Biology concepts – internal anatomy, asymmetry, symmetry
breaking, primary ciliary dyskinesia, situs solitus, situs inversus
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You hold your right hand over
your heart for the national
anthem, correct? So what
happened here? Photoshop - they
even reversed the buttons on
his jacket and the lapel pin to
sell it. But notice the medals on the marine behind
him; the
photoshopper didn’t switch
them back to the left side.
Michelle came much closer to
covering her heart. He missed
by a mile. He must be
honoring the pack of cigarettes in his
breast pocket.
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But the heart is actually located in the middle of your
chest, protected by the bony sternum. True, it’s tilted so some of it sticks
out to the left side. This is why your left lung is smaller and has the cardiac
notch (see this post). The reality is that some of the heart is located right
along your midline and some of it is just
barely in the left half of your thoracic cavity.
So if you want to cover your heart when the national anthem
is played, put your hand over the center of your chest – but your going to look
silly next to all those people who don’t really know their own anatomy. Or
maybe they do; the heart isn’t always where the anatomy textbooks say it is
supposed to be. And neither are the rest of the internal organs.
We’ve talked a lot in the previous weeks about internal and
external asymmetries. Despite the fact that most animals are mostly bilaterally symmetric, there are
parts of animals that just can’t be symmetric; we only have one of them. Unless
they position themselves right along our midline and each half looks exactly
like the other, internal asymmetry just isn’t possible.
Even for single organs that are on the midline, they're
often not completely symmetric – see our posts on the brain (here and here). The heart itself
isn’t symmetric, with the left heart ventricle being much thicker and a
stronger pump than the right ventricle. We talked about the thyroid being larger on the right side; the pancreas crosses the midline but the head of
the pancreas is much larger than the tail.
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The abdomens of most mammals
look pretty similar. The rat
on the left has a slightly
more centrally located liver, and the
uterus is very different, but
you can’t see it here. The spleen
(#6 in rat) is larger and
wraps around to the front in the rat
as compared to the human.
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Your thoracic organs are indispensible – you might be able
to live without one lung, but every try getting along without both of them? And
forget about going without a heart; although the Grinch did fine for a while
with one that was three sizes too small.
Paired organs aren’t necessarily symmetric either, but they
are most often located symmetrically within their cavity. Each kidney is
located pretty much the same distance from the midline. And even though your
lungs are asymmetric, their location on each side of the thoracic cavity is
fairly symmetric. Part of the advantage of paired organs (kidneys, lungs,
adrenal glands, testes, ovaries) is that you have a back up if something goes wrong
with one of them.
For single organs, there is no back up. If they go bad,
you’re in trouble. You don’t have another source of insulin outside your
pancreas, no other organ makes bile besides your gall bladder, and your spleen
is crucial for removal of old blood cells and immune complexes. Yet, you can get
along without some of your abdominal organs.
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If Hannibal Lecter had eaten just
part of the census man’s liver and
left him living, it is very
possible that his liver would have grown
regeneration. The hepatocytes
start to split and regrow the
mass. But they don’t have the
signals to produce the original
shape; they just form a
functional mass of tissue.
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The injury often involves an automobile, but football players (American football) and rugby players have also lost spleens after
tackles. One clinical case detailed a splenic rupture that didn’t occur until
70 days after an abdominal injury. You can
get along without your gall bladder too, but you’ll have to read about that
yourself - and don't eat potato chips while you read about it.
So how are our pieces fitted together – your heart points to
the left of center, the liver and gallbladder are on the right. The stomach is
on the left, and so is the spleen. The pancreas is about in the middle. For the digestive tract, the situation makes
sense and is driven by the position of the stomach. Food exits the stomach to
the right side, so all the things that help digest the food should be on that
side – liver for glucose storage from small bowel, gall bladder for fats, head
of pancreas for proteins and other things.
The normal arrangement of internal thoracic and abdominal
organs (stomach, spleen and heart on left; liver pancreas, gallbladder on
right) is called situs solitus. This
is the picture you see in your anatomy textbooks and in bodies ripped open by
movie werewolves and zombies. But sometimes the pictures aren’t right…. or
left.
Some people have mirror image internal organs; what is
usually on the right is found on the left, and what usually points to the left
now points to the right. This situation is called situs inversus totalis. Luckily, the inversion of organs doesn’t really present a
medical problem on its own. Since everything is reversed, the connections
from organ to organ and from blood supply to organ are maintained. Sometimes there is a reason for the inversion,
but other times it’s random.
A study from Norway indicated that the chance of situs
inversus increases with maternal age, and it is also more common in cultures
with small gene pools and higher incidence of inbreeding. However, it is not
more common in twins than in multiple single births of a family.
In the cases of situs inversus that are not sporadic
(random), what controls the differentiation of right and left and how does it
go wrong?
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The nodal cilia rotate rather
than beat. The third image shows
how they tilt backwards while
positioned in the posterior of
each cell.
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The system goes back to the cilia that we talked about last Fall and Spring. The node cells that run along the midline of the embryo have monocilia
(one cilium/cell). These are specialized cilia that don’t have the central pair
of microtubules, instead they have a 9 + 0 configuration. They gyrate instead of beating.
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Follow the debris to see the
leftward flow
of the fluid.
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The leftward flow
is somehow responsible for turning on different genes in the embryonic cells
that will be on the right and left sides, but people and other animals with a defect in nodal cilia are just as likely to exhibit situs inversus as situs solitus. It isn’t that non-functioning nodal
cilia cause situs inversus, they just
don’t promote situs solitus as they normally would.
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Nodal is important for the
growth of some cancer cells. If you
harvest lefty from embryonic
stem (ES) cells, you can use it to
inhibit nodal and stop the
cancers cells from proliferating. This
could be one of the new
therapies for cancer in the next few years.
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It’s true that there is strong asymmetric gene expression on
the left and right sides. The controllers are a couple of proteins related to
an immune system protein called TGF-beta (reviewed here and here). The nodal protein is expressed only on the
left side, while lefty protein is
expressed on the right side. Nodal drives development of a left side, while
lefty is a feedback inhibitor of nodal and therefore prevents a left side
development on the right side. The asymmetry of nodal and lefty expression was
supposedly driven by the concentration gradient of some morphogen generated by
the cilia.
However, no one could find the morphogen. Meanwhile, it was
discovered that mutations in another type of cilium also resulted in situs inversus.
These cilia are immotile; they’re the sensory cilia we also talked about last fall. This led to the two cilia model to
compete with the morphogen concentration
hypothesis.
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In some people with primary
ciliary dyskinesia, or immotile
cilia syndrome, the
mucociliary elevator isn’t operable, so they
are subject to recurrent
respiratory infections.
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All this was discovered by accident; different researchers
were looking several different diseases. Primary ciliary dyskinesia (PCD) is a
rare genetic disease where the motile cilia don’t move. About half the people with
PCD have situs inversus, if they do then this PCD is called Kartagener’s Syndrome. Other
researchers were looking at polycystic
kidney disease (PKD). These people had a defect in immotile cilia in the kidneys,
but also had a high incidence of situs inversus.
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In polycystic kidney disease
(PKD), the defective cilia don’t
sense flow and they trigger
overgrowth of epithelium to
form cysts. A normal kidney is on the
right.
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For more information or
classroom activities, see:
Situs inversus –
Liver regeneration –
Primary ciliary dyskinesia –
Polycystic kidney disease –
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