lecture 6-7 Hematopoiesis Flashcards
hematopoietic stem cells leads to ___
every type of blood cells
Blood is:
- body fluid that delivers nutrients and oxygen to cells and transports waste
- blood cells suspended in blood plasma
- type of connective tissue
why is blood considered a connective tissue
- embryologically, mesoderm layer origin
- blood connects the body systems together
Major cell types in circulating blood are
- enucleated or nucleated(bird) erythrocytes (red blood cells)
- mono and poly nucleated leukocytes or white blood cells
white blood cells are
leukocytes
red blood cell other name is
erythrocytes
composition of blood
- 45% formed elements
- 55% plasma
formed elements of blood
45% of blood
-red blood cells (erythrocytes)
transport O2 and CO2
-white blood cells (leukocytes)
fight infection
-platelets (thrombocytes)
form clots
plasma part of blood
55% of blood
-Water 90% of plasma
-Plasma proteins 8% of plasma
Globulins
Fibrinogen
-Salts 1 %
-Gases, Nutrients, Wastes, Hormones
what is the function of water in blood
major part (90%) of the plasma
maintains blood volume, transports molecules
what is the function of plasma proteins
8% of plasma
maintains blood osmotic pressure and pH
Globulins: transport and fight infection
Fibrinogen: Blood clotting
what are two plasma proteins and what do they do
Globulins: transport and fight infection
Fibrinogen: Blood clotting
What function does salt have on blood
1% of plasma
maintain blood osmotic pressure and pH, aid metabolism
what function does gases have on blood
O2 and CO2- cellular respiration
what function does nutrients have on blood
lipids, glucose, and amino acids
food for cells
What function does waste have in blood
urea and uric acid
end product of metabolism, excretion by kidneys
What function does hormones have in blood
aid metabolism
type of white blood cells
neutrophils (40-70%)
lymphocytes (20-45%)
monocytes (4-8%)
eosinophils (1-4%)
basophils (0-1%)
mixture of methylene blue and derivates of azure blue and eosin
romanowsky dye
nucleus: purple
hemoglobin: pink or tan
Leukocytes: blue to blue grey
Granules
eosinophilic: red
Basophilic: blue
Neutral: stain neither
label
band cell is immature white blood cell, shouldn’t be in slide
aspirate of bone marrow
gives a jumble of all cells from that area
suspension of cells
biopsy of bone marrow shows
organized structure of bone marrow
accumulating abnormal numbers or types of cells means ___
disorders
cancers, severity and metastasis (leukemia, lymphoma, multiple myeloma, anemia, pancytopenia, parasites and infection)
___ can be missed in aspirate and may require biopsy
lymphoma
marrow elements
granulocytes and their precursors (50-75%)
erythroid precursors (25-50%)
hematopoietic
stromal cells
types of hematopoietic cells that are found in marrow
monoblasts/monocytes <5%
megakaryocytes-few
macrophages- few
lymphocytes- few
types of stromal cells found in marrow
osteoblasts, preosteocytes
adipocytes
mesenchymal stem cells
which one is bone marrow, which one is blood
bone marrow is on the right
blood smear is on the left
most blood cells live for only ___ and thus they must be constantly replenished
days or weeks
In healthy adults, approximately ___ new blood cells are produced daily in order to maintain steady state levels in the peripheral circulation
1011-1012
variation in ___ or maturation state of hematopoietic cells in bone marrow and in circulation are key indicators of health vs ___
steady state levels
disease
hematopoietic stem cells break into what two groups
- red blood cells and megakaryocytes/platelets
- white blood cells (leukocytes)
the mechanism by which a single common pluripotent hematopoietic stem cell can change into every type of cell
lineage specification
hematopoiesis requires a specialized ____ to survive
microenvironment/ niche
cells need to be able to self replenish and differentiate
gestational hematopoiesis occurs in
yolk sac
then liver and spleen
then bone marrow and lymph nodes
T lymphocytes further differentiate in the ___
thymus
In avian species, B Cell development happens in the ___
Bursa of Fabricius
seeding of self renewing tissues happens all over the body for ____
macrophages
(hematopoietic cells destined to be a macrophage are dispersed all over the body and can turn into macrophages as needed within those tissues, does NOT need to happen in bone marrow exclusively)
self renewing- maintain themselves without bone marrow
as you age hematopoiesis stops in certain bones, order is
Tibia
femur
lymph nodes
ribs
sternum
vertebral and pelvis
when hematopoiesis occurs outside of bone marrow
extramedullary hematopoiesis
rare- occurs in organs outside of bone marrow in diverse conditions: fetal development, immune responses, and pathological circumstances/stress response
can happen in spleen
example of extramedullary hematopoiesis
spleen
splenic extramedullary hematopoiesis
hematopoietic stem cells
can self renew (symmetric division)
multipotent stem cells- can change into a bunch of other things (differentiate) through lineage specification
symmetric division of hematopoietic stem cells
create two identical stem cells
or
makes two differentiated cells (short term)
asymmetric division of hematopoietic stem cells
makes itself and makes a differentiated cell
bone marrow/ HSC transplant can be performed to ___ damaged bone marrow with healthy bone marrow stem cells
replace
some diseases that use stem cell replacement
leukemia, myelodysplasis, immune deficiency disease, inherited metabolic disorders, anemia and marrow failure
bone marrow has two compartments
red and yellow
yellow or stromal marrow makes:
fat, cartilage and bone
yellow color from the carotenoids in the fat droplets in high number of fat cells
-paucity of vasculature
two niches of trabecular bone
spongy bone
endosteal niche: outer edge of bone marrow, contains osteocytes, bone matrix, KitL, CXCL12, PGI2 and relatively quiescent HSCs, support HSC self renewal
perivascular niche: inner core of bone marrow closer to vasculature. contains actively dividing HSCs, sinusoidal endothelium, stromal cells (CXCL12high reticular cells and mesenchymal stem cells) supports lineage specification
sinusoid
holes
endosteal niche
outer edge of bone marrow, contains osteocytes, bone matrix, KitL (ligand), CXCL12(cytokine) , PGI2 and relatively quiescent HSCs, support HSC self renewal
long term self renewal
hypoxic- low O2
perivascular niche:
inner core of bone marrow closer to vasculature. contains actively dividing HSCs, sinusoidal endothelium, stromal cells (CXCL12high reticular cells and mesenchymal stem cells) supports lineage specification
higher O2
as specialized liquid connective tissue blood can
- transport substances to and from the capillaries
- regulate body temperature
- form clots
two main components of blood
plasma
formed elements
formed elements of blood
red blood cells
(carry oxygen and carbon dioxide)
white blood cells
(fights infection)
platelets
(coagulation)
as red blood cells mature in bone marrow ___
start big, gets smaller
nucleus starts as most of the cell then shrinks and eventually disappears
what are the stages of red blood cell maturation in bone marrow
pronormoblast (proerythroblast)
basophilic normoblast (erythroblast)
polychromatic normoblast (erythroblast)
orthochromatic normoblast (erythroblast)
polychromatic erythrocyte
erythrocyte
erythroblast is another name for
normoblast
proerthroblast
blue arrows
basophilic erythroblast
smaller, little condensation of nucleus
red arrow
polychromatic erythroblast
black arrows
orthochromatic normoblast (erythroblast)
even smaller nucleus, darker
yellow
pink
reticulocytes/ polychromatic erythrocyte
(no nucleus, slightly bigger then RBC)
erythrocytes
(red blood cell smallest no nucleus, discoidal in shape)
what are these ?
red blood cell development in bone marrow
proerythroblast
basophilic erythroblast
polychromatic erythroblast
orthochromatic erythroblast
what are these
immature and mature red blood cells, can be seen in bone marrow and in blood
bigger, reticulocyte/ polychromatic erythrocyte
smaller, erythrocyte (RBC)
what animal has nucleated red blood cells
birds
what animal is this from
non mammal
red blood cells survive:
dog -110 days
cat- 70 days
horse -150 days
mouse- 20-30 days
what animal
turtle
what animal
chicken red blood cells
red blood cells can change in shape, size and color depending on species
platelets come from
megakaryocytes
during development of megakaryocytes cells ___
get bigger and nucleus becomes lobulated, cytoplasm gets more complex: (1000s) which are platelets
sit close to sinusoids
megakaryocytes are situated in perivascular niches close to ___
sinusoids
what are these
green: immature megakaryocyte
pink: mature megakaryocyte
precursor to platelets
what is this and what is the green arrow pointing to?
megakaryocyte
green arrow pointing to platelets
platelets
- small cellular fragments derived from megakaryocytes
- mammals
- no nucleus
- <1 % of whole blood volume
- 100,000-500,000/ microL (very prevalent but so little they take up only a little space)
- forms clots
Thrombocytes
“platelets” of non- mammals
- nucleated cells
- look similar to lymphocytes
- 20,000-40,000/ microL
- less abundant because they last longer
in non mammals cells that act like platelets
thrombocytes
in mammals ___ have a similar function to ___ in non mammals
platelets
thrombocytes
GMP can form
granulocytes
monocytes
dendritic cells
dendritic cells come from
GMP and GMLP
erythrocytes and platelets come from the same ___
progenitor, branches earlier from all other blood cell type
Type of Granulocytes
basophil
eosinophil
neutrophil
steps of neutrophil
myeloblast
N. promyelocyte (progranulocyte)
N. Myelocyte
N. Metamyelocyte
N. Band (band nuetrophil)
Neutrophil
label
neutrophils immature and mature in blood
myeloblast, promyelocyte (progranulocyte), myelocyte, metamyelocyte, band neutrophil, segmented neutrophil
neutrophils
most abundant WBCs
- first line of defense
- important in inflammatory responses
- attack and destroy bacteria and viruses by phagocytosis
-live only a few days
-granules are neutral except in rabbits, guinea pigs and non mammals
granules of neutrophils are ___ expect for ___
granules are neutral except in rabbits, guinea pigs and non mammals
what is this
mature neutrophil in blood
granules, neutral
purple, lobulated nucleus
bigger then red blood cells
in non mammals what is the same as neutrophils in mammals
heterophils
Heterophils
“neutrophils” of non-mammals
have large distinct granules, makes it hard to distinguish from eosinophils
what is this
nucleated red blood cell
heterophil (neutrophil of non mammal)
Basophil
type of granulocyte
very dark granules- basophilic (will be purple)
long lobulated nucleus
what are these
basophils
dark, basophilic (purple) granules
lobulated, long nucleus
granules and nucleus same/similar colors
Eosinophils
type of granulocytes
big acidophilic (eosin) granulocytes (pink)
Granules can be different shapes depending on species
long lobulated/segmented nucleus
cat has __ shaped granules in eosinophils
rod
dogs have __ shaped eosinophil granules
variably sized
horses have ___ shaped eosinophil granules
large, round, bright pink
what is this
eosinophil of horse
large, pink granules
what is this?
eosinophil of cat
rod shaped granules
Monopoiesis is
monocyte to macrophage
can you tell the steps of maturation of a monocyte in the bone marrow?
no look almost identical
monocyte
bean shaped nucleus
turn into macrophage
most tissue-resident ___ are established prenatally and maintained through adulthood by longevity and ____. Their generation and maintenance are thus ___ from ongoing hematopoiesis although the cells can be complemented by adult monocyte-derived ___
macrophages
self renewal
independent
macrophages
Aside from being immune sentinels, tissue macrophages form integral components of their host tissue. This entails their ___ in response to local environmental cues to contribute to the development and specific function of their tissue of residence
specialization
monocyte/macrophage can turn into
in spleen macrophages are
- white pulp
- red-pulp
- marginal zone
- metallophilic
monocytes can either be __ or __
inflammatory monocytes
or
resident monocytes
type of dendritic cells
classical Dendritic Cells- two types cDC1 and cDC2
present antigens
plasma Dendritic Cells
have lots of ER looks like plasma cell
Mast cells
most like basophils
- mast cells circulate in immature form and mature to connective tissue or mucosal mast cells in tissues depending on environment
- granules rich in histamine and heparin and anti-coagulant
- express high affinity IgE receptors (worms, allergies)
Mast cells
most like basophils
- mast cells circulate in immature form and mature to connective tissue or mucosal mast cells in tissues depending on environment
- granules rich in histamine and heparin and anti-coagulant
- express high affinity IgE receptors (worms, allergies)
mast cell granules are rich in
histamine
heparin
anti-coagulant
Lymphoid cells
Natural Killer cells (large granular lymphocyte)
B lymphocytes
T lymphocytes
(adaptive immune system)
immature T cells move into
thymus
mature and learn self from non-self
CD4 and CD8 cells
B cells
pro B cells
Pre B cells
Leave bone marrow
become mature
gets activated into plasma cells that make antibodies and memory cells
in birds: will mature in Bursa of Fabricius
what is this
Lymphocyte
B or T cell
nucleus is round, takes up most of cell
red blood cells form ___
rouleau
in cats and horse
the presence of antibodies on the surface of the erythrocytes which joins them together
anisocytosis
cow
blood cells are different sizes
poikilocytosis
goat blood look weird shapes
weird shaped blood
what animal
poikilocytosis
different sized blood
anisocytosis
bovine
