Respiration Flashcards
what two processes are part of lung ventilation?
inspiration and expiration
what happens to atmos and alveo pressures during inspiration and expiration?
inspiration- atmos press is greater than alveolar. air moves into the lungs
expiration- alveo press greater than atmosp, air moves out of lungs
what inflation factors have to be overcome?
elastic recoil
surface tension in alveoli
airway resistance
what happens to elastic forces in the chest and lungs when at rest?
they balance
what does the elastic nature of the lungs cause?
collapse inwards
what does the elastic forces of the chest cause?
causes them to expand
what is compliance?
it is the measure of elasticity, distencibility, the ease with which the lungs and thorax expand during pressure changes.
what disease causes low compliance? what does this cause?
pulmanory fibrosis. means more work is required to inspire.
what disease causes high compliance? what does this cause?
emphysema, causes it to be more difficult to expire.
what is overall compliance made up of?
lung compliance and thoratic compliance
what happens to the lungs and chest at equilibrium position
collapsing force of the lungs matches the expanding force of the chest wall. Palv = P atm giving FRC
what happens to the chest and lung when volume is less than FRC? (exp)
there’s a smaller volume in the lung, forces favouring elastic collapse are low, the forces on the chest favour expansion, overall the system wants to expand
what happens to the chest and lung when the volume is greater than FRC? (insp)
elastic forces favouring collapse are higher, forces on the chest for expansion are small. overall system collapses.
how does fibrosis effect lung compliance?
decrease in compliance, the same change in pressure has a smaller change in volume leading to a decrease in FRC
how does emphysema effect compliance?
increases compliance, the same change in pressure has a larger change in volume. this leads to an increase in FRC.
what are the two components of elastic recoil in the lung? which one is the greater factor?
anatomical components- elastic nature of cells and ECM
surface tension - surface tension at the air-fluid interface
surface tension is the greater factor, being responsible for 50% of the recoil.
what happens if the lungs are inflated with saline? what does this mean?
as pressure increases there’s a fairly linear increase in lung volume, this tails when approaching max lung capacity. there’s a similar relationship when decreasing pressure. this means it’s easy to inflate the lungs with Saline.
what happens when lungs are inflated with air? why is this?
when pressure is increased at first there is very little change in volume, then at a certain point there is a very steep relationship between pressure and volume. this is due to surface tension having to be overcome.
when pressure is reduced the lungs collapse more evenly meaning there’s a difference between inflation and deflation curves.
why does surface tension develop?
because of a difference in forces on water molecules at the air/water interface.
in a gas bubbles what happens between pressure and surface tension?
pressure pushes out (pressure created by surface tension pulling downwards) surface tension pulls it down. these two balance out.
what equation is used for surface tension?
LaPlaces equation
what is pressure like in a small and a large alveoli
small - high pressure
large - low pressure.
why do the alveoli in the lung not collapse with the pressure differences of the different sized alveoli?
this is due to surfactant.
what is surfactant produced by?
type 2 pneumocytes.
what is surfactant composed of?
80-90 % phospholipids
30-40 % of these phospholipids is DPPC.
5-10% is protein
what are proteins SP-A and SP-D important in? what are these soluble in?
innate immunity, they are water soluble
what are proteins SP-B and SP-C important in? and what are they soluble in?
they speed up the formation of the monolayer, they are lipid soluble.
what does surfactant act to reduce? what can it help and prevent?
reduces surface tension
helps inflation and prevents over inflation.
how does surfactant prevent over inflation?
as the alveoli expands the surfactant is diluted resulting in surface tension increasing and making it harder for them to expand further.
what are three factors that have a role in determining air flow?
type of air flow
resistance of the pathway
the pressure gradient generated across the airways
under laminar flow conditions what is the flow of air like?
it’s proportional to the pressure gradients and inversely proportional to resistance
what is laminar flow? where is flow rate maximal?
where does this occur?
steady flow down a uniform direction and speed.
the maximal flow rate is in the centre of the tube but reduces towards the edges.
occurs in the very terminal airways at the alveolar level.
why does turbulent flow develop? what is turbulent flow? what is the difference between this and laminar?
when the flow rate moves beyond a critical value there’s irregular currents and vortices develop.
the rate of gas movement is proportional to the square root of the pressure difference.
a greater pressure gradient is needed to obtain the same flow seen in lamina, meaning more effort is required.
what is the relationship between flow rate and driving pressure for both turbulent and laminar flow.
laminar - linear relationship between flow and driving force
turbulent - as driving pressure increases it’s hard to get an increase in flow rate.
what is the third type of airflow in the lungs? why does this occur?
transitional flow.
this occurs because the lungs are constantly dividing, a high number of bifurifications disrupt flow and creat eddies.
what does transitional flow allow?
a good mixing of gases.
what is determination of flow type governed by?
the reynolds number.
what are the reynolds number under ideal conditions for laminar, turbulent and an unstable flow that switches between both.
laminar - 1500
what happens to velocity as air enters and goes down the airways?
velocity increases as it’s coming into the airways
velocity decreases as going down the airways as there’s a rapid increase in cross sectional area.
what is the impact of flow determined by? what is this?
Poiseuilles law
airway resistence is proportional to gas viscosity and the legnth of the tube but is inversely proportional to the fourth power of the radius
what does a small change in radius do to resistance and flow rate?
a small change in resistance leads to a big change in resistance. this has a huge impact on flow rate
in a normal individual what is the total airway resistance?
2.5 cm H20.S.litres-1
why is it that the upper airways with a larger diameter have such a large proportion of resistance? how does this differ to lower airways?
because the resistance is in series.
these add up which leads to a large overall resistance.
lower airways have a smaller diameter but there are in parralell meaning you take the sum of the inverse of resistances.
what happens to the airways in COPD patients and what does this do?
there’s swelling around the airways which leads to a large increase in resistance.
how does increase mucuou secretion effect airway resistance?
reduces the airway diameter leading to increased resistance.
how does oedema impact on airway resistance?
leads to increased fluid retention in lung tissue, this causes swelling and narrowing of airways. this increases resistance.
what happens to higher airways during inspiration and expiration?
inspiration, forced expansion
expiration, forced collapse.
what happens to compression of airways in patients with emphysema?
how does slow exhalation help this?
how does breathing through pursed lips help this?
compression is exaggerated, elastic tissue and alv walls are broken down, during expiration the airways are less able to resist the collapse.
- breathing takes place at a higher volume
- greatest point of resistance preventing airway collapse.
what does dynamic compression of airways cause when breathing outas hard as possible?
you reach a maximal flow, the harder you try the more there’s dynamic compression. this is because the airflow has become effort independant.
how does lung volume impact on resistance?
at low lung vols = high resistance because the airways are narrowed down.
as vol increases the diameter of airways increases leading to a decreased resistance.
what is airway smooth muscle dependant on?
on GPCRcascades. Gq, Gs, Gi receptors.
what happens when an agonist binds to the Gq receptor? (9)
the G-protein is stimulated,
the alpha subunit goes on to activate PLC
Plc breaksdown PIP2 to Diacylglycerol and IP3
IP3 acts on IP3 receptors in the calcium store
calcium released into cytoplasm,
calcium binds to carmodulin
calcium/carmodulin activates MLCK
MLCK phosphorylates myosin
resulting in muscle contraction,
what receptors act throught the Gq pathway?
M3 muscarinic
H1 histomine
Bk bradykinin
what happens when protein kinase c is activated in the Gq pathway?
this can lead to cell growth
in the Gs pathway:
what happens when the GPCR is activated?
the alpha subunit stims adenylyl cyclase
adenylyl cylase activates cyclic AMP (uses ATP)
cyclic AMP activates protein kinase A
PKA activates MLCP (myosin dephosphorylated)
MLCK is inhibited
K channel is activated = hyperpolarisation
cell membrane is more negative
this prevents further ca2+ entry
this all inhibits muscle contraction resulting in muscle relaxation
what receptors are acting in the GS pathway?
B2 adrenergic and VIP receptors
what happens when Gi receptors are activated?
adenylate cyclase is inhibited
the Gs pathway is stimulated
this opposed the relaxation of smooth muscle and also inhibits the BK channel
which receptors are active in the Gi pathway?
M3 muscarinic
how does the autonomic NS control bronchial smooth muscle using:
- Parasympathetic
- Sympathetic
- Acetylcholine is released from the vagus which acts on muscarinic receptors leading to constriction
- Noradrenaline is released from nerves, this is a weak agonist and leads to dilation.
how does adrenaline and histamine effect bronchial smooth muscle?
Adrenaline is an agonist which leads to dilation
histamine leads to constriction
where are M1, M2 and M3 receptors found? what are these controlled by?
m1- postganglionic receptors
m2- nerve fibres (major role) and the airway smooth muscle
m3- airway smooth muscle.
this uses parasympathetic control
what is muscle contraction controlled by? what feedback does this lead to and what receptors are involved in this feedback?
muscle contraction is stim by m3 receptors
negative feedback, this involves the M2 receptors on the postganglionic nerve
how does muscle contraction occur using M3 receptors?
Ach acts on m3 receptors
phospholipase C is stimulated, IP3 is produced and ca2+ is released
ca2+/carmodium is activated
MLCK is activated
the muscle contracts
ca2+ channels are activated allowing ca2+ to move into the cell
what happens when the B2 agonist stimulates the B2 adrenoreceptors on the airway smooth muscle?
the receptor is stimulated, this activates adenylate cyclase
this leads to the production of cyclic AMP
this stimulates PKA which inhibits MLCK and stimulates MLCP
this reverses muscle contraction, leading to relaxation.
also the alpha subunit interacts with the K channel BK = hyperpolarisation,leading to a decrease in ca2+ in the cell and muscle relaxation.
what is different about an asthma sufferers airways?
they are hyperactive
what are the two types of asthma triggers? give examples
Atropic (extrinsic) - allergies, contact with inhaled allergens
Non-Atropic (intrinsic) - respiratory infections, cold air, stress, excersise, inhaled irritants, drugs etc.
what is the asthma sufferers body’s response to triggers?
inflammatory cells move into the airways releasing inflammatory mediators such as histamine, this causes brachoconstriction.
in Asthma what happens to FEV1, FEV1% and FVC?
FEV1 and FEV1% decrease (below 80%) and FVC is unaltered
what’s the link between m2 receptors and airway hypersensitivity?
asthma is linked to ParaS activity increase, this manifests as an increase in basal tone and increased muscle constroction in response to irritants.
what experiments were done to test the link between m2 receptors and hypersensitivity?
what were they done on?
what were the results?
antigen challange, viral infection, ozone exposure and vitamin A deficiency
these were perfomed on animal models
in all of them there was an increase in paras activity.
there was no change in function of m1 and m3 receptors however there was a decrease in neuronal m2 function
what does a decrease in m2 receptor function lead to?
oversensitivity because the negative feedback pathway is lost.
in the case of the antigen challange experiment, what happens to m2 receptors and what does this cause?
eosinophrills cluster around nerve fibres, these activated eosinophrills release MBPwhich in turn inhibits m2 receptors leading to no neg feedback and oversensitivity.
what’s the most commonly used asthma treatment?
what are the two subtypes of this?
b2 adrenergic agonists
short acting- salbutamol
long acting- salmeterol
what does salmeterol have to be delivered with?
cortocosteroids
how do anticholinergics work?
they block the effects of endogenous Ach and block the m3 receptor
what kind of drug is tiotropium bromide, how does it act?
it’s an anticholinergic, acts mainly via m1 and m3 receptors
how do glucocortocoids work?
they have anti-inflammatry actions
inhaled steroids, they have genomic effects as they effect the mRNA. making them longer term.
what kind of process is breathing?
it’s an automatic rythmical process
what is the basic respiratory rhythm generated by?
centres in the medulla
what would happen if the spinal cord was severed below the medulla? why is this?
breathing will cease, a pattern will still be generated but the link with the phrenic nerve is severed (phrenic nerve goes to the diaphragm)
what happens to breathing if a section is made above the medulla?
breathing still continues
what happnes if sections are made in the pons?
breathing will be altered slightly.
what groups are located in the medulla?
the dorsal and ventral respiratory groups
what is the DRG responsible for and how does it do this?
responsible for inspiration, primarly quiet.
signals down the phrenic nerve to the diaphragm and spinal nerves to the external intercostals
what is the VRG responsible for? how does it do this?
inspiration and FORCED expiration
phrenic nerve and spinal cord for insp
other pathways for muscles involved in forced insp
other pathways down spinal nerves for forced exp
where is the central pattern generator found?
in the pre-botzinger complex in the tip of the central respiratory group
what’s the evidence for the pre-botzinger complex?
electrophysiological measurements from electrodes over PB-complex and the cranial nerve 12, the firing is matched in both.
what kind of activity do the DRG have?
spontaneous activity, this is because patterning shuts of during quiet expiration
how can the basic patterning of breathing be modified?
by the Pneumotaxic centre(-) and the Apneustic centre(+) in the pons
where do the pons centres send signals to?
the medulla
what does the pneumotaxic centre work?
increases the rate of breathing by shortening breaths, it has an inhibitory effect on the inspiratory centre
how does the apneustic centre work?
increases depth and reduces the rate by prolonguing inspiration. this stimulated the inspiratory centre
how does the hering breuer reflex work and what does it do?
stretch receptors send signals up the vagus nerve to the medulla to limit inspiration.
this prevents over inflation.
what do central chemoreceptors do?
why are they located where they are?
they monitor conditions in the CSF, sensing CO2 and pH
if CO2 levels rise then ventilation is increased. csf is weakly buffered compared to plasma making it much more sensitive to pH changes
what do peripheral chemoreceptors do? where are they located?
respond to CO2, pH and O2 changes, when stimulated they increase ventilation
located in carotid body and aortic arch.
if giving oxygen to some one with COPD why do you have to be careful with the O2 partial pressure?
because they become climatised to having increased CO2 levels, meaning their primary response is to O2 levels. if have too much oxygen then resp is inhibited.
what is dalton’s law?
the total pressure of a mixture of gases is the sum of their individual partial pressures
how can the conc of gas dissolved in a solution be worked out?
Henry’s law
what is the O2 partial pressure like in arterial blood and venous blood at sea level?
arterial - 100ml/mmHg
venous 40ml/mmHg
what are problems with deep sea diving linked to?
the increases in amount of different gases dissolved in the blood due to pressure increases
what does pressure increase by for every 10 meters descended?
by 1 atm = 760mmHg
what causes Nitorogen Narcosis? what are the symptoms? how is it prevented?
conc of N2 in blood increases, n2 has a higher solubility in lipids than blood, it acts as a volatile anesthetic.
symptoms are like drunk symptoms
prevented by limiting depth and duration of dive
in gas composition can replace n2 with helium
what is oxygen toxicity? what can it cause? what is the solution to this?
haem almost fully sat at sea level, any extra O2 is dissolved in plasma. long term exposure leads to rep tract damage and CNS problems.
breathing air at 90m can lead to seizures and coma.
reduce O2 levels in the mixture
what causes decompression sickness? how is this overcome?
N2 build up in tissue with time and depth.
if return to sea level too quickly then the gas comes out of the solution and forms bubbles.
this is overcome by slowly returning to sea level.
what happens to pressure when altitude increases… leading to?
Patm decreases, meaning the partial pressures decrease.
there’s a small gradient for O2 reuptake into the blood.
