Transcription
Hi again. This is Medical Professionals. Welcome to my channel. Today's topic is extravascular hemolysis. This is a series on anemia. We're now talking about normocytic anemia. So let's get started.
Symptoms of anemia are universally the same: tired, pale, headache, angina, dyspnea on exertion, exercise intolerance. From the signs, we can have a murmur, if low murmur, usually systolic, because diastolic murmurs are always abnormal.
So what is extravascular? Extravascular literally means the spleen. Oh, only the spleen? No, other organs as well. But please be aware of the fact that when you hear extravascular hemolysis, it means it occurs in the spleen versus intravascular hemolysis, which occurs inside the blood vessel, any blood vessel. And this is your hematopoiesis slide: multipotent stem cell, myeloid, lymphoid. The RBCs come from the myeloid. MCV always determines if the anemia is microcytic, normocytic, or macrocytic, because MCV depends on the size of the red blood cell. If it's small in size, it's microcytic; bigger, macrocytic; normal, normocytic. We're talking about hemolytic anemia, and it is usually normocytic anemia. You'll have a normal MCV, ranging between 80 and 100.
Okay, so here we have the normal sites of anemia: acute blood loss, underproduction, or overdestruction. Overdestruction means hemolysis. Hemolysis can be intrinsic, i.e., the problem is inside the red blood cell, or extrinsic, a problem outside of the red blood cell. But these are the types; the mechanisms are different. Mechanisms will include extravascular hemolysis and intravascular hemolysis, not to be confused with intrinsic defect versus extrinsic defect. These are the types; extravascular versus intravascular are the mechanisms. All right, onto the mechanisms of hemolysis: intravascular, inside the blood vessel; extravascular, inside the spleen, the spleen only. No, all of the reticulo-endothelial system organs, also known as the mononuclear phagocyte system, which will include spleen, liver, and lymph nodes. Which cell will phagocytose? Monocytes, macrophages, and histiocytes. There is a very, very slight difference between them and among them. Let me know in the comments what are the differences among these cells; very slight difference, if any.
NATO topics of extravascular hemolysis will mean spleen, liver, or lymph node. Which one is the most common? Spleen. So extravascular: spleen, spleen, extravascular. And now to the big story: extravascular hemolysis. We're in the spleen. We have an abnormal RBC. Why is it abnormal? Many different causes. Maybe there is an antibody there: IgG. Okay, IgG makes this blood cell delicious and tasty to the macrophage. This process is called opsonization. Opsin or opsonin comes from a Greek word, literally means delicious side dish, which is very cool. So maybe an IgG. IgA is very good for opsonization. IgD is not good for opsonization. IgM is good for complement. IgG is good for opsonization, making the RBC delicious to the nasty macrophage. That's the first problem. Or maybe there's another problem with the shape of the red blood cell. The shape is abnormal, such as sickle cell disease, where the shape is sickle, or spherocytosis, usually the red blood cell is biconcave. Spherocytosis is abnormal. This gets destroyed because they are abnormal, or inclusion bodies. You know the Heinz bodies present in G6PD deficiency; those are inclusion bodies that must be eradicated, sort of. The red blood cell is phagocytosed in the spleen by the splenic macrophages.
So back to our story. Here's our abnormal red blood cell. Fine, gets attacked by the macrophage. However, the hemoglobin inside the red blood cell is always bound to something called haptoglobin. It's a protein bound to the hemoglobin. So when the RBC gets attacked, both of them are attacked; both, both the hemoglobin and the haptoglobin are attacked. So in extravascular hemolysis, there is a decreased serum level of haptoglobin, why? Because it gets attacked by the same macrophage that attacked the hemoglobin inside the red blood cell. That's fine. Now, the red blood cell, after getting attacked by the macrophage, will give us—of course, it has the hemoglobin, and you know hemoglobin has heme and globin. Heme consists of iron and protoporphyrin. Protoporphyrin will be converted into unconjugated bilirubin. It goes to the liver to get conjugated into conjugated bilirubin. In normal circumstances, the liver can handle all of the amount of the unconjugated bilirubin and transform it to the conjugated bilirubin. But this is not normal. There is hemolysis. The spleen is destroying an insane amount of RBCs. A huge amount of RBCs are getting destroyed. A huge amount of protoporphyrin is being released. A huge amount of unconjugated bilirubin. The liver doesn't have the capacity to do all of this. So the level of unconjugated bilirubin in the blood will be increased, why? Because the liver can't handle this insanity. Fine. What else will happen? When the RBC gets destroyed, an enzyme comes out called LDH, lactate dehydrogenase. If you remember your biochemistry, lactate dehydrogenase converts pyruvate into lactate and vice versa. Does the red blood cell need this enzyme? Of course, it does. What are we talking about? The RBC uses glycolysis in the absence of oxygen to give it a minimal amount of ATP. This is the reaction. Glycolysis gives us pyruvate. In the absence of oxygen or where there is very little oxygen, pyruvate is converted to lactate. Thank you, lactate dehydrogenase. So lactate dehydrogenase is present in the red blood cell as well as every other cell. So this reaction, pyruvate to lactate, is part of glycolysis. Lactate to pyruvate is the Cori cycle in the liver. That's just for you to know. So lactate dehydrogenase is abundant in the red blood cell. When it gets destroyed, the levels of LDH in the plasma will increase.
So let's summarize extravascular hemolysis: I have an abnormal RBC. Get an antibody, or maybe abnormal shape, or an inclusion body. The splenic macrophage will attack the red blood cell. Haptoglobin will decrease because it is attacked. Lactate dehydrogenase is secreted after hemolysis, so the level of lactate dehydrogenase is increased in the plasma. Hemoglobin is destroyed. Protoporphyrin will increase. Unconjugated bilirubin will increase because the liver cannot handle this huge amount of hemolysis. This is the story, morning glory, of the extravascular hemolysis. In the next video, we will discuss intravascular hemolysis. But please know that problems like sickle cell disease, spherocytosis, G6PD deficiency are all due to extravascular hemolysis, which is the main issue in all of these conditions that we will discuss later. For now, take care and study hard. I'll see you in the next video. Happy holidays everybody. Enjoy your medicine.