L1-4 Respiration Flashcards
Describe the relationship between pressure gradient resistance and flow during laminar flow
Flow rate proportional to the pressure gradient and inversely proportional to the resistance
Equation for laminar flow
V = delta P / R
Equation for turbulent flow
V=k ROOT(delta P)
Three types of flow in the lungs
Laminar turbulent and transitional
Describe laminar flow
Steady flow down a tube with uniform direction and speed
During laminar flow, where is flow rate the highest
The centre
What are present in turbulent flow
Vorticies and eddie currents
A change in pressure gradient will have a greater effect on flow rate in laminar or turbulent
Laminar - turbulent flow requires a larger change in pressure gradient for the same effect to be seen on flow rate
Transitional flow arises as a result of
High number of biurification
Transitional flow is charaterised as
The switching between laminar and turbulent
What number is used to determine flow type
Reynolds
Give the equation for Reynolds number
Re = (2rvp)/n
In the Reynolds equations what does the following character represent: Re
Reynolds number
In the Reynolds equations what does the following character represent: r
Radius
In the Reynolds equations what does the following character represent: v
Velocity
In the Reynolds equations what does the following character represent: p
Density of the gas
In the Reynolds equations what does the following character represent: n
Viscosity
What type of flow if Re less than 1000
Laminar
What type of flow if Re greater than 1500
Turbulent
What type of flow if Re between 1000 & 1500
Transitional
In the lung a Re of around ___ is required for laminar flow
10
Why may a Re less than 1000 not give laminar flow in the lungs
Not uniform shapped tubes
Why does velocity initially increase in the lungs
Tube gets smaller - must increase velocity to maintain flow rate
At the top: High/low CSA
Low
At the bottom: High/low CSA
High
At the top: high/low velocity
High
At the bottom: High/low velocity
Low
At the top: laminar/turbulent
Turbulent
At the bottom: Laminar/turbulent
Laminar
What does Poiseulles law determine
Resistance
What is the key point of Poiseulles law?
That a small change in airway diameter will have a large effect in R
What is the relationship between radius and resistance
Inversely proprtional to the 4th root of the radius
Give Poiseuilles Law
R = (8/pi) X (nl/r^4)
In healthy lungs, what is the contribution of the following to total resistance: Pharynx and larynx
40%
In healthy lungs, what is the contribution of the following to total resistance: Airways with a diameter greater than 2mm
40%
In healthy lungs, what is the contribution of the following to total resistance: Airways with a diameter less than 2mm
20%
In COPD lungs, what is the contribution of the following to total resistance: Pharynx and larynx
12%
In COPD lungs, what is the contribution of the following to total resistance: Airways with a diameter greater than 2mm
18%
In COPD lungs, what is the contribution of the following to total resistance: Airways with a diameter less than 70%
70%
What is total resistance in healthy lungs
1.5 cm H20 s /L
What is total reistance in COPD lungs
5 cm H20 S /L
Why is resistance greater in the larger airways
Resistances in series, in later (smaller) airways the resistances are in parallel
How do resistances sum when in series
R = R1 + R2 + R3
How do resistances sum when in parallel
R = 1/R1 + 1/R2 + 1/R3
Two factors which may affect the diameter of the airway
Mucus secretions
Oedema
Pa
Alveolar pressure
Paw
Airway pressure
Pb
Barometric pressure
Pip
Intrapleural pressure
Ptm
Transmural pressure
Ptp
Transpulmonary pressure
Pip =
Pip = (-Ptp) + Pa
Ptm =
Ptm = Paw - Pip
Describe how airway compression occurs in emphysem
Tethering between adjoining airspaces is reduced, airways are flimsy, during a forced expiration the airways are less able to resist collapse
Characteristics of emphysema
Loss of elastic tissue and breakdown of the alveolar walls
What techniques may people suffering with emphysema use to prevent airway collapse
Slow exhalation
Breathing at a higher lung volume
Breathing through pursed lips
At any given volume airway _____ is higher for people suffering with COPD
Resistance
Define ventilation
Total ventilation is the volume of air moved out of the lungs per unit time
Equation for ventilation
V. = v/t (volume/time)
Normal tidal volume
0.5 L
Normal ventilation rate
12 per min
What is total ventilation at rest
61 L per min
What is another word for the conducting zone
Anantomical dead space
Because of the anatomical dead space, what does this mean for the amount of fresh air reaching the alveoli
Not all will reach the alveoli
First portion of air reaching the respiratory zone is the stale air that was in the conducting zone ~0.15L
Define alveolar ventilation
The volume of fresh air reaching the repsiratory zone
What is the formula for alveolar ventilation
Total ventilation - dead space ventilatio
Normal value for alveolar repsiraition
6 - (0.15 x 12)
=4.2 L/min
Ventilation rate has an effect on _________ and ___________ gas compositions
Alveolar and aterial
At low alveolar ventilation ….
200 ml CO2 produced, less air to dilute it so greater p CO2
At a higher alveolar ventilation …
200 ml CO2 produced, more air for it to dilute into, so lower PCo2
Slowly breathing could cause
Respiratory acidosis (more Co2 in the blood)
Hyperventilating could cause
Repiratory alkalosis
Which area of the lung has greatest ventilation
Base
Which area of the lung has poorest ventilation
Apex
What causes these regional variations in lung ventilation
Posture and gravity
Different starting volumes of the alveoli
Based on alveoli starting volumes, why is the apex the least vetilated
Larger starting volume –> lowest compliance
Based on alveoli starting volumes why is the base the best ventilated
Smaller starting volume, highest compliance
Define perfusion
The passage of fluid through the circulatory system to an organ or tissue
Pulmonary circulation has ________ pressure
Low
When is the pulmonary resistance the lowest
When lungs are at their functional residual volume
Describe alveolar vessels
Surrounded on all sides by alveoli
Resistance in alveolar vessels can be linked to
Transmural pressure and lung volume
Resistance in extra alveolar vessels can be linked to
Intrapleural pressure
Describe extra alveolar vessesl
Not surrounded by alveoli
At TLC what is higher - Alveolar BV pressure or extra alveolar BV pressure
Alveolar
At FRC what is higher - Alveolar BV pressure or extra alveolar BV pressure
Neither, both equal
At RV what is higher - Alveolar BV pressure or extra alveolar BV pressure
Extra alveolar
The total pulmonary vascualr resistance is the sum of
Alveloar BV resistance and extra alveolar resistane
When is extra alveolar BV resistance at its lowest
TLC
When is the resistance of alveolar vessels lowest
RV
When is extra alveolar BV resistance at its highest
Rv
When is the resistance of alveolar vessels highest
TLC
Describe the three stages of capillary recruitment from at a low pressure and then after an increase in P
1] Some BV collapsed, some open but dont conduct, some conducting
INCREASE PRESSURE
2] Previously non conducting conduct, previously closed open but dont conduct
INCREASE PRESSURE
3] Previously non conducting now conduct blood
Capillary recruitment is a mechanism to
Accomodate an increase in pulmonary pressure and flow rate
What is the reference point for pulmonary system circulation pressures
Outside of the heart at the level of the left atrium
Typical Ppa
15 mm Hg
20 cm H2O
Typical Ppv
8 mm Hg
10 cm H2O
Ppa and Ppv change by what for every ______ ______ the level of the left atrium
Increase by 1 cm H2O below
Decrease by 1 cm H2O above
Define Pa
Alveolar pressure relative to atmospheric pressure at point where there is no movement of air
At the time there is no movement of air what can be said about Pa and Palv
Patm + P alv = 0
No difference
What is Ptm
Transmural pressure across the wall of a vessel
Three main factors which cause dilation
Inc Pa O2
Dec Pa CO2
Inc Pa pH
Other factors which cause dilation
Histamine (or other H2 agonists) PGE1 PGI2 B adrenergic receptor agonists Bradykinin Theophyline Acetylcholine NO
Three main factors which cause constriction
Dec Pa O2
Inc Pa CO2
Dec Pa pH
Other factors which cause contrstiction
Histamine (H1 agonists) Thromboxane A2, PGF 2a, PGE2 Alpha adrenergic receptor agonists Serotonin Angiontensin II
In zone 1, which is higher Ppa or Ppv
Ppa is higher
In zone 2, which is higher Ppa or Ppv
Ppa is higher
In zone 3 which is higher Ppa or Ppv
Ppa higher
Draw what would be seen at all 4 zones of the lungs
Refer to notes
Define, ventilation:perfusion
Ratio of the rate of alveolar ventilation and the pulmonary blood flow
Think of a small group of alveloi
If not ventilated ratio –>
Gas comp –>
Ration –> 0
Gas composition of the avleoli will become same a mixed venous blood 40 mmHg O2 46 mmHg CO2
Mixed venous blood
Pressure of O2 and CO2
40 mmHg O2 46 mmHg CO2
Think of a small group of alveloi
If not perfused ratio –>
Gas comp –>
To infinity
Gas comp of alveoli will become same as inspired humidified air
149 mmHg O2 0 mmHg CO2
Gas comp of inspired humidifed air
149 mmHg O2 0 mmHg CO2
V/Q at apex
3.3
V/Q at base
0.6
Average v/q
0.84
Alveolar dead space ventilation (mismatch)
Local reduction in perfusion - e.g. due to a pulmonary embolism
No exchange so gas composition becomes same as inspired humid air
V/Q –> 0
Describe a Shunt
Local reduction in ventilation
Because gas cant be removed from the area the gas composition becomes the same as mixed venous blood
3 controls of airway diameter
Airway smooth muscle
Parasympathetic NS
Sympathetic NS
3 controls for central control of respiration
Basic rhythm
Chemoreceptors
Stretch receptors
A gq coupled pathway would have what effect on airway smooth muscle
Contraction
Describe how the Gq coupled pathway causes contraction of the airway smooth muscle
Active Aq subunit (GTP bound)
Causes activation of PLC-b
PLC converts PIP2 to IP3 and DAG
DAG opens Ca channels in the membrane uses this Ca to activate PK-C –> causes growth
IP3 acts on intracellular calcium stores
Ca out of the stores combines with calmodulin to form calcium calmodulin
Calcium calmodulin phosphorylates mysoin light chain kinase causing activation and formation of cross bridges
What (3) receptors are involved in the Gq coupled pathway
M3 muscarinic
H1 histamine
BK bradykinin
Which G protein coupled pathway causes relaxation of the ariway smooth muscle
Gs coupled pathway
How does a Gs coupled pathway cause relaxation of the smooth muscle
As with GTP bound
Activated adenylyl cyclase
ATP –> cAMP
Activation of PK-A - gene regulation/relaxation/channel regualtion/ - growth
Opening of BK K channels
Eflux of K - hyperpolarisation - closes Ca channels
What receptors are involved in the Gs coupled patway
B2 adrenergic receptors
VIP receptors
Which G protein coupled pathway oppsoes the relaxation of smooth muscle
Gi
Describe how the Gi coupled pathway opposes the relaxation of smooth muscle
Inhibition of adenylyl cyclase
Counters the stim effects of Gi activation
Opposes relaxation of the smooth muscle
Also closes the BK K channels
How does the parasympathetic division control the bronchial smooth muscle
Ach released from the vagus
Acts of muscarinic receptors
CONSTRICTION
How does the sympathetic division control the bronchial smooth muscle
NA released from nerve terminals
Weak agonist
DILATION
Does parasymp cause dilation or constriction
CONSTRICTIOn
Does symp cause dilation or constriction
DILATION
Two humoral factors which interact with the airway smooth muscle
Circulating adrenaline and histamine
Explain how adrenaline acts on the bronchial smooth muscle
Circulating in the blood
Better agonist
DILATIOn
Explain how histamine acts of the bronchial smooth muscle
Released during the inflammatory processes
CONSTRICTION
What is the feedback involved in the parasympathetic control of bronchial smooth muscle
M2 receptor on the postganglionic nerve terminal
What receptors are found on the bronchial smooth muscle
M2 and M3
Describe the pathway after activation of one of the M3 receptors
Gq
Aq subunit with GTP bound
Activates PLC
PLC causes breakdown of PIP2 to IP3 and DAG
DAG –> Activates PK-C - Ca channels open (Ca in)
IP3 acts on intracellular calcium stores –> raised IC levels
Ca combines with calmodulin forming calcium calmodulin which then phosphroylates myosin light chain kinase (activating) - cross bridge formation
Describe the pathway after activation of a sympathetic B2 receptor on the bronchial smooth muscle
Gs
As with GTP bound activated adenylyl cyclase
ATP –> cAMP
cAMP activates EPAC and PK-A
PK-A phosphorylates MLCK causing inhibition
PK-A causes opening of the BK K channel –> K eflux –> hyperpolarisation –> Ca channels close
Asthma is characterised by having
Hyperactive airways
Atopic is
Extrinsic
Give examples of some atopic triggers
Allergies, contact with inhaled allergens
Give examples of some non-atopic triggers
Drugs, infections
Non-atopic
Intrinsic
What is the response to the trigger in asthma
Inflammatory cells move into the airways
Release of inflammatory mediators - histamine
Bronchoconstriction
What is seen in an asthma patients spirometry
Decrease in Fev1 and FEV1%
FVC ofen unaltered
What receptors in asthma show an increase parasympathic activity
M2
What is significant about the M2 receptors in asthma
They show an increase in activity
In asthma animal models what was seen in
m1 function
m2 function
m3 function
m1 - no change
m2 - decrease in neuronal m2 function
m3 - no change
What did the antigen challenge reveal about M2 and eosinophils
Change in function linked to eosinophils
Eosinophils cluster around nerve fibres
Activated eosinophils released major basic protein
MBP inhibts the M2 receptors
Short acting asthma treating
Salbutamol
Long acting asthma treatment
Salmeterol
Salmeterol must be administered with
Corticosteroids
How may anticholinergics be used in the treatment of asthma
Block effects of endogenous Ach
E.g. tiotropium bromide
Inhaled 1x daily
Act via M1 and M3 receptors
How can glucocorticoids be used to treat asthma
Anti-inflammatory action
Inhaled steroids such as beclomesadone
What other drugs may be used to treat asthma
Theophylline
Leukotriene Modifiers
Breathing is an _________ and __________ process
Automatic and rhythmical
Basic respiratory rhythm is generated by
Centres in the medulla
Two ways in which breathing can be consciously altered are
Hyperventilating and breath holding
Activity in the hypoglossal nerve matches
Pre Botzinger Complex
3 types of breath
Eupneic
Sigh
Gasp
Two cell types of the pre-botzinger complex
Pacemaker cells and non pacemaker cells
What two types of activity can be seen in pacemaker cells
Spiking - slow background depolarisation due to Na leak current
Bursting - membrane remains depolarised - activation of Na persistent channel
What current does spiking rely on
Na leak current
What current does bursting rely on
Na persistent current
Which type of pacemaker activity is linked to an inspiration
Bursting
Activity in the pre botxinger complex leads to
BUrsting phase in neurones
What is the NALCN
Sodium leak channel
What is shown in mice which are knockouts for NACLN
Die in 24hrs Cant maintian breathing pattern Develop aponeia (lack of inspiration for certain time)
What happens if EC [K] concentration is increased from 3mmol to 8mmol
Depolarisation of the cell
Takes the cell closer to the threshold value
Increased chanve of bursting
Increase period/ammount of bursting
Transition to bursting is dependent on
Pesistent Na current (INaP)
CAN cation current (Ican)
Pacemaker cells are split depending if they are sensitive to
Cadmium
If Ican is relied on for bursting
Cadmium sensitive
If Inap relied on for bursting
Cadmium insensitive
If cells are cadmium sensitive what current is relied on for bursting
Ican
If cells are cadmium insensitive what current is relied on for bursting
Inap
Ican =
CAN cation current
Inap
Persistent Na current
What are some effects of hypoxia on the pre-Botzinger complex
Eupenic --> Sighing --> Gasping EPSPs shut off for sighing but start again when gasping Autonomous spiking neurons drop off CS neurones drop off CI neurones REMIAN
What neurones are likely to be responsible for sigh breathing
Cadmium insensitive neurones
What does the DRG control
Inspiration
How does the DRG control inspiration
Sending signals to the inspiratory muscles
Describe the activity of the DRG
Spontaneous
Active - shuts off - active
When is the VRG inactive
During quiet respiration
When is the VRG active
During forced respiration
Does the pneumotaxic centre increase or decrease the rate
Increase
How does the pneumotaxic centre increase rate
Has an inhibitory affect on inspiratory centre
Increases rate by shortening inspirations
Does the apneustic centre increase or decrease the rate
Decrease
How does the apneustic decrease the rate
Stimulates the inspiratory centre
Increases the depth of breaths
What is the the effect of the pneumotaxic centre on the inspiratory centre
Inhibitory
What is the effect of the apneustic centre on the inspiratory centre
Stimulatory
What does the Hering Breuer reflex prevent against
Over inflation of the ling
Describe the hering breuer reflex
Inspiratory centre –> phrenic nerve –> diaphragm contracts –> strech receptor in the lung feeds back to the inspiratory centre via the vagus which has an inhibitory effect on the inspiratory centre
Proof for hering breuer reflex
When no activity in the Vagus - phrenic nerve continues to fire causing contraction of the diaphragm even more. No shut off