A crash course in respiratory physiology

1. Oxygen delivery to the tissues.
2. Lung volumes
3. The alveolar gas equation
4. The concept of hysteresis.
5. West's zones & Ventilation - perfusion relationships
6. Hypoxic Pulmonary vasoconstriction
7. Gas exchange abnormalities

Dead Space
Shunt
Difffusion abnormalities

Control of breathing

You will recall the following equation from the haemodynamics tutorial:

The Delivery of oxygen to the tissues is determined by:

The amount of oxygen in the blood: the oxygen binding capacity of haemoglobin x the concentration of haemoglobin x the saturation of haemoglobin + the amount of dissolved oxygen all Multiplied by the Cardiac Output.

The cardiac output is determined by preload, afterload and contractility.

The haemoglobin concentration is determined by production, destruction and loss.

The SaO2 (the saturation of haemoglobin at arterial level with oxygen - as opposed

to the SpO2 which is measured by pulse oximetery) is determined by:

The oxygen saturation curve: which equates PaO2 (arterial oxygen tension) against SaO2.

The PaO2 is determined by:

The alveolar gas equation - which relates the FiO2 (inspired concentration) to the PAO2 (the alveolar concentration).

The diffusion capacity of oxygen across the alveolar-capillary interface.

Ventilation-Perfusion matching, where mismatches lead to 1. Dead space ventilation (alveoli are ventilated but not perfused). 2. Shunt (alveolar units are perfused but not ventilated).

The dissolved oxygen tension is determined by the atmostpheric pressure - the higher the pressure, the more O2 that is dissolved (hence the concept of hyperbaric oxygen in carbon monoxide poisoning).

The alveolar ventilation is determined by the expired minute volume (TV x RR) minus that part of the MV that is not available for gas exchange - the dead space ventilation. Anatomically this is the gas in the conducting airways. Physological dead space also exists, as we will see, in the upper regions of the lungs.

This is an essential component in the understanding respiratory physiology:

PAO2 = (FiO2 x P)* - PaCO2/R *PiO2

PAO2 = the alveolar concentration of oxygen; this is related to:

FiO2 = the concentration of oxygen in inspired air

P = Barometric pressure minus water vapour pressure (usually 47 mmHg). This explains the effect of altitude on oxygen delivery - at altitude the PiO2 is considerably lower, and a relatively hypoxic mixture is inspired.

PaCO2 = concentration of CO2 in the alveoli (usually expired) .

R = the respiratory quotient - the ratio of CO2 in ml produced (by metabolism) per ml of O2 consumed. Under normal conditions this is 0.8, but can be reduced by feeding the patient high fat feeds (higher calories per gram, lower CO2 production).

The alveolar gas equation is important as it explains why, when a patient is hypercarbic (increased pCO2), they require more oxygen e.g. following opioid administration.

This is an important mechanical property of the lungs, related to the elasticity of the lung units and the surface tension reducing effect of surfactant (which reduces the tendency of alveolar units to collapse into one another).

Effectively, what occurs in hysteresis is that when inflating pressure is compare to lung volume, inspiration and expiration follow different paths.

The lung volumes are relatively higher in expiration at equivalent pressure levels than in inspiration.

From this one can deduce that the greatest workload in the respiratory cycle is in early inspiration, where the pressure-volume curve is relatively flat (i.e. it takes a lot of pressure to expands the lungs a little). I compare this to the early phase of blowing up a balloon - it is initially very difficult an then suddenly there is a "give" and the balloon inflates easily. This occurs in the same way in the lungs - one hits the steep point of the pressure volume curve and the lung suddenly inflates quite easily. The point where the curve steepens (i.e. greater inflation per unit pressure) is known as the inflection point. This has an important role in mechanical ventilation.

Key point: the pressure-volume curve is flattest at low lung volumes, and consequently, the work of breathing is highest. If the lungs were left filled with air so that the resting state is at or above the inflection point, then the work of breathing would be reduced considerably. This is akin to letting a balloon deflate incompletely and then re-inflating it ® it's much easier. This is the basis of PEEP or Positive End Expiratory Pressure.

All rivers flow down to the sea. The reason for this is the effect of gravity. Think of the lungs as being like a waterfall - blood that pours in from the pulmonary arteries tends to flow downwards towards the base, and therefore perfusion to the base is relatively better than the apex. Gas is affected by gravity, but less so than liquid; the efffect of gravity on air is demonstrated by the "thinning" of the air at altitude (decreased barometric pressure). Consequently, even though air/gas also tends to fall towards the bases of the lungs (in the erect position), it's distribution throughout the lungs is more uniform than that of blood/liquid. The result is that both perfusion and ventilation are greater in the bases than at the apices (of the lungs), but perfusion (blood flow) is relatively greater than ventilation in the base (shunt) and ventilation is relatively greater than perfusion in the apices (dead space).

West described the ventilation-perfusion relationships at different levels in the lungs, and demonstrated 3 clear zones. In zone 1, in the apices, alveolar pressure is greater than both arterial and venous pressures (in the blood vessels). In zone 2, the mid zone, arterial pressure > alveolar pressure > venous pressure. In zone 3 arterial pressure > venous pressure > alveolar pressure. The practical applications of this are: 1. Application of excessive pressures into the alveoli (i.e. PEEP), can increase dead space ventilation. 2. Likewise dead space is also increased in hypovolaemia - the fluid level in the lungs drops - worsening gas exchange. 3. Measurement of pulmonary capillary wedge pressure must be made in zone 3, where alveolar pressure does not influence the readings.

In terms of ventilation-perfusion (V/Q) matching, dependent regions of the lungs tend to have the best V/Q relationships. Consequently, if one lung is injured (pulmonary contusion for example), the most effective means of improving V/Q matching is to position the patient on his side with the good lung in the dependent position. Moreover, the prone position has been shown to be very effective at improving V/Q matching in ARDS.

A simple three compartment theory of ventilation perfusion relationships has been around for some time (Riley & Cournard 1949). There areas of perfect ventilation perfusion matching, areas where there is relative shunting and thus venous admixture (diluting down nicely oxygented blood with poorly oxygenated mixed venous blood), and areas where there is relative dead space ventilation. By and large, excess dead space can be overcome by manipulating airway pressures and circulating volume and administering enriched oxygen. Shunt, is an entirely different matter. You have to do one of two things, 1. Reduce the blood flow through the shunt (i.e. divert it to better ventilated segments) or 2. Improve ventilation to the segments causing the shunt. The former is the body's physiological response, the latter is the focal point of ventilatory assistance in intensive care.

The physiological response to shunt is hypoxic pulmonary vasoconstriction, whereby local reflexes shut off blood supply to poorly ventilated segments. The constriction occurs in small arteries and arterioles when the PaO2 is reduced below 8 kPa. This effect is reduced by advancing age, anaesthetic agents and in diseased lungs.

We have seen that, in order to maintain normal arterial oxygenation, it is essential to have an intact respiratory drive, diaphragm, patent airways and ventilated and perfused lung units with adequate haemoglobin to upload the oxygen in the blood. The three main problems with oxygenation encountered in intensive care are: diffusion abnormalities, shunt and dead space ventilation.

Diffusion abnormalities are mostly related to the thickness of the alveolar walls, and the presence of interstitial fluid. The former occurs in all forms of fibrotic lung disease and in particular in hyaline membrane disease associated with late ARDS. Interstitial oedema is most often seen in cardiac failure but also may be a prominent feature of "capillary leak syndrome" and ARDS.

Any form of material that fills the alveoli can cause shunting. Examples of this include fluid, consolidation, blood (alveolar haemorrhage or contusion) or aspirated vomitus. There are effectively three types of alveolar units: 1. Those that are functioning normally. 2. Those that are completely filled with material and unavailable for gas exchange. 3. Those that are partially filled and therefore recruitable. One of the objectives of PEEP is to recruit these units for gas exchange.

Dead space ventilation is the main feature of emphysema ("pink puffers"). Excretion of CO2 is more efficient than oxygenation. In shunt mixed venous blood recirculates, and, not being available for gas exchange, contains an increased amount of CO2 ("blue bloaters"). Any obstructive disease of the pulmonary circulation causes increased dead space ventilation: the classic example is an acute pulmonary embolism. The treatment is enriched oxygen, and PEEP tends to be ineffective.

The workload of breathing is determined by:

1. The effort to expand the elastic tissues of the chest wall and lungs [compliance is the rate of change of volume in relation to applied pressure and can be calculated from a pressure-volume curve].
2. The effort required to expand the inelastic tissues of the chest wall and lungs (viscous work) this represents tissue resistance.
3. The effort required to move air against the resistance of the airways (resistance work).

With stiff lungs - reduced compliance - patients tend to take rapid small breaths, to minimize the elastic (and to an extent viscous) workload.

With high airway resistance (asthma) patients take large slow breaths.

Factors that increase the work of breathing:

• Pulmonary Edema - cardiogenic / non cardiogenic
• Consolidation
• Pulmonary haemorrhage
• Pulmonary contusions
• Airway obstruction
• Bronchoconstriction
• Dynamic airways collapse

The lungs dangle downwards in the pleural cavity supported by a vacume of negative pressure. As you would expect, the magnitude of this negative pressure is greater in the apices than in the bases. The effect of this is to splint airways open at the end of the tidal volume - the FRV. Apical alveoli are more inflated at rest than basal, but during inspiration, because the latter are at the steep part of the pressure-volume curve, the gas turnover (ventilatory excursions) are greater. With age, there is a tendency for distal, particularly basal airways to collapse in expiration - the closing volume. As one nears one's 65^th year the closing volume impinges on and begins to exceed FRV, and atelectasis occurs at the end of quiet expiration.

The respiratory system is under neurological control, both voluntary and involuntary.

Abnormalities in blood chemistry are detected by chemoreceptors in the medulla and in the carotid and aortic bodies.

Central chemoreceptors in the medulla respond to changes in the hydrogen ion concentration in the brain extracellular fluid (ECF). The hygrogen ions are derived from carbon dioxide which diffuses across the blood-brain barrier, and therefore the primary stimulus to ventilation is hypercarbia.

Peripheral chemoreceptors respond to: increased CO2,  decreased O2 and decreased pH. Responses to PaO2 occurs in the carotid body only and these responses do not occur until the PaO2 level is less than 14 kPa and does not become fully effective until the PaO2 < 8 kPa. The carotid body, alone also responds to decreases in pH. The aortic body responds to changes in PaCO2.

Only 20% of the ventilatory response to increased PaCO2 is mediated through the peripheral chemoreceptors.

Positive end expiratory pressure (PEEP) and Continuous Positive Airway Pressure (CPAP) are, for all intents and purposes, the same thing.

PEEP and CPAP are used to improve oxygenation in spontaneous breathing and with mechanical ventilation.

PEEP is an airway pressure above atmosphere (i.e. positive) at the end of a ventilator cycle.

PEEP is indicated when a Fio₂ of 0.5 fails to maintain Sao₂ over 90%.

The purpose of using PEEP/CPAP is to improve Pao₂ by reducing ventilation—perfusion mismatch.

• PEEP/CPAP increases functional residual capacity (FRC) through alveolar recruitment and prevention of alveolar derecruitment.
• Lung water redistributes from the alveolar to perivascular interstitial space.
• Recruitment of atelectatic areas also leads to less ventilator-induced lung injury from shear forces.
• Both PEEP and CPAP can also reduce the work of breathing.
• Airway resistance and lung compliance may improve with the improvement of functional residual capacity (FRC).
• In the setting of flow limitation with dynamic hyperinflation (e.g. acute asthma), PEEP will decrease the difference between airway pressure and intrinsic or auto-PEEP (the positive alveolar pressure at end-expiration); thus less patient effort is required to initiate inspiration.
• CPAP may also have a prophylactic role, enabling some patients with moderate respiratory dysfunction to avoid endotracheal intubation and / or mechanical ventilation.
• A usual range of PEEP or CPAP is 5—15 cm H₂0 (0.5—1.5 kPa).
• The optimal level is disputed, but is one that optimizes oxygen delivery and keeps lung units open (as recognized by an increase in lung compliance). This is represented by the inflection point on the pressure-volume curve.
• High levels reduce cardiac output and oxygen delivery (even though Pao₂ may be increased).
• The risk of barotrauma associated with hyperinflation and high intrathoracic pressures is increased.
• Hyperinflation also increases work of breathing and reduces the efficiency of inspiratory muscles.
• Low levels less than the opening pressure (inflection point) of the pressure—volume curve can cause progressive lung injury.

Although PEEP assists in ventilation in the expiratory phase by effectively splinting the alveolar units open, and reducing the workload required to re-inflate them (compare blowing up a partially inflated balloon to a completely deflated balloon - the latter is much more difficult), it has little effect on the inspiratory phase of the respiratory cycle (CPAP has a mild pressure supporting effect).

• Pressure support ventilation was developed to assist in the inspired phase of spontaneous ventilation.
• The patient initiates the breath - triggering the ventilatory assistance.
• The airway is subsequently pressurized to a preset level (eg. between 5 & 30 cmH₂0).
• The overall effect is akin to being pushed as one attempts to ride a bicycle - you start peddling and your assistant helps you by reducing the amount of work you have to do.
• In most forms of airway disease there is an increase in the workload of breathing due to:
• Reduced pulmonary compliance (stiff consolidated lungs).
• Increased airways resistance (bronchospasm or an artificial airway such as an endotracheal tube).
• Pressure support ventilation aims to overcome this.
• The level of pressure support is titrated against the patient's tidal volume and respiratory rate.
• Pressure support is always used with PEEP.
• As positive pressure is applied in both the inspired and the expired phases, this is sometimes known as bi-level positive airway pressure (BiPAP*), but is more properly known as Pressure Support Ventilation (PSV).
• Most Patients can be ventilated in this way so long as they retain the ability to initiate their own breaths.
• The pressure supported breath terminates when the inspiratory flow decelerates to 25%.
• Many intensivists consider PSV to be the gold standard mode of ventilation, as it has theoretical physiological advantages over mandatory modes.
• PSV is usually used in addition to mandatory breathing, such that any spontaneous breaths that the patient takes are pressure supported.
• Pressure support ventilation may be applied through an artificial airway or through an external mask (BiPAP* machine or Nippi).

Pressure Assist Ventilation

• This is similar to pressure support, except that a "I" (inspiratory) time is set. What this means is that the patient triggers the breath, the airway pressurizes to the assigned pressure support level, but the duration of inspiration is set by the ventilator. This is a useful way of controlling tachypnea in patients on PSC.

* This should not be confused with BIPAP (biphasic positive airway pressure) on new Drager ventilators, a pressure controlled mode of ventilation which permits spontaneous breathing (analogous to Airway Pressure Release Ventilation [ARPV]).

Intermitttant mandatory ventilation (IMV) was introduced in the early 1970s. This added a demand valve into the ventilatory circuit, allowing the patient to take a breath from an external resevoir bag, and circumvent the ventilator, thus reducing the workload of breathing somewhat. It did not prevent stacking, but did enhance weaning, by gradually reducing the number of ventilator assisted breaths allowing the patient to take over. The most effective way of weaning subsequently is to put the patient on an external CPAP circuit.

Assist Control Ventilation

This is an IMV like mode in which patients are either given a mandatory volume controlled breath, or given a volume controlled assisted breath. This differs from pressure support, as, although  the breath is patient triggered, a set volume is given, regardless of airway pressure.

• Pressure controlled ventilation
• Inverse ratio ventilation
• High frequency jet ventilation
• Airway pressure release ventilation
• Biphasic positive airway pressure (BiPAP)

A recurrent theme in the field of mechanical ventilation is that of Ventilator Associated Lung Injury. It has been shown that patients ventilated with large tidal volumes have a worse outcome than those who receive lower volumes. It appears that the phasic opening and closing of damaged lung units, alongside excessive stretch causes significant damage to the lungs. Current strategies involve minimizing the amount of stretch, by a number of different methods:

• Small tidal volume ventilations, with minimal regard to the CO2 level (permissive hypercapnia). This is provided as part of a volume controlled mode.
• Pressure control: whereby the patient is ventiated to an specific airway pressure, which is not exceeded, even if this leads to low tidal volumes and hypercarbia. It may be necessary to increase the inspiratory time to maintain oxygenation (normal inspired to expired i:e ratio is 1:2, this ratio may require reversal - 2:1 etc, leading to increased mean intrathoracic pressure, and hemodynamic effects [reduced preload]). This is known as "inverse ratio ventilation". 
• A modification of pressure control ventilation has been to allow the patient breath spontaneously, even at mid inspiration, by using dynamic valves. This leads to more patient comfort, and less sedation. This mode is incorporated into BiPAP, in some of the newer ventilators.
• There is some evidence to suggest that keeping the lungs inflated and ventilating patients on the expired limb of the pressure-volume curve, is the method least likely to cause lung injury. APRV (airway pressure release ventilation) works this way. The resting position for the lung is, for all intents an purposes, full volume: this is maintained by applying a constant pressure - which recruits lung units. Intermittantly, the pressure is released to a lower (CPAP) level, to allow replacement of gas, particularly to remove CO2, and replenish O2. 
• A further modification of this technique is to constantly ventilate the patient at maximal tidal volume, and change the gases by oscillating them in, by diffusion, at high frequency (thousands of breaths per minute). This is known as High Frequency Jet Ventilation/oscillation