6.2 the blooD SyStem
Capillaries acivi
Blood fows through tissues in capillaries with permeable bruiss
walls that allow exchange o materials between cells in
the tissue and the blood in the capillary. Bruises are caused by
damage to capillary walls
Capillaries are the narrowest blood vessels with diameter o about and leakage o plasma and
1 0 m. They branch and rejoin repeatedly to orm a capillary network blood cells into spaces
with a huge total length. Capillaries transport blood through almost all between cells in a tissue.
tissues in the body. Two exceptions are the tissues o the lens and the The capillaries are quickly
cornea in the eye which must be transparent so cannot contain any repaired, hemoglobin is
blood vessels. The density o capillary networks varies in other tissues broken down to green and
but all active cells in the body are close to a capillary. yellow bile pigments which
are transported away and
The capillary wall consists o one layer o very thin endothelium cells, phagocytes remove the
coated by a lter-like protein gel, with pores between the cells. The remains o the blood cells
wall is thus very permeable and allows part o the plasma to leak out by endocytosis. When you
and orm tissue fuid. Plasma is the fuid in which the blood cells are next have a bruise, make
suspended. Tissue fuid contains oxygen, glucose and all other substances observations over the days
in blood plasma apart rom large protein molecules, which cannot ater the injury to ollow the
pass through the capillary wall. The fuid fows between the cells in a healing process and the
tissue, allowing the cells to absorb useul substances and excrete waste rate at which hemoglobin
products. The tissue fuid then re-enters the capillary network. is removed.
The permeabilities o capillary walls dier between tissues, enabling
particular proteins and other large particles to reach certain tissues but
not others. Permeabilities can also change over time and capillaries
repair and remodel themselves continually in response to the needs o
tissues that they peruse.
Veins
Veins collect blood at low pressure rom the tissues
o the body and return it to the atria o the heart.
Veins transport blood rom capillary networks back to the atria o the
heart. By now the blood is at much lower pressure than it was in the
arteries. Veins do not thereore need to have as thick a wall as arteries
and the wall contains ar ewer muscle and elastic bres. They can
thereore dilate to become much wider and thus hold more blood
than arteries. Around 80% o a sedentary persons blood is in the veins
though this proportion alls during vigorous exercise.
Blood fow in veins is assisted by gravity and by pressures exerted on them
by other tissues especially skeletal muscles. Contraction makes a muscle
shorter and wider so it squeezes on adjacent veins like a pump. Walking,
sitting or even just dgeting greatly improves venous blood fow.
Each part o the body is served by one or more veins. For example blood
is carried rom the arms in the subclavian veins and rom the head in
the jugular veins. The hepatic portal vein is unusual because it does not
carry blood back to the heart. It carries blood rom the stomach and
intestines to the liver. It is regarded as a portal vein rather than an artery
because the blood it carries is at low pressure so it is relatively thin.
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activity Valves in veins
Stnding on your hed Valves in veins and the heart ensure circulation o blood
by preventing backow.
Pocket valves and vein
walls become less efcient Blood pressure in veins is sometimes so low that there is a danger o
with age, causing poor backfow towards the capillaries and insucient return o blood to the
venous return to the heart. heart. To maintain circulation, veins contain pocket valves, consisting o
Have you ever perormed three cup-shaped faps o tissue.
gymnastic moves such as
headstands or handstands, I blood starts to fow backwards, it gets caught in the faps o the
or experienced very high pocket valve, which ll with blood, blocking the lumen o the vein.
g-orces on a ride at an
amusement park? Young When blood fows towards the heart, it pushes the faps to the
people can mostly do any sides o the vein. The pocket valve thereore opens and blood can
o these activities easily fow reely.
but older people may not
be able to. What is the These valves allow blood to fow in one direction only and make
explanation? ecient use o the intermittent and oten transient pressures provided
by muscular and postural changes. They ensure that blood circulates in
the body rather than fowing to and ro.
Identifying blood vessels
Identication o blood vessels as arteries, capillaries or
veins rom the structure o their walls.
Blood vessels can be identied as arteries, capillaries or veins by looking
at their structure. Table 1 below gives dierences that may be useul.
artery Cpillry Vein
Diameter Larger than 10 m Around 10 m Variable but much
larger than 10 m
Relative Relatively thick Extremely thin wall
thickness wall and narrow Relatively thin
Figure 5 Which veins in this gymnast will o wall and lumen wall with variable
need valves to help with venous return? diameter o but oten wide
lumen lumen
Figure 6 Artery and vein in transverse section. Number o
The tunica externa and tunica intima are layers in wall Three layers, Only one layer the Three layers
stained more darkly than the tunica media. tunica externa, tunica intima which tunica externa,
Clotted blood is visible in both vessels Muscle and media and intima. is an endothelium media and intima
elastic bres These layers may consisting o a
294 in the wall be sub-divided to single layer o very Small amounts
Valves orm more layers thin cells
Abundant None
None None Present in many
veins
Table 1
6.2 the blooD SyStem
The double circulation lungs
pulmonary
There is a separate circulation for the lungs. circulation
There are valves in the veins and heart that ensure a one- way fow, heart
so blood circulates through arteries, capillaries and veins. Fish have a
single circulation. Blood is pumped at high pressure to their gills to be systemic circulation
oxygenated. Ater fowing through the gills the blood still has enough other
pressure to fow directly, but relatively slowly, to other organs o the organs
body and then back to the heart. In contrast, the lungs used by mammals
or gas exchange are supplied with blood by a separate circulation. Figure 7 The double circulation
Blood capillaries in lungs cannot withstand high pressures so blood is
pumped to them at relatively low pressure. Ater passing through the
capillaries o the lungs the pressure o the blood is low, so it must return
to the heart to be pumped again beore it goes to other organs. Humans
thereore have two separate circulations:
the pulmonary circulation, to and rom the lungs
the systemic circulation, to and rom all other organs, including the
heart muscles.
Figure 7 shows the double circulation in a simplied orm. The
pulmonary circulation receives deoxygenated blood that has returned
rom the systemic circulation, and the systemic circulation receives blood
that has been oxygenated by the pulmonary circulation. It is thereore
essential that blood fowing to and rom these two circulations is not
mixed. The heart is thereore a double pump, delivering blood under
dierent pressures separately to the two circulations.
Heart structure semilunar valve aorta
vena cavae pulmonary artery
Recognition of the chambers and valves
of the heart and the blood vessels pulmonary veins
connected to it in dissected hearts or in
diagrams of heart structure. semilunar
valve
The heart has two sides, let and right, that
pump blood to the systemic and pulmonary right atrium atrioventricular
circulations. valve
right ventricle
Each side o the heart has two chambers, septum left ventricle
a ventricle that pumps blood out into the
arteries and an atrium that collects blood rom Figure 8 Structure of the heart
the veins and passes it to the ventricle.
Each side o the heart has two valves, an
atrioventricular valve between the atrium and
the ventricle and a semilunar valve between
the ventricle and the artery.
Oxygenated blood fows into the let side o
the heart through the pulmonary veins rom
the lungs and out through the aorta.
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Deoxygenated blood fows into the let side 4 Left ventricle
o the heart through the vena cava and out in
the pulmonary arteries. Identiy the let ventricle. It has a smooth wall,
with a tree-like pattern o blood vessels. Using a
The heart is a complicated three-dimensional sharp scalpel, make an incision as shown by the
structure. The best way to learn about its structure dashed line X in gure 9. This should open up the
is by doing a dissection. A resh specimen o let ventricle. Look at the thick muscular wall that
a mammalian heart, with blood vessels still you have cut through.
attached, a dissecting dish or board and dissecting
instruments are needed. 5 Atrioventricular valve
1 Arteries and veins Extend the incision urther towards the atrium
i necessary until you can see the two thin faps
Tidy up the blood vessels attached to the heart o the atrioventricular valve. Tendons attached
by removing membranes and other tissue rom to the sides o the let ventricle prevent the valve
around them. Identiy the thick-walled arteries inverting into the atrium.
and the thin-walled veins.
6 Left atrium and pulmonary vein
2 Pulmonary artery and aorta
Identiy the let atrium. It will look surprisingly
Push a glass rod or other blunt-ended instrument small as there is no blood inside it. The outer
into the heart through the arteries and eel surace o its wall has a wrinkled appearance.
through the wall o the heart to where the end Extend the incision that you have already made,
o the rod has reached. Identiy the pulmonary either with the scalpel or with scissors, to cut
artery, through which you will reach the through the wall o the let atrium as ar as the
thinner-walled right ventricle, and the aorta, pulmonary vein. Look at the thin wall o the
through which you will reach the thicker-walled atrium and the opening o the pulmonary vein or
let ventricle. veins (there may be two) .
3 Dorsal and ventral sides 7 Aorta
Lay the heart so that the aorta is behind the Find the aorta again and measure the diameter
pulmonary artery, as in gure 9. The ventral o its lumen, in millimetres. Using scissors, cut
side is now uppermost and the dorsal side through the wall o the aorta, starting at its end
underneath. The dorsal side o an animal is and working towards the let ventricle. Look at
its back. the smooth inner surace o the aorta and try
stretching the wall to see how tough it is.
right aorta 8 Semilunar valve
artrium
pulmonary Where the aorta exits the let ventricle, there
coronary artery will be three cup-shaped faps in the wall. These
artery left atrium orm the semilunar valve. Try pushing a blunt
instrument into the faps to see how blood
Y X fowing backwards pushes the faps together,
closing the valve.
Figure 9 Ventral view of the exterior of the heart
9 Coronary artery
Look careully at the inner surace o the
aorta, near the semilunar valve. A small hole
should be visible, which is the opening to the
coronary arteries. Measure the diameter o the
lumen o this artery. The coronary arteries supply
the wall o the heart with oxygen and nutrients.
296
right ventricle septum left ventricle 6.2 the blooD SyStem
10 Septum
Make a transverse section through the heart
near the base o the ventricles, along the dotted
line marked Y in gure 9. Measure the thickness
in millimetres o the walls o the let and right
ventricles and o the septum between them
(gure 1 0) . The septum contains conducting
bres, which help to stimulate the ventricles
to contract.
Figure 10 Transverse section through the ventricles
Atherosclerosis acivi
Causes and consequences of occlusion of the Srucur nd funcin f
coronary arteries. r
One o the commonest current health problems is atherosclerosis, the Discuss the answers to
development o atty tissue called atheroma in the artery wall adjacent these questions.
to the endothelium. Low density lipoproteins (LDL) containing ats and
cholesterol accumulate and phagocytes are then attracted by signals 1 Why are the walls of the
rom endothelium cells and smooth muscle. The phagocytes engul the atria thinner than the
ats and cholesterol by endocytosis and grow very large. Smooth muscle walls of the ventricles?
cells migrate to orm a tough cap over the atheroma. The artery wall
bulges into the lumen narrowing it and thus impeding blood fow. 2 What prevents the
atrioventricular valve
Small traces o atheroma are normally visible in childrens arteries from being pushed into
by the age o ten, but do not aect health. In some older people the atrium when the
atherosclerosis becomes much more advanced but oten goes ventricle contracts?
unnoticed until a major artery becomes so blocked that the tissues it
supplies become compromised. 3 Why is the left ventricle
wall thicker than the
Coronary occlusion is a narrowing o the arteries that supply blood right ventricle wall?
containing oxygen and nutrients to the heart muscle. Lack o oxygen
(anoxia) causes pain, known as angina, and impairs the muscles 4 Does the left side of the
ability to contract, so the heart beats aster as it tries to maintain heart pump oxygenated
blood circulation with some o its muscle out o action. The brous or deoxygenated blood?
cap covering atheromas sometimes ruptures, which stimulates the
ormation o blood clots that can block arteries supplying blood to the 5 Why does the wall
heart and cause acute heart problems. This is described in sub-topic 6.3. of the heart need its
own supply of blood,
The causes o atherosclerosis are not yet ully understood. Various brought by the coronary
actors have been shown to be associated with an increased risk o arteries?
atheroma but are not the sole causes o the condition:
6 Does the right side
high blood concentrations o LDL (low density lipoprotein) of the heart pump a
greater volume of blood
chronic high blood glucose concentrations, due to overeating, per minute, a smaller
obesity or diabetes volume, or the same
volume as the left?
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activity chronic high blood pressure due to smoking, stress or any
other cause
Crnitine nd coronry
occusion consumption o trans ats, which damage the endothelium
o the artery.
A chemical called carnitine
that is ound in certain oods There are also some more recent theories that include microbes:
is converted into TMAO by
bacteria in the gut. Find inection o the artery wall with Chlamydia pneumoniae
out what oods contain the
highest concentrations production o trimethylamine N-oxide (TMAO) by microbes in
o carnitine and discuss the intestine.
whether this nding should
infuence dietary advice.
Figure 12 The sinoatrial node Figure 11 A normal artery (left) has a much wider lumen than an artery that is
occluded by atheroma (right)
298
The sinoatrial node
The heartbeat is initiated by a group o specialized muscle
cells in the right atrium called the sinoatrial node.
The heart is unique in the body as its muscles can contract without
stimulation rom motor neurons. The contraction is called myogenic,
meaning that it is generated in the muscle itsel. The membrane o a
heart muscle cell depolarizes when the cell contracts and this activates
adjacent cells, so they also contract. A group o cells thereore contracts
almost simultaneously at the rate o the astest.
The region o the heart with the astest rate o spontaneous beating
is a small group o special muscle cells in the wall o the right atrium,
called the sinoatrial node. These cells have ew o the proteins that
cause contraction in other muscle cells, but they have extensive
membranes. The sinoatrial node thereore initiates each heartbeat,
because the membranes o its cells are the frst to depolarize in each
cardiac cycle.
6.2 the blooD SyStem
Initiating the heartbeat
The sinoatrial node acts as a pacemaker.
Because the sinoatrial node initiates each heartbeat, it sets the pace or
the beating o the heart and is oten called the pacemaker. I it becomes
deective, its output may be regulated or even replaced entirely by an
artifcial pacemaker. This is an electronic device, placed under the skin
with electrodes implanted in the wall o the heart that initiate each
heartbeat in place o the sinoatrial node.
Atrial and ventricular contraction Figure 13 Heart monitor displaying the heart
rate, the electrical activity of the heart and the
The sinoatrial node sends out an electrical signal that percentage saturation with oxygen of the blood
stimulates contraction as it is propagated through the
walls o the atria and then the walls o the ventricles.
The sinoatrial node initiates a heartbeat by contracting and simultaneously
sends out an electrical signal that spreads throughout the walls o the atria.
This can happen because there are interconnections between adjacent fbres
across which the electrical signal can be propagated. Also the fbres are
branched so each fbre passes the signal on to several others. It takes less
than a tenth o a second or all cells in the atria to receive the signal. This
propagation o the electrical signal causes the whole o both let and right
atria to contract.
Ater a time delay o about 0.1 seconds, the electrical signal is conveyed
to the ventricles. The time delay allows time or the atria to pump
the blood that they are holding into the ventricles. The signal is then
propagated throughout the walls o the ventricles, stimulating them to
contract and pump blood out into the arteries. Details o the electrical
stimulation o the heartbeat are included in Option D.
TOK
Wa ars r in ica dcisin aking: inn r cnsquncs?
There are some circumstances in which prolonging the lie o an individual
who is sufering brings in to question the role o the physician. Sometimes, an
active pacemaker may be involved in prolonging the lie o a patient and the
physician receives a request to deactivate the device. This will accelerate the
pace o the patients death. Euthanasia involves taking active steps to end the
lie o a patient and it is illegal in many jurisdictions. However, there is a widely
accepted practice o withdrawing lie-sustaining interventions such as dialysis,
mechanical ventilation, or tube eeding rom terminally ill patients. This is oten
a decision o the amily o the patient. The withdrawal o lie support is seen as
distinct rom euthanasia because the patient dies o their condition rather than
the active steps to end the patients lie in the case o euthanasia. However,
the distinction can be subtle. The consequence is the same: the death o the
patient. The intent can be the same: to end the patients sufering. Yet in many
jurisdictions, one action is illegal and the other is not.
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The cardiac cycle
Pressure changes in the left atrium, left ventricle and aorta during the
cardiac cycle.
The pressure changes in the atrium and 0.15 0.4 seconds
ventricle o the heart and the aorta during The pressure in the ventricles rises
a cardiac cycle are shown in gure 1 5 . To
understand them it is necessary to appreciate above the pressure in the arteries so
what occurs at each stage o the cycle. Figure 1 4 the semilunar valves open and blood
below summarizes the events, with timings is pumped rom the ventricles into the
assuming a heart rate o 75 beats per minute. arteries, transiently maximizing the
Typical volumes o blood are shown and also an arterial blood pressure.
indication o the direction o blood fow to or
rom a chamber o the heart. Pressure slowly rises in the atria as
blood drains into them rom the veins
0.0 0.1 seconds and they ll.
The atria contract causing a rapid but
0.4 0.45 seconds
relatively small pressure increase, The contraction o the ventricular muscles
which pumps blood rom the atria
to the ventricles, through the open wanes and pressure inside the ventricles
atrioventricular valves. rapidly drops below the pressure in the
arteries, causing the semilunar valves
The semilunar valves are closed and blood to close.
pressure in the arteries gradually drops to
its minimum as blood continues to fow The atrioventricular valves remain closed.
along them but no more is pumped in.
0.45 0.8 seconds
0.1 0.15 seconds Pressure in the ventricles drops below the
The ventricles contract, with a rapid
pressure in the atria so the atrioventricular
pressure build up that causes the valves open.
atrioventricular valves to close.
Blood rom the veins drains into the atria
The semilunar valves remain closed. and rom there into the ventricles, causing
a slow increase in pressure.
vein
atrium atrium 25 ml atrium relaxing 45 ml
contracts atrium relaxing atrioventricular valve
25 ml atrioventricular valve open
atrioventricular valve valve open closed ventricle relaxing
ventricle
ventricle ventricle semilunar valve closed
relaxing contracting 70 ml
semilunar valve valve closed valve open
artery diastolic systolic diastolic
tissues of the body 0.1 0.15 0.4 0.45 0.8
0 time (seconds)
Figure 14 One cardiac cycle is represented on the diagram, starting on the let with contraction o the atrium. Vertical
arrows show fows o blood to and rom the atrium and ventricle
300
6.2 the blooD SyStem
D-sd qusins: Heart action and blood pressures
Figure 1 5 shows the pressures in the atrium,
ventricle and artery on one side o the heart,
during one second in the lie o the heart.
1 Deduce when blood is being pumped pressure /mm Hg ventricle
rom the atrium to the ventricle. Give both 120
100
the start and the end times. [2] artery
2 Deduce when the ventricle starts to contract. [1 ]
3 The atrioventricular valve is the valve 80
between the atrium and the ventricle. State 60
when the atrioventricular valve closes. [1 ] 40
4 The semilunar valve is the valve between
the ventricle and the artery. S tate when
the semilunar valve opens. [1 ]
5 Deduce when the semilunar valve closes. [1 ]
6 Deduce when blood is being pumped 20 atrium
rom the ventricle to the artery. Give 0
both the start and the end times. [2]
7 Deduce when the volume o blood in the 20
ventricle is: 0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8
a) at a maximum [1 ] time /s
b) at a minimum. [1 ]
Figure 15 Pressure changes during the cardiac cycle
Changing the heart rate acivi
The heart rate can be increased or decreased by impulses lisning r sunds
brought to the heart through two nerves rom the medulla
o the brain. Sounds produced by blood
fow can be heard with a
The sinoatrial node that sets the rhythm or the beating o the heart simple tube or stethoscope
responds to signals rom outside the heart. These include signals rom placed on the chest near the
branches o two nerves originating in a region in the medulla o the heart. The consequences
brain called the cardiovascular centre. Signals rom one o the nerves o this whole cardiac cycle
cause the pacemaker to increase the requency o heartbeats. In or the fow o blood out o
healthy young people the rate can increase to three times the resting the heart can be elt as the
rate. Signals rom the other nerve decrease the rate. These two nerve pulse in a peripheral artery.
branches act rather like the throttle and brake o a car.
(a)
The cardiovascular centre receives inputs rom receptors that monitor
blood pressure and its pH and oxygen concentration. The pH o the (b)
blood refects its carbon dioxide concentration.
Figure 16 Taking the pulse: (a)
Low blood pressure, low oxygen concentration and low pH all radial pulse (b) carotid pulse
suggest that the heart rate needs to speed up, to increase the fow
rate o blood to the tissues, deliver more oxygen and remove more
carbon dioxide.
High blood pressure, high oxygen concentration and high pH are all
indicators that the heart rate may need to slow down.
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16 H U MC EALNLPBHIYOSLIOOGLYO G Y
Figure 17 Adventure sports such as rock Epinephrine
climbing cause epinephrine secretion
Epinephrine increases the heart rate to prepare or
vigorous physical activity.
The sinoatrial node also responds to epinephrine in the blood,
by increasing the heart rate. This hormone is also sometimes
called adrenalin and is produced by the adrenal glands. The
secretion o epinephrine is controlled by the brain and rises
when vigorous physical activity may be necessary because o a
threat or opportunity. S o epinephrine has the nickname ght or
fight hormone.
In the past when humans were hunter-gatherers rather than armers,
epinephrine would have been secreted when humans were hunting
or prey or when threatened by a predator. In the modern world
athletes oten use pre-race routines to stimulate adrenalin secretion
so that their heart rate is already increased when vigorous physical
activity begins.
6.3 Defence against infectious disease
Understanding Applications
The skin and mucous membranes orm a Causes and consequences o blood clot
primary deence against pathogens that cause ormation in coronary arteries.
inectious disease.
Efects o HIV on the immune system and
Cuts in the skin are sealed by blood clotting. methods o transmission.
Clotting actors are released rom platelets. Florey and Chains experiments to test penicillin
on bacterial inections in mice.
The cascade results in the rapid conversion o
brinogen to brin by thrombin. Nature of science
Ingestion o pathogens by phagocytic white Risks associated with scientic research:
blood cells gives non-specic immunity to Florey and Chains tests on the saety o
diseases. penicillin would not be compliant with current
protocols on testing.
Production o antibodies by lymphocytes in
response to particular pathogens gives specic
immunity.
Antibiotics block processes that occur in
prokaryotic cells but not in eukaryotic cells.
Viral diseases cannot be treated using
antibiotics because they lack a metabolism.
Some strains o bacteria have evolved with
genes which coner resistance to antibiotics
and some strains o bacteria have multiple
resistance.
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6.3 DeFenCe againSt inFeCtiouS DiSeaSe
Skin as a barrier to infection Figure 1 Scanning electron micrograph of
bacteria on the surface of teeth. Mucous
The skin and mucous membranes orm a primary deence membranes in the mouth prevent these and
against pathogens that cause inectious disease. other microbes from invading body tissues
There are many different microbes in the environment that can grow acvy
inside the human body and cause a disease. Some microorganisms
are opportunistic and although they can invade the body they also im hm sk
commonly live outside it. Others are specialized and can only survive
inside a human body. Microbes that cause disease are called pathogens. A digital microscope can be
used to produce images o
The primary defence of the body against pathogens is the skin. Its the diferent types o skin
outermost layer is tough and provides a physical barrier against the covering the human body.
entry of pathogens and protection against physical and chemical Figure 2 shows our images
damage. Sebaceous glands are associated with hair follicles and they produced in this way.
secrete a chemical called sebum, which maintains skin moisture and
slightly lowers skin pH. The lower pH inhibits the growth of bacteria
and fungi.
Mucous membranes are a thinner and softer type of skin that is found in
areas such as the nasal passages and other airways, the head of the penis
and foreskin and the vagina. The mucus that these areas of skin secrete
is a sticky solution of glycoproteins. Mucus acts as a physical barrier;
pathogens and harmful particles are trapped in it and either swallowed
or expelled. It also has antiseptic properties because of the presence of
the anti-bacterial enzyme lysozyme.
Cuts and clots
Cuts in the skin are sealed by blood clotting.
When the skin is cut, blood vessels in it are severed and start to bleed.
The bleeding usually stops after a short time because of a process called
clotting. The blood emerging from a cut changes from being a liquid to
a semi-solid gel. This seals up the wound and prevents further loss of
blood and blood pressure. Clotting is also important because cuts breach
the barrier to infection provided by the skin. Clots prevent entry of
pathogens until new tissue has grown to heal the cut.
platelets and blood clotting
Clotting actors are released rom platelets.
Blood clotting involves a cascade of reactions, each of which produces
a catalyst for the next reaction. As a result blood clots very rapidly. It is
important that clotting is under strict control, because if it occurs inside
blood vessels the resulting clots can cause blockages.
The process of clotting only occurs if platelets release clotting factors.
Platelets are cellular fragments that circulate in the blood. They are
smaller than either red or white blood cells. When a cut or other injury
involving damage to blood vessels occurs, platelets aggregate at the site
forming a temporary plug. They then release the clotting factors that
trigger off the clotting process.
Figure 2
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61 H u mC EaLnLpBHIyOsLiOoGlYo g y
Fibrin production
platelets red blood cell The cascade results in the rapid conversion o fbrinogen
to fbrin by thrombin.
lymphocyte phagocyte
The cascade o reactions that occurs ater the release o clotting actors
Figure 3 Cells and cell ragments rom rom platelets quickly results in the production o an enzyme called
blood. Lymphocytes and phagocytes thrombin. Thrombin in turn converts the soluble protein fbrinogen
are types o white blood cell into the insoluble fbrin. The fbrin orms a mesh in cuts that traps more
platelets and also blood cells. The resulting clot is initially a gel, but i
exposed to the air it dries to orm a hard scab.
Figure 4 shows red blood cells trapped in this fbrous mesh.
Coronary thrombosis
Causes and consequences o blood clot ormation in
coronary arteries.
In patients with coronary heart disease, blood clots sometimes orm
in the coronary arteries. These arteries branch o rom the aorta close
to the semilunar valve. They carry blood to the wall o the heart,
supplying the oxygen and glucose needed by cardiac muscle fbres or cell
respiration. The medical name or a blood clot is a thrombus. Coronary
thrombosis is the ormation o blood clots in the coronary arteries.
Figure 4 Scanning electron I the coronary arteries become blocked by a blood clot, part o the
micrograph o clotted blood with heart is deprived o oxygen and nutrients. Cardiac muscle cells are
fbrin and trapped blood cells then unable to produce sufcient ATP by aerobic respiration and their
contractions become irregular and uncoordinated. The wall o the
heart makes quivering movements called fbrillation that do not pump
blood eectively. This condition can prove atal unless it resolves
naturally or through medical intervention.
Atherosclerosis causes occlusion in the coronary arteries. Where
atheroma develops the endothelium o the arteries tends to become
damaged and roughened; especially, the artery wall is hardened by
deposition o calcium salts. Patches o atheroma sometimes rupture
causing a lesion. Coronary occlusion, damage to the capillary
epithelium, hardening o arteries and rupture o atheroma all increase
the risk o coronary thrombosis.
There are some well-known actors that are correlated with an
increased risk o coronary thrombosis and heart attacks:
smoking
high blood cholesterol concentration
high blood pressure
diabetes
Figure 5 Early intervention during a obesity
heart attack can save the patients lie
so it is important to know what to do by lack o exercise.
being trained
O course correlation does not prove causation, but doctors
nonetheless advise patients to avoid these risk actors i possible.
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6.3 DeFenCe againSt inFeCtiouS DiSeaSe
phagocytes
Ingestion o pathogens by phagocytic white blood cells
gives non-specifc immunity to diseases.
I microorganisms get past the physical barriers o skin and mucous
membranes and enter the body, white blood cells provide the next line
o deence. There are many dierent types o white blood cell. Some are
phagocytes that squeeze out through pores in the walls o capillaries and
move to sites o inection. There they engul pathogens by endocytosis
and digest them with enzymes rom lysosomes. When wounds become
inected, large numbers o phagocytes are attracted, resulting in the
ormation o a white liquid called pus.
Antibody roduction Figure 6 Avian infuenza viruses. In this
electron micrograph o a virus in transverse
Production o antibodies by lymphocytes in response to section, alse colour has been used to
particular pathogens gives specifc immunity. distinguish the protein coat that is recognized
as antigens by the immune system (purple)
I microorganisms get past the physical barriers o the skin and invade rom the DNA o the virus (green)
the body, proteins and other molecules on the surace o pathogens are
recognized as oreign by the body and they stimulate a specifc immune
response. Any chemical that stimulates an immune response is reerred
to as an antigen. The specifc immune response is the production o
antibodies in response to a particular pathogen. The antibodies bind to
an antigen on that pathogen.
Antibodies are produced by types o white blood cell called lymphocytes.
Each lymphocyte produces j ust one type o antibody, but our bodies
can produce a vast array o dierent antibodies. This is because we have
small numbers o lymphocytes or producing each o the many types o
antibody. There are thereore too ew lymphocytes initially to produce
enough antibodies to control a pathogen that has not previously inected
the body. However, antigens on the pathogen stimulate cell division o
the small group o lymphocytes that produce the appropriate type o
antibody. A large clone o lymphocytes called plasma cells are produced
within a ew days and they secrete large enough quantities o the
antibody to control the pathogen and clear the inection.
Antibodies are large proteins that have two unctional regions: a hyper-
variable region that binds to a specifc antigen and another region
that helps the body to fght the pathogen in one o a number o ways,
including these:
making a pathogen more recognizable to phagocytes so they are
more readily enguled
preventing viruses rom docking to host cells so that they cannot
enter the cells.
Antibodies only persist in the body or a ew weeks or months and
the plasma cells that produce them are also gradually lost ater the
inection has been overcome and the antigens associated with it are no
longer present. However, some o the lymphocytes produced during an
inection are not active plasma cells but instead become memory cells
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61 H u mC EaLnLpBHIyOsLiOoGlYo g y
that are very long-lived. These memory cells remain inactive unless
the same pathogen inects the body again, in which case they become
active and divide to produce plasma cells very rapidly. Immunity to an
inectious disease involves either having antibodies against the pathogen,
or memory cells that allow rapid production o the antibody.
Human immunodefciency virus
Efects o HIV on the immune system and methods o transmission.
The production o antibodies by the immune diseases or the latter stages o HIV inection, or
system is a complex process and includes dierent example Kaposis sarcoma. A collection o several
types o lymphocyte, including helper T- cells. The diseases or conditions existing together is called
human immunodefciency virus (HIV) invades a syndrome. When the syndrome o conditions
and destroys helper T-cells. The consequence due to HIV is present, the person is said to have
is a progressive loss o the capacity to produce acquired immune defciency syndrome (AIDS) .
antibodies. In the early stages o inection, the
immune system makes antibodies against HIV. I AIDS spreads by HIV inection. The virus only
these can be detected in a persons body, they are survives outside the body or a short time and
said to be HIV- positive. inection normally only occurs i there is blood
to blood contact between inected and uninected
HIV is a retrovirus that has genes made o RNA people. There are various ways in which this
and uses reverse transcriptase to make DNA copies can occur:
o its genes once it has entered a host cell. The
rate at which helper T-cells are destroyed by HIV sexual intercourse, during which abrasions
varies considerably and can be slowed down by to the mucous membranes o the penis and
using anti-retroviral drugs. In most HIV- positive vagina can cause minor bleeding
patients antibody production eventually becomes
so ineective that a group o opportunistic transusion o inected blood, or blood
inections strike, which would be easily ought products such as Factor VIII
o by a healthy immune system. Several o
these are normally so rare that they are marker sharing o hypodermic needles by intravenous
drug users.
Figure 7 Fleming's petri dish which frst Antibiotics
showed the inhibition o bacterial growth by
penicillin rom a mycelium o Penicillium Antibiotics block processes that occur in prokaryotic cells
but not in eukaryotic cells.
An antibiotic is a chemical that inhibits the growth o microorganisms.
Most antibiotics are antibacterial. They block processes that occur
in prokaryotes but not in eukaryotes and can thereore be used to
kill bacteria inside the body without causing harm to human cells.
The processes targeted by antibiotics are bacterial DNA replication,
transcription, translation, ribosome unction and cell wall ormation.
Many antibacterial antibiotics were discovered in saprotrophic ungi.
These ungi compete with saprotrophic bacteria or the dead organic
matter on which they both eed. By secreting antibacterial antibiotics,
saprotrophic ungi inhibit the growth o their bacterial competitors. An
example is penicillin. It is produced by some strains o the Penicillium
ungus, but only when nutrients are scarce and competition with
bacteria would be harmul.
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6.3 DeFenCe againSt inFeCtiouS DiSeaSe
Testing penicillin acvy
Florey and Chains experiments to test penicillin on Wrld aiDS Dy
bacterial inections in mice.
The red AIDS awareness
Howard Florey and Ernst Chain ormed a research team in Oxord ribbon is an international
in the late 1 930s that investigated the use o chemical substances symbol oawareness and
to control bacterial inections. The most promising o these was support or those living with
penicillin, discovered by Alexander Fleming in 1 928. Florey and HIV. It is worn on World AIDS
C hains team developed a method o growing the ungus Penicillium Day each year December 1st.
in liquid culture in conditions that stimulated it to secrete penicillin.
They also developed methods or producing reasonably pure samples Are you aware how many
o penicillin rom the cultures. people in your area are
afected and what can be
The penicillin killed bacteria on agar plates, but they needed to done to support them?
test whether it would control bacterial inections in humans. They
frst tested it on mice. Eight mice were deliberately inected with
Streptococcus bacteria that cause death rom pneumonia. Four o the
inected mice were given injections with penicillin. Within 24 hours
all the untreated mice were dead but the our given penicillin were
healthy. Florey and C hain decided that they should next do tests on
human patients, which required much larger quantities.
When enough penicillin had been produced, a 43 -year-old policeman
was chosen or the frst human test. He had an acute and lie-
threatening bacterial inection caused by a scratch on the ace rom
a thorn on a rose bush. He was given penicillin or our days and his
condition improved considerably, but supplies o penicillin ran out and
he suered a relapse and died rom the inection.
Larger quantities o penicillin were produced and fve more patients
with acute inections were tested. All were cured o their inections,
but sadly one o them died. He was a small child who had an inection
behind the eye. This had weakened the wall o the artery carrying
blood to the brain and although cured o the inection, the child died
suddenly o brain hemorrhage when the artery burst.
Pharmaceutical companies in the United States then began to produce
penicillin in much larger quantities, allowing more extensive testing,
which confrmed that it was a highly eective treatment or many
previously incurable bacterial inections.
Figure 8 Penicillin the green ball represents a variable part of the molecule 307
16 H u mC EaLnLpBHIyOsLiOoGlYo g y
penicillin and drug testing
Risks associated with scientifc research: Florey and Chains tests on the saety o
penicillin would not be compliant with current protocols on testing.
When any new drug is introduced there are risks drug today with the methods that they used
that it will prove to be ineffective in some or all for penicillin. They tested the drug on human
patients or that it will cause harmful side effects. patients after only a very brief period of animal
These risks are minimized by strict protocols that testing. Penicillin was a new type of drug and
pharmaceutical companies must follow. Initial there could easily have been severe side effects.
tests are performed on animals and then on small Also the samples that they were using were not
numbers of healthy humans. Only if a drug passes pure and there could have been side effects from
these tests is it tested on patients with the disease the impurities.
that the drug is intended to treat. The last tests
involve very large numbers of patients to test On the other hand, the patients that they used
whether the drug is effective in all patients and were all on the point of death and several
to check that there are no severe or common were cured of their infections as a result of the
side effects. experimental treatment. Because of expeditious
testing with greater risk-taking than would now
There are some famous cases of drugs causing be allowed, penicillin was introduced far more
problems during testing or after release. quickly than would be possible today. D uring the
D-day landings in June 1 944 penicillin was used to
Thalidomide was introduced in the 1 950s treat wounded soldiers and the number of deaths
as a treatment for various mild conditions from bacterial infection was greatly reduced.
but when it was found to relieve morning
sickness in pregnant women it was prescribed
for that purpose. The side effects of the
drug on the fetus had not been tested and
more than 1 0,000 children were born with
birth deformities before the problem was
recognized.
In 2006 six healthy volunteers were given
TGN1 41 2, a new protein developed for
treatment of autoimmune diseases and
leukemia. All six rapidly became very ill and
suffered multiple organ failure. Although the
volunteers recovered, they may have suffered
long-term damage to their immune systems.
It is very unlikely that Florey and Chain would Figure 9 Wounded US troops on Omaha beach 6 June 1944
have been allowed to carry out tests on a new
Viruses and antibiotics
Viral diseases cannot be treated using antibiotics because
they lack a metabolism.
Viruses are non-living and can only reproduce when they are inside
living cells. They use the chemical processes of a living host cell,
instead of having a metabolism of their own. They do not have their
own means of transcription or protein synthesis and they rely on the
308
6.3 DeFenCe againSt inFeCtiouS DiSeaSe
host cells enzymes or ATP synthesis and other metabolic pathways. acvy
These processes cannot be targeted by drugs as the host cell would also
be damaged. Dssh bw
bcrl d vrl fcs
All o the commonly used antibiotics such as penicillin, streptomycin,
chloramphenicol and tetracycline control bacterial inections and are How can a doctor distinguish
not eective against viruses. Not only is it inappropriate or doctors to between bacterial and
prescribe them or a viral inection, but it contributes to the overuse o viral infections, without
antibiotics and increases in antibiotic resistance in bacteria. prescribing an antibiotic
and seeing if it cures the
There are a ew viral enzymes which can be used as targets or drugs to infection?
control viruses without harming the host cell. Only a ew drugs have
been discovered or developed to control viruses in this way. These are
known as antivirals rather than antibiotics.
Resistance to antibiotics Figure 10 Many viruses cause
a common cold. Children lack
Some strains of bacteria have evolved with genes which immunity to most of them
confer resistance to antibiotics and some strains of so frequently catch a cold.
bacteria have multiple resistance. Antibiotics do not cure them
In 201 3 the governments chie medical ofcer or England, Sally Davies,
said this:
The danger posed by growing resistance to antibiotics should be ranked
along with terrorism on a list of threats to the nation. If we dont take
action, then we may all be back in an almost 1 9th-century environment
where infections kill us as a result of routine operations. We wont be
able to do a lot of our cancer treatments or organ transplants.
The development o resistance to antibiotics by natural selection is
described in sub-topic 5.2. Strains o bacteria with resistance are usually
discovered soon ater the introduction o an antibiotic. This is not o
huge concern unless a strain develops multiple resistance, or example
methicillin-resistant Staphylococcus aureus ( MRS A) which has inected the
blood or surgical wounds o hospital patients and resists all commonly
used antibiotics. Another example o this problem is multidrug-resistant
tuberculosis (MDR-TB) . The WHO has reported more than 300,000 cases
worldwide per year with the disease reaching epidemic proportions in
some areas.
Antibiotic resistance is an avoidable problem. These measures are
required:
doctors prescribing antibiotics only or serious bacterial inections
patients completing courses o antibiotics to eliminate inections
completely
hospital sta maintaining high standards o hygiene to prevent cross-
inection
armers not using antibiotics in animal eeds to stimulate growth
pharmaceutical companies developing new types o antibiotic no
new types have been introduced since the 1 980s.
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Data-based questions: Antibiotic resistance b) Suggest a reason or the pattern shown. [2]
Bacterial resistance to antibiotics is a direct 2 Calculate the percentage dierence in [2]
consequence o the overuse o these drugs. In antibiotic resistance between 2002 and
the USA, currently more than hal o the doctor 1992.
visits or upper respiratory tract inections (URIs)
are prescribed antibiotics, despite knowledge that 3 Evaluate the claim that reduction in the
most URIs are caused by viruses.
In the early 1 990s, Finnish public health use o erythromycin has led to a reduction
authorities began discouraging the use o the
antibiotic erythromycin or URIs in response to in the incidence o antibiotic resistance in
rising bacterial resistance to the antibiotic, and
the national erythromycin consumption per S. pyogenes. [3]
capita dropped by 43 per cent.
% antibiotic resistance20
The data in fgure 1 1 shows the incidence in 19 9 215
Finland, over a 1 0-year period, o Streptococcus 19 9 310
pyogenes strains that are resistant to the antibiotic 19 9 45
erythromycin. S. pyogenes is responsible or the 19 9 50
condition known as strep throat. 19 9 6
19 97
19 9 8
19 9 9
2000
2001
2002
1 a) Describe the pattern o erythromycin year
resistance over the period rom 1 992 Figure 11 The incidence of Streptococcus
pyogenes strains that are resistant to the
to 2002. [3] antibiotic erythromycin over a 10-year period
in Finland
6.4 gas exchane
Understanding Applications
Ventilation maintains concentration gradients External and internal intercostal muscles,
o oxygen and carbon dioxide between air in and diaphragm and abdominal muscles as
alveoli and blood fowing in adjacent capillaries. examples o antagonistic muscle action.
Type I pneumocytes are extremely thin alveolar Causes and consequences o lung cancer.
cells that are adapted to carry out gas exchange. Causes and consequences o emphysema.
Type II pneumocytes secrete a solution Skills
containing suractant that creates a moist
surace inside the alveoli to prevent the sides Monitoring o ventilation in humans at rest and
o the alveolus adhering to each other by ater mild and vigorous exercise. (Practical 6)
reducing surace tension.
Nature of science
Air is carried to the lungs in the trachea and
bronchi and then to the alveoli in bronchioles. Obtain evidence or theories: epidemiological
studies have contributed to our understanding
Muscle contractions cause the pressure o the causes o lung cancer.
changes inside the thorax that orce air in and
out o the lungs to ventilate them.
Dierent muscles are required or inspiration
and expiration because muscles only do work
when they contract.
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6.4 gaS exChange
Ventilation
Ventilation maintains concentration gradients o oxygen
and carbon dioxide between air in alveoli and blood
fowing in adjacent capillaries.
All organisms absorb one gas rom the environment and release a
dierent one. This process is called gas exchange. Leaves absorb carbon
dioxide to use in photosynthesis and release the oxygen produced by this
process. Humans absorb oxygen or use in cell respiration and release the
carbon dioxide produced by this process. Terrestrial organisms exchange
gases with the air. In humans gas exchange occurs in small air sacs called
alveoli inside the lungs (gure 1 ) .
type I pneumocytes
in alveolus wall
phagocyte
100 m
network of blood type II pneumocytes
capillaries in alveolus wall
Figure 1
Gas exchange happens by diusion between air in the alveoli and
blood fowing in the adjacent capillaries. The gases only diuse because
there is a concentration gradient: the air in the alveolus has a higher
concentration o oxygen and a lower concentration o carbon dioxide
than the blood in the capillary. To maintain these concentration
gradients resh air must be pumped into the alveoli and stale air must be
removed. This process is called ventilation.
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Data-based questions: Concentration gradients
Figure 2 shows the typical composition o 1 Explain why the oxygen concentration in
atmospheric air, air in the alveoli and gases the alveoli is not as high as in resh air that is
dissolved in air returning to the lungs in the inhaled. [2]
pulmonary arteries. oxygen 2 a) Calculate the dierence in oxygen
concentration between air in the alveolus
700 carbon dioxide and blood arriving at the alveolus. [1 ]
nitrogen
600 598 570 570 565 b) Deduce the process caused by this [1 ]
concentration dierence.
partial pressure /mm Hg 500 c) (i) Calculate the dierence in carbon
400 dioxide concentration between air
inhaled and air exhaled. [1 ]
300 (ii) Explain this dierence. [2]
200 159 120 d) Despite the high concentration o
27
100 105 nitrogen in air in alveoli, little or none
3 40
40 45 diuses rom the air to the blood. Suggest
0 air in alveoli
atmospheric air blood travelling air exhaled reasons or this. [2]
that is inhaled to alveoli
Figure 2 Partial pressures of gases in the pulmonary system
Ventilation experiments
Monitoring of ventilation in humans at rest and after mild and vigorous exercise.
(Practical 6)
In an investigation o the eect o exercise on Either or both o these can be the dependent
ventilation, the type or intensity o exercise is variable in an investigation o the eect o
the independent variable and the ventilation exercise on ventilation rate. They should be
parameter that is measured is the dependent measured ater carrying on an activity or long
variable. enough to reach a constant rate. The example
methods given below include a simple and a more
A simple approach or the independent advanced technique that could be used or the
variable is to choose levels o activity ranging investigation.
rom inactive to very active, such as lying
down, sitting and standing, walking, jogging 1 Ventilation rate
and sprinting. A more quantitative approach is The most straightorward way to measure
to do the same activity at dierent measured ventilation rate is by simple observation.
rates, or example running at dierent speeds Count the number o times air is exhaled
on a treadmill. This allows the ventilation or inhaled in a minute. Breathing should
parameters to be correlated with work rate in be maintained at a natural rate, which is
joules per minute during exercise. as slow as possible without getting out o
breath.
Ventilation o the lungs is carried out by drawing
some resh air into the lungs and then expelling Ventilation rate can also be measured
some o the stale air rom the lungs. The volume by data logging. An infatable chest belt
o air drawn in and expelled is the tidal volume. is placed around the thorax and air is
The number o times that air is drawn in or pumped in with a bladder. A dierential
expelled per minute is the ventilation rate. pressure sensor is then used to measure
312
6.4 gaS exChange
pressure variations inside the belt due to To ensure that the experimental design is
chest expansions. The rate o ventilations rigorous, all variables apart rom the independent
can be deduced and the relative size o and dependent variables should be kept constant.
ventilations may also be recorded. Ventilation parameters should be measured
several times at all levels o exercise with each
2 Tidal volume person in the trial. As many dierent people as
possible should be tested.
Simple apparatus is shown in gure 3.
One normal breath is exhaled through bell jar with
the delivery tube into a vessel and the graduations
volume is measured. It is not sae to use
this apparatus or repeatedly inhaling and delivery tube
exhaling air as the CO2 concentration will pneumatic trough
rise too high.
Figure 3
Specially designed spirometers are
available or use with data logging. They
measure fow rate into and out o the
lungs and rom these measurements lung
volumes can be deduced.
Type I pneumocytes bronchiole
Type I pneumocytes are extremely thin alveolar cells that 0.25 mm a l ve o l u s
are adapted to carry out gas exchange.
The lungs contain huge numbers o alveoli with a very large total surace
area or diusion. The wall o each alveolus consists o a single layer o
cells, called the epithelium. Most o the cells in this epithelium are Type
I pneumocytes. They are fattened cells, with the thickness o only about
0.1 5 m o cytoplasm.
The wall o the adjacent capillaries also consists o a single layer o very
thin cells. The air in the alveolus and the blood in the alveolar capillaries
are thereore less than 0.5 m apart. The distance over which oxygen
and carbon dioxide has to diuse is thereore very small, which is an
adaptation to increase the rate o gas exchange.
Type II pneumocytes epithelium of
alveolus wall
Type II pneumocytes secrete a solution containing nucleus of
surfactant that creates a moist surface inside the alveoli epithelium cell
to prevent the sides of the alveolus adhering to each other
by reducing surface tension. basement membrane
Type II pneumocytes are rounded cells that occupy about 5 % o the endothelium of capillary
alveolar surace area. They secrete a fuid which coats the inner surace a l veo l u s
o the alveoli. This lm o moisture allows oxygen in the alveolus to
dissolve and then diuse to the blood in the alveolar capillaries. It also blood plasma
provides an area rom which carbon dioxide can evaporate into the air erythrocyte
and be exhaled.
1 m
Figure 4 Structure of alveoli
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air in alveolus water The fuid secreted by the Type II pneumocytes contains
surface a pulmonary suractant. Its molecules have a structure
monolayer of similar to that o phospholipids in cell membranes.
su rfa cta n t They orm a monolayer on the surace o the moisture
lining the alveoli, with the hydrophilic heads acing
Figure 5 Pulmonary suractant molecules on the surace o the the water and the hydrophobic tails acing the air. This
flm o moisture lining the alveoli reduces the surace tension and prevents the water
rom causing the sides o the alveoli to adhere when
trachea air is exhaled rom the lungs. This helps to prevent
collapse o the lung.
intercostal muscle
Premature babies are oten born with insucient
pulmonary suractant and can suer rom inant
respiratory distress syndrome. Treatment involves
giving the baby oxygen and also one or more doses
o suractant, extracted rom animal lungs.
right bronchus
right lung bronchioles Airways for ventilation
ribs
diaphragm Air is carried to the lungs in the trachea
and bronchi and then to the alveoli in
Figure 6 The ventilation system bronchioles.
(a) inspiration ver tebra l Air enters the ventilation system through the nose or
ribs column mouth and then passes down the trachea. This has
rings o cartilage in its wall to keep it open even when
diaphragm ribs air pressure inside is low or pressure in surrounding
tissues is high. The trachea divides to orm two
bronchi, also with walls strengthened with cartilage.
One bronchus leads to each lung.
Inside the lungs the bronchi divide repeatedly to
orm a tree-like structure o narrower airways, called
bronchioles. The bronchioles have smooth muscle
bres in their walls, allowing the width o these airways
to vary. At the end o the narrowest bronchioles are
groups o alveoli, where gas exchange occurs.
(b) expiration air movement pressure changes during ventilation
ribcage movement
Figure 7 Ventilation o the lungs diaphragm movement Muscle contractions cause the pressure
changes inside the thorax that force air in
and out ofthe lungs to ventilate them.
Ventilation o the lungs involves some basic physics.
I particles o gas spread out to occupy a larger
volume, the pressure o the gas becomes lower.
C onversely, i a gas is compressed to occupy a smaller
volume, the pressure rises. I gas is ree to move, it
will always fow rom regions o higher pressure to
regions o lower pressure.
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6.4 gaS exChange
During ventilation, muscle contractions cause the pressure inside the
thorax to drop below atmospheric pressure. As a consequence, air is
drawn into the lungs rom the atmosphere (inspiration) until the lung
pressure has risen to atmospheric pressure. Muscle contractions then
cause pressure inside the thorax to rise above atmospheric, so air is
orced out rom the lungs to the atmosphere (expiration) .
Antagonistic muscles Figure 8 Diferent muscles are used or bending
the leg at the knee and or the opposite
Dierent muscles are required or inspiration and expiration movement o straightening it
because muscles only do work when they contract.
Muscles can be in two states: contracting and relaxing.
Muscles do work when they contract by exerting a pulling orce
(tension) that causes a particular movement. They become shorter
when they do this.
Muscles lengthen while they are relaxing, but this happens passively
they do not lengthen themselves. Most muscles are pulled into an
elongated state by the contraction o another muscle. They do not exert
a pushing orce (compression) while relaxing so do no work at this time.
Muscles thereore can only cause movement in one direction. I
movement in opposite directions is needed at dierent times, at least
two muscles will be required. When one muscle contracts and causes a
movement, the second muscle relaxes and is elongated by the frst. The
opposite movement is caused by the second muscle contracting while
the frst relaxes. When muscles work together in this way they are
known as an antagonistic pair o muscles.
Inspiration and expiration involve opposite movements, so dierent
muscles are required, working as antagonistic pairs.
Antagonistic muscle action in ventilation
External and internal intercostal muscles, and diaphragm and abdominal muscles
as examples o antagonistic muscle action.
Ventilation involves two pairs o opposite movements that change the volume and thereore the
pressure inside the thorax:
Diaphragm isprto eprto
Ribcage Moves downwards and fattens Moves upwards and becomes more domed
Moves upwards and outwards Moves downwards and inwards
Antagonistic pairs o muscles are needed to cause these movements.
Volume and pressure isprto eprto
changes
The volume inside the thorax The volume inside the thorax decreases and
increases and consequently the consequently the pressure increases
pressure decreases
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Movement Diaphragm The diaphragm contracts and so it The diaphragm relaxes so it can be pushed
upwards into a more domed shape
of the moves downwards and pushes the
diaphragm abdomen wall out
Abdomen Muscles in the abdomen wall relax Muscles in the abdomen wall contract pushing
wall allowing pressure from the diaphragm the abdominal organs and diaphragm upwards
muscles to push it out
M o ve m e n t External The external intercostal muscles The external intercostal muscles relax and are
of the intercostal contract, pulling the ribcage upwards pulled back into their elongated state.
ribcage muscles and outwards
The internal intercostal muscles contract, pulling
Internal The internal intercostal muscles the ribcage inwards and downwards
intercostal relax and are pulled back into their
muscles elongated state
Epidemiology
Obtain evidence for theories: epidemiological studies have contributed to our
understanding of the causes of lung cancer.
Epidemiology is the study o the incidence and also have an eect on the incidence. They can
causes o disease. Most epidemiological studies are cause spurious associations between a disease
observational rather than experimental because and a actor that does not cause it. For example,
it is rarely possible to investigate the causes o an association has repeatedly been ound by
disease in human populations by carrying out epidemiologists between leanness and an increased
experiments. risk o lung cancer. C areul analysis showed that
among smokers leanness is not signifcantly
As in other felds o scientifc research, theories associated with an increased risk. Smoking reduces
about the causes o a disease are proposed. To appetite and so is associated with leanness and
obtain evidence or or against a theory, survey data o course smoking is a cause o lung cancer. This
is collected that allows the association between explains the spurious association between leanness
the disease and its theoretical cause to be tested. and lung cancer.
For example, to test the theory that smoking
causes lung cancer, the smoking habits o people To try to compensate or conounding actors it is
who have developed lung cancer and people usually necessary to collect data on many actors
who have not are needed. Examples o very large apart rom the one being investigated. This allows
epidemiological surveys that provided strong statistical procedures to be carried out to take
evidence or a link between smoking and lung account o conounding actors and try to isolate
cancer are included in sub-topic 1 .6. the eect o single actors. Age and sex are almost
always recorded and sometimes epidemiological
A correlation between a risk actor and a disease surveys include only males or emales or only
does not prove that the actor causes the disease. people in a specifc age range.
There are usually conounding actors which
Causes of lung cancer
Causes and consequences of lung cancer.
Lung cancer is the most common cancer in the general causes o cancer are described in sub-
world, both in terms o the number o cases and topic 1 .6. The specifc causes o lung cancer are
the number o deaths due to the disease. The considered here.
316
6.4 gaS exChange
and smoke rom burning coal, wood or other
organic matter.
Radon gas causes signifcant numbers o cases
in some parts o the world. It is a radioactive
gas that leaks out o certain rocks such as
granite. It accumulates in badly ventilated
buildings and people then inhale it.
Asbestos, silica and some other solids can cause
lung cancer i dust or other particles o them are
inhaled. This usually happens on construction
sites or in quarries, mines or actories.
The consequences o lung cancer are oten very
severe. Some o them can be used to help diagnose
Figure 9 A large tumour (red) is the disease: difculties with breathing, persistent
visible in the right lung. The tumour coughing, coughing up blood, chest pain, loss o
is a bronchial carcinoma appetite, weight loss and general atigue.
Smoking causes about 87% o cases. Tobacco In many patients the tumour is already large
smoke contains many mutagenic chemicals. As when it is discovered and may also have
every cigarette carries a risk, the incidence o metastasized, with secondary tumours in the
lung cancer increases with the number smoked brain or elsewhere. Mortality rates are high.
per day and the number o years o smoking. Only 1 5% o patients with lung cancer survive
or more than 5 years. I a tumour is discovered
Passive smoking causes about 3% o cases. This early enough, all or part o the aected lung may
happens when non-smokers inhale tobacco be removed surgically. This is usually combined
smoke exhaled by smokers. The number o with one or more courses o chemotherapy.
cases will decline in countries where smoking is O ther patients are treated with radiotherapy.
banned indoors and in public places. The minority o patients who are cured o lung
Air pollution probably causes about 5% o cancer, but have lost some o their lung tissue,
lung cancers. The sources o air pollution that are likely to continue to have pain, breathing
are most signifcant are diesel exhaust umes, difculties, atigue and also anxiety about the
nitrogen oxides rom all vehicle exhaust umes possible return o the disease.
Emphysema
Causes and consequences of emphysema.
In healthy lung tissue each bronchiole leads to a Phagocytes inside alveoli normally prevent lung
group o small thin-walled alveoli. In a patient with inections by engulfng bacteria and produce
emphysema these are replaced by a smaller number elastase, a protein-digesting enzyme, to kill
o larger air sacs with much thicker walls. The them inside the vesicles ormed by endocytosis.
total surace area or gas exchange is considerably
reduced and the distance over which diusion An enzyme inhibitor called alpha 1 -antitrypsin
o gases occurs is increased, and so gas exchange (A1 AT) usually prevents elastase and other
is thereore much less eective. The lungs also proteases rom digesting lung tissue. In
become less elastic, so ventilation is more difcult. smokers, the number o phagocytes in the
lungs increases and they produce more elastase.
The molecular mechanisms involved are not ully
understood, though there is some evidence or Genetic actors aect the quantity and
these theories: eectiveness o A1 AT produced in the lungs.
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16 H u mC EaLnLpBHIyOsLiOoGlYo g y
In about 30% o smokers digestion o proteins than normal carbon dioxide concentrations. As a
in the alveolus wall by the increased quantity result the patient lacks energy and may eventually
o proteases is not prevented and alveolus fnd even tasks such as climbing stairs too
walls are weakened and eventually destroyed. onerous. In mild cases there is shortness o breath
during vigorous exercise but eventually even mild
Emphysema is a chronic disease because the activity causes it. Ventilation is laboured and tends
damage to alveoli is usually irreversible. It causes to be more rapid than normal.
low oxygen saturation in the blood and higher
Data-based questions: Emphysema and gas exchange
Figure 1 0 shows healthy lung tissue and tissue rom a lung with
emphysema, at the same magnifcation. Smoking usually causes
emphysema. Breathing polluted air makes the disease worse.
1 a) Place a ruler across each micrograph and count how many
times the edge o the ruler crosses a gas exchange surace.
Repeat this several times or each micrograph, in such a
way that the results are comparable. State your results
using suitable units. [3]
b) Explain the conclusions that you draw rom the results. [3]
2 Explain why people who have emphysema eel tired all the
time. [3]
3 Suggest why people with emphysema oten have an enlarged
and strained right side o the heart. [1 ]
Figure 10 Healthy lung tissue (top) and lung
tissue showing emphysema (bottom)
318
6.5 neuronS anD SynapSeS
6.5 ns d sss
Understanding Applications
Neurons transmit electrical impulses. Secretion and reabsorption o acetylcholine by
neurons at synapses.
The myelination o nerve bres allows or
saltatory conduction. Blocking o synaptic transmission at
cholinergic synapses in insects by binding
Neurons pump sodium and potassium ions o neonicotinoid pesticides to acetylcholine
across their membranes to generate a resting receptors.
potential.
Skills
An action potential consists o depolarization
and repolarization o the neuron. Analysis o oscilloscope traces showing resting
potentials and action potentials.
Nerve impulses are action potentials
propagated along the axons o neurons. Nature of science
Propagation o nerve impulses is the result o Cooperation and collaboration between groups
local currents that cause each successive part o scientists: biologists are contributing to
o the axon to reach the threshold potential. research into memory and learning.
Synapses are junctions between neurons and
between neurons and receptor or efector cells.
When pre-synaptic neurons are depolarized
they release a neurotransmitter into the
synapse.
A nerve impulse is only initiated i the threshold
potential is reached.
Neurons
Neurons transmit electrical impulses.
Two systems o the body are used or internal communication: the
endocrine system and the nervous system. The endocrine system
consists o glands that release hormones. The nervous system
consists o nerve cells called neurons. There are about 85 billion
neurons in the human nervous system. Neurons help with internal
communication by transmitting nerve impulses. A nerve impulse is
an electrical signal.
Neurons have a cell body with cytoplasm and a nucleus but they
also have narrow outgrowths called nerve fbres along which nerve
impulses travel.
Dendrites are short branched nerve fbres, or examples those used
to transmit impulses between neurons in one part o the brain or
spinal cord.
Axons are very elongated nerve fbres, or example those that transmit
impulses rom the tips o the toes or the fngers to the spinal cord.
319
61 H u mC EaLnLpBHIyOsLiOoGlYo g y
cell body
axon
dendrites skeletal muscle (eector)
Figure 1 Neuron with dendrites that transmit impulses to the cell body and an axon that transmits impulses a considerable
distance to muscle fbres
Figure 2 Nerve fbres (axons) transmitting myelinated nerve fbres
electrical impulses to and rom the central
nervous system are grouped into bundles The myelination o nerve fbres allows or saltatory
conduction.
myelin nucleus of node of
sheath Schwann cell Ranvier The basic structure o a nerve fbre along which a nerve impulse is
transmitted is very simple: the fbre is cylindrical in shape, with a plasma
axon membrane enclosing a narrow region o cytoplasm. The diameter in
most cases is about 1 m, though some nerve fbres are wider than this.
Figure 3 Detail o a myelinated nerve A nerve fbre with this simple structure conducts nerve impulses at a
fbre showing the gaps between adjacent speed o about 1 metre per second.
Schwann cells (nodes o Ranvier)
Some nerve fbres are coated along most o their length by a material
called myelin. It consists o many layers o phospholipid bilayer. S pecial
cells called Schwann cells deposit the myelin by growing round and
round the nerve fbre. Each time they grow around the nerve fbre a
double layer o phospholipid bilayer is deposited. There may be 20 or
more layers when the Schwann cell stops growing.
There is a gap between the myelin deposited by adjacent Schwann cells.
The gap is called a node o Ranvier. In myelinated nerve fbres the nerve
impulse can jump rom one node o Ranvier to the next. This is called
saltatory conduction. It is much quicker than continuous transmission
along a nerve fbre so myelinated nerve fbres transmit nerve impulses
much more rapidly than unmyelinated nerve fbres. The speed can be as
much as 1 00 metres per second.
Figure 4 Transverse section o axon showing the myelin sheath ormed by the Schwann
cell's membrane wrapped round the axon many times (red)
320
6.5 neuronS anD SynapSeS
Resting potentials uid outside neuron
Neurons pump sodium and Na+ K+ Na+ K+
potassium ions across their Na+ Na+ Na+ Na+
membranes to generate a resting channel
potential. closed Na+ Na+
Na+
A neuron that is not transmitting a signal Na+
has a potential dierence or voltage across its
membrane that is called the resting potential. N a+ /K+
This potential is due to an imbalance o positive pump
and negative charges across the membrane.
K+ K+ K+
Sodiumpotassium pumps transer - Na+
sodium (Na+) and potassium (K+) ions K+ K+ K+ channel
across the membrane. Na+ ions are pumped -- K+ closed
out and K+ ions are pumped in. The K+ K+
numbers o ions pumped is unequal when - K+ K+
three Na+ ions are pumped out, only two - -
K+ ions are pumped in, creating
concentration gradients or both ions. K+ - - K+ K+ -
-
Also the membrane is about 50 times more - K+
permeable to K+ ions than Na+ ions, so
K+ ions leak back across the membrane protein K+ K+
aster than Na+ ions. As a result, the
Na+ concentration gradient across the K+
membrane is steeper than the K+ gradient,
creating a charge imbalance. cytoplasm
Figure 5 The resting potential is generated by the sodiumpotassium pump
In addition to this, there are proteins inside the nerve fbre that are
negatively charged (organic anions) , which increases the charge
imbalance.
These actors together give the neuron a resting membrane potential o
about - 70 mV.
Action potentials
An action potential consists of depolarization and
repolarization of the neuron.
An action potential is a rapid change in membrane potential, consisting
o two phases:
depolarization a change rom negative to positive
repolarization a change back rom positive to negative.
Depolarization is due to the opening o sodium channels in the
membrane, allowing Na+ ions to diuse into the neuron down the
concentration gradient. The entry o Na+ ions reverses the charge
imbalance across the membrane, so the inside is positive relative to
the outside. This raises the membrane potential to a positive value o
about + 3 0 mV.
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16 H u mC EaLnLpBHIyOsLiOoGlYo g y
uid outside neuron uid outside neuron
Na+ K+ Na+ Na+ K+ K+
Na+ Na+ Na+ K+ K+
channel Na+
open Na+ channel K+ Na+ Na+
Na+ closed K+
Na+ K+
Na+ K+
K+
K+
N a+ N a+/K+ N a+ /K+ K+
pump pump
K+ Na+ Na+ Na+ K+ K+ Na+ K+
- K+ channel - Na+ channel
K+ closed
-- K+ Na+ - K+ - K+ Na+ - K+ open
K+ - K+ - K+ Na+ K+ - -
K+ K+ - - K+ K+ - K+ - Na+ -
Na+ K+ K+ Na+
Na+ K+ - - K+ - K+ Na+ K+ -
- Na+ K+ Na+ protein K+
Na+ protein K+ K+ Na+
K+
cytoplasm cytoplasm
Figure 6 Neuron depolarizing Figure 7 Neuron repolarizing
impulse movement Repolarization happens rapidly after depolarization and is due
to the closing of the sodium channels and opening of potassium
+++++++++ cell membrane channels in the membrane. This allows potassium ions to diffuse
cytoplasm out of the neuron, down their concentration gradient, which makes
A the inside of the cell negative again relative to the outside. The
potassium channels remain open until the membrane has fallen to
++++++++ a potential close to - 7 0 mV. The diffusion of potassium repolarizes
the neuron, but it does not restore the resting potential as the
B + concentration gradients of sodium and potassium ions have not yet
been re-established. This takes a few milliseconds and the neuron can
NNaa++ then transmit another nerve impulse.
+++++++ proagation of action otentials
C ++ Nerve impulses are action potentials propagated along
the axons of neurons.
N aN+a +
A nerve impulse is an action potential that starts at one end of a neuron
K+ and is then propagated along the axon to the other end of the neuron.
The propagation of the action potential happens because the ion
++++++ movements that depolarize one part of the neuron trigger depolarization
in the neighbouring part of the neuron.
D +++
Nerve impulses always move in one direction along neurons in humans
Na+ Na+ and other vertebrates. This is because an impulse can only be initiated at
one terminal of a neuron and can only be passed on to other neurons or
K+
+++ +++
E +++
Na+ Na+
Figure 8 Action potentials are propagated
along axons
322
6.5 neuronS anD SynapSeS
dierent cell types at the other terminal. Also, there is a reractive period activit
ater a depolarization that prevents propagation o an action potential
backwards along an axon. ns i s m
d mfsh
loca currents Anemonesh have a nervous
system similar to ours, with a
Propagation o nerve impulses is the result o local central nervous system and
currents that cause each successive part o the axon to neurons that transmit nerve
reach the threshold potential. impulses in one direction
only. Sea anemones have
The propagation o an action potential along an axon is due to no central nervous system.
movements o sodium ions. Depolarization o part o the axon is due to Their neurons orm a simple
diusion o sodium ions into the axon through sodium channels. This network and will transmit
reduces the concentration o sodium ions outside the axon and increases impulses in either direction
it inside. The depolarized part o the axon thereore has dierent sodium along their nerve bres. They
ion concentrations to the neighbouring part o the axon that has not yet both protect each other rom
depolarized. As a result, sodium ions diuse between these regions both predators more efectively
inside and outside the axon. than they can themselves.
Explain how they do this.
Inside the axon there is a higher sodium ion concentration in the
depolarized part o the axon so sodium ions diuse along inside the axon Figure 9 Anemonefsh among
to the neighbouring part that is still polarized. Outside the axon the the tentacles o a sea anemone
concentration gradient is in the opposite direction so sodium ions diuse
rom the polarized part back to the part that has just depolarized. These
movements are shown in fgure 1 0. They are called local currents.
Local currents reduce the concentration gradient in the part o the neuron
that has not yet depolarized. This makes the membrane potential rise rom
the resting potential o - 70mV to about - 5 0 mV. Sodium channels in the
axon membrane are voltage-gated and open when a membrane potential
o - 50mV is reached. This is thereore known as the threshold potential.
Opening o the sodium channels causes depolarization.
Thus local currents cause a wave o depolarization and then
repolarization to be propagated along the axon at a rate o between one
and a hundred (or more) metres per second.
impulse movement
outside Na+ diusion
inside Na + diusion
membrane
part that has just depolarized part that has not yet depolarized
(action potential) (resting potential)
Figure 10 Local currents
323
16 H u mC EaLnLpBHIyOsLiOoGlYo g y
action potential peakpotential dierence Analysing oscilloscope traces
+35across membrane (mV)
Analysis o oscilloscope traces showing resting
0 depolarization potentials and action potentials.
repolarization
50 threshold potential Membrane potentials in neurons can be measured by placing
70 undershoot resting potential electrodes on each side o the membrane. The potentials can be
displayed using an oscilloscope. The display is similar to a graph
01234567 with time on the x-axis and the membrane potential on the y-axis.
time/ms I there is a resting potential, a horizontal line appears on the
oscilloscope screen at a level o - 7 0 mV, assuming that this is the
stimulus resting potential o the neuron.
Figure 11 Changes in membrane polarity I an action potential occurs, a narrow spike is seen, with the rising
during an action potential and alling phases showing the depolarization and repolarization.
The oscilloscope trace may also show the potential rising beore
the depolarization until the threshold potential is reached. The
repolarization does not usually return the membrane potential to
- 70 mV immediately and there is a phase in which the potential
changes gradually until the resting potential is reached.
Data-based questions: Analysing an oscilloscope trace
The oscilloscope trace in gure 1 2 was taken rom 1 State the resting potential o the mouse
a digital oscilloscope. It shows an action potential hippocampal pyramidal neuron. [1 ]
[2]
in a mouse hippocampal pyramidal neuron that 2 Deduce with a reason the threshold
happened ater the neuron was stimulated with a potential needed to open voltage-gated
pulse o current. sodium channels in this neuron.
50 membrane voltage (mV) 3 Estimate the time taken or the [2]
0 depolarization, and the repolarization.
50 4 Predict the time taken rom the end o the
0
depolarization or the resting potential
Figure 12
to be regained. [2]
resting potential 5 Discuss how many action potentials
could be stimulated per second in this
neuron. [2]
50 100
time (ms)
6 Suggest a reason or the membrane
potential rising briefy at the end o the [1 ]
repolarization.
Synapses
Synapses are junctions between neurons and between
neurons and receptor or efector cells.
Synapses are junctions between cells in the nervous system. In sense organs
there are synapses between sensory receptor cells and neurons. In both
the brain and spinal cord there are immense numbers o synapses between
neurons. In muscles and glands there are synapses between neurons and
324
6.5 neuronS anD SynapSeS
muscle bres or secretory cells. Muscles and glands are sometimes called
eectors, because they eect (carry out) a response to a stimulus.
Chemicals called neurotransmitters are used to send signals across
synapses. This system is used at all synapses where the pre-synaptic
and post-synaptic cells are separated by a fuid-lled gap, so electrical
impulses cannot pass across. This gap is called the synaptic clet and is
only about 20 nm wide.
Synaptic transmission
When pre-synaptic neurons are depolarized they release Figure 13 Electron micrograph o a synapse.
a neurotransmitter into the synapse. False colour has been used to indicate the
pre-synaptic neuron (purple) with vesicles o
Synaptic transmission occurs very rapidly as a result o these events: neurotransmitter (blue) and the post-synaptic
neuron (pink) . The narrowness o the synaptic
A nerve impulse is propagated along the pre-synaptic neuron clet is visible
until it reaches the end o the neuron and the pre-synaptic
membrane.
Depolarization o the pre-synaptic membrane causes pre-synaptic cell nerve
calcium ions (Ca2+) to diuse through channels in the impulse
membrane into the neuron.
Infux o calcium causes vesicles containing C a 2 + d i u s e s synaptic knob
neurotransmitter to move to the pre-synaptic into knob synaptic vesicles
membrane and use with it.
neurotransmitter pre-synaptic
Neurotransmitter is released into the synaptic clet by (e.g. acetylcholine) membrane
exocytosis. neurotransmitter
activates receptors synaptic cleft
The neurotransmitter diuses across the synaptic 20nm approximately
clet and binds to receptors on the post-synaptic
membrane.
The binding o the neurotransmitter to the receptors
causes adjacent sodium ion channels to open.
Sodium ions diuse down their concentration gradient ion channel opened
into the post-synaptic neuron, causing the post-
synaptic membrane to reach the threshold potential. post-synaptic
membrane
An action potential is triggered in the post-synaptic
membrane and is propagated on along the neuron. post-synaptic cell
The neurotransmitter is rapidly broken down and Figure 14 A nerve impulse is propagated across a synapse by the
removed rom the synaptic clet. release, difusion and post-synaptic binding o neurotransmitter
Dt-bsd qstis: Parkinsons disease metabolic pathways involved in the ormation
and breakdown o dopamine.
Dopamine is one o the many neurotransmitters
that are used at synapses in the brain. In 1 Explain how symptoms o Parkinsons disease
Parkinsons disease, there is a loss o dopamine- are relieved by giving the ollowing drugs:
secreting neurons, which causes slowness in
initiating movement, muscular rigidity and a) L- D O PA [1 ]
in many cases shaking. Figure 1 5 shows the
325
16 H u mC EaLnLpBHIyOsLiOoGlYo g y
b) selegeline, which is an inhibitor o tyrosine COOH tyrosine L-DOPA COOH
monoamine oxidase-B (MAO-B) hydroxylase
[1 ] HO CH2 CH HO CH2 CH
c) tolcapone, which is an inhibitor [1 ] HO NH2
o catechol-O-methyl transerase (FOOD) NH2 COMT dopa
(COMT)
COOH dopamine decarboxylase
d) ropinirole, which is an agonist o CH3O CH2 CH HO CH2 CH2 NH2
dopamine [1 ] HO NH2 HO MAO-B
e) safnamide, which inhibits reuptake O
o dopamine by pre-synaptic [1 ] HO CH2 C
neurons. HO H
2 Discuss how a cure or Parkinsons disease aldehyde
dehydrogenase
might in the uture be developed by: CH3O CH2 COOH COMT HO CH2 COOH
a) stem cell therapy [3] HO
HO
b) gene therapy. [2 ] Figure 15 The formation and breakdown of L-DOPA and
dopamine. The enzymes catalysing each step are shown in red
choline Acetylcholine
acetyl group Secretion and reabsorption of acetylcholine by neurons
at synapses.
Figure 16 Acetylcholine
Acetylcholine is used as the neurotransmitter in many synapses,
326 including synapses between neurons and muscle fbres. It is produced
in the pre-synaptic neuron by combining choline, absorbed rom the
diet, with an acetyl group produced during aerobic respiration. The
acetylcholine is loaded into vesicles and then released into the synaptic
clet during synaptic transmission.
The receptors or acetylcholine in the post-synaptic membrane have a
binding site to which acetylcholine will bind. The acetylcholine only
remains bound to the receptor or a short time, during which only
one action potential is initiated in the post-synaptic neuron. This is
because the enzyme acetylcholinesterase is present in the synaptic
clet and rapidly breaks acetylcholine down into choline and acetate.
The choline is reabsorbed into the pre-synaptic neuron, where it is
converted back into active neurotransmitter by recombining it with an
acetyl group.
Neonicotinoids
Blocking of synaptic transmission at cholinergic
synapses in insects by binding of neonicotinoid
pesticides to acetylcholine receptors.
Neonicotinoids are synthetic compounds similar to nicotine. They
bind to the acetylcholine receptor in cholinergic synapses in the
central nervous system o insects. Acetylcholinesterase does not
6.5 neuronS anD SynapSeS
break down neonicotinoids, so the binding is irreversible. The activit
receptors are blocked, so acetylcholine is unable to bind and
synaptic transmission is prevented. The consequence in insects is rsch dts
paralysis and death. Neonicotinoids are thereore very eective ictiids
insecticides.
There are currently
One o the advantages o neonicotinoids as pesticides is that they intense research eforts
are not highly toxic to humans and other mammals. This is because to try to discover whether
a much greater proportion o synapses in the central nervous neonicotinoids are to blame
system are cholinergic in insects than in mammals and also because or collapses in honeybee
neonicotinoids bind much less strongly to acetylcholine receptors in colonies. What are the most
mammals than insects. recent research ndings
and do they suggest that
Neonicotinoid pesticides are now used on huge areas o crops. In these insecticides should
particular one neonicotinoid, imidacloprid, is the most widely used be banned?
insecticide in the world. However, concerns have been raised about
the eects o these insecticides on honeybees and other benefcial
insects. There has been considerable controversy over this and
the evidence o harm is disputed by the manuacturers and some
government agencies.
Threshold potentials Figure 17 Research has
shown that the neonicotinoid
A nerve impulse is only initiated i the threshold pesticide imidacloprid reduces
potential is reached. growth of bumblebee colonies
Nerve impulses ollow an all-or-nothing principle. An action potential is only
initiated i the threshold potential is reached, because only at this potential
do voltage-gated sodium channels start to open, causing depolarization. The
opening o some sodium channels and the inward diusion o sodium ions
increases the membrane potential causing more sodium channels to open
there is a positive eedback eect. I the threshold potential is reached there
will thereore always be a ull depolarization.
At a synapse, the amount o neurotransmitter secreted ollowing
depolarization o the pre-synaptic membrane may not be enough to cause
the threshold potential to be reached in the post-synaptic membrane.
The post-synaptic membrane does not then depolarize. The sodium ions
that have entered the post-synaptic neuron are pumped out by sodium
potassium pumps and the post-synaptic membrane returns to the resting
potential.
A typical post-synaptic neuron in the brain or spinal cord has synapses
not just with one but with many pre-synaptic neurons. It may be
necessary or several o these to release neurotransmitter at the same
time or the threshold potential to be reached and a nerve impulse to
be initiated in the post-synaptic neuron. This type o mechanism can
be used to process inormation rom dierent sources in the body to
help in decision-making.
327
16 H u mC EaLnLpBHIyOsLiOoGlYo g y
Figure 18 Many synapses are visible in this Research into memory and learning
scanning electron micrograph between the cell
body o one post-synaptic neuron and a large Cooperation and collaboration between groups of
number o diferent pre-synaptic neurons (blue) scientists: biologists are contributing to research into
memory and learning.
Figure 19 Memory and learning are unctions
o the cerebrumthe olded upper part o Higher unctions o the brain including memory and learning are
the brain only partly understood at present and are being researched very
actively. They have traditionally been investigated by psychologists
but increasingly the techniques o molecular biology and biochemistry
are being used to unravel the mechanisms at work. Other branches o
science are also making important contributions, including biophysics,
medicine, pharmacology and computer science.
The Centre or Neural Circuits and Behaviour at Oxord University is
an excellent example o collaboration between scientists with dierent
areas o expertise. The our group leaders o the research team and the
area o science that they originally studied are:
Proessor Gero Miesenbck medicine and physiology
Dr Martin Booth engineering and optical microscopy
Dr Korneel Hens chemistry and biochemistry
Proessor Scott Waddell genetics, molecular biology and
n e u r o b io lo g y.
The centre specializes in research techniques known as optogenetics.
Neurons are genetically engineered to emit light during synaptic
transmission or an action potential, making activity in specifc
neurons in brain tissue visible. They are also engineered so specifc
neurons in brain tissue respond to a light signal with an action
potential. This allows patterns o activity in the neurons o living
brain tissue to be studied.
There are many research groups in universities throughout the world
that are investigating memory, learning and other brain unctions.
Although there is sometimes competition between scientists to be the
frst group to make a discovery, there is also a strongly collaborative
element to scientifc research. This extends across scientifc disciplines and
national boundaries. Success in understanding how the brain works will
undoubtedly be the achievement o many groups o scientists in many
countries throughout the world.
328
6.6 hormoneS, homeoStaSiS anD reproDuCtion
6.6 hs, sss d dc
Understanding Applications
Insulin and glucagon are secreted by and Causes and treatment o type I and type II
cells in the pancreas to control blood glucose diabetes.
concentration.
Testing o leptin on patients with clinical
Thyroxin is secreted by the thyroid gland to obesity and reasons or the ailure to control
regulate the metabolic rate and help control the disease.
body temperature.
Causes o jet lag and use o melatonin to
Leptin is secreted by cells in adipose tissue alleviate it.
and acts on the hypothalamus o the brain to
inhibit appetite. The use in IVF o drugs to suspend the
normal secretion o hormones, ollowed
Melatonin is secreted by the pineal gland to by the use o artifcial doses o hormones to
control circadian rhythms. induce superovulation and establish
a pregnancy.
A gene on the Y chromosome causes
embryonic gonads to develop as testes and William Harveys investigation o sexual
secrete testosterone. reproduction in deer.
Testosterone causes prenatal development Skills
o male genitalia and both sperm production
and development o male secondary sexual Annotate diagrams o the male and emale
characteristics during puberty. reproductive system to show names o
structures and their unctions.
Estrogen and progesterone cause prenatal
development o emale reproductive organs Nature of science
and emale secondary sexual characteristics
during puberty. Developments in scientifc research ollow
improvements in apparatus: William Harvey
The menstrual cycle is controlled by negative was hampered in his observational research
and positive eedback mechanisms involving into reproduction by lack o equipment. The
ovarian and pituitary hormones. microscope was invented 17 years ater
his death.
Control of blood glucose concentration
Insulin and glucagon are secreted by and cells in the
pancreas to control blood glucose concentration.
Cells in the pancreas respond to changes in blood glucose levels. If
the glucose concentration deviates substantially from the set point of
about 5 mmol L-1, homeostatic mechanisms mediated by the pancreatic
hormones insulin and glucagon are initiated.
329
61 H u mC EaLnLpBHIyOsLiOoGlYo g y
Figure 1 Fluorescent light micrograph of the The pancreas is eectively two glands in one organ. Most o the pancreas
pancreas showing two islets of Langerhans is exocrine glandular tissue that secretes digestive enzymes into ducts
surrounded by exocrine gland tissue. Alpha leading to the small intestine. There are small regions o endocrine tissue
cells in the islets are stained yellow and beta called islets o Langerhans dotted through the pancreas that secrete
cells are stained red hormones directly into the blood stream. The two cell types in the islets
o Langerhans secrete dierent hormones.
Alpha cells ( cells) synthesize and secrete glucagon i the blood
glucose level alls below the set point. This hormone stimulates
breakdown o glycogen into glucose in liver cells and its release into
the blood, increasing the concentration.
Beta cells ( cells) synthesize insulin and secrete it when the blood
glucose concentration rises above the set point. This hormone
stimulates uptake o glucose by various tissues, particularly skeletal
muscle and liver, in which it also stimulates the conversion o
glucose to glycogen. Insulin thereore reduces blood glucose
concentration. Like most hormones, insulin is broken down by the
cells it acts upon, so its secretion must be ongoing. Secretion begins
within minutes o eating and may continue or several hours ater
a meal.
Diabetes
Causes and treatment of type I and type II diabetes.
Diabetes is the condition where a person has process or respond to insulin because o a
consistently elevated blood glucose levels even defciency o insulin receptors or glucose
during prolonged asting, leading to the presence transporters on target cells. Onset is slow
o glucose in the urine. Continuously elevated and the disease may go unnoticed or many
glucose damages tissues, particularly their proteins. years. Until the last ew decades, this orm o
It also impairs water reabsorption rom urine while diabetes was very rare in people under 50 and
it is orming in the kidney, resulting in an increase common only in the over 65s. The causes o
in the volume o urine and body dehydration. this orm o diabetes are not well understood
I a person needs to urinate more requently, is but the main risk actors are sugary, atty diets,
constantly thirsty, eels tired and craves sugary prolonged obesity due to habitual overeating
drinks, they should test or glucose in the urine to and lack o exercise, together with genetic
check whether they have developed diabetes. actors that aect energy metabolism.
There are two main types o this disease: The treatment o the two types o diabetes is
dierent:
Type I diabetes, or early- onset diabetes, is
characterized by an inability to produce Type I diabetes is treated by testing the blood
sufcient quantities o insulin. It is an glucose concentration regularly and injecting
autoimmune disease arising rom the insulin when it is too high or likely to become
destruction o beta cells in the islets o too high. Injections are oten done beore a
Langerhans by the bodys own immune meal to prevent a peak o blood glucose as the
system. In children and young people the ood is digested and absorbed. Timing is very
more severe and obvious symptoms o the important because insulin molecules do not
disease usually start rather suddenly. The last long in the blood. Better treatments are
causes o this and other autoimmune diseases being developed using implanted devices that
are still being researched. can release exogenous insulin into the blood
as and when it is necessary. A permanent cure
Type II diabetes, sometimes called late- onset may be achievable by coaxing stem cells to
diabetes, is characterized by an inability to become ully unctional replacement beta cells.
330
6.6 hormoneS, homeoStaSiS anD reproDuCtion
Type II diabetes is treated by adj usting the i it has a low glycemic index, indicating that
diet to reduce the peaks and troughs o blood it is digested slowly. High- fbre oods should
glucose. Small amounts o ood should be be included to slow the digestion o other
eaten requently rather than inrequent large oods. Strenuous exercise and weight loss
meals. Foods with high sugar content should are benefcial as they improve insulin uptake
be avoided. Starchy ood should only be eaten and action.
D-bsd qss: The glucose tolerance test acvy
The glucose tolerance test is a method used to diagnose diabetes. Fds f y ii dbcs
In this test, the patient drinks a concentrated glucose solution. The Discuss which o the oods
blood glucose concentration is monitored to determine the length o in fgure 2 are suitable or a
time required or excess glucose to be cleared rom the blood. person with type II diabetes.
They should be oods with a
concentration / mg 100 cm3 400 low glycemic index.
350 Figure 2
300
250 diabetic
200
150
100 unaected
50
0 5
0 0.5 1 2 3 4
time after glucose ingestion / h
Figure 3 A person with diabetes and an unafected person
give very diferent responses to the glucose tolerance test
With reerence to fgure 3, compare the person with normal glucose
metabolism to the person with diabetes with respect to:
a) The concentration o glucose at time zero, i.e. beore the
consumption o the glucose drink.
b) The length o time required to return to the level at time zero.
c) The maximum glucose level reached.
d) The time beore glucose levels start to all.
tyx
Thyroxin is secreted by the thyroid gland to regulate the
metabolic rate and help control body temperature.
The hormone thyroxin is secreted by the thyroid gland in the neck. Its
chemical structure is unusual as the thyroxin molecule contains our
atoms o iodine. Prolonged defciency o iodine in the diet thereore
prevents the synthesis o thyroxin. This hormone is also unusual as
almost all cells in the body are targets. Thyroxin regulates the bodys
metabolic rate, so all cells need to respond but the most metabolically
active, such as liver, muscle and brain are the main targets.
Higher metabolic rate supports more protein synthesis and growth
and it increases the generation o body heat. In a person with normal
physiology, cooling triggers increased thyroxin secretion by the thyroid
gland, which stimulates heat production so body temperature rises.
331
16 H u mC EaLnLpBHIyOsLiOoGlYo g y
Figure 4 Structure of thyroxin with atoms of Thyroxin thus regulates the metabolic rate and also helps to control
iodine shown purple body temperature.
Figure 5 Mouse with obesity due to lack of The importance o thyroxin is revealed by the eects o thyroxin
leptin and a mouse with normal body mass defciency (hypothyroidism) :
lack o energy and eeling tired all the time
orgetulness and depression
weight gain despite loss o appetite as less glucose and at are being
broken down to release energy by cell respiration
eeling cold all the time because less heat is being generated
constipation because contractions o muscle in the wall o the gut
slow down.
impaired brain development in children.
leptin
Leptin is secreted by cells in adipose tissue and acts on
the hypothalamus of the brain to inhibit appetite.
Leptin is a protein hormone secreted by adipose cells (at storage cells) .
The concentration o leptin in the blood is controlled by ood intake and
the amount o adipose tissue in the body. The target o this hormone is
groups o cells in the hypothalamus o the brain that contribute to the
control o appetite. Leptin binds to receptors in the membrane o these
cells. I adipose tissue increases, blood leptin concentrations rise, causing
long-term appetite inhibition and reduced ood intake.
The importance o this system was demonstrated by research with a
strain o mice discovered in the 1 95 0s that eed ravenously, become
inactive and gain body weight, mainly through increased adipose tissue.
They grow to a body weight o about 1 00 grams, compared with wild
type mice o 2025 grams. Breeding experiments showed that the obese
mice had two copies o a recessive allele, ob. In the early 1 990s it was
shown that the wild-type allele o this gene supported the synthesis
o a new hormone that was named leptin. Adipose cells in mice that
have two recessive ob alleles cannot produce leptin. When ob/ob mice
were injected with leptin their appetite declined, energy expenditure
increased and body mass dropped by 30% in a month.
leptin and obesity
Testing of leptin on patients with clinical obesity and reasons for the failure
to control the disease.
The discovery that obesity in mice could be caused out. Seventy-three obese volunteers injected
by a lack o leptin and cured by leptin injections themselves either with one o several leptin doses
soon led to attempts to treat obesity in humans in or with a placebo. A double blind procedure was
this way. Amgen, a biotechnology company based used, so neither the researchers nor the volunteers
in Caliornia, paid $20 million or the commercial knew who was injecting leptin until the results
rights to leptin and a large clinical trial was carried were analysed.
332
6.6 hormoneS, homeoStaSiS anD reproDuCtion
The leptin injections induced skin irritation and tissue develops, causing a rise in blood leptin
swelling and only 47 patients completed the trial. concentration but the leptin resistance prevents
The eight patients receiving the highest dose lost inhibition o appetite. Injection o extra leptin
7.1 kg o body mass on average compared with inevitably ails to control obesity i the cause is
a loss o 1 .3 kg in the 1 2 volunteers who were leptin resistance, just as insulin injections alone
inj ecting the placebo. However, in the group are ineective with early-stage type II diabetes.
receiving the highest dose the results varied very
widely rom a loss o 1 5 kg to a gain o 5 kg. Also A very small proportion o cases o obesity in
any body mass lost during the trial was usually humans are due to mutations in the genes or
regained rapidly aterwards. Such disappointing leptin synthesis or its various receptors on target
outcomes are requent in drug research the cells. Trials in people with such obesity have shown
physiology o humans is dierent in many ways signifcant weight loss while the leptin injections
rom mice and other rodents. are continuing. However leptin is a short-lived
protein and has to be injected several times a
In contrast to ob/ob mice, most obese day and consequently most o those oered this
humans have exceptionally high blood treatment have reused it. Also leptin has been
leptin concentrations. The target cells in the shown to aect the development and unctioning
hypothalamus may have become resistant o the reproductive system, so injections are not
to leptin so ail to respond to it, even at high suitable in children and young adults. All in all
concentrations. Appetite is thereore not inhibited leptin has not ulflled its early promise as a means
and ood intake is excessive. More adipose o solving the human obesity problem.
melatonin Figure 6 Until a baby is about three months old
it does not develop a regular day-night rhythm
Melatonin is secreted by the pineal gland to control o melatonin secretion so sleep patterns do
circadian rhythms. not ft those o the babys parents
Humans are adapted to live in a 24-hour cycle and have rhythms in 333
behaviour that ft this cycle. These are known as circadian rhythms.
They can continue even i a person is placed experimentally in
continuous light or darkness because an internal system is used to
control the rhythm.
Circadian rhythms in humans depend on two groups o cells in the
hypothalamus called the suprachiasmatic nuclei (SCN) . These cells set
a daily rhythm even i grown in culture with no external cues about
the time o day. In the brain they control the secretion o the hormone
melatonin by the pineal gland. Melatonin secretion increases in the
evening and drops to a low level at dawn and as the hormone is rapidly
removed rom the blood by the liver, blood concentrations rise and all
rapidly in response to these changes in secretion.
The most obvious eect o melatonin is the sleep-wake cycle. High
melatonin levels cause eelings o drowsiness and promote sleep through
the night. Falling melatonin levels encourage waking at the end o the
night. Experiments have shown that melatonin contributes to the night-
time drop in core body temperature, as blocking the rise in melatonin
levels reduces it and giving melatonin artifcially during the day causes a
drop in core temperature. Melatonin receptors have been discovered in
the kidney, suggesting that decreased urine production at night may be
another eect o this hormone.
When humans are placed experimentally in an environment without
light cues indicating the time o day, the S C N and pineal gland usually
61 H u mC EaLnLpBHIyOsLiOoGlYo g y
maintain a rhythm o slightly longer than 24 hours. This indicates that
timing o the rhythm is normally adjusted by a ew minutes or so each
day. A special type o ganglion cell in the retina o the eye detects light
o wavelength 460480 nm and passes impulses to cells in the SCN. This
indicates to the SCN the timing o dusk and dawn and allows it to adjust
melatonin secretion so that it corresponds to the day-night cycle.
Jet lag and melatonin
Causes of jet lag and use of melatonin to alleviate it.
Jet lag is a common experience or someone who Jet lag only lasts or a ew days, during which
has crossed three or more time zones during air impulses sent by ganglion cells in the retina to
travel. The symptoms are diculty in remaining the SCN when they detect light help the body to
awake during daylight hours and diculty adjust to the new regime. Melatonin is sometimes
sleeping through the night, atigue, irritability, used to try to prevent or reduce jet lag. It is taken
headaches and indigestion. The causes are easy orally at the time when sleep should ideally
to understand: the SCN and pineal gland are be commencing. Most trials o melatonin have
continuing to set a circadian rhythm to suit the shown that it is eective at promoting sleep
timing o day and night at the point o departure and helping to reduce jet lag, especially i fying
rather than the destination. eastwards and crossing ve or more time zones.
Figure 7 X and Y chromosomes Sex determination in males
334 A gene on the Y chromosome causes embryonic gonads to
develop as testes and secrete testosterone.
Human reproduction involves the usion o a sperm rom a male with an
egg rom a emale. Initially the development o the embryo is the same in all
embryos and embryonic gonads develop that could either become ovaries
or testes. The developmental pathway o the embryonic gonads and thereby
the whole baby depends on the presence or absence o one gene.
I the gene SRY is present, the embryonic gonads develop into testes.
This gene is located on the Y chromosome, so is only present in 50%
o embryos. SRY codes or a DNA-binding protein called TDF (testis
determining actor) . TDF stimulates the expression o other genes
that cause testis development.
50% o embryos have two X chromosomes and no Y so they do not
have a copy o the SRY gene. TDF is thereore not produced and the
embryonic gonads develop as ovaries.
Testosterone
Testosterone causes prenatal development of male
genitalia and both sperm production and development of
male secondary sexual characteristics during puberty.
The testes develop rom the embryonic gonads in about the eighth week
o pregnancy, at the time when the embryo is becoming a etus and is
about 30mm long. The testes develop testosterone-secreting cells at an
early stage and these produce testosterone until about the teenth week
6.6 hormoneS, homeoStaSiS anD reproDuCtion
o pregnancy. D uring the weeks o secretion, testosterone causes male
genitalia to develop, which are shown in fgure 8.
At puberty the secretion o testosterone increases. This stimulates sperm
production in the testes, which is the primary sexual characteristic o
males. Testosterone also causes the development o secondary sexual
characteristics during puberty such as enlargement o the penis, growth
o pubic hair and deepening o the voice due to growth o the larynx.
Sex deterination in feales
Estrogen and progesterone cause prenatal development
of female reproductive organs and female secondary
sexual characteristics during puberty.
I the gene SRY is not present in an embryo because there is no
Y chromosome, the embryonic gonads develop as ovaries. Testosterone
is thereore not secreted, but the two emale hormones, estrogen and
progesterone, are always present in pregnancy. At frst they are secreted
by the mothers ovaries and later by the placenta. In the absence o etal
testosterone and the presence o maternal estrogen and progesterone,
emale reproductive organs develop which are shown in fgure 9.
During puberty the secretion o estrogen and progesterone increases,
causing the development o emale secondary sexual characteristics. These
include enlargement o the breasts and growth o pubic and underarm hair.
male and feale reproductive systes
Annotate diagrams of the male and female reproductive system to show names
of structures and their functions.
The tables on the next page indicate unctions that should be included when diagrams o male and
emale reproductive systems are annotated.
bladder seminal vesicle bladder seminal vesicle
sperm duct prostate gland
sperm duct prostate
penis gland erectile tissue epididymis
epididymis penis scrotum
urethra scrotum testis
testis
urethra
foreskin
Figure 8 Male reproductive system in front and side view
335
61 H u mC EaLnLpBHIyOsLiOoGlYo g y
opening oviduct uterus ovary oviduct
cervix uterus
to ovary vagina bladder cervix
urethra vagina
oviduct large
intestine
labia (vulva) vulva
Figure 9 Female reproductive system in front and side view
male reproductive syste Feale reproductive syste
Testis Produce sperm and testosterone Ovary Produce eggs, estrogen and progesterone
Scrotum Hold testes at lower than core body Oviduct Collect eggs at ovulation, provide a site
temperature or ertilization then move the embryo to the
uterus
Epididymis Store sperm until ejaculation
Sperm duct Transer sperm during ejaculation Uterus Provide or the needs o the embryo and
then etus during pregnancy
Seminal vesicle Secrete fuid containing alkali, Cervix Protect the etus during pregnancy and then
and prostate proteins and ructose that is added dilate to provide a birth canal
gland to sperm to make semen
U re th ra Transer semen during ejaculation Vagina Stimulate penis to cause ejaculation and
and urine during urination provide a birth canal
Penis Penetrate the vagina or ejaculation Vulva Protect internal parts o the emale
o semen near the cervix reproductive system
menstrual cycle
The menstrual cycle is controlled by negative and
positive eedback mechanisms involving ovarian and
pituitary hormones.
The menstrual cycle occurs in most women rom puberty until the
menopause, apart rom during pregnancies. Each time the cycle occurs
it gives the chance o a pregnancy. The frst hal o the menstrual cycle is
called the ollicular phase because a group o ollicles is developing in the
ovary. In each ollicle an egg is stimulated to grow. At the same time the
lining o the uterus (endometrium) is repaired and starts to thicken. The
most developed ollicle breaks open, releasing its egg into the oviduct.
The other ollicles degenerate.
The second hal o the cycle is called the luteal phase because the
wall o the ollicle that released an egg becomes a body called the
corpus luteum. Continued development o the endometrium prepares
336
6.6 hormoneS, homeoStaSiS anD reproDuCtion
hormone level /ng ml1 it or the implantation o an embryo. I ertilization does not occurmenstruation TOK
menstruationthe corpus luteum in the ovary breaks down. The thickening o the
endometrium in the uterus also breaks down and is shed during t w x d vs
menstruation. w jdgg ly f c?
Figure 1 0 shows hormone levels in a woman over a 36-day period, Human eggs can be obtained by
including one complete menstrual cycle. The pattern o changes is using FSH to stimulate the ovaries,
typical or a woman who is not pregnant. The hormone levels are then collecting eggs rom the ovaries
measured in mass per millilitre. The actual masses are very small, using a micropipette. Women have
so progesterone, FSH and LH are measured in nanograms (ng) and sometimes undergone this procedure
estrogen is measured in picograms (pg) . Figure 1 0 also shows the state to produce eggs or donation to
o the ovary and o the endometrium. another woman who is unable to
produce eggs hersel.
The our hormones in fgure 1 0 all help to control the menstrual
cycle by both negative and positive eedback. FSH and LH are protein Recently stem-cell researchers have
hormones produced by the pituitary gland that bind to FSH and LH used eggs in therapeutic cloning
receptors in the membranes o ollicle cells. Estrogen and progesterone experiments. The nucleus o an egg is
are ovarian hormones, produced by the wall o the ollicle and corpus removed and replaced with a nucleus
rom an adult. I the resulting cell
1000 developed as an embryo, stem cells
LH could be removed rom it and cloned.
It might then be possible to produce
800 FSH tissues or organs or transplanting to
the adult who donated the nucleus.
600 There would be no danger o tissue
rejection because the stem cells
400 would be genetically identical to
the recipient.
200
There is a shortage o eggs both
0 or donation to other women and
or research. In 2006, scientists
follicle starting follicle nearly corpus progesterone level/ng ml1 in England got permission to ofer
luteum women cut-price IVF treatment, i they
to develop mature were willing to donate some eggs or
400 8 research. In Sweden only travel and
estrogen level/pg ml1 6 other direct expenses can be paid to
300 progesterone 4 egg donors, and in Japan egg donation
estrogen is banned altogether.
200 1 Is there a distinction to be drawn
between donating eggs or
100 2 therapeutic cloning experiments
and donating eggs to a woman
thickness of endometrium0 who is unable to produce eggs
26 28 2 4 5 8 10 12 14 16 18 20 22 24 26 28 2 4 hersel, or example because her
days of menstrual cycle ovaries have been removed? Can
the same act be judged diferently
ovulation depending on motives?
28 7 14 21 28
Figure 10 The menstrual cycle
337
16 H u mC EaLnLpBHIyOsLiOoGlYo g y
luteum. They are absorbed by many cells in the emale body, where
they infuence gene expression and thereore development.
FSH rises to a peak towards the end o the menstrual cycle and
stimulates the development o ollicles, each containing an oocyte
and ollicular fuid. FSH also stimulates secretion o estrogen by the
ollicle wall.
Estrogen rises to a peak towards the end o the ollicular phase.
It stimulates the repair and thickening o the endometrium ater
menstruation and an increase in FSH receptors that make the
ollicles more receptive to FSH, boosting estrogen production
(positive eedback) . When it reaches high levels estrogen
inhibits the secretion o FSH (negative eedback) and stimulates
LH secretion.
LH rises to a sudden and sharp peak towards the end o the
ollicular phase. It stimulates the completion o meiosis in the
oocyte and partial digestion o the ollicle wall allowing it to burst
open at ovulation. LH also promotes the development o the
wall o the ollicle ater ovulation into the corpus luteum which
secretes estrogen (positive eedback) and progesterone.
Progesterone levels rise at the start o the luteal phase, reach a
peak and then drop back to a low level by the end o this phase.
Progesterone promotes the thickening and maintenance o the
endometrium. It also inhibits FSH and LH secretion by the pituitary
gland (negative eedback) .
Data-based questions: The female athlete triad
The emale athlete triad is a syndrome consisting 2 Explain the reasons or some o the
o three interrelated disorders that can aect runners having:
emale athletes: osteoporosis, disordered eating
and menstrual disorders. Osteoporosis is reduced a) higher bone density than the mean [2]
bone mineral density. It can be caused by a diet
low in calcium, vitamin D or energy, or by low b) lower bone density than the mean. [4]
estrogen levels. Figure 1 1 shows the bone mineral
density in two parts o the emur or emale 3 a) Suggest reasons or emale athletes
runners who had dierent numbers o menstrual having ew or no menstrual cycles.
cycles per year. The t- score is the number o [2]
standard deviations above or below mean peak
bone mass or young women. b) Suggest one reason or eating disorders
and low body weight in emale athletes. [1 ]
t-score (SD) 1 neck of femur trochanter of femur
0.5
1 a) Outline the relationship between number 0
o menstrual cycles per year and bone 0.5
d e n s ity. [3] 1
menstrual cycles per year
b) Compare the results or the neck o the 03 410 1113
emur with the results or the trochanter. [3]
Figure 11 Bone mass in women grouped by number of
menstrual cycles
338
6.6 hormoneS, homeoStaSiS anD reproDuCtion
In vitro fertilization
The use in IVF o drugs to suspend the normal secretion o hormones, ollowed by
the use o artifcial doses o hormones to induce superovulation and establish
a pregnancy.
The natural method o ertilization in humans is a consequence ar more ollicles develop than
in vivo, meaning that it occurs inside the living usual. Twelve is not unusual and there can be
tissues o the body. Fertilization can also happen as many twenty ollicles. This stage o IVF is
outside the body in careully controlled laboratory thereore called superovulation.
conditions. This is called in vitro ertilization,
almost always abbreviated to IVF. This procedure When the ollicles are 1 8 mm in diameter they
has been used extensively to overcome ertility are stimulated to mature by an injection o HCG,
problems in either the male or emale parent. another hormone that is normally secreted by
the embryo. A micropipette mounted on an
There are several dierent protocols or IVF, but ultrasound scanner is passed through the uterus
the rst stage is usually down-regulation. The wall to wash eggs out o the ollicles. Each egg
woman takes a drug each day, usually as a nasal is mixed with 50,000 to 1 00,000 sperm cells in
spray, to stop her pituitary gland secreting FSH sterile conditions in a shallow dish, which is then
or LH. Secretion o estrogen and progesterone incubated at 3 7 C until the next day.
thereore also stops. This suspends the normal
menstrual cycle and allows doctors to control I ertilization is successul then one or more
the timing and amount o egg production in the embryos are placed in the uterus when they are
womans ovaries. about 48 hours old. Because the woman has not
gone through a normal menstrual cycle extra
Intramuscular injections o FSH and LH are progesterone is usually given as a tablet placed
then given daily or about ten days, to stimulate in the vagina, to ensure that the uterus lining is
ollicles to develop. The FSH injections give a maintained. I the embryos implant and continue to
much higher concentration o this hormone grow then the pregnancy that ollows is no dierent
than during a normal menstrual cycle and as rom a pregnancy that began by natural conception.
William Harvey and sexual reproduction Figure 12 IVF allows the earliest stages in a
human life to be seen. This micrograph shows a
William Harveys investigation o sexual reproduction zygote formed by fertilization. The nuclei of the
in deer. egg and sperm are visible in the centre of the
zygote. There is a protective layer of gel around
William Harvey is chiefy remembered or his discovery o the the zygote called the fertilization membrane
circulation o the blood, but he also had a lielong obsession with how
lie is transmitted rom generation to generation and pioneered research
into sexual reproduction. He was taught the seed and soil theory o
Aristotle, according to which the male produces a seed, which orms an
egg when it mixes with menstrual blood. The egg develops into a etus
inside the mother.
William Harvey tested Aristotles theory using a natural experiment.
Deer are seasonal breeders and only become sexually active during the
autumn. Harvey examined the uterus o emale deer during the mating
season by slaughtering and dissecting them. He expected to nd eggs
developing in the uterus immediately ater mating, but only ound signs
o anything developing in emales two or more months ater the start o
the mating season.
339
16 H u mC EaLnLpBHIyOsLiOoGlYo g y
He regarded his experiments with deer as proo that Aristotles theory
o reproduction was alse and concluded the etus doth neither
proceed rom the seed o male or emale in coition, nor yet rom any
commixture o that seed. Although Aristotles seed and soil theory
was alse, Harveys conclusion that the etus did not result rom events
during coitus (sexual intercourse) was also alse.
Harvey was well aware that he had not discovered the basis o
sexual reproduction: neither the philosophers nor the physicians o
yesterday or today have satisactorily explained, or solved the problem
o Aristotle.
Figure 13 William Harveys book on the
reproduction of animals Exercitationes de
Generatione Animalium published in 1651
Improvements in apparatus and research breakthroughs
Developments in scientifc research ollow improvements in apparatus: William
Harvey was hampered in his observational research into reproduction by lack o
equipment. The microscope was invented seventeen years ater his death.
Harvey was understandably reluctant to William Harvey ailed to solve the mystery
publish his research into sexual reproduction, because eective microscopes were not available
but he did eventually do so in 1 651 when he when he was working, so usion o gametes
was 73 years old in his work Exercitationes de and subsequent embryo development remained
Generatione Animalium. He knew that he had not undiscovered. He was unlucky with his choice
solved the mystery o sexual reproduction: o experimental animal because embryos in the
deer that he used remain microscopically small
When I plainly see nothing at all doth or an unusually long period. Microscopes were
remain in the uterus ater coition, ... no invented seventeen years ater Harveys death,
more than remains in the braine ater allowing the discovery o sperm, eggs and early
sensation, ... I have invented this Fable. stage embryos.
Let the learned and ingenious ock o men
consider o it; let the supercilious reject it: Scientifc research has oten been hampered or a
and or the scofng ticklish generation, let time by defciencies in apparatus, with discoveries
them laugh their swinge. Because I say, only being made ollowing improvements.
there is no sensible thing in the uterus This will continue into the uture and we can
ater coition; and yet there is a necessity, look orward to urther transormations in our
that something should be there, which understanding o the natural world as new
may render the animal ruitul. techniques and technology are invented.
340
QueStionS
Questions
1 Using the data in table 1 : accidents during the daytime as a result of
disrupted sleep and tiredness. Figure 1 5 shows
a) outline the relationship between the [3] the percentage oxygen saturation of arterial
age of the mother and the success rate blood during a night of sleep in a patient with
of IVF severe obstructive sleep apnea.
b) outline the relationship between the 100
1
number of embryos transferred and
70
the chance of having a baby as a result
100
of IVF [3] 2
c) discuss how many embryos fertility centres 70
should be allowed to transfer. [4] 100
3
prcg f rgcs r iVF cycl
70
ag f ccrdg h mbr f mbrys rsfrrd
100
mhr 1 2 3 4
liver glycogen levelsingle single twins single twins triplets 70
hours O2%
< 30 10.4 20.1 9.0 17.5 3.6 0.4
100
3034 13.4 21.8 7.9 18.2 7.8 0.6 5
3539 19.1 19.1 5.0 17.4 5.6 0.6 70
> 39 4.1 12.5 3.5 12.7 1.7 0.1 100
6 70
Table 1
100
7
70
2 Figure 1 4 shows variations in liver glycogen 100
over the course of one day. 8
a) Explain the variation in liver 70
glycogen.
0 10 20 30 40 50 60
minutes
[3] Figure 15
b) Evaluate the contribution of glycogen to a) Hour 8 shows a typical pattern due to
obstructive sleep apnea.
blood sugar homeostasis. [2]
(i) Explain the causes of falls in saturation. [2]
an evening snack (ii) Explain the causes of rises in [2]
saturation.
(iii) Calculate how long each cycle of
falling and rising saturation takes. [2]
lunch dinner breakfast b) Estimate the minimum oxygen saturation
4:00 8:00
8:00 12:00 16:00 20:00 24:00 that the patient experienced during the
time ofda
Figure 14 night, and when it occurred. [2]
c) Deduce the sleep patterns of the patient
during the night when the trace was
3 Sometimes the ventilation of the lungs stops. taken. [2]
This is called apnea. One possible cause
is the blockage of the airways by the soft 4 The action potential of a squid axon was
palate during sleep. This is called obstructive recorded, with the axon in normal sea water.
sleep apnea. It has some potentially harmful The axon was then placed in water with a Na+
consequences, including an increased risk of concentration of one- third of that of sea water.
341
16 h u m an p h yS i o lo g y
The action potential was recorded again. a) Using only the data in gure 1 7, outline the
Figure 1 6 shows these recordings. eect o reduced Na+ concentration on:
(i) the magnitude o depolarization [2]
membrabe potential (mV) +40 sea water (ii) the duration o the action [2]
+20 33% potential.
0 b) Explain the eects o reduced Na+
-20 concentration on the action potential. [3]
-40
-60 c) Discuss the eect o reduced Na+
-80
concentration on the time taken to return
Figure 16
to the resting potential. [2]
1 2 d) Compare the action potentials o shaker
time (ms)
and normal ruit fies. [3]
5 Geneticists discovered a mutant variety o ruit e) Explain the dierences between the
fy that shakes vigorously when anaesthetized action potentials.
with ether. Studies have shown that the shaker
mutant has K+ channels that do not unction
properly. Figure 1 7 shows action potentials in
normal ruit fies and in shaker mutants.
membrabe potential/mV 40 wild-type drosophila
normal action potential
0
-40
4 8 12 16
40 shaker mutant
abnormal action potential
0
-40
4 8 12 16
time (ms)
Figure 17
342
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IB Biology - Course Companion - Oxford 2014
- 1 - 50
- 51 - 100
- 101 - 150
- 151 - 200
- 201 - 250
- 251 - 300
- 301 - 350
- 351 - 400
- 401 - 450
- 451 - 500
- 501 - 550
- 551 - 600
- 601 - 650
- 651 - 700
- 701 - 730
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