Hematology Week 1: Diminished Erythropoiesis Flashcards
Hemolytic anemia Structural protein defects in one of these skeletal proteins
- Ankyrin
- Band 3
- Spectrin
- Band 4.2
G6PD function
Important in making the reduced form of glutathione (GSH) which is critical in protecting against oxidant injury to the RBCs
G6PD Deficiency Genetics
X linked
G6PD Deficiency Triggers for hemolysis
3 listed
Infection - most common
Drugs - antimalarial
Food - Fava beans
G6PD Deficiency is most more common in? because?
Males because it is X-linked
G6PD Deficiency forms what kind of cells
Bite cells from the spleen removing precipitated Hb
Hemoglobin S AKA
Sickle Cell Disease
Most common hemoglobinopathy
Hemoglobin S (Sickle Cell Disease)
Hemoglobin S Mutation
Point mutation on Beta Globin gene leads to valine replacing glutamic acid at the 6th amino acid position
Hemoglobin S Prognosis
Often leads to severe lifelong hemolytic anemia
Hemoglobin S etiology
Vascular obstruction -> tissue Infarction -> Sickle Cell Crisis
Hb will form tetramer and will not be flexible and will have difficulty traveling through the vasculature and the spleen
Hemoglobin S Diagonisis
- Gold standard is hemoglobin electrophoresis
- Identify HBS based on mobility
β Thalassemia etiology
- absent or reduced synthesis of β globin chains
- increased α globin chains cause erythroid precursor damage
- causing marrow expansion and extramedullary hematopoiesis
β Thalassemia Mutation
Due to >170 β gene mutations
α Thalassemia
deletion of α gene resulting in a lack of α subunits and β subunits
α Thalassemia Mutations
- Gene deletions are common
- 2 deletions (asymptomatic mild anemia)
- 4 deletions is fatal in utero (hydrops fetalis)
α Thalassemia genes
α 1 and α 2 on chromosome 16
so each person has 4 copies
Hydrops fetalis
α Thalassemia deletion of all 4 copies of α genes
α Thalassemia 3 copies deleted
- soluble tetramers of β globins called H bodies
- H bodies are minimally damaging to RBCs
Characteristic cell type of diminished erythropoiesis
Macroovalocytes
diminished erythropoiesis PBS findings
- macroovalocytes
- reticulocyte count is low
- nucleated Red Cell Progenitors appear when anemia is severe
- neutrophils are larger than normal and show nuclear hypersegmentation (macropolymorphonuclear)
Aplastic Anemia AKA
empty bone marrow
Myelophthisic Anemia
Question 1
B Kidney damage
because EPO is low despite anemia
Iron deficiency anemia
if you cant get enough iron you cant make enough Hb and you cant make as many RBCs
Causes of iron deficiency
3 listed
Impaired cytoplasmic maturation
Polychromasia meaning
many colors
Peripheral smear of iron deficiency anemia
decreased RBC
reduced Hct
decreased Hb
Microcytic decreased MCV
hypochromic decreased MCHV
CBC of iron deficiency anemia
decreased RBC
decreased HGB
Decreased HCT
Decreased MCV
Decreased MCHC and MCH
Increased RDW
Iron absorption
- Iron in the duodenum and ferroportin imports iron to blood stream
- transferrin binds to iron and dleivers it to sotrage places of iron such as bone marrow and liver and is stored as ferritin
- ferritin is used as the stored iron source for erythropoiesis
Serum iron in iron deficiency anemia
Decreased
Transferrin Iron Saturation in iron deficiency anemia
Decreased
Total Iron Binding Capacity in iron deficiency anemia (TIBC)
Increased
TIBC AKA
Total Iron Binding Capacity
Ferritin in iron deficiency anemia
Decreased
Bone Marrow Iron Stain
Prussian Blue Stain
Laboratory portrait of iron deficiency
Anemia of Chronic Disease
Anemia of Chronic Disease arises in settings of?
Chronic Inflammation due to
- infection
- neoplasms
- other sources of inflammation
Anemia of Chronic Disease Purported mechanism
to deprive infectious organisms from getting iron for proliferation
The most common cause of anemia in hospitalized patients
Anemia of Chronic Disease
Chronic inflammations role in the absorption and processing of iron
Chronic Inflammation leads to production of many cytokines but particularly in this circumstance is the production of Hepcidin
Hepcidin blocks ferroportin and blocks the ability to use stored ferritin and decreases responsiveness to EPO
results in decreased production of RBC
Hepcidin effects
4 listed
- Hepcidin blocks ferroportin
- blocks the ability to use stored ferritin
- decreases responsiveness to EPO
- reduces Erythropoiesis
Serum Iron in Anemia of Chronic Disease
decreased
Transferrin iron saturation in Anemia of Chronic Disease
decreased
Total Iron Binding Capacity in Anemia of Chronic Disease
normal or decreased
Ferritin in Anemia of Chronic Disease
normal or increased
Laboratory portrait of in Anemia of Chronic Disease
Why is anemia of chronic disease not microcytic and hypochromic?
usually, the responsiveness to EPO is the predominant effect
so basically not enough RBCs are being produced
Failure of nuclear maturation cellular characteristics
macrocytic
Pathway of DNA Synthesis
need to take folate to tetrahydrofolate (FH4) by methylating B12 into methyl-cobalamin
Methyl-cobalamin is restored to B12 by methylating homocysteine to methionine
B12 deficiency and Folate Deficiency decrease DNA synthesis
B12 deficiency and Folate Deficiency cause?
B12 deficiency and Folate Deficiency decrease DNA synthesis
Megaloblastic anemia
B12 deficiency leads to?
Megaloblastic anemia + demyelinating neurological symptoms
Causes of vitamin B12 Deficiency
Diphyllobothrium latum
Intestinal tapeworm absorbs B12 and competes for it
Intestinal tapeworm absorbs B12 and competes for it
Diphyllobothrium latum
How is vitamin B12 absorbed into the body?
R binder is secreted in saliva which binds to B12
Gastric parietal cells produce intrinsic factor
intrinsic factor binds to B12 after R binder is cleaved off
intrinsic factor receptors on intestinal epithelial cells bind to the B12+intrinsic factor complex absorbing it
intrinsic factor Is produced by?
Gastric Parietal Cells
Autoimmune attack to parietal cells causes
Pernicious Anemia
AKA
(B12 deficiency and megaloblastic anemia)
Causes of Folate Deficiency
How to differentiate Folate deficiency from B12 deficiency?
B12 increased homocysteine and increased methylmalonic acid-CoA
Folate Deficiency Increased homocysteine
Folate Deficiency vs B12
Folate Deficiency Increased homocysteine only
B12 deficiency vs folate deficiency
B12 increased homocysteine and increased methylmalonic acid-CoA
Laboratory portrait of megaloblastic anemia with B12 and Folate indices
large RBC precursors (megaloblasts)
Macroovalocytes in the blood
hypersegmented neutrophils
Megaloblastic anemia Histological features
large RBC precursors (megaloblasts)
Macroovalocytes in the blood
hypersegmented neutrophils
Megaloblastic Anemia RBC#
low
Megaloblastic Anemia Hb
Low
Megaloblastic Anemia Hct
Low
Megaloblastic Anemia MCV
High
Megaloblastic Anemia RDW
High
MCV as a tool for categorizing anemias
Microcytic anemias examples
3 listed
Iron deficiency
Thalassemia
Lead poisoning
Iron deficiency anemia treatment
Oral or IV (Oral is not tolerated well by many patients) (GI issues)
must identify the cause of the deficiency
remember Occult GI bleeding due to undiagnosed colon cancer
Iron Deficiency Anemia Caveat
remember Occult GI bleeding due to undiagnosed colon cancer!
Anemia of Chronic Disease treatment
Treat underlying condition
(+/- erythropoietin injection)
(+/- RBC transfusion)
Megaloblastic Anemia Treatment
Supplementation of B12 (Oral or Intramuscular) or folate (Oral or IV)
DONT CONFUSE THESE CAN MAKE PATIENT WORSE!
Megaloblastic Anemia Caveat
Be Careful don’t mix up folate deficiency from B12 deficiency
the folate might lessen the anemia but can make the neurological symptoms worse
