Hematopiosis Flashcards

1
Q

Primitive & definitive haemopoiesis occur where?

A

embryonic yolk sac

definitive haemopoiesis’ derives from a population
of stem cells first observed on the aorta-gonads-mesonephros
(AGM) region of the developing embryo

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2
Q

From 6 weeks until 6–7 months of fetal life, the ______ are the major haemopoietic organs and continue to
produce blood cells until about 2 weeks after birth & ______ also contribute

A

Liver & spleen
Placenta

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3
Q

The bone marrow becomes the most important afte

A

6-7 months

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4
Q

The developing cells are situated outside the bone marrow sinuses; mature
cells are released into the sinus spaces, the marrow microcirculation and so into the general circulation

A
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5
Q

What’s extramedullary haemopoiesis’

A

Production of red blood cells by the spleen and liver due to disease conditions

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6
Q

Which of an adult skeleton is capable of hemapoasis

A

Vertebrae, ribs, sternum, skull, sacrum and
pelvis, proximal ends of femur

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7
Q

Morphologically, HSCs have
the appearance of a

The are also heterogeneous

A

small or medium-sized lymphocyte

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8
Q

List the bone marrow stromal cells and they secrete ____ to form ECM

A

Messenchymal stem cells, fibroblast, macrophages, adipocyte, endothelial cells and osteoblast

Glycoprotein, collagen, glycoaminoglycan,

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9
Q

Messenchymal stem cells Together with _____ or &_______ cells, they form niches and provide some of the growth factors, adhesion molecules and cytokines which support stem cells, maintaining
their viability and reproduction.

A

osteoblasts or endothelial

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10
Q

What’s mobilization and homing of stem cells
Its enhanced by? (M)

A

Mobilization is the process by which stems cells exit the bone marrow and the cells cross the blood vessel Emdothelium and is enhanced by granulocyte colony stimulating factor.

While homing is the reverse amd depends on Chemokine gradient

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11
Q

Question: What happens during stem cell division?

A

Answer: In stem cell division, one cell replaces the stem cell (self-renewal), while the other commits to differentiation.

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12
Q

What factors influence which cell lineage a progenitor cell follows?

A

Answer: The cell lineage selection depends on both chance and external signals received by progenitor cells.

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13
Q

Which transcription factors regulate stem cell survival during hematopoiesis?

A

Answer: Transcription factors such as SCL, GATA2, and NOTCH1 play a role in stem cell survival.

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14
Q

Which transcription factors commit cells to the myeloid lineage?

A

Answer: PU.1 and the CEBP family of transcription factors are involved in myeloid lineage commitment.

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15
Q

What roles do GATA2, GATA1, and FOG1 play in hematopoiesis?

A

Answer: GATA2 initiates the process, while GATA1 and FOG1 have essential roles in erythropoietic and megakaryocytic differentiation.

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16
Q

What proteins do transcription factors induce synthesis of?

A

Answer: Transcription factors induce synthesis of proteins specific to a cell lineage. For example, erythroid-specific genes have binding motifs for GATA1

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17
Q

Question: What is the significance of binding motifs for transcription factors?

A

Answer: Binding motifs determine which genes are activated, leading to lineage-specific protein synthesis

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18
Q

How do early committed progenitors express transcription factors?

A

Answer: Early committed progenitors express low levels of transcription factors that may commit them to discrete cell lineages.

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19
Q

What are the regulators of hemopeisis

A

Transcription factor
Cell lineage selection

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20
Q

How do growth factors act?

A

Cell to cell contact
Circulate in plasma
Or ecm

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21
Q

The growth factors may cause cell proliferation,
but can also stimulate differentiation and maturation, prevent
apoptosis and affect the function of mature cells

A
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22
Q

Stromal cells are the major source of
growth factors except for _____&, 90% of which is synthesized
in the kidney, and , made largely in
the liver.

A

EPO erythropiothin
thrombopoietin (TPO)

23
Q

Which growth factors act locally on pluripotential stem cells and myeloid/lymphoid progenitors?

A

Answer: SCF, TPO, and FLT3 ligand have local effects on these cell populations.

24
Q

What is the widespread activity of Interleukin-3 (IL-3)?

A

Answer: IL-3 has activity on both lymphoid/myeloid and megakaryocyte/erythroid progenitors.

25
Q

Which growth factors enhance neutrophil and macrophage/monocyte production?

A

Answer: Granulocyte–macrophage colony-stimulating factor (GM-CSF), G-CSF, and macrophage colony-stimulating factor (M-CSF) play this role.

26
Q

What does IL-5 specifically enhance in terms of blood cell production?

A

Answer: IL-5 boosts eosinophil production.

27
Q

Which growth factor influences mast cell development?

A

Answer: KIT is involved in mast cell development.

28
Q

How do lineage-specific growth factors interact with other factors during early hematopoiesis?

A

Answer: These lineage-specific growth factors enhance the effects of SCF, FLT3-L, and IL-3 on the survival and differentiation of early hematopoietic cells.

29
Q

What’s the life span of rbc and plately

A

They have a 4-month lifespan,
whereas the smallest cells, platelets involved in haemostasis,
circulate for only 10 days

30
Q

Erythropoietin stimulates erythropoiesis by increasing
the number of progenitor cells committed to erythropoiesis which is?

A

CFU Erythroid —+ pronormoblast

31
Q

What are hypoxia-inducible factors (HIFs), and how do they relate to EPO production?

A

Answer: HIFs are proteins that stimulate EPO production during hypoxia. They also play a role in new vessel formation and transferrin receptor synthesis.

32
Q

Which transcription factor initiates erythroid differentiation from pluripotential stem cells?

A

Answer: The transcription factor GATA2 is involved in initiating erythroid differentiation.

33
Q

Which transcription factors are activated by EPO receptor stimulation?

A

Answer: GATA1 and FOG1 are activated by EPO receptor stimulation and enhance expression of erythroid-specific genes.

34
Q

What is the role of GATA1 and FOG1 in erythropoiesis?

A

Answer: They enhance expression of erythroid-specific genes, anti-apoptotic genes, and the transferrin receptor (CD71).

35
Q

Which cells have erythropoietin receptors?
Answer: Late BFUE and CFUE (erythroid progenitors) have erythropoietin receptors.

A
36
Q

What can plasma EPO levels indicate in clinical diagnosis?

A

Answer: High EPO levels are seen in anemia, except in cases of renal failure or tumor-secreted EPO. Low levels occur in severe renal disease or polycythemia vera.

37
Q

What are the glucose metabolic pathway that occur in the RB cell?

A

Embden–Meyerhof Pathway
Hexose Monophosphate (Pentose Phosphate) Shunt

38
Q

What’s Embden–Meyerhof Pathway
What’s is special functions

A

This pathway is a series of biochemical reactions where glucose is broken down to produce energy for red blood cells (RBCs)
Glucose enters the RBC from the plasma and is metabolized to lactate.

This pathway also generates NADH, which is essential for converting methemoglobin (a non-functional form of hemoglobin with ferric iron) back to functional hemoglobin with ferrous iron. About 3% of hemoglobin oxidizes daily, needing this repair process

The Luebering–Rapoport shunt, a side branch of this pathway, produces 2,3-DPG, which helps regulate how tightly hemoglobin holds onto oxygen.

39
Q

What’s Hexose Monophosphate (Pentose Phosphate) Shunt

A

This pathway handles about 10% of glucose breakdown in RBCs, focusing on protection against oxidative damage.

Process: Glucose-6-phosphate is converted through several steps to ribulose-5-phosphate.

It produces NADPH, which works with glutathione to protect cell structures, including hemoglobin and the cell membrane, from oxidative damage.

40
Q

What is the primary pathway involved in red cell metabolism?

A

Answer: The Embden–Meyerhof pathway (glycolysis) metabolizes glucose to lactate, generating ATP for energy.

41
Q

What is the function of the Luebering–Rapoport shunt in the Embden–Meyerhof pathway?

A

Answer: The shunt generates 2,3-DPG, which plays a crucial role in regulating hemoglobin’s oxygen affinity.

42
Q

What percentage of glycolysis occurs through the hexose monophosphate (pentose phosphate) shunt?

A

Answer: Approximately 10% of glycolysis occurs through this oxidative pathway.

43
Q

What is the end product of the hexose monophosphate shunt?

A

Answer: The end products are NADPH and ribulose-5-phosphate

44
Q

What components make up the red cell membrane?

A

Answer: The red cell membrane comprises a lipid bilayer, integral membrane proteins, and a membrane skeleton.

45
Q

What percentage of the red cell membrane is protein?

A

Answer: Approximately 50% of the membrane is protein.

46
Q

Where do carbohydrates occur in the red cell membrane?

What are the two main types of proteins in the red cell membrane?

A

Answer: Carbohydrates occur only on the external surface of the membrane

Answer: The two main types of proteins areperipheralandintegralproteins.

47
Q

Which protein is the most abundant in the membrane skeleton?

A

Answer: Spectrin is the most abundant protein.

48
Q

What are the two chains that make up spectrin?

A

Answer: Spectrin consists of two chains: α and β.

49
Q

What’s Methaemoglobinaemia

A

This is a clinical state in which circulating haemoglobin is
present with iron in the oxidized (Fe3+) instead of the usual
Fe2+ state. It may arise because of a hereditary deficiency of
methaemoglobin reductase or inheritance of a structurally
abnormal haemoglobin (Hb M).

50
Q

What’s the normal values for hemoglobin?

A

Males 135.0–175.0

Females 115.0–155.0
Haemoglobin (g/L)

51
Q

After puberty what hemoglobin values represent anemia?
The lower limit for infants is?

A

110g/l
140g/L

52
Q

After acute major blood loss, anaemia is not immediately
apparent because the total blood volume is reduced. It takes up to a day for the plasma volume to be replaced and so for the degree of anaemia to become apparent (see p. 385). Regeneration of red cells and haemoglobin mass takes substantially
longer. The initial clinical features of major blood loss are
therefore a result of reduction in blood volume rather than of
anaemia.

A
53
Q

Symptoms of anemia

A

Rerina hemorrhage
Lethargy
Weakness
Headache