• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
Front

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

image

PLAY BUTTON

image

PLAY BUTTON

image

Progress

1/39

Click to flip

Card Range To Study

through

39 Cards in this Set

  • Front
  • Back
What is the source of all blood cell lineages?
Hematopoietic stem cells
What are the two key features of hematopoietic stem cells?
Self renewal

Generation of lineage-committed progenitor cells
How do hematopoietic stem cells differ from progenitor cells?
HSCs
- Relatively quiescent

Progenitor cells
- Highly proliferative
- Lineage-committed
What is Pancytopenia?
Reduction in blood counts of all three lineages:
- WBC (leukopenia)
- RBC (anemia)
- Platelets (thrombocytopenia)
What are are clinical manifestations of leukopenia, anemia, and thrombocytopenia?
Leukopenia:
- Recurrent, severe, or unusual infection

Anemia:
- Fatigue
- Dyspnea
- Pallor

Thrombocytopenia
- Bruising
- Bleeding
From where is bone marrow usually obtained?
Superior iliac crest
What is bone marrow aspirate and what is its clinical usage?
Semi-liquid bone marrow

Used to investigate state of bone marrow through smear and microscopy
What is bone marrow biopsy and what is its clinical usage?
Cylindrical piece of bone marrow

Used to investigate state of bone marrow through immunocytochemistry
What is Aplastic Anemia and what causes it?
Pancytopenia

Bone marrow aplasia

Caused by deficiency of HSCs from:
- Intrinsic defects
- Immune reaction against HSCs
What are the primary and secondary causes of Aplastic Anemia?
Primary
- Congenital
- Acquired

Secondary
- Ionizing radiation
- Chemicals
- Viruses
- Drugs
What type of anemia is Fanconi Anemia?
Aplastic anemia
- Congenital
What type of anemia is Dyskeratosis Congenita?
Aplastic anemia
- Congenital
What kinds of drugs cause aplastic anemia?
Predictable
- Cytotoxic chemotherapy
- Chloramphenicol

Idiosyncratic
- NSAIDs
- Antibiotics
- Gold
What is the most common type of aplastic anemia?
Idiopathic aplastic anemia
How is the immune system involved in aplastic anemia?
Lymphocytes inhibit hematopoiesis of bone marrow

CD8+ T cells present
How are immune conditions in aplastic anemia treated?
Immunosuppressive therapy
What is the underlying cause of aplastic anemia?
Immune suppression
How does paroxysmal nocturnal hemogloboinurea relate to aplastic anemia?
PNH arises in patients with AA being treated with immunosuppressive therapy
What is the cause of paroxysmal nocturnal hemoglobinurea?
Grannulocytes lack CD16 and CD66 antigens due to a loss of PIG-A gene on HSCs
What leads to cell lysis in paroxysmal nocturnal hemoglobinurea?
Mutation in PIG-A causes lack of cell surface receptors:
- CD55
- CD59

Reduced inhibition of complement activation by CD55/CD59
What are clinical manifestations of paroxysmal nocturnal hemoglobinuria?
Acquired hemolytic anemia

Pancytopenia that may progress to:
- Aplastic anemia
- Myelodysplasia
- Acute leukemia

Hypercoagulable state
How is paroxysmal nocturnal hemoglobinuria treated?
Supportive:
- Folic acid
- Transfusions
- Antibiotics: Eculizumab binds C5 and inhibits complement activation
- Stem cell transplantation


Immunosuppression (if aplastic anemia)
What is normal MCV?
80-95 fL
What are the types of macrocytic anemias?
Megaloblastic anemia

Non-megaloblastic anemia
How does megaloblastic anemia differ from non-megaloblastic anemia?
Megaloblastic
- Abnormal nuclear-cytoplasmic asynchrony (delayed nuclear maturation)
What causes megaloblastic anemias?
Deficiency or abnormal metabolism of:
- B12
- Folate

Congenital or acquired defects in DNA synthesis
Where is vitamin B12 found?
Synthesized by microorganisms
- Internal bacteria
- Eating animals
- Eating food w/bacteria

Meat
Liver
Fish
Dairy
How is vitamin B12 absorbed (mechanism)?
1. B12 binds glycoprotein Intrinsic Factor (IF) from gastric parietal cells

2. B12-IF complex binds receptor in distal ileum and undergoes endocytosis
How is vitamin B12 transported?
Binds transcobalamin (TC) which delivers B12 to tissues
How is vitamin B12 found in the plasma and what is the limitation of this?
Bound to haptocorrin
- Cannot deliver to bone marrow
What are the major biochemical functions of vitamin B12?
Methyl-B12 is a cofactor for methionine synthase to make methionine from homocysteine

Deoxyadenosyl B12 (ado-B12) aids in the conversion of methylmalonyl CoA to succinyl CoA
How can you investigate B12 levels?
Plasma level of B12

Plasma levels of
- Homocysteine
- Methylmalonyl CoA
How is folic acid absorbed and transported(mechanism)?
1. Folic acid binds enterocyte folate receptors

2. Folates converted to methyl THF (plasma)

3. Methyl THF converted to THF via B12 (cells)

4. THF converted to THF polyglutamate (cells)
What role do folates play in DNA synthesis?
THF polyglutamate goes to 5,10 methylene THF polyglutamate

5,10 methylene THF polyglutamate converts dUMP to dTMP
What are clinical manifestations of megaloblastic anemias?
Pancytopenia

Ineffective erythropoiesis

Neuropathy
- Subacute combined degeneration of spinal cord (only B12 deficiency)

Neural tube defects

Sterility
What can cause vitamin B12 deficiency?
Vegan diet

Gastric defects
- Pernicious anemia
- Surgical
- Congenitally abnormal IF

Intestinal defects
What is pernicious anemia?
Destruction of gastric mucosa

Lymphoid infiltrate

Intestinal metaplasia

Achlorhydria
What can cause folate deficiency?
Nutritional (alcoholism)

Malabsorption

Increased utilization
- Pregnancy
- Lactation

Pathologic excess utilizsation
- Hemolytic anemia
- Cancer
- Inflammatory diseases

Drugs
- Anticonvulsants
- Sulfa
How does treatment of megaloblastic anemia differ between folate and B12 deficiencies?
Folate given may ameliorate hematologic symptoms but neurologic findings will progress until B12 is administered