Microcytic Anemia

Question 1

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

Answer 1

RBC size (via mean corpuscular volume/ MCV)

microcytes: <80 MCV
normocytes: 80-100 MCV
macrocytes: >100 MCV

Question 2

regarding RBC size, what constitutes a microcyte, normocyte, and macrocyte, respectively?

Answer 2

microcyte: <80 MCV (mean corpuscular volume)

normocyte: 80-100 MCV (about the same diameter as nucleus of a lymphocyte)

macrocyte: >100 MCV

Question 3

what is believed to regulate RBC maturation, and what is the significance of this on anemia?

Answer 3

hemoglobin concentration within RBC is believed to regulate RBC maturation

so decrease in hemoglobin can cause microcytic anemia (possibly)

Question 4

microcytic anemia can occur when any part of Hgb molecule is not made, which can be caused by a decrease in… (3 things)

Answer 4

1. globin (alpha or beta)
2. iron
3. protoporphyrin

Question 5

what does the mnemonic TAILS tell you about causes of microcytic anemia?

Answer 5

TAILS:
decreased globin production:
Thalassemia

low iron:
Anemia of chronic disease
Iron deficiency anemia

low protoporphyrin:
Lead poisoning
Sideroblastic anemia

Question 6

most prevalent cause of anemia worldwide is…

Answer 6

iron deficiency

iron is critical for function of all cells (esp. RBC), but free iron is toxic

lack of iron impairs hemoglobin synthesis

Question 7

how is iron excreted from the body?

Answer 7

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

Question 8

T/F: diet that is calorically rich typically has enough dietary iron in it

Answer 8

TRUE: iron is absorbed from intestine

dietary iron is closely related to total caloric intake

Question 9

where is iron found in the body and in what ratio?

Answer 9

20% iron is in storage (as ferritin in duodenal enterocytes, bone marrow/spleen macrophages, hepatocytes)

80% in circulating RBC, in hemoglobin

Question 10

how is iron transported into the plasma?

Answer 10

transported out of cell via ferroportin

carried by transferrin

Question 11

what would be the consequence of a lack of ferroportin?

Answer 11

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

Question 12

low stores of iron in cells triggers an increase in _____

Answer 12

transferrin (in liver) - carries iron

Question 13

____ stores intracelular iron, and is made by all the cells of the body to store iron

Answer 13

ferritin

*serum ferritin levels correlate with total body iron stores

*note that hemosiderin is clumped ferritin particles that also contain iron

Question 14

______ is clumped ferritin particles that also contain iron

Answer 14

hemosiderin

Question 15

iron levels in the body are regulated by:
a. absorption
b. excretion

explain.

Answer 15

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

Question 16

when iron stores are high, hepatocytes increase ____ synthesis

Answer 16

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

Question 17

how does iron deficiency cause a deficiency in hemoglobin?

Answer 17

heme = protoporphyrin + iron

need iron for heme, need heme for hemoglobin

Question 18

3 causes of iron deficiency anemia

Answer 18

1. inadequate diet: 1mg Fe/day, almost directly related to caloric intake, or increased requirement for pregnancy/growth
2. impaired intestinal absorption (celiac disease)
3. RBC cell loss (chronic blood loss)

Question 19

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….

Answer 19

iron deficiency anemia

*note that in US, chronic blood loss is most common cause of iron deficiency anemia

[menorrhagia = heavy menstrual periods]

Question 20

describe, pica, a specific symptom of iron deficiency anemia

Answer 20

pica is craving for non-foodstuffs (clay, flour, dirt, chewing ice, etc)

Question 21

what are specific signs of iron deficiency anemia in epithelial cells?

Answer 21

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)

Question 22

what results from a CBC would be indicative of iron deficiency anemia (IDA)? (6, 2 of these are specific)

Answer 22

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

Question 23

what do hypochromic RBC indicate?

Answer 23

less hemoglobin

normally, central pallor should be ~1/3 of RBC —> hypochromic cells have larger central pallor (look more like rings)

Question 24

key laboratory studies to confirm IDA (iron deficiency anemia): (4)

Answer 24

1. serum iron (reflects iron bound to transferrin - free iron is toxic)
2. serum transferrin/total iron binding capacity (TIBC): remember that transferrin is increased when iron stores are low (seek and find protein)
3. transferrin saturation = serum iron/ TIBC (normal would be 1/3 bound)
4. serum ferritin: ferritin reflects iron stores (would be low)

Question 25

how is serum transferrin vs total iron binding capacity measured?

Answer 25

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)

Question 26

what does transferrin saturation represent?

what is a normal value and what is a value for iron deficiency anemia?

Answer 26

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]

Question 27

explain how high levels of protoporphyrin in blood indicate iron deficiency anemia

Answer 27

last step of heme synthesis is adding iron to protoporphryin

if no iron, protoporphyrin accumulates (and gets bound by zinc)

Question 28

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)

Answer 28

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

Question 29

anemia of chronic disease is associated with…

Answer 29

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

Question 30

during infection, cancer, and inflammation, how does cytokine production affect a. hepcidin and b. EPO, and what are the downstream effects of this?

Answer 30

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

Question 31

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

Answer 31

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

Question 32

contrast the values of each between iron deficiency anemia and anemia of chronic disease:
a. serum ferritin
b. transferrin (TIBC)
c. hepcidin

Answer 32

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)