Pulmonary

Question 1

Ventilation

Definition

Answer 1

How gases get into the alveoli.

Question 2

Diffusion

Definition

Answer 2

How gases move across the alveolar walls into the blood or vice versa.

Question 3

Perfusion

Definition

Answer 3

How blood vessels remove gas from the lungs.

Question 4

Pulmonary Functions

Answer 4

1. Gas exchange
2. Metabolize certain compounds
3. Filter small clots out of the blood
4. Reservoir of blood

Question 5

Conducting Zones

Answer 5

• first 16 generations including:
  
  • trachea
  • bronchi
  • bronchioles
  • terminal bronchioles
• do not contain alveoli = no gas exchange
  
  • makes up the anatomical dead space (~150ml)
• serves to warm and humdify incoming air

Question 6

Transitional & Respiratory Zones

Answer 6

• after the 16th generation including:
  
  • respiratory brohnchioles
  • alveolar ducys
  • alveolar sacs
• alveoli start to appear = gas exchange
• increased cross-sectional area = decreased resistance = increased flow = decreased velocity

Question 7

Alveolar Structure

Answer 7

• Blood-gas barrier consists of:
  
  • alveolar epithelia
  • capillary epithelia
  • associated basement membranes
• Contains:
  
  • Type I Pneumocytes
    
    • Thin and flat
    • comprise ~ 90% of alveolar surface area
  • Type II Pneumocytes
    
    • smaller cells
    • filled with lamellar inclusions
      
      • contain pulmonary surfactant
    • can transform into Type I pneumocytes if needed
  • Macrophages present

Question 8

Pulmonary Vasculature

Answer 8

Lungs receive blood from two different sources:

1. Pulmonary circulation
   
   • brings O₂-poor venous blood via pulmonary arteries to blood-gas interface in alveoli
   • O₂/CO₂ exchange occurs
   • oxygenated blood travels via pulmonary veins to left-sided heart
   • receives entire cardiac output (~5 L/min at rest)
   • low pressure (~15 mmHg)
2. Bronchial Circulation
   
   • part of systemic circulation
   • supplies conducting airways
   • comes from aorta and bronchial capillaries
   • drain into:
     
     • bronchial veins
     • anatomoses with pulmonary capillaries into veins of pulmonary system = physiological shunt
       
       • Allows small amount of deoxygenated blood to enter systemic circulation
       • Decreases pulmonary vein spO₂ by 1-2%

Question 9

Pleural Pressure

( P_pl )

Answer 9

Pressure in the pleural fluid between the lung and the chest wall.

Subatmospheric at rest, approximately -5 cm H₂O.

Due to inward elastic recoil of the lungs and outward recoil of the chest wall.

Question 10

Airway Pressure

( P_aw )

Answer 10

Pressure within the airway.

Question 11

Alveolar Pressure

( P_A )

Answer 11

Pressure inside the alveoli.

At rest with no airflow = 0 cm H₂O.

Question 12

Transpulmonary Pressure

( P_L )

Answer 12

Difference between the alveolar pressure and pleural pressure.

P_L = P_A - P_Pl

~ -5 cm H₂O at rest

Question 13

Transairway Pressure

( P_ta )

Answer 13

Pressure difference across the airways.

P_ta = P_aw - P_pl

Responsible for keeping the airways open during forced expiration.

Question 14

Tidal Volume

(V_T)

Answer 14

The amount of air that enters and leaves the lung during quiet breathing.

~ 500 ml

Question 15

Total Lung Capacity

(TLC)

Answer 15

Total air capacity of the lungs.

~ 6 L

TLC = VC + RV

= IRV + V_T + ERV + RV

Question 16

Functional Residual Capacity

(FRC)

Answer 16

The amount of air remaining in the lungs after a tidal exhalation.

Cannot be determined by spirometry.

FRC = RV + ERV

Question 17

Inspiratory Reserve Volume

(IRV)

Answer 17

The additional air brought in beyond the tital volume by deep inspiration.

Question 18

Inspiratory Capacity

(IC)

Answer 18

The total amount of air which can be brought in.

Sum of the tidal volume and IRV.

Question 19

Expiratory Reserve Volume

(ERV)

Answer 19

The additional air beyond a tital expiration which can be moved out due to deep exhalation.

Question 20

Residual Volume

(RV)

Answer 20

The air that remains in the lung after a deep exhalation.

Cannot be determined by spirometry.

Question 21

Vital Capacity

(VC)

Answer 21

The maximal amount of air that can be exhaled after a deep inspiration.

VC = ERV + V_T + IRV

Question 22

Spirometry

Answer 22

Measurement of the volume and speed of airflow under conditions of quiet breathing, maximal inspiration, and maximal expiration.

Question 23

Helium Dilution Technique

Answer 23

Used to measure the residual volume and thus determine the FRC and TLC.

Helium insoluble in the blood so entire volume remains in the lungs.

C₁ + V₁ = C₂ x (V₁ + V₂)

V₂ = V₁ x [(C₁ - C₂)/C₂]

1. Subject breaths in air containing known concentration of helium (C₁).
2. Amount of helium in the system before equilibrium mest be the same as after equilibrium with the lungs.
3. If inspiration of He starts and ends at the end of a tidal breath, V₂ = FRC
4. If inspiration starts and ends with forced expiration, V₂ = RV.

Question 24

Rates of Airflow

Spirometry

Answer 24

Forced vital capacity (FVC) = air expired as rapidly as possible after a maximal inspiration ⇒ ~ 5 L in healthy adult male

FEV₁ = volume of forced air expiration in 1 second

FEV₁ / FVC = ratio of air expired over 1 second over the total ⇒ normal ~ 80%

Usually lung diseases involve mixed restrictive and obstructive patterns.

Ex. asthma.

Question 25

Obstructive Lung Disease

Answer 25

Allows air to enter the lungs but makes expiration difficult.

Ex. emphysema, bronchitis, and bronchiectasis.

Both FEV₁ and FVC are reduced.

FEV₁ reduced to a greater extent.

FEV₁ / FVC ratio decreased.

Question 26

Restrictive Lung Disease

Answer 26

Makes inspiration difficult but do not affect expiration.

Ex. fibrosis, bronchitis, and respiratory distress syndrome (due to surfactant deficit or lung injury).

FEV₁ and FVC reduced to more or less the same extent.

FEV₁ / FVC ratio is normal or sometimes increased.

Question 27

Inspiration

Answer 27

Active Process

1. During tial breath, diaphragm controlled by the phrenic nerve contracts
2. Abdomen pushed downward and forward
3. Ribs lifted and moved out
4. During forced inspiration/exercise, additional muscles such as the external intercostal muscle recruited
5. All serves to increase transverse diameter of the thorax
6. P_pl and P_A​ becomes more negative drawing air in.

Question 28

Expiration

Answer 28

Passive process during quiet breathing.

Active process during forced expiration.

1. Diaphragm relaxes.
2. Chest wall and lung return to equilibrium positions.
3. P_pl becomes less negative and P_A become positive. Air is moved out.
4. During forced expiration/exercise, additional muscles such as abdominal muscles and internal intercostal muscles contract.
5. P_pl becomes positive (only time). Air forced out at greater rate.

Question 29

Pulmonary

Pressure-Volume Curves

Answer 29

As P_pl becomes more negative and P_A falls below atmospheric pressure, the lungs will expand.

Volume measured with spirometry as a function of pressure.

Slope of the curve represents compliance.

Question 30

Hysteresis

Answer 30

Pulmonary pressure-volume curves during inflation and deflation are different.

Mostly due to differences in compliance.

Lung volume at any given pressure during deflation is larger than during inflation.

Question 31

Lung Compliance

Answer 31

C = ΔV / ΔP

• In the normal range of expanding pressures (-5 to -10 cm H₂O):
  
  • Lung very compliant
  • P-V curve steep
• As expanding pressures get higher:
  
  • Lung becomes stiffer due to elastic recoil
  • Seen as flattening of the P-V curve at higher expanding pressures
• During deflation, lungs start at a lower compliance state:
  
  • Deflation curve starts out flat

Question 32

Factors Affecting

Lung Compliance

Answer 32

1. Surface tension decreases compliance
2. Fibrosis decreases compliance
   
   • seen in restrictive disorders
3. Alveolar edema decreases compliance
   
   • excess fluid accumulation in the lungs
4. Increased pulmonary venous return reduces compliance
   
   • excess blood accumulation in the lungs
   • seen in heart failure
5. Loss of elastic tissue increases compliance
   
   • seen with emphysema or aged lungs

Question 33

Pulmonary Disease

PV-Loop & Compliance Changes

Answer 33

Restrictive diseases decrease lung compliance.

Results in narrowing of the PV-loop.

Obstructive diseases increase lung compliance.

Results in widening of the PV-loop.

Question 34

Total Pulmonary Compliance

Answer 34

Chest wall elastic recoil pulls outward.

Greater at low lung volumes.

Tendency for the lung to expand indicated as negative transmural pressure.

Alveoli elastic recoil pulls inward.

Greater at high lung volumes.

Tendency for the lung to collapse indicated as positive transmural pressure.

Combined pulmonary compliance is the sum of the two.

At FRC, lung elastic recoil = chest elastric recoil so transmural pressure ⇒ 0.

Question 35

Pulmonary Disease

Combined Compliance Changes

Answer 35

Chest wall compliance remains constant.

Pulmonary diseases affects compliance of the lung.

Alters equilibrium point of the lung and chest wall.

Obstructive disorders increase compliance & equilibrium point (i.e. FRC).

Restrictive disorders decrease compliance & equilibrium point (i.e. FRC).

Question 36

Surface Tension

Answer 36

Thin liquid film coats each alveolus affecting the P-V relationship.

Molecules of liquid more attracted to each other than to gas accounting for surface tension.

Saline-filled lung more compliant than air-filled lung = no hysteresis.

Foam from pulmonary edema with tiny air bubbles extremely stable = low surface tension.

Question 37

LaPlace’s Law

Answer 37

Pressure (P) required to keep an alveolus of radius (r) open affected by surface tension (T).

P = 2T / r

If surface tension constant, pressure in smaller alveolus greater than in larger one.

Pressure gradient drives air from smaller to larger alveolus causing collapse of the smaller alveolus ⇒ atelectasis.

Common at lower lung volumes.

Question 38

Surfactant

Answer 38

Lipid/protein mixture secreted by Type II pneumocytes.

Mostly dipalmitoyl phosphatidylcholine (DPPC).

Alters the surface tension with changes in diameter.

• Surfactant density increases with lung deflation ⇒ reduces surface tension ⇒ decreases pressure
• Lowers surface tension to a greater extent in smaller alveoli
• Prevents atalectasis

Increases lung compliance.

• As lung inflates, surfactant / area decreases
• Compliance will decrease as lung inflates
• Partially accounts for flattening of the inflation curve at high volumes

Helps prevent pulmonary edema.

• Surface tension promotes fluid movement from capillaries to alveolar spaces.
• Surfactant decreases surface tension preventing movement of fluid into alveoli.

Question 39

Infant Respiratory Distress Syndrome

(IRDS)

Answer 39

• Surfactant production starts ~ 34 weeks gestation
• Insufficiency seen with premies
• Difficulty in inflating lungs due to high surface tension
• Treat with CPAP and exogenous surfactant until neonate able to synthesize enough

Question 40

Regional Compliance

Upright Lung

Answer 40

Compliance is greater at the base of the upright lung than the apex.

• Gravity causes weight of the lung to pull down on the alveoli.
• P_pl more negative at apex compared to base.
  
  • Alveoli at the apex more inflated at rest.
• Apex rests at higher point on compliance curve than base.
  
  • Alveoli at the base inflate more easily

Question 41

Respiratory Cycle

Answer 41

1. Before inspiration:
   
   • P_pl negative due to elastic recoil of lung
   • P_A = 0
   • No airflow
2. Inspiration:
   
   • P_pl more negative due to diaphragm contraction
   • P_A becomes negative
     
     • Alveoli mechanically tethered to chest wall
   • Pressure difference draws air in
   • Alveoli expand ⇒ P_A increases ⇒ stops becoming more negative ⇒ still subatmospheric so airflow continues
3. End of Inspiration / Beginning of Expiration:
   
   • P_pl more negative
   • P_A = 0
   • No airflow
4. Expiration:
   
   • Breathing muscles relax
   • Alveolar elastic recoil high
   • P_pl becomes less negative
   • P_A starts to become positive
   • Air flows out of alevoli

Question 42

Airflow

&

Airway Resistance

Answer 42

Airway diameter main determinant of airflow.

Main site of resistance in the intermediate-sized airways.

Governed by Poiseuille’s Law and Ohm’s Law:

Question 43

Airway Resistance

Factors

Answer 43

1. Lung Volume
   
   • Higher volume ⇒ airway opened ⇒ greater diameter ⇒ decreased resistance
2. Bronchial Smooth Muscle
   
   • ANS ⇒ vagus nerve ⇒ Ach ⇒ β₂-adrenergic receptors ⇒ bronchodilation ⇒ decreased resistance
     
     • Albuterol = β₂-adrenergic agonist

Question 44

Dynamic Compression

of

Airways

Answer 44

Flow rate is independent of effort towards low lung volumes.

• During forced expiration, flow rate declines as more air expired.
• Occurs whether expiration starts with maximal effort or slowly and accelerates
• Due to airway compression by increased P_pl

Question 45

Forced Expiration

Answer 45

1. Pre-inspiration (A)
   
   • Pleural pressure (P_pl) = -5 cm H₂O
   • Alveolar pressure (P_A) = 0
   • Transairway pressure (P_L) = +5 cm H₂O
2. Beginning of Inspiration (B)
   
   • Diaphragmatic contraction causes both P_pl and P_A to become -2 cm H₂O more negative
   • Airflow causes 1 cm H₂O pressure drop in airway
   • P_L = +6 cm H₂O
3. End of Inspiration (C)
   
   • P_A = O
   • P_PL = -8 cm H₂O
   • P_L = +8 cm H₂O
4. Forced Expiration (D)
   
   • Both P_pl and P_A increase by +38 cm H₂O
   • Outward airflow causes a pressure drop along the airway
   • P_L drops along the airway until P_pl = P_A
   • When P_L = 0 ⇒ equal pressure point
   • Negative P_L beyond this point ⇒ tendancy to close airway
     
     • EPP in healthy person occurs at a point high enough where cartilage present and prevents closure
   • As expiration continues, EPP moves deeper into lung

Question 46

EPP Changes

Obstructive Lung Disease

Answer 46

• Emphysema causes loss of alveoli and elastic recoil
• Lowers P_A further during forced expiration
• Pushes EPP lower in the lung
• Causes airway to collapse closer to alveoli where cartilage not present
• Results in difficulty with expiration ⇒ hyperinflated lungs ⇒ barrel chest
• Breathing through pursed lips inc. resistance at the mouth causing a pressure drop
  
  • Moves EPP back up to conducting zone

Question 47

Flow-Volume Loops

Answer 47

Airway resistance stable during quiet breathing.

Forced expiration causes compression of airways resulting in greater airway resistance.

Flow-volume loops generated by:

1. Inhale to TLC
2. Forced expiration to RV as quickly and forcefully as possible
3. Forcibly inhale back to TLC

Upper part of the loop is the flow-volume curve.

Can be used to detect various types of airways diseases.

Question 48

Pulmonary Disease

Flow-Volume Curves

Answer 48

• Restrictive Disorders
  
  • Lung fills to lower volume.
  • Maximum flow rate decreased.
  • Total volume exhaled reduced.
• Obstructive Disorders
  
  • Lung fills to a greater volume.
  • Maximum flow rate decreased.
  • Total volume exhaled reduced.

Question 49

Dalton’s Law

Answer 49

P_Igas = F_Igas x P_B

P_Igas = partial pressure of the inspired gas

F_Igas = fraction of that gas in total mixture

P_B​ = barometric pressure (760 mmHg @ sea level)

The total pressure of a gas mixture is equal to the sum of the partial pressure of each gas.

Each gas exerts a partial pressure that is proportional to its concentration and independent of the other gases.

Question 50

Alveolar Humidified Air

Answer 50

Conducting zones warm and humidify air so it contains water vapor when it reaches the alveoli.

Partial pressure water vapor at 37° is 47 mmHg.

Taken into account via modied Dalton’s Law:

P_Igas = F_Igas x (P_B - P_H2O)

Question 51

Partial Pressures

of

Respiratory Gases

Answer 51

Question 52

Minute Ventilation

(V̇_E)

Answer 52

The amount of air that enters per minute.

(mls/min)

V̇_E = B_f x V_T

B_f = breathing frequency (breaths/min)

V_T = tidal volume

Question 53

Dead Spaces

Answer 53

• Anatomic dead space
  
  • Volume of air which remains in the conducting zone and is unavailable for gas exchange.
  • Normal ~ 150 mls
• Alveolar dead space
  
  • Volume of functional dead space which is unable to participate in gas exchage due to pathological process
  • Ex. poor perfusion
• Physiological dead space (V_D)
  
  • Anatomical dead space + alveolar dead space
  • Normally, V_D = anatomic dead space

Question 54

Bohr Equation

Answer 54

Physiological dead space determined using partial pressure of CO₂ in alveolar gas (P_ACO2) and expired gas (P_ECO2).

Assumptions:

No CO₂ in inspired gas.

All of the CO₂ in expired gas comes from the alveoli.

Because P_CO2 in alveolar gas virtually identical to arterial P_CO2​ in healthy individuals, values from standard blood gas measurements used.

Question 55

Alveolar Ventilation Rate

(V̇_A)

Answer 55

V̇_A = B_<em>f</em> x (V_T - V_D)

The amount of gas that actually makes it to the alveoli and is available for gas exchange.

Question 56

Alveolar Ventilation Alterations

Answer 56

• Two main ways of altering alveolar ventilation:
  
  1. Breathing frequency (B_{<em>f </em>})
  2. Volume inspired
• Dead space constant under normal conditions.
• Alveolar ventilation is best increased by increased tidal volume.
• Hyper-respiration essentially moving air in and out of conducting zones without inspiring fresh air into lungs.

Question 57

Alveolar Ventilation Estimation

Answer 57

Alveolar ventilation rate can be estimated without knowing the dead space volume.

Question 58

Alveolar Ventilation

&

P_CO2

Answer 58

If rate of CO₂ production is constant:

Alveolar ventilation rate is inversely proportional to alveolar (and arterial) P_CO2.

• Decreased B_<em>f</em> results in hypercapnea.
• Hyperventilation is a physiological response to hypercapnia.
• If CO₂ production increases, alveolar ventilation will increase to paintain a constant P_aCO2.

Question 59

Alveolar Gas Equation

Answer 59

Relationship between P_AO2, P_ACO2, and the rate of CO₂ generation and O₂ consumption.

Estimates alveolar O₂ levels using easily obtained parameters.

• P_IO2 = O₂ partial pressure in moist inspired air
• R = respiratory quotient
  
  • amount of CO₂ relative to O₂ consumed in one breath
  • R = 0.8 for typical diet with carbs and fats
• F = correction factor
  
  • ~ 2 mmHg
  • often ignored
• Arterial CO₂ used as surrogate for alveolar CO₂

Question 60

Regional Ventilation

Upright Lung

Answer 60

Ventilation is the highest at the base of the lung and lowest at the apex.

• Gravity causes a more negative pleural pressure at the apex compared to base.
• Top is already partially inflated and can inflate less upon inspiration.
• Bottom somewhat compressed and can expand more upon inspiration.
• Determined using radioactive ¹³³Xe

Question 61

Typical Lung

Volumes and Flows

Answer 61

Question 62

Pulmonary & Cardiovascular

Typical Partial Pressures

Answer 62

Question 63

Pulmonary Hemodynamics

Basics

Answer 63

• Low resistance, low pressure system
  
  • Pulmonary vascular resistance (PVR) ~ 1/10th of systemic circulation
• Pulmonary arteries less elastin and smooth muscle
• Pulmonary arterioles thin-walled and less smooth muscle
  
  • Less ability to constrict compared to systemic arterioles
• Pulmonary capillary beds form mesh-like network
  
  • Blood flows as a sheet over alveoli

Question 64

PVR

Effects of Cardiac Output

Answer 64

Inc. CO ⇒ Inc. pulmonary arterial pressure ⇒ Dec. PVR ⇒ Inc. blood flow.

Due to two mechanisms:

1. Recruitment of capillaries
   
   • Some capillaries partially or fully closed at rest
     
     • Particularly at the top due to low perfusion pressure
   • As CO increases, vessels “inflate” to decrease PVR
     
     • Added in parallel
2. Distention of capillaries
   
   • Increases diameter of the vessels lowering PVR

Recruitment precedes distension.

Question 65

PVR

Effects of Lung Volume

Answer 65

Extra-alveolar vessels affected by pleural pressure.

Alveolar vessels affected by alveolar pressure.

• High lung volumes:
  
  • Pleural pressure most negative
    
    • Extra-alveolar vessel resistance at minimum
  • Alveolar volume/pressure is highest
    
    • Alveolar vessel resistance at maximum
• Low lung volumes:
  
  • Pleural pressure less negative
    
    • Extra-alveolar vessel resistance at maximum
  • Alveolar volume/pressure is lowest
    
    • Alveolar vessel resistance at minimum

​

Total resistance of the circulation is the combination of both types of vessels.

Lowest resistance at FRC.

Question 66

PVR

Effects of Oxygen

Answer 66

PVR increased by alveolar hypoxia or hypoxemia.

Hypoxia induces vasoconstriction of small pulmonary arteries.

Two types of alveolar hypoxia can occur:

1. Regional hypoxia:
   
   • vasoconstriction localized to a region
   • useful in shifting blood away from poorly-ventilated alveoli
   • does not usually cause increased PVR due to parallel pulmonary capillaries
2. Generalized hypoxia:
   
   • vasoconstriction throughout lungs
   • increased PVR
   • occurs in low oxygen environments
   • can lead to pulmonary edema
     
     • can result in right-sided hypertrophy and heart failure

Question 67

Pulmonary Fluid Exchange

Answer 67

Forces regulating pulmonary capillary fluid flow:

1. Starling forces:
   
   • Capillary hydrostatic pressure ⇒ fluid out
   • Capillary oncotic pressure ⇒ fluid in
   • Interstitial hydrostatic pressure ⇒ fluid out ⇒ ~ 0
   • Interstitial oncotic pressure ⇒ fluid in
2. Surface tension
   
   • Pulls inward lowering interstitial hydrostatic pressure (P_i)
   • Help to draw fluid into interstitial space
3. Alveolar pressure
   
   • Compresses interstitial space increasing interstitial hydrostatic pressure
   • Helps prevent fluid from leaving capillary

Normally, net movement of fluid is from the alveoli to the interstitial space.

Removed by the lymphatic system.

Question 68

Causes of Pulmonary Edema

Answer 68

1. Increased capillary hydrostatic pressure
   
   • Due to increased pumonary venous pressure
     
     • Heart failure
     • Mitral valve stenosis
2. Increased capillary permeability
   
   • pulmonary vascular injury
   • inflammation
   • neurogenic shock
3. Increased surface tension
   
   • Loss of surfactant
     
     • Adult respiratory distress syndrome

Question 69

Regional Blood Flow

Upright Lung

Answer 69

Pulmonary blood flow greatest at the base.

Due to relationship between pulmonary artery pressure, alveolar pressure, and pulmonary vein pressure caused by gravity.

Creates 3 functional zones of the lung:

• Zone 1: P_A > P_a > P_v
  
  • Alveolar pressure greater than arterial pressure
  • Collapses blood vessels
  • Allows no blood flow
  • Absent under normal condition
  • Can occur with:
    
    • positive pressure ventilation
    • low pulmonary blood flow (ex. hemorrhage)
• Zone 2: P_a > P_A > P_v
  
  • Arterial pressure greater than alveolar pressure
  • Blood flow determined by difference between P_a and P_A
  • Occurs in the middle of the lungs
  • As we move further down into the lung:
    
    • P_a increases while P_A stays fairly constant
    • Pressure difference increases ⇒ inc. pulmonary blood flow through recruitment
    • Continuous increase in pressure difference as one moves down the lungs ⇒ waterfall effect
• Zone 3: P_a > P_v > P_A
  
  • Venous pressure greater than alveolar pressure
  • Blood flow dictated by difference between P_a and P_v
  • Inc. in pulmonary blood flow due to distention

Question 70

Other Functions of the Lung

Answer 70

1. Reservoir of blood
2. Filter out small thrombi
3. Secretion of mucous as a protective system
4. Metabolic functions
   
   • Activation of Ang I → Ang II
   • Inactivation of many vasoactive substances

Question 71

V/Q Relationships

Answer 71

• Normal conditions (A)
  
  • Alveolar gas content between between venous and atmospheric
    
    • O₂ entering
    • CO₂ leaving
• Airflow blocked / Perfusion normal (B)
  
  • No ventilation (V=0)
  • V/Q ratio = 0
  • Blood equilibrates with gases in alveoli
  • Alveolar gas similar to venous blood gas values
    
    • Low O₂
    • High CO₂
• Airflow normal / No perfusion (C)
  
  • Q = 0
  • V/Q ratio = ∞
  • Alveolar gas similar to atmospheric air
    
    • High O₂
    • No CO₂

_​

As V/Q ratio increases, P_AO2 increases and P_ACO2 decreases.

Question 72

V/Q Ratios

Regional Variations

Answer 72

Both ventilation and perfusion greatest at the base.

Perfusion varies to a greater extent.

V/Q ratio will vary along the height of the lung with greatest value at the apex.

Between 0.5 and 2.5.

Question 73

Alveolar Gas Composition

Regional Variations

Answer 73

Alveolar gas composition varies along the height of the lung.

Highest P_AO2 and lowest P_ACO2 at the apex.

Due to regional V/Q variations.

Question 74

V/Q Variations

Effects on Oxygenation

Answer 74

Lung is not as efficient at oxygenating arterial blood due to uneven V/Q ratios.

Apex with higher P_AO2 (~ 132 mmHg) but lower perfusion.

Base with lower P_AO2 (~89 mmHg) but greater perfusion.

Majority of the blood leaves from the base.

Arterial blood has values closer to that of the base than the apex.

Question 75

V/Q Mismatch

Answer 75

Normal (Left)

• Ventilation and perfusion more or less matched
• Majority of ventilation and blood flow goes to regions with V/Q ratio ~ 1

COPD

• Much of the ventilation and blood flow associated with normal V/Q ratios ~ 1
• Significant blood flow associated with areas with V/Q << 1
  
  • Ineffective movement of O₂ into and CO₂ out of the blood
    
    • Alveolar & arterial P_O2 low ⇒ hypoxia
    • Alveolar & arterial P_CO2 high ⇒ hypercapnea
  • Depresses overall P_aO2 returning to systemic circulation
• Compensate by increasing ventilation to other regions
  
  • Results in V/Q ratios greater than normal
  • Due to insuffient blood flow, regions may be ineffective at eliminating CO₂
  • Increased ventilation to compensate for hypercapnea
    
    • Not as effective for oxygen due to dissociation curves
  • Results in normal P_aCO2 but arterial hypoxia

Question 76

Alveolar-arterial (A-a) Oxygen Gradient

Answer 76

The difference between alveolar and arterial oxygen concentrations

Normal A-a gradient ~ 5-15 mmHg.

P_AO2 = ~ 100 mmHg and P_aO2 = ~ 85-95 mmHg

• In a healthy person due to:
  
  1. Regional V/Q variations
  2. Mixing of venous blood with arterial blood due to anatomical shunts (~1-2% of total blood)
     
     • Bronchial circulation drains into pulmonary vein
     • Coronary venous blood drains directly into left ventricle via Thebesian veins
• A-a gradient determined using:
  
  • Measurements of arterial blood gasses (P_aO2 and P_aCO2)
  • Alveolar gas equation to determine P_AO2

Question 77

Hypoxemia

Answer 77

Defined as P_aO2 < 85 mmHg.

A-a gradient and response to O₂ therapy can distinguish among the 4 types of respiratory causes.

• Respiratory causes
  
  • regional hypoventilation
  • generalized hypoventilation
  • larger than normal anatomic shunt
  • diffusion block across blood-gas barrier
• Non-respiratory causes
  
  • reduced O₂ content of inspired air

Question 78

Fick’s Law

Answer 78

Describes the diffusion of gases across the blood gas barrier:

• A = area for diffusion
• T = thickness of diffusion path (~0.3 µm in blood-gas barrier)
• D = diffusion coefficient
  
  • proportional to solubility
  • inversely proportional to sq. rt of MW
• (P₁ - P₂) = partial pressure gradient of gas

Question 79

Factors Affecting Diffusion Rates

Answer 79

1. Emphysema
   
   • Destruction of alveoli
   • Decreased SA for gas exchange
2. Pulmonary edema
   
   • Inceases thickness of path gas must traverse
3. High altitudes
   
   • Decreases barometric pressure
   • Reduced P_IO2
4. Cardiac output
   
   • Changes transit time of RBC through pulmonary circulation
   • Unlikely to change CO so much that equilibrium does not occur

Question 80

Nitrous oxide

(N₂O)

Answer 80

Perfusion-limited gas

• Diffuses across blood-gas barrier
• No affinity for hemoglobin
• Partial pressure rises in blood rapidly
• Equilibrates between blood and alveoli quickly
  
  • No additional diffusion occurs d/t no gradient
  • Only way to increase amount absorbed is to increase blood flow

Question 81

Carbon Monoxide

(CO)

Answer 81

Diffusion-Limited Gas

• Diffuses through alveolar-capillary membrane
• Strong affinity for hemoglobin
  
  • Essentially all of it rapidly binds to Hb
  • P_aCO ~ 0
• Partial pressure gradient never becomes 0
  
  • Driving force present throughout entire RBC transit time
• Diffusion-limited gas but not limited by blood flow

Question 82

Oxygen

(O₂)

Answer 82

Perfusion-limited

• Diffuses across blood-gas barrier
• Affinity for hemoglobin
• Equilibrates in blood in ~ 0.25 sec
  
  • RBC transit time ~ 0.75 sec
• Normally perfusion-limited
• Some diseases can cause thickening of interface effecting kinetics of O₂ uptake
  
  • Measure diffusing capacity

Question 83

Diffusing Capacity

Answer 83

Rate of gas transfer relative to a partial pressure gradient.

Diffusing capacity (D_L) = AD/T

Fick’s Law becomes:

V̇ = D_L x (P₁ - P₂)

Question 84

Diffusing Capacity of Carbon Monoxide

(D_LCO)

Answer 84

D_LCO = V̇_CO / P_ACO

• Measures rate of CO disappearance in alveolar gas.
• CO diffusion-limited so partial pressure gradient is P_ACO.
• Provides information about the integrity of the alveolar-capillary surface for gas exchange.
• Pulmonary fibrosis
  
  • Increases thickness of alveolar wall
  • Decreases in D_LCO
• Decreased hematocrit
  
  • Fewer RBC arriving at the lungs
  • Decreases D_LCO

Question 85

Oxygen Transport

Answer 85

O₂ transported in the blood in two forms:

Dissolved in blood (2%)

Bound to hemoglobin (98%)

Question 86

Henry’s Law

Answer 86

Amount of oxygen dissolved in the blood:

[O₂] = 0.003 x P_{<strong>O2</strong>}

0.003 ⇒ solubility constant for O₂ in the blood at 37°

(ml O₂/dL-mmHg)

Concentration of O₂ (ml O₂/dL blood)

Question 87

O₂ Saturation

Answer 87

• % saturation of Hb with O₂ (S_aO2)
  
  • ratio of oxygen content to capacity
• Oxygen content ([HbO₂])
  
  • the actual amount of O₂ bound to hemoglobin
  • most important guage for oxygenation
  • normal ~ 20 ml / 100 ml
• Oxygen-carrying capacity ([HbO₂]_max)
  
  • maximal capacity for Hb to carry O₂ in the blood
  • assuming normal Hb concentration is ~ 20.1 ml O₂/dL blood

The amount of oxygen bound to Hb depends on both O₂​ partial pressure and amount of Hb present.

Aortic blood S_aO2 ~ 98%

Mixed venous blood S_aO2 ~ 75%

Question 88

Oxyhemoglobin Dissociation Curve

Answer 88

S-shaped curve provides key physiological advantages:

• Plateau region ⇒ loading region
  
  • O₂ loaded onto Hb in pulmonary circulation
  • Allows saturation of Hb in the high partial pressure areas of the lung
  • Increasing P_O2 above 100 mmHg does not increase amount of O₂ bound to Hb
  • P_O2 down to ~60 mmHg before there is significant drop in Hb saturation
  • Safety net ensuring Hb saturation over wide range of P_aO2
• Steep region ⇒ unloading region
  
  • Large changes in oxygen saturation with small changes in P_O2
  • Allows Hb to release large amounts of O₂ to tissues with small changes in P_O2​
• P₅₀ = P_aO2 where Hb is 50% saturated

Question 89

Hemoglobin Oxygen Affinity

Effectors

Answer 89

Physiologically relavent effectors:

Decreases Hb oxygen affinity

Shifts dissociation curve to the right

Greatest effect on the unloading or steep phase.

Facilitates release of O₂.

Assessed via P₅₀ → normal ~ 28 mmHg.

• Increased levels of CO₂
• Increased temperature
• Increased 2,3-BPG
• Decreased pH
• Decreased P_O2 due to tissue consumption

*Effects of CO₂ and pH termed Bohr effect.

Question 90

Effects of Hb Content

Answer 90

Anemia

• Decreased Hb content
• Reduced O₂ content
• Normal P_aO2
• • Depends only on solubility of gas in plasma
• Normal S_aO2
  
  • oxygen content and max O₂ capacity reduced to similar degrees

Polycythemia

• Increased Hb content
• Increased O₂ content
• Unchanged S_aO2 and P_aO2

Question 91

Effects of Carbon Monoxide

Answer 91

Reduces O₂ content without affecting S_aO2 or P_aO2.

• CO has much stronger affinity for Hb than O₂
• See reduction in O₂ content if 33% of sites bound with CO
• Shifts dissociation curve slightly left
• Makes it harder to unload any O₂ bound to Hb

Question 92

CO₂ Transport

Answer 92

CO₂ transported in the blood in 3 forms:

1. Dissolved in plasma (~10%)

Governed by Henry’s Law:

[CO₂] = 0.67 x P_CO2

2. Bicarbonate (HCO₃ ~ 60%)

CO₂ + H₂0 ↔︎ H₂CO₃ ↔︎ H⁺ + HCO₃^-

Catalyzed by carbonic anhydrase in RBCs.

H⁺ cannot exit & binds to Hb unloading O₂ ⇒ Bohr effect.

HCO₃^- exchanged for Cl^- by Cl/HCO₃^- exchanger ⇒ Chloride shift.

3. Carbamino Proteins (~30%)

CO₂ + Hb-NH₂ ↔︎ Hb-NHCOOH

CO₂ reacts with terminal amine groups on Hb producing carbaminohemoglobin.

Hb can bind more CO₂ than it can bind O₂ to heme.

Question 93

CO₂-Hb Dissociation Curve

Answer 93

More or less linear over normal arterial CO₂ range.

(35-50 mmHg)

Higher [O₂] shifts curve downward ⇒ Haldane effect.

Load more CO₂ at the tissues (low P_O2)

Unload CO₂ at the lungs (high P_O2)

Question 94

Blood O₂ and CO₂

Answer 94

• Arterial content of CO₂ much greater than O₂.
• Slope and linearity of CO₂ curve:
  
  • allows lungs to remove large amounts of CO₂ over extended range as P_CO2 increases

Question 95

Respiratory Acid-Base Regulation

Answer 95

Role of pulmonary system in the regulation of pH.

• HCO₃^- is the major physiological buffer
• Ability of cells to maintain stable pH affected by:
  
  • alveolar ventilation rate
  • P_aCO2​
• Decreased alveolar ventilation ⇒ increased P_aCO2​
  
  • Increased [H⁺]_plasma via carbonic anhydrase
• Increased alveolar ventilation ⇒ decreased P_aCO2​

Question 96

Blood pH

Answer 96

• Buffers
  
  • HCO₃^- is the major physiological buffer
  • Proteins and phosphates act as non-bicarbonate buffers
• Calculate blood pH using the Henderson-Hasselbach equation
• Since CO₂ obeys Henry’s Law, equation can be modified as below.
  
  • Use solubility constant of 0.03 due to conversion from mmHg to molar
• Normal plasma [CO₂] = 40 mmHg and [HCO₃^-] = 24 mM
• Normal plasma pH = 7.4

Question 97

Davenport Diagram

Answer 97

Relationships between pH, P_CO2, and HCO₃^-.

We exist at the intersection of:

Buffer line (BAC)

CO₂ isopleths ⇒ represents constant P_CO2

Question 98

Acid-Base Disturbances

Answer 98

Respiratory Disturbances

When P_CO2 altered by respiratory mechanisms, the change in [HCO₃^-] will alter pH by traveling along the buffer line.

Compensation via renal regulation of:

HCO₃^- levels

H⁺ production/excretion

Moves up or down to a new buffer line.

• Respiratory Acidosis (A ⇒ B)
  
  • Decreased alveolar ventilation → increased P_CO2
  • Kidney increases plasma [HCO₃^-] (B ⇒ D)
• Respiratory Alkalosis (A ⇒ C)
  
  • Increased alveolar ventilation → decreased P_CO2
  • Kidney reduces plasma [HCO₃^-] (C ⇒ F)

Metabolic Disturbances

Underlying cause due to alteration in plasma [HCO₃^-].

Alter P_CO2 via respiratory compensation.

Moves to a new CO₂ isopleth.

Question 99

Respiratory Control

Overview

Answer 99

Automatic process with a certain degree of voluntary control.

Alter breathing rate and alveolar ventilation in response to blood chemistry.

Functions through feedback loops:

• Central and peripheral sensors
  
  • Chemoreceptors - detect blood gases
  • Proprioceptors - detect position
  • Mechanoreceptors - deter strest and irritants
• Feed into the respiratory center - central controller
• Controls muscles of respiration - effectors

Question 100

Medullary Respiratory Center

Answer 100

Breathing mainly regulated by two centers with some degree of cross-communication and synchrony:

Dorsal Respiratory Group (DRG) ⇒ inspiratory center

• Cell membrane potential with an intrinsic oscillatory activity
  
  • Increases in magnitude until threshold cross and action potential generated
• AP → Phrenic nerve → Diaphragm and inspiratory muscles → initiate inspiration

Ventral Respiratory Group (VRG) ⇒ expiratory center

• Quiescent during quiet breathing
  
  • Tidal exhalation is a passive process
• Role in forced expiration
• Cells turn off inspiration to start expiration
• Activate expiratory muscles to increase depth of expiration

Output modulated by inputs from peripheral sources

Breathing rate proportional to P_CO2 and inversely proportional to P_O2.

Question 101

Pontine Respiratory Group

Answer 101

Involved in fine-tuning the medullary centers:

Apneustic Center

• In lower pons
• Excitatory effect on the inspiratory center

Pneumotaxic Center

• In upper pons
• Switch off inspiration

Question 102

Cerebral Cortex

Answer 102

Alters the pulmonary system through conscious effort.

Allows for fine control of breathing movements.

Voluntary control eventually overidden by the central control systems in response to blood gas concentrations.

Question 103

Central Chemoreceptors

Answer 103

Sensitive to P_CO2 only through changes in pH.

60-80% of P_aCO2 effect on ventilation rate due to central chemoreceptors.

1. When P_CO2 rises, CO₂ diffuses across BBB into CSF and brain extracellular fluid (BECF)
   
   • BBB impermeable to HCO₃^- and H⁺
2. H⁺ generated through formation of bicarbonate
3. H⁺ activates central chemoreceptors in medulla
4. Alters breathing rate via unknown mechanism

• CSF and BECF with lower non-bicarb buffering capacity than plasma due to lower protein content
  
  • For given P_CO2 rise, change in [H⁺] greater in CSF than plasma
  • With prolonged respiratory acidosis, HCO₃^- levels increase
  • Blunts or eliminates the response to increases in P_CO2

Question 104

Peripheral Chemoreceptors

Answer 104

Sensitive to P_CO2, P_O2, and pH.

Located in carotid (more important) and aortic bodies.

20-40% of P_aCO2 effect on ventilation rate due to peripheral receptors.

• Only carotid receptors respond to fall in arterial pH
  
  • Both respiratory and metabolic causes
  • H⁺ transported into cells where they stimulate the cell
• Do not resond to changes in P_O2 unti < ~ 80 mmHg (hypoxia)
  
  • Tracks arterial blood O₂ saturation
  • Mechanism likely involves inhibition of K⁺ channels leading to depolarization
  • Leads to neurotransmitter release to excite sensory afferents to CNS
• O₂ and CO₂ chemoreceptors interact
  
  • Ex. drop in pH or P_O2 increases sensitivity of receptors to changes in P_CO2

Question 105

Central and Peripheral Chemoreceptors

Combined Responses

Answer 105

Central and peripheral chemoreceptors vie for respiratory center control.

Central receptors predominate until P_aO2 below 60 mmHg.

Response to mild hypoxia over-diffen in favor of stable CO₂ concentration.

• Increased P_CO2
  
  • Peripheral receptors act almost immediately
    
    • Leads to rapid increase in ventilation rate
  • Central receptors slower to respond
    
    • Eventually predominate to drive up ventilation rate
    • System resets to new higher P_CO2 with increased [HCO₃^-] in CSF
• Decreased P_O2
  
  • Peripheral receptors not activated until very low P_O2
  • Changers in P_O2 between 60-100 mmHg have little effect
• Interactions between P_O2 and P_CO2
  
  • At given P_AO2, increases in P_ACO2 increase ventilation rate due to central and peripheral receptors.
  • Hypoxia increases sensitivity of the response to P_ACO2
    
    • Seen as changing slopes of curve in left panel
  • At given P_ACO2, decreasing P_O2 increases ventilation due to peripheral receptors
  • Hypercapnea increases sensitivity of the response to hypoxia
    
    • Seen as curves becoming steeper in the higher P_AO2 region of right panel

Question 106

Cheyne-Stokes Breathing

Answer 106

Cyclic breathing pattern (~30-100 secs):

1. Periods of apnea
2. Series of breaths of progressively increasing respiratory effort towards a maximum
3. Waning back to apnea

Seen mostly in heart failure or at high altitudes.

Low perfusion rates diminishes brainstem’s ability to monitor effects of changing ventilation rates on gas composition in real time.

• Time delay between central increase in ventilation rate and observation of changes in blood gas.
• Overshoot in response reduces P_aCO2 below desired levels causing suppressed ventilation.
• Same delay occurs with response to hypocapnia causing periods of apnea.

Question 107

Pulmonary Receptors

Overview

Answer 107

Afferent fibers located within vagus nerve.

Three main groups of pulmonary receptors:

1. Pulmonary Stretch Receptors
2. Irritant Receptors
3. Juxtapulmonary Capillary REceptors (J-receptors)

Question 108

Pulmonary Stretch Receptors

Answer 108

Slowly Adapting Pulmonary Stretch Receptors

Hering-Breuer Reflex

• Located within airway smooth muscle
• Discharge in reponse to distention of the lung
• Activation triggers excitation of the inspiratory OFF switch
• Prolongs expiration
• Reflex inactive in humans unless tidal volume > 1 L
  
  • Role in humans unclear

Question 109

Irritant Receptors

Answer 109

Rapidly Adapting Receptors

• Located in epithelium of larger conducting airways
• Stimulated by:
  
  • noxious gases
  • cigarette smoke
  • inhaled dust
  • cold air
• Inpulses travel up vagus nerve
• Stimulation results in:
  
  • bronchoconstriction
  • mucous secretion
  • coughing
• Relatively inactive during normal breathing
• Can be stimulated by lung inflation
  
  • Responses wanes after a short period
• Implicated in bronchoconstriction triggered by histamine release with asthma attacks

Question 110

Juxtapulmonary Capillary Receptors

(J-receptors)

Answer 110

• Unmyelinated C fibers located within alveoli
• Similar characteristics and responses to irritant receptors
  
  • Rapidly adapting
• Impulses travel via vagus nerve
• Can trigger:
  
  • rapid shallow breathing
  • bronchoconstriction
  • mucous secretion

Question 111

Chest Wall Proprioceptors

Answer 111

• Joint, tendon, and muscle spindle receptors
• Located in chest wall
• Sense wall movement and effort associated with breathing
• Stimulation allows for increased movement of chest wall when movement impeded

Question 112

Limb Proprioceptors

Answer 112

• Proprioceptors located in limb joints
• May trigger increased inhalation and exhalation during exercise