Topic 16-18: Anemia and non-neoplastic hematology Flashcards
Based on general pathogenesis, there are three types of anemias. what are they?
Hemolytic anemias, blood loss anemia, and anemia due to lack of erythropoiesis.
what are the 6 types of anemias due to decreased synthesis?
- Iron deficient
- megaloblastic
- pernicious
- aplastic
- anemia of chronic disease
- myelophthisic
what are the pathogenesis possibilities for iron deficient anemia?
- chronic blood loss
- low iron intake in diet
- increased demand (due to pregnancy, childhood growth)
- malabsorption (celiac, pancreatitis, gastrectomy)
what is the morphology of RBCs with iron deficiency anemia?
microcytic hypochromic anemia
megaloblastic anemia is caused by which deficiency?
folic acid and vit B12 - both are important for DNA synthesis
what are the 3 pathomechanisms at play in megaloblastic anemia?
- cell gigantism due to the slow replication of DNA but normal speed replication of RNA and protein leading to too many organelles and RNA with less DNA.
- also: defective DNA replication stops cell division thus the cell just keeps replicating the DNA –> 4n, 8n
- DNA defects cause apoptosis, thus less blood cells reach maturity –> low numbers of large blood cells
morphology of megaloblastic anemia?
- large megaloblastic (erythroid precursors), diffuse chromatin
- RBCs are hyperchromatic (but have normal hemoglobin levels!)
- giant metamyelocytes (granulocyte precursors)
- large megakaryocytes with bilobed nuclei
- hypersegmented neutrophils
which has worse consequences, folate or B12 deficiency?
B12
folate deficiency is normally due to what?
poor diet
what is another name for B12 def? what is the pathogenesis of B12 def?
pernicious anemia or cobalamin deficiency
- poor diet (strict vegans normally)
- lack of intrinsic factor due to autoimmune gastritis (anti-parietal cell rxn)
- gastrectomy or ileal resection
- crohn’s, whipple
what is one significant symptom of B12 def that isn’t seen in the blood?
demyelination of peripheral nerves and of posterior and lateral column
what is aplastic anemia?
suppression of multipotent stem cells leading to bone marrow failure (hypocellular marrow)
pathogenesis of aplastic anemia? 5
- most are idiopathic! (viral infections, etc)
- the remaining are due to myelotoxic agents such as radiation therapy, chloramphenicol, sulfonamides
- some viral infections
- autoreactive T cells
- genetic (defect in telomerase)
anemia of chronic disease is due to what?
suppression of erythropoiesis due to chronic inflammation with infectious disease, cancer, or immune disorders
pathogenesis of anemia of chronic disease?
- high levels of hepcidin
- inflam blocks EPO production
myelophthisic anemia is what?
bone marrow failure due to infiltration of the marrow by tumor metastasis (breast, lung, prostate)
morphology of myelophthisic anemia?
teardrop RBCs, misshapen,
thrombocytopenia
mild leukocytosis and precursors in peripheral blood
anemia of blood loss can be what two types?
hemolytic and hemorrhagic
what is the difference between acute and chronic hemorrhagic blood loss?
in acute you first develop hypovolemic shock and anemia only develops a few days later
in chronic, there is iron deficient anemia
hemolysis can be what general type?
Intrinsic- inheritied hemolytic disorders
extrinsic - aquired
intravascular - RBC stress or damage (toxins, turbulance,)
extravascular - tissue macrophages in spleen or liver remove damaged cells
intravascular hemolysis is associated with what symptoms?
hemoglobinemia,
hemoglobinuria
hemosiderinuria
ATN - due to casts
jaundice
low haptoglobin,
High LDH
extravascular hemolysis is associated with what symptoms?
NOT hemoglobinuria and hemoglobinemia!!!
low haptoglobin
jaundice, bile stones
high LDH
generally in hemolytic anemia, what are common features?
-BM hyperplasia
-low RBC lifespan
- inc in erythropoiesis
in severe cases, extramedullary hematopoiesis
what are the 6 specific types of hemolytic anemia?
- hereditary spherocytosis
- sickle cell
- thalassemia
- G6PP deficiency
- mechanical trauma
- autoimmune
spherocytosis is associated with which types of abnormalities in the membrane?
- Mostly ankyrin mutations, ankyrin is part of the spectrin protein structure.
- p3 can also be mutated
morphology of sperocytosis
- spherical RBCs
- splenomegaly
- hemosiderosis
- bilestones
what type of hemolysis is spherocytosis? what is the treatment?
intra and extravascular hemolysis due to the osmotic fragility of the RBCs,
treatment is splenectomy
sickle cell anemia is a mutation where?
in the beta globin gene where a valine at aa6 is replaced with a glutamic acid
lifespan if RBC is sickle cell anemia is?
20 days due to the constant sickling and unsickling that leads to influx of calcium, irreversible sickling and hemolysis
other factors that lead to sickling
- other hemoglobins that interact with HbS (heterozygotes)
- inc HbS concentration in the RBC due to dehydration
- slow blood flow areas (spleen, bm, inflammation)
list a few consequences of HbS?
- fatty change due to hypoxia of organs (heart, liver, kidney)
- BM hyperplasia
- splenomegaly
- hemosiderosis, gallstones,
- vaso-occlusive crises
- lack of malaria
what are vaso-occlusive crises? tx how?
blood vessels is obstructed by sickled red blood cells, causing ischemic injuries
treat with hydroxy urea to inhibit DNA synthesis
- increases HbF
- decreases WBC to dec inflamm
- inc RBC size (like megaloblastic anemia, causes decreased Hemoglobin concentration)
- also creates NO, causes vasodilation
thalassemia is associated with what mutations?
decreased synthesis of alpha or beta globin chains
- alpha is 2 genes of chrom 11. mutation is a deletion of 4 areas of the genes. less common
- beta is one gene of chrom 16. there are more than 100 types of mtaitons, mostly RNA splicing
alpha thalassemia’s severity depends on what?
number of deletions
1 = silent carrier
3 = HbH. less function RBCs, some hypoxia
4= death in utero
beta thalassemia is based on beta globin allele deletions. what are the categories?
remember there are two genes and therefore 4 alleles that can be mutated.
- Beta - thal minor - asymptomatic, one bad allele
- beta - thal intermedia - inherited two alleles that cause reduced Beta chain production
- beta -thal major - inherited two alleles that cause no Beta globin chains to be produced, and two allele that has reduced production.
the causes of anemia in thalassemia is due to?
- reduced Beta synth causes poorly hemoglobinized RBCs, thus hypochromic and microcytic
- with too much alpha globin there is an aggregation that causes membrane damage
glucose-6-phosphate dehydrogenase deficiency is what?
RBC are more susceptible to oxidative damage due to abnormal glutathione synthesis (this abnormal glutathione synth is due to G6PD deficiency)
what is the mutation involved in g6pdd?
over 400 types of mutations on the X chromosome,
most common is G6PD A- in 10% of african americans that causes dec RBC half-life.
what histological feature is present in G6PD def?
heinz bodies, oxidized hemoglobin that is denatured and precipitated. will damage the membrane and cause intravascular hemolysis
Bite cells - when macrophages try to remove the heinz body and cause extravascular hemolysis
immunohemolytic anemia is what?
antibodies generated against RBCs
classified in which two categories?
warm (IgG in most parts) and cold (IgM in acral areas) antibodies
warm antibodies are generated how?
IgG antibodies generation is idiopathic (60%) in the primary case and due to B cell neoplasm, autoimmune and drugs in the secondary cases (25%)
cold antibodies are generated how?
in acute cases, they can be from mycoplasma and mononucleosis infections
in chronic, it can be due to idiopathic or b cell neoplasm
mechanical trauma also leads to anemia. this trauma can be due to what?
mostly karate chopping and bongo drumming.
less common reasons for mechanical trauma anemia:
- turbulent flow, especially with defective valve transplants
- lesions that cause RBC damage such as HUS (hemolytic uremic syndrome), cancer, DIC, SLE
non-neoplastic disorders of the WBC system can fall into 2 categories:
deficiency - leukopenia
proliferation - reactive leukocytosis or reactive lymphadenitis
leukopenia mostly occurs in which cell line?
granulocytes
due to increased destruction and decreased production
- leads to increased infections
-leukopenia is typically rare
reactive leukocytosis is associated with proliferation. what problems are associated with the different WBC proliferations?
Neutrophils - Bacterial infections
eosinophils - allergies and parasite, certain drugs
basophils - rare, usually CML
monocytes - chronic infections (TB), bacterial endocaritis, rickettsiosis, malaria, sle, IBD
lymphocytosis - chronic infections (TB), viral infections, bordatella pertussis
mononucleosis is associated with which proliferation?
reactive leukocytosis due to EBV
Mono pathogenisis
EBV infects oropharynx and spreads to lymph nodes. there it infects mature B cells by binding CD21
B cells undergo polyclonal activation and proliferation
what is a characteristic finding in the peripheral blood of a mono pt?
virus specific cd8 t cells and atypical lymphocytes
what are characteristic cells seen in the lymph nodes?
reed-sternberg cells
reactive lymphadenitis can be 2 categories
acute
-due to local infection
chronic
- follicular hyperplasia
- paracortical hyperplasia
- sinus histiocytosis
follicular hyperplasia has an activation of which cells and are normally due to what infection? generally what does it look like histologically
B cells create large follicles
- bacterial infections, but also rhematoid arthritis, toxo or HIV
histo: preserved lymph node architecture, variation of size and shape of GC, B cell zones are enlarged
paracortical hyperplasia has an activation of which cells and are normally due to what infection? generally what does it look like histologically
T cells in the parafollicular area cause proliferation of parafollicular space
- viral infections
histo: parafollicular space is large, smaller GC
sinus histiocytosis has an activation of which cells? generally what are the causes?
lymphatic sinusoid are large due to hypertrophy of endothelial lining cells and infiltration of macrophages
can be due to cancer draining lymph nodes or dust phagocytosis in the mediastinal lymph nodes
other causes of lymphadenitis: (2)
cat scratch disease and toxoplasma
