Haematopoiesis and disease Flashcards
Where does embryonic haematopoiesis occur?
Yolk sac, liver and spleen and bone marrow
Where does infant haematopoieses occur?
All of it is produced in the bone marrow
Where does adult haematopoiesis occur?
In the central skeleton as well as proximal ends of femur
difference between red bone marrow and yellow bone marrow?
red marrow is the part which produces the blood cells whereas the yellow marrow refers to the fat spaces.
How do all blood cells form?
Due to the hematopoietic stem cells (hemocytoblasts) present in the bone marrow.
thrombocytes is another word for…
Platelets.
What is noticed from this image?
As the cells mature, the cells become smaller in size, and the presence of the nucleus no longer remains
HSC niche in the bone marrow?
HSC thought to be maintained by endothelial cells and stromal cells maintain them by secreting various factors.
signals help in survival and proliferation as well as homing and mobilisation.
Control of adult haematopoiesis is caused by:
extrinsic signalling (growth factors - survival/ proliferation, differentiation e.t.c) and intrinsic signalling (transcription factors)
example of Growth Factors and what they do?
Erythropoietin - regulates the production of RBC’s, predominantly produced by the kidneys and some in the liver. Production is stimulated by tissue oxygen levels.
Thrombopoietin - produced in the liver and controls platelet count in the bone marrow via a feedback mechanism
G-CSF, M-CSF, IL-5 - produced via myelopoiesis in the bone marrow
Normal peripheral blood is used to obtain a full blood count. How is a reference range formed?
The Blood counts are made using healthy populations and the mean +/- 95% CI is used to form the range.
Most common type of WBC?
Neutrophils
too many RBC?
Too many WBC?
Too many platelets?
Eryhtrocytosis
Leucocytosis
Thrombocytosis
Too little RBC?
Too little WBC?
Too little Platelets?
Too little of everything?
Anaemia
leucopenia
thrombocytopenia
pancytopenia
How can there be a malignant disorder?
There can be myeloproliferative disorders which lead to excess blood cell formation
Reasons for benign excess BC conditions?
erythrocytosis e.g. smoking, alcohol, altitude, lung disease
leucocytosis e.g. infection, inflammation
thrombocytosis e.g. iron deficiency, infection
cytopenias are caused by?
failure of production in the bone marrow, or excess loss or consumption in the periphery
symptoms of anaemia
lethargy, breathlessness, chest pain, headache/ dizziness, pallor
Leucopaenia is usually caused by…
Low neutrophil count. This is usually caused by cancer or due to a range of infections such as mouth ulcers, overwhelming sepsis.
What causes thrombocytopenia?
low platelet count (<150 x10^9/ litre)
symptoms caused by levels less than 20 x10^9/l
symptoms include bruising, gum bleeding, nose bleeds, petechiae, or even prolonged bleeding after cuts
Example of red cell disorders…
Erythrocytes have a primary function to carry oxygen in the circulation
they have a Biconcave disc 8 micrometre diameter
10^12 new RBC made per day - lifespan around 120 days - reticuloendothelial system - removal and recycling
Haemoglobin…
Binds to O2 - haemoglobin has 4 globin chains and 4 haem moieties
anaemia can be caused due to:
- blood loss,
- reduced RBC production
- iron deficiency, B12 deficiency, malignancy, thalassaemia - Increased RBC destruction e.g. haemolysis and sickle cell disease
Reasoning for Iron deficiency:
- chronic blood loss - menstruation and gastrointestinal bleeding
dietary - vegetarian, vegan, toddlers
Malabsorption - coeliac disease, gastric surgery
Increased requirements - pregnancy/ growth
what changes are observed in blood when examined under a microscope in patients with iron deficiency anaemia?
Megaloblastic anaemia?
- Defective DNA synthesis during RBC production causing cell growth without division
- macrocytic anaemia (increase MCV)
- Unusually due to B12/ folate deficiency - these can be tested and replaced via treatment
Folate deficiency is caused by
Not eating your greens, inadequate intake, malabsorption, excess consumption e.g. due to pregnancy, and drugs such as anticonvulsants
Vitamin B12 deficiency occurs…
Due to a vegan diet, autoimmune disorderds such as pernicious anaemia, and malabsorption
haemolytic anaemia occurs via..
Excessive or premature RBC breakdown
- spherocytes or fragments
- anaemia and reticulocytosis
- Raised bilirubin and LDH
This can be inherited or acquired
Examples of heridary haemolysis
membrane and cytoskeleton defects
- defective RBC metabolism
- haemoglobinopathies
Autoimmune haemolysis occurs due to:
Antibodies being produced by the body against its own RBC
Direct Coombs/ antiglobulin test positive - tests if RBC coated in immunoglobulin or complement in vivo
white blood cells are split into 2 groups known as…
myeloid cells and lymphoid cells
Examples of myeloid cells
neutrophils, eosinophils and basophils, and monocytes. The first three are examples of granulocytes.
examples of lymphoid cells
T lymphocytes, B lymphocytes and natural killer cells
Neutrophils typically have 3-4 lobes to their nucleus. Having 6 or more is known as
hypersegmented
functions of neutrophils:
- chemotaxis
- phagocytosis (ingest and degrade microparticles)
- degranulation
- Neutrophil extracellular traps
eosinophils are:
red staining granules, and they have a special role in allergic responses and parasitic defence
basophils are
basophilic (blue staining) cytoplasmic granules,
They contain heparin and histamine,
They have IgE receptors
They are similar to mast cells but the difference is the location by which mast cells are found. Mast cells are found in connective tissue.
Monocytes have a role of
phagocytosis, antigen presentation, and cytokine production
neutrophila is..
when there are too many neutrophils in the body. This can occur due to infection, inflammation, and even pregnancy.
monocytosis is
where there are too many monocytes in the blood. most likely due to acute or chronic infection, and connective tissue disease.
Eosinophilia is where…
there are high eosinophil levels in the blood. This can occur due to allergic reactions, parasitic or skin disease, and certain drugs.
Neutropenia is a
benign disorder of low neutrophil level. Typically levels of neutrophil have to be less than 2 x10^-9/ litre but there is ethnic variation which needs to be accounted for. Anything less than 0.5x10^-9/ litre suggests significant infection risk. The cause of this could be autoimmune or even drug induced after chemotherapy
Lymphocytes are
part of the adaptive immune system, consisting of T, B and NK cells.
They carry a degree of antigenic specificity and are even stored as memory cells.
They are produced in the bone marrow, and T cells become mature in the thymus.
B lymphocytes’s primary role is to
secrete antibodies and act as memory cells
T lymphocytes can be categorised by receptors they express. 2 cases are…
CD8+ cells which are cytotoxic (they bind to the infected or damaged cell) and cause lysis or apoptosis.
CD4+ cells are helper cells (they produce cytokines which activate macrophages, B cells and NK cells.)
NK cells are
cytotoxic cells, which are part of the innate immune system, act against viral infections and tumour cell destruction, and they induce lysis or apoptosis.
immunophenotyping is used to
identify which type of blood cells are present based on the expression of specific markers on the cell surface.
There is a cluster of differentiation (CD) antigens on cell surface
- some are lineage specific
- some change as a cell matures
Genetics behind heamotological malignancies
which genetic investigations can be done for haemotological malignancies?
cytogenetics - karyotyping of cells in metaphase
Molecular studies such as PCR and FISH
