F - Respiratory physiology Flashcards
Describe the structure and function of the upper airway (excluding the larynx)
The upper airway is comprised of:
- Mouth
- Soft palate + uvula form a valve to cut off the nasopharynx while eating
- Nasal cavity
- Turbinates - cirulates + warms air
- Secretion of mucous which filters air
- Sinuses
- Pharynx
- naso, oro + laryngopharynx
Describe the anatomy of the trachea (including its relations)
- 10cm long
- It is a conducting airway - ie. Does not take part in gas exchange
- Split into cervical and mediastinal portions.
- Mediastinal portion travels from anterior to posterior mediastinum
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Borders + Relations:
- Upper border = larynx, begins at C6 & branches at the sternal angle (T4-5)
- Anteriorally, made up of 16-20 C-shaped cartilage separated by fibroelastic tissues.
- Posteriorally, made up of trachealis muscle
- Its relations on the right are lung & pleura
- Relations on left are descending aorta, lungs, pleura
- Relation inferior is the pulmonary trunk/right pulmonary artery
- Posterior relation is oesophagus
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Histology:
- Made up of pseudostratified columnar ciliated epithelium, goblet cells (mucin secreting) + basal cells
- Blood supply: inferior thyroid artery & bronchial arteries + drains to inferior thyroid venous plexus
- Innervation: pulmonary plexus
Describe the anatomy + function of the larynx
(excluding blood/venous/lymph/nerves)
Functions = airway protection, speech + breathing, cough reflex
Relations
* Superior - hyoid bone
* Anteriorarly - skin and covered by thyroid cartilage
* Inferiorly - continuous with trachea at C6
* Posteriorly - projects into laryngopharynx
Structural anatomy
* Lined by pseudostratified columnar epithelium
* Divides respiratory tract into upper and lower
Cartilages - 3 paired, 3 unpaired
* Unpaired: epiglottis, thyroid, cricoid
* Paired: arytenoids, corniculate, cuneiform
Muscles - various muscles attaching to the various structures. Important movements:
* Phonation: cricothyroid (brings cords together by moving thyroid down), interarytenoid (transverse + oblique), vocalis (subset of muscles from thyroarytenoid) - mediates tension in vocal ligament to modulate pitch
* Inspiration: + cricoarytenoid (posterior + lateral) - rotate arytenoids outwards
* Expiration: thyroarytenoid adduct cords to increase resistance and provide intrinsic PEEP (3-4 cmH2O), which maintains patency of small airways & maintains FRC
* Effort closure - aryepiglottic muscles contract strongly to act as a sphincter, allowing airway to withstand up to 120cmH2O pressure
Ligaments
* Intrinsic - Cricothyroid ligament and quadrangular membrane
* Extrinsic: thyrohyoid membrane, median and lateral thyrohyoid, hyo-epiglottic, cricotracheal ligaments
Outline the anatomy of the bronchi + the bronchial tree to the level of the segmental bronchi. Briefly describe the anatomy of bronchioles
Bronchi
- The left and main bronchi split into lobar, then segmental, then small bronchi
- RMB shorter + wider than left
- The bronchi are cartilaginous + bronchioles are not
- Blood supply: bronchial arteries and pulmonary circulation
- Venous drainage: azygos + accessory hemiazygos vein
- Innervation: vagus + T2-6 sympathetic fibres
- Bronchial wall
- Made up of pseudostratified columnar epithelium, composed of goblet + basal cells (stem cells responsible for goblet + epithelial cell production)
- Basement membrane
- Submucous layer
Bronchioles
- Terminal bronchioles - cuboidal + ciliated epithelium
- Respiratory bronchioles - cuboidal and squamous epithelium
- Less goblet cells
Describe the structure of alveoli and relate it to its function
Macroscopic characteristics:
- Large no of airspaces connected by septae
- large SA to facilitate diffusion
- Interconnected network of walls allows mechanical stress to be shared across large area (alveolar interdependence)
- Pores of Kohn - allows collateral ventilation
- Blood-gas barrier (capillary endothelium-basement membrane- type I cell)
- short diffusion distance (0.2-0.5um) - high permeability to gas, low to water
- polyhedral shape
Histological features:
- Elastic basement membrane
- Increases elastic recoil of distended lung & increases resistance to atelectasis
- Capillary endothelium
- Alveolar epithelial cell Type I
- Make up most of the surface area & are the cells through which gas diffuses
- Alveolar epithelial cell Type II
- Responsible for surfactant production
- Granular pneumocytes
- Lamellar bodies (pools of phopholipids) are excreted + form tubular myelin, which then forms the phospholipid lining of the surfactant layer
- Replenish Type I cells (which cannot replicate)
- Pulmonary alveolar macrophages (PAMs)
- Phagocytose small partciles
- Can release lysosomal products into EC space in response to eg. Cigarette smoke/other irritants
What are the differences encountered in the upper airway for neonates, children + adults?
Anatomical airway differences are more prominent in children <12months old, and these differences become less pronounced at around age = 8
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Head and neck - neonates have:
- Large occiput + proportionally short neck. Neck is flexed in supine position + favours airway obstruction in this position. Optimal intubation is in neutral vs ramped position
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Oral + nasal cavity - neonates have:
- Smaller mandible - less anterior excursion + smaller mouth opening
- Large tongue - compared to size of oral cavity - interferes with intubation
- “Obligate nose breathers” - nasal obstruction will impair respiration
- Larger tonsils + adenoids - can cause airway obstruction. NPA may cause bleeding + aspiration
- Nil dentition
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Larynx - neonates have:
- Large, floppy epiglottis - projects further into the airway + covers more of the glottis
- Superior laryngeal position - lies at C4 rather than C6 in adults
- Narrowest part of airway is at the cricoid, not the transverse diameter of the vocal cords as in adults
- Subglottic narrowing - can have FBs lodged below cords - resolves age 10-12
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Trachea - neonates have:
- Short trachea - ~4cm. L & R bronchi arise at similar angles so easy for endobronchial intubation on either side. Accidental extubation also easier
- Soft trachea + cricoid - cricoid pressure may collapse airway
- Narrow - smaller target for needle/surgical cricothyroidotomy. Also risk of tracheal stenosis following prolonged intubation
Describe the anatomy + function of the diaphragm
Structural anatomy
- Complex dome shaped membranous structure with two discrete muscular portions (costal + crural diaphragm) + circumferential attachment (which allows diaphragm to increase intrathoracic volume)
- Skeletal muscle - predominately slow twitch fibres (to facilitate sustained contraction)
- Connects to lower six costal cartilages and posterior aspect of xiphoid process
- Three main tendons
- Central noncontractile tendon (level of xiphisternum)
- R crus
- L crus
- 3 arcrurate ligaments connect the diaphragm to the posterior abdominal wall
- Median
- Medial (over psoas)
- Lateral (over quadratus lumborum)
- Three perforations:
- T8 vena cava (8 letters)
- T10 oesophagus (10 letters)
- T12 aorta, thoracic duct, azygos vein
Innervation/blood supply/venous drainage:
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Innervation:
- Motor: L + R phrenic nerves (C3, 4 and 5 keeps the diaphragm alive). Motor innervation solely from C3,4,5 – vulnerable to high spinal cord damage
- Proprioceptive: to periphery from lower intercostal nerves
- Blood supply: phrenic arteries from abdominal aorta
- Venous drainage: to IVC via tributaries of brachiocephalic + azygous
Function:
- Contributes to majority of inspiratory work of breathing
- Moves 1cm during tidal breathing
- Can move up to 10cm in forced breathing
- Can dramatically increase intrabdominal pressure (cough, sneezing, vomiting)
- Maintains lower oesophageal spincter tone
- Contraction: downward movement, flattening, tilt anterioposteriorly, increase circumference
Describe the structure of the chest wall and its function in respiration
Chest wall is composed of:
- Ribs: antero-inferior slope, connected by intercostal muscles
- Intercostal muscles:
- Skeletal muscles
- External intercostals slope antero-inferiorly
- Internal + innermost intercostals slope infero-posteriorly
- Motor innervation from intercostal nerves at same level
- Function: bucket handle movement + elevation of ribs
- Incr diameter of thoracic cavity
- Minor muscles: levator costae (upper edge of rib to veterbral transverse process); transversus thoracis/triangularis sterni (? Function), scalene muscles (elevate rib case)
List the muscles involved in respiration
- Pharyngeal
- Genioglossus, palatal muscles, hyoid muscles
- Inspiration: Dilate the upper airway as reflex response to negative pressure
- Expiration: Relax passively
- Laryngeal
- Inspiration: Vocal cords abduct (decrease resistance to airflow)
- Expiration: Vocal cords adduct (increases airway resistance and prevents lower airway collapse
- Chest wall muscles
- Diaphragm (see diaphragm)
- Intercostals (see structure of chest wall)
- Scalenes, transversus thoracis
- Inspiration:‘bucket handle’ elevation of the ribs (mainly by external intercostals); ‘pump handle’ elevation of sternum
- Expiration: mainly internal intercostals
- Abdominal muscles
- Rectus abdominus, transversus abdominus, external + internal obliques, pelvic floor muscles
- Inspiration: apply counterpressure to flattening diaphragm to facilitate lateral + anteroposterior expansion of ches
- Expiration: Maintain intra-abdominal pressure + push diaphragm back up into chest. Active role whenever respiratory effort is increased
- Accessory muscles
- SCN, trapezius, pectoralis, extensors of the vertebral column, serratus anterior, latissimus dorsi
- Recruited to assist respiratory effort when energy requirements of ventilation are increased
Outline the anatomy of the pulmonary and bronchial circulations
Pulmonary
- Arises from pulmonary trunk
- Low pressure, highly elastric
- Blood supply: arises from bronchial circulation via vaso vasorum
- Nerve supply: SNS fibres>PSNS
- Structure:
- Elastic arteries - large, contain elastin. Less susceptible to changes in ITP
- Transitional arteries - less elastin & increasing amounts of muscle fibres running circumferentially
- Muscular arteries - enough smooth muscle to allow vasoreactivity
- Non-muscular arteries - small endotherlial vessels, which can be affected by transmitted alveolar pressures
- Capillaries - form a vascular sheet. This is the level at which gas exhange occurs
- Pulmonary veins return oxygenated blood to the LA. Thinner walled, contain more collagen & less elastic. Indistinguishable from LA endothelium & even contains myocytes (can be source of AF)
Bronchial circulation
- Arises from systemic circulation & forms the circulation for pulmonary malignancies
- R bronchial artery arises from an IC artery & on left there are usually 2 ateries with separate origins from the aorta
- Supplies blood to bronchi
Describe the relationship between PaCO2 & ventilation; & PaO2 & ventilation
Describe the features of central chemoreceptors
Medullary chemoreceptors
- Anatomically separate to medullary respiratory centres
- On ventral surface of medulla (~200-400microns deep to surface)
- Surrounded by brain ECF, with CSF next to the ventral surface, and blood vessels on the other side of chemoreceptors - ie. The pH changes depend on CSF, local blood flow, ECF
- The blood-brain barrier is relatively impermeable to ionic H+ & HCO3 -, but molecular CO2 diffuses across easily. This then contributes to release of H+ ions which results in decreased pH
- Normal CSF pH is 7.32. It has lower buffering capacity than blood due to lower protein count, therefore there is a greater difference in CSF pH compared to blood pH for any given change in PCO2. It also responds more quickly to renal compensation - it therefore has a more important effect on the level of ventilation and arterial pCO2.
- Eg. In CO2 retainers (COPD), chronic pCO2 change results in compensatory increase in HCO3- & CSF pH approaches neutral. This causes a lower respiratory rate than would be expected with the observed arterial pCO2
Describe the peripheral afferents involved in respiratory control
Lung receptors (all impulses travel via vagus)
- Pulmonary stretch receptors - discharge in response to distension of lung & activity is sustained with lung inflation - ie. They show little adaptation
- Stimulation of these receptors results in slowing of respiration due to increase in expiratory time.(Hering-Bruer reflex)
- opposite is true for expiration
- Irritant receptors - rapidly respond to airway irritants - eg. Cigarette smoke/noxious gases/cold air
- J receptors - respond to chemicals injected into the pulmonary circulation –> results in rapid, shallow breathing
- Bronchial C fibres - respond to chemical injected into the bronchial circulation –> results in rapid, shallow breathing
Other receptors:
- Nose + upper airway receptors
- Joint + muscle receptors
- Thought to provide feedback to ventilatory centres via proprioceptive info
- During exercise, descending control of muscle activity may stimulate the central respiratory control centres
- Pain + temperature
- Temperature increases the sensitivity of peripheral chemoreceptors to O2 - rise in temp will increase minute volume at any given PaCO2 + PaO2
- Baroreceptors
- May also have a role in ventilation - hypertension increases respiratory rate while hypotension decreases it
Describe the control of breathing
Describe transmural pressure and its role in the inspiratory and expiratory process
Intrapleural pressure:
- Space between the lung and the chest wall (or between visceral and parietal pleura
- Balance between outward recoil of chest wall + inward recoil of lungs
- Usually negative –> -5cmH2O at rest
- Varies with vertical distance in the lung
- Gravity pulls lung parenchyma inferiorly
- IPP therefore more negative at apex (typically -10cmH2O at FRC), less negative at base (typically -2.5-3cmH2O at FRC)
- During inspiration, pleural pressure changes evenly throughout the lung, however basal alveoli are better ventilated because their compliance is increased (due to lower resting volume)
Inspiration
- Negative IPP (-8cmH2O); Ppl > Pel (pl = IPP, el = elastic recoil of lungs)
Expiration
- Ppl falls to -5cmH2O
Define compliance
Compliance:
- Measure of the ‘distensibility’ of lung - change in unit volume per change in unit pressure (see equation 1)
- Compliance of the lung: equals transpulmonary pressure = alveolar pressure - Intrapleural pressure
- Compliance of the chest wall: = intrapleural pressure - ambient pressure (usually atmospheric)
- Total compliance is calculated from the alveolar-ambient pressure gradient
- Elastance = 1/compliance (the elastic recoil)
- Compliance of the respiratory system as a whole is a function of both lung and chest wall compliance: (see equation 2)
- In the normal range (-5 to -10cmH2O), both lung and chest wall compliance is independently stated as 200ml/cmH2O, therefore compliance of the respiratory system as a whole is 100mL/cmH2O
Static compliance
- Compliance in the absence of flow - ie. Compliance of the system at any given volume when there is no flow
- It is a function of elastic recoil of the lung and surface tension of alveoli
- In ventilated patients, this can be measured by tidal volume/(Pplat - PEEP)
Dynamic compliance
- Measured during respiration, using continuous pressure and volume measurements
- Includes pressure required to generate flow by overcoming resistance forces - therefore always less than static compliance
- It is a function of respiratory rate
Specific compliance
- Compliance per unit volume of lung (see equation 3)
- This is usually ~ 0.05/cmH2O - this is used to compare difference sized lungs. It is the same between adults and neonates
- Lung compliance exhibits hysteresis (compliance is different in inspiration and expiration)
- In static compliance curves - hysteresis is due to viscous resistance of surfactant and the lung
- In dynamic compliance curves - hysteresis is due to airways resistance (which is a function of flow rate), which is maximum at beginning of inspiration and end-expiration
Describe the different ways of measuring compliance
Static compliance:
- Supersyringe method - large syringe used to titrate known volumes of air into lung (usually increments of 100mLs). The pressure at each of these volumes is measured (?oesophageal balloon)
- Limitations:
- Gas is compressible - (not taken into consideration) at higher pressures, some volume will be lost (compliance will look better)
- Ventilator has to be disconnected to attach syringe - may lose some PEEP (not measuring true compliance)
- Method takes a long time - ~2-3 seconds are allowed for diffusion prior to measuring pressure therefore some volume of gas may be absorbed (compliance will look better)
- Temperature changes - heated/humidified gas will expand (compliance will look worse)
- Limitations:
- Multiple occlusions method - during normal ventilator function, breath occlusions are repeated at different volumes with normal breaths in between (eg. Breath hold at 200mLs, measure pressure, then normal breaths + breath hold at 400mL, etc)
- Doing an inspiratory pause in a pt with mandatory ventilation - compliance is measured by Vt/(Pplat - PEEP) - this is measuring compliance at the highest volume of that breath
- Continuous flow method - Low rates of inspiratory flow used on ventilator, in attempt to reduce respiratory resistance (~1.7L/min) over 10-15seconds, followed by low expiratory flow rate
- Tends to underestimate inspiratory compliance (due to airway resistance) & overestimate expiratory compliance
- Limitations of all methods of static compliance - all pts need to be sedated + paralysed, possible escape of gas into pulmonary circulation, ignores changes in gas pressure + temp
- Pressure in ventilators is measured using integrate silicon waver transducers. An aneroid manometer may be used to measure pressure during supersyringe inflation/deflation
Dynamic compliance:
- Occurs during normal ventilator function - makes no attempt to correct for pressure produced by airway resistance
- Built into modern ventilators
What are the factors affecting compliance?
What are the properties of surfactant?
- Surfactant is 85% phospholipid lecithin (dipalmitoyl phosphatidylcholine DPPC major constituent -produced by Type II alveolar epithelial cells); 10% protein; 5% neutral lipid
- DPPC = amphipathic
- hydrophobic at one end and hydrophilic at the other end
- align themselves on the surface
- their intermolecular repulsive forces oppose the normal attracting forces between liquid molecules that are responsible for surface tension
- Surfactant release stimulated by: catecholamines, cholinergic, vasopressin, adenosine
- Surfactant is inhibited by high conc surfactant proteins, lectins, inflammatory mediators
- Produced by Type II alveolar cells + secreted via lamellar bodies
- T1/2 = 5-10 hours; removed by: resorption to Type II cells, transported up airways and eliminated as aerosol; degraded in alveolar macrophages, extracellular enzymatic degradation, clearance via lymph / blood
What is surface tension?
Surface Tension is the force that arises due to attractive forces (hydrogen bonds in water) between adjacent molecules of liquid being much greater than those between gas and liquid; where liquid surface area becomes as small as possible
- Liquid surface area contracts as much as they can (i.e into a bubble) and generates a pressure as per LaPlace Law
- P = 2(gamma) / r P = pressure inside elastic sphere
- Thus, at any given (gamma)(surface tension), reduced r -> higher transmural pressures (want to collapse more)
- Smaller alveoli promote their own demise by emptying into larger neighbouring alveoli
- High surface tension causes three problems
- Compliance falls when alveolus is empty
- as r falls pressure required to open it at given is increase -> incr work of breathing
- Small alveoli will preferentially empty into bigger alveoli
- smaller alveoli require greater transmural pressure to remain inflated -> causes smaller alveoli to empty into larger ones
- Fluid transudation
- surface tension draws fluid from interstitial spaces and contributes to pulmonary oedema
How does surfactant influence respiratory mechanics?
Functions of Surfactant
- Reduce surface tension – increase lung compliance + reduce work
- Alveolar surface tension decr to virtually zero – particularly when alveoli deflate and phospholipid particles are brought closer together
- increase lung compliance from decr surface tension
- Alveolar stability + interdependence
- when alveoli are fully inflated, surfactant phospholipid molecules are farther apart, which decr compliance on lung deflation -> hysteresis (compliance is different in inspiration + expiration)
- Reduce alveolar transudate
- decreased surface tension -> decreased capillary-alveolar hydrostatic pressure gradient, decr ultrafiltration of fluid
What are the factors that influence FRC?
See table
Describe the factors that affect airways resistance
Can be derived from components of Reynold’s number and Hagen-poiseuille equation
- Factors that affect gas properties - eg. Viscosity and density
- Factors that affect airway diameter
- Intraluminal e.g. sputum plugging, airway oedema, water in circuit, low lung volumes (eg in anaesthesia - airways tend to collapse)
- Luminal (Tone): SNS b2 receptors in lung cause bronchodilation, PSNS causes bronchoconstriction via musc R
- Extraluminal: Dynamic airway compression (Starling resistor) e.g. on forced expiration (occurs in COPD as well due to ¯ elastin), artificial airway
- Factors affecting length
- Tracheostomy - decreases airway length; ETT - elongation of large airways at high volume
- Factors affecting flow rate:
- Respiratory rate ( RR = turbulence as seen with Reynold’s number)
- Inspiratory/expiratory work/effort - as in forced expiration
List the ways of measuring airway resistance + how flow changes can be detected
Measurement of respiratory resistance
- Direct measurement of air flow, airway pressure and alveolar pressure (eg. Oesophageal balloon)
- Body plethysmography
- Forced oscillation technique
- Airway resistance interrupter technique (Rint)
- Inspiratory hold (in mechanically ventilated patient)
- Rhinomanometry
Methods of determining flow + detecting increased resistance to flow
- Spirometry
- Mechanical ventilator data
- End-tidal gas monitoring
Describe and explain the oxygen cascade
The Oxygen Cascade describes the drop in the partial pressure of oxygen from the atmosphere to the mitochondria
- Atm 159mmHg at sea level + 37OC (Or, 21% of total atmospheric pressure of 760mmHg)
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Airway 149mmHg
- Drops due to water vapour pressure
-
Alveolar 99mmHg
- Drops due to oxygen uptake by pulmonary capillaries + CO2 influx into alveoli
- Cannot be measured - calculated by alveolar gas equation
- End-capillary ideally the same as Alveolar
-
Arterial (PaO2) is 92mmHg
- Drops due to venous admixture
- Degree of drop = A-a gradient (7 = normal in adults - up to 14 can be normal in older adults)
- Tissue - varies between tissues (10-30mmHg) - brain is 33mmHg. Drops due to diffusion distance
- Mitochondrial - drops due to diffusion distance. Between 1-10mmHg
Explain time constants, what is meant by the term ‘pendelluft’ and its effect on ventilation
- ‘Time constant’ is a term derived from mathematics and applied to respiratory physiology to describe the filling/emptying behaviour of alveoli with varying properties:
- One time constant (tau) refers to the time it takes for an alveolus to fill/empty by 63% of its total amount
- It takes 3 time constants for an alveolus to fill/empty by 95%
- For normal lungs, an expiratory time constant is usually given as approx. 100-200ms, so that over 0.6s, 95% of volume should be emptied
- tau = compliance X resistance (given flow is constant)
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‘pendelluft’ refers to the equilibration process between ‘fast’ and ‘slow’ alveoli via interconnectedness (pores of Kohn)
- Can be observed via inspiratory hold on ventilator - initial drop in pressure (airways resistance), followed by longer/slower downtrend in plateau pressure (as alveoli equilibrate)
- Examples via disease processes:
- Pulmonary fibrosis: is same or decreased “fast”, compliance is decreased, resistance increased
- Emphysema: is increased “slow”, compliance increased, resistance increased
- Effect on ventilation:
- At the beginning of expiration, the abnormal region may still be inhaling while the rest of the lung has begun to exhale with the result that gas moves into it from adjoining units (pendelluft - swinging air)
- As breathing frequency increases, the proportion of tidal volume that goes to the partially obstructed region becomes smaller - less of lung participates in TV changes & lung appears to become less compliant
Explain the significance of the vertical gradient of pleural pressure and the effect of positioning
Compared to alveoli at the base, alveoli at the apex:
- Are larger at end-expiration
- Have lower ventilation + perfusion but higher V/Q ratio
- This results in differences in gas composition. Compared to basal alveoli, apical alveoli have pO2 132mmHg vs 89mmHg(base); pCO2 29mmHg vs 42mmHg (base)
- The differences in oxygen uptake and CO2 output result in higher respiratory exchange ratio at apex (RER = 2) vs base (RER = 0.67)
- There is a difference in hydrostatic pressure of the between the top and bottom of the erect lung of 30cms H2O (or 23mmHg)
- Perfusion differences due to gravity are described by wests zones
- Ventilation differences are an indirect consequence of the effect of gravity
- Intrapleural pressure gradient - the weight of the lung causes a gradient of intrapleural pressure between the top and bottom of the lung (-10cmsH2O & -2.5cmsH2O). Greater negative pressure of apical alveoli causes greater distention (and thus greater size)
- Ventilation gradient - gradient in alveolar sizes at FRC means that alveoli will increase in size by different amounts with inspiration because they are on different parts of the lung’s compliance curve. Smaller basal alveoli increase in size more than apical
- Note: if a person is tidal breathing from just above RV (low lung volumes), IPP at apex is decreased to -4cmsH2O, base to +3.5cmsH2O (constant gradient of 7.5cmsH2O as lung weight unchanged). However, ventilation at apex is better than base (positive pressure at base results in airway closure - this represents a move along the curve as outlined (image below)
*Note: the V/Q gradient exists because the vertical gradient in perfusion is larger (steeper) than the vertical gradient in ventilation*
Describe the pressure and volume relationships in the respiratory system
Pressure + volume loops in the respiratory system display hysteresis (see below)
This is due to the effect of surface tension on lung mechanics
Describe how the pressure-volume loop changes as compliance decreases
Describe the flow-volume relationship of the lung
Describe the work of breathing and its components
Work of breathing = Pressure x Volume (measured in Joules)
- This gives the work for a single respiratory cycle. Tidal breathing is efficient and uses <2% of BMR
- In a normal person at rest, WOB is 0.35J/L
- Energy expenditure over time is called the “power of breathing” and is roughly equal to 2.4J/min
- The oxygen requirement of breathing at rest is 2-5% of VO2 or 3ml/min
Components of the work of breathing:
- Elastic work - about 65% of total work and stored as elastic potential energy. The energy required to overcome elastic forces are:
- Elastic recoil of the lung
- Elastic recoil of the chest
- Resistive work - about 35% of total work & is lost as heat. This is due to energy required to overcome frictional forces:
- Between tissues (increased with interstitial lung disease)
- Between gas molecules - increased with high flow rates, turbulent flow (rate, density), decreased airway radius (eg. Low lung volume/inadequate PEEP, bronchoconstriction, apparatus)
The below refers to attached graph:
- The area between the compliance line and the inspiratory line is additional resistive inspiratory work done
- The area between the compliance line and expiratory line is additional resistive expiratory work done
- This is work typically done by elastic recoil of lungs
- If this area falls within the area of elastic work of breathing, it is a purely passive process (using stored elastic potential energy of inspiration).
- If part of the area falls outside the area of elastic work, it demonstrates additional active work of expiration, which may occur in obstructive lung disease or when minute ventilation is high
State the normal lung volumes and capacities
Outline the clinical significance and measurement of closing capacity
Clinical significance:
- Increased CC decreases the effect of pre-anaesthetic preoxygenation (difficult to denitrogenate collapse airways)
- Increased CC increases dependent atelectasis
- Which can in turn cause lung injury via cyclic atelectasis (eg. In the setting where CC overlaps with tidal volume - airspaces may start closing at the end of normal expiration, and the repeated open and closing of these airspaces may cause injury similar to VILI)
- Responsible for age related decrease in PaO2 over time
How is it measured?
- Fowler’s method can be carried out with either tracer gas (xenon) or resident gas (nitrogen)
- Method:
- Patient expires to RV (residual volume). At this volume, dependent airways have collapsed and upper lobe (non-dependent) airways remain open with nitrogen-containing air
- Patient inspires 100% FiO2 to TLC
- Patient expires and nitrogen concentration of expired gas is measured:
- Phase I - dead space air, containing no N2 comes out
- Phase II - increasing N2 containing gas comes out as alveoli are emptied
- Phase III - N2 concentration plateaus as N2 containing air from upper lobe mixes with pure 100% O2 from dependent airways, creating a constant concentration of N2
- Phase IV - as dependent airways collapse, N2 concentration of expired gas rises again (no more mixing with 100% O2 containing gas).
- The point at which N2 starts to rise again is the closing volume
*closing capacity = closing volume + residual volume
Describe the balance between hydrostatic and oncotic pressures in the pulmonary circulation
(Starling equation below). In the pulmonary circulation, these are:
- LpS - surface area ~140m2 (compared to 4000-7000m2 in systemic circulation)
- Pc = 4-12mmHg
- Pi = interstitial hydrostatic pressure - essentially equal to alveolar pressure = atm pressure. Increases during PPV
- Surfactant decreases hydrostatic pressure by decreasing surface tension
- Pi(c) = 25mmHg throughout circulation; affectd by blood protein count
- Pi(i) = ~3mmHg at alveoli
- Sigma = 0.5-0.7 in lung
Define pulmonary vascular resistance and outline the factors affecting it
- Defined as the resistance to blood flow for a given pressure gradient across a vessel
Factors that affect PVR:
- Recruitment + distension
- At normal pressures and flows, some pulmonary capillaries are partially narrowed or collapsed
- As blood flow increases, capillaries that were collapsed are recruited, and capillaries that are narrowed are distended
- Lung volume
- PVR and lung volume have a ‘U’ shaped relationship, with lowest PVR at FRC
- At larger lung volumes, smaller capillaries are compressed. At smaller lung volumes, larger vessels/capillaries are collapse
- Hypoxia
- Hypoxia causes vasoconstriction of the pulmonary capillaries - this increases PVR
- Hypercapnoea causes vasoconstriction to a degree as well
- Acidaemia causes pulmonary vessels
- Gravity
- Blood has to flow against gravity to reach the upper lobes & resistance to flow is higher. Resistance to flow is lower in the middle + lower lobes (phenomena known as West’s zones)
- Autonomic nervous system + drugs affecting it
- α1 receptors - vasoconstriction
- β2 receptors - vasodilation
- M3 muscarinic receptors - vasodilation
- Local mediators
- Vasoconstriction - histamine, endothelin, serotonin
- Vasodilation - nitric oxide, prostacyclin, isoprenaline
**Note: should reproduce below graph when talking about PVR**
Compare the differences between the pulmonary and systemic circulations
Table
Describe the causes for differences in regional ventilation and perfusion & display on a graph how ventilation and perfusion are distributed throughout the lung
Ventilation:
- Global - minute volume is average of 4L/min (eg TV 400mL & RR 10)
- Regional - there may be multiple different reasons for uneven ventilation:
- Gravity-related vertical gradient of pleural pressure
- Posture (changes the direction of this gradient)
- Bases have more room to expand than apices
- Compliance differences between lung regions
- Pattern of breathing - it has been shown that there is a difference in pleural pressure distribution & radioactive xenon washout between breathing which engaged intercostal muscles as compared to ‘routine’ diaphragmatic breathing
Perfusion:
- Global - roughly equal to cardiac output
- Regional - regional blood flow is affected by multiple factors:
- Variation in alveolar oxygenation (hypoxic pulmonary vasoconstriction)
- Gravity related hydrostatic pressure
- Basic architecture of pulmonary vessels - this appears to be pretty heterogenous
Explain ventilation-perfusion matching and mimatching
Ideally, perfusion would be matched to ventilation (V/Q = 1) & gas exchange would be ideal under these conditions. Due to differences in blood and gas supply to different lung regions (see above), there is a range of V/Q ratios from 0-infinity
- When plotting blood/gas flow against V/Q ratio, you get a bell curve
- Typical minute ventilation = 4L/min & typical CO is about 5L/min, so global V/Q ratio would be about 0.8, if the whole lung was averaged
- Below is from a 22yo male
- V/Q ratios generally range between 0.3-3.
Define dead space and its components. Explain how these may be measured and describe the physiological impact of increased dead space
Definition: Dead space is the fraction of tidal volume which does not participate in gas exchange. It can be classified in multiple ways:
- Anatomical dead space:
- Volume of the conducting airways
- This is equal to about 150mLs in an adult (~2.2mLs/kg), higher in infants (~3mL/kg)
- Nunn - decreases in tidal volume will decrease the amount of dead space proportionately
- Physiological dead space:
- The part of tidal volume which does not participate in gas exchange
- This definition is designed to include alveoli that may be well ventilated but not so well perfused (for whatever reason)
- In healthy adults, physiological and anatomical dead space will be pretty similar & the gap (alveolar dead space) widens in pathology
- It includes anatomical dead space + alveolar dead space
- Apparatus dead space - related to volume within ventilatory devises eg. ETT/trache
How to measure dead space:
- Anatomical dead space - can be measured by Fowler’s method –> with initial breath of 100% FiO2 to flush out nitrogen
- Anatomical dead space will contain 100% O2 and 0% nitrogen
- Alternatively, can use CO2 instead of N2 for Fowlers - all CO2 containing air will have to have come from areas of the lung that participated in gas exchange. This will measure physiological dead space
- Physiological dead space calculation - can use the Bohr (/Enghoff) equation to calculate this (see pic)
Physiological impact of increased dead space:
- As dead space is a fraction of tidal volume not undergoing gas exchange, increasing dead space would be effectively the same as reducing tidal volume
- Increasing alveolar dead space (eg. In PE) will increase your minute volume proportionally to the change in the ratio of dead space to alveolar ventilation
Explain venous admixture, its relationship to shunt and ventilation-perfusion (V/Q) mismatch. List the causes of venous admixture
Definition: a volume of blood that needs to be added to ideal (ie lung unit where V/Q = 1) pulmonary end capillary blood to explain the observed difference between pulmonary end capillary oxygen content and arterial oxygen content. Ie. It is a calculated volume which appears to have bypassed the pulmonary gas exchange surface
- Often used interchangeably with ‘shunt’, however ‘true shunt’ in the pulmonary system refers to lungs with V/Q = 0
- Can’t measure shunt directly (can’t separate V/Q= 0 vs scatter) so calculate venous admixture
Calculation: measured by the shunt equation (Berggren equation - shown below). The shunt fraction is the ratio of venous admixture to total cardiac output
- Normal shunt fraction/venous admixture is 3%
Increased venous admixture occurs when perfusion (Q) exceeds ventilation (V), resulting in a V/Q mismatch, where V/Q< 1.0
Causes:
- Physiological/anatomical - sometimes referred to as ‘true anatomical shunt’
- Thebesian veins
- Bronchial veins
- Pathological
- Intrapulmonary - pulmonary AVM or fistula; anoxic lung tumour
- Intracardiac - ie congenital heart disease
- Other - porto-pulmonary shunt in liver disease (sats increase in supine vs standing)
- Either pathological or physiological
- True shunt - lung units with V/Q = 0. A certain amount of lung units will be like this under physiological conditions, with an increasing number with age (due to raised closing capacity), however this can also occur in disease (pneumonia/atelectasis/etc)
- V/Q scatter - lung units with V/Q<1.0. Similar to above
Explain the effect of ventilation-perfusion mismatch on oxygen transfer and carbon dioxide elimination
The V/Q ratios throughout the upright lung vary (see figure 1):
- V/Q= infinity –> dead space ventilation
- infinity > V/Q > 1 –> towards apicies
- V/Q = 1 –> ideal & occurs in the mid zones of the lung at ~ 3rd rib
- 0 towards bases
- V/Q = 0 –> true shunt
Effect on gas exchange (see figure 2):
- As lung units have increasing V/Q ratio, the closer the composition of pulmonary veins approaches that of alveoli
- As V/Q decreases below 1 & approaches zero, the closer the partial pressure of oxygen in pulmonary venous approaches that of mixed venous blood
- The effect of the V/Q ratio dropping from 1 to 0.1 causes a comparatively large drop in PaO2 and small rise in PaCO2
- The relationship between PaO2 and V/Q is steeper and more sigmoid than the relationship between PaCO2
- The greatest useful improvement in gas exchange occurs in the V/Q range of 0.1-1.0 (usually in bases of lungs) - small change in V/Q yields substantial improvement in oxygenation
Explain perfusion-limited and diffusion-limited transfer of gases
Diffusion limited:
- Rate of gas uptake in capillary is determined by the rate of diffusion across the blood-gas barrier
- Rate of diffusion from alveolus to blood is very slow
- For all 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 diffusion
- Eg. Carbon monoxide
Perfusion limited:
- Rate of gas uptake in the capillary is determined by capillary blood flow
- The rate of gas diffusion into the capillary is very rapid
- Equilibration between the alveolus and capillary occurs shortly after blood enters the alveolar capillary
- For most of its length, the capillary blood is fully saturated with the gas
- Increasing the blood flow rate will increase the rate of total gas uptake, until the capillary transit time is faster than the gas diffusion time
- Increasing the partial pressure gradients between the alveolus and capillary does not significantly increase the rate of gas uptake into the blood if the blood flow remains the same
- Eg. O2, CO2 & nitrous oxide
List the physiological factors affecting the diffusion of oxygen across the alveolar membrane. Describe how this changes with exercise.
DLO2 = oxygen uptake/PO2 gradient
(measured in mL/min/mmHg)
[* Note - DL is closely related to Fick’s Law of diffusion. DL = AK/T (or AK/dx), so conceptually, Fick’s Law can be rearranged to give: DL = -J/dx]
Factors affecting diffusion of gases across the blood-gas barrier:
- Factors affecting gas properties (“D” (diffusion coefficient))
- Molecular size
- Density + viscosity
- Temperature
- Factors affecting the gas exchange surface area (“A”)
- Age
- Body size
- Lung volume
- Shunt, dead space, V/Q inequality
- Factors influencing membrane characteristics (“dx”)
- Disease states - eg. Pulmonary oedema, pulmonary fibrosis
- Factors affecting uptake by erythrocytes
- Affinity of Hb for O2
- Hb concentration
- Cardiac output (capillary transit time)
In exercise:
- Oxygen uptake increases
- Increased cardiac output –> increased pulmonary blood flow
- Better V/Q matching - perfusion of previously non-perfused areas
- Increased tidal volumes (Surface area increases)
- Partial pressure gradient “dP” increases
- Oxygen extraction ratio increases (Mixed venous PO2 will be lower)
- Increased minute ventilation will cause decreased PACO2 + therefore increased PAO2
- Increased delivery of Hb to absorptive surface acts as an oxygen sink and maintains a low capillary partial pressure
Explain the oxyhaemoglobin dissociation curve and factors that may alter it including the Bohr and Double Bohr effect
The oxygen dissociation curve is a graph displaying the relative association between partial pressure of oxygen and the affinity of oxygen to haemoglobin (i.e. oxyhaemoglobin saturation)
- The flat upper plateau decreases variability in in blood oxygen content even with large changes of PaO2
- The steep lower part allows the increased release of oxygen from haemoglobin with only a small change in PaO2
- P50: shows the partial pressure of O2 where haemoglobin is 50% saturated (P50 = 26.6mmHg)
- The properties of haemoglobin that affect the shape of the curve:
- Hb is a tetramer with 2x alpha & 2x beta subunit
- Each subunit has a heme porphyrin (with central Fe atom)
- Central Fe has total 6 binding sites - 4 taken up by purines, one by histidine & one spot available for molecular O2
- The Tensed state “T” is the deoxygenated form with 0 O2 molecule & “R” state is the oxygenated state with 4 O2 molecules
- Binding of O2 results in conformational change to the rest of the haemoglobin molecule which increases the affinity of further O2 binding
- This is called positive cooperativity and results in O2-Hb dissociation curve to be sigmoid
Factors affecting it:
Conditions which shift the curve to the right:
- Increased PCO2, temperature, 2,3-DPG
- Presence of sulfhaemoglobin
- Decreased pH
The above reduces affinity for O2 to Hb and oxygen offloading at the tissues
Conditions which shift the curve to the left:
- PCO2, temperature, 2,3-DPG, pH and carbon monoxide (CO)
- Unusual haemoglobin species shift the curve to the left (methaemoglobin, carboxyhaemoglobin, foetal haemoglobin)
The above increases the affinity of O2 to Hb and reducing offloading
[Note: 2,3-DPG: promotes the offloading of oxygen. It is produced from a side reaction of glycolysis and is upregulated in anaemia (due to relative tissue hypoxia), at altitude and is reduced in stored blood]
Bohr effect: reduced affinity of O2 for Hb when pH is low, and vice versa when high à promotes offloading
Double Bohr effect: aids to offload O2 to foetus à the curve shifts to the right in the mother and to the left in the foetus facilitating transfer across placental circulation to foetus
Explain the carbon dioxide dissociation curve
The CO2 dissociation curve describes the relationship between PCO2 and total CO2 concentration of blood
- The lower the Hb saturation with O2, the higher the total CO2 concentration for every pCO2. This is because of the increased affinity of Hb for CO2 when Hb is deoxygenated (Haldane effect)
- The arterial point corresponds to the CO2 content of arterial blood PCO2 is 40mmHg and CO2 content is 480ml/L. The total CO2 content in venous blood at the same PCO2 would be ~ 500mL/L (mostly due to Haldane effect)
- The mixed venous point corresponds to the CO2 content of mixed venous blood, where PCO2 is 46mmHg and CO2 content is 520mL/L. Due to Haldane effect, if this blood was ‘arterialised’ by addition of O2 while total CO2 content remained the same, the extra CO2 liberated by the oxygenation of Hb would produce an increase in the PCO2
The ‘physiological CO2 dissociation curve’ refers to the line that is draw between the arterial point and mixed venous point. This describes the change in CO2 in blood as it travels in the circulation (see attached image)
Explain the similarities and differences between myoglobin and adult haemoglobin (60% of marks) and their physiologic relevance (40% of marks)
(Exam length question)
See image
Describe the Helium dilution method of measuring FRC
(own)
Tracer gas dilution
* ○ Closed circuit system where spirometer is filled with a mixture of He + O2 (conc and volume of spirometer gas is known)
* ○ The subject breathes in the mixture starting from FRC. They inhale this volume and it is distributed widely and evenly in their lung volume
* ○ There is equilibration of helium throughout the spirometer and lungs & the new concentration of helium in the spirometer is measured
* ○ From this concentration, the volume of distribution of that gas can be calculated (ie. Intrathoracic volume):
C1 × V1= C2 ×(V1+ V2 )
C1 = Initial tracer concentration V1 = Initial volume C2 = tracer concentration after equilibration V2 = FRC
Note:
* In practice O2 must be added to make up for that absorbed by the patient and CO2 must be absorbed.
* This technique only measures gas in alveoli that communicate with the mouth. Gas trapped behind closed airways is not measured
Describe how body plethysmography can be used to measure FRC
(own)
Body plethysmography
- This is a method that uses Boyle’s law to measure lung volumes. The experiment is conducted as follows:
- The patient and equipment are situated in a tight box with known volume and pressure
- The patient breathes through a tube connected to the outside & the tube is clamped off at the start of the experiment, when the patient is at FRC
- The patient attempts to breathe in through the tube (No air flows as the tube is clamped) & the negative pressure generated to draw in that breath is measured at the mouth (Pm)
- Given that all volumes and pressures can be measured, and the only unknown is the volume inside the chest, the volume can be calculated using the equations below (see image)
Describe the carbon dioxide and oxygen response curves and how these may be used to assess the control of breathing
(exam length question, never before asked)
The carbon dioxide and oxygen response curves describe what happens to minute ventilation with changes in partial pressures of these gases in the circulation
- As PaCO2 increases, minute ventilation increases in a linear and reproducible way (given PaO2 remains constant)
- Minute volume should increase by 3L/min for every 1mmHg PaCO2
- As PaO2 decreases, minute ventilation increases (in a non-linear way, given PaCO2 is constant)
- MV should triple when PaO2 drops to 40mmHg/sats 60%
If other pulmonary function tests are normal, but a patient remains hypoxic or hypercapnoeic, the following tests can be done to asses control of breathing:
Hypoxic challenge:
- Patient is given a hypoxic gas mixture to breathe in with constant CO2 (usually have a closed circuit with a CO2 scrubber)
- With each breath, the content of O2 will decrease
- The patient’s MV is expected to increase - increased RR, or tidal volume or both
- This is mainly a test of peripheral chemoreceptor function
- Reasons for abnormal response:
- Intrinsic chemoreceptor issue
- Problem with central integration
- Poor sensitivity to hypoxia
- Chronic exposure to: high altitude; hypoxia due to disease; high oxygen demand (endurance athletes)
- Age-related desensitisation
Hypercapnoeic challenge:
- Similar to above, but the circuit is filled with 100% FiO2 + CO2 scrubber removed
- Therefore patient is breathing in an increasingly hypercapoeic gas mixture (overall hyperoxic too)
- MV should increase in response to hypercapnoea
- This is a test of central chemoreceptos
- Reasons for abnormal response:
- COPD, OSA, OHS
- Metabolic alkalosis
- Elderly patients
- Endurance athletes
- Hypothyroidism
Mouth Occlusion Pressure:
- Measures the maximum pressure which is generated over the period of a 100-ms occlusion of the airway (occlusion so brief that no voluntary response is possible)
- Pressure represents pressure generated by inspiratory muscles
