1.1 Haematopoiesis and its regulation Flashcards Preview

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Flashcards in 1.1 Haematopoiesis and its regulation Deck (38):
1

What are the characteristics of haematopoietic stem cells?

Perpetual
Extensive proliferation
Self renewal
Pluripotency
Quiescence

2

What are the characteristics of progenitor cells?

Non perpetual
Limited proliferative capacity
Diminished or no self renewal
Lineage commitment
Mor actively cycling

3

What will you see for Haematopoietic Stem Cells on flow cytometery?

CD34+ CD45 RA -/low

4

Where does haemopoiesis occur at different stages of gestation?

Aorta Gonad Mesonephros (4-5 weeks)

Yolk sac (4-6 weeks)

Fetal liver (6-22 weeks)

Bone marrow (16 weeks onwards)

5

In what adult bones does haempoiesis occur?

pelvis, ribs, spine, skull and proximal parts of arm/leg bones

6

What types of blood cells arise from the CLP?

B, T and NK cells

7

What types of blood cells arise from the CMP?

platelets, RBC, mast cells, basophils, neutrophiles, eosinophils, monocytes

8

Describe the process of erythropoiesis

The kidneys detect low levels of circulating oxygen and this stimulates the production of EPO. EPO will travel to the bone marrow and stimulate precursors to make RBCs and increase the oxygen carrying capacity of the blood. This will feedback to the kidneys to stop further production of EPO

9

Describe the mechanism of the JAK/STAT pathway

A cytokine will bind to the cytokine receptor and activate the JAK protein. This causes phosphroylation of the STAT transcription factors. This results in their dimerization and translocation to teh cell nucleus. Here the STAT dimers activate transcription of specific genes

10

Describe the mechanism of the JAK/STAT pathway

A cytokine will bind to the cytokine receptor and activate the JAK protein. This causes phosphroylation of the STAT transcription factors. This results in their dimerization and translocation to teh cell nucleus. Here the STAT dimers activate transcription of specific genes

11

What regulates erythropoiesis?

Erythropoietin.

12

What is the role of erythroferrone?

Erythroferrone is released in response to increased EPO levels. This will supress the hepcidin production by the liver allowing an increased availability of iron to be used for oxygen transport

13

Describe the breakdown of RBCs

Macrophages in the bone marrow and spleen break down the RBCs into heme and then bilirubin. The bilirubin travels linked to albumin to the liver. Here the bilirubin is conjugated and secreted in the bile. In the small intestine the conjugated bilirubin is converted back into bilirubin and into urobilinogen. If it remains in the colon it is converted into stercobilin and excreted in teh feces, if it enters the plasma and is filtered by the kidney it is converted to urobilin and excreted in the urine.

14

What is the structure of the red cell membrane?

Phosopholipid bilayer with membrane proteins and a membrane skeleton

15

What forms the red cell membrane skeleton?

alpha and beta spectrin, ankyrin, protein 4.1 and actin

16

What are the two pathways for RBC energy production?

Glycolysis and antioxidant production

17

What is the pathway of granulocyte production called and what are the blood cells formed?

Granulopoiesis - neutrophils, eosinophils, monocytes, macrophages, basophils/mast cells

18

What is the role of GCSF?

stimulate the production of neutrophils - can be given therapeutically

19

What is the role of IL-6 in grabulopoiesis?

Stimulates emergency white cell production. The production of IL6 indicates an infection which will sitmulate macrophages into making an enzyme ADAM which will go to teh surface of immature immune cells and macrophages cleaving off teh IL6 receptor. This receptor wil form a complex which will travel to the bone marrow to stimulate emergency granulopoiesis

20

Describe the production of platelet formation and what is this process called?

Thrombopoiesis
TPO will go to the bone marrow causing stimulation of megakaryocytes to make platelets

21

Describe the production of platelet formation and what is this process called?

Thrombopoiesis
TPO will go to the bone marrow causing stimulation of megakaryocytes to make platelets

22

What are the processes involved in platelets forming clots?

Adhesion, activation, aggregation and formation of a haemostatic plug

23

Describe adhesions of platelets

Glycoproten Ib binds to von willebrand factor leading to the adhesion to teh subendothelium

24

Describe activation of plateleys

Adhesion triggers glycoprotein IIb/IIa activation causing irreversible binding

25

Describe aggregation of platelets

Activated GP IIb/IIa mediates aggregation of fibrinogen and VW factor

26

What do you need for stem cells to survive?

the haemopoietic microenvironment including glial cells, neurons, MSC, endothelial cells, CEMP cells and adipocytes

27

What are the disorders of too much, too little and poor quality RBCs?

too much: polycythaemia

Too little: anaemia

Poor quality: haemaglobinopathy, RC enzymopathy, RC membrane defects

28

What are the disorders of too much, too little and poor quality white cells?

Too much: leucocytosis, leukaemia, lymphoma

Too little: leucopenia, lymphopenia

Poor quality: chronic granuloma disease

29

What are the disorders of too much, too little and poor quality platelets?

Too much: thrombocytosis/cythaemia

Too little: thrombocytopaenia

Poor quality: functional platelet disease, storage pool disease

30

What are the primary and secondary causes of polycythaemia?

Primary: bone marrow diseases

secondary: EPO mediated (bone marrow told to make too much)

31

What are the causes of true polycythaemia?

Sensitization of EPO receptor
JAK-2/CAL-R mutation in stem cell progenitor cells
Defective EPO receptor
Reduced O2 carrying capacity
Polycystic kidney disease
post transplant erythrocytosis
any hypoxic conditions

32

What are the causes of anaemia?

Defective EPO receptor
congenital conditions
B12/folate deficiency
Marrow damage (drugs, radiation)
Anaemia of chronic disease
Blood loss
premature mechanical or immune destruction of RBC
chronic kidney disease
Immune deficiency of EPO

33

What are the causes of anaemia?

Defective EPO receptor
congenital conditions
B12/folate deficiency
Marrow damage (drugs, radiation)
Anaemia of chronic disease
Blood loss
premature mechanical or immune destruction of RBC
chronic kidney disease
Immune deficiency of EPO

34

What is leukaemia?

disruption of the normal processes that regulate differentiation and development characterised by the accumulation of malignant haemopoietic precursors

35

What are the causes of reduced granulopoiesis?

Acquired mutations
stromal cell damage
increased destruction (immune, splenic)
Immunosuppressive drugs
Increased magrination
B12/folate deficiency
Infection
Drugs
Immune insult
Defective GCSF receptor
Genetic abnormalities (Downs)

36

What causes increased thrombopoiesis?

Infection and inflammation
Acquired mutations in JAK2, CALR, bcr-abl and TPOR

37

What causes reduced thrombopoiesis?

Liver diease
B12/folate deficiency
Acsuired muattions in MDS
Congenital syndromes: TARS
Immune insult
Drugs
Marrow insults (radiation)
Increased destruction (immune, mechanical, spleen)

38

What causes reduced thrombopoiesis?

Liver disease
B12/folate deficiency
Acquired mutations in MDS
Congenital syndromes: TARS
Immune insult
Drugs
Marrow insults (radiation)
Increased destruction (immune, mechanical, spleen)