Physiology Flashcards
Define lung compliance
The volume displaced within the lung per unit pressure change i.e. the gradient of the pressure-volume curve
Specific lung compliance is the same, but indexed to total lung volume
Compliance is higher in expiration
What forces are balanced at the end of expiration?
The elastic recoil of the lungs (causes passive expiration) and the elastic recoil of the chest wall (opposes the lung’s collapse)
Give factors that increase and decrease lung compliance
Compliance is increased with age, surfactant, and emphysema
Compliance is decreased by high pulmonary venous pressures, fibrotic lung disease, and alveolar oedema. Compliance is also lower at extremes of lung volumes.
What is a Reynold’s number?
The ratio between inertial and viscous forces, and a number which can therefore be used to predict the switch from laminar to turbulent flow
At low rates of flow, viscous forces predominate i.e. a gas has an inherent resistance to deformation at a given rate. At higher rates of flow this inherent resistance is overcome, so inertial forces predominate, which leads to more complex fluid dynamics with eddies etc. which is turbulent flow.
A Reynolds number describes the balance of these forces within a given liquid or gas, and so can be used to predict the change in flows.
In which airways is turbulent flow more likely?
Larger airways, or those with bifurcations/ changes in diameter.
Larger airways have higher flow (Hagen-Pouiseulle equation) so inertial forces will trump viscous ones (i.e. the Reynolds number will be higher)
What effect would xenon have on flow through an airway?
More laminar flow
Xenon has a very low density, and density is proportional to the Reynolds number. Since turbulent flow begins at a threshold Reynolds number, the lower the density of gas, the more laminar flow.
When is density important in gas flow through airways?
In turbulent flow
In laminar flow, the Hagen-Poiseulle equation governs, and it is not affected by density but viscosity
Explain closing capacity
At any time, patency of the smallest airways of the lungs depends on the elastic stretch within the lung. This decreases as the lungs contract, and at a certain point the stretching forces will not be sufficient to keep the smallest airways open.
Closing capacity is the volume at which this collapse first occurs. A higher capacity will be caused by anything that reduces these elastic forces, or adds extra pressure that leads to small airway collapse e.g. obesity, advanced age, smoking. Young healthy lungs exert enough elastic force at end expiration that airways don’t collapse, and this is expressed as them having a low closing capacity
Define:
Dead space
Physiological dead space
Dead space is the volume of inspired air that does not take part in gas exchange (~30%)
Dead space consists of apparatus, anatomical, and alveolar
Physiological dead space discounts the apparatus
How does Fowler’s method work?
A vital capacity breath of pure O2 is taken, after which the forced expiration is analysed for nitrogen. The volume exhaled between the start, and halfway up the slope of nitrogen detection is the anatomical dead space, as there was nitrogen present in the lung but pure oxygen in the anatomical dead space.
Give an overview of perfusion vs. ventilation in a healthy lung
Zone 1/ Apex: higher resting volume due to less compression secondary to gravity, which means it doesn’t ventilate that well as it can’t expand that much more (lower compliance). Comparatively poorly perfused due to gravity, in cases of IPPV or hypovolaemia, intrapleural pressure max exceed capillary pressure and splint them shut.
Zone 2/ Mid: well balanced, capillaries aren’t splinted shut, venous pressure isn’t high enough to affect perfusion, and ventilation is okay.
Zone 3/ Base: lower resting volume due to compression from the above lung/ surrounding tissue, so ventilation is better because it has further capacity to expand than the apex (higher compliance). Higher capillary pressures because of the advantage of gravity, so perfusion is good, and even outstrips ventilation. Venous pressure may exceed alveolar pressure.
Summarise body plethysmography, helium dilution, and nitrogen washout
Body plethysmography uses an airtight box and measures change in pressure within the box to extrapolate volumes during respiration
Nitrogen washout measures FRC - the subject breathes pure oxygen on a closed circuit and de-nitrogenates their lungs. The total amount of nitrogen washed out is then measured which gives the FRC, assuming the FRC was full of atmospheric air at the start (79% nitrogen)
What is the most influential driver of ventilation?
PaCO2 stimulating Central chemoceptors by making CSF more acidic (CO2 + H2O -> HCO3 + H), this accounts for 80% of response to high CO2, though peripheral chemoceptors generate a faster response.
It’s unknown how the chemoceptors detect pH changes
Why is the central response to hypercarbia blunted over time?
increased bicarbonate in CSF, either through active transport or passive diffusion - it’s unclear
What is the difference in sensitivity between the carotid and aortic bodies?
Carotid bodies respond to hypoxia, hypercarbia, and pH. Aortic bodies do not respond to pH.
Aortic bodies have a lesser blood supply and so rely more on haemoglobin for their oxygen delivery i.e. will respond to differences in oxygen delivery related to Hb. Conversely the carotid bodies have such a good blood supply they can be oxygenated purely by oxygen dissolved in solution and so will respond mostly just to PaO2.
Describe the role of peripheral chemoceptors in responding to changes in gas tensions
Hypoxia is sensed breath to breath by the carotid bodies, which are very sensitive and have a massive blood flow through them. This response is increased by hypercarbia and acidosis, and they generate much faster responses than central chemoceptors.
What is the Hering-Breur reflex?
A stretch reflex in the lungs that can act to terminate respiration, but doesn’t seem to have any real effect on normal respiration in adults
Describe the early features that compensate for cellular hypoxia
Local:
- pH drops due to anaerobic metabolism which shifts the Hb curve to the right allowing O2 to unload into the tissue more easily. Metabolites cause local vasodilation and improve perfusion
Ventilatory:
- Hypoxia and hypercarbia at peripheral chemoceptors stimulates an increase in minute ventilation
Cardiovascular:
- Hypoxia and hypercarbia at peripheral chemoceptors leads to vasoconstriction and tachycardia to improve perfusion
Which of the following is true of adrenoceptors?
A) Voltage gated potassium channels trigger noradrenaline release
B) Amitryptilline activates NET
C) Most of the noradrenaline released is metabolised in the synapse by MAO
D) Cocaine increases synaptic noradrenaline concentration through MAO inhibition
E) Ephedrine works by exchanging for noradrenaline
E) Ephedrine works by exchanging for noradrenaline
Ephedrine has a modest direct agonism of post-synpatic α1 receptors, but mostly works as it is structurally similar enough to be transported across the pre-synpatic membrane by NET, and into noradrenaline vesicles by VMAT. This displaces, and exchanges with, noradrenaline which is pushed into the synapse. Because of this, ephedrine’s sfficacy is reduced in patients with depleted catecholamine reserves e.g. sepsis, or in patient’s taking inhibitors of NET (e.g. TCAs, SNRI).
For the other options:
- Noradrenaline release is triggered by voltage-gated calcium channel release
- Amitryptilline inhibits NET, and so reduces ephedrine efficacy as it can’t cross the pre-synaptic membrane
- Most of the noradrenaline release into the synapse is recycled into pre-synaptic vesicles via NET and VMAT, with only 25% being metabolised by MAO (and this takes place pre-synaptically rather than in the synapse). Outside of noradrenergic nerve terminals, noradrenaline may akso be metabolised to normetanephrine by COMT.
- Cocaine inhibits NET and EMT to prevent catecholamine reuptake
Which two NANC (non-adrenergic, non-cholinergic) substances augment the action of noradrenaline?
ATP and neuropeptide Y
Which of the following is true of α adrenoceptors?
A) In the gut, α receptors stimulate voltage gated calcium channel opening
B) Clonidine acts exclusively on α2 receptors
C) Activation has minimal effect on the vasculature of the heart and brain
D) Noradrenaline does not stimulate α2 receptors
E) The majority of the body’s α2 receptors are found pre-synaptically
C) Activation has minimal effect on the vasculature of the heart and brain
Clonidine exerts most of its action at α2 receptors, but also activates α1 and so may cause transient hypertension. Dexmedetomidine is 10 times more selective selective α2 than clonidine.
α1 receptors have an unusual activity in the gut - they do not activate calcium channels but instead allow potassium to cross the cell membrane. This hyperpolarises the membrane and inhibits action potentials that would cause contraction of gut smooth muscle.
Noradrenaline does stimulate α2 receptors - this is the natural negative feedback mechanism. The majority of α2 receptors are found outside the synapse.
Which of the following is false of β adrenoceptors?
A) β2 receptors act to relax smooth muscle
B) Noradrenaline has a lesser affinity for β than α receptors
C) They stimulate NO-mediated splanchnic vasodilation
D) β1 receptors stimulate glucose and free fatty acid production from stores
E) β2 receptors are more important in sick hearts
B) Noradrenaline has a lesser affinity for β than α receptors
Contrary to popular belief, adrenaline is more potent at α and β2, and noradrenaline is more potent at β1, with a much lower affinity at β2. Both adrenaline and noradrenaline have greater affinity for β than α receptors, even though noradrenaline primarily acts as a vasoconstrictor and adrenaline as an inotrope. This is mostly explained by adrenaline’s significantly greater action at β2 which acts to reduce SVR and offsets its α1 activity. Furthermore, β2 receptors are particularly concentrated in the atria and SA node of the heart, hence stimulation of β2 causes more chonotropy.
β2 receptors account for only 20% of beta adrenoceptors in healthy hearts, but in heart failure there is de-coupling and de-population of β1 receptors such that β2 receptors make up ~50% of the beta adrenoceptor complement.
What is the generic structure of a catecholamine?
A catechol ring (benzene ring with two hydroxyl groups) with a terminal amine group
Which of the following is true regarding catecholamine production?
A) Dopamine is synthesised from noradrenaline
B) Tyrosine is made from phenylalanine in the adrenal medulla
C) Phenylalanine hydroxylase deficiency leads to profound deficiency of tyrosine
D) Dopamine exerts positive feedback on tyrosine hydroxylase
E) Tyrosine hydroxylase catalyses the rate-limiting step of catecholamine production
E) Tyrosine hydroxylase catalyses the rate-limiting step of catecholamine production
Tyrosine is the starting point for catecholamine production and can be acquired in the diet, or via conversion of phenylalanine in the liver, after which it is concentrated in chromaffin cells in the adrenaline medulla. Tyrosine undergoes hydroxylation to L-dopa, and then decarboxylation to dopamine, which is converted to noradrenaline (by dopamine-B hydroxylase), which is converted to adrenaline (by PNMT). Dopamine and noradrenaline exert negative feedback to tyrosine hydroxylase.
Which of the following would cause a cell to depolarise?
A) Sodium channel opening
B) Potassium channel opening
C) Increased Na/K/ATPase pump activity
D) Increased frequency of chloride channel opening
E) Decreased intracellular cAMP
A) Sodium channel opening
Which ion channel acts to prolong depolarisation in cardiac myocytes?
A) Magnesium channels
B) Chloride channels
C) Sodium channels
D) Potassium channels
E) L-type calcium channels
E) L-type calcium channels
After initial depolarisation (mediated by sodium and T-type calcium channel opening), potassium channels open as they would in a standard neuron to repolarise the membrane through potassium efflux. However the opening of L-type calcium channels and subsequent calcium influx prevents repolarisation of the membrane - this is the absolute refractory period. This is one of the heart’s mechanisms to ensure the whole ventricle is depolarised together. As a result the cardiac myocyte action potential is 200-300 times longer than a standard neuron’s. These cells also display prolonged refractory periods mediated by ion channel inactivation, to prevent tetanic contraction that would prevent ventricular filling.
Rank these from lowest to highest trough membrane potential (i.e. most negative to least negative)
Cardiac myocyte
Cardiac pacemaker cell
Standard neuron
Cardiac myocyte: -85mV
Standard neuron: -70mV
Cardiac pacemaker cell: -60mV
Which of the following is false of cardiac pacemaker cells?
A) Main depolarisation is not mediated by sodium
B) They have no resting phase/ membrane potential
C) Tachycardia is mediated by reducing membrane permeability to sodium
D) There is continuous membrane permeability to sodium
E) They don’t display the same depolarisation plateau as myocytes
C) Tachycardia is mediated by reducing membrane permeability to sodium
Cardiac pacemaker cells are found in the SA node in the RA, and throughout the heart’s conducting system. Their membrane potential decays spontaneously towards a threshold potential of -40mV due to continuous permeability of their membrane to sodium, and progressive impermeability to potassium. Firing rate is modified by increasing membrane permeability to sodium (tachycardia) or potassium (bradycardia) during the pre-potential (phase 4).
Once the threshold potential is met, L-type calcium channels open and are the main drivers of depolarisation of the cell. The membrane is repolarised by potassium efflux, but there is no resting phase in the cycle. T-type calcium channels also play a role in decay towards threshold potential alongside sodium channels.
Describe the three main factors that govern resting membrane potential
Resting membrane potential (i.e. the potential difference in electrical charge across the membrane of a quiescent cell) is governed by:
- Activity of the Na/K/ATPase pump which pumps 3 sodium out and 2 potassium in, and is responsible for 70% of energy consumption in the average neuron
- Differential permeability of the membrane to sodium versus potassium. At rest, the cell membrane is 100 times more permeable to potassium than sodium.
- The Donnan effect: charged particles that cannot cross the membrane such as proteins (like albumin) and phosphate that therefore keep the intracellular charge more negative irrespective of the above.
Summarise CICR
Action potentials move along t-tubules (deep invaginations in the cell membrane) causing opening of voltage-gated L-type calcium channels. The calcium moves intracellularly and activates ryanodine receptors on the sarcoplasmic reticulum, causing calcium efflux into the cell. The influx of calcium through L-type channels is modulated by adrenaline - this is the mechanism of positive inotropy.
Describe the action of surfactant
Surfactant is a phospholipid that acts to interrupt surface tension. Surface tension is a result of asymmetry of the normal attractive forces between fluid molecules because of an interface with gas. The alveolus is lined interiorly with fluid, and the net effect of surface tension here will be to crumple and collapse the alveolus (P=2T/R). This also increases the pressure required to increase lung volume i.e. compliance, which has been illustrated in experiments with saline-filled lungs having higher compliance.
Surfactant interrupts surface tension and so prevents alveolar collapse. It becomes more effective at lower lung volumes as the hydrophobic tails come closer together, increasing hydrostatic repulsion. Hence surfactant makes the biggest difference to compliance at low lung volumes.
Which of the following is false of surfactant?
A) It is produced in type 2 pneumocytes from free fatty acids
B) It has a hydrophilic head and hydrophobic tails
C) It opposes Laplace’s law
D) It increases alveolar fluid transudation
E) It has the greatest effect at low lung volumes
D) It increases alveolar fluid transudation
Surfactant forms a hydrophobic layer on the inside of alveoli, and so reduces fluid moving into the alveoli.
Which of the following is false?
A) Airway resistance is overcome passively in expiration using stored elastic energy
B) Lower RR and higher Vt minimise work of breathing in obstructive defects
C) Area under the hysteresis curve equates to compliance
D) The integral of the hysteresis curve equates to work done
E) The 2 components of work of breathing are elastic and friction
C) Area under the hysteresis curve equates to compliance
It equates to work done.
The two components of work of breathing are elastic and resistive. Elastic forces are applied by the lung parenchyma as it is stretched, and so change with volume. Resistive forces are airway resistance and friction, and so are more constant with changed in lung volume, though the total work done will increase with RR.
Which of the following regarding V/Q is false?
A) Atelectasis increases dead space
B) Increased dead space will increase EtCO2
C) A shunt will cause equilibration in gas composition between alveolus and capillary
D) A normal 45 year-old lying supine will develop a basal shunt
E) Where V/Q is ♾, PAO2 will tend towards PiO2
B) Increased dead space will increase EtCO2
The best example of dead space is cardiac arrest - none of the lung is perfused so there is almost no EtCO2. A normal 45 year old lying supine will generally have a closing capacity that impinges on their FRC, as FRC decreases by ~15% in the supine position.
Give the four classifications of hypoxia
Hypoxic
Anaemic
Circulatory
Cytotoxic
Describe how a shunt develops as a consequence of general anaesthetic
FRC is reduced under GA due to alveolar collapse, this is due to loss of intercostal muscle tone and supine/ head down positioning). Additionally the inhaled gas mix contains more oxygen and less nitrogen than air, which promotes atelectasis as oxygen is more soluble than nitrogen.
Reduction in FRC shifts the lung down the compliance curve - the volumes are now lower which shifts the apices onto a steeper segment i.e. better compliance, and the bases onto a shallower segment i.e. worse compliance.
The bases are still better perfused, but now have worse compliance and so less ventilation - this is a shunt.
How does hypoventilation cause hypoxaemia?
Not generally through a lack of oxygen. Hypoventilation causes hypercarbia, so the PaCO2 rises which reduces the PaO2 (as these two are balanced)
Explain why the hysteresis loop exists
Some energy is dissipated during inspiration without being recovered in expiration, therefore higher pressure (i.e. more work done) is required to inflate the lung and account for inefficiency.
Which of the following is false regarding CO2 transport in blood?
A) CO2 is largely buffered within plasma
B
C) Carbamino carriage accounts for most of the Haldane effect
D) RBCs actively transport HCO3- out the cell for Cl-
E) Buffering power of proteins is a result of their histidine content
A)
Exlain
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