The Respiratory System

• The respiratory system facilitates oxygen intake and carbon dioxide removal, essential for energy production at the cellular level.

Key Processes of the Respiratory System

• Pulmonary ventilation: Air movement into and out of the lungs.
• Pulmonary diffusion: Gas exchange between lungs and blood.
• Gas transport: Oxygen moves from lungs to tissues, while carbon dioxide moves from tissues to lungs via the blood.
• Capillary gas exchange: Gas exchange occurs between blood and tissues.
• Oxygen utilization: Cells use oxygen to produce energy.

Structure of the Respiratory System

• Key structures include the nose/nostrils, nasal cavity, pharynx, larynx, trachea, bronchi, bronchioles, terminal bronchioles, respiratory bronchioles, and alveoli.

Conductive Zone

• The conductive zone spans from the nose to the terminal bronchioles.
• Primary function: transports air.
• It does not participate in gas exchange, hence being called anatomical dead space.
• The conductive zone warms and humidifies incoming air to body temperature, 99.5% saturation, safeguarding the lungs and maintaining core temp.
• Most air enters the mouth, bypassing humidification, which may cause dryness.
• Incoming air is filtered by ciliated mucus membranes, which can be damaged by smoke and pollutants.

Respiratory Zone

• The respiratory zone is the region of gas exchange.

Alveoli

• Alveoli facilitate gas exchange with a large surface area.
• They are surrounded by capillaries, enabling efficient oxygen transfer into the bloodstream.
• The respiratory membrane is thin (0.3 micrometers) to optimize diffusion.
• The respiratory membrane is composed of alveolar and capillary epithelium.

High-Altitude Pulmonary Edema (HAPE)

• HAPE involves fluid accumulation in the lungs/alveoli impacting gas exchange.

Mechanics of Ventilation

• Ventilation relies on pressure gradients over resistance: Airflow (L/min) = pressure gradient/resistance.
• Gas moves from high to low concentration areas.
• Airway resistance is determined by airway size/smoothness, with size being the most important factor, because small changes in diameter cause large changes in resistance.
• Nasal strips may reduce nasal resistance and increase ventilation, but there is no proven impact.

Asthma

• Asthma narrows and inflames airways due to triggers, increasing airway resistance.
• Asthma medication aims to normalize airway resistance.

Exercise-Induced Bronchoconstriction (EIB)

• EIB is caused by increased breathing rate and depth during exercise.
• Normally, bronchodilation decreases resistance, but EIB causes bronchoconstriction in some.
• EIB affects 30-70% of elite athletes, especially in endurance, aquatic, and cold-weather sports.
• Treatment includes warming up, medication, and avoiding cold air.

Boyle's Law

• Boyle's Law shows pressure and volume of gas are inversely related.
• Low pressure corresponds to high volume, and high pressure to low volume.

Establishing a Pressure Gradient

• Inhalation reduces intrapulmonic pressure below atmospheric pressure, while exhalation increases it above atmospheric pressure.

Pressures at Rest

• Atmospheric pressure (PAtm) and intrapulmonic pressure are both 760 mmHg, resulting in no air movement.

Mechanics of Breathing

• Inspiration: Increase volume decreases intrapulmonic pressure, causing air to rush in.
• Expiration: Decrease volume increases intrapulmonic pressure, causing air to rush out.

Mechanics of Breathing: Inspiration

• At rest, the diaphragm contracts to increase volume and decrease pressure.
• During exercise, external intercostals and accessory muscles contract, moving ribs up and out. Accessory muscles include sternocleidomastoid, scalenes, and pectoralis minor.

Pressures During Inspiration

• During inspiration: PAtm = 760 mmHg, PIntrapulmonic = 758 mmHg, ΔP = -2mmHg, which causes air to move into the lungs.

Mechanics of Breathing: Expiration

• During rest, inspiratory muscles and the diaphragm relax causing the chest cavity recoils.
• During exercise, the rectus abdominus, internal obliques, and internal intercostals contract to pull the ribs down.

Pressures During Expiration

• During expiration, PAtm = 760 mmHg, PIntrapulmonic = 763 mmHg, ΔP = +3 mmHg, causing air to flow out.

Mechanics of Breathing: Pleura

• Parietal pleura lines the inner surface of the thoracic cavity and diaphragm.
• Visceral pleura lines the outer surface of the lungs.
• A pleural fluid lubricates and fills the space between layers creating intrapleural pressure allowing smooth lung gliding.

Function: Intrapleural Pressure

• Intrapleural pressure is less than atmospheric pressure (760 mmHg).
• Intrapleural pressure keeps the lung inflated.
• Affects intrapleural pressure resulting in pneumothorax.

Pulmonary/Minute Ventilation (VE)

• Minute ventilation measures the volume of air moved in and out of the lungs per minute (L/min).
• VE = tidal volume (VT) x breathing frequency (F).

Anatomical Dead Space

• Not all inspired air reaches the alveoli for gas exchange, some remains in the conducting zone called "dead space".

Alveolar Ventilation (VA)

• Alveolar Ventilation refers to the amount of air that reaches the alveoli.
• Minute ventilation = (Dead space x frequency) + Alveolar ventilation or VE = (VD x F) + VA.
• The calculation VA= (tidal volume- dead space)  frequency, can determine efficient breathing patterns.

Gas Exchange

• Adequate alveolar ventilation ensures sufficient gas exchange.
• Gas exchange allows for oxygen replenishment and carbon dioxide removal in the lungs.
• At the muscles, oxygen is delivered and carbon dioxide removed.
• The direction and rate of gas exchange is determined by Fick's Law of Diffusion.

Factors Influencing Pulmonary Diffusion

• Thickness of respiratory membrane, surface area for diffusion, and concentration/pressure gradient influence pulmonary diffusion.

Optimizing Pulmonary Diffusion

• Pulmonary diffusion is optimized by decreasing membrane thickness, increasing surface area (millions of alveoli), and increasing the pressure gradient.

Diffusion: Fick’s Law

• Fick’s Law of Diffusion states that diffusion depends on surface area, diffusion coefficient, and pressure gradient and is inversely proportional to membrane thickness.

Emphysema

• Emphysema results in alveolar destruction, reducing surface area with affects gas exchange.

Partial Pressure

• Air is a mixture of gases: 79.04% Nitrogen, 20.93% Oxygen, 0.03% Carbon dioxide.
• In a mixture of gases, the total pressure is the sum of the individual pressures

Partial Pressure of Gas: Dalton’s Law

• Partial pressure is the pressure exerted by an individual gas in a mixture.
• PG = PB  FG (Partial pressure = Total pressure (mmHg)  fraction of the gas).

Partial Pressure of Gas: High Altitude

• Barometric pressure goes down with higher elevations but the gas % does not change with altitude.

Partial Pressure: Alveoli

• Atmospheric and alveolar PO2 are not equal because inhaled air mixes with air in the lungs and water vapor

Oxygen Diffusion

• Oxygen diffuses from the lung to the blood down a pressure gradient until equillibrium is reached.

External Respiration

• External Respiration facilitates gas exchange at the alveolar level.

Carbon Dioxide Diffusion

• Carbon dioxide diffuses from the muscle to the blood, and from the blood to the lung, down a pressure gradient until equillibrium is reached.

Partial Pressure: Gas exchange

• The driving force for O2: ΔP = ~ 60 mmHg.
• The driving force for CO2: ΔP = ~ 6 mmHg.
• Membranes are more permeable to CO2, helping it diffuse quickly.

Oxygen Transport

• Oxygen is transported in two ways: dissolved in the blood (1.5-3% of all O2 transported), and bound to hemoglobin (97-98.5% of all O2 transported).

Hemoglobin (Hb)

• Hemoglobin contains heme (iron) and globin (protein).
• Iron binds oxygen to form Oxyhemoglobin (HbO2).
• Deoxyhemoglobin (HHb) is hemoglobin with no oxygen bound.

Oxygen/oxyhemoglobin saturation

• Oxygen/oxyhemoglobin saturation is the percent of hemoglobin saturated with oxygen.
• Normal (healthy) saturation is 97/98%.

Carbon Monoxide

• Carbon monoxide binds more favorably to hemoglobin than oxygen which prevents oxygen transport.

Oxygen Dissociation Curve

• It illustrates the relationship between PO2 and oxygen saturation.
• Oxygen saturation depends on PO2 levels in the blood.

Temperature

• An Increase in temperature corresponds to a decrease affinity, so it facilitates unloading.
• An Increase in temperature results in a right shift.
• A Decrease in temperature corresponds to an increase affinity, so it facilitates the binding.
• A Decrease in temperature results in a left shift.

pH/H+/ acidity

• Increase H+ = decrease pH= increase acidity.
• Increase acidity - Decreases affinity, so it facilitates unloading -> Right shift
• Decrease acidity- Increases affinity, so it facilitates binding -> Left shift

Partial Pressure of Carbon Dioxide

• An Increase in PCO2 occurs: Decreases affinity, so it facilitates unloading -> Right shift
• A Decrease in PCO2 occurs: Increase affinity, so it facilitates binding -> Left shift

Gas Exchange at the Muscle

• Exchange occurs due to partial pressure differences in O2 and CO2 between tissue and blood.
• Oxygen delivered (VO2) = cardiac output X arterial-venous O2 difference. VO2 = Q x av-O2 diff.

Gas Exchange at the Muscle: Myoglobin

• Myoglobin is an oxygen transport molecule similar to hemoglobin.
• Myoglobin is found in skeletal & cardiac muscle, specifically slow twitch.
• Myoglobin acts as a O2 shuttle to mitochondria and functions as an oxygen reserve at start of exercise.

Carbon Dioxide Transport

• 7% to 10% is dissolved in plasma.
• 20% is bound to hemoglobin, but not in competition with O2.
• 70% is transported as bicarbonate.

Carbon Dioxide Transport: Bicarbonate

• At the tissue where there is high PCO2: CO2 diffuses into the blood.

Carbon Dioxide Transport: Hemoglobin

• At the tissue: High tissue PCO2, means more deoxyhemoglobin.
• CO2 then binds to hemoglobin forming Carbaminohemoglobin.

Carbon Dioxide Transport: Bicarbonate

• In the RBC: CO2 is converted to bicarbonate: CO2 + H2O H2CO3 H+ + HCO3-.
• Bicarbonate diffuses out of the RBC and chloride (CL-) moves into the cell (Chloride shift).
• Hemoglobin acts as a buffer and can release O2 and then bind H+.

Carbon Dioxide Transport: Hemoglobin

• At the lungs: High lung PO2, causes a conformational change in the shape of hemoglobin.
• Decreases hemoglobin’s affinity for CO2 and CO2 is released at the lungs.

Control of Ventilation

• Ventilation matches oxygen supply and carbon dioxide removal to demand.
• Monitoring of PO2, PCO2 and H in blood and cerebral spinal fluid controls ventilation.
• Decrease PO2, increase PCO2, and increase H+ = increase in pulmonary ventilation.
• Mostly involuntary control.
• The respiratory control center is in the brain stem, including the medulla and pons.
• Input from higher brain centers is also factored in.

Control of Ventilation: Chemoreceptors

• Chemoreceptors respond to chemical stimuli

Central Chemoreceptors

• Located in the medulla.
• Respond to Changes in PCO2 and H+/ pH in cerebral spinal fluid.
• Inc PCO2 , inc H+/dec pH stimulate receptors resulting in increased Ventilation.
• H+ is the main stimulus for the central chemoreceptors due to CO2 effects.

Peripheral Chemoreceptors

• Located in the carotid arteries and aortic arch.
• Respond to Changes in PCO2 , H+/ pH, PO2, and K+.
• Inc PCO2 , Inc H+/Dec pH, Dec PO2 Inc K+ stimulate receptors resulting in increased Ventilation.
• PCO2 is a stronger stimulus for ventilation than PO2.
• Other neural input includes stretch receptors in bronchioles, stretch and metabolic receptors in diaphragm and abdominals, proprioceptors and chemoreceptors in muscles, and neural activity in the motor cortex.

Potassium and Ventilation

• During exercise K+ moves from muscles to blood.
• K+ stimulated the carotid bodies.

Control of Ventilation During Exercise

• Changes in exercise ventilation could be due to changes in medulla respiratory center sensitivity, neural message from the motor cortex, muscle proprioceptors and hypothalamus SNS, increases in H+ and K+.

Effects of Exercise on Pulmonary Ventilation

• An increase in cardiac output needs to occur for an increase in ventilation to be a benefit.

Ventilation Response to Submaximal Exercise

• Phase 1 results in abrupt impact in VE due to Proprioceptors/ motor cortex activity.
• Phase 2 results in effect of motor cortex and feedback from muscles/ peripheral chemoreceptors.
• Steady State O2 requirements have been satisfied.
• Intensity, fitness level, and environmental conditions influence the size of the response.

Ventilation Response During Incremental Exercise to Max

• Generally, VE increases with Intensity, but there is also a point of disproportionate increase called ventilatory threshold.
• VT1 occurs approximately 50-70% the maximum.
• VT2 occurs approximately 80-90% the maximum.

Ventilatory Response: Summary

• Ventilation does not normally limit exercise with rapid response to change in demand due to multiple sensors to affect regulation.
• Ventilation increases by frequency and tidal volume (= increase in VE).
• Blood leaving the lungs is typically 98% saturated with O2, exception being in exercise-induced asthma, exercise-induced arterial hypoxemia, respiratory disease.