3 - Anemia Flashcards
When talking about anemias, “cytic” refers to ____ and “chromic” refers to _____
cell size
hemoglobin content
Microcytic-hypochromic anemias are caused by:
disorders of hemoglobin synthesis (usually iron deficiency)
macrocytic anemias are usually caused by:
abnormal maturation in the bon marrow
Why do some patients with anemia become febrile?
release of leukocyte pyrogens from ischemic tissues
Describe the CBC of a post-hemorrhagic patient (minor hemorrhage) after 24 hours
decreased hematocrit as plasma is replaced by fluid and electrolytes from tissues/interstitium
rapid elevation of circulating neutrophils and platelets
increase in immature circulating RBCs
Megaloblastic (macrocytic) anemias are the result of _____
diminished erythropoiesis due to impaired DNA synthesis
What are the two causes of megaloblastic anemia?
Folate Deficiency
Vitamin B12 Deficiency
Why do megaloblastic anemias cause large RBCs?
They have a very difficult time making DNA, but no problem making RNA
This means the nucleus doesn’t mature at the same rate as the rest of the cell
When the cell reaches a size that would usually spark cell division, the nucleus isn’t mature enough to do so
So it keeps growing until the nucleus matures, resulting in a larger cell
Why do megaloblastic cells lead to anemia?
The large cells get killed off much more quickly in the circulation
Individuals with pernicious anemia commonly have autoantibodies against:
gastric H-K ATPase
the major protein constituent of parietal cells
What are the hallmark s/s of megaloblastic anemia?
classic anemia (weakness, fatigue, weight loss)
Also beefy red tongue “atrophic glossitis”
Sallow skin (pallor and icterus)
Why is folate deficiency caused by malabsorption a vicious cycle?
Malabsorption from impaired mucosa causes Folate deficiency, which is integral to intestinal mucosal proliferation
Microcytic-hypochromic anemias are characterized by blood cells that are:
abnormally small with abnormally low amounts of Hgb
What percentage of ingested iron is absorbed?
10-15%
Who is at highest risk for Iron Deficiency Anemia (IDA)?
Black females living in urban poverty
A blood loss of _____ ml/day is required to cause IDA
only 2-4 ml
What are the most common causes of IDA in developed nations?
Pregnancy
Chronic blood loss
Exposure to ____ and ____ can cause IDA. Why?
Pb and Cd
Increased competition for absorption
In addition to the s/s of anemia, individuals with IDA may also manifest:
gastritis
neuromuscular changes
irritability
headache
numbness/tingling/parasthesia
How can you differentiate IDA from anemia of chronic disease?
by comparing the ratio of serum transferrin receptors to ferritin levels
If the ratio is high, that means the body is upregulating receptors due to a lack of ferritin
If it’s unchanged, there is enough iron in the body
Describe the morphology of anemia of chronic disease
begins as normocytic/normochromic, but will eventually become microcytic/hypochromic
What causes Anemia of Chronic Disease?
- decreased erythrocyte lifespan
- suppressed production of erythropoietin
- ineffective bone marrow response to erythropoietin
- altered iron metabolism and iron sequestration within macrophages
Aplastic anemia would cause a reduction in which cell type?
All of them: pancytopenia
What percentage of aplastic anemias or idiopathic?
75%
Caused by autoimmune disease
What is Pure Red Cell Aplasia?
Form of aplastic anemia where only erythrocytes are affected
What is Fanconi anemia?
aplastic anemia caused by a defect in bone marrow DNA repair genes
Which cells appear to be the culprit in aplastic anemia?
Cytotoxic T cells
Where do extravascular and intravascular hemolysis occur?
Which is more common?
Extra: within lymphoid phagocytes
Intra: in the blood
Extra is more common
Name two congenital hemolytic anemias caused by defective RBC membranes
Hereditary spherocytosis
paroxysmal nocturnal hemoglobinuria
Which hemolytic anemia results from altered enzymatic pathways?
G-6-PD deficiency
What are the three types of autoimmune hemolytic anemias?
- Warm reactive antibody type
- Cold agglutinin type
- Cold hemolysis type
Based on the optimal temperature at which the antibody binds to erythrocytes
What causes Warm autoimmune hemolytic anemia?
IgG binds to erythrocytes at body temperature
The erythrocytes then bind to monocytes and macrophages and are phagocytized
What causes cold agglutinin hemolytic anemia?
IgM antibodies bind to erythrocytes at cold temperatures
usually manifests during the recovery phase from a major illness like mono
severe but self-limiting
When these people are out in the cold, IgM binds to erythrocytes in finger/toes/ears etc and causes acrocyanosis or gangrene
IgM falls off again once the body rewarms
What causes cold hemolysin hemolytic anemia?
exposure to cold initiates acute and severe intravascular hemolysis that results in hemoglobinuria
Mediated by IgG
What are characteristics of drugs that cause hemolytic anemia?
Called the hapten model:
Usually LMW
functions as a hapten
binds to proteins on the surface of erythrocytes
More than 90% of hapten model hemolytic anemias are due to which drug?
cephalosporins
What are the three models of Drug-induced hemolytic anemia?
Give an example of each
- Hapten (Penicillin)
- Immune complex formation (quinidine)
- Autoimmune (Alpha methyldopa)
What is the most common cause of aplastic crisis?
human parvovirus B19
What is the first and second line treatment for hemolytic anemias?
First: corticosteroids
Second: splenectomy and administration of rituximab
What is rituximab?
monoclonal antibody directed against the CD20 antigen
specifically depletes or suppresses B cells throughout the body
Why is folate often given to people with a hemolytic anemia?
to prevent secondary megaloblastic anemia due to increased folate demand
List the Chronic Myeloproliferative Disorders
Polycythemia Vera
Essential thrombocytosis
chronic idiopathic myelofibrosis
chronic myeloid leukemia
chronic neutrophilic leukemia
chronic eosinophilic leukemia
All chronic myeloproliferative disorders result from:
abnormal regulation of the multipotent hematopoietic stem cells
What are the major characteristics shared by all chronic myeloproliferative disorders?
- involvement of a hematopoietic stem cell
- overproduction of one thing
- Dominance of one progenitor cells
- marrow hypercellularity or fibrosis
- cytogenic abnormalities
- predisposition to thrombus and hemorrhage
- spontaneous transformation to acute leukemia
What causes polycythemia vera
chronic, neoplastic, nonmalignant
clonal proliferation of RBCs in the bone marrow independent of erythropoietin
More than 95% of people with PV have a mutation in which gene?
Janus Kinase 2 Gene
it’s a cytoplasmic tyrosine kinase
Gets rid of the self-regulatory function of JAK2, meaning the erythropoietin receptor is pretty much always active regardless of the presence of erythropoietin
Almost every individual with polycythemia presents with:
splenomegaly and abdominal pain
Does polycythemia increase the risk of bleeding or clotting?
Mild to moderate: clotting
extreme: bleeding
What are two vascular complications associated with polycythemia?
thromboangiitis obliterans
Raynaud phenomenon
What skin symptom is caused by polycythemia?
aquagenic pruritis
Hereditary hemochromatosis causes deposition of iron in which tissues?
increased GI iron absorption leads to
tissue iron deposition (liver, pancreas, heart, joints, endocrine glands)
Individuals with HH should avoid foods containing:
iron
Vitamin C
raw shellfish
What are the clinical manifestations of HH?
fatigue, malaise, abdominal pain, arthralgias
hepatomegaly, bronzed skin, cardiac dysfunction
