Respiratory System - Vocabulary

Physiological Regulation of Respiration

• Model of Physiological Regulation:

  • Regulated variables: Blood gases (CO2, O2) and pH.

  • Controlled variables: Ventilation rate and depth, controlled by respiratory muscles.

  • Chemoreceptors detect blood gas/pH levels and send signals to the dorsal and ventral respiratory groups (DRG and VRG) in the brainstem.

  • DRG and VRG send messages to effector organs (skeletal muscles of the respiratory pump).

  • Changes in breathing rate/depth alter air intake, influencing blood gases and restoring homeostasis.

Respiratory Regulation Components

• Chemoreceptors and their influence on breathing.

• Pulmonary ventilation (air in and out of lungs).

• Pulmonary circulation (blood supply to the lungs).

• Gas exchange processes.

Anatomical Divisions of the Respiratory System

• Upper Airway: Nose to larynx (voice box).

  • Nasal cavity: Humidifies, warms, and cleans incoming air.

  • Oropharynx and Laryngopharynx: Passageways for air.

  • Epiglottis and Glottis: Must be open to allow air into the trachea; food goes to the esophagus.

• Lower Airway: Trachea to alveoli.

  • Trachea splits into left and right primary bronchi.

  • Right lung has three lobes, left lung has two (due to the cardiac notch accommodating the heart).

  • Primary bronchi divide into secondary and tertiary bronchi.

  • Conducting airways end at terminal bronchioles, which transport air but do not participate in gas exchange.

  • Respiratory zone begins at respiratory bronchioles where gas exchange occurs.

  • Alveolar ducts and sacs (containing individual alveoli) produce surfactant to minimize surface tension and keep alveoli open.

Generations of Airways

• Each split in the airway is considered a generation (Z = generation number).

• Conducting zone includes the upper airway and serves for air transport.

• Site of gas exchange is where oxygen is picked up from the air, and CO2 is expelled.

• Taking a bigger breath can slightly increase the conducting zone.

Pulmonary and Systemic Circuits & Gas Exchange

• Pulmonary Circuit: Blood travels from the heart to the lungs for gas exchange and back to the heart.

• Systemic Circuit: Oxygenated blood goes from the heart to the body for cellular gas exchange, then deoxygenated blood returns to the heart and lungs.

  • Deoxygenated blood from the lower body enters the heart via the inferior vena cava; from the arms and head, it enters via the superior vena cava.

  • Pulmonary veins bring oxygenated blood back to the left atrium and then to the left ventricle.

  • The left ventricle has a thick wall to pump blood into the high-pressure systemic circuit via the aorta.

  • Deoxygenated blood surrounds the alveoli, releasing CO2 into the air and picking up oxygen, which returns to the heart and is distributed via the systemic circuit.

Respiratory Membrane

• The respiratory membrane is where gas exchange occurs in the lungs. It has air on one side and blood on the other.

• The membrane must be thin for efficient gas exchange.

Hemoglobin (Hb)

• Consists of red heme pigment bound to the protein globin.

• Enables oxygen to be bound in blood.

  • Four heme groups, each with an iron molecule in the center that binds to oxygen.

  • Globin: 4 polypeptide chains (2 alpha and 2 beta subunits).

  • Each subunit binds to a ring-like heme group.

  • Each heme group contains an atom of iron that reversibly binds one molecule of oxygen.

  • Each Hb molecule can bind 4 oxygen molecules.

  • Each red blood cell contains 250 million Hb molecules, allowing a binding capacity of 1 billion oxygen molecules.

Mechanics of Ventilation

• Changes in pressure and volume facilitate air movement in and out of the lungs.

• Boyle's Law explains the relationship between pressure and volume.

About Pressure

• Pressure drives respiration and is always relative to atmospheric pressure.

  • Atmospheric pressure at sea level is 760 \, mmHg (1 atm).

  • Negative pressure: Pressure is lower than atmospheric pressure.

  • Positive pressure: Pressure is higher than atmospheric pressure.

• Partial Pressure of a Gas: The pressure exerted by a specific gas if it alone fills a volume, standardized to temperature.

  • Total Pressure: Sum of partial pressures of all gases in a container.

Boyle's Law

• P1V1 = P2V2

• Describes the inverse relationship between pressure and volume.

• If volume doubles, pressure halves; if volume halves, pressure doubles.

Pleural Cavity

• Thin, fluid-filled space between the visceral pleura (lining the lung) and the parietal pleura (lining the chest wall), providing lubrication.

Pressures in the Respiratory System

• Intrapulmonary Pressure (PPul): Pressure in the alveoli, which rises and falls with breathing phases.

• Intrapleural Pressure (Pip): Pressure in the pleural cavity, always less than atmospheric pressure (on average, 4 mmHg less than PPul).

• Transpulmonary Pressure (Ptp): Difference between intrapulmonary and intrapleural pressure (PTP = PPul - Pip).

Importance of Pressure Relationship

• Intrapleural pressure must always be less than intrapulmonary pressure to maintain a negative vacuum in the pleural cavity, preventing lung collapse.

• Greater negative pressure at the top of the lung when standing, due to gravity, keeps alveoli open more.

• Less fresh gas enters alveoli at the top of the lung compared to the bottom because of less vacuum at the bottom helping to prop them open.

Lung Collapsing Factors

• Lungs' natural tendency to recoil due to elasticity.

• Surface tension of alveolar fluid: Molecules of fluid covering alveoli attract each other, collapsing the alveoli.

  • Surface tension is reduced by surfactant.

Factors Opposing Lung Collapse

• Elasticity of the chest wall pulls the thorax outwards, enlarging the lungs.

• The thoracic wall's stickiness to lung tissue, due to water cohesion, stretches the lung tissue along with thoracic wall expansion.

• The balance between collapsing and opposing factors ensures lungs remain expanded.

Basic Mechanics of Ventilation

• Inspiration: Diaphragm and external intercostals contract; diaphragm moves down, increasing thoracic cavity volume; ribs elevate, and sternum flares as external intercostals contract.

  • Volume increases and pressure decreases, becoming lower than room air pressure, causing air to flow into the lungs down the pressure gradient until it reaches zero.

• Expiration: Muscles relax; phrenic nerve switches off (if not forced).

  • Decreased thoracic cavity volume increases intrapulmonary pressure above atmospheric pressure, causing air to flow out of the lungs.

Respiration and Diffusion

• Diffusion: Fundamental mechanism for O2 and CO2 transport, driven by concentration gradients (high to low) without energy expenditure.

Henry's Law

• At the site of gas exchange, the partial pressure of a gas in the air determines how quickly it dissolves into the blood.

• A higher concentration of gas in the gas phase results in faster dissolution into the liquid phase.

Factors Affecting Gas Exchange

• Diffusion of O2 and CO2 is proportional to the surface area and inversely proportional to the width of the barrier.

• Increased surface area (provided by alveoli) enhances gas exchange.

• High surface area and thin walls result in 3-fold faster gas exchange than required at sea level.

Lung Volumes and Capacities

• Cannot calculate Residual Volume (RV) without specific equipment.

• Capacities are combinations of different volumes.

  • TV (Tidal Volume): Normal breathing volume.

  • IRV (Inspiratory Reserve Volume): Air volume inspired above tidal volume.

  • ERV (Expiratory Reserve Volume): Air volume expired below tidal volume.

  • IC (Inspiratory Capacity): TV + IRV (total air that can be inspired from a normal breath).

  • VC (Vital Capacity): IRV + TV + ERV (working lung volume).

  • FRC (Functional Residual Capacity): ERV + RV (air remaining after normal breath).

  • TLC (Total Lung Capacity): Sum of all volumes.

  • FEV1: Forced Expiratory Volume in 1 second.

  • FVC forced vital capacity. How much air you can forcefully breathe out.

• Tidal Volume (Vt): Amount of air entering and leaving the lungs with each breath (~500 ml).

• Inspiratory Reserve Volume (IRV): Amount of air that can be inspired in addition to Vt (~1900-2500 ml).

• Expiratory Reserve Volume (ERV): Amount of air that can be removed from the lung beyond Vt (~1100-1500 ml).

Factors Affecting IRV and ERV Magnitudes

• Current lung volume (greater volume after inspiration = smaller IRV).

• Lung compliance (ease of lung inflation).

• Muscle strength and innervation (weakness decreases IRV).

• Comfort (injury, pain, or disease may decrease IRV).

• Skeletal flexibility (joint stiffness decreases IRV).

• Posture (stooping decreases IRV due to load on the diaphragm).

Residual Volume (RV)

• Air volume remaining in the lungs after maximal expiration.

• Complete air removal leads to lung collapse, requiring high pressure for re-inflation.

• Ventilation is episodic, but blood flow is continuous.

Lung Capacities

• Total Lung Capacity (TLC): Maximum amount of air contained in lungs after maximum inspiration = Vt + IRV + ERV + RV

• Vital Capacity (VC): Maximum amount of air that can be expired after a maximum inspiration = Vt + IRV + ERV

• Inspiratory Capacity (IC): Maximum amount of air that can be inspired after a normal tidal volume expiration = Vt + IRV

• Functional Residual Capacity (FRC): Volume of air remaining in lungs after normal tidal volume expiration = ERV + RV

• RV and TLC cannot be measured without body plethysmography.

Lung Function Changes with Age

• Lung elasticity decreases, and FEV1 decreases with age.

• Loss of elasticity results in air trapping and higher inflation, worsened by disease.

Pathologies and Smoking

• Normal lung function declines over time; smoking accelerates this decline.

• Stopping smoking can slow the rate of decline.

• Vaping is increasing, especially among adolescents, and its long-term impacts on lung function are largely unknown.

Detrimental Impacts of Vapes

• Formaldehyde: Used in glue and can cause irreversible lung damage.

• Propylene glycol: Found in paint and is toxic to human cells.

• Nicotine: Addictive and can harm the brain, especially in areas controlling attention, learning, mood, and behavior.

Pulmonary Diseases

• Obstructive: Airflow is restricted, such as by mucus or swelling. Can get air out, but it takes longer.

• Restrictive: Lung tissue is modified and stiffer, requiring more pressure to change volume.

• Mixed: Combination of obstructive and restrictive properties.

Respiratory Lab Practice - Breathing Conditions

• Open circuit breathing system (normal room air, no re-breathing).

• Closed circuit rebreathing system:

  • Hypoxia (CO2 scrubbed out).

  • Hypercapnia (CO2 allowed to increase).

Response to Hypercapnia

• Normal breathing:

  • Airflow vs. time loop with pauses before breathing out and after expiration.

• Under hypercapnia:

  • Faster breathing with shorter breaths.

  • Increased mean inspiratory flow.

• Chemoreceptors in the brain detect increased CO2 levels, triggering changes in breathing to dilute CO2.

Definitions Relevant to Lab Practice

• Eupnea: Normal, quiet breathing.

• Hyperventilation: Over-breathing, reduces PaCO2.

• Hypoventilation: Under-breathing, increases PaCO2.

• Apnea: Absence of breathing (at least 10 seconds).

• Bradypnea: Abnormal slowness of breathing.

• Tachypnea: Rapid breathing.

• Dyspnea: Sensation of breathlessness.

• Hyperpnea: Increased ventilation in proportion to metabolic demand (e.g., during exercise).

Pulmonary Blood Flow

• Blue arteries: Going to the lungs for gas exchange (high in CO2).

• Red arteries: Bringing oxygenated blood from the lungs to the rest of the body.

• Pulmonary arteries are part of the pulmonary circuit, supplying deoxygenated venous blood straight from the heart.

• Arise from the right ventricle, bifurcating along the bronchial tree.

• Capillaries are 8 micrometers in diameter and 10 micrometers in length.

• The average erythrocyte spends 0.75 seconds in pulmonary capillaries.

• Post gas exchange, blood goes into pulmonary veins, returning oxygenated blood to the left atrium.

Bronchial Arteries

• Branch of the aorta, carrying oxygenated blood to supply conducting airways.

• Capillaries anastomose with capillaries from pulmonary arteries at the level of the respiratory bronchioles.

• Capillaries of bronchial circulation drain partially into pulmonary veins, causing venous admixture.

Ventilation to Perfusion Ratios

• Quantify ventilation (air to lungs, L/min) vs. perfusion (blood to alveoli, L/min).

• Expressed as a fraction (no units).

• Maintain a good range for efficient gas exchange.

• External factors can impact this ratio.

Respiratory Abbreviations and Subscript Notations

• V (volume of air), Q (perfusion - blood volume).

• V with dot (air flow), Q with dot (blood flow).

• f (frequency: breathing and cardiac).

• P (pressure or partial pressure).

• F (fractional concentration).

• C (concentration).

• Subscript notations: A (alveolar), a (arterial), v (venous), c (capillary), I (inspired), E (exhaled).

Ventilation to Perfusion Ratios (Alveolar)

• Ratio of alveolar ventilation to right ventricular output.

  • VA \dot{}/Q = (VT - VD) \dot{} \times fb

• Normal resting person:

  • Expired minute volume (including conducting airways) (\dot{V}e) \approx 5L/min

  • \dot{V}A \approx 4.5L/min

  • \dot{Q} \approx 5L/min

  • VA/Q = 4.5/5 \approx 0.9

• Some alveoli are not ventilated but are perfused (VA/Q = 0).

• Some alveoli are ventilated but not perfused (VA/Q = infinity).

Measuring Ventilation-Perfusion practically

• Using radioactive substances in breathing and blood supply to observe V/Q ratios.

Anatomical Dead Space

• Region ventilated but not perfused (e.g., conducting airways).

• Volume: Normal 150 ml.

• Increases with: Lung volume, age, body size, exercise.

Measuring Anatomical Dead Space

• Single breath N2 washout exhalation trace.

• Monitor nitrogen output after a single big breath.

• Dead Space volume: ~25% of ventilation
  Increased with: Tidal volume increased, during exercise, 40% older people

Alveolar Dead Space

• Ventilated alveoli that do not receive blood flow
  *~20 mL

Physiological Dead Space

*Blood goes to alveoli but there is no gas exchange
*~~2% of cardiac output- termed venous admixture
Anatomical Arteriovenous Shunts:
Physical connection between arterial and venous side
Blood bypasses alveoli completely-adds to venous admixture
Pulmonary blood flow distribution is dependent upon the pressure balance within the thorax
BP- (systolic+ 2diastolic)/3= Mean Arterial Pressure or SBP-DBP/3 +DBP

Determinants of Blood Flow

Little vasomotor activity
Pulmonary arterial to venous differential: Drives blood flow (pulmonary v systemic)
12 (arterial) -7.5 (venous) =4.5 mmHg\Little Structure to pulmonary capillaries- easy to dilate and collapse
External forces cause: Alveolar pressure Pa
Diameter determined by elastic tissues of lungs

External Internal Forces

*Alveolar pressure
*Arterial pressure
*Venous Pressure
*Hydrostatic pressure- apical or basal
*Interstitial pressure
*Spongy tissue expanding +compressing vessels= blood determination.

Zones of Blood Flow Distribution

Apical Flow <50% Basal 100% 10cm above Basal region:120% Pa>Pa>Pv= Zone 1: Not in standard conditions
Pa>Pa>Av= Zone 2: Does happen under normal conditons
Pa>Pv>PA= Zone 3: Open Vessels happening under normal conditions

Hypoxic Vasoconstriction

Blood vessels in lungs constrict with low oxygen level
Stimulus: Alveolar= Hypoxia PA02
Normal AO2 ~103 mmHg
Vasoconstriction with Pao2,8 kPA (60 mmHg)
Reflex present in foetus and aduly
Action opposite that of muscles arterioles which dilate with hypoxia in the muscle arterioles.
altitude 4200 meters- systemic hypoia
Local Obstruction= Localized Hypoxia

Rspiratory control- Modification of volume

Nervr activation of phrenic nerves-> diaphragm
Second is altered with rate
Inspiratory time
Experatory time
Post-Inspiration pause
Post Expiration pause
Cycle

Why Do We Need to Control Our Breathing -2 things.

Establish Automatic Rhythm for contraction of repiratory muscles
Accomodate changing conditions
Metabolic demands\Mechanical Conditions
Episodic non-ventilatory Behaviours: Speaking eating sniffing etc…
Primary: Diaphragm and external intercostals
Expiration (Secondary)
Relaxed diaphram + intercostals (primary relaxed breathing)
internal intercoatal and abdominals
C 345 keeps you alive

Central Control of Breathing

Autonomic centres in brainstem activate respiratory muscles
Rhytm and Subconscious
Respiratory Rythm generated by CPG in Mudella
Changes in blood gasses- messages
Brainstem neurons send signals to motor neurons that innervate respiratory muscles

Central Pattern Generator

Clock that times automatic rythm of inspiration and expiration
CPG recieves tonic input from multiple sources
Most Important- Central and Peripheral Chemorecepotors

Chemoreceptors

Alter CPG- Changes is Ventilation Depth and Frequency\TWO Main Locations- Peripheral
Increase in CO2- Only responsible for 20% of change
Central chemecorreptors- Breaain + Protected by Blood Barrier\Hydrogen inos result in reduction of pH and signal to change breathing rate

Chemoreceptors- TOnic Drive to CPG

Both peripheral and central\O2 and Arterial Levels
Carotid vs Aortic
CNS- changes in alveolar ventilation to return variables to normal
Respiratory- Related Neurons- that fire actione potentials mor e rapidly
Motor Nuerons
Pre motor Neurons orchestrate patterns
Eupnea-Alternating pattern
Medulla-DRG vs VRG
Bilateral 1/3\Contains Inspiratory Neurons
DRG- Integrates sensory input- Proect sensory input to VRB.
VRG- Big Commands to repiratory system
Pre motor\Minor Sensory inputs triggered peripheral chemoreceptore -signaling to dorsal respiratory group and premotor influence the nerves.
VRG- Main Motor Outputs

Medulla- Ventral Repiratory Group

Vrg Main Efferent motor
Consist of three regions
Rosteral- Botzinger complex: By inhibiting inspiration-Turning ir off\By activating Caudal VRS
Intermediate VRG- Inspiration
Pre Boatzinger Complex: Nuersions generate Repiratory rythm_Nuceus Ambigious- Random forend inspiration\Controls force of inspiration intercoatal nerves\CAUDAL vrg EXHAULATION \Pre motor : Expitorary

PUTTING IT ALL TOGETHER

InhalationOnly Intermediate
Exhalation switch off ( Rostral or Caudal Tidal breath) Hypernia Running
Inspiration+ recriut other upper air
Peripheral - most sensitive to Pao2 Hypoxia can be caused due to acidosis.

Peripheral Chemos

-Acidosis respiratory in CO2 or Metablic low bicarbonate due to consumption or renal failure.

Carotid body

Chemerecptive cells called glomus= type 1 cells
10 merons diamter sphericl clusters- neurton like- innverted by SYm and Parasym-
Contain voltage gates ion channels- Action potentials\Release NE ACh- controls firing sensit
High Metablic rate -Sympathic fool Caroti body that hypoxais state.
Glossopharyngeal n feed back
Central Chemo\Peripheral chemo respond to oxgyen levels