Respiratory System

Respiratory System Overview

• The respiratory system is essential for life, operating at multiple levels:

  • Pulmonary gas exchange: Blood picks up $O<em>2$ and drops off $CO</em>2$ in the lungs.

  • Tissue gas exchange: $O<em>2$ is delivered to cells, and $CO</em>2$ is carried away.

  • Cellular respiration: Cells use $O<em>2$ to produce energy and create $CO</em>2$ as waste.

Anatomy of the Respiratory System

The respiratory system consists of seven main structures:

• External nose: Used for air inspiration.

• Nasal cavity: Cleans, warms, and humidifies air.

• Pharynx: A common passageway for food and air.

• Larynx: The voice box, which also keeps the airway open.

• Trachea: The air-cleaning tube leading into the lungs.

• Bronchi: Tubes that direct air into the lungs.

• Lungs: A network of alveoli and capillaries facilitating gas exchange.

Functions of the Respiratory System

The respiratory system performs several key functions:

• Pulmonary ventilation (breathing): The movement of air into and out of the lungs.

• Gas exchange:

  • Pulmonary gas exchange (external respiration): Occurs between air in the lungs and blood.

  • Tissue gas exchange (internal respiration): Occurs between the blood and tissues.

• Divisions of the Respiratory Tract:

  • Upper respiratory tract: Includes structures from the nose to the larynx.

  • Lower respiratory tract: Includes structures from the trachea through the alveoli.

• Conducting zone: Structures from the nose to the small air tubes in the lungs, strictly for pulmonary ventilation.

• Respiratory zone: Specialized small tubes and alveoli where gas exchange occurs.

Simultaneous Processes for Gas Exchange

To facilitate gas exchange, four simultaneous processes occur:

• Pulmonary ventilation: Breathing.

• Pulmonary gas exchange: Gas diffusion across alveoli; $O<em>2$ moves from alveolar air to blood, and $CO</em>2$ moves from blood to alveolar air.

• Gas transport: Gases travel in the blood.

• Tissue gas exchange: Gas exchange at the tissues; $O<em>2$ from blood to cells and $CO</em>2$ from cells to blood.

Additional Functions of the Respiratory System

Besides gas exchange, the respiratory system performs these functions:

• Regulation of blood pH: Altered by changing blood carbon dioxide levels.

• Production of chemical mediators: ACE, an enzyme involved in blood pressure regulation.

• Voice production: Movement of air past vocal folds allows for sound and speech.

• Olfaction: Smell occurs when airborne molecules are drawn into the nasal cavity.

• Protection: Prevents microorganism entry and removes them from respiratory surfaces.

Structures and Histology of the Upper Respiratory Tract - Nose and Nasal Cavity

• Nose

  • External nose: Consists of hyaline cartilage plates covered by skin.

  • Nasal cavity: Extends from nares (nostrils) to choanae (openings into the pharynx).

    • Vestibule: Just inside nares, lined with stratified squamous epithelium.

    • Hard palate: Floor of the nasal cavity covered by highly vascular mucous membrane.

    • Nasal septum: Partition dividing the cavity; anterior cartilage, posterior vomer, and perpendicular plate of ethmoid.

    • Conchae: Bony ridges on lateral walls with meatuses between; openings to paranasal sinuses and the nasolacrimal duct.

Functions of the Nasal Cavity

The nasal cavity serves multiple functions:

• Air passageway.

• Air cleaning: Hairs in the vestibule and cilia in the nasal conchae clean the air; the conchae also create turbulence and increase surface area.

• Humidification and warming: Pseudostratified ciliated columnar epithelium with goblet cells and tears draining from the nasolacrimal duct humidifies and warms the air.

• Olfaction: Contains olfactory epithelium for the sense of smell.

• Resonance: Along with paranasal sinuses, are resonating chambers for speech.

Pharynx

The pharynx is a common opening for the digestive and respiratory systems, divided into three regions:

• Nasopharynx

  • Epithelium: Pseudostratified columnar epithelium with goblet cells.

  • Function: Mucous and debris are swallowed; contains openings of Eustachian (auditory) tubes.

  • Features: Floor is the soft palate; the uvula is a posterior extension of the soft palate; the posterior wall houses the pharyngeal tonsil or adenoids.

• Oropharynx

  • Shared with the digestive system.

  • Fauces: The region where the oral cavity and oropharynx join.

  • Epithelium: Lined with moist stratified squamous epithelium; contains the palatine tonsils and lingual tonsil.

• Laryngopharynx

  • Extends from the epiglottis to the esophagus.

  • Epithelium: Lined with moist stratified squamous epithelium.

Larynx

The larynx, or voice box, houses ligaments used for speech and consists of both unpaired and paired cartilages:

• Unpaired Cartilages

  • Thyroid: Largest cartilage, known as the Adam’s apple.

  • Cricoid: Most inferior cartilage, forming the base of the larynx.

  • Epiglottis: Attached to the thyroid and has a flap near the base of the tongue; made of elastic rather than hyaline cartilage.

• Paired Cartilages

  • Arytenoid: Attached to the cricoid.

  • Corniculate: Attached to the arytenoids.

  • Cuneiform: Contained in mucous membrane anterior to the corniculates.

• Ligaments

  • Extend from arytenoids to thyroid cartilage.

  • Vestibular folds (false vocal folds).

  • Vocal folds (true vocal cords): Responsible for sound production; the opening between them is the glottis.

Muscles of the Larynx

The larynx wall contains two sets of skeletal muscles:

• Intrinsic muscles: Attach to the arytenoid and corniculate cartilages and aid in closing and opening the glottis.

• Extrinsic muscles: Include the sternohyoid and sternothyroid, which elevate the larynx during swallowing.

Functions of the Larynx

The larynx has several vital functions:

1. Maintain an open passageway for air movement via the thyroid and cricoid cartilages.

2. Prevent swallowed material from entering the larynx using the epiglottis and vestibular folds.

3. Serve as the primary source of sound production; the greater the amplitude of vibration, the louder the sound; the frequency of vibration determines pitch.

4. Trap debris with pseudostratified ciliated columnar epithelium, preventing entry into the lower respiratory tract.

Lower Respiratory Tract - Trachea

The trachea, or windpipe, is composed of several layers:

• Structure: A membranous tube of dense regular connective tissue and smooth muscle, supported by 15 to 20 hyaline cartilage C-shaped rings (tracheal rings) open posteriorly.

• Posterior Surface: Elastic ligamentous membrane and bundles of smooth muscle called the trachealis muscle, which contracts during coughing.

• Location: The esophagus lies posterior to the cartilage-free wall of the trachea.

• Inner Lining: Pseudostratified ciliated columnar epithelium with goblet cells; mucus traps debris, cilia push it superiorly toward the larynx and pharynx.

• Divisions:

  • Left and right main or primary bronchi.

  • Carina: Cartilage at the bifurcation that is especially sensitive to irritation, initiating the cough reflex.

Tracheobronchial Tree

The tracheobronchial tree includes the trachea and the network of air tubes in the lungs.

• Structure: The trachea to terminal bronchioles is ciliated for the removal of debris; cartilage holds the tube system open, and smooth muscle controls the tube diameter.

• Changes: As tubes become smaller, the amount of cartilage decreases, while the amount of smooth muscle increases.

• Classes of Passages (largest to smallest):

  • Lobar (secondary) bronchi: Arise from the main bronchi; each serves a lobe of the lungs; contain cartilage plates and are lined with pseudostratified ciliated columnar epithelium.

    • Three on the right and two on the left.

  • Segmental (tertiary) bronchi: Supply bronchopulmonary segments.

  • Bronchioles: Less than 1 mm in diameter; larger bronchioles are lined with ciliated simple columnar epithelium.

  • Terminal bronchioles: No cartilage in walls, but prominent smooth muscle; lined with ciliated simple cuboidal epithelium.

Changes in Air Passageway Diameter

Bronchi and bronchioles can change their diameter through:

• Bronchodilation: Smooth muscle relaxes, decreasing resistance to airflow and increasing airflow.

• Bronchoconstriction: Smooth muscle contracts, increasing resistance to airflow and decreasing airflow.

  • Asthma attack: An inflammatory reaction causes severe bronchoconstriction.

Alveoli

Alveoli are the primary sites of gas exchange in the lungs:

• Branching: Terminal bronchioles branch into:

  • Respiratory bronchioles: Have very few alveoli.

  • Alveolar ducts: Arise from respiratory bronchioles, with alveoli opening up from them.

  • Alveolar sacs: Chambers connected to two or more alveoli at the end of an alveolar duct.

• Features: No cilia in alveoli; debris is removed by macrophages, which then move into nearby lymphatics or terminal bronchioles.

Alveolar Structure

There are approximately 300 million alveoli in the two lungs, formed by two types of cells:

• Type I pneumocytes: Thin squamous epithelial cells that form 90% of the alveolar surface, facilitating gas exchange.

• Type II pneumocytes: Round or cube-shaped secretory cells that produce surfactant to ease alveolar expansion during inspiration.

The Respiratory Membrane

The respiratory membrane is where gas exchange occurs:

• Function: Oxygen enters the blood, and carbon dioxide exits the blood.

• Structure: The membrane is very thin, composed of alveolar cell layer, capillary endothelial layer, and interstitial space.

• Layers:

  • Thin layer of fluid lining the alveolus.

  • Alveolar epithelium (simple squamous epithelium).

  • Basement membrane of the alveolar epithelium.

  • Thin interstitial space.

  • Basement membrane of the capillary endothelium.

  • Capillary endothelium composed of simple squamous epithelium.

Thoracic Wall and Muscles of Pulmonary Ventilation

The thoracic wall is composed of:

• Thoracic vertebrae

• Ribs

• Costal cartilages

• Sternum

• Associated muscles

• The thoracic cavity is the space enclosed by the thoracic wall and the diaphragm.

• Muscles change the cavity size during pulmonary ventilation.

Muscles of Ventilation in Quiet vs. Labored Breathing

• Quiet Inspiration (Active)

  • Diaphragm contracts and flattens downward.

  • External intercostals contract and raise the ribs and sternum.

• Forced Inspiration

  • Pectoralis minor and scalenes contract to raise the ribs and sternum more, increasing thoracic volume.

• Quiet Expiration (Passive)

  • Diaphragm relaxes and raises.

  • External intercostals relax, and ribs rebound down.

• Forced Expiration

  • Abdominal muscles contract and push the diaphragm up more.

  • Internal intercostals contract to pull the ribs inward, decreasing thoracic volume more.

Relationship Between Pressure Gradients and Pulmonary Ventilation

• Boyle’s Law: $P = {k}/V$, where $P$ = gas pressure, $V$ = volume, and $k$ = constant at a given temperature.

  • As the volume of a container increases (e.g., thoracic cavity during inspiration), pressure inside decreases, and vice versa (inverse proportion).

• Air flows down its pressure gradient, from higher to lower pressure.

  • During inspiration, air flows into the lungs.

  • During expiration, air flows out of the lungs.

Measurement of Lung Function

• Spirometry: Measures volumes of air that move into and out of the respiratory system using a spirometer.

• Pulmonary Volumes:

  • Tidal volume (TV): Amount of air inspired or expired with each breath; $500$ mL at rest.

  • Inspiratory reserve volume (IRV): Amount that can be inspired forcefully after inspiration of the tidal volume; $3000$ mL at rest.

  • Expiratory reserve volume (ERV): Amount that can be forcefully expired after expiration of the tidal volume; $1100$ mL at rest.

  • Residual volume (RV): Volume remaining in respiratory passages and lungs after the most forceful expiration; $1200$ mL.

• Pulmonary Capacities: Sum of two or more pulmonary volumes.

  • Inspiratory capacity (IC): Tidal volume plus inspiratory reserve volume.

  • Functional residual capacity (FRC): Expiratory reserve volume plus residual volume.

  • Vital capacity (VC): Sum of inspiratory reserve volume, tidal volume, and expiratory reserve volume.

  • Total lung capacity (TLC): Sum of inspiratory and expiratory reserve volumes plus tidal volume and residual volume.

• Forced Vital Capacity:

  • Forced expiratory volume in 1 second (FEV1): The amount of air expired within the first second of a forced vital capacity test; the lower the value, the more advanced the disease.

• Respiratory Rate: Number of breaths taken per minute.

• Minute Volume: Total air moved into and out of the respiratory system each minute; tidal volume X respiratory rate ($TV {X} respiratory {rate}$).

• Alveolar Ventilation:

  • Measure of volume of air available for gas exchange per minute.

  • Anatomic dead space: Conducting zone spaces formed by the nasal cavity, pharynx, larynx, trachea, bronchi, bronchioles, and terminal bronchioles.

  • Physiological dead space: Anatomic dead space plus the volume of any alveoli in which gas exchange is less than normal.

  • Alveolar ventilation ($V_A$): Volume of air available for gas exchange/minute.

Factors Affecting Pulmonary Ventilation

• Increased vital capacities correlate with male gender, taller height, being active, being slender, and being healthy.

• Well-trained athletes can have a vital capacity 30 to 40% higher than sedentary people.

• Healthy individuals have nearly equal anatomical and physiological dead spaces, meaning most alveoli are functional.

• Lung disease (e.g., emphysema) leads to enlarged alveoli with degenerated walls, reducing surface area for gas exchange and increasing physiological dead space.

Compliance of the Lungs and Thorax

• Compliance: A measure of the ease with which the lungs and thorax expand; measured as the volume by which they increase for each unit of change in intra-alveolar pressure.

• Normal compliance is $0.18$L/mm Hg.

• A lower value means expansion is more difficult during inspiration; a higher value means expansion is easy, but elastic recoil force for expiration is less.

Behavior of Gases and Gas Exchange

• Partial Pressure: The pressure exerted by each type of gas in a mixture.

• Dalton’s Law: Total pressure is the sum of the individual pressures of each gas.

  • $P<em>{nitrogen} + P</em>{oxygen} + P<em>{carbon {dioxide}} + P</em>{water {vapor}} = Atmospheric {pressure}$

• Solubility coefficient: measure of how soluble a gas is in a liquid.

• Henry’s law: Concentration of a gas in a liquid is determined by its partial pressure and its solubility coefficient at a given temperature.

Measurement of Lung Function 3

• Diffusion coefficient: rate at which gas diffuses into an out of a liquid or tissue. Factors involved = solubility coefficient and molecular weight of the gas.

• For example, the diffusion coefficient for $O<em>2$ is 1 and the relative diffusion coefficient for $CO</em>2$ is 20 which means $CO<em>2$ diffuses about 20 times more readily than $O</em>2$ does.

• The diffusion coefficient for $CO_2$ is 20:1.

Physiology of the Respiratory System

• Mechanisms of alveolar Pulmonary ventilation.

  • Barometric air pressure = air pressure outside body.

  • Intra-alveolar pressure = air pressure in alveoli.

• Alveolar Pulmonary ventilation during quiet resting.

  • Alveolar pressure equals atmospheric pressure; no air movement.

  • Alveolar pressure less than atmospheric; due to increase in thoracic volume, air moves into lungs.

  • Alveolar pressure again equals atmospheric; at the end of inspiration; no air movement.

  • Alveolar pressure greater than atmospheric; due to decrease in thoracic volume, air moves out of lungs.

Factors Affecting Alveolar Ventilation

• Lung Recoil: The tendency for lungs to decrease in size after being stretched, due to elastic recoil and surface tension.

  • Elastic Recoil: Elastic fibers in the alveolar walls return to their original shape after being stretched.

  • Surface Tension: A film of fluid lines the alveoli; polar water molecules have a great attraction for each other, creating a net pull inward that tends to collapse the alveoli.

    • Surfactant: Prevents the tendency of lungs to collapse by reducing surface tension; produced by type II pneumocytes.

    • Infant Respiratory Distress Syndrome: Common in premature babies due to inadequate surfactant.

• Pleural Pressure: Pressure within the pleural cavity (between parietal and visceral pleura).

  • Negative pressure causes lungs to expand during inspiration.

  • Alveoli expand when pleural pressure is low enough to overcome lung recoil.

  • Pneumothorax: An opening between the pleural cavity and air that causes a loss of pleural pressure and lung collapse.

Factors Affecting Diffusion Through the Respiratory Membrane

Diffusion of gases through the respiratory membrane depends on three major factors:

• Partial pressure gradients: Gas moves from an area of higher partial pressure to an area of lower partial pressure.

• Membrane thickness: The thicker the respiratory membrane, the lower the diffusion rate.

• Surface area: Decreased surface area decreases the diffusion rate.

Oxygen and Carbon Dioxide Transport in the Blood

• Hemoglobin:

  • A protein synthesized by immature red blood cells, occupying much of the red blood cell volume.

  • Types: Embryonic, fetal, adult, and hemoglobin-S (in those with sickle-cell disease).

  • Embryonic and fetal hemoglobin have a higher concentration of hemoglobin and a greater affinity for $O_2$ than maternal hemoglobin.

  • Adult has 4 subunits, each containing one iron-based heme group, so 1 hemoglobin can carry up to 4 $O_2$.

• Transport of Oxygen

  • About 98.5% of $O_2$ transport is by hemoglobin.

  • About 1.5% is dissolved in plasma.

• Transport of Carbon Dioxide

  • About 7% dissolves in the plasma.

  • About 23% binds to the globin of hemoglobin.

    • Haldane Effect: As hemoglobin binds to $CO<em>2$, its affinity for $O</em>2$ is reduced. The less $O<em>2$ that is bound to hemoglobin, the more $CO</em>2$ can bind and vice versa.

  • About 70% is transported as bicarbonate ion dissolved either in the cytoplasm of RBCs or in the plasma of the blood.

Carbon Dioxide Transport

• At tissue capillaries: as $CO<em>2$ enters red blood cells, reacts with water to form bicarbonate and hydrogen ions. Chloride ions enter the RBC and bicarbonate ions leave: chloride shift. Hydrogen ions combine with hemoglobin. Lowering the concentration of bicarbonate and hydrogen ions inside red blood cells promotes the conversion of $CO</em>2$ to bicarbonate ion.

• At pulmonary capillaries: $CO<em>2$ leaves red blood cells, resulting in the formation of additional $CO</em>2$ from carbonic acid. The bicarbonate ions are exchanged for chloride ions, and the hydrogen ions are released from hemoglobin.

Carbon Dioxide Transport 2

• Reaction to form bicarbonate

• The enzyme carbonic anhydrase catalyzes both steps of the reversible reaction.

• At the tissues, where $CO<em>2$ levels are higher, is removed from the red blood cell by an antiporter. This process is called the chloride shift. In the chloride shift, diffuses out of the red blood cell while diffuses in through the antiporter. This exchange maintains electrical neutrality in the red blood cells and plasma. Removing from inside the red blood cells also promotes greater $CO</em>2$ transport. As concentrations decrease within the red blood cell, more $CO_2$ reacts with water to form additional

Systemic Gas Exchange

1. In the tissues, carbon dioxide ($CO_2$) diffuses into the plasma and into red blood cells. Some of the carbon dioxide remains in the plasma.

2. In red blood cells, carbon dioxide reacts with water ($H<em>2O$) to form carbonic acid ($H</em>2CO_3$) in a reaction catalyzed by the enzyme carbonic anhydrase (CA).

3. Carbonic acid dissociates to form bicarbonate ions and hydrogen ions

4. In the chloride shift, a membrane transporter allows to diffuse out of the red blood cells and chloride ions to diffuse into them, which maintains their electrical neutrality.

5. Oxygen ($O_2$) is released from hemoglobin (Hb). Oxygen diffuses out of red blood cells and plasma into the tissue.

6. Hydrogen ions combine with hemoglobin, which promotes the release of oxygen from hemoglobin.

7. Carbon dioxide combines with hemoglobin. Hemoglobin that has released oxygen readily combines with carbon dioxide.

Physiological Factors Affecting Gas Transport

• Chemoreceptors detect changes in pH, $PO<em>2$, and $PCO</em>2$.

• Central chemoreceptors located in the chemosensitive area of the medulla oblongata are connected to the respiratory center.

• Peripheral chemoreceptors found near carotid and aortic bodies.

Effect of on O$PO_2$ 2 Transport

• Oxygen-hemoglobin dissociation curve describes the percent saturation of hemoglobin at different $PO_2$ values.

• At $PO_2$ of 104 mm Hg, hemoglobin is 98% saturated.

• At $PO_2$ of 60 mm Hg, hemoglobin is 90% saturated.

• Due to the affinity of hemoglobin for oxygen over a wide range of values.

• At $PO<em>2$ of 40 mm Hg (such as at the tissues), $PO</em>2$ is 40 mm Hg and so blood leaving is 75% saturated.

• Used as a reserve if blood $PO_2$ levels decrease further, as during exercise.

Effect of pH and $PO<em>2$ on $O</em>2$ Transport

• Bohr Effect: The effect of pH on the oxygen-hemoglobin dissociation curve; as the pH of blood declines, the amount of oxygen bound to hemoglobin at any given $PO_2$ also declines.

• Occurs because decreased pH yields an increase in that combines with hemoglobin, changing its shape, and oxygen cannot bind to hemoglobin.

• Also, when $CO<em>2$ binds to the globin chains, hemoglobin’s affinity for $O</em>2$ is reduced.

Effect of pH and $PCO<em>2$ on $CO</em>2$ Transport

The principal effect of pH and $PCO<em>2$ is on the affinity of hemoglobin for $O</em>2$. However, a higher $PCO<em>2$ results in a larger decrease in pH. The decrease in pH triggers an increased respiratory rate. The sensitivity to $CO</em>2$ is valuable for maintaining appropriate blood pH levels.

Effect of Temperature on $O_2$ Transport

• An increase in temperature decreases the tendency for oxygen to remain bound to hemoglobin, so as metabolism goes up, more oxygen is released to the tissues.

• When hemoglobin’s affinity for $O<em>2$ decreases, the oxygen-hemoglobin dissociation curve is shifted to the right, and hemoglobin released more $O</em>2$.

Local Control

• Pulmonary capillary perfusion: flow of blood to alveoli through pulmonary capillaries.

• Pulmonary ventilation-perfusion coupling: relationship between pulmonary ventilation of alveoli and blood flow.

• Not 100% of cardiac output is fully saturated with oxygen due to physiological shunt.

  • Anatomical shunt – due to deoxygenated blood from the bronchi and bronchioles mixing with blood in the pulmonary veins.

  • Blood that passes through pulmonary capillaries without becoming fully oxygenated is also shunted blood.

  • Physiological shunt – the combination of anatomical shunt and blood that is incompletely oxygenated. Makes up about 1 to 2% of cardiac output.