Respiratory System - Physiology

Front 1

What is meant by V/Q matching?

Back 1

Ventilation (in L/min) must match the cardiac output (in L/min). Both are approximately equal to 5L/min in humans so that V/Q ≈ 1

Front 2

Describe the 8 variables quantifying lung volumes. Which ones can be measured with a spirometer?

Back 2

RV, FRC and TLC cannot

Front 3

Why is the Functional residual capacity (FRC) larger than zero?

Back 3

Because, during expiration, lung membranes move inwards and chest wall moves outward, creating a negative pressure (< atmospheric pressure) in the intrapleural space which prevents the lung from collapsing.

Front 4

Name two pathologies that alter FRC and explain how and why they alter it.

Back 4

Lung fibrosis ⇒ Increased elastic recoil ⇒ FRC ➘

Emphysema ⇒ Loss of alveolar tissue ⇒ Reduced elastic recoil ⇒ FRC ➚

Front 5

Name 3 functions of the dead space

Back 5

➚ air T°C

Filters air

➚ air humidity

Front 6

Define dead space

Back 6

Part of the airway not contributing to gas exchange

Front 7

Define anatomical dead space

Back 7

all airways upstream from respiratory bronchioles (~ 150mL)

Front 8

Define alveolar dead space

Back 8

alveoli that have lost blood supply and hence cannot participate in gas exchange

Front 9

Define physiological dead space

Back 9

anatomical dead space + alveolar dead space

Front 10

Formulate alveolar ventilation as a function of tidal volume, dead space and respiratory rate

Back 10

VA = (VT - VD - VDA) x RR

where VT is tidal, VD is anatomical dead space and VDA is alveolar dead space

Front 11

How does the dead space relate to measurable quantities?

Back 11

Bohr’s equation:

Vdead/VT = (PaCO2 -PeCO2)/PaCO2,

where

PaCO2 is the arterial partial pressure of CO2 (the one reaching the alveoli)

PeCO2 is the expired partial pressure of CO2.

Front 12

Using Bohr's equation, how can one measure the physiological, anatomical and alveolar dead space?

Back 12

Bohr’s equation:

Vdead/VT = (PaCO2 -PeCO2)/PaCO2

If PeCO2 is taken as the average over expiration, then Vdead is physiological.

If PeCO2 is taken as the end expiratory, the Vdead is alveolar.

Anatomical is taken as the difference between the two.

Front 13

Define minute ventilation

Back 13

Tidal volume x Respiratory rate

Front 14

Define alveolar ventilation

Back 14

(tidal volume - dead space) x respiratory rate

Front 15

Name two measurable factors that alveolar ventilation depends on and explain how they relate to alveolar ventilation.

Back 15

VA = K x VCO2/PCO2

where VCO2 is the amount of CO2 expired every minute and PCO2 is alveolar (or, equivalently arterial)

Front 16

How is CO2 mostly transported in arterial and venous blood?

Back 16

As HCO3

Front 17

What are the three ways in which CO2 can be transported in the blood?

Back 17

HCO3

Dissolved

Carbamino haemoglobin

Front 18

In which of arteries or veins is the proportion of CO2 carried as HCO3 higher? What about dissolved CO2? And CO2 as carbamino Hb?

Back 18

Front 19

Name 4 types of hypoxia

Back 19

Hypoxic hypoxia: low O2 content in air (e.g. altitude)

Anaemic hypoxia: low O2 carrying capacity in blood

Circulatory hypoxia: low cardiac output

Histotoxic hypoxia: tissues cannot use the O2 delivered to them

Front 20

Express the total amount of gas diffusing at alveoli in a given time as a function of gas properties and blood gas barrier geometry.

Back 20

Proportional to A∆t/T x D x (Pin-Pout)

where

A: Surface area

T: Thickness

∆t: Time interval

D: Diffusivity of the gas (proportional to solubility)

(Pin-Pout): Difference of pressure between alveoli and capillary

Front 21

How does fibrosis affect diffusion at blood-gas barrier? Why?

Back 21

Amount of gas diffusing is proportional to:

A∆t/T x D x (Pin-Pout)

Fibrosis ⇒ thicker blood-gas barrier (T➚) ⇒ V ➘

Front 22

How does exercise affect diffusion at blood-gas barrier? Why?

Back 22

Amount of gas diffusing is proportional to:

A∆t/T x D x (Pin-Pout)

Exercise ⇒ Cardiac output ➚ ⇒ ∆t ➘ ⇒ V ➘

Front 23

How does high altitude affect diffusion at blood-gas barrier? Why?

Back 23

Amount of gas diffusing is proportional to:

A∆t/T x D x (Pin-Pout)

Alveolar PO2 ➘ (e.g. high altitude) ⇒ Pin ➘ ⇒ V ➘

Front 24

What two forces are applied to walls of extra-alveolar vessels?

Back 24

Extra-alveolar vessel walls are subjected to two opposite forces:

1) Smooth muscles of the extra-alveolar vessels tend to pull the vessel walls towards each other.

2) Alveolar tissue actively pulls on them to keep them open during lung expansion.

Front 25

How is resistance to blood flow affected by pulmonary blood pressure? Why?

Back 25

Resistance decreases when the pressure increases due to :

1) Distension of the capillaries due to increased flow

2) Recruitment of additional capillaries when pressure increases.

Front 26

Why isn't the expiratory reserve volume not zero?

Back 26

Because there is an optimum lung volume at which resistance of pulmonary blood vessels is minimum.

Front 27

What determines the blood flow in an area of the lung where the alveolar pressure is higher than the venous pressure?

Back 27

The difference between arterial (Pa) and alveolar (PA) pressure: Pa-PA

Front 28

What determines the blood flow in an area of the lung where the alveolar pressure is lower than the venous pressure?

Back 28

The difference between arterial (Pa) and venous (Pv) pressure: Pa-Pv

Front 29

Where is perfusion the largest in the lung when a subject is standing up? Why?

Back 29

At the base of the lung because arterial pressure increases more than the alveolar pressure as we move down the height of the lung since blood vessels form a continuous tree within which hydrostatic pressure exists.

Front 30

What happens to blood flow in areas that receive less oxygen?

Back 30

Hypoxic vasoconstriction

PO2 ➘ ⇒ Vasoconstriction ⇒ Resistance ➚ ⇒ Blood flow ➘

Front 31

What phenomenon explains that, at birth, pulmonary vascular resistance goes down rapidly to allow more blood to reach the lungs?

Back 31

Hypoxic vasoconstriction

Front 32

How can alveolar PO2 be measured?

Back 32

Using alveolar gas equation.

Front 33

Name four causes of hypoxia

Back 33

Hypoventilation

Challenges to diffusion

Shunts

V/Q mismatch

Front 34

Name two causes of CO2 retention

Back 34

Hypoventilation

V/Q mismatch

Front 35

Name 5 causes of hypoventilation

Back 35

1. Medulla impairment (e.g. morphine)

2. Spinal cord impairment (e.g. dislocation)

3. Poliomyelitis damaging anterior horn cells

4. Nerve impaired (e.g. damage to the phrenic nerves or Guillain-Barré syndrome)

5. Disease of the neuromuscular junction (e.g. myasthenia gravis)

6. Muscle disease (e.g. muscular dystrophy)

7. Damage to chest wall (e.g. trauma)

8. Obstruction of the respiratory tract

Front 36

Name 2 pulmonary causes of right-left shunts

Back 36

Pneumonia

Pulmonary oedema

(Non-pulmonary:

Congenital heart disease)

Front 37

Which hypoxia can be reversed with 100% O2?

Back 37

All but shunts

Front 38

How is ventilation distributed in the lung?

Back 38

V is higher at the base because intrapleural pressure is less negative at the base and thus apical alveoli are more expanded and have less capacity for further expansion during inspiration.

Front 39

How is V/Q distributed in the lung?

Back 39

Q is more affected than V by gravity so that V/Q increases from the base to the apex of the lung.

Front 40

For each of the following quantities, state whether they increase, decrease or remain constant from base to apex of the lung:

PO2

PCO2

PN2

O2 concentration

CO2 concentration

pH

O2 inflow [ml/min]

CO2 outflow [ml/min]

Back 40

Most can be explained by V/Q distribution:

PO2 ➚

PCO2 ➘

PN2 ➘

O2 concentration ➚

CO2 concentration ➘

pH ➚

Flows are lower at apex because blood flow is lower:

O2 inflow [ml/min] ➘

CO2 outflow [ml/min] ➘

Front 41

Where in the lung is TB most likely to occur? Why?

Back 41

TB is more likely to be present at the apex because the bacteria thrives more in an environment with high O2.

Front 42

Name one pathology that results in a large V/Q ratio and one that results in a low V/Q ratio

Back 42

Emphysema: high V/Q (because Q≈0 due to capillaries being destroyed)

Bronchitis: low V/Q (because V≈0 due to inflammation of the airway causing obstruction)

Front 43

What two configurations of blood gas can occur in low V/Q? What drives the transition from one to the other?

Back 43

Acute: PO2 ➘, PCO2 ➚

Chronic: PO2 ➘, PCO2 normal (PO2 can never return to normal because a low V/Q cannot easily be compensated by a high one)

Acute to chronic is driven by chemoreceptors sensing high PCO2 leading to hyperventilation. However, the reverse transition may occur in patients who trade-off the discomfort of hyperventilation for acidosis.

Front 44

Why is the lung important in metabolism?

Back 44

Because it receives all the blood.

Front 45

Name two metabolic functions of the lung

Back 45

Conversion of Angiotensin I to Angiotensin II

Inactivation of bradykinin, serotonin, PG E1, PG E2, PG F2α and noradrenaline

Front 46

Define compliance

Back 46

Compliance = ∆V/∆P

Front 47

Name two factors that guarantee lung compliance

Back 47

Collagen and elastin (not only through fibers extension but also through changes in geometry)

Surfactants

Front 48

Define surface tension and explain how it is related to pressure and radius of a sphere.

Back 48

Surface tension is the force applied orthogonally to a unit length of liquid, in the plane of that liquid.

Laplace's law: P = 4T/r

Front 49

What produces surfactants?

Back 49

Type II pneumocytes

Front 50

Name 3 functions of surfactants

Back 50

Stabilises the lung by making the surface tension increase with the relative area

Increase compliance of the lung

Reduces the chances of alveolar oedema

Front 51

Where in the lung is the intra-pleural pressure highest?

Back 51

At the base (when upright position)

Front 52

Draw the volume of alveoli as a function of intrapleural pressure and indicate where on the curve the apex and base of the lung are.

Back 52

Front 53

What is the alveolar volume at the base of the lung when working at RV (instead of FRC)?

Back 53

Volume is null because intrapleural pressure at the base of the lung becomes positive so that alveoli collapse.

Front 54

How does the intrapleural pressure evolve as we breath?

Back 54

Decreases (more negative) during inspiration to allow the alveoli to dilate.

Increases (less negative) during expiration to follow the contraction of the alveoli.

Front 55

How does the intrapleural pressure evolve if we exhale forcedly?

Back 55

Increases even more so that part of the lung (at the base) may even have positive pressure.

Front 56

What airways are the principal determinant of airway resistance?

Back 56

Most of the resistance comes from medium-sized airways because they are a trade-off between number of airways in parallel (the lower the higher the resistance) and the airway radius (the lower the higher the resistance).

Front 57

How and why does airway resistance vary with lung volume?

Back 57

Resistance is inversely proportional to lung volume, because as they expand, alveoli pull on airways through radial traction (exactly as they pull on blood vessels)

Front 58

Name three factors that affect airway resistance.

Back 58

Lung volume ➚ ⇒ Resistance ➘

β2-adrenergic receptors ⇒ Resistance ➘

Pollutants (e.g. cigarette smoke) ⇒ Reflex constriction of airways ⇒ Resistance ➚

Front 59

Draw the flow-volume curve during forced expiration.

Back 59

Front 60

What explains the effort-independent region of the flow-volume curve?

Back 60

Dynamic compression of airways

If intrapleural pressure is positive, then flow is defined by PA-Pintra and not PA-Patm.

Increase in expiratory force will increase alveolar pressure and intrapleural pressure by the same amount so that flow does not change.

Front 61

How does the point of dynamic compression collapse move in COPD?

Back 61

Increase in resistance of small airways ⇒ Increase the spacial rate of decrease of intra-airway pressure so that the point of collapse moves distally towards the alveoli

Front 62

Effect of emphysema on compliance

Back 62

Emphysema ⇒ Loss of alveolar tissue ⇒ Reduced elastic recoil ⇒ Lung compliance ➚

Front 63

Name three types of receptors that are involved in control of respiration and their action

Back 63

Central chemoreceptors: senses low pH and high PCO2 and increases RR

Peripheral chemoreceptors: senses PO2 (mostly) and also PCO2 and pH

Pulmonary stretch receptors: respond to differences in volume of the lung

Irritants receptors: cause bronchoconstriction in respond to irritants

Juxta-capillary (J) receptors in alveoli wall: cause rapid shallow breathing

Front 64

Where are central chemoreceptors located?

Back 64

Pons and medulla

Front 65

Where are peripheral chemoreceptors located?

Back 65

Carotid bodies (signalling via CN IX) and, less importantly in the aortic bodies (signalling via vagus nerve).

Front 66

Compare central and peripheral chemoreceptors in terms of what they sense and their response.

Back 66

Central: senses mostly pH and PCO2; stronger slower response

Peripheral: senses mostly PO2; weaker and faster response

Front 67

Name four receptors in the lung that control respiration

Back 67

Pulmonary stretch receptors

Irritant receptors

J receptors

Bronchial C receptors

Front 68

What prevents the lung from hyperinflating? Which receptors are responsible for that?

Back 68

Hering–Breuer reflex mediated by pulmonary stretch receptors signalling to the pons and medulla

Front 69

Name two causes of reduced ventilatory response to CO2

Back 69

Training (e.g. swimming)

Increased work of breathing (e.g. obstruction)

Front 70

Why should you not give high flow O2 to patients with COPD?

Back 70

In COPD, ventilatory drive is mostly derived from the low PO2 and not the high PCO2 to which they accommodate. Therefore, high flow O2 should not be given to those patients as they may stop breathing.

Front 71

What is the first receptor to drive increased RR when pH is low?

Back 71

Peripheral chemoreceptors (central chemoreceptors are more effective but have slower onset)

Front 72

How does the volume of oxygen absorbed per minute [L/min] evolve with exercise power [Watts]?

Back 72

Front 73

Two impacts of carbon monoxide on oxygen content in the blood.

Back 73

A.CO binds to haemoglobin reducing the capability of haemoglobin to bind other O2

B. CO increases affinity of O2 to haemoglobin thus reducing the delivery of O2 to tissues by haemoglobin

Front 74

Name three mechanisms through which aerosols deposit in airways.

Back 74

Impactation (due to turning point) for large particles

Sedimensation (due to gravity) for medium particles

Diffusion for small particles

Front 75

Name a representative site for the deposition of aerosols of different sizes: > 5µm, 1-5µm, < 1µm

Back 75

> 5µm: impactation in nasopharynx

1-5µm: sedimentation in small airways

< 1µm: diffusion in alveoli

Front 76

Briefly outline how the mucociliary system works

Back 76

Superficial layer (gel layer) trap the particles

Cilia move the gel by touching its base and beating at 20Hz.

Front 77

What produces the mucous in the respiratory tract?

Back 77

Mucous gland and goblet cells.

Front 78

Two microstructural features of bronchitis

Back 78

Mucous glands grossly hypertrophied thus increasing the thickness of the layer of mucous glands

Front 79

Name three pathologies that may affect the mucociliary function

Back 79

Too much mucous (e.g., bronchitis)

Change in mucous composition (e.g. cystic fibrosis, asthma)

Paralysis of cilia by toxic gas

Congenital defect of ciliary motion

Front 80

How can one increase power of exercise past VO2max

Back 80

By anaerobic glycolysis

Front 81

Define anaerobic threshold

Back 81

Exercise intensity at which lactate starts to accumulate in the blood

Front 82

Define VO2max

Back 82

Maximum rate of oxygen consumption

Front 83

What happens to ventilation [l/min] once the threshold VO2max has been reached?

Back 83

Ventilation increases even faster due to detection by chemoreceptors of low pH caused by lactate

Front 84

Name four pathological conditions with low V/Q ratio

Back 84

Pneumonia

Bronchitis

Asthma

Pulmonary oedema

Front 85

Name two pathological conditions with high V/Q

Back 85

PE

Emphysema

Front 86

What type of acid-base state would you have if you were dropped from a pressurised plane at 4000m of altitude? Why?

Back 86

Acute response:

Atmospheric pressure ➘ ⇒ Pressure of inspired O2 ➘ ⇒ PO2 ➘ ⇒ Hyperventilation ⇒ PCO2 ➘ ⇒ Respiratory alkalosis

Front 87

What happens to acid-base status and respiratory rate after 2 hours spent at 4000m of altitude?

Back 87

Alveolar gas equation: PA,O2 = PI,O2 - PA,CO2/R

PI,O2 cannot change

R is defined by tissues

=> Since PA,O2 cannot fall to negative values, there is hypoventilation to reduce PA,CO2.

Mechanism: Chemoreceptors detect high pH and decrease RR to decrease pH

Front 88

What happens to Hb and Hb saturation after several weeks spent at 4000m of altitude?

Back 88

Hb ➚➚ and O2 saturation ➘ (~ 80%) ⇒ O2 concentration ➚

Front 89

What happens to O2 dissociation curve at high altitude?

Back 89

Shift to the right at moderate altitude and to the left at very high altitude (because of respiratory alkalosis)

Front 90

Name one physical damage that can occur in the lungs at high altitude.

Back 90

High altitude pulmonary oedema

Uneven pulmonary vasoconstriction ⇒ Some capillaries are exposed to high pressure ⇒ Damage and leaks

Front 91

What can you do to a patient with CO poisoning?

Back 91

Hyperbaric therapy

Pt put in high pressure chamber ⇒ PO2 ➚ ⇒ Solubility of O2 ➚ ⇒ O2 concentration ➚ regardless of Hb sat.

Front 92

How does alveolar size evolve along the height of the lung? Why?

Back 92

Alveolar size increases from base to apex due to the more negative intrapleural pressure at the apex.

Front 93

What airflow pattern leads to highest airway resistance?

Back 93

Turbulent