What's the point of the appendix?
In this edition of The Naked Scientists, we take a fresh look at the appendix. Despite its historical reputation of being a useless part of the body, have new studies shone a light on the pivotal functions that the appendix may have?
In this episode
00:47 - What your appendix does for you
What your appendix does for you
Marta Zaraska
Finger-sized and dangling off the bottom of the right side of the large intestine, the appendix is a worm-shaped, blind ended tube that forms part of the human gastrointestinal tract. Long dismissed as of little clinical consequence or use to modern man, most of us ignore it until it occasionally goes wrong and ends up being removed by a surgeon. Indeed, we’ll talk to one about that shortly.
But, more recently, scientific research has begun reappraising this enigmatic organ. It is now believed that it performs potentially valuable roles in the body - including as a reboot-refuge for friendly bacteria, and it might even serve to protect us from a serious infection and even Parkinson’s Disease. On the other hand, some studies claim it might even be a risk factor for Parkinsons.
Either way, we need to look more closely. So, today, we’re going to be doing our own biopsy on the appendix. What is it? How did it evolve? What’s its role? And what might be the consequences of taking it away?
To kick us off, here’s the science writer and author of Growing Young, Marta Zaraska. She recently wrote a fascinating piece in Medscape about why it might be time to completely reconsider what we know about this fascinating organ…
Marta - I think it caught my attention, this story, because I don't have an appendix myself, and it was something that I completely disregarded in the past. So whenever I would go to see a doctor and they would ask me whether I had any surgeries in the past, I would say that I did indeed have an appendectomy, my appendix removed, when I was 17. But really, what does it matter, right? It's been such a long time and it's not an issue. It's gone. It doesn't matter. Then I came across a research paper that was actually a study done by French researchers on primates in a French zoo, and they discovered that the primates that had an appendix actually suffered much fewer episodes of diarrhoea. And it really caught my attention because it said that, you know, there was something to the appendix that was actually important, and here I was not having one. So I started digging into research and then I came across another paper by the same group of researchers from France that showed that mammals that have an appendix actually live longer. And I started reading more and more papers, and indeed I found all those connections between appendix and plenty of different conditions such as Parkinson's disease, colon cancer, ulcerative colitis, even allergies in children.
Chris - Has this been a recent kind of flourishing interest in the appendix, or have scientists been looking at this for a long time and, because it was regarded as a bit backwater-y, people didn't pay much attention.
Marta - I mean, scientists have been looking at the appendix for a very long time. Indeed it was discovered in the 16th century by an Italian surgeon, but it took a very, very, very long time for us to realise that the appendix actually had a function. And this is a very recent change in perspective because even Darwin thought that the appendix is completely useless. He basically thought it was some kind of remnant of our past. When our ancestors switched our diets from eating leaves to fruits. Some physicians went so far, there was this American physician in the early 20th century called Miles Breuer, that actually suggested that people who have an appendix are some kind of inferior. And those who have an infected appendix, like I did myself, should be left to perish because their inferior DNA should be removed from the gene pool. And this view has only very recently begun to change. I've actually even stumbled upon a paper from 2019 that still said that appendix was basically a useless organ.
Chris - We used to be a bit more gung ho, medically, didn't we? 'If in doubt, chop it out' was one of the things that surgeons used to sometimes say. Is it now that we are beginning to say then, well, maybe we should be a bit more conservative and a bit more minimally invasive maybe, rather than just default straight to surgical options. Are doctors increasingly beginning to question maybe treating it with antibiotics and letting an appendicitis settle down before we go in with the scalpel?
Marta - I mean, definitely there have been some very big studies done recently that do show that in certain cases antibiotics may be enough. Of course, it's not always the case and in more severe cases you have to have your appendix removed. But certainly just assuming that, if it's infected it has to come out, is no longer seen as a given. So the view is definitely changing here. You know, in North America there are about 400,000 cases of appendicitis every single year. So there are lots of appendixes being removed each year. Some of them might have perhaps been cured simply with antibiotics. So definitely there is a change in perspective right now that it doesn't always have to come out.
05:60 - How did the appendix evolve?
How did the appendix evolve?
Heather Smith, Midwestern University
So, what exactly is the appendix; where is it; how did it evolve, and when, and what does it do? To find out more, we put in a call to Heather Smith, professor of anatomy at Midwestern University in Glendale and the editor-in-chief of The Anatomical Record…
Heather - My name's Heather Smith. I'm a professor of anatomy at Midwestern University. I'm the editor-in-chief of The Anatomical Record, which is an official journal of the American Association for Anatomy. The appendix is essentially a little blind pouch. It's what anatomists call a diverticulum, and it projects off part of the large intestine, the colon, called the caecum. And in humans it's referred to as vermiform in shape, which just means worm-like. So it's a little cylindrical tube about a centimetre in diameter, and it's found in the lower right hand quadrant, lower right hand part, of the abdomen. And then you can actually locate the position of your appendix roughly at a position that's called McBurney's point. So if you draw a line between your navel, your belly button, and the point of your hip that kind of sticks out on the right side, anatomists call it your anterior superior iliac spine. About two thirds of the way along that line is about where your appendix will lie. So in cases of suspected appendicitis, it's common that the doctor will apply pressure at that point. And if the patient responds with sensitivity or pain, it's suggestive that they might have appendicitis. And in the old days before laparoscopic surgery, this was the location that surgeons would use to kind of guide their surgical incision.
Chris - And do all animals have one or is it uniquely a human trait?
Heather - Interestingly, not all animals have an appendix, but it's also not unique to humans. So we see appendices in the clade that's referred to as euarchontoglires, which just means primates, rodents, rabbits. But we don't see it in species like carnivores or ungulates, which are just hoofed mammals. So things like deer and horses. But interestingly, the appendix can take different shapes, so it doesn't always look like our vermiform type. So in primates we tend to see this, this vermiform little worm-like type like ours, a little cylinder. But in things like rabbits, we tend to see this very elongated caecum, which is part of the large intestine, that just kind of tapers into an appendix. And in things like marsupials and monotremes, it's straight off the large intestine in the absence of a caecum. And there are even some unusual species like the Florida manatee that have two appendices.
Chris - And do any humans have two appendices and why do manatees need more than one?
Heather - That is a very good question, and I don't know that we know the answer to that. So manatees have two little strange projections, but whether they function like our appendix is unclear. Humans can do okay without it. I mean, it's definitely more beneficial to have an appendix, but those of us who have had ours removed know that we can function okay without it.
Chris - And what do we think it does? Because if it's evolved multiple times, has it evolved each time to do the same job? And what is that job or does it do different jobs in different animals?
Heather - So my research team compiled data from the published literature on the distribution of appendices across the mammal tree of life. And we found that the appendix has evolved independently about 30 different times throughout the course of mammalian evolution. And this is in different groups that have different shaped appendices. So it seems unlikely that the appendix is doing the same thing in all of those different species because the appendix takes a different shape and a different size. So it's probably doing something different in different species. What we know in humans is that the appendix has a healthy layer of bacteria called a biofilm. And so it seems likely that the purpose of the appendix in humans is partly as a reservoir of this good bacteria. So during times of gastrointestinal distress, when all the good healthy gut bacteria gets kind of flushed out of the body, the appendix is a little safe house that kind of preserves the good bacteria of the gut and allows it to kind of repopulate the gut. After the episode, it also contains what we call lymphoid tissue, which is just a type of immune tissue. So it helps the body to kind of mount its immune response against invading pathogens. But whether it does that same function in all mammals is not really well understood.
Chris - And in people who end up with a problem with their appendix, do we know why that happens? Is it just bad luck or are there any kind of strong pointers towards what's happening in people that end up with this, and by and large end up having to have it removed?
Heather - There are several different causes of appendicitis, but they all relate back to the appendix becoming inflamed. And it typically happens because the lumen, the diameter, the hole inside the appendix, is relatively narrow. And so it's very easy for things like bits of food, what we call digesta, to get stuck in the appendix. And that causes a lack of blood flow to the area and therefore inflammation.
11:41 - What does an appendicectomy entail?
What does an appendicectomy entail?
Irum Amin, Cambridge Surgical Training Centre
Irum Amin is a consultant surgeon and clinical lead for the Cambridge Surgical Training Centre. I wanted to know how a person tends to present with the condition, how they’re investigated, how the surgery is carried out, and whether, actually, antibiotics might be a better alternative…
Irum - They would start off talking about feeling unwell, maybe having a temperature, having some pain, which initially starts off around the belly button, can't quite localise exactly where the pain is. And then over a number of hours it then changes and it moves to the right hand side. If, for example, they are being driven to the hospital, they may complain when they go over any speed bumps or, if they move, the pain is made worse. So when they come into the hospital, they will have observations taken and we will take a history. Something that can present very similarly to appendicitis, particularly in children, is if they have a viral illness. So if you get a virus, like you get lymph nodes that come up in your neck, well you have very similar lymph nodes that are near your appendix in your abdomen. So if they swell up, then you can present with very similar symptoms. So part of it is taking a history and then it is actually examining the patient, seeing where they are tender when you examine their abdomen. Bedside investigations such as a urine dip test. Have they got a water infection that might be mimicking appendicitis? And then also a number of blood tests which look for marks of infection. Most people tend to have some form of imaging, particularly in girls or young women because the symptoms can be mimicked by problems with their ovaries. For example, if there has been a cyst in the ovary that has ruptured and there's a little bit of blood in the abdomen, or if the ovary has become twisted and that can mimic exactly appendicitis.
Chris - And then when you do go off to theatre, what's actually involved?
Irum - The majority of these surgeries are done laparoscopically. This normally entails three small cuts to be made. So one cut is made at the belly button, one cut just above the pubic bone, and then there's one cart made on the left hand side so that you have the camera plus two instrument ports. Initially the patient is put head down, tilted, so their feet are up, their head is down so that the small bowel or the, or the bowel in the abdomen moves towards the head end. It moves out of the way. You then locate the appendix, which is attached to the caecum, which is the beginning of the large bowel or the colon, which is on the right hand side. And the position of the appendix can vary. It can be behind the caecum, it can be to the side of it, it could be going down into the pelvis. So you first identify where it is and then you free it up from all its attachments. And then there is something called an endoloop. So if you can imagine a suture that's in a loop, usually two loops are put at the end of the appendix, the appendix is taken out in a bag, and then the holes are sutured up.
Chris - You make it sound really easy. I mean that's because you are a transplant surgeon who's done a lot of surgery, but how long does that take you, if you were doing one now if you did that on me?
Irum - So essentially it depends on your experience. If somebody is learning compared to somebody who has done hundreds and hundreds, it can be anywhere between half an hour up to maybe an hour, maybe even longer. And sometimes it's not possible to do it keyhole. And you then have to convert to an open operation. And that can happen in a small number of cases if the appendix is particularly inflamed or if part of the colon is also involved.
Chris - And when you take them out, I know you said you put them in a bag to get them out safely, but what do they look like? Do they look grotty and ropey?
Irum - So sometimes yes, when you go in they can be quite red and inflamed. Or sometimes they can be a funny colour because it's quite an advanced appendicitis. And you put them in the bag so that when you take them out through the wound, it doesn't cross infect the skin as well. But sometimes it can do.
Chris - What would've happened to people then back in the day before, people like you came along and could fix it surgically? Would they have died?
Irum - Certainly before antibiotics, potentially yes. So for example, during Covid, laparoscopic surgery, certainly in our hospital and other hospitals, were stopped. So when somebody came in with what we call an uncomplicated appendicitis, they were sent home with antibiotics. And those people that we felt actually had a more advanced appendicitis had open surgery, which hadn't been done for many, many years as routine. Now there are lots of studies that have happened in the US, in Europe and also in the UK. And it shows that people who are treated just with antibiotics, about a third of them come back needing surgery to have the appendix taken out at a later date. But certainly pre antibiotics, some of these patients, if they'd had a mild appendicitis, may have recovered, but many of them may have died as a result.
Chris - So is the mood shifting then towards a more kind of watch and wait approach, not going straight in with the surgery and perhaps monitoring people and giving them antibiotics. Or is it still very much a let's just cut it out and be done?
Irum - So I think certainly in the UK, if somebody comes in with appendicitis, you take out the appendix. Now there are studies that are done in Europe and the US in selected groups of patients with careful follow up where they are given antibiotics and they're followed up quite closely where you potentially can have some people who are treated just with antibiotics, but still at least a third of them will need an appendicectomy within the first year.
Chris - So you're not totally doing yourself out of a job?
Irum - No, not completely <laugh>. Not just yet.
The appendix as a bacterial refuge
William Parker, University of North Carolina, Chapel Hill
What does the appendix actually do for us? One idea gaining traction is that it serves as a refuge for beneficial bacteria. The idea is that, if something upsets the colonic applecart and disturbs the normal spectrum of microbes that live there and help to keep us healthy, the appendix works a bit like a biobank and can re-colonise the colon after the storm has passed with the right cross-section of microflora. That’s possibly why, living in the cleaner, modern world that we do, that we can get away without a working appendix. William Parker is based at the University of North Carolina, Chapel Hill and has been looking at the role the appendix plays for many years…
22:45 - Is the appendix linked to Parkinson's Disease?
Is the appendix linked to Parkinson's Disease?
Claire Bale, Parkinson's UK
One thing that the medical literature is not quite clear about is whether having your appendix removed might put you at greater risk of developing Parkinson’s disease. One recent study - carried out in Denmark - found exactly that. But another - which was based on data from millions of people in Sweden and the US - claimed the opposite. So, what is going on, and what has Parkinson’s got to do with the gut in the first place? Here’s Claire Bale, associate director of research at Parkinson’s UK…
Claire - Parkinson's is a condition that causes people to have difficulties with their movement. So people will probably be familiar with people who shake, people who are very slow and stiff. So that's in a nutshell, what people think of as Parkinson's. And it's caused by cells in the brain that make a chemical called dopamine being slowly lost, damaged over time. Without that precious chemical, the messages that we need to control our movements cannot get through. And that leads to the physical symptoms, but it can also have many other symptoms that are not so obvious. So things like changes in mood, changes in sleep, changes in the gut as well, which we'll talk about a little bit more.
Chris - What are those gut issues? Because that's surfaced in more recent years, the association between other things changing around the body, including complaints in the intestinal system.
Claire - Yes, absolutely. So probably the most prominent gut issue that people with Parkinson's experience is constipation. Some studies estimate up to 90% of people with Parkinson's experience constipation and that this can actually precede their diagnosis. This has led to a lot of research looking at, well, what is going on inside the gut in Parkinson's? What could be at the root of this constipation problem? And we know now that there are changes in the gut microbiome in people with Parkinson's, so the bacteria that are living in the gut. This has also led to research looking at the nerves around the gut, which do have a connection directly into the brain and a theory that perhaps Parkinson's may start in the gut for some people with Parkinson's and travel up those nerves into the brain before it leads to the classic symptoms of Parkinson's. So yes, it's a hugely active area of research and I think there's still a lot of work to be done to clarify exactly how the gut is involved, but certainly it's an emerging and very important area of research.
Chris - Do the microbes go off kilter and then cause those symptoms and possibly transmit the problem into the brain? Or does something else cause things to change in the function of the intestine and that has a knock-on effect for the microbes and transmits the problem to the brain?
Claire - I think this is the question that we still don't know the answer to, but we do think that a protein called alpha-synuclein may be important here. So this is the protein that when you look inside the brain of someone with Parkinson's after they passed away, we almost always see clumps of sticky proteins called Lewy bodies. And a huge constituent of those Lewy bodies is a protein called alpha-synuclein, which misfolds, so becomes misshapen and toxic we believe, to the brain cells affected in Parkinson's. Now what some research is suggesting is that we can actually see that same protein becoming misfolded and misshapen in the nerves, in the gut, in people with Parkinson's, although we still need to do a lot more research into this. So perhaps something happens in the gut. It could be exposure to things in our environment. For example, toxins, environmental chemicals, pollution, who knows? Something causes changes in the gut, perhaps in the microbes in the gut, and that ultimately causes this trigger that causes alpha-synuclein to start misfolding and then it can travel up into the brain. But this is all still quite speculative, but certainly this is an area of research that we need to do more in.
Chris - And how does the appendix come into the picture?
Claire - This is a great question. As you've said already, there's really conflicting evidence so far as to whether people who have their appendix removed are more or less likely to get Parkinson's later. There's been studies that show people are more likely to, if they have their appendix removed and studies that show, they're less likely. There have also been studies more recently that show there's no difference in risk. So the picture is very mixed. One thing that I think is really interesting is that research has shown that in the appendix there does seem to be quite a lot of alpha-synuclein, this protein that I was speaking about, that we believe to be really at the heart of the problems in Parkinson's. So potentially the appendix could be the source of alpha-synuclein becoming misfolded and then travelling up through the nervous system into the brain, potentially. Of course, there's also this idea as well that's been discussed of the appendix being a safe haven for good bacteria. So we know that people with Parkinson's struggle to have the right bacteria in their gut. They have issues with constipation and things like this. So perhaps the appendix also has a protective role in Parkinson's in helping people to maintain good healthy microbiomes. So it might be that it has a dual role and it can have good and bad impacts for Parkinson's, and that's why we're seeing such different outcomes in some of the studies that have been done so far. But certainly it's part of this whole mystery we're trying to unravel in what role does the gut play in Parkinson's.
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