Hematopoiesis & Its Impairments Flashcards
What percentage of BM cells are pluripotent stem cells?
1 in 20 million
What receptors do pluripotent stem cells have on their surface?
The have growth factor receptors, i.e. GM-CSF.
What are Burst Forming Units (BFU) and Colony Forming Units (CFU)?
They are the precursors to Red Blood Cells, from Common myeloid progenitor cells.
What can we normally see microscopically in the bone marrow? Percentages?
Erythropoiesis (20-30%)
Myelopoiesis (60-70%)
Thrombopoiesis
What is the order of differentiation of granulocyte precursors?
Blasts - Promyelocytes - Myelocytes - Metamyelocytes - Bands and Neutrophils
What mnemonic can be used to remember the differentiation order of granulocyte precursors?
Blast and Play My Metal Bands and Nothing (Else)
What is a characteristic of blast cells visibly?
They have smudgy chromatin
What is a charac of promyelocytes?
Larger than blasts with immature nucleus. Has primary blue granules.
What is a charac of myelocytes?
Small, prominent golgi with red granules.
What is a characteristic of metamyelocyte?
Nucleus beings to indent
At what two stages of granulocyte development can we regulate maturation with G-CSF?
Between Blasts and Promyelocytes
Between Promyelocytes and Myelocytes
What are the three end products that can form from blast cells?
Bands and Neutrophils
Megakaryocytes
Normochromic Erythroblasts
What do megakaryocytes make?
Platelets
What is the prominent characteristic of megakaryocytes?
They are more segmented than neutrophils. Also, they are polyploidy.
Explain the regulation of thrombopoeisis.
The liver produces a constant amount of TPO. In normal people, this binds to platelets and megakaryocytes (producing more platelets). In thrombocytopenia, more able to bind to megakaryocytes , leading to increased thrombopoeisis.
What are the stages of development to erythroblasts from blasts?
Blast to pronormoblast to basophilic erythroblast to polychromatophilic erythroblast to normochromic erythroblast.
What is the mnemonic to remember the development of erythroblasts?
Bored Princes Bump Plenty of Nights
What are characteristics of pronormoblasts?
Large with dark blue cytoplasm
What are characteristics of basophilic erythroblasts?
Smaller Nucleus with blue nucleus
What are characteristics of polychromatophilic erythroblasts?
Grey cytoplasm
What must normochromic erythroblasts do before they become mature?
They must extrude their nucleii.
Visually compare the BM of someone age 5 and age 35
Age 5 has 80-90% cellularity
Age 35 has 40% cellularity
Has increasing amounts of fatty deposits.
What does heme synthesis require?
Iron, B6, Succinyl CoA, Glycine (B12 and Folate)
What does globin synthesis require?
Normal Globin Genes, Amino Acids
What does DNA synthesis require?
Deoxynucleoside Triphosphates Ribonucelotide Reductase (which required Thymidine which requires B12 and Folate)
What are the three ways to become anemic?
Losing red cells
Not making enough red cells
Both
What ways do we describe cells that are iron deficient?
Microcytosis, Hypochromia, Anisocytosis, Poikilocytosis
When giving someone an iron supplement, what is a good co-administration to recommend that they take as well?
Vitamin C, which reduces Dietary Ferric Iron to Ferrous Iron (absorbable).
Explain the overall iron uptake process?
Dietary Ferric Iron in the GI tract is reduced to Ferrous Iron by Vitamin C or low pH. Then, it’s transported into the plasma. Once here, it’s oxidized to Ferric Iron again, where it becomes bound to transferrin. Organs possess transferrin receptors, allowing the iron to brought into cells.
Why is the transferrin important in the plasma?
Prevents free iron from making superoxides
What is serum ferritin?
Safely stored iron
What is serum iron?
The amount of iron that is bound to transferrin in the plasma
What levels change during iron deficiency?
Reduced serum iron
Reduced iron saturation
Increased soluble transferrin receptor (allowing as much iron uptake as possible)
Transferrin will be upregulated
What is the TIBC?
Total Iron Binding Capacity. The blood’s ability to bind iron to transferrin. Functions as an indirect measure of transferrin levels (which is more expensive to directly measure)
In iron deficiency how do macrophages in the spleen and liver assist?
They contain ferritin, which they release into the plasma. At this point, the iron is available to be brought into the bone marrow macrophages to be used as red cell precursors.
What are characteristics of beta thalassemia?
Microcytic, Hypochromic, frequent target cells, normal or increased numbers of red blood cells.
What CBC values change in Beta Thalassemia?
RBC goes up
Hg, Hct, and MCV go down
What is the beta gene located?
On chromosome 11, with 6 total copies
What is hemoglobin a?
alpha2 beta2
What is hemoglobin a2?
alpha2 delta 2
What is fetal hemoglobin?
alpha2 gamma2
Where the gene locus for alpha globin?
On chrom 16, with 4 fxnal copies (harder to knock out)
What area has a high rate of alpha thalassemia with one defective allele
SE asians
1 Defective allele in alpha thalassemia leads to what?
Almost nothing
2 defective alpha allels leads to what?
mild microcytic anemia, xs hg gamma4 at birth. 3% of african americans
3 defective alpha alleles?
hb H disease, variable degree of microcytic anemia
Four defective alpha allels?
you’re dead, common in SE asia
What is the significance of comparing nuclear and cytoplasmic development in impaired dna synthesis of rbcs?
normal/enhanecd maturation of cytoplasm with reduced nuclear maturation
What causes megalobastic anemia?
Impaired b12 uptake
impaire folate uptake
drug effect
intrinsic bm dysfunction
Is delayed nuclear development common in megaloblastic anemias?
Yes, it’s the central feature
What comes from the spleen that is essential in causing increased erythropoeisis?
EPO
What does hepcidin do?
Impairs the release of Fe2+ to transferrin from storage .
How does IL6 regulated hepcidin?
It upregulates it’s release because iron is great food for bacteria. So IL6 works to diminish serum iron
