welcome back to twelve days in March in this section we'll pick up our discussion of iron deficiency anemia and anemia of chronic disease focusing on key diagnostic features recalling our discussion of iron homeostasis let's move toward the diagnosis of iron deficiency anemia starting with smear features and hemoglobin indices so what do you need to know about this mirror pictured here is a drawing of a normal red cell it has a normal MCV and is referred to as normocytic it has a zone of central pallor that is approximately one-third the size of the cell pictured next to it is a microcytic hypochromic cell microcytic implies a smaller cell with an M CV less than eighty hypochromic refers to the increased own of central power this is a graphic you will need to be familiar with there's a high likelihood you'll be seeing one of these on the nbme fortunately however on most questions about iron deficiency anemia data is supplied that helps you figure out what you were viewing please note the poi Colo site while we're in the neighborhood boy closest refer to abnormally shaped red cells Rason isso cytosis refers to cells of abnormal size pertinent to the smear and our differential diagnosis of microcytic anemia this mirror helps exclude other causes thalassemia patients also have a low MCV but their smear will be replete with target cells patient miss fira cytosis start with normal-sized red blood cells when emerging from the bone marrow after a few trips through the spleen where microphages gobble up that delicious abnormal membrane the cells start to shrink but they are not hypochromic and that leads into our discussion of indices we want to pay attention to for this discussion is MCHC the MCHC is a measure of hemoglobin concentration in diseases of hemoglobin such as iron deficiency anemia and thalassemia the MCHC is decreased that makes sense hemoglobin production is impaired compare and contrast that was Faro cytosis in spherocytosis there is nothing wrong with the hemoglobin this is a disease of the membrane so even though these cells become microcytic the MCHC actually increases so in iron deficiency anemia MCHC is decreased as for the board's spherocytosis probably the only condition you'll be questions about that has an increase in MCHC this will be further addressed in a later section of 12 days in March as for the diagnostic studies the following information is the most important section for you to focus on so go stretch your legs or grab a delicious piece of chocolate and let's forge ahead let's start with a summary of the specific findings necessary to the diagnosis of iron deficiency anemia these include a low serum iron level it is iron deficiency anemia so a low iron makes sense you have a high total iron binding capacity iron binding capacity is probably the most confusing but important of the diagnostic tests I like to describe it as a functional assessment of transferrin it doesn't tell us that the transferring level is high or low but rather it describes transfer ins ability to transport iron we'll cover this in more detail shortly iron deficiency anemia also has a low saturation the iron or transferrin saturation is simply a ratio of iron to tea IBC in patients with iron deficiency anemia a low ferritin is noted recall that ferritin is the best reflection of total iron body stores so an iron deficiency anemia it should be finally include a note on the bone marrow in patients with our deficiency anemia the iron stores are depleted this information will occasionally be provided in the clinical vignette but principally appears in discussions of the anemia of chronic disease so we'll review it in further detail in that section alright so iron binding capacity is an indirect measure of transferrin it is measured by adding a fixed amount of iron to plasma and measuring the amount of iron that didn't become bound in so doing one can assess the binding capacity under normal circumstances approximately one third of the available sites on transferrin a bound by iron it is important for you to appreciate the transferrin is literally a trolley to transports iron you need to recognize that a high total iron binding capacity means there are plenty of seats available on the trolley a low iron binding capacity means those seats are saturated with passengers think about getting on the green after a night at Fenway Park the capacity is low there are too many passengers so here we have the normal saturation compared with iron deficiency anemia note less iron and therefore more capacity to bind iron in elevated T IBC what makes this even easier in iron deficiency anemia the body increases transparent synthesis so not only is it empty there is more of it the bottom line in iron deficiency anemia you have an increase in binding capacity compare and contrast that with iron overload lots of iron and it is bound by transparent the transferrin is binding all that excess iron so the IBC is decrease sorry we're full there's no more capacity under transparent trolly iron saturation also called transferrin saturation is simply the ratio of iron to tea IBC in iron deficiency anemia as shown in our patient the iron to tea IBC ratio is 4 percent the simply iron of 18 / iron binding capacity of 511 that equals 4 percent that is pretty darn low you can see the lab list the saturation in the 20 to 50 percent range iron deficiency anemia is diagnosed with a value of less than 10 percent anemia of chronic disease Alice will discuss is generally below normal but not by much the serum ferritin is also ordered and a low value confirms the diagnosis of iron deficiency anemia again just by way of comparison here is iron overload a high iron level is noted a low binding capacity because the trolley is full iron / t IBC gives a high saturation greater than 50 percent this is one of the tests used to screen for hemochromatosis and those are the diagnostic studies be familiar with these values it is their very favorite way to come after you when discussing iron disorders of all sorts we'll finish up iron deficiency anemia with a brief discussion of how they will present the diagnostic ideologies in terms of ideologies blood loss from any cause will cause iron deficiency anemia including pulmonary bleeding GU bleeding donation any cause whereas acute blood loss will lead to iron deficiency anemia that isn't the typical scenario chronic GI blood loss is the typical vignette it is their favorite losing a little bit of iron over an extended time core sets the stage from mystery so chronic GI blood loss is big money they'll present indices of iron deficiency anemia you'll be proud to figure it out then they ask the most likely underlying etiology and they'll use language such as chronic GI blood loss which is pretty straightforward or colon cancer and specifically right-sided the cancer will be right-sided as left-sided causes obstructive symptoms the right side allows chronic undetected blood loss plus some weight loss anemia and weight loss they love that you'll need to note the anemia is iron deficiency to know that they are talking about colon cancer and by the way they can do this in the reverse patient with right-sided colon cancer is most likely to present with which of the following iron deficiency will be one of the choices these questions should be a gift menstrual blood loss is another common etiology and the presentation will be the same they'll present indices of iron deficiency you know figure it out again then they're gonna ask the most likely underlying etiology they'll present something a Colt such as uterine fibroid in working with students this is always a fun question the list an obvious GYN bleeding's worse but students become so paranoid after doing hundreds of Q Bank questions the options on a question like this will include myeloproliferative diseases and they'll look so tempting they may say the patient has SLE or rheumatoid arthritis so you'll think a naming of chronic disease but it is a straightforward question iron deficiency anemia due to GYN bleeding but nobody ever picks fibroids they think the nbme is trying to trick them so they all pick leukemia or SLE even after they figured out the patient had iron deficiency anemia students love to trick themselves other common causes include nutritional deficiency and malabsorption syndromes nutritional is most common worldwide so of course they never ask about it insofar as malabsorption in a classic vignette they'll describe a patient with diarrhea and low iron you'll need to put two together to conclude the presence of silly AK disease treatment is really straightforward you correct the underlying etiology and give iron reticular cytosis will be robust by 10 days but it takes a long time to replete in the bone marrow under special notes again advise you to be familiar with how anemia affects the oxygen content and the cardiovascular response to anemia both of which are covered in the introductory sections also note that reactive thrombocytosis is seen commonly in iron deficiency anemia so low iron and high platelets doesn't mean myeloproliferative disease it means iron deficiency anemia so that's how iron deficiency anemia that's with other sections there were only a finite number of ways they can come after you so let's forge ahead and finish up with anemia of chronic disease this is the one they like to trip you up with when compared with iron deficiency anemia this banner is probably the most important thing to remember some call it anemia of chronic disease but calling it anemia of chronic inflammatory disease is so much more useful if you get the notion of inflammatory cytokines mediating this anemia everything will make perfect sense so the lab manifestation and lab findings are all related to cytokine release il-6 causes a rise in Hep C what does that do have seed into grades ferroportin so iron is trapped in the cell including the entry site and the bone marrow macrophage it is not available to the urethra blast bingo you have anemia the transferrin level decreases it is a negative acute phase reactant in inflammation that explains the important laboratory findings so here is the data that we'll cover twice these patients generally have mild anemia the MCB is reduced but only mildly and there is no reticular cytosis the low transferrin means low total iron binding capacity there are less trolleys running iron saturation is low ish or normal we'll review this in the next slide but remember iron is trapped inside the cells so we have low iron but we also have reduced trolleys ferritin which is low in iron deficiency anemia is normal or elevated in this inflammatory disorder ferritin is an acute phase reactants and finally the bone marrow chose normal iron stores that is hemosiderin is trapped in the bone marrow macrophages and stained positively these findings are the money in an emu of chronic disease look at this light it's a pictorial representation of what we just discussed this is crazy but you have a low iron because the iron is trapped in the cells due to the high hepcidin you have a low transferrin because transferrin is a negative acute phase reactant so the TI bc is well iron saturation is in the low normal range both iron and transparent are proportionately loved ferritin as normal or elevated there is no shortage of iron it just isn't being circulated the bone marrow stains positive for the same reason iron is trapped iron deficiency anemia would not stain positively please note if they tell you the bone marrow stains positively with Prussian blue stain the answer is not iron deficiency anemia here it is again but this time compared with iron deficiency anemia in iron deficiency anemia the iron binding capacity is high in anemia chronic disease the iron binding capacity is low in iron deficiency anemia the iron saturation is low in anemia of chronic disease it is in the low normal range here are the ferritin values ferritin is low in iron deficiency anemia normal are elevated in the emu chronic disease and finally the bone marrow description iron deficiency anemia decreased iron stores anemia of chronic disease normal iron stores and here is the classic question they'll come after you with an old tired weak patient with inflammatory symptoms such as hand and wrists pain or swelling she will be anemic the MCV will be 75 the serum iron will be low they will give you TI b c and or iron saturation you will need to choose the underlying cause of her anemia is it rheumatoid arthritis or chronic GI blood loss or a GI neoplasm and there's the summary again they'll both have low iron but the iron binding capacity will distinguish the two as will ferritin and the iron saturation finally for you erythropoietin lovers why has in rethrick wheaton fix this answer inflammatory cytokines also shutdown Ipoh production one would expect an elevated Ipoh production in nimi of chronic disease but that is not what is seen and that will do it there's been a long journey through anemia iron metabolism and iron deficiency anemia as well as an emu of chronic disease but this is another important topic that is well worth your investment of time if you have any questions or concerns please email me at 12 days in March thank you