Respiration Lectures Flashcards
Describe the pressure differences in inspiration
Patmos is greater than Palv so air moves in to the lungs
Describe the pressure differences in expiration
Palv is greater then Patmos so air is forced out of the lungs
What are the 3 factors which must be overcome for ventilation to occur?
1) Elastic recoil of tissues
2) Surface tension in the alveoli
3) Airway resistance - how easy is it to inflate and deflate the lungs
Describe how a vacuum is formed in the lungs when at rest
The inside of the chest has a subatmospheric pressure creating a relative vacuum
The chest wall would tend to expand whereas the elastic nature of the lungs would tend to cause them to collapse inwards
These two forces balance so as a result pressure in the interpleural space is lower than atmospheric pressure.
What is compliance
The measure of distensibility
What is the equation for compliance?
compliance = change in volume / change in pressure
What could low compliance mean?
The patient has to work harder to inspire
What is pulmonary fibrosis?
The lung parenchyma is more rigid meaning that there is low compliance and the patient has to work harder to inspire
What could a high compliance mean?
Difficulty in expiring due to loss of elastic recoil
Name a disease which causes high compliance?
Emphysema
What is the transmeural pressure when the lungs collapse down to their residual volume?
0
What happens in the lungs if the volume is greater than the full residual capacity?
The elastic forces in the lung favouring collapse are higher. The forces on the chest wall for expansion also decrease so the overall system collapses
How does FRC change in patients change in emphysema?
It increases due to the higher compliance
What are the two major components of elastic recoil?
The anatomical component (the nature of the cells and their extracellular matrix)
Elastic recoil also occurs due to surface tension which is generated at the air-water interface
What does Laplace’s equation explain?
The relationship between the gas and surface tension at the gas/water border
What is Laplace’s equation?
Pressure = 2T / r T= tension on the alveolus r = radius
Why are smaller alveolar sacs likely to collapse?
Because of Laplace’s equation the pressure in larger sacs is lower than smaller sacs. Air will flow from smaller alveolar to larger ones, leading to their collapse
How is the problem of alveolar sacs being likely to collapse overcome?
Surfactant is produced
Which cells produce surfactant?
Type 11 pneumocytes
What is surfactant composed of?
35 to 40% dipalmitoyl phosphatidylcholine (DPPC) 35 to 40% other phospholipids 5 to 10% protein (SP - A,B,C and D) Cholesterols Trace amount of other substances
What are the roles of the proteins in surfactant?
A - soluble in water, role in innate immunit
B and C - soluble in lipids, role in spreading up the formation of the monolayer
D - soluble in water, role in innate immunity
How does surfactant act to reduce surface tension?
It decreases the density of water molecules at the air-water interface
The hydrophobic tail pulls the surfactant molecule upwards so the resultant vector is minimal
What three factors have a role in determining airflow?
Type of airflow, resistance of the pathway, pressure gradients generated across the airways
In laminar flow what is the movement of air proportional to?
It is proportional to the pressure gradient and inversely proportional to the resistance
In turbulent flow what is the movement of air proportional to?
The square root of the pressure difference
What is used to determine flow type?
Reynolds number
If Re <1000 = laminar flow
If Re is between 1000 to 1500 flow is unstable switching between laminar and turbulent
If Re is >1500 = turbulent flow
What does Poiseulle’s law determine?
The impact of resistance on flow
What is the equation for poiseulle’s law?
R = (8/ pie) x (nl/r^4)
Airway is resistance is proportional to gas viscosity and the length of the tube but is inversely proportional to the fourth power of the radius
What do the individual sections of the airways contribute to resistance?
Pharynx to the larynx - 40%
Airways >2mm diameter - 40%
Airways <2mm diameter - 20%
What factors can impact on airway diameter?
Increased mucus secretion will effectively reduce airway diameter = increased resistance
Oedema- increased fluid retention in the lung tissue will cause swelling and narrowing of the airways = increased resistance
What disease causes a big increase in resistance of the airways?
COPD
In a healthy person how much air is inspired after 1 second of inspiring?
96%
In a patient with COPD after 1 second of inspiration how much air has been inspired?
60%
What are the three pathways involved in smooth muscle control?
Gq, Gs and Gi
What are the steps in the Gq pathway to cause muscle to contract?
Activation of the GPCR causes the Alpha Q subunit to be activated
This activates Phospholipase C
This stimulates the breakdown of PIP2 to DAG and IP3
IP3 activates the IP3 receptors in the ER and calcium stores so calcium is released into the cytoplasm
Calcium binds to CaM to form calcium calmodulin complex
This interacts with Myosin light chinase kinase which promotes the contraction of smooth muscle
DAG also activates protein kinase C which causes stimulation of the voltage dependent calcium channels so calcium enters the cell
Protein kinase C also stimulates cell growth and down regulates other proteins by phosphorylation such as MLCP
What 3 receptors does the Gq pathway use?
1) M3 muscarinic receptors
2) H1 histamine receptors
3) BK bradykinin receptors
What are the steps in the Gs pathway?
GPCR activation causes the Alpha S subunit to be activated
This stimulates the production of cAMP
cAMP activates protein kinase A
Protein Kinase A has various effects in the cell:
1) It acts on IP3 receptors by phosphorylating them, causing them to have a decrease in sensitivity to IP3, inhibiting contraction thus causing relaxation
2) It also phosphorylates MLCK = reduces sensitivty to calcium calmodulin
3) It also phosphorylates MLCP = activation of calcium eflux causing relaxation
The alpha S subunit can also stimulate potassium channels to increase potassium eflux, causinf hyperpolarisation
What are the receptors used in the Gs pathway?
B2 Adrenergic receptors
VIP receptors
What are the steps in the Gi pathway?
Activation of Gi receptors causes the inhibition of adenylate cyclase
This counteracts the Gs system, therefore opposing the relaxation of the smooth muscle
It also inhibits the BK channel
Receptors acting through the Gi pathway prevent hyperolarisation
What is the sympathetic systems effect on smooth muscle?
The release of norepinephrine from nerves leads to smooth muscle dilation
What is the parasympathetic systems effect on smooth muscle?
The release of acetylcholine from the vagus nerve acts on muscarinic receptors leading to smooth muscle contraction
Which system does histamine stimulate?
The Gq pathway as it causes smooth muscle constriction
What is the function of the M3 receptors on smooth muscle?
Smooth muscle contains M3 receptors which acetylcholine binds to causing their activation
This activates the Gq pathway so the smooth muscle contracts
Calcium causes the contraction of muscles
What is the role of M2 neurons on the postganglionic nerve?
Ach binds to it which inhibits further Ach being released which is an example of negative feedback
What are the triggers of asthma?
Atopic eg allergies, contact with inhaled allergens
Non-atopic eg respiratory infections, cold air, stress, exercise, inhaled irritants and drugs
What information from a spirometer indicates a patient has asthma?
They have a reduced FEV1 and FEV%
Their FEV1 is less than 80% of their FVC
FVC is not changed
A reduction in the function of which receptor is linked to asthma and what is this changed linked to?
M2 receptors on the neurons
It is linked to oesinophils which cluster around nerve fibres and release MBP which inhibits the M2 receptors
How can asthma be treated and how do these treatments work?
1) B2 Adrenergic receptor agonists eg salbutamol
2) Anticholinergics block the effect of endogenous Ach eg Tiotropium bromide
3) Glucocorticoids are antinflammatory drugs eg beclometasone. They activate glucoreceptors, decreasing mRNA stability for inflammatory genes so there is no protein for inflammation
Where is the basic respiratory rhythm generated?
Centres in the medulla
Where does damage in the medulla occur for there to be a loss of breathing patterns?
Damage below the medulla
Which nerve controls inspiration?
The phrenic nerve
What does the dorsal root ganglia control?
Quiet inspiration
Sends signals to the inspiratory muscles
Spontaneously active eg shows a period of activity and then switches off
What does the ventral root ganglia control?
Inspiration and expiration
Inactive during quiet respiration
Activity helps control forced respiration
What does the pre-botzinger complex do?
It generates the pattern to control respiration
Where is the pre-botzinger complex located?
The medulla in ventral roots
The activity in which nerve matches activity in the pre-botzinger complex?
The hypoglossal nerve
What type of cells make up the pre-botzinger complex?
Pacemaker cells which generate action potentials linked to the control of breathing
What are the three types of pattern output that the pre-botzinger complex can generate?
Eupneic = normal breathing Sigh = increase in activty/ intensity Gasp = Hypoxic conditions
What are the two classes of neurons?
Pacemaker
Non-pacemaker
Which channel is important in the pre-botzinger complex?
NALCN - sodium leak channel
What happens in NALCN knockout mice?
They die within 24 hours if they are homozygous and they show periods of not breathing (apnia)
Why is NALCN important in the pre-botzinger complex?
It generates breathing patterns as its inward current is important in generating initial depolarisation
What is the role of potassium in the pre-botzinger complex?
If K+ concentration changes the pattern of bursting is affected
If there is high potassium outside the cell there is a steep change in membrane potential causing increased intensity of bursting = more depolarised
The transition to bursting activity depends on what two currents?
ICAN (CAN cation current)
INaP (The persistant sodium current)
Which neurons (ICAN or INaP) are cadmium sensitive?
ICAN (INaP neurons are insenstive to cadmium)
Modulation of bursting is carried out by what?
GPCRs
Which receptors does substance P act on and what is its subsequent effect?
It acts on NK1 receptors, stimulating the Gq pathway
This stimulates breathing ie the leak in the sodium current causing a spike is made
This activates the pre-botzinger complex
What is the effect of hypoxia on the pre-botzinger complex?
Gradual hypoxia causes changes from a eupneic pattern to a sigh pattern
If hypoxia continues the pattern changes again from sigh to gasp
In hypoxic situations cadmium sensitive cells are switched off
This means that cadmium insensitive cells are relied on to generate the gasp pattern
What are the two centres in the pons which send stimuli to the medulla to regulate depth of breathing?
Pneumotaxic centre
Apneustic centre
What is the role of the pneumotaxic centre?
Increases the rate of breathing by shortening inspirations
It has an inhibitory effect on the inspiratory centre
What is the role of the apneustic centre?
Increases the depth and reduces the rate of breathing
Stimulates the inspiratory centre
What is the Hering-Bruer reflex?
Stretch receptors in the lungs send signals back to the medulla to limit inspiration and prevent over inflation of the lungs
phrenic nerve = diaphragm contracts = stretch receptor activated = vagus nerve stimulated = inspiratory centre is inhibited
What is the importance of the vagus nerve?
Lungs expand then the vagus nerve is inactive
Signals from the brain to the lungs travel down the phrenic nerve
What is the role of central chemoreceptors?
They monitor conditions in the cerebral spinal fluid and detect CO2 and pH - they increase ventilation in a response to an increased level of CO2
Where are peripheral chemoreceptors located?
the carotid body and the aortic arch
What do peripheral chemoreceptors respond to?
Increase in CO2, decrease in pH, decrease in O2
Increases ventilation
