B3.083 Big Case Anemia Flashcards
definition of anemia
defined as decreased red cell mass
usually decrease hematocrit, hemoglobin, RBC
describe the progression of normal Hb levels at various ages
decreases from neonates to 3 months
slowly increases over childhood
levels out at about age 10
men > women
most common cause of anemia worldwide
iron deficiency anemia
what given reticulocytes their bluish color
RNA in cytoplasm
what are the 3 stages of RBC development
normoblast (nucleated RNC)
reticulocyte
mature RBC
what cell type recycles old/damaged RBCs?
macrophages
what happens to iron from old RBCs?
transported in circulation from macrophages to bone marrow via transferrin
signs and symptoms of anemia
pallor
conjunctival pallor
fatigue
chest discomfort, palpitations
3 primary causes of anemia
- decreased RBC production
- increased RBC destruction
- bleeding
how do you check to see if bone marrow is working?
other blood counts reticulocyte count (best indicator)
RBC lifespan
120 days
how many RBCs normally replaced each day?
1/120 or 1%
how long are newly released RBCs identifiable as reticulocytes?
a day
1% of circulating RBCs
normal absolute reticulocyte count
50,000
why are reticulocytes released earlier in most types of anemia?
anemia causes EPO levels to rise
EPO stimulation leads to early release
result of EPO stim on retic count
can potentially double reticulocyte count even in absence of increased RBC production
what is an expected retic count for an anemic patient with a normal bone marrow
50000 x 2 x 2 = 200000
doubles release rate
live for 2 days instead of 1
retic count >200000
adequate marrow function in anemic pt
retic count >300000
hemolysis likely
retic count <100000 in anemic
suboptimal RBC production
RPI
retic production index
makes corrections for Hct and RBC lifespan
RPI = retic % x (HCT/45) x (1/RMT)
where RMT is retic maturation time
RPI = 1
individual without hemolysis or blood loss
RPI > 2-3
increased
RPI < 2 in an anemic
inappropriately low
what are two causes of inadequate RBC production (retic normal or low)
- hypoproliferative: impaired RBC production, lower than normal RBC precursors in marrow
- ineffective erythropoiesis: impaired RBC production despite increased marrow RBC precursors
what are two causes of increased RBC destruction
hemolysis
blood loss
red cell indices
Hgb
Hct
RBC count
MCV
mean corpuscular volume
Hct/RBC count
primary classification of anemia
MCH
Hgb/ RBC count
MCHC
Hgb/Hct
macrocytic
MCV > 100
defective DNA synthesis or reticulocytosis
microcytic
MCV < 80
decreased Hgb production
normocytic
MCV 80-100
poikilocytosis
variation in RBC shape
aniscytosis
variation in RBC size
RDW quantifies this variability
how much iron/day is eaten/absorbed
10-15 mg/day in diet
5-10% absorbed
more absorbed in iron def, pregnancy, erythroid hyperplasia, hypoxia
can you absorb Fe2+ or Fe3+ better
Fe2+
ability to regulate absorption is limited
where does iron absorption occur
proximal small intestine
describe the pathways of iron transport and storage
Fe2+ absorbed and oxidized to Fe3+
Fe3+ bound tightly to transferrin in blood
Fe3+ is transferred to cells and reduced to Fe2+ form, then inserted into heme or stored
storage iron (Fe3+) bound to ferritin
ferritin in blood
correlated with body iron stores
what is hepcidin and what does it do?
peptide produced in the liver
interacts with ferroportin to inhibit iron release from villus enterocytes and macrophages (less iron in blood)
what is ferroportin
iron transport channel that moves iron from cells into blood
what modulates hepcidin levels
high plasma iron or inflamm = more hepcidin
low iron = less hepcidin (more iron let into blood)
HFE gene modulates production
reasons for decreased hepcidin
iron def
HFE mutation
ineffective erythropoiesis
liver disease
why does hepcidin increase in inflammation
make less iron available to pathogen
lab tests used to assess iron status
serum iron
TIBC
serum ferritin
serum iron
transferrin
bound iron being transported in the blood
TIBC
total iron binding capacity
total amount of transferrin in the blood
transferrin saturation
serum iron/TIBC (%)
serum ferritin
reflect body iron stores
when is serum iron low
iron def
inflammation
when is TIBC high
iron def
when is TIBC normal or low
inflammation
when is serum ferritin low
iron def
when does serum ferritin increase
inflammation
acute phase reactant
sTfR
soluble transferring receptor
circulating protein derived from cleavage of the membrane transferrin receptor on erythroid precursor cells
what does sTfR concentration in serum indicate
directly proportional to erythropoietic rate
inversely proportional to tissue iron availability
similar to serum transferrin
usually increased in iron def patients
what is the sTfR-ferritin index
sTfR/log[ferritin]
sTfR reflects erythropoiesis
ferritin reflects tissue iron stores
high index - sign of iron deficiency
sTfR-ferritin index in patients with ACD
<1
sTfR-ferritin index in patients with iron def anemia or iron def plus ACD
> 2
where is most of your iron located
RBCs
how much iron / day is required for erythropoiesis
20 mg
most recycled from old RBCS
1-2 mg new from gut
1-2 mg lost via sloughing of enterocytes
what are 3 pathogeneses of iron def
- blood loss
- failure to meet increased requirements
- inadequate absorption
what is the usual cause of iron def anemia
chronic blood loss
women - menstrual blood
characteristics of iron def anemia
microcytic, hypochromic retic count not increased anis- and poik- in more severe cases serum ferritin usually low serum iron low, TIBC high
describe the evolution of iron def anemia
- depletion from stores
- depletion or stores and transport
- all stores and transport gone, erythron iron starts to decrease
treatment for iron def anemia
most patients are initially with oral iron unless there is an absorptive problem
dietary sources + FeSO4 BID
severe = RBC transfusion
indication for iv iron
severe symptomatic anemia requiring accelerated erythropoiesis
failure of oral from gi intolerance of absorption issues
cancer w chemo associated anemia
chronic renal disease
heavy ongoing bleeding
when do different lab tests reflect oral iron therapy
peak retic count 7-10 d
increased Hb and Hct 14-21 d
normal Hb and Hct 2 mo
normal iron stores 4-5 mo
other causes of microcytic anemia
iron withheld from red cell precursors (inflamm)
globin gene defects (thalassemias)
defects in heme synthetic pathways (sideroblastic)
lab findings in anemia of inflamm
normocytic or mild microcytic
not many shift cells
low serum iron, normal or low TIBC, normal or high ferritin
relatively low EPO level for degree of anemia
