Download Dr. Miriam Frommer

PHYSIOLOGY LOGIC EXERCISES
to
PHLEX your mental muscles
Dr. Miriam Frommer
Department of Physiology
University of Sydney
1
INDEX OF CONTENTS
What is PHLEX?
Exercise categories
Extra notes on additional material
Concept maps with triggers
Practical classes covered (order performed may vary)
Model:
 Human cardiovascular system (BP)
In vitro:
 Electrophysiology of nerve
 Skeletal muscle mechanics
In vivo:
 Human nervous system -Senses

Human nervous system -Reflexes

Human respiratory system
 Human endocrine system
Simulation:
 Gastrointestinal physiology
 Renal physiology
Links to Answers (time delay before activation)
Exercise category 4
Extra notes on additional material (some answers)
Concept maps with triggers
2
Online resources (links to related topic areas)
A.
No Frills Generic Skills Guide
 General Introduction
 9 Questions
 Exercises on Data Handling: Statistics&Graphs
 Exercises Preparatory to Writing Essays
and Reports: Logical Thinking
 Exercises Testing Concepts: Force&Velocity,
Resistance&Flow
 Answers to Exercises
 Appendix B “Data Analysis”
 Appendix D “Concept Mapping”
 Appendix E “Confusing Terms”
B.
No Frills Statistics Skills Guide
 General Introduction
 5 Questions
C.
FLERT (Flexible Report Writing Template)
 Help with Report Writing
 Help with Report Content
D.
Post-tests
Answers with explanations
3
What is PHLEX?
PHLEX is a follow-up to the No Frills Generic Skills Guide (NFGS), focusing
on the need to support students in the logical thinking necessary to substantiate and
test the hypotheses they formulate before each practical class, as well as explain
discrepancies between their predicted and observed results. It should help the
development of the generic skill of clear communication, encompassing the
knowledge, practical and thinking skills which are often very poorly developed in a
number of science students.
The 8 practicals covered are: electrophysiology of nerve; skeletal muscle
mechanics; human nervous system (reflexes & senses), cardiovascular, respiratory,
and endocrine systems; gastrointestinal and renal physiology.
Since the NFGS Guide used the blood pressure practical as the example of
how to approach experimental design, PHLEX will begin with this practical to
illustrate how different types of exercises can be incorporated into students’ learning.
However students should follow the order in which their practicals are carried out.
There are 5 exercises for each practical; these should be done chronologically
so that understanding is progressively built up and the links between the theoretical
and the experimental aspects become consolidated. Some answers to these and other
exercises will be provided online when sufficient time has elapsed after the relevant
class for them to have been attempted.
Exercise categories
1) Confusing terms glossary (of paired similar terms)
2) Misconception MCQs (and best explanations) with answers
3) Logical fallacies (and how to avoid them)
4) Sequences which make sense (as a concept map)
5) The three most important facts (for introduction/discussion of a
report)
Exercises 1) to 3) vary somewhat but 4) and 5) have a fairly standardized format. The
topics covered in these are summarized in the table below.
Specific topics per practical
Practical
Blood pressure
Nerve
Muscle
Reflexes/Senses
Respiration
Endocrine
Gastrointestinal
Renal
4) Sequences
Standing up
Errors in description
Isotonic force production
Stretch reflex/ Pacinian corp.
Rebreathing expired air
Carbohydrate ingestion
Protein ingestion
Water ingestion
5) Facts/Relationships
BP & postural change
CAP & inter-electrode distance
Active force & muscle length
CAP & stimulus strength/2pt discrimin.
Alveolar gases & ventilation
Blood glucose & carbohydrate type
Gastric secretion & drugs
Urine osmolality & diuretics
4
Extra notes on additional material
Once the questions in the 5 exercise categories have been attempted, it will
have become apparent where there are gaps in a student’s knowledge and
understanding. The most common of these are addressed in the extra notes provided,
which focus especially on particularly difficult, more mathematical concepts and
inter-relationships. Some of this material is in the form of questions and answers, and
it is important to attempt to work out an answer first, before reading the one supplied.
Extra notes are preceded each time by the following statement:
When answering some of the questions on xxxx activity, the concepts
below may be relevant.
Specific topics per practical
Practical
Blood pressure
Nerve
Muscle
Reflexes/Senses
Respiration
Endocrine
Gastrointestinal
Renal
Additional material
Systolic/diastolic pressures, ejection, TPR, HR, resistance & flow
Myelin/size & resistance/capacitance, threshold, population code,
CAP, CV/saltatory conduction, excitability/refractory periods
Isometric/isotonic recording, muscle dimensions & force/velocity,
in vivo vs in vitro stimulation
EMG interpretation, pupillary reflex pathways & blocking drugs
Gaseous equilibria, gas stores, breathing higher O2 concentrations
Insulin-cation interactions, hormones & pregnancy maintenance
Luminal stimuli for gastric secretion, saliva & pancreas secretions
Salt & water transport, differential effects of diuretics
Concept maps with triggers
Concept maps provide a very powerful tool for summarizing relationships
between physiological variables, and are employed throughout this course. Each
practical has at least 2 concept map exercises associated with it, and each exercise
contains a trigger to provide useful clues which help focus on the influence of
particular variables. Note that though not all of these will have been under
experimental control, they may nonetheless be important in determining the final
status of the physiological variable. Suggested map solutions will be provided online;
some overlap with additional material content, as is apparent by comparison with the
previous table.
Specific topics per practical
Practical
Blood pressure
Nerve
Muscle
Reflexes/Senses
Respiration
Endocrine
Gastrointestinal
Renal
Concept map 1
Posture, baroreceptors & BP
Nerve characteristics & CAP
All influences on force
All influences on stretch reflex
Receptive field
Ventilation & alveolar gases
Thyroid hormone & heat
Protein & gastric secretion
Influences on renal pressures
Concept map 2
Bike riding & BP
Nerve characteristics & CV
All influences on velocity
All influences on pupil reflex
Temperature perception
Inhaled gases & ventilation
Insulin resistance & tolerance
Acid chyme & neutralization
Influences on renal salt & water
5
BLOOD PRESSURE PRACTICAL
1)
Confusing terms glossary
This exercise is an extension of Appendix E on Confusing Terms in the No
Frills Generic Skills Guide (link). Read the introduction there, then scroll down to
find the terms which are relevant to the blood pressure practical. Below are some
from that list, but you should be able to add more from your lectures and textbooks.
Have a look at Appendix D on Concept Mapping for ideas.
Chronotropic – inotropic
Constriction – contraction
Negative feedback – long loop negative feedback
Relaxation - dilation
Resistance of arterioles - resistance of bronchioles
Smooth muscle cells – cardiac muscle cells
Starling’s Law – Starling’s hypothesis
Vasodilator – bronchodilator
Here are some additional ones:
Diastole – diastolic
Systole – systolic
Choose 5 pairs and write down your own definitions of the two terms in
each. This is absolutely critical to your understanding of these words, as you
are required to draw out both the commonalities and the differences between
them, and express these in a manner which is clear to your reader. Obviously,
if you are confused and it’s not clear to you, that confusion will be conveyed
to them.
i)
ii)
iii)
iv)
v)
Now see how well you do in choosing the correct answer for the definitions in
the Confusing Terms exercise.
6
CONFUSING CARDIOVASCULAR TERMS
The technical language of physiology can be very confusing, as many terms are
specialized jargon not used in everyday speech, and derive from Latin and Greek
roots. One way to test your understanding of these is to consider pairs of terms
which, although superficially similar, are actually different. In this exercise you
must choose from the list of statements about each pair the one which you believe
is MOST correct.
1) Adrenaline – noradrenaline
a)
Adrenaline and noradrenaline are both sympathetic nervous system
neurotransmitters, but adrenaline acts mainly on beta receptors and noradrenaline
on alpha receptors
b)
Adrenaline is a hormone released by the adrenal medulla and
noradrenaline is a neurotransmitter released by sympathetic nerve endings
c)
Adrenaline and noradrenaline are both released at pre-ganglionic
sympathetic nerve endings in the adrenal medulla
[Answer b]
2) Chronotropic - inotropic
a)
Chronotropic effects of sympathetic nerves are those which relate to
the heart rate whereas inotropic effects are those which relate to contractility of
the cardiac muscle
b)
Both chronotropic and inotropic refer to actions of the sympathetic
nerves on cardiac muscle, chronotropic relating to the duration of the contraction
and inotropic to its intensity
c)
The difference between chronotropic and inotropic is that the former
describes stimulation of cardiac activity while the latter describes its inhibition
[Answer a]
3) Conductance – conduction
a)
Conductance refers to action potentials spreading within one cardiac
chamber whereas conduction refers to their spread between chambers
b)
Conductance and conduction have the same meaning and are used
interchangeably
c)
Conductance is a property of membrane ion channels or cytoplasm and
refers to the ease of passage of charged particles, while conduction is used to refer
to the spread of a potential along an excitable cell
[Answer c]
4) Constriction – contraction
a)
Constriction of smooth muscles is what follows as a consequence of
their contraction
b)
Constriction and contraction are both the opposite of relaxation
c)
Constriction refers to the narrowing of a contained space and can result
from the contraction of muscles surrounding that space
7
[Answer c]
5) Contractility – stroke volume
a)
Cardiac muscle contractility determines the peak isometric force
achieved for a given pre-load and after-load, and stroke volume is the volume
ejected by each ventricular contraction
b)
Contractility is an intrinsic property of cardiac muscle whereas stroke
volume varies from beat to beat
c)
Pre-load and after-load changes affect both contractility and stroke
volume, since these both depend on the length of the cardiac muscle fibres and
the pressure against which they eject
[Answer a]
6) Diastole – diastolic pressure
a)
Diastole is the phase of the cardiac cycle during which the ventricles
are passively filled by the venous return, while diastolic pressure is the lowest
pressure reached in the arteries
b)
Diastole is the phase of the cardiac cycle during which the heart
relaxes and filling occurs, while diastolic pressure is the lowest pressure reached
in the arteries
c)
Diastole is the phase of the cardiac cycle during which the heart
relaxes and filling occurs, while diastolic pressure is the lowest pressure reached
in the ventricles
[Answer b]
7) Diastolic pressure - end-diastolic pressure
a)
Diastolic pressure is the pressure in the ventricles at the beginning of
diastole and end-diastolic pressure is the pressure in the ventricles at the end of
diastole
b)
Diastolic pressure is the lowest pressure reached in the arteries, while
end-diastolic pressure is the lowest pressure reached in the ventricles
c)
Diastolic pressure is the lowest pressure reached in the arteries, while
end-diastolic pressure is the pressure in the ventricles at the end of diastole
[Answer c]
8) End-diastolic volume – stroke volume
a)
End-diastolic volume is the volume of the ventricles at the end of
diastole whereas stroke volume is the volume ejected by each ventricular
contraction and is equal to end-diastolic volume minus end-systolic volume
b)
End-diastolic volume is the volume of the ventricles at the end of
diastole whereas stroke volume is the volume ejected by each ventricular
contraction and is equal to end-systolic volume minus end-diastolic volume
c)
End-diastolic volume is the volume of blood in the aorta at the end of
diastole while stroke volume is the volume which is added to this by each
ventricular contraction
[Answer a]
8
9) Flow- flux
a)
Flow refers to the movement of blood, whereas flux refers to the
movement of substances dissolved in blood
b)
Flow refers to movement of a substance while flux refers to the net
transfer of a substance from one bodily compartment to another
c)
Flow describes movement due to passive forces, whereas flux can be
due to either passive or active forces
[Answer b]
10) Pulse rate – pulse pressure
a)
Pulse rate and pulse pressure are different names for the same
parameter, the number of times per minute the heart beats and exerts a pressure
which can be felt as a pulse in arteries near the body surface
b)
Pulse rate is the same as heart rate whereas pulse pressure is the same
as arterial pressure
c)
Pulse rate is the number of heartbeats per minute (same as heart rate)
while pulse pressure is the difference between the value of systolic and diastolic
pressure
[Answer c]
11) Systole- systolic pressure
a)
Systole is the phase of the cardiac cycle during which all the valves are
closed, while systolic pressure is the highest pressure reached in the ventricles
b)
Systole is the phase of the cardiac cycle during which the heart
contracts, while systolic pressure is the highest pressure reached in the ventricles
c)
Systole is the phase of the cardiac cycle during which the heart
contracts, while systolic pressure is the highest pressure reached in the arteries
[Answer c]
12) Starling’s Law – Starling’s hypothesis
a)
Starling’s Law says that the heart must beat more forcibly whenever
the stroke volume is increased, while Starling’s hypothesis says that fluid will be
lost from capillaries if the hydrostatic forces exceed the osmotic ones
b)
Starling’s Law refers to the increased contractility due to sympathetic
nerve stimulation, while Starling’s hypothesis refers to the increased blood
pressure resulting from this
c)
Starling’s Law refers to the relationship between end-diastolic volume
and stroke volume, whereas Starling’s hypothesis refers to the balance of
hydrostatic and osmotic forces causing fluid movement across the capillary wall
[Answer c]
9
2)
Misconception MCQs
This exercise is somewhat similar to the Post-test questions, but focused on
teasing out the most common misconceptions which trip students up even before they
begin an experiment, and prevent them from “seeing the wood for the trees”. Because
practical classes are run according to a set protocol laid down in the notes, it is all too
easy to gloss over the connections between the background theory and the aims of the
experiment. When students write practical reports, the introduction, which is
supposed to set out the reasoning behind what they will do in the laboratory, often
fails to cover this adequately, again suggesting a failure to come to grips with key
concepts and their inter-relatedness. Essential connections become hidden in vague
generalities which often are quite irrelevant to the actual procedures followed and
hence the outcomes obtained.
The first exercise is a simple one requiring you to choose the correct option
which best completes the statement in the stem.
Q1
Vasoconstriction of arterioles immediately results in:
a) a fall in diastolic pressure because there is a drop in venous return to
the heart
b) a rise in diastolic pressure because flow-off of blood from the arteries
is slowed down
c) a larger stroke volume because the systolic pressure rises in the aorta
d) a higher heart rate because the heart has to increase its cardiac output
Q2
When heart rate increases following postural change:
this must be due to baroreceptors sensing a fall in arterial pressure
stroke volume must have decreased to keep cardiac output constant
it indicates that sympathetic outflow has risen
arterial blood pressure will increase proportionally
a)
b)
c)
d)
[Answers: 1b 2c]
The second exercise requires you to first choose the best option then choose
the best explanation for why the other options should not be chosen. Concepts are
listed to help you focus on the relevant physiology.
Concepts:
heart rate, diastolic pressure, venous return, muscle pump, cardiac
output, end-diastolic volume, sympathetic, stroke volume, arteriolar muscle
contraction, total peripheral resistance, vasodilator metabolites, systolic
pressure, mean arterial pressure, venous pooling, baroreceptor reflex
10
The two experimental situations below are each followed by 5 statements explaining
relevant physiological relationships. First choose the correct statement which BEST
deals with the concepts involved. You will then be required to choose the reasons
giving the best explanation for rejecting the other explanatory statements.
Experimental situation 1) When a person exercises vigorously on a bike, their
heart rate increases while their diastolic pressure decreases.
A.
As there is an increased venous return due to muscle pump activity, the
increase in cardiac output means that heart rate must increase, but the decreased
filling time means that end-diastolic volume is less, hence the drop in diastolic
pressure.
B.
Bike riding is a stressful activity resulting in increased sympathetic outflow to
the cardiovascular system, hence heart rate and stroke volume both increase, resulting
in a drop in pressure during diastole.
C.
During bike riding there is increased sympathetic stimulation of heart rate and
arteriolar muscle contraction, but the total peripheral resistance decreases because of
the release of vasodilator metabolites, resulting in a decreased diastolic pressure.
D.
As the heart rate increases during bike riding, this causes a rise in systolic
pressure which must be offset by a drop in diastolic pressure, otherwise mean arterial
pressure will rise too high.
E.
The increase in heart rate during bike riding is accompanied by a decrease in
stroke volume in order to keep cardiac output constant, and this lowers diastolic
pressure.
Experimental situation 2) Although gravity influences pressures in the
cardiovascular system, changing from a lying to a standing position causes very
little change in mean arterial pressure (MAP) despite a rise in heart rate.
Remember: MAP = HR x SV x TPR, so a nearly constant MAP with an
increased HR implies that either SV or TPR or both must have decreased
A.
Since gravity makes it harder for blood to flow back to the heart on standing,
the body manages to maintain cardiac output by increasing both heart rate and total
peripheral resistance.
B.
Changing position from lying to standing results in greater skeletal muscle
activity, producing a change in total peripheral resistance which stabilizes MAP.
C.
The fact that heart rate rises but MAP does not means that total peripheral
resistance must have fallen, since cardiac output has risen.
D.
Venous pooling on standing is accompanied by pooling in the arteries and
arterioles in the legs as well, because the extra column of blood increases the
hydrostatic pressure in the feet compared to at the level of the heart.
E.
The explanation for an almost constant MAP with postural changes is that
venous return is not restored despite the increased sympathetic outflow caused by the
baroreceptor reflex, so that stroke volume remains below normal.
11
The correct statement which best deals with the concepts in the previous exercise is
indicated by an asterisk. For each of the other statements, 2 or 3 possible reasons are
provided for why certain elements are NOT correct. Choose the reason(s) which you
think provide the BEST explanations.
Experimental situation 1) When a person exercises vigorously on a bike, their
heart rate increases while their diastolic pressure decreases.
A.
As there is an increased venous return due to muscle pump activity, the
increase in cardiac output means that heart rate must increase, but the decreased
filling time means that end-diastolic volume is less, hence the drop in diastolic
pressure.
This is wrong because:
a)
the increased heart rate does not occur because of an increased cardiac output
due to increased venous return, as heart rate is regulated by the autonomic nervous
system
b)
both the increase in heart rate and the decrease in total peripheral resistance
which occur during bike riding contribute to the drop in diastolic pressure
c)
a drop in diastolic pressure is not causally related to a drop in end-diastolic
volume, and a rise in heart rate does not cause a decreased filling time until extremely
high rates are achieved
B.
Bike riding is a stressful activity resulting in increased sympathetic outflow to
the cardiovascular system, hence heart rate and stroke volume both increase, resulting
in a drop in pressure during diastole.
This is wrong because:
a)
increased heart rate and stroke volume will always increase arterial blood
pressure, both systolic and diastolic
b)
increased heart rate and stroke volume may increase arterial blood pressure,
both systolic and diastolic, but this depends on concurrent changes in total peripheral
resistance
c)
diastole refers to the heart, being the period during the cardiac cycle when the
muscle is relaxed, and cardiac pressures during this period are not normally related to
heart rate and stroke volume
*C.
During bike riding there is increased sympathetic stimulation of heart rate and
arteriolar muscle contraction, but the total peripheral resistance decreases because of
the release of vasodilator metabolites, resulting in a decreased diastolic pressure.
This is correct.
D.
As the heart rate increases during bike riding, this causes a rise in systolic
pressure which must be offset by a drop in diastolic pressure, otherwise mean arterial
pressure will rise too high.
This is wrong because:
a)
even if systolic pressure were to rise due to heart rate increases during
exercise, the way this would affect diastolic pressure would be to cause it to rise as
well
b)
the factor which prevents mean arterial pressure from rising too high is not a
rule saying it must not do so, but a mechanism involving metabolic autoregulation of
peripheral resistance
12
E.
The increase in heart rate during bike riding is accompanied by a decrease in
stroke volume in order to keep cardiac output constant, and this lowers diastolic
pressure.
This is wrong because:
a)
the product of heart and stroke volume, namely cardiac output, is not kept
constant by any feedback control mechanism operating during exercise
b)
even if stroke volume were to fall, diastolic pressure would not necessarily
also decrease
c)
during bike riding there is a trade-off between the increased cardiac activity
and the metabolically induced vasodilatation, so that systolic pressure rises slightly
while diastolic pressure falls, and mean pressure shows only a small increase
Correct explanations for Experimental situation 1
[A a and c, B b and c, D a and b, E a, b and c]
Experimental situation 2) Although gravity influences pressures in the
cardiovascular system, changing from a lying to a standing position causes very
little change in mean arterial pressure (MAP) despite a rise in heart rate.
A.
Since gravity makes it harder for blood to flow back to the heart on standing,
the body manages to maintain cardiac output by increasing both heart rate and total
peripheral resistance.
This is wrong because:
a)
gravity does not make it harder for blood to return to the heart as there is a
greater pressure gradient from the veins to the right atrium due to venous pooling
b)
increasing total peripheral resistance does not maintain cardiac output
c)
increasing heart rate may not maintain cardiac output
B.
Changing position from lying to standing results in greater skeletal muscle
activity, producing a change in total peripheral resistance whch stabilises MAP.
This is wrong because:
a)
although there may be an increase in skeletal muscle activity when upright, it
is the smooth muscle of the arterioles that is responsible for changes in total
peripheral resistance
b)
if arteriolar smooth muscle has constricted more when upright due to
increased sympathetic tone, this could not explain little change occurring in MAP
since it would result in a larger rise
C.
The fact that heart rate rises but MAP does not means that total peripheral
resistance must have fallen, since cardiac output has risen.
This is wrong because:
a)
the fact that heart rate rises but MAP does not, implies that cardiac filling has
been compromised by the shorter time for diastole
b)
cardiac output may not have risen, even if heart rate has, so a fall in total
peripheral resistance may not be the reason for the almost constant MAP
c)
since heart rate has risen, sympathetic tone has increased, so total peripheral
resistance has probably also risen, implying a fall in stroke volume
13
D.
Venous pooling on standing is accompanied by pooling in the arteries and
arterioles in the legs as well, because the extra column of blood increases the
hydrostatic pressure in the feet compared to at the level of the heart.
This is wrong because:
a)
pooling occurs in the veins because they are distensible, but not in the arteries
and arterioles because they have smooth muscle in their wall, making them more
rigid
b)
hydrostatic pressure increase occurs in both the venous and arterial sides of the
circulation but the pressure gradient between them remains constant, so flow into the
veins does not change
c)
venous pooling results in a smaller pressure gradient for returning blood from
the veins to the heart
*E.
The explanation for an almost constant MAP with postural changes is that
venous return is not restored despite the increased sympathetic outflow caused by the
baroreceptor reflex, so that stroke volume remains below normal.
This is correct.
Correct explanations for Experimental situation 2
[A b and c, B a and b, C b and c, D a,b and c]
3)
Logical fallacies (and how to avoid them)
Following are statements written by students which either contain errors of
fact or logic or are insufficient in terms of the physiological mechanisms involved.
Explain as concisely as possible what you think is wrong with each and how they
could best be corrected.
a)
To calculate mean arterial pressure from measurements made of systolic
and diastolic pressure, the correct formula is:
MAP = Diastolic Pressure + 1/3 Pulse Rate
Explanation: Pulse rate is number of heartbeats per minute and is not a pressure.
MAP is equal to diastolic pressure plus one-third of the difference between diastolic
and systolic pressure, or pulse pressure.
Extra useful information:
The reason that it is one-third and not one half of the pulse pressure( i.e. that MAP is
not halfway between diastolic and systolic pressure) is that the pressure versus time
curve is not sinusoidal but has a steep rise and a slower fall as a result of the heart
spending longer in diastole than in systole. So the mean pressure is nearer to
diastolic than it is to systolic.
b)
As the muscles need more oxygen during dynamic exercise, CO and HR
must increase.
Explanation: This statement is not sufficient to demonstrate an understanding of the
physiological mechanisms involved in the response of the heart to dynamic exercise.
There must be some processes which operate to increase heart rate, and since cardiac
14
output is the product of heart rate and stroke volume, it (CO) will also increase
provided that stroke volume is not decreased when heart rate increases . The principal
mechanism for achieving these changes is the sympathetic nervous system outflow to
the heart, which causes positive chronotropic and inotropic effects i.e. increases both
rate and contractility. This then increases stroke volume and cardiac output.
Extra useful information:
As a consequence of both the increased cardiac output and the locally produced
metabolites causing vasodilatation, there is an increased blood flow to the exercising
muscles (receive a greater proportion of the greater total flow).
c)
When HR rises, ventricular filling is compromised, so SV falls to keep CO
constant.
Explanation: The first part of this statement is fine – when heart rate rises (albeit to
very high values) ventricular filling can be compromised because there is such a short
time before the next ejection. As a result of the decreased end-diastolic volume
stroke volume falls (Starling’s Law). So what’s wrong?
The above sequence of inter-related mechanisms has just explained the fall in SV,
which does not happen IN ORDER to keep cardiac output constant. CO may or may
not remain constant, depending on the net trade-off between an increased HR and a
decreased SV, since CO = HR x SV.
One recurring error which students make when discussing variables representing
physiological parameters in an equation, is to ignore the number of these determining,
or contributing to, the value of a particular parameter, and to assume that change in
just one of them will produce a proportional change in the other parameter.
d)
When HR rises, MAP must also rise.
Explanation: Given that MAP = HR x SV x TPR, it is NOT correct to say that, just
because HR has increased, MAP will also increase, since SV and TPR may have also
changed, with each either increasing or decreasing, and this may not necessarily result
in an overall increase in the product of the 3 terms on the RHS of the equation.
The reverse is also NOT correct i.e. because MAP has increased, this does not imply
that HR must have increased, as one of the other 2 terms could be responsible for the
overall increase in their product.
Logical errors like this are one of the main reasons why students fail to
gain marks in exam questions. Answers are expected to be
mathematically correct and not just include a series of physiological
relationships which may or may not be relevant.
15
4)
Sequences which make sense
Rearrange the following 20 concepts relating to postural change into a
numbered chronological sequence which shows how one leads to the next (as
in a concept map).
1. Standing up
Decreased systolic pressure
Distension of veins
Decreased stroke volume
Decreased central venous volume
Decreased venous return
Decreased cardiac output
Decreased end diastolic volume
Decreased pulse pressure
Decreased atrial natriuretic peptide secretion
Decreased MAP
Pooling of blood
Increased heart rate
Increased hydrostatic pressure below the heart
Increased sympathetic activity
Increased adrenaline secretion
Increased renin and angiotensin secretion
Increased antidiuretic hormone secretion
Increased peripheral resistance
Increased contractility
1. Standing up
16
5)
The three most important facts
In this exercise you have to make a choice from all the relationships you have
covered in the previous exercises, which THREE are the most vital to
underpin a hypothesis about blood pressure variation with posture. Since it
is essential that the hypotheses evolve from what you have written in the
Introduction, these would constitute the three most important sentences as
they would be the ones from which your hypotheses could then be predicted.
i)
ii)
iii)
Repeat this exercise now for the Discussion, where the THREE relationships
are those which best explain how your data have supported your hypotheses.
i)
ii)
iii)
17
When answering some of the questions on cardiovascular activity, the concepts
below may be relevant.
a)
Systolic pressure is the highest pressure reached in the arteries. It is
increased by a more forceful ejection and a larger volume of ejected blood per unit
time, which in turn are the result of increases in stretch of cardiac muscle (i.e.
increases in end diastolic volume) and/or increases in contractility (due to
sympathetico-adrenal activity). It also depends on the distensibility of the arteries i.e.
their ability to accommodate an increase in volume.
Determinants of systolic BP
Systolic BP = highest pressure in artery
Force/velocity of L ventricular contraction
Volume of blood ejected/stroke volume
Distensibility of artery
Determinants of Ejection
Force and volume of ejection
Pre-load/stretch of cardiac muscle fibres
i.e. end-diastolic volume
Sympathetic stimulation/adrenaline
i.e. contractility
After-load/aortic pressure
i.e. systemic arterial pressure
18
Diastolic pressure is the lowest pressure reached in the arteries, just before the next
stroke volume begins to be ejected. A rise in heart rate and a rise in peripheral
resistance both increase diastolic pressure, because the former produces the next
ejection before the pressure has had time to drop as low, and the latter slows down the
flow-off into the periphery, so that the next ejection occurs while there is a higher
pressure.
Determinants of diastolic BP
Diastolic BP = lowest pressure in artery
Previous systolic pressure reached
Time between ejections ie. Heart rate
Ease of flow-off into arterioles i.e. TPR
b)
Total peripheral resistance is given by the formulae:
TPR = 8ηl/∏ r4 where η = blood viscosity and l = length of vessel, and
TPR = MAP/CO where MAP = mean arterial pressure & CO = cardiac output
Determinants of TPR
Decrease in
Diameter
Of
Arterioles
Increase in
TPR
Increase in
Blood
Viscosity
Increase in
Length of
Blood
Vessels
19
Determinants of HR
Stimulation of
Sympathetic
Nerves to
Pacemaker
(SA node)
Increase in
Heart
Rate
Inhibition of
Parasympathetic
(vagal) nerves to
Pacemaker
(SA node)
Increase in
Circulating
Adrenaline
Concentration
Extra note on gravity
Gravity increases all pressures below the heart and decreases those above –
this applies equally to arteries, arterioles, capillaries, veins and venules. Those below
the heart will tend to distend, those above will tend to collapse. This is because there
is the added pressure of the column of blood extending from the heart to the vessels
below, and the lesser pressure of the points above the heart equal to the column of
blood between them and the heart (think of a U-tube and comparison of hydrostatic
pressures if there are points higher up).
However the arteries and arterioles are thick-walled enough to withstand these
pressures without either distending or collapsing, whereas the veins and venules are
too thin-walled. They therefore become distended if pressure is sufficiently high
below the heart, which reduces the volume of blood returning to the heart because it
pools there. At levels beginning a few centimetres above the heart, similar vessels
have a distending pressure which becomes increasingly sub-atmospheric the further
up you go (the level of the heart is considered to be atmospheric), resulting in
collapse. However the vessels in the skull are attached to tissues which prevent their
collapse.
When a person stands up, all the vessels at any particular levels are subjected
to the same change in hydrostatic pressure, hence the DIFFERENCE in pressure
which drives the blood around the circulation, from the arterial to the venous side,
remains constant. It is only when some of that pressure gradient is lost, due to
pooling in distensible vessels, that the driving pressure decreases. One way of
thinking of this is in terms of electrical equivalents, where the extra venous capacity is
like a capacitor which stores charge (blood) and reduces current (flow). Hence venous
compliance is much greater than arterial compliance.
Resistance and flow
The following mathematical relationships are relevant to understanding the
theory of practicals on the cardiovascular, respiratory and renal systems. (For the
nervous system the electrical relationships apply directly.)
20
Blood is pumped out of the heart and distributed to the different organs of the
body along a series of parallel blood vessels. This process can usefully be modelled
by an electrically equivalent circuit, in which:
the pressure P generated by the heart contracting is represented by a
battery of emf = V
total blood flow is represented by the current I
total resistance to blood flow is represented by R, which is made up of
a number of individual organ resistances, R1, R2, etc.
Let us assume for simplicity that initially there are only 2 organs of identical
resistance in the circuit. You should draw a simple diagram to illustrate it.
1.
What are the mathematical relationships between V, I and R, and between R1
and R2 and R?
P/V = I x R 1/R = 1/R1 + 1/R2 = 2/R2
R = R2/2
i.e. total resistance is half either individual resistance
For a given V, I or current is divided equally between the resistances
2.
Describe what happens to both total blood flow and its distribution between
organs 1 and 2 when:
a)
resistance R2 doubles (due to narrowing of the vessels)
1/R = 1/R1 + 1/2R2 = 1/R2 + 1/2R2 = 3/2R2
R = 2R2/3
i.e. total resistance is now increased to two-thirds the original resistances
i.e. it has increased by one-sixth
For a given V, flow I will be decreased by one-sixth, and will be distributed
between the two resistances in a ratio of 2:1
i.e. the original resistance will get 2/3 of 5/6 (5/9) of the original flow, and the
doubled resistance will get 1/3 of 5/6 (5/18) of the original flow
b)
resistance R3 equal to R1 is added in parallel to R2 (due to opening up
of vessels).
1/R = 1/R1 + 1/R2 + 1/R3 = 3/R2
R = R2/3
i.e. total resistance is now one-third either individual resistance, while
flow I has trebled for a given V and is again divided equally between the
resistances, with each receiving one-third of the total flow.
3.
What changes in the circuit could make blood flow to a particular organ
cease?
Blood flow will cease when the resistance of that organ becomes infinitely
large by comparison with the resistance of other organs in parallel i.e. when
there are alternate pathways of lower resistance. This is equivalent to making
R2 in a) very large, so that 1/R2 becomes very small, and R approaches R1.
Notice though that any parallel resistance lowers the total R, and the smaller
it is, the more the total resistance decreases. This is what happens when the
blood vessels in an organ vasodilate.
21
Concept Maps for Blood
Pressure Prac
Map the cardiovascular variables which
influence the MAP when posture is
changed.
Trigger: Did standing up suddenly from a
crouching position produce a different
cardiovascular response from when
measurements were made after 2 minutes in
the standing position? How do these
outcomes demonstrate the differences
between passive and active responses?
Map the cardiovascular variables which
influence the MAP when riding a bike.
Trigger: Given that that most important
functional outcome of a bike riding exercise
is increased blood flow to the active
muscles, how does the body regulate the
“cardio” and the “vascular” functions so as
to achieve this?
22
NERVE PRACTICAL
1)
Confusing terms glossary
This exercise is an extension of Appendix E on Confusing Terms in the No
Frills Generic Skills Guide. Read the introduction there, then scroll down to find the
terms which are relevant to the electrophysiology of nerve practical. Below are some
from that list, but you should be able to add more from your lectures and textbooks.
Refractoriness – refraction
Here are some additional ones:
Action potential – threshold potential
Capacitance - conductance
Conductance – conduction
Electronic conduction – saltatory conduction
Electrical potential – electrochemical equilibrium
Nernst potential – resting potential
Pacemaker potential – threshold potential
Write down your own definitions of 5 of these pairs of terms, then have a
look at the Confusing Terms list.
CONFUSING NERVE TERMS
1) Action potential – compound action potential
An action potential is recorded from a single excitable cell with one
electrode being intracellular, whereas a compound action potential is
recorded from a number of cells with both electrodes being extracellular.
2) Capacitance – conductance
Capacitance refers to the ability of the membrane to build up and hold
charge, while conductance is a measure of the ability of a current to pass
across the resistant membrane.
23
3) Conductance – conduction
The difference between these terms is that conductance is used to refer to
ions moving through membrane channels, whereas conduction is used to
refer to currents moving along excitable cells.
4) Electrotonic conduction – saltatory conduction
Electrotonic conduction occurs when the membrane potential changes
(depolarisations or hyperpolarisations) spread passively, depending only
on the membrane capacitance and the membrane and axoplasmic
conductances. Saltatory conduction occurs when the action potential
jumps from one node of Ranvier to the next due to the passive electrotonic
spread of the depolarisation from node to node.
5) Electrical potential – electrochemical equilibrium
Electrical potentials are the consequence of charge separation, so that
when there is no change in the charge stored on the membrane capacitance
the potential remains constant, whereas when ions flow as current through
membrane channels and alter the charge separation a change in potential
occurs, referred to as a depolarisation or a hyperpolarisation.
Electrochemical equilibrium for a particular ion occurs when the
membrane potential is equal to its Nernst potential, since this is when the
electrical force acting on the ion is exactly balanced by the chemical force
due to its concentration gradient.
6) Nernst potential - resting potential
Nernst potential for a particular ion is that potential where the electrical
and chemical forces acting on that ion are equal and opposite. Resting
potential refers to the steady potential across the membrane of an excitable
cell which is not being depolarized or hyperpolarized, and is the weighted
average of the Nernst potentials of all the ions which are able to cross the
membrane; although each one of them is not in equilibrium because the
resting potential is not at its Nernst potential, overall there is zero net
current flowing, a necessary condition for a steady potential.
7) Pacemaker potential – threshold potential
A pacemaker potential derives its name from the fact that the cell in which
it is occurring sets the pace for other linked cells; its characteristic feature
is a non-steady resting potential, so that gradual depolarisation to threshold
occurs periodically due to alterations in ion conductances. The threshold
potential is the potential at which the net flow of positive charge across the
membrane is inward, producing the escalating increase in Na conductance
which characterizes the Hodgkin cycle.
24
2)
Misconception MCQs
This exercise is designed to give you practice in logical thinking.
For each pair of statements, choose which one of the linking final statements
correctly completes the logical sequence.
1.
A. Increasing diameter of nerve fibres increases conduction velocity.
B. Measured velocity was that of the fastest fibres.
Therefore:
C. The largest fibres had the fastest velocities.
D. Measured velocity was that of the largest diameter fibres.
E The fastest fibres had the greatest velocity.
2.
A. Increasing diameter of nerve fibres reduces the length of their refractory
period.
B. Nerve excitability was reduced to 50% when a test stimulus was given 4
msec after the conditioning one.
Therefore:
C. The nerve fibres contributing to the test response were those of smaller
diameter.
D. Shorter refractory periods are associated with reduced excitability.
E. Larger diameter fibres are more likely to respond to a test stimulus 4 msec
after a conditioning one.
[Answers: 1D 2E]
3)
Logical fallacies (and how to avoid them)
Following are statements written by students which do not pursue their arguments to a
correct conclusion. Explain as concisely as possible what you think is wrong with
each and how they could best be corrected.
a)
The population code means that different nerve fibres, with different
physical properties such as diameter and myelination, contribute different
amounts to a compound action potential.
b)
Conduction velocity depends on the distance between the stimulating and
recording electrodes, so it is greater in longer nerve fibres.
c)
Measuring the latencies to the beginning of the compound action
potentials for different inter-electrode distances gives values from which the
conduction velocity at each distance can be calculated.
Explanations of errors:
a)
This statement mixes up two ideas, both of which are correct on their own, but
cannot be linked giving one as the explanation for the other.
While it IS true that:
(i)
different fibres have different physical properties
25
(ii)
(iii)
these result in their contributing different amounts to a compound action
potential (since larger fibres have larger extracellular current flows),
it is NOT true that:
the population code means they contribute DIFFERENT amounts, only that
they contribute to a combined response.
b)
This statement confuses conduction TIME, which does depend on the interelectrode distance, with conduction VELOCITY, which is obtained by dividing
distance by time. It is predicated on the assumption that longer fibres “need” faster
velocities of conduction of the information in the form of action potentials,
presumably so that the “far reaches” of the organism can respond quickly enough.
However, for the actual distances involved, given that conduction velocities are of the
order of 50-100 metres/sec, or 5-10 cm/msec, the time it would take to reach the ends
of the limbs is of the order of a few msec, even in humans. What the conduction
velocity does depend on is diameter and myelination, which will be very close to
constant along the length of a nerve fibre, so that the velocity will also be constant.
c)
This statement suffers from an assumption that conduction velocity
varies along the length of a fibre, so that dividing inter-electrode distances by the
corresponding latencies will give a series of different numbers, when in fact they will
give the same number. This is the reason why the two variables are plotted against
each other; this yields a straight line and calculation of its SLOPE then gives the
velocity.
4)
Sequences which make sense
Although it is sometimes not very hard to arrange a sequence of steps in logical order,
what is difficult is avoiding errors in the correct use of scientific language. The
following sentences contain various errors in describing experiments on stimulating
and recording from nerves. What are they?
1. Stimuli were applied to the nerve with an inter-stimulus delay of 5 msec.
2. The inter-stimulus was 5 msec.
3. The criteria used was a response bigger than 1 mV.
4. The phenomena investigated was the response to increasing stimulation.
5. The data shows that there was a big increase in response.
6. Less fibres were active during the relative refractory period.
7. The conduction velocity is the time taken to travel from A to B.
8. The latency is the time it takes for the stimulus artifact to illicit a response.
9. The conduction velocity is proportional to the latency.
10. The distance traveled by the stimulus was determined by the length of the
nerve.
Explanations of errors:
1. It is better to use the term inter-stimulus “interval” rather than “delay”, as
this clearly describes the time between the applications of successive stimuli
to the nerve, whereas “delay” refers to the time which elapses after a single
stimulus until the next one is applied; it also is used to refer to the elapsed time
26
between a stimulus artifact and the beginning of the compound action
potential.
2. The word “interval” is missing after “inter-stimulus”.
3. “Criteria” is plural and refers to more than one criterion, so needs a plural verb
“were”; however as only one criterion is mentioned the sentence should read
“The criterion used was a response bigger than 1 mV”.
4. A similar error is often made with the word “phenomena” which is the plural
of “phenomenon”, so it is necessary to write “The phenomenon investigated
was…” or “The phenomena investigated were……”.
5. “Data” is also plural, this time of the word “datum” (sorry, but that’s the
difference between Latin and Greek!), so “data show….”.
6. “Less” is used for amounts, “fewer” for numbers.
7. A velocity cannot be a time, since it has units of distance divided by time.
8. “Latency” is another word for “delay”, as mentioned in 1. The stimulus
artifact doesn’t even “elicit” a response which would be quite “illicit” for it to
do, given that it is itself a response! The stimulus elicits the response.
9. The conduction velocity is able to be read off as the slope of the line
expressing the relationship between distance and latency, which are
proportional to each other if the line goes through the origin.
10. The stimulus didn’t travel anywhere, the action potential did, and what the
length of the nerve determined was how long it took for the potential to reach
recording electrodes at the other end.
5)
The three most important facts
In this exercise you have to make a choice from all the relationships you have
covered in the previous exercises, which THREE are the most vital to
underpin a hypothesis about compound action potential variation with
inter-electrode distance. Since it is essential that the hypotheses evolve from
what you have written in the Introduction, these would constitute the three
most important sentences as they would be the ones from which your
hypotheses could then be predicted.
i)
ii)
iii)
Repeat this exercise now for the Discussion, where the THREE relationships
are those which best explain how your data have supported your hypotheses.
i)
ii)
iii)
27
When answering some of the questions on nerve activity, the concepts below may
be relevant.
1.
Structural variation in nerve fibre populations
Nerves are composed of nerve fibres or axons, which not only subserve
different functions such as motor or sensory (touch, pressure, temperature) but also
have different structures. The most important structural parameters with respect to
their functioning are the diameter and the presence or absence of myelin. These
variables determine a number of their electrical characteristics, which in turn
determine how the fibre responds to a stimulus by generating local and propagated
potentials. Three important properties relating to this are discussed below – threshold
for excitation, conduction velocity of action potentials, and refractory periods. This
section also addresses the issue of how the responses of nerves are built up from the
responses of their individual contributing fibres.
2.
Correlation of structure with electrical properties
A simple electrical model of a nerve fibre consists of resistances for
membrane and cytoplasmic current flow and a capacitance for membrane storage of
charge. When the resting potential is temporarily changed in the direction of
becoming less negative i.e. depolarization, the voltage difference between the
depolarized and resting sections of the fibre drives a current round the resulting
circuit, the magnitude of which depends on the total resistance in the membrane plus
cytoplasm. The fraction of this voltage which drops across each resistor is
proportional to its contribution to the total resistance (see Extra notes on Resistances).
Both the diameter and the myelination of a fibre impact on these electrical properties.
a)
Diameter
An increased diameter results in a decreased longitudinal resistance
(inversely proportional to cross-sectional area) and also membrane resistance
(inversely proportional to surface area). However the longitudinal decrease is greater
than the trans-membrane, so more of the voltage drop occurs across the membrane
and less along the fibre length. There is also an increase in the membrane
capacitance, since this is proportional to area.
b)
Myelin
Myelination produces an increase in membrane resistance and a decrease in
capacitance.
c)
Time and space constants
These changes then impact on two important constants – the time constant and
the space constant. Each of these is a measure of the ease of achieving a particular
outcome - either the time needed to change the membrane voltage by a certain
fraction or the distance for which the membrane voltage is maintained above a certain
fraction. Both increased diameter and myelination result in a smaller time constant
and a bigger space constant.
The net result of this is that large fibres reach threshold quicker and the
electrotonic potentials travel further than in small fibres. These have obvious
28
implications for the speed of propagation of the action potential along these fibres
(see 6. Conduction velocity).
The implications for spread along myelinated fibres are more complicated
because the myelin is interrupted periodically by non-myelinated areas known as
nodes of Ranvier. Hence the comparison of properties includes different sections of
the same fibre, as well as different fibres. The increased membrane resistance and
decreased capacitance due to myelin means that reaching threshold will be more
difficult than in an unmyelinated region; the converse of this is that little current will
leak out where myelin is present. In addition, at the nodes there is an approximately
50-80-fold increase in the number of voltage-gated Na channels compared to internodal regions, while totally unmyelinated axons have a maximum of a tenth of the
number of these Na channels that are present at the nodes.
The increased space constant due to myelin increasing membrane resistance
means that current is effectively forced to exit the cytoplasm at the nodes only.
Because of the distances between these depolarized regions, this makes for much
faster spread, a phenomenon called saltatory conduction (see 6.). The shorter time
constant is less relevant here because the threshold in the inter-nodal regions is
significantly raised due to the paucity of voltage-gated Na channels and the
simultaneous increase in membrane capacitance necessitating a much larger current
flow to produce a given depolarisation.
Myelin & size
29
Myelin/size & activity
• Time constant less
√Rm x √Rc x Cm
• Faster to threshold
• (Faster spread)
• Size – √less x √much
less x more = less
• Myelin – √more x
same x less = less
3.
• Space constant more
√ (Rm /Rc)
• Faster spread
• Size – Membrane &
Cytoplasmic R less,
but Rm drops less
than Rc (surf.vs.XS)
• Myelin -Membrane R
Rm more
Threshold for excitation
The main determinant of the threshold for excitation is the ease with which a
given stimulus is able to produce the necessary depolarization of the membrane
potential from its resting value to the value at which flow of positive charge inward
initiates the Hodgkin cycle of increased Na conductance leading to further
depolarization in an irreversible manner. The threshold is thus dependent on the
degree to which a membrane is depolarized, which in turn will vary with the
fractional voltage change which occurs here compared to along the length of the fibre.
Since larger diameter fibres have lower internal resistances, more current will flow
and more of the voltage drop will happen across the membrane, yielding a lower
threshold of stimulus voltage necessary to reach a particular membrane voltage
and trigger the Hodgkin cycle.
4.
Population code
When explaining the shape of the stimulus-response curve, it is necessary to
refer to the different thresholds of fibres of different sizes making up the sciatic nerve.
Sub-threshold stimuli, giving no AP, are too weak to bring any fibres to their
threshold. At the threshold stimulus, when there is a tiny response, the most sensitive
fibres of lowest threshold have been activated. As the stimulus strength increases
more and more fibres, of progressively increasing threshold, are recruited, until all the
fibres are contributing to the CAP with a maximal stimulus, and the curve reaches a
plateau for supra-maximal stimuli.
This section also refers to the distinction between the frequency code and the
population code. It is the population code which is exemplified in the stimulusresponse curve, and even if the fibres were increasing their frequency of firing with
increasing stimulus strengths (i.e. the frequency code was also operating), the method
of recording did not display this.
30
5.
Shape of CAP
The amplitude of the CAP is not physiologically significant, as it is not an
absolute measure of any particular event of physiological significance as say the
blood pressure is, and varies with the recording conditions. However it gives an
indication of the amount of activity in a particular group of nerve fibres, so that
relative changes reflect variations in the number of contributing fibres.
As the CAP is an envelope of potential change over time, it reflects the
addition of all the APs generated at the stimulating electrodes and travelling down
fibres of different sizes and myelination, and hence having different velocities of
conduction. This means that the AP in the fastest fibres reaches the recording
electrodes first and hence contributes to the beginning of the CAP, the average
velocity fibres contribute to the peak, and the slowest contribute to the tail. Since the
duration of the CAP is longer than that of a single AP, several single ones travelling at
different velocities could sum to give a wider, but not a higher, CAP. It is therefore
necessary to divide the area under the curve of the CAP by that under a single AP to
obtain an estimate of the number of fibres contributing.
The summation of subthreshold responses to successive stimuli which are
sufficiently close together in time illustrates that only the complete membrane
potential reversals which occur during an AP are picked up by the external recording
electrodes, but that depolarisations are still occurring, which outlast the duration of an
AP, as charge is stored on the membrane, which acts as a capacitor.
Since local anaesthetics first affect the smallest pain fibres - which is their
whole raison d’etre – they alter the shape of the CAP. Such drugs block action
potential transmission by blocking voltage-gated sodium channels. Since surface area
of the membrane is proportional to size, smaller fibres will have fewer channels
needing blocking and hence respond to lower doses. Can you think of any other
reasons for the differential responsiveness e.g. drug accessibility?
AMPLITUDE
of CAP from
NERVE
No. of nerve fibres
depolarised to
threshold for AP
Threshold for
depolarisation and
EC current & voltage
Strength of stimulus
Myelination and size
distribution of
nerve fibres
Spread of CAP
i.e.duration
Spread of
conduction velocities
31
6.
Conduction velocity
The speed with which nerve axons transmit action potentials is another
property which is affected by both their diameter and their myelination. There are 2
quite separate events contributing to the total time which elapses between the
beginning of stimulation and the recording of a response: the time needed to
depolarize the membrane to threshold, and the time it takes for the action potential to
spread along the axon. Both of these are faster in larger fibres, and myelin
additionally allows for a specialized form of conduction called “saltatory”, where the
action potential “jumps” between nodes of Ranvier, giving a faster transmission.
Saltatory Conduction
•
Nodes of Ranvier are only part of axon which is not myelinated
•
Cm here is much greater than in myelinated inter-nodal parts
•
Rm here is much less than in myelinated inter-nodal parts
•
Na channels here are much more frequent
•
Thus threshold reached only at nodes
One reason why the velocity is slower in toad than human nerves is their lower
body temperature.
CONDUCTION
VELOCITY
in axons
of NERVE
AP jumps from
node to node (gNa)
Saltatory conduction
↑Space constant
and spread
↓Time constant
to threshold
Speed of chemical
reactions
Myelination
(↑Rm ↓Cm)
Size
(↓Rm ↓↓Rc ↑Cm)
Temperature
32
7.
Reduced excitability (refractory periods) of single fibres
For a very short period of time after firing an action potential nerve fibres are
unable to fire again, being “refractory” to repeated stimulation. For the period when
they cannot respond at all, no matter how large the stimulus size, the term “absolute”
refractory period is used, and this is followed by a period when a response can be
obtained, but only with a larger stimulus than before, hence the term “relative”
refractory period.
The mechanisms which underpin this variation in excitability have been
covered in your lectures. Basically they are the conductance properties of the voltagegated channels for Na and K, which undergo a cycle of availability followed by nonavailability each time an action potential occurs. The diagram and discussion below
explain this.
A nerve fibre cannot fire a second AP until it is just outside its absolute
refractory period, so the maximum frequency of its firing is a little less than the
reciprocal of this period e.g. if the ARR is measured as 1 ms, the fibre cannot fire
every ms or 1000 times per second, but slightly less frequently. Published
frequencies should be obtained by referring to graphs of nerve firing rates in your
textbooks, and will vary depending on the type of nerve.
As mentioned above, it is changes in sodium and potassium channel
conductances which underlie absolute and relative refractoriness. The diagram
below is taken from Dr. W. Phillips’ Supplementary Notes on Single Cells.
Membrane potential
sodium conductance
potassium conductance
0
1
2
Time (msec)
3
Fig. 3 Conductance changes contributing to the action potential
The sequence of events is as follows:
(i)
Depolarisation of the membrane potential to threshold (see 3.) results in the
opening of voltage-gated Na channels and the Na conductance rises.
(ii)
Net inward flow of positive ions pushes the membrane towards the Na
equilibrium potential.
(iii) As the depolarisation approaches the peak of the action potential these Na
channels close and are inactivated.
(iv)
There is a delayed opening of the voltage-gated K channels at this time and
thus a rise in the K conductance.
33
(v)
The Na channels became capable of re-opening as the membrane becomes less
depolarized due to outward flow of K, with this process being complete
approximately when the membrane potential has fallen to the threshold value.
This marks the end of the absolute refractory period, and it is now possible to
depolarize to threshold for another action potential.
(vi)
However, the increased K conductance eventually results in membrane
hyperpolarisation, so that a greater stimulus voltage is required to bring the
membrane to threshold as the net outward flow of positive ions pushes the
membrane towards the K equilibrium potential.
(vii) It is therefore now in its relative refractory period.
(viii) The voltage-gated K channels close and the membrane potential returns to its
resting level, as determined by the relative conductances of the K and Na
leakage channels. It has now fully recovered its excitability and is no longer
refractory to stimuli of the original voltage strength.
During the period of reduced responsiveness of the whole nerve, a second
AP is obtained from that fraction of the population which is not refractory. The
length of both the absolute and the relative refractory periods varies between different
nerve fibres, being shortest for the largest (presumably because the swing in favour
of available voltage-gated Na channels over available voltage-gated K channels
occurs sooner in the latter). For an individual fibre to fire an AP, it MUST be out of
its absolute refractory period, but can be in its relative if the stimulus strength is
increased. Accordingly, at any time when whole nerve excitability is reduced, but not
zero, the contributing fibres will be partly in their relative refractory periods, partly
completely beyond even this, i.e. completely recovered.
34
Concept Maps for Nerve prac
Map the nerve characteristics which
influence the shape of a CAP and how
they influence it.
Trigger: Did the CAP change shape when the
responses were obtained at different stimulus
strengths?
How do structural variations between groups
influence their functional behaviour?
Map the nerve characteristics which
influence the conduction velocities
derived from a CAP and how they
influence it.
Trigger: Did the CAP change shape when the
responses were obtained with different
conduction distances?
How do structural variations between groups
influence their functional behaviour?
35
MUSCLE PRACTICAL
1)
Confusing terms glossary
This exercise is an extension of Appendix E on Confusing Terms in the No
Frills Generic Skills Guide. Read the introduction there, then scroll down to find the
terms which are relevant to the skeletal muscle practical. Below are some from that
list, but you should be able to add more from your lectures and textbooks.
Constriction – contraction
Relaxation - dilation
Smooth muscle cells – cardiac muscle cells
Here are some additional ones:
Active force – passive force
Cross-bridge – filament overlap
Isometric contraction – isotonic contraction
Optimal length – sarcomere length
Twitch – tetanus
Write down your own definitions of these 5 pairs of terms.
Check your answers by referring to the programmed text for the muscle
practical. Topics covered there include:
 the sarcomere
 thick filament and thin filament
 cross-bridges
 optimal sarcomere length
 excitation-contraction coupling
 power stroke
 twitch
 tetanus
 isometric contraction
 resting length
 active tension
 passive tension
 elastic components
 optimal length
 isotonic contraction
 force-velocity curve
 fast and slow fibres
36
2)
Misconception MCQs
Choose the correct option which best completes the statement in the stem.
Q1
a)
b)
c)
d)
Q2
a)
b)
c)
d)
Passive force recorded from a stretched muscle:
is inversely proportional to the degree of stretch
is generated in the series-elastic components only
is generated in the parallel-elastic components only
is generated in both the series- and the parallel-elastic
components
Active force can be recorded during a muscle contraction:
only when the actin and myosin filaments slide past each other
when the muscle is constrained so that its length cannot change
if there is no filament overlap
when sarcomere length is less than 2 μm
[Answers: 1d 2b]
3)
Logical fallacies (and how to avoid them)
Explain what is wrong with each of the following statements.
a)
When the muscle was stimulated electrically, maximum optimal force was
produced at the optimal length of the muscle.
Explanation: This illustrates a typical confusion between “optimal” and “maximal”.
Maximal or maximum force means the greatest value for this measurement; optimal
means the best outcome, which in this case refers to the maximum force achieved.
Hence “optimal length” is the length at which maximum force occurs, although the
force may not be optimal for a particular purpose e.g. minimum energy consumption.
b)
Stretching the muscle increased the overlap between actin and myosin
and hence decreased the sarcomere length.
Explanation: Since the actin and myosin filaments slide past each other, stretching
the muscle will DECREASE their overlap and INCREASE sarcomere length.
c)
Measurements of sarcomere length at two muscle lengths showed that
there was a linear relationship between sarcomere and muscle length.
Explanation: A relationship will always be linear when only two pairs of (x,y) values
are plotted, since one can always join two points by a straight line. However it may
not be proportional and go through the origin, if there is a constant which displaces
the line on either the x- or the y-axis. An example of this would be if the
measurement of muscle length included tendons at the ends which are not included in
the laser diffraction measurement of sarcomere length.
37
d)
A fatter muscle produces a greater maximum force because each
sarcomere is able to form a larger number of cross-bridge attachments.
Explanation: As the myofilaments have constant lengths in a given muscle as well as
across different muscles, the number of possible cross-bridge connections in a
sarcomere will be determined only by the degree of filament overlap i.e. muscle, and
hence sarcomere, length (providing Ca supply is maintained). The only way for more
cross-bridges to attach and produce a greater force maximum force (providing the
muscle is at its optimal length) is if there are more sarcomeres lying in parallel. This
is what occurs in a fatter muscle with a greater cross-sectional area.
4)
Sequences which make sense
Rearrange the following 10 concepts relating to isotonic force production in
skeletal muscle into a numbered chronological sequence which shows how
one leads to the next (as in a concept map). Indicate by arrows (↑↓) the
direction of each change.
Loaded muscle
Shortening of muscle
DHP receptor conformational change
Development of isometric force to match load
Generation of muscle action potential
Electrical stimulation
Sliding of filaments
Ryanodine receptor Ca release
Actin-myosin cross-bridge detachment
Actin-myosin cross-bridge attachment
1. Loaded muscle
38
5)
The three most important facts
In this exercise you have to make a choice from all the relationships you have
covered in the previous exercises, which THREE are the most vital to
underpin a hypothesis about active isometric force variation with muscle
length. Since it is essential that the hypotheses evolve from what you have
written in the Introduction, these would constitute the three most important
sentences as they would be the ones from which your hypotheses could then
be predicted.
i)
ii)
iii)
Repeat this exercise now for the Discussion, where the THREE relationships
are those which best explain how your data have supported your hypotheses.
i)
ii)
iii)
39
When answering some of the questions on muscle activity, the concepts below
may be relevant.
Factors influencing muscle force
What did you learn from both the isotonic and the isometric experiments about
the factors which influence the force produced by a muscle when it contracts? Are
there other structural properties or characteristics of the muscle which also have an
influence? (Hint: how do muscles in different parts of the body or in different people
compare?)
The isometric experiment showed that maximum isometric force is achieved when a
muscle is at its optimal length (greatest number of possible myosin-actin crossbridges formed) and is stimulated at a frequency which produces a fused tetanic
contraction (greatest Ca availability). The isotonic experiment showed that the force
produced also depends on the load, so that the maximum isometric force is achieved
only when the muscle is contracting against a load which equals or exceeds that
capacity. With smaller loads it begins to shorten before it has generated its maximum
isometric force, as cross-bridges detach more easily and fewer maintain the tension.
Muscles also differ in size or cross-sectional area with larger muscles having a
greater number of sarcomeres in parallel. Whether the total population is activated
depends on how many motor units are recruited for a particular movement and in real
life this is achieved unconsciously as we match the effort to the load. When
attempting to move big loads we also position our joints in such a way that the
muscles are at or near their optimal length.
Factors influencing muscle velocity
What did you learn from the isotonic experiment about the factors which
influence the velocity produced by a muscle when it moves? Are there other
structural properties or characteristics of the muscle which also have an influence?
(Hint: how do muscles in different parts of the body or in different people compare?)
The isotonic experiment showed that the velocity produced depended on the load, with
maximum velocity being achieved when the external load was zero. Muscles also
differ in length with longer muscles having a greater number of sarcomeres in series.
In the experiment and in real life a muscle must first overcome any internal loads or
resistance to movement before it is able to shorten and move an external load, and
this is achieved by operating at the optimal length so as to produce the necessary
force. Again we use our muscles to our best advantage in an unconscious way. As
well, different muscles are adapted to different tasks as their myosin ATP-ase activity
is matched to their role in the body. Postural muscles are slow muscles which need to
maintain body position against gravity, whereas fast twitch muscles have appropriate
ATP-ase to enable rapid cross-bridge cycling and hence rapid movement.
In vitro versus in vivo muscle stimulation
How are muscles normally stimulated to contract in a person? Which of the
above factors can be voluntarily controlled?
Normally a motoneurone in the ventral horn of the spinal cord stimulates a motor
unit. This is under voluntary or conscious control via descending pathways from the
CNS, as well as being influenced by inputs from other reflexes, which all converge on
the cell body. As noted above, joint position determines initial length, while conscious
effort impacts on motor unit recruitment.
40
Concept Maps for Skeletal
Muscle Prac
Map the muscle characteristics that
influence force production and how
they influence it.
Trigger: In what ways were the
experimental conditions manipulated so
that the muscle would produce its
maximum possible active force? Are
there any structural variations between
muscles which could increase this?
Map the muscle characteristics that
influence velocity of a muscle
contraction and how they influence it.
Trigger: In what ways were the
experimental conditions manipulated so
that the muscle would produce its fastest
possible velocity? Are there any structural
variations between muscles which could
increase this?
41
REFLEXES PRACTICAL (including tonic vibration reflexes and
pupillary reflexes from SENSES PRACTICAL)
1)
Confusing terms glossary
This exercise is an extension of Appendix E on Confusing Terms in the No
Frills Generic Skills Guide. Read the introduction there, then scroll down to find the
terms which are relevant to the reflexes practical. Below are some from that list, but
you should be able to add more from your lectures and textbooks.
Constriction - contraction
Refractoriness – refraction
Relaxation – dilation
Here are some additional ones:
Extrafusal fibres – intrafusal fibres
Final common pathway – motor unit
Muscle end-plate – muscle spindle
Write down your own definitions of these 3 pairs of terms.
2)
Misconception MCQs
Choose the correct option which best completes the statement in the stem.
Q1
a)
b)
c)
d)
Q2
a)
b)
c)
d)
A decrease in reflex muscle contraction can occur by all of the
following mechanisms EXCEPT:
inhibition of the muscle end-plate by inhibitory motoneurones
hyperpolarisation of its alpha-motoneurone cell body
evoking a stretch reflex in its antagonist
increased activity of inhibitory interneurones in the spinal cord
The efferent neural pathway for constriction of the pupil is:
pre-ganglionic fibres to superior cervical ganglion, postganglionic fibres to radial iris muscle
pre-ganglionic fibres to ciliary ganglion, post-ganglionic fibres
to radial iris muscle
pre-ganglionic fibres to superior cervical ganglion, postganglionic fibres to circular iris muscle
pre-ganglionic fibres to ciliary ganglion, post-ganglionic fibres
to circular iris muscle
42
Q3
a)
b)
c)
d)
Vibrating both Achilles tendons of a blind-folded subject
produces:
The subjective feeling that they are falling backwards
The experimental observation that they are falling backwards
The experimental observation that they are falling forwards
Stimulation of the Golgi tendon reflex in their Achilles tendons
[Answers: 1a 2d 3b]
3)
Logical fallacies (and how to avoid them)
Explain what is wrong with each of the following statements.
a)
As the ankle is further away from its spinal cord synapse than the
knee, the conduction velocity of action potentials travelling along its
stretch reflex pathway will be faster.
Explanation: The underlying assumption here is that a longer distance
requires a faster propagation, which is a type of teleological argument saying
that the time to react should be the same irrespective of which muscle is
involved. Although this might be true, the determinants of conduction
velocity in nerve fibres are primarily their size and myelination. If the fibres
in the ankle and knee jerk pathways are similar in both these respects, then
their velocities will also be very similar, and reflex times will in fact differ.
b)
Since there are two synapses in the reflex pathway, it is necessary
to add on two synaptic delays to the latency of the EMG in order to
calculate the total time taken by the nerve action potentials.
Explanation: Since the two synaptic delays due to the two synapses are
included in the latency of the EMG, they are already part of the total time, and
must therefore be subtracted from this in order to give just the time taken by
the nerve action potentials.
c)
Type Ia and Type Ib sensory fibres from skeletal muscles carry
information from primary and secondary spindle endings respectively.
Explanation: Type Ia and Type II fibres are the ones which do this, and their
central connections are part of the reflex pathways which eventually result in
contraction of the same stretched muscle. Type Ib fibres carry information
from Golgi tendon organs in the joint capsules, and their central connections
produce inhibition of muscle contraction as a protective mechanism; this
occurs when they have been over-stretched by either external pulling on the
tendon or excessive internal contraction of the muscle.
d)
Vibrating the Achilles tendon and hence stretching the
gastrocnemius muscle spindle causes a subject to compensate by leaning
backwards to contract the muscle back to normal length.
43
Explanation: This implies some sort of intent on the part of the subject, as it
they were responding voluntarily. However their response is involuntary, and
is a result of a message being sent to the CNS in the form of an increased
firing rate of action potentials originating in the gastrocnemius muscle
spindles. This initiates the reflex response of an increased output from the
alpha-motoneurones to that muscle, whose contraction causes ankle flexion
which makes the body lean back.
e)
When light is shone in the eye, it causes the circular iris muscle to
constrict and the pupil to contract.
Explanation: This illustrates a typical confusion between “constrict” and
“contract”. Muscles contract, and this may cause a space to constrict. Light
produces a reflex contraction of the circular iris muscle, leading to constriction
of the pupil.
4) Sequences which make sense
This exercise lists 7 steps which occur in a stretch reflex sequence, in
chronological order. Each step is preceded by questions designed to focus your
thinking on factors influencing that event. When you have written down your
answers to these you may then read an explanation of what would happen if
they were not optimized.
Question
a) What difference does either stretching or contracting the muscle prior to
tapping the tendon make to the functioning of the different components of
the reflex pathway?
Answer:
1.Knee joint in “neutral position” so quadriceps muscle is
neither over-stretched nor over-contracted
Explanations:
If the muscle is stretched or contracted i.e. the joint is not in its “neutral” position,
then
i) the intrafusal fibres (muscle spindles) will be less sensitive to stretch if they
are slack due to extrafusal muscle fibre contraction
ii) the extrafusal fibres will either not be at their optimal length when stimulated
(if stretched) or resist the stretch (if contracted)
Questions
a) What influences the sensitivity of the spindle response (hint: related to 1)?
b) What regulates the sensitivity of the spindle response?
Answer:
2. Tendon tap produces stretch of muscle spindle
44
Explanations:
a) The spindle is most sensitive at an intermediate length
b) The gamma-efferent motoneurones regulate the sensitivity of the spindle
response by producing contraction of the ends of the intrafusal fibres i.e. taking up
the slack
Questions
a) What determines how many sensory nerve fibres are activated?
b) What controls the sensitivity of individual motoneurones to activation (i.e.
depolarization to threshold)?
c) What else determines the relationship between total input to, and total
output from, the spinal cord?
Answer:
3.APs travel along afferent sensory nerve fibres to somas of alphamotoneurones
Explanations:
a) The greater the intensity of the tendon tap, the larger the number of sensory
fibres activated
b) The sensitivity of individual motoneurones, or stimulus strength required for
depolarization to threshold, depends on the net of the total excitatory and
inhibitory inputs from descending neural pathways
c) Input from antagonistic muscles via inhibitory interneurones also influences
the alpha-motoneurone potential
Questions
a) What determines how many muscle fibres are activated (hint: related to
3b&c)?
b) Where in the pathway, spinal cord or neuromuscular junction, can this
activation be inhibited?
Answer:
4. APs travel along efferent motor nerve fibres to end-plates of extrafusal
muscle fibres
Explanations:
a) The number of muscle fibres activated depends on the number of motor units
activated i.e. the number of alpha-motoneurones brought to threshold
b) This activation can be inhibited ONLY at the spinal cord level i.e. the soma of
the motoneurone, as there are no inhibitory synapses from motoneurones onto
skeletal muscle fibres
45
Questions
a) What recorded response reflects the number of extrafusal muscle fibres
activated?
b) What aspect of this response would change if a different number of fibres
had been activated?
Answer:
5. APs generated in extrafusal muscle fibres
Explanations:
a) The electromyogram or EMG reflects the number of extrafusal muscle fibres
activated
b) The amplitude of this response would change if a different number of fibres
had been activated i.e. it gives an indication of the muscle response
Questions
a) What are the parameters of the stimulus from a motoneurone to an
individual muscle fibre which influence the size of the contractile force?
b) What are the parameters of the muscle fibre which influence the size of
the contractile force?
c) What are the parameters of the whole muscle which influence the size of
the contractile force (hint: related to 4)?
Answer:
6. Contraction occurs in extrafusal muscle fibres
Explanations:
a) The only parameter is the frequency of the action potentials, since this
determines the extent of summation producing a tetanus
b) The contractile force developed by muscle fibres is greatest if
i) the muscle is contracting at its optimal length
ii) its movement is restricted to an isometric contraction
c) Number of motor units contributing and cross-sectional area of the muscle
both influence the size of the contractile force
Questions
a) What type of muscle contraction is occurring in the quadriceps muscle?
b) What has to happen in which other muscles to allow this to occur?
c) What are the pathways which achieve this?
Answer:
46
7. There is extension of knee joint
Explanations:
a) The contraction is isotonic
b) There has to be concurrent relaxation of the antagonistic hamstrings
c) The pathway involves interneurones in the spinal cord being activated by the
1A afferent from the quadriceps and inhibiting the alpha-motoneurones
innervating the hamstring muscle fibres (reciprocal inhibition)
NB Whenever a muscle contracts, its antagonist is stretched (e.g. biceps and
triceps, quadriceps and hamstrings). This would then initiate its own stretch
reflex, causing it to contract and oppose the movement of the joint, unless its own
alpha-motoneurones were inhibited. Although the Golgi tendon organ is
traditionally thought to be activated by EXCESS FORCE, and to function to
protect THE SAME MUSCLE from excessive further contraction, it here plays a
role in controlling contraction of the antagonist.
5) The three most important facts
In this exercise you have to make a choice from all the relationships you have
covered in the previous exercises, which THREE are the most vital to underpin a
hypothesis about muscle CAP variation with stimulus strength.
Since it is essential that the hypotheses evolve from what you have written in the
Introduction, these would constitute the three most important sentences as they
would be the ones from which your hypotheses could then be predicted.
i)
ii)
iii)
Repeat this exercise now for the Discussion, where the THREE relationships are
those which best explain how your data have supported your hypotheses.
i)
ii)
iii)
47
When answering some of the questions on reflex activity, the concepts below may
be relevant.
EMG interpretation
It is vitally important to appreciate what is being recorded on the screen, and what
physiological events are responsible for each component of the EMG. Before the
tutorial, see if you can answer the following questions (some of them relate to your
skeletal muscle class).
a)
At what time is the tendon being tapped?
Zero time, as the microswitch in the hammer triggers the computer sweep.
b)
What is occurring during the latency period or delay to the beginning of the
muscle compound action potential?
This period is the sum total of the time taken to generate action potentials in
the 1A afferent fibre endings in the muscle spindles, transmit them along the axon to
the synapse in the spinal cord with the somas of the alpha-motor neurones, synaptic
transmission here, generation and transmission of action potentials in the alphamotor neurones to the muscle end-plates of each motor unit, neurotransmission here,
generation of end-plate, then action potentials in the muscle fibres. Therefore, to
calculate the conduction velocity along the afferent and efferent nerve axons it is
necessary to subtract the time taken by the two neurotransmissions.
c)
What events follow the muscle action potential?
Excitation-contraction coupling follows the muscle action potential, as
voltage-gated calcium channels are opened and the sarcoplasm is flooded with
calcium, which then triggers the cross-bridge cycle. Note that we are not measuring
the contraction here.
d)
What type of muscle contraction is occurring?
Since the joint is constrained but is free to move, the muscle contraction is
isotonic.
e)
a
What is the basic structural unit which is recruited by the stretch to bring about
contraction?
As mentioned in b), the basic structural unit recruited is the motor unit i.e. the
muscle fibres innervated by one alpha-motor neurone, which includes their muscle
spindles.
f)
How can more of these units be recruited?
A more effective/stronger stimulus may stretch more muscle spindles more
effectively.
g)
What experimental parameters could be varied to make the extrafusal muscle
fibres produce more force?
There are two main variations which could be tried – a sharper tap with the
hammer and having the muscle in as ideal a starting position as possible, fully
relaxed. This is because the main extrinsic factors influencing muscle force are its
initial length (which should be close to rest-length to be optimal) and the frequency of
stimulation from its alpha-motor neurone (so as to produce a tetanic contraction);
48
this latter condition is most likely to be achieved with a sharper tap. Unloading the
muscle so that there is no external resistance to overcome also results in the
maximum force being produced.
h)
What intrinsic properties of the extrafusal muscle fibres influence the amount
of force they are capable of producing?
The main structural characteristic influencing force is muscle cross-sectional
area, since the force generated by sarcomeres in parallel is additive.
Pupillary Reflexes (Senses practical)
The pupillary reflexes, particularly the light reflexes, are of great clinical importance.
The length of the reflex pathways, as well as their location, makes the reflexes
vulnerable to intracranial damage; abnormal light reflexes are an important indicator
of brain damage after head injuries. Light activates an afferent pathway from the
retinal photoreceptors to the Edinger-Westphal nucleus, then the efferent pathway
goes via the ciliary ganglion. Darkness, or emotions such as fear, can cause reflex
pupillary dilation, via a sympathetic nervous system pathway.
The pupillary reflexes:
a)
are triggered by changes in the intensity of light entering the eye, and improve
the quality of the resultant image via mechanisms illustrated in the acuity
experiment
b)
are part of the triad of accommodation, convergence and pupillary
constriction, triggered when focusing on an object nearer to the eyes, when the
lens, visual axes and pupil diameter all alter in ways which improve image
quality (here the stimulus is not a change in light intensity)
c)
are mediated by autonomic nervous system pathways, as detailed above;
parasympathetic motoneurons contract the circular muscle and sympathetic
ones, the radial muscle, resulting in opposite changes in pupil diameter. In
accommodation, ciliary muscle contraction results from parasympathetic
motoneurons, allowing the lens to become more rounded (powerful), whereas
sympathetic stimulation of the muscle causes it to relax and the lens to flatten.
Knowing these actions you can predict the consequences of applying drugs to the eye,
as is done in visual examinations. What will happen to pupil diameter and lens power
if (i) atropine (ii) adrenaline is used?
(i)
(ii)
Atropine is a muscarinic cholinergic antagonist, so will block transmission
from all the motoneurons onto the smooth muscles in the parasympathetic
pathways. The circular muscle of the iris of both pupils will relax,
resulting in dilation of both pupils. The ciliary muscle of the lens will also
relax, resulting in flattening of the lens and less power.
Adrenaline is a sympathetic agonist, so will stimulate the smooth muscles
activated by sympathetic pathways. The radial muscle of the iris of both
pupils will contract, also resulting in dilation of both pupils. The ciliary
muscle of the lens will also relax, producing the same lens flattening and
decreased power as with atropine.
49
Concept Maps for Reflexes Pracs
Map the sequence of events in the
stretch reflex pathway leading to
muscle contraction.
Trigger: As there are a number of different
tissues and physiological mechanisms
involved in a stretch reflex, in what way
could changes at different points in this
pathway produce a better response?
Map the sequence of events in the
pupillary light reflex pathway leading
to pupillary constriction.
Trigger: As there are a number of different
nerves and muscles involved in the light
reflex, in what way do these become either
stimulated or inhibited when light is shone
into one eye?
50
SENSES PRACTICAL (including cutaneous and visual sensation)
1)
Confusing terms glossary
Write down your own definitions of these 5 pairs of terms.
Receptor – receptive field
Frequency code – population code
Adaptation – accommodation
Blind spot – optic disc
Myopia - hyperopia
2)
Misconception MCQs
Choose the correct option which best completes the statement in the stem.
Q1
When the temperature of the skin rises from 30 to 35OC:
a) Heat loss to the environment will always be possible
b) Cold receptors do not change their firing rate
c) Warm receptors increase their firing rate
d) Pain receptors are stimulated
Q2
When plotting visual fields by the hand perimetry method:
a) Each blind spot is easily found
b) The plotted outline of the visible field is exactly the same for both
eyes
c) The temporal field extends beyond the plot
d) The nasal field exceeds the temporal in extent
[Answers: 1c 2c ]
51
Logical fallacies (and how to avoid them)
Explain what is wrong with each of the following statements.
a)
Because there are both cold and warm receptors which sense the
skin temperature, the brain is able to determine the absolute temperature
of an object placed there very accurately.
Explanation: Although there are both cold and warm receptors, which are
defined by the direction of the temperature change which excites them, it
depends on the initial temperature of the skin as to whether the new object
causes heat to flow away from or towards them, and hence the change in the
firing rate of their afferent nerves. Starting at a temperature within the range
to which both the cold and warm receptors are able to respond produces an
increase in firing frequency of one and a decrease in the other, but this signals
the amount and direction of change, not the actual temperature i.e. the new
temperature relative to the old one.
b)
A myopic/short-sighted person has a smaller range of
accommodation because their near point is so much closer to the eye.
Explanation: Range of accommodation is given by 1/dn -1/df.
Although the near point of a myopic person is less than that of an emmetrope
(e.g. 1-2 cm compared to 9-10 cm), and hence the first term in the equation is
larger, this has much less of an influence on the equation than do the
differences in the second term, since it is approximately zero in an emmetrope
whose far point is effectively infinity, while a myope may not be able to see
clearly beyond half a metre, making the inverse of this term very large and the
difference between the two terms very small.
c)
The range of accommodation decreases with age because the far
point gets closer.
Explanation: As people age their lens becomes less able to accommodate to
view near objects, so their near point increases. This decreases their range of
accommodation without there necessarily being any decrease in their far point,
although it may also eventually decrease. Hence, like the myope, their near
and far points end up much closer together than for an emmetrope.
d)
As the size of the optic disc does not change when viewing different
objects, neither does the size of the blind spot.
Explanation: While is it correct that the size of the optic disc does not change,
because it is an anatomical structure, the size of the blind spot is entirely
dependent on the distance at which an object is viewed, since the light rays
which fall on the disc, and hence cause “blindness” to what is at that position,
form a cone which increases in cross-sectional area as the object is moved
further away from the eye.
52
4)
Sequences which make sense
Rearrange the following 10 concepts relating stimulation of a Pacinian
corpuscle into a numbered chronological sequence which shows how one
leads to the next (as in a concept map). Indicate by arrows (↑↓) the direction
of each change.
1. Vibrator applied to skin
Firing of action potentials down axon
Generator potential develops at initial segment
Rapid adaptation of membrane potential
Na influx and K efflux occurs
Synaptic transmission occurs in thalamus
Deformation of connective tissue layers
Threshold for action potential reached in axon
Cation channels mechanically opened
Awareness of sensation occurs in somatosensory cortex
1. Vibrator applied to skin
5)
The three most important facts
In this exercise you have to make a choice from all the relationships you have
covered in the previous exercises, which THREE are the most vital to
underpin a hypothesis about the variation of two-point discrimination with
location. Since it is essential that the hypotheses evolve from what you have
written in the Introduction, these would constitute the three most important
sentences as they would be the ones from which your hypotheses could then
be predicted.
i)
ii)
iii)
53
Repeat this exercise now for the Discussion, where the THREE relationships
are those which best explain how your data have supported your hypotheses.
i)
ii)
iii)
54
Concept Maps for Senses Pracs
Map the anatomical characteristics
which influence the size of the receptive
field of a cutaneous sensory neuron for
touch/pressure and how they influence
it.
Trigger: Did the use of different tests for
cutaneous sensation give uniform results
across different body locations?
How do the structures of the pathways explain
this?
Map the functional characteristics
which determine the perception of
temperature when the hand is immersed
in a beaker of hot water, left there for a
while, then removed.
Trigger: Which receptors sense temperature,
how are they stimulated/inhibited, and how do
they interact? Does time of exposure make
any difference?
55
RESPIRATION PRACTICAL
1)
Confusing terms glossary
This exercise is an extension of Appendix E on Confusing Terms in the No
Frills Generic Skills Guide. Read the introduction there, then scroll down to find the
terms which are relevant to the respiratory practical. Below are some from that list,
but you should be able to add more from your lectures and textbooks.
Constriction - contraction
Flow – flux
Renal medulla – medulla of brainstem
Resistance of arterioles - resistance of bronchioles
Vasodilator – bronchodilator
Add your own additional pairs:
Write down your own definitions for the following pairs of terms, and
give their units and typical values where appropriate. Consider any
mathematical relationships which are relevant.
i)
total pulmonary ventilation – alveolar ventilation
ii)
hyperventilation – hypoventilation
iii)
tidal volume – residual volume
iv)
end-tidal alveolar gas – dead space gas
v)
central chemoreceptors – peripheral chemoreceptors
2)
Misconception MCQs
Choose the correct option which best completes the statement in the stem.
Q1
a)
b)
c)
d)
Q2
a)
b)
c)
d)
Under steady state conditions of metabolism:
alveolar pCO2 is directly proportional to alveolar ventilation
alveolar pO2 is directly proportional to alveolar ventilation
alveolar pCO2 is inversely proportional to alveolar ventilation
alveolar pO2 is inversely proportional to alveolar ventilation
The greatest impact of the diversion of gases into and out of
body stores when holding one’s breath is in producing:
a faster rise in alveolar pO2
a slower fall in alveolar pO2
a faster fall in alveolar pCO2
a slower rise in alveolar pCO2
[Answers: 1c 2d]
56
3)
Logical fallacies (and how to avoid them)
Explain what is wrong with each of the following statements.
a)
Alveolar ventilation is proportional to tidal volume, dead space volume
and respiratory rate.
Explanation: Alveolar ventilation is equal to (tidal volume – dead space volume)
times respiratory rate. Since proportional means that the two variables change
together by the same fraction, alveolar ventilation will change proportionally to
respiratory rate change, but only to the difference between the two volumes and not
each individually. Furthermore, if a simultaneous change in this volume difference
were to occur when the rate was changed, then alveolar ventilation would be equal to
a product in which no term had been kept constant, and hence would not be
proportional to any variable.
b)
During end-tidal expiration, due to diffusion of oxygen and carbon
dioxide down pressure gradients, the pressure in blood equates that of the
alveoli, producing an equilibrium.
Explanation: This statement contains a number of common errors. End-tidal
expiration should rather be expressed as end-tidal volume in order to make a claim
about equality of gas pressures. The pressure in blood must be defined as a particular
gas partial pressure (and not hydrostatic or osmotic pressures). Diffusion of oxygen
and carbon dioxide down their pressure gradients does produce an equilibrium
between alveolar and dissolved blood gas, so that the values for each gas in the two
compartments are equal. It is this equality which allows one to use a sample of endtidal gas as a proxy for arterial blood, as the dead space gas has already been exhaled.
c)
The amounts of pCO2 and pO2 are different in different subjects, as these
are dependent on age, sex, weight etc.
Explanation: Although one might hypothesize that physical differences between
individuals would result in different blood gas levels, counteracting this are the
physiological homeostatic mechanisms which maintain pCO2 and pO2 at
approximately the same values within the normal range, so that metabolism can
proceed efficiently.
d)
Breathing pure oxygen containing a small fraction of carbon dioxide
causes all alveolar nitrogen to be replaced within a couple of breaths.
Explanation: As the amount of air remaining in the lungs at the end of a normal
expiration (functional residual capacity) is about 2300 ml, and only about 350 ml of
new air is brought into the alveoli with each normal inspiration, it obviously requires
many more than a couple of breaths to completely replace the alveolar air, including
the major nitrogen fraction, with pure oxygen.
57
4)
Sequences which make sense
Rearrange the following 10 concepts relating to ventilatory change into a
numbered chronological sequence which shows how one leads to the next (as
in a concept map). Indicate by arrows (↑↓) the direction of each change.
1. Rebreathing own expired air
Alveolar pCO2
Arterial pCO2
Alveolar pO2
Arterial pO2
Oxyhaemoglobin
Carbaminohaemoglobin
Plasma bicarbonate concentration
Alveolar ventilation rate
Medullary chemoreceptor stimulation
1. Rebreathing own expired air
5)
The three most important facts
In this exercise you have to make a choice from all the relationships you have
covered in the previous exercises, which THREE are the most vital to
underpin a hypothesis about alveolar gas composition variation with
ventilation pattern. Since it is essential that the hypotheses evolve from what
you have written in the Introduction, these would constitute the three most
important sentences as they would be the ones from which your hypotheses
could then be predicted.
i)
ii)
iii)
Repeat this exercise now for the Discussion, where the THREE relationships
are those which best explain how your data have supported your hypotheses.
i)
ii)
iii)
58
When answering some of the questions on respiratory activity, the concepts
below may be relevant.
Gaseous equilibria
The respiratory system is the site of exchange of gases between the outside air
and the body. Cellular respiration uses O2 and produces CO2 when food is
oxidised/metabolised in the tissues, with O2 being supplied by the systemic arterial
blood and CO2 being removed by the venous blood. At the venous end of the
pulmonary capillaries which surround the alveoli, blood enters with a pO2 of about 40
mm Hg and a pCO2 of about 46 mm Hg. When inspiration occurs and a tidal volume
of room air enters the respiratory system, about a quarter remains in the dead space,
where no exchange is possible, and three-quarters mixes with the alveolar air
(functional residual capacity). As end-expiratory alveolar air had a pO2 of about 100
mm Hg and a pCO2 of about 40 mm Hg, this extra volume alters the alveolar gas
concentrations so that the pO2 rises above 100 mm Hg (though much below inspired)
and the pCO2 falls below 40 mmHg.
Under these conditions there are pressure gradients for O2 to diffuse into, and
CO2 to diffuse out of, the capillary blood. Equilibration with alveolar air is very rapid
and results in the blood at the arterial end of the pulmonary capillaries leaving at
partial pressures for O2 and CO2 of 100 and 40 mm Hg respectively. When air is
now breathed out, the first fraction will be dead space gas, while the air at the end of
the expiration will be pure alveolar gas. Hence taking an end-tidal sample avoids
contamination with dead space gas while at the same time providing the closest
approximation to arterial blood gas values.
It is important to appreciate that the pressure gradient created by the active
contraction of muscles during inspiration results in bulk flow of air into the lungs, and
is different from the simple diffusion down partial pressure gradients which results in
equilibration between alveolar air and blood. [This is obvious when you consider that
pCO2 is almost zero in room air, but this does not result in CO2 in lung air flowing out
along the CO2 gradient.]
During a breath-hold, gas exchange between the body and the outside air is
prevented, but gas exchange continues between the lungs and the blood as the tissues
continue to metabolise. Assuming that the metabolic rate does not change, CO2 will
accumulate in, and O2 will be withdrawn from, alveolar air, so that pCO2 will rise and
pO2 will fall. During hyperventilation, gas exchange between the body and the
outside air is increased above the level which normally balances metabolism. As a
result extra CO2 will be lost from the body and extra O2 will accumulate in the body,
so that pCO2 will fall and pO2 will rise.
With hypoventilation the pCO2 increase can result in cerebral blood vessels
dilating, which may produce a headache because of the inrush of blood. Conversely,
with hyperventilation the pCO2 decrease can constrict cerebral blood vessels, with the
reduced blood flow then producing a tissue hypoxia in the brain, again causing a
headache. Additionally in hyperventilation, the alkalosis which accompanies the
blowing off of the extra CO2 from stores exacerbates the arteriolar vasoconstriction. It
may also cause "pins and needles" and muscle cramps due to a decrease in free Ca2+
as more becomes bound to albumin, and may produce disturbances of cardiac
function. Some or all of these symptoms may develop simply as a result of anxious
over-breathing.
59
Gas stores
Since the oxidation of carbohydrate uses up one O2 for every CO2 produced,
the respiratory quotient RQ is 1, and when ventilation matches metabolism, the
respiratory exchange ratio is also 1, i.e. volume of CO2 produced equals volume of
O2 consumed. This implies that a change in alveolar partial pressure of one gas
should be paralleled by an equal, though opposite, change in the alveolar partial
pressure of the other gas. Even though assuming an RQ of 0.8 because a mix of food
types is being oxidised would change alveolar pCO2 by only 0.8 of the amount pO2
changes, the data obtained when hypo- and hyper-ventilating show that the absolute
changes in pO2 are very much greater than those in pCO2, typically 2-3 times as big.
The explanation for this is that the CO2 being generated in the tissues when
breath-holding does not all escape into the lungs, but is diverted into chemical stores
in the form of bicarbonate ion and carbaminohaemoglobin. The CO2 enters into
reversible chemical reactions as follows:
CO2 + H2O ↔ H2CO3 ↔ H+ + HCO3CO2 + Hb ↔ Hb-CO2
Under opposite conditions, when CO2 is escaping from the body faster than it
is being generated by metabolism, these reactions are reversed. In both situations the
change which would occur in CO2 concentration in plasma, and hence in alveolar gas,
is mitigated by an additional sink or source of the gas.
The greater the size of the stores which can function as either sources or sinks,
the more possible is a temporary imbalance between the metabolic and alveolar gases.
Body stores for O2 are much more limited, and in this experiment the lungs were
deliberately not over-filled before breath-holding to keep this store constant.
Oxyhaemoglobin is the chemical store which can buffer changes in the plasma O2
concentration, according to the reversible chemical reaction:
O2 + Hb ↔ Hb-O2
However the position of the oxyhaemoglobin dissociation curve (or Hb saturation
curve) is such that Hb is about 90% saturated above a pO2 of 60 mm Hg and almost
fully saturated at the normal arterial pO2 of 100 mm Hg, leaving little extra room for
O2 to be added as the pO2 rises during hyperventilation. Note that the correct
explanation of the failure of Hb saturation to rise above 100% is NOT that it has a
limited carrying capacity (which it does) but that whatever its capacity, 100% means
full saturation and no more possibility of more O2 being added.
Despite this store being full, the extra O2 can dissolve in the plasma, thereby
raising the pO2. It is important to bear in mind that the two gases will not be present
in equal concentrations in the plasma when their partial pressures are the same. This
is because their solubilities in aqueous solution are very different, with CO2 being
about 20 times as soluble as O2. In contrast to alveolar-plasma gas exchange, tissueplasma CO2 uptake and O2 release is not usually given as much emphasis, but exactly
the same principles apply.
Breathing higher oxygen concentrations
Normally the O2 in inspired air constitutes 20% of the total gases, the CO2 is
negligible, and the remaining 80% is N2 (minus the very small amounts of H2O and
rare gases). However, in the Respiration practical class, two different gas mixtures
are used in addition to room air. In the Alveolar Ventilation experiment, pure O2 is
inhaled for several minutes. In the Demonstration of Control of Ventilation
experiment, a 5% CO2 – 95% O2 mixture is initially inhaled, and the addition of the
subject’s expired CO2 then progressively increases the contribution of CO2 to the
inhaled mixture, while the O2 is simultaneously being removed from it.
60
It has been shown that, with a normal tidal volume, it requires about 16
breaths to completely replace alveolar air with new room air. Thus, it would take the
same number of breaths to replace a subject’s alveolar air with a new inspired gas
mixture, such as 100% O2. If this is the case, then several minutes of breathing pure
O2 will be more than enough time to achieve this total replacement, and to increase
the pO2 towards 760 mmHg. A much lower value therefore implies that the mask
being used was inadequate to prevent air as well as pure O2 being inhaled. Of course
CO2 being produced by metabolism will still be added to the alveolar gas, but will
constitute only a tiny fraction of the total (about 40 mmHg). If the subject
experiences discomfort or anxiety and over-breathes as a result, the pCO2 will drop
below this. Note that, despite the extremely high pO2 levels in the blood perfusing the
carotid and aortic bodies (peripheral chemoreceptors), there is no evidence that
ventilation is reduced. Note also that the increase in body levels of O2 is not being
achieved by greater amounts being bound to haemoglobin, since saturation is almost
100% to start with. Where the O2 is being increased is in the plasma, where amounts
of O2 dissolved can rise indefinitely.
The O2 will be progressively replacing mainly N2 in the lungs, but as gas
exchange between the alveolus and the pulmonary capillary is so efficient, it will also
be replacing N2 dissolved in the plasma, which will be diffusing out along its large
gradient caused by the absence of any N2 in the inhaled gas. Whatever the
composition of the air being breathed, the principle of mixing applies, with the total
pool of gases being made up of the lung and plasma volumes, and the alveolar endtidal gas pressures being in equilibrium with, and thus giving a measure of, the arterial
gas pressures.
In the rebreathing experiment, the first few breaths are deliberately made
much larger than a normal tidal volume, so as to speed up the mixing process. Thus
the recording begins at a pCO2 of about 50 mmHg, and this then increases to about 60
mmHg over a period of a couple of minutes. As there is no possibility in this
experiment for N2 to be lost from this closed system, the final gas composition will be
determined by the extent to which the original N2 in the lungs and plasma has
equilibrated with the bag, the original O2 in the bag, lungs and plasma has been
depleted by metabolism, and the original CO2 in the total system has been increased
by metabolism. As predicted, the recording demonstrates the increase in CO2 being
accompanied by a decrease in O2.
The high pCO2 levels in the circulating blood produce high H+ levels at the
medullary chemoreceptors, stimulating ventilation. This is evident in the gradually
increasing tidal volumes, but the durations of breaths (and hence the instantaneous
frequencies) do not appear to increase as systematically.
The arterial pCO2 is monitored directly by the peripheral chemoreceptors,
contributing 20% of the response to this gas, and indirectly by the central
chemoreceptors in the medulla, contributing 80% of the CO2 response. As the
medullary CO2 is first converted to H+, the central response is somewhat slower. H+
ions themselves are unable to cross the blood-brain barrier, so blood pH is monitored
by the peripheral chemoreceptors. However their main stimulus is a low arterial pO2,
to which they respond even more when arterial pCO2 is above normal; conversely the
pO2 needs to be very low if the pCO2 is below normal. Likewise the central
chemoreceptor response to pCO2 is increased under hypoxic conditions, until the
brain becomes so deprived of O2 that respiration fails. Note that even when pO2 is
extremely high, this does not of itself suppress ventilation, but very high pCO2 (above
80 mm Hg) does depress respiration.
61
Concept Maps for Resp. Prac
Map the influence of ventilation pattern
on alveolar oxygen and carbon dioxide
partial pressures.
Trigger: How do hypo- and hyperventilation alter the normal equilibrium
between cellular respiration (metabolism)
and respiratory gas exchange?
Do gas stores play any role?
Map the influence of inhaled gas
composition on alveolar ventilation.
Trigger: What is the result of mixing a
small tidal volume of a certain composition
with a much larger lung volume of different
composition?
Which gas compositions would make a
significant difference to the drive to breathe?
62
ENDOCRINE PRACTICAL
1)
Confusing terms glossary
This exercise is an extension of Appendix E on Confusing Terms in the No
Frills Generic Skills Guide. Read the introduction there, then scroll down to find the
terms which are relevant to the endocrine practical. Below are some from that list, and
you may be able to add more from your lectures and textbooks.
Aldosterone – antidiuretic hormone
Diuresis – diabetes
Dysmenorrhea – premenstrual tension
Glucose tolerance – immunological tolerance
Glycogen-glucagon
Granular cells – zona granulosa
Inhibin – inulin
Inulin – insulin
Lacteal – lactation
Melatonin – melanotropin
Milk secretion – milk ejection
Proliferative – progestational
Renal cortex – adrenal cortex
Renal medulla – adrenal medulla
Thyroglobulin – thyroxine binding globulin
Thyrotropin releasing hormone- thyroid stimulating hormone
Trophic – tropic
Zona granulosa – zona glomerulosa
2)
Misconception MCQs
Choose the correct option which best completes the statement in the stem.
Q1
In a glucose tolerance test:
a) glucose absorption in the small intestine occurs by a secondary active
transport process
b) only one hormone, insulin, changes its secretion rate
c) peak plasma glucose concentration reached is lower after prior
carbohydrate restriction
d) plasma glucose concentrations never go below the fasting level
Q2
a)
b)
c)
d)
Abnormalities of thyroid hormone secretion:
occur only when TSH secretion is abnormal
do not usually produce significant clinical signs or symptoms
may be the result of abnormal antibody stimulation of the gland
cannot be treated by pharmacological means but require surgery
Q3 In relation to the use of arginine to stimulate growth hormone secretion:
a) this depends on the arginine first stimulating insulin secretion
b) a positive response can occur in the absence of hypoglycemia
c) this does not mimic what happens physiologically
d) any rise in growth hormone levels is considered significant
[Answers: 1a 2c 3b]
63
3)
Logical fallacies (and how to avoid them)
Explain what is wrong with each of the following statements.
a)
As insulin and growth hormone are the two main anabolic hormones, they
have similar effects on all aspects of carbohydrate metabolism.
Explanation: Insulin and growth hormone both have anabolic actions on protein
metabolism leading to protein synthesis, but have opposite actions on both fat and
carbohydrate metabolism. Insulin is anabolic for both of these, producing glycogen
and triglyceride synthesis, but growth hormone is catabolic, resulting in a higher
blood glucose level by opposing its uptake and promoting gluconeogenesis, and a
higher blood fatty acid level by promoting lipolysis.
b)
As adrenaline and noradrenaline are both secreted by the adrenal
medulla in response to stress, their actions on the cardiovascular system
are the same.
Explanation: Being secreted together in response to a common stimulus such as stress
does not mean that adrenaline and noradrenaline act in identical ways to counteract
that stress. Although they both stimulate beta-1 adrenergic receptors in the heart and
hence increase both heart rate and contractility, resulting in a rise in cardiac output,
their actions on the blood vessels are different. Noradrenaline acts primarily on alpha
adrenergic receptors which contract vascular smooth muscle, causing vasoconstriction
and a rise in total peripheral resistance, while adrenaline is more potent on beta-2
adrenergic receptors which relax vascular smooth muscle and result in vasodilatation
and a fall in total peripheral resistance. Obviously it will depend on the balance
between these opposing actions as to the final direction of change of the vascular
resistance, and then on the total effect of this and the changed cardiac output as to
how the blood pressure changes.
Note that the adrenal cortex also secretes hormones in response to stress,
including cardiovascular stress such as a drop in arterial blood pressure; they are
aldosterone and cortisol. However their actions are not as immediate and direct as for
the adrenal medullary hormones, although cortisol is permissive for the
vasoconstrictor effect. Do not make the mistake of including angiotensin in any
discussion of ADRENAL hormones, except to state that it is one of the stimulators of
aldosterone secretion from the zona glomerulosa, which then results in distal tubular
salt and eventually water retention, after ADH is also released, thereby raising
extracellular volume and hence BP. ATII promoting thirst and causing proximal
tubular salt reabsorption and vasoconstriction is NOT an adrenal hormone response.
c)
As positive feedback would result in an ever-increasing level of hormone
activity, it does not occur anywhere in the endocrine system.
Explanation: There are a few examples of positive feedback in the reproductive
system e.g. estrogen surge producing LH surge before ovulation, oxytocin being
released in ever-increasing amounts during labour, prolactin and oxytocin being
secreted in proportion to the degree of suckling by the baby.
64
4)
Sequences which make sense
Rearrange the following 10 concepts relating to carbohydrate ingestion into a
numbered chronological sequence which shows how one leads to the next (as
in a concept map).
Note: Food and water ingestion produces combined endocrine, gastrointestinal
and renal effects, and each sequence contains only a small selection of
possible physiological consequences.
1. Eat starch
Glycogen synthesis in hepatocyte
Maltose breakdown by maltase in brush border
Starch breakdown by pancreatic amylase
Glucose transport into portal vein blood
Starch breakdown by salivary amylase
Glucose transport into hepatocyte
Glucose transport into enterocyte with Na
Cholecystokinin stimulation of exocrine pancreas
Parasympathetic stimulation of salivary acini
1. Eat starch
5)
The three most important facts
In this exercise you have to make a choice from all the relationships you have
covered in the previous exercises, which THREE are the most vital to
underpin a hypothesis about blood glucose concentration variation with
food carbohydrate composition. Since it is essential that the hypotheses
evolve from what you have written in the Introduction, these would
constitute the three most important sentences as they would be the ones from
which your hypotheses could then be predicted.
i)
ii)
iii)
Repeat this exercise now for the Discussion, where the THREE relationships
are those which best explain how your data have supported your hypotheses.
i)
ii)
iii)
65
The previous two exercises were focused on glucose release from food into
blood and its arrival in the liver, while the next two will be focused on growth
and metabolism.
4)
Sequences which make sense
Rearrange the following 10 concepts relating to growth into a numbered
chronological sequence which shows how one leads to the next (as in a
concept map).
1. Increased somatoliberin secretion
Increased bone length
Increased muscle protein synthesis
Increased somatomedin (IGF1) production
Increased width of epiphyseal growth plate
Increased height
Increased somatotropin (GH) secretion
Decreased plasma aminoacid level
Decreased adipose tissue triglycerides
Decreased body mass index (BMI)
1. Increased somatoliberin secretion
5)
The three most important facts
In this exercise you have to make a choice from all the relationships you have
covered in the previous exercises, which THREE are the most vital to
underpin a hypothesis about hepatic glucose metabolism variation under
the influence of different hormones. Since it is essential that the hypotheses
evolve from what you have written in the Introduction, these would
constitute the three most important sentences as they would be the ones from
which your hypotheses could then be predicted.
i)
ii)
iii)
Repeat this exercise now for the Discussion, where the THREE relationships
are those which best explain how your data have supported your hypotheses.
i)
ii)
iii)
66
When answering some of the questions on endocrine activity, the concepts below
may be relevant.
Insulin-cation interactions
The relationships between plasma and cellular K+ and H+ concentrations and
insulin are quite complex, and become even more complicated in situations such as
diabetes where a metabolic acidosis and dehydration often occur. As abnormal
plasma levels of both these cations can have very damaging effects on excitable cells,
and even lead to death, it is important to understand how they interact.
For insulin and K+ levels, there is a two-way inter-relationship. The secretion
of insulin from β-cells in the pancreas is stimulated not only by a rise in plasma
glucose, but also by a rise in plasma K+ concentration. The consequence of both these
changes is depolarisation of the β-cell membrane, which raises intracellular Ca2+ and
promotes insulin secretion. Insulin then acts on its receptor in muscle and adipose
tissue cells to recruit GLUT4 transporters as well as stimulate K+ uptake via the
Na/K/ATP-ase and Na/K/2Cl symport. Hence diabetics who lack insulin are prone to
hyperkalaemia, a raised plasma K+ concentration.
H+ levels also feed into this system, in that a rise in plasma H+ concentration
(or drop in plasma pH) leads to an intracellular acidosis which inhibits the Na pump
and symport, thus preventing K+ uptake, as well as displacing K+ from proteins and
driving it out of the cell. Hence the metabolic acidosis which accompanies diabetes
will also produce hyperkalaemia. This is frequently stated as H+ ions “shifting into
cells in exchange for” K+ ions, or as a rule of thumb that a rise in plasma K+
accompanies a rise in plasma H+, and that they similarly fall together.
The clinical situation is complicated by any dehydration which occurs as a
result of the osmotic diuresis caused by the hyperglycaemia and glycosuria (glucose
loss in the urine). Since extra K+ can also be lost under these circumstances, the
patient’s body may be K+ depleted, and this will have been exacerbated by the rise in
aldosterone secretion as a consequence of both the raised plasma K+ level and the
reduced extracellular volume stimulating the renin-angiotensin system.
Hormones and pregnancy maintenance
After conception has occurred with the fertilization of an ovum by a sperm in
the upper third of the fallopian tube, the zygote begins a hazardous journey in which it
must travel down to implant in the endometrium of the uterus, contribute to the
establishment of a placenta, develop and grow until it is ready to be expelled in the
process of labour. Each of these events may not proceed normally and the pregnancy
may then terminate spontaneously in a miscarriage or premature birth. Apart from
fetal genetics, the hormonal environment is critical to pregnancy maintenance and
success, and it can be compromised in the following ways:
1. Inadequate hCG secretion by blastocyst trophoblast layer→failure to maintain
corpus luteum estrogen (E) and progesterone (P) secretion
2. Incorrect E:P ratio→inappropriate motility of tube →arrival at uterus too early
or too late in relation to its chemical changes
3. Inadequate luteal P secretion→failure to develop secretory endometrium with
appropriate nutrients
4. Failure of placenta to take over P secretion→inadequate suppression of
myometrial contractions→miscarriage
5. Failure to secrete sufficient hCS and/or other maternal endocrine
abnormalities→incorrect rate of growth and baby of abnormal size
67
Concept Maps for Endo. Prac
Map the mechanisms by which an
excess of thyroid hormone causes
symptoms of sensitivity to heat.
Trigger: How is heat generated and
dissipated by the body and how does thyroid
hormone normally influence these processes?
Map the mechanisms by which an
increase in insulin resistance can
eventually result in an impairment of
glucose tolerance.
Trigger: What is meant by insulin resistance
and how does it develop? How is impaired
glucose tolerance demonstrated and what
does it signify?
68
GASTROINTESTINAL PRACTICAL
1)
Confusing terms glossary
This exercise is an extension of Appendix E on Confusing Terms in the No
Frills Generic Skills Guide. Read the introduction there, then scroll down to
find the terms which are relevant to the gastrointestinal practical. Below are
some from that list, but you should be able to add more from your lectures and
textbooks.
Absorption – reabsorption
Bile pigment – bile acid
Constriction – contraction
Flow – flux
Lacteal – lactation
Add your own additional pairs:
2)
Misconception MCQs
Choose the correct option which best completes the statement in the stem.
Q1
a)
b)
c)
d)
Q2
Acetylcholine acting on muscarinic receptors on the parietal cell:
increases cyclic AMP levels which stimulates the K-H-ATPase
can be blocked by H2-antagonists such as ranitidine
antagonizes the stimulatory effect of caffeine on acid secretion
is released during the cephalic and gastric phases of digestion
Neutralization of gastric chyme occurs after:
a) gastrin stimulates the parietal cell to secrete bicarbonate into the lumen
b) secretin stimulates the pancreatic duct cell to secrete bicarbonate into
the lumen
c) cholecystokinin stimulates the pancreatic acinar cell to secrete
proteolytic enzymes
d) fat incorporates the acid into micelles in the duodenum
[Answers: 1d 2b]
3)
Logical fallacies (and how to avoid them)
Explain what is wrong with each of the following statements.
a)
Secondary active transport of HCO3 out of the parietal cell occurs because
of the presence of carbonic anhydrase in the cell.
Explanation: Carbonic anhydrase in the parietal cell enables CO2 and H2O to
combine and form carbonic acid at a fast rate, which then dissociates into H+ and
HCO3-. However the transport of the HCO3- out of the cell in exchange for Clmoving in across the basolateral membrane is a not a secondary active transport
process, but occurs because the active removal of H+ via the luminal membrane K-HATPase generates a concentration gradient for HCO3- which drives the antiport for
these two anions. The rise in intracellular pH also pushes the reaction between CO2
69
and H2O to the right, generating more of both H+ and HCO3-. It is the Cl- which is
secreted by secondary active transport into the lumen, entering the parietal cell from
the blood against its concentration gradient and exiting by diffusion down its
electrochemical gradient through the luminal Cl- channel.
b)
K+ and Cl - movement through their channels on the luminal membrane
of the parietal cell is an active transport process dependent on their
electrochemical gradients.
Explanation: There are a number of incorrect associations in this statement.
Movement through channels is passive, not active, and active transport processes
depend on ATP, not electrochemical gradients, which drive the channel movements.
c)
Just as water is never secreted into the filtrate in the lumen of the
proximal tubule, so it is also never secreted into the lumen of the gut.
Explanation: Although the transport mechanisms in the epithelia of the gut and
kidney are similar in many respects, the movement of water can be very different. In
the nephron the osmotic gradient between the lumen of the tubule and the surrounding
capillary blood always promotes reabsorption of water, although whether or not this
can occur also depends on how permeable the epithelium is at that point. In the gut
the same processes usually establish a net gradient for water reabsorption – active
reaborption of Na and metabolites of digestion such as glucose and aminoacids.
However there are also secretory processes which form part of the normal physiology
of the gut, such as acid secretion by the parietal cells in the stomach, salt and water
secretion by the crypt cells of the small intestine, similar secretions by the acini of the
salivary and pancreatic exocrine glands, and bicarbonate and other secretions by
surface epithelial cells throughout. The final secretions from all of these sites are
often isotonic or hypotonic solutions, and in addition, the absorption of solutes usually
leads, rather than follows, transepithelial water movement.
However when complex food components are broken down in digestion, they
generate a much larger number of osmotically active products, hence increasing the
luminal osmolality; normally these are the only ones which could potentially lead to
secretion rather than reabsorption of water. Yet it is only under circumstances in
which they are not being aborbed rapidly enough that the gradient for water will be
into the lumen, and hence it will be secreted. This can occur in such situations as
dumping syndrome, where removal of part of the stomach produces a loss of negative
feedback mechanisms which control gastric emptying, so that volumes in excess of
the capacity of the upper small intestine to absorb are suddenly dumped there, which
is followed by water being secreted into the lumen.
d)
The tonicity of saliva is lowest when there is a high rate of secretion by the
acini and a high rate of flow through the ducts.
Explanation: The acini secrete an isotonic solution independently of the rate at which
this occurs, and the tonicity of the saliva is determined by the rate of flow through the
ducts, which are impermeable to water. When this is slow, the reaborption of NaCl
exceeds the secretion of KHCO3 and hence the tonicity is round its lowest value.
Note that this is different from what happens in the exocrine pancreas, whose
secretion is always isotonic at the outlet from the pancreatic duct into the duodenum.
70
4)
Sequences which make sense
Rearrange the following 10 concepts relating to carbohydrate ingestion into a
numbered chronological sequence which shows how one leads to the next (as
in a concept map).
Note: Food and water ingestion produces combined endocrine,
gastrointestinal and renal effects, and each sequence contains only a small
selection of possible physiological consequences.
1. Eat starch
Glycogen synthesis in hepatocyte
Maltose breakdown by maltase in brush border
Starch breakdown by pancreatic amylase
Glucose transport into portal vein blood
Starch breakdown by salivary amylase
Glucose transport into hepatocyte
Glucose transport into enterocyte with Na
Cholecystokinin stimulation of exocrine pancreas
Parasympathetic stimulation of salivary acini
1. Eat starch
5)
The three most important facts
In this exercise you have to make a choice from all the relationships you have
covered in the previous exercises, which THREE are the most vital to
underpin a hypothesis about gastric secretion variation with drugs. Since it
is essential that the hypotheses evolve from what you have written in the
Introduction, these would constitute the three most important sentences as
they would be the ones from which your hypotheses could then be predicted.
i)
ii)
iii)
Repeat this exercise now for the Discussion, where the THREE relationships
are those which best explain how your data have supported your hypotheses.
i)
ii)
iii)
71
When answering some of the questions on gastrointestinal activity, the concepts
below may be relevant.
Luminal stimuli in gastric phase
Antrum & body/corpus:different outcomes of luminal physical & chemical
stimulation
•
Corpus: distension→+vagal reflexes to G,
ECL & parietal cells, - reflex to D cell
•
Antrum: distension→local reflex to G cell
aminoacids/peptides→direct on G cell
→ G (→ paracrine stimulation of D cell)
acid→direct on D cell → SS (→ paracrine
inhibition of G cell) &→ECL & parietal cells
Chief cell pepsinogen: via stimulation by vagus, G, histamine + acid, CCKA, - by SS
Salivary & pancreatic secretion
•
Acini secrete digestive enzymes
•
Acini secrete salt & water by same mechanism in both glands →isotonic
solution like plasma
•
Salivary ducts impermeable to water
absorb NaCl & secrete KHCO3 →more hypotonic at faster secretion rates
•
Pancreatic ducts permeable to water
absorb Cl (& Na paracellularly)
secrete KHCO3 →isotonic (Na&K as in plasma)
•
Neural stimulation of saliva (symp.&parasymp.) neural & hormonal of
pancreatic juice (vagus) (CCK – acini secretin – ducts)
72
Concept Maps for Gastric Prac
Map the mechanisms which increase
gastric secretion when protein is eaten.
Trigger: What is the effect of protein on
the stomach? What mechanisms result in
stimulation of the parietal and chief cells to
secrete acid and enzymes?
Map the mechanisms which increase
luminal pH in response to acidic chyme.
Trigger: What is the effect of acidic chyme
on gastric and small intestinal neural and
hormonal reflex responses? What
mechanisms result in neutralization of the
acid?
73
RENAL PRACTICAL
1)
Confusing terms glossary
This exercise is an extension of Appendix E on Confusing Terms in the No
Frills Generic Skills Guide. Read the introduction there, then scroll down to find the
terms which are relevant to the renal practical. Below are some from that list, and you
may be able to add more from your lectures and textbooks.
Absorption – reabsorption
Aldosterone – antidiuretic hormone
Counteract – countercurrent
Countercurrent flow – countercurrent multiplication
Countercurrent exchange – countercurrent multiplication
Diuresis – diabetes
Flow – flux
Granular cells – zona granulosa
Inhibin – inulin
Inulin – insulin
Juxtaglomerular body – juxtaglomerular cells
Mesangial cells – extraglomerular mesangial cells
Renal clearance – total clearance from renal blood
Renal cortex – adrenal cortex
Renal cortex – cerebral cortex
Renal medulla – adrenal medulla
Renal medulla – medulla of brainstem
Resorption – reabsorption
Secretion – excretion
Urine - urea
2)
Misconception MCQs
Choose the correct option which best completes the statement in the stem.
Q1
Glucose begins to appear in the urine:
a) when its Tmax for renal reabsorption exceeds its renal threshold
b) when its plasma concentration exceeds its renal threshold
c) when its Tmax for renal reabsorption is reduced below its renal
threshold
d) when the amount of glucose filtered is more than that secreted
Q2
a)
b)
c)
d)
In relation to water handling by the nephron:
an osmotic gradient is necessary, but not sufficient, for reabsorption
80% of the volume filtered is reabsorbed in the proximal tubule
20% of the volume filtered is reabsorbed in the thick ascending limb
antidiuretic hormone is required for reabsorption in all segments
[Answers: 1b 2a]
74
3)
Logical fallacies (and how to avoid them)
Although students intuitively feel that GFR “ought to” change after diuretics or
ADH treatment, they often have problems with giving a mechanism to justify
this prediction, and to explain the link to urinary volume changes. [An
alternative argument could be that you would NOT expect GFR to change after any of
the treatments because they all act POST-glomerulus.]
Wrong Explanation!
Furosemide solute excretion  water excretion urine volume per min
Therefore, to supply the increased volume, GFR must 
ADH  distal tubule permeability to water   water secretion   urine volume
per min
Therefore GFR must 
The above is additionally wrong because water
never is secreted, only reabsorbed less
Water loading   plasma osmolality which in turn  urinary osmolarity *
Therefore there must be an water excretion and GFR must 
*This is inadequate without the missing link of  plasma ADH   water
reabsorption  water excretion
Right Explanation!!
The right logic could have been any one of the following:
Furosemide  water excretion   ECV/BP   glomerular capillary hydrostatic
pressure
And  glomerular capillary oncotic pressure
  GFR
N.B. Furosemide   solute excretion   glomerular capillary osmotic pressure 
 GFR
is not correct because the only solutes which make a difference to filtration are the
plasma proteins, and these would in fact have become more concentrated as just
indicated
Water loading   ECV/BP   glomerular capillary hydrostatic pressure
And  glomerular capillary oncotic pressure
 GFR
N.B. Again, it is not correct to argue that there is a  glomerular capillary osmotic
pressure   GFR
Note also that these results pre-suppose that there has NOT been local auto-regulation
of GFR maintaining it constant. They also pre-suppose an absence of homeostatic
reflexes maintaining MAP.
It is therefore clear that there is no one RIGHT ANSWER, but as long as your
arguments are physiologically sound, you will be given credit for what you have
written.
75
4)
Sequences which make sense
Rearrange the following groups of concepts relating to water ingestion into
numbered chronological sequences which shows how one leads to the next (as
in a concept map). You will need to have two parallel sequences converging
on the final outcome.
1.Water ingestion
Decreased aquaporins in collecting duct
Increased net filtration pressure
Decreased plasma osmolality
Decreased oncotic pressure
Increased urine volume
Increased urine volume
Increased plasma volume
Increased plasma volume
Decreased water reabsorption
Decreased water reabsorption
Decreased hypothalamic osmoreceptor
Decreased proximal tubular
stimulation
Na&H2O reabsorption
Decreased ADH secretion
Increased glomerular filtration
rate
1.Water ingestion
76
5)
The three most important facts
In this exercise you have to make a choice from all the relationships you have
covered in the previous exercises, which THREE are the most vital to
underpin a hypothesis about urinary osmolality variation with diuretics.
Since it is essential that the hypotheses evolve from what you have written in
the Introduction, these would constitute the three most important sentences as
they would be the ones from which your hypotheses could then be predicted.
i)
ii)
iii)
Repeat this exercise now for the Discussion, where the THREE relationships
are those which best explain how your data have supported your hypotheses.
i)
ii)
iii)
77
When answering some of the questions on renal activity, the concepts below may
be relevant.
Mechanisms of salt and water transport in the kidney
The kidney is a particularly difficult organ to consider in relation to salt and water
movement because of the variability in the properties of different segments of the
nephrons and the flow-on effects due to the anatomical proximity of different tubular
and vascular structures. As an example, the countercurrent multiplication mechanism
for generating the vertical osmotic gradient in the medullary interstitium depends
for its maintenance on the countercurrent exchange mechanism of the vasa recta.
Yet the permeability of these tubular and vascular elements to different solutes and to
water varies uniquely with the structure concerned, as well as their movement being
influenced by chemical factors such as hormones or drugs, and physical factors such
as pressures. Therefore, when considering the effects of any treatment on urinary
composition it is necessary to take into consideration changes in the following:
(i) ion transport from lumen to interstitium and vice versa
(ii) effects of (i), if any, on osmolality of the filtrate and of the interstitium
(iii) potential effects of (ii), if any, on the passive reabsorption of water
(iv) water permeability in the part of the tubule where osmotic gradients occur
Remember that for a substance to move passively from one compartment to another,
there must be BOTH a force or gradient and a pathway. The luminal surface of the
epithelial cells is the site of those transport mechnisms which remove from, or add to,
the filtrate, whereas the interstitial surface of the epithelial cells is the site of those
mechanisms which exchange material with the interstitial space. This in turn can
exchange with the capillary blood, which perfuses that part of the kidney. Whatever
remains in the tubule becomes urine and whatever remains in the capillaries becomes
the renal venous blood which is returned to the systemic circulation. These are, thus,
the two routes of excretion of material from the medullary interstitium and that if
allowed to accumulate would cause a rise in pressure. Apart from the gradients and
available pathways, rate of flow of filtrate or of capillary blood past the exchange
sites will influence the time available for material to move between the
compartments, as well as the absolute capacity to remove it in urine or renal venous
blood. Remember that water movement is always passive, along an osmotic gradient.
Also remember that ANTI-diuretic hormone (ADH), which acts in the distal nephron
to increase luminal membrane permeability to water, has the exactly opposite effect
to diuretics, reducing, rather than enhancing, the excretion of water.
Differential effects of diuretics
Diuretics exploit known transport mechanisms to block solute absorption and hence
the water which follows. Depending on their site of action, they produce urine of
varying solute composition and osmolality. The most powerful diuretics are those
which block the Na/K/2Cl symport in the thick ascending limb of the loop of Henle.
This is because 25% of filtered Na is normally reabsorbed here, and because this site
is the driver for the countercurrent multiplier mechanism. Blocking the reabsorption
makes the filtrate osmolality higher and the interstitial osmolality lower, hence
reducing the osmotic gradient for water reabsorption more distally, where the
nephron is permeable. Loop diuretics thus interfere with both the dilution and the
concentration of urine, which reaches very large volumes which are not as hypotonic
as when pure water is drunk and ADH is completely suppressed.
78
Concept Maps for Renal Prac
Map the hydrostatic pressures along the
length of the renal vasculature,
emphasizing the unique sequence of
blood vessel types in the kidney.
Trigger: What are the physical factors which
influence hydrostatic pressure in blood
vessels? How do they produce a differential
between the pressure in the afferent arteriole
and that in the peritubular capillaries?
Map the hydrostatic and osmotic
pressures which affect proximal tubular
reabsorption of salt and water.
Trigger: What are the factors which influence
hydrostatic pressure and osmotic pressure?
How do they interact to affect reabsorption of
salt and water from the proximal tubule via the
interstitium?
79