Respiratory

Question 1

How much Co2 is produced by an average adult? How much CO2 is stored in the body?

Answer 1

Typically when well an adult produced CO2 at a rate of approximately 200ml/min, however during vigorous exercise this can increase to up to 4000mL/min.
About 120L of CO2 is stored in the body in various forms.

Question 2

how is Co2 circulated in the body?

Answer 2

There are 3 forms in which Co2 is transported in the circulation;
1) dissolved in plasma, similar to O2 it is proportional to the partial pressure, however CO2 has a solubility co efficient 20 times greater than that of O2 meaning this contribution is much greater.
2) bound to Hb and other proteins. Terminal amine groups can react with Co2.
3) bicarbonate: the enzyme carbonic a hydrate catalyses CO2 and H2O to form H2CO3. CA is present in the cytoplasm of red blood cells but is absent in plasma. So the reaction occurs in RBCs and then dissociates out as HCO3- and H+. The transport out of cells is mainly facilitated by the HCO3-/chloride co transporter. H+ is bound to histidine residues which are Hb side chains.

Fun fact- deoxygenated blood is more effective at binding H+ so the reaction can occur. The reaction results in a net gain of 1 Cl- ion which is osmotically active (vs CO2). This is the reason why the volume of venous RBCs is 3% greater than that of arterial RBCs.

Question 3

Describe the Haldane effect.

Answer 3

The Haldane effect is the observation that Deoxyhaemoglobin is a more effective net carrier of CO2 than Oxyhaemoglobin.

It is due to;
1) DeoxyHb more readily forms carbamino compounds (directly binding CO2)
2) DeoxyHb is a stronger base than OxyHb, thereby accepting H+ ions more readily facilitiating carboinic anhydrase to create HCO3-

Question 4

Describe the Bohr effect

Answer 4

This describes the finding that increased CO2 tension and/or reduced pH shifts the p50 of Hb to higher P02 values. (Aka a right shift in the oxyhaemoglobin dissociation curve.)
So O2 has a lower binding affinity to Hb.

Question 5

How do the haldene and Bohr effects facilitate gas exchange and acid-base balance

Answer 5

Haldene- DeoxyHb is a more effective carrier of Co2 vs OxyHb
Bohr- increased Co2 and H+ cause a R shift if the oxyhaemoglobin dissociation curve.

So O2 is released at tissues that are more metabolically active and CO2 is more readily removed from regions of the body that has circulating DeoxyHb.
The converse is also true, as in the lungs with a high P02, DeoxyHb is converted to oxygenated Hb, meaning its ability to bind H+ and Co2 is decreased. So H+ is combined with HCO3- to form H2CO3 which is catalysed by carbonic anhydrase back to CO2 and H20 which dissolves out of RBC to the alveoli and out of the blood.
Thus the liberated Co2 diffusing away from the blood facilitates the loading of O2 onto Hb (Left shift in the oxyhaemoglobin dissociation curve.)

Question 6

How can airway resistance be measured?

Answer 6

To ascertain the resistance of the airways one requires simultaneous measurement of the pressure difference between the airway and alveoli, as well as the flow of gas at the level of the mouth.

There are no non invasive methods to directly measure the alveolar pressure so oesophageal balloon manometry can be used as a surrogate.

There are 5 main methods which are; Body plethysmography, Forced oscillation technique, interruptor resistance measurement, Inspiratory pause, and Rhinomanometry.

1) Body plethysmography

A subject breathing in a closed chamber generates pressure changes in that chamber, which are recorded.
Flow is measured simultaneously.
The changes in pressure and the flow are used to calculate respiratory resistance.  Can also calculate respiratory volumes. 

2) Forced oscillation technique

A pump or oscillator produces a sinusoidal pattern of airflow into a relaxed subject
The pressure changes at the airway are measured during this oscillation, and recorded for a range of frequencies (from 1 to 20 Hz)
The ratio of pressure measured to flow applied is analyzed across the frequency domain by mathmatical means (fast Fourier transformation)
The number produced by this is respiratory impedance (a combination of resistance and compliance) from which resistance can be calculated. 

3) interruptor resistance measurement

A normally breathing subject has their airway transiently occluded during respiration, for a short (100 msec) period.
The flow immediately before the occlusion and the pressure immediately after are used to calculate resistance

4) Inspiratory pause

Inspiratory breath hold is performed during mechnical ventilation
Flow delivered by the ventilator must be constant (square waveform)
The pressure difference between the peak pressure and the early plateau pressure are used to calculate resistance

5) Rhinomanometry

A normally breathing subject has probes inserted into both nasal cavities to measure pressure
Flow is measured simultaenously via a tight-fitted nasal mask
Recorded flow and pressure measurements are used to calculate resistance

Question 7

describe interruptor resistance measurement

Answer 7

Resistance is equal to the difference in pressure over flow.

This technique is based on the assumption that, when you transiently interrupt the respiratory gas flow by blocking the airway, the airway pressure and the alveolar pressure are equal. The occlusions are very brief, in the order of 100 milliseconds, and the devices designed for this purpose are generally automated, performing one of these occlusions in every breath. The airway pressure measured during the occlusion is opposed against atmospheric pressure to produce the ΔP.

The transient occlusion gives three pressures, of which the earliest measurement (the initial pressure measured immediately following the occlusion) is the one most closely related to airway resistance. In order to get the pressure closes to the occlusion (which can be obscured by post-occlusion pressure oscillations) the pressure trace is back-extrapolated from later pressures, to get a value about 15 milliseconds post occlusion.

Question 8

Describe how you can approximate airway resistance using mechanical ventilation.

Answer 8

When a mechanical ventilator delivers a breath, the pressure generated by a constant flow of gas into the patient is a combination of lung compliance and airway resistance. By ending the inspiration and holding the breath, one can eliminate the contribution of resistance.

The early drop in respiratory pressure is said to be wholely due to the airway resistance. A slower more gradual decline is later seen, which represents some combination of tissue relaxation and gas equilibration between lung units with different time constants. The most accurate means of measuring this is in an anaesthetised patient who is paralysed by muscle relaxant

Question 9

What factors effect airway resistance?

Answer 9

In summary the Gas properties, factors effecting airway diameter, airway length, and flow rate.
There is also resistance to the deformation of tissue (lung parenchyma 70%, chest wall 30%)
And inertia of gas and tissue.

Question 10

Describe some factors by which airway diameter can be effected.

Answer 10

Effects on smooth muscle tone:
Increased tone= bronchospasm, histamine release, parasympathetic nervous system agonists.

Decreased smooth muscle tone= bronchodilators, sympathetic nervous system agonists.

Decreased internal cross section=
Oedema, mucosal hypertrophy, encrusted secretions.

Mechanical obstruction/compression
Extrinsic masses/tumours
Dynamic compression as in forceful expiration
ETT kinking/obstruction.

Question 11

describe the volumes of the lung relative to weight

Answer 11

Question 12

what are the names and definitions of the lung volumes?

Answer 12

Question 13

Describe the FRC and what affects it?

Answer 13

FRC (functional residual capacity) is the volume of gas present in the lung at end expiration during tidal breathing
Composed of ERV and RV
This is usually 30-35 ml/kg, or 2100-2400ml in a normal sized person
It represents the point where elastic recoil force of the lung is in equilibrium with the elastic recoil of the chest wall, i.e. where the alveolar pressure equilibrates with atmospheric pressure.
The measurement of FRC is an important starting point for the measurement of other lung volumes.

This is important as
At FRC, the small airway resistance is low.
At FRC, lung compliance is maximal
FRC maintains a oxygen reserve which maintains oxygenation between breaths
At FRC, pulmonary vascular resistance is minimal (lungs too inflated=compression, too deflated=collapse of vessles and less diameter).
FRC acts to keep small airways open; If closing capacity is greater than the FRC, gas trapping and atelectasis can develop.

FRC can be effected by
Factors which influence lung size (height and gender)
Factors which influence lung and chest wall compliance (emphysema, ARDS, PEEP or auto-PEEP , open chest, increased intraabdominal pressure, pregnancy, obesity, anaesthesia and paralysis)
Posture (FRC is lower in the supine position)

If FRC decreases the consequences are;
Decreased lung compliance
Increased airway resistance
Increased work of breathing
Decreased tidal volume and increased respiratory rate
Decreased oxygen reserves
Increased atelectasis
Increased shunt
Increased pulmonary vascular resistance
Increased right ventricular afterload

Question 14

What methods can measure the volumes of the lungs?

Answer 14

To determine the volumes of the lungs, one must first measure the functional residual capacity (FRC).
FRC can be measured by 3 emain methods; 1) body plethysmography 2) inert gas dilution (I.E helium) or 3) nitrogen washout.

After FRC is determined ERV and IC can be determined by spirometry.
TLC= FRC + IC.

Question 15

how can you calculate FRC by means of body plethysmography?

Answer 15

The subject and the equipment are all confined in a rigid box which contains a known gas volume. subject breaths into a tube that measures pressure.

So the volume of the chest is unknown but the volume of the box is as well as the pressures in the box and chest are all known/measured.

Boyles law states P1V1=P2V2

Therefore the only unknown component, being the chest volume can be determined.

Body Plethysmography can also be used to calculate airway resistance.

Question 16

How can FRC be calculated by means of nitrogen washout?

Answer 16

The subject is made to breathe 100% FiO2.
The nitrogen concentration of exhaled gas is measured
As the intrathoracic nitrogen content approaches zero, the total exhaled nitrogen volume can be calculated from its concentration in the exhaled gas
The intrathoracic gas volume can then be calculated from the total volume of exhaled nitrogen gas and the nitrogen concentration of the first breath as;

total volume (ml) = total amount divided by concentration.

Nitrogen washout can also be used to determine the closing capacity of the lung.

Question 17

How can FRC be calculated by means of inert gas dilution?

Answer 17

A container is filled with a known volume and concentration of an inert tracer gas (typically helium) and then this mixture is introduced to a closed circuit with the respiratory system.

The new concentration of the inert tracer gas can then be measured.

The intrathoracic volume can then be measured using the equation :

C1V1= C2 (V1+V2)

there are some issues with this method;
No gas is perfectly insoluble and some tracer will be lost.
relies on the tracer being evenly mixed across the intrathoracic gas volume, which may not happen if there are areas of gas trapping.

Question 18

Define closing volume and closing capacity

Answer 18

closing volume can be defined as
“The maximal lung volume at which airway closure can be detected in the dependent parts of the lungs”
(from Nunns)

In other words, the closing capacity is the point in expiration where the lung volume falls enough for small airways to collapse. Any volume above this capacity is therefore characterised by nice open terminal bronchioles and alveolar ducts. When the small airways collapse, they tend to first collapse at the bases of the lung, because that is where the lung is at its most squashed.

The closing capacity is a capacity of the lungs, which by convention means that it is a composite space, created by the combination of residual volume and closing volume. The latter is the volume of gas which represents the difference between closing capacity and residual volume.

Question 19

In short why do small airways tend to collapse?

Answer 19

The peripheral small airways (terminal bronchioles and alveolar ducts) constantly tend to collapse, partly due to the Law of Laplace and partly because they are largely devoid of rigidity-enhancing cartilage.
During normal respiration, these airways are kept splinted open by the stretch of alveolar septal elastic tissue

As the lung inflates, this stretch increases 
This accounts for the decrease in airway resistance associated with increases in lung volume

Thus, as the lung volume decreases, so the airway diameter decreases
Therefore there is a lung volume at which the stretch can no longer oppose the forces acting to collapse the airway, and the airway closes, trapping some of the gas.
Because of the effects of gravity on the lung, the airways in the dependent regions of lung are the smallest, and therefore the most prone to collapse.

Question 20

How can closing capacity be measured?

Answer 20

The gas bolus method described by Dollfuss et al can be used to measure the closing volume of the lungs. to determine capacity RV needs to be determined and added to the closing volume. To measure closing volume;

1) subject exhales maximally to residual volume- this closes the dependent airways.
2) subject slowly inhales up to TLC
3) as they are doing this a small bolus of a tracer gas is delivered (this was radioactive xenon in the original study).
4) Because of the closure of the dependent airways at RV, the the upper alveoli get the majority of the tracer.
5) after filling their lungs the subject slowly exhales back down to RV
6) measuring the tracer volume during this maneuver shows 4 distinct stages, with the 4th stage being able to be used to measure closing volume.

The stages are;
Phase 1- dead space gas comes out, which has no tracer gas in it
Phase 2- tracer gas concentration increases as alveolar gas comes out.
Phase 3- a plateau of tracer concentration is reached, as the tracer content of these “middle” alveoli will be relatively even.
Phase 4- as closing capacity is reached, the dependent (tracer less) alveoli close, and only the open tracer-rich alveoli continue with the exhalation. As this happens, the tracer concentration being exhaled is no longer diluted by the air of these dependent alveoli. The effect of this is an increase in the measured tracer concentration.

Question 21

what factors alter the closing capacity?

Answer 21

factors include;
1) expiratory airflow- closing capacity increases with increased exp air flow (to the extent that it doubles when flow goes from 30 to 60L/min)

2) expiratory effort- closing capacity is increased with forceful exp efforts, through additional pressure/strain on the dependant alveoli exerted by the chest wall.

3) small airway disease- asthma and COPD increase the mucous content of the peripheral airways which makes their collapse earlier in the respiratory cycle.

4) increased pulmonary blood volume- more blood= more weight = more collapse.

5) Decreased pulmonary surfactant- increased surface tension- more collapse.

6) parenchymal lung disease- decreased lung elasticity

7) Age- older age= larger closing capacity which is largely just an increase residual volume due to decreased elasticity.

Question 22

how does age change the various lung volumes?

Answer 22

as age progresses-
tidal volume remains similar
residual volume gradually increases from age 40.

approximately age 75 an erect man will have a closing capacity greater than their FRC.

Question 23

why do I care about closing capacity?

Answer 23

1) effects denitrogenation- collapsed lung cannot participate in preoxygenation for induction.
2) It influences atelectasis, once closed if the remaining gas is absorbed the area will become atelectasis, and the shunt form this is a significant contributor to hypoxia in anesthetized patients.
3) it aggravates lung injury- cyclic atelectasis is bad for the lung and is a component of ventilator associated lung injuries.

Question 24

how does absolute humidity differ from relative humidity? what implication does this have on inspired air?

Answer 24

Absolute humidity is the mass of water vapour present in a given volume of air.

Relative humidity is the ratio of the mass of water vapour in a given volume of air to the mass required to saturate that given volume of air at the same temperature. It is usually expressed as a percentage.

at higher temperatures the vapour pressure of water also increases meaning a certain saturation of air at a cooler temperature will only be a fraction of that once at body temperature.

Let’s say the absolute humidity of air at 20°C is something like 17g/m3, which represents a relative humidity of 100%. When warmed to body temperature, the absolute humidity remains the same (17g/m3. However, fully saturated air at 37°C actually contains 44g/m3. Thus, warming this air to body temperature reduces the relative humidity to 39%. Additional energy is expended on evaporating additional water so that the inspired gas reaches 100% humidity by the time it gets into the bronchi.

Question 25

Why is it necessary for the respiratory system to humidify inspired air? how does this typically occur?

Answer 25

Humidification of inspired air is important to avoid drying out mucosa and sputum, which leads to tissue damage and failure of the mucociliary elevator.

Optimal function requires a relative humidity of greater than 75%

The nose is: optimised for humidification as the septum and turbinates increase contact of air with mucosal surfaces by:
1) Increasing surface area
2) Generating turbulent flow

Humidifies inspired gas to 90%, compared to 60% for the mouth

In expiration:
Air cools in the upper airway
As cooler air has a lower saturated vapour pressure, moisture condenses on the airway and moisture is reabsorbed. This reduces potential water losses from the airway from 300ml.day-1 to 150ml.day-1.

Question 26

what are some of the limiting factors about the application of laplaces law in regards to alveoli?

Answer 26

Alveoli are not spherical. They are polygons. Laplace law applies only to to the very small curved region in the fluid where these walls intersect.

Alveoli do not collapse like deflating balloons, they fold like cardboard boxes. 

Alveoli are not independent, but rather interconnected and suspended against each other with bands of elastic connective tissue, which serves to support them and prevent their collapse.

Question 27

What is the effect on compliance for a water filed lung inflating vs air inflation? why is this relationship seen?

Answer 27

in 1929 Kurt von Neergaard experimented with a cats lungs demonstrating a pressure volume loop with normal air insuflation vs with saline.

the compliance was much greater with saline inflation.
This is because surface tension makes lung much more difficult to inflate, the act of filling the lungs with saline abolished the surface tension.

Of note the early poorly compliant aspect for the curve is also lost and a more linear initial pressure is seen.

Question 28

what is the effect on compliance of a lavaged lung?

Answer 28

The main difference in a lavaged lung is that it has had its surfactant removed.

With no substantial means to reduce alveolar surface tension the compliance of the lungs is effected accordingly.

The graph is a pressure volume loop from a study using rabbits lungs with vs without surfactant; your compliance is about halved.

Question 29

what is the composition of surfactant?

Answer 29

It is a complex soup of phospholipid
Of its dry mass,
85-90% is phospholipid
8-10% is protein - mainly SP proteins A B and C, all small (~4-5 kDa )
2-5% is neutral lipid, eg. cholesterol

Of the phospholipid components;

Dipalmitoyl phosphatidylcholine (DPPC, or lecithin) is about 2/3rds of the total phospholipid content, and does most of the surfactant work.

The rest are random phospholipids (a heterogeneous group), including phosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine, sphingomyelin and phosphatidylserine.

These latter elements are essential as they contribute to the stability of the mixture. For example, DPPC the star player surfactant is not really soluble in water, and tends to be a solid up to a temperature of 41.6 °C, unless there is a decent amount of phosphatidylglycerol in the mixture

Question 30

what are the differences in pulmonary and systemic vascular circulation?

Answer 30

The differences can be summed up as into 4 areas; anatomical, pressure/resistance, regulation and function

1) Anatomical
pulmonary- arteries are thin with minimal smooth muscle which are dependent on the alveolar pressure and effected by radial contraction with lung inflation. volume is about 500ml in a 70kg adult.
Systemic- arteries are thick walled with abundant smooth muscle. volume is 4500ml.

2) Pressure/resistance
Both systems receive the entirety of the cardiac output form the right and left ventricles, being about 5L/min at rest.
Pulmonary- low blood pressures 25-18 (sys) and 15 to 8 (dia) with a low trans pulmonary intravascular pressure gradient of only 10mmHg (difference between arteries and veins). this is owing to a low resistance
Systemic- relatively much higher pressures and resistance with a trans vascular pressure gradient of 100mmHg. The majority of the the resistance and pressure drop is in the arterioles.

3) Distribution/regulation-
pulmonary- limited ability to regulate flow other than hypoxic vasoconstriction. otherwise blood flow is effected by gravity, alveolar recruitment.
systemic- significant variation in the regional flow of blood based on organ demand. vessels dilate in response to hypoxia and hypercapnea.

4) function-
Pulmonary- facilitate gas exchange at the alveolar blood gas barrier- absorb oxygen and release carbon dioxide.
metabolism of angiotensin 1 and porstaglandins.
synthesises thromboplastin and heparin.
physically acts as a filter for emboli larger than 8um.
Systemic- delivery of oxygen and other substrates to tissue,
deoxyhaemoglobin binds CO2 and other metabolic waste is also cleared by the systemic circulation for delivery to the liver and kidneys.
synthesis’s nitric oxide and pro/anticoagulants.