haematopoiesis, stem cells and bone marrow Flashcards
what are pluripotent stem cells
completelty undifferentiated stem cells - can form any tissue in the body
what kind of stem cells are harmatopoietic stem cells
multi potent
where are adult haematopoietic stem cells found
bone marrow
haematopoetic stem cell differentiation pathways (3)
- stem cell -> myeloid stem cell -> myeloblast -> granulocytes (eosinophils, neutrophils, basophils etc.);
- stem cell -> myeloid stem cell -> RBC;
- stem cell -> lymphoid stem cell -> lymphoblast -> B/T lymphocyte, NK cells
where is blood formed in the foetus
yolk sac
what is red marrow
the bone marrow that contains blood stem cells
what happens to red marrow as ppl age
it is replaced by yellow marrow (fatty tissue) and haematopoiesis is restricted to the axial skeleton
what is extramedullary haematopoeisis and when does to occur
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
what is myelofibrosis
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
what are platelets formed from
they are small particles of cytoplasm that have budded off from megakaryocyte cells (they are not themselves cells)
2 common properties of stem cells
the ability to self re-new; ability to differentiate into more specialised cells
what determines the function of the stem cell (proliferation vs specialisation)
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)
components of the blood in a centrifuge (bottom to top)
erythrocytes (45%) -> buffy coat (platelets +WBCs) ->plasma
volume of blood in an avg man/women
man - 5/6L
women - 4/5L depending on body size, during pregnancy this can increase by 50%
features of a neutrophil on a blood film
purple granules; lobed nucleus (2-5 lobes)
features of an eosinophil on a blood film
large cell, brick-red granules (acidic stain taken up), lobed nucleus (2 lobes)
features of a basophil on a blood film
stain blue (basic stain taken up)
features of a lymphocyte on a blood film
small; small spherical nucleus which stains darkly
features of a monocyte on a blood film
largest WBC, kidney bean shaped nucleus, abundant cytoplasm with pink/purple granules, vacuole often present
what are the important haematopoietic growth factors (4)
- erythropoetin -rbc production, released from kidney;
- thrombopoetin - produced by liver and kidney;
- granulocyte colony stimulating factor (GCSF) - produced by endothelium;
- interleukins/cytokines - released by immune cells to promote further immune cell differentiation
what causes stimulation of erythropoietin
low blood oxygen
what suppresses erythropoietin synthesis
increase in oxygen carrying capacity of the blood (incr. O2 levels)
2 causes of high blood counts
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
leucocytosis causes (primary, secondary)
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
causes of thrombocytosis (primary, secondary)
primary - thrombocythemia (clonal cell disorder);
secondary - response to environment e.g. infection, inflammation, infarction, tumour
what is primary thrombocytosis treated with
a chemotherapy agent - hydroxycarbamide (+ aspirin due to incr risk of thrombosis)
what is the haematocrit (+usual value)
the ratio of RBCs to total blood volume - usually 40-45%
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
what is a pt at risk of with polycythemia
increase risk of thrombosis - blood is thicker
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
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
how is polycythemia vera treated
hydroxycarbamide + aspirin or venesection + aspirin
2 main causes of low blood cell counts
- underproduction
- reduced survival in circulation
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)
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
6 malignant conditions that cause reduced blood cell production (+2 other non malignant causes)
- myeloma (plasma cells);
- myelodysplasia (myeloid cells);
- metastatic malignancy;
- myelofibrosis (haemopoetic stem cells);
- leukaemia (WBCs, over produciton of one type is a detriment to all others)
- lymphoma (lymphocytes + lymphatic system)
- aplastic anaemia (empty bone marrow due to stem cell failure)
- haematinic deficiency (check for B12/folate levles)
what defines acute myeloid leukemia on a blood film
the presence of myeloblasts - immature precursors that get stuck in this point of differentiation
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
lymphoid cell malignancies (important!!)
immature cells - acute lymphoblastic leukaemia;
mature cells - chronic lymphocytic leukaemia, lymphoma, myeloma
what is special about myelodysplasia
there is abnormal maturation and proliferation (not just one)
what causes aplastic anaemia
damage to pluripotent/multipotent stem cell by drugs, viruses, radiation, immune suppression etc.
aplastic anaemia blood test findings
pancytopenia, reduced reticulocyte count
myelofibrosis pathophys
malignant proliferation of reticulin fibres in bone marrow resulting in anaemia + splenomegaly
what is seen on a myelofibrosis blood film
leucoerythroblastic blood film - immature RBCs and WBCs in the peripheral blood
what can myelofibrosis develop secondary to
myeloproliferative neoplasms -> thye pt may have had polycythemia vera or essential thrombocythemia first
what can myelofibrosis transform into
myeloid leukaemia
4 causes of low blood count with normal bone marrow (i.e. reduced cell survival cause)
- immune cellular destruciton;
- drugs;
- haemorrhage;
- hypersplenism
examples of autoimmune conditions resulting in low blood counts (3)
Immune thrombocytopenia (ITP); AIHA; autoimmune neutropenia
what is an auer rod
pink needle-shaped structures resulting from an abnormal fusion of azurophilic granules - typically found in acute myeloid leukemia
4 causes for hyposplenism
- splenectomy (therapeutic for a blood disorder, trauma);
- auto-infarction (sickle cell);
- infiltration (metastatic malignancy);
- underfunctioning (e.g. coeliac disease)
what is the hallmark of hyposplenism on a blood film
Howell-Jolly bodies (remnants of RBC nuclei that are normally removed by the spleen)
8 causes of neutrophilia
- bacterial infection;
- inflammatory conditions;
- burns;
- cigarette smoking;
- steroids;
- granulocyte colony stimulating factor (G-CSF);
- solid tumours;
- myeloproliferative disorders (CML etc.)
how does chronic myeloid leukemia cause neutrophilia
expansion of the myeloid lineage which results in neutrophiliaa
6 causes of lymphocytosis
- viral infection (EBV) - most common;
- hyposplenism;
- TB;
- brucellosis;
- CLL;
- lymphoma with “spillover”
5 causes of eosinophilia
- allergic reactions;
- vasculitis;
- drugs;
- worm infestations;
- cancer
why should blood test results be compared to past tests
to see if the abnormality is new or lifelong
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
what can cause failure of blood cell production (4)
- hornome deficiency;
- marrow infiltration;
- toxic effects of alcohol/infection/drugs;
- marrow aplasia
what can cause ineffective blood cell production (4)
- iron deficiency;
- B12/folate deficiency;
- myelodysplasia;
- thalassaemia major
