1-13-10 Approach to anemia 1.

Students will be able to establish the categories of anemia by recounting the role of reticulocyte count, indirect bilirubin, and kinetics or rbc production and destruction. Anemia must be caused by one of the following: Decreased productionhypoproliferative Aplastic anemia: caused by drugs, radiation, infection, immune disorders, or idiopathic Iron deficiency: in adults, its due to chronic blood loss, while in infants it can be dietary or due to blood loss Anemia of chronic disease: multiple inflammatory, infectious, or neoplastic diseases Infiltration of abnormal cells in the marrow: leu emias and lymphomas in !" Renal failure #ncreased destructionhemolytic Hemolytic anemias: defects intrinsic to the red cell that include$ membrane abnormalities: hereditary spherocytosis, hereditary elliptocytosis hemoglobin abnormalities: sic le cell, thalassemia, unstable hemoglobins en%yme abnormalitites: reduced &'(D, pyruvate inase all the above are hereditary conditions) *he only form of ac+uired hemolytic anemia is paro,ysmal nocturnal hemaglobinuria -(./0 #neffective production Megaloblastic anemias: !11 or folate deficiency Acute blood loss 2edistributionenlarged spleen #f the /b of the patient is low -a a anemic0, the retic count should be higher than normal to try to ma e up for the anemia) #f the retic count does not rise, it means that the marrow is not functioning properly, and the patient is either hypoproliferative or has ineffective erythropoeisis) 332etic inde, is calculated if you see shift cells on a (! smear -shift cells live 1 days in circulation, first day as a shift cell, 1nd day as a retic0) !. Students will be able to recount the normal "alues for Hb and hematocrit in men and women. Hb for males: 145 -13-160 /b rises 1-1 in adolescents relative to adult ranges Hb for females: 175 -11-1'0 *hus, the criteria for anemia s #1$ for men, and #1! for women) /ere are a few other normal ranges for: "89 -.:;0-1000 "8/ -.:1;-330

"8/8 -.:31-340

$. Students will be able to recount the morphologic changes which characteri%e the common types of anemia. /eres now each of the following would loo li e: Megaloblastic anemia& !11 or folate deficiencydecreased -ineffective0 production resulting in megaloblastic anemia: (! smear wound show oval macrocytes, hypersegmented polys, poi ilo and anisocytosis !" would be HYPERcellular -total erythropoeisis actually increases when its ineffective0 with cytoplasmic dissociation and giant metamyelocytes <tiology is either !11 or folate deficiency !11 functions to get folate into rbcs, conversion of homocysteinemet, and conversion of proprionic acidsuccinyl 8oA =olate acid donates a carbon for deo,yuridine -2.A0 thymidine -D.A0 Iron deficiency anemiablood loss in adults -or iron deficiency in infants0 (! smear would show hypochromic, microcytic anemia "89 would be below ;0 -i)e) around 600 Spherocytic anemia (! reveals loss of central pallor "8/8 is greater than 34 -i)e) around 360 Sickle 'ell Anemia (! reveals sic led cells and cells containing malaria Homo%ygous Hb ' (isease >ee /b 8 crystals ). Students will be able to discuss specific studies which should be obtained to clarify the causes of anemia. Anemia is an imbalance between two factors: 2!8 production and destruction) 2!8 production -asses with the appearance of ?new rbcs@ in peripheral blood0 Reticulocyte count A corrected retic count is the calculated by adAusting for the patients rbc count compared with normal rbc count) #ts done normally in the lab and stated as a 5) 15 corrected retic ct : 40,000 reticsBul An absolute retic count is the actual number of reticulocytes Reticulocyte inde* -corrected retic count divided by 1 with shift cells in smear0 A retic inde, + $ e+uals increased production of rbcs) *his could indicate hemolysis or acute blood loss and would not be an 2!8 production problem) "ay see marrow retics -shift cells, which have more 2.A than retics, allowing them to be seen without the special retic stain0 and orthochronic normoblasts -nucleated, and has a pin cytoplasm due to /b0 2!8 destruction

Indirect bili Extravascular hemolysis causes a rise in indirect bili via the following mechanism: 1) spleen macrophages phagocytose senescent rbcs, releasing$ =e1C, which is saved up for new /b 8D, which is released for e,cretion Indirect bilirubin, which binds to albumin and enters the circulation as bilirubin-albumin) 1) bilirubin-albumin is transported to hepatocytes, which contains glucoronyl transferase that converts the indirect bili into direct bilirubin 3) Direct bilirubin is e,creted into bile, which enters the &# tract 7) intestinal bacteria convert direct bilirubin into urobilinogen and stercobilinogen urobilinogen is reabsorbed into serum and e,creted in urine -responsible for urines yellow color0 stercobilinogen is not reabsorbed and is released in stools -responsible for stools brown color0 Intravascular hemolysis causes a rise in indirect bili via the following mechanism: 1) hemolysis in circulation releases free , !imers, which bind to haptoglobin one will see a decrease in haptoglobin with intravascular hemolysis the dimers are delivered to liver macrophages, where the pathway converges with that of e,travascular hemolysis, with production of$ indirect bilirubin stercobilinogen in stools urobilinogen in urine 1) hemolysis also releases "e#$, which results in several findings: =e1C e,creted results in pin% urine dipstic% =e3C -methemoglobin0 is generated by Hemope&in -thus, one will see a drop in hemope,in in intravascular hemolysis0 =e3C e,creted results in brown urine dipstic%) *his hemosiderin in urine is indicative of 8/2D.#8 intravascular hemolysis 3) one will also see positive iron stain in urine samples and pin dipstic #n summary, the lab tests that are important to remember are: 8ommon to both e,travas and intravas hemolysis: increased indirect bili, increased stercobilinogen, increased urobilinogen Eni+ue to intravas hemolysis only: decreased haptoglobin, decreased hemope,in, increased methemoglobin, pin urine dipstic $or brown dipstic for chronic intravascular hemolysis)

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/eres how the retic count and indirect bili levels will be li e for each of the following conditions: Decreased production: reduced retic, normal indirect bili #ncreased destruction: increased retic, incrased indirect bili #neffective production: reduced retic, increased indirect bili Acute blood loss: increased retic, normal indirect bili 2edistribution: normal retic, normal indirect bili