Flo Hyman had always been a tall girl. I mean... really tall. By her 12th birthday, she was already six feet, and by 17 she’d topped out at just over 6’5’’. Initially self-conscious about her stature, she learned to use it to her advantage when she started playing volleyball. She attended the University of Houston as the school’s first female scholarship athlete, and at the age of 21, she was competing in World Championships. Nine years later she made it to the 1984 Olympics and helped her team win the silver medal. After the Olympics, Hyman moved to Japan where she gained fame playing professional volleyball. But all of that ended in 1986 when out of nowhere, she collapsed and died during a game. She was 31 years old. Hyman’s initial cause of death was thought to be a heart attack, but an autopsy revealed that she died from a tear in her aorta, caused by an undiagnosed condition known as Marfan Syndrome. Marfan Syndrome is a genetic disorder of the connective tissue. People suffering from it have a defect in their connective tissue that substantially weakens it over time. And you’ve got connective tissue pretty much everywhere in your body, so it can cause big problems. Outwardly, those with Marfan’s tend to to be especially tall and thin, like Flo Hyman, with loose, flexible joints and noticeably longer limbs and fingers. Those long fingers and bendy joints have actually helped some athletes and musicians do things that the rest of us can’t -- famous blues guitarist Robert Johnson, piano virtuoso Sergei Rachmaninov, and Italian violinist Niccolo Paganini are all believed to have had Marfan Syndrome. But these abilities come at a great cost -- as people with Marfan’s get older, their weakening tissue can cause serious problems in the joints, eyes, lungs, and heart. The fact that a single genetic mutation can affect your bones, cartilage, tendons, blood vessel walls, and more, shows that all of those structures are closely related, no matter how different they may seem. We’ve covered the basic properties of nervous, muscle, and epithelial tissue, but we haven’t gotten to the most abundant and diverse of the four tissue types -- our connective tissue. This is the stuff that keeps you looking young, makes up your skeleton, and delivers oxygen and nutrients throughout your body. It’s what holds you together, in more ways than one. And if something goes wrong with it, you’re in for some havoc. And that means we’re gonna be talkin’ about Jello today. Uh…we’ll get to that in a minute. The springiness here? That’s connective tissue. So is the structure in here, and the stuff inside here, and the tendons popping out here Connective tissue is pretty much everywhere in your body, although how much of it shows up where, varies from organ to organ. For instance, your skin is mostly connective tissue, while your brain has very little, since it’s almost all nervous tissue. You’ve got four main classes of connective tissue -- proper, or the kind you’d find in your ligaments and supporting your skin, along with cartilage, bone, and blood. Whaaaa? Sounds a little weird, but your bones and your blood are just types of connective tissue! So, despite the name, your connective tissues do way more than just connect your muscles to your bones. Your fat -- which is a type of proper connective tissue -- provides insulation and fuel storage -- whether you like it or not -- but it also serves structural purposes, like holding your kidneys in place, and keeping your eyeballs from popping out of your skull. Your bones, tendons, and cartilage bind, support, and protect your organs and give you a skeleton so that you can move with a purpose, instead of blobbing around like an amoeba. And your blood transports your hormones, nutrients, and other material all over your body. There’s no other substance in you that can boast this kind of diversity. But if they’re so different, how do we know that anything is a connective tissue? Well, all connective tissues have three factors in common that set them apart from other tissue types. First, they share a common origin: They all develop from mesenchyme, a loose and fluid type of embryonic tissue. Unlike the cells that go on to form, say, your epithelium, which are fixed and neatly arranged in sheets, mesenchymal cells can be situated any-which-way, and can move from place to place. Connective tissues also have different degrees of vascularity, or blood flow. Most cartilage is avascular, for example, meaning it has no blood vessels; while other types of connective tissue, like the dense irregular tissue in your skin, is brimming with blood vessels. Finally -- and as strange as it may sound -- all connective tissues are mostly composed of nonliving material, called the extracellular matrix. While other tissue types are mainly made of living cells packed together, the inert matrix between connective-tissue cells is actually more important than what’s inside the cells. Basically, your connective tissue, when you see it up close, looks and acts a lot like this. Yeah. The most abundant and diverse tissue in your body, that makes all of your movements and functions possible? Turns out it’s not that different from the dessert that Aunt Frances brings to every holiday party. The jello that gives this confection its structure is like that extracellular matrix in your connective tissue. The actual cells are just intermittent little goodies floating around inside the matrix -- like the little marshmallows. And although it may not look like it in this particular edible model, the extracellular matrix is mostly made of two components. The main part is the ground substance -- a watery, rubbery, unstructured material that fills in the spaces between cells, and -- like the gelatin in this dessert -- protects the delicate, delicious cells from their surroundings. The ground substance is flexible, because it’s mostly made of big ol’ starch and protein molecules mixed with water. The anchors of this framework are proteins called proteoglycans. And from each one sprouts lots and lots of long, starchy strands called glycosaminoglycans, or GAGs, radiating out from those proteins like brush bristles. These molecules then clump together to form big tangles that trap water, and if you’ve ever made glue out of flour, you know that starch, protein and water can make a strong and gooey glue. But running throughout the ground substance is another important component: fibers, which provide support and structure to the otherwise shapeless ground substance. And here, too, are lots of different types. Collagen is by far the strongest and most abundant type of fiber. Tough and flexible, it’s essentially a strand of protein, and stress tests show that it’s actually stronger than a steel fiber of the same size. It’s part of what makes your skin look young and plump, which is why sometimes we inject it into our faces. In addition, you’ve also got elastic fibers -- which are longer and thinner, and form a branching framework within the matrix. They’re made out of the protein elastin which allows them to stretch and recoil like rubber bands; they’re found in places like your skin, lungs, and blood vessel walls. Finally, there are reticular fibers -- short, finer collagen fibers with an extra coating of glycoprotein. These fibers form delicate, sponge-like networks that cradle and support your organs like fuzzy nets. So, there’s ground substance and fibers in all connective tissue, but let’s not forget about the cells themselves. With a tissue as diverse as this, naturally there are all kinds of connective tissue cells, each with its unique and vital task -- from building bone to storing energy to keeping you from bleeding to death every time you get a paper cut. But each of these signature cell types manifests itself in two different phases: immature and mature. You can recognize the immature cells by the suffix they all share in their names: -blast. “Blast” sounds kinda destructive, but literally it means “forming” -- these are the stem cells that are still in the process of dividing to replicate themselves. But each kind of blast cell has a specialized function: namely, to secrete the ground substances and fiber that form its unique matrix. So chondroblasts, for example, are the blast cells of cartilage. When they build their matrix around them, they’re making the spongy tissue that forms your nose and ears and cushions your joints. Likewise, osteoblasts are the blast cells of bone tissue, and the matrix they lay down is the nexus of calcium carbonate that forms your bone. Once they’re done forming their matrix, these blast cells transition into a less active, mature phase. At that point, they trade in -blast for the suffix -cyte. So an osteoblast in your bone becomes an osteocyte -- ditto for chondroblasts becoming chondrocytes. These cyte cells maintain the health of the matrix built by the blasts, but they can sometimes revert back to their blast state if they need to repair or generate a new matrix. So, the matrices that these cells create are pretty much what build you -- they assemble your bone and your cartilage and your tendons and everything that holds the rest together. Not bad for a bunch of marshmallows floating in jello. BUT! There is another class of connective tissue cells that are responsible for an equally important role. And that is: protecting you, from pretty much everything. These are cells that carry out many of your body’s immune functions. I’m talking about macrophages, the big, hungry guard cells that patrol your connective tissues and eat bacteria, foreign materials, and even your own dead cells. And your white blood cells, or leukocytes that scour your circulatory system fighting off infection, they’re connective tissue cells, too. You can see how pervasive and important connective tissue is in your body. So a condition that affects this tissue, like Marfan Syndrome, can really wreak havoc. One of the best ways of understanding your body’s structures, after all, is studying what happens when something goes wrong with them. In the case of your connective tissue, Marfan Syndrome affects those fibers we talked about, that lend structure and support to the extracellular matrix. Most often, it targets the elastic fibers, causing weakness in the matrix that’s the root of many of the condition’s most serious symptoms. About 90 percent of the people with the disease experience problems with the heart and the aorta -- the biggest and most important artery in the body. When the elastic fibers around the aorta weaken, they can’t provide the artery with enough support. So, over time, the aorta begins to enlarge -- so much so that it can rupture. This is probably what happened to Flo Hyman. She was physically exerting herself, and her artery -- without the support of its connective tissue -- couldn’t take the stress, and it tore. There's SO MUCH going on with your connective tissue -- so many variations within their weird diversity -- that we’re going to spend one last lesson on them next week, exploring the subtypes that come together to make you possible. But you did learn a lot today! You learned that there are four types of connective tissue -- proper, cartilage, bone, and blood -- and that they all develop from mesenchyme, have different degrees of blood flow, and are mostly made of extracellular matrix full of ground substance and fibers. We touched on different blasts, and cyte, and immune cell types, and discussed how Marfan Syndrome can affect connective tissue. Thanks for watching, especially to our Subbable subscribers, who make Crash Course possible for themselves and also for the rest of the world. To find out how you can become a supporter, just go to subbable.com. This episode was written by Kathleen Yale, edited by Blake de Pastino, and our consultant, is Dr. Brandon Jackson. Our director and editor is Nicholas Jenkins, the script supervisor and sound designer is Michael Aranda, and the graphics team is Thought Café.