Transcription
Greetings, once again. Today's topic is intravascular hemolysis.
In the last video, our discussion was on extravascular hemolysis. Intravascular means inside the vessel; hemolysis that occurs inside the blood vessel. Symptoms of anemia are the same: tired, pale, headache, dizziness, dyspnea on exertion (shortness of breath), fatigue, exercise intolerance, angina. You can hear a flow murmur with your stethoscope; the flow murmur is a systolic one. Diastolic murmurs are always bad. Again, the RBCs originate from the myeloid stem cells, which come from the multipotent stem cells. The MCV determines the type of anemia depending on its size—the size of the red blood cell. Hemolysis, either intravascular or extravascular, is a normal setting. The MCV is normal anemia, i.e., normo-acidic anemia, or the MCV is eighty to one hundred. This occurs due to three main reasons: acute blood loss, underproduction, or overdestruction. By overdestruction, I mean hemolysis. Hemolysis can have different causes; intrinsic versus extrinsic are causes of hemolysis.
Mechanisms of hemolysis are a completely different animal. Mechanisms include intravascular versus extravascular. That's not the same as intrinsic versus extrinsic. Intrinsic versus extrinsic regarding that red blood cell is: is the defect inside the blood cell, or is it outside of the red blood cell? Intravascular versus extravascular: where does the hemolysis occur—in the blood vessel or in the tissue? So these were the intrinsic extrinsic defects. Of course, hemolysis will have a reticulocyte index more than 2.5 because the bone marrow responds to hemolysis by producing more blood cells, and reticulocytes are the baby RBCs.
Mechanisms of hemolysis: in the last video we discussed extravascular hemolysis. Again, quick review: reticulo-endothelial system, i.e., the mononuclear phagocyte system. These include spleen, liver, lymphocytes. The cells that will attack the red blood cells are these, mainly macrophages. So extravascular means that the hemolysis occurs in the tissue, in the reticulo-endothelial tissue. The lab results that were kind of unique: increased lactate dehydrogenase, increased unconjugated bilirubin, and low haptoglobin.
In the next video, you'll discover that these are not unique to intravascular hemolysis. The hemolysis occurs inside the blood vessel. Fine. Why? Maybe a complement is mediating a damage and destruction to the nice red blood cell. Maybe an enzyme defect, such as glucose-6-phosphate dehydrogenase deficiency. Also, maybe a valve, a calcific or thick valve, that's so thick and calcified and stiff that the RBCs, in order to get through the valve, have to be sheared and smashed into schistocytes, which is a sheared red blood cell. This is called macroangiopathic hemolytic anemia because the pathology is big—the valve, the calcific valve, is something macro. There is also microangiopathic hemolytic anemia in conditions such as DIC (disseminated intravascular coagulopathy), HUS (hemolytic uremic syndrome), and TTP (thrombotic thrombocytopenic purpura). HELP syndrome stands for hemolysis, elevated liver enzymes, low platelets. There is a song: DIC, TTP, HUS, help me. DIC, TTP, HUS, help me. Microangiopathic hemolytic anemia: what happens is that the platelets get clumped together, so the platelets are consumed, and also that coagulation factors are consumed as well, in a very big clump like this, or a very big clot. Again, the RBCs, in order to pass in the blood vessel, get mashed and sheared into schistocytes, sheared red blood cells. All of this occurs where? Inside the nice blood vessel. There is a giant blood vessel, okay? That's why it's intravascular hemolysis. And this was the mechanism of the extravascular hemolysis discussed in the previous video.
Now, to the intravascular hemolysis: again, complement, enzyme, macroangiopathic, or microangiopathic hemolytic anemia. There is a problem with the red blood cell, okay? The red blood cell gets destroyed by macrophages, again, but not in the tissue, in the blood vessel. Fine. Then this RBC has hemoglobin, and it's bound to haptoglobin. When haptoglobin gets attacked, hemoglobin gets attacked at the same exact time. And of course, you know that hemoglobin has heme and globin. Heme has protoporphyrin. Our friend turns into unconjugated bilirubin, goes to the liver to be conjugated. So, will I say increased unconjugated bilirubin in intravascular hemolysis? Absolutely, yes. Many students confuse this point; they think that unconjugated hyperbilirubinemia and jaundice only occur with extravascular. That's not true; they occur in both extravascular hemolysis as well as intravascular hemolysis. There is hemoglobin because the RBCs are destroyed; whether they're destroyed in the blood vessel or in the tissue doesn't matter. Hemoglobin is destroyed and attacked, and hemoglobin has heme, which has protoporphyrin, which is converted to unconjugated bilirubin that goes to the liver. Normally, the liver can handle all of the amount of unconjugated bilirubin, but when there is hemolysis, the liver is overwhelmed and tired and cannot do all of that, so the levels of unconjugated bilirubin increase. In order for you to have the symptoms of jaundice, which is the yellow discoloration of skin and mucous membrane, you have to get—and the sclera—you have to get the unconjugated bilirubin level more than 2.5 in order for you to have jaundice. That's fine, but there's another story. When we have discussed extravascular hemolysis in the previous video, this destruction occurred in the tissue. This tissue can use the iron, this tissue can use that globin and destroy it into some nice amino acids, and it's kind of okay, but this tissue cannot handle the protoporphyrin. That's why we have elevated unconjugated bilirubin. But in intravascular hemolysis, is the process occurring in the blood vessel. Some of this hemoglobin, unfortunately, will go as it is, as hemoglobin, to the kidney, of course, because this is the blood vessel, and the kidney has a nice renal artery going into it. So some hemoglobin will go to the kidney—actually a lot of hemoglobin. Some of it will be secreted in the urine, giving us hemoglobinuria (hemoglobin in the urine). The kidney will try to reabsorb some of the hemoglobin, and the hemoglobin has heme, which has iron, and the kidney tubules can store it in the form of hemosiderin. Eventually, these tibial cells will get sloughed off and are excreted in the urine, giving us hemosiderinuria.
So what are the lab results of intravascular hemolysis? How about decreased serum haptoglobin? Yes, indeed. How about increased LDH (lactate dehydrogenase enzyme)? Yes, indeed. How about increased hemoglobin level in the blood and in the urine (hemoglobinuria)? Yes, indeed. Have hemosiderinuria? Of course, it will happen. This hemoglobin is lost in the urine, and the hemoglobin has iron. Can I get iron deficiency? Of course, you can. So all of these occur in intravascular hemolysis: again, low haptoglobin, increased hemoglobin in the blood and in the urine (hemoglobinemia, hemoglobinuria), hemosiderinuria, and of course iron deficiency anemia because you're losing the iron that when the red blood cell gets destroyed. Lactate dehydrogenase will increase in the serum. That's intravascular hemolysis. Very simple, very easy: complement, enzyme, mechanical problem, or microangiopathic hemolytic anemia.
I'll see you in the next video. A nice comparison between extravascular hemolysis and intravascular hemolysis will be very high yield for your exam. Study hard and see you in the next section. Bye.