Microcytic Anemia Flashcards

1
Q

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

A

RBC size (via mean corpuscular volume/ MCV)

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

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2
Q

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

A

microcyte: <80 MCV (mean corpuscular volume)

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

macrocyte: >100 MCV

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3
Q

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

A

hemoglobin concentration within RBC is believed to regulate RBC maturation

so decrease in hemoglobin can cause microcytic anemia (possibly)

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4
Q

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

A
  1. globin (alpha or beta)
  2. iron
  3. protoporphyrin
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5
Q

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

A

TAILS:
decreased globin production:
Thalassemia

low iron:
Anemia of chronic disease
Iron deficiency anemia

low protoporphyrin:
Lead poisoning
Sideroblastic anemia

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6
Q

most prevalent cause of anemia worldwide is…

A

iron deficiency

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

lack of iron impairs hemoglobin synthesis

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7
Q

how is iron excreted from the body?

A

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

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8
Q

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

A

TRUE: iron is absorbed from intestine

dietary iron is closely related to total caloric intake

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9
Q

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

A

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

80% in circulating RBC, in hemoglobin

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10
Q

how is iron transported into the plasma?

A

transported out of cell via ferroportin

carried by transferrin

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11
Q

what would be the consequence of a lack of ferroportin?

A

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

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12
Q

low stores of iron in cells triggers an increase in _____

A

transferrin (in liver) - carries iron

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13
Q

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

A

ferritin

*serum ferritin levels correlate with total body iron stores

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

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14
Q

______ is clumped ferritin particles that also contain iron

A

hemosiderin

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15
Q

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

explain.

A

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

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16
Q

when iron stores are high, hepatocytes increase ____ synthesis

A

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

17
Q

how does iron deficiency cause a deficiency in hemoglobin?

A

heme = protoporphyrin + iron

need iron for heme, need heme for hemoglobin

18
Q

3 causes of iron deficiency anemia

A
  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)
19
Q

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….

A

iron deficiency anemia

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

[menorrhagia = heavy menstrual periods]

20
Q

describe, pica, a specific symptom of iron deficiency anemia

A

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

21
Q

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

A

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)

22
Q

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

A

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

23
Q

what do hypochromic RBC indicate?

A

less hemoglobin

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

24
Q

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

A
  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)
25
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)
26
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]
27
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)
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)
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
29
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*
30
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*
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
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
32
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)