Anemia Flashcards
Anemia definition
a significant decrease in the mass of circulating RBCs
How is anemia measured?
- concentration of hemoglobin in blood
- hematocrit
Hematocrit
ratio of volume of red cells to total volume of blood
Why are anemic patients pale?
because blood is shunted away from the skin to more vital organs
What are the 3 primary causes of anemia?
- decrease RBC production
- increased red cell destruction (hemolysis)
- blood loss
How is decreased RBC production further classified?
microcytic, normocytic and macrocytic
How can non-immune hemolytic anemia be further classified?
inherited or acquired
HbS
form of hemoglobin found in individuals with sickle cell
polymerizes in low O2 conditions
anisocytosis
have 2 populations of RBCs with markedly different size
What does anisocytosis correspond to?
large RDW
What does an increased retic indicate?
there is no production problem
increased retic is usually in response to increase hemolysis that the cell is trying to make up for
What further classification should hemolytic anemia be broken into?
auto-immune or non-immune
How do you differentiate if hemolytic anemia is auto-immune or non-immune?
look at the DAT
+ DAT
indicates immune hemolytic anemia
What does a low retic indicate?
there is a problem with RBC production and we should consider morphological differences
When is there a concern for malignancy?
when there is low retic but still elevated MCV
Hematocrit
what % of blood is RBC
Relationship between hemoglobin and hematocrit
Hematocrit is 3x hemoglobin
Effects of reticulocytes on MCV
they drive MCV up since they are slightly larger
RDW
in a normal distribution, the range +/- 2 SDs from the MCV
Shistocyte
fragement of RBC
is very microcytic
What is thalassemia?
abnormal ratios of alpha/beta chains
Which configuration of alpha-thalassemia is more dangerous?
cis configuration
When in HbA2 increased?
in people with B-thalassemia
HbA2
two alpha and two delta chains
see this form in B-thalassemia when the beta chains normally in HbA are affected
B-thalassemia affects which chain?
beta chains
A-thalassemia affects which chain?
alpha chain
What is sickle cell an example of?
protein aggregation disease
Where do post-translation modifications like glycoslation occur?
in the golgi
What does SRP do?
says if ribosome should go to the ER
protein aggregation disease
misfolding causing aggregation
ex: Parkinson’s, Alzheimer, Huntington’s
What is mutated in sickle cell?
glutamine to valine
What is one cause of protein aggregation disorders (not sickle cell)?
nucleotide repeat expansions
DNA slips during replication and forms hairpin which leads to an expansion
Where is nucleotide repeat expansion in Huntington’s?
PolyQ expands glutamine in coding region
Where is nucleotide repeat expansion in Fragile X?
expansion in 5’ UTR leads to increased methylation / silencing
halposufficiency
a single copy of the gene is enough to maintain normal function
disease is recessive to normal gene
ex: Cystic Fibrosis
haploinsufficiency
a single copy of a normal gene cannot maintain normal function
disease in dominant over normal gene
ex: hypercholesterolemia
Gain of function mutation
affects heterozygotes
is dominant / haploinsufficient
Why is sickle cell autosomal recessive?
haplosufficient
one normal gene in heterozygotes can maintain normal function
therefore, you need two copies of missense allele to form mutation
mutation in sickle cell
missense mutation of glutamine to valine
What is the primary antioxidant in RBCs?
glutathione
G6PD
enzyme that normally produces NADPH
What does NADPH do?
regenerates and preserves reduced form of glutathione
In G6PD deficiency what happens?
you can’t regenerate glutathione, so there is nothing to detoxify free radicals
lack of glutathione means that RBC will have to be hemolyzed
When does B-thalassemia present? Why?
a couple months into life
the protective effects of HbF wane
you should produce HbA but the beta chains are affected
What tells you if anemia is hypoproliferative or hyperproliferative?
the retic
How much should total body stores of iron be?
3 grams
How much iron does GI tract take in daily?
1-2 mg
What happens when hepcidin is downregulated?
ferratin is uptaken into cells during iron deficiency
Where does majority of serum transferrin deposit Fe?
into the bone marrow
deposits 20 mg from plasma to bone marrow
bone marrow places Fe on new RBCs
What organ delivers some serum transferrin back?
spleen
deposits 18 mg from spleen to plasma
Where is a majority of iron stored?
liver
