WEEK 1: Haematopoiesis and Anaemias Flashcards
what’s the main function of rbcs?
transport O2 and CO2
what’s the main function of neutrophils?
phagocytose and destroy invading bacteria
what’s the main function of eosinophils?
destroy larger parasites and modulate allergic inflammatory responses
what’s the main function of basophils?
release histamine
what’s the main function of monocytes?
become tissue macrophages, which phagocytose and digest invading microorganisms and foreign bodies as well as damaged senescent cells
what’s the main function of B cells?
making antibodies
what’s the main function of T cells?
kill virus infected cells and regulate activities of other leucocytes
what’s the main function of NK cells?
kill virus infected cells and some tumour cells
what’s the main function of platelets?
initiate blood clotting
what does totipotent mean?
form all cells including extraembryonic and placental cells
what does pluripotent mean?
give rise to all cell types
what does multipotent mean?
give rise to more than one cell type but limited, eg all blood cells have common ancestral cell - multipotent stem cell
what is the stem cell theory of haematopoiesis?
- All cells derived from a pool of stem cells that are self-renewing
- Pluripotential & multipotential stem cells give rise to committed stem cells for each cell line
- Committed stem cells have receptors for specific growth factors
- Respond to stimulation by division & maturation (precursor cell stages) into end-stage cells
what are the characteristics of hematopoietic stem cells?
- Stem cells defined as capable of both self
renewal and multi-lineage differentiation - HSC are multi-potent stem cells that occur at a
frequency of 1:5000 in bone marrow - HSC can be defined by:
Function: the capacity to give rise to non-self renewing populations that generate multiple terminally-differentiated cell types
explain the development of blood cells in a fetus.
3 wk : formation of blood islands from yolk sac
6 wk : liver becomes hematopoietic organ
6-8 wk : spleen (until 8th month)
~20wk : bone marrow (life-long)
what is a stem cell niche?
a specific site (microenvironment) in adult tissues where stem cells reside and undergo renewal and differentiation
which 2 distinct hematopoietic niches does bone marrow harbour and where?
(1) Osteoblastic niche at the endosteal surface
(2) Vascular niche involving sinusoidal blood vessels
what function does the osteoblastic niche have to help balance self-renewal with differentiation?
Osteoblastic niche maintains quiescence and harbours the Long Term-HSC
what function does the vascular niche have to help balance self-renewal with differentiation?
Vascular niche supports proliferation, differentiation and mobilization (transendothelial migration) of Short Term-HSC to the blood stream in response to physiological demands and act as back up outside the BM for HSC during times of BM stress
what is erythropoiesis ?
the generation of red blood cells
what are the stages of erythropoiesis?
Proerythroblast
Erythroblast
Normoblast
Reticulocyte
Erythrocyte (fully mature red blood cell)
how long is the erythropoiesis process?
5-7 days
what is a proerythroblast?
it is the first committed to rbc
what is a reticulocytye?
a young red blood cell
what are 3 characteristics of reticulocytes?
- still have small amounts of RNA
- tend to stain more blue than mature RBC’s on Wright stain (polychromatophilic)
- slightly larger than mature RBC
- undergo removal of RNA on passing through spleen in 1st day of life
- important marker of RBC production
what is a common myeloid progenitor? (CMP)
a stem cell specialised with the ability to mature into all of the different blood cell types
what is an erythrocyte?
a mature red blood cell
how long does it take a reticulocyte to become an erythrocyte?
approx. 1 week
what is erythropoietin?
a hormone that stimulates the production of rbcs. Erythropoietin levels increase with decrease in hemoglobin.
what is the structure of erythropoietin?
165 amino acid glycoprotein with 4 carbohydrate chains
what produces erythropoietin and where?
it is produced predominantly by specialised cells called interstitial cells in the kidney
why do rbcs have no nucleus and no mitochondria?
enhances flexibility, increases size, increasing O2
carrying capacity
how do rbcs make atp?
glycolysis of glucose to pyruvate forming Adenosine TriPhosphate (ATP) and Nicotinamide Adenine Dinucleotide (NADH) and lactate.
list some extrinsic abnormalities that can cause anaemia
- blood loss
- infection
- hypersplenism
- chemical/physical
list some intrinsic abnormalities that can cause anaemia
- membrane defect
- enzyme defect
- globin abnormalities
what measurements of haemoglobin cause anaemia in men and women according to WHO?
< 13g/dL (men), <12g/dL (women), <11g/dL if pregnant
what are some symptoms of anaemia? give 4
-Weakness
- Shortness of breath
- Pallor
- Fatigue
- Palpitations/Tachycardia (pulse >100/min
- Jaundice
- Koilonychia (spoon nails)
- Dark urine
- Dizziness
what is normocytic anaemia?
patient has normal sized rbcs but a reduced number of them
what is haemolytic anaemia?
patient’s rbcs are destroyed faster than they are synthesized
what are some causes of normocytic anaemia?
bleeding, chronic disease, bone marrow failure, many haemolytic anaemias
what is macrocytic anaemia?
Macrocytic anaemia is a blood disorder that happens when your bone marrow produces abnormally large red blood cells. These abnormal blood cells lack nutrients red blood cells need to function normally.
what is microcytic anaemia?
the presence of small rbcs. Most common cause is iron deficiency
what is polycythemia vera?
a type of blood cancer where there is an increase in production of all blood cells
what is erythemia?
increase in rbcs
what 4 ways is anaemia diagnosed?
- Physical examination
- Full blood count
- Reticulocyte count
- Bone marrow biopsy
what 4 factors are observed in a RBC assessment?
- number
- size
- shape
- colour
what is aplastic anaemia?
anaemia occurring when bone marrow does not function.
what causes aplastic anaemia?
damage to stem cells inside bone marrow due to infections, tumours, autoimmune disease or drugs.
how is aplastic anaemia treated?
transfusions, corticosteroids, bone marrow transplant
what can cause macrocytic anaemia?
- disorder of DNA synthesis
- B12 or folate deficiency
what are the 3 main types of anaemia?
normochromic/normocytic
microcytic
macrocytic
why does a shortened life span of rbcs not always lead to anaemia?
bone marrow can increase production 6-8 fold and maintain normal Hb level.
what is intravascular haemolysis?
destruction of rbcs within circulation.
what is extravascular haemolysis?
premature destruction of rbcs in the spleen/bone marrow
why does extravascular haemolysis cause jaundice?
destroyed rbcs are removed by macrophages.
Haem breakdown in macrophage generates bilirubin.
Bilirubin is released and bound onto albumin to the liver for conjugation and excretion in bile.
Rise in unconjugated bilirubin.
Jaundice occurs.
what is intrinsic haemolytic anaemia?
it is hereditary and a defect in the rbc is causing it
what are some examples of intrinsic haemolytic anaemia? (5)
membrane defects
abnormal haemoglobin
sickle cell anaemia
enzyme deficiency
glucose-6-phosphate dehydrogenase deficiency
what is extrinsic haemolytic anaemia?
haemolytic anaemia that is acquired. Could be caused by drugs, immune-mediated causes.
