F6 + F7 - diffusion and V/Q Flashcards

1
Q

How long does it take a blood cell to pass through the pulmonary capillaries?

A

0.75 seconds

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2
Q

Carbon dioxide takes how long to complete diffusion - equalisation of partial pressures?

A

0.1 seconds

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3
Q

How logn does oxygen take to equalise its partial pressures/complete diffusion at the respiratory membrane

A

0.3-0.4 seconds

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4
Q

Relate Fick’s diffusion laws to the diffusion capacity of the lungs analysed?

A

Small quantity of carbon monoxide in inhaled gas and the amount taken up analysed by difference between inspired and expired gas. It is highly soluble so the uptake is not flow limited

Utilising Fick’s law of diffusion the amount fo gas transferred across a sheet fo tissue is proportional to area, diffusion constant and difference in partial pressure, and inversely proportional to thickness. It is re-written as area nd thickness cannot be measured as

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5
Q

What factors are incorporated in the ‘diffusion capacity of the lung’ as measured using carbon monoxide

A

area, thickness, diffusing proprties of the membrane and gas –>

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6
Q

Describe the measurement technique for diffusion capacity

A
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7
Q

Define dead space

A

Dead space is the fraction of tidal volume which does not participate in gas exchange.

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8
Q

What components are there of dead space

A

physiological dead space and apparatus dead space

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9
Q

What is physiological dead space composed of

A

Anatomical deead space
Alveolar dead space

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10
Q

What is anatomical dead space

A

the volume of gas in the conducting airways from the lips to the innermost terminal bronchioles i.e. the volume of gas (150mls) exchaled before the CO2 concentration rises to its alveolar plateau

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11
Q

What is alveolar dead space

A

the fraction of tidal volume which passes beyond the anatomical dead space to mix with alveolar gas without participating in gas exchange i.e. where ventilation exceeds perfusion to a lung segment; otherwise known as the difference between

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12
Q

What is artifiical dead space

A

is the volume of gas not involved in respiration in an artificial breathing circuit. It can reduce or increase the dead space

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13
Q

What is the Bohr equation

A

Difference between exhaled CO2 and alveolar CO2 - hard to measure

◦ V(D)/V (T) = [F(A)CO2 - F(E)CO2]/F(A)CO2
◦ VTx F(e)CO2 = (VT - VD) x FaCO2 (alveolar)
◦ F is for fraction; can use partial pressures to yield the same result 
◦ Problem is regional alveolar CO2 varies throughout the lung significantly due to different V/Q ratios
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14
Q

What is the equation for the Bohr equation

A

◦ V(D)/V (T) = [F(A)CO2 - F(E)CO2]/F(A)CO2
◦ VTx F(e)CO2 = (VT - VD) x FaCO2 (alveolar)
◦ F is for fraction; can use partial pressures to yield the same result
◦ Problem is regional alveolar CO2 varies throughout the lung significantly due to different V/Q ratios

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15
Q

What is the problem with PACO2 in the Bohr equation

A

Difficult to measure
And regional alveolar CO2 varies throughout the lung significantly

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16
Q

What modificationo to the Bohr equation is instead used?

A

Enghoff modification

PaCO2 instead of PACO2

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17
Q

What is the basis for PaCO2 being used instead of PACO2 in the Enghoff modification of the Bohr equation

A

easier to measure and represented an average of the CO2 across all the alveolar units assuming good gas exchange and no shunting)

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18
Q

What is the Enghoff equation

A

Vd/VT = PaCO2 - P-mixed expired CO2/PaCO2

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19
Q

What is the assumptions of the Enghoff equation

A

Assumes good gas exchange
Assumes no shunting

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21
Q

What flaws are there in the Enghoff modification of the Bohr equation

A

Right to left shunt will appear as dead sapce
V/Q heterogeneity
Diffusion impairment and bronchospasm makes finding plateau for expired CO2 difficult

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21
Q

What can be used to calculate anatomical dead space

A

Fowlers method

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22
Q

What is Fowlers method

A

Attach the patient to a pneumotachograph to measure flow over time with a sensitive nitrogen sensor

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23
Q

What is the pneumotachograph

A

measures flow over time when attaching a patient to it

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24
Q

What does the patient breathe in Fowlers method of anatomical dead space calculation?

A

Single breath 100% FiO2
Same tidal volume as usual and do not pause between breaths

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25
What happens as a patient inhales 100% oxygen for 1 breath
O2 replaces nitrgoen in the anatomical dead space
26
How is a Fowlers method test done
◦ Single breath of 100% oxygen, same tidal volume as usual and gap between breaths cannot be too long ◦ Oxygen replaces nitrogen in anatomical dead space ◦ Exhaled breath has its volume and nitrogen concentration measured (flow over time graph --> i.e. volume) ◦ Graph of nitrogen concnetration over volume cna be used to caclulate the anatomical dead space ◦ Phase 1 --> pure Oyxgen from dead space ◦ Phase 2 --> exhaled nitrogen rises rapidly and represents gas from fast time constant alveoli mixing with gas from more distal airways, half of this is counted as dead space ◦ Phase 1 and half of phase 2 in the single breath nitrogen washout test =dead space ◦ Phase 3 = plateau --> alveolus entirely ◦ Phase 4 - another increase in nitrogen concentration representing closing capacity as small airways in more compliant regions close and only poorly compliant alveoli exhale nitrogen rich gas without it being diluted
27
Describe the phases of the single breath nitrogen washout test
◦ Single breath of 100% oxygen, same tidal volume as usual and gap between breaths cannot be too long ◦ Oxygen replaces nitrogen in anatomical dead space ◦ Exhaled breath has its volume and nitrogen concentration measured (flow over time graph --> i.e. volume) ◦ Graph of nitrogen concnetration over volume cna be used to caclulate the anatomical dead space ◦ Phase 1 --> pure Oyxgen from dead space ◦ Phase 2 --> exhaled nitrogen rises rapidly and represents gas from fast time constant alveoli mixing with gas from more distal airways, half of this is counted as dead space ◦ Phase 1 and half of phase 2 in the single breath nitrogen washout test =dead space ◦ Phase 3 = plateau --> alveolus entirely ◦ Phase 4 - another increase in nitrogen concentration representing closing capacity as small airways in more compliant regions close and only poorly compliant alveoli exhale nitrogen rich gas without it being diluted
28
What is the impact of increased dead space
Reduction in TV - Decreased CO2 clearance for a given minute volume - Decreased oxygenation due to increased alveolar CO2 - Increased work of breathing due to decreased efficacy - Proportional increase in required minute ventilation to the change in ratio of dead space to alveolar ventilation
29
if you had a large lobar PE and this halved your alveolar ventilation what do you have to do to reach normal gas exchange
Double minute volume
30
If you add dead space through apparatus how do you account for this in target TV
add the volume of the increased dead space to the TV
31
How do you measure alveolar dead space
You don't but if you measure physiological dead space (Bohr method) then subtract anatomical dead space with Fowlers method you get alveolar dead sapce
32
Draw a diagram to represent Fowlers method
33
Alveolar ventilation =
= Tidal ventilation - dead space ventilation = VCO2/PCO2 x K
34
VCO2 =
VCO2 = VA x %CO2/100 %CO2/100 = FCO2 Therefore VCO2 = FCO2 x VA As PCO2 = FCO2 x k VA = VCO2/PCO2 x K
35
Alveolar ventilation equation
VA = VCO2/PCO2 x K
36
Why is there V/Q mismatch in the lung?
Gravity and its effect on blood flow through low presurre pulmonary circulation Variation in pulmonary perfusion due to - Lung volume - pulmonary vascular architecture - Hypoxic pulmonary vasoconstriction (improves V/Q mismatch) Vertical gradient of pleural pressure - transpulmonary pressures affecting alveoli are different throughout the lung, as changes to the shape of the horacic cavity are unequal. Base expands more than apex. Compliance differences - more compliant areas are better ventilated for a given pressure, apical lung is more inflated and distended at baseline, leaving the base more compliant and therefore better ventilated Ventilation based pathology Perfusion based pathology
37
V/Q ratio in the normal upright lung - Apex - V/Q 1 - Bases
Apex V/Q >1 usually around 3' At the 3rd rib equal to the midzones is the V/Q ratio of 1 Lung bases have aV/Q ratio of 0.6 usually when upright
38
What does V/Q of infinity mean
Dead space ventilation
39
What does a V/Q of 0 mean
No ventilation, shunt
40
Average V/Q ratio of the lung is?
0.8
41
What is the V/Q ratio when supine?
Close to 1 throughout the lung
42
The lower the V/Q ratio what happens?
Close to true shunt and mixed venous blood
43
What is the relationship between PaO2 and V/Q? How does this compare to PACO2
◦ The relationship between PaO2 and V/Q is steeper and more sigmoid than the relationship between PaCO2 and V/Q.
44
Draw the relationship between PaO2 and VQ
◦ The relationship between PaO2 and V/Q is steeper and more sigmoid than the relationship between PaCO2 and V/Q.
45
Draw the relationship between PaCO2 and VQ
◦ The relationship between PaO2 and V/Q is steeper and more sigmoid than the relationship between PaCO2 and V/Q.
46
Draw the relationship between blood oxygen content and VQ
◦ The relationship between PaO2 and V/Q is steeper and more sigmoid than the relationship between PaCO2 and V/Q.
47
What effect does low V/Q have on oxygen? How can it be reversed? Under what conditions can it not be reversed?
◦ The relationship between PaO2 and V/Q is steeper and more sigmoid than the relationship between PaCO2 and V/Q. ◦ Low V/Q values (V/Q ratios between 0 and 1) result in hypoxia ◦ The hypoxia due to low V/Q ratio is reversible with increased FiO2 ◦ "True" shunt where V/Q = 0 does not improve with increased FiO2
48
Why does Low VQ effect oxygen so markedly
‣ Areas with reduced ventilation have marked reduction in oxygen delivery in proportion to blood flow and have an effluent oxygen saturation markedly reduced comparted to V/Q 1 ‣ Areas with higher V/Q ratios elsewhere in the lung will have reduced blood flow - and due to fixed amoutn of oxygen blood is able to carry due to the maximum oxygen carrying capacity of haemoglobin (plateau of oxyhaemoglobin dissociation curve) the oxygen content of the combined blood flows is not markedly raised by these areas
49
What is normal minute vnetilation
4L/min
50
Draw a diagraph presenting blood flow vs ventilation as a function of areas of the lung
51
What is the normal V/Q ratio for the lungs? Relate this to normal physiology
0.8 Ventilation - 4L/min on average Cardiac output 5L/min on average
52
Why is there regional varition in perfusion 4
Gravity and its effect on blood flow through low presurre pulmonary circulation - Pulmonary vascular architecture ‣ Lung volume (atelectasis increases pulmonary vascular resistance) ‣ Hypoxic pulmonary vasoconstriction
53
Why is there regional variation in ventilation 4
Gravity - weight of lung producing a vertical gradient i pleural pressure Posture - changes the direction of the pleural gradient Anatomical expansion potential - bases have more room to expand than the apices Lung compliance - improved in the bases compared to the apices Pattern of breathing
54
Explain the pleural pressure gradient
55
What is V/Q scatter
* The distribution of lung units along a spectrum of V/Q ratios is referred to as "V/Q scatter" * In a normal young person, this "scatter" spans a V/Q range between 0.6 and 3.0
56
Draw a V/Q scatter plot for the effect of age on lungs
This reflects rising closing capacity and basal shunt
57
2 methods of measurnig V/Q mismatch
Functional techniques - MIGET, 3 compartment model Imaging techniques - radionucleitide imaging, SPECT V/Q sacns, PET scans and MRI using IV gadolinium and 3He or 129Xe
58
What is the MIGET model used to measure? How does it do this?
V/Q mismatch Multiple inert gas elimination technique using 6 dissolved gasses infused IV - AV difference concentration and known blood:gas partition coeffcient is used to determine the distribution of V/Q
59
What is the 3 compartment model and what is it used for?
Assumes 3 gas exchange units - Dead space - True shunt - V/Q 1 Requires PaO2, PaCO2 and estimation fo alveolar O2 and CO2 partial pressures Magnitude of shunt as a proportion of cardiac output and magnitude of dead space
60
How do imaging technqiues for V/Q mismatch work
◦ SPECT V/Q scans- regional distribution of blood flow and ventilation can be calculated - poor V/Q matching is visually inspected. Regional distribution of these radionuclides is measured by a camera detecting gamma rays, perfusion measured using IV Tc labelled albumin; 133 Xenon used for ventilation ◦ PET scans - same as above but positron emitter isotopes (13N2) instead of gamma ray emitters ◦ MRI using IV gadolinium and 3He or 129Xe
61
What is the difference between V/Q scatter and true shunt
Distinguishing true shunt from V/Q scatter - V/Q scatter is where areas have reduced ventilation and therefore contribute a reduced oxygen supply to the blood supply, but for it to be true shunt the V/Q ratio needs to be zero * V/Q scatter hypoxia will improve with supplemental O2 --> as even with reduced ventilation you can deliver a normal oxygen supply to the alveolus just with reduced volume and hgiher FiO2
62
What area of V/Q does the largest change in gas exchange occur
betwen 0.1 and 1 Improving the ventilation of a severely underventilted region from V/Q 0.01 to 0.1 doesn't accomplish much
63
What effect do high V/Q areas have in the lung
* Due to alveolar content having high oxygen and low CO2 the increased equilibration can lead to dramatic changes in effluent blood * Effluent blood closely resembles alveolar gas - what little blood flows is maximally ventilated and therefore increasing ventilation further has no effect on increasing gas exchange - and increasing FiO2 does not add a great deal as oxygenation is already maximal * Their total contribution to gas exchange is minimal because blood flow as a proportion is minimal
64
What impact does emphysema have on V/Q
Large excess ventilation with poor perfusion - large dead space
65
What impact does chronic bronchitis have on V/Q
Large amount of blood flow to poorly ventilated regions --> hypoxia as effluent resembles mixed venous blood
66
What effect does asthma have on V/Q
25% of blood flow to poorly ventilated lung units with V/Q of 0.1 - similar to chronic bronchitis patients this leads to hypoxia. The low shunt value is probably due to collateral pendelluft and therefore get enough oxygen
67
How much dead space is there?
150mls 20-35% fo tidal volume
68
What is an average expired CO2
25mmGHg
69
How might alveolar dead space be increased
Arterial pressure based - Reduced cardiac output - Posture - sitting up increased alveolar dead space in apices, lying down reduces it - Extremes of graivty or accelarations Focal - Pulmonary vascular occlusion Alveolar pressure based - High posiutive pressure ventilation pushing blood out of well ventilated reginos, increased PEEP may actually increased dead sapce - Lung parenchymal disease
70
What affects anatomical dead space 4
◦ Body size - ~2ml/kg of IBW (higher in infancy at 3ml/kg) ◦ Posture - intrathoracic anatomical dead space decreases as lung volume decreases (smaller when supine as all volumes smaller) ◦ Airway manoeuvres - jaw thrust and chin lift adds 40ml ◦ Lung volume - dead space increases with hyper expansion as smaller airways pulled apart by traction ◦ Age - minimal change, but the extra thoracic airway does change a little ◦ Bronchospasm - potentially but has not been proven to ◦ Bronchiectasis - no change found in test subjects although theoretically with dilated bronchioles it would be increases
71
Describe the effects of different apparatus to dead sapce
‣ ETT - smaller volume than upper airway (decreases anatomical dead space by up to 50%) ‣ Tracheostomy - bypass upper airway altogether (decreases anatomical dead space by up to 50%) ‣ BiPAP mask - increases anatomical dead space by 50ml
72
Why does anatomical dead space vary with tidal volume?
* TV below expected anatomical dead space does lead to some gas exchange * Anatomical dead space decreases in proportion to tidal volume * Why? ◦ Laminar flow - low flow rates lead to the less turbulent flow so a relatively small central column can move in and out of alveoli while peripheral gas in conducting airways remains undisturbed ◦ Expiratory gas mixing - slow movement of gas allows for diffusion
73
Define shunt
* Shunt is the blood which enters the systemic arterial circulation without participating in gas exchange
74
What is venous admixture
* Venous admixture is that amount of mixed venous blood which would have to be added to ideal pulmonary end-capillary blood to explain the observed difference between pulmonary end-capillary PO2 and arterial PO2
75
How is venous admixture different to shunt
◦ Venous admixture is different to shunt - as venous admixture accounts ofr contribution of Thebesian veins and alveolar regions with V/Q ratios between 0 -1 (i.e. treats alveoli like they either have V/Q off 1 or 0) - it is only calculated
76
What is the shunt equation eponymous name
Berrgren equation
77
Berrgren equations i
The shunt equation * Qs/Qt = (CcO2 - CaO2) / (CcO2 - CvO2) * where ◦ Qs/Qt = shunt fraction (shunt flow divided by total cardiac output) ◦ CcO2 = pulmonary end-capillary O2 content, same as alveolar O2 content * CtO2 (A) is the alveolar oxygen content * CcO2 - CvO2 is the difference between mixed venous and perfect end capillary blood ◦ CaO2 = arterial O2 content - lower than the CcO2 ◦ CvO2 = mixed venous O2 content - returning to the lungs at a flow rate equal to cardiac output (Qt) ◦ O2 content can be calculated by removing the dissolved oxygen from the equation for oxygen content and calculating based on Sats x 1.39 x Hb
78
What is the shunt equation
* Qs/Qt = (CcO2 - CaO2) / (CcO2 - CvO2) * where ◦ Qs/Qt = shunt fraction (shunt flow divided by total cardiac output) ◦ CcO2 = pulmonary end-capillary O2 content, same as alveolar O2 content * CtO2 (A) is the alveolar oxygen content * CcO2 - CvO2 is the difference between mixed venous and perfect end capillary blood ◦ CaO2 = arterial O2 content - lower than the CcO2 ◦ CvO2 = mixed venous O2 content - returning to the lungs at a flow rate equal to cardiac output (Qt) ◦ O2 content can be calculated by removing the dissolved oxygen from the equation for oxygen content and calculating based on Sats x 1.39 x Hb
79
How can the shunt equation actually measure true shunt
Make the aptient breathe 100% FiO2 deecreasing the contribution of V/Q scatter
80
Even with 100% FiO2 what is the problem with the shunt fraction calculated?
Does not separate true shunt from anatomcal shunt - Cardiac defects - Thebesian veins - Bornchial veins
81
What is normal veinous admixture
3%
82
What is normal shunt fraction
0.4 - 1% Some places say 0
83
What does normal veinous admixture come from 4
1. Anatomical - Physiological shunt through bronchial veins and thebesian veins - true intrapuilmonary shunt - intracardiac shunts 2. V/Q scatter - V/Q <1 3. Pathological anatomical shunts e.g. AVM, tumours, portopulmonary shunts 4. Measurement shunt where mixed venous sample is not available
84
What % of cardiac output do the bronchial veins contribute as shunt
<1% Unless COPD or bronchiectasis when can by 10% of cardiac output, or higher in ARDS etc
85
Thebesian veins contribute what % of cardiac output
0.1-0.4%
86
In the shunt equation what is the numberator and what does this mean
(CcO2 - CaO2) is the difference in oxygen content between "perfect" endcapillary blood and systemic arterial blood; this drop in oxygen content is due to the venous admixture.
87
In the shunt equation what is the denominator and what does that mean?
(CcO2 - CvO2) is the difference in oxygen content between mixed venous and "perfect" endcapillary blood
88
What effect does shunt have on oxygenation
◦ With worsening shunt, the oxygenation of arterial blood will decrease ◦ PaO2 of arterial blood decreases roughly in proportion to increasing shunt
89
What effect does increasing FiO2 on shunt have? When does this stop being effective?
◦ The greater the shunt, the less effect increasing FiO2 has on improving oxygenation ◦ With a shunt fraction of 50% or more, increasing the FiO2 will have minimal effect on the PaO2 ◦ At a shunt of 50% at room air - arterial oxygen tension is 53mmHg; even a shunt fraction of 25% drops arterial oxygen saturation to low 90%
90
What effect does shunt have on PaCO2
little effect
91
Why does shunt not have a large effect on PCO2?
◦ The main reason is the increase in alveolar ventilation associated with hypercapnia and also hypoxic triggered ventilation ‣ The only reason CO2 will increase is if there is a failed capacity to increase minute ventilation
92
If alveolar ventilation was not increased how much would PaCO2 change at a shunt fraction of 50%?
15-30%
93
Under what circumstances are you more likely to see shunt affecting PaCO2?
◦ In patients who are unable to increase their alveolar ventilation, PaCO2 may increase sllightly (eg. by up to 15-30% with a shunt fraction of 50%) ◦ Low cardiac output and metabolic acidosis increase the effect of shunt on PaCO2 ‣ Metabolic acidosis suppresses the Haldane effect increasing PaCO2 ‣ Poor cardiac output = increased mixed venous CO2 and more CO2 going through the shunt
94
Shunt vs PaO2 graph
95
Draw a diagram relating PaCO2 to ventilation and what FiO2 is required to normalise PaO2
96
Draw a diagram showing the effect of shunt on PaO2 at different FIO2
97
Describe the steps of oxygen cascade
Atmospheric air 21% FiOw 159mmHg Airway gas diluttion by water vapour --> 21% of 713mmHg --> 150mmHg Alveolar gas mixture diluted by CO2 --> 99mmHg Diffusion to end carpillary blood essentially the same but some veinous admixture Arterial blood PaO2 92mmHg Tissue oxygen tension 10-30mmHg depending on the tissue Mitochondrial oxygen tension 1-10mmHg Pasteur point 1mmHg
98
What is the Pasteur point
0.8mmHg The oxygen tension at which aerobic metabolism ceases
99
Atmospheric air has what PaO2
159 at sea level
100
Airway gas mixture once humidified - what PaO2
149mmHg
101
What is the isothermic boundary
Water tension 47mmHg 5cm below the trachea
102
Alveolar gas mixture can be defined by
‣ PaO2 = (FiO2 x (p atmos - p H20)) - (PaCO2/RespQ)
103
Why is PaO2 lower in the alveolus
It is diffusing into the blood stream And CO2 is present diluting it
104
WHat i the respiratory gas equation
‣ PaO2 = (FiO2 x (p atmos - p H20)) - (PaCO2/RespQ)
105
What is the alveolar gas equation
‣ PaO2 = (FiO2 x (p atmos - p H20)) - (PaCO2/RespQ)
106
How do you calculate the PaO2 in an alveolus
‣ PaO2 = (FiO2 x (p atmos - p H20)) - (PaCO2/RespQ)
107
How do you calculcate the CcO2 in the pulmonary shunt equation?
‣ PaO2 = (FiO2 x (p atmos - p H20)) - (PaCO2/RespQ)
108
Diffusion has what effect on PaO2 in the normal lung
◦ There is a minor difference due to V/Q mismatch which occurs at a baseline in health, but for those adequately perfused and ventilated there is no difference ◦ It is only with exercise that diffusion became a reason for difference ◦ Blood entering the lung has an oxygen content of 97ml/L if Hb 100, and blood exiting has a oxygen content of 130ml/L ◦ At mild- moderate exercise the diffusion difference accounts for a 11mmHg difference
109
What is the normal A-A gradient
age/4 + 4 Young people it is 7 Old is is 14
110
What is tissue oxygen tension
◦ Drops due to the diffusion distance, and is drastically different between different tissues ◦ Varies from tissue to tissue, usually about 10-30mmHg ‣ As high as 72 in the kidney and as low as 8 in peripheral skin
111
What is mitochondrial oxygen tension at baseline
1-10mmHg
112
What is Grahams law
Reflects the rate of diffusion of a gas is inversely proportional to the square root of the molar mass of its particules --> the denser the gas the slower the transfer Thus if the molecular weight of one gas is 4x the other then it diffuses at 1/2 the speed
113
What are the 3 factors that determine diffusion in the lungs
1. Ficks factors 2. Capillary transit time 3. Protein binding reactions and their rate
114
What 4 factors affect diffusion coefficient
* The diffusion coefficent of gasses is influenced by ◦ Molecular size - stable and predictable ◦ Temperature - mostly stable in human lungs ◦ Fluid viscocity/chemical properties of the membrane - altered by disease e.g. pulmonary fibrosis ◦ Density of the gas - in so far as it factors into graham's law
115
What is the alveolar surface area for diffusion? What affects this
◦ Alveolar membrane surface area ‣ Maximum available surface area is around 140 meters squared ‣ INfluenced by old age and disease ‣ Degree fo pulmonary alveolar recruitment - atelectasis, posture, FRC volume, closing capacity
116
What is the cpillary surface area of diffusion? What affects this?
‣ Maximum available surface area around 125meters squared ‣ Influenced by degree of pulmonary capillary recruitment, pulmonary blood flow and blood volume
117
What is the minimum capillary transit time for adequate gas exchange
0.25 - 0.45 seconds
118
What si the usual cpillary transit time for gas exchange
0.75 seconds
119
What factors will influence capillary transit time
Cardiac output Blood volume
120
Rate of protein binding reaction and its influence on diffusability of gasses
◦ Oxygen haemoglobin association - finite reaction rate, it is much faster than the diffusion rate though --> bound oxygen does not exert a partial pressure thus there is a constant gradient ◦ Carbonic anhydrase conversion of HCO3 to CO2 ◦ Other gasses e.g. volatile anaesthetics also bind to serum proteins and triglycerides ◦ Carbon dioxide also binds serum and erythrocyte proteins, but most important chemical reactions which influences its diffusion is the conversion of bicarboante into CO2 by carbonic anhydrase
121
What are the layers of diffusion for gases in the lung
Layers of diffusion required * Diffusion of one gas through another, in the alveolar gas mixture * Diffusion though aqueous compartments ◦ Alveolar surfactant water ◦ Cytosol of the alveolar lining cells, capillary endothelium and erythrocytes ◦ Plasma * Diffusion through lipid compartments ◦ Cell membranes ◦ Surfactant layer lipids * Diffusion though protein layers ◦ Alveolar basement membrane ◦ Protein contents of surfactant layer and the cell cytosol Layers: * Alveolar gas transfer * Surfactant * Type 1 cell * Basal lamina * Capillary endothelium * Plasma * Red cell
122
What effect does exercise have on diffusion
It improves it from 20-30ml/min/mmHg --> 100-120ml/min/Hg It increases because oxygen uptake is increased because of - Increased surface area with larger tidal volumes - Pulmonary blood flow increases - V/Q matching improves with recruitment of capillary beds
123
What 3 factors accoutn for improved observed diffusion in exercise
- Increased surface area with larger tidal volumes - Pulmonary blood flow increases - V/Q matching improves with recruitment of capillary beds
124
Why does the partial pressure of oxygen improve during exercise? 3
◦ Oxygen extraction ratio increases, decreasing the PO2 of mixed venous blood ◦ Increased minute ventilation decreases the alveolar PCO2 (thus increasing the alveolar PO2, all other things remaining equal) ◦ Increased delivery of haemoglobin to the absorptive surface acts as an oxygen sink and maintains a low capillary partial pressure
125
What is the diffusion capacity?
The diffusing capacity is defined as the volume of gas that will diffuse through the membrane each minute for a partial pressure difference of 1mmHg. * Net rate of gas transfer/ partial pressure gradient * For O2 - 20-30ml/min/mmHg. * For CO2 20x greater than O2
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What is the normal value at rest for diffusion capacity
20-30ml/min/mmHg
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What factors introduce error into the measurement of diffusion capacity?
◦ Loss of carbon monoxide to extravascular alveolar haemoglobin, eg. in the context of alveolar haemorrhage due to Goodpasture syndrome ◦ Presence of "homegrown" carbon monoxide, due to smoking or extensive haemoglobin breakdown (eg. intravascular haemolysis) which could limit CO uptake ◦ Competition between CO and oxygen (if the patient had been previously breathing 100% FiO2, for example) ◦ Haemoglobin concentration, when low, can falsely decrease the DLCO measurement even though the performance of the alveolar/capillary complex remains completely healthy
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What is the principle of diffusion measurement?
Small dose of carbon monoxide to inhale, hold their breath for 10 seconds then exhale. Any carbon dioxide not exhaled has diffused
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DLCO =
= carbon monoxide uptake / carbon monoxide gradient ‣ Gradient is assumed to be between alveolar partial pressure of CO (known as you gave the dose) and arterial pressure of CO which is 0 as it is all bound to Hb
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How is diffusing capacity measures?
Single breath carbon monoxide test ‣ Breathing room air, then exhales maximally down to RV ‣ Then inhales with a vital capacity breath 0.3% carbon monoxide and 10% helium (helium measuring alveolar volume) ‣ Breath hold for 10 seconds - ideally hoping for equal distrbiution of CO between lung units regardless of time constant. Avoid valsalva ‣ Exhales - first 0.75L ignored as dead space ‣ Gas sample then take * Total alveolar volume measured from expiratory helium - tracer gas dilution measurement * CO determined from difference between inhaled and exhaled partial pressure
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What does diffision limited gas exchange mean?
* Exchange where the rate of gas uptake in the capillary is determined by the rate of diffusion across the blood-gas barrier Where the rate of diffusion is slow ◦ For all of the length of the capillary, the gradient between the alveolus and the blood remains high ◦ An increase in the capillary blood flow rate will have minimal effect on gas uptake ◦ An increase in the partial pressure gradient between the alveolus and the capillary will increase the rate of difffusion ◦ An example of a diffusion-limited gas is carbon monoxide
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Perfusion limited gas exchange means what
* Exchange where the rate of gas uptake in the capillary is determined by capillary blood flow:
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In a perfusion limited gas what is the rate of diffusion
Rapid
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Where does equilibration occur between alveolus and capillary in a perfusion limited gas
Very early in the capillary
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Where does equilibration occur between a alveolus and a capillary in a diffusion limited gas
Towards the end of the capillary
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In a diffusion limited gas what is the rate of diffusion
Slow
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What is the effect of increasing blood flow on a diffusion vs a perfusion limited gas
Diffusion limited gas - it will have no effect Perfusino limited gas it will increase gas uptake until capillary transit time is faster than gas diffusion time
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Increasing partial pressure between gas and blood has what effect on perfusion limited gasses?
Minimal as they are only limited by blood flow
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What are examples of perfusion limited gasses
Oxygen Carbon dioxide Nitrous oxide
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Under what conditions does oxygen become diffusion limited
◦ Gas exchange membrane affected by oedema or fibrosis ◦ Low oxygen environments due to insufficient partial pressure gradient ◦ Extreme exercise
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Outline West zone 1 and the determinants of flow
West zones (upright lung) - describe regional blood flow through the lungs accounting for the starling resistory moel where the resistive force is alveolar pressure • Definition ◦ PA = alveolar ◦ Pa = arterioles ◦ Pv veinous • Zone 1: PA > Pa > Pv ◦ Practically no blood flow in these regions as BV collapse producing V/Q >1 and dead space (V/Q = infinity). Does not occur in healthy lung • Zone 2: Pa > PA > Pv ◦ Rate of blood flow determined by difference between Pa and PA - BF increases linearly from the upper parts of the zone to the lower parts of the zone as hydrostatic pressure increases Pa ◦ V/Q ~3 in the upper lung falling to 0.6 in the lower parts of the lung • Zone 3: Pa > Pv > PA ◦ Blood flow determined by arteriovenous driving pressure, blood flow highest and V/Q <1 • Zone 4: the interstitial pressure is higher than alveolar and pulmonary venous pressure (but not pulmonary arterial pressure)
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Outline Wests zone 2 and the determinants of flow
West zones (upright lung) - describe regional blood flow through the lungs accounting for the starling resistory moel where the resistive force is alveolar pressure • Definition ◦ PA = alveolar ◦ Pa = arterioles ◦ Pv veinous • Zone 1: PA > Pa > Pv ◦ Practically no blood flow in these regions as BV collapse producing V/Q >1 and dead space (V/Q = infinity). Does not occur in healthy lung • Zone 2: Pa > PA > Pv ◦ Rate of blood flow determined by difference between Pa and PA - BF increases linearly from the upper parts of the zone to the lower parts of the zone as hydrostatic pressure increases Pa ◦ V/Q ~3 in the upper lung falling to 0.6 in the lower parts of the lung • Zone 3: Pa > Pv > PA ◦ Blood flow determined by arteriovenous driving pressure, blood flow highest and V/Q <1 • Zone 4: the interstitial pressure is higher than alveolar and pulmonary venous pressure (but not pulmonary arterial pressure)
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Outline West zone 3 and what it corresponds to
West zones (upright lung) - describe regional blood flow through the lungs accounting for the starling resistory moel where the resistive force is alveolar pressure • Definition ◦ PA = alveolar ◦ Pa = arterioles ◦ Pv veinous • Zone 1: PA > Pa > Pv ◦ Practically no blood flow in these regions as BV collapse producing V/Q >1 and dead space (V/Q = infinity). Does not occur in healthy lung • Zone 2: Pa > PA > Pv ◦ Rate of blood flow determined by difference between Pa and PA - BF increases linearly from the upper parts of the zone to the lower parts of the zone as hydrostatic pressure increases Pa ◦ V/Q ~3 in the upper lung falling to 0.6 in the lower parts of the lung • Zone 3: Pa > Pv > PA ◦ Blood flow determined by arteriovenous driving pressure, blood flow highest and V/Q <1 • Zone 4: the interstitial pressure is higher than alveolar and pulmonary venous pressure (but not pulmonary arterial pressure)
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Why are there regional differences in perfusion
1. Gravity 2. Lung volume 3. Hypoxic pulmonary vasoconstriction 4. Variation in PAP during cardiac cycle causes some units to move from West Zone 1 to West zone 2 between diastole and systole 5. Anatomical architecture
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How does gravity cause a regional variation in pulmonary perfusion
◦ Gravity - The lower pressure of pulmonary vasculature causes hydrostatic pressure variations to have a proportionally greater influence on flow ‣ Gravity causes increased hydrostatic pressure in dependent areas --> increasing pressure and perfusion (i.e. base is better perfused than apex) ‣ posture (upright vs supine) - supine positioning causes perfusion to equalise between apex and base with some smaller regional changes between anterior and posterior. Upright effects described above
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Why is there regional differences in ventilation?
1. Gravity 2. Anatomical expansion potential - bases have more room to expand due to the shape of the thoracic cavity 3. Lung compliance - more compliant lung regions will be better ventilated at any trans pulmonary pressure 4. Mode of breathing - voluntary, shallow/deep, mechanical
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What is the vertical pleural pressure gradient
‣ Gravity (the weight of the lung) which produces a vertical gradient in pleural pressure - pleural pressure mor enegative at the apex than the base, apical alveoli are more distended with reduced capacity to distend on inspiration. Base better ventilated * Posture, which changes the direction of this vertical gradient
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Define dead space
The area of the lung not participating in gas exchange
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What does the alveolar CO2 vary between in the lung
28 and 42 due to V/Q differences in the upright lung 42 at the base
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What causes the drop in PO2 from 149 --> 100mmHg in inspired gas to the alveolar gas
Balance of delivery of oxygen to the alveoli in inspired gas an uptake of oxygen in pulmonary capillaries The dilution of oxygen by inspired water only accounts for the drop from 159mmHg in dry air to 149mmHg in fully saturated inspired gas
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Why is PO2 of arterial blood lower than alveoli?
Veinous admixture
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Average PO2 dependent on age =
100 - 1/3 age
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What 6 differences are there between the base adn apex of the lung in a healthy uprgiht adult?
Alveoli at the top of the lung 1. Larger at end expiration 2. Lower ventilation 3. Lower perfusion 4. Higher V/Q ratio 3 vs 0.6 V/Q difference results in different PO2 and PCO2 - PO2 132mmHg vs 89mmHg - PCO2 28mmHg vs 42mmHg pH therefore 7.51 vs 7.39
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How different are the pulmonary artery pressures betweent he top and bottom of an upright lung if healthy
30mmhG
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Ventilation gradient in the lung due to
1. Intrapleural pressure gradient - weight of the lung causing a gradient of intrapleural pressure from the top -10cm H20 to -2.5cmH20 2. Gradient of alveolar size - apical alveoli larger because more negative apical intrapleural pressure 3. Ventilation gradient - gradient in alveoalr size at FRC means alveoli increase in size byb different amounts as they are on different parts of the compliance curve
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How is a ventilation gradient impacted by a person breathing at just above residual volume? Describe the effect
Ventilation of the apex is now better than the base, as the IPP of the apex is lower now around -3cmh20 and IPP at the base is +3.5 and the lower lung volume decreases the ize of the lungs elastic recoil forces This will exacerbate V/Q mismatch
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Define hypoxia
Presence of tissue PO2 levels low enough to have adverse effects on tissue function OR when the process of oxidative phosrphorylation stops due to inadequate utilisation of oxygen
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Hypoxaemia
Presence fo abnormally low PO2 levels in arterial blood
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Hypoxia mechanisms
Hypoxic Anaemic Circulatory Histotoxic/cytotoxic
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Define shunt
Blood which enters the arterial system without passing through ventilated areas of the lung
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Veinous admixture
The amount of mixed veinous blood that would have to be added to end pulmonary capillary blood to account for differences with arterial blood
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