Flashcards in Respiratory Deck (37)
Flow of gases dependent on
Rate of airflow=[Pressure (alveoli)-Pressure (atmosphere)]/Resistance
Bronchoconstriction under parasympathetic control=increased resistance
Bronchodilation=under sympathetic control=decreased resistance
Airway resistance in the lungs
1/3 resistance is in the upper airways –nose/pharynx/larynx (reduced by nose breathing)
2/3 resistance in the tracheobronchial tree mostly in the medium sized bronchi
Resistance in the terminal bronchi is very low, as volume increases resistance decreases.
In the upright lung position the upper lung regions are less well ventilated c.f. lower lung regions due to:
- weight of lungs
- compliance curve is sigmoid
Basic mechanisms controlling respiration: controllers
Medullary Centre (Medulla)
Inherent rhythmicity of respiration. Divided into inspiratory (dorsal) and expiratory (ventral)
Apneustic Centre (Pons)
Function unclear, possibly initiates inspiration
Pneumotaxic Centre (Pons)
Inhibits inspiration beyond a certain point
(Ventral surface of medulla). Most affected by CSF.
Voluntary control of respiration are the most important sensors in ventilatory control. Surrounded by ECF and very sensitive to changes in H+ concentration.
Peripheral Chemoreceptors (Carotid Bodies at common carotid bifurcation and aortic arch).
Glomus cells containing high dopamine content. Very high blood flow compared to size. They respond to:
- Decreased PaO2
- Decreased pH
- Increased PaCO2
Respond to a fall in PaO2 or in pH, or an increase in PaCO2. All these result in increased ventilation. (Only the carotid bodies are sensitive to pH)
At 13.5kPa the firing rate increases dramatically to Pa02
Basic mechanisms controlling respiration: sensors
Stretch Receptors (lung)
Sense lung distension sending impulses via vagus which result in decreased respiratory effort ‘Herring-Breuer Reflex’
Irritant Receptors (airway)
Respond to chemical irritation e.g. smoke with coughing and bronchospasm
J-Receptors (near lung capillaries)
Respond to chemicals in the pulmonary circulation causing rapid shallow breathing – function unclear
Receptors outside the lung
(Joint and muscle receptors, nasal receptors)
Relay information about force of respiratory effort, sense noxious stimuli for
Basic mechanisms controlling respiration: Effectors
Aortic and Carotid Sinus baroreceptors
Sudden increases in blood pressure produce hypoventilation and
sudden falls in blood pressure produce hyperventilation – function unclear
Diapragm: Expands the volume of the thorax
Intercostals: Expands the volume of the thorax (bucket handle effect)
Abdominal wall: Forced expiration and coughing
Accessory Muscles: Maximal inspiratory effort and volume
The most important determinant of ventilation control is the PaCO2.
1) Increasing CO2 increases rate and depth of respiration increase
2) If the amount of CO2 inspired is allowed to increase to very high levels (15%) then no further increase in minute volume occurs and the subject may become drowsy and exhibit depressed ventilation.
3) Conversely, if PaCO2 levels are allowed to fall (e.g. following hyperventilation), then ventilation becomes depressed. This can easily occur when mechanically ventilating patients.
1) Arterial oxygen tensions do not control respiration on a minute to minute basis in the same way as PaCO2.
2) Lowering PaO2 has no effect until PaO2 < 6.5 kPa. These are very low levels of arterial O2 occurring in illness (e.g. pneumonia) or on ascent to high altitude.
3) When PaCO2 is raised, the effects of a low PaO2 are seen at levels approaching 13 kPa.
4) In severe, longstanding, lung disease, patients may exhibit a persistent PaCO2 elevation with a low PaO2.
A decrease in arterial pH gives rise to increased ventilation. Metabolic acidosis causes increase in minute volume. Mediated by peripheral chemoreceptors (the blood-brain barrier is relatively impermeable to hydrogen ions).
1) A rise in PaCO2 or H+ stimulates respiration via the central and peripheral chemoreceptors.
2) Hypoxia stimulates only the peripheral chemoreceptors.
3) Stimulation of either sensor mechanism increases both rate and depth of respiration
Lung volume mechanics
1) As negative pressure increases, so the lung volume increases, up to a point where further negative pressure does not increase lung volume.
2) When the pressure around the lung decreases, the lung volume also decreases, but it does not follow the same curve.
This is called hysteresis. The lung volume at any given pressure during deflation is larger than that during inflation.
The volume change per unit pressure is known as the compliance.
Lung compliance can also be reduced in:
1) Pulmonary venous engorgement or in alveolar oedema.
2) The compliance of the lung falls if the lung remains unventilated for a long period. E.g. following anaesthesia, resulting in atelectasis.
3) Lung compliance is decreased by fibrosis of the lung and certain diseases.
Age and emphysema increase compliance.
Specific compliance is compliance per unit volume of lung to take into account lung volume size.
Factors affecting compliance
Increasing lung size increases the volume per unit pressure change
1) Compliance decreases on adopting a supine position;
2) Small tidal volumes decrease compliance, probably due to changes in alveolar size.
3) Breathing 100% oxygen decreases compliance, probably because of alveolar collapse, as oxygen is rapidly absorbed in the alveoli with no nitrogen to maintain pressure.
4) Fibrosis and inflammation, and engorgement
1) A decline in pulmonary blood flow will increase compliance. This will occur, for example, when a patient is put on a ventilator.
2) Age increases compliance
3) Emphysema increases compliance
1) Lungs inflated with air >compliance than lungs filled with water
2) Surface tension alone n the alveoli decreases the compliance of the lungs, by 50%.
3) Specialised cells within the alveolar epithelium secrete surfactant, a lecithin-rich, detergent-like substance that significantly decreases surface tension.
4) Plentiful in adult life they are not productive until a late stage of fetal maturity. Premature babies are very prone to develop respiratory distress, characterised by stiff lungs, atelectasis and pulmonary oedema.
5) Lung Surfactant has the following benefits:
- Lowers surface tension within the alveoli hence lessening atelectasis. Smaller alveoli have a tendency to inflate larger alveoli due to higher pressures
- Surfactant helps keep the alveoli dry and free from oedema.
- Surface tension forces within the alveoli tend to force liquid from the capillaries into the alveoli. This tendency is reduced by surfactant
- Increased lung compliance
- Decreased work of respiration.
Ventilation of the lung does not occur uniformly due to:
• the weight of the lung
• the shape of the compliance curve
In the dependent regions of the lung, resting intrapleural pressure is lower than in the apical regions. The dependent parts of the lung are on the steeper part of the compliance curve and are more easily distended. Thus ventilation is about 50% greater at the lung bases than at the apex.
When the lung is ventilating at low volumes this situation changes to the opposite.
Under these circumstances the lung tissue at the base becomes compressed after full expiration. The intrapleural pressures are now positive at the lung base and much less negative at the apex.
When the lung expands, the non-dependent region is in the most advantageous part of the compliance curve, so that its volume will increase rapidly, whilst the dependent lung cannot increase its volume at all until the intrapleural pressures become subatmospheric.
This situation can occur during anaesthesia in a spontaneously breathing patient.
Closure of small airways At low lung volumes as the volume of the lung decreases during expiration the intrapleural pressure in the dependent regions becomes positive.
The small airways begin to close, trapping gas within the distal alveoli. In normal subjects this airway closure only occurs at very low lung volumes.
However in patients whose lungs have lost elastic tissue (for example, the elderly or those with emphysema), airway closure occurs at higher lung volumes.
This airway closure can begin before the lung has reached its normal post-expiratory resting volume or functional residual capacity (FRC). The distal alveoli involved may be incompletely ventilated.
One method is to measure the amount of air trapped in the alveoli after expiration. The subject takes a full (TLC, total lung cap- acity) breath of 100% helium and then breathes out. The helium concentration of expired gas is measured and four discrete phases can be recognised:
1. Pure dead space is exhaled
2. Mixed alveolar and dead space are exhaled
3. Pure alveolar gas is exhaled (plateau phase)
4. There is preferential emptying of the apex of the
lungs, which have a relatively high concentration of helium. This indicates closure of small airways at the base of the lung. There is more helium in the apex of the lungs because, as we have seen, this region expands less, and nitrogen is less diluted here
The closing volume is normally about 10% of vital capacity in a young, healthy subject, but by age 65 it has reached 40% of vital capacity. The closing capacity is increased by airway disease.
Major factors affecting closing capacity are as follows.
2) Increases with age
3) posture: in the supine position lung volume
declines and closing capacity reaches FRC at 40-years-old. At 60 closing capacity reaches FRC in the erect position
4) Anaesthesia: the decline in lung volumes during anaesthesia contributes to an increase in closing capacity, which exceeds FRC even in the youngest patients.
Sites of airway resistance
1) Airways penetrate toward the periphery of the lungs becoming narrower but more numerous.
2) The major site of resistance is in the medium-sized bronchi.
3) Since the peripheral airways contribute so little to resistance, the detection of lung disease here is made much more difficult.
Just as gas transport within the airways contributes to resistance, so do the frictional forces between tissues. The tissue resistance accounts for about 20% of the total in a fit and healthy adult.
The sum of tissue and airway resistance is sometimes called pulmonary resistance to distinguish it from airway resistance.
Factors affecting airway resistance
• Lung volume – the bronchi are supported by elastic tissue of the lungs; thus, when the lungs expand, the bronchi are widened.
• Conversely at very low lung volume the airway calibre is reduced and airway resistance increased. Patients with significant chronic obstructive airways disease often breathe at high lung volumes in order to decrease airway resistance.
• Bronchial smooth muscle – contraction of bronchial smooth muscle decreases airway calibre, increasing airways resistance e.g. asthma, allergens (smoke or pollen).
• The nerve supply to bronchial smooth muscle is via the vagus nerve. The resting tone is under the control of the autonomic nervous system.
• Sympathetic stimulation causes bronchial dilatation, whilst parasympathetic stimulation causes bronchial constriction.
• Bronchodilation= Adrenaline, isoprenaline and noradrenaline Bronchial constriction= Acetylcholine causes bronchial constriction (reversed by atropine). A fall in PCO2 in alveolar gas increases airway resistance, for example, in pulmonary embolism.
• At high altitude the density of air is reduced, so that airway resistance is also reduced. Conversely, during deeper dives under the ocean, increased pressure increases the density of inspired gases so that airway resistance is increased. This is one reason why deep-sea divers breathe mixtures of helium and oxygen.
• When a subject takes a maximal inspiration and
then forcefully expires, not only are the lungs compressed but also the small airways. Under these conditions flow becomes ‘effort independent’: no matter how forcefully the subject expires, the factor limiting expiratory flow rate will always be the compression of the small airways
• Anaesthesia, for a variety of reasons, increases resistance: e.g. narrowed endotracheal tube; release of bronchial constrictors, e.g. histamine-releasing drugs.
Uneven ventilation within the lungs
See uneven ventilation (Due to compliance and resistance)
• Normal lung unit (a). Here the volume change in inspiration is both large and rapid, so it is completely filled before expiration begins.
• Lung unit (b) has stiff walls of low compliance; its volume change is rapid but small, although it is complete before expiration begins.
• Lung unit (c) has increased airway resistance, so that filling is slow and, therefore, incomplete before expiration begins.
Another mechanism is incomplete diffusion beyond the fifteenth generation of airways
• The airways here constitute the respiratory zone, distances are so short that diffusion of gas is the dominant mechanism of transport.
• The rate of diffusion of gas molecules is so rapid that differences in concentration are abolished within 1s, despite the low velocity of gas within this region.
• In the diseased lung the terminal airways may be dilated hence the distances within this region will be greatly increased and diffusion ceases to be an adequate mechanism for gas transport.
WORK OF BREATHING
Work required to move the lung and chest wall.
Work = Pressure X Volume, SEE pressure-volume diagram
As the respiratory rate increases, flow rates become faster and the viscous work becomes larger. When tidal volumes increase, the elastic work area increases. Expiration is normally passive and so the energy used is stored in the area 0ABCD0.
In fibrotic lung disease there is reduced compliance, breaths tend to be rapid and small.
In chronic obstructive lung disease patient tend to take slower, deeper breaths. These breathing patterns are optimized for decreasing respiratory work.
Normal ventilation values
Tidal volume (TV)
Vital capacity (VC) 4.5 L
Total lung capacity (TLC) 7.5 L.
Functional residual capacity (FRC) = amount of gas in the lungs after a normal breath (2.8 L).
Although most lung volumes can be measured by a simple spirometer, the FRC can only be measured by helium dilution, body plethysmography, or by a nitrogen washout technique.
See diagram: The simplest (and most useful) bedside test of lung function is the single forced expiration using a simple vitalograph.
Usual measurement is the volume forcefully expired over 1s after a maximum inspiration: the FEV1.
This is compared with the total volume expired after a maximal inspiration: the FVC.
The ratio of FEV1/ FVC is normally about 80% but is altered in disease states-restrictive and obstructive patterns (Frequently overlap).
Restrictive lung disease comprises small, stiff lungs with low compliance: for example, pulmonary fibrosis.
Both the FEV1 and the FVC are reduced, so that the ratio FEV1/FVC is normal or even increased.
Obstructive lung disease implies a reduction in FEV1, with a normal FVC giving a low FEV1/FVC ratio.
ANATOMICAL DEAD SPACE
• The volume of the conducting airways where gas in this part of the respiratory tree does not take part in the exchange of respiratory gases.
• This volume is normally about 150mL but increases with inspiration due to elastic forces on the bronchial tubes.
• Anatomical dead space is measured by Fowler’s method. The patient breathes from a tube connected to a rapid nitrogen analyser. After a single intake of pure oxygen, the subject breathes out.
• Initially nitrogen concentration increases as dead space gas is washed out by alveolar gas.
Towards the end of expiration the subject is expiring pure alveolar gas, giving rise to a ‘plateau phase’.
• The expired volume is also recorded and the dead space found by plotting nitrogen concentration against expired volume (See diagram).
• The dead space is the volume expired up to a point where a line intersects the curve such that areas x and y are equal.
PHYSIOLOGICAL DEAD SPACE
The lung volume including the anatomical dead space and also the alveoli that are not ventilated (the alveolar dead space).
• Anatomical dead space represents the volume of gas which is undiluted by that which is already in the lungs.
• The physiological dead space is the total volume of gas that has not taken part in gas exchange. The physiological dead space will include any gas from the alveoli which have not been perfused (the alveolar dead space).
• Factors increasing anatomical dead space are:
1 ) Increasing size of subject;
2) A standing position;
3) Increased lung volume
4) Adrenaline, isoprenaline (isoproterenol)
and noradrenaline, all of which cause bronchodilatation.
• Factors increasing alveolar dead space are:
• Hypotension, which decreases apical perfusion; this leads to some alveoli being underperfused (but still ventilated)
• Hypoventilation, which decreases apical perfusion, again resulting in poor perfusion of some apical lung units
• Emphysema and pulmonary embolism
• Positive pressure ventilation, which decreases the capillary flow through lung units with low perfusion pressure, typically the upper zone. Such units will make a reduced contribution to gas exchange.
• Normal arterial oxygen tension is about 13.3kPa, which corresponds to a saturation of 97%.
• Mixed venous blood has a tension of about 5.3kPa, giving a saturation of 75%. The oxyhaemoglobin dissociation curve is shifted to the right in
1) Exercising muscle where temperature increases; PaCO2 rises; and pH falls.
2) An increase in 2,3 DPG inside the red cells also shifts the curve to the right, enabling haemoglobin to more readily give up oxygen. Levels of 2,3 DPG are often raised in chronic obstructive airway disease. (It is important to note by way of contrast that the carboxyhaemoglobin dissociation curve is straight and does not have a flat top.)
A rise in temperature or a fall in pH or PCO2 shifts the curve to the right. This will increase unloading of oxygen, for example, in capillaries in exercising muscle. Increased 2,3 DPG also shifts the curve to the right, for example, in prolonged hypoxia of chronic lung disease.
The introduction of carbon monoxide into the alveoli severely decreases oxygen transport because it combines with haemoglobin to form carboxyhaemoglobin. The affinity of haemoglobin for carbon monoxide is much greater than for oxygen. The presence of carbon monoxide also shifts the curve to the left, which decreases the unloading of oxygen in the tissues.
The degree of shift of the curve can be gauged from the value of oxygen tension for a 50% saturation. This is known as the P50 and is normally about 3.5kPa.
There are five primary causes of hypoxaemia:
2. Impaired diffusion
4. Ventilation and perfusion inequality
5. Reduction in inspired oxygen tension.
Hypoxaemia and hypoventilation
1) Hypoventilation is always associated with an increase in PaCO2 and a decrease in PaO2.
However, the magnitude of the increase in PaCO2 is much greater than the decrease in PaO2.
2) If the alveolar ventilation is halved, the PaCO2 is doubled – the change in PaO2 is much less.
3) Hypoxaemia is not the dominant feature of hypoventilation. The hypoxaemia caused by hypoventilation can always be decreased by administration of oxygen.
Hypoxaemia and impaired diffusion
Impairment of diffusion implies that equilibration does not occur between oxygen tension in the alveolar gas and that within the capillaries.
• In a normal alveolar capillary unit the capillary blood oxygen tension has reached that of alveolar gas by the time it has traversed one-third distance along the capillary. Even in extreme exercise, as the cardiac output rises, there is sufficient reserve for equilibration to be complete before the blood has left the capillary.
• In some diseases the blood gas barrier (the alveolar membrane) is thickened, slowing diffusion and rendering equilibration incomplete, especially during exercise.
• Diseases that may cause impaired diffusion include asbestosis, sarcoidosis and diffuse interstitial fibrosis.
• Since diffusion across a membrane is proportional to the concentration gradient of the gas diffusing across that membrane, hypoxaemia which is caused by diffusion impairment can be corrected by the administration of oxygen.
• Diffusion is also proportional to the solubility of the gas in question (Graham’s law). CO2 is very soluble. For this reason, CO2 elimination is probably unaffected by impaired diffusion.
Hypoxaemia and shunting
Shunting describes the passage of blood through the lungs without coming into contact with ventilated alveoli
1) E.g. the bronchial circulation and Thebesian veins.
2) This is greatly increased in patients with atrial or ventricular septal defects or PDA. In pneumonia the passage of blood through a consolidated lobe will also constitute a shunt.
3) Administering oxygen does not greatly overcome this form of hypoxaemia. The reason for this is the flat top of the oxyhaemoglobin dissociation curve. If the patient is given 100% oxygen to breathe, capillary blood coming into contact with ventilated alveoli will develop a high oxygen tension, but because of the shape of the dissociation curve the oxy gen content will only rise a little.
4) Conversely blood traversing unventilated alveoli will have an oxygen tension equal to mixed venous blood. When the two pools of blood mix on leaving the alveoli, oxygen tensions will be significantly below normal. This is because well-oxygenated blood contributes little extra oxygen content.
The hypoxaemia resulting from hypoventilation, diffusion impairment and ventilation perfusion inequality can all be improved by administration of oxygen. Hypoxaemia resulting from a shunt is not significantly corrected by giving extra oxygen
Ventilation and perfusion scan
Here ventilation (VA) and blood flow (VQ) are mismatched causing inefficient gas exchange. This mechanism is responsible for most of the hypoxaemia seen in chronic lung disease, e.g. COPD and pulmonary embolism.
If we consider three different types of lung unit, it is possible to illustrate the effects of uneven ventilation and perfusion.
(a) Shows a normal lung unit and the gas tensions within it.
(b) Shows the gas tensions in a unit which is completely unventilated but normally perfused. In an unventilated unit the gas tensions become equal to those of mixed venous blood.
(c) Shows a unit which has no perfusion but which is normally ventilated. There will be no blood leaving this unit to mix with arterial blood, and the gas tensions within this unit will be equal to those of inspired air.
In normal patients, ventilation-perfusion inequalities within the lung result in only a small depression in arterial PO2, from what might be expected in the ideally ventilated lung, where alveolar and arterial PO2 would be equal. In practice there is about a 0.5kPa difference in oxygen tension between alveoli and artery. This is known as the alveolar-arterial difference for PO2, or A-a difference.
Ventilation and PC02
There are two major causes of CO2 retention: hypoventilation and ventilation-perfusion inequality.
We have already seen that hypoventilation must cause CO2 retention and hypoxaemia, but the effect on CO2 is much greater.
We have also seen that ventilation-perfusion inequality is frequently accompanied by a normal PaCO2 because of stimulation of the chemoreceptors and resulting hyperventilation.
Patients who cannot hyperventilate, possibly because the increased work of breathing is beyond them, will have an elevated PaCO2.