nm0228: i said that er [0.5] today was going to be [0.3] er a short lecture er 
an hour and a bit i think [0.5] next week will be normal length and the week 
after that will be a bit longer than usual [0.3] er will will run about an 
extra quarter of an hour [3.2] last week i was talking about [0.6] fluid 
balance between plasma and tissue [0.6] and i talked to you about er [0.5] the 
fact that Starling had elucidated the factors governing this [0.5] and that we 
therefore call it the Starling balance [1.6] and i [0.9] put up and explained 
[1.3] an equation which defined the [1.3] factors determining the flux of water 
J-V [0.6] across a capillary wall [0.8] and er for the first part of this 
lecture i'm going to carry on [0.5] talking about that and in particular what 
happens when it goes wrong [1.5] and er [1.7] to start off with can anybody 
tell me [0.7] what's missing [laughter] [0.4] and so i'm not asking for the 
symbols but [0.5] the [0.2] principles what [0.3] does the volume flux [0.5] 
depend on what are the two gradients that drive [0.6] the water flux can 
anybody remember that [0.4] 
sf0233: 
nm0228: what kind of pressure [0.6] 
ss: hydrostatic [0.4] 
nm0228: hydrostatic pressure is one of them and the 
other [0.5] 
sm0234: oncotic [0.2] 
nm0228: oncotic [0.2] plasma colloid osmotic or oncotic pressure [0.5] so we 
have the pressure in the capillary [0.4] minus the pressure in the c-, [0.2] in 
the interstitium [1.4] the oncotic pressure in plasma minus the oncotic 
pressure [0.7] in the interstitium [1.3] what kind of sign do i have [0.6] in 
the middle [0.2] a minus sign [0.4] because remember [0.4] we define it's just 
the way we define these pressures [0.5] that [0.2] the high [0.2] oncotic 
pressure tren-, tends to draw [0.4] water towards it [0.4] and a high 
hydrostatic pressure [0.3] pushes water away from it so they work in opposite 
directions [1.2] we have three membrane [1.2] characteristics in this equation 
[1.1] one of them 
sm0235: permeability [0.3] 
nm0228: [laughter] what [0.2] 
sm0235: permeability 
nm0228: yes which for water we call hydraulic conductivity [0.9] multiplied by 
[1.9] surface area [0.4] if the surface area is low there's no exchange [0.6] 
and then we have one more which shows how good [0.5] a semi-permeable membrane 
[0.3] the capillary wall is and that's called [0.5] 
sf0236: 
nm0228: yeah what does that represent what's the technical term [0.7] 
[laughter] [0.6] the reflection coefficient [0.4] okay [1.4] we're going to 
start off 
today by talking about [0.7] two normal conditions [0.4] that occur [0.5] which 
[0.2] elevate [0.4] P-C [0.3] the hydrostatic pressure in the capillary [0.6] 
and therefore [0.4] you can see from this equation elevate [0.5] the flux of 
water out of the blood into the tissue [1.3] and the first one is one that 
you've studied [0.5] in your practical class and that is standing up [0.9] 
because when you stand up [2.2] the [0.2] pressure [0.4] in your feet [0.5] is 
much higher than it is when you're lying down we have the normal blood pressure 
that's being provided by the heart all the time [0.4] when you stand up you 
have in addition [0.4] the hydrostatic pressure [0.4] from that column of water 
or column of blood more accurately [0.3] between the heart and your foot so 
there's somewhere between [0.4] a metre and two metres [0.4] extra hydrostatic 
pressure of water there [0.4] and that's a lot compared to the blood pressure 
[1.1] and that's er in the arteries [0.5] but er some of this pressure is 
transmitted through to the capillaries as well the pressure goes up [0.5] in 
the capillaries [1.4] so when you stand up [0.6] there is an extra 
flux of water out of the capillaries in your feet [0.4] into the tissue [0.5] 
in your feet [1.4] and the question is what does the body do about this [2.7] 
how do we prevent that from happening [2.2] well [0.3] to a certain extent we 
can't do anything about it and if you do stand up for a long time your feet 
will swell [0.9] er [1.1] i-, [0.3] it's not often that you do stand still for 
very long periods of time but you sit still for very long periods of time [0.6] 
er in an aeroplane for instance if you're on a eight hour aircraft ride you 
would definitely notice [0.5] that your feet swell if you take your shoes off 
at the beginning of the flight it's difficult to get them back on at the end 
and that is because [0.4] you've been sitting immobile for many hours [0.4] and 
[0.3] although when you're sitting the hydrostatic pressure isn't [0.4] as 
great as when you're standing it's still a lot more than when you're lying down 
[0.4] and that forces fluid [0.4] out of the capillaries [0.4] into the tissue 
[2.3] the [0.2] body tries to compensate and what it does [0.4] is to increase 
the 
resistance of the arterioles [4.7] so the arterioles constrict the s-, muscle 
cells in the arterioles constrict [0.8] and this does [0.3] three things [3.2] 
first of all it reduces [0.9] the pressure in the capillaries it reduces [0.6] 
P-C [1.4] remember that [0.2] pressure [0.4] is connected to the potential 
energy of a fluid [0.6] and if we have to force that fluid through a higher 
resistance [0.3] more energy is dissipated [0.5] so if if the arterioles 
constrict [0.4] more of that pressure the energy that's represented by that 
pressure [0.4] will be used up forcing the fluid through the arterioles [0.4] 
and the pressure in the capillaries [0.3] will be lower so that's the first 
thing that happens [0.4] and obviously we can't shut the arterioles down 
completely [0.4] otherwise your feet wouldn't get [0.4] the oxygen that they 
require [3.7] so the r-, that [0.3] also gives us a reduced flow [0.3] in the 
capillary [6.3] and because there's a reduced flow in the capillary [0.5] we're 
getting [0.4] the filtration [0.4] that is the water is being removed [0.4] 
from a smaller volume of blood than normal [5.1] we're 
reducing the amount of blood throwing flowing through the capillary [0.3] and 
therefore all this water that's coming out of the blood is coming from a 
relatively small volume of it [1.1] and that [0.6] concentrates the blood we're 
losing water [0.4] but we're not losing solutes [0.4] and we get an increase [0.
4] in the oncotic pressure of the plasma [0.5] so because we're losing a lot of 
fluid from a small volume of blood [0.4] the oncotic pressure goes up the blood 
is becoming concentrated essentially [0.7] and if you go back to the Starling 
equation [0.4] you will see that having [0.3] a high oncotic pressure in plasma 
[1.0] opposes more water leaving it tends to pull water back into the plasma [0.
8] so that also helps [9.2] the final thing [0.4] is that we may [0.8] shut 
down some capillaries [7.0] remember that [0.4] capillaries are opening and 
closing all the time well 
that's not [0.2] that's not strictly accurate [0.4] it's the arterioles that 
are opening and closing all the time [0.4] and allowing blood either to perfuse 
the capillary or not to [0.2] perfuse it [0.4] and i've mentioned that this is 
called vasomotion [3.0] and if we [0.3] increase the resistance of [0.4] 
arterioles [0.3] that means that more of the capillaries will be shut down more 
of the time [0.7] so [0.6] they have [0.4] no flow going through them [0.2] 
there's no there's no blood in them [3.2] and then he-, [0.4] and hence [0.5] 
no filtration while they're [0.3] closed down [2.4] so those are three ways in 
which the body [0.2] tries to combat this effect [0.5] but as i've said [0.3] 
the body can't [0.5] prevent it completely and our our feet certainly do swell 
if we stand [0.5] for a long period of time [3.6] you 
can see from this [0.4] that [0.3] exercise is also going to [1.6] cause 
problems [3.8] i've [0.4] talked about the control of arteriole return [0.5] 
and i've said that when our [0.3] tissue is metabolizing more [0.5] as it does 
during exercise [0.4] that causes arterioles to dilate [1.5] so during exercise 
[0.4] our arterioles dilate [0.8] and that is [0.4] to provide the tissue with 
more blood [2.7] but you can see from what i've just said [0.4] i mean that 
that is of course equiv-, [0.2] equivalent to a decreased resistance in the 
arterioles [2.0] that this will have the opposite effect of all these [0.8] 
protective mechanisms that i've just talked about [0.7] for the [0.3] effects 
of posture [0.8] by [0.2] when we exercise we decrease [0.4] the resistance in 
our arteries [0.3] and that will do the opposite of points one two and three [0.
8] so it will tend to increase [0.2] filtration [1.5] it's exactly the opposite 
effect [9.1] and again [0.6] you may very well have noticed that if [0.3] you 
do exercise [0.3] there is a lot of movement of water from the blood into 
tissue [0.5] if you wear rings for instance and they come off easily [0.4] if 
you do a 
lot of exercise with your arms or hands you'll find that the rings won't come 
off [0.6] and that's because [0.5] the [0.2] arterioles supplying blood to the 
arm muscles have dilated [0.6] reduced the resistance and more fluid has 
filtered out into the tissue and swollen your fingers [0.4] you can sometimes 
feel this if you exercise [0.4] your skin will feel tight over the muscles 
compared to normal [0.4] and that's due to this tissue swelling [4.1] are there 
any questions about this so far [2.7] okay [0.4] well these are two cases [0.3] 
where [1.5] things [0.5] go wrong for the Starling balance but there [0.4] er 
we can cope with it the body can er er [0.4] put up with this sort of level of 
increased filtration [1.2] but it's not always the case [1.4] and i said last 
week i apologize for leaving a [0.5] a a figure behind that is [0.5] an extreme 
clinical case of [0.5] er [0.6] movement of [0.2] fluid from [0.6] the blood 
vessels into the tissue it's affected [0.4] one leg in this patient [0.4] and 
not others and not the other [4.8] and this [0.4] inappropriate this 
pathological movement of water [0.7] we call oedema [0.9] and i'm going to 
say [0.5] quite a bit about oedema [2.3] again if you're using American 
textbooks that will be spelled [0.3] without the O [0.3] spelled just E-D [0.4] 
E-M-A [8.0] and [1.0] oedema is [0.4] er [0.5] fluid accumulation [0.4] in the 
interstitium [0.7] pathological er accumulation of fluid in the interstitium [0.
6] and it occurs [0.5] when this flux of water out of the blood that i've 
talked about [0.4] is greater [0.4] than the flow of lymph [1.2] so this is the 
net [1.6] flux of water out of the [0.3] capillaries [0.9] is greater than the 
lymph flow [0.4] which returns [0.3] water from the interstitium back to the 
blood system [7.1] and if you go back to this [2.7] to the Starling equation [1.
8] you can see [0.3] the various factors that will cause this to be too high [3.
4] so i'm going to give you a list of [0.6] factors that are of clinical 
importance that can cause [0.4] oedema [0.4] and the first one is the one we've 
just been talking about [0.4] to do with posture and exercise [0.3] that's when 
[0.3] the pressure in the capillaries is too high [0.5] so that's the first 
cause [0.5] of oedema [1.4] it's when P-C is too high [7.3] and this tends to 
occur [0.6] 
if [0.3] the [1.0] if there's a problem with the veins [0.4] and in particular 
[0.4] if there's a high pressure in the veins [3.0] because of course the 
capillaries empty into the venules and then thereby into the veins [0.4] and if 
there's a high pressure [0.4] in the veins [0.4] that pressure will back up 
into the capillaries the capillaries won't be able to [0.3] move fluid into the 
veins until their pressure also [0.3] has become elevated [0.6] so the main 
cause of having too high [0.3] a capillary pressure [0.4] is to have too high a 
venous pressure [0.4] it prevents the fluid coming out of the capillaries [0.5] 
and so it's venous problems [0.3] that tend to [0.7] to er [0.6] cause this [0.
4] and particularly [0.4] er thrombosis [0.3] blood co-, clots [0.2] forming [0.
3] inside the veins [0.4] or other kinds of venous failure [1.1] such as 
varicose veins [0.4] when the valves in the veins [0.2] er are reversed [0.9] 
and i i'm sure you've seen [0.6] er [0.3] people [0.5] it seems particularly to 
affect elderly women [0.5] who've got [0.4] er [0.6] varicose veins or problems 
with the veins in their legs [0.3] and also swollen [0.2] legs swollen ankles 
and those two 
go together [0.5] it's because [0.5] these venous problems are causing a high 
pressure in the veins [0.4] that's causing a high [0.2] pro-, pressure in the 
capillaries [0.4] and the high pressure in the capillaries is forcing fluid out 
[0.4] into the tissue [11.0] again if we go back to this [0.3] equation [1.8] 
you can see that [0.8] another [0.3] cause of problems [0.3] could be if we had 
something wrong with the oncotic [0.4] pressure [0.3] in plasma [0.6] so i'll 
talk about that [3.7] if the oncotic pressure in plasma is too low [1.4] we 
will get [0.4] problems [0.4] s-, remember that these work in the opposite 
directions that's why [0.6] the hydrostatic pressure has to be too high [0.4] 
and the oncotic pressure has to be too low to cause problems [0.4] if the 
oncotic pressure is too low [0.5] that will stop water being attracted to the 
blood [6.3] what is the [0.3] oncotic pressure in blood caused by [0.6] what is 
it [0.2] that gives us the [0.6] this osmotic pressure this oncotic pressure [4.
5] plasma proteins [3.8] and particularly albumin [2.9] which is made in the 
liver [1.9] it's the plasma proteins [0.6] that [0.2] draw water towards 
the blood [0.8] and [0.2] that's particularly the role of albumin which is 
about three-quarters of the total protein mass in the plasma [3.9] so [0.6] the 
first thing that will cause [0.9] oedema [0.4] is malnutrition [0.7] because [0.
7] we need [1.3] amino acids we need protein in our diet in order to 
manufacture [0.6] proteins and if we don't [0.5] have enough [0.2] intake then 
we can't make the proteins [0.7] and [0.5] when you see these [0.4] pictures of 
starving [0.2] children [0.7] in the developing countries [0.3] with very 
swollen stomachs that's a form of oedema [0.4] that's caused by [0.5] 
malnutrition they're not able to make enough protein [0.5] and that allows 
fluid to leak into the [0.4] abdominal cavity [6.1] we can also [0.5] get [0.2] 
oedema [0.4] if we have poor [0.6] gut absorption of protein [2.1] even if you 
have a normal diet [0.4] and your gut is not working properly it doesn't absorb 
the amino acids [0.4] then again [0.4] you will not be able to make [0.2] 
enough plasma proteins [0.4] to keep the water in the plasma [6.3] even if you 
do synthesize the protein [0.3] you can [0.8] that that won't be enough if you 
lose it again so if you have some 
condition [0.5] that causes protein loss [0.8] then again [0.3] you can be [0.
2] prone to oedema [0.4] and protein loss can occur [0.7] er [0.4] by the 
kidney [0.4] this is a common complication of pregnancy [0.4] for example [0.6] 
er protein urea is when we get [0.5] a large quantity of protein in the urine 
[0.8] or again if [0.3] one has problems with the gut [0.3] then protein can be 
[0.4] can be lost [0.5] [0.2] excuse me [0.4] can be lost through the gut [3.8] 
and finally [0.3] if we have liver problems [2.1] then we can [0.3] have [0.5] 
oedema [0.3] because it's the liver that synthesizes the plasma proteins [0.6] 
the albumen is synthesized in the liver [0.4] and if you have lime-, liver 
damage [0.5] er alcoholism for example [0.6] causing cirrhosis of the liver [0.
6] er [0.4] er [0.3] protein production will be lowered [0.7] and er [1.6] 
oedema will result [15.2] 
another [0.2] way in which we can get [0.4] oedema [0.8] is if [0.6] the [1.0] 
permeability of the capillary to water its hydraulic conductivity [0.4] becomes 
too high [24.0] so again [2.2] if we get an increase in capillary permeability 
we will get a swelling [0.3] because [0.4] fluid leaks from the capillary [0.7] 
into the [0.4] tissue [0.4] where did you see this in your practical [4.9] 
sm0229: when you scratch a little bit of you 
nm0228: good [0.3] scratching the skin [0.4] you got a weal [0.3] a raised [0.
2] area of redness [0.5] because the capillaries had been damaged [0.4] and 
leaked water into the tissue [0.5] so this is a form [0.4] of inflammation [7.
0] and of course any other kind of inflammation will do the same if you have a 
local [0.4] infection [0.7] or local tissue damage [0.3] you get leaky 
capillaries [0.3] and the area swells you know that from personal experience if 
you have a [0.3] a local injury the tissue around it will swell up [11.7] and 
the final point [0.5] and i said at 
the start [0.4] that oedema occurred [0.4] if the movement of fluid out the net 
movement i say net movement here because there's water moving backwards and 
forwards into the capillaries [0.3] so we're concerned with [0.4] the net [0.3] 
flux out of the capillaries [0.6] if this is [0.4] greater [0.4] than lymph 
flow then we get accumulation in the tissues [0.4] so [0.3] even if this stays 
normal even if J-V stays normal [0.3] we can still get oedema [0.5] if 
something happens to the lymph [0.6] if our lymph flow goes down for some 
reason [0.4] so [0.4] a final [0.3] group of causes [0.3] are concerned with 
lymphatic problems [9.8] and [0.7] we can have problems with our lymph [0.5] er 
through developmental problems if the lymph vessels aren't [0.2] formed 
properly [4.3] through [0.4] damage [0.2] to lymph vessels and lymph nodes [0.
4] and that's the case in this er [3.1] rather [0.3] revolting picture what's 
happened here [0.5] is that this is [0.2] er [0.7] a patient who's had surgery 
[0.4] and the surgery has damaged the lymph nodes in the groin [0.4] on one 
side [0.4] and so this leg is being inadequately [0.3] drained of lymph [0.5] 
while this leg is being drained 
properly so this is not a [0.3] a problem with J-V [0.3] this is a problem with 
[0.4] lymphatic drainage [0.3] 
sm0230: all this water's coming out of your blood system does your blood become 
more viscous or 
nm0228: well it will become more concentrated but this tends to develop over a 
long period of time so your water intake will [0.5] compensate for that [2.0] 
and then er a final group of causes [0.6] are [0.3] er parasites [0.4] which 
can block the lymphatic [0.2] system and again i'm sure you've seen [0.4] 
pictures of elephantiasis and similar conditions [0.3] which look very similar 
to this [0.3] patient that i've just shown you [0.4] for the same reason [0.3] 
that the lymph nodes are being blocked [0.5] er in in most cases by nematode 
worms [0.4] and that that er causes a poor [0.2] drainage of fluid [0.4] back 
from the tissue [1.3] 
sf0231: what was that called [1.3] 
nm0228: er well that particular one is called elephantiasis [3.6] i think 
that's how you spell it i wouldn't swear to it [2.0] so called because the [0.
2] limbs swell to [0.5] elephant-like er [1.4] proportions [0.9] er [4.4] i 
think that's the technical [0.4] term for it [0.2] filariasis filariasis i'm 
not sure how you pronounce that either [0.4] but it's a filarial [0.4] worm a 
nematode worm [0.4] 
which is causing this blockage but there are many [0.4] similar sorts of 
conditions that have the same effect [5.4] so [0.5] when we when we do have 
oedema when the [0.3] er [0.6] flux of water into the tissue overcomes the 
lymphatic flow [0.8] then we get [0.6] an [0.3] accumulation of free water in 
the tissue [0.8] and that's unusual [0.5] i talked er [2.1] last week i think 
it was last week [0.4] about the fact that the [0.7] er [1.6] that the tissues 
filled with proteoglycans [0.7] and have a high osmotic [0.3] charge [0.4] a 
high er a high charge density and hence a high osmotic pressure [0.7] and that 
these tend to retain the water [0.3] it's not strictly in chemical terms a gel 
[0.4] but your interstitium acts like a gel the the water won't move through it 
easily [0.4] and when you get [0.3] er oedema [0.7] the water is free water 
it's not trapped in this network of proteoglycans [0.4] it's swishing around 
inside you free to move [3.3] and the commonest place for it to [0.5] to occur 
is under the skin [1.4] which we call [0.3] subcutaneous [3.9] and you can 
actually feel that it's free water [1.5] if [0.3] if [0.9] if you don't have 
oedema [0.2] and you [0.8] 
er [0.5] press your finger against your arm [0.6] then [1.3] when you push the 
finger down the [0.3] flesh is depressed the tissue is depressed but when you 
release the pressure [0.5] the tissue bounces right back up again [0.6] but w-, 
in oedema that's not the case [0.3] if you push the f-, [0.2] finger down you 
get a depression and when you take the finger up [0.3] the depression stays 
there for a while [0.4] because you've pushed this free water away it can 
actually flow [0.3] and then it slowly [0.3] flows back again [0.5] and [0.6] 
because of that we call this pitting oedema [1.5] because [0.7] you're able to 
make pits in it simply by pushing your finger in it [5.7] th-, this is not a 
dangerous condition although the the pictures look horrific [0.5] they are [0.
4] not life-threatening [0.7] you can get [0.3] local problems [0.5] because 
this mass of water [0.4] makes it hard for the cells to get nourished and to 
get rid of the their waste products it increases all these diffusion distances 
[0.5] then individually cells can die [0.4] so we get necrosis cell necrosis [0.
2] that's cell death [3.1] and this can give rise to ulcers [1.1] 
and local tissue problems but it's [0.2] unlikely to be [0.2] a life-
threatening [0.6] er [0.7] a life-threatening problem [4.4] the second [0.8] 
place in which you can have oedema though is very dangerous [0.8] and that's 
when it's in the lungs [7.3] which we call pulmonary oedema [8.1] i've said [0.
5] that [0.4] one of the causes [0.4] of [0.4] oedema [0.3] is when we get a 
high [1.4] pressure in the veins [0.9] and that's the usually the case for 
pulmonary oedema [0.4] and it occurs when we get a failure of the left 
ventricle [5.1] remember that the [0.3] blood from the lungs [0.5] comes back 
to the heart [0.2] through the pulmonary veins [0.4] comes back into the left 
side of the heart first into the atrium [0.5] and then into the left ventricle 
[0.4] where it's pumped around the body [2.2] if the left ventricle is damaged 
[0.4] then it cannot pump the blood away around the body so effectively [0.6] 
the the left ventricle if its pumping action is damaged [0.4] tends to be 
filled with blood [0.6] and that backs up into the left atrium [0.3] and that 
backs up into the pulmonary veins [0.2] and that backs up into the capillaries 
of the lungs 
themselves [0.3] so if the heart can't pump the blood away from the lungs [0.4] 
the pressure [0.4] in the lungs [0.2] will increase [0.4] so left ventricle 
damage [1.6] gives us [0.2] an increased [0.2] P-C capillary pressure [0.4] in 
the lungs [0.4] and that's a common er effect of [0.2] a heart attack [0.7] 
because it's it's extremely common for heart attacks to damage [0.5] the muscle 
of the [0.4] left ventricle [5.0] now when this happens [0.5] the lung starts 
to [0.3] er [0.2] fill with water [1.4] and initially [0.3] that makes the 
lungs very stiff [1.6] that would be the first thing [0.4] that would be 
noticed it would be hard to breathe [6.6] that would be the first step just a a 
stiffening of the lungs due to [0.4] er [0.8] to [0.3] water accumulation [1.4] 
but also [0.3] the [0.5] w-, extra water there increases the diffusion 
distances [5.7] i've talked about [0.3] how the lungs are very carefully 
designed to bring the gas as close as possible to the blood [0.7] the gas in 
the blood is separated only by a fraction of a micron [0.5] and diffusion takes 
place over that distance [0.5] but if the lungs are filled with fluid [0.4] 
then the gas has to diffuse through the fluid before it can get into the blood 
[0.5] and so [0.3] we get an increase in diffusion distances [0.3] and that 
gives us [0.4] poor gas exchange [4.5] 
so [0.9] it seems unusual [0.6] i mean it seems [0.3] not unusual it seems [0.
7] strange that when somebody's had a heart attack [0.4] they start to have 
problems with breathing and you often see people with [0.3] chronic heart 
complaints they have to use [0.3] oxygen masks they will have oxygen cylinders 
at home [0.5] and it's not easy in your mind to see [0.4] what the connection 
is between the breathing and the heart attack but it's this [0.5] that if the 
heart can't pump the blood away [0.4] then the lungs the [0.2] capillary 
pressure goes up in the lungs [0.3] lungs will fill with fluid [0.3] and that 
makes it harder to breathe [3.4] and this is a dangerous condition [0.4] 
meaning that it can easily be [0.4] fatal you can just have inadequate [0.4] 
gas exchange [0.6] and er [0.6] this is the death rattle that's referred to in 
Victorian melodramas that [0.2] the the death rattle was [0.4] the gases in the 
lungs bubbling through the fluid that has accumulated in the lungs [0.4] in 
pulmonary oedema [9.1] are there any questions about [0.5] what i've said so 
far [2.3] no [0.4] okay [23.6] i'm going to finish up [0.4] with two short 
topics [0.8] the the first is the return how how the [0.6] water and solutes 
are returned to the heart [0.7] and the second is [0.2] on the control of blood 
pressure [0.6] so let's start with [1.1] the return of [0.7] water and solutes 
[0.8] to the heart [17.2] and [0.6] you know already from what i've said that 
there are two rou-, [0.2] two routes back to the heart [0.5] one through the 
blood system [0.3] and one through the lymphatic system [0.4] so let's start 
with the [0.6] blood system [0.6] and it's of course the veins [0.3] the venous 
system [0.6] which is involved in this [5.3] and i've mentioned already [0.7] 
that as the [0.3] capillaries converge as they come out of tissue beds [0.4] 
they converge to form vessels called venules [1.0] and then the venules 
converge [0.5] to form the veins [0.5] and the veins also [0.5] converge [0.4] 
and the largest veins are called vena cavae [4.2] and there are three of these 
[0.4] which enter the [0.5] right side of the heart [13.3] and the veins [0.4] 
have [0.7] the [0.3] function not only of [0.4] moving the blood back to the 
heart [0.4] but they are also where we store our blood [0.7] they are the [0.2] 
the body's reservoir for 
blood [0.5] and at any particular time about two-thirds of the blood [0.4] will 
be in the venous system [4.3] and [0.2] i th-, i think i mentioned in the first 
lecture that we call [0.4] veins capacitance vessels [7.4] because they have 
this capacity to store blood [0.4] and it's a variable capacity it's under 
control [3.4] the veins are [0.4] very [0.7] stretchy [1.1] they are very 
compliant [4.0] that means that it doesn't take [0.2] a big change in pressure 
to get a big change in volume even a little change in pressure [0.4] will 
increase the volume substantially [2.4] the reason for that [0.4] is that the 
veins are very [0.8] floppy [0.3] structures and if you look at them in c-, [0.
2] cross-section [0.4] they can collapse very easily [0.4] so we might have a 
normal round vein [0.4] but if we decrease the pressure in it it will become [0.
4] oval in cross-section [0.3] and if we decrease the pressure even more [0.3] 
it will collapse completely [0.4] to look something like [0.5] a dumbbell shape 
like that [0.5] and obviously the amount of blood that can be stored has 
dropped dramatically [0.4] as you go from the round shape to the dumb-bell 
shape [0.4] but it doesn't need much pressure [0.5] to inflate the veins again 
so they're very compliant [11.3] and the [0.8] the veins [0.3] have [0.4] er [0.
3] smooth muscle cells in the walls [0.4] and their smooth muscle cells are 
under nervous control [0.5] so the the diameter of the veins [2.0] is under 
nervous control and i'll come back to that when i talk about [1.6] blood [0.2] 
the control of blood pressure [7.5] now the other peculiarity about the veins 
[0.5] is that there isn't enough pressure [0.4] to bring the blood back to the 
heart [0.6] when the blood comes out of the capillaries it has a very low 
pressure [0.6] certainly not enough [0.4] to drive the blood f-, say from your 
feet [0.4] back to your heart [0.4] so there's a problem there the body has to 
work out some [0.2] additional way [0.4] of getting that blood to [0.6] t-, [0.
3] to er [1.4] to to elevate that blood though that metre or two metres [1.5] 
and [0.8] it does this by [1.2] having valves the veins have valves in them [2.
4] and they get squeezed the veins ge-, get squeezed from the outside so 
supposing we have a vein like this [2.2] and it has two [2.1] 
valves in it [3.5] so that's supposed to be a cross-section through a vein and 
there's [0.6] er [0.9] a se-, a segment of the vein enclosed [0.5] by [0.4] 
valves and there's blood in here [1.5] then if that vein gets squashed from the 
outside [2.0] so if there's a pressure applied from the outside [0.5] then the 
blood can only move in one direction [0.6] it has to move back towards the 
heart [0.4] so every time a vein gets squeezed from outside [0.4] even though 
the blood pressure is normally low [0.4] that [0.2] is what moves the blood 
back towards the heart [0.5] and this kind of squeezing [0.7] can occur [0.6] 
when you use your muscles [1.1] and er [1.2] this is a trick that's taught to 
soldiers when they stand on parade [0.5] because if you stand completely still 
for a very long period of time [0.4] there isn't any muscular action bringing 
the pressure back to the heart [0.5] and you can easily faint because the blood 
pressure will drop [0.5] as a result of there being a low [0.3] cardiac output 
and i'm sure you've seen these pictures of a [0.5] of a row of soldiers 
standing at attention and [0.4] one of them was 
lying on the ground horizontally because he's fainted [0.6] and and soldiers on 
[0.2] parade are taught to twitch their calf muscles [0.4] and their feet [0.3] 
from time to time [0.3] to squeeze their veins [0.9] and this [0.3] pushes the 
blood back to the heart [0.4] by the Frank Starling mechanism that we've talked 
about [0.4] that will increase the cardiac output [0.4] and hence keep the 
blood pressure up [1.3] but it's not just this voluntary [0.2] sort of muscle 
use that er [0.2] does this [0.4] it's also [0.3] when you breathe [2.0] and 
also [0.5] to a smaller extent the peristaltic movements of the gut [0.3] so 
it's not just your voluntary muscles but also these er [0.8] automatic things 
that are going on [0.6] and in particular when you breathe [0.7] when you [0.3] 
inflate your chest you reduce the pressure [0.4] in the thorax [0.2] and also 
in the abdomen as well because they're connected via the diaphragm [0.5] and as 
you incr-, [0.3] er decrease the pressure when you inflate your chest [0.3] 
that will tend to draw blood up [0.8] the veins and towards the heart [0.3] and 
if you look at a blood pressure recording which 
shows the blood pressure beat by beat [0.5] then er [7.0] you might expect a 
blood pressure trace [2.8] to look like this oscillating with each heartbeat 
but it doesn't look that it looks like this [6.5] it has an extra longer wave 
superimposed on it and that's your breathing rhythm [0.5] this is the heart 
beating [0.4] and this slower wave [0.5] is the breathing rhythm every time you 
breathe in [0.4] more blood is drawn back towards the heart and the blood 
pressure goes up a little bit [1.7] and conversely [0.5] if you increase the 
pressure in your chest that reduces the blood flow back to the heart [0.3] so 
if you cough [0.2] for example [0.4] that will reduce the the pressure during 
coughing [0.4] in the chest gets extremely high [0.4] and if you have a 
prolonged coughing fit [0.5] that will stop the blood coming back to the heart 
long enough for you to faint [0.5] so er babies that have whooping cough for 
instance one of the diagnostic features is that they lose consciousness [0.4] 
during a coughing fit they go blue and lose consciousness [0.5] and that's 
because [0.4] the 
increased pressure in the thorax [0.5] er [0.2] s-, [0.6] prevents the blood 
from coming back up the veins [0.5] and er [0.6] therefore the cardiac output 
goes down and not enough blood gets to the head [9.6] 
so let's move on the other way of getting fluid [0.3] and solutes back to the 
heart [0.5] is through the lymphatic system [4.4] and i introduced this system 
[0.5] last week [0.6] remember that i said that they were blind-ended 
capillaries this system lies parallel only to the venous side of the 
circulation [0.5] there's a lymphatic equivalent to [0.3] capillaries and 
venules and veins but not to [0.3] arteries and arterioles so this is [0.4] 
lying parallel just to the venous side [0.6] and er remember that i said it has 
valves in it [0.8] both at the [0.2] capillary end where the endothelial cells 
act like flaps but also further up the lymphatic system it has [0.3] proper 
valves [0.4] and that it ac-, acts just like the venous system if it gets 
squeezed from outside [0.4] that forces blood along the along the network of 
lym-, lymphatic vessels [1.5] but the lymphatic system also [0.3] has its 
own pump [1.8] there is smooth muscle in the walls of the larger lymph vessels 
[0.4] and it contracts rhythmically it's rather like the sort of primitive 
heart that you get in [0.4] worms [0.4] in in lower invertebrates [0.7] that f-,
it forces blood back er f-, shouldn't say blood it forces lymph back along the 
lymphatic system [0.4] and as i mentioned last week it can generate [0.4] high 
pressures [1.2] though what i didn't mention last week was where [0.8] all that 
lymph ends up [0.5] and this diagram is in your handout [3.2] and it just shows 
the large scale anatomy [0.4] of the lymphatic system [0.7] and most of the 
lymph comes up this large vessel [0.7] called [0.2] the [0.4] thoracic duct 
which i've underlined in green here [0.5] and that lies very close to the aorta 
and the vena cava along the backbone [0.4] so [0.3] most of the lymph from your 
body [0.4] tends to [0.5] collect into this large thoracic duct [0.7] and then 
it's er returned into the subclavian vein [1.4] that duct joins onto the left 
[0.3] subclavian de-, vein [0.8] and that's how we return the lymph into the 
blood [0.3] system the 
water just simply pours into one of the veins [0.9] that's about eighty per 
cent of the lymph about twenty per cent comes [0.4] through [0.2] another 
vessel on the right side of the body [0.8] and this is lymph that's collected 
from the right [0.3] thorax the right arm and the right side of the head [0.7] 
it enters into [0.4] another vessel which i've also lined in underlined in 
green here that's the right [0.3] lymph duct [0.4] that's about twenty per cent 
of the lymph comes in that [0.4] route [0.3] and that enters into the right 
subclavian vein [0.3] instead of the left subclavian vein [15.7] are there any 
questions about [0.2] veins or [0.2] the lymphatic system [2.9] no [0.2] good 
[0.4] okay [0.7] well i'll move on to the final topic [0.2] a brief topic [3.0] 
and that is [0.4] the control of blood pressure [20.7] er the reason that i've 
had to leave this topic until the end we've i i [0.3] hope you've noticed that 
i've gone around the circulation starting with the heart going around the 
arteries to the capillaries [0.4] and then back to the heart [0.8] and er [0.2] 
the reason i've left the control of blood pressure 
till the end [0.4] is that it involves just about every aspect of the 
circulation so i couldn't introduce that until [0.5] er [1.5] er until i've 
discussed everything else [2.4] and you should note that when people talk about 
[0.2] blood pressure [0.5] they are generally talking about arterial [0.4] 
blood pressure when you go and have your [0.5] blood pressure measured or as 
you measured it in the practicals [0.5] that's the blood pressure in the large 
arteries near the heart [0.5] usually the brachial artery [8.0] as well as 
involving all the vessels that i've talked about [0.8] this involves a 
specialized set of receptors [1.1] that are called baroreceptors [0.6] and you 
should have come across these when you [0.7] wrote up your [1.4] er [1.4] wrote 
up your practical [1.3] and the baroreceptors [0.5] the [0.2] prefix the baro 
here comes [0.5] er means pressure [0.3] in the in the same way as you find it 
in barometer for instance so these are pressure [0.2] sensors [1.0] and they're 
found in two locations in the arterial system [0.9] one is the [0.5] carotid 
sinus [4.2] at [0.3] two main locations i could say i should say there 
there are other [0.5] less important locations too [0.5] the first one is in 
the carotid sinus the carotid artery's the large artery [0.4] coming up either 
side of the neck [0.4] and it splits into two [0.4] one side helps to feed the 
brain and the other side [0.3] feeds the face and the scalp [0.7] and [0.4] 
where the artery splits in two [0.4] there's a kind of swelling at that 
bifurcation that's the carotid sinus [1.6] and the other location [0.4] is the 
aortic arch [3.7] so that's as the [0.5] er aorta is [0.3] coming out of the 
heart it comes up and turns [0.2] curves in two dimensions before it goes down 
[0.3] along the backbone [0.4] and at the [0.2] top of the arch there are more 
of these receptors [0.9] which are not to be confused with chemoreceptors [0.5] 
remember that i talked to you about chemoreceptors when i was talking about the 
control of ventilation [0.4] and the chemoreceptors are in the same place [0.4] 
that's a separate system so don't get these two [0.4] confused [3.6] so if we 
have [0.4] an increase in pressure [0.6] or an increase [0.2] in pulse pressure 
[2.2] and by pulse pressure [1.2] is meant the difference 
between systolic blood pressure and diastolic blood pressure [0.3] so it's how 
much the blood pressure [0.3] jumps each heartbeat [2.2] if these increase [0.
6] then we get [0.3] an increase in firing [0.5] of the baroreceptors [8.0] and 
this is sent to the medulla [6.1] where there's something that used to be 
called [0.3] the cardiovascular centre [0.4] but it's unfashionable to call it 
that these days [0.6] it used to be thought that [0.5] each [0.3] physiological 
system had a centre in the brain there'd be a cardiovascular centre and a 
respiratory centre [0.4] and that's now believed to be too simplistic but 
you'll probably still see that in textbooks [0.5] it will be referred to as the 
medullary cardiovascular [0.3] centre but it's in the brain stem a set of 
neurones in the brain stem that are [0.5] concerned with regulating [0.5] er 
blood pressure [1.7] and [1.0] the m-, medulla reacts [0.4] by [0.3] er 
changing the [0.4] firing of the [0.9] parasympathetic and the sympathetic 
nervous system [0.4] so in this case we'd get an increase [0.4] in the 
parasympathetic [0.5] nervous system firing [0.3] and a decrease in the 
sympathetic [0.4] nervous system firing [1.5] these are the two components of 
the autonomic nervous system [3.9] and these changes [0.6] decrease pressure [2.
1] and we'll see how in a moment [2.9] so we have a nice little negative 
feedback loop here a reflex [0.5] and it's called the baro-, [0.6] baroreceptor 
reflex [0.4] or the baroreflex [0.4] for short [1.7] and i hope you've come 
across this when you wrote up your [0.6] cardiovascular practical that's the 
baroreflex [2.6] now before i say what this does [0.3] i just want to say [0.7] 
a few [0.2] words about [1.1] what [0.5] blood pressure actually is [1.8] and 
remember that we've got these variables [1.5] blood flow [0.7] blood pressure 
[0.6] and [0.5] resistance [1.0] and who can tell me [0.2] how i arrange those 
[1.0] into an equation what's the relationship this is so important to remember 
this equation [5.5] [laughter] [1.2] please learn this [9.9] in fact it's it's 
more strictly written [0.2] delta-P equals Q-R [0.6] that is the difference in 
pressure that drives the flow [0.3] to drive flow round a pipe we have to have 
a a higher pressure at one end [0.4] than another please please [0.4] do learn 
this [0.6] and [0.2] 
as i've pointed out several times already it's the same [0.4] as Ohm's law if 
you know Ohm's law you shouldn't have any trouble remembering this [7.1] now [0.
7] in the circulation [0.5] if we take apply this equation to the circulation 
as a whole [0.7] we can say that this is the blood pressure [0.6] coming out of 
the heart [9.5] minus the blood pressure [1.9] coming into the heart [5.0] 
that's the pressure gradient that drives [0.3] blood flow around the whole 
circulation [0.3] the pressure generated by the heart [0.3] minus the pressure 
of the blood when it returns to the heart [1.6] and that equals [0.5] the flow 
rate but the flow rate for the whole circulation [0.3] is the same as the 
cardiac output [5.1] that is the flow of blood around the circulation [0.3] the 
flow of blood around the whole circulation is obviously the blood that's been 
pushed out by the heart [0.4] so we can say that the flow rate is the cardiac 
output [0.5] and cardiac output equals [1.7] [laugh] [1.2] come on guys 
[laughter] [4.5] 
sm0232: five litres [0.4] 
nm0228: sorry [0.2] 
sm0232: five litres per minute [0.5] 
nm0228: yes [0.2] right [0.5] five litres per minute but w-, [4.0] what [0.2] i 
said [0.3] 
sm0232: stroke volume times heart rate 
nm0228: 
stroke volume times heart rate [3.0] stroke volume [0.8] times heart rate [0.8] 
and then we have [0.4] the resistance [0.4] and where does the resistance of 
the circulation lie [1.4] in the arterioles and we call it we have a [0.3] a 
name for it [1.4] total peripheral resistance [0.3] T-P-R [1.5] now [0.4] the 
blood pressure coming into the heart i've just told you is very low [0.3] 
there's almost no pressure in the blood [0.5] by the time it gets to the heart 
it has to be sucked back up by our breathing muscles and something [0.3] so i'm 
going to cross that out [1.6] and call that zero [0.8] so the blood pressure 
coming into the heart is zero [0.4] and the blood pressure coming out of the 
heart into the large arteries [0.3] i've just told you is what we call [0.3] 
blood pressure [0.3] when you measure the blood pressure in a large artery [0.
3] that's effectively the pressure just outside the heart [0.3] so we can 
simplify this whole thing [0.4] as the blood pressure [0.7] yeah [0.3] what we 
[0.4] conventionally call blood pressure [0.5] equals cardiac output [0.6] that 
is [0.3] stroke volume times heart rate [1.6] multiplied by the resistance 
in the arterioles [0.4] which we call [0.4] total peripheral resistance and 
please do [0.5] learn how to arrive at that point [2.9] and that's all i want 
to say [0.4] about blood pressure except to show you on your di-, on your 
handout [1.8] that you have [0.2] the baroreflex here [0.3] [6.2] here you have 
[0.3] at the top [0.8] the [0.2] arterial pressure [2.3] and its being detected 
by the baroreceptors [1.4] and the baroreceptors [0.9] have to alter the blood 
pressure to bring it back to normal [0.4] if if say [0.3] this this example [0.
3] is given in the case of a fall in arterial [0.2] pressure which would happen 
[0.3] if you had a bad accident say and lost a lot of blood [0.3] through 
haemorrhage [0.7] or if you stood up quickly [0.3] and a lot of your blood 
remained in your feet and didn't return to the heart [0.4] then your blood 
pressure would drop [0.4] and that would be picked up by the baroreceptors [0.
4] and the baroreceptors would have to do something about it [0.5] and from 
this [0.3] equation [0.4] you can see exactly what they have to do [0.4] if you 
want to increase blood pressure [0.4] you have to increase 
cardiac output [0.4] that is you increase the stroke volume [0.3] and the heart 
rate [0.9] and you increase total peripheral resistance you constrict the 
arterioles [0.4] so if you want to [0.4] to raise blood pressure [0.6] you have 
to make the heart beat faster [0.5] make it beat stronger [0.3] and constrict 
your blood vessels [2.9] now i've asterisked [0.2] here [0.7] those three [3.4] 
parts of the feedback loop [0.3] the increase in heart rate [0.3] the increase 
in stroke volume [0.3] and the increase in peripheral resistance where did you 
see the increase in heart rate [3.1] in the practical [0.8] when you stood up 
you measured blood pressure [0.5] which stayed more or less constant that's 
because the baroreflex was working [1.2] but the heart rate went up [0.6] went 
up a lot ten or fifteen beats per minute a big percentage increase [0.5] that's 
this part of the loop the baroreflex increasing the heart rate [0.4] to try and 
keep your blood pressure up [2.8] er i just want to point out here [0.4] that 
it's not just your arterioles that constrict [0.5] but also your veins that 
constrict i've just 
talked about your veins being under control [0.5] here we have constriction of 
the veins [0.3] and what that does is to squeeze blood towards the heart [0.6] 
and [1.1] makes the heart beat faster [0.6] er [0.2] beat stronger [0.6] and 
what i want you to do [0.8] some time between now and the exams [0.4] is to go 
through this diagram we've covered all the bits individually [0.3] in different 
lectures [0.4] throughout the [0.3] lecture course so far [0.3] and i want you 
to make sure [0.4] that you understand what's going on [0.5] at each [0.6] at 
each er step [0.4] so if for instance if i point out to you here [0.5] that an 
increase in end-diastolic volume [0.4] makes the heart [0.2] pr-, pump out more 
blood [0.4] that's something we've already covered can anybody remember what 
that's called [0.9] an increase in end-diastolic volume increase in [0.3] the 
stroke volume [1.7] [laughter] [0.8] i've obviously left a deep impression [0.
4] that's the 
Frank Starling mechanism [0.2] at the out [0.3] the [0.3] heart pumps out [0.5] 
what is returned to it [0.3] so i want you to go through this diagram and make 
sure that you can do that for each step in the diagram [0.4] because we have 
covered all the individual bits [2.7] okay [0.9] the next two lectures the next 
two weeks will be on [0.4] much broader topics next week i'm going to be 
talking about some specialized circulations which are rather interesting [0.5] 
and the week after that i'm going to talk about how the circuli-, [0.2] s-, how 
the circulation [0.3] adapts to special [0.2] conditions and i'm going to be [0.
4] taking the aviation world as an example of that [0.8] er and i have [0.2] er 
the marked practicals [0.4] if you want to come and collect your practicals 
that were handed in last week i have them here