haemopoiesis + the spleen Flashcards
blood cell precursors
“blasts” = nucleated precursor cells (erythro-, myelo-)
megakaryocytes = platelet precursor, polyploid
reticulocytes = immediate red cell precursor, “polychromasia”
myelocytes = nucleated precursor between neutrophils + blasts
division of haemopoitic stem cells
divides in asymmetrical fashion
- one of daught cells is identical to parent (self-renewal)
- other is different -> progenitor
self-renewal = property of stem cells, lost in descendants
in adults, most haemopoietic stem + progenitor cells are bone marrow based
- more primitive progenitors (stem cells) are quiescent/dormant during steady-state haemopoiesis - might only divide every few weeks
overlap between developmental events - proliferation + maturation can occur simultaneously
embryonically where do stem cells originate?
mesoderm
- circulating committed progenitors detectable as early as week 5
where is a bone marrow sample taken in adults vs kids
adult - posterior iliac crest
kids - tibia
stem cells are mobilised from marrow into blood for collection + transplantation
bone marrow compartments
cellular
- haemopoietic cells
- non-haemopoietic cells - adipocytes, fibroblasts, osteoclasts, osteoblasts
- connective tissue matrix
- vascular elements
bone marrow venus sinuses - “sinusoids”
arteriole drain into “sinus” - wide venous vessels, which open into larger central sinuses
- in contrast to capillaries, sinuses are larger + have discontinous membrane
- fenstrations (gaps) in endothelial cells
- discontinous basement membrane - adventitial cells can open gaps further
release of mature cells from marrow
formed blood cells can pass through fenestration in endothelial cells to enter circulation
- release of red cells is assoc with sinusoidal dilation + increase blood flow
neutrophils actively migrate towards sinusoid
megakaryocytes extend long branching processes called proplatelets into sinusoidal blood vessels (pop off platelets)
red vs yellow marrow
red = haemopoietically active
yellow = fatty, inactive
- increase in yellow marrow with age - results in reduction in marrow cellularity in older individuals
myeloid:erythroid ratio
relationship of neutrophils + precursors to proportion of nucleated red cell precursors
- can change e.g. reversal in haemolysis as a compensatory response
cell maturation regulators
RBC - erythropoietin
neutrophil - G-CSF (granulocyte-colony stimulating factor)
megakaryocytes - thrombopoietin
how can we identify normal, more mature non-lymphoid cells?
morphology
cell surface antigens - glycophorin A = red cells
enzyme expression - myeloperoxidase = neutrophils
how can we identify normal progenitors/stem cells?
(morpholofically indistinguishable cells)
cell surface antigens -> immunophenotyping (CD34)
cell culture assays
animal models - not practical in routine diagnostic practice
immunophenotyping
identify patterns of protein (antigen) expression unique to a cell lineage
use antibodies (in combination) specific to different antigens
-> to see how many stem cells are harvested - they are “marked”
spleen
secondary lymphoid organ
not usually palpable unless substantially enlarged
communications
- diaphragmatic surface
- visceral surface - left kidney, gastric fundus, tail of pancreas, splenic felxture of colon
blood supply of spleen
supplied by splenic artery - branch of coeliac axis
drained by splenic vein - forms portal vein with SMV
rupture is a surgical emergency
- trauma
- a diseased spleen is more prone to rupture
structure + function of spleen
encapsulated organ
parenchyma includes red pulp + white pulp
sinusoids are: fenestrated, lined by endothelial cells, supported by hoops of reticulin
acts as filter for blood
- detects retain + eliminate unwanted, foreign or damaged material
- facilitate immune responses to blood borne antigens
white pulp of spleen
white pulp comprises the periarteriolar lymphoid sheath (PALS) - CD4+ lymphoid cells
- this is expanded by lymphoid follicles - may show reactive changes as in lymph node
- antigen reaches white pulp via the blood
- APCs in the white pulp present antigen to immune reactive cells
- when stimulated by antigen, T + B cell responses may occur
hyposplenism causes
most commonly - spenectomy (need for immunisation)
coeliac disease
sickle cell disease
sarcoidosis
iatrogenic
blood features of hyposplenism
mainly from reduced red pulp function
- Howell-jolly bodies
- siderocytes
may also be some immune deficiency - esp if spleen removed in childhood
causes of splenomegaly
infection
congestion - portal
-> hepatic cirrhosis, cardiac failure, portal/splenic vein thrombosis
haematological disease
- lymphoma/leukaemia
- haemolytic anaemia
- myeloproliferative disorders
inflammatory conditions
others - amyloid, tumours
splenomegaly presentation
dragging sensation in LUQ
discomfort when eating, early satiety
pain if infection
hypersplensism triad
- splenomegaly
- fall in one or more cellular components of blood
- correction of cytopenias by splenectomy
