Microcytic anemias Flashcards
What is microcytosis?
An extra division of RBC progenitor cells which occurs to maintain haemoglobin concentration
What is hemoglobin made of?
Heme and globin
What is heme made of?
iron and protoporphyrin
Causes of microcytic anemias?
Iron deficiency anemia
anemia of chronic disease
sideroblastic anemia
thalassemia
stages of iron deficiency
Storage depleted - decreased ferritin, increased TIBC
Serum iron depleted - decreased serum iron, decreased saturation
Normocytic anemia - bone marrow makes fewer but normal-sized RBCs
Microcytic, hypochromic anemia –bone marrow makes smaller and fewer RBCs
Clinical features of iron deficiency
Anemia, koilonychia, pica
Lab findings in iron deficiency anemia
Decreased ferritin Decreased serum iron Decreased saturaiton Increased TIBC Increased free erythrocyte protoporphyrin
plummer-vinson triad
iron deficiency anemia, esophageal webs, atrophic glossitis
Pathophys in anemia of chronic disease
Chonric inflammation leads to production of hepcidin, which sequester iron in storage sites by limiting transfers of iron from macrophages to erythroid precursors and suppresses EPO
This is done to prevent bacteria from accessing iron
Lab findings in anemia of chronic disease
increased ferritin, decreased TIBC, decreased serum iron, decreased iron saturation
increased free erythrocyte protoporphyrin
protoporphyrin synthesis pathway
succinyl coa –> ALA via ALAS
ALA –> porphobilinogen via ALAD
porphobiliniogen ———> protoporphyrin
Protoporphyrin + Iron –> Heme via ferrochetalase
pathophys of sideroblastic anemia
Congenital defect involve ALAS or acquired. Results in protoporphyrin deficiency and buildup of Iron in mitochondria
Mitochondria form a ring around nucleus of erythroid precursors
What is the cause of sideroblastic anemia?
Deficiency of protoporphyrin
Causes of acquired sideroblastic anaemia
Alcoholism - mitochondrial poison
Lead poisoning - inhibits ALAD and ferrochetalase
Vitamin B6 def - needed for ALAS
Lab findings in sideroblastic anemia
Increased ferritin
decreased TIBC
increased serum iron
increased iron saturation
HbF
alpha 2 gamma 2
HbA
alpha 2 beta 2
HbA2
alpha 2 delta 2
cause of alpha thalassemia
gene DELETION
cause of beta-thalassemia
gene MUTATION
What chromosome has the alpha genes?
16
What chromosome has the beta genes?
11
Presentation if one alpha gene is deleted?
asymptomatic
Presentation if two alpha genes are deleted?
mild anemia with increased RBC count
who more commonly has cis deletion of alpha gene?
asian persons
who more commonly has trans delation of alpha gene?
african descent
Presentation if three alpha genes are deleted?
severe anemia
Beta chains form tetramers (HbH) that damage RBCs
Presentation if four alpha genes are deleted?
Hydrops fetalis in utero – gamma chains form tetramers that damage RBCs
HbH
tetramers of beta chains
Hb Barts
tetramers of gamma chains
beta thalassemia minor presentation
mild disease usually asymptomatic with increased RBC count
what will hemoglobin electrophoresis show in Beta thalassemia minor?
increased HbA2 and increased HbF
explain the pathophys of Beta-thalassemia major
Most severe form of disease.
Unpaired alpha chains precipitate and damage RBC membranes causing ineffective erythropoiesis and intravascular hemolysis
Presentation of beta-thalassemia major
Massive erythroid hyperplasia –> crewcut appearance from hematopoiesis in the skull, chipmunk facies, hepatosplenomegaly, risk of aplastic crisis from parvovirus
