What are the major factors that effect pulmonary vascular resistance in the normal lung?

  • Increased Art or Ven Pressure (A > V)
  • Lung volume ( U/J shaped curve)
  • Alveolar hypoxia > increased PVR via hypoxic vasoconstriction
  • Vascular Smooth Muscle Tone – response to endogenous/ exogenous factors
  • Area of lung (apex partic < base)
  • Position change

Pass Criteria:

  • Must list 3 properties

Why is pulmonary flow so sensitive to pulmonary vascular pressures?

  • V low Pressure system – few resistance vessels
  • Easily distensible vessels
  • Recruitment
  • Only just enough P for normal gravity/ position to get apical flow

Pass Criteria:

  • 2 out of 4 to pass


Draw the curve demonstrating the relationship between O2 concentration v pO2
Prompt: How does this change in anaemic and polycythaemic individual?


respiratory 1


What is the effect of carbon monoxide on these curves?


respiratory 2


What are the physiological changes that allow survival at high altitude?

  1. Hyperventilation >  decreases CO2, > O2
  2. Increased Hb (> EPO ),
  3. Alkalosis moderated by movement of  bicarbonate from CNS (1-2/7) and renal excretion
  4. Increased  2,3,DPG – R shift,
  5. Pulm hypertension (due to alveolar hypoxia inducing pulm vasoconstriction)  –
  6. RV hypertrophy – not really an “adaptation”
  7. Decreased work of breathing

Pass Criteria:

  • 3 of 7 to pass


Describe the distribution of blood flow in the lung of an upright subject at rest

  • Decreases linearly from base to apex
  • Due to hydrostatic pressure
  • Under normal conditions, flow almost ceases at apex
  • Distribution more uniform with exercise
  • Explanation of West’s zones 1 – 3  +/- zone 4
  • Zone 4 only at very low lung volumes

Pass Criteria:

  • Bold to pass

What are the main determinants of flow in these three zones?

  1. Zone 1  PA>Pa>Pv(not under normal conditions and is  alv. dead space)
  2. Zone 2   Pa>PA>Pv (recruitment)
  3. Zone 3  Pa>Pv>PA (distension + recruitment)

Pass Criteria:

  • Identify 3 pressures and their relationship to pass

How does the distribution of blood change when the subject becomes supine?

  • Blood flow from base to apex is almost uniform but flow in posterior segments exceeds that in anterior segments


How is carbon dioxide transported from the tissues to the lungs?

  • In plasma:
    • Dissolved
    • Carbamino compounds with plasma protein.
    • Hydration – H+ buffered – HCO3 in plasma.
  • In red blood cells:
    • Dissolved.
    • Formation of carbamino–Hb.
    • Hydration – H+ buffered – 70% of HCO3 enters plasma.
  • Of the approximately 49 mL of CO2 in each decilitre of arterial blood, 2.6 mL (5%) is dissolved, 2.6 mL (5%) is in carbamino compounds, and 43.8 mL (90%) is in HCO3
  • In the tissues, 3.7 mL of CO2 per decilitre of blood is added; 0.4 mL (10%) stays in solution, 0.8 mL (20%) forms carbamino compounds, and 2.5 mL (70%) forms HCO3
  • The pH of the blood drops from 7.40 to 7.36.

Pass Criteria:

  • Bolded

What is meant by the term ‘chloride shift’?

  1. About 70% of the HCO3 formed in the red cells enters the plasma in exchange for Cl. The exchange is called the chloride shift.
  2. This process is mediated by Band 3, a major membrane protein and is essentially complete in 1 second.
  3. Note that for each CO2 molecule added to a red cell, there is an increase of one osmotically active particle–either an HCO3 or a Cl–in the red cell. Consequently, the red cells take up water and increase in size.

Pass Criteria:

  • Bolded


What is the role of central chemoreceptors in control of ventilation?

  • Located near ventral surface of medulla
  • Rise in blood CO2 increases CO2 in CSF
  • CSF has poor buffering capacity so pH changes rapidly
  • Liberated Hions stimulate chemoreceptors (increasing pH has reverse effect)
  • Efferents stimulate medullary respiratory centre to increase ventilation and return CO2 to normal
  • Chronic CO2 elevation gives normal CSF pH and insensitivity

Pass Criteria:

  • Bolded to pass

What is the role of the peripheral chemoreceptors?

  • Located in carotid and aortic bodies that have high blood flow
  • Respond mostly to decrease in O2 below 100mmHg
  • Impulses transmitted to respiratory centre to increase ventilation
  • Responsible for all of the ventilatory response to hypoxaemia
  • Also responsible for small but rapid response to rise in CO2 and decrease in pH (carotid bodies)

Pass Criteria:

  • 3 out of 5 to pass


What is thoracic compliance?

Change in lung volume per unit change in airway pressure (DV/DP)

Measure of elastic recoil of lungs and chest wall

Normally 200 mL/mmHg in intact thorax

Pass Criteria: Bolded points

What are the main determinants of compliance of the thorax?

  • Surface tension of the alveoli (2/3rds)
  • Elastin/collagen fibres (1/3rd)
  • Alveolar surface tension depends on alveolar pressure, alveolar radius, surfactant
    • Law of Laplace – P=2(or4) x T/R

Pass Criteria:

  • 2 to pass

How does compliance vary throughout the upright lung?

  • Higher at base than apex because apex is already more distended

Pass Criteria:

  • Must say that base > apex


Explain the difference between alveolar and arterial oxygen concentrations in the healthy adult.

  • Physiological shunt of lung (PAO2>PaO2)
  • Blood enters arterial system without passing through a ventilated area of lung
  • Bronchial arterial blood flows to pulmonary veins
  • Coronary arterial blood flows to coronary veins then thebesian veins in left ventricle
  • Atelectasis in lung

Pass criteria:

  • Bold PLUS 1 other


What sensors are involved in control of ventilation?
Prompt: What senses changes in blood gases?

  • Chemoreceptors and mechanical receptors
  • Central chemo in medulla  respond to H+
  • Peripheral chemo in carotid and aortic bodies respond to O2, CO2, H+
  • Stretch receptors in lungs, muscles, joints
  • Irritant receptors in airways
  • J receptors respond to engorged capillaries

Pass criteria:

  • Need peripheral and central


What are the basic elements of the respiratory control system?

  • Sensors;
  • Central Controller;
  • Effectors.

What inputs are there into the respiratory control system?

  • Cortical
  • Central and peripheral chemoreceptors,
  • Lung and other receptors.

What are the basic elements of the respiratory control system?

  • Respond to changes in HI- concentration.
  • CO2 regulates ventilation by effects on pH



Describe the distribution of blood flow in the lungs.

  • Linear increase from top to bottom
  • 3 zones explained by hydrostatic pressures

Explain how V/Q matching varies from apex to base in the normal lung.

  • Slow increase in ventilation from top to bottom but not as much as perfusion.
  • Highest V/Q at apex

What factors effect pulmonary vascular resistance?

  • Hypoxia – arteriolar smooth muscle to contract
  • One of low pH, autonomic or passive factors


What are the acute respiratory adaptations to altitude?

  • Hyperventilation. (Oxygen-haemoglobin curve shifts right or left.)

What are the longer term physiologic effects of altitude exposure?

  • Polycythaemia;
  • one of increased 02 carriage and viscosity;
  • RVH;
  • more capillaries;
  • increased oxidative enzymes.


Describe how blood flow is regulated at the level of the endothelium.

  • Vasodilators: prostacyclins, NO, kinins
  • Vasoconstrictors: endothelinthromboxane, serotonin

What other general effects do endothelins have on the cardiovascular system?

  • Positive inotrope and chronotrope
  • Rise in ANP/renin/aldosterone
  • Decreased GFR and renal blood flow



Describe how the renin-angiotensin system regulates blood pressure and flow.

  • Describes pathway
  • Fall in renal blood flow leads to renin
  • Renin, angiotensin I > II
  • Vasoconstrictor

What factors regulate renin secretion?

  • Stimulate:
    • sympathetic nervous system, catechols, prostaglandins
  • Inhibit:
    • Na and Cl reabsorp, inc BP, angio II, vasopressin


What changes in arterial blood pressure do baroreceptors respond to?

  • Carotid sinus (rise or fall)
  • Aortic arch (rise)

What happens when the baroreceptors detect a fall in arterial pressure?

  • Decreased firing rate of Hering’s nerve
  • CN IX transmits to vasomotor centre
  • Decreased parasympathetic outflow to heart
  • Increased sympathetic outflow to heart
  • Increased sympathetic outflow to vessels
  • Increased heart rate, contractility
  • Arteriolar and venous constriction

What is the Set Point?

  • Neutral MAP for vasomotor centre Around 100 mm Hg


Please explain the concept of compliance as it relates to the lung.

  • Volume change per unit pressure change (slope of pressure volume curve) =~200ml/cm H2O
  • Depends on lung volumes and demonstrates hysteresis , may draw compliance curve, point out that inc compliance at low volumes
  • Depends on structural proteins and surface tension


What factors affect compliance?

  • Decrease
    • Fibrosis, pulmonary oedema,  not ventilated, increased pulmonary venous pressure
  • Increase
    • Emphysema, asthma surfactant



What are the metabolic functions of the lung?
Prompt: What substances are metabolised in the lung?

Metabolism of vasoactive amines

  1. Activation of Angiotensin 1 à AT 2 (ACE in capillary endothelium)
  2. Inactivation of bradykinin (ACE); PGs E/F
  3. Uptake & storage of Serotonin
  4. Arachadonic acid metabolites à leukotrienes / SRS-A & Prostaglandins

Synthesis of

  1. Surfactant
  2. IgA
  3. Phospholipids
  4. Proteases (collagen/elastin breakdown)

Pass criteria:

  • 2 of each


What factors influence the rate of transfer of oxygen from the alveolus into a pulmonary capillary?

  • Process is passive diffusion ( ficks law of diffusion)
  • Affected by – surface area,  membrane thickness, gradient of p O2 ( o2 in alveolus and O2 binding capacity of Hb)
  • Also – constant –solubility and MW
  • (V = A/T x D x (P1-P2)
  • D = Sol/MW1/2

Could you give some clinical examples of when these may be affected?

  • Exercise alveolar hypoxia and thickening of blood gas barrier


What factors determine the work of breathing?

  • Elastic forces of the lungs and chest wall
  • Viscous resistance of the airways and tissues

Pass Criteria:

  • Bold to pass

What variables affect elastic workload?

  • Larger tidal volumes
  • Reduced compliance due to:
    • lung volume – a person with only one lung has halved compliance;
    • slightly less during inflation than during deflation;
    • increased by increased tissue mass – fibrosis or pulmonary congestion or chest wall restriction;
    • loss of surfactant

What variables affect viscous resistance?

  • Higher respiratory rates increasing flow rates
  • Decreased airway radius due to:
    • Lower lung volumes;
    • Bronchoconstriction;
  • Increased air density (eg SCUBA diving)
  • Increased air viscosity

Pass Criteria:

  • Bold to pass



What is the relationship between intrapleural pressure and lung volume?

  • Sigmoid curve of IP pressure vs volume, does not reach 0% lung volume
  • Shows lung volume is higher during deflation than inflation for any given pressure = Hysteresis
  • Shows that lung contains residual air, without any expanding pressure (due to airway closure)
  • Shows that compliance decreases at higher lung volumes – lung becomes stiffer due to reaching limits of elasticity

respiratory 3.jpg


Pass Criteria:

  • 3 out of 4 to pass

What variables affect pulmonary compliance?

  • Slightly greater during deflation than during inflation as noted above;
  • Lung volume – at very low and very high volumes compliance is reduced;
  • Increased when tissue elasticity is reduced, as in emphysema;
  • Decreased by increased tissue mass – fibrosis or pulmonary congestion;
  • Decreased by loss of surfactant

Describe how regional differences in intrapleural pressure affect the ventilation.

  • States that the intrapleural pressure is higher at the apex than at the base of the lung – to keep the lung expanded against its own weight
  • Increased compliance at base, hence better ability to ventilate base compared with apex

Pass Criteria:

  • Bonus if gives values 10cm H2O at apex, 2.5cm at base



Describe the difference between diffusion limited and perfusion limited gas exchange in the lung.

  • Blood in pulmonary capillary has 0.75 seconds for gas exchange
  • Ability to reach partial pressure equilibrium depends on reaction with substances in the blood
  • No reaction with substances in blood – gas dissolves only on plasma – rapid equilibrium reached, gas uptake limited by perfusion
  • Example of N2O as perfusion limited
  • Describes reaction of CO with Hb, such great affinity that PCO in capillary falls rapidly – slow equilibrium, diffusion limited

Explain how oxygen exchange is limited across the pulmonary capillary?

  • Perfusion limited
  • Describes O2 and Hb combination, and time frame of combination (0.3 sec)

What would you expect to be the effect of heavy exercise on oxygen uptake in the pulmonary capillary?

  • Describes reduced time for combination with Hb (0.25 seconds), possible reduced O2Hb saturation
  • Describes possible effect of altitude



What is the initial effect on respiration with ascent to 6000 metre?

  • The ambient pressure is about half the atmospheric pressure
    • Hyperventilation
    • Shift oxygen dissociation curve to the right

Pass Criteria:

  • 2 out of 2

If the person remains at the same altitude for 6 months, what additional changes would occur?

  • Polycythaemia
  • Increase in 2,3 DPG
  • Increase in the number of capillaries in peripheral tissues
  • Increase maximal breathing capacity
  • Pulmonary vasoconstriction resulting in pulmonary hypertension and right ventricular hypertrophy

Describe the symptoms of acute mountain sickness.

  • Headache, fatigue, dizzy, palpitations, nausea, loss of appetite & insomnia



Describe the relationship between ventilation and perfusion of the lung in a person while standing?

  • Max ventilation 3-4x greater at apex
  • PO40mmHg higher at lung apex
  • Max perfusion basally Q nearly 20x greater at base
  • Prompt: are there regional variations in either

What are the effects of V/Q inequality on gas exchange?

  • V/Q inequality impairs uptake or elimination of all gases
  • Majority of blood returns from lung bases where the oxygen saturation is low
  • Results in blood PO2 being lower than that of mixed alveolar PO2

What effect does increasing ventilation to the lungs have on arterial PO2 and PCO2?

  • PCO2 reduces much more than PO2 increases



What factors impact on resistance in airways?

  • Size of airway:  R highest in medium sized bronchi, low in very small airways.
  • Lung volume:  R decreases with expansion as airways pulled open
  • Bronchial smooth muscle tone:  controlled by B sympathetics
  • Gas density:  eg heliox -> low R
  • Forced expiration:  intrathoracic pressure compresses airways = ‘dynamic compression’

What factors cause turbulent flow in airways?

  • Expressed by Reynold’s number
  • Where:
    • p is the fluid density;
    • D is the diameter of the tube;
    • V is the velocity of flow;
    • n is the viscosity of the fluid
  • The higher the value of Reynold’s number the greater the probability of turbulence’ which usually occurs when Reynold’s number is between 2000-3000
  • Laminar flow only in small airways, transitional most areas, turbulent in trachea (rapid breathing)

respiratory 4



Define lung compliance?

  • Change in volume / change in pressure
  • (Slope of pressure-volume curve)
  • (Lung “stiffness”)

What factors influence lung compliance?

  • Fibrosis
  • Alveolar oedema
  • Elastic tissue
  • Emphysema / age
  • Volume / Size of lung
  • Surface tension in alveoli (Surfactant)

Pass Criteria:

  • 3 out of 6

What else does surfactant do?

  • Reduces WOB
  • Prevents collapse
  • Keeps alveoli dry

Pass Criteria:

  • 2 out of 3



What is the effect of ventilation perfusion inequality on gas exchange?

  • Impedes exchange of oxygen and carbon dioxide
  • Hypoxia which cannot be corrected by increased ventilation
  • Hypercapnia can be corrected by increased ventilation

Pass criteria:

  • 2 out of 3

Can increasing ventilation correct these problems?

  • The oxygen dissociation curve is s shaped which means that increasing ventilation to units with high VQ ratios cannot compensate for the shunt caused by low VQ units
  • The carbon dioxide dissociation curve is more linear so that increasing ventilation will blow off CO2 from lung units with both high and low VQ ratios

Pass criteria:

  • Pass = oxygen explanation
  • Others additional information

How can we determine the effect of VQ mismatch on oxygenation in clinical practice?

  • Calculate the AA gradient (= PAO2-PaO2)
  • PAO2=PIO2-PaCO2/R
  • Give normal values for each



What is pulmonary compliance and what are the factors that influence it?

  • Volume change per unit pressure change
  • Elastic recoil of the lung especially the geometry of  the elastin fibres
  • Surface tension in the alveoli
  • Disease such as fibrosis, oedema decrease compliance
  • Ageing and emphysema increase compliance

Pass criteria:

  • Bold to pass

What are the physiological advantages of surfactant?

  • Increases compliance and reduces work of breathing
  • Prevents small alveoli collapsing
    • P = 2 x Tension / Radius
  • Reduces transudation

Pass criteria:

  • 2 out of 3
  • Law is additional information

Can you draw the pressure volume curve of a normal lung?

  • Hysteresis
  • Closing volume
  • Lung becomes stiffer at higher volumes

Pass criteria:

  • 2 out of 3



How would you calculate pulmonary vascular resistance?

  • R = Change is pressure / Blood flow
  • Normally very low
    • Prompt for comparison with systemic vascular resistance if necessary

Pass Criteria:

  • Bold to pass


What are the determinants of pulmonary vascular resistance?

  • Increasing pressure as in exercise causes a reduction in resistance by recruitment and distension
  • Large lung volumes pull open extra-alveolar vessels but may narrow pulmonary capillaries so that resistance rises
  • Small lung volumes also cause increased resistance of extra-alveolar vessels because smooth muscle tone closes them if critical opening pressure is not reached
  • Hypoxic pulmonary vasoconstriction directs blood away from hypoxic lung

Pass criteria:

  • 2 out of 4

Describe Hypoxic Pulmonary Vasoconstriction.

  • Alveolar hypoxia constricts pulmonary blood vessels
  • Direct effect of alveolar PO2 on smooth muscle
  • Important at birth
  • Directs blood away from hypoxic areas

Pass criteria:

  • 2 out of 4




Describe the synthesis and metabolism of cAMP.

  • Formed inside the membrane
  • ATP is converted to cAMP via adenyl cyclase
  • Metabolised by phospho-diesterase

Pass Criteria:

  • 2 out of 3 to pass

Discuss the function of cAMP.

  • Intracellular second messenger
  • Stimulate protein synthesis
  • Activate an intracellular enzyme system in the neurone



What are the factors which keep fluid out of the alveoli?

a) Starling’s Law (Theoretical Concept, exact values of pressures unknown)

I.             Hydrostatic pressure (of column of blood)

  • In the capillaries (positive thus outwards) = Pc
  • In the interstitium (probably negative and thus also outwards) = Pi

2.            Colloid osmotic pressure (of proteins in blood)

  • In the capillaries (inwards) = ;cc
  • In the interstitium (outwards) = xi

Net pressure probably slightly outward
Net fluid out = K[(Pc-Pi)-s(7rc-.76)] K = Filtration Coefficient a = reflection coefficient (capillary wall barrier)

b) Lymphatic drainage
c) alveolar epithelial cells

Pass: Demonstrate understanding of hydrostatic pressure & colloid osmotic pressure
Plus one other



What are the causes of hypoxaemia in a person breathing room air.

Hypoventilation, diffusion limitation, shunt, V/Q inequality

Pass: 3 of 4



Please draw a diagram showing static lung volumes.

respiratory 5

  1. TV = 500ml
  2. DS = 150 ml
  3. TLC = 7L
  4. FRC = 2L
  5. VC = 6L

Pass criteria:

  • Draw diagram
  • Label diagram

How does physiological dead space differ from anatomical dead space?

  • Anatomical dead space, conducting zones of lung 150 mls
  • Physiological dead space- Parts of lung with ventilation but no perfusion



In the lung, what is surfactant and how does it work?

a)      Surfactant is a phospholipid. Dipalmitoyl phosphatidylcholine (DPPC) is an important constituent)

b)      Produced in type 2 alveolar cells. Lamellated bodies within them are extruded into the alveoli and transform into surfactant.

c)       Fast synthesis with rapid turnover

d)      Formed relatively late in foetal life.

e)      With surfactant present, surface tension changes greatly with surface area. It falls to very low values when area is small

f)       Molecules of DPPC are hydrophobic at one end and hydrophilic at the other. When aligned on the surface, their repulsive forces oppose the normal attractive forces between the liquid surface molecules.

What are the physiological advantages of surfactant ?

a)      Reduction in surface tension is greatest when film is compressed and molecules of DPPC are closest together.

b)      Lower surface tension in the alveoli increases lung compliance and decreases work of breathing

c)       Promotes alveolar stability (reduces tendency for small alveoli to empty into large alveoli)

d)      3) Keep the alveoli dry (surface tension “sucks” fluid into alveolar spaces from capillaries, by reducing hydrostatic pressure in the tissue)

Core Knowledge in Bold



How is carbon dioxide transported in the blood?

respiratory 6

Figure: CO2 dissociation curves for blood of different O2 saturations. Note that oxygenated blood carries less CO2 for the same PCO@. The inset shows the ‘physiological’ curve between arterial and mixed venous blood.

  • Dissolved
  • As carbamino compounds with proteins, especially Hb.
  • Hydrated in red cells – H buffered – HCO3 in plasma.

Pass: 2 of 3

How does venous blood carry more CO2 than arterial blood?

  • Deoxygenated haemoglobin binds more H and forms more carbamino compounds than oxyhemoglobin so venous blood carries more CO2 than arterial blood
  • This is known as Haidance effect

Pass: Does the curve move towards the left or the right, and why?



What is the alveolar gas equation?



  • PA02 is the alveolar oxygen partial pressure
  • P102 is the oxygen partial pressure of inspired air
  • PACO2 is the alveolar CO2 partial pressure.
  • R is the respiratory quotient; CO2 production/02 consumption, typically 0.8

Note that a small correction factor F of 2mmHg has been omitted from the equation.

Pass: 4 out of 4

How do you calculate the alveolar- arterial gradient?

Difference between PAO2 (alveolar) and PaO2 (arterial).

What is the physiological significance of the A-a gradient?

V/Q mismatch (eg: shunting or dead space)


Please describe the relationship between pulmonary vascular resistance and pulmonary vascular pressure?
Prompt: What mechanisms are involved in the vascular response to rising pulmonary vascular pressure?

A low resistance system

Capacity for resistance to DECREASE with INCREASE pressure*
(both INCREASED pulmonary art & INCREASED pulm venous)

Mechanisms: vascular ‘recruitment’ (with rises in pressure from low levels); vascular `distension’ (with rises in pressure at higher levels) *

respiratory 7

Pass: *
Drawing diagram not essential

How does lung volume influence pulmonary vascular resistance?

Vascular resistance initially decreases as lung volume increases, then rises (see diagram below) *

At very low lung volumes (eg. lung collapse) must reach a ‘critical opening pressure’ (several cm H2O above downstream pressure) to enable any flow *

Very high lung volumes, when alveolar pressure exceeds pulmonary capillary pressure, pulmonary vascular resistance will increase (pulm capillaries squashed).

respiratory 8


Pass: *
Drawing diagram not essential


What factors influence the distribution of pulmonary arterial blood?

  1. Alveolar Hypoxia *
  2. Gravity * :3 main zones
    1. Z1 (apical) PA>Pa>Pv
    2. Z2 (middle) Pa>PA.>Pv
    3. Z3 (basal) Pa>Pv>PA
  3. vascular resistance pulmonary HT / PE
  4. pulmonary disease : asthma /COAD / infection/ infarction/ cancer / fibrosis / pneumothorax / chest trauma
  5. vasoactive substances * (NO, endothelin, prostaglandin)
  6. low blood pH leads to pulm vasoconstriction
  7. Sympathetic stimulation leads to stiff pulmonary arteries leads to vasoconstriction.

Pass: * plus 2 others

What EXTRA-PULMONARY factors influence pulmonary blood flow?

  1. blood volume
  2. cardiac output
  3. atmospheric pressure
  4. temperature
  5. pathology eg, anaemia, cancer, infection
  6. exercise
  7. posture

Pass: 4 of 7



Describe the effect of high altitude on respiration.
Prompt if required: Explain the mechanism underlying hyperventilation at altitude.

*Hyperventilation – Most important factor in acclimatisation to altitude.

*Mechanism: Hypoxic stimulation of peripheral chemoreceptors [carotid bodies, aortic bodies].

Low pCO2 and alkalosis work against this but CSF pH `normalised’ by movement of bicarbonate out of CSF [-1-2 days] and renal excretion of bicarbonate [2-3 days] ‘normalises’ arterial pH taking this brake off. Sensitivity of carotid bodies to hypoxia increases during acclimatisation.

Pass: *

What other processes are involved in acclimatisation to high altitude?

*Polycythaemia [hypoxia, erythropoietin]

Shifts in the 02 dissociation curve

Right at moderate altitude 2° 2,3 DPG favouring unloading in tissues; left at high altitude 2°

respiratory alkalosis favouring loading in lungs.

Changes in capillary numbers/ density

Changes to oxidative enzymes in cells

Increased maximum breathing capacity

Pass: Polycythaemia with Mechanism and one other



What factors affect the diffusion of gases across the alveolar capillary membrane?

Ficks law diffusion is proportional to tissue area and concentration gradient of gas and inversely proportional to the tissue thickness x R
R = diffusion constant and relates to gas and tissue solubility

Pass: Need to mention diffusion, concentration gradient              & thickness.




How is oxygen transported in the blood?

02 dissolved


Heme protein

Pass: Need to name both

Describe the oxygen dissociation curve.

Name the axis Hb saturation and p02 & name 50% saturation (p02= 27 mmHg) or p40 = 75% saturation.

In what forms are carbon dioxide transported in the blood?

CO2 dissolved 10%, Bicarbonate (60%) Carbamino compounds (30%)
deoxygenated blood is better at carrying CO2 = Haldane effect

All 3 to pass



Discuss the factors that determine airway resistance.

1. Flow resistance R=8x viscosity x length / pieXr4

Pass: Need to say that radius is the most important determining factor, 2 out of 3 to pass.

2. Directly proportional to viscosity & length. Inversely proportional to radius to the power of 4 (le:  half the radius increases resistance 16 fold).


What factors affect the radius of the airway?

  1. Bronchial smooth muscle tone: sympathetic and parasympathetic activity
  2. Lung volume

Need 2 to pass



Describe the relationship of pressure and wall tension in connected bubbles.

Law of Laplace: P = 4T/r. Two bubbles connected (same surface tension), the smaller with higher pressure will blow up the larger with lower pressure. Smaller bubble will collapse.

What are the effects of surfactant in alveoli?

Surfactant reduces surface tension. Alveolar bubbles are stable because of very low surface tension when small (on expiration). Hysteresis curve demonstrates very low pressures on expiration to small volumes = bubble stability. Increased compliance = ease of expansion. Also keeps alveoli dry = opposes transudation fluid into bubble.

How does surfactant achieve this?

  • Bipolar molecules oppose the normal increasing attracting forces as molecules get closer in a smaller surface
  • The ends of surfactant molecules repel each other and oppose collapse.


What are the causes of hypoxaemia in a patient breathing room air?

  1. Hypoventilation
  2. Diffusion limitation
  3. Shunt
  4. Ventilation/perfusion (V/Q) inequality

Pass Criteria:

  • 3 of 4 to pass

How does the ventilation/perfusion ratio change in different regions of the lung?

  • V/Q ratio is high at apex (blood flow minimal) and decreases down the lung to the base
  • PO2 highest at apex but blood flow is greatest at the base where PO2 is lowest (can be 40 mmHg difference)
  • Respiratory exchange ratio (CO2 output/O2 uptake) highest at apex where blood flow is lower

Pass Criteria:

  • Bold + general concepts to pass

What is the effect of ventilation-perfusion inequality on arterial PO2 and arterial PCO2?

PROMPT – Why does V/Q inequality cause reduced arterial PO2 while arterial PCO2 remains relatively normal?

  • Much greater influence on PO2 than CO2.
  • O2 dissociation curve nonlinear. Areas with high V/Q ratio add relatively little O2 with increased ventilation. Whereas areas with low V/Q ratio have lower PO2 (close to mixed venous) overall PO2 is reduced
  • CO2 dissociation curve is linear in the working range. Chemoreceptor stimulation increases ventilation and CO2 output especially in lung areas with high V/Q ratios. Normal PCO2 (minimal change).

Pass Criteria:

  • Bold + demonstrates understanding


How is oxygen carried in the blood?

  • Dissolved: amount dissolved proportional to partial pressure (Henry’s law) – 0.3mL O2/100mL blood at PO2 100mmHg
  • Most combined with Hb: 20.8mL O2/100mL blood (at Hb level of 15g/dL).

Pass Criteria:

  • Bold to pass

Draw and label the oxygen dissociation curve.

Pass Criteria:

  • Draw correct shape and have 2 points of saturations e.g.
    • 27mmHg SaO2 50%
    • 30mmHg SaO2 60%
    • 40mmHg SaO2 75%
    • 56 mmHg SaO2 90%
    • 80mmHg SaO2 95%
    • 90mmHg SaO2 97%

What are the implications of this curved shape?

PROMPT – What happens to the top and bottom?

  • Upper – If PO2 alveolar gas falls (e.g. ARDS in acute pancreatitis) loading of O2 little affected
  • Lower – Steep lower part means large amounts of O2 unloaded at peripheral tissues for only small drop in capillary PO2

Pass Criteria:

  • Explain concept of loading and unloading of oxygen



  • Portion of the tidal volume that does not participate in gas exchange – VT = VD + VA

Pass Criteria:

  • Demonstrate principle of bold to pass

What types of dead space are there?

PROMPT – Explain difference between the two types.

    • Volume of conducting airways – trachea, bronchi, terminal bronchi (16 generations)
    • About 150mLs of 500mL VT
    • Measured by Fowler’s method
    • Determined by
      • Increased diameter of airways during inspiration
      • Size & posture of individual
    • Volume of gas that does not eliminate CO2
    • Same as anatomical dead space in normal individuals
    • Increased in lung disease because of inequality of blood flow and ventilation within the lung

Pass Criteria:

  • Two types dead space and describe

How is dead space measured?

  • Measured by Bohr method


Describe the different types of tissue hypoxia.

PROMPT  – Hypoxia is a deficiency of O2 at at the tissue level.

  • Hypoxaemia (hypoxic hypoxia) – arterial PO2 reduced
  • Anaemic hypoxia – arterial PO2 normal but Hb reduced
  • Ischaemic/stagnant hypoxia – blood flow & O2 delivery decreased
  • Histotoxic hypoxia – because of toxin cells cannot use it

Pass Criteria:

  • 3 to pass

Describe the respiratory mechanisms leading to hypoxaemia and give examples.

  • Reduced ventilation – Asthma
  • VQ mismatch – Pulmonary Embolism
  • Shunt – Congenital heart disease
  • Diffusion limitation – Acute pulmonary oedema, left ventricular failure, ulmonary fibrosis)

Pass Criteria:

  • 2 mechanisms and correct example

Describe the clinical effects of acute hypoxia.

  • Disorientation
  • Confusion
  • Headache
  • Loss of consciousness
  • Tachycardia
  • Hypertension
  • Hypotension
  • Acute myocardial infarction
  • Arrest
  • Diaphoresis
  • Tachypnoea

Pass Criteria:

  • 2 to pass


Please draw and label the oxygen dissociation curve.

Pass Criteria:

  • Draw correct shape – have points of 90% (58-60) saturation.

What factors can cause the curve to shift to the right (reduced affinity of Hb for O2)?

  • Increased temperature
  • Increased PCO2
  • Increased 2,3 DPG
  • Drop in pH (increased H+)

Pass Criteria:

  • At least 3

What are the physiological advantages of the curved shape?

  • Upper
    • If pO2 alveolar gas falls, loading of O2 little affected. Also as RBC takes up O2 along pulmonary capillary, diffusion process hastened as large partial pressure different maintained when most of O2 has been transferred.
  • Lower
    • Steep lower part means peripheral tissues can withdraw large amounts of O2 for only small drop in capillary pO2.

Pass Criteria:

  • Concept of loading and unloading of oxygen being facilitated


Please draw and label the oxygen dissociation curve.

Pass Criteria:

  • Draw correct shape – have points of 90% (58-60) saturation.

What factors can cause the curve to shift to the right (reduced affinity of Hb for O2)?

  • Increased temperature
  • Increased PCO2
  • Increased 2,3 DPG
  • Drop in pH (increased H+)

Pass Criteria:

  • At least 3

What are the physiological advantages of the curved shape?

  • Upper
    • If pO2 alveolar gas falls, loading of O2 little affected. Also as RBC takes up O2 along pulmonary capillary, diffusion process hastened as large partial pressure different maintained when most of O2 has been transferred.
  • Lower
    • Steep lower part means peripheral tissues can withdraw large amounts of O2 for only small drop in capillary pO2.

Pass Criteria:

  • Concept of loading and unloading of oxygen being facilitated


How is carbon dioxide transported from the tissues to the lungs?

  • In plasma:
    • Dissolved
    • Carbamino compounds with plasma proteins
    • Hydration – H+ buffered – HCO3- in plasma
  • In RBC
    • Dissolved
    • Formation of carbamino-Hb
    • Hydration – H+ buffered – 70% of HCO3- enters plasma
  • Each 49mL CO2/dL arterial blood – 5% dissolved, 5% in carbamino compounds, 90% hydrated as HCO3

Pass Criteria:

  • Bold to pass

Draw and explain the carbon dioxide dissociation curve.

Pass Criteria:

  • Concept to pass

What is meant by the term 'chloride shift'?

  • 70% of HCO3- formed in red cells enters the plasma in exchange for chloride – exchange is the chloride shift

Pass Criteria:

  • Reasonable definition to pass


What are the major components of the control of ventilation (or respiration)?

  • Voluntary versus automatic
  • Medulla pacemaker cells
  • Pons pneumotactic centre modifies th emedulla activity
  • Higher centres – hypothalamus, limbic system, cerebral cortex
  • Vagal afferents from lung
  • Central chemoreceptors – CSF (medulla, floor 4th ventricle) – increased H+
  • Peripheral chemoreceptors – carotid and aortic bodies – pO2, decreased pH, increased pCO2
  • Integrated response: PaCO2, PO2, pH
  • Lung receptors – stretch, irritant, bronchial C fibres (J receptors)

Pass Criteria:

  • 5 of 7 bold

How does a rise in CO2 affect ventilation?

  • Direct effect on central and peripheral chemoreceptors, due to both high CO2 and lower pH
  • Increase in rate and depth of ventilation

Pass Criteria:

  • 4 of 5 bold 


How is CO2 carried in the blood?

  • CO2 is carried in the blood in 3 forms:
    • Dissolved – approximately 5-10%
    • As bicarbonate – approximately 90%
    • Combined with proteins as carbamino compunds – approximately 5-10%

Pass Criteria:

  • Bold + 1 other

How is bicarbonate formed in the blood?

PROMPT – Can you write an equation?

  • CO2+ H2O  H2CO3  H+ + HCO3
  • The first reaction is very slow in plasma but fast within the red blood cell because of the presence there of an enzyme carbonic anhydrase (CA). The second reaction, ionic dissociation is fast without an enzyme.

Pass Criteria:

  • Talk through equation + bold 

What is the chloride shift?

  • HCO3– diffuses easily out of the cell. Hdoesn’t because the cell membrane is relatively impermeable to cations. Therefore to maintain cell neutrality, Cl- diffuses from the plasma into the cell.

Pass Criteria:

  • At least 1 bold 

What is the Haldane effect?

  • H+ + HbO2  H+Hb + O2
  • The Haldane effect: Deoxy Hb binds more H+ than oxyHb and forms carbamino compounds more readily. Binding of O2 to Hb reduces its affinity for CO2
    1.  Enhances the removal of CO2 from O2 consuming tissues (e.g. muscles) into the blood. CO2 can bind to amino groups on Hb to form carbaminoHb. CarbaminoHb is the major contributor to the Haldance effect.
    2. Promotes the dissociation of CO2 from Hb in the presence of O2 (e.g. the lungs) which is vital for alveolar gas exchange.


What happens to the V/Q ratio from top to bottom of the upright lung?

PROMPT – What happens to the relative values of ventilation and perfusion?

  • Both ventilation and perfusion increase with blood flow (perfusion (Q) increasing more than ventilation (V) and this results in V/Q ratio DECREASING down the lung

Pass Criteria:

  • 3 of 3 bold to pass (be able to explain the concept)

Explain the reasons for the normal Alveolar-arterial O2 difference.

  • Normally 5-10mmHg. A-a Gradient = measure of the difference between alveolar and arterial concentration of O2
    • Even though P Alv O2 at apex 40mmHg above base, most of blood flow (Q) comes from base where P Alv O2 is low -> decrease in P Art O2
    • Shunt: Bronchial blood & coronary blood
  • Also non-linear shape of O2 dissociation curve means that addition of small amount of shunted blood with low O2 concentration greatly decreases PO2 of arterial blood and units with high PO2 have little effect on O2  concentration because curve is flat at high O2 concentration.

Pass Criteria:

  • Bold

What is the formula for A-a gradient?

  • PAO2 = PIO2 – (PACO2)/R + F


Draw a diagram that demonstrates the components of total lung volume.


  • Should correctly include TLC, VC, FRC, TV, RV, IRV, ERV

Pass Criteria:

  • Bold to pass
  • TLC, VC, FRC, TV, RV correct

In an adult, what are the typical volumes of these components?

  • TLV: ~7000mL
  • VC: ~4500 – 5000mL
  • RV: ~1200mL
  • FRC: ~2400mL
  • TV: ~500mL

Pass Criteria:

  • 2/4 (reasonable approximations)

Which lung volumes can be measured in the ED?

  • Spirometer for FEV1 and FVC. TV on ventilator.
  • Helium dilution or body plethysmography for TLC, FRC and RV.

Pass Criteria:

  • 1/2 spirometer


What are the receptors involved in the control of ventilation?

  • Central chemoreceptors
  • Peripheral chemoreceptors
  • Pulmonary stretch receptors
  • Irritant receptors
  • J receptors
  • Bronchial C fibres
  • Nose and upper airway receptors
  • Joint and muscle receptors
  • Gamma system
  • Arterial baroreceptors
  • Pain and temperature receptors

Pass Criteria:

  • Bold + 3 others

Where are the central chemoreceptors located?

  • 200-400 um below ventral surface of medulla

Pass Criteria:

  • Medulla must be stated

How do these receptors function?
Prompt: How do H+ ions affect their function?

  • BBB permeable to CO2; relatively impermeable to HCO3
  • Increase in blood pCO2 –> increased CSF pCO2 –> increased H+ in CSF
  • Increased H+ in CSF stimulated ventilation
  • Decreased H+ in CSF inhibits ventilation; causes cerebral vasodilation –> enhanced diffusion of  pCO2 into CSF
  • CSF pH 7.32 – less buffering than blood, CSF pH chenges more for given pCO2
  • Prolonged pH changes compensated by HCO3 transport across BBB
    • Chronic CO2 retention has near normal CSF H+

Pass Criteria:

  • Bold concepts to pass


In an alveolus, what factors affect oxygenation?

  • Ventilation
  • Perfusion
  • Diffusion across the blood gas barrier
  • Alveolar-pulmonary capillary pO2 gradient

Pass Criteria:

  • Bold

Describe the oxygen uptake along a pulmonary capillary.

  • Alveolar pulmonary capillary O2 gradient
    • Alveolar pO2 = 100 mmHg
    • Pulmonary capillary pO2 = 40 mmHg
  • Blood gas barrier thickness 0.3 microns
  • RBC transit time = 0.75s
  • Under normal circumstances O2 uptake is perfusion limited (complete in 0.25s) & alveolar end capillary O2 difference is minimal
  • Rate of rise of end capillary pO2 is steep
    • O2 -Hb dissociation curve

Pass Criteria:

  • Must have knowledge of 3 of 4 concepts in bold
  • Numbers not required to pass

How does hypoxia affect oxygenation?

  • Alveolar pulmonary capillary O2 gradient is decreased
  • O2 diffusion is decreased & rate of rise of pO2 for given O2 concentration in blood is less

Pass Criteria:

  • Can draw graph to explain



Draw a diagram that demonstrates the components of total lung volumes.

respiratory 5

Pass Criteria:

  • 3 of 6 to pass

What are the typical volumes?

  • TLC ~ 7000 mL
  • VC ~ 4500-5000 mL
  • FRC ~2400 mL
  • TV ~500 mL
  • RV ~ 1200 mL

Pass Criteria:

  • 2 of 4 reasonable approximations

Optional: Which of these volumes can be measured in the ED?

  • FEV1, FVC, or TV