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48 Cards in this Set

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  • Back
Blood: basic description of amount in a person, and composition
70cc/kg in a normal person
the only liquid organ
composed of cells (erythrocytes, leukocytes, thrombocytes) and plasma (electrolytes, proteins, lipids)
Proteins in blood plasma and serum
albumin, globulins (antibodies), clotting factors

serum has no fibrinogen or clotting factors
What are the life times of blood cells, and why are they as such?
-short life span (except lymphocytes and macrophages)
-multiplicity of cell types
-widely distributed throughout body
-bone marrow must respond quickly to emergency needs for additional cells (7-8x)
-stem cells must be maintained in adequate numbers throughout life, i.e. self renewal
Describe the maturation of red blood cells right before they leave the bone marrow.
In the stage right before it fully matures: orthochromatic erythroblasts. They have small nuclei, which become extruded and the left over cell leaves the bone marrow into the peripheral blood stream. It is now slightly bluer than fully mature blood cells (polychromasia-- a sign of newly synthesized cells: reticulocytes)
These continue to circulate for 48 hours to make Hemoglobin to make normochromic, normocytic (normal sized) red blood cells.
How are polychromatic reticulocytes stained?
Methylene blue stain which precipitates rRNA to make hemoglobin
How many reticulocytes are made per day
Normally are made 50-100,000 reticulocytes/ul per day
Erythrocytes
Anucleate, lack organelles, 5-6 x 10^6/ul, 7-8μm biconcave disc, anaerobic respiration (no mitochondria), increased Hexose monophosphate shunt (NADPH, G6PDH) for reducing oxidants (keep Fe2+ reduced), 120 day life span to travel 300 miles
What hormone regulates RBC production? How is production of this hormone affected by anemia?
erythropoietin, which is synthesized in the kidney, and acts on blood cell precursors in bone marrow. Erythropoietin secretion increases in anemia.
Why is the shape of the RBC important?
The biconcave shape increases surface to intracellular volume ratio for gas exchange

8μm RBC is deformable, to fit through 2μm capillaries.
Adult hemoglobin concentration, composition, and function
12-14 gm/dL of blood
Adult Hgb A:
2 α chains, 2 β chains
4 heme molecules with iron in center
Transports O2 from lungs to tissues
Transports carbon dioxide from tissues to lungs
Describe RBC membrane
Keeps membrane slippery, maintains electrolyte exchange, deformability
1. Lipid bilayer
2. Integral membrane proteins - ankyrin which attaches to spectrin
3. Cytoskeleton proteins - spectrin dimer
How do RBCs die?
Senescent RBCs go to spleen to die: enters through a splenic artery through white pulp. Some arteries dilate into sinuses, then veins which leave the spleen; others empty out into extravascular red pulp. Plasma easily diffuses back into circulation, but RBC's need to squeeze through cords back into circulation. If not, eaten by macrophages --> extracellular hemolysis.
white pulp = lymphoid tissue
red pulp = where macrophages are
Platelets (thrombocytes)
Used to be called "blood dust" because they are so small.
Arise from megakaryocytes (largest cell in bone marrow).
Have darker section called Granulomere: where organelles are.
Have lighter section: Hyalomere.
No nuclei, live for about a week, 150-400,000/ul. Contain all organelles. Contain electron dense granules. Main function of platelets: stop blooding-- primary hemostatic plug. Contain microtubules: canilucular system leading to platelet membrane. Contractile proteins to change shape (actin, mysosin).
Membrane proteins: GP Ib, IIb/IIIa -- mediate adhesion
Megakaryocytes
Do not undergo cellular division, only nuclear division. Fragments of the cell become platelets.
Describe the electron dense contents of platelets and their contents
Alpha: VWF, fibrinogen, PDGF, platelet factor 4, V, VIII
Dense bodies: serotonin
Lysosomes, peroxisomes
platelet function
First line of defense in hhemostasis of vessel injury
-adhesion, activation, aggregation
-plasma membrane is platform for fibrin formation (clot)
mediate inflammation
mediate vascular constriction
release of PDGF
Leukocytes types, percentage of each
5-10x10^3/ul
Granulocytes:
Neutrophil 55-65%
Eisonophil 2-5%
Basophil 1%

Agranulocytes (some do have granules though):
Monocyte 3-8%
Lymphocyte 20-25%
Neutrophils
55-65% of leukocytes
12-15u
6 hour life span in blood
1-5 day life span in tissues
multilobed nucleus
contractile proteins (actin, myosin) - "move, and eat"
Cytoplasmic granules: specific (lysozyme, alk.phos.), and non specific
Neutrophil function
Motility (contractile proteins)
-chemotaxins (released at the site of tissue damage) attract PMNs to infected or inflammed tissue
Endocytosis/Phagocytosis
-pseudopodiaform phagosome around organism
phagosome fuse with granules
H2O2 production
Opsonization (antibody/complement coating) enhances phagocytes
Endotoxin (in bacteria) mediates G-CSF, GM-CSF release from marrow stromal cells --> neutrophil production
Band neutrophil
neutrophil with less lobed nuclei. slightly less mature neutrophils-- sign of neutrophil production
Eisonophils
Bilobed nucleus
Bright red granules
Basophils
Granulocutes
Specific, 2ndary basophilic granules - prominent purple granules
-contain heparin and histamine
Receptors for IgE, when bound, degranulation and release of histamine
Monocyte
Eccentric, horseshoe-shaped nucleus
Up to 20u
Azurophlic granules with lysosomal enzymes
Have MHC and complement receptors on surface
-phagocytize antibody or complement coated cells/organism
Motile and phagocytic
Differentiate into tissue macrophages, living for months to years (reticuloendothelial system)
Lymphocytes
8-10um
20-25% of blood leukocytes
effectors of immune response
T-cell: cell mediated immunity (most numerous)
Can become activated --> reactive "atypical" lumphocytes
B-cells: humoral immunity
Lifetime of granulocytes
Less than 10 hours
Lifetime of platelets
7-10 days
Site of normal blood production
axial skeleton, sternum, skull, pelvic bone, spinal column
Blood production progression by location
yolk sac -> liver -> spleen -> long bones
Bone marrow description
microenvironment with 1) cellular matrix: support and elaboration of cytokines and growth factors: contains cells
2) ECM: scaffolding that keeps cellular material withing contact of cellular matrix
fibronectin, proteoglycans, collagen

hematopoietic stem cells (cellular component), fibroblasts, lymphoid progenitor, growth factors, nutrients (B12, folate, Fe),
Bone marrow components
Yellow marrow (fat)
Red marrow
integrating sinuses that lead to peripheral blood
thin layer of endothelial cells separate precursor RBCs from peripheral circulation
Description of hematopoietic stem cell: properties, behavior, etc.
Sustains hematopoiesis - generates all blood cells
Capable o self renewal throughout life
High proliferative capacity: potential to give rise off millions of cells; but mitotically inactive (the actual stem cell is mostly quiescent)
Pluripotent
Not morphologically identifiable
Extremely rare: <1 per 100,000 marrow cells
Circulate in blood and cord blood
Hematopoietic progenitor cell
Progeny of stem cells
No/limited self-renewal capacity
Lower proliferative capacity
More mitotically active than stem cells
Uni- or bi-potent
Not morphologically identifiable
Greater in number than stem cells (1000/100,000)
Precursor cells
Morphologically identifiable
Most numerous cells in bone marrow
No self-renewal capacity
Lower proliferative capacity than progenitor cells: 1 cell ultimately provides fewer progeny than 1 progenitor cell
Unipotent: commited to 1 lineage
Regulation of hematopoiesis
By hematopoietic growth factors
-glycoproteins
-hormone-like: erythropoietin, thrombinpoietin
Paracrine: SCF, IL's, GM-CSF
How are thrombopoietin levels regulated?
Thrombopoietin made at a constant level, and is degraded by platelets
fewer platelets --> less degraded --> [thrombopoietin] increases --> more platelets synthesized
Myeloblast
the most immature precursor in the granulocyte lineage: the first one that's morphologically "identifiable"-- although more needed.
Becomes pathologic in acute leukemia.
Intensely basophilic cytoplasm, immature nucleus.
Promyelocytes
Easily identifiable: relatively smooth unclumped chromatin in nucleus, large purple primary granules that completely cover nucleus and cytoplasm, larger than blasts.
Myelocyte
Pink cytoplasm develops-- secondary granules. Nucleus is more condensed. Big purple primary granules are lost. The myelocyte is the last stage that undergoes mitosis.
metamyelocyte
Pretty much like a myelocyte but the nucleus is more mature (indented),
Bands
Indentation in nucleus shape of a banded neutrophil.
Erythroid nuclei
Tend to be in center of cell
Proerythroblasts
Earliest precursor in erythrocyte lineage. Immature cell: big, intensely basophilic nucleus, unclumped chromatin. Becomes a basophilic erythroblast.
Erythroblast
Nucleus smaller, cytoplasm
polychromatophilic erythroblast
less blue, more pink cytoplasm (hemoglobin being made = pink, less RNA = blue)
Orthochromatic erythroblast
Small clumped nucleus that's about to be extruded, it's more blue: these are the reticulocytes that are stained blue
Normal bone marrow aspirate
One should see all of the stages of maturation of the different lineages
Megakaryopoiesis
CFU-Mega (progenitors)
Megakaryoblasts (precursors) 2N
Endoreduplication (DNA replication without cell division) 16-32N
Cytoplasm maturation
Fragmentation of cytoplasm --> platelets
Each lobe of nucleus is 2N
Azurophilic granules
lysosomal = contain lysosomal enzymes
primary gr= appear first in granulopoiesis
nonspecific gr = present in all granulocytes (including monocytes and lymphocytes)

Specific granules - present in specific granulocytes