Macrocytic Anemia: Clinical Pathology

by Carlo Raj, MD

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    00:00 With macrocytic, what are we looking for? Lab findings, decreased hemoglobin.

    00:06 Increased MCV, greater than 100.

    00:09 Folate deficiency.

    00:10 Now, pay attention here because we will now differentiate between folate and B12 deficiency.

    00:15 If it’s folate, you will have increased homocysteinemia or hyperhomocysteinemia and hyperhomocysteinuria, but you do not find what here? Good, you don’t find methylmalonic aciduria.

    00:29 Correct? Folate deficiency.

    00:31 B12, decreased serum B12 and what have I added here that folate deficiency doesn’t have? Methylmalonic aciduria.

    00:41 You see that? And do you remember what biochemical pathway dealt with methylmalonic aciduria? Good.

    00:47 That’s your myelination pathway, wasn’t it? And what is that enzyme that B12 was a co-factor there? Methylmalonic-CoA or methylmalonic mutase, right? And then if it was homocysteine, you’re dealing with methionine synthase.

    01:01 A lot of M’s there for B12.

    01:03 Signs and symptoms of anemia with macrocytic.

    01:06 Now under B12, I’m going to first walk you through those neurologic symptoms that I was referring to earlier.

    01:12 When I was referring to our ataxic gait, spinocerebellar.

    01:17 If it’s proprioception and positive Romberg, that will be posterior column or dorsal column.

    01:21 And lateral corticospinal tract will then give you positive Babinski sign referring to your upper motor neuron lesion.

    01:29 You’re taking a tongue depressor and in an adult, you take the lateral aspect of the foot and you caress it.

    01:34 And as you do so, as an adult normally, we should then flex our toes, okay? However, if it’s positive Babinski in an adult where the toes then fan out upon lateral caressing of the toe -- Or excuse me, lateral caressing of the foot.

    01:49 And then this is going to be a sign of upper motor neuron lesion.

    01:53 And this is not good, this is not good.

    01:55 Last little thing that I wish to add in here and just stick with me, the physiology aspects of treatment of B12 deficiency.

    02:04 The boards love asking questions like this so that they know that you know that you have an understanding of B12.

    02:11 Earlier, I said that if you find a substance within your urine upon consumption of it or that food or whatever it may be, then you know that it had to have been reabsorbed first, then filtered, and gotten into urine.

    02:27 Okay.

    02:29 Let me walk you through the following.

    02:31 Let’s say your patient has all the signs and symptoms of B12 deficiency, here’s megaloblastic anemia and, unfortunately, there is neurologic deficit that is occurring.

    02:39 And that neurologic deficit is going to be irreversible.

    02:43 Now, you don’t find any B12 in the urine because whatever that the patient is not consuming, let’s say now, there is dietary deficiency either in a nursing home with an elderly patient or maybe, maybe it’s a vegan that we talked about for years.

    02:58 Years.

    03:00 Well now, at this point, there is consumption of it and there is supplementation of B12, and there is no problem inside your body, just lack of diet, right? So therefore, after consuming it, you can then expect to find B12 in your urine because then it has been reabsorbed and filtered and taken up to the liver and so forth.

    03:21 Keep that in mind.

    03:22 Now understand though, in a true Schilling test, you will then have to saturate all the receptors in the liver for B12 and that will not be asked because that’s radio-labeled.

    03:32 But the concept here becomes important.

    03:35 Next, well, if your patient had B12 deficiency and now at this point, you’re suspecting that there is something like pernicious anemia.

    03:46 Well, let’s say that you give intrinsic factor and now you find that there reabsorption of B12 from the terminal ileum into the plasma and it has been filtered.

    03:59 But let’s say that you give intrinsic factor and you still do not find the B12 in the urine.

    04:04 Your diagnosis cannot be pernicious anemia.

    04:08 So what’s your next step? You need to find out where this B12 deficiency is occurring.

    04:13 The diet doesn’t help, the supplementation, intrinsic factor didn’t help.

    04:17 Let’s go ahead and give this patient a pancreatic enzyme.

    04:20 Would you tell me physiologically why you required a pancreatic enzyme? Good.

    04:24 To remove the R-factor from your B12 so that it then gets properly reabsorbed in the terminal ileum with intrinsic factor.

    04:34 So now, you give pancreatic enzyme and you find B12 in the urine, what’s your diagnosis? Pancreatitis, good.

    04:40 So now, let’s say the diet didn’t work with supplementation.

    04:44 The intrinsic factor didn’t work.

    04:45 How do you know? Because you ended up finding B12 in the stool and it wasn’t in the urine.

    04:50 And in pancreatic enzyme, you had given it and that didn't work.

    04:55 Next maybe, you give antibiotics.

    04:58 You have antibiotics and you find B12 in the urine.

    05:00 Theoretically, what happens here? Well, your diagnosis should be? Good, bacterial overgrowth, right? So bacterial overgrowth there, you kill off the overgrowth with antibiotics.

    05:10 The B12 is now properly reabsorbed and it ends up in the urine.

    05:14 Do you understand the concept of how there are certain attributes of the Schilling test that you’re going to use from head to toe so that you can then properly diagnose your patient.

    05:26 And how they will most likely wear this with B12 is going to be the fact that you have cobalamin, okay? C-O, cobalamin.

    05:32 Keep that in mind.

    05:33 And whether or not you find that in urine and that table that I showed you with B12, all the different methods by which you can develop it is important.

    05:43 Last little thing that I wish to bring to your attention, is it megaloblastic anemia that you only find? Meaning megaloblastic RBCs.

    05:50 No.

    05:51 Remember that the neutrophils also are not properly developing because this is pancytopenia, you would expect to find -- Well, can you think of what a normal neutrophil should look like? Okay.

    06:02 Should they be segmented? Yes.

    06:04 But what if you end up finding 8-12 segments? That’s called a hypersegmented neutrophil.

    06:11 And that to you should clue you in, Oh! I must be suffering from -- or your patient is suffering from megaloblastic anemia.

    06:18 Last little bit that I wish to bring to your attention is, earlier when I set up the overview for anemias, I said there was megaloblastic and non-megaloblastic anemia.

    06:28 Up until this point, your focus should be strictly upon megaloblastic anemia.

    06:34 And where is my problem with megaloblastic anemia? It’s a fact that DNA or in the bone marrow, you don’t have proper maturation.

    06:40 Maybe either due to lack of DNA synthesis or as you saw with Diamond Blackfan anemia, we have a problem with erythroid progenitor, right? If it’s non-megaloblastic macrocytic, then you‘re thinking about alcohol, liver disease, or reticulocytosis.

    06:58 Think about those.

    06:59 Liver has nothing to do with the bone marrow.

    07:02 Alcoholism has nothing to do with the bone marrow.

    07:04 And reticulocytosis means the bone marrow is producing too many reticulocyte which is immature RBC into circulation.

    07:14 Would you tell me the size of a cell that is always a little bit immature or premature than the mature cell, the size? The size is always bigger.

    07:22 So reticulocyte's always larger than an RBC.

    07:27 And so therefore, you can have non-megaloblastic macrocytic anemia.

    07:33 The big ones here, liver disease, alcoholism and reticulocytosis.

    07:38 Keep those in mind and that gives you big time high yield information for all macrocytic anemias that you have to be familiar with on your boards.

    About the Lecture

    The lecture Macrocytic Anemia: Clinical Pathology by Carlo Raj, MD is from the course Macrocytic Anemia – Red Blood Cell Pathology (RBC).

    Included Quiz Questions

    1. Elevated methylmalonic acid
    2. Normal methylmalonic acid and homocysteine
    3. Elevated homocysteine
    4. Low methylmalonic acid
    5. Low homocysteine
    1. Dorsal and lateral white matter
    2. Dorsal and anterior white matter
    3. Gray matter
    4. Lateral and anterior white matter
    5. Anterior white matter only
    1. Hypersegmented neutrophils
    2. Blasts
    3. Nucleated erythrocytes
    4. Howell-Jolly bodies
    5. Rouleaux formation

    Author of lecture Macrocytic Anemia: Clinical Pathology

     Carlo Raj, MD

    Carlo Raj, MD

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