hematopoiesis Flashcards
Hematopoiesis is
the production of blood cells and platelets
Leukocytes
WBC
Leukopoiesis is
the production of WBC
Erythrocytes is
red blood cells
Erythropoiesis is
the production of RBCs
Thrombocytes are
platelets
Thrombopoiesis is
the production of platelets
Agranulocytes are
lymphocytes and monocytes
Occasionally contain granules but they will be in low numbers
When granules are present, they are often difficult to see
Granulocytes are
neutrophils, eosinophils, basophils
Characterised by a segmented nucleus
Blood cell life span
Blood cells are constantly dying and being replaced
When does hematopoiesis begin
Hematopoiesis begins during early embryonic life
In the prenatal animal, hematopoiesis occurs in the liver, spleen, thymus and red bone marrow
Where does hematopoiesis happen
Red bone marrow is the primary site for blood cell production in the neonate and juvenile animals
Red bone marrow is found in almost every bone of the foetus and young animal
In adult animals, the red bone marrow is the primary production site as well, but there are fewer bones that contain red bone marrow
It is found in the long bones, ribs, sternum and hips
The spleen and liver can help with hematopoiesis during periods of stress
All blood cells arise from the same pluripotent hematopoietic stem cells
Pluripotent stem cells can develop into various types of cells
These cells are capable of regeneration
They stay at constant, low numbers within the bone marrow
Hematopoietic stem cells differentiate into two progenitors
Common myeloid progenitor
Common lymphoid progenitor
The pathway is determined by interactions with various chemical messengers known as cytokines (~24)
Erythropoiesis is
The production of erythrocytes or RBCs
Erythropoietin (EPO) is the primary cytokine responsible for RBC production
Where is erythropoietin produced
Primarily production in the kidney
Small amounts produced in liver
Normally presents in small amounts in the plasma to replace ageing or dying RBC
EPO travels within the blood to the bone marrow, here it binds to erythroid precursor cells to stimulate erythropoiesis
Stimulated by hypoxia
How does bone marrow do eryhtropoiesis
The bone marrow is constantly replacing ageing and dead cells in the peripheral circulation
These cells are usually removed by the phagocytic cells in the spleen
Splenectomised patients have a more bizarrely shaped red cells in theri circulation
In healthy animals, only mature and possibly a few near-to mature cells are released from the bone marrow
In cattle, the maturation process takes about 4 days, while in dogs it requires about 7 days
Erythropoiesis and hypoxia
With prolonged hypoxia, the bone marrow can increase its production of red cells by 4-5 times normal
Provided that all of the necessary materials are available
The time required for the release of the new red cells to peripheral blood following hypoxic stimulus is about 3-4 days
How is erythropoiesis in dogs affected by the kideny
In dogs, the kidney is the source of erythropoietin
Dogs with severe renal disease may have anemia as a complication
This is a significant problem in cats with severe renal disease as well
In the cat, the carotid body is involved with erythropoiesis
How long do RBC live
The red cells life span varies greatly from species to species
Longest living RBC is in cattle- about 5 months
The shortest is in the pig at about 2 months
Characteristics of Rubriblast in Erythropoiesis
Large cel (slightly bigger than neutrophil)
Round cell and nucleus
Thin rim of dark blue (basophilic) cytoplasm
Nucleoli preston (paler in colour, 1 or more will be present)
Perinuclear clear zone is often observed
A rubriblast can produce 8-16 mature cells
Charatereistics of Prorubricyte in Erythropoiesis
Slightly smaller than the rubriblast
No nuclei
Nucleus is more condensed
Often prominent perinuclear clear zone
Basophilic cytoplasm
Characteristics in Rubicyte in erythropoiesis
Significantly smaller than the prorubricyte
Nuclear chromatin shows an alternating light/dark pattern
Nucleus is dark purple
In the early stages, the cytoplasm is blue
The cytoplasm will gradually lighten and turn pink as hemoglobin (Hgb) matures
characteristics of Metarubricyte in erythropoiesis
Nucleus appears as a dark blue circle
Cytoplasm is deep red and skewed off to one side producing a comet tail appearance
Slightly larger than a mature erythrocyte
No longer capable of cell division
Hemoglobin formation is complete
Characteristics of Reticulocyte (polychromasia) in erythropoiesis
Nuclear
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 a reticulocyte stain (dark blue)
characteristics of Erythrocyte in erythropoiesis
Anuclear
No ribosomal remnants remaining
Cytoplasm is pink due to mature Hgb
Thrombopoiesis is
The production of thrombocytes (platelets)
Triggered by thrombopoietin as well as several other cytokines
Thrombopoiesis happens in what
Trombopotiten is primarily produced in the liver
Small amounts are also produced in the kidneys and bone marrow
Characteristics of magakaryoblast in theombopoiesis
Larger than other blast cells in the bone marrow
Contains a single nucleus
Very basophilic, scant cytoplasm
Characteristics of Promegakaryocyte in thrombopoiesis
Contains 2-4 nuclei- nuclei continue to replicate
Nuclear lobes remain connected
Cytoplasm does not divide and consists of a rim around the nuclear mass
Characteristics of megakaryocyte in thrombopoiesis
Extremely large (50-200 micrometres in diameter) at maturity
Numerous nuclear lobes are present
Cytoplasm is abundant, pale blue and contains reddish granules
The cytoplasm extends into thin, finger like projections that become platelets as they get sheared off of the cell
Characteristics of platelets in thrombopoiesis
This is the stage at which platelets leave the bone marrow
They are not true cells→ they are fragments of the megakaryocytes cytoplasm
There is a great deal of variation in size and shape of platelets
Platelet maturation is
Species such as reptiles, amphibians, and birds whose platelets possess nuclei, follow a different maturation phase than mammals
There Is are true thrombocytes (unlike platelets)- they are true cells
Leukocytes are classified by
Classified by the presence or absence of granules
Agranulocytes- lymphocytes and monocytes
Granulocytes- neutrophils, eosinophils, basophils
Granulopoiesis refers to what
Refers to the production of granulocytes
Neutrophils, eosinophils and basophils
These cells have a segmented nucleus
Granulopoiesis is triggered by what
the hormone leukopoietin as well as several other cytokines
The developing granulocytes are divided into two groups
Proliferation pool
Maturation pool
Proliferation pool is waht for granulocytes
These cells are capable of mitosis
Includes myeloblasts, promyelocytes and myelocytes
Maturation pool is waht for granulocytes
These cells can no longer divide
Includes metamyelocytes and band cells
Maturation series of ganulocytes in regards to the nutrophilic series
The following maturation series is in regards to the neutrophilic series
Eosinophils and basophils follow the same developmental stages, though the colour of the granules varies
Neutrophilic production is
Produced exclusively in active bone marrow of healthy, adult animals
In young animals, some production will occur in the spleen
With chronic inflammatory disease, production of neutrophils will occur in the spleen, liver and lymph nodes of adults
Characteristics of Myeloblast in granulopoiesis
Large cell
Round to oval nucleus
Nucleus contains one or more nucleoli
A few reddish granules may present in the cytoplasm
Pale gray-blue cytoplasm
Difficult to distinguish from other primitive blast cells
Larger and lighter in colour than rubriblasts
Characteristics of promyelocyte in granulopoiesis
Slightly smaller and lighter than myeloblasts
Contain azurophilic granules (pink or purple)
Occasionally nuclei may be present- will be less prominent than in the myeloblast
More cytoplasm than myeloblast
Characteristics of myelocyte in granulopoiesis
Slightly smaller and lighter in colour than promyelocytes
Nucleus is round and eccentrically placed
Nu nucleoli
Granules are visible as neutrophilic, eosinophilic or basophilic
Characteristics of metamyelocyte in granulopoiesis
Similar to the myelocyte but nucleus is indented
Lighter coloured cytoplasm
Can no longer undergo cell division
Characteristics of band nutrophil in granulopoiesis
Same colour as the mature segmented neutrophil
Nucleus is indeed to the point of being “U-shaped” with parallel sides and clubbed ends
Characteristics of segmented nutrophil in granulopoiesis
purple/lavender coloured nucleus
Nucleus is segmented
Granules may or may not be distinct
Hypersegmented neutrophils- as cells age, the number of lobes of the nucleus increase- if >5 segments are present, the cells is classified as hypersegmented
How to tell if its a band or segmented neutrophil
The narrowest region of the nucleus needs to be less than or equal to 2/3 of the width widest part of the nucleus to be classified as a segmented neutrophil (as opposed to a band cell)
Maturation and orderly production
Because cells develop in a specific sequence, you won’t see a stage skipped on the smear
If you are seeing myelocytes as well as mature neutrophils on a smear, you will see all of the stages in between
There should always be a greater number of the most mature stages of cells unless the animal is very ill- left shifts
In healthy animals, you should only see segmented neutrophils an a few, if any band cells
ALWAYS categorize the cell by the more mature stage when you are unsure.
The only time we count disintegrating cells is when they total more than 10 % of the WBCs counted
Transit time in neutrophilic kinetics is
the amount of time needed for the myeloblast to mature into a segmented neutrophil
In a healthy animal, normal transit time is 7 days
When stimulated due to inflammation, it can be as little as 2 days
Circulation time in neutrophilic kinetics is
the amount of time between the release of the cell into blood and its arrival in tissue
In healthy animals, about 6-10 hours
The neutrophil pool is renewed 2-3 times per day
Samples down a few hours apart can be very different
Monopoiesis is
The same pluripotent stem cell as the granulocytic cells
Monocytic series is
Inst responsive to an infection in the way the neutrophilic series is
Only rarely overcome by a neoplastic disorders
Won’t be seen unless you do bone marrow worm
Characteristics of monoblast in monopoiesis
Located in the bone marrow
Similar to appearance to myeloblasts but have an irregularly shaped nucleus
Characteristics of promonocyte in monopoiesis
Located in the bone marrow
Similar in appearance to myelocytes and metamyelocytes
Characteristics of monocyte in monopoiesis
Mature monocytes move into peripheral blood
May develop into macrophages if exposed to specific cytokines
Lymphopoeisis is
Triggered by cytokines and antibodies
Starts with the common lymphoid precursor stem cell
Found in the bone marrow
Differentiate into T-lymphocyte, NK precursor or B-lymphocytes precursor
Characteristics of lymphoblast
High nuclear to cytoplasmic ratio (N:C ratio)–the cell is comprised mostly of the nucleus, very little cytoplasm present
Oval to indented, eccentrically placed nucleus
Dark blue cytoplasm
Characteristics of prolymphocyte
Decreased N:C ratio– cytoplasm makes up a greater volume of the cell
Large nucleoli
Lighter staining cytoplasm
Characteristics of lymphocyte
Round to slightly indented nuclei
Dense, relatively smooth chromatin
Small amount of basophilic cytoplasm
Juvenile B-lymphocytes mature:
In the bone marrow or ileal Peyer’s patches in dogs, pigs and ruminants
Bursa of Fabricius in birds
Where do lymphocytes mature
T-lymphocytes mature in the thymus
Natural Killer cells mature in the bone marrow
Can also develop in the thymus and other lymphoid tissue
Immature stages may be seen in the peripheral blood due to neoplastic disease–relatively common in cats
Usually we would only note that immature stages are present (this along with c/s & Hx are diagnostic)
Why do we only see imature lymphocytes
Usually due to a virally-induced neoplastic disorder
These cells are usually seen at the feathered edge
They will be abnormal in size &/or colour
May see nucleoli
May contain mitotic figures (cells that are seen to be dividing)
