Anemia of Chronic Disease: Iron Studies

00:01 Let’s walk through now the pathogenesis of your anemia of chronic disease and have you pay attention to what’s in bold here – the increase or normal ferritin.

00:11 In other words, no decrease in ferritin.

00:12 Are we clear? What’s your patient suffering from? Oh, some type of chronic disease including -- Maybe it’s a female that has something like Hashimoto or maybe there is rheumatoid arthritis, maybe infection, cancer, malignancies.

00:30 That’s the underlying issue.

00:32 Next, what happens? Let me take you step by step.

00:35 Anemia of chronic disease, number one, serum iron might be mildly decreased.

00:41 Number two, take a look at the ferritin here.

00:44 And here, in the graph, something that we have not seen in any other graph of iron study is this little discussion.

00:53 See that arrow coming out of the liver moving towards this hepcidin.

00:58 Well, that’s another substance that we have not seen in any other iron study graph.

01:03 So this acute phase reactant that is being released by the liver, in response to this chronic disease, which is inflammatory, is specifically known as hepcidin.

01:14 This you have to know.

01:17 This hepcidin, as you see here, you see that green block? That green block is blocking literally the release of iron from your ferritin.

01:26 Where are we going with this? Well, if you block or release or inhibitor the release of iron from your ferritin, guess what? Tell me about your ferritin level.

01:38 It is abnormally either normal or perhaps even increased.

01:44 In iron deficiency, did you have such a hepcidin? Of course not.

01:48 So therefore, whenever you had iron deficiency, serum iron was decreased, thus ferritin was decreased, are we clear? Here, however, the case, definitely different.

01:59 We have hepcidin coming in, blocking the release.

02:00 But this important.

02:03 So what is ferritin? Well, for the most part, you think of this as being a bone marrow macrophage.

02:07 Number two, where else would you perhaps reabsorb some of that iron? You should know this from the discussion of hemochromatosis.

02:15 If it’s hereditary hemochromatosis, then you know that there is unobstructed, unopposed reabsorption of iron from the intestine, intestine, intestine, isn’t that the definition of hemochromatosis? Too much reabsorption of iron from the intestine, putting it into your blood.

02:29 Correct? That’s hemochromatosis.

02:32 What do you think normally regulates the amount of iron that is being reabsorbed from the intestine? Wow! It’s hepcidin? Yeah, it is.

02:41 So now, if you have too much hepcidin, guess what it does? It inhibits the release of iron, period.

02:47 Either from ferritin, bone marrow macrophage or number two, the intestine.

02:52 Is that clear? So you might have a patient that has slightly decreased levels of iron serum-wise.

03:00 Ferritin, however, will be normal or increased.

03:02 Let’s go with your microcytic though.

03:03 So if it’s microcytic and you have complete blockage of your ferritin, you have an increase in ferritin, what is my TIBC relationship here? Inverse, isn’t it? So you have an increase – Increase or decrease? Good. You have a decrease in TIBC, inverse relationship.

03:21 And what is it that’s saturating transferrin? That’s that question that I had post to you early on.

03:28 This is where it becomes really important.

03:31 Good. It’s the ferritin.

03:32 So if the ferritin’s blocked, how in the world can you possibly saturate the transferrin? You cannot.

03:39 So what’s my transferrin saturation? Decreased.

03:42 Is that clear? One more time.

03:43 What about serum iron? Maybe mildly decreased.

03:47 Number two, increased ferritin if it’s microcytic.

03:50 Number three, a decrease in TIBC, good.

03:53 And number four, you have a decrease in transferrin saturation.

03:57 This is for microcytic.

03:57 However, is it a possibility that you might have normocytic ACD? Absolutely.

04:04 And at that point, you’ll have some of these interleukins, which is then shutting down my bone marrow, resulting in non-hemolytic and normocytic type of picture.

04:11 Do not forget that.

04:13 Not to worry.

04:15 I’ll repeat it when the time is right as well.

04:17 Anemia of chronic disease.

04:19 We’ll take a look at iron accumulating in your Prussian blue stain.

04:24 This is important for you to understand this.

04:26 There is bone marrow macrophage and there’s your ferritin, okay? So we’re in the bone marrow, you’re seeing large open spaces here.

04:32 And in your bone marrow, what is it that allows for iron to be then delivered to your bone marrow? That of course would be transferrin.

04:40 So transferrin is going to then bring the iron into your bone marrow, great.

04:43 Next, well, the iron is then going to start accumulating in your bone marrow macrophage.

04:48 We’ll go ahead and call this the ferritin, clear? At some point in time when ferritin degrades, you call this hemosiderin.

04:56 Hemosiderin usually is not going to kill you, not going to cause – Usually doesn’t cause massive tissue damage.

05:04 However, if it accumulates in abnormal tissue, it may indicate the pathology.

05:09 For example, you’ve heard of hemosiderin-laden macrophages in the lung.

05:11 Correct? And that’s your heart failure cell.

05:15 It’s not that the hemosiderin is actually fully causing damage to the tissue, but my goodness gracious, it’s presence in the lung parenchyma or interstitium, definitely means that pathology is occurring.

05:26 Is that clear? Versus hemochromatosis, which is also going to be increased iron, but that increased iron will then actually cause damage to organs such as the skin, the bronze cause damage to the pancreas, no insulin, diabetes.

05:43 Bronze, diabetes.

05:45 Let’s take a look at some other factors here.

05:47 Ferritin synthesis.

05:47 Macrophages, hepatocytes and cytochrome system is going to help you with all of this.

05:55 So ferritin, bone marrow or coming from your liver.

05:59 Next, usually, we have a decrease in serum ferritin.

06:03 This is equivalent to a decrease in iron stores whereas if you have an increase in serum ferritin, this is equivalent to increase in iron stores.

06:13 But the one big exception where we saw an increase in ferritin but still resulting in a type of anemia, was once again, anemia of chronic disease.

06:20 This is a nice little discussion here so that you can see when applying your Prussian blue stain, then what you’re only seeing here staining is the iron.

06:32 Everything else that you see here, well, it’s not containing the increased amount of iron here.

06:36 The only other thing that I wish to bring your attention is that if you did an H and E stain, which they will give you, then this iron is going to appear what color? Brown.

06:47 So those of you that have gotten into the habit of only seeing blue iron, get away from that.

06:51 It only depends on the stain.

06:54 So if you’re suspecting hemochromatosis on H and E, you find it to be brown.

07:00 If it’s Prussian blue and you’re ordering this, then this will then show you the blue.

07:04 I hope that’s clear.

07:06 A very important point.