Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
113 Cards in this Set
- Front
- Back
|
sideroblastic anemias are a heterogenous group of disorders characterized by ... |
anemia of varying severity
|
|
|
how is sideroblastic anemia diagnosed ?
|
by finding ring sideroblasts in the bone marrow aspirate
|
|
|
what is the common etiology of sideroblastic anemia ? |
impaired biosynthesis of heme in erythroid cells of the marrow
|
|
|
what is the impaired biosynthesis of heme in sideroblastic anemia due to ?
|
impaired production of protoporphyrin or defetive insertion of iron into protoporphyrin in the erythroid cell
|
|
|
what are the 2 enzymes that are responsible in the hemoglobin synthetic pathway and are deficient in sideroblastic anemia ?
|
gamma aminolevulinic acid synthase, heme synthetase
|
|
|
what is another name for heme synthetase ?
|
ferrochelatase
|
|
|
where does heme synthesis take place ?
|
in the mitochondrion
|
|
|
what does ferrocheletase do ?
|
inserts iron into protophorin IX ring in the mitochondria
|
|
|
What happens to the regulation of iron in sideroblastic anemia ?
|
it is not down regulated and continues to be transported normally to the mitochondria
|
|
|
where does the continued drainage of iron in the mitochondria go ?
|
it stays in the mitochondria and form a ring like structure around the nucleus
|
|
|
what stain is used to identify the iron deposits ?
|
Perl's Prissian Blue stain
|
|
|
what percentage of the normoblasts need to show ring sideroblasts to be considered positive ?
|
15%
|
|
|
what are the 2 general classifications of sideroblastic anemia ?
|
hereditary or acquired
|
|
|
what are acquried sideroblastic anemias further classified as ?
|
idiopathic (RARS)secondary to drugs or toxins
|
|
|
list the 5 causes that lead to congenital sideroblastic anemia ?
|
Xlinked, Autosomal recessive, Mitochondrial disorders, pearson syndrome, DIDMOAD syndrome
|
|
|
what are the reasons behind the acquired type of sideroblastic anemia ?
|
MDS, Nutritional deficiences Cu B-6, Pb poisoning, alcohol, drugs, hypothermia, idiopathic
|
|
|
Is inherited sideroblastic anemia common and how is genetically and clinically ?
|
uncommon and genetically and clinically heterogenous
|
|
|
what is the most common cause behind a hereditary sideroblastic anemia ?
|
X linked recessive trait found in males
|
|
|
what do most patients with heriditary sideroblastic anemia have ?
|
decreased gamma aminolevulinic acid synthase activity
|
|
|
what does ALA-S catalyze ?
|
condesation of glycine and succinyl CoA
|
|
|
what coenzyme does ALA-S require ?
|
Pyridoxal phosphate form of vit B-6
|
|
|
what are the possible causes of the decreased ALA-S activity ?
|
enzyme might have reduced affinity for the cofactor or it is sensitive to a degrading mitochondrial protease
|
|
|
in both cases of reduced affinity of ALA-S what do they respond to ?
|
Pyridoxine therapy
|
|
|
will ALA-S always respond to pyridoxine therapy ?
|
no not always
|
|
|
at what phase of life is hereditary sideroblastic anemia manifested ?
|
during infancy
|
|
|
they symptoms in general of patients with hereditary sideroblastic anemia resemble those of ?
|
anemia
|
|
|
what clinical manifestaton is present in hereditary sideroblastic anemia ?
|
iron overload including mild to moderate enlargment of the liver and spleen
|
|
|
is the liver function in sideroblastic anemia of the hereditary type disturbed ?
|
normally not but it might slightly disturbed
|
|
|
iron depositis in pancereatic cells cause what clinical manifestation in 1/3 of patients with HSA ?
|
diabetes
|
|
|
what is the most dangerous manifestation of iron overload in the HSA ?
|
cardiac arrhythmias
|
|
|
when do cardiac arrhythmias occur in HSA ? |
late in the disease secondary to accumulating iron deposits in mycardial cells
|
|
|
in severly affected infants or young children what tends to be impaired ?
|
growth and development
|
|
|
what are RBC indices in HSA ?
|
severe anemia with Hb of 6 g/dl , MCV , MCH, MCHC decreased and increased RDW
|
|
|
what is the hemoglobin leve in HSA ?
|
6 g/dl
|
|
|
what is the red cell morphology in HSA ?
|
anisocytosis, poikilocytosis, microcytosis hypochromic picture , with target cells and occasional siderocytes
|
|
|
what is furtherly increased in the peripheral blood picture of HSA ?
|
basophilic stippling but the number of circulating reticulocytes is not elevated
|
|
|
in milder cases of HSA how is the peripheral blood picture ?
|
it contains erythrocyte dimorphism with microcytic hypochromic and normocytic normochromic picture |
|
|
how is the leukocyte and platelet counts in mild cases of HSA ?
|
normal
|
|
|
how does the bone marrow look in the HSA ?
|
erythroid hyperplasia
|
|
|
how is the erythropoeisis in HSA?
|
ineffective erythropoeisis
|
|
|
what happens to the iron stores in macrophages in HSA ?
|
it is increased due to ineffective erythropoeisis
|
|
|
what happens to iron absorption from the intestine in HSA ?
|
increased iron absorption
|
|
|
what is the percentage of ring sideroblasts in the bone marrow of HSA ?
|
40% and found in the late non dividing erythroblasts
|
|
|
what do we see ocassionaly in the bone marrow of HSA due to complicating folate def ?
|
megaloblastic changes
|
|
|
what type of tests are really important in diagnosis of sideroblastic leukemia?
|
iron kinetics
|
|
|
how is the ferriting levels in HSA ?
|
high due to high stores
|
|
|
how is the serum iron in HSA ?
|
high
|
|
|
how is the level of transferin in HSA ?
|
saturated with above 80%
|
|
|
what does high transferrin indicate ?
|
iron is being delivered adequatly to the developing erythrocytes in the bone marrow but not utilized into hemoglobin
|
|
|
how is the total iron binding capacity in HSA ?
|
normal to low
|
|
|
how are the FEB levels in HSA ?
|
low or normal
|
|
|
what is the treatment for HSA ?
|
pyridoxine but it rarely works and prognosis is variable
|
|
|
what is the treatment in extreme cases ?
|
transfusions
|
|
|
what is essential to treat the iron overload ?
|
iron chelation
|
|
|
what do you give patients with megaloblastic changes ?
|
folic acid
|
|
|
what is another name for idiopathic aquired sideroblastic anemia ?
|
refractory anemia with ring sideroblasts
|
|
|
the idiopathic refractory anemia is included in what classification of diseases?
|
myelodysplatic syndromes
|
|
|
what is the pathophysiology of the ISA?
|
clonal disorder with an abnormal proliferating erythroid cell line.
|
|
|
what enzyme is found to have decreased ativity with IASA ? |
ALA-S
|
|
|
in what age group is IASA seen ?
|
older than 50 years of age
|
|
|
how is IASA found in patients ?
|
on routine examination due to its insidious type
|
|
|
what are some abnormal clinical findings in IASA ?
|
anemia slight enlargement of the spleen or liver or both in the 40% of patients
|
|
|
how is the Hb content in IASA?
|
mild anemia with Hb between 8-10 g.dl
|
|
|
how is the Hct range in IASA ?
|
25-35 %
|
|
|
what is the most consistent and useful erythrocyte index in the diagnosis of the anemia ?
|
MCV
|
|
|
how is the MCV in IASA ?
|
larger than 100 fl and might be as high as 130 fl
|
|
|
as a result of the macrocytosis what are some patients diagnosed with ?
|
vit b12 or folate def
|
|
|
would IASA patients respond to vit B12 and folate ?
|
no
|
|
|
how is the WBC count in IASA ?
|
low normal or high
|
|
|
what might leukopenia in IASA reflect ?
|
hypersplenism with destruction of leukocytes and or clonal disorder of the bone marrow in which more than on cell type is affected
|
|
|
how is the platelet count in IASA ?
|
low normal or high
|
|
|
why do you might have decreased platelet counts ?
|
hypersplenism or clonal disorder
|
|
|
what does the PB smear show ?
|
varying degrees of anisocytosis and poikilocytosis
|
|
|
the RBCs in IASA look ?
|
normocytic normochromic or macrocytic normochromic and some are microcytic hypochromic
|
|
|
what type of cells are seen in the PB of the IASA ?
|
target cells, siderocytesm heavily stippled and hypochromic cells
|
|
|
what cells are ocassionally seen in the pb of IASA ?
|
normoblasts
|
|
|
how do normoblasts look in the cytoplasm ?
|
coarse cytoplasmic badophilic stippling
|
|
|
what do the nuclei of these normoblasts demonstrate in IASA ?
|
megaloblastoid features
|
|
|
what bodies can be seen in the normoblasts of IASA ?
|
howel jolly bodies
|
|
|
what does the bone marrow show in IASA ?
|
significat erythroid hyperplasia
|
|
|
the BM picture of the IASA has mild ... and ... changes
|
dyerythropoiesis (multinuclearity, nuclear budding ) and megaloblastoid changes
|
|
|
myelopoiesis and megakaryopoiesis in IASA are ?
|
normal
|
|
|
the BM of IASA may resemble what marrow ?
|
erythroleukemic marrow with minimal or lack of PAS positive material
|
|
|
how do iron stains look in macrophages of IASA?
|
increased amounts
|
|
|
what is the percentages of ring sideroblasts of normoblasts ?
|
95%
|
|
|
where are the ring sideroblasts present in IASA ?
|
all stages of erythroid maturation
|
|
|
serum iron in IASA is ?
|
increased
|
|
|
how is the transferrin saturation levels in IASA ?
|
very high
|
|
|
how is the serum ferritin levels in IASA ?
|
increased
|
|
|
how is the FEP in IASA ?
|
increased or normal
|
|
|
in 50% of the cases what is seen in IASA?
|
chromosomal changes
|
|
|
what chomosomal changes are seen in IASA ?
|
monosomy 7, trisomy 8 , deletetion of chromosome 5,7,11,20
|
|
|
why is treatment not required in number of patients with IASA ?
|
because its non progressive
|
|
|
what drug is usally given but does not get a response ?
|
pyridoxine
|
|
|
when a patient in IASA has Hb level less than 8 what is the treatment method ?
|
transfusions
|
|
|
what myelodysplastic syndrome has the most favorable outlook ?
|
AISA
|
|
|
what is the median survival of AISA?
|
50 months
|
|
|
what is the percentage of leukemic progression ?
|
8-12%
|
|
|
what factors are related to prognosis in AISA?
|
severity of anemia, neutropenia and thrombocytopenia, presence of dysplastic features, abnormal marrow karyotype
|
|
|
what is secondary or reversible sideroblastic anemia ?
|
it is secondary to another cause
|
|
|
what are the primary causes that lead to secondary sideroblastic anemia ?
|
alcohol abuse, chloramphinecol, drugs used in the treatment of tuberculosis such isoniazid, cytotoxic drugs used in treatment of CA and other toxins
|
|
|
what other toxins lead to a special kind of sideroblatic anemia secondary to this toxin ?
|
lead poisoning
|
|
|
all drugs and toxins affect one of the two following causing sideroblastic anemia ...
|
ALA-S or heme synthase
|
|
|
what is the clinical manifestation of secondary sideroblastic anemia ?
|
infection, inflammation, neoplastic diseases, most are due to the primary cause but some would show secondary anemia clinical findings
|
|
|
how is the anemia in the laboratory findings of sec sideroblastic anemia?
|
moderate to severe
|
|
|
how does the peripheral blood characteristics in secondary sideroblastic anemia ?
|
similar to those in other acquired sideroblastic anemias
|
|
|
what is the percentage of ring sideroblasts in the peripheral blood of the secondary sideroblastic anemia ?
|
65%
|
|
|
what is shown in the alcoholic patients bone marrow ?
|
megaloblastoid changes and vacuolization of the erythrocyte precursors
|
|
|
how is the storage of iron in the marrow in alcoholic patients ?
|
it is increased
|
|
|
serum iron in SSA ?
|
increased
|
|
|
% transferin in SSA ?
|
increased
|
|
|
serum ferritin in SSA ?
|
increased
|
|
|
what is the treatment of SSA ?
|
treat the primary site cause the SSA and the administration of pyridoxine might be helpful |
