Anemia of chronic inflammation Flashcards
what are the conditions associated with anemia of chronic inflammation?
Chronic infections: pulmonary abscess, granulomatous diseases –tuberculosis, histoplasmosis, coccidioidesmycosis, subacute bacterial endocarditis, osteomyelitis, etc.
Chronic non-infectious inflammation: rheumatoid arthritis, rheumatic fever, systemic lupus erythematosis, burns, sterile abscess, etc.
Malignant disease: carcinoma, sarcoma, Hodgkin’s disease etc.
What are the features of anemia of chronic inflammation?
A. Up-regulated macrophage & splenic function –>shortened RBC survival; failure of erythropoietic response (reticulocytosis)
B. Decreased erythropoiesis (faulty iron re-utilization): lactoferrin, hepcidin
C. Blunted Erythropoietin response:
IL-1, TNF-a, DM, CRF
D. Inhibition of marrow erythropoiesis:
y-IFN, IL-1, TNF-a, IL-6
How does faulty iron re utilization lead to decreased erythropoiesis?
- Lactoferrin from PMNs bind and deliver iron to macrophages instead of RBCs
- Hepcidin, produced by liver as response to inflammation, causes Fe retention by macrophages. Upregulates DMT1.
- Acute increase in hepcidin–>DMT1 and ferroportin down regulation–>reduced intestinal absorption and decreased absorption into plasma by villous duodenal cells.
- response to Il-6 - less serum Fe, higher Fe in macrophages as ferritin/hemosiderin
- increase ferritin in serum
- reduced release in macrophages and reduced GI absorption–>decrease Fe in serum
- low serum iron–>decreased Fe to erythroblasts in marrow
What causes blunted EPO response in anemia of chronic inflammation?
- Il-1 and TNF-a inhibit EPO mRNA via ROS
How do cytokines inhibit erythropoiesis in ACD?
- y-IFN directly inhibits CFU-E colony growth
- Il-1 inhibits CFU-E colony growth in the presence of T cells
- TNF-a inhibits colony growth (CFU_GM and BFU-E). Treatment with an antibody to TNF results in improvement in the anemia
What are minor features of ACD?
- Anemia fluctuates with disease activity
- MCV may be low due to faulty iron re-utilization
- Degree of anemia & microcytosis correlate with disease severity
How is ACD different from Fe2+ deficiency?
- serum iron binding capacity is low in ACD, reflected in lower transferrin
- serum ferritin higher in ACD, but can be elevated also by chronic renal failure
Additional assays
a. direct assessment of Fe stores in bone marrow biopsy to diagnose Fe deficiency
b. sTfR (serum transferrin receptor): proportional to number of erythroid precursors
-increased in Fe def
-depressed in ACD by blunted EPO and cytokine inhibition
c)free erythrocyte protoporphyrin (FEP: last porphyrin step before formation of Hb
-increase in Fe def, rate limiting in heme synthetase without Fe
d)serum/urine hepcidin levels
-increase in ACD
What are the features of anemia of chronic renal disease?
- creatinine clearance half normal
- decreased RBC survival
- dominated by underproduction of EPO
- acid pH–>burr cell
What are the features of anemia of chronic liver disease?
- increased plasma volume dilutes RBC mass
- altered lipid metabolism–>mild macrocytosis (MCV 105) and target cells initially (phospholipid and cholesterol) and spur cell (cholesterol) with hemolysis later
- hypersplenism from portal hypertension and splenomegaly
- bleeding with esophageal varices
What are the features of anemia of HIV?
-anemia corresponds to measures to disease severity
pure RBC aplasia: parvo, drugs
myelophthisis-displacement of hemopoietic bone-marrow tissue into the peripheral blood: infections, neoplasms
What are the features of anemia due to malignancy?
- corresponds to disease severity
- myelophthisis-marrow invasion by metastasis can occur
What are the features of anemia due to plumbism aka lead poisoning?
- shorted RBC lifespan
- inhibits several steps in protoporphyrin metabolism: ALA dehydrate, heme synthetase, copropporhyrinogen oxidase–>increased ALA and coproporphyrin in urine
- microcytic hypochromic anemia resembles thalassemia minor
- basophilic stippling due to inhibition of pyrimidine 5’ nucleotides
- ringed sideroblasts in bone marrow due to inhibition of heme synthetase
- accumulates in tissues (braine, bones, gum line)–>ab colic, gout, decrease IQ, decrease growth and development, lead line on x ray
What are the features of anemia due to pregnancy?
-increase in RBC mass but increase in plasma volume–>dilution
