Microcytic Anemia Flashcards
in differential diagnosis for anemia, if reticulocyte count is normal (1-2%), indicating RBC production is diminished, you should then use _____ to determine possible causes
RBC size (via mean corpuscular volume/ MCV)
microcytes: <80 MCV
normocytes: 80-100 MCV
macrocytes: >100 MCV
regarding RBC size, what constitutes a microcyte, normocyte, and macrocyte, respectively?
microcyte: <80 MCV (mean corpuscular volume)
normocyte: 80-100 MCV (about the same diameter as nucleus of a lymphocyte)
macrocyte: >100 MCV
what is believed to regulate RBC maturation, and what is the significance of this on anemia?
hemoglobin concentration within RBC is believed to regulate RBC maturation
so decrease in hemoglobin can cause microcytic anemia (possibly)
microcytic anemia can occur when any part of Hgb molecule is not made, which can be caused by a decrease in… (3 things)
- globin (alpha or beta)
- iron
- protoporphyrin
what does the mnemonic TAILS tell you about causes of microcytic anemia?
TAILS:
decreased globin production:
Thalassemia
low iron:
Anemia of chronic disease
Iron deficiency anemia
low protoporphyrin:
Lead poisoning
Sideroblastic anemia
most prevalent cause of anemia worldwide is…
iron deficiency
iron is critical for function of all cells (esp. RBC), but free iron is toxic
lack of iron impairs hemoglobin synthesis
how is iron excreted from the body?
no formal mechanism - either menstruation/bleeding or through normal cell turnover
balance of iron is tightly controlled, default is to conserve iron - iron is recaptured and recycled in spleen after RBC die
T/F: diet that is calorically rich typically has enough dietary iron in it
TRUE: iron is absorbed from intestine
dietary iron is closely related to total caloric intake
where is iron found in the body and in what ratio?
20% iron is in storage (as ferritin in duodenal enterocytes, bone marrow/spleen macrophages, hepatocytes)
80% in circulating RBC, in hemoglobin
how is iron transported into the plasma?
transported out of cell via ferroportin
carried by transferrin
what would be the consequence of a lack of ferroportin?
ferroportin is required to transport iron out of cells
without ferroportin, iron would accumulate in these cells, and there would be a lack of hemoglobin (which requires iron)
ferroportin expression regulates iron availability
low stores of iron in cells triggers an increase in _____
transferrin (in liver) - carries iron
____ stores intracelular iron, and is made by all the cells of the body to store iron
ferritin
*serum ferritin levels correlate with total body iron stores
*note that hemosiderin is clumped ferritin particles that also contain iron
______ is clumped ferritin particles that also contain iron
hemosiderin
iron levels in the body are regulated by:
a. absorption
b. excretion
explain.
a. absorption
we get iron through diet, body regulates iron absorption in intestinal tract to regulate body iron levels —> iron cannot leave cell (down-regulate ferroportin), so it is trapped within enterocytes and excreted via normal cell turnover
when iron stores are high, hepatocytes increase ____ synthesis
hepcidin: binds ferroportin (iron transporter out of cell) and causes it to be internalized on all storage cells
so hepcidin limits iron uptake / decreases iron availability
—> storage iron levels increase (in enterocytes), but serum iron levels decrease
how does iron deficiency cause a deficiency in hemoglobin?
heme = protoporphyrin + iron
need iron for heme, need heme for hemoglobin
3 causes of iron deficiency anemia
- inadequate diet: 1mg Fe/day, almost directly related to caloric intake, or increased requirement for pregnancy/growth
- impaired intestinal absorption (celiac disease)
- RBC cell loss (chronic blood loss)
pregnancy, infancy/adolescence, periods or rapid growth, vegan diet, celiac disease, and intermittent blood loss of any kind (menorrhagia, GI cancer, parasites) are all conditions that could put a patient it risk for….
iron deficiency anemia
*note that in US, chronic blood loss is most common cause of iron deficiency anemia
[menorrhagia = heavy menstrual periods]
describe, pica, a specific symptom of iron deficiency anemia
pica is craving for non-foodstuffs (clay, flour, dirt, chewing ice, etc)
what are specific signs of iron deficiency anemia in epithelial cells?
epithelial cells have high iron requirements (grow rapidly, high turnover)
symptoms:
- koilonychia (spoon nails)
- esophageal webbing (Plummer-Vinson syndrome —> difficulty swallowing)
- smooth, glossy tongue (atrophy)
what results from a CBC would be indicative of iron deficiency anemia (IDA)? (6, 2 of these are specific)
common:
1. low RBC
2. low hemoglobin/hematocrit
3. low reticulocyte
4. low MCV (mean corpuscular volume)
specific:
5. low mean corpuscular hemoglobin concentration (MCHC): amount of hemoglobin in each RBC
6. increased RBC distribution width (RDW): large distribution (range) of RBC sizes with non-uniform shapes
what do hypochromic RBC indicate?
less hemoglobin
normally, central pallor should be ~1/3 of RBC —> hypochromic cells have larger central pallor (look more like rings)
key laboratory studies to confirm IDA (iron deficiency anemia): (4)
- serum iron (reflects iron bound to transferrin - free iron is toxic)
- serum transferrin/total iron binding capacity (TIBC): remember that transferrin is increased when iron stores are low (seek and find protein)
- transferrin saturation = serum iron/ TIBC (normal would be 1/3 bound)
- serum ferritin: ferritin reflects iron stores (would be low)
how is serum transferrin vs total iron binding capacity measured?
serum transferrin measured directly via ELISA
or indirectly via total iron binding capacity (TIBC): measure serum iron in plasma, then add more iron to it and see how much sticks, and add both results together for total iron binding capacity (equivalent to transferrin)
what does transferrin saturation represent?
what is a normal value and what is a value for iron deficiency anemia?
remember transferrin is the carrier protein for iron that is increased when iron stores are low
transferrin saturation = serum iron/ TIBC (total iron binding capacity)
normal: 1/3 (30%) bound
iron deficiency: <16%
[remember that iron is not free in plasma because it is toxic, but bound by transferrin]
explain how high levels of protoporphyrin in blood indicate iron deficiency anemia
last step of heme synthesis is adding iron to protoporphryin
if no iron, protoporphyrin accumulates (and gets bound by zinc)
in iron deficiency anemia, how are the following parameters affected?
a. hemoglobin
b. RBC size/appearance
c. ferritin
d. serum iron
e. TIBC/transferrin
f. transferrin saturation
g. bone marrow iron
h. protoporphryin
i. MCV, MCH (corpuscular volume)
j. RDW (distribution width)
a. hemoglobin —> LOW
b. RBC size/appearance —> microcytic, hypochromic
c. ferritin —> LOW
d. serum iron —> LOW
e. TIBC/transferrin —> HIGH
f. transferrin saturation —> LOW
g. bone marrow iron —> LOW
h. protoporphryin —> HIGH
i. MCV, MCH —> LOW
j. RDW —> HIGH
anemia of chronic disease is associated with…
chronic inflammation - evolutionary defense strategy to limit iron availability during invasion
autoimmune disease, cancer, trauma, infection
common in hospitalized patients
serum iron is LOW, iron stores are HIGH
during infection, cancer, and inflammation, how does cytokine production affect a. hepcidin and b. EPO, and what are the downstream effects of this?
a. increase hepcidin —> decreased ferroportin (iron cannot leave cells)
b. decrease EPO (erythropoietin) —> decreased growth signal
overall, decreases iron availability and therefore hemoglobin
seen in anemia of chronic disease - low serum iron, high stored iron
how will the following values look in anemia of chronic disease?
a. serum ferritin
b. transferrin (TIBC)
c. MCV, MCH
d. RDW
e. serum iron
f. transferrin saturation
g. hepcidin
a. ferritin: normal or HIGH (reflects iron stores)
b. transferrin (TIBC): normal or LOW (decreased when iron stores are high)
c. MCV, MCH: LOW
d. RDW: HIGH
e. serum iron: LOW
f. transferrin saturation: LOW
g. hepcidin: HIGH
contrast the values of each between iron deficiency anemia and anemia of chronic disease:
a. serum ferritin
b. transferrin (TIBC)
c. hepcidin
iron deficiency (low serum iron, low iron stores):
a. serum ferritin —> LOW
b. transferrin (TIBC) —> HIGH
c. hepcidin —> LOW
chronic disease (low serum iron, high iron stores):
a. serum ferritin —> HIGH
b. transferrin (TIBC) —> LOW
c. hepcidin —> HIGH
*remember that ferritin is reflective of iron stores, transferrin carries iron in plasma (increased when stores are low), and hepcidin downregulates ferroportin (increased when stores are high)
