hematology - disorders of iron kinetics and heme metabolism

anemias associated with iron and heme

categorized as anemias of impaired production due to lack of raw materials

iron restricted

when lack of iron is the limiting factor, iron deficiency anemia and anemia of chronic inflammation

protoporphyrin

inadequate production of _____ reduces production of heme/hemoglobin and leads to iron excess, sideroblastic anemia

porphyriasis associated anemias

blockages at points during protoporphyrin production

hemachromatosis

disruption of iron metabolism without anemia

iron loading anemias

involve inherited mutations and are discussed with hemoglobinopathies and thalassemias

microcytic hypochromic anemias

characterized by red cells that are abnormally small and contain reduced amounts of hemoglobin

irone deficiency anemia and anemia of chronic inflammatino

disorders of iron metabolism

sideroblastic anemia

disorders of porphyrin and heme synthesis

thalassemia

disorders of globin synthesis

iron deficiency anemia

most common type of anemia worldwide

inadequate intake of iron

IDA: iron is lost through mitochondria in desquamated skin and sloughed GI epithelium, the stores become depleted and RBC production slows over time

increased need of iron

IDA: develops when the level of iron intake becomes inadequate to meet the needs for expanding RBC production, during times of rapid growth and pregnancy, normal intake is no longer sufficient

functional iron deficiency

adequate iron stores but not able to mobilize them fast enough

impaired absorption of iron

IDA: inability to absorb iron even through dietary intake, can be caused by celiac disease or inherited mutations in iron regulatory proteins that prevent the absorption, as well as diseases that decrease stomach acid

chronic blood loss

IDA: can develop from excessive loss of hemoglobin from the body by slow hemorrhage or hemolysis, things like menstruation, GI bleeds, tumors, etc

stage 1

IDA stage: progressive loss of storage iron, deplete stores so that transport and RBC development are normal, serum iron and RBC levels are normal, ferritin levels are low, individuals appear healthy

stage 2

IDA stage: exhaustion of storage pool of iron, RBC production will remain normal for short time, hemoglobin starts to drop, iron dependent tissues are affected, ferritin and serum iron are decreased, transferrin and TIBC are increased

stage 3

IDA stage: obvious anemia, low H&H, RBCs do not develop normally, fatigue, weakness, SOB, pallor; sore tongue, inflamed cracks in lips, spooning of fingernails, pica

iron deficiency anemia

lab: aniso, microcytosis, hypochromia, decreased hemoglobin, high RDW, RBC and Hct fall, maybe polychromasia, target cells, elliptocytes, thrombocytosis

serum iron

measure of iron bound to transferrin

TIBC

indirect measurement of transferrin and available binding sites for iron

serum ferritin

measurement of intracellular storage iron, secreted into the blood

ferrous sulfate oral supplementation

IDA treatment, common side effects are nausea and constipation, only given if they have malabsorption

anemia of chronic inflammation

most common anemia among hospitalized patients, associated with chronic inflammatory diseases, chronic infections such as TB or HIV and malignancies

anemia of chronic inflammation

impaired iron kinetics, involved with hepcidin, during inflammation, intestinal absorption is decreased and release from macrophages decreases due to hepcidin

hepcidin

regulates absorption of iron and releases from macrophages and enterocytes into plasma, degrades ferroportin (protein for iron transport)

lactoferrin

neutrophil granule component that sequesters iron; during inflammation and infection it is released from dying neutrophils and scavengers iron, macrophages bind it, but iron is stuck in macrophages due to increased hepcidin in anemia of chronic inflammation

anemia of chronic inflammation

diminished erythropoiesis and shortened RBC lifespan

anemia of chronic inflammation

lab: mild anemia, no increased retics, normochromic and normocytic, may see increase in WBC and PLT, low iron and TIBC

anemia of chronic inflammation

treatment: treat the underlying condition, EPO and iron together

sideroblastic anemia

caused by diseases that interfere with protoporphyrin synthesis, iron is abundant and is seen when staining bone marrow

sideroblastic anemia

available in mitochondria and ready for incorporation into heme, ringed in marrow characteristics of sideroblastic anemia

sideroblastic anemia

inherited or acquired

inherited sideroblastic anemia

treatment with vitamin B6 can help - cofactor in first step of heme synthesis

acquired sideroblastic anemia

lead poisoning - interferes with heme, may have high retic count, hemolytic component, basophilic stippling (lead inhibits an enzyme that breaks down RNA which aggregates)

sideroblastic anemia

hereditary porphyrias, impaired production of porphyria portion of heme, leads to build up of products before defect

hereditary hemochromatosis

mutations in genes for proteins controlling iron kinetics, causes iron overload

iron overload

secondary to chronic anemias and their treatment (repeated transfusions)

iron overload

lab: transferrin saturation and serum iron increases for screening, decreased albumin