Hypoproliferative Anemia Application Exercises - (Harrington) Flashcards
What is this? What is biochemical abnormality might be associated with this finding?
Hypersegmented neutrophil
Due to tetrahydrofolate or vitamin B12 deficiency
Given these CBC results: (WBC 2.5K, platelets 60K, Hb 9 g/dL), which of the following is most compatible?
- Paroxysmal nocturnal hemoglobinuria
- Anemia of renal disease
- Anemia associated with pica
- Anemia of chronic disease/inflammation
- Anemia of the elderly
- Paroxysmal nocturnal hemoglobinuria
Name (2) forms of hypoproliferative anemia characterized by impaired proliferation or differentiation of stem cells
aplastic anemia
pure red cell aplasia
Name (5) forms of hypoproliferative anemia characterized by impaired proliferation/maturation of erythroid precursors (ineffective erythropoiesis)
megaloblastic anemia
anemia of renal failure
anemia of chronic disease
anemia of liver disorders
myelodysplastic syndromes
Name (3) forms of hypoproliferative anemia characterized by defective hemoglobin synthesis
iron deficiency anemia
sideroblastic anemia
thalassemias
Name (3) causes of hypoproliferative anemia characterized by marrow replacement or infiltration
hemoatopoietic tumors
metastatic tumors
granulomatous inflammation
Give two invariant lab features of all hypoproliferative anemias
anemia
low reticulocyte count
Approximately what proportion of platelets are normally stored in the spleen?
1/3
Give (5) differential diagnoses for hypersplenism
Portal hypertension
Extramedullary hematopoiesis
Leukemias/lymphomas
Myeloproliferative neoplasms
Storage disorders
Methionine sythetase requires what two cofactors?
methyl-THF and vitamin B12
Name the enzyme responsible for the conversion of folate to tetrahydrofolate.
Is this a one-step process?
Which drug blocks the action of this enzyme?
dihydrofolate reductase
No. Two-steps (both performed by DHFR)
Methotrexate (MTX)
Describe this cell
What caused this?
What disease is this associated with?
Bite cell
Mononuclear cell phagocytosis of denatured protein (Heinz bodies) in the RBC cytoplasm
G6PD deficiency
Describe the morphologic changes seen in the peripheral blood and bone marrow in megaloblastic anemia
Peripheral blood
- hypersegmented neutrophils (5 or more nuclear lobes)
- macrocytic anemia with oval macrocytes
- anisopoikilocytosis (size and shape variation)
Bone marrow
- hypercellularity
- giant bands
- nuclear to cytoplasmic dyssynchrony
Which type of cell found in the stomach secretes acid? What other important product does it secrete?
Which cell type secretes pepsin?
Parietal cells. Also secrete intrinsic factor (IF)
chief cells
In which part of the GI tract is vitamin B12 normally absorbed. What else is required?
Vitamin B12 is absorbed chiefly in the ileum, bound to IF.
Name the two deficiencies that cause megaloblastic anemia
Vitamin B12, Folate
Where do we normally get vitamin B12?
What can cause vitamin B12 deficiency?
Animal products
Causes:
- Impaired absorption (IF deficiency, ileal resection, pancreatic insufficiency)
- Increased requirement (example: pregnancy)
- Decreased intake (vegans)
- Tapeworm (diphyllobothrium latum)
If dietary B12 is eliminated, how fast does B12 deficiency develop?
What about folate?
Very slowly. Stores within the body can last for years
Folate stores deplete faster (months)
Which is normally associated with neurological issues - folate deficiency or vitamin B12 deficiency?
vitamin B12 deficiency
Define pernicious anemia
What are some typical lab findings?
Deficiency of vitamin B12 secondary to IF abnormalities (due to Ab against IF)
Labs: low B12, low reticulocyte count, auto-Ab to IF or parietal cells, elevated methylmalonic acid
Where do we normally get dietary folate?
What can cause folate deficiency?
In the setting of pregnancy, what does folate deficiency lead to?
Green veggies
Causes:
- Increased requirement (pregnancy, states of high cell turnover)
- Decreased intake (alcoholism, malnutrition)
- Defective absorption (jejunal resection)
- Folic acid antagonists
Pregnancy: neural tube defects, including spina bifida occulta, anencephaly, etc
Describe these cells
Name the disease(s) typically associated with these.
Schistocytes
Red cell fragmentation disorders: DIC, TTP/HUS, traumatic hemolysis (mechanical heart valve)
What hemoglobin concentration is considered severely low?
<7 g/dL Hb
Name (5) physiologic compensatory mechanisms seen in the setting of anemia
Increased 2,3-DPG (increase unloading in tissues)
Shunting
Increased cardiac output
Increased respiratory rate
Increased red cell production
Give the differential diagnosis for microcytic, hypochromatic anemia (3 diseases)
Iron deficiency anemia (IDA)
thalassemias
Anemia of chronic disease (ACD)
Name some causes of iron deficiency
Dietary lack (i.e. milk-fed infants)
Impaired absorption
Increased requirement
Chronic blood loss (GI, menstrual bleeding)
Describe the process by which heme iron is absorbed into the blood
- heme iron in the intestinal lumen is transported through the cell membrane by the heme transporter
- heme iron is transferred to mucosal ferritin
- The ferroportin-1 channel transfers ferritin-bound iron (Fe2+) through the basolateral surface of the cell, where it is converted to Fe3+ by hephaestin
- Fe3+ is bound and transported by plasma transferrin
Describe the process by which non-heme iron is absorbed into the blood
- Non-heme iron (Fe3+) in the intestinal lumen is converted to Fe2+ by duodenal cytochrome C
- Fe3+ enters the cell via the DMT1 transporter and is bound by mucosal ferritin
- Fe2+ leaves the basolateral face of the endothelium via Ferroportin 1
- Fe2+ is converted to Fe3+ via hephaestin (basolateral surface of endothelial cell)
- Fe3+ is bound by plasma transferrin
What enzyme is secreted by the liver in response to elevated iron?
What specifically does it block?
Hepcidin
Blocks ferroportin, the Fe2+ transporter located on the basolateral surface of the duodenal epithelial cells
What is the most sensitive assay for iron deficiency anemia?
What is a relatively insensitive assay for IDA?
Serum ferritin - very high sensitivity and specificity
Serum iron
What is total iron binding capacity (TIBC)?
Reflects the amount of protein available to bind iron in the blood - essentially equivalent to transferrin concentration
How is % iron saturation calculated?
% iron saturation = serum iron / TIBC
For IDA, describe each of the follow as increased, decreased, or no change:
- Reticulocytosis
- Marrow storage iron
- Sideroblastic iron
- Serum ferritin
- Serum iron
- TIBC
- % iron saturation
- decreased
- decreased
- decreased
- decreased
- decreased
- increased
- decreased
For IDA, describe each of the follow as increased, decreased, or no change:
- Reticulocytosis
- Marrow storage iron
- Sideroblastic iron
- Serum ferritin
- Serum iron
- TIBC
- % iron saturation
- decreased
- increased
- decreased
- increased
- decreased
- no change / decreased
- no change / increased
What is the most common anemia in hospitalized patients?
How severe is the anemia (generally)?
What are its major clinical associations?
What is the general mechanism behind the anemia?
Anemia of chronic disease (ACD)
usually mild to moderate
Clinical associations: chronic infections, immune dysfunction disorders, neoplastic disorders
Heptcidin-mediated (acute phase reactant) block in iron transport from macrophages into erythroid precursors.
Name (4) major physiologic responses to inflammatory stimulus that leads to ACD
All due to activated monocytes and T-cells (INF-gamma, TNF-alpha, IL-1, IL-6)
- Increased hepatic synthesis of hepcidin
- inhibited EPO release -> decreased erythropoiesis
- Direct inhibition of erythroid proliferation
- Augmented hematophagocytosis
Is ACD microcytic, normocytic, or macrocytic?
normocytic (80%) or microcytic (20%)
What is the treatment for ACD?
treatment of underlying disorder
EPO or iron therapy
What is anemia or renal failure?
Decreased EPO production due to kidney damage
Describe pure red cell aplasia
selective abscence of erythroid precursors
often associated with thymic hyperplasia, thymomas, autoimmune disorders, drugs, LGLL
What is myelophthisic anemia?
Anemia secondary to bone marrow infiltration by metastatic carcinoma
Leukoerythroblastic reaction with teardrop cells may be observed
