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1. hematology > Hematopoiesis > Flashcards

Hematopoiesis Flashcards

1
Q

Cell Types in the periphery

A

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

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2
Q

Bone marrow

A

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

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3
Q

Bone marrow generates diverse cell types

A

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+)
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4
Q 
CD (cluster of differentiation) markers
CD3
CD4
CD8
CD13
CD14
CD15
CD19
CD20
CD34
CD45
A 
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
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5
Q

Colony forming units ands Colony stimulating Factors

A

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)

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6
Q

Lineage nomenclature and morphology

A

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

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7
Q

blood consists of 2 parts

A

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

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8
Q

Erythrocytes

A

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)

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9
Q

Sickle cell disease

A

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)

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10
Q

Erythrocyte development

A

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

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11
Q

leukocytes

A

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

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12
Q

Neutrophils

A

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

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13
Q

Eosinophils

A

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

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14
Q

Basophils

A 
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

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15
Q

Mononuclear inflammatory cells

A

monocytes and lymphocytes

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16
Q

Monocytes

A 
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

17
Q

lymphocytes

A

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

18
Q

Platelets

A

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

19
Q

hematopoiesis/hemopoiesis

A

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)

20
Q

erythropoieses

A

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)

21
Q

Proerythroblast

A

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

22
Q

Polychromatophilic erythroblast

A

medium (1.5 x RBC),

small, round, condensed chromatin, cytoplasm (blue to grayish blue)

23
Q

Orthochomatophilic erythroblast–> reticulocyte–> erythrocyte

A

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

24
Q

Granulopoiesis

A

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

25
Q

Monocytes

A

Abundant grey-blue cytoplasm with variably present, delicate pink granules, reniform/kidney bean shaped nucleus, no nucleoli

26
Q

Lymphocytes

A

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

27
Q

Thrombopoiesis

A

formation of thrombocytes, CFU meg produces megakaryoblasts undergo incomplete mitoses, huge cells

28
Q

Bone marrow age

A

bone marrow cellularity is percentage of hematopoeitic cells to fat
Normal cellularity= 100- age

1. hematology (8 decks)

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