Transcription
Welcome back. Let's continue our discussion of anemia, and today's topic is anemia of chronic disease, aka anemia of inflammation, or anemia of chronic inflammation. Anemia. So tired and pale, pale and tired. Rheumatoid is killing me. Let's get some facts about anemia of chronic disease.
It's the most common anemia in rheumatoid arthritis, tuberculosis, Crohn's disease—you can say chronic inflammation—most commonly in hospitalized patients. Most common anemia in malignancy such as Hodgkin's lymphoma. Most common anemia in alcoholics. So chronic inflammation, hospitalized patients, malignancy, and alcoholics. Remember this: anemia can coexist with iron deficiency anemia. So any patient with chronic illness should be screened for anemia.
Once the pathogenesis: we have three theories. Number one: the body is keeping the iron away from the bacteria because the bacteria or the microbe needs iron to flourish, to grow, become more virulent, and to replicate. So if we keep iron away from the microbe, we are doing a favor to our bodies. How can we keep it away from it? By storing it in macrophages, in iron stores. Because remember, we have serum iron, goes on to transferring, and then goes to stores to be stored. Okay. Is there any piece of evidence supporting this theory? Yes. Patients with anemia of chronic disease or chronic illnesses, and no, when we give them blood—okay, that contains iron, of course—they tend to get worse. The data suggests that giving blood to patients with chronic illnesses worsens the outcome. Why? They are not sure yet. Maybe because the blood contains iron, I don't know, the bacteria flourish, and of course, when we have iron that we cannot use, okay, we cannot form heme, and we cannot form hemoglobin. That's easy. Okay. What will happen to the protoporphyrin? It will be left alone because there is no iron to join it, and it will start to pile up and accumulate.
Second theory: the erythropoietin theory. So in chronic inflammation, we have cytokines such as interleukin 6, go to the kidney, tell her to shut down producing EPO, or EPO is insufficient. However, the bone marrow response is poor, so it's even less EPO, or less response to EPO. Either way, the end result is anemia, because we need EPO to stimulate the bone marrow to form new RBCs.
Theory number 3: the hepcidin theory. As we've said before when we were discussing iron absorption, iron here is the end, the enterocyte goes through that ferroportin, get converted to Fe3+, the ferric bound to transferring in the blood vessel, then either goes to the bone marrow to form new RBCs or go to the liver, get stored, and stimulate something called hepcidin. It's a regulator or inhibitor of iron absorption. Hepcidin works by two mechanisms: block that door, so that not more iron comes, okay, or block the macrophage from releasing iron. So there is a theory that the cytokine such as interleukin 6 leads this hepcidin to increase and upregulate and deliver to produce more hepcidin. So we block macrophages from releasing iron, and it gets trapped in the stores, trapped in the stores. So therefore, we have anemia of chronic disease: iron trapped in the stores means iron cannot be used to form new RBCs. Remember as well, ferritin: when we have more ferritin, okay, the liver will sense that and produce less transferrin, less plasma protein that binds iron. This one. That's why we have told you that ferritin and transferrin are always in inverse relation to each other: ferritin up, transferrin down; ferritin down, transferrin up. So that's anemia of chronic disease in a nutshell: you are protecting yourself from the microbe by keeping iron away from it, okay, but in life you can't have it both ways. The drawback is that the iron that's kept away in stores cannot be used to form new RBCs; therefore, you get anemia.
Symptoms as usual: pale and tired, tired and pale. Sometimes I get flow murmur, sometimes I get angina, especially if I have a heart problem. I'm weak, I'm irritable, I can't exercise: weakness, irritable, exercise intolerance. And in anemia of chronic disease, we will have the main condition, be it rheumatoid arthritis or tuberculosis or Crohn's disease or malignancy or alcoholism or hospitalization, etc., etc., etc.
Okay, the lab results: what's predicted? Hemoglobin and hematocrit, both are decreased; it's anemia. However, the hemoglobin will not be less than 9; it's usually 9 to 11 in that range. It's not that severe to be below 9, okay, not below 9. MCV, okay, that's a tricky one: usually normocytic, sometimes microcytic, especially when we have rheumatoid arthritis or Crohn's disease. Why? I don't know. So, but usually, most of the time, it's normocytic. The free erythrocyte protoporphyrin will be increased because there is no iron to bind it. We have iron and protoporphyrin; they join to form heme; heme joins to globin; okay, heme plus globin gives us what? Hemoglobin. So if iron cannot be used because it's trapped, protoporphyrin will start to pile up, increase free erythrocyte protoporphyrin. How about the reticulocyte? If the bone marrow cannot produce mature RBCs, usually it cannot produce immature RBCs. Why? The iron is trapped; the problem is in the iron. So reticulocytes will be low. White blood cells and platelets are usually kind of normal. Serum iron will be decreased. You know why? Because iron is trapped in the ferritin form, trapped in the macrophage, trapped in the stores, okay. Also, ferritin will be high. You do a second reason: 'cause ferritin is an acute phase reactant, increases in case of inflammation. So it's called anemia of chronic inflammation, okay. Of course, ferritin will be up; that's a no-brainer. TIBC is always opposite to ferritin, so ferritin up, TIBC down. Percent saturation equals the serum iron over the TIBC. So serum iron is low, TIBC is low, that's why percent saturation can be normal, but if the problem in iron is more, which is usually the case, then we'll have decreased percent saturation. What about the soluble transferrin receptor concentration? It will be normal. Huge difference between anemia of chronic disease and iron deficiency anemia, where the STFR was high. Okay. How about RDW, or RDW is the red cell distribution width? It's usually not significant in anemia of chronic disease; don't worry about it.
Treatment: how to treat anemia of chronic disease? To remember the three theories in pathogenesis, yes? What were they? Number one: keeping iron away from the microbe, okay, to prevent it from reproducing. So we treat the underlying condition. If I have Crohn's disease, treated; TB treated; rheumatoid arthritis treated. First, we can give parenteral iron, means IV or IM; it's usually IV. Yes, we can. Sometimes helps. EPO, the artificial form, EPOETIN ALPHA, we can give them because sometimes they are deficient in EPO, or they cannot use it inside the body, so we can give it artificially. Hepcidin was the third theory, so they're trying to develop hepcidin antagonists these days to help with this condition. That's it for anemia of chronic disease. Thank you very much for watching. Next, we'll discuss leukemia. Thank you very much.