Author: Kyle Slinn, RN, MEd
Editor: Rishi Desai, MD, MPH, Tanner Marshall, MS
So these three words look the same: Arteriosclerosis, Atherosclerosis, and Arteriolosclerosis. Arteriosclerosis is a general umbrella term describing diseases where the wall of the artery becomes thicker, harder, and less elastic than normal. You can figure that out right from the name: “arterio” which is Greek for artery, and sclerosis which is Greek for “hardening”. Now the word arteriolosclerosis is any sort of hardening of small arteries in arterioles. This is also pretty easy to remember since the “olo” in the middle of the word indicates small arterioles. And then finally, atherosclerosis is the hardening of any artery ( even though it’s usually medium- to large-sized arteries) which is caused by the buildup of plaque. These plaques are called atheromatous plaques and happen in the innermost wall of the blood vessel called the tunica intima or endothelium. (Woo), okay now that we’ve differentiated been all three of those words, let’s first take a look at atherosclerosis (up close first).
So the blood vessel endothelium is made up of a single layer of cells and does two jobs:
First,it protects the rest of the blood vessel wall from the blood, like a coat of varnish on your wood furniture and then,
secondly,it secretes proteins on its surface to prevent the blood from clotting, because blood just inherently likes to clot whenever it gets the chance. Now, Your endothelium can become damaged in lots of different ways. Low density lipoproteins, chemicals from smoking cigarettes, and high blood pressure all wreak havoc on the endothelium because these irritants break down the endothelium.
The damaged endothelium allow low-density lipoproteins to enter the endothelial wall. The white blood cells called monocyte follow the low-density lipoproteins and break them down through oxidation. Okay, so you might think macrophages eating the embedded low-density lipoproteins is a good thing, but if there is a lot of low-density lipoprotein, then the macrophage will eat so much cholesterol that it can die. It basically eats itself to death. . When the macrophage full of low-density lipoprotein dies)After it dies, it deposits itself under the damaged endothelium. So now we have a dead macrophage filled with low density lipoprotein stuck in the damaged endothelium as well. (Arguably, not an improvement.) These dead macrophages are called foam cells and that’s because some guy a while back looked at these things in a microscope and thought they looked like foam on the beach, hence the name.
Also, when the macrophage dies, it releases cytokines, which calls over more monocytes which come over and) eat low-density lipoprotein, inevitably dying while doing so, and thus this vicious cycle of gross overeating and massive fatalities has begun. As more and more of these foam cells build up, they form a lesion we call a fatty-streak.
Now the fatty streak is thrombogenic meaning that blood can clot on it. Platelets begin to gather at the damaged endothelium and release platelet-derived growth factor, which in turn encourages the growth of smooth muscle cells. Now normally smooth muscle cells are suppose to stay within the middle layer of the blood vessel, the tunica media. The release of platelet-derived growth factor draws the media smooth muscle cells to the tunica intima where they multiply. The growing smooth muscle secretes collagen, proteoglycans, and elastin fibrous cells that help form a wall around the fatty streak, preventing blood clotting. We call this extracellular matrix wall a fibrous cap, and together both the fatty streak and the surrounding fibrous cap is called plaque.
The presence of fatty streaks cause the underlying smooth muscle in the blood vessel wall to also start depositing calcium into the plaque, creating crystals. Normally calcium is deposited into the vessel wall by low-density-lipoproteins and is then removed by high-density lipoproteins. The accumulation of plaque in the vessel messes up the ability of high-density lipoproteins to remove calcium from the vessel, so a buildup of calcium occurs in the vessel wall and it crystallizes.
Now remember calcium makes stuff hard, which is why your bones are full of calcium, right? This deposit of calcium into the plaque is what stiffens the walls of the arteries.
Now remember the word that describes the immune system getting involved with something is called inflammation, so atherosclerosis is an inflammatory disease. Now as another aside, the protein called C-reactive protein increases in the blood during an infection or when inflammation is occurring somewhere in the body. While an elevated C-reactive protein isn’t specific enough to diagnose atherosclerosis, it can act as like a red flag that atherosclerosis might be occurring, especially if someone has atherosclerosis symptoms or other risk factors.
From time-to-time that fibrous cap can crack and expose the underlying thrombogenic foam cells to blood.
And, this can happen randomly, and when it does, within moments you can see a blood clot start form within the already partially occluded artery, quickly leading to even less blood being able to flow by. After about 70% of a blood vessel is occluded from the plaque and the new overlying blood clot, cell injury and death begin in the areas that were relying on the blood flow. If blood flow is reduced in the coronary arteries, angina and myocardial infarctions can occur.
Seriously occluded internal carotid and middle cerebral arteries lead to strokes and cerebral atrophy, an occluded superior mesenteric artery affects the small intestine, and an occluded popliteal artery can cause peripheral vascular ischemia, like gangrene or claudication, which is frequent leg cramping during exercise. Now, the building up of plaque also weakens the artery walls, which means it can lead to aneurysms which explains why atherosclerosis is a main cause of abdominal aortic aneurysms.
But the complications of atherosclerosis don’t stop there! If we move on to the kidneys, plaque build up in the renal arteries reduces blood flow to the kidney, and tricks the kidney into thinking blood pressure is low. The kidneys then activate the renin-angiotensin-aldosterone system which unnecessarily increase blood volume in the body, causing hypertension.
Occasionally, some of the plaque can also break off from the main plaque deposit and become an embolism, floating around in the blood stream until it gets stuck in a smaller blood vessel or another artery with significant atherosclerotic plaque build up. And you can totally see this in a tissue biopsy, as the affected blood vessel will have cholesterol clefts, these big white entities in the middle of the blood vessel.
Moral of the story, atherosclerosis isn’t great. There are a few things you can do to prevent it though. Maintaining a normal blood pressure, not smoking, and avoiding excessive sugary and fatty foods and drinks all reduce your risk of the disease. There are other risk factors that may be out of your control though. You’re more likely to get atherosclerosis as you get older. Males and postmenopausal females are also more prone to the disease, but premenopausal females are less at risk because higher levels of estrogen have a protective effect against atherosclerosis. No big surprise here, but people who have a family history with atherosclerosis are also more at risk. Ok, that’s enough atherosclerosis for one day.
Another type of arteriosclerosis is called Monckeberg Sclerosis or Medial Calcific Sclerosis. And this is caused by the formation of calcium crystals in the muscular layer of the blood vessel wall, leading to hardening of the blood vessel, but it this does not affect the diameter of the lumen. Since blood flow isn’t impaired, it doesn’t really cause any signs and symptoms, so it’s usually detected during a diagnostic procedure for something else like mammograms, since mammographies are used to look for calcification as a sign of breast cancer. So the last arteriosclerosis category we’ll talk about is arteriolosclerosis. Arteriolosclerosis is a category of blood vessel hardening diseases that affect small blood vessels and is caused by high-blood pressure and diabetes.
Hyaline arteriolosclerosis is one type of arteriolosclerosis where instead of a buildup of plaque on the walls of the arteries, the high-pressured blood flowing through the blood vessels causes proteins floating around in the blood to leak into the blood vessel walls. Overtime these you’ll see these walls begin to build up a lot of these proteins, making the blood vessels stiffer. When you look at a blood vessel through a microscope, you’ll see a pink hyaline material that is making the blood vessel very thick.
Thick walls means that the lumen of the vessels start to get narrower. And this basically reduces blood flow to the organs that are supplied blood through these vessels, and the organs get starved of oxygen. And, this is usually seen in the kidneys where not enough blood is supplying the small glomeruli blood vessels and the glomerulus itself, causing the glomerulus to scar (which summed up nicely by the term arteriolonephrosclerosis). If we don’t do something to stop it, we’ll see scarring occur to enough glomeruli that a person develops chronic renal failure.
People with diabetes can have hyaline arteriolosclerosis through a different mechanism. Chronic exposure to high blood sugar can directly damage the endothelium, likely by altering carbohydrate and fat metabolism, which in turn damages the basement membrane of the blood vessels.
Another type of arteriolosclerosis is called hyperplastic arteriolosclerosis, which is also happens due to thickening of the blood vessel walls, and occurs when a person has extreme hypertension. The blood vessels compensate for this high blood pressure by adding additional layers of smooth muscle and basement membrane, to the blood vessel wall, making the blood vessel stronger. The downside is this extra muscle is that it decreases the space in the lumen for blood to pass through.
If you look at these hyperplastic blood vessels under a microscope, you can see the rings of smooth muscle with a small lumen. Which kind of looks like an onion. Just like in hyaline arteriolosclerosis, hyperplastic arteriolosclerosis can then cause ischemia in the organs it supplies.
Also just like hyaline arteriolosclerosis, hyperplastic arteriolosclerosis typically affects the arteriole walls of the kidney. The high blood pressure destroys the blood vessels in the kidneys, causing renal ischemia. What’s unique in hyperplastic arteriolosclerosis is the kidneys themselves will look a bit like they have insect bites everywhere. That’s because the high-blood pressure ruptures the weakened renal blood vessel walls, causing small hemorrhages all over the kidneys. These small blood vessel hemorrhages give the kidney tissue the appearance that they have been bitten by insects!