Exam 2 Flashcards
List the order of RBC maturation
polychromatic normoblast
pronormoblast
BFU-E
erythrocyte
reticulocyte-BM
CFU-E
orthochromic normoblast
reticulocyte-PB
basophilic normoblast
BFU-E- burst forming unit- rise to large colonies
CFU-E- colony forming units- rise to smaller colonies
pronormoblasts
basophilic normoblast
polychromatic normoblast
orthochromic normoblast
reticulocyte-BM
reticulocyte-PB
Erythrocyte
What are the 5 rules of maturation
size of cell decreases
N:C ratio decreases
nuclear chromatin becomes coarser, clumped, condensed
nucleoli disappear
cytoplasm changes blue to grey blue to pink
How many divisions are there in the erythrocyte cell line
there are usually 3 or up to 5
How many RBCs are formed from 1 pronormoblast
8 to 32
What stages of RBC precursors are capable of division/ mitosis
pronormoblast to polychromatic normoblast
No nucleus, mostly pink but still a blue tinge, non biconcave, irregular shape, in BM for 1-2 days then in periferal blood
polychromatic / reticulocyte
No nucleus, biconcave disk, only in peripheral blood, salmon pink color
erythrocyte
What is the blue tinge in retics?
residual ribosomes and RNA
Nucleus, dark blue colors, can undergo miotsis, present only in BM
NRBC
What does EPO do?
Where is it produced
What stimulates it
triggers RBC production
the kidney
stimulated by hypoxia
what are the 3 major effects of EPO
allowing early release of reticulocytes from the BM
preventing apopototic cell death
reducing the time needed for cells to mature in BM
Intravascular vs Extravascular
intra-macrophage mediated- more common
extra-damage due to external factors
What is the purpose of the Emben Meyerhof pathway
glycolysis
RBC enters Glut-I-> pyruvate to pyruvic acid -> 4ATP generated per glucose mol
Through which transmembrane protein does glucose enter the RBC?
Glut I
What is the initial substrate of anaerobic glycolysis
glucose
What is the final products of anaerobic glycolysis
lactate and NAD
What are the 3 alternative pathways/ shunts to glycolysis
hexose monophosphate shunt
methemoglobin reductase pathway
rapoport leubering pathway
What is the action of the pentose phosphate shunt
Hexose monophosphate-detoxifies peroxide which arises from O2 reduction
What is the purpose o the hexose monophosphate pathway
extends life of RBCs, denatures unneeded proteins and lipids
How much G6P is diverted to HMP
5-10%
What is the action of the methemoglobin reductase pathway
methemoglobin is reduced to methemoglobin reductase
Explain what happens with peroxide iron in the methemoglobin reductase pathway
peroxide oxides heme iron from the ferrous to the ferric state
Explain what happens with methemoglobin in the methemoglobin reductase pathway
hg bound to ferric iron
What is the action of Rapoport leubering pathway
Generates 2,3 bisphosphoglycerate 2.3 BPG
What is the purpose Rapoport- Leubering pathway
enhances O2 delivery to tissues
Utilizes glucose-6-phosphate-dehydrogenase (G6PD)
Hexose monophosphate pathway
Hexokinase generates glucose-6-phosphate and ADP from glucose and ATP
Embden meyerhof
Generates 2,3-BPG
Rapaport
Utilizes an enzyme that reduces ferric iron to ferrous iron
Methemoglobin
Leads to an ATP deficit
Rapaport
Detoxifies peroxide
hexose monophosphate
What is the function of transmembrane proteins
transport sites, adhesion sites, signaling receptors
What are the 2 major macromolecular complexes formed by transmembrane proteins
Ankyrin complex
actin junctional complex
List the transmembrane proteins
aquaporin I
Band 3
Ca2+ ATPase
Duffy
Glut-I
Glycophorin A
Glycophorin B
Glycophorin C
Duffy
transmembrane
Glut-I
transmembrane
Glycophorin A B and C
transmembrane
Ca2+ ATPas
transmembrane
Band 3
transmembrane
Aquaporin I
transmembrane
What are the principal cytoskeleton proteins
alpha spectrin and beta spectrin
What is the cytoskeleton morphology
hexagonal lattice
What is the function of cytoskeletal proteins
provides lateral/ horizontal membrane stability
spectrin stability
membrane deformation
What substances is the RBC membrane impermeable to
Na+, K, Ca
What substances is the RBC membrane permeable to
HCO3
What are the 2 progenitor cells from which leukocytes arise
CMP (CFUGEMM)
CLP
List the order of maturation for myeloid precursors from blast to segmented neutrophil
myeloblast
promyelocyte
myelocyte
metamyelocyte
Band
neutrophil
Large, slightly basophilic cytoplasm, azurophilic granules
darker chromatin, purple cytoplasm
myeloblasts
largest, round to oval, paranuclear halo “hof”
cytoplasm is basophilic, azurophilic granules
chromatin is clumping, heterochromatin may be visible
promyelocyte
Dawn of neutrophilia, secondary pinker granules,
primary dark purple granule eccentric nucleus, flat edge
myelocyte
Kidney shape, no nucleoli, little to no basophilia, chromatin is more clumped
metamyelocytes
nucleus is indented but not segmented
no basophilia, tertiary granules
highly clumped chromatin
band
nucleus is indented but not segmented
no basophilia, tertiary granules
highly clumped chromatin
band
2-5 nuclear lobes
neutrophil
Many primary granules
pro
large, visible nucleoli
blast
largest cell in neutrophil maturation
pro
dawn of neutrophilia
myelocyte
last stage capable of mitosis. For neutrophils
myelo
What is the percentage of these cells in blood
band
meta
myelo
pro
blast
neutrophil
band- 0-5%
meta- none
myelo- none
pro-none
blast- none
neut- 50-70%
What is diapedesis
when neutrophils leave the blood and enter the tissues
What is neutrophils lifespan when there is inflammation/ infection? When there is not?
-present-extended
-absent- a few hours
What are the major functions of neutrophils
phagocytosis and destruction
What are the steps of extravasation/ diapedesis
put in order and explain
aadhere
crawl
roll
active
transmigration
chemotactic agents bind to neutrophil
neutrophil rolls along endothelial cells
adhesive mols adhere to endothelial cells
active crawling toward site of migration
transmigration between endothelial cells
What are the steps of phagocytosis
put in order and explain
attachment
kill
recognition
digest
recognition
attachment
kill
digest
bilobed nucleus, refractile orange red secondary granules
eosinophil
What is the normal percentage of eosinophils in the blood
1-3%
blue-black secondary granules, slightly condensed chromatin, blue cytoplasm,
basophils
How many basophils are normally in peripheral blood
0-2%
largest normal WBC, ground glass
indented nucleus
vacuoles
macrophage
What is the normal amount of monocytes in peripheral blood
2-11%
What type of immunity do
B
T and NK cells give
B-humoral
T and NK cellular
What is the normal amount of lymphs in blood
18-42%
What do B lymphs turn into?
What do basophils turn into
What do T cells turn into
B- plasma cell
basophil- mast cell
T-CD4 or CD8, memory
Where does antigen independent lymphoid development occur
and dependent
independent primary organs
dependant- secondary
What causes reactive atypical lymphs
viral infections
What is the function of B lymphs
T lymphs
NK cells
B- antibody production
T- pathogen response
NK- virus and cancer infected cells
small, chromatin arranged in blocks, nucleolus very rare
lymphs
List the order of maturation for platelets
BFU-Meg
CFU-Meg
LD-CFU-Meg
endomitosis
MK-I megakaryoblast
MK-II promegakaryocyte
MK-III megakaryocyte
What is endomitosis? Which cell can do this
mitosis without telophase an cytokenesis (separation into daughter cells)
multiple DNA copies synthesize cytoplasm, differentiates into platelets
LD-CFU-Meg
Describe MK I
megakaryoblast
blebs
alpha granules
demarcation system (delineates platelets during thrombopoiesis)
Describe MK II
promegakaryocytes
lobular nuclei, indentation
reaches full ploidy
Describe MK III
very large
intensely lobulated
this is where thrombopoiesis occurs
azurophilic cytoplasm- lavender color
What are the steps of platelet shedding
DMS dilates -> bundles of tubules -> proplatelet process develop -> processes pierce through between endothelial cells into the venous blood -> transverse constrictions appear through processes -> platelets are broken off / shed
Put the steps in order
processes pierce through between endothelial cells into the venous blood
platelets are broken off / shed
proplatelet process develop
transverse constrictions appear through processes
DMS dilates
bundles of tubules form
DMS dilates -> bundles of tubules -> proplatelet process develop -> processes pierce through between endothelial cells into the venous blood -> transverse constrictions appear through processes -> platelets are broken off / shed
What is TPO and where is it produced
in the liver
hormone that stimulates platelet differentiation
Acts with TPO to induce early differentiation of stem cells
IL-3
Act with TPO to enhance endomitosis, megakaryocyte maturation, and thrombocytopoiesis
IL-6
IL-11
Other cytokines and hormones that work with TPO
Stem cell factor (kit ligand)
GM-CSF
G-CSF
Cytokines and hormones that INHIBIT megakaryocyte growth
Platelet factor 4 (PF4)
β-thromboglobulin
Neutrophil activating peptide 2
IL-8
What are reticulated platelets
stress platelets appear to compensate for thrombocytopenia
circular to irregular, lavender and granular, clear or slightly blue-grey cytoplasm, biconvex
platelet
Outer layer plasma phospholipids
phosphatidycholine
sphingomyelin
Innter cytoplasm layer phospholipids
phosphatidylinositol
phosphatidylethanolamine
phosphatidylserine
What are the 3 steps of platelet activation
adhesion
aggregation
secretion
