3. Anemia: Normocytic Flashcards
what are the two main categories of normocytic anemia? what do these categories indicate?
with high reticulocyte count and with low retic count. indicates if problem is hypoproliferation (bone marrow) or incr destruction (hemolysis).
normocytic anemia: MCV is what?
80-100 fL
anemia of chronic disease is normocytic anemia with what retic count?
low.
anemia of chronic disease is due to what underlying condition?
inflammation, infection, malignancy.
ACD: typically normochromic or hypochromic? normocytic or microcytic?
can actually be any of these, though typically normochromic and normocytic.
due to chronic condition and related cytokines, what are the downstream effects?
incr hepcidin, inhibition of EPO production, incr ferritin/sequestration of iron in macrophage, inhibition of erythropoiesis
what are the effects of having increased hepcidin?
decr iron absorption in the small int
decr iron release from macrophages
inhibition of erythropoiesis
generally, why would the body be sequestering iron and making it inaccessible in a state of chronic disease?
bacteria like having iron, so the body is trying to keep bacteria from having this food.
anemia of chronic disease: is the iron deficiency true deficiency? or what?
body has plenty of iron but can’t access it; stuck in storage. “functional iron deficiency”
Iron Deficiency Anemia: levels of these labs: ferritin, transferrin (TIBC), transferrin sat (TS), serum iron, marrow iron, RPI, sed rate (inf marker)
ferritin: low TIBC: high TS: low serum iron: low marrow iron: low RPI: low sed rate: normal
Anemia of Chronic Disease: levels of these labs: ferritin, transferrin (TIBC), transferrin sat (TS), serum iron, marrow iron, RPI, sed rate
ferritin: NL or high TIBC: NL or low TS: NL or low serum iron: low marrow iron: high RPI: low sed rate: high
ferritin measures what?
storage of iron in macrophages
TIBC measures what?
number of transferrin molecules in blood (iron carriers/scavengers)
TS measures what?
saturation of the transferrin molecs in blood
RPI measures what?
response of marrow to low RBCs
sed rate measures what?
inflammatory marker
what can cause aplastic anemia? what is most common cause?
damage to HSC from a variety of sources, such as cytokines, radiation, drugs, viruses. IDIOPATHIC is most common.
define aplastic anemia
pancytopenia with empty bone marrow. badly named because not only about RBCs
aplastic anemia: what are the biggest clinical problems?
leukopenia (low WBCs) and thrombocytpenia (low platelets)
besides ACD and aplastic anemia, a few causes of hypoproliferative normocytic anemia? (sort of miscellaneous category)
anemia of chronic kidney disease: decr EPO due to decreased renal cortical cells. also, blood loss, shortened RBC lifespan.
chemo: direct marrow suppression
alcohol: marrow suppression.
malignancy or infection of bone marrow
normocytic anemia with incr retics means that what is going on to cause the anemia?
destruction/hemolysis somewhere
definition of hemolytic anemia?
anemia due to a destruction of the RBC before the usual 120 day lifespan.
when RBCs are broken down normally, where does it occur? where do the components go?
usually occurs extravascular: spleen, liver
Hgb is broken down
iron is recovered, stored in macrophage ferritin or transported back to marrow
heme ring is metabolized to bili, taken to liver, excreted as bile.
what is a sign of intravascular hemolysis?
incr LDH, because RBCs are leaking out their contents after being destroyed.
what binds free hgb in circulation? what does it do with the hgb?
haptoglobin. complexes to hgb, brings to liver where it can be broken down, excr in bile.
why is it impt to remove free Hgb from circulation?
prevents the iron from being used by bacteria
why might someone get low haptoglobin?
if there is so much intravascular hemolysis and the haptoglobin is overwhelmed.
combination of incr LDH, decr haptoglobin, incr indirect bili signifies what?
lots of intravascular hemolysis. bad situation
if haptoglobin is overwhelmed with intravascular hgb, where will the excess hgb go?
hemoglobinemia and hemoglobinurea.
schistocytes: what do they look like? what do they signify?
fragment of an RBC. aka helmet cells. something is causing the fragmentation: intravascular hemolysis.
intravascular hemolysis: what will these labs be? RBC, HCT, Hgb indirect bili haptoglobin LDH reticulocytes
RBC, HCT, Hgb ALL LOW indirect bili HIGH haptoglobin LOW LDH HIGH reticulocytes HIGH
intravascular hemolysis: clinical manifestations?
pallor, fatigue, tachycardia, jaundice, hemoglobinemia and hemoglobinurea.
extravascular hemolysis: what will these labs be? RBC, HCT, Hgb indirect bili haptoglobin LDH reticulocytes
RBC, HCT, Hgb ALL LOW indirect bili HIGH haptoglobin LOW LDH HIGH reticulocytes HIGH
extravascular hemolysis: where is the hemolysis taking place?
spleen
extravascular hemolysis: clinical manifestations
pallor, fatigue, tachy, jaundice. SAME as intravascular but no hemoglobinemia or hemoglobinurea.
Immune hemolytic anemias: cause by what, in general?
antibodies directed against RBC antigens.
how can we distinguish immune hemolytic anemia from non-immune?
Coombs test
Explain how the Coombs test works.
Blood sample from patient, wash away everything except RBCs. Add Coombs reagent (antihuman antibodies). if RBCs clump together (agglutinate), indicates that there is an immune process going on because there were already antibodies on the antigens of the RBCs. Coombs reagent attached to these antibodies and caused clumping.
how is a microspherocyte formed?
start with RBC coated with antibodies. the macrophages of the spleen take off little chunks of RBC and antibody bits, which makes the RBC smaller and smaller. Yields a microspherocyte which eventually is destroyed by spleen.
Presence of microspherocytes indicates what?
immune-mediated hemolysis
Treatment for autoimmune hemolytic anemia?
address the underlying cause if possible steroids immunosuppression anti-CD20 therapy (rituximab) splenectomy
Microangiopathic hemolytic anemia: general process?
non-immune hemolytic process with prominent RBC fragmentation. Physical destruction of cells in small vessels.
Microangiopathic hemolytic anemia: prominent feature?
RBC fragmentation: schistocytes
Microangiopathic hemolytic anemia: three types/causes?
TTP/HUS (thrombocytopenia/RBC fragmentation)
DIC (coag cascade activation->fragmentation)
malfunctioning heart valves (shear forces)
hereditary spherocytosis is a problem with what exactly?
deficiency of spectrin, which anchors RBC cytoskeleton to membrane. this is a menbranopathy.
hereditary spherocytosis: what happens?
spectrin-deficient spherocytes have decr mechanical stability; not able to pass through splenic microcirculation so they due prematurely.
hereditary spherocytosis: treatment?
splenectomy
hereditary spherocytosis: lab finding?
MCHC elevation (incr concentration of Hgb in a volume of RBCs)
Paroxysmal nocturnal hemoglobinuria (PNH): describe the disorder in general terms
acquired disorder, RBCs are missing a membrane anchor molecule due to a defective gene. Therefore other proteins not able to stick to the RBC. Results in complement attack of RBCs and intravascular hemolysis
PNH: typical clinical picture?
patient wakes in morning with dark urine
PNH: concern is for what?
significant risk of thrombosis. stroke, heart attack
PNH: how diagnosed?
by flow cytometry. RBCs are missing surface proteins CD59 and CD55.
G6PD deficiency: overall picture. what is going on?
G6PD-deficient RBCs cannot generate enough NADPH or protective glutathione, therefore are subject to oxidative stress. Result: Hgb denatures in cytoplasm, aggregates into Heinz bodies, yields bite cells and ultimate hemolysis
what is the protein that protects RBCs from oxidative stress? what precursor is required to make this protein?
Reduced glutathione. requires NADPH. G6PD is the enzyme that reduces the glutathione.
without glutathione, what happens inside RBCs?
oxidant radicals can damage Hgb, which denatures and aggregates into Heinz bodies.
Heinz bodies: appearance histologically?
small pink aggregations at edge of cytoplasm
G6PD deficiency: genetic pattern? treatment?
X linked
supportive treatment, avoid oxidative stressors
G6PD deficiency: characteristic cellular markers?
Heinz bodies
Bite cells
most common cause of hemolytic anemia worldwide?
malaria
a few genetic polymorphisms that are protective for malaria?
G6PD def
thalassemia
sickle cell
these polymorphisms interfere with the ability of the malaria parasites to invade the RBCs
Hemoglobinopathy: caused by what?
qualitative or quantitative disorder of hgb?
-caused by mutation of globin genes
-QUALitative disorders of Hgb.
(Recall that thalessemias are QUANTitative disorder. let the word help you: Hemoglobinopathy = pathology of Hgb.)
Sickle Cell Anemia: what is the cause?
amino acide SUBSTITUTION of valine for glutamic acid on the B globin chain.
HbAS would be Sickle Cell Trait or Anemia
HbAS is heterozygous with one good B globin –> trait
why does the abnormal B globin chain cause problems with SCAnemia?
it has a tendency to form tetramers, esp in the deoxygenated state. These tetramers then polymerize and change the shape of the RBC.
precipitating factors for SCAnemia?
infection, dehydration, O2 dep, cold, heavy exercise
what is the lifespan for a sickled cell? where are they destroyed?
10-20 days. most removed by the spleen.
Clinical presentation of SC Disease?
most common is vaso-occlusive crisis. joints of hands can be affected, lung problems, priapism. also microcirculation can be affected -> avascular hip necrosis
Also anemia, jaundice, gallstones.
SC disease: treatment
- prophylaxis to avoid precipitating factors
- treatment of painful episodes: hydration, 02, pain meds
- hydroxyurea can increase % of Fetal Hgb
- HSCT
