Red Blood Cell Disorders Flashcards
Definition of anemia
Decrease in Red Blood Cell Mass
Microcytic, Normocytic, and Macrocytic Anemia MCV cutoff
Normo = 80 - 100
Microcytic anemias have increased/decreased Hgb production
decreased. - maintains “concentration” of hgb by decreasing cell size
Mechanism of anemia of chronic disease
Iron is stored in macrophage, not available for heme synthesis, leading to decreased Hgb and microcytic anemia
Heme is composed of
Iron + Protoporphyrrin
Low protoporphyrin leads to which anemia
Sideroblastic anemia
4 Microcytic Anemias
IDA
Chronic Disease
Sideroblastic anemia
Thalassemia
Most common type of anemia
IDA
Iron absorption occurs in which part
Duodenum
How is iron absorbed?
Iron absorbed
Ferroportin takes iron from enterocyte to blood
Transferrin transports iron and delivers to liver and bone marow
Iron is stored as ferritin bound in macrophage
Measurements of iron status and function
Serum iron - iron in blood
TIBC - number of transferrin molecules present in blood
% Sat - number of bound Transferrin
Serum Ferritin
Red cell morphology in early vs late iron deficiency
Early - Normocytic
Late - microcytic, hypochromic anemia
3 clinical features of iron deficiency
Anemia
Koilonychia
Pica
Iron deficiency anemia associated with esophageal web and atrophic glossitis, and presents with anemia, dysphagia, and beefy-red tongue
Plummer-Vinson syndrome
Most common anemia in hospitalized patients
Anemia of chronic disease
Acute phase reactant increased in anemia of chronic disease which sequesters iron
Hepcidin
Effects of hepcidin
- Sequesters iron in storage sites which limits iron transfer and limits iron use
- Suppresses EPO production
Logic behind hepcidin
Iron is used by bacteria - it is a protective mechanism for infection
Protoporphyrin is produced from which part of Krebs Cycle?
Succinyl CoA
Iron-laded mitochondria around nucleus of erythroid precursors seen in sideroblastic anemia
Ringed sideroblasts
No porphyrin so iron accumulates in mitochondria
Prussian blue stain identifies which substance in the microscope?
Iron
Rate limiting step in porphyrin synthesis, which is most common cause of congenital sideroblastic anemia
ALAS
Acquired causes of sideroblastic anemia
Alcoholism
Lead poisoning
Vitamin B6 deficiency
Decreased synthesis of globin chains of hemoglobin
Thalassemia
Carriers of thalassemia are protected against which infection
Plasmodium falciparum
3 normal types of HgB
HbF (Fetal Hgb)(A2Y2)
HbA (A2B2)
HbA2 (A2d2)
How many alpha alleles (hgb) are present and in what chromosome are they located?
4 alleles
Chromosome 16
Number of gene deletions in alpha thalassemia and effect
1 gene - asymptomatic
2 genes - mild anemia, slightly increased RBC
(cis deletion - risk of severe thalassemia in offspring)
3 genes - Hemoglobin H disease (beta chain tetramers damage RBC) (severe anemia)
4 genes - Hydrops fetalis (gamma chain tetramers, Hb Barts)
Number of beta genes and in what chromosome
2 beta genes
Chromosome 11
Alpha vs Beta thalassemia in terms of genetics
Alpha - deletions
Beta - mutations
Red blood cell with a stained area in the center, found in beta thalassemia
Target cell
What is increased in beta thalassemia minor
HbA2
HbA needs beta chain so this is very low/none
What is massive erythroid hyperplasia
Hematopoeisis occuring in skull and facial bones as a result of increased EPO
X ray finding in massive erythroid hyperplasia
Crew cut appearance
Chipmunk like face
In megaloblastic anemia - why is there less cell divisions
Less DNA precursors
Function of Vitamin B 12 in DNA precursor synthesis
Takes methyl group from tetrahydrofolate so that it can participate in DNA synthesis, and transfers methyl to homocysteine to convert it to methionine
Macrocytic anemia causes not caused by B12 and folate
Alcoholism
Liver Disease
5-FU use
Folate is absorbed in
Jejunum
Vitamin B 12 is absorbed in
Vit B 12 binds to intrinsic factor and absorbed in ileum
Autoimmune destruction of parietal cells in stomach, leading to intrinsic factor deficiency
Pernicious anemia
Parasite associated with vitamin B12 deficiency
Diphyllobothrium latum
Homocysteine and methylmalonic acid levels in Folate and B12 deficiency
homocysteine - both high
methylmalonic acid - normal in folate, high in B12
Major causes of normocytic anemia
Peripheral destruction
Underproduction
Reticulocyte morphology
larger cells with bluish cytoplasm - residual RNA
How to differentiate normocytic anemia etiology based on retic count
> 3% = peripheral destruction (hemolytic anemia)
<3% = marrow problem, underproduction
Extravascular hemolysis involves destruction by>
Reticuloendothelial system (spleen, macrophages)
Unconjugated bilirubin from hemolysis comes from ____ and is transported bound to ____
Protoporphyrrin
albumin
What molecule binds hemoglobin which escaped from RBC in intravascular hemolysis
Haptoglobin
it takes it to spleen
Pathophysio of hemosiderinuria
Hemoglobin is absorbed in renal tubular cells, then iron accumulates, and the cells are sloughedo off in urine
RBC defect where cytoskeleton is not tethered to the cell membrane due to defect in tethering proteins ankyrin, spectrin, and band 3.1
Hereditary Spherocytosis
Cause of anemia in hereditary spherocytosis
Cells more easily consumed by spleen due to shape, more hemolysis
CBC parameters increased in hereditary spherocytosis
Increased RDW, MCHC
Increased risk of aplastic crisis with which infection in erythroblasts
Parvovirus B19
Diagnostic Test for hereditary spherocytosis
Osmotic fragility test - cell is round, so when water comes in, it bursts easity
Treatment for Hereditary Spherocytosis
Splenectomy
Peripheral blood smear feature of Hereditary Spherocytosis post splenectomy
Howell-Jolly bodies - DNA fragments unremoved by missing spleen
Type of mutation in Sickle Cell Anemia
Autosomal Recessive
Amino acid change in sickle cell anemia
Glutamic acid to Valine
Primary hemoglobin present in sickle cell anemia
HbS - which aggregate into needle like structure when polymerized
Factors which increase/protect against sickling
Increase - hypoxemia, Dehydration, Acidosis
Decrease - HbF (why it doesnt present until 6mo), Hydroxyurea
Effect of repeated sickling
RBC damage - hemolysis, irreversible sickling leading to vasoocclusion
Common presenting sign of sickle cell disease in infants
above 6 months
Dactylitis
Sickle Cell trait patients do not have sickle cells, except in which organ
Renal Medulla
Laboratory test for Sickle Cell Disease and Trait
Metabisulfite screen: any amount of HbS will cause cell to sickle
Hemoglobin Electrophoresis: confirms presence and amount of HbS
In Hemoglobin C, what is the protein change in hemoglobin?
Glutamic Acid to Lysine (Ly-C-ine)
Peripheral blood smear feature of Hemoglobin C
Hemoglobin C crystal
Acquired defect in myeloid stem cell leading to absent GPI making it susceptible to complement
Paroxysmal Nocturnal Hemoglobinuria
Why does intravascular hemolysis occur at night in PNH
Mild respiratory acidosis from shallow breathing at night activates complement
Laboratory test for PNH
Screen - sucrose test
Confirmatory - acidified serum test, flow cytometry
Main cause of death in PNH
Thrombosis from destroyed platelet fragments
G6PD deficiency is what type of mutation
X linked
Pathophysio of G6PD
Reduced half life of G6PD. G6PD is enzyme in reaction which produces NADPH, which is required to convert used glutathione back. Low NADPH makes patient susceptible to oxidative stress
Examples of oxidative stress in G6PD deficiency
Infections, drugs (primaquine, sulfa drugs, dapsone), fava beans
Precipitated hemoglobin presents as ____ (morphology), and the cells where this Hgb is removed are called ______
Heinz bodies
Bite Cells
Antibody mediated IgG or IgM destruction of RBC
Immune hemolytic anemia
IgG mediated hemolytic anemia leads to (morphology)
Spherocytes
