Atherosclerosis: Pathogenesis

00:00 Next, let us talk about the actual pathogenesis of an atherosclerotic plaque taking place. Let me explain this figure to you. We have here on top is going to be lumen of your blood vessel and here we are going to go ahead to refer it to this as being the coronary artery. Is that clear? Now I want you to focus upon something here, you see that green endothelium. That is a cap and that is going to be a fibrous cap in which it is trying to house in this case, it is trying to prevent that atherosclerotic plaque. You see what it says cholesterol and necrotic cellular debris. Well, it is building up in there, isn't it? As it continues to build, what is this? This is not hyalin or hyperplastic type of arteriolosclerosis. This is atherosclerosis and I have referred to this a few times. Now with that atherosclerosis, which is building up, could you imagine what then happens to that cap? At some point, the fibrous cap, which is made up of smooth muscle cells, made up of fibromuscular type of tissues, then the cap may becomes little thin that it might just rupture. And if that cap ruptures, then what then happens to that necrotic debris that you see in the middle? It is then able to then escape and then it embolizes. And if it embolizes, where it going to go? Where are you right now? Good. You are in the coronary artery and if you embolize what then happens to the diameter of the coronary arteries as move distally.

01:30 Obviously, it gets smaller. Therefore embolization of the necrotic debris in the middle. Distally, you are going to have complete occlusion. Isn’t that myocardial infarction? Sure it is. So the protective mechanism of all of this, at first, begins with pathophys.

01:47 So step 1, the endothelium most commonly here might then become injured. Just goes back to those concepts of hemodynamics. What do you mean? Remembering hemodynamics with endothelial injury. What does that mean to you? You are then exposing the underlying collagen.

02:05 That underlying collagen then is going to express what? You got this, come on, tell me. Good. Your von Willebrand factor. So point is if you damage that endothelial cell, are you not promoting thrombi formation? Of course, you are, as part of the workout trial, isn't it? Next, accumulation of lipoproteins, mainly what type here, LDL. What does LDL mean to you? LDL contains what? You remember this from biochemistry. Good, cholesterol, not triglycerides. Cholesterol, is that clear. Keep it simple, keep it clear, always keep it clinically relevant and if you keep that in mind you will never miss a question. Let's continue. Number 3, so what then come in? You see these.

02:45 These are monocytes. Why am I having you focus on monocytes? What is that monocyte? Where am I? In circulation. Your monocyte is part of where? It is from part of your bone marrow.

02:57 Remember all of this is just a continuation. It is just a story and your bone marrow is one of your granulocytes, isn't it? And so therefore, of should I say it is one of your agranulocytes and it is actually part of your myeloid lineage. And so monocyte, which is being released, is traveling in circulation, but what you call monocyte when you gets embedded into a tissue? You now call this a macrophage. So now the monocyte, which then buries itself into the intima, which is then going to do what? It is a phagocytic cell. It is trying to then consume, you see that necrotic debris that right there in the middle that center point. It is trying to consume it. So what do you call macrophage when it's trying to then consume the cholesterol? It is then called, please take a look at, foam cells.

03:41 Next what do you have? Well the factors released by macrophages, the platelets, endothelial cells, all of this is going to recruit the smooth muscle cells from the intima or should I say from the media towards the intima and so of therefore, you are going to help form the fibrous cap and it is exactly what you have here, smooth muscle hyperplasia is taking place, extracellular matrix and all this is then going to further recruit more lymphocytes.

04:09 Then finally as for as the middle is concerned, this is the necrotic debris. You have created an environment where everything in there is then going to perish. And this is made up of what? Made up of your WBCs, lymphocytes, your macrophages, your foam cells now, you also have your LDL and this LDL has now become oxidiser. For the most part, it behaves like what? It behaves like a free radical. Is that clear? This is the process of what? Atherosclerotic disease.

04:37 Every one of these points is very crucial for you to understand of developing atherosclerotic plaque. As you do so, then what then happens to the coronary artery? A coronary artery becomes more and more occluded and depending as to the percentage, let us keep it at 70 percent as being the magic number. If it is less than 70 percent and you have occlusion, understand that you can still may be supply enough blood to the heart at rest, so the patient is not going to feel chest pain. However, beyond that, let us say there is 80 to 90 percent and the patient is now going to feel pain even at rest. Welcome to unstable angina.

05:12 We'll repeat this over and over again until you are eventually getting to what is known as your myocardial infarction. So now we have completed the supply aspect of our pathology and what then happens when it is cut off.