Exam 3: Circulatory System - Blood Flashcards
functions of blood (6)
- transportation of dissolved substances
- defense against infection
- pH regulation
- fluid balance
- thermoregulation
- clotting
what is blood?
specialized connective tissue
formed elements of blood
suspended in plasma matrix
-erythrocytes, leukocytes, thrombocytes
plasma composition (5)
albumin: maintains oncotic P, some transport
alpha and beta globulins: transport proteins and coagulation factors
gamma globulins: immunoglobulins
complement proteins: defense
fibrinogen: clot structural proteins
serum
plasma without the clotting factors
what is the origin of hematopoietic stem cells (HSC)
mesenchymal
where do HSC develop during late gastrulation
extraembryonic, yolk sac membrane
initial hematopoiesis is transient with
stem cells migrating to the fetal liver
in early through mid-gestation what is the primary site of hematopoeisis
liver
from the liver stem cells migrate through the circulatory system to ___ and ___
spleen and bone marrow
at birth spleen production declines and what becomes the main hematopoietic site
bone marrow
what happens at 4-5yrs old - bone marrow development
adipose tissue infiltrates marrow cavity at diaphysis and spreads toward the epiphysis replacing hematopoietic tissue
what happens at 4-5yrs old - bone marrow development
adipose tissue infiltrates marrow cavity at diaphysis and spreads toward the epiphysis replacing hematopoietic tissue
by adulthood where is hametopoietic marrow limited to
flat bones, vertebrae, epiphyses of humerus and femur
hematopoiesis
production of blood cells
begins with multi-potent stem cell - hemocytoblast
hemocytoblasts go through mitosis - one stays behind and remains hemocytoblast and the other is sensitized in 2 ways
2 ways hemocytoblast is sensitized
become lymphoid stem cell: only gives lymphocytes (b cells, t cells, natural killer)
myoloid stem cell: can become all of the others (platelets, macrophages, other WBC)
precursor cells for erythropoiesis contain receptors for…
EPO
transferrin
fibronectin
EPO
directs maturation with receptors increasing in proerythroblasts
what happens when our oxygen level goes down (erythropoiesis)
kidney interstitial cells release EPO which circulates to bone marrow and binds to receptor on stem cell
this triggers the stem cel to start increasing transferrin receptors - once this happens NO going back - determined to differentiate into mature erythrocyte
transferrin
transport molecule for iron
circulates to bone marrow and takes in iron which is the raw material for hemoglobin
reticulocytes
show a decrease in fibronectin receptors - correlating with their release from marrow stoma into circulation
they eject nuclei prior to release
what is high reticulocytes a sign of
red flag!!
something is happening to cause them the up the production of RBC
what happens to reticulocytes that are still expressing fibronectin receptors
they are sequestered in the spleen until the “stickiness” is lost
what happens to the erythrocyte after the expulsion of the nucleus as a reticulocyte
it becomes a biconcave disc which the shape causes an increased surface area for more gas exchange
as erythrocyte ages what happens?
dec in enzyme activity, membrane, water, and ability to bend and deform under stress
ones that lose flexibility cannot navigate through the stresses of spleen and are destroyed
composition of hemoglobin
4 subunits (2 alpha, 2 beta) - each subunit has a heme group
heme group
porphyrin ring with a central iron
- the iron attracts and binds oxygen forming oxyhemoglobin
carbon monoxide
irreversibly binds hemoglobin lowering the cell’s oxygen carrying capacity
- it ruins the cooperativity since each subunit influences the binding of another
hemoglobin dissociation curve
sigmoidal so cooperative binding
- when partial pressure of O2 high, loading is favored
- when partial pressure of O2 low, unloading is favored
shifting left vs right on hemoglobin dissociation curve
left: produces hyperbolic curve, increasing affinity for oxygen favors loading
right: release more O2 into the tissues affinity decreased
2,3-DPG
used to help hemoglobin give sigmoidal curve, favor unloading
- shelf life of blood bank - as it goes down you go to the left, hyperbolic, will not be good at delivering oxygen bc affinity is so high
what is a shift left characteristic of
dec T, dec 2,3-DPG, dec hydrogen level, inc carbon monoxide - favor loading
what is a shift right characteristic of
inc T, inc 2,3-DPG, inc acid level
- caused by lots of exercise
fetal vs adult hemoglobin
fetal: no beta chains - it has 2 gamma instead
- gamma dos not interact with 2,3-DPG which shifts curve to left
- this allows fetal Hb to load while the mother Hb unloads
shift fom fetal to adult Hb is at 6 months old
main buffering system in the body
bicarbonate system
erythrocytes and buffering
CO2 diffuses into erythrocyte and small amounts bind to Hb and are transported as carbaminoHb
most CO2 tho is converted by carbonic anhydrase into carbonic acid and then bicarbonate and H+
H+ can be buffered vy Hb and other cytoplasmic proteins
what protein is in erythrocyte membranes that acts as the chloride exchanger?
band 3 protein
why would you expect band 3 protein to be in the kidney
homeostasis
- the kidney exchanges carbonate and chloride
erythrocyte breakdown
- erythrocytes removed from circulation by macrophages in spleen, liver, bone marrow
- iron salvaged; transported by transferrin to bone marrow for new cell production or liver for storage
- proteins broken down into AA and can be recycled or used
- bilirubin excreted via bile through GI tract
- microbial activity converts bilirubin to urobilinogen and stercobilins
- some urobilins diffuse into bloodstream and eliminated by kidneys
most common blood type for transfusion
ABO
bombay O phenotype
homozygous recessive
do not make any antigens
difficult for these people to receive blood
have antibodies opposite glycosylation
if type A you have antibodies to B
second most important antigen for transfusions
Rh factor
if antigen D present = Rh+
if antigen D absent = Rh -
leukocytes
involved in defense/immune response
once released in bone marrow they migrate to tissues to be functional
granulocytes or agranulocytes
shape of leukocytes in bloodstream vs tissue
blood: spherical
tissue: amoeboid (dendritic cells)
what do granulocytes include
neutrophils, eosinophils, basophils
what do agranulocytes include
lymphocytes
monocytes
production of granulocytes
cytokine known as granulocyte-monocyte colony stimulating factor (GM-CSF)
triggers determination of precursor myeloid cell into granulocyte or monocyte developmental pathway
secretion of GM-CSF comes from
endothelium, mesenchymal tissue, fibroblasts, macrophages, and lymphocytes
what indicates an upregulation in response to immune activity
the fact that activated macrophages and lymphocytes can secrete these growth factors
neutrophils
60-70% of the circulating leukocytes
first to respond to infection/injury
engulf bacteria into vacuoles called - phagosomes
granules and lysosomes fuse with vacuoles (lower pH and release enzymes)
lactoferrin binds to iron depriving bacteria
leads to bacterial death if no iron available
apoptotic neutrophils, bacteria, cell debris, and ECF form…
pus
eosinophils
2-4% leukocytes
phagocytize antigen-antibody complexes
modulates inflammatory responses
- cells produce substances that inactivate leukotrienes and histamines
- have toxins and enzymes with cytotoxic effect on parasites (protozoa, helminths)
- found in connective tissue of bronchi, GI, female reproductive tract
what inc eosinophils?
what dec eosinophils?
inc: helminthic infection and allergic reaction
dec: corticosteroids
why are you inactivating histamines wih eosinophils if you are increasing inflammation?
there are other ways to get inflammation
they have interplay with worms: worms release histamine which slows down response of eosinophils to counteract the eosinophils inactivate histamines
basophils
less than 1% of circulating leukocytes
mediate inflammation
what do basophils contain
histamine, leukotrienes, platelet activating factor, eosinophil and neutrophil chemotaxic factors and heparin
what do basophils express on surface
IgE
secrete in response to certain antigens
mast cells
nearly identical to basopohils
- share common progenitor but have different development
what can occur from repeat exposure to basophils
inc in IgE which could result in hypersensitivity reaction - allergic response
anaphylactic shock
