7/29/2019 Anemia of chornic disease lecture notes

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Define the kinetics of the anemias:

The kinetics of a patient without anemia can be summarized as RBC production = RBC

destruction. Consequently, anemia involves an imblanace of this equelimlim in either

direction and Hb/Hctfall until a new equilibrium is reached. The kinetics of this anemia are

measured by reticulocyte count, indirect bilirubin, and LDH.

Decreased production: reducted ricular count, reduced indirect bilruibin, reduced LDHHemolysis: increased recicular count, increased increased nilibruin, increaedd LDH

Ineffective: reduced reticular count increased direct bilirubin, greatly incread LDH

Acute blod loss: increased reticular coutn ,ow to normal indreict bilirubin, low LDH

What can cause decreaed production?

Thalassemia minor Iron deficiency anemia Anemias of chornic inflammation/disease (ACD) Lead poisioning and Sideroblastic anemias

RBC apliasia (acute or chronic)

What diseases are considered ACD?

1. chronic infections: granulatmous diseases like TB, histoplasmosis, ccidiomycocis,osteomyelitis , pulmonary abscess

2. non-infectious inflammation: rheumatoid arthiritis,systemic lupus erthyematosus,,burns, sterile abscesses

3. malignancy: caricinoma, sarcoma2. describe the pathophysiology common to anemias of chronic disease

1) increases in pro-inflammatory cytokines: upregulated macrophages and splenicfunction (macropahges in spleen) leda to ehtryophagocytosis.a. Consequence shrotedned rbc survival by 10-20 days, wcihc requires a slight

increase in erthyropeoisi to maintain balance. If this trivial erthropeitic

response does not occur, anemia results

2) Faulty iron reutilization: lactoferrin is realaes by PMNs and binds iron in circulationmore avidly than transferrin, delivering Fe to macrophages. Hepcidin is relased by the

liver ( va DMTI upregulation) resulting in ron retention by macrophages.

Downregulation of ferroprotin leads to decreased iron absorption in the plasma villous

endothelial cells.

a. Consequence: diversion of iron from the plasma circulation to macrophagestorage as ferritin/hemosiderin. The resulting lwo serum iron levels causeddecreased erthropeoeis.

3) Blunted EPO response: IL-1 and TNF aplpha dieretly inhibit EPO mRNA by releaseingROSs that destroy EPO producing cell

a. Consequence: higher EPO doesse are required to form CFU-E in cell culture4) Cytokine inhibition of marrow erthropoeis: IFn-gamma and IL1 directly inhiibit CFU-E

colonly growth, while TNF-alpha is increased

a. Consequence: anemia5) Minor features common to all ACD

7/29/2019 Anemia of chornic disease lecture notes

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a. Time to develop anemia s aobut 2months, sincethere is parital replacement ofcirculating rbc mass

b. Anemia fflunctuates with disease activiey and improves with resolution of ACDc. Low MCV due to faulity internal Fe2+ deficiencyd. Degree of anemia and microcytosis correlate with disease severity

***hepcidin is the principle regulator iron hmeostais. Its nthesis increases with iron

loading/excess and decreases with iron deficiency/hypoxia. It is alos increased with

inflammation or infection by Il-1 and IL-6. It acts by binding to ferrportin and inducing itsinternalization and degradation. Hepcidin and efforprotin are found in heaptocytes,

enterocytes, and macrophates (but liver release is what casues ACD symptoms)

3. Identify the features specific to each group of disorders

Three types of Hb synthesis defets leads to microlytic anemia:

Defect in iron incorptation into heme: iron deficiency, hrnoic inflmammation,malignancy

Defect In protoporyhyrin incoropation into heme: siderobastic anemia Defect in globin incorpation into heme: thalessemias

Anemia of chornic renal disease: evident when renal function is half normal, as measure ed by

creatinine clearance.

Non specifc inflammation features: altered Fe kinetics, reduced rbc survival,suprpression of erthyropeosis

Specific features: very obvious underproduction of EPO, will see renal insuffiencey,deficiencies in in Fe, folic acid, protein and colories

o Will see burr cells due to acid pHo Responds to recombiantn EPO in dose depedent fashion

Anemia of chornic liver disease:

Non specific inflammation features: altered Fe ietnceis, reduced RBC survival,suppression of erthyropeosis

Specific features: increased polasma volume dilte RVC mass (will aso see ascites),altered lipid metabolis may casue mild carocytosis

o Hypersplenism/splenomeglaly from portal hypertensiono Bleeding from esophageal varices due to acute/chronic Fe deficiencyo Bleeding from espohagela varies due to acute chornic Fe deiency

HIV infection

Nonspecific: altered Fe kinetics, reduced RBC survival, suppression of erthropoeisis Specific features:

o Pure RBC aplasia- caused by parvovirus and durgs Will see inclusion bodies in pronomrblast

o Myelophtsis Displament of marrow into the PB Caused by metastatis resulting in marrow invasion

Plumbism (lead poisoning) ingestion of lead ased paint, automobile exhaust