Introduction to Hematology Flashcards
Blood centrifugation
Major types of “formed elements”
Erythrocytes, leukocytes, platelets
Erythrocyte lifespan
120 days
Thrombocyte lifespan
7-10 days
Methods for measuring formed elements
- Electrical impedence: The change in resistance produced when a cell or cell fragment passes through an electric current conducted across a small aperture
- Flow cytometry
Obtaining blood counts
Normal red cell indices
Most important plasma proteins
Proteins of the coagulation cascade, certain coagulation cascade regulatory factors, von Willebrand factor, and proteins that promote the lysis of clots, such as plasmin.
By adulthood, hematopoiesis is normally confined to . . .
. . . the axial skeleton, the proximal long bones, and the skull.
Organization of bone marrow
Decrease in all myeloid cells
Pancytopenia
Increase in all myeloid cells
Pancytosis
When the marrow is examined, in most instances . . .
. . . both an aspirate and biopsy are taken, usually from the posterior iliac crest.
Megakaryocyte
Reticulocyte
Orthochromic normoblast
basophilic (black arrow) and polychromatophilic (red arrow) normoblasts
Erythroblast
Metamyelocyte
Myelocyte
Promyelocyte
Myeloblast
Thymus on H and E
Splenic “slits”
The splenic arteries eventually give rise to small, arborizing arterioles, which empty into the splenic red pulp, an interstitial space separated from the venous sinuses of the spleen by a basement membrane with slit-like openings. Red cells that have normal deformability are able to push through the slits and return to the circulation, but cells that are rigid are retained and removed by resident macrophages.
Splenic red pulp diagram
Lymph node diagram
Sites of hematopoiesis throughout development
Hematopoietic stem cell lineage
Extramedullary hematopoiesis
In extreme circumstances of cellular demand, substantial numbers of HSCs and early progenitors may leave the marrow and migrate to the liver, spleen, and lymph nodes, where they can produce lineage cells outside of the medulla.
What typically keeps HSCs in the bone marrow?
CXCL12-CXCR4 interaction is the main factor. Bone marrow capillaries are rich with it, and HSCs express chemokine receptors that are constantly attracted to these sources. This is why bone marrow transplants work: the transplanted stem cells will all home there due to CXCL12 levels.
Under conditions of stress, HSCs localize around blood vessels and interact with mesenchymal, endothelial, and neural cells, which create a specialized niche rich in CXCL12. This niche also promotes quiescence through a poorly understood mechanism.
Hematopoietic stem cells are indistinguishible from ___ on H and E.
Hematopoietic stem cells are indistinguishible from lymphocytes on H and E.
HSC marker
CD34
As differentiation proceeds, myeloid progenitors lose multipotency andthe capacity for self-renewal, but in turn, they acquire two other key properties:
- an increased capacity for cell division (transit amplification)
- surface expression of specific receptors for hematopoietic growth factors
Hematopoietic growth factors
TPO regulation
Constant amount is produced, but level of thrombopoiesis is instead regulated by competition for ligand by megakaryoctytes and thrombocytes.
Why doesn’t mass sequestration of thrombocytes in the spleen increase thrombopoiesis?
Because of the way TPO is regulated: Those thrombocytes can still bind plasma TPO, preventing additional platelet synthesis.
Epo signaling
Unlike myelopoiesis, lymphopoiesis . . .
. . . occurs at both the level of lymphocyte progenitors and mature lymphocyte
Major early lymphoid growth factor
IL-7
NK cell growth factor
IL-15
azurophilic granules
Visualized by Romanowsky stain. Aka ‘primary granules.’ Contain cathelicidins, defensins, elastase, peptidase-3, cathepsin-G, etc.
In NK cells and CD8+ T cells, but not in neutrophils, they also contain perforins and granzymes.
The Notch pathway in lymphoid development
Lymphoid progenitors exposed to factors that activate the Notch pathway become T cells, and those that are not exposed become B cells or NK cells.
PAX5
Transcription factor vital for B cell development, but not for other lymphoid lineages.
CEBPA
Mutations in this transcription factor block granulopoiesis.
BCL6
BCL6 protects germinal center (GC) B cells against DNA damage–induced apoptosis during somatic hypermutation and class-switch recombination. Without it, you will have no mature B cells.
Hematopoietic transcription factors
PAX5 mutations are found in ___, whereas BCL6 mutations are confined to ___.
PAX5 mutations are found in tumors composed of early B-cell progenitors, whereas BCL6 mutations are confined to tumors derived from germinal center B cells.
Some disorders treated with bone marrow transplant
- Inherited blood disorders that qualitatively or quantitatively impair the function of HSCs or their progeny
- Acquired bone marrow failure (aplastic anemia)
- Some cancers, particularly those of hematopoietic origin
___ is primarily used in the treatment of drug-induced neutropenia, particularly following high-dose chemotherapy
Recombinant G-CSF is primarily used in the treatment of drug-induced neutropenia, particularly following high-dose chemotherapy
G-CSF vs GM-CSF
- G-CSF: stimulates production of just neutrophils
- GM-CSF: stimulates production of macrophages and neutrophils
If a patient is severely neutropenic, they are essentially gauranteed to be infected by a bacterium within ____.
If a patient is severely neutropenic, they are essentially gauranteed to be infected by a bacterium within 3 weeks.
Endoreduplication
Membrane invagination and cytoplasmic fracturing (on megakaryocytes it gives rise to platelets)
Erythropoiesis diagram
Granulopoiesis diagram
___ are the engine of blood cell production
Progenitors are the engine of blood cell production
G-CSF increases levels of the transcription factor ___
G-CSF increases levels of the transcription factor C/EBPa
Common locations of ectopic hematopoiesis
Spleen, lymph nodes, pleura, liver
May occur when there is extreme production demand for blood cells or when bone marrow is being destroyed (like in myelofibrosis)
Stages of stem cell transplantation
Lineage ‘choice’ is specified by. . .
. . . the balance between competing transcription factors
Notch1 v EBF
T cell v B cell
GATA1 v PU.1
Meg/Ery v GranMono/Lym
Granulocyte v Monocyte
C/EBPa v PU.1
EKLF v Fli-1
Ery v Meg
Acute Promyelocytic Leukemia can be treated with. . .
. . . retinoic acid. This forces cells undifferentiated leukemia cells to differentiate and subsequently lose replicative ability.
