Flashcards in Chapter 3: Hypochromic Anemia Deck (59):
What is the most common cause of anemia in the world?
Iron deficiency is the most important cause of which anemia?
Microcytic hypochromic anemia.
What Red cell indicies are reduced in iron deficiency anemia?
MCV (mean corpuscular volume) and MCH (mean corpuscular hemoglobin)
What are the indications of iron deficiency anemia on blood film?
Small (mircocytic) and pale (hypochromic) RBCs.
What is the major differential diagnosis for microcytic hypochromic anemia?
Why is iron deficiency common?
Because iron is not easily absorbed by the body and loss of iron through hemorrhage is frequent.
What are the three proteins involved in iron transport and storage?
Transferrin, Transferrin receptor 1, and Ferritin.
What is transferrin?
Transferrin can contain up to two atoms of iron and delivers the iron to tissue that express the transferrin receptor (such as RBCs) When RBCs die transferrin then recollects the released iron.
Where does the iron on transferrin originate?
Most of the iron bound to transferrin is recycled from RBCs. A small proportion is from the diet.
What is ferritin?
Ferritin is found in macrophages and is a storage molecule for Iron. Ferritin is a water soluble apoprotein shell with an iron core that contains up to 4000-5000 iron atoms.
What is hemosiderin?
Hemosiderin is a protein iron complex created by the lysosomal digestion of ferritin. Vissible with prussian blue stain.
What happens to ferritin and transferrin receptor 1 when there is iron overload?
Levels of ferritin rise and levels of transferrin receptor fall
What happens to ferritin and transferrin receptor when there is iron deficiency?
ferritin levels fall, and transferrin receptor levels rise
What regulates iron trafficking?
iron regulatory protein (IRP) and Iron response elements (IREs). IRP binds to IREs on the upstream or down stream sites of the ferritin and transferrin receptor mRNAs.
When is IRP able to bind to mRNAs?
Iron deficiency increases the ability of IRP to bind the mRNAs. Thus blocking ferritin translation and stabilizing transferrin receptor translation.
What causes the pathological findings associated with iron overload?
When transferrin is saturated excess iron accumulates in parenchymal tissues causing pathology.
What is Hepcidin?
Hepcidin is the major hormonal regulator of iron homeostasis. It is produced in the liver (and also an acute phase reactant)
What is the function of hepcidin?
hepcidin inhibits the release of iron form macrophages, intestinal epithelium, and placental cells by blocking ferroportin production.
When is hepcidin production reduced?
in iron deficiency, hypoxia, and ineffective erythropoiesis.
What is transferrin receptor 2?
A receptor that senses the degree of transferrin saturation. High saturation leads transferrin receptor 2 to stimulate hepcidin synthesis.(found in erythroid, duodenal crypt, and liver cells)
How much iron is consumed in the typical western diet?
10-15g a day of which only 5-10% is normally absorbed.
How is dietary iron absorbed in the gut?
The HCP-1 receptor absorbs heme from the lumen
The DMT-1 receptor absorbs iron from the lumen
Ferroportin releases iron on the basolateral surface to the blood stream.
How is dietary iron absorbtion regulated?
When transferrin receptor 2 on duodenal crypt cells senses iron deficiency DMT-1 is upregulated by IRP-IRE (takes 24-48 hours).
When are iron requirements highest?
In pregnancy, adolescence, and mentruating females.
Are reticuloendthelial stores of hemosiderin and ferritin present in anemia?
No they are depleted before anemia occurs.
What are the clinical features of iron deficiency anemia?
(1) The typical signs of anemia
(2) painless glossitis
(3) angular stomatitis
(4) abnormal or spoon nails
(6) Neurological symptoms in children.
What is the dominant cause of iron deficiency?
chronic or excessive blood loss. (commonly uterine or from gastrointestinal ulcer)
How long does it usually take for iron deficiency from poor diet alone to develop?
About 8 years (not entirely uncommon in developing countries where lifelong poor diet is frequent).
What are the Red cell indicies for iron deficiency anemia?
Red cells may be microcytic and hypochromic progressively even before clinical anemia has been reached. (Poikilocytes may also be seen)
When are dimorphic blood films seen?
Dimorphic blood films occur with iron deficiency associated with severe folate or B12 deficiency, or with anemic patients that have just received iron supplementation or blood transfuion.
Is bone marrow examination essential for assesment of iron stores?
Not unless the case is particularly complicated.
What happens to the serum iron and the total iron binding capacity (TIBC) in iron deficiency anemia?
In iron deficiency anemia the serum iron falls and the TIBC rises so that the TIBC is less than 10% saturated.
When are serum transferrin receptor levels increased?
When there is iron deficiency anemia or increased erythropoiesis. But it is not increased in anemia of chronic disease or thalassemia.
What are the causes of reduced serum ferritin?
iron deficiency anemia increases serum ferritin
What causes an increase in serum ferritin?
Iron overload, damaged tissue, acute phase reaction, or possibly the anemia of chronic disease.
What are the most common causes of iron deficiency in pre menopausal women?
Menorrhagia or repeated pregnancies are the most common causes.
What often causes menorrhagia?
A clotting or platelet abnormality
What is the most common cause of iron deficiency in men and post menopausal women?
GI blood loss. (possible Hookworm or gluten induced enteropathy)
If GI bleed is negative what are some alternative causes of iron deficiency?
Pulmonary hemosiderosis (chest xr)
How is iron deficiency treated?
By treatment of the underlying cause and supplemental iron.
What are some possible side effects of oral iron supplements?
nausea, abd pain, constipation, or diarrhea.
Why is iron supplementation for anemia usually continued for 6 months?
Because both functional iron levels and iron stores must be replenished.
When is parenteral iron administration used?
When is severe bleeding (menorrhagia, GI bleed), erythropoietin therapy, or chronic hemodialysis and oral iron is ineffective.
What causes oral iron to be ineffective?
oral iron is ineffective when there is malabsorption in the GI tract.
(Gluten induced enteropathy, atrophic gastritis, active crohn's disease)
What are the characteristic features of anemia of chronic disease?
(1) Normochromic cells (or mildly hypochromic)
(2) Normocytic cells
What happens to serum iron and TIBC in anemia of chronic disease?
They both are reduced.
What happens to serum transferrin receptor levels in anemia of chronic disease?
serum transferrin receptor levels remain normal.
What happens to bone marrow (reticuloendothelial) iron stores in anemia of chronic disease?
it remains normal
What happens to erythroblast iron stores in anemia of chronic disease?
erythroblast iron stores are reduced
How does chronic disease cause anemia?
(1) decreased iron release from macrophages ( acute phase reaction)
(2) reduced RBC lifespan
(3) reduced erythropoietin response (inflammatory cytokines)
What are the characteristics of sideroblastic anemia?
Hypochromic cells in peripheral blood.
increased marrow iron.
>15% of marrow erythroblasts are ring sideroblasts.
What causes sideroblastic anemia?
A defect in heme synthesis.
(1) ALA deficiency
(2) B6 deficiency
(3) Lead poisoning
How is sideroblastic anemia treated?
Pyradoxal-6-phosphate supplementation can be used in rare cases however repeated blood transfusions are usually the only way to maintain hemoglobin concentrations.
What effect does lead poisoning have on the blood?
Lead poisoning inhibits both heme and globin synthesis. It also inhibits RNA breakdown (basophilic stippling).
How is iron deficiency anemia differentiated from thalassemia?
iron deficiency anemia exhibits MCV and RBC counts the fall in proportion to the severity of the anemia.
Thalassemia shows lower MCV regardless of anemia severity, and RBC counts are markedly increased.
How can iron deficiency anemia be differentiated from anemia of chronic disease other than by ferritin levels?
iron deficiency anemia will have increased serum transferrin receptor .
What method is used to diagnose sideroblastic anemia?
By bone marrow examination.
What is hereditary hemochromatosis?
Diseases characterized by excessive uptake of iron by the GI tract. (most commonly due to mutations in the HFE gene)