Haematopoiesis, stem cells + bone marrow Flashcards by Jasmine Henson

Define haematopoiesis

making blood

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Define stem cells

undifferentiated cells that have the capacity to differentiate and multiply into all human cell types

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Define pluripotent stem cell

completely undifferentiated
can form any tissue

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Define haematopoietic stem cell

in bone marrow
multipotent
can differentiate into blood cells

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Where does haematopoiesis occur in the foetus?

yolk sac
liver
spleen
lymph nodes

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Where does haematopoiesis occur in babies and children?

made my all bone marrow (mainly red bone marrow)

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What happens to bone marrow as you age?

red marrow turns into yellow marrow

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Where does haematopoiesis occur in adults?

bone marrow of axial skeleton, proximal long bones + skull

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What happens with haematopoiesis in bone marrow disease?

yellow marrow can be recruited to produce blood cells again in an adult
as can liver and spleen (extramedullary haematopoiesis)
can cause hepatosplenomegaly

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Define myelofibrosis

bone marrow space occupied by fibrotic tissue
no space for blood cell production
body tries to compensate by producing cells elsewhere

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Define erythropoiesis

production + development of RBCs

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Define granulopoiesis

production + development of granulocytes

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Define thrombopoiesis

production + development of platelets

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Are platelets cells?

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How long does it take a stem cell to become a formed blood element?

2-3 weeks

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2 properties of stem cells

differentiation
self-renewal

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What is the average blood volume in women and men?

women = 4-5L
men = 5-6L

What are the layers when blood is centrifuged?

Plasma
Buffy coat (leukocytes + platelets)
Erythrocytes

When would haematopoiesis increase?

bleeding
infection

Which haematopoietic growth factors stimulate increased production of blood cells?

EPO (erythropoietin)
TPO (thyroperoxidase)
G-CSF (granulocyte colony stimulating factor)
interleukins (cytokines)

2 causes for high blood counts

primary = abnormal bone marrow

secondary = normal bone marrow (being stimulated by environment to produce extra cells)

Define leucocytosis and list some primary and secondary causes

high WBCs

primary = clonal stem cell disorder:
leukaemia/lymphoma/myeloproliferative disorders

secondary = response to environmental factors:
- infection
- inflammation
- infarction (eg. MI)
- tumour

Define thrombocytosis and list some primary and secondary causes

high platelets

primary = clonal stem cell disorder:
- essential thrombocythaemia

secondary = reactive thrombocytosis:
- infection
- inflammation
- infarction
- tumour

Define erythrocytosis and list some primary and secondary causes

high RBCs

primary = clonal stem cell disorder:
- polycythaemia vera

secondary = increased EPO levels:
- less oxygen (eg. COPD)
- tumours
- doping
- high affinity Hb

Describe the difference between true erythrocytosis (polycythaemia) and apparent polycythaemia

polycythaemia: - increased number of RBCs, decreased amount of plasma apparent polycythaemia: - same number of RBCs (higher % so haematocrit increases), decreased amount of plasma - reduced plasma volume (eg. dehydration)

2 general causes of low blood counts

underproduction reduced survival in circulation

What can cause underproduction of WBCs?

drugs affecting stem cell part of pancytopenia due to marrow failure (all cell lines low)

What can cause decreased survival of WBCs?

autoimmune drugs consumption (flu) combination (eg. viral hepatitis)

What can cause underproduction of platelets?

drugs affecting stem cell liver failure (TPO underproduction) part of pancytopenia due to marrow failure

What can cause peripheral destruction of platelets?

autoimmune (ITP) hypersplenism drugs (eg. penicillin, NSAIDs, furosemide) infection/inflammation/sepsis

7.5 causes of low blood counts caused by decreased production (MMMMLLAh)

Myeloma Myelodysplasia Metastatic malignancy Myelofibrosis Leukaemia Lymphoma Aplastic anaemia [haematinic deficiency]

Do platelet counts vary with age/sex?

Describe myelodysplasia

haematopoietic stem cell malignancies related to myeloproliferative disorders abnormal maturation + proliferation proliferation of cells in bone marrow, but as cells deformed (dysplastic) they don't get into blood active, cellular marrow but low blood counts 20% progress to AML

Describe aplastic anaemia

damage to pluripotent stem cell by drugs, viruses, radiation reduced erythropoiesis, granulopoiesis, thrombopoiesis pancytopenia 'empty' bone marrow

Define myelofibrosis

malignant proliferation of reticulin fibres in bone marrow causing anaemia, leucoerythroblastic blood film + splenomegaly can be primary of develop from myeloproliferative neoplasms (MPN) can progress to AML

What can cause decreased cell survival with a normal bone marrow?

immune cellular destruction (eg. ITP, AIHA) drugs haemorrhage hypersplenism

Causes of hyposplenism

splenectomy auto-infarction (eg. sickle cell disease) infiltration (eg. metastatic malignancy) under-functioning (eg. coeliac disease)

Neutrophilia causes

bacterial infection inflammatory conditions burns cigarette smoking steroids (glucocorticoids) G-CSF solid tumours myeloproliferative disorders (eg. CML)

Lymphocytosis causes

viral infection hyposplenism TB Brucellosis CLL Lymphoma with 'spillover'

What mutation causes polycythaemia vera?

JAK2 mutation