in embryo: yolk sac
in fetus: liver and spleen
in adult: bone marrow; liver and spleen can make blood cells if needed= extra-medullary hematopoiesis (EMH)
Young marrow vs. older marrow
Young= red, active marrow
young animal produces high numbers of blood cells.
older= yellow marrow in middle, with fat and supporting cells. network of reticular cells.
red marrow still exists at ends of long bones and flat bones
Broad overview of commitment of cell lines
Multipotent stem cell--> primitive progenitor cells CMP or CLP
CMP--> committed precursor cells MEP and GM
MEP (erythroid line): platelets and RBCS
GM: monocytes, neutrophils, eosiniphils and basophils
CLP--> committed precursors TNK and BCP
TNK: T-cells and natural killer cels
Bone marrow: (proliferating mitotic pool) multipotent stem cell-->unipotential stem cell--> rubriblast/proerythroblast-->prorubricyte/basophilic erythroblast/early normoblast--> rubricyte/polychromatophilic erythroblast
Post-mitotic pool: -->metarubricyte/orthocromatic erythroblast/late normoblast--> reticulocyte-->
in blood: erythrocyte
First recognizable cells: rubriblast/proerythroblast- first cell we can see on a microscope. blue nucleus. nucleus starts to get small and darker.
Normoblast/metarubricyte: shiny black nucleus, can see it poking out of side of cell.
Reticulocyte and normoblast appearances
Normoblast: dark nucleus poking out of side of cell
Reticulocyte: on new methylene blue stain: supervital stain taken up-- dotted blue throughout cell.
Life of an erthyrocyte
Bone marrow: 3-5d
Reticulocute: maturation in blood for 2 days
Mature RBC: 100 day life span
Aged/damaged rbcs to SPLEEN, liver and BM by macrophages.
Spleen recycles iron and bilirubin and protein; iron to bone marrow and bilirubin to liver.
Bilirubin transported to liver by albumin and liver conjugates it to make it water souble; removed in bile.
Splenic sequestration: horses and some dogs- when stressed, can show up as a transient erythrocytosis- normalizes after 30 mins.
RBC life span in circulation: species differences
Dog: 120 days
Horse: 145 days
Cat: 70 days
Cow: 130 days
Mice: 43 days
Hormone produced by kidney
disease of kidney affect ability to produce EPO: chronic renal failure-->less able to produce EPO--> unable to replace RBCs
Stimulates proliferation of erythroid progenitors (precursors)
Fundamental stimulus to EPO production is hypoxia--> if levels of O2 in blood decrease, kidney stimulates EPO production, increased blood cell production.
Bone marrow: multipotential stem cell-->unipotential stem cell-->myeloblast
Myeloblast=first recognizable cells. Big, pinky nucleus; nucleoli, light blue cytoplasm
Myeloblast-->promyelocyte (pink granules)-->myelocyte-->metamyelocyte
Maturational post mitotic pool: metamyelocyte (bean-shaped nucleus)--> band neutrophils (horseshoe shaped nucleus)-->mature neutrophils/segmenters (storage pool).
Life of a neutrophil
6 days to get produced in bone marrow
circulating neutrophil--> marginating neutrophil--> tissues (7-14 hours)
Once in tissues, lost from body surfaces or destroyed by macrophages.
N'phils in 2 pools:
circulating: central column of blood- that's what we see when we take a blood sample
marginating: creep along blood vessel walls looking for damage triggers (receptors, CKs); squeeze through walls and into tissues.
No re-entry into circulation occurs after emigration into tissue.
Lives of other leukocytes
eosinophils: take 2-6 days to develop in BM--> 1-24 hours in circulation--> exit to tissue (skin, GI, resp)--> last for 2d to 2weeks
Monocytes: have short transit time in blood-->recruited into tissue where the differentiate into macrophages (lifespan is variable)
lymphocytes-lymphopoiesis occurs in BM (B-cells) or thymus (T-cells)
can keep reycling lymphocytes.
Red cell size: dogs>horses>cats>ruminants
No release of immature red cells (reticulocytes) from BM in horses, even when they're anemic. Need to take serial samples in monitoring anemia.
Rouleaux formation: in horses (normal), in cats, sign of inflammation. Negative charge prevents RBCs from sticking. With increased blood viscosity, RBCs stack. In cat inflammation, lots of globulin-->viscous blood.
Breed differences: healthy greyhounds have an increased number of RBCS, greater than other breeds.
Age: very young animals tend to have lower RBCs than mature adult
Seals have HUGE rbcs, llamas have bery small and elliptical rbs.
with immune-mediated destruction of RBCs, almost impossible to tell difference between a spherocyte and a small RBC.
Cat RBCs and WBCs
eosinophils: more rod shaped granules
basophil: don't see many in dogs and cats, but sometimes looks like nucleus has holes in it
RBC: less obvious areas of central pallor
v. small RBCs
lymphocytes: quite large in circulation
eosinophil looks like a raspberry
tend to see more reticulocytes in lagomorphs and rodents (healthy) likely due to shorter lifespan of RBCs.
Reptile and fish blood
reptile (lizard): n'phil equivalent=heterophil. have staining granules
platelets= ragged cytoplasmic edges
fish: nucleated rbcs.
RBC: erythrocyte concentration
HCT: hematocrit= PCV (packed cell volume): volume percentage of RBCs in blood
MCV: mean cell volume
MCHC: mean cellular hemoglobin concentration
RDW: red cell distribution width (don't often look at this)
WBC: leukocyte concentration
PLT: platelet concentration
Normoblasts: nucleated red blood cells.