Microcytic Anemias Flashcards
What are the types of Microcytic anemias (MCV<80 fL)
- Iron deficiency (most common)
- Anemia of chronic disease (ACD)
- Thalassemia (thal; α and β)
- Sideroblastic anemias (least common)
Pathogenesis:
All microcytic anemias have a decrease in_________ synthesis.
Due to a decrease in the synthesis of ________ or a decrease in synthesis of _______ chains.
In Sideroblastic anemias there is a decrease in ______ synthesis.
Pathophysiology of microcytic anemias. All microcytic anemias have a decrease in hemoglobin synthesis.
A decrease in hemoglobin synthesis could be due to a decrease in the synthesis of heme or a decrease in the synthesis of globin chains.
ALA, Aminolevulinic acid
-In Sideroblastic anemias there is a decrease in heme.
Iron deficiency anemia
What are the primary stores of iron in the body?
Iron absorption
Who frees elemental iron from heme and nonheme products?
Iron from plants is in what form?
Iron in the ferric form is converted to reduced iron by what enzyme in the duodenal mucosa?
Reduced iron is absorbed by what transporter in the mucosal cell?
Iron from meat is in what form?
What are the two faiths of iron once it enter the mucosal cells of the duodenum?
What is the protein that stores iron in the mucosa?
If the iron wants to get into the blood, it goes through which protein channel?
Once Fe2+ is outside the cell, it get reoxidized to Fe3+ by what enzyme?
a.Gastric acid frees elemental iron from heme and nonheme products.
•Underscores why achlorhydria (absent stomach acid) decreases the availability of iron for absorption.
b. Iron from plants is in a nonheme or oxidized form (ferric, Fe3+).
(1) Cannot be absorbed in the duodenum
(2) Converted by cytochrome B in the duodenal mucosa into reduced iron (Fe2+)
(3) Reduced iron absorbed by divalent metal transporter 1 (DMT1) into the mucosal cell
c. Iron from _mea_t is in a heme or reduced form (ferrous, Fe2+).
•Ferrous form of iron is directly absorbed in the duodenum by heme carrier protein 1.
Reduced Fe2+ directly reabsorbed in duodenum
d. Absorbed iron is stored as mucosal ferritin or it enters the ferroportin 1 port and is immediately converted by hephaestin or ceruloplasmin to ferric iron (Fe3+) so that it can bind to transferrin in the blood.
Transferrin brings iron to developing erythroid precursors in the marrow.
Regulation of amount of Iron absorbed:
What regulated iron absorption?
What is the function of the HFE gene?
HFE protein product regulates the production of _______, which is a hormone synthesized by the liver.
What is the function of hepcidin?
Iron bound to transferrin regulates iron absorption
(1) Absorption is dependent on total iron stores in the body, which is reflected by the amount of iron bound to transferrin.
(2) Transferrin with iron binds to transferrin receptors in immature precursor cells of normal enterocytes, which serve as iron sensors in the duodenum.
(3) HFE gene (hemochromatosis gene) protein product in the sensor cells acting with the transferrin receptor causes differentiation of these cells into mature enterocytes that absorb iron.
HFE protein product + transferrin receptors differentiate sensor cells to enterocytes
(4) HFE protein product also regulates the production of hepcidin, a hormone synthesized in the liver.
(a) Hepcidin is the “master” iron regulatory hormone and determines whether iron is absorbed or not absorbed in the duodenum and whether iron is released from macrophages or not released.
(b) A decreased level of transferrin-bound iron binding to transferrin receptors in enterocytes indicates iron depletion, which leads to reduced hepcidin synthesis in the liver.
•This upregulates ferroportin 1, causing more iron to be reabsorbed in the duodenum to bind to transferrin and more iron to be released from bone marrow macrophages to bind to transferrin for erythropoiesis.
↓Transferrin-bound iron → ↓hepcidin synthesis → ↑iron bound to transferrin → ↑iron released from macrophages
(c)An increased level of transferrin-bound iron binding to transferrin receptors in enterocytes indicates iron excess, which leads to increased hepcidin synthesis in the liver.
• This downregulates ferroportin 1, causing iron accumulation in enterocytes, which are eventually shed into the bowel. A reduced level of ferroportin 1 also causes iron blockade in bone marrow macrophages, so less is released for binding to transferrin.
↑Transferrin bound iron → ↑hepcidin synthesis → ↓iron bound to transferrin → ↓iron released from macrophages (iron blockade)
In what conditions is the percentage of iron absorbed from the diet is increased?
Percentage of iron absorbed from the diet is increased (i.e., decreased hepcidin) in the following conditions:
a. Normal menstrual cycle
b. Pregnancy and lactation
c. Any anemia, regardless of type
• Underscores the danger of iron overload, if iron supplements are improperly prescribed.
Iron deficiency clinical and laboratory findings:
Clinical and laboratory findings
a. Chronic iron deficiency
(1) Esophageal web (Plummer-Vinson syndrome)
• Produces dysphagia for solids but not liquids
(2) Achlorhydria
•Absence of hydrochloric acid in the stomach
(3) Glossitis and angular cheilosis
• Inflammation of the tongue and corner of the mouth, respectively
(4) Spoon nails (koilonychia)
b. Pallor of the conjunctivae and palmar skin creases
c. Craving (pica) for ice
What are the laboratory findings for Iron deficiency anemia?
Laboratory findings
(1) Decreased MCV
(2) Decreased serum iron and iron saturation
(3) Decreased serum ferritin
(4) Increased TIBC and RDW
(5) Microcytic and normocytic cells are present with increased central area of pallor (due to decreased production of hemoglobin).
(6) Increased serum level of free erythrocyte protoporphyrin (FEP)
• Less iron to combine with protoporphyrin to form heme
(7) ****Thrombocytosis*****
(a) Common finding in chronic iron deficiency
(b) Reactive phenomenon to increase blood viscosity and prevent high-output heart failure.
(8) WBC count is usually normal
• Eosinophilia occurs in hookworm infestations.
Anemia of Chronic Disease
This anemia is common in what kind of patients?
The pathogenesis is due to decreased: __________
Is serum ferritin decreased or increased?
MCV can be _______ to _________.
Thalassemias
Epidemiology:
Alpha-Thalassemia:
Decrease in alpha-globin chain is mostly due to what?
What is important about RBC count being elevated?
Hb H disease is due to how many deletions?
Hb H disease is associated with what type of anemia? What is the cause?
Four gene deletions is called what?
Alpha-thalassemia
Laboratory findings:
In comparisson to MCV, Hg, and Hct, how is the RBC count?
What two type cells are inconsistently present?
How is the RDW, ferritin, FEP, and Hb electrophoresis?
B-thalassemia
What is the difference in cause of mild or severe anemia in patient?
B-thalassemia minor
What type of cells are consistently present?
Hb A1 is decreased, but which other two Hemoglobins are increased?
B-thalassemia Major (Cooley’s disease)
Characterized by what type of anemia? Why does it happen?
What kind of erythropoiesis occurs?
What is seen in radiographs?
Are reticulocytes increased or decreased?
What are Howell-Jolly bodies?
Sideroblastic Anemia
Sideroblastic Anemia
Sideroblastic Anemia causes:
Alcoholism?
Pyridoxine deficiency?
Sideroblastic anemia
Lead Poisoning
Sideroblastic Anemia:
Lead poisoning
What is fancony syndrome?
Summary of microcytic anemias
