Strom 2

Question 1

Describe Pluripotent Stem Cells

Answer 1

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

Question 2

What two lineages do Pluripotent stem cells give rise to ?

Answer 2

Common Myeloid Progenitors and Common Lymphoid Progenitors

Question 3

What are burst forming units and colony forming units defined by ?

Answer 3

Responsiveness to growth factors.

Question 4

What stimulates erythropoietin production ?

Answer 4

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.

Question 5

What does erythropoietin do ?

Answer 5

It will stimulate progenitor cells to undergo erythropoiesis

Question 6

What kind of cell is this ?

Answer 6

Blast Cell which make up 3-4 % of the bone marrow

Question 7

What kind of cell is this ?

Answer 7

Promyelocyte which is right after the band on the granulocyte lineage line

Question 8

What kind of cell is this ? It is on the granulocyte lineage

Answer 8

Myelocyte- which can both proliferate and regenerate

Question 9

What kind of cell is this ?

Answer 9

Meta Myelocyte, It comes after the myelocyte and before the bands and neutrophils on the granulocyte differentiation pathway

Question 10

What kind of cell is this ?

Answer 10

This is a band and a neutrophil. Notice the band has a horse shoe shaped nucleus

Question 11

What growth factor stimulates production of granulocytes ?

Answer 11

G-CSF which is also Filgastrum

Question 12

What kind of cell is this ?

Answer 12

Megakaryocyte- notice the segmented polyploid nucleus

Question 13

What stimulates platelet production ?

Answer 13

Thrombopoietin. It is thought to bind platelets and when they are absent it will bind to megakaryocytes and stimulate production of platelets

Question 14

What kind of cell is this and what lineage is this a part of ?

Answer 14

This is a pronormoblast, notice the blue sytoplasm this is the basophilic staining of RNA and the hyperchromatin in the nucleus

Question 15

What kind of cell is this ?

Answer 15

Basophilic Erythroblast

Question 16

What kind of cell is this ?

Answer 16

Polychromatophillic Erythroblast

Question 17

What kind of cell is this ?

Answer 17

Normochromatic Erythroblast which will then form RETICULOCYTES and go on to form nascent RBC’s and Mature RBC’s

Question 18

Describe the difference between adult marrow and juvenile marrow

Answer 18

The Adult marrow will have lower cellularity and less fat cells

Question 19

What are the 4 requirements of red blood cell production ?

Answer 19

1. Heme Synthesis
2. Globulin Synthesis
3. DNA Synthesis
4. Regulation

Question 20

Describe Heme Synthesis, Where does it take place, and what is an essential cofactor ?

Answer 20

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

Question 21

What are the requirements for globin synthesis ?

Answer 21

Alpha and Beta Globin Genes

Question 22

In Hematopoiesis what is essential to making DNA ?

Answer 22

Thymidine which requires B12 and Folate

Question 23

What are the three components that you should be able to identify in mature marrow ?

Answer 23

Myeloid

Erythroid

Megakaryocytes

Question 24

What molecule regulates hematopoiesis ?

Answer 24

Erythropoietin which requires normal kidneys and normal stromal microenvironment

Question 25

What are the three ways to become anemic ?

Answer 25

Losing RBC's Not Making enough RBC's Both

Question 26

What will Anemia due to Iron Deficency do to RBC's and what step in hemaglobin synthesis will this interfere with ?

Answer 26

It will make the RBC's small without a lot of hemaglobin

Question 27

RBC Variation in Size ? RBC Variation in Shape ?

Answer 27

Ansicytosis Poikilocytosis

Question 28

What type of Iron is absorbed ? What reduced iron ?

Answer 28

Ferrous Fe2+ It is reduced from Ferric iron ( Fe 3+ ) by low pH and ascorbate

Question 29

What molecule transferrs iron in the serum ?

Answer 29

Transferrin

Question 30

What is the difference between plasma and serum ?

Answer 30

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

Question 31

What are the general symptoms of anemia ?

Answer 31

Shortness of breath Weakness Lethargy Palpitation and Headaches Cardiac Failure and Angina

Question 32

What are the general Signs of Anemia ?

Answer 32

Pallor of the mucous membranes Greyish skin color Tachycardia and Bounding Pulse

Question 33

Jaundice is generally what ... ?

Answer 33

Hemolytic or Megaloblastic anemia

Question 34

Leg Ulcers ?

Answer 34

Sickle Cell or Hemolytic Anemia

Question 35

Spoon Nails ?

Answer 35

Iron Deficency

Question 36

Bone Deformity ?

Answer 36

Thalasaemia Major

Question 37

What is the Mean corpusular volume ?

Answer 37

The volume of RBC's in the body

Question 38

What are the three basic types of anemia ?

Answer 38

Microcytic - smaler than normocytic Normocytic - RBC is the size of a small lymphocyte nucleus Macrocytic- larger than the lymphocyte nucleus

Question 39

MCV below 80 MCH below 27

Answer 39

Microcytic and Hypochromic anemia

Question 40

What are the MCV and MCH values for normocytic cormochromic anemia ?

Answer 40

MCV is between 80- 95 MCH is above 27

Question 41

When there is a decrease in dietary iron what happens to transferrin and the transferrin receptor ?

Answer 41

When there is a decrease in dietary iron there will be reduced serum iron, reduced iron saturation and increased Transferratin receptor

Question 42

What are the three aspects of Beta Thalassema morphology discussed in lecture ?

Answer 42

1. Microcytosis and Hypochromia 2. Frequent nontarget cells 3. It can be severe if homozygous

Question 43

What will the lab values indicate in Beta Thalisima ?

Answer 43

RBC's will be increased Hgb will be decreased Hct will be decreased MCV will be decreased

Question 44

When you sus[ect Beta Thalissima and the CBC indicates, what is the next step ?

Answer 44

Hgb electrophoresis

Question 45

Where is the beta globulin locus ?

Answer 45

Chromosome 11 1 " Beta Globin Gene" 4 Beta Globin homologues 1 Psudogene

Question 46

What will the globulin defect be in the Beta Thal ?

Question 47

Where is the alpha chain locus ?

Answer 47

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

Question 48

What is the alpha thal -1 trait ?

Answer 48

When you only have the recessive deletion in one of the alpha thal genes and there is no abnormal phenotype

Question 49

What happens when you have two defective alpha thal genes ?

Answer 49

You will have the alpha thal trait which you will have mild microcytic anemia but your Hgb electrophoresis will be normal

Question 50

What happens when you have three defective alleles for Alpha thal ?

Answer 50

You will have a varying degree of microcytic anemai Hgb electrophoresis will show 15-30 % Hgb H

Question 51

If you have 4 defective alpha thal genes what will happen ?

Answer 51

You will not survive until birth, it will be bad

Question 52

Folate and B 12 are essential to what part of DNA synthesis ?

Answer 52

The syntheis of Thymidine

Question 53

What happens to hematopoiesis when DNA synthesis is inhibited ?

Answer 53

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

Question 54

What is wrong with this premature RBC ?

Answer 54

Macrocytic Anemia due to folate or B12 deficiency. Notice the abnormal nucleus

Question 55

What is the problem with these cells ?

Answer 55

Megaloblastic Anemia in the bone marrow

Question 56

What is the source of megaloblastic anemia ? What are the 4 causes ?

Answer 56

Megaloblastic anemia mainly affects the bone marrow 1. Impaired B12 uptake 2. Impaired Folate Uptake (Impaired Uptake and Impaired Absorption) 3. Drug Effects (Nucleoside Analoges ) 4. Defective Bone marrow ( Myeloplastic Syndromes )

Question 57

What mechanism could impair RBC production ?

Answer 57

Ineffective Erythropoitein

Question 58

What is Hepcidin ? What stimulates its release ?

Answer 58

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.

Question 59

What molecule releases Iron from the intestinal epithelial cells and macrophages ?

Answer 59

Ferroportin

Question 60

Characterize Anemia of chronic disease

Answer 60

Normocytic Anemia Increased Ferritin Reduced or normal Serum Iron Increassed Bone Marrow Fe stores