4. Hematopoiesis Flashcards
What is hematopoiesis?
Production of new blood cells
What are agranulocytes?
Includes lymphocytes and monocytes
Occasionally contain granules but they will be low in numbers
when granules are present, often difficult to see
What are granulocytes?
Includes neutrophils, eosinophils and basophils
Characterized by granules and segmented nucleus
What is the lifespan of blood cells?
Neutros - 4-6hrs
Eosino - 30min
Baso - 4-6hrs
Monos - 2-3days
Lymphos - months to years
Erythrocytes - 2-5 months
Platelets - 4-6 days
When and where does hematopoiesis begins
Begins during early emryonic life
In the prenatal animal, occurs in the liver, spleen, thymus and red bone marrow
Red bone marrow is primary site for blood cell prod in the neonate and juvenile animals - found in the foetus and yng animal
in adult animals, where is hematopoiesis?
The red bone marrow is primary production site, but few bones contain red bone marrow.
Spleen and liver can help with hematopoiesis during periods of stress
Where is red bone marrow found in adult animals
Long bones, ribs, sternum and hips
What cell do all blood cells arise from?
Pluripotent stem cells, capable of regen, stay at constant, low numbers within the bone marrow
What do hematopoietic stem cells differentiate into?
Two progenitors
Common myeloid progenitor
Common lympoid progenitor
How they divide is determined by interactions with cytokines (~24)
What is erythropoiesis and how does it work?
Production of RBC’s
Erythropoietin (EPO) is primary cytokine for RBC production
Primarily prod in kidney (sm in liver)
Normally present in sm amounts in plasma to replace dying or aging RBC
EPO travels within blood to bone marrow, then binds to erythroid precursor cells to stimulate erythropoiesis. Stimmed by hypoxia
With erythropoiesis, where are dead cells removed?
Removed by the phagocytic cells in the spleen
At what age stage are RBC’s released? How long does it take dogs, cattle?
Only mature and possibly a few near-to mature cells are released from the bone marrow
Cattle takes 4 days, dogs is 7 days
What happens with hypoxia and erythropoiesis?
Bone marrow can inc its prod of RBC by 4-5 times normal
Provided that all the necessary materials are available
The time req for release of new red cells to peripheral blood following hypoxic stimulus is about 3-4 days
What happens in dogs with hypoxia and erythropoiesis
In dogs, the kidney is the sole source of erythropoietin
Dogs with several renal dz may have anemia as a complication
this is significant problem in cats with severe renal dz as the carotid body is involved with erythropoiesis
What is a rubiblast
A large cell (slightly bigger than neutrophil)
round cell and nucleus, thin rim of dark blue (basophilic) cytoplasm
Nucleoli present (paler in color, one or more present)
preinuclear clear zone is often preserved
A rubiblast can prod 8-16 mature cells
What is a prorubricyte?
Slightly smaller than the rubriblast
no nucleoli
nucleus more condense
often prominent pernuclear clear zone
basophilic cytoplasm
What is a rubricyte?
Significantly smaller than prorubricyte
nuclear chromatin shows an alternating light/dark pattern
Nucleus is dark purple
In early stages, cytoplasm is blue
Cytoplasm will gradually lighten and turn pink as hemoglobin (Hgb) matures
What is metarubricyte?
Nucleus appears as a dark blue circle
Cytoplasm is deep red and skewed off to one side prod a comet tail appearance
Slightly lger than a mature erythrocyte
No longer capable of cell division
Hemoglobin formation is complete
What is a reticulocyte?
Polychromasia
Anuclear
contains ribosomal material which gives the cell a blue/purple appearance when stained
macrocytic
Seen as polychromasia on Wright’s stain
seen as aggregated material with reticulocyte stain (Dark blue)
What does an erythrocyte look like?
Anuclear
no ribosomal remnants remaining
cytoplasm is pink due to mature Hgb
What is a megakaryoblast?
Larger than other blast cells in the bone marrow
contains a single nucleus
very basophilic, scant ctyoplasm
What is a promegakaryocyte
Containts 2-4 nuclei - nuclei continue to replicate
Nuclear lobes remain connected
cytoplasm doesn’t divide and consists of a rim around the nuclear mass
What is a megakaryocyte
Extremely large (50-200uM) in diameter at maturity
Numerous nuclear lobes are present
Cytoplasm is abundant, pale blue and contains reddish cranules
The cytoplasm extends into thin, finger-like projections that become platelets as they get sheared off the cell
What does a platelet lok like?
stage at which they leave the bone marrow
not true cells bc they have no nucleus. They are fragments of the megakaryocyte cytoplasm
lots of size and shape variations
Which species have different maturation phase?
Reptiles, amphibians, birds posses a nuclei and are true thrombocytes
How is granulopoiesis triggered?
Triggered by the hormone leukopoietin as well as several other cytokines
What are the two groups that granulocytes divide into?
Prliferation pool - cells capable of mitosis, includes myeloblasts, promyelocytes and myelocytes
Maturation pool - cells can no longer divide, includes metamyelocytes and band cells
How are neutrophils produced?
Prod exclusively in the active bone marrow of healthy, adult animals
Yng animals, some prod will occur in the spleen
With chronic inflam dz, prod of the neutrophils will occur in spleen, liver and lymph nodes of adults
What is a myeloblast?
Involved in granulopoiesis
lg cell, round to oval nucleus
nucleus contains one or more nucleoli
A few reddish granules may be present in cytoplasm
Pale gray-blue cytoplasm - difficult to distinguish from other primitive blast cells
larger and lighter in color than rubriblasts
What is promyelocyte
Slighter smaller and lighter than myeloblasts
contains azurophilic granules (pink or purple)
Occasionally nucleoli may be present - will be less prominent than in myeloblast
More cytoplasm than the myeloblast
What are myelocyte
Slightly smaller and lighter in color than promyelocytes
Nucleus is round and ccentrically placed
no nucleoli
granules are visible as neutrophilic, eosinophilic or basophilic
What is a metamyelocyte
similar to the myelocyte but nucleus is indented
lighter colored cytoplasm
can no longer undergo cell division
What is a band neutrophil
same color as the mature, segmented neutrophil
nucleus is indented to the point of being U-shape, with parallel sides and clubbed ends
What is a segmented neutrophil
purple/lavender colored nucleus
nucleus is segmented
granules may or may not be distinct
Hypersegmented neutrophil - lobes inc with age so >5 is hypersegmented
How to know if its band cell or segmented neutrophil
narrowest region of nucleus needs to be less than or equal to 2/3 of the width widest part of the nucleus to be classed as a segmented neutrophil
If you see the start of a hematopoiesis sequence, will you see all cell stages, or just the start?
You wil not see a stage skiped on a smear.
If you see myeloblasts, you will see all the stages in btw
If you see band neutrophils, then you will see those + segs but won’t see the predecessors
How should we categorize cells?
What about if you count disintegrating cells?
Always categorize cells by the most mature stage if unsure
only count disintegrating cells if >10% of the WBC’s counted
What is the transit time of neutrophils?
the amount of time needed for the myeloblast to mature into a segmented neutrophil
In healthy animals, transit time is 7 days
When stimulated due to inflam, can be as little as 2 days
What is circulation time in neutrophils
The amount of time btw the release of the cell into the blood and its arrive in tissue
in good health, ~6-10hrs
The neutrophil pool is renewed 2-3 times per day
Samples drawn within a few hours can be very different
What should we keep in mind with monocytic series?
isn’t responsive to an infection in the way the neutrophilic series is
Only rarely overcome by a neoplastic disorders
wont be seen unless you do bone marrow work
For monopoiesis, what is the order of maturity and where are they located
Monoblast - Loc in bone marrow, similar to myeloblasts but had irregularly shaped nucleus
Promonocyte - loc in bone marrow, similar to myelocytes and metamyelocytes
Monocyte - mature monocyte move into peripheral blood, maye develop if exposed to specific cytokines
Macrophage - loc in tissues
What are lymphopoiesis triggered by and what do they differentiate into?
tiggerd by cytokines and antibodies
starts with the common lymphoid precursor stem cell - found in bone marrow
differentiate into T-lymp, NK precursor or B-lympho precurso
What does a lymphoblast look like?
high nuclear to cytoplasmic ratio (N:C ratio) - the cell is comprised mostly of nucleus, very little cytoplasm present
oval to indented, eccentrically placed nucleus, dark clue cytoplasm
What is a prolymphocyte
decreased N:C ratio - cytoplasm makes up a greater volume of the cell
large nucleoli
lighter staining cytoplasm
What does a lympocyte look like?
round to slightly indented nuclei
dense, relatively smooth chromatic, small amount of basophilic cytoplasm
Where do juvenile B-lymphocytes mature?
in the bone marrow or ileal peyer’s patche in dogs, pigs and ruminants
bursa of fabricius in birds
Where do t0lymphocytes mature
Thymus
Where do NK cells mature in the bone marrow
Can develip in thymus and other lymphoid tissue
Where might immature stages be seen with lymphopoiesis
may be seen in peripheral blood due to neoplastic dz - relatively common in cats
usually would only note that immature stages are present (this along with c/s & hz are diagnostic)
usually due to a virally-induced neoplastic disorder
cells usually seen @ feathered edge
will be abnormal in size &/or color
may see nucleoli
may contain mitotic figured (cells that are seen to be dividing)
