Anemia: Overview of the Approach to a Patient

Question 1

Define anemia and discuss the laboratory tests used to determine its existence in an individual, keeping in mind the influence of age and gender.

Answer 1

Anemia is insufficient red cell mass to adequately deliver oxygen to peripheral tissues.

Measurements to define existence of anemia:
Hb concentration, Hematocrit, Red blood cell count, RDW, red cell morphology, reticulocyte count, reticulocyte production index

Question 2

Define reticulocyte count, absolute reticulocyte count, and reticulocyte index and discuss how these measurements are used in assessing the rate of RBC production.

Answer 2

Reticulocyte count: % of 1000 red cells
Absolute reticulocyte count: %of retic. * red cell count
Reticulocyte index: retic count * (patient Hb/normal Hb) * (1/stress factor)

Low reticulocyte count with anemia: decreased production of reticulocytes and ergo, rbc’s.

High reticulocyte count with anemia: loss of red blood cells causing increased compensatory production of reticulocytes to replace lost rbc’s/

Question 3

Recognize critical findings in the history and physical examination important in determining the cause of anemia.

Answer 3

Onset of sx,

History of gallstones, jaundice, spenomegaly/splenectomy, cholecystectomy—> hemolytic anemia.

Renal, liver, endocrine disease, malignancy, infection or inflammation.

Physical exam: vital signs, color of skin/conjunctiva, lymph nodes, size of liver/spleen, cardiovascular and pulmonary findings.

Question 4

Draw a general classification scheme of anemias based on mean corpuscular volume (MCV) and reticulocyte count.

Answer 4

Appropriate reticulocyte response:
Hemolysis or hemmorhagic based anemia

Lack of appropriate reticulocyte response:

MCV>100 macrocytic anemia
MCV 80-100 normocytic anemia
MCV <80 microcytic anemia

Question 5

Describe iron metabolism and the iron cycle, and describe where iron is distributed in the body. Describe the route by which iron from the diet becomes incorporated into hemoglobin (including absorption, transport, delivery, storage, and loss of iron in humans). List factors that increase or decrease iron absorption.

Answer 5

Majority of Fe is in Hb (65%), 6% in myoglobin, Ferritin and hemosiderin are primary storage forms of iron (25% of total body iron, mostly intracellular). Very small about is bound to transferrin. Remained is associated with a variety of enzymes.

Iron from food transits stomach, gastric pH and gastroferrin maintain Fe solubility until it reaches the duodenum where it’s absorbed.

Dietary non-heme Fe enters the duodenum as Fe3+ and is converted to Fe2+ by surface reductase activity, mediated via DCYTB. Ferric iron enters the cell through divalent metal iron transporter DMT1. Within the cell, some Fe is stored in ferritin and some is transported across the basolateral membrane. Ferroportin acts as a basolateral membrane transport, assisted by hephasestin, which oxidizes Fe as it exits the cell.

Iron cycle:
Once through the mucosal cell and bound to transferrin, Fe enters to Fe cycle. Transferrin w/ Fe goes to bone marrow and binds to transferrin receptors, transferrin receptor directs Fe into the maturing normoblast and is incorporated into Hb. As erythrocytes are produced they are released into circuation and are removed by macrophages in the spleen after 120 days. Once intracellular, macrophages turn over the cells and sequester the Fe in ferritin stores.

THE IMPORTANCE OF THE FE CYCLE IS THAT IT ALLOWS MOST OF THE RECYCLABLE FE TO BE RE-USED AND MINIMIZES THE AMOUND OF FE required from absorption each day.

Fe absorption is affected by several factors:

Intraluminal:

• Gastric factors (low pH, gastroferrin)
• Presence of protein, amino acids
• vitamin c
• phytates, oxalates
• amount of iron ingested

Extraluminal: Erythropoietic activity

Question 6

Describe the hematologic changes associated with the development of iron deficiency and the timeline by which they occur. Recognize some of the major causes for iron deficiency.

Answer 6

Decrease in Hb, decrease in cell proliferation, very mild hemolytic component. Over time, low mcv, and hypochromia, increased RDW.
Normal–> iron depletion–> iron deficient erythpoiesis–> iron deficiency anemia

Causes include: excessive bleeding, failure to accumulate iron b/c of small ongoing losses or inability to gain iron during growth.

Question 7

Describe the symptoms, signs, and laboratory findings associated with iron deficiency anemia.

Answer 7

Decrease O2 carrying capacity (Hgb, crit)
decreased red cell production (reticulocyte count)
microcytosis (MCV)
hypochromia (MCHC)
Wide range in size of cell (rdw

signs: mild defect in muscle performance, neuropsych dysfunction, ridges in nails, papillary atrophy in tongue

Upper gi: gastritis, dysphagia, esophageal webs, achloridia

Pica

Question 8

Describe the effects of over accumulation of iron in the body and describe two treatments for iron overload.

Answer 8

Increase serum Fe, Increase ferritin, Increase liver iron

Organ damage:
Cardiac: arrhythmia, failure
Liver: dysfucntion, failure
Endocrine dysfunction

Treatment:
Hemochromatosis—> therapeutic phlebotomy
Hemosiderosis–> Iron chelators (Desferal, exjade)