Respiratory Physiology Flashcards
1
Q
Function of the respiratory system
A
Gas exchange
Immune defence
Metabolic
Filter for small emboli
Acid base
2
Q
During quiet nasal breathing how much of total airway resistance comes from the upper airways?
A
2/3rds
3
Q
Functions of the upper airways
A
Conduction of gas
Warm and humidify gas
Filter and immune
Vocalisation
4
Q
Function of the larynx
A
Regulation of expiratory air flow - important for vocalisation, cough and control of end expiratory volume
Protection of lower airway
Vocalisation
5
Q
Roughly how many times does an airway branch from trachea to alveoli
A
23
6
Q
Adult tracheal length and diameter
Epithelium
Special function
A
11cm 18mm
Ciliates columnar with goblet cells
Mechano and chemical receptors to mediate cough
7
Q
Angle of right main bronchi to trachea vs left
A
25o vs 45o
8
Q
At what weibel level does cross sectional area rapidly increase?
Implication for air flow?
A
5-11 (small bronchi)
Lower flow velocity
9
Q
Distinction between bronchi and bronchioles
A
No cartilage in bronchioles
10
Q
Epithelial changes between large bronchi, small bronchi and bronchioles
A
Columnar epithelium of bronchi becomes cuboidal in respiratory bronchioles with gradual transition between the two over small bronchi and non-respiratory bronchioles. No goblet cells in bronchioles.
11
Q
Diameter of bronchioles
A
<1mm
12
Q
Character of respiratory bronchioles
A
Intermittent alveolar out pockets
Still has muscle layer and sphincters around alveoli
13
Q
Size of alveoli
Total surface area
A
0.3mm diameter
50-100m2
14
Q
Types of alveolar cell and function + adaptation
A
Type 1 - 80% of surface, gas exchange, very thin layer of cytoplasm, metabolically limited.
Type II - manufacture surfactant, high metabolic capacity
Type III - alveolar macrophages - proteolytic enzymes
15
Q
How are alveoli connected?
Significance
A
Via respiratory bronchioles
Small (8-10micrometer holes) - pores of kohn - allows collateral ventilation
16
Q
What composes the alveolar capillary membrane?
A
Alveolar epithelium
Interstitial tissue (fused alveolar and endothelial basement membranes)
Capillary endothelium
17
Q
How are capillaries arranged around alveoli for gas and fluid exchange?
A
A close ‘thin’ connection for gas exhange
A thick side with interstitial space where fluid exchange can occur
18
Q
Why are lymphatics important in the lungs
A
Accumulation of fluid would be bad and impair gas exchange
19
Q
What are the lung volumes?
A
Inspiration reserve
Tidal
Expiratory reserve
Residual
20
Q
What are the lung capacities
A
Total lung (all volumes)
Vital (inspiratory reserve, tidal and expiratory reserve)
Inspiratory (tidal and inspiratory reserve)
Functional residual (expiratory reserve and residual)
21
Q
Total lung capacity of a male vs female
Where is most of the difference?
A
6000ml vs 4200ml
Inspiratory reserve volume 3300 vs 1900
Small differences in residual and expiratory reserve volume. Tidal volumes the same.
22
Q
What determins vital capacity?
A
Body size
Strength of respiratory muscles
Chest and lung compliance
23
Q
What is functional residual capacity?
A
The volume left in the lung at the end point of passive expiration where the tendency of the lung to collapse and the thoracic cage to expand are equal.
24
Q
What causes reduced functional residual capacity
A
Supine or head down positioning
Age, posture
Pulmonary fibrosis, pulmonary oedema
Obesity, abdominal swelling
Thoracic wall distortion, reduced muscle tone
25
What increases functional residual capacity
Positive intrathoracic pressure
Emphysema
Asthma
26
How is functional residual capacity measured?
Helium dilution - fixed circuit spirometery with known concentration helium (insoluble), patient breaths mixing volume of gas mixture with FRC - amount helium is diluted gives FRC.
Body plethysmograph - patient in closed chamber and measure pressure and volume changes when subject makes inspiratory effort.
27
What gas law is needed to determine FRC by body plethysmograph
Boyles law
28
What needs to be introduced into the system during helium dilution measuring of FRC and why?
Oxygen to compensate for oxygen consumption.
29
What is closing capacity of the lungs
The volume at which airways collapse during expiration
30
What is the relationship between closing capacity and functional residual capacity
FRC always > CC under normal circumstance
If FRC decreases of CC increases in disease (e.g loss of elasticity) then airway closure may occur at end of normal expiration producing large areas of atelectasis on induction of anaesthesia.
31
Limitation of helium dilution
Non communicating air spaces
32
Mechanism of body plethysmograph for FRC measurement
Sit in sealed box with mouthpiece. At end normal expiration mouthpiece sealed but pt told to breath in. FRC volume thus expands. Pressure in box changes as fixed volume. Given pressure change volume change can be calculated by Boyles law.
33
Common dynamic lung volumes
Forced vital capacity - volume forcibly expired after maximal inspiration
FEV1 - volume forcibly expired in first second following vital capacity breath
34
Normal fev1:Fvc ratio
95%
Declining to 85% in elderly
35
What is ventilation
Process of fresh gas reaching the area of the lungs where fresh gas exchange takes place
36
What is dead space
Subdivisions
Areas of the lungs which are ventilated but that do not take part in gas exchange
Anatomical - conducting airways
Alveolar - areas ventilated but not perfused
37
How much anatomical dead space is there in an adult?
2ml/kg or 150ml on average
38
How can anatomical dead space be measured?
Taking a cast of the airways - historical
Fowler’s method
39
What is fowlers method for measuring anatomical dead space
patient takes a single vc breath of 100% o2 and exhales through a rapid nitrogen gas analyser
Nitrogen concentration is then plotted against expired volume
Three phases
1 - no nitrogen
2 - increasing nitrogen as alveolar air introduced
3 - plataeu
Dead space volume is the dividing line on phase 2 that gives an equal volume above the curve the right as below to the left (look at a picture)
40
What factors could influence anatomical dead space?
Changes in bronchial tone
Changes in position of head and neck
External breathing apparatus eg ett
Changes in tidal volume - low Tv causes laminar flow and decreasing dead space
41
What is the term for the proportion of a breath that reaches the alveoli (ie tidal volume - anatomical dead space)
Alveolar volume
Can be multiplied by respiratory rate to give alveolar ventilation
42
What equation is used to calculate physiological dead space?
Bohr equation
Vd/Vt = (PACO2 - PECO2)/PACO2
Or
Vd/Vt = PaCO2 - PECO2)/PaCO2
PA - alveolar co2 pressure
PE - expiratory gas co2 pressure
Pa - arterial co2 pressure - substituted in in clinical practice
43
What is physiological dead space
Anatomical dead space + alveolar dead space
44
Muscle actions of inspiration
Diaphragmatic flattening
External intercostals
Strap muscles (sternocleidomastoid, anterior serrati, scalenes)
45
Proportion of quiet ventilation provided by diaphragm alone?
Adaptation to constant use
75%
Lots of slow twitch so fatigue resistant
46
Main function of accessory muscles of inspiration during quiet inspiration? Forced inspiration?
Quiet - stabilisation of upper rib cage to prevent indrawing
Forced - elevation and expansion of rib cage.
47
Muscles used in quiet and forced expiration
Quiet - nil
Forced - abdominal muscles, internal intercostals
48
What determines resting volume of the lung at FRC
Pulmonary elasticity would cause collapse of lungs to smaller than FRC
Chest wall volume would be larger than FRC due to recoil
Thus combination of two opposing forces results in FRC volume as it is.
49
What couples the thoracic Cage (chest wall and diaphragm) to the components of the lung
The trans pulmonary pressure gradient
50
What is the interpleural pressure at end expiration?
How does it change on inspiration, normal and forced?
-0.3kpa
Normal inspiration -1kPa
Forced inspiration -4kPa
51
How can interpleural pressure be measure
Intrapleural catheter
Balloon cather in mid oesophagus
52
What is normal airway pressure during spontaneous respiration?
Atmospheric - the changes are all in the interpleural pressure
53
What causes lung expansion (sequence)
Contraction of respiratory muscles
Expansion of thoracic cage
Decreased interpleural pressure
Lung expansion to equalise
54
What is trans pulmonary pressure
The pressure difference between airway pressure and interpleural pressure
55
What is lung compliance
Lung compliance = change in volume / change in trans pulmonary pressure
Ie the amount of expansion achieved at a given transpulmonary pressure
56
Around normal FRC what is the relationship between interplumonary pressure and vital capacity
Roughly linear
57
What happens to compliance at high and low lung volumes
Reduced at high as elastic fibres are stretched to limit
Reduced at low because of airway collapse
58
Rough value for healthy lung and chest wall compliance at FRC
200ml / cm H2O
59
What reduces chest wall compliance
Diseases like ankalosing spondylitis making chest wall rigid
60
What is the overall respiratory system compliance
A combined chest wall and lung compliance
Overall compliance less than the individual ones
61
How can respiratory system compliance be measured?
Statically - apply a known distending pressure and wait to come to equilibrium (all movement to shift) and measure volume change
Dynamically - during spontaneous or mechanical ventilation plot change in vol with change in pressure constantly. Dynamic compliance derived from slope of curve produced
62
What would give a lower reading (less volume change for given pressure), static or dynamic compliance measurements?
Why?
Dynamic
Airflow may not have completely ceased on measurement (further volume increases could occur as air moves from less to more distendable regions)
A sustained pressure (as in static) causes relaxation of tissues due to their viscoelastic nature, thus gives a larger volume change
Inter pulmonary pressure will be lower than applied pressure due to resistance thus underestimate of compliance.
63
How does positioning change compliance?
Decreased compliance on moving from stood to supine
64
Effect of age on resp system compliance
Lower in infants and elderly
65
Diseases that can lower compliance
Ards
Pulmonary oedema
Ankylosing spondylitis
Pregnancy
66
What is the term for the phenomena of inspriatory and expiratory pressure volume curves not coinciding - what does it form?
Hysteresis
A pressure volume loop
67
What is the representation of the area of the pressure volume loop with hysteresis?
Lost energy as a result of viscous losses during stretching and recoil of the tissues and frictional losses of airway resistance
68
What way does a pressure volume loop run? Which limb is inspiration and expiration
Anti-clockwise
Rightmost limb (ascending) expiration
69
What is surfactant
A phospholipid secreted by type ii alveolar cells
70
Effects of surfactant
Reduces surface tension causing
- more even distribution of compliance
- stabilisation of small alveoli
- reduction of the energy lost in inspiration thus reduced hysteresis
- helps keep alveoli dry
71
How does decreased surface tension from surfactant act to increase and even compliance
Small alveoli disproportionately effected by surface tension with tendancey to collapse, thus surfactant reduces this and reduces overall tendency of alveoli to collapse
72
How does surfactant act to keep alveoli dry
Surface tension creates a negative pressure drawing fluid in, this is reduced by surfactant
73
What is the gravitational model of distribution of ventilation and perfusion in spontaneously breathing patient
Lung behaves as a volume of fluid with hydrostatic pressure greater at the base than apex.
This results in less negative interpleural pressure at base.
As a result apex is overdistended (on the flattening upper part of pressure volume curve with less compliance) and base is well distended with good compliance.
Thus on inspiration bases expand well delivering air to the well perfused (also due to gravity) lung bases.
74
What occurs to the gravitational model for distribution of ventilation and perfusion on ppv?
FRC is reduced thus bases now become at the flat part of the curve needing more pressure to ventilate and apexs enter good compliance zone - thus preferential distribution of air to poorly perfused apexes
75
What casts doubt on gravitational model of distribution of ventilation and perfusion
Heterogeneity in ventilation and perfusion seen in zero gravity
Differences in V/Q on same gravitational level can be bigger than the apex base gradient
Expected changes aren’t always seen in postural changes
76
What is the structural model of ventilation perfusion matching
That VQ remains matched due to changes in regional vascular resistance largely influenced by changes in lung volume (due to twinned system of vessels with airways). Still influenced by gravity but not dependant on it. Main determinant is local airway resistance allowing variation over the one gravitational level.
77
What influences gas flow through the airways
Transpulmonary pressure gradient
Airway resistance
Pattern of gas flow
78
What formulae determins gas flow through the airways
Hagen Poisuelle law
Flow = pi . pressure difference . r^4 / 8 . length . viscosity
79
What are the characteristics of laminar gas flow
Smooth
Circumferential layers sliding over one and other with fastest flow in centre
80
Characteristics of turbulent gas flow
Disordered
Eddies and whirls
Relatively flat velocity in overall direction of flow
81
How is likelihood of turbulent flow predicted?
Reynolds number
Re = 2 . radius . average velocity . gas density / viscosity of gas
82
What are the significant Reynolds number cut offs
<1000 likely laminar flow
>2000 likely turbulent flow
83
What impact does turbulent flow have on the pressure flow relationship of a gas in the airways compared to laminar
Increases the effective resistance
- pressure gradient proportional to velocity^2
- dependant on gas density not viscosity
- inversely proportional to radius^5
84
Where does turbulent flow commonly occur in the respiratory tree
Laryngeal opening
Large bronchi weibel 1-5
85
Normal sites of resistance to gas flow in airways
Why
Upper airways (nose)
Major bronchi
Cross sectional area increases exponentially with branching.
86
How can airway resistance be accurately measured
Simultaneous recording of airflow and pressure gradient in more than and alveoli! Hard!
Could do interpleural pressure monitoring instead but some small variation in pressures due to resistances - especially in pulmonary oedema and fibrosis
87
Clinical measures of airway resistance
Pitfall
FEV1
PEFR
Also rely on expiratory muscle activity, not just resistance.
88
What factors influence airway resistance
Lung volume - higher volume decreases resistance
Bronchial smooth muscle tone
Histamine release
Properties of inspired gas - density and viscosity
Lower and upper airway obstructions
Anaesthesia
89
Why do patients with high airway resistance purse lip breath?
Increases FRC (PEEP)
90
What is the main determinant of bronchial smooth muscle tone
What causes reflex constriction
Parasympathetic control via the vagus
Stimulation of larynx, trachea or bronchi
91
What are the effects of H1 and H2 receptor stimulation on airway resistance
H1 - bronchoconstriction
h2 - bronchodilator
Overall effect is bronchoconstriction
92
What inhaled gas reduces airway resistance
Helium
93
Causes of lower airway obstruction increasing resistance
Mucus plug
Tumour
Epithelial desquamation
Foreign body
94
Quantitative Effect of anaesthesia on airway resistance
Why
Doubles it
Reduced FRC
Increased upper airways resistance
95
Causes of decreased FRC under anaesthesia
Supine positioning - or worse, head down/pneumoperitoneum
Muscle relaxation (diaphragm rises), chest wall decreases in circumference
Atelectasis
96
What elements of work are required for inspiration
Work to overcome elastic forces of the lung (compliance) stored as elastic energy
Work to overcome airway resistance during movement of air into the lungs
Work to overcome the viscosity of the lung and chest wall tissue (tissue resistive work)
97
What are the fates of the energy used in the work of inspiration during normal respiration
Work to overcome in elastic energy returned as contraction on expiration
Work to overcome tissue and airway resistance lost as heat
98
How can pathology of the lung effect work done
Need for expiratory work - asthma
Increased airway resistive work - copd
Increased compliance work - pulmonary fibrosis
99
What is oxygen tension at sea level kPa
In mitochondira?
21.3 (0.21 x 101.3)
0.5
100
What is the partial pressure of oxygen in the lower airways? Why different to atmosphere
Addition of saturated water vapour
0.21 x (101.3-6.3) = 0.21x95 = 20kPa
101
Why is the partial pressure of oxygen in the alveoli different to that of the lower airways (after saturated water vapour has been accounted for)?
What does this depend on
Some oxygen is absorbed and co2 is secreted
Depends on:
Rate oxygen is introduced into alveoli (alveolar ventilation and FiO2)
Rate of removal by absorption into alveolar capillary blood
Rate of delivery of co2 by pulmonary capillary blood
102
How do we calculate amount of oxygen absorbed in the alveoli?
Estimate using amount of carbon dioxide excreted (approximated as PACO2) x the respiratory quotient (as less CO2 excreted as O2 absorbed)
103
What is the alveolar gas equation?
PAO2 = PIO2 - PaCO2/RQ
104
Why is calculating PAO2 important
Determins pp gradient across alveolar membrane
105
Rough normal oxygen consumption per min
250ml/min
106
What would decreases alveolar oxygen concentration
Hypoventilation (at normal demand <4lpm)
Hyper metabolic states (eg sepsis)
Sodium bicarb infusion - increases co2
Decreased fiO2
107
What determins alveolar co2 tension
Rate of delivery of co2
Rate of alveolar ventilation
108
What is the effect of increasing alveolar ventilation on CO2 at low volumes compared to high
More marked reduction per unit increase below 6 litres then diminishing returns above this.
109
What does the rate of gas transfer depend on
Properties of membrane - surface area, thickness
Properties of gas - solubility, molecular weight
Pressure gradient
110
What is Ficks law of gas transfer
Rate of gas transfer = k x A x deltP / D
= (solubility / square root molecular weight) x area x pressure gradient / distance
111
What Favours oxygen transfer over Co2 in the alveoli
Lower molecular weight
Greater partial pressure gradient
112
What favours Co2 over o2 in diffusion across alveoli?
Higher solubility (blood gas coefficient) - 24x that of oxygen
113
How far does a red blood cell get past an alveoli before it is fully o2 saturated in health and normality?
What is the effect on o2 and co2 of making the diffusion gradient harder?
Around half
Harder gradient (e.g. fibrosis, oedema increasing depth or decreased area) effect o2 much more than co2
114
What proportion of oxygen is transported in blood by what means
Hb 97%
Dissolved 3%
115
What determins how much oxygen is dissolved in blood?
How much oxygen is typically dissolved in blood
Linear relationship with PAO2
0.023 ml/kPa/100ml
Thus at PAO2 of 13 = 0.3ml/100ml dissolved O2
116
How much oxygen would be dissolved in blood if FiO2 was 100% and pCO2 5 and RQ 0.8
PAO2 = 95 - 5/0.8 = approx 90
Dissolved O2 = 90 x 0.023 = 2.07ml/100ml blood
117
What is the structure of haemoglobin
Iron state?
4 subunits each with ferrous (Fe2+) atom
118
Normal adult Hb proportions
98% HBA1 - 2 alpha 2 beta
2% HBA2 - 2 alpha 2 delta
119
Fetal Hb chains
Other difference to adult chains
2 alpha 2 gamma
Lower affinity for binding 23DPG increasing affinity for oxygen
120
How does 23 DPG work?
Binds to deoxygenated haemoglobin significantly reducing affinity for o2 facilitating unloading of oxygen in tissues with low oxygen tensions
121
When is fetal hb replaced by adult hb
Beta chain production starts after birth replacing gamma chains over first year of life
Majority is HbA by 6 months
122
What are key capharacteristics of oxygen binding to Hb
Expends primerily in local oxygen tension PaO2
Is effected.p by local mediators (co2, 2.3.dpg, ph temp)
Produces an a,listeria changing in hb to relaxed form creating cooperative binding (as one binds easier for more to bind)
123
What is the effect of co2 binding to hb called, how does it work
Haldane effect
Deoxygenation of hb increases affinity of proton binding sites enhancing ability to transport co2 from tissues to lungs
124
What is the effect of a left or right shift on the oxyhaemoglobin dissociation curve
Left shift, higher saturation at given tension, more likely to retain o2 (higher affinity)
Right shift reverse
125
Causes of left shift on oxyhaemoglobin dissociation curve
Hypothermia
Alkalosis
Decrease CO2
Decreased 2.3.DPG
Presence of HbF
126
What cause right shift on oxyhaemoglobin dissociation curve
Acidosis
Raised co2
Raised temp
Raised 23DPG
127
What causes the sigmoid shape of the oxyhaemoglobin dissociation curve
What value can be used to characterise it?
The allosteric modulation of hb by o2 causing cooperative binding
The p50 - oxygen tension at which 50% hb is saturated
128
What is the name for the effect of the shift in the oxyhaemoglobin dissociation curve caused by co2 entering or leaving blood
How does it work
Bohr effect
Co2 enters red cell combines with water and dissociated to h and bicarb
Increased h then shifts ohd curve to right releasing o2
Bicarb moves out of RBC and Cl in
Process reversed at lungs
129
How much o2 can be carried on Hb
1.34 ml per g Hb (practically, theoretically 1.39)
= SaO2 x 1.34 x Hb x 0.01
So with some easy typical values
= 100 x 1.34 x 15 x 0.01 = 20.4ml/100ml
130
What is the theoretical oxygen carrying capacity of Hb? Why is it higher than the actual?
1.39ml/gHb
Higher than actual of 1.34 because of abnormal Hb like COHb
131
What is the formulae for the total oxygen carrying capacity of blood
CaO2 = (SaO2 x 0.01 x Hb[g/dl] x 1.34) + (0.023 x PAO2)
132
What is oxygen delivery
How is it calculated
Rough values
The amount of o2 delivered to the peripheral tissues per minute
CaO2 x Cardiac output
20ml/100ml x 5L/min
1L oxygen delivered per minute
133
What is oxygen uptake?
Formula
Typical values
Amount of oxygen taken up by tissues per minute
VO2 = Delivery of oxygen (CaO2 x CO) - return of oxygen (CvO2 x CO)
= 1000 - 750
= 250ml/min
134
How does the body increase do2
What occurs in extreme demand?
Increase Co as hb and SpO2 pretty fixed
Cardiac output can’t increase enough, tissue demand exceeds body’s capacity to deliver, SvO2 falls, extraction ratio increases and tissue hypoxia occurs.
135
What is the difference between venous and arterial co2 in blood
Pressure and Volume
About 0.7kpa
Around 4ml/100ml
136
Out of the 4ml of CO2 added to arterial blood through the capillary bed where does it distribute?
2.8ml 70% enters erythrocytes forming carbonic acid, this dissociates then is buffered by deoxHb with tissue exchange of bicarb for Cl ions
0.9 ml 22% as carbamino compound - mainly with Hb
0.3ml 8% in solution
137
Why is the hct of venous blood greater than arterial
Shift of Cl ions in causes increase in erythrocyte volume
138
What are the body stores of oxygen (volume and location)
How long will these last before low enough that severe hypoxia occurs
1.5L
50% in Hb
30% in lungs
20% in myoglobin
3-4mins
139
If normal body oxygen stores are around 1.5L how much are they increased to with preoxygenation
4.25L by increasing lung storage
140
Rough body store of co2?
Effect of apnea on this?
Around 120L
Apnea increases it by about 1kPa in first minute then about 0.4kPa a minute after as passive diffusion up the apneic airways occurs
141
What are the characteristics of the pulmonary circulation in terms of pressure and resistance
Low pressure - about 20% of systemic
Low resistance
142
Rough time frame that blood takes to pass through pulmonary capilaries
0.5-1s
143
What are the effects of alpha and beta adrenergic stimulation and vagal stimulation on pulmonary circulation?
Alpha - constricts
Beta - dilates
Vagal - dilates
144
What is the supply of blood to the supporting tissue of the lungs (connective tissue, septa, bronchi)? Where does it drain?
Bronchial arteries from the thoracic aorta
Drains into the pulmonary veins causing anatomical shunt
145
Why is left ventricular output greater than the right
1-2% of blood is supplied by the bronchial arteries draining directly back into the pulmonary vein and thus left ventricle bypassing the right.
146
Normal pulmonary artery, capillary and vein pressures?
Artery 25/8mmHg MAP 15
Capillaries 10mmHg
Vein 4 mmHg
147
What happens to right ventricular and pulmonary artery pressures on increased cardiac output?
Not much change due tot he distensibility of the pulmonary vasculature
148
Factors that influence pulmonary vascular resistance?
Autonomic innervation
Nitric oxide
Prostacyclin
Endothilins
Vascular transmural pressure
Lung volume
Lung disease
Hypoxia vasoconstriction.
149
What is the role of autonomic innervation on pulmonary vascular resistance
Pretty minimal, no tone at rest, sympathetic tone causes some vasoconstriction when triggered
150
What is the origin of nitric oxide in the lungs? How does it act?
Derived from l-arginine in endothelium
Increases intracellular concentration of cGMP causing vasodilation
151
What is the effect on lung vasculature of the endothelium dervived determinants of PVR
NO dilates
Prostacyclin dilates
Endothelinis constrict
152
Origins of prostacyclin and endothelins
Prostacyclin - arachidonate
Endothelins - peptide
153
What is the impact of vascular transmural pressure on PVR? Why?
Relevance to anaesthetics
Thin collapsible vessel walls
Higher airway pressures cause collapse and increase PVR
Thus PPV under anaesthesia can cause increased PVR
154
How does change in lung volume effect PVR
Effects vessel calaber
As lung increases in volume vessels stretch and elongate becoming narrower
155
How does lung diseases alter PVR
Acute and chronic lung disease can increase pvr
156
How does pulmonary hypoxia alter pvr
Hypoxia vasoconstriction causing increase pvr
157
What acts to initiate hypoxia pulmonary vasoconstriction
Small pulmonary arteries
To a lesser extent capillary bed and venous system
158
Function of hypoxic pulmonary vasoconstriction
Improves vq matching diverting blood away from poorly oxygenated areas
Can be generalised however and can cause significant increases in PVR eg in foetus or at high altitude
159
What drugs potentiate hypoxic pulmonary vasoconstriction
Cox inhibitors
Propranolol
Almitrine
160
What drugs attenuate hypoxic pulmonary vasoconstriction
Volatile anaesthetics
Nitrates
Nitroprusside
Calcium channel blockers
Bronchodilators
161
What factors can result in pulmonary hypertension?
Intracardiac shunt (asd/vsd)
Increased lvedp (mitral stenosis, constrictive pericarditis)
Obilteration - pulmonary fibrosis
Obstruction - emboli
Vasoconstriction - sleep apnea, high altitude
Idiopathic
162
What are the functional zones of the lungs in the gravitational model for ventilation perfusion
Issues with model
Zone 1 (apex) - alveolar pressure created than arteriolar pressure and venous pressure, both arteriole and vein collapse obstructing blood flow. This part of the lung becomes alveolar dead space.
IN PRACTICE ZONE 1 DOES NOT EXIST, ARTERIOLAR PRESSURE ALWAYS MORE THAN ALVEOLAR - except in cases of decreased blood pressure such as hypovolaemia or increased alveolar pressure such as PPV or PEEP.
Zone 2 - alveolar pressure greater than venous pressure but less than arterial pressure, blood flow is partially obstructed - the collapsed veins open in systole or if pulmonary artery pressure increases
Zone 3 - alveolar pressure less than venous and arterial pressure. Blood vessels patent. Blood flow increases by recruitment of closed vessels and dilation of those already open. Causes decreased PVR
163
Where does zone three of VQ lung gravity model extend?
To about 10cm above heart
164
What are the terms for the zone 2 effect in the VQ of the lungs
Starling resistor
Waterfall effect
165
Looking at the zone theory of VQ matching in the lungs what happens on lying supine? What about exercise
All zones become like zone 3 pattern
166
What is a physiological shunt
When blood passes an inadequately ventilated alveoli with too greater perfusion for gas exchange to occur
V/Q <1
167
What is alveolar dead space
Where full alveoli do not receive perfusion
V/Q >1
168
What casts doubt on the gravitational model of VQ matching
There is significant heterogeneity over one gravitational plane of the lung
The VQ ratio at the apex is around 3.3 and base 0.6 so isn’t perfect by any stretch
169
What is the normal A-a gradient
What causes it
0.5 - 1 kPa
Sum of the pO2 gradients across alvolar capillary membrane
Effect of shunted blood
170
What would cause an increase in A-a gradient
Increase in diffusion barrier
Increase in shunt
171
Causes of physiological shunt
Venous blood entirely bypasses lung (eg thebesian veins, bronchial veins, cardiac shunts)
Blood passes through areas that are not adaquetly ventilated V/Q <1 (eg pneumonia)
Blood passes through areas that are not ventilated at all V/Q 0
172
What proportion of physiologically shunted blood becomes an issue?
<10% not clinically significant
>30% poor survival
173
What is the shunt equation
Shunt flow/total flow = reduction in oxygen due to shunt/total oxygen added by lungs
174
What are the different levels of ventilatory control?
Medulla - inspiratory and expiratory centres
Pontine - pneumotaxic and apneustic centres
Cortical and limbic areas
175
How do the medullary centres of respiration control interact?
Reciprocal innervation
As activity increases in one centre inhibitory signals are relayed to the other.
176
Where is the inspiratory centre of the medulla?
Function
Dorsal medullary reticular formation
Source of basic ventilatory rhythm
During inspiration increased activity to muscles of inspiration.
During expiration increasing amounts of activity increase inhibition of expiratory centre until inspiration begins.
177
Where is the expiratory centre?
Function
In the ventral medullary reticular formation
During inspiration gradually increasing activity arises from the expiratory pool inhibiting the inspiratory pool until expiration begins.
178
What is the location and function of the pontine centres of respiration
Pneumotaxic centre in upper pond fine tunes ventilatory rate and tidal volume to minimise work - it limit the inspiratory centre limiting tidal volume and causing variation in respiratory rate.
The apneustic centre in the lower pons prolongs the inspiratory phase by stimulating the inspiratory centre
The area above this centre causes apneustic breathing (slow breath in, rapid out)
179
What would happen to respiration if the pons was destroyed.
Medulla centres would keep on going - breathing would continue just without the fine tuning.
180
What reflexes are involved in ventilation control
Chemoreceptors
Chemical and pressure receptors in airways
Stretch receptors in lungs
Golgi organs and muscle spindles
181
Where are chemoreceptors located
Central - bilaterally beneath ventral surface of medulla
Peripheral - carotid bodies bilaterally at bifurcation of common carotid and aortic bodies along arch of aorta.
182
What is the key stimuli at chemoreceptors?
Central - hydrogen ion concentration
Peripheral - oxygen delivery (concentration/flow)
183
What receptors sense change in carbon dioxide/hydrogen ion concentration (speed and magnitude of response)
Much greater magnitude from central chemoreceptors however, peripheral stimulation occurs five times more rapidly so initiates response
184
Neuronal supply to peripheral chemoreceptors
Carotid - Herings nerve to glossophayngeal
Aortic - vagal
185
What is the effect of simulation of the chemical and irritant receptors of the upper airways and trachea?
Laryngeal closure
Apnea
Hyperpnoea
Bronchoconstriction
186
What are the location function of the pressure receptors of the airways?
Located in smooth muscle of all airways and help control depth of respiration.
187
What are the J receptors and what is their role in respiratory control
Located in alveolar walls
Triggered by engorgement of pulmonary capillaries eg heart failure
Stimulation results in rapid shallow breathing or apnoea
188
What and where are the pulmonary stretch receptors
Eponymous name of reflex evoked? Strong or weak in humans?
In airway smooth muscle
Hering-Breuer reflex
Inhibit inspiration on response to lung distension - in humans quite significant though, can breath spontaneously with CPAP of 40 and probably only activates as protective mechanism with tidal volumes >1.5L
189
Where are golgi tendon organs located in the control of ventilation
What do they do
Intercostal muscles
Inhibitory to the inspiration centres on distension
190
What is the effect of muscle spindle in diaphragm and inspiratory muscles on control of ventilation?
Activate when particularly intense ventilation required eg airway obstruction.
May be responsible for sense of dysponea
191
What is the response of the lungs to co2 levels?
No effect when below normal. When >4 increasing PaCO2 increases alveolar ventilation in a linear manner - around 1L/min extra for every 0.1kPa increase in PaCO2
Flattens at very high levels of co2 due to central depression, narcosis and respiratory depression.
192
What factors would alter the curve of PaCO2 and alveolar ventilation? How?
Sleep, barbiturates, and morphine - reduces gradient of line and displaces to right (lower alveolar ventilation at a given PaCO2)
Work of breathing - high work of breathing also causes reduced response to CO2
Oxygen levels - concomitant decrease in pO2 causes marked shift to left (increased response to raising CO2)
Effected by age, genetics and race.
193
How does raised CO2 cause increase alveolar ventilation?
Increased H+ centrally
Small response to increased H+ and PaCO2 peripherally
194
How do sleep, very high Co2 and sedative medications cause decreased response to PaCO2?
Decreased in the central sensitivity of respiratory centers
195
How does increased work of breathing decrease sensitivity to CO2
Reduced peripheral response to central drive
196
What is the response to prolonged raised CO2 (timeframes)
Why
Maximal response over first few hours
Decreases to about 20% of maximum after 48hrs
Renal adjustment of H by reabsorption of bicarb
Bicarb diffusing centrally to normalise central pH
197
What is the effect of varying PaO2 on alveolar ventilation
Very little until PaO2 <8kPa then exponential increase in ventilation
198
How is the ventilatory response to hypoxia controlled
Virtually all peripherally
Hypoxia depresses central function which results in Cheyne Stokes breathing
199
What is the effect of varied PaCO2 on ventilatory response to changes in PaO2
Marked increase in sensitivity and exaggerated effect
200
What is the effect of voletile anaesthetics on hypoxic ventilatory drive
Suppresses it
201
What is the effect of altitude on ventilatory drive
Hypoxia drives tachypnea but this is blunted by lower than normal CO2 production
On acclimatisation CO2 production increases and ventilatory response to the hypoxia increases
202
Mechanisms of airway in immune defence
Filtration in nasal passage
Sneeze and cough reflex
Mucociliary clearance
T and B lymphocytes
Macrophages and neutrophils
203
Effect of anaesthesia on lung immune defence
Bypasses filtration of nose
Paralyses cilia in mucociliary escalator
204
Immunoglobulin types secreted in the airways?
IgA - promotes clearance of microorganisms
IgG - opsinoisation of microorganisms
205
What is a nine respiratory function of the lungs that arise from all blood passing through its small capillary bed?
How else is it adapted to this function
Filtration - catches small clots for fibrinolysis
Rich in endogenous heparin
206
What metabolic processes occur in the lungs?
Extracellular metabolism of bradykinins and adenine nucleotides
Intracellular metabolism of NA, prostaglandins, ANP
Activation of angiotensin 1
Sythesis of somatostatin, substance P, nitric oxide, prostacyclin
Release of prostaglandins, histamine, kallikreins, platelet activation factor
Surfactant production
Uptake and metabolism of anaesthetic agents
207
What is the proposed mechanism of lung injury in ARDS
Abnormal actions of oxidative radicles and elastases on lung tissue
208
What is kPa pressure at approx 5500m
What would PIO2 be at this level?
What can PAO2 fall too, how does the body adapt to this
50 (half of sea level)
50-6.3 x 0.21 = 9.2kPa (compared to 20 at sea level)
PAO2 can fall to 2.6kPa (9.2-(5.3/0.8))
Adapts with marked hyperventilation which lowers pCO2 and thus raises PAO2
209
What is the pattern in response of alveolar ventilation to high altitude
Initial rapid increase in resp rate (due to hypoxic stimulation of chemoreceptors, then inhibition due to reduced Co2 and alkalosis) then a slow steady rise of over a number of days (renal elimination of bicarb, bicarb shifts out of CSF densinsitising chemoreceptors)
210
What are the main changes of acclimatisation?
Hyperventilation
Polycythaemia
Increased 23DPG with right shift of oxyhaemoglobin curve
Increased capillary density
Increased mitochondrial density
Increased pulmonary artery pressure (due to hypoxic vasoconstriction)
Increased ventilatory capacity
More even distribution of perfusion (as less pressure gradient and higher PA pressures)
211
What pathological processes can occur at high altitude
HAPE and HACE
right ventricular hypertrophy
Muscle atrophy and catabolism
Anti diuresis and oedema
Increased thyroid activity
Sleep disturbance
Impaired nervous system performance
