Biology 1A - Lecture 30: Osmoregulation


Uploaded by UCBerkeley on 07.11.2012

Transcript:
>>INSTRUCTOR: Good morning. Survived the election.
And what we were talking about lastハ on Monday, was gas exchange, we started addressing
the question of gas exchange in various systems. And remember that there were sort of direct
contact between the gas exchange organs and the aqueous environment in aquatic animals
so you have gills in marine worms, anilines and arthropods and you've deuterostomes such
as echinoderms, also invertebrate fish, you have the gill filaments extending out into
the water directly. And we talked about the efficiency that's gained by having a counter
current exchange system. You have the oxygenatedハ deoxygenated blood
flowing in from the downstream side of the water flow.
And the oxygen rich blood going out at the upハ at the oxygenハ at the upstream end
of the water flow. And you should be aware of how this works
in favor of the efficient gas exchange in the fish.
Then we talked about the tracheole system where you have a bellow system.
Finely divided tubes called trachea that extend through out the body, branching into finer
and finer vessels that eventually allow immediate exchange between the trachea and the surrounding
cells. And now, we're coming to theハ mammalian
vertebrate systems, for example, mammals have lungs, obviously, so that the blood flows
out from the right ventricle of the heart, into the pulmonary circulation and again it
goes through extensive branching that is matched by the branching in the structures of the
airways, so you have the trachea branching into the bronchus and the brachials and finer
and finer things that finally terminate in these little, like clusters of grape like
spherical structures called alveoli. And as far the digestive system, etc., you
have this tremendous increase in surface area of the actual exchange surface, whether they're
talking about the surface of the small intestine, with the folds and the villi and the microvilli,
here you have itハ the same sort of general principle in the respiratory exchange system.
And these veins from the heart come in and interact, exclusively here, so you have a
short pathway with a huge surface area so that oxygen can diffuse directly into the
blood and CO2 can diffuse out here. Okay.
There's sort of again a structural problem with these, what you need to do then when
you're breathing, is expand this whole system, right?
These alveoli included. So get the air exchanging, right it's working
like a pump, of bellows. But you can think about a principle when you have these alveoli
that are cells, so they still have to be in a fundament aqueous environment. So even this
thin epithelium in here has to be covered with a layer of fluid.
Right? And so that fluid is basically spherical,
lining the alveoli, right. Each individual sphere, right?
Now, so this is a basically a drop of liquid and there's principal called surface tension
thatハ you know the reason soap bubbles and bubbles generally are spherical is that there
areハ there's aハ drive to minimize the surface to volume ratio, right?
That's why you don't see cubic soap bubbles. Because they have a higher surface to volume
ratio. So it's always trying to minimize this, and
it'sハ it's trying to contract so that the bubbles always trying to get as small as possible.
Again to minimize surface area. And when you multiply this by the huge numbers
of alveoli that are there, when you're trying to stretch that, as you inhale, that amounts
to a significant amount of work that has to be done on the system. Right.
So, how can you minimize that to have more efficient respiratory, easier respiration.
What was appreciated is that there was a surfactant protein. Surfactants like soap, or other sorts
of molecules are things that that reduce surface tension.
Okay. By intercalating into this fluid and disrupting
the interactions between the water molecules themselves.
Okay. That are trying to pull together.
Okay. So, the appreciation of the role of surfactants
in the lung function, was we need one head toハ there, thank you.
Who's thatハ somebody's way tall up there. That head right thereハ there you go, thank
you. So, turns out that, you know, in the 1950s,
asハ what? >>STUDENT: [Indiscernible]
>>INSTRUCTOR: As neonatal techniques were improving you could have infants morn earlier
at times, premature infants, they were born okay, but they tended to die of a syndrome
called respiratory syndrome, and they weren't getting enough air in their lungs. So that
was bad. And theseハ so lots of babies were dying
that way. And there's a team of researchers that realized
that thisハ that was happening is that in these early babies, they had not yet startedハ
because they were still expecting to be breathing in the fluid filled environment of the womb,
they had not yet generated the surfactant proteins that normally coat the alveoli.
And by supplying them with external source of surfactant, I think a mist that you can
squirt inハ I'm sorry I'm fuzzy on the details, they can provide the surfactants and this
is no longer a problem for pre-term babies. Okay.
Questions about this? Yes, sir?
>>STUDENT: [Indiscernible] >>INSTRUCTOR: Surfactants are molecules that
reduce surface tension. The coating of the alveoli is stillハ it
has to be aqueous based, right. But when youハ when you put the surfactant in the aqueous
coating that reduces surface tension, so moleculesハ so you can expand it more easily.
So the other thing we wanted to say hereハ yeah.
Thin wall chambers for gas exchange. So now you can think about different mechanisms for
generating respiration in frogs there's an interesting system, let's see if I can remember
it you probably read it in the book too. The frogハ how does it blow up its lungs.
It sucks in air to its mouth, and then closes its nose and [Indiscernible] and breathes
this again and that blows out the lungs, okay. So that's one way of doing it.
Makes it awkward for talking though. What we do, obviously, is contract the diaphragm
and rib muscles to expand, so we're sort of pulling out the lungs mechanically, and sucking
air in and then reversing that motion to constrict the lungs and press it out, so that's good,
works for us. I was blown away to discover that birds have this amazing system where
they useハ birds have real oxygenハ when you're flying you've got to get a lot of oxygen
to the muscles, and where as in a mammals, you have air coming in, and then out, in and
out. So again there you have that sort of problem of reversing the flow and that's sort
of limits the efficiency system. In the birds, they have these posterior and
anterior air sacs and they use those to generate a unidirectional air flow through the lungs,
so instead of having alveoli, they have these structures called: Parabronchi that are sort
of continuous tubes through which air is flowing in the same direction and exchangesハoccurring,
at these very narrow surfaces, as we said before, highly enriched with blood flow. So
I've got a little animation here that shows that.
What's my name again? Yeah.
Sign in. So here's the bird.
Here are the air sacs. Anterior and posterior. And there must be
some valves in here as well they're not mentionedハ these are the lungs.
When theハ in taking in air, these lungsハ these air sacs expand, air comes in here,
okay. And then as they contract it's pushed through the lungs. And out.
Now it's coming through here. Okay. And as this one expands it's pulling the air through
the lungs, right? And now, within the lungs, you again have
the principle of counter current exchange so here's the oxygen rich air, oops. No.
So you have capillaries interacting, oxygen flowing through here, okay. And being taken
up here. So, again, because you have this unidirectional
flow, high oxygen, low oxygen, which way would you want to have the blood flowing?
Should this be the low flow of blood? Low flowハ ah, oxygen, help! I'm not making sense.
I better get this right, huh? If you have air flowing through the bronchiole
tubes in the bird's lung like this, so this is going to be the high oxygen side.
And this is where it's flowing out to the low oxygen side.
Okay. If you have the blood flowing against that,
okay. Here's the blood entering the lungs, it's
low in oxygen, but it's still hasハ so the air, even though the air is low in oxygen
it's still has more than the blood, and you can get exchange all the way through this.
And asハ as the blood flows through these tubes, it's picking up more and more oxygen
more and more oxygen, but it's encountering air that's also has higher and higher levels
of oxygen. So exchanges occurring through out this flow process.
So that's counter current exchange. And if you tried to do it the other way, so
that the air is flowing, again, this direction... [Instructor writing on board]
High O 2, okay. If we were flowing blood in the same direction,
whenハ so this is the blood flow now. When it first enters you're going to have
great exchange because low oxygen in the blood, high oxygen in the air, but as soon as you
get part way through, the oxygen in the blood will be meeting the level of the oxygen in
the air and after that point, no more exchange can occur, because it would start going back
the other direction. Right.
So, you'd be limiting the total amount of oxygen that can get into the blood.
By parallel flow verses the counter current flow. Okay. Any questions on that?
Now, big surprise. Counter current exchange, iClicker question.
Counter current exchange is illustrated by all of the following except: Break down of
lipid drops in small intestine by emulsification. Thermoregulation in bird legs and seal flippers.
Gas exchange in bird lungs and fish gills. Passive diffusions of monosaccharides through
simple membrane transporters. Both A and D.
Oh. Timing. Man, I'll learn this eventually. We'll give
you 30 seconds. That's ridiculous. Yeah.
Oh. Time's up. And the answer is: E, right.
So, now there's thisハ let's talk about the respiratory pigments.
The reason that respiration works so well in vertebrates is that we have specialized
molecules to absorb the oxygen in the red blood cells, the hemoglobin. And it's analogous
to the problem that people are approaching with electric vehicles or hydrogen fuel cells
that you're trying to have as much capacity to say hydrogen, which wants to be this gas
expanding. If you can and that's a problem for maintaining the distance in the vehicles.
If you can figure out a chemical means of bonding the hydrogen, in the cell, reversibly,
in the fuel cell, and then you can put in lots of hydrogen without having high pressure
tanks and with hazards and implicit in that. So, of course theseハ the binding has to
be reversible in order to be useful. And so, what you see is cooperativity among
the hemoglobin chains. Preponderance cooperativity means that when you've bound one molecule
of oxygen, in the hemoglobin oligomer, it makes it more likely, more easy for the next
molecule to bind and so forth, and so you get the sigmoid curve of saturation.
Okay. If there was no cooperativity, you'd just have a linear curve with PO 2 and oxygen
binding. Right. So the fact that you have something like this...
That's indicative of cooperativity. And this works because then when you getハ
when you're in the lungs, and you're trying to unload, it also means that when you get
to low oxygen pressure, in the tissues, it makes it easier to unload oxygen. Because
again, once you unload the first oxygen, the others come off more easily.
There's also a pH sensitivity in this, so this is the curve at pH 7.4, which is the
normal physiological pH. But when you're working hard, say in an actively
contracting muscle, the producing lots of CO2, that tends to lower the fluid pH and
you see that at pH 7.2 the oxygen carrying capacity is lower. And that means when the
hemoglobin gets to a slightly lower pH environment in an actively working muscle it makes it
easier for it to dump the oxygen. Again, this sort of works in favor of what
you're trying to accomplish. So it CO2 delivery to active tissues. Questions about that?
So finally the flip side of all of this is getting carbon dioxide back from the tissues
that's produced during respiration so that's sort of a complicated process involves parallel
pathways. First, the CO2 diffuses out from the cells
where it's being produced. And it can also diffuse into the red blood
cells and there's a enzyme that catalyzes this simple reaction of H2O +CO 2 to form
carbonic acid that tends to disassociate under these neutral pH conditions that will disassociate
in bicarbonate and proteins the proteins are bound by the hemoglobin and the bicarbonate
can diffuse out into the plasma where it's carried. Other CO2 molecules bind directly
to the ammite(?), amino terminal ofハthe hemoglobin itself.
So you have these protein chains, and at the end terminal end, when you react with CO2,
you can get forms like this... Readily reversible reaction of CO2 binding to the ammite(?)ハ
to the amino terminal of the hemoglobin. So that's another way of carryingハ additional
carbon dioxide back. And then again when you get to a low CO2 environment these processes
can all reverse. And the CO2 diffuses out from the blood into
the alveoli. Okay.
Any questions about that? Yes?
>>STUDENT: [Indiscernible] >>INSTRUCTOR: Hemoglobin is in the red blood
cells that's a little thing I've stipulated we didn't talk about that.
>>STUDENT: [Indiscernible] >>INSTRUCTOR: That's theハ so the pick up
of the protons that will beハ that's again very reversible, so here, under high CO2 conditions,
you get formation of carbonic acid, disassociation of carbonic acid and the hemoglobin acts as
sort of a buffer, picking up thoseハ carrying those protons and when you get to the lungs,
the hemoglobin releases both the CO2, that might be bound, and the protons that are bound
because the carbonate comes back in you form carbonic acid and that forms into CO2 and
gas, so it's a reverse of what happens in the tissues.
Okay. Yes?
>>STUDENT: [Indiscernible] >>INSTRUCTOR: I think that's right.
>>STUDENT: [Indiscernible] >>INSTRUCTOR: Ahハ the pH isハ you're leaving
CO2 so the pH is tending to go up. Right?
Yeah. >>STUDENT: [Indiscernible]
>>INSTRUCTOR: This is whereハ here? Well, this is just the hemoglobin giving up
protons to the bicarbonate that's diffusing back into the cells, okay.
And then, so then you have that carbonic acid and then the same enzyme carbonicハ carbonic
anhydrase, is that what it's called can reverse this formation of carbonic, reverses to form
water and CO2 and then the CO2 can diffuse out as a gas. So this is what's happening
in the high CO2 environment of the tissues, this is what's happening in the low CO2 environment
of the lung, it's just reverseハ reversal of a basic equilibrium, as you change the
concentrations of the key reactant. The carbon dioxide.
Yes? >>STUDENT: [Indiscernible]
>>INSTRUCTOR: Well, justハ itハ this is notハ this is all doneハ it's just equilibrium,
right? And that's the problem with a lot of theseハ you'll see this over and over again
in explanations of biological phenomenon, well how does the proton know to go this direction
here and this direction here? It's not. These are allハ it's all chemistry.
It's just basic diffusion, highly random, diffusion of molecules and interactingハ
and the rates are based on the basic kinetic constant K x the concentrations, and as the
concentrations change, the overall direction of the reaction will change.
Okay. So it's equilibrium chemistry.
Okay. I'll try and bring that up again itユs a
really important point thatハ aweハ biology is chemistry, right?
Oh, another iClicker question. So, this oneハ this is sort of a thought
question. All of the freshly oxygenated blood from the lungs goes straight back to the left
atrium and vertical of the heart. Right?
So, all of that oxygenated blood is going right into your heart, but why does the heart
then require a separate system of arteries and veins?
Okay. If it's got the whole pulmonary system dumping
oxygenated blood right into the center of the heart.
A. to compensate for the deoxygenated blood that flows into the right side of to heart.
B. these parts of the circulatory system are actually redundant and on they're way out,
you don't need coronary arteries that's the evolutionary back water.
C. the heart muscle is too thick to obtain oxygen and nutrients by diffusion from the
lumen of the heart. D. the only function of the coronaries is
to circulate regulatory hormones to the heart. 30 seconds.
All right. All right. I'll get it. 3 seconds left.
Hurry, hurry, hurry. All right. Let's stop.
Let's see how we did here. Oh. Yeah.
Oh, yeah. Very good.
So, this concludes our discussion of respiration circulation and gas exchange.
And we will now proceedハto our discussion of the immune system.
Covered in Chapterハ43. So in terms of where we are, thisハ we're
not going to get anywhere near through this material, we'll be talking about this today
and Friday for sure. With luck I'll get through it on Friday. So
then you won't be getting any new material until a week from today.
Because no class on Monday. The immune system.
It's one of my least favorite, but nonetheless real appreciated organ systems that's incredibly
complicated for someone of my intellect. And I think it's made worse byハ there's
a predilection if immunologist, some of whom I count as my best friends, they have amazing
Pantheon of acronyms and abbreviations. And it's like a Russian novel, they will be like
5 or 6 different names for the same molecule or the same cell, right?
And then if that's not bad enough they will take the same name and apply it to 2 or 3
different cells. So, it's a wonderful topic, there's been some
brilliant work done, it's still very very exciting if it's interesting you should also
plan on taking MCB 150, is a better introduction to the immune system, but we'll get you some
of the basic ideas here. So the problem is this: That with all of the
microbial life and different forms of life, it's continual interaction, an ecosystem,
everybody's trying to make a living, bacteria and viruses also. And our insides, with all
of their nutrients and proteins and everything make a wonderful environment for bacteria
to thrive. It actually has beenハ there's sort of a
notion that we can discuss at some point, office hours maybe, that multicellular life,
metazoans, actually evolved as a response to bacteria signaling.
Okay. They're one bacteria might be singling these
other types of cells to accumulate and form an ecological niche for the prokaryotes to
live in. Sort of the oppositeハ all multicellular life to evolve so it's easier to eat bacteria.
But it could be just the opposite. And when you think about it, the fact thatハ
of all of the cells in you, at any one time, most of them are bacteria. Right.
Yourハ the cells with your DNA are out numbered about, I think it's 10 to 1 by the bacteria,
most of which are in your gut and most of which of course are benign, helping you to
make certain vitamins like vitamin K and stuff like that.
But they're the bad actors. And actually, this is sort ofハ it could also be that's
going on when we see pathogenesis, is sort of early rough stages of an evolutionary relationship
between species. Okay. You first get to meet someone and, you know,
for whatever reason, you start seeing all of these places where you disagree and where
you argue and fight. And either you leave, one person, you know,
just wipes out the other, or if you have a long term stable relationship you learn to
adapt. Some of those rough edges get smoothed out. And I think that's the same sort of thing
that happens in interspecies interactions, first one may be lethal to the other, but
if they spend enough time together they often liveハ learn to coexist.
So, and there's this continual sort of battle it's always called. Always phrased in battle.
But the notion that we're all trying to fight off these invaders and the immune system is
used for that. There are two basic forms ofハunity, one
is called innate immunity it's not just innate, it's all in different animals. Do we have
anyone named Nate in the audience, that one is lost then. So it's in all different kinds
of animals, and this isハ based on a recognition of traits that are shared by a broad range
of pathogens, using a small set of preformed shovel ready receptors, right? So the innate
immune system can opハrate very quickly he. Okay.
And with any sort of did I have fence system, first you have a barrier did I have fence
system, skin, mucus membranes, secretions, etc., where yourハ the pathogen, or the foreign
invaders on the outside of the animal and so you can deal with it as an outハcider
and then once on the inside you need to think about a different strategy.
Okay. And we'll talk about some of these things.
Okay. The basic analogy is, I don't know how many
of you have played laser tag, but there'sハtwo versions of laser tag. One, if you think of
yourself as the organism, you're trying toハjust kill anybody that moves, you shoot anything
that you see. Right. So that would be like barrier defenses, anything that is on the
outハside, you're trying to eliminate. But once the invaders are inside the organism,
then it becomes more like team laserハ version of laser tag, where you have to distinguish
between the invader and the cells that areハ or people that are on your own team. Okay.
So, a basic question right ask also is, if an innate immunity is seen in all of these
different animals that was the it mean it was present in the ancestor or an example
of evolutionary convergence that's been invented multiple times. So then there's another process,
the one with that you probably think of, mainly is called: Adaptive immunity it's a specialization
of vertebrates. And in this there'sハ it's only for internal invaders. There is a humoral
response in which special molecules called antibodies defend against infections, in the
fluids, and there's a cellular mediated response where we can kill our own cells once they've
been compromised. Cytotoxic cells. And I know you've heard that the immune system
has this remarkable array of traits that can be recognized millions and millions of different
molecules, and we'll talk about how that's done.
The problem is that by the time you generate unadaptive immune response to an infection
you'd be dead already because that takes quite a while and so we normally respond, depend
on innate immunity to hold off infections until the adaptive immune system can kick
in. Okay.
So, again, for this question that I probably won't answer since we don't know.
Is how did this adaptive immune system arise in vertebrates?
And again, for both of these systems, the fundamental issue in immune defense is how
does the system recognize the host cells that you want to save from the non self ハ the
external cells that are trying to get rid of.
So, innate immunity has been studied extensively in Drosophila, and again this is Bio1A not
Bio MCB 150, you just need to know that what happens in innate immunity the there's a molecular
pattern associated with most pathogenic molecules that are different from theハ the molecules
that are seen inside the host. Has anybody seen the eraser?
Whoa, there's a whole other room over here. My Godハ oh. You wouldn't believe it.
The eraser's jump down here they're breeding like flies.
There's thousands of erasers on there. Wow.
[Instructor writing on board] So, it turns out that the cell walls of bacteria,
the coats of viruses, etc., they oftenハ because of to different evolutionary pathways
that the microbes and eukaryotes have been on for so many years, they're often biochemically
pretty reproducible differences in things like lipopolysaccharides that are associated
with bacterial cell walls but not seen in vertebrate cells. Okay. Mammalian cells.
And so, if you can have sets of receptors that recognize these pathogen associated molecular
patterns or PAMPs, okay. You can design receptors that will bind to those and be activated and
then initiate some response in the host. Okay. And in one case, many cases this solves the
receptor being as a transmembrane protein binds and there's a confirmational change,
when it binds to the pathogens, the PAMPs. And that triggers, molecular cascade inside
of the cell that it leads eventually to the production and secretion for example of anti
microbial peptides that go out that are secreted and then somehow interact to detour the deterrentハ
the invaders. Now, peopleハ you'll see this, so you'll
see this name PAMP, a lot. Other people say it's not really pathogenic pattern, but it's
microbial of all sorts. Some people say it might be MAMPs, microbial associated patterns
but the idea is there. Questions about this?
Yes? >>STUDENT: [Indiscernible]
>>INSTRUCTOR: Um, yea, or to theseハ the molecules that are associated with it.
They might be secreted by the invading cell or fragmented of the invading cell. We'll
talk more about receptor binding and signaling pathways in the section on development actually.
So, a lot of the work on this has been done with Drosophila, and it was discovered that
there's a ton of different anti microbial peptides made, and so the question is, why
are there so many different ones? Okay.
And there's two alternative explanations, one is that none of these peptides on its
own works very well. But if you have a lot of them, a lot of different
weapons then they will be more effective, that's the notion of complement tear.
The alternative is that each of these different peptides is specific for a particular pathogen,
so like a magic bull let for each different invader. So how could you test that? How could
you investigate this further. Well, in Drosophila, they can make mutants
that wipe out the entire response system. Okay.
And then into these mutants which have essentially no microbial peptides they can reproduce a
single one. For example a molecule called drosomycin,
orハa molecule called defensin, these are two different peptides. Okay.
So, and then they can test these mutant constructs by expose your to the bacteria M. luteus and
the wild type with the microbial peptides survives very well, post infection.
And the mutant with no peptides dies quite quickly. Survival rate is very low.
Okay. Now, if you insert only the peptide defensin,
you rescue the wild type survival. And if you use a single different peptide drosomycin,
you're no better off than the one with that lacks all of them. So how do you interpret
this? This single peptide accounts for the entire affect against M. luteus, so that suggests
the magic bullet hypothesis so it's always good to repeat experiments. How general is
this conclusion? So now they did the same experiment testing
against a fungus, neurospora crassa, and in this caseハhow would you interpret the results?
I would say it's a little more in between, here, defensin now has little affect, but
some effect, I would say. And drosomycin is almost as good as wild type
but not necessarily as good. Okay.
I should have a question, what's missing on this graph to be able to more confidently
interpret these results? Air bars, excellent. You would like to know
how reproducible is this data point verses this one, this one verses this one, etc. Are
these the same curve within the margin of error are they significantly different. Very
good. But, toハme as I just look at this it suggests
that one single peptide doesn't really account for the full effect.
Any other questions about this? So, again, it's a mixture of the two hypotheses.
And that's generally what you seeハ when you're doing biology you have two explanations
it's either this or now this, let's start doing experiments and it usually turns out
to be something in between. We'll stop there and resume on Friday.