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Biomedical Science L2 > Integrated Physiology and Pharmacology > Flashcards

Integrated Physiology and Pharmacology Flashcards

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1
Q

what is the fluid composition of the cell membrane?

A

Lipids - 42% weight
Proteins - 55% weight
Carbohydrates - 3% weight

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2
Q

what are the 3 types of transport proteins?

A

Carriers (fascilitated transport proteins - requires concentration gradient)
Pumps (ATPase)
Ion channels (gated)

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3
Q

what are the 3 classifications of transport proteins?

A

Uniporter e.g. K channel
Symporter (cotransporter) e.g.
Antiporter (exchanger) e.g. Na+/K+ exchanger

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4
Q

what kind of gradient does passive transport follow?

A

an electrochemical gradient - for the potential and the concentration

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5
Q

what are the 3 steps of action once a molecule binds to a carrier?

A
  1. binding
  2. conformational change
  3. release
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6
Q

what is primary active transport?

A

when the energy stored is a direct result of ATP breakdown

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7
Q

what is secondary active transport?

A

is also known as co transporters - the energy used to carry molecules across the membrane is not directly from the ATP but is formed by the resultant ionic gradient that arises from the movement of ions across the membrane.

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8
Q

is the channel turnover higher in passive or active transport and what are the figures?

A

turnover is higher in passive transport
Passive - 10^6 - 10^8
Active - 10^2 - 10^3

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9
Q

is the rate of uptake higher in carrier mediated diffusion or regular diffusion ?

A

there is a higher rate of stake for carrier mediated diffusion

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10
Q

what does it mean if a graph showing rate of uptake of a substrate plateaus?

A

it means that all the transport proteins are working at their maximal rate

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11
Q

who made the patch clamp technique and discuss it

A

Nehr and Sakman
makes it possible to record currents of single ion channel molecules for the first time,
improves understanding pH channels in fundamental cell processes e.g. nerve impulses and allows the study of single/multiple ion channels in cells

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12
Q

what are Kv channels activated by ?

A

they are activated by a change in transmembrane voltage - activated by cell membrane depolarisation

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13
Q

how many transmembrane spanning domains do Kv, Nav and CFTR Cl- channels have >?

A

Kv - 6 transmembrane spanning domains
Nav - 24 transmembrane spanning domains
CFTR Cl- channel - 12 transmembrane spanning domains

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14
Q

describe the structure of the K+ channel

A

it has a crystal structure

4 different subunits with a pore in the middle of it

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15
Q

is there a resting potential or the ability to fire action potentials in all cells?

A

there is a resting potential in all cells

not all cells can fire an action potential

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16
Q

what does the Na+/K+ ATPase contribute to the negative charge of the cell?

A

it generates the negative membrane potential directly 20%, indirectly by the intracellular Na+and K+

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17
Q

what does the K+ channel contribute to the negative membrane potential?

A

as potassium leads, it takes positive change with it and therefore leaving behind a negative charge. this attracts the positive charge back and so creates a driving force

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18
Q

what are the two membrane potential driving forces?

relate it to Nernst potential

A

CONCENTRATION driving force and POTENTIAL driving force - at some point they will be equal and opposite
Nernst potential is when therein no et flow and no current flow as there is a perfect balance of ions that are moving in and the that are moving out of the membrane

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19
Q

what does the sodium channel contribute to the negative membrane potential ?

A

sodium moves positive charge into the cell so that it is more positive inside. this increased positivity repels sodium (as this is positively charged) so there is more sodium pushed out via the positive membrane potential. eventually, sodium in by the concentration gradient will equal the sodium going out due to the repelling which is the potential driving force.

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20
Q

what does it mean if the resting membrane potential is closer to the equilibrium potential of sodium?

A

if the membrane potential is closer to ENa, then this means that it is sodium channels that are open

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21
Q

what is the role of phenylamine in the membranes

A

it acts to maintain transport

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22
Q

what is the normal intracellular and extracellular concentration of sodium?

A

extracellular - 145mM
intracellular - 15mM
therefore there is a 10 fold gradient for sodium intake

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23
Q

why is it important to maintain low intracellular sodium in epithelial cells?

A

in epithelial cells and excitable cells.
Epithelial cells - the function of the thick ascending limb of the loop of henle is to reabsorb NaCl in preference to H20.
Relies on the basolateral Na/K ATPase.
Na intracellular allows more Na+, Cl- and K+ to enter due to the electrochemical gradient
Cl- leaves through the CRCK6
There is not enough K in the lumen to allow more na to come in and so k is recycled through the channels.
This creates a transepithelial osmotic gradient that is responsible for counter current multiplication.
Activity of the NKCC depends upon the inward Na gradient
if intracellular sodium is increased, the NaCl reabsorption is inhibited and transepithelial osmotic gradient is dissipated which leads to diuresis and increased Na and Cl in the urine

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24
Q

why is it important to maintain low intracellular sodium in the excitable cell?

A

This is because issues arise if there is an increase from 15nm to 150nm
there is a decrease in the inward chemical gradient and so decrease in the electrochemical gradient
this means that it takes longer for a potential to develop
there is a problem wit the propagation of action potentials (slower conduction of the AP)
there is also a problem with the contraction of the muscle and so it does this with less strength

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25
Q

what is the action of the Na/K pump and what does inhibits it?

A

the pump maintains a low intracellular Na concentration and a high intracellular K concentration
it is inhibited by cardiac glycosides for example oubain and digoxin

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26
Q

what contributes to the overall negative charge of the membrane potential?

A
  • -Movement of 3 positive charges outside the cell and 2 positive charges aside the cell and so the net effect is to make the cell more negative
  • -Accumulation of K inside the cell creates the driving force for K to leave the cell through K channels - making the cell negative
  • -Passive entry of Na into the cel =l - greatly favoured due to already set conditions
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27
Q

what is the normal intracellular and extracellular concentration of Calcium?

A

Extracellular - 1mM

Intracellular - 100nM

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28
Q

what inflation factors must the lungs overcome?

A
  • elastic recoil of tissues
  • surface tension in alveoli
  • airways resistance
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29
Q

how do the elastic forces of the lungs and the chest balance ?

A
  • the elastic nature of the lungs all cause them to collapse inwards
  • the chest wall tends to expand
  • these inward and outward forces balance and os as a result the intrapleural space is less than that of the atmospheric pressure
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30
Q

what is compliance ?

A

compliance = distensibility

it is the ease with which the lungs and thorax expand during pressure changes

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31
Q

how does having a low compliance affect breathing?

A

a low compliance means that there is more work required to inspire e.g. in pulmonary fibrosis - lung parenchyma is more rigid

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32
Q

how does having a high compliance affect breathing?

A

a high compliance often involves more difficulty expiring (loss of elastic recoil)
eg emphysema

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33
Q

what is the equation for compliance ?

A

C = Δ V/Δ P

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34
Q

how do different disease states affect the FRC?

A

in emphysema, the lungs are more compliant and there is an increase in FRC
in fibrosis, the lungs are less compliant and so there is a decrease in FRC

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35
Q

what are the two major components to the elastic recoil of the lungs?

A
  • Anatomical component - elastic nature of cells and extracellular matrix
  • Elastic recoil due to surface tension generated at air-fluid interface
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36
Q

what equation describes the relationship between pressure exerted by a gas and the surface tension at the gas/water border?

A

Laplace’s equation : P=2T/r

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37
Q

according to Laplace’s equation, what leads to collapse of air bubbles?

A

larger air sacs in the lungs have a lower pressure than in smaller sacs. air will therefore flow from smaller alveoli to larger ones leading to their collapse.

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38
Q

what overcomes the problem of smaller alveoli collapsing?

A

surfactant

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39
Q

what cells produce surfactant? and what is it composed of ?

A

Type II pneumocytes.

components lipids and proteins

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40
Q

what is the action of surfactant ?

A

it acts to reduce the surface tension

the presence of surfactant can help inflation and prevent over inflation

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41
Q

what are the factors that affect air flow?

A
  • Type of air
  • resistance of the pathway
  • pressure gradients generated across the airways
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42
Q

describe laminar flow

A

movement of air into or out of the lungs is proportional to the pressure gradient and inversely proportional to the resistance
steady flow down tube in uniform direction and speed
flow rate is maximal in the centre but reduces at the edges
occurs in only very terminal ends of the airways

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43
Q

describe turbulent flow

A

gas movement is proportional to the square root of the pressure difference.
occurs if the flow rate moves beyond critical value, then irregular currents called vortices develop.
occurs in many areas of the lungs

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44
Q

describe transitional flow

A

due to the high number pf bifurcations in the airways which disrupts flow and causes eddies

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45
Q

what is used to determine flow rate?

A

Reynolds number
Re <1000 = laminar flow
Re between 1000-1500 = flow is unstable (switches between laminar ad turbulent flow)
Re > 1500 = turbulent flow

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46
Q

what equation describes the resistance of airways and what does it state?

A

Poisellues law - airway resistance is proportional to the length of the tube but is inversely proportional to the fourth power of the radius

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47
Q

what does Poisellues law say about changes in the airway diameter

A

small changes in the airway diameter a have a big impact on the resistance and hence the flow rate

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48
Q

what is the normal value for airway resistance in the lungs?

A

1.5cm H2O slitres-1

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49
Q

state the airway resistance in the pharynx-larynx, the airways with a diameter of >2mm and airways <2mm

A

Pharynx-larynx = 40%
Airways >2mm = 40%
Airways <2mm = 20%

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50
Q

compare the normal value for airway resistance with that of a disease state
and state the airway resistance in the pharynx-larynx, airways over and under 2mm

A 
Normal = 1.5cm H2O slitres-1
COPD sufferers = 5.0 H2O slitres-1
Pharynx-larynx = 40%
Airways >2mm = 17%
Airways <2mm = 70%
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51
Q

what airways have a bigger increase in the total resistance in a diseased stare?

A

lower airways have a huge increase in total resistance. this is due to its turbulent flow

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52
Q

what factors impact on airway diameter and how do they do this?

A

increased mucus secretion will effectively reduce airway diameter and therefore increase resistance
oedema - increased fluid retention in the lung tissue will cause swelling and narrowing of the airways which the increases resistance

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53
Q

what is the effect of dynamic pressures on airflow

A

during inspiration - forces expansion of some higher airways

during expiration - forced collapse of some higher airways

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54
Q

describe the pressure differences in the lungs during inspiration

A

the dilation of the airways causes a decrease in the resistance. the pressure gradient decreases as maximum pressure difference is in the alveoli so as the air moves up, it dissipates and becomes closer to the Patmos.
an increase in transmeaural pressure causes airways to expand and so flow rate increases and resistance decreases.

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55
Q

describe the pressure differences in the lungs during expiration

A

there is a positive gradient from the alveoli t the atmosphere (positive pressure gradient) so gas moves down the pressure gradient and goes out

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56
Q

what is the effect of emphysema on pressure differences in the lungs

A

the compression of the airways that happens in normal individuals is exaggerated. the loss of elastic tissues and breakdown of alveolar walls. the tethering between the walls adjoining airspaces is reduced. airways are flimsy, during forced expiration, the airways are less able to resist the collapse.

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57
Q

what techniques while breathing do emphysema patients use in order to overcome the problem of collapsing walls?

A

slow exhalation
breathing takes place at higher lung volumes
exhale through pursed lips

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58
Q

how does the lung volume impact on airway resistance?

A

as lung volume decreases, airway resistance increases as they are constricting (decreasing the diameter)

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59
Q

what is the tidal volume for normal individuals with healthy lungs and COPD patients?

A

in normal individuals - t=0.25

in COPD patients - t=15

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60
Q

what happens as the frequency of breathing for the cold increases, how does this affect their tidal volume?

A

as frequency of breathing increases, a bigger difference is observed as it is more difficult for them to get enough oxygen into their body in order to meet their metabolic demands

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61
Q

what is the control of airway diameter dependent on?

A

airway smooth muscle is heavily dependent on the Gq, Gs and Gi pathway GPCR cascades.

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62
Q

what receptors act through the Gq pathway?

A

M3 - muscarinic receptors
H1 - histamine receptors
Bk - Bradykinin receptors

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63
Q

what is the action of the Gq pathway?

A

muscle contraction and cell growth

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64
Q

what are the steps of things that happen during the Gq signalling pathway?

A

activation of PLC
increased production of IP3
activates receptors in calcium stores ub coming calcium into the cytoplasm
calcium binds to calmodulin which forms CaM
this complex acts on myosin, causing the contraction of smooth muscle
protein kinase c is stimulated by DAG when this happens which phosphorylates MLCK

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65
Q

what receptors act through the Gs pathway ?

A

B2 - adrenergic receptors

VIP receptors

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66
Q

what is the action of the Gs pathway?

A

it controls bronchial smooth muscle

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67
Q

what are the steps of things that happen during the Gs signalling pathway?

A

alpha s subunit stimulates adenylate cyclase and so produces cAMP.
cAMP produces/stimulates PKA which:
— phosphorylates IP3 receptors which decrease the sensitivity of IP3 and so down regulates it and promotes relaxation of smooth muscle
— phosphorylates MLCK ands reduces its sensitivity of CaM so decreases the activation of it
— phosphorylation of MLCP stimulates phosphatase which promotes relaxation of muscle fibres (inhibits inhibition) and so there is less contraction of the muscle therefore there is relaxation of the muscle fibres

alpha s subunit also interacts wth potassium channels in the membrane and stimulate them so there is a K+ flux into the cell which hyperpolarises the membrane therefore reduces the influx of Ca2+ through the voltage gated calcium channels so the muscle can’t contract therefore the calcium channel opens due to the depolarisation so hyper polarisation shuts it down
this leads to a reduction of cell growth and gene activation

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68
Q

what receptors act through the Gi pathway?

A

M2 muscirinic receptors

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69
Q

what is the action of the Gi pathway?

A

activation of this pathway counteracts the affects of the Gs pathway

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70
Q

what are the steps of things that happen during the Gi signalling pathways?

A

activation of this pathway leads to inhibition go adenylate cyclase
there is a knockoff effect of this which is to counteract the stimulatory effect of Gs activation
opposes relaxation of smooth muscle
inhibits Bk channels which leaves the membrane in a depolarised state

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71
Q

what do parasympathetic and sympathetic controls do to bronchial smooth muscle

A

ANS:
Parasympathetic NS - ACh is released from the vagus, acts on muscirinic receptors leads to CONSTRICTION
Sympathetic NS - release of noradrenaline from nerves - weak agonist that leads to DILATION

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72
Q

what are humeral factors that affect bronchial smooth muscle?

A

Adrenaline - circulating in the blood - better agonist leads to DILATION
Histamine - released during inflammatory process - leads to CONSTRICTION

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73
Q

where is the M2 receptor?

A

in the post ganglion nerve

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74
Q

where are the M2 & M3 receptors?

A

in the airway smooth muscle

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75
Q

what receptor is muscle contraction controlled by?

A

the muscle contraction is controlled by stimulation of M3 receptors

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76
Q

what is the role of M2 receptors?

A

it is an important feedback mechanism by M2 receptors - prevents the overstimulation of muscirinic receptors

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77
Q

describe the activation pathway of the M3 receptors

A
  • – release of ACh, stimulates M3 - muscle contraction - from post-ganglionic
  • – activation of M3 receptors
  • – contraction of muscle
  • – some of ACh released will bind to to M2 on post ganglionic ionic membrane - when this happens it inhibits further release of ACh
  • – problems in this pathway leads to hypersensitivity / hyperstimulation of smooth muscle
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78
Q

describe what happens

A

B2 adrenoreceptors on ASM
activation of B2 by adrenaline / noradrenaline
- stimulates K+ channel so increases hyperpolarisation so decreases calcium release
there is now a change in sensitivity of IP3 receptors so decrease calcium leaves its store

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79
Q

what is the problem with asthma sufferers smooth muscle?

A

the sufferer has hyperactive airways

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80
Q

what are the two classes of triggers to cause hyperactivity in the airways of asthma patients ?

A

Atropic (extrinsic) - allergies, contact with inhaled origins
Non-Atropin (intrinsic) - respiratory infections, cold air, stress, exercise, inhaled, irritants and drugs

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81
Q

what is the response of the body to triggers in asthma patients?

A

movement of inflammatory cells into the airways, release of inflammatory mediators such as histamine and subsequent bronchoconstriction

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82
Q

what does a spirometer of asthma show?

A

there is a decrease in FEV1 and FEV1%

in many cases FVC is unaltered but there is a decrease in FEV1

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83
Q

what is the link between M2 receptors and airway hypersensitivity?

A

asthma is associated with an increase in parasympathetic activity. manifests as an increase in basal tone with and increase in muscle constriction in response irritants

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84
Q

what proves the link between M2 receptors and airway hypersensitivity ?

A

treatments - antigen challenge, viral infection, ozone exposure and vitamin A deficiency .
all treatment produced an increase in parasympathetic activity
in all these models - no change in function of M1/M3 receptors and a decrease in neuronal M2 function

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85
Q

what is the link between M2 receptors and asthma?

A

in the case of antigen challenge, the change in M2 function is linked to eosoniphils
the eosinophils cluster around the nerve fibres
activated eosoniphils release major basic protein
MBP inhibits the M2 receptors
this inhibits a negative feedback mechanism.
an increase in ACh releases obstructs airways
Each is inhibited by M2 receptors
a decrease in M2 receptors increases ACh release

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86
Q

what are examples of short and long acting treatments of Asthma?

A

ST - Salbutamol

LT - Salmeterol (which must be delivered with corticosteroids)

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87
Q

what is an example of an anti cholinergic drug?

A

Trotropium bromide - inhaled daily with an action mainly via M1 and M3 receptors

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88
Q

what is a glucocorticoid and give an example?

A

long term anti-inflammatory action
eg bedometasone / other inhaled steroids
-decreases mRNA stability, decrease in regulation inflammatory genes : cytokines, chemokine
-increases regulation of anti-inflammatory genes e.g. MKP-1,SLP1, GLC2

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89
Q

what is breathing?

A

it is an automatic rhythmical process

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90
Q

where is the basic respiratory rhythm generated?

A

in centres in the medulla

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91
Q

how can breathing be altered consciously ? what is the problem with this?

A

hyperventilation and breath holding

this is a temporary control

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92
Q

what are the two types of respiratory groups in the medulla?

A

the dorsal respiratory group

the ventral respiratory group

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93
Q

what does the DRG control?

A

it controls quiet inspiration and also quiet breathing

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94
Q

why doesn’t the DRG control quiet expiration?

A

this is a passive process which doesn’t need muscle to control it

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95
Q

what does the VRG control?

A

it controls forced inspiration and forced expiration which both require extra muscle groups

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96
Q

in the medulla, what nerve controls the contraction of the diaphragm?

A

the phrenic nerves control the contraction of the diaphragm

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97
Q

what nerve controls the external intercostal muscles?

A

spinal nerves control the external intercostal muscles for expiration

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98
Q

what is the pre-botzinger complex?

A

it contains pacemaker cells which generate APs that are linked to the control of breathing - located near the VRG
activity in hypoglossal nerve matches pre-botzinger complex output
cranial nerve send inputs to the diaphragm and muscles in the chest walls to control inspiration

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99
Q

what experiment was done to show that ……

A

brain slices were taken and they put an electrode to measure changes in the membrane potential. this showed spontaneous bursts of acton potentials - signals sent 12th cranial nerve hypoglossal is responsible for inputs

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100
Q

what are the three types of pattern inputs in the pre-botzinger complex?

A

Eupneic - normal breathing rhythm. increase in spikes (activity) then cuts off and returns to the baseline
Sigh - increases u activity level and intensity. increases output (inhale increases for a long-time)
Gasp - in hypoxic conditions (often)

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101
Q

what are the two types of cells in the PBC?

A

pacemaker cells

non-pacemaker cells

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102
Q

what do the pacemaker cells do?

A

they demonstrate spiking and bursting forms of activity

103
Q

what are the bursts and gaps for pacemaker cells?

A

the bursts are inspirations and the gaps when there is a repolarisation of cells, followed by quiet expiration

104
Q

what is the NACLN and what does it do?

A

it is a sodium slow leak channel that plays a critical role in the regular rhythm generation of spiking and bursting activity

105
Q

what is the responsibility of the NACLN?

A

it is responsible for slow depolarisation of pacemaker cells in the pre-botszinger complex. also contributes to the depolarisation phase

106
Q

what does an experiment into the WT and mutant NACLN in mice show?

A

it indicates that the inward sodium current - important in generating the initial depolarisation . this leads to the firing of action potentials.

107
Q

what is the role of potassium in pacemaker cells?

A

K+ gives repolarisation phase and the concentration of K+ has an important effect on the resting membrane potential. the majority of cells have a background leak of potassium channels.

108
Q

how does the change of potassium outside of a cell change the pattern of bursting?

A

changing K outside cells in a region, changes the pattern of bursting in that region
increasing [K+] - much steeper change in the potential of the cell - high intensity of bursting
decreasing [K+] - change in background K before going into a bursting phase - slow
dec

109
Q

what are the classes of pacemaker cells?

A

the transition of bursting activity depends on two different types of inward current:

  • – persistent sodium current (INAP)
  • –CAN cation current (ICAN)
110
Q

what can pacemaker cells be split into depending on?

A

depends on if the cells bursting activity is sensitive to cadmium

  • –neurones relying on ICAN for busting - cadmium sensitive
  • –neurons relying on INAP for bursting - cadmium insensitive
111
Q

what is the effect of hypoxia on the pre botzinger complex?

A

a decrease in 02 availability leads to a sigh bursting activity then gasping bursting activity. the cadmium sensitivity bursting cells become activated ad turn off therefore rely on caddie insensitive cells which leads to the basic gasping pattern of breathing

112
Q

how does the DRG control inspiration?

A

it controls inspiration by sending signals to the inspiratory muscles
it is spontaneously active and shows a burst of activity but when it shuts off, there is a period of inactivity

113
Q

how does the VRG control breathing?

A

it controls inspiration and expiration. it is inactive during quiet respiration and during activation, helps control forceful inspiration and expiration

114
Q

where are the two centres that modulate the pre botzinger complex and what are they called?

A

they are in the PONS

  • –pneumotaxic centre - increases the rate of breathing by shortening inspirations - inhibitory effect on inspiratory centre
  • –apneustic centre - increases the depth of breathing and reduces the rate of prolonged inspirations - stimulates the inspiratory centre
115
Q

what is another feedback mechanism in the lungs?

A

the stretch receptors e.g. Hering-brewer reflex. these are stretch receptors in the lungs that send signals back to the medulla to limit inspiration and prevents over-inflation of the lungs

116
Q

what do the phrenic and vagus nerves do in respiration?

A

the phrenic nerve activity promotes lung inflation and contraction of the diaphragm
the vagus nerve activity from lungs stretch receptors to the brain causing inhibition of the inspiratory centre

117
Q

when the lungs are full, what is the activity of phrenic and vagus nerves?

A

when the lungs are full, phrenic activity stops and vagus activity starts

118
Q

what is the role of chemoreceptors?

A

central chemoreceptors monitor conditions in thecerero-spinal fluid. sensing CO2 and pH changes
an indirect respond to a rise in CO2 then stimulation leads to an increase in ventilation
peripheral chemoreceptors are located in the carotid body of the aortic arch and responds to an increase in CO2, decrease inch and a decrease in O2.
stimulation leads to an increase in ventilation

119
Q

how does COPD and/or emphysema affect chemoreceptors?

A

COPD patients have a chronically raised love of CO2 and so they lose sensitivity of these receptors - O2 therefore becomes the primary driving force for respiration

120
Q

describe the hering-brewer reflex

A

phrenic nerve vagus nerve

downward arrow

121
Q

how many receptor families are there and what are they?

A

type 1 - ligand gated ion channel (ionotropic)
type 2 - G-protein coupled receptors (metabotropic)
type 3 - kinase-lined receptors
type 4 - nuclear receptors

122
Q

define occupancy

A

the proportion of receptors occupied that will vary with the drug concentration

123
Q

what is the equation for occupancy?

A

occupancy = the proportion of receptors occupied/total number of receptors

124
Q

what are the values normally seen for occupancy and what do they mean?

A

occupancy ranges from 0-1
0 = no drug present
1 = all receptors occupied

125
Q

how do we measure occupancy?

A

measure the response when an agonist binds to a certain number of receptors

126
Q

what is the technique used when measuring occupancy?

A

Radioligand Binding assays of a ligand to a protein target

127
Q

what is the method of the radioligand binding assay?

A
  1. prepare cells or membranes e.g. guinea pig ileum - detergent treatment and centrifugation
  2. aliquot out membranes onto filters
  3. add radiojlabel at different concentrations and equilibrate
  4. when equilibrated, remove unbound drug by filtration (bound drug remains attached to filter)
  5. count radioactivity of filter
128
Q

what are the different steps to the radio ligand binding practical?

A
  1. non specific binding
  2. applying radio labels to the ligand
  3. the tissue and incubation conditions
  4. separation of bound from free
  5. data analysis - stat chard plot
129
Q

what is non-specific binding and how can it be reduced in assay?

A

most ligands bind non-specifically to filter aper, glass etc. there is non specific binding to filters and glass which can only be reduced by anti-absorbants e.g. albumin or collagen for peptides, o-catechiol or catecholamines. but this does not stop non specific binding to the tissue under study.

130
Q

what is the key element to the radioligand binding assay?

A

measuring the proportion of specific and non-specific binding.

131
Q

why must the ligand be biologically active?

A

because it is binding to the recognition and is supposed to correlate wit a pharmacological action (agonist/antagonist).

132
Q

what are three important things that must be addressed in terms of the radio ligand?

A

the radioligand must be chemically extremely pure, the labelling of the drug with radioactivity must achieve a very high specific activity to allow very low (‘tracer’) concentrations. also must prevent degradation

133
Q

what are ways to stop degradation of a radioligand?

A
  1. free radical scavenger (e.g. ethanol) in drug solution
  2. store at low (not freezing) temperature
  3. avoiding light (dark bottles to store)
  4. incorporation of antioxidant (e.g. ascorbic acid)
134
Q

what are the advantages and disadvantages of different radio labels?

A

3H and 125i are the two options and both have different advantages and disadvantages

135
Q

what are the advantages and disadvantages of 3H?

A

A = the labelled product is undistinguishable from the native compound
high specific activities can be obtained (>80ci/mmol)
good stability when properly stored
long half life (-12.5yrs)
D = specialised labs are requires
labelling is expensive and difficult

136
Q

what are the advantages and disadvantages of 125i

A

A = if the compound has an aromatic hydroxyl group (e.g. tyrosine residues in peptides), it can be incorporated at very high specific activities (>200 ci/mmol)
iodination is easy in most labs and is cheap
D = more readily degradable/digested
biological activity of ligand can be reduced ; not functional invisible
short had life (-67 days)

137
Q

what are the desired tissue and incubation conditions?

A

the tissue selected must contain the recognition sites (receptors) of interest
they can be: isolated membranes, slices, synaptosomes, cultured cells or solubilised/purified receptors. from total brain or specific brain region. this all depends on the receptor to be studied and the hypothesis that is being tested

138
Q

what happens during the incubation process and what must it achieve?

A

must try to preserve the integrity of both the ligandd and the binding site
the protein concentration needs to be in the range of 0.1-1mg membrane protein with the assay volumes 0.25-1ml
additives are used to protect the tissue/ligand (e.g. protease inhibitor for peptides, antioxidants like catecholamines if the ligand is oxidisable
temperature isan important parameter and should be usually low room-0 degrees. thesis because there are free enzymes that wrk to cleave proteins and male them inactive and so at lower temperatures, these don’t work to break down the proteins.

139
Q

how is a tissue + bound ligand separated from free ligand ?

A

usually done by filtration or centrifugation unless it is a solubilised receptor

140
Q

what are the techniques used when separating a ligand bound to a solubilisied receptor? what is the problem with this?

A

the techniques used are: dialysis (theres a solid membrane on one side of at barrel and so diffusion only happens to one side), column chromatography, precipitation/adsorption.
the problem is the rate of dissociation of ligand-receptor complex. the speed of separation must be compatible with the affinity of ligand receptor complex. lower affinity (high kd) requires faster/more efficient seperation

141
Q

how does the affinity and K+1/K-1 rate relate to separation time?

A

if the affinity is high, K-1 rate is faster than K+1 rate and so the complexes don’t last long therefore the separation time must be fast
if the affinity is low, K+1 rate is slower than K-1 rate and so the complexes are more stable therefore there is time for separation.
so if drugs have a lower stability, a process must be found to separate them very fast

142
Q

what is affinity?

A

the strength of attraction between a chemical and a receptor. a high affinity requires a low drug dosage

143
Q

what is the formula for specific binding?

A

specific binding = total bound - non specific binding

144
Q

what is the shape of the graph curve for specific binding? and explain why

A

rectangular shape. this is because there is a finite number of receptor proteins and once every receptor has a protein bound to it, it cannot get anymore and so the graph plateaus (saturable binding)

145
Q

what is the difference between specific and non specific binding curves?

A

non specific binding curves have an infinite number of receptors which are relative to the number of drug molecules that are put in. it is non saturable so continues to increase

146
Q

what is the prob,em wit plotting the specific and non specific binding on a linear scale?

A

it is difficult to read off of it and so a semi logarithmic scale s preferred.

147
Q

is radioligand binding saturable or non saturable?

A

it is SATURABLE. this is because the total number of receptors in the prep tissue is limited. since receptors are present in finite numbers, it is inevitable that there will be a concentration of ligand where all the sites will be labelled ad the ending curve will plateau.

148
Q

what is an important property that a radioligand should have?

A

it should be stereospecific

149
Q

is it possible to get a maximum response without getting 100% occupancy?

A

yes. some tissues can even get a maximum response with <5% occupancy

150
Q

what is a receptor reserve? where is it seen

A

its the idea that cells will express a lot more receptors then it needs - these act as a spare capacity and is seen in autoimmune diseases

151
Q

what is EC50?

A

the effective concentration giving 50% maximal response

152
Q

what could be a reason for a reduced KD and EC50 value?

A

because there are spare receptors

153
Q

what is the shape of a concentration response curve?

A

sigmoidal

154
Q

what is the downstream process of ACh causing contraction in a guinea pig ileum?

A 
Each binds to receptor which sets off a chain of events
activation of G proteins
2nd messenger systems are activated
rise in intracellular calcium
activation of contractile machinery
contraction
155
Q

what can influence the size f a response?

A

the eficacyof theagonist - aslongas an agonist remans bound to a receptor, it is capable of inducing a response. this is because a single receptor that is occupied may be activating multiple copies of receptors/multiple enzymes/ multiple responses. is the agonist is very good at stimulating signal cascades, the response will be very large and shift the curve to the rigt

156
Q

what is efficacy?

A

how good an agonist is at inducing a response when bound to a receptor

157
Q

what is the hill slope factor?

A

the number of molecules that must bind to a receptor to provoke a response

158
Q

what are some limiting factors of a concentration -effect curve?

A

machinery of cell - what is being activated downstream, the enzymes all activated 2nd messengers so there would be no more response

159
Q

what is the curve for a nicotinic:ACh receptor?

A

there is a 1:2 relationship between nicotine and ACh. there will therefore be a steep curve as 2 ACh to 1 nicotine at a time is needed to create a response. so, n>1 as you need more than one agonist binding.

160
Q

what does potency depend on?

A

it depends on the affinity, efficacy and spare receptors

161
Q

what is EC50 a measure of?

A

agonist potency. the ability of a drug to induce a response is the same as there is an increase in potency however, the amount of drug needed to make 50% of a max response (EC50) is different. the furthest on the left on the graph has the highest potency as it requires the smallest concentration to have 50% of themas response.

162
Q

can you determine affinity from a concentration response curve?

A

no

163
Q

is it possible for a partial agonist to be more potent then a full agonist?

A

yes, could also be less so. the EC50 and potency are determinedly affinity and efficacy.

164
Q

will agonist with different efficacies have the same maximal responses?

A

agonists with different efficacies produce different maximal responses.

165
Q

what is needed in order to get a max response for a partial agonist?

A

100% occupancy is required. so EC50 will equal to KD.

166
Q

what are the benefits to the fact that you can’t evoke a full response from a partial agonist?

A

less overdoes likelihood
less desensitisation of receptors
when alleviating here addicts, can are them off the drug slowly by giving them lower dosages. this is because when a partial agonist binds ti a receptor, it will reduce the effect of added full agonist as it competes for the spaces on the receptors

167
Q

wat is efficacy?

A

a measure of a single agonist-receptor complies ability to generate a response
an efficacy of 0 = an antagonist
and efficacy of 1 = full agonist

168
Q

what ere the tree properties tat determine the effect of a drug in a living system?

A 
specificity: how it interacts with structurally defined sites / receptor chemical properties/molecular structure
affinity : agonist and antagonist
its ability to bind to a receptor
efficacy - agonist (NOT ANTAGONISTS)
ability to activate a receptor 0,E.1
full ag E=1
ant E = 0
169
Q

what happens when proteins move around?

A

they become different shapes and could come activated.
this doesn’t happen for long if there is no agonist to stabilise it
if enough of them are active, constitutive activity is background love of activation without an agonist

170
Q

what is the new class of drug designed that has a efficacy of below 0?

A

inverse agonists. these stabilise receptors so ir cannot assume an active configuration, the efficacy = -1 so GCPRs may have allosteric sites the alter the efficacy of an agonist, this can make it easier for an agonist to provoke a response.

171
Q

are agonists or antagonists most clinically useful?

A

antagonist

172
Q

what is an antagonist?

A

a drug that prevents the response of an agonist

173
Q

what are the 5 different classes of antagonists?

A
  1. chemical antagonism
  2. pharmacokinetic antagonism
  3. physiological antagonism
  4. non-competitive antagonism
  5. competitive antagonism
174
Q

describe chemical antagonism

A

they are substances that combine in solution so that he effect of the active drug is lost i.e. the agonist is chemically altered by the antagonism. e.g. inactivation heavy metals whose toxicity is reduced by the addition chelating agents

175
Q

describe pharmacokinetic antagonism 1 and 2

A

reduction in the amount of drug absorbed e.g. drugs that inhibit gut motility e.g. opiates will reduce absorption by oral route.
change in drug metabolism e.g. for patients taking warfarin (anticoagulant and thins blood, reduces risk of heart attack and stroke) have to be careful who treating with some antibiotics as they may stimulate the metabolism of warfarin so reducing its effective concentration in the blood stream

176
Q

describe physiological antagonism

A

its the interaction of 2 drugs with opposing actions in the body
not due to competition, just different/opposite physiological mechanisms
eg noradrenaline ; higher arterial blood pressure on peripheral blood vessels and heart. histamine = lower arterial blood pressure by causing vasodilation. the term is generally used when describing the actions through separate cells or different cells or different transduction/receptor systems

177
Q

describe non-competitive antagonism

A

blocks some steps in the process between receptor activation and response - interferes in singling mechanism/pathway rather than directly with the receptor. i.e. it doesn’t compete with the agonist for the receptor site and so is termed non competitive
eg nifedipine - works at the level of the voltage gated L type channels which are usually found in the smooth muscle - is used to reduce blood pressure (used in the elderly with hypertension)

178
Q

describe competitive antagonists

A

these compete with an agonist for the ligand binding site on a receptor. structurally, they are similar to the agonists but when they bind to the receptor, they aren’t stabilising the receptor in order to cause a reaction. binds reversibly to a receptor. a higher concentration of agonist means that there is a higher possibility that it will be on the ligand binding site - can overcome drug effect by increasing the agonist concentration. this is different to all the others

179
Q

what does the graph of a reversible competitive antagonist look like?

A

there is a parallel rightward shift in the concentration-response curve with increasing competitive antagonist (atropine to ACh) but no change in the max value. the slope of the curve is also the same.

180
Q

how is the parallel shift of a curve quantified?

A

how many more times an agonist is needed in the presence of an antagonist is the dose ratio

181
Q

what is the equation for dose ratio?

A

concentration of agonist in presence of antagonist/ concentration pf agonist in absence of antagonist. seen on a child plot

182
Q

what is the pA2?

A

the -log10 of the molar concentration that gives a dose ratio of 2.

183
Q

what is the relationship between pA2 and affinity?

A

the higher the pA2, the higher the affinity

184
Q

what is an irreversible competitive antagonist?

A

an antagonist that cannot be reversed by washing the tissue. it is time dependent.

185
Q

describe the desensitisation of a drug

A

the effect of a drug may decline over time when given continuously or repeatedly. (as time increases, max response increases).
theres a loss of receptors from the cell surface - internalisation followed by recycling or degradation tolerance,
change in the receptor itself e.g. phosphorylation - decreased coupling of receptors to effectors,
exhaustion of mediators,
increased metabolic degradation or extrusion of the drug
physiological adaptation

186
Q

what does the concentration of a drug in the tissues depend on?

A

absorption of the drug
distribution of the drug
metabolism
excretion

187
Q

what are the three principle mechanisms of how drug distribution is regulated?

A

diffusion through lipid
diffusion through aqueous channel
carrier

188
Q

what size of drug is optimum to be able to diffuse through lipid?

A

a small molecules drug

189
Q

what physiological properties does the diffusion of a drug through lipids depend on?

A

the lipid solubility partition coefficient

diffusivity - diffusion coefficient : depends o size of molecule, small molecule= small DC

190
Q

what are the advantages of an uncharged molecule as a drug?

A

non polar molecules dissolve freely in lipids and penetrate cell membranes freely
high rate of absorption from gut
high penetration into the brain and other tissues
high renal distribution

191
Q

what is one factor that influences drug absorption in the body and how does it do this?

A

route of administration -
Intravenous route : the quickest and should void gut to not be metabolised
however, need a qualified practitioner to do this
Intramuscular route: depends on the muscles e.g. insulin avoids gut so straight into plasma
Inhalation route: drugs directly into lungs. is a localised response i.e. stays in the lungs. e.g. gas general anaestheic
Oral/rectal route: most common/desirable due to its ease of use. the drug must be passed through the gut as it goes through the whole body. must consider how the drug will leave the gut - usually through diffusion

192
Q

what is the equation for the bioavailability of a drug?

A

bioavailability = fraction of drug ingested / fraction of drug in plasma

193
Q

what are the sublingual, rectal and subcutaneous methods ?

A

oral - under the tongue, not broken down in the gut
rectal - avoids the gut - desirable for local action
skin - through patches /cream and absorption happens across the skin. it is a very slow but continuous process.

194
Q

what are the 5 factors that affect absorption of a drug?

A

site/method of administration
molecular weight - affects rate of diffusion
lipid solubility - affects ability to cross lipid membrane by diffusion
pH and ionisation - as many drugs are weak acids/bases as at low pH weak acids will be unionised and only uncharged molecules can pass the lipid.
carrier mediated transport - passive/active polar molecules e.g. sugars its are dependent upon saturation and competitive inhibitors and so the rate of diffusion is affectedly the amount of transporters available

195
Q

in what state of pH is favoured as a drug?

A

as a weak acid. in basic environments, it favours the dissociation of acids. weak acids become trapped. so uncharged molecules can diffuse rapidly across the membrane into the plasma so is very efficient

196
Q

what would happen to the drug if it was a weak base?

A

it would be poorly absorbed through the gut,poorly excreted and basically the inverse to what happens if it was a weak acid

197
Q

how is the mechanism of weak acids and bases in the body manipulated in poison?

A

the poison could be administered as sodium bicarbonate which would alter the pH and make it higher in basic conditions in he gut. this draws the drugs out of the plasma/CNS where they may be causing poisoning. high excretion of the drug occurs through the kidneys

198
Q

what influences drug distribution in the body?

A

the distribution of a drug through the body is based on its permeability and lipid solubility through the major body compartments e.g.
extracellular fluids (plasma 45%, interstitial fluid 10%, lymph 1-2%)
intracellular fluids (50-40%)
transcellular fluids (CSF 2.5%)
fat (20%) - there is a lipid accumulation in this fat compartment

199
Q

what part of the CNS is outside the blood brain barrier?

A

the chemoreceptor trigger zone - specifically located where BBB is sparse

200
Q

what is the relevance to the chemoreceptor tigger zone in relation to drug targeting?

A

causes vomiting as it senses bad things and makes you vomit them out. is a problem for drugs e.g. of Parkinson’s as they target dopamine receptors and this zone has many dopamine receptors. taking this drug will trigger this zone and cause nausea. its combatted by co-administerting with another drug that inhibits this zone.

201
Q

what is the role of the BloodBrainBarrier?

A

it is used to regulate the access of drugs to the CNS

202
Q

what kind of molecules are restricted from getting into the CNS?

A

molecules with a large surface area cannot get into the CNS due to tight junctions that are impermeable to water soluble molecules. lipid soluble molecules can cross the BBB easily ands have good access to the CNS. tight junctions can become leaky during inflammation (e.g. meningitis) which could allow access to antibiotics into the CNS.

203
Q

what is the clinical significance of treating a patient with possible inflammation disease with antibiotics? with examples

A

Clinically, a person with for e.g. meningitis, should be immediately treated with antibiotics (penicillin) as if they have the disease, they can be treated. if, after checking they don’t have the disease, there is no problem as the antibiotics word not have been able to cross the BBB anyway.

204
Q

what are other factors that affect drug distribution and elimination?

A

binding of drugs to plasma proteins - albumin binds mainly acidic drugs
partition into specific tosses e.g. body fat

205
Q

explain how storage of drugs in body fat can be an issue

A

body fat can be an issue when drugs try to cross the CNS because in e.g. surgery, general anaethestics given to patients to get to the CNS have high fat solubility (in order to cross the BBB) but this means that it can easily become stored in body fat. this causes a problem when trying to administer GA to have a desirable concentration taking into account how much would be lost.

206
Q

how any phases are involved in the metabolisation of drugs in the body and where does it occur?

A

in the liver, there are 2 biochemical reactions
PHASE 1: catabolic reactions
can produce a more ‘reactive’ compound
PHASE 2: synthetic (anabolic) reactions
involves conjugation to produce the inactive product

207
Q

describe the process of drug metabolisation

A 
there are microsomal enzymes in the liver e.g. cytochrome p450, alcohol dehydrogenase and MAO. the drugs must cross the plasma membrane (be lipid soluble/bind to a specific transporter) to be metabolised
some drugs ('pro-drugs') only become active after they are metabolised. metabolism can alter/prolong the pharmacological actions of a drug
208
Q

what is the function of a pro drug?

A

it is a small molecule drug that is altered as we know it must undergo the 1st phase of reactions in order to release the active substance. it slows down the rate that the active dog can be distributed around the body and also slows down its gradual rise in concentration

209
Q

what is the process of eliminating a drug. give an example

A

drug goes through phase 1 then becomes the derivative then goes through phase 2 and becomes the conjugate
aspirin goes through phase 1 as the OH group is joined by the p450 enzyme. then it goes through phase 2 and becomes glucoronide .This can no longer interact with the target and promotes excretion.

210
Q

how many variations of p450 have been found and what is a difference between them?

A

the human genome project found 57 genes coding for the p450 enzyme which also have endogenous functions (not just metabolisation of the drug)
different isoforms of the p450 enzyme react with different drugs

211
Q

how are drugs eliminated from the body?

A

there are different routes that drugs take to be excreted. the majority are excreted through the kidney to the urine. some drugs may bypass this and go straight to the faeces
some drugs can be trapped in milk and sweat - drug can be passed inform mother to baby
inhalation -some drugs are expired out into the air

212
Q

what controls the rate of metabolism?

A

the health of the liver

serosis of the liver can cause less metabolism of the liver

213
Q

what is pharmacokinetics?

A

the time course of drug concentrations attained in the body during and after dosing.

214
Q

what is the shape of the time course of clearing a drug?

A

a mono-exponential decay, the time course of which is determined by the rate of metabolism and excretion.

215
Q

what is the t1/2 of a drug?

A

it is a time constant. the amount of time it takes for the concentration of drug to decrease by half

216
Q

is t1/2 directly proportionate to the starting concentration ?

A

no it is not.

it is affected by the metabolism and exertion of the drugs.

217
Q

what are the saturation kinetics involved in some drugs?

A

processes responsible for metabolism and excretion become overwhelmed and this is very dangerous. there is a disproportionate increase in steady state plasma concentration. the clinical side effects are toxicity.

218
Q

explain in terms of alcohol consumption, what happens to the enzymes involved

A

due to the enzyme alcohol dehydrogenase being overwhelmed, the drug concentration increases as it can’t be metabolised or excreted. the enzyme is working too hard of the amount of alcohol.

219
Q

what is the difference in graph shapes of a normal/saturated drug affect

A 
normal = curve
saturated = linear
220
Q

what is the cardiac cycle?

A

the mechanical and electrical events that repeat with every heartbeat

221
Q

what are the four major steps of the cardiac cycle?

A
  1. inflow of blood
  2. isovolumetric contraction
  3. outflow of blood phase
  4. isolvolumetric relaxation
    1&4 = diastole
    2&3 = systole
222
Q

what initiates the cardiac cycle?

A

it is initiated by the P wave

223
Q

why do both atria contract simultaneously in the cardiac cycle?

A

they both contract simultaneously thanks to faster conduction velocity in Bachmann’s branch

224
Q

what happens when the atria contract ?

A

blood pressure in each atrium increases, blood is squeezed into the ventricles

225
Q

what is the duration of blood going from the atria to the ventricles?

A

o.1 seconds

226
Q

how much of the blood flowing from the atria to the ventrcelss done passively ?

A

80% is passive (gravity)

227
Q

what is the contribution of the left atria to the flow into the ventricles?

A

10%

228
Q

where does the additional atria contribution come from?

A

the atrial kick contributes to 20% of ventricular preload -caused by the active contraction of the atria

229
Q

what happens after the atrial contraction is completed?

A

the atrial press begin to fall, causing a pressure gradient reversal across the AV valves. this causes the valves to float upward (pre-position) before closure

230
Q

describe phase 1 of the cardiac cycle

A

this is where the ventricular volumes are maximal which is termed the end-diastolic volume (EDV). the LVEDV (120ml), represents ventricular preload

231
Q

what are the end diastolic pressure of the left and right ventricles?

A 
LV = 8-12 mmHg
RV = 3-6 mmHg
232
Q

describe phase 2 of the cardiac cycle?

A

starts with the appearance of the QRS complex the ECG, which represents the ventricular depolarisation.
this triggers excitation-contraction coupling, myocyte contraction and a rapid increase in intraventricular pressure.
early in this phase, the rate of pressure development becomes maximal ‘dp/dt’
the AV valves close wen intraventricular pressure exceeds atrial pressure
ventricular contraction triggers contraction of the papillary muscles with their chordae tendinae that are attached to the valve leaflets. this tension on the AV valve leaflets prevent them from bulging too far into the atria and becoming incompetent (leaky)
closure of the AV valves results in the first heart sound (s1). this sound is normally split (-0.04seconds) because mitral valve closure precedes tricuspid closure.

233
Q

describe what happens in phase 3

A

during theme period between the closure of the AV valvesand the opening of the aortic and pulmonic valves, ventricular pressure rises rapidly without a change in ventricular volume (i.e. no ejection occurs)
isovolumetric
the rate of pressure increase in the ventricles determined by the rate if contraction of the muscle fibres, which is determined by mechanisms governing ‘excitation’ - contraction coupling

234
Q

what is the c wave in the LA due to ?

A

the bulging of mitral valve leaflets back into the left atrium

235
Q

describe phase 4 - ejection

A

the aortic and pulmonic valves open; AV valves remain closed
ejection begins when the intraventricular pressures exceed the pressures within the aorta and pulmonary artery, which causes the aortic and pulmonic valves to open.
maximal outflow velocity is reached early in the ejection phase, and maximal (systolic) aortic and pulmonary artery pressures are achieved.
left atrial pressure initially decreases as the atrial base is pulled downward, expanding the atrial chamber. blood continues to flow into the atria from their respective venous inflow tracts and the atrial pressures begin to rise. the mis in pressure continues until the AV valves open at the end of phase 5.

236
Q

why can no heart sounds heard during ejection?

A

because during ejection, the opening of healthy valves is silent

237
Q

describe what happens in phase 5 - isovolumetric relaxation?

A

when the intraventricular pressures fall sufficiently at the end of phase 4, the aortic and pulmonic valves abruptly close (aortic recedes pulmonic) causing the second heart sounds
valve closure is associated with a call back flow of blood into the ventricles and a characteristic notch (dicrotic notch) in the aortic and pulmonary artery pressure tracings
after valve closure, the aortic and pulmonary artery pressures riseslightlu(dicrotic wave) following slow decline in pressure

238
Q

what is the rate of relaxation of the muscle fibres called?

A

lusitropy

239
Q

what is the relaxation of muscle fibres regulated by?

A

largely done by the sarcoplasmic reticulum that are responsible for rapidly re-sequestering calcium following contraction

240
Q

what happens to the volume and ventricular pressures during phase 5?

A

ventricular pressures decrease but volumes do not change because all the valves are closed. the volume of blood that remains in a ventricle is called the end-systolic volume and i.e. is around 50ml in the left ventricle.

241
Q

what is the difference between the end diastolic and systolic volume?

A

around 70ml and represents the stroke volume

242
Q

why does the let atrial pressure continue to rise?

A

due to the venous return from the lungs. the peak LAP at the end of this phase is termed the v-phase

243
Q

describe phase 6 - rapid filing

A

as the venrtrciels continue to relax at the end of phase 5, the intraventricular pressures will at some point fall below their respective atrial pressures. when this occurs, the AV valves rapidly open and passive ventricular filling begins.
despite the inflow blood from the atria, intraventricular pressure continues to briefly fall because the ventricles are still undergoing relaxation . once the ventricles are completely relaxed, their pressures will slowly rise as they fill wth blood from the atria

244
Q

what happens after the mitral valve is opened?

A

the opening of the mitral valve causes a rapid fall in the LAP. the peak of the LAP just before the valve opens is the v-wave. this is followed by the y-descent of the LAP. A similar ave and descent are found in the right strum and in the jugular vein

245
Q

what is the sound heard when the ventricles are filling?

A

this is normally silent. when a third heart sound is audible during rapid ventricular filling, it may represent tensing of chordae tendinae and AV ring during ventriclular relaxation and filling.

246
Q

describe phase 7

A

as the ventricles continue to fill up with blood andegpand, they become less compliant and the intraventricular pressures rise. this increase in intraventricular pressure reduces the pressure gradient across the AV valves so that the rate of filling falls late in diastole.

247
Q

what is the normal amount of the ventricles that is filled by the end of phase 7?

A

90% in normal resting hearts. so 90% of ventricular filling occurs before atrial contraction (phase 1) and therefore is passive

248
Q

what happens to aortic and pulmonary arterial pressure during phase 7?

A

they continue to fall during this period

249
Q

how many heart sounds are they?

A

3

250
Q

what is the first heart sound caused by?

A

it is produced by the closure of the mitral and tricuspid valves. it corresponds to the end of diastole and the beginning of ventricular systole.

251
Q

what is the second heart sound produced by?

A

the closure of the aortic and pulmonary valves at the end of systole

252
Q

what is the third heart sound produced by?

what is the best thing to use to hear it?

A

it is a low pitched, early diastolic sound audible during the rapid entry of blood from the atrium to the ventricle. these are best heard with the bell of a stethoscope

253
Q

what is asynchrony in relation to the right and left sides of the heart?

A

right atrial before left atrial
left ventricular before right
right ventricular ejection before left

254
Q

what is the normal heart rate in a newborn, infant, children (1-10yrsold) and children over 10 and adults and well trained athletes?

A

newborn (0-30days); 70-190bpm
infants (1-11months); 80-120bpm
children

Biomedical Science L2 (2 decks)

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