Anemia of chronic inflammation Flashcards
1
Q
Typical causes of anemia
A
- Decreased RBC production
- Hemolysis
- Ineffective erythropoiesis
- Acute blood loss
2
Q
Effects of decreased RBC production
A
- Would have low retic count
- Low indirect bilirubin
- Low LDH levels
3
Q
Effects of hemolysis
A
- High retic count
- High bili
- High LDH
4
Q
Effect of ineffective erythropoiesis
A
- Low retic count
- High bili
- Very high LDH
5
Q
Effect of acute blood loss
A
- High retic count
- Low bili
- Low LDH
6
Q
Anemias of decreased production
A
- Fe deficiency (usually due to blood loss)
- Anemias of chronic inflammations/disease
- Lead poisoning and other sideroblastic anemias
- RBC aplasia (i.e. acute or chronic leukemia)
7
Q
Anemias of chronic inflammation/disease (ACD)
A
- Chronic infections: granulomatous disease (TB, coccidiomycosis, osteomyelitis, pulmonary abscess)
- Non-infectious inflammation: RA, lupus, malignancy, burns, Hogkin’s lymphoma
8
Q
Proinflammatory anemia
A
- Proinflammatory cytokine up-regulation increases macrophage erythrophagocytosis and heightened splenic function (due to RBC membrane changes and activation of macrophages by TNFa)
- Shortens RBC survival by 10 to 20 days
- Requires slight increase in erythropoiesis to maintain balance
- Failure of increased erythropoiesis results in anemia
9
Q
Fe re-utilization anemia
A
- Faulty Fe re-utilization leads to decreased erythropoiesis (microcytic anemia)
- Lactoferrin, released from PMNs, binds to Fe w/ higher affinity than transferrin and delivers Fe to macrophages
- Hepcidin is synthesized in liver and released in response to inflammation
10
Q
Functions of hepcidin 1
A
- Causes Fe retention of macrophages by up-regulation of divalent metal transporter DMT1 on macrophage, leading to more influx of Fe into macrophage
- Hepcidin also causes a reduction in DMT1 expression on the apical surface of duodenal cells, reducing their uptake of Fe
- Further, it leads to the internalization and degradation of ferroportin from the basolateral surface of the duodenal cells (and macrophages)
- Ferroportin allows efflux of Fe into the blood stream, thus decreasing it leads to lower Fe absorption
11
Q
Functions of hepcidin 2
A
- There is a diversion of Fe from plasma to storage forms in macrophages (ferritin/hemosiderin)
- Serum ferritin increases, but free serum Fe falls (causing a fall of transferrin saturation)
- Low serum Fe and decreased transferrin delivery to erythroblasts in BM leads to Fe-restricted erythropoiesis
- Decrease in erythropoiesis due to this inability to transport Fe leads to anemia
12
Q
Controlling factors of hepcidin
A
- Malignancy, infection, chronic inflammation (inflammatory cytokines), and saturated transferrin all induce hepcidin release
- IL6 injections decrease serum Fe by 30% in 2 hrs
- Snadd is TF for hepcidin, and an increase in Snadd results in more hepcidin (and lower serum Fe)
- Erythroferrone inhibits hepcidin production, thus increasing serum Fe
13
Q
Blunted EPO response and erythropoiesis
A
- Lower EPO can result in decreased erythropoiesis and eventual anemia
- EPO and hypoxia reduce hepcidin levels to allow for increased serum Fe for erythropoiesis
- IL1 and TNFa directly inhibit EPO mRNA via ROS damage to EPO producing cells
- IL1, IFNg and TNFa decrease erythropoiesis
- IFNg does this directly
- IL1 does this directly only in presence of T cells
- TNFa is associated w/ decreased stem cell growth and anemia (Abs to TNFa improves anemia)
- Normally there is a strong inverse relationship btwn EPO and Hct, but w/ blunted EPO response the relationship is much weaker
14
Q
Fe deficient anemia vs ACD 1
A
- Direct measurement of Fe stores by BM biopsy (prussian blue stain) is gold standard for Dx
- Also look at serum ferritin and transferrin levels, as they will differentiate Fe deficiency (low ferritin) from ACD (high ferritin)
- Transferrin will be low in ACD, but high in Fe deficiency anemia
- Transferrin is proportional to erythroid precursor mass in BM, so when erythropoiesis in inhibited in ACD (due to blunted EPO and cytokine inhibition), transferrin will decrease in serum
- In contrast, erythropoiesis is increased in Fe deficiency (but not completed) which results in an increase in transferrin
15
Q
Fe deficient anemia vs ACD 2
A
- Ferritin serum levels (an indication of excess Fe) will be high in ACD due to inhibition of erythropoiesis (could also be due to renal failure- not as reliable)
- However in Fe deficiency ferritin serum levels will be low
- Can also check free erythrocyte protoporphyrin (FEP) which will go up in Fe deficiency due to the inability to convert protoporphyrin to heme (requires Fe, last step of heme synthesis)
- Measure serum/urine hepcidin (high in ACD, low in Fe deficiency)
