape remains identical between normal and anemic individuals.

  • Total oxygen content ($\text{mL } O_2 / 100\,\text{mL blood}$) is markedly reduced in anemia across all $PO_2$ levels due to the reduced quantity of functional hemoglobin molecules available to bind oxygen.

• Hemoglobin as a Buffer System:

  • Deoxyhemoglobin acts as a weak base that binds excess free hydrogen ions ($H^+$) produced during carbon dioxide transport in systemic capillaries, preventing significant drops in intracellular and systemic blood $\text{pH}$.

Neural Control and Regulation of Breathing

• Central Brainstem Respiratory Centers:

  • Respiratory Center: Group of loosely organized neuronal clusters in the medulla oblongata and pons responsible for generating and adjusting breathing rhythm.

  • Pacemaker Center (Medullary Rhythmicity Center): Generates the intrinsic, baseline rhythmic neuronal impulses that drive automatic breathing.

  • Pneumotaxic Center (located in upper pons): Regulates respiratory rate and depth by sending inhibitory signals to the inspiratory center, limiting tidal volume and preventing over-inflation of the lungs.

  • Apneustic Center (located in lower pons): Sends stimulatory signals to the inspiratory center to prolong inspiration and promote deep breathing.

• Motor Neural Pathways:

  • Phrenic Nerve: Originates from spinal cord segments $C3$, $C4$, and $C5$ ("C3, 4, 5 keep the diaphragm alive") and transmits motor nerve impulses from the respiratory center down to innervate the diaphragm.

• Automatic Regulation of Ventilation:

  • Chemoreceptors:

  • Central Chemoreceptors (in medulla): Highly sensitive to changes in hydrogen ion ($H^+$) concentration and $PCO_2$ in cerebrospinal fluid ($\text{CSF}$).

  • Peripheral Chemoreceptors (in carotid and aortic bodies): Monitor arterial blood levels of $PO_2$, $PCO_2$, and $\text{pH}$, triggering hyperventilation when $PO_2$ drops severely ($<60\,\text{mm Hg}$) or $PCO_2$ increases.

  • Lung Receptors:

  • Monitor breathing patterns, pulmonary compliance, and lung volume changes (e.g., stretch receptors initiating the Hering-Breuer reflex to prevent over-inflation).

• Voluntary Regulation of Ventilation:

  • Cortical Integration: Integrates respiration with voluntary behaviors such as speech, singing, blowing, coughing, or breath-holding.

  • Brain Regions Involved: Initiated directly by neural pathways originating in the primary motor and premotor cortex.

  • Mechanism: Cortical signals bypass brainstem automatic centers to temporarily override or suspend automatic respiratory patterns until metabolic demands force automatic control to resume.

Protective Airway Mechanisms and Clinical Symptoms

• Cough Reflex:

  • Functions as a primary defense mechanism of the respiratory system designed to protect lower airways.

  • Response Sequence: Inhalation of a small amount of air, glottic closure, contraction of expiratory muscles to dramatically increase intrapulmonary pressure, followed by sudden glottic opening to forcefully expel irritants, mucus, or foreign bodies.

  • Impaired Cough Reflex: Results from neurological impairment, muscle weakness, sedation, or endotracheal intubation, significantly elevating the risk of foreign body aspiration, mucus plugging, atelectasis, and secondary pulmonary infections (aspiration pneumonia).

• Dyspnea:

  • Defined as a subjective sensation of breathlessness, difficult breathing, or uncomfortable awareness of breathing effort.

  • Caused by a mismatch between central respiratory drive and mechanical ventilation achieved by the lungs and chest wall.