RESPIRATORY SYSTEM

Functions of the Respiratory System

● Oxygen (O2) Acquisition & Carbon Dioxide (CO2) Removal:

○ O2 is required for ATP production (energy).
○ CO2 is a by-product of ATP production and must be removed to prevent blood
pH from decreasing (acidosis).
○ Blood pH must be maintained within narrow limits for homeostasis.

Respiratory Structures

1. External Nose: Encloses the chamber for air inspiration. Air can also be inspired
through the mouth, though it belongs to the digestive system.
2. Nasal Cavity: Cleans, warms, and humidifies air.
3. Pharynx (Throat): Shared passage for air and food.
4. Larynx (Voice Box): Keeps the airway open and facilitates voice production.
5. Trachea (Windpipe): Air-cleaning tube that funnels air into the lungs.
6. Bronchi: Tubes directing air into the lungs.
7. Lungs: Contain air tubes and alveoli (air sacs) for gas exchange with the blood.

Functions of the Respiratory System

1. Ventilation: Movement of air into and out of the lungs.

2. External Respiration: Gas exchange between alveoli and blood. O2 moves into the
blood, and CO2 moves out into the alveoli.
3. Gas Transport: O2 and CO2 are transported in the blood to and from cells.
4. Internal Respiration: Gas exchange between the blood and body cells. O2 moves into
cells, and CO2 moves out into the blood.

Zones of the Respiratory Tract

● Upper Respiratory Tract: From the nose, nasal cavity, pharynx, and to the larynx (air
passage for ventilation).
 ● Lower Respiratory Tract: From the trachea, bronchi, bronchioles, lunges and to alveoli
(site of gas exchange).
○ Conducting Zone: Involved in ventilation (movement of air), includes the nose to
smallest air tubes. (Nose, throat, trachea, bronchi)
○ Respiratory Zone: In the lungs, includes alveoli where gas exchange occurs.

Processes in Gas Exchange

1. Ventilation: Breathing, air moves in and out.

2. External Respiration: Gas exchange in alveoli (O2 into blood, CO2 into alveoli).
3. Gas Transport: O2 and CO2 are transported via blood.
4. Internal Respiration: Gas exchange between blood and tissues (O2 into cells, CO2
out).

Other Functions of the Respiratory System

1. Regulation of Blood pH: CO2 levels affect blood pH, and the respiratory system helps
regulate this.
2. Production of Chemical Mediators: Lungs produce ACE (angiotensin-converting
enzyme), important in blood pressure regulation.
3. Voice Production: Air moving past vocal folds enables speech.
4. Olfaction (Smell): Molecules are drawn into the nasal cavity for smell sensation.
5. Protection: The respiratory system helps filter and remove microorganisms to prevent
infection.

Key Terms:

● External Respiration: Gas exchange between the alveoli and blood.

● Internal Respiration: Gas exchange between the blood and cells.
● Ventilation: Movement of air in and out of the lungs.
● Alveoli: Air sacs in the lungs where gas exchange occurs.
● Conducting Zone: Airways that facilitate ventilation.
● Respiratory Zone: Area in the lungs where gas exchange occurs.
● ACE (Angiotensin-Converting Enzyme): Enzyme involved in blood pressure
regulation.
Upper Respiratory Tract Overview

The upper respiratory tract includes the nose, nasal cavity, pharynx, and larynx. These
structures play key roles in air intake, humidification, warming, cleaning, and voice production.

Nose and Nasal Cavity

● External Nose: Composed of hyaline cartilage (majority) and bone (bridge).

● Nasal Cavity: The chamber where air enters. Begins at the nares (nostrils) and extends
to the choanae (posterior openings to the pharynx).
● Nasal Septum: Divides the nasal cavity into two halves; made of cartilage (anterior) and
bone (posterior).
● Conchae (Turbinate Bones): Three bony ridges that increase surface area and create
turbulence to ensure air contacts the mucous membrane.
 ● Mucous Membrane: Lined with pseudostratified ciliated columnar epithelium that
contains goblet cells secreting mucus. This traps debris and sweeps it to the pharynx
for elimination.
● Functions:
1. Air Passageway: Ensures open air flow.
2. Cleans the Air: Mucous traps debris; cilia move mucus to pharynx.
3. Humidifies and Warms Air: Moistens air; blood warms it.
4. Contains Olfactory Epithelium: Responsible for the sense of smell.
5. Voice Sound: Nasal cavity and sinuses resonate to influence voice tone.
● Sinusitis: Inflammation of the sinus mucous membrane due to infection, causing mucus
buildup and pain. Treatment includes antibiotics, decongestants, hydration, and steam
inhalation.

Pharynx (Throat)
The pharynx is a shared passage for both the respiratory and digestive systems, divided into
three regions:

1. Nasopharynx:
○ Located posterior to the nasal cavity, it houses the pharyngeal tonsil
(adenoids) and is connected to the middle ear via auditory tubes to equalize air
pressure.
○ The soft palate prevents food from entering the nasopharynx.
2. Oropharynx:
○ Located posterior to the mouth, it serves as the pathway for food, drink, and air.
○ Lined with stratified squamous epithelium for protection against abrasion.
○ Contains palatine tonsils and lingual tonsils near the fauces.
3. Laryngopharynx:
 ○ Extends from the epiglottis to the esophagus and larynx.
○ Lined with stratified squamous epithelium.

Larynx (Voice Box)

● The larynx connects the pharynx to the trachea and houses the vocal folds.
● Location: anterior part of the larynxgopharynx
● The rigid wall of it maintains an open passageway between pharynx and trachea.
● Composed of cartilage (9 pieces in total 6 paired; 3 unpaired ), some paired and others
unpaired:
 1. Thyroid Cartilage: The largest, known as the Adam’s apple.
2. Cricoid Cartilage: Forms the base of the larynx.
3. Epiglottis: Elastic cartilage flap that directs food away from the trachea.
4. Arytenoid Cartilage: articulate with the superior border of the posterior cricoid.
5. Corniculate Cartilage: articulate with the superior tip of the arytenoid.
6. Cuneiform Cartilages: contained in mucuous membrane, anterior to the
corniculate; Smaller cartilages involved in sound production and airway
protection.
● Vestibular and Vocal Folds:
1. Vestibular Folds (False Vocal Cords): Protect the vocal cords and help with
swallowing.
2. Vocal Folds (True Vocal Cords): Vibrate to produce sound when air passes
over them.
■ Pitch: Determined by the frequency of vibration; tension and length of
vocal folds.
■ Loudness: Depends on the force of air passing through.
 ● Functions:
1. Maintains Open Airway: Keeps the passage between pharynx and trachea
open.
2. Prevents Aspiration: Closes during swallowing to block food from entering the
airway.
3. Voice Production: Vibrating vocal folds generate sound.
4. Protects Lower Respiratory Tract: Prevents entry of foreign materials.
● Laryngitis: Inflammation of the vocal folds leads to loss of voice due to swelling.

Lower Respiratory Tract

Trachea

● Commonly called the windpipe; allows air flow into the lungs.

Structure:

● Membranous tube attached to the larynx.

● Composed of dense regular connective tissue and smooth muscle.
● 15–20 C-shaped hyaline cartilage (TRACHEAL) rings support and prevent collapse.
● Cartilage on anterior and lateral sides; protects and maintains an open airway.

Dimensions:

● Diameter: 12 mm.
● Length: 10–12 cm.
● Extends from the larynx to the 5th thoracic vertebra.

Cartilage:

● Incomplete rings with thickest cartilage on the anterior wall.

● Posterior wall lacks cartilage, contains elastic ligamentous membrane and smooth
muscle.

Smooth muscle aids in coughing by narrowing the trachea, forcing air to expel mucus and
foreign objects.
Esophagus lies directly posterioly the cartilage-free posterior wall of the trachea.

Smokers can cause tracheal epithelium to become moist stratified squamous epithelium
which lacks cilia and goblet cells which is responsible for the movement of foreign substance to
the larynx.

Whooping Cough
Whooping cough is a bacterial infection of the trachea caused by Bordetella pertussis. It leads
to severe coughing, especially in infants. Vaccination helps prevent it.

Bronchi

● Trachea divides into two main bronchi (primary bronchi).

 ● Each main bronchus leads to a lung.
● Carina (cartilage ridge) marks the division of the trachea into the main bronchi.
● Carina is a key landmark in x-ray readings.
● The mucous membrane of the carina is sensitive to mechanical stimulation and triggers
a strong cough reflex if foreign matter is inspired.
● Materials beyond the carina typically do not trigger this reflex.

Tracheobronchial Tree (Bronchioles)

● The tracheobronchial tree consists of the trachea and branching air tubes in the lungs.
● Trachea divides into:
○ Left and right main bronchi (right is larger, cuz it’s more aligned with the
trachea, so foreign objects are more likely to lodge there).
○ Cartilage rings in the main bronchi, similar to the trachea.
○ Approximately 16 levels of branching occur from the trachea to the smallest
air tubes.

Four Classes of Air Passageways (from largest to smallest):

1. Lobar bronchi (secondary bronchi):

○ Branch directly from main bronchi.
○ Cartilage plates (no longer C-shaped rings).
○ Pseudostratified ciliated columnar epithelium.
○ 2 lobar bronchi in the left lung, 3 in the right lung.
○ Supply lung lobes.
2. Segmental bronchi (tertiary bronchi):
○ Supply bronchopulmonary segments within lung lobes.
○ As bronchi become smaller, cartilage becomes sparse, smooth muscle
increases.
3. Bronchioles:
○ Result from branching of segmental bronchi.
○ Less than 1 mm in diameter, more smooth muscle, less cartilage.
 ○ Larger bronchioles lined with simple ciliated columnar epithelium.
4. Terminal bronchioles:
○ Arise from several bronchioles.
○ No cartilage, prominent smooth muscle.
○ Lined with ciliated simple cuboidal epithelium.

Changes in Air Passageway Diameter

● Bronchodilation: occurs when smooth muscle relaxes, making the bronchioles larger.
● Bronchoconstriction: occurs when smooth muscle contracts, making the bronchioles
smaller.
● Asthma: Bronchoconstriction occurs when there’s a decrease in the airway, which
increases resistance to airflow. (Albuterol helps counteract the effect of this)
Alveoli

● Alveoli are small, air-filled chambers in the lungs where gas exchange occurs (external
respiration). It’s where the air and blood comes into contact.
● 300 million alveoli are in the two lungs.
● Respiratory bronchioles: Smallest branches of the bronchioles with a few attached
alveoli. As they divide, the number of alveoli increases.
● Alveolar ducts: Branch from the respiratory bronchioles. They are long, branching
pathways with many openings (alveoli) along the sides. Eventually, the walls consist
solely of alveoli as the number of it becomes larger.
● Alveolar sacs: Chambers at the end of alveolar ducts, connected to two or more alveoli.
● The alveolar ducts and alveoli consist of simple squamous epithelium.
● Although it’s not ciliated, debris from the air can be removed by macrophages that
move over the surfaces of the cells.

Two types of cells in the alveolar wall:

1. Squamous epithelial cells (90% of surface)

○ The main site for gas exchange between alveolar air and blood
 2. Surfactant-secreting cells (round/cube-shaped)
○ Produce surfactant to ease alveoli expansion during inspiration

Respiratory Membrane

● location of external respiration.

● It is where O2 enters the blood and CO2 exits the blood.
● the respiratory membrane is extremely thin

Components:

1. Alveolar fluid
2. Alveolar epithelium (simple squamous cells)
3. Basement membrane of the alveolar epithelium
4. Interstitial space
5. Basement membrane of the capillary endothelium
6. Capillary endothelium (simple squamous cells)

Thoracic Wall and Muscles of Respiration:

 ● Components of the thoracic wall:
○ Thoracic vertebrae
○ Ribs
○ Costal cartilages
○ Sternum
○ Associated muscles (important for ventilation)
● Thoracic Cavity:
○ Enclosed by the thoracic wall and diaphragm.
○ Diaphragm: Skeletal muscle that separates the thoracic cavity from the
abdominal cavity.
● Role of Muscles in Respiration:
○ Changes thoracic volume during ventilation (expansion and contraction of the
thoracic cavity).

Lungs:

● Shape & Location:

○ Conical shape, extends from diaphragm to just above the clavicle.
○ Right lung: Larger, weighs ~620 g.
 ○ Left lung: Smaller, weighs ~560 g.
● Lung Anatomy:
○ Hilum: Medial surface indentation where structures like bronchus, blood vessels,
nerves, and lymphatic vessels enter/exit.
○ Root of the lung: All structures passing through the hilum.
○ Lobes: Right lung has 3 lobes, left lung has 2 (due to heart's location).
○ Bronchopulmonary segments: Subdivisions of lobes, each supplied by
segmental bronchi (9 in the left lung, 10 in the right).
○ Lobules: Smallest subdivision, each supplied by bronchioles.
○ Fissures: a deep fold that separates the different lobes of the lungs.
○ Cardiac notch: Indentation on the left lung to accommodate the heart.

Blood Supply to the Lungs:

● Oxygenated Blood:
1. Blood that has passed through the lungs and absorbed oxygen.
● Deoxygenated Blood:
1. Blood that has released oxygen in tissues and returned to the lungs.
● Blood Flow Routes:
1. Alveolar blood flow: Deoxygenated blood from pulmonary arteries to alveoli
for oxygenation, returns via pulmonary veins.
2. Bronchial blood flow: Oxygenated blood to the tissues of the bronchial tree.

Lymphatic Supply to the Lungs:

The lungs have two lymphatic supplies:

● Superficial Lymphatic Vessels:

○ Surrounds visceral pleura
○ Drain lymph from superficial lung tissue and visceral pleura (lining of the lung).
● Deep Lymphatic Vessels:
○ Drain lymph from the bronchi and associated connective tissues.
 ● Phagocytosis:
○ Phagocytic cells within the lungs engulf foreign particles from inspired air, which
are moved to lymphatic vessels.
● Lung Changes:
○ Smoking or long-term exposure to pollution can lead to gray/black lung surfaces
from accumulated particles.
● Cancer Metastasis:
○ Cancer cells can spread via the lymphatic vessels to other body parts.

Pleura:

● Pleural Cavities:
○ Lined with serous membrane
○ Two cavities in the thoracic cavity, each housing one lung.
● Pleural Membrane:
○ Parietal Pleura: Lines the inner thoracic wall, superior diaphragm, and
mediastinum.
○ Visceral Pleura: Covers and line the surface of the lung, continuous with the
parietal pleura at the hilum.

Ventilation:

● Definition: The movement of air into and out of the lungs.

● Key Aspects of Ventilation:
1. Actions of the Muscles of Respiration: Change thoracic volume, allowing
airflow into and out of the lungs.
2. Air Pressure Gradients: Changes in air pressure facilitate airflow during
breathing.

Muscles of Respiration:

Muscles of Inspiration (Increase Thoracic Volume):

 ● Contraction moves the central tendon downward, increasing thoracic space.
● Abdominal muscles relax to allow abdominal organs to shift for diaphragm movement.
● In deeper inspiration, the diaphragm flattens as the lower ribs elevate.
● As we inhale, the diaphragm moves down.
○ Diaphragm: Dome-shaped muscle with central tendon at top that accounts for
about ⅔ of thoracic volume increase.
○ External Intercostals: Elevate the ribs to expand thoracic volume.
○ Pectoralis Minor: Helps elevate ribs during deep inspiration.
○ Scalene Muscles: Assist with rib elevation.
○ Sternocleidomastoid

Muscles of Expiration (Decrease Thoracic Volume):

○ As we exhale, the diaphragm moves up, pushing the organs up.

○ Internal Intercostals: Depress ribs.
○ Transverse Thoracis: Also depress ribs.
○ Abdominal Muscles: Aid in compressing the abdomen and pushing organs
upward, helping the diaphragm move upward during expiration.
○ Passive Process: During quiet breathing, expiration is passive due to the elastic
recoil of the thorax and lungs.

Muscles of Respiration in Quiet vs. Labored Breathing:

● Quiet Breathing:
○ Inspiration: Involves diaphragm and external intercostals.
○ Expiration: Passive process with the diaphragm relaxing and thorax recoil.
● Labored Breathing:
○ Inspiration: All inspiratory muscles (including pectoralis minor, and scalene) are
active, leading to a greater increase in thoracic volume.
○ Expiration: Active process with forceful contraction of internal intercostals and
abdominal muscles, resulting in a more rapid and greater decrease in thoracic
volume.
Pressure and Volume Relationship:

● Inverse Relationship: As the volume of a container (thoracic cavity) increases, the

pressure inside the container decreases, and vice versa.
○ Inspiration: Thoracic volume increases, pressure decreases, allowing air to flow
into the lungs.
○ Expiration: Thoracic volume decreases, pressure increases, pushing air out of
the lungs.

Pressure Gradients and Airflow:

● Pressure Gradient: Air flows from areas of higher pressure to areas of lower pressure.
○ During Inspiration: Air flows into the lungs from outside the body because
atmospheric pressure is higher than in the alveoli.
○ During Expiration: Air flows out of the lungs as the pressure inside the lungs
becomes higher than the atmospheric pressure.
● Faster Flow with Larger Pressure Difference: The greater the pressure difference, the
faster the airflow.
● Effect of Altitude: At higher altitudes, atmospheric pressure is lower, reducing the
pressure gradient, making it harder to breathe.

At higher altitudes:

● Air pressure decreases, meaning there is less air pushing down on you.
● Since the total amount of air decreases, there is less oxygen available to breathe,
even though the percentage of oxygen in the air stays the same (about 21%).
● Because the air is thinner, the oxygen molecules are spread out farther apart, and
your body has to work harder to get enough oxygen from each breath.

Pulmonary Volumes and Capacities:

● Spirometry: The process of measuring the air volumes that move into and out of the
respiratory system, using a device called a spirometer.
 ● Pulmonary Volumes:
1. Tidal Volume (TV): The amount of air inspired and expired during normal
breathing. Average value: 500 mL.
2. Expiratory Reserve Volume (ERV): The amount of air (extra air) that can be
forcefully expired after normal expiration. Average value: 1100 mL.
3. Residual Volume (RV): The amount of air remaining in the lungs after the most
forceful expiration. Average value: 1200 mL.
4. Inspiratory Reserve Volume (IRV): The amount of air (extra air) that can be
forcefully inspired after a normal inspiration. Average value: 3000 mL.

“The tidal volume increases when a person is more active. Because the maximum volume of
the respiratory system does not change from moment to moment, an increase in tidal volume
causes a decrease in the inspiratory and expiratory reserve volumes.”

● Pulmonary Capacities (Sum of two or more volumes):

1. Inspiratory Capacity (IC): Tidal volume + Inspiratory reserve volume. Amount of
air that can be inspired after normal expiration. Average value: 3500 mL.
2. Vital Capacity (VC): Tidal volume + Inspiratory reserve volume + Expiratory
reserve volume. Maximum volume of air expelled after maximum inspiration.
Average value: 4600 mL.
3. Functional Residual Capacity (FRC): ERV+ Residual volume. The air
remaining in the lungs after normal expiration. Average value: 2300 mL.
4. Total Lung Capacity (TLC): Sum of all volumes (IRV + TV + ERV + RV). Total
volume of air in the lungs. Average value: 5800 mL.

Alveolar Ventilation:

● Definition: The volume of air available for gas exchange per minute.
○ Dead Space: remaining areas where no gas exchange occurs. It is divided into
two types:
1. Anatomical Dead Space: Air in the conducting zones (upper and lower
respiratory tract until the terminal bronchioles). Approx. 1 mL per pound
of ideal body weight.
 2. Physiological Dead Space: Includes anatomical dead space plus any
alveoli with reduced or no gas exchange.

Factors Affecting Ventilation:

● Gender: Females typically have 20-25% lower vital capacity than males.
● Age: Vital capacity is highest in young adults and decreases with age.
● Body Size: Taller people usually have a larger vital capacity. Slender individuals tend to
have a higher vital capacity than obese individuals.
● Physical Fitness: Athletes can have vital capacities 30-40% higher than sedentary
individuals.
● Diseases: Conditions like spinal cord injury, polio, and muscular dystrophy can reduce
vital capacity, which can be life-threatening if it falls below 500-1000 mL.
● Emphysema: A disease where alveolar walls degenerate, leading to fewer, larger alveoli
with decreased surface area for gas exchange. This increases physiological dead space.

Behavior of Gases and Respiration:

● External Respiration: The process where gases (O₂ and CO₂) diffuse between the
alveoli and the blood in the pulmonary capillaries.
○ Oxygen (O₂) moves from the alveoli (higher partial pressure) into the blood
(lower partial pressure).
○ Carbon Dioxide (CO₂) moves from the blood (higher partial pressure) into the
alveoli (lower partial pressure).
● Partial Pressure: The pressure exerted by an individual gas in a mixture of gases.
○ Atmospheric pressure at sea level: 760 mm Hg.
○ Partial pressure of each gas is the portion of total atmospheric pressure exerted
by that gas (e.g., oxygen, carbon dioxide).

Diffusion of Gases:
 ● Gas Movement: Gases move from areas of higher partial pressure to lower partial
pressure, either into liquids (like blood plasma) or out. The amount of gas dissolved also
depends on the gas’s solubility. CO₂ is 24 times more soluble in water than O₂, meaning
it dissolves more easily in the blood.

Scuba Diving and Gas Solubility:

● Increased Pressure: As a diver descends, the higher pressure causes more gas
(especially nitrogen) to dissolve into the body.
● Decompression Sickness (The Bends): Ascending too quickly causes dissolved
nitrogen to form bubbles, which can block blood flow and cause tissue damage.

Mechanisms of Alveolar Ventilation:

Ventilation is driven by pressure differences between atmospheric air and the alveolar air.
Here’s how the pressure changes during a respiratory cycle:

1. Alveolar Pressure Equals Atmospheric Pressure:

○ At the end of expiration, the pressures inside the alveoli and the atmospheric
pressure are the same. No air movement occurs.
2. Alveolar Pressure is Less Than Atmospheric Pressure (Inspiration):
○ As the inspiratory muscles contract, thoracic volume increases, causing lung
expansion. This expansion increases the volume of the alveoli, which reduces
the intra-alveolar pressure below atmospheric pressure.
○ Since atmospheric pressure is greater than alveolar pressure, air flows into the
lungs.
3. Alveolar Pressure Equals Atmospheric Pressure (End of Inspiration):
○ At the end of inspiration, the thorax and alveoli stop expanding. The alveolar
pressure becomes equal to atmospheric pressure, and no air moves.
○ However, the volume of the lungs has increased compared to the end of
expiration.
4. Alveolar Pressure is Greater Than Atmospheric Pressure (Expiration):
 ○ During expiration, the diaphragm relaxes, and the thorax recoils, reducing
thoracic volume. This reduction in volume leads to a decrease in alveolar volume,
which increases alveolar pressure above atmospheric pressure.
○ Since alveolar pressure is greater than atmospheric pressure, air flows out of
the lungs. The expiration ends when thoracic volume stops decreasing.

Factors Affecting Alveolar Ventilation

1. Lung Recoil:
○ Elastic fibers and surface tension cause the lungs to shrink after being stretched.
Surfactant reduces surface tension to prevent alveolar collapse.
○ Insufficient surfactant in premature infants causes Infant Respiratory Distress
Syndrome (IRDS).
2. Pleural Pressure:
○ The pressure between the pleurae helps expand the lungs. If the pleurae are
separated (e.g., trauma), it causes pneumothorax or tension pneumothorax,
impairing lung function.

Factors Affecting Gas Diffusion

1. Partial Pressure Gradients:

○ Gases move from high to low pressure. The steeper the gradient, the faster the
exchange.
2. Thickness of Respiratory Membrane:
○ Thicker membranes slow diffusion.
3. Surface Area:
○ Larger surface area increases gas exchange.

Oxygen Partial Pressure Gradients

1. Alveolar to Blood:
 ○ Alveolar PO₂ (104 mm Hg) is higher than blood PO₂ (40 mm Hg), causing O₂ to
diffuse into the blood.
2. Pulmonary Veins:
○ PO₂ drops slightly to 95 mm Hg due to mixing with deoxygenated blood.
3. Arterial to Tissues:
○ PO₂ (95 mm Hg) is higher than tissue PO₂ (40 mm Hg), causing O₂ to diffuse into
the tissues for ATP production.
4. Venous Blood:
○ PO₂ equilibrates with tissue levels (around 40 mm Hg).

Carbon Dioxide Partial Pressure Gradients

1. Tissues to Blood:
○ Cells produce CO₂, raising intracellular PCO₂ to 46 mm Hg. Blood arriving in
tissues has PCO₂ of 40 mm Hg, so CO₂ diffuses into the blood. Blood reaches 45
mm Hg by the venous end.
2. Blood to Alveoli:
○ Blood PCO₂ is 45 mm Hg, while alveolar PCO₂ is 40 mm Hg. CO₂ diffuses into
the alveoli. Blood reaches equilibrium at 40 mm Hg.

Respiratory Membrane Thickness

● Increased thickness reduces diffusion rate (e.g., pulmonary edema, tuberculosis).

● Conditions causing thickening: Left heart failure, pneumonia, inflammation, and
tuberculosis.

Respiratory Membrane Surface Area

● Normal surface area is ~70 m².

● Diseases like emphysema and lung cancer decrease surface area, impairing gas
exchange, especially during exertion.
● Surgical removal or lung damage can also reduce surface area.
Oxygen and Carbon Dioxide Transport in Blood

1. Hemoglobin:
○ Transports O₂ (98.5%) and CO₂ (via binding and bicarbonate conversion).
○ Sickle-cell hemoglobin: Causes red blood cells to become sickle-shaped under
low O₂, blocking blood flow.
2. Transport of O₂:
○ 98.5% bound to hemoglobin, 1.5% dissolved in plasma.
3. Transport of CO₂:
○ Dissolved in plasma: 7%
○ Bound to hemoglobin: 23%
○ Converted to bicarbonate (HCO₃⁻): 70% (via carbonic anhydrase).

Carbon Dioxide Transport Mechanisms

1. Plasma:
○ 7% dissolves in plasma.
2. Hemoglobin:
○ 23% binds to hemoglobin, affecting O₂ binding affinity.
3. Bicarbonate:
○ 70% as bicarbonate (HCO₃⁻) in red blood cells and plasma.
○ CO₂ combines with H₂O to form H₂CO₃, dissociating into H⁺ and HCO₃⁻, affecting
blood pH.
4. Tissue Exchange:
○ HCO₃⁻ exits red blood cells, Cl⁻ enters via antiporter for electrical neutrality.

CO2 Transport and Oxygen Release in the Lungs and Tissues

In the Lungs:

1. CO2 Diffusion: Carbon dioxide (CO2) diffuses from red blood cells and plasma into the
alveoli for exhalation.
 2. Carbonic Anhydrase Action: Carbonic anhydrase catalyzes the conversion of carbonic
acid (H2CO3) into CO2 and water (H2O).
3. Chloride Shift: In red blood cells, bicarbonate ions (HCO3-) are exchanged with
chloride ions (Cl-) to maintain electrical neutrality.
4. Oxygen Uptake: Oxygen (O2) diffuses into red blood cells and binds to hemoglobin,
promoting O2 transport.
5. Hemoglobin Release of H+: The binding of oxygen causes hemoglobin to release
hydrogen ions (H+), which aids in O2 uptake.

In the Tissues:

1. CO2 Diffusion: CO2 diffuses from tissues into plasma and red blood cells.
2. Formation of Carbonic Acid: In red blood cells, CO2 reacts with water to form carbonic
acid (H2CO3), catalyzed by carbonic anhydrase.
3. Dissociation of Carbonic Acid: Carbonic acid dissociates into bicarbonate ions
(HCO3-) and hydrogen ions (H+).
4. Chloride Shift: Bicarbonate ions move out of red blood cells, and chloride ions move in
to maintain electrical neutrality.
5. Oxygen Release: Oxygen is released from hemoglobin and diffuses into the tissues.
6. Release of Oxygen by Hemoglobin: Hydrogen ions bind to hemoglobin, promoting the
release of oxygen.
7. CO2 Binding: Hemoglobin, after releasing O2, binds to CO2 for transport back to the
lungs.

Physiological Factors Affecting Gas Transport

● Respiratory System Function: Maintains blood O2, CO2, and pH within normal ranges.
Deviations influence hemoglobin’s affinity for gases.
● Chemoreceptors: Specialized neurons that detect changes in pH, PO2, and PCO2,
helping regulate respiration.

Effect of PO2 on O2 Transport

 ● Hemoglobin and O2: Hemoglobin binds to O2 at heme groups. Hemoglobin is fully
saturated at 4 O2 molecules per hemoglobin molecule.
● 50% Saturation: Hemoglobin is 50% saturated with 2 O2 molecules bound.

Effect of PO2 on CO2 Transport

● Low PO2 Levels: Hemoglobin binds more CO2 at low PO2, decreasing hemoglobin’s
affinity for O2.

Effect of pH and PCO2 on O2 Transport

● Low pH (High H+): Reduces hemoglobin’s affinity for O2, enhancing O2 release in
tissues (Bohr effect).
● High pH: Increases hemoglobin’s affinity for O2.
● High PCO2: Reduces hemoglobin’s ability to bind O2, contributing to O2 release in
tissues.
● CO2 Binding to Hemoglobin: Reduces O2 affinity, favoring O2 release.

CO2 Movement in Fetal-Maternal Blood Exchange

● Fetal-Maternal CO2 Transfer: CO2 moving from fetal blood to maternal blood
decreases maternal hemoglobin's affinity for O2, increasing O2 transfer to the fetus.

Effect of pH and PCO2 on CO2 Transport

● High PCO2: Causes a decrease in pH, stimulating increased respiratory rate to remove
excess CO2.
Hyperventilation and Breath-Holding Effects on Blood pH

1. Hyperventilation: Reduces CO2 levels, increasing blood pH (alkalosis).

2. Breath-Holding: Increases CO2 levels, lowering blood pH (acidosis).

Effect of Temperature on Gas Transport

● O2 Transport: Higher temperatures reduce hemoglobin’s affinity for O2, increasing O2

release into tissues.
● CO2 Transport: Increased temperature increases CO2 production and conversion into
H+ and HCO3-, lowering pH and stimulating respiratory rate.

Effect of Glucose Metabolism on O2 Transport

● Glucose Metabolism: Reduces hemoglobin’s O2 affinity through by-products (e.g.,

lactic acid), promoting O2 release.
● Blood Bank Storage: Reduced by-product levels after storage make blood unsuitable
for transfusion after 6 weeks.

Respiratory Control in the Brainstem

● Medulla Oblongata: Controls the respiratory rate by regulating the basic rhythm of
ventilation through stimulation of respiratory muscles.
○ Neurons in the medulla control the basic rhythm by stimulating muscles of
respiration.
○ Muscle Recruitment: Stronger muscle contractions and increased depth of
respiration are due to the recruitment and frequent stimulation of muscle fibers.
○ Respiratory Rate: Determined by how frequently respiratory muscles are
stimulated.

Respiratory Areas in the Brainstem

 ● Neurons for Respiration: Aggregated in specific areas of the brainstem, intermingling
neurons active during inspiration and expiration.
● Medullary Respiratory Center: Located in the medulla oblongata, consisting of:
○ Dorsal Respiratory Group (DRG): Active mainly during inspiration, stimulates
diaphragm contraction.
○ Ventral Respiratory Group (VRG): Active during both inspiration and expiration,
coordinates respiratory movements.
○ PreBötzinger Complex: Part of VRG, believed to establish the basic rhythm of
respiration.
● Communication:
○ Between the two halves of the medulla to ensure symmetrical respiratory
movements.
○ Between the dorsal and ventral respiratory groups to coordinate inspiration and
expiration.

Pontine Respiratory Group (PRG)

● Location: Found in the pons, previously called the pneumo-taxic center.

● Function:
○ Regulates Respiratory Rate: Some neurons are active during inspiration, others
during expiration.
○ Role in Breathing Pattern: Helps fine-tune the transition between inspiration
and expiration.
○ Not Essential: While it helps adjust the breathing rhythm, the PRG is not
essential for generating the respiratory rhythm.

Generation of Rhythmic Ventilation

● 1. Starting Inspiration:
○ Neurons in the medullary respiratory center establish the basic rhythm of
ventilation.
 ○ Constant stimulation from receptors (monitoring blood gas levels, temperature,
muscle and joint movements) and parts of the brain responsible for voluntary
movements and emotions influences inspiration.
○ Inspiration begins when combined inputs generate action potentials, stimulating
respiratory muscles.
● 2. Increasing Inspiration:
○ Gradual activation of more neurons leads to stronger stimulation of respiratory
muscles, lasting approximately 2 seconds.
● 3. Stopping Inspiration:
○ Neurons in the medullary respiratory center that stop inspiration receive input
from the pontine respiratory group, stretch receptors in the lungs, and other
sources.
○ Activation of inhibitory neurons relaxes respiratory muscles, leading to expiration
for about 3 seconds.
○ The next inspiration cycle begins again at step 1.

Effect of Po2 on Respiratory Rate

● Hypoxia: Reduced Po2 levels in blood stimulate an increase in ventilation, especially

when Po2 drops to 50% of normal levels.
● Normal Po2 Range: O2 has minimal effect on respiration regulation within normal Po2
values.
● Severe Hypoxia: Po2 decreases too much, respiratory center failure may occur, leading
to death.

Effect of Pco2 on Respiratory Rate

● CO2 as Principal Regulator: Even small increases in blood CO2 (hypercapnia) cause a
significant rise in ventilation rate and depth.
○ Example: A 5 mm Hg increase in Pco2 doubles ventilation rate.
● Hypocapnia: Lower than normal CO2 levels can reduce or stop breathing temporarily.
 ● Chemoreceptors: Located in the chemosensitive area of the medulla oblongata and
carotid/aortic bodies, monitor CO2 and pH changes, influencing respiratory rate.
○ The medullary chemoreceptors are more significant in regulating Pco2 and pH
than the carotid and aortic bodies.

Effect of pH on Respiratory Rate

● pH Detection: Central chemoreceptors in the medulla oblongata detect pH changes due

to CO2, while carotid/aortic bodies detect pH changes due to H+ concentrations.
● Lower pH: Results from increased CO2, stimulating the respiratory center to increase
breathing rate and depth, lowering CO2 and restoring normal pH.

Hering-Breuer Reflex and Respiratory Rate

● Function: Prevents overinflation of the lungs, limiting the depth of inspiration.

● Mechanism: Stretch receptors in bronchi/bronchioles send inhibitory signals to the
respiratory center during lung inflation, promoting expiration.
● Role in Infants: Important for regulating the basic rhythm of breathing and preventing
overinflation.
● Role in Adults: More significant during deep breathing or exercise.

Cerebral and Limbic System Control of Respiratory Rate

● Voluntary Control: The cerebral cortex controls breathing during activities like talking
or singing.
● Exercise: Respiratory rate increases rapidly at first due to limb movement, then
gradually levels off. At high intensity, it can exceed the anaerobic threshold, leading to
a drop in blood pH and increased ventilation.
○ Anaerobic Threshold: The highest level of exercise that doesn’t significantly
affect blood pH.
 ○ Athletes: More efficient cardiovascular and respiratory systems, lower resting
respiratory rate, and higher rate during maximal exercise.
● Limbic System: Emotional responses can affect respiration, causing hyperventilation or
sobbing.

Other Modifications of Ventilation

● Touch, Thermal, or Pain Receptors: Can trigger reflexes that modify ventilation.
○ Nasal irritants: Cause sneezing.
○ Lung irritants: Cause coughing.
○ Increased body temperature: Stimulates increased ventilation due to higher
metabolism and CO2 production, needing expulsion.