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Haematology > Hematopoiesis and its Impairments > Flashcards

Hematopoiesis and its Impairments Flashcards

1
Q

How are pluripotent stem cells defined?

A

They are defined by their ability to salvage all the elements of hematopoiesis after it has been wiped out.

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2
Q

What are BFU?

A

Burst Forming Units are early hematopoietic progenitor cell stages of erythroid and megakaryocytic cell lines characterized by their tissue culture growth pattern in which large colonies are produced.

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3
Q

What is (TPO) Thrombopoietin?

A

Platelet growth factor. Hormone produced by renal and hepatic tissue that recruits stem cells to the megakaryocyte cell maturation line and stimulates megakaryocyte mitosis and maturation in response to thrombocytopenia.

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4
Q

What is (EPO) Erythropoietin?

A

Glycoprotein hormone synthesized by the kidney in response to anoxia, the hormone acts to stimulate and regulate the bone marrow production of red blood cells.

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5
Q

Where does most lymphopoiesis occur?

A

Outside of the bone marrow. (except in early childhood)

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6
Q

“Blasts” make up what percentage of cells in the bone marrow?

A

3-4%

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7
Q

What is the first step of Granulopoiesis ?

A

Granulopoiesis begins with differentiation of “blasts” into Promyelocytes.

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8
Q

Describe promyelocyte

A
  1. Larger than Blasts
  2. Large immature nucleus with multiple nucleoli
  3. Has lots of blue primary granules in the cytoplasm
  4. Can self differentiate and replicate
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9
Q

What are some morphological differences as promyelocytes start to mature into myelocytes and metamyelocytes.

A
  1. Cells become smaller
  2. Have more prominent golgi apparatus
  3. Development of secondary (red) granules
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10
Q

What is indicative of the metamyelocyte stage?

A

Beginning of indentation of the nucleus.

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11
Q

What do metamyelocytes proliferate into?

A

Bands

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12
Q

What cells regulate the maturation of Granulocytes?

A

Bone marrow stromal cells through their secretion of G-CSF and GM-CSF.

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13
Q

What cells produce platelets?

A

Megakaryocytes.

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14
Q

Facts about Megakaryocytes?

A
  1. Large and easily spotted under low power microscope.
  2. Multinucleated
  3. Polyploid usually up to 16-32n
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15
Q

First identifiable form of erythrocyte production?

A

Pronormoblast

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16
Q

What does the Pronormoblast progress to?

A

The Basophilic Erythroblast. Stains blue due to chromatin.

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17
Q

What are the co-factors required for Heme synthesis?

A
  1. Iron
  2. Vitamin B6
  3. Succinyl CoA
  4. Glycine
  5. B12
  6. Folate
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18
Q

What are co-factors required for Globin synthesis?

A
  1. Normal Alpha globin genes
  2. Normal Beta globin genes
  3. Amino Acids (malnutrition causes anemia through this)
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19
Q

Erythrocyte generation requires DNA synthesis True or False?

A

True.

The nucleus is discarded but still necessary for maturation etc

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20
Q

Co-Factors required for DNA synthesis?

A
  1. Deoxynucleoside triphosphates
  2. Thymidine
  3. B12
  4. Folate
  5. Ribonucleotide reductase
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21
Q

What are other requirements for erythropoiesis?

A
  1. Normal Kidney

2. Normal Bone marrow environment

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22
Q

What is the form of iron best absorbed in the duodenum?

A

Fe2+ aka the Ferrous form

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23
Q

How can one increase their absorption of iron?

A

Create an acid environment i.e take vitamin c tablets with the iron etc

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24
Q

What happens to Ferrous iron once taken up?

A

Gets oxidized to ferric form

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25
Q

Why is free iron floating in the system a bad thing?

A
  1. Can catalyze reactions generating free radicals (fenton’s reaction)
  2. Would augment bacterial growth.
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26
Q

What molecule plays the major role in iron uptake?

A

Ferroportin in membrane of enterocytes.

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27
Q

How is iron transported in the blood?

A

Bound to Transferrin.

28
Q

How is iron taken up by erythroid precursors?

A

Erythroid precursors have Transferrin receptors on their surface that facilitate uptake of iron.

29
Q

Where are the body’s major stores of iron?

A
  1. In Bone marrow macrophages
  2. In the liver
  3. In the Spleen
30
Q

How is Iron stored?

A

Bound to ferritin.

31
Q

Serum iron assay measures?

A

Transferrin-bound iron (but does not assess iron stores)

32
Q

What is the “soluble Transferrin receptor” amount?

A

Measure of the small number transferrin receptor molecules that are sloughed off the storage pool cells.

33
Q

The amount of ferritin present in the serum is is proportional to what?

A

The amount of storage pool iron in the body.

34
Q

What is the most useful measure of iron metabolism available.

A

Serum Ferritin

35
Q

What is TIBC?

A

Measure of the amount of Transferrin in circulation.

36
Q

How do macrophages react to low storage pool iron?

A

Increase surface transferrin receptor molecule.

37
Q

Serum levels of soluble tranferrin receptor molecules increase when?

A

There is low storage iron.

38
Q

In iron deficiency what gets upregulated?

A

Transferrin

39
Q

The lab findings for anemia due to decreased dietary intake is identical to findings in?

A

Anemia of chronic blood loss.

40
Q

What is the expected morphology in Beta Thalassemia?

A
  1. Microcytosis
  2. Hypochromia
  3. Sometimes target cells (but not specific for Beta Thalassemia)
41
Q

What important finding can separate your microcytic anemia of Beta Thalassemia from iron deficiency?

A

NUMBER of red cells

42
Q

On what chromosome is the Beta Globin chain gene located?

A

Chromosome 11

43
Q

What is the normal structure of the Globin chain in haemoglobin?

A

A2B2 with traces of A2D2

44
Q

How many copies of the Globin gene on each chromosome?

A

6
1 “Beta Globin” gene
4 Beta Globin homologues
1 pseudogene

45
Q

What is the order in which the Globin genes are expressed?

A
  1. Epsilon
  2. G-Gamma
  3. A-Gamma
  4. Psi Beta (pseudo gene)
  5. Delta
  6. Beta
46
Q

How is Alpha2Delta2 referred to?

A

It is referred to as Hemoglobin A2.

47
Q

What are the chains present in fetal hemoglobin?

A

Alpha2Gamma2.

48
Q

How does one conform a diagnosis of Thalassemia?

A

Haemoglobin Electrophoresis

49
Q

Where is the Alpha locus (of Globin)

A

Chromosome 16

50
Q

What happens in cases of beta globin allele mutation?

A

The relative amount of Delta globin in increase giving ingreased levels on haemoglobin A2 which migrates differently from Haemoglobin A (normal haemoglobin) on electrophoresis

51
Q

What is haemoglobin F?

A

Haemoglobin made up of the Alpha2-Gamma2 chains.

52
Q

What genes of the Alpha chains are expressed during fetal development?

A

Zeta2-Zeta1

53
Q

What genes of the Alpha chains are expressed during adult life?

A

Alpha2-Alpha1

54
Q

With one defective Alpha allele one would have?

A

Alpha Thalassemia 1 trait (almost no clinical findings)

55
Q

With 2 defective Alpha alleles one would have?

A

Alpha Thalassemia 2 trait

56
Q

What are the clinical symptoms of Alpha Thalassemia 2 trait?

A
  1. Mild microcytic anemia
  2. Excess Hgb Bart’s (gamma)4 at birth
  3. Normal Hgb electrophoresis as adults
57
Q

How do you diagnose Alpha Thalassemia 2 trait?

A

PCR

58
Q

What is Haemoglobin Barts?

A

Haemoglobin containing Globin chains of $ gamma molecules

59
Q

What is Haemoglobin H disease?

A

Three alpha gene mutations. usually yeilding Beta4 molecules.

60
Q

How is HbH disease diagnosed?

A

Hb electrophoreisis

61
Q

What is Hydrops Fetalis?

A

Lethal inutero disease resulting from deletion of all 4 copies of the alpha gene.

62
Q

What drugs can inhibit DNA synthesis and cause anemia?

A

Anti-neoplastic drugs.

63
Q

What does the impairment of DNA synthesis cause in eerythroid precursors?

A

Megaloblastic Anemia

64
Q

How is epo production regulated?

A

Oxygen sensors in peritubular cells in the renal cortex sense o2 conc and stimulate the kidney to increase epo production.

65
Q

What is Hepcidin?

A

Antimicrobial peptide produced by the Liver.

66
Q

How does Hepcidin affect iron metabolism etc

A
  1. Negative regulator of intestinal iron absorption

2. Suppresses release of iron from iron stores (macrophages)

67
Q

How is Hepcidin production regulated?

A

During infection and inflammation certain cells, predominantly lymphocytes and macrophages to some extent release Il-6 to cause the liver to augment Hepcidin production.

Haematology (16 decks)

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