Hematopoiesis Flashcards
T or F. Hematopoiesis is regulated at both levels of differentiation and cell division.
T
How is a pluripotent stem cell defined?
By its ability to salvage all the elements of hematopoiesis after it has been wiped out by irradiation or chemotherapy.
How can pluripotent stem cells be identified?
Characteristic cell surface markers (CD34+ CD38-). Cannot be identified by morphology.
T or F. Pluripotent stem cells are common.
F. <1 in 20 million.
T or F. Pluripotent stem cells express receptors for key growth factors.
T
T or F. Pluripotent stem cells are critical for bone marrow transplants and gene therapy methods.
T
What does BFU stand for?
Burst Forming Units
What does CFU stand for?
Colony Forming Units
BFU and CFU are currently defined by their responsiveness to what?
A handful of key known growth factors.
What are the 4 key growth factors in hematopoiesis?
- TPO
- EPO
- G-CSF
- GM-CSF
What are the 5 cells in the morphologic maturation of granulocyte precursors?
- Blast
- Promyelocyte
- Myelocyte
- Metamyelocyte
- Bands and Neutrophils
What is the key regulator of granulopoiesis?
G-CSF
What are the 3 ways in which disease states can affect granulopoiesis?
- Increase in overall numbers
- Shifted left or right
- Maturation arrest (blocked part way through)
What cell is responsible for platelet production?
Megakaryocytes
What is special about megakaryocytes?
They are polyploid. Their nuclei have divided multiple times, so instead of being diploid (2n) they contain an average of 16-32 haploid genomes.
How do megakaryocytes make platelets?
They extend snake-like tubes called proplatelets into fenestrated bone marrow blood vessels (sinuses). Mature platelets are shed off one at a time from the ends of proplatelets.
What is the major regulator of thrombopoiesis?
TPO (thrombopoietin)
T or F. TPO is synthesized at a constant rate in the liver.
T
What cells can TPO bind to?
Both platelets and megakaryocytes.
What happens when TPO binds to megakaryocytes?
Stimulates platelet production from immature precursors and mature megakaryocytes.
What allows more TPO to bind to megakaryocytes thus stimulating thrombopoiesis?
Low platelet count.
What are the 5 cells in erythryopoiesis?
- Blasts
- Pronormoblasts
- Basophilic erthyroblasts
- Polychromatophilic erythroblasts
- Normochromic erythroblasts
How many cell divisions are there in erythropoiesis?
5
Nascent red cells are known as what?
Reticulocytes (polychromasia)
As a patient ages, the cellularity of the bone marrow does what?
Declines
What are the 4 requirements for red cell production?
- Heme synthesis
- Globin synthesis
- DNA synthesis
- Regulation
What are the 4 requirements for heme synthesis?
- Iron
- B6
- Succinyl CoA
- Glycine (which requires B12 and folate)
What are the 2 requirements for globin synthesis?
- Normal globin genes (alpha and beta)
2. Amino acids
What 2 things can cause problems with globin production?
- Malnutrition
2. Gene mutations (more common in ‘Merica)
T or F. The nucleus must be replicated several times in red cell production.
T
What is required in DNA synthesis in red cell production?
Adequate nutrition and deoxynucleoside triphosphates (which requires ribonucleotide reductase and thymidine). Thymidine requires B12 and folate.
What hormone regulates red cell production?
EPO (erythropoietin)
Where is EPO produced?
Kidneys
What 2 things are required for EPO?
- Normal kidneys
2. Normal bone marrow micro-environment
Is anemia a diagnosis?
No. It is a labratory finding. It remains undiagnosed until you find a cause for it.
What are the 3 ways in which a patient can become anemic?
- Losing red cells
- Not making enough red cells
- Both
What is the morphology of an anemic patient’s red blood cells?
Small without much hemoglobin. Microcytosis=small red cells. Hypochromic=loss of color bc of low hemoglobin.
Lots of variation in size and shape. Anisocytosis=varying size. Poikilocytosis=varying shape.
In regards to anemic red blood cells on a peripheral blood smear, what is the rule of thumb for the area of central pallor?
If the diameter of the enlarged central pallor area is greater than 1/3 of the red cell’s diamter, the cell is hypochromic aka lacking hemoglobin.
What is another characteristic (besides microcytic hypochromic) of anemic red cells?
Lots of variation in size and shape. Anisocytosis=varying size. Poikilocytosis=varying shape.
What form is dietary iron in?
Ferric (Fe3+). Must be reducted to ferrous (Fe2+) in the stomach before it can be taken up in the small bowel.
What 2 things are required for dietary iron to be reduced from Fe3+ to Fe2+?
- Low pH
2. Ascorbate
What molecule handles the transport of iron in the plasma?
Transferrin
What oxidizes ferrous iron in the plasma to its ferric state so it can be bound to transferrin?
Serum oxidases
Why would free iron in the plasma be a bad thing?
- Augment bacterial growth
2. Catalyze formation of superoxide radicals from oxygen
What are the 2 fates of iron bound to transferrin?
- Transferred to red cell precursors in the BM via transferrin receptor
- Transferred to ferritin for the iron storage pool
Where is the storage pool of iron located?
Bound to ferritin in macrophages located in the BM, liver, and spleen.