PBL 7 - Haematopoiesis Flashcards
what is the buffy coat?
- between plasma and the red of formed elements when centrifuged
- essentially WBCs and platelets
- less than 1%
give the overview of haematopoiesis starting with a multi potent stem cell
what is haematopoiesis?
the process by which blood cells are formed
what is the lifespan of platelets?
9-10 days
what is the lifespan of erythrocytes?
120 days
what is the lifespan of leucocytes?
a few days to a few years:
- 175 billion new RBCs per day
- 175 billion new platelets per day
- 1.1 million new blood cells formed every second!!
where does haematopoiesis take place in foetus?
0-2 months = yolk sac — blood islands
2-7 months = liver, spleen
5-9 months = bone marrow = more representative of a living person
where does haematopoiesis occur in an infant?
bone marrow — practically all bones
where does haematopoiesis occur in an adult?
vertebrae, ribs, sternum, skull, sacrum and pelvis, proximal ends of femur
where does extramedullary haematopoiesis occur? what can this show?
= outside of bone marrow
- liver, thymus, spleen
- signs of this show there is a pathology
where are stem cells located?
bone marrow
at brith, what colour is all bone marrow?
red
what is red marrow?
haematopoietic tissue
what is yellow marrow?
fat cells, micro environment — stromal cells and stromal matrix (vital for the haematopoietic process)
what stromal cells are there in yellow marrow and what do they do?
- fibroblasts
- fat cells
- endothelial cells
- reticulum cells
- macrophages
— express adhesion molecules
— secrete growth factors
what is the stromal matrix in yellow marrow for?
physical support for haematopoietic stem cells
stem cells mostly exist in a state known as quiescence. what does this mean?
a state of of reversible growth arrest
what happens when a stem cell leaves a state of quiescence? what does this allow?
- begin actively dividing again
- this allows the movement between states in order to be able to differentiate and proliferate when necessary to ensure we have a stem cell population that is available for production for our different cells
when our cell moves from quiescence and becomes active, what does it proliferate, multiply and differentiate into for a specific lineage?
progenitor cells
haematopoietic stem cells are also self-renewing, why is this important?
when they differentiate, at least some of their daughter cells can remain as haematopoietic stem cells — pool of stem cells is not depleted — consistent maintenance of our stem cell pool
where do all blood cells originate?
bone marrow
all blood cells originate from 1 type of haematopoietic stem cell (HSC), capable of what?
- self renewal — able to proliferate and divide forming an exact copy of the cell
- differentiating into other blood cell types — cells start to become more specialised for the task and function they have to do
what do lymphoid stem cells give rise to?
lymphocytes
what do myeloid stem cells give rise to?
all other blood cells than lymphocytes — neutrophils, eosinophils, basophils, monocytes, erythrocytes and platelets (thrombocytes)
what is an MK cell? what do they differentiate into?
megakaryocyte — differentiates into platelets
what does __blast indicate?
immature cell — should remain in bone marrow and not be seen in circulation
what is CFU-GEMM?
= colony-forming unit - GEMM
- generates myeloid cells
G = granulocyte E = erythrocyte M = monocyte M = Mk cell
describe erythropoiesis
- myeloid stem cell
- proerythroblast — most immature committed precursor to the RBC. large cell with cytoplasm that stains dark blue
- early erythroblast
- late erythroblast
- normoblast — smaller cells, cytoplasm starts to stain lighter blue. late normoblast have extruded nucleus — becoming more like a mature RBC
- reticulocyte — contains some ribosomal RNA. circulates in peripheral blood (1-2 days)
- erythrocyte — endpoint. RNA lost
what is the approx duration of erythropoiesis?
7 days
when is Hb made?
- before organelles are lost
- majority made from proethryoblast up to normoblast
where is the haem part of Hb made?
in the mitochondria in the cytoplasm
where is the globin part of Hb made?
ribosomes in the cytoplasm
what is thrombopoiesis?
how platelets are made
what is endomitosis used to make?
megakaryoblasts
what is endomitosis?
- replication of chromosomes occurs but cells don’t divide
- cells become larger
once fully mature, endomitosis ceases resulting in what?
granulated cytoplasm
how long does thrombopoiesis last?
2-3 days
each megakaryocyte “fragment” produces how many platelets?
roughly 4000
what are the steps of thrombopoiesis?
- blood stem cell
- myeloid stem cell
- megakaryoblast
- pro megakaryocyte
- MK
- platelets
what is monopoiesis?
production of monocytes
describe the steps of monopoiesis
- blood stem cell
- myeloid stem cell
- monoblast
- promonocyte
5.monocyte
( 6. macrophage )
how long do monocytes stay in circulation for?
20-40 days
what is the shape of the nucleus of monocytes?
kidney shape
what is the size of monocytes like?
very large — up to 20um
much larger than RBCs and lymphocyte
what is granulopoieis?
the production of neutrophils, basophils and eosinophils
describe a myeloblast
varying size, large nucleus, no cytoplasmic granules
describe granulopoiesis
- myeloid stem cell
- myeloblast
- promyelocytes
- (eosinophilic/basophilic/neutrophilic) myelocyte
- (eosinophilic/basophilic/neutrophilic) mega-myelocyte
- (neutrophil band cell)
- eosinophil, neutrophil, basophil
describe promyelocytes
primary cytoplasmic granules
describe myelocytes
smaller cells with specific cytoplasmic granules, no noticeable nucleoli
describe metamyelocytes
indented or horse-shoe nucleus, lots of cytoplasmic granules
B lymphocytes differentiation in foetus vs adult
foetus - in liver
adult - in bone marrow
where are plasma cells formed?
lymph nodes
describe NK cells
large cells with cytoplasmic granules
what is the lifespan of NK cells?
weeks to years
what initiates haematopoiesis?
stem cell division
what is differentiation of cells regulated by? examples?
transcription factors eg/
- PU.1 — cells are differentiated along the myeloid lineage
- GATA.1 — differentiates cells along the erythropoietic and megakaryocytic cell lineages
what are some growth factors that play a role in haematopoiesis?
describe erythropoietin (EPO)
- growth factor
- regulates erythropoiesis
- reduction in red cell number results in decreased O2 to tissues
- development of hypoxia in kidneys and liver
- leads to increased production of RBCs
released when host is:
- anaemic
- has declining blood perfusion to the kidneys
- has low O2 saturation
- has damaged respiratory surfaces of the lungs
- this corrects hypoxia and EPO synthesis is turned off
—> stimulates increased cell division rates in erythroblast and stem cells
—> speeds up the maturation of RBCs by accelerating the rate of Hb
describe thrombopoietin (TPO)
- mainly produced in liver
- stimulates megakaryocytes and platelet production (THROMBOPOIESIS)
describe stem cell factor (SCF)
synergies with cytokines such as IL-3 and GM-CSF to increase proliferation of stem cells
describe IL-3
works in conjunction with GM-CSF to proliferate most haemopoietic progenitor cells
describe IL-5
- produced by T cells
- plays a role in growth and differentiation of eosinophils
describe 3 wider ranging GFs
1) Granulocyte Macrophage Colony Stimulating Factor (GM-CSF)
- necessary for growth and development of granulocyte and macrophage progenitor cells
- stimulates myeloblasts and monoblasts
2) Macrophage Colony Stimulating Factor (M-CSF)
- plays a role in proliferation and differentiationof haemopoietic stem cells to produce monocytes and macrophages
3) Granulocyte Colony Stimulating Factor (G-CSF)
- is similar to M-CSF but acts on precursor cells which give rise to granulocytes
