Blood and hematopoesis Flashcards Preview

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Flashcards in Blood and hematopoesis Deck (62)
1

Blood

Connective tissue - 7-8% total body weight 6L. Delivery of O2, nutrients. Transports waste, Co2, transport of hormones and other substances, maintainaince of homeostasis by acting as buffer, etc.

Delivery of O2 and nutrients to cells
Transport of wastes and CO2 from cells
Transport of hormones and other regulatory substances
Maintenance of homeostasis by acting as buffer and participating in coagulation and thermoregulation
Protective role via transport of immune cells and immune components

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Blood composed of

1. Formed elements
2. Plasma

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Formed elements

Cells and cell fragments. Both derived from hematopoetic stem cells. Cells = erythrocytes*(not a true cell type), leukocytes.
Cell fragments = thrombocytes (platelets).

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Plasma

Protein rich fluid extracellular matrix

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Hematocrit

Volume of packed red blood cells in a sample of blood. Measured by centrifuging blood sample and calculating percentage of tube volume occupide by RBCs as compared to whole blood.

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RBC hematocrit volume

45%

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Relative volume of plasma

55%

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Buffy coat (leukocytes/platelets)

1%

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Men - normal hematocrit

39-50%

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Woman - normal hematocrit

35-45%

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Plasma components

Water (90%) - solvent, solutes help maintain homeostasis (pH, osmolarity)

Plasma proteins 7-8%: Albumin, Globulins, Fibrinogen

Other Solutes: **FINSIH THIS

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Plasma proteins

7-8%. Albumin
Globulins
Fibrinogen

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Albumin

About half of plasma proteins. Produced in liver, has an important role in maintaining concentration gradient for osmotic pressure. Acts as a carrier protein, for substances such as hormones, metabolites and drugs.

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Edema

Too much albumin escapes, and takes water with it.

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Globulins

Immunoglobulins (gamma) - antibodies secreted by plasma cells.
Nonimmune globulins (alpha and beta) - produced by liver, help maintain osmotic pressure and serve as carrier proteins.

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Fibrinogen

Made in liver, soluble, via series of cascade reactions, transformed into insoluble protein fibrin which helps form blood clots.

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Blood smear

Drop of blood placed directly on slide and spread thinly over surface with edge of aanother slide.

-Produces monolayer of cells
-air dried and stained with Wright's Stain.

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Wrights stain

mixture of methylene blue (basic), azures (basic) and eosin (acidic).

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Erythrocytes (RBCs)

Anucleate cells - devoid of typical organelles. Bind and deliver O2 (99%) to tissues and bind CO2 (30%) to remove from tissues.
Biconcave discs with diameter of 7.8 microm. Edge thickness of 2.6 microm, and central thickness of 0.8 microm.

Shape maximizes surface area - important in gas exchange.

Histologic ruler - shape relatively constant in fixed tissue.

Producetion occurs in red bone marrow via erythropoesis.

120 day life span

Rate of release - 2 million/sec

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Hemoglobin

Protein binds to O2 and CO2.

Structure: Composed of 4 polypeptide chains of globin with four iron containing heme groups. Iron ions bind one O2 molecule - each protein binds 4 O2. Most common type of hemoglobin (96%) is composed of two alpha and 2 beta chains.

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Leukocytes

2 groups of white blood cells based on morphology (whether or not they have specific granules within cytoplasm and by nuclei shape).

1. Polymorphonuclear granulocytes
2. Mononuclear agranulocytes

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Polymorphonuclear granulocytes

Contain *specific granules* and have multilobed nuclei. Also possess azurophilic granules***

-neutrophils
eosinophils
basophils

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Mononuclear agranulocytes

No specific granules, have rounded nuclei. Also have azurophilic granules.
-Lymphocytes
B lymph, T lymph, natural killer cells (NK)
-Monocytes

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Neutrophils

Granulocytes. Most numerous leukocyte (49-67%). 12 microm to 15 microm in diameter. Small faint lavender granules in cytoplasm. Granule contents: lysozyme (specific granules), peroxidases (azurophilic granules)

Darkish nucleus, several lobes (2-5)
Function:
- First responders to infection
- Acute inflammation
-phagocytose bacteria within tissues, accumulate as pus.

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Eosinophil

Comprise 1-5% of leukocytes. 12 microm to 15 microm in diameter. Cytoplasm - large coarse acidophilic granules. Granule contents - peroxidase, histaminase, arylsulfatase. Light bilobed nucleus.

Function:
-contribute to defense of parasitic infections (major role in defense against helminths worms)
-associated with allergies release of histaminase and arylsulfatase moderates potentilaly harmful effects of inflammatory vasoactive mediators
-Chronic inflammation

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Basophils

Least abundant leukocytes (0%-0.3%)
Diameter: 12μm-15μm
Cytoplasm: large coarse basophilic granules
Granule contents: histamine, serotonin, heparin sulfate
Nucleus: light, bilobed
Function:
Involved in regulating immune response to parasites
Role in allergies via release of vasoactive agents (e.g. histamine)

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Lymphocytes (agranulocyte)

Comprise 26%-28% of leukocytes
Diameter: 6µm-18µm
Cytoplasm: narrow rim of blue cytoplasm
Nucleus: very dark, takes up all of the cell, round, slightly indented
T Lymphocytes
Adaptive immune cells; cell-mediated immunity
Mature in the thymus
B Lymphocytes
Adaptive immune cells; humoral immunity
Production of antibodies
Natural Killer (NK) cells
Innate immune cells; kill virally infected and malignant cells

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T Lymphocytes

Adaptive immune cells; cell-mediated immunity
Mature in the thymus

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B lymphocytes

Adaptive immune cells; humoral immunity
Production of antibodies

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Natural killer cells

innate immune cells; kill virally infected and malignant cells

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Monocytes

Comprise 3-9% of leukocytes
Diameter: 12μm-20µm
Cytoplasm: gray “foamy” texture
Nucleus: darkish; large, off-center; oval, kidney, or horseshoe shaped
Function:
Differentiate into macrophages within body tissues
As macrophages, serve as phagocytic cells involved in antigen presentation

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Thrombocytes (Platelets)

Thrombocytes (platelets) derived from large cells within the bone marrow called megakaryocytes
Small bits of cytoplasm separate from peripheral margins of megakaryocyte forming thrombocytes (platelets)
Small, disc-shaped structures (2 μm-3 μm); lifespan ~10 days
Function: blot clot formation and repair of tears in blood vessel wall

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Hematopoiesis

process of blood cell production and maturation
Purpose: to maintain constant level of the different blood cell types within blood:
Erythropoiesis
Leukopoiesis
Granulopoiesis
Monocytopoiesis
Lymphopoiesis
Thrombopoiesis
Initiated in early embryonic development
Yolk-sac phase
Hepatic phase
Bone marrow phase
After birth: red bone marrow - children is in long bones, adults is in flat bones.

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Monophyletic Theory

all blood cells are derived from a common pluripotential stem cell: hematopoietic stem cell (HSC)
Capable not only of differentiating into all the blood cell lineages, but also capable of self-renewal:

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Hematopoietic stem cell

Gives rise to all blood cells. From mesenchyme.

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HSC differentiation

In the bone marrow, descendents of the HSC can differentiate into 2 major colonies of mulitpotential progenitor cells:

Common Myeloid Progenitor (CMP)
Common Lymphoid Progenitor (CLP)

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Common Myeloid Progenitor

Differentiate into lineage-restricted progenitors:
Megakaryocyte/Erythrocyte
Granulocyte/Monocyte

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Common Lymphoid Progenitor

Common lymphoid progenitor gives rise to lymphocytes:
T cells
B cells
Natural Killer (NK) cells

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Precursor Cells or Blasts

Progenitor cells develop into precursor cells or blasts
With these blast cells:
Morphological characteristics begin to differentiate
Large amount of mitosis – but only produce cells on the way to differentiation

Blast Cells
Start to get an idea or suggestion of what they will become
Lots of mitosis – stem and progenitor cells undergo some mitosis, but that mitosis is really to maintain their relatively small populations; the blast cells under great mitosis, producing only cells on their way to differentiation, unlike stem and progenitor cells, which undergo asymmetric mitosis.

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Proerythroblast

Large cell (12-20μm); large, spherical nucleus with 1 to 2 nucleoli
Cytoplasm shows mild basophilia (free ribosomes)

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Basophilic Erythroblast

Nucleus 10-16μm in diameter; progressively more heterochromatic
Cytoplasm strongly basophilic  large numbers free ribosomes (polyribosomes) that synthesize hemoglobin

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Polychromatophilic erythroblast:

Cytoplasm displays both acidophilia (hemoglobin) and basophilia (ribosomes),
gives overall gray/lilac color
Nucleus becoming smaller; coarse heterochromatin granules  checkerboard pattern

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Orthochromatic erythroblast (normoblast):

Small, compact, densely stained nucleus
Eosinophilic cytoplasm (large amount of hemoglobin)
No longer capable of cell division

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Polychromatophilic erythrocyte (reticulocyte)

No nucleus
Some polyribosomes still present, impart slight basophilia to eosinophilic cells
Can be found within bloodstream (1-2% of total RBC count)

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Granulopoiesis

Eosinophils
Basophils
Neutrophils

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Monocytopoiesis

Monocytes

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Lymphopoiesis

B cells
T cells
NK cells

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Granulocytes and Monocytes

Originate from common myeloid progenitor which differentiates into granulocyte/monocyte progenitors

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Granulopoiesis

neutrophils, eosinophils, and basophils undergo similar morphologic maturation process:

myeloblast  promyelocyte  myelocyte  metamyelocyte  (*band cell)  mature cell

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Lymphocytes

HSC  CLP  Lymphocytes

T cells
B cells
NK cells

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Thrombocytes (platelets

derived from megakaryocytes via thrombopoiesis:
HSC  CMP MEP MKP  Megakaryoblast  Megakaryocyte  Platelets


HSC = hematopoietic stem cell
CMP = common myeloid progenitor
MEP = megakaryocyte/erythrocyte progenitor
MKP = megakaryocyte progenitor

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Megakaryoblast

large cell (30μm diameter); nonlobed nucleus
Megakaryoblast undergoes successive endomitoses to become a platelet-producing megakaryocyte

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Megakaryocyte

50 to 70μm in diameter; complex, multilobed nucleus and scattered azurophilic granules; polyploid cells (64N)

Megakaryocytes located near sinusoids within bone marrow; send cytoplasmic extensions that break off as platelets
Small bits of cytoplasm separated from peripheral regions of megakaryocytes by extensive platelet demarcation channels, lined by invaginations of plasma membrane
Cytoplasmic fragments partitioned, forming individual platelets
“foamy” peripheral cytoplasm represents areas where segmentation of platelets is occurring

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Karyo

nucleus

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Endomitoses

chromosomes replicate, but neither karyokinesis nor cytokinesis occurs
Ploidy increases from 8N to 64N before chromosomal replication ceases; megakaryocytes are polyploid cells (cells whose nuclei contain multiple sets of chromosomes)

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Bone Marrow

Located within medullary cavity and spaces of spongy bone
Consists of sinusoids (sinusoidal capillaries) and hematopoietic cords

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Hematopoietic cords

developing blood cells, megakaryocytes, macrophages, mast cells, adipocytes
Cells develop in clusters/nests located near sinusoids

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Adventitial cells (reticular cells):

Send sheetlike extensions into hematopoietic cords  provide support for developing blood cells; stimulate differentiation of progenitor cells

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Bone marrow cellularity

ratio of hematopoietic cells to adipocytes
Bone marrow cellularity: 100 – age ± 10%
Number of hematopoietic cells decreases with age

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HSCCMPMEPErP

HSC = hematopoietic stem cell
CMP = common myeloid progenitor cells
MEP = Megakaryocyte/Erythrocyte progenitor cell
ErP = Erythrocyte-Committed Progenitor

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Normoblast

General term - do not use this.

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Band cell

only affiliated with neutrophils. This stage helps get nucleus to be multilobular.