Respiratory Physiology (Lectures 1-7)
Under exercise conditions the diffusing capacity of oxygen can triple. How?
1) Increased blood flow through lungs due to dilated capillaries and opening of precapillary sphincters (increase in surface area) 2) Better ventilation/perfusion (V/Q) match
What are the 4 types of dead space?
1) Anatomical 2) Alveolar 3) Physiological 4) Equipment (mechanical)
What are the 3 forms CO2 can take in the blood?
1) Carbonic acid (H⁺+HCO₃⁻) (main form) 2) Bound to Hb and plasma proteins (CO₂Hb) 3) Dissolved in plasma (CO₂) (least)
What 4 things determine the composition of alveolar air?
1) Composition of inspired air 2) Rate of alveolar ventilation 3) Effects of dead-space 4) Gas exchange with pulmonary circulation
What are the 4 triggers for a right shift of O2?
1) Decreased pH (acidosis) 2) Increased CO2 (decreases pH, displaces O2) 3) Increased temperature 4) Increased BPG (metabolites) (increased tissue metabolism/need for oxygen)
What are the 3 major components of the medullary respiratory center?
1) Dorsal respiratory group (Intrinsic) 2) Ventral respiratory group (Active) 3) Pneumotaxic center (Active)
What are the 2 forces that need to be overcome during the respiratory cycle (these forces oppose ventilation)?
1) Elastic forces (lung compliance) of lung tissue and those caused by surface tension 2) Airway resistance
Describe the 6 layers of an alveolus from alveolus to capillary.
1) Fluid layer containing surfactant 2) Alveolar epithelium 3) Epithelial basement membrane 4) Interstitial space 5) Capillary basement membrane 6) Capillary endothelial membrane
Ventilation is an interplay between what 3 structures of the thorax? How?
1) Lungs 2) Intrapleural fluid 3) Chest wall; Chest wall drives inspiration by changing pleura fluid pressure changing alveolar pressure
What are the 3 general controllers of airway resistance and thus respiration?
1) Nervous 2) Endocrine 3) Local/paracrine
What 3 things is oxygen transport determined by?
1) PO2: Driving force for diffusion 2) Percent saturation (HbO2/Hb+HbO2) 3) Content: Absolute quantity of oxygen in blood
What 3 things determine oxygen availability to a cell?
1) Quantity of O2 in blood 2) Tissue blood flow 3) Distance of a cell from capillary
What 2 things is the partial pressure of O2 determined by? (rate in, rate out)
1) Rate of alveolar ventilation (rate in) 2) Rate of O2 removal by pulmonary capillaries- O2 consumption (rate out)
What 2 things is the partial pressure of CO2 determined by? (rate in, rate out)
1) Rate of alveolar ventilation (rate out) 2) CO2 production (rate in)
Describe the process of inspiration.
1) Respiratory muscles contract 2) Thoracic cavity expands 3) Decreased pleural pressure (-8) 4) Increased transpulmonary pressure 5) Lungs inflate 6) Alveolar pressure less than atmospheric pressure 7) Air flows into lungs
Describe the process of expiration.
1) Respiratory muscles relax 2) Thoracic cavity collapses 3) Pleural pressure becomes less negative (-5) 4) Transpulmonary pressure decreases 5) Lungs deflate 6) Alveolar pressure greater than atmospheric pressure 7) Air flows out of lungs
What 5 things determine the net gas diffusion through the respiratory tract?
1) Thickness (inverse) 2) Surface area (direct) 3) Solubility (direct) 4) Molecular weight (inverse) 5) Partial pressure difference (of the gas between the two sides of the membrane) (direct)
What are the 2 types of alveolar epithelial cells? What is their function?
1) Type I pneumocytes: Provide structure to alveoli 2) Type II pneumocytes: Produce surfactant which reduces surface tension of water promoting alveolar expansion
Metabolic rate is doubled but alveolar ventilation is not changed. This animal will likely be: A) Hypercapnic B) Hypocapnic C) No change
A
Diffusing capacity (Gas and membrane)
Ability of the respiratory membrane to exchange gas between the alveoli and pulmonary blood (permeability); DL = SA x Solubility/Thickness x MW
Content
Absolute quantity of O2 (ml O2/100 ml blood)
Surfactant
Acts like detergent (mix of lipids/proteins); DPPC (main)
Residual volume (RV)
Air left in lungs after complete expiration (after ERV)
Where does surface tension occur? How? How can surface tension negatively affect alveoli?
Air/water interface (alveoli- air/blood); Water molecules attract each other and form a tight membrane; Cause alveoli to collapse
What is an important determinant as to whether airflow is laminar or turbulent?
Airflow velocity; Increased velocity creates more turbulence
Hyper/hypoventilation relates to the amount of ____ ventilation relative to blood _____ demands, which typically relate to P___.
Alveolar; Gas; PCO2
Alveolar dead space
Alveoli that are under-perfused limiting gas exchange (not working)
What are the primary sites of gas exchange in the lungs? What are they surrounded by to aid in the gas exchange?
Alveoli; Capillaries
Contraction of the diaphragm and/or intercostal muscles ____ thoracic cavity volume during _____ causing alveolar air pressure to _____.
Expand; Inspiration; Decrease
During inspiration pleural pressure becomes more _____. What is the pleural pressure at expiration? Inspiration?
Expiration: -5 cm H₂O Inspiration: -8 cm H₂O
Dead space ventilation
Amount of gas per unit time that ventilates areas that don't have gas exchange (i.e. dead space); Dead space ventilation (Vd) = VdxRR (Vd= dead space volume)
Anatomical dead space
Areas of upper respiratory tract down through conducting airways (no gas exchange)
Medullary Respiratory center: Dorsal respiratory group
Automatic; Drives inspiration
Where are the peripheral chemoreceptors located? A) Pulmonary artery B) Aortic arch and carotid sinus C) Atria D) Medulla E) Brain
B
What statement(s) best describe the relationship between velocity, flow, and cross-sectional area? A) Velocity is directly proportional to cross-sectional area B) Velocity is indirectly proportional to cross-sectional area C) Velocity is directly proportional to flow D) Velocity is indirectly proportional to flow
B, C (V=F/A)
Concerning minute ventilation, a dog needing to ventilate at 6 L/min could respire with a ____ respiratory rate and a reduced tidal volume compared to normal. (_____ breather) Conversely, the 6 L/min ventilatory demand could also be achieved with a _____ respiratory rate and elevated tidal volume. (_____ breather)
Faster; Fast; Slower; Slow
The greater the transpulmonary pressure (Ptp), the ____ the lung inflation. Transpulmonary pressure (Ptp) ______ during inspiration and _____ during expiration.
Greater; Increases; Decreases
How is 97% of O2 transported in the blood? The other 3%?
Hemoglobin (O2+Hb↔HbO2); Dissolved in blood
Air will always move from ___ pressure to ____ pressure. Air moves into the lungs when alveolar air pressure is ____ than atmospheric pressure.
High; Low; Lower
The partial pressure gradient for O2 is about 10 times greater than the gradient for carbon dioxide. How does CO2 compensate for the small difference in partial pressure?
Higher solubility
O2 partial pressure is usually ____ in alveoli making it diffuse from ____ to ____. CO2 partial pressure is usually ____ in blood making it diffuse from ____ to ____.
Higher; Gas; Liquid (blood); Higher; Liquid; Gas
Controllers of airway resistance (respiration): Local/paracrine
Histamine, leukotrienes cause bronchoconstriction (due to edema)
Vital capacity (VC)
IRV+TV+ERV
Medullary Respiratory center: Ventral respiratory group
Inactive during quiet respiration; Regulates active inspiration/expiration during high demand
Increased tissue metabolism will ____ peripheral PCO2.
Increase
What is the best way to overcome the effects of dead space?
Increase tidal volume; Reduce respiratory rate
The diameters of individual airways decrease along the respiratory tree (similar to arteries and capillaries), but total cross-sectional area _____. Therefore, total airway resistance _____ and airflow velocity is _____.
Increase; Decreases; Decreased (V=F/A)
Left shift of O2
Increased affinity; Tissue doesn't require as much O2
What are the effects of Chronic Obstructive Pulmonary Disease (COPD) on the lungs and spirometry?
Increased airway resistance during forced expiration from alveolar/airway compression; Animals tend to maintain larger ERV minimizing effort required to ventilate and prevent compression
Increasing blood flow ____ PO2 in peripheral tissues. Increasing O2 consumption (metabolism) _____ PO2 in peripheral tissues.
Increases; Decreases
As the alveolar ventilation increases, the alveolar PO2 ______. As the rate of O2 consumption increases, alveolar PO2 _____. As the alveolar ventilation increases, the alveolar PCO2 _____. As the rate of CO2 production increases, alveolar PCO2 _____.
Increases; Decreases; Decreases; Increases
For any given lung volume change, there needs to be higher pressure during _____ than _____. Why?
Inspiration; Expiration; More pressure to open than to close
Describe lung anatomy in the thorax.
No attachment to chest walls i.e Suspended ("float" in thoracic cavity); Surrounded by thin layer of pleural fluid that lubricates lung movement
During inspiration, alveolar pressure drops to ___ cm H₂O to bring air ____ the lungs. What is the resting alveolar pressure? Inspiration? Expiration?
-1; Into; Resting: 0 cm H₂O Inspiration: -1 cm H₂O Expiration: 1 cm H₂O
Blood leaving the lungs and entering the systemic arteries PO2 is ___ mmHg and oxygen saturation is ____%. In venous blood returning from the peripheral tissues the PO2 is ___ mmHg and oxygen saturation is ___%.
100; 97; 40; 75
Why is only 98% of the blood that enters the left atrium oxygenated?
2% is shunt flow from blood from the aorta that was used to oxygenate conducting airways (shunted to pulmonary vein rather than systemic vein)
Blood reaches maximal O2 saturation and delivers most CO2 in the first ___% of the length of the pulmonary capillaries. What is this called and why is it important?
25%; Safety factor; Blood has remaining 75% of capillaries to pick up more O2 if needed (Ex. Exercise)
Ina 70kg dog, the functional residual capacity of the lungs (volume of air remaining in the lungs at the end of normal expiration) measures about 2300 mL. The tidal volume of this animal is about 500 mL and its dead-space volume is about 150 mL. How many mL of new air are brought into the alveoli with each normal inspiration? What does this mean?
350 mL (15%); Multiple breaths are needed to exchange most of the alveolar air; This prevents rapid changes in blood gas concentrations making it more stable (prevents drastic changes in tissue oxygenation, CO2, and pH when respiration is interrupted)
If arterial PCO2 is significantly less than ____ mmHg (hypocapnia), one is ______. Conversely, if arterial PCO2 is significantly greater than 40 mmHg (hypercapnia), one is ______.
40 (normal PCO2); Hyperventilating (getting rid of too much CO2); Hypoventilating (not getting rid of enough CO2)
Hemoglobin is comprised of ___ heme groups that each bind to a single _____.
4; Oxygen
Bohr effect in the lungs: As ____ diffuses from blood to alveoli blood ____ decreases which ____ H2CO3 and H+ concentrations. Oxygen-hemoglobin dissociation curve will shift to the ___ and upward. This ____ affinity of hemoglobin to oxygen and causes oxygen to ____ hemoglobin.
CO2; PCO2; Decreases; Left; Increases; Bind
Bohr effect in peripheral tissues: As blood passes through the tissue, ____ diffuses from tissues to blood. This raises blood ____ which causes an increase in _____ and ___ concentration. Oxygen-hemoglobin dissociation curve with shift to the ____ with ____ O2 affinity. This forces oxygen ____ from hemoglobin therefore _____ the delivery of oxygen to tissues.
CO2; PCO2; H2CO3; H+; Right; Decreased; Away; Increases
How is lung compliance calculated?
Change in lung volume/Change in transpulmonary pressure (∆V/∆P)
Surface tension opposes _____ and _____. Therefore removing surface tension _____ hysteresis.
Compliance; Ventilation; Eliminates
Conducting airways vs. Respiratory airways
Conducting: Conduct air to lungs (no gas exchange) Respiratory: Gas exchange (tissue is thinner)
Expired air is a combination of ____ air and ____ air.
Dead space; Alveolar
What do pulmonary surfactants do to alveolar surface tension? What do they do overall?
Decrease surface tension by reducing the number of water molecules at the interface decreasing the attraction between molecules; Increase lung compliance and alveolar stability
Right shift of O2
Decreased Hb affinity to O2; Tissue requires O2
The intrinsic elastic properties of lung tissue are determined by a ratio of extracellular matrix molecules of lung parenchyma. Collagen expression _____ compliance, while elastin expression _____ compliance. Pulmonary fibrosis involves scarring of the lung caused from enhanced deposition of ____ during inflammation causes _____ lung compliance. Emphysema involves enhanced ____ deposition causing ____ lung compliance.
Decreases; Increases; Collagen; Decreased; Elastin; Increased
As the lungs are filled to total lung capacity, airway diameter increases, thereby ____ airway resistance. The opposite is true as the lungs approach the residual volume.
Decreasing
Not all blood flowing to the lungs is from the pulmonary branch of the cardiovascular system. (OXYGENATED/DEOXYGENATED) blood from the right heart goes to alveoli, whereas (OXYGENATED/DEOXYGENATED) blood from the left heart goes to the conducting airways for their energy demands. Almost all blood returns to left heat via (OXYGENATED/DEOXYGENATED) pulmonary veins.
Deoxygenated; Oxygenated; Oxygenated
Transpulmonary pressure
Difference between alveolar and pleural pressures (Ptp = Palv-Ppl); Measure of lung elastic forces; Determines extent of lung inflation or lung volume
Hysteresis
Difference between inflation and deflation paths (pressure vs. volume); Due to the greater transpulmonary pressure required to open closed airways than to keep them open
The diffusion of oxygen in peripheral tissues is driven by what?
Difference in PO2 (100 to 40 to 40 mmHg)
Gas exchange
Diffusion from high to low concentration between alveoli and capillaries
Diffusion capacity (DL) is _____ proportional to net diffusion (flow).
Directly
Controllers of airway resistance (respiration): Endocrine
E/Ne from adrenal gland cause bronchodilation
Functional residual capacity (FRC)
ERV+RV (air that remains in lungs after normal expiration)
Laminar flow vs. Turbulent flow
Laminar flow: Movement in parallel layers; Velocity greatest towards the center and zero on the margins Turbulent flow: Disorganized motion; Less efficient
Lung receptors: Irritant receptors
Located in nasal mucosa, upper airways; Bronchoconstriction; Cough, sneeze
Lung receptors: Stretch receptors
Located in smooth muscle of airways; When stretched, send signal to respiratory center to stop inspiration; prevent excessive lung inflation
Expiratory reserve volume (ERV)
Maximum expired air beyond TV
Inspiratory reserve volume (IRV)
Maximum inspired air beyond TV
How does pulse oximetry measure O2 saturation of arterial blood only?
Measures both total absorbance and non-pulsatile absorbance (capillaires, veins, tissue); The difference between the total and non-pulsatile components is the pulsatile component (arteries)
Pulse oximetry
Measures oxygen saturation of arterial hemoglobin using the difference between oxy (bright red) and deoxyhemoglobin (darker red) light absorbance
What is the central controller of respiration? What does it direct concerning respiration?
Medullary respiratory center; RR, rhythm, depth
Pleural pressure (pressure of the fluid in the space between the lung pleura and chest wall pleura) is _____. Why?
Negative; Slight suction of excess fluid into lymphatic vessels
Tidal volume (TV)
Normal breathing (Volume of air with each normal breath)
What is the diffusion coefficient of oxygen? Carbon dioxide?
O2: 1 CO2: 20.3 (more soluble)
Surface tension of the fluid that lines the inside walls of the alveoli and other lung air spaces tends to ____ the expansion of the lung tissue (elastic force). By eliminating surface tension (via surfactant) during lung inflation/deflation maneuvers, the lung becomes much more _____.
Oppose; Compliant
The ultimate goal of respiration is to maintain proper concentrations of ____, ____, and ____ in the tissues.
Oxygen; Carbon dioxide; H+
In the lungs there is higher _____ in alveoli than in pulmonary blood so _______ diffuses from alveoli to blood of pulmonary capillaries. There is higher _____ in pulmonary blood than in alveoli so _____ diffuses from the blood of pulmonary capillaries into alveoli. In the peripheral tissues, there is higher ____ in capillary blood than in tissues so ____ diffuses out of capillaires into tissues. There is higher ____ in tissues than in capillary blood so _____ diffuses from tissues into capillaries.
PO2; O2; PCO2; CO2; PO2; O2; PCO2; CO2
Molar amount of gas dissolved in a solution and the net diffusion from gas (alveoli) to liquid (blood) depends on the difference of _____ and _____ of the gas.
Partial pressure; Solubility; [gas] = Pgas x Sgas
Saturation
Percent Hb that has oxygen bound (%)
Solubility of oxygen for blood plasma is relatively ____. Therefore ____ is needed to transport 30 to 100 times as much oxygen in the blood as could be transported in the ____ oxygen form.
Poor; Hemoglobin; dissolved (CO2 also combines with substances to increase transport in the blood)
Partial pressure
Pressure a gas would have if it occupied the volume alone; Pgas = Ptotal x %gas
Minute ventilation
Product of TV and RR; ( (Ve) (L/min) = Vt (L/breath) xRR (breaths/min)); Rough index of blood gas demand (dependent on body size and metabolic rate)
The number of collisions at the air/water interface and thus exchange is ______ to the partial pressure of that gas (Pgas = Ptotal x %gas)
Proportional (↑partial pressue→↑collisions→↑diffusion into blood)
Airflow is ____ to the difference between alveolar and atmospheric _____, but inversely proportional to airway ____. (F =Pa-Pb/Raw) Airway ______ determines how much ___ is required to move air between the alveolar space and the atmosphere.
Proportional; Pressure; Resistance; Resistance; Effort
Medullary Respiratory center: Pneumotaxic center
Regulates dorsal respiratory group (drives inspiration); Limits duration of inspiration; Regulates rate/depth of breathing
Ventilation/perfusion (Va/Q) match
Relationship between ventilation of alveoli and blood flow to alveoli (If there is no diffusion impairment then the PO2 and PCO2 between an alveolus and systemic arterial capillary blood are usually the same)
In order to keep minute ventilation the same you either have to increase ____ rate and decrease ____ volume or decrease _____ rate and increase ____ volume.
Respiratory; Tidal
What structures are used in resting and active inspiration?
Resting: Diaphragm only Active: Diaphragm and intercostal muscles
What structures are used in resting and active or forced expiration?
Resting: Passive process based on elasticity of lungs and ribs and surface tension of fluid in lungs Active or forced: Abdominal and intercostal muscles
The regulation of respiration includes ____ which gather information, a ____ which will integrate those signals, and effectors which are the _____.
Sensors (reflexes); Central controller (medullary respiratory center); Muscles of breathing
Having a _____ respiratory time constant (τ) ensures that adequate lung filling and emptying will occur during the respiratory cycle. With a _____ τ, the amount of air movement may be insufficient for the respiratory demands of the animal.
Small; Large
Diffusion coefficient (gas)
Solubility/MW; Depends on solubility and molecular weight of gas
If two gases (Ex. O2, CO2) are brought to equilibrium with water (at the same partial pressures) the gas with the highest ____ will have the greatest dissolved amount. ___ is 20 times more soluble than ___.
Solubility; CO2; O2
The diffusion coefficient is directly proportional to _____ and inversely proportional to _____.
Solubility; Molecular weight
Physiological dead space
Sum of anatomical and alveolar dead space
The diffusing capacity (permeability) is directly proportional to ____ and ____ and inversely proportional to ____ and ____.
Surface area (membrane); Solubility (gas); Thickness (membrane); Molecular weight (gas)
The rate of net diffusion (gas flow) is directly proportion to ______, ______, and _______, and inversely proportional to ______ and ______.
Surface area; Solubility; Partial pressure gradient; Thickness; Molecular weight
Controllers of airway resistance (respiration): Nervous (Sympathetic vs. Parasympathetic)
Sympathetic: Epinephrine binds β2 receptors causing bronchodilation Parasympathetic: AcH causes bronchoconstriction
O2 and CO2 partial pressures: Systemic venous blood, Alveolar air, Systemic arterial blood
Systemic venous blood O2: 40 Systemic venous blood CO2: 46 Alveolar air O2: 100 Alveolar air CO2: 40 Systemic arterial blood O2: 100 Systemic arterial blood CO2: 40
Expiratory capacity (EC)
TV+ERV
Pulmonary capacities are two or more volumes together. Inspiratory capacity (IC)
TV+IRV
What are the 2 physical states of hemoglobin? What causes the change between these 2 states?
Tensed state (T): Low affinity for O2 (deoxyhemoglobin) Relaxed state (R): High affinity for O2 (oxyhemoglobin); Binding of O2 at one site increases affinity at another site
If airway resistance is above normal, an increased respiratory rate will decrease ____. In healthy lungs (normal τ) as RR increases, ____ changes very little, but in lungs with high τ, _____ begins to fall even at a relatively low RR. The greater the respiratory frequency the smaller the _____.
Tidal volume
Time constant of the lungs (τ)
Time to fill (or empty) the lungs to 63%; Determines how fast lungs can inflate; Determined by lung compliance and airway resistance
Hemoglobin acts as a _____. How?
Tissue oxygen buffer; Hb carries large amount of O2 in case of higher demand
Most airflow through the respiratory tract is termed _____ flow. What does this mean?
Transitional; Fluid tends to go back and forth between laminar and turbulent flow with more laminar and transitional flow in lower respiratory tract due to decreased velocity
Not all air in an alveolus is exchanged at each breath. (TRUE/FALSE)
True
Total lung capacity (TLC)
VC+RV (maximum volume lungs can be expanded with the greatest possible effort)
What would be the Va/Q in areas where alveolar walls and/or capillaries have been destroyed but there is still alveolar ventilation? Why?
Va/Q higher than normal (Va/Q = ∞); Inadequate blood flow to transport gases (poor perfusion- physiological dead space)
What would be the Va/Q in areas with poor alveolar ventilation due to obstruction of the airways? Why?
Va/Q lower than normal (Va/Q = 0); Alveoli unventilated (poor ventilation- physiologic shunt)
Rate of net diffusion (gas and membrane)
Vnet (flow of gas) = DL (diffusion capacity) x ∆P; Depends on partial pressure gradient and diffusion capacity (permeability)
Equipment (mechanical) dead space
Volume of air that fills ventilator (Ex. Endotracheal tube extending past incisors)
Ventilation
Volume of exhaled air per unit time (L/min); Describes rate air moves between the atmosphere and the respiratory tract (≅CO) (Minute, Alveolar, Dead-space)
Alveolar ventilation
Volume of respired air capable of gas exchange (opposite of dead space); Difference between minute ventilation (Ve) and dead space ventilation (Vd) (Va = Ve-Vd)
When does O2 bind hemoglobin in the blood? When is it released?
When PO2 is high in pulmonary capillaries O2 binds Hb; When PO2 is low in tissue capillaries O2 is released from Hb
