haematopoiesis, stem cells and bone marrow Flashcards

1
Q

what are pluripotent stem cells

A

completelty undifferentiated stem cells - can form any tissue in the body

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2
Q

what kind of stem cells are harmatopoietic stem cells

A

multi potent

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3
Q

where are adult haematopoietic stem cells found

A

bone marrow

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4
Q

haematopoetic stem cell differentiation pathways (3)

A
  1. stem cell -> myeloid stem cell -> myeloblast -> granulocytes (eosinophils, neutrophils, basophils etc.);
  2. stem cell -> myeloid stem cell -> RBC;
  3. stem cell -> lymphoid stem cell -> lymphoblast -> B/T lymphocyte, NK cells
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5
Q

where is blood formed in the foetus

A

yolk sac

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6
Q

what is red marrow

A

the bone marrow that contains blood stem cells

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7
Q

what happens to red marrow as ppl age

A

it is replaced by yellow marrow (fatty tissue) and haematopoiesis is restricted to the axial skeleton

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8
Q

what is extramedullary haematopoeisis and when does to occur

A

when the liver and spleen are recruited to produce blood cells (yellow marrow may also be converted back to red); occurs under stress e.g. myelofibrosis

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9
Q

what is myelofibrosis

A

bone marrow cancer that leads to the occupation of bone marrow space with fibrotic tissue -> no space for blood cell production and so body compensates by producing it else where (liver, spleen) -> enlargement of these organs is seen

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10
Q

what are platelets formed from

A

they are small particles of cytoplasm that have budded off from megakaryocyte cells (they are not themselves cells)

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11
Q

2 common properties of stem cells

A

the ability to self re-new; ability to differentiate into more specialised cells

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12
Q

what determines the function of the stem cell (proliferation vs specialisation)

A

the micro environment - growth factors and interactions with neighboring cells determine the type of cell division the stem cell undergoes (symmetric to form specialised cells or asymmetric for self renerwal)

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13
Q

components of the blood in a centrifuge (bottom to top)

A

erythrocytes (45%) -> buffy coat (platelets +WBCs) ->plasma

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14
Q

volume of blood in an avg man/women

A

man - 5/6L
women - 4/5L depending on body size, during pregnancy this can increase by 50%

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15
Q

features of a neutrophil on a blood film

A

purple granules; lobed nucleus (2-5 lobes)

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16
Q

features of an eosinophil on a blood film

A

large cell, brick-red granules (acidic stain taken up), lobed nucleus (2 lobes)

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17
Q

features of a basophil on a blood film

A

stain blue (basic stain taken up)

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18
Q

features of a lymphocyte on a blood film

A

small; small spherical nucleus which stains darkly

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19
Q

features of a monocyte on a blood film

A

largest WBC, kidney bean shaped nucleus, abundant cytoplasm with pink/purple granules, vacuole often present

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20
Q

what are the important haematopoietic growth factors (4)

A
  1. erythropoetin -rbc production, released from kidney;
  2. thrombopoetin - produced by liver and kidney;
  3. granulocyte colony stimulating factor (GCSF) - produced by endothelium;
  4. interleukins/cytokines - released by immune cells to promote further immune cell differentiation
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21
Q

what causes stimulation of erythropoietin

A

low blood oxygen

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22
Q

what suppresses erythropoietin synthesis

A

increase in oxygen carrying capacity of the blood (incr. O2 levels)

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23
Q

2 causes of high blood counts

A

primary - abnormal bone marrow and the usual mechanisms that control cell production/inhibit proliferation have been overcome i.e. cancer;

secondary - normal bone marrow that is being stimulated by environmental factors to produce more cells

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24
Q

leucocytosis causes (primary, secondary)

A

primary - clonal stem cell disorder, usually in pts w leukaemia, lymphoma and myeloproliferative disorders;

secondary - response to environment e.g. infection, chronic inflammation states, post infarction, other tumours

25
causes of thrombocytosis (primary, secondary)
primary - thrombocythemia (clonal cell disorder); secondary - response to environment e.g. infection, inflammation, infarction, tumour
26
what is primary thrombocytosis treated with
a chemotherapy agent - hydroxycarbamide (+ aspirin due to incr risk of thrombosis)
27
what is the haematocrit (+usual value)
the ratio of RBCs to total blood volume - usually 40-45%
28
polycythemia vs erythrocytosis
polycythemia - any increase in hematocrit and/or hemoglobin; erythrocytosis - an increase specifically in the number of red blood cells in the blood
29
what is a pt at risk of with polycythemia
increase risk of thrombosis - blood is thicker
30
what is apparent polycythemia and what are its causes (4)
a raised Hct despite a normal/minimally raised red cell volume due to a reduced plasma volume; causes - smoking, excess alcohol, drugs (diuretics), being overweight
31
causes of erythrocytosis (primary, secondary)
primary - polycythemia vera (mutuaiton in JAK2 gene); secondary - raised erythropoietin levels due to low O2 (e.g. COPD), tumours (some secrete epo, esp lung and renal), doping, high affinity Hb variant
32
how is polycythemia vera treated
hydroxycarbamide + aspirin or venesection + aspirin
33
2 main causes of low blood cell counts
1. underproduction 2. reduced survival in circulation
34
causes of leukocytopenia
underporduction - drugs affecting stem cells, part of pancytopenia due to marrow failure; reduced survivial - autoimmune, drugs, consumption (while fighting an infection), combination (e.g. viral hepatitis)
35
causes of Thrombocytopenia
underproduction - drugs affecting stem cells, liver failure (↓TPO produciton), part of pancytopenia due to marrow failure; peripheral destruction - autoimmune (e.g. ITP), hypersplenism, drugs (e.g. NSAIDs), infection/inflammation/sepsis
36
6 malignant conditions that cause reduced blood cell production (+2 other non malignant causes)
1. myeloma (plasma cells); 2. myelodysplasia (myeloid cells); 3. metastatic malignancy; 4. myelofibrosis (haemopoetic stem cells); 5. leukaemia (WBCs, over produciton of one type is a detriment to all others) 6. lymphoma (lymphocytes + lymphatic system) 7. aplastic anaemia (empty bone marrow due to stem cell failure) 8. haematinic deficiency (check for B12/folate levles)
37
what defines acute myeloid leukemia on a blood film
the presence of myeloblasts - immature precursors that get stuck in this point of differentiation
38
what are the myeloid cell malignancies (important!)
immature cells (blasts) - acute myeloid leukaemia; mature cells - myeloproliferative disorders (polycythemia vera, chronic myeloid leukemia, essential thrombocythaemia, myelofibrosis), myelodysplasia
39
lymphoid cell malignancies (important!!)
immature cells - acute lymphoblastic leukaemia; mature cells - chronic lymphocytic leukaemia, lymphoma, myeloma
40
what is special about myelodysplasia
there is abnormal maturation and proliferation (not just one)
41
what causes aplastic anaemia
damage to pluripotent/multipotent stem cell by drugs, viruses, radiation, immune suppression etc.
42
aplastic anaemia blood test findings
pancytopenia, reduced reticulocyte count
43
myelofibrosis pathophys
malignant proliferation of reticulin fibres in bone marrow resulting in anaemia + splenomegaly
44
what is seen on a myelofibrosis blood film
leucoerythroblastic blood film - immature RBCs and WBCs in the peripheral blood
45
what can myelofibrosis develop secondary to
myeloproliferative neoplasms -> thye pt may have had polycythemia vera or essential thrombocythemia first
46
what can myelofibrosis transform into
myeloid leukaemia
47
4 causes of low blood count with normal bone marrow (i.e. reduced cell survival cause)
1. immune cellular destruciton; 2. drugs; 3. haemorrhage; 4. hypersplenism
48
examples of autoimmune conditions resulting in low blood counts (3)
Immune thrombocytopenia (ITP); AIHA; autoimmune neutropenia
49
what is an auer rod
pink needle-shaped structures resulting from an abnormal fusion of azurophilic granules - typically found in acute myeloid leukemia
50
4 causes for hyposplenism
1. splenectomy (therapeutic for a blood disorder, trauma); 2. auto-infarction (sickle cell); 3. infiltration (metastatic malignancy); 4. underfunctioning (e.g. coeliac disease)
51
what is the hallmark of hyposplenism on a blood film
Howell-Jolly bodies (remnants of RBC nuclei that are normally removed by the spleen)
52
8 causes of neutrophilia
1. bacterial infection; 2. inflammatory conditions; 3. burns; 4. cigarette smoking; 5. steroids; 6. granulocyte colony stimulating factor (G-CSF); 7. solid tumours; 8. myeloproliferative disorders (CML etc.)
53
how does chronic myeloid leukemia cause neutrophilia
expansion of the myeloid lineage which results in neutrophiliaa
54
6 causes of lymphocytosis
1. viral infection (EBV) - most common; 2. hyposplenism; 3. TB; 4. brucellosis; 5. CLL; 6. lymphoma with "spillover"
55
5 causes of eosinophilia
1. allergic reactions; 2. vasculitis; 3. drugs; 4. worm infestations; 5. cancer
56
why should blood test results be compared to past tests
to see if the abnormality is new or lifelong
57
what is aquagenic pruritus and what is it associated with
a skin disease characterized by the development of severe itching on contact with water without observable skin lesions - assoicated with polycythemia (rubra) vera
58
what can cause failure of blood cell production (4)
1. hornome deficiency; 2. marrow infiltration; 3. toxic effects of alcohol/infection/drugs; 4. marrow aplasia
59
what can cause ineffective blood cell production (4)
1. iron deficiency; 2. B12/folate deficiency; 3. myelodysplasia; 4. thalassaemia major