Strom 2 Flashcards
Describe Pluripotent Stem Cells
They are rare cells found in the bone marrow ( 1 in 20 million) They are difficult to identify clearly by morphology and express receptors for key growth factors
What two lineages do Pluripotent stem cells give rise to ?
Common Myeloid Progenitors and Common Lymphoid Progenitors
What are burst forming units and colony forming units defined by ?
Responsiveness to growth factors.
What stimulates erythropoietin production ?
Hypoxia Inducing Factor Alpha and Beta. The erythropoietin gene contains receptors for this factor and will be upregulated in conditions of hypoxia. Thus in anemiaErythropoietin production will be increased.
What does erythropoietin do ?
It will stimulate progenitor cells to undergo erythropoiesis
What kind of cell is this ?
Blast Cell which make up 3-4 % of the bone marrow
What kind of cell is this ?
Promyelocyte which is right after the band on the granulocyte lineage line
What kind of cell is this ? It is on the granulocyte lineage
Myelocyte- which can both proliferate and regenerate
What kind of cell is this ?
Meta Myelocyte, It comes after the myelocyte and before the bands and neutrophils on the granulocyte differentiation pathway
What kind of cell is this ?
This is a band and a neutrophil. Notice the band has a horse shoe shaped nucleus
What growth factor stimulates production of granulocytes ?
G-CSF which is also Filgastrum
What kind of cell is this ?
Megakaryocyte- notice the segmented polyploid nucleus
What stimulates platelet production ?
Thrombopoietin. It is thought to bind platelets and when they are absent it will bind to megakaryocytes and stimulate production of platelets
What kind of cell is this and what lineage is this a part of ?
This is a pronormoblast, notice the blue sytoplasm this is the basophilic staining of RNA and the hyperchromatin in the nucleus
What kind of cell is this ?
Basophilic Erythroblast
What kind of cell is this ?
Polychromatophillic Erythroblast
What kind of cell is this ?
Normochromatic Erythroblast which will then form RETICULOCYTES and go on to form nascent RBC’s and Mature RBC’s
Describe the difference between adult marrow and juvenile marrow
The Adult marrow will have lower cellularity and less fat cells
What are the 4 requirements of red blood cell production ?
- Heme Synthesis
- Globulin Synthesis
- DNA Synthesis
- Regulation
Describe Heme Synthesis, Where does it take place, and what is an essential cofactor ?
Heme Synthesis takes place in the mitochondria and the rate limiting step is the condensation of glycine and succinyl CoA under the action of the key rate limiting enzyme ALA.
Vitamin B6 is a cofactor for the rate limiting enzyme
What are the requirements for globin synthesis ?
Alpha and Beta Globin Genes
In Hematopoiesis what is essential to making DNA ?
Thymidine which requires B12 and Folate
What are the three components that you should be able to identify in mature marrow ?
Myeloid
Erythroid
Megakaryocytes
What molecule regulates hematopoiesis ?
Erythropoietin which requires normal kidneys and normal stromal microenvironment
What are the three ways to become anemic ?
Losing RBC’s
Not Making enough RBC’s
Both
What will Anemia due to Iron Deficency do to RBC’s and what step in hemaglobin synthesis will this interfere with ?
It will make the RBC’s small without a lot of hemaglobin
RBC Variation in Size ?
RBC Variation in Shape ?
Ansicytosis
Poikilocytosis
What type of Iron is absorbed ?
What reduced iron ?
Ferrous Fe2+
It is reduced from Ferric iron ( Fe 3+ ) by low pH and ascorbate
What molecule transferrs iron in the serum ?
Transferrin
What is the difference between plasma and serum ?
Plasma has been anticoagulated and then spun in a centrifuge and serum has been allowed to clot and then the liquid portion was taken off
What are the general symptoms of anemia ?
Shortness of breath
Weakness
Lethargy
Palpitation and Headaches
Cardiac Failure and Angina
What are the general Signs of Anemia ?
Pallor of the mucous membranes
Greyish skin color
Tachycardia and Bounding Pulse
Jaundice is generally what … ?
Hemolytic or Megaloblastic anemia
Leg Ulcers ?
Sickle Cell or Hemolytic Anemia
Spoon Nails ?
Iron Deficency
Bone Deformity ?
Thalasaemia Major
What is the Mean corpusular volume ?
The volume of RBC’s in the body
What are the three basic types of anemia ?
Microcytic - smaler than normocytic
Normocytic - RBC is the size of a small lymphocyte nucleus
Macrocytic- larger than the lymphocyte nucleus
MCV below 80
MCH below 27
Microcytic and Hypochromic anemia
What are the MCV and MCH values for normocytic cormochromic anemia ?
MCV is between 80- 95
MCH is above 27
When there is a decrease in dietary iron what happens to transferrin and the transferrin receptor ?
When there is a decrease in dietary iron there will be reduced serum iron, reduced iron saturation and increased Transferratin receptor
What are the three aspects of Beta Thalassema morphology discussed in lecture ?
- Microcytosis and Hypochromia
- Frequent nontarget cells
- It can be severe if homozygous
What will the lab values indicate in Beta Thalisima ?
RBC’s will be increased
Hgb will be decreased
Hct will be decreased
MCV will be decreased
When you sus[ect Beta Thalissima and the CBC indicates, what is the next step ?
Hgb electrophoresis
Where is the beta globulin locus ?
Chromosome 11
1 “ Beta Globin Gene”
4 Beta Globin homologues
1 Psudogene
What will the globulin defect be in the Beta Thal ?
Where is the alpha chain locus ?
There are two adult alpha globin genes that are both located on chromosome 16
We all have two copies of chromosome 16 and therefore have 4 genes controlling alpha thal
What is the alpha thal -1 trait ?
When you only have the recessive deletion in one of the alpha thal genes and there is no abnormal phenotype
What happens when you have two defective alpha thal genes ?
You will have the alpha thal trait which you will have mild microcytic anemia but your Hgb electrophoresis will be normal
What happens when you have three defective alleles for Alpha thal ?
You will have a varying degree of microcytic anemai
Hgb electrophoresis will show 15-30 % Hgb H
If you have 4 defective alpha thal genes what will happen ?
You will not survive until birth, it will be bad
Folate and B 12 are essential to what part of DNA synthesis ?
The syntheis of Thymidine
What happens to hematopoiesis when DNA synthesis is inhibited ?
Fewer cells are produced
There will be enhanced maturation of the cytoplasm
There will be impared nuclear maturation
**The impared maturation will be evident after the pro-normoblast
What is wrong with this premature RBC ?
Macrocytic Anemia due to folate or B12 deficiency. Notice the abnormal nucleus
What is the problem with these cells ?
Megaloblastic Anemia in the bone marrow
What is the source of megaloblastic anemia ?
What are the 4 causes ?
Megaloblastic anemia mainly affects the bone marrow
- Impaired B12 uptake
- Impaired Folate Uptake (Impaired Uptake and Impaired Absorption)
- Drug Effects (Nucleoside Analoges )
- Defective Bone marrow ( Myeloplastic Syndromes )
What mechanism could impair RBC production ?
Ineffective Erythropoitein
What is Hepcidin ?
What stimulates its release ?
It inhibits Iron release from macrophages and absorption of intestinal epithelial cells by its interaction with the transmembrane iron exporter FERROPORTIN.
Bone morphogenic protein, ferroportin, hemojuvuelin, IL-6, transferritin, transcription of Smad-4.
What molecule releases Iron from the intestinal epithelial cells and macrophages ?
Ferroportin
Characterize Anemia of chronic disease
Normocytic Anemia
Increased Ferritin
Reduced or normal Serum Iron
Increassed Bone Marrow Fe stores
