Hematopoiesis Flashcards
Cell Types in the periphery
erythrocytes (RBCs): 4.6 -6.1 million/ul
Leukocytes (WBCs): 4-10 thousand/ul
A: Granulocytes (have specific granules), Neutrophils, eosinophils, and basophils
Agranulocytes: monocytes and lymphocytes
All these cells are born in the bone marrow
Bone marrow
blood cell formation begins in the embryo:
First in the yolk sac–> liver–> bone marrow (5th month)
Bone marrow comprimises 5% of the body mass
Peripheral blood also comprimises 5%
Bone marrow produces >10e11 cells/day
Red marrow is hematopoietic, in long bones red marrow becomes fat by 20yo, in flat bones, red marrow persists for life
Bone marrow generates diverse cell types
all bone marrow cells derive from a Multipotent master stem cell which gives rise to mesentchymal stem cells (becomes bone and cartilage), and hemangioblasts (gives rise to endothelial cells, and Hematopoietic stem cells
Hematopoietic stem cells (CD117/ckit, CD34+, Lin-)
become a myeloid or lymphoid stem cell
Myeloid cells become: Erythroid lineage (RBC, CFU-E, CD45-) Megakaryocyte (CFU-meg, CD45-) Monocytes (CD45+) Granulocytes (CFU-G, CD45+
Lymphoid cells become: B cells (CFUB, CD45+) T cells (CFU-T, CD45+)
CD (cluster of differentiation) markers CD3 CD4 CD8 CD13 CD14 CD15 CD19 CD20 CD34 CD45
integral cell membrane protein CD3- T cells CD4- Helper T Cells CD8- Cytotoxic T cells CD13- Granulocytes, monocytes CD14- monocytes CD15- Granulocytes, monocytes CD19- B cells CD20- B cells CD34- blasts/ stem cells CD45- leukocytes
Colony forming units ands Colony stimulating Factors
each lineage arises from a CFU
CSFs- growth factors or cytokines that induce CFUs
Multipotent CSFS: Stem cell factor (SCF) binds CD117 (cKit) on HSCs
Unipotent CSFs:
EPO–> CFU-E (erythropoiesis)
C-CSF (Granulocyte- colony stimulating factor)–> CFU-G (PMNs)
M-CSF-> monocyte-> macrophage
Thrombopoietin -> CFU-meg (thrombopoiesis)
Lineage nomenclature and morphology
RBC cytoplasm: blue (mRNA immature)–> red (protein, mature)
Granulocyte cytoplasm–> specific granules
Nuclear morphology: -> extruded (RBCs), –> segmented (granulocytes)
Smaller cells= more mature cells
Erythroid lineage: proerythroblast–> basophilic erythroblast–> polychromatic erythroblast–> orthochromatic erythroblast (normoblastic)–> reticulocyte–> erythrocytes
Granulocyte lineage: common myelobast–> B,N,or E promyelocyte–> myelocyte(golgi clearing)-> metamyelocyte-> band-> basophil, neutrophil, eosinophil
blood consists of 2 parts
blood consists of 2 parts: the formed elements (which includes cells and platelets) and plasma
Plasma is 90% water which evaporates during the drying process, the other components of plasma are rarely cisible
In addition to water, the plasma contains electrolytes (Na, Cl, K, PO4, and HCO3 ions, glucose, amino acids, immunoglobulin, complement proteins, steroids and clotting factors
Erythrocytes
most of the cells present in a blood smear are erythrocytes (red blood cell)
The color intensity helps identify as normochromatic and is directly related to the concentration of hemoglobin in the RBCs
Hypochromasia referes to decreased staining intensity and hyperchromasia reefers to increased staining intensity and a lack of a central palor., normal RBC shouldnt have a nucleus, shortening its lifespan
The color of RBCs is a useful reference for identifying other formed elements
RBCs have a biconcave shape, the center of RBCs stain pale because there is less material in it
The function of the erythrocytes biconcave shape is to maximize surface to colume ratio facilitating gas exchange
Cytoskeletal elements maintain the erythrocyte shape (spectrin, actin, ankyrin)
Anisocytosis (variation in cell size), Poikilocytosis (variation in cell shape)
Sickle cell disease
Theres an altered shape of certain RBCs due to a hereditary hemoglobinopathy
SCA patients have severe anemia (sickeled cells are fragile and lyse), vaso-occlusive complication (normal appearing cells whose membranes have been altered by repeated sickling adhere to the endothelium causing narrowing of small vessels which leads to trapping of sckled cells, vascular occlusion and ischemic tissue damage, manifests as painful crises, chronic hyperbilirubinemia (jaundice)
Erythrocyte development
erythrocytes develop in the bone marrow from stem cells in a process called erythropoieses, this process is divided into several morphologically recognizable stages. The cell type that is the immediate precursor stage of the erythrocyte is called a reticulocyte, typically reticulocytes cannot be stained differently than RBCs, but when stained with cresyl blue (basic dye), polyribosomes of reculocytes show
Or wright giemsa stain, (slightly larger, have a bluish/purple hue– polychromasia
increased reticulocytes in peripheral blood indicates an increased demand for erythrocytes, premature release of reticulocytes from the bone marrow into peripheral blood may be needed because of hemorrage or anemia
leukocytes
purple dots, usually have granules
Granules come in two types:
Non-specific (primary azurophilic)
Specific (secondary)
Granulocytes (neutrophils, eosinophils, and basophils)- contain non-specific and specific granules.
Monocytes and lymphocytes- lack specifc granules but may contain non-specfic granules
Neutrophils
30-70% of leukocytes in normal blood are neutrophils
10 um in diameter (RBC 7 um), the nuclei of mature neutrophils have several lobes 3-5, connected by thin filaments
Immature neutrophils lack complete segmentation, termed bands and have a C shaped nucleus
Female pt neutrophils may have a drum stick- shaped nuclear appendage: Inactive X chromosome– Barr body
Neutrophilic granules dont stain with either basic or acidic dyes, usually there are 2 types of granules
Non specific (primary) granules are fewer in number in normal mature granulocyte/neutrophils, specific are more neumorous in mature ones, Granules contain enzymes
Non specific granules: lysosomes (acid hydrolaes), lysozyme, other enzymes
Specific granules contain alkaline phosphatase, amino peptidase, and collagenase
Neutrophil function: phagocytosis and destruction of microorganisms and initiation of the inflammatory process
Eosinophils
slightly larger than neutrophils, have a reddish (eosiniphilic) granules within their cytoplasm
elliptical specifc granules with a charactersitc electron dense crystalloid body
A bilobed nucleus is another feature of eosinophils, the specific (secondary) granules contain MAJORBASIC PROTEIN with other basic proteins that combat parasites
Eosinophils are increased in number for parasitic worms and allergic reactions
Eosinophil function outside of the circulation in the dermis of the skin and in connective tissue, components of the respiratory tree, GIT, uterus and vagina, they are within tissue spaces so that they can encounter foreign microorganisms and Ag
Basophils
make up <1% leukocyte population SMall leukocytes (8-10 um) primary granules and large specific secondary granules, very dark purple that obscures the irregular nucleus
Antihistamines inhibit degranulation of basophils
Mononuclear inflammatory cells
monocytes and lymphocytes
Monocytes
largest WBC (15-20 um), 5-15% of leukocyte population Nucleas is large eccentric, pale staining, and indented(like a kidney bean), cytoplasm is gray-blue and variably vaculated
When monocytes enter peripheral tissues they differentiate into macrophages
Monocytes originate in bone marrow and use blood as a vehicle for passing into the tissues Kupffer cell (liver, microglial cell (CNS), alveolar (lung), and Histiocyte (connective tissue) all refer to Macrophages which were once circulating monocytes
Macrophages phagocytose and present Ag oligopeptides to cell surface via MHC, presented to T cells
lymphocytes
20-50% of the population of circulating WBCs
vary in size, most of it is nucleus, cytoplasm is only a thin blue rim
Larger lymphocytes may be activated B cells which secrete antibodies
Platelets
between the RBCs blue granules
Platelets are derived from large bone marrow cells- megakaryocytes
Functions of plateltes involved in the blood clot formation
Nuclei- 0 in platelt
1 huge nucleus in megakaryocyte
Thryombocyte are also called to platelets, thrombocytopenia when there a really low number of platelets in peripheral blood– leads to mucocutaneous bleeding
hematopoiesis/hemopoiesis
process of formation and development of the various types of blood cells and other formed elements. In the adults, this process normally takes place in the skull, vertebrae, ribs, sternum, ilia, and proximal epiphyses of some long bones
Fatty yellow bone marrow in other bony cavities
Begins with pluripotent hematopoietic stem cells which give rise to progressively more differentiated cells
These progenitor cells develop coony forming units (CFUs) that generate a given type of blood cell.
cells in the bone marrow with granules are maturing (granulopoiesis)
erythropoieses
RBC formation, RBC needs to be small inorder to circulate easily, contains abundant hemoglobin for gas exchange and is biconcave to maximize the surface area for gas exchange
As erythroid maturation ensues, cell size reduction is accomplished by having the nucleus become progressively smaller until it is ultimately extruded from the cell, hemoglobin will continue to accumulate and protein synthesis will be shut down–> diminished polyribosomes (mRNA) in the cytoplasm
cytoplasm goes from blue (polyribosomes, Hb mRNA) to red (hemoglobin, protein)
Proerythroblast
Cell size (large, >2 x the size of RBC), nucleus is large (occupies 80% of cell volume, round, centrally located, prominent nucleolus), cytoplasm is basophilic (due to presence of polyribosomes Hb mRNA)
Basophilic erythroblast: cell size (medium), nucleus is large round, clumped chromatin, cytoplasm is very basophilic a royal blue
Polychromatophilic erythroblast
medium (1.5 x RBC),
small, round, condensed chromatin, cytoplasm (blue to grayish blue)
Orthochomatophilic erythroblast–> reticulocyte–> erythrocyte
Orthochromatophilic erythroblast: small, nucleus is small round eccentrically located, very condesed chromatin, cytoplasm staining identical to that mature RBC
Reticulocyte: cannot be distinguised from RBCs in this slide, distinguishable from RBCs when stained witha supravital dye because residual polyribosomes stain blue
Erythrocyte polyribosomes in the early stages of erythrocyte production syntheisize Hb
Cytoplasm changes color as the erythropoietic series differentiate–> increase in Hb content and the decrease in polyribosome Hb mRNA
Iron deficiency affects the morphology of the erythrocyte makes it smaller and hypochromatic, stains only at the periphery of the cell due to increased central pallor
reticulocytes lose their mitotic ability
If reticulocytes are normally in peripheral blood in the 1st 24-48 hrs, excessive reticulocytes in periphery is indicative of anemia
EP is a hormone that promotes devlopment of of erythroid progenitors by inhibiting cell death, comes from kidney and liver
Granulopoiesis
Formation of PMNs, eosinophils, and basophils
Myeloblast- large, cytoplasm is thin rim of light blue, nucleus is large with delicate chromatin, prominent nucleolus
Myelocyte: large cell, specific granules are present, nucleus is not indented
Metamyelocyte: smaller than the myelocytes, pink granules, a kidney shaped nuclues
Band/Stab cell- cell is the same size as the mature cell, pink granules, horseshoe-shaped, deeply indented nucleus
Segmented neutrophil: multiple loulated nucleas and pink granules
Eosinophils and basophils: mature in a similar way as granulocyte
Monocytes
Abundant grey-blue cytoplasm with variably present, delicate pink granules, reniform/kidney bean shaped nucleus, no nucleoli
Lymphocytes
smallest nucleated cell in the marrow, roughly the same size as an RBC, high NC ratio, uniformly condensed chromatin w/o nucleoli
mature T and B cells
T cells mature in thymes B cellsare hematogones
Thrombopoiesis
formation of thrombocytes, CFU meg produces megakaryoblasts undergo incomplete mitoses, huge cells
Bone marrow age
bone marrow cellularity is percentage of hematopoeitic cells to fat
Normal cellularity= 100- age
