"Microscopic Anatomy Bone Marrow Ira Ames" GABY Flashcards
Romanovsky Type Blood Stain*
Basic (+ or cationic)
- methylene blue ( RNA )
- azure B ( DNA & GAGs )
Acidic (- or anionic)
-eosin ( proteins )
Variations on Romanovsky Type Blood Stain
Wright’s
Giemsa
May-Grunwald
Hematopoiesis
continuous production of blood cells
Hematopoietic organs
Bone marrow:
rbcs
granulocytes
monocytes
Lymphoid organs:
lymphocytes
Monophyletic theory of hematopoiesis
All blood cells are derived from a common pluripotential stem cell (hematopoietic stem cell)
Granulopoiesis
development of granulocytes
neutrophils
eosinophils
basophils
Blast (precursor cell)
Large cell (10-15micro)
Large euchromatic nucleus
High nucleocytoplasmic ratio Heavenly blue cytoplasm
No cytoplasmic granules
Neutrophil Differentiation
Condensation of nuclear chromatin -(disappearance of nucleoli) Lobulation of nucleus Appearance of cytoplasmic granules -(primary & secondary) Decrease in cytoplasmic basophilia
Under normal conditions blasts, n. promyelocytes, n. myelocytes, and n. metamyelocytes can only be observed in bone marrow
True
Where are band cells and mature neutrophils seen?
In normal peripheral blood
Neutrophilic promyelocyte
same size as blast
spherical nucleus
more condensed chromatin
*azurophilic granules
Azurophilic granules are ___
primary lysosomes
*they contain hydrolytic enzymes
Neutrophilic myelocyte
round-oval nucleus
more heterochromatic
no longer makes azurophylic granules
appearance of specific granules
color of cytoplasm shifts from heavenly blue to salmon pink
What do lysozymes and lactoferrin in neutrophil specific granules do?
Lysozyme: hydrolyzes glycosides in bacterial cell wall
Lactoferrin: binds iron
Together they kill bacterial cells
Neutrophilic metamyelocyte
can no longer undergo mitosis
kidney-shaped nucleus (beginning of lobulation)
more condensed chromatin
numerous specific granules
few azurophilic granules
salmon-pink cytoplasm
When can we say the metamyelocyte has differentiated into a band?
When the indentation exceeds 1⁄2 the diameter of the round nucleus
Neutrophilic band
curved rod shaped nucleus
more condensed chromatin
cytoplasm just like mature neutrophil
can be observed in normal peripheral blood (1-5% of wbcs)
What can the % of bands in peripheral blood provide information about?
They provide a rough indication of the rate of neutrophil production in your patient
What does a shift to the left mean?
Increase in the % of bands in pb indicates that stress is being placed on the bone marrow to produce more neutrophils
When can we say that the band has differentiated into a mature neutrophil?
When the segments between lobes have become thin heterochromatic filaments
What is the life span of neutrophils?
15-20 days
9-14 days in bone marrow
1 day in peripheral blood
5 days in surrounding tissue
What are the two types of diapedesis?
Paracellular (between endothelial cells)
Transcellular (through endothelial cells)
Do eosinophils and basophils go through the same sequence of events during their maturation?
It is believed so and that the kinetics of the process is about the same
What does red bone marrow consist of?
small blood vessels
discontinuous sinusoids
hematopoietic cords
Where is red bone marrow found?
sternum vertebrae ribs clavicles pelvis skull
Where is there more adipose tissue, red of yellow bone marrow?
Yellow
What is the function of yellow bone marrow?
To store energy
To serve as hematopoietic tissue reserve
Hemopoietic stem cell niche
An interactive structural unit that nurtures stem cells and facilitates their activity
What can we find in HSC niche?
Osteoclasts: create spaces in spongy bone surface
Osteoblasts: play a role in the localization of stem cells, and they support hematopoiesis
Other cells that may be involved: endothelial cells, pericytes, bone marrow macrophages (osteomacs)
Important ecm proteins:
fibronectin, laminin, agrin
Importance of the hematopoietic stem cell niche
Hematopoietic stem cells are not randomly distributed in bone marrow
They live in specific microenvironments called stem cell niches
Interaction of the stem cells with the elements of the stem cell niche (cellular & ecm) is critical
Alterations to the hematopoietic stem cell niche can lead to myeloproliferative disease,
that is a preleukemic condition
Erythrocyte differentiation
Decrease in cell volume
Decrease in nuclear diameter
Increase in heterochromatin
Disappearance of nucleoli
Loss of nucleus
Decrease in cytoplasmic basophilia
Increase in cytoplasmic eosinophilia (due to accumulation of Hb)
Basophilic erythroblast (BEB)
First recognizable stage in erythropoiesis
Smaller than a blast
Checkerboard nucleus
Loss of nucleolus
Navy blue cytoplasm (due to increase in free ribosomes which participate in production of Hb)
Capable of cell division (1-2 times)
Polychromatophils are capable of dividing ___ times
3-4
Normoblast (NB)
smaller cell
smaller heterochromatic nucleus
slightly polychromatophilic cytoplasm
terminal cell: can no longer undergo mitosis
What is the fate of normoblasts?
- 80% become reticulocytes
2. 20% become orthochromatic erythroblasts
Maturation time for RBCs
Total time: 8-9 days
1-2 days as a basophilic erythrocyte
3 days as a polychromatophil
3 days for normoblast to reticulocyte transition
1 day for reticulocyte to RBC transition
Orthochromatic erythroblast (OCE)
Uses up its residual RNA before it extrudes its nucleus
Resembles a nucleated rbc
*not present in normal peripheral blood
Erythropoietin
Glycoprotein hormone
Produced in the kidney cortex
(probably by endothelial cells of the peritubular capillary plexus)
Increases rate of mitosis (in blasts, basophilic erythroblasts and polychromatophils)
Increases RNA synthesis in developing rbcs (especially mRNA for hemoglobin)
Attenuates the degree of brain damage after stroke
Synthesis is stimulated by hypoxia
Erythroblastic island
Developing rbcs cluster around reticular cells in bone marrow
Reticular cells phagocytose extruded nuclei
Plasma cell (in marrow smear)
basophilic cytoplasm
negative image of Golgi
acentrically placed nucleus
“clock face” chromatin
Megakaryocyte Differentiation
Cell enlargement
Lobulation of nucleus
Increase in level of ploidy ( 32-64n )
Shift in cytoplasmic basophilia to acidophilia
Accumulation of azurophilic cytoplasmic granules
Formation of platelet demarcation channels
Proplatelet model of platelet production
- Extension of thick pseudopods
- Formation of long extensions (proplatelets)
- Platelets are released from ends of proplatelets
Megakaryocytes
Megakaryocytes lie just outside of the discontinuous sinusoids
They release platelets into the lumen of the sinusoids
Platelets circulate for about 10 days
They are then destroyed within the spleen and liver
They contain a functional repertoire of mRNAs
Platelets may be able to produce functional progeny??
Lymphocyte Differentiation
Decrease in cell size Condensation of chromatin
Disappearance of nucleoli
Acquisition of cell surface receptors
- Some cells migrate to the thymus (T lymphs)
- Some cells begin differentiation in the bone marrow (B lymphs)
Monocytes
bone marrow (2-3 days)
circulation (1-2 days)
tissues (as macrophages) (1-3 months)