RBC Disorders 2 Flashcards
What are the 4 stages of iron deficiency?
(1) storage iron is depleted (dec. ferritin, inc. TIBC)
(2) serum iron depleted (dec. serum iron, dec. % sat)
(3) normocytic anemia –bone marrow makes fewer, normal-sized RBCs
(4) microcytic, hypochromic anemia –bone marrow makes smaller and fewer RBCs
What syndrome is associated with iron-deficiency anemia?
Plummer-Vinson syndrome
What is Plummer-Vinson syndrome?
iron-deficiency anemia with esophageal webs and atrophic glossitis; presents with anemia, dysphagia, and beefy-red tongue
What is anemia of chronic disease?
Anemia associated with chronic inflammation (e.g., endocarditis or autoimmune conditions) or cancer.
How does chronic disease lead to the production of anemia?
(1) Chronic disease results in the production of acute phase reactants from the liver, including hepcidin
(2) Hepcidin sequesters iron in storage sites
(3) dec available iron –> dec. heme –> dec. Hb –> microcytic anemia
How does hepcidin sequester iron in storage sites?
(1) by limiting iron transfer macrophages to erythroid precursors
(2) by suppressing EPO production
**the aim is to prevent bacteria from accessing iron, which is necessary for their survival
What are the lab findings of anemia of chronic disease?
(1) inc. ferritin
(2) dec. TIBC
(3) dec. serum iron
(4) dec. % sat
(5) inc. free erythrocyte protoporphyrin (FEP)
How do you treat anemia of chronic disease?
(1) Address the underlying cause
(2) exogenous EPO useful in some patients, especially those with cancer
(decreasing inflammation will decrease the amount of hepcidin produced)
What is sideroblastic anemia?
anemia due to defective protoporphyrin synthesis
dec. proto –> dec. heme –> dec. Hb –> microcytic anemia
Breifly sum the reactions involved in the synthesis of protoporphyrin
How does a defect in protoporhyrin synthesis lead to anemia?
Iron is transferred to erythroid precursors and enters the mitochondria to form heme. If protoporphyrin is deficient, iron remains trapped in the mitchondria.
Iron-laden mitochondria form a ring around the nucleus of erythroid precursors; these cells are called ringed sideroblasts.
Sideroblastic anemia can be congenital or acquired. What is the most common congenital defect?
Congenital defect most commonly involves ALAS (aminolevulinic acid synthase), which is the rate-limiting step
Sideroblastic anemia can be congenital or acquired. What are the acquired causes?
(1) alcoholism (EtOH is a mitochondrial poison, and can damage the production of protoporphyrin)
(2) lead poisoning – inhibits ALAD and ferrochetolase
(3) B6 deficiency –required cofactor for ALAS
Sideroblastic anemia due to B6 deficiency is most commonly due to what?
It is most commonly seen as a side-effect of isoniazid treatment for tuberculosis
What are the laboratory findings in sideroblastic anemia?
(1) inc. ferritin
(2) dec. TIBC
(3) inc. serum iron
(4) inc. % sat.
(iron-overloaded state)
What is thalassemia?
anemia due to decreased synthesis of the globin chains of Hb
dec. globin –> dec. Hb –> microcytic anemia
Carriers of a mutation in the globin gene are protected against what infection?
plasmodium falciparum malaria
What is usually the cause of alpha-thalassemia?
it is usually due to gene deletion
Normally, there are 4 alpha genes present on chromosome 16
In alpha thalassemia, what is the result of one deleted gene?
asymptomatic
In alpha-thalassemia, what is the result of 2 genes deleted?
mild anemia with increased RBC count.
What are the two ways in which alpha-thalassemia can genetically manifest when two genes are deleted?
The deletions can be cis (both deletions on the same chromosome) or trans (one deletion on each chromosome)
**cis deletion is associated with an increased risk of severe thalassemia in offspring
In alpha-thalassemia, what is the result of 3 genes deleted?
severe anemia
beta-chains form tetramers (HbH) that damage RBCs
HbH can be seen on electrophoresis
In alpha-thalassemia, what is the result of 4 genes deleted?
lethal in utero (hydrops fetalis)
gamma-chains form tetramers (Hb Barts) that damage RBCs
Hb Barts is seen on electrophoresis
What is Hb Barts?
a tetramer of gamma globin chains.
This is seen in alpha-thalassemia when 4 genes are deleted