deck_16029902 Flashcards
cardiovascular system consist of
Heart
blood vessels (arteries, capillaries, veins)
blood
major function of cv system
oxygen/CO2
waste/nutrient exchange
hematology
study of blood
study of disorders associated w/ blood
major function of blood
transportation (O2, CO2, waste, nutrients
2 fluids of body that responsible for transport
blood
ISF
blood vs ISF
.
blood is
liquid CT
liquid ECF –> called blood plasma
cellular portion –> WBC, RBC, platelets,
blood plasma contains
water (92%)
Plasma proteins
dissolved solutes (ions, etc.)
blood plasma vs ISF
similar to ISF
ISF has less proteins
serum vs plasma
blood serum is plasma without clotting factors /proteins
body composition
40-45% solid
55-60% fluid
body fluid composition
2/3 ICF
1/3 ECF
ECF composition
20% plasma
80% ISF
3 functions of blood
1) transport
2) regulate
3) protect (WBC)
what does blood transport?
dissolved gasses, nutrients, hormones, metabolic wastes
E.g.
O2 (lungs to tissue)
CO2 (tissue to lungs)
nutrients (GI tract or liver/adipose to other tissue)
hormones (glands to tissue)
wastes (to kidneys)
what does blood regulate?
regulation of pH, temperature, ion composition of ISF
E.g.
absorb/neutralize acid
diffusion b/w blood-ISF balances ions
maintain body temperature (36-37)
–> high body temp = blood to superficial
–> low body temp = blood to deep
how does blood protect?
restrict fluid/blood loss @ injury (blood clotting)
clot = temporary patch
–> enzyme-directed when vessel wall is broken
blood defends against toxins/pathogens
–> Via WBC/Ab (immunity)
some physical characteristics of blood
more viscous than water
temp 38 (ONE DEGREE HIGHER THAN BODY TEMP)
pH –> 7.35-7.45
colour –> bright to dark red
–> oxygenated = bright
about 5 litres of blood in average person
blood composition
fluid CT
blood with all components = WHOLE BLOOD
2 major components:
plasma
Formed elements (cells/cell fragments)
“whole blood”
blood with all components
formed elements
cellular portion of blood CT
cells and cell fragments (E.g. platelets)
blood composition percent
about 55% plasma
about 45% formed elements
can range
46-63 plasma,
37-54 formed elements
plasma consists of
plasma proteins
other solutes
water
formed elements consist of
platelets
WBC
RBC
more about plasma
similar composition to ISF (less proteins)
constant exchange of water/ions/solutes across capillary walls
some differences b/w ISF and plasma
presence of respiratory gases (O2, CO2) in blood
dissolved proteins in blood (plasma proteins cannot cross capillary walls
plasma proteins in blood vs ISF
each 100mL has 7.6g protein
–> 5x more than ISF
cannot leave bloodstream
–> due to large, globular shape
liver synthesizes 90% of plasma proteins
which organ synthesizes more than 90 percent of plasma proteins?
LIVER
main proteins in plasma?
Albumins
Globulins
Fibrinogen
other enzymes/hormones
what percentage of plasma water
92 percent water
7 percent plasma proteins
1 percent other solutes (electrolytes, organic nutrients/wastes)
plasma protein composition
mostly ALBUMINS (60% albumins)
some GLOBULINS (35% globulins)
least FIBRINOGEN (4%)
1% (?) enzymes/hormones
which plasma protein most?
mostly albumins
which plasma protein least?
least = fibrinogen
what are Albumins for?
for osmotic pressure
what are globulins for?
E.g.
antibodies (immunoglobulins) vs foreign proteins/pathogens
E.g.
transport globulins
–> bind ions, hormones, lipids, other compounds
what is fibrinogen for?
blood clotting –> they form FIBRIN
fibrin = large insoluble protein strands
fibrin
large insoluble protein strands
for clotting
other solutes (1%) of plasma
electrolytes
organic nutrients
organic wastes
electrolytes of plasma
major ions
E.g.
Na+, K+, Ca2+, Mg2+, Cl-, HCO3-, HPO4-, SO4^2-
organic nutrients of plasma
lipids
carbohydrates (CH2O)
amino acids
–> used for cell ATP production, growth/maintenance
organic wastes of plasma
taken to site of excretion/breakdown
E.g.
urea, uric acid, creatinine, bilirubin, NH4+ (ammonium)
blood composition – formed elements (“about 45%”)
RBC
WBC
platelets
what percentage of formed elements are RBC
99.9%
vast majority
what percentage of formed elements are WBC/platelets
<0.1% WBC
<0.1% platelets
platelets, AKA
thrombocytes
what are platelets?
small membrane-bound cell fragments, involved in clotting
which cells do platelets come from?
megakaryocytes
@ bone marrow
about WBC
body defense, 5 classes, each class different function
what are 5 classes of leukocytes (WBC)
Neutrophils
Lymphocytes
Monocytes
Eosinophils
Basophils
what are RBC mainly known for?
transport O2
Hematrocrit
“ratio of the volume of red blood cells to the total volume of blood.”
other definition:
“Percentage of whole blood from formed elements (mainly RBCs)”
why hematocrit generally concerned w/ RBC
(I.e. why WBC/platelet left out in other definition?)
99.9% of formed elements = RBC
hematocrit etymology
of blood
judge
average hematocrit
45%
(range 37-54%)
males slightly higher than females
male average 47%
female average 42%
why male hematocrit higher?
androgens stimulate RBC production
what does low hematocrit indicate?
anemia
high hematocrit
Polycythemia (also called Erythrocytosis?)
polycythemia
poly
cyte
hemia
many cell blood
erythrocytosis, luekocytosis
.
formation of blood cells
hematopoiesis (aka hemopoiesis)
hematopoiesis
process of formed elements developing
hemato
poiesis
= blood making
how long to RBCs live?
about 120 days
why RBC not live long?
no nucleus
no DNA, no regulatory/repair proteins, no repair wear/tear
no ER
what is rate of RBC replacement
3 million per second
about RBM
found b/w trabeculae of spongy bone
site of hematopoiesis –> production of RBC, WBC, platelet
where does hematopoiesis begin in embryo/fetus?
begins in yolk sac during Embryonic development
switches to liver, spleen, thymus
continues @ RBM during last 3 months pregnancy
continues @ RBM after that
blood cells –> which germ layer
all blood cells are from mesenchymal cells
from mesoderm
also from mesoderm:
blood, RBM, kidneys/ureters, muscle, cartilage/bone,
6 steps in formation of blood cells ****
1) pluripotent stem cells
2) specialized stem cells (myeloid/lymphoid)
3) progenitor cells (CFU – colony forming units)
4) precursor cells (blast cells)
5) “optional step” (for RBC/platelets)
6) fully developed formed elements
1) pluripotent stem cells
from Mesenchyme (mesenchymal cells)
(mesenchyme originates from mesoderm)
pluripotent stem cells give rise to 2 types of stem cells
a) lymphoid cells
b) myeloid cells
lymphoid cells
B cells, T cells, NK cells
myeloid cells
everything else:
RBC, platelet, Mast cell, Eosinophil, Basophil, neutrophil, monocyte/macrophage
2) the specialized stem cells (myeloid/lymphoid)
again lymphoid –> B cell, T cell, NK cell
myeloid –>
RBC
platelet
Mast cell
Neutrophil
Eosinophil
Basophil
monocyte/macrophage
what can myeloid/lymphoid cells do
can reproduce/differentiate
3) progenitor cells (CFU – colony forming units)
most myeloid stem cells become progenitor cells before becoming precursor cells (BLAST cells)
some myeloid stem cells develop directly into precursor (blast) cells
Lymphoid stem cells always directly develop into precursor (blast) cells, without intermediate progenitor cell (CFU)
which specialized stem cell does not differentiate into progenitor (CFU) cell, and directly develops into precursor (Blast) cell?
lymphoid stem cells
can progenitor (CFU) cells reproduce?
no
committed to differentiate into specific elements within blood
list progenitor (CFU) cells
CFU-E:
colony forming unit ERYTHROID
CFU-Meg (or CFU-MK):
colony forming unit Megakaryocyte
CFU-GM:
colony forming unit Granulocyte - Macrophage
CFU-E
CFU-E becomes erythrocyte (RBC)
CFU-E
–> Proerythroblast
–> (nucleus ejected) Reticulocyte
–> RBC (erythrocyte)
CFU-Meg (CFU-MK)
CFU-Meg becomes platelets
CFU-Meg
–> Megakaryocyte
–> platelets
CFU-GM
CFU-GM becomes
–> granulocytes (neutrophils, eosinophils, basophils)
–> and monocytes (macrophage)
granulocytes
neutrophils, eosinophils, basophils
“granular WBCs” (cytoplasm)
4) precursor cells
blast cells
immature cells
blasts then differentiate into actual blood cells
blasts cells E.g.
proerythroblast
megakaryoblast
myeloblast (to neutrophil)
eosinophilic myeloblast
basophilic myeloblast
monoblast
**
From lymphoid stem cells:
T lymphoblast
B lymphoblast
NK lymphoblast
granular vs agranular leukocytes
GRANULAR:
neutrophils
eosinophils
basophils
AGRANULAR:
3 lymphocytes
monocytes
5) “optional step” (for RBC & platelets)
one extra differentiation for RBCs and Platelets:
b/w blast cell and fully developed mature cell there is:
–> Reticulocyte (nucleus ejected) before RBC
–> Megakaryocyte before Platelet
6) developed formed element
blast cells become developed formed elements:
RBC (erythrocyte)
platelet (thrombocyte)
neutrophil
eosinophil
basophil
monocyte
T lymphocyte
B lymphocyte
NK cell
Hematopoietic growth factors
hormones that regulate steps within differentiation process
impact differentiation/proliferation
Esp:
differentiation of particular progenitor (CFU) cells
Hematopoetic growth factors E.g.
EPO – Erythropoietin
TPO – Thrombopoietin
Cytokines
EPO (erythropoietin)
stimulates production of RBC
released from KIDNEYS
where is EPO released?
KIDNEYS
TPO (thrombopoetin)
stimulates production of thrombocytes (platelets)
released from LIVER
where is TPO released?
LIVER
cytokines
stimulates WBC production
glycoproteins –> act as local hormones
–> colony-stimulating factors (CSFs)
–> Interleukins (from RBM)
Hematology Tests
..
why blood tests?
determine blood type
evaluate type/# of RBC, WBC, platelets
abnormal values indicate pathological conditions
how are blood samples generally obtained?
venipuncture
(withdrawal of blood from vein)
most commonly @ median cubital vein
other method is via finger/heel stick
CBC
complete blood count
1 cubic mL of blood (1uL):
RBC count
WBC count
erythrocyte indices (hemoglobin)
hematocrit
other
WBC differential count
part of CBC (?)
identified # of each WBC type
RBC tests
several types
Assess #, size/shape, maturity of RBCs
can detect problems that don’t have signs/symptoms (?)
–> E.g. internal bleeding (??)
RBC what percentage of cells in body
almost 85 %
20-30 trillion RBC
what percentage of volume of blood is RBC
about 45% (45 = formed elements; RBC = 99.99 of “)
major protein in RBC
hemoglobin
transport O2
some CO2 (?)
single drop of blood # of RBCs
slides say 260 million
–> overestimate most likely
single drop may have about 5 million RBCs
RBC death rate vs production rate
death rate = production rate
about 3 million die per second
how long RBC last?
about 120 days
why 120 days?
no nucleus, no ER, no regulatory/repair proteins etc
erythrocytes (RBC)
biconcave discs
(surface area)
–> also to facilitate movement in capillaries
when is nucleus ejected from precursor to RBC?
proerythrocyte –> reticulocyte (no nucleus) –> Erythrocyte
nucleus ejected @ reticulocyte
RBC structure/function (surface area)
filled w/ hemoglobin (protein that carries O2)
large surface area allows more oxygen exchange
total RBC surface area = 2000x total surface area of body
what are rouleaux
stacks that are formed by overlapping RBCs
facilitate transport in small vessels (I.e. capillaries)
RBC other physical properties (flexible/bendable)
RBCs can move through capillaries w/ smaller diameter than RBC
RBC anatomy (hemoglobin)
RBC cytosol = contains hemoglobin
” synthesized before loss of nucleus (lost @ reticulocyte)
what percentage of weight of RBC is hemoglobin?
about 1/3 (33%)
RBC plasma membrane
strong/flexible
RBC glycolipids
glycolipids acting as antigens for blood types
how many hemoglobin molecules per RBC
about 280 million
hemoglobin structure
globin protein
–> 4 polypeptide chains
(2 alpha chains, 2 beta chains)
+
heme
–> 4 ring-like structures
–> non-protein “
–> bind to each pp chain
centre of each heme
–> an IRON ion
oxyhemoglobin (HbO2)
each heme + iron ion
–> interacts w/ O2 molecule
–> forms OXYHEMOGLOBIN (HbO2)
–> makes “oxygenated blood”
(bright red)
Deoxyhemoglobin
reversible oxygen binding
–> hemoglobin not bound to oxygen = blood becomes dark red
what does RBC w/ 280million Hb molecules do?
carry oxygen from lungs to tissue –> carry CO2 from tissue to lungs
how many O2 molecules per RBC?
4 Heme rings per Hb –> so 4 O2 molecules per Hb
4*280 million (Hb)
= 1.1 billion O2 molecule per RBC
nitric oxide and Hemoglobin
Where does NO bind on Hb
nitric oxide binds on Heme ring of Hb
NO carried by Hb dilates microvasculature
–> increaes blood flow & oxygen delivery
how does Hemoglobin regulate blood pressure & blood flow?
NO binding to Heme ring on Hemoglobin regulates blood pressure & blood flow
what percentage of oxygen in blood is bound to Hemoglobin?
98-99% (VAST MAJORITY)
–> bound to Hb
–> remained is dissolved in PLASMA
carbon monoxide
toxic
byproduct of vehicle, furnace, heater fumes, even cigarette smoke
binds to heme group
–> @ 200x affinity vs O2
–> decreases O2 carrying capacity of Hb/RBC
can be fatal unless treated w/ pure O2
(E.g. oxygen chamber)
ERYTHROPOIESIS
.
where does erythropoiesis start?
starts in RBM
what are the steps in RBC production?
pluripotent stem cell
–> Myeloid stem cell
–> CFU-E progenitor cell
–> Proerythroblast precursor cell
–> Reticulocyte
–> Erythrocyte
proerythroblast – divide?
“divides several times”
–> previous notes said progenitor & blast cells do not divide, only differentiate
–> are there some exceptions?
about reticulocyte
reticulocyte gains BICONCAVE shape
unlike RBC, has some
–> mitochondria
–> ribosomes
–> ER
where do reticulocytes go?
pass from RBM to blood stream
–> develop into mature RBC within 1-2 days
a few extra steps b/w Proerythroblast & reticulocyte
proerythroblast becomes
–> Erythroblast
–> Normoblast
Normoblast ejects nucleus and becomes Reticulocyte
at which stage does Hemoglobin production begin?
Erythroblasts begin creating Hb
what percentage of Hemoglobin of mature RBC does Reticulocyte have?
80% of the 280million Hb molecules are already prepared in Reticulocyte
hypoxia
cellular oxygen deficiency
E.g.
high altitude (less O2 in air)
anemia (not enough Hb or RBC = not enough O2)
circulatory problems (problem w/ O2 delivery?)
Erythropoietin (EPO)
hormone produced by KIDNEYS
increases/facilitates Erythropoiesis
Liver
Thrombopoietin (TPO)
> 90% of Plasma proteins
Kidney
Erythropoietin (EPO)
negative feedback loop of Erythropoietin from kidneys
decreased O2 delivery to tissues (including kidney)
–> kidney cells detect low O2
–> increase EPO production/secretion
–> Proerythroblast activity increases
–> more reticulocytes
–> more RBC
–> more Hb –> more O2 to tissues
–> return to homeostasis when kidney receives increased O2
what happens to dead RBC?
removed from circulation
destroyed/recycled via FIXED macrophages
–> @ Spleen/Liver
breakdown products E.g. (Hb):
–> Globin (4 pp chains)
–> Heme ring (red/brown pigment w/ iron)
RBC BREAKDOWN STEPS
..
which macrophages break down RBC?
fixed macrophages
@ Spleen
@ Liver
or @ RBM
what happens after macrophages break down RBC?
Which two parts of important molecules inside are split apart?
Globin & Heme portion of Hb molecules split apart
–> recall Globin protein = 4 Polypeptide chains
–> Hemes = Ring-shaped pigment structure
what happens to Globin
4 polypeptide chains are broken into amino acids
–> recycled in other protein synthesis
what happens to Heme structures?
I.e. what happens to Iron ion?
Iron is removed from heme portion
what does Iron do?
Iron binds to Plasma protein TRANSFERRIN
(Iron transporter protein)
–> transports iron in blood
where does Iron go?
Iron goes to
–> muscle fibres
–> liver cells
–> macrophages (liver/spleen)
then
–> detaches from Transferrin (@BV)
–> attaches to FERRITIN
Ferritin
–> Iron storage protein (@ cells)
transferrin vs ferritin location
transferrin = plasma protein inside BV
ferritin = protein inside cells
where does Iron go when released from storage (Ferritin)
or when absorbed via GI tract?
attaches to Transferrin (plasma protein) to be transported
–> to RBM (for Hb)
when not needed?
–> back to storage
–> @liver, spleen, marrow, duodenum, skeletal muscle and other anatomic areas.
what happens to excess iron?
how can iron be excreted?
liver can excrete iron to some extent (?)
–> some sources state “
some sources also state some Iron can be excreted via sweat
+ shedding intestinal cells
also via blood loss
what happens to Iron-Transferrin complex that goes to RBM
(after leaving storage)
RBC precursor cells use Iron
(proerythroblast? erythroblast? normoblast? reticulocyte?)
–> take Iron via Receptor mediated endocytosis
–> used for Hemoglobin synthesis
(reattached to Heme pigment portion)
back to RBC breakdown –> what happens to non-iron portion of Heme?
converted to Biliverdin (green pigment)
Biliverdin converted to Bilirubin (yellow-orange pigment)
what happens to bilirubin?
where is it taken?
what happens there?
enters blood –> transported to Liver
@ liver
–> bilirubin released to bile (component of bile?)
where does bile+bilirubin go?
what happens there?
bile passes from liver (or gallbladder?)
–> to small intestine
–> then large intestine
Bacteria @ large intestine
–> converts bilirubin to UROBILINOGEN
what happens to some urobilinogen
some urobilinogen goes to kidneys
–> via blood
converted to UROBILIN (yellow)
–> excreted in urine
what happens to most urobilinogen
excreted via feces
–> in form of STERCOBILIN (brown)
“sterco” = excrement
Iron overload
too many free iron ions can be damaging
Transferrin (plasma protein)
and
Ferritin (storage protein @ cells)
–> are protective
–> prevent too much free iron ions
what happens if iron overload
amount of free iron increases
can cause damage
–> of heart
–> of liver
–> pancreas
–> gonads
can increase number of iron dependent MICROBES
iron elimination
notes say:
“We have NO method of elimination excess iron”
–> other sources say liver can excrete to some extent
–> also say sweat can excrete to some extent
–> also via shedding of intestinal cells
otherwise iron is lost when blood is lost
WHITE BLOOD CELLS
leukocytes
contribute to body defense
no hemoglobin
but nucleus/organelles present (unlike RBC)
5 types of WBCs
neutrophils (majority)
eosinophils (2-3%)
basophils (<1%)
Monocytes (become macrophages)
Lymphocytes (T, B, NK cells
granular vs agranular WBCs
neutrophil, eosinophil, basophil
= granular
monocyte, lymphocytes
= agranular
what are similarities & shared characteristics of diferent WBCs
1) spend only short time in circulation
2) most located @ loose/dense CT (where infection occurs)
3) can migrate out of bloodstream
where does infection often occur?
loose/dense CT
what do all WBCs do to migrate out of bloodstream?
adhere to vessel walls @ infection site
squeeze out b/w adjacent endothelial cells
what is it called when WBCs squeeze out of BV via adjacent endothelial cells?
“Emigration”
or
“Diapedesis”
dia = through
pedesis = leaping
other shared characteristics b/w all WBCs
4) are attracted to chemical stimuli
–> this characteristic is called “POSITIVE CHEMOTAXIS” (or just chemotaxis)
chemotaxis guides WBCs to pathogens, damaged tissue, or other active WBCs
what is (positive) chemotaxis?
here refers movement of WBCs up concentration gradient
–> going toward pathogens, damaged tissues, or other active WBCs
what is similarity b/w Neutrophils, Eosinophils, and monocytes?
capable of phagocytosis
–> engulf pathogens/debris
monocyte/macrophage
“Macrophages are monocytes that have moved out of the bloodstream”
WBC count
about 7000 WBC per uL of blood
–> # can increase during infection, inflammation, injury, allergy, etc
recall “differential count”
number of each type of WBC in sample
reported as percentage (per 100 WBCs)
two classificaitons of WBC (granular vs agranular)
granular (granulocytes)
–> cytoplasmic granules
(secretory vesicles + lysosomes)
–> absorb “Histological Stains”
agranular (agranulocytes)
–> “smaller secretory vesicles/lysosomes”
–> “don’t absorb stains”
histological staining
“Histological stains are chemical dyes used to treat histological specimens to make tissues more readily visible by light microscopy and demonstrate underlying characteristics of the tissue.”
“Staining is a technique used to enhance contrast in samples, generally at the microscopic level. Stains and dyes are frequently used in histology, in cytology, and in the medical fields of histopathology, hematology, and cytopathology that focus on the study and diagnoses of diseases at the microscopic level.”
about granulocytes – including percentage (differential count)
“absorb histological stains (so are visible under the microscope)”
numbers (as % of WBCs):
Neutrophils (about 50-70%)
Eosinophils (about 2-4%
Basophils (<1%)
about Neutrophils
“pale” colour – neutral stain
most numerous WBC
1st to arrive
engage in phagocytosis of bacteria
uses enzymes for destruction:
a) oxidants
b) LYSOZYMES
c) “defensins”
about Eosinophils
“red/orange” colour – acidic stain
relationship to HISTAMINE (?)
–> note says “antihistamine” (???)
destroys parasites
destroys Ag-Ab complexes
about Basophils
“blue/purple” colour – basic stain
releases
–> serotonin
–> heparin
–> histamine
important during allergic reactions
defensins?
“Defensins are small … proteins … They are host defense peptides … either direct antimicrobial activity, immune signaling activities, or both.”
about agranulocytes – including percentage (differential count)
“few, if any, cytoplasmic granules that absorb histological stain”
= not visible under the microscope
numbers (as % of WBCs):
Lymphocytes (20-40%)
Monocytes (2-8%)
most vs least numerous WBC?
–> lymphocytes = second most numerous WBC
–> neutrophil = most numerus
–> monocytes = usually 3rd most numerus
–> eosinophil = 4th
–> basophil = 5th
about Monocytes
kidney bean shaped (?) –> b/c of nucleus (???) “indented nucleus”
called monocytes @ blood
called macrophages @ tissue
main role:
phagocytosis of cells/debris
can be:
Fixed or Wandering
about Lymphocytes –> includes 3 subtypes
T cells –> attack cancer cells, foreign/viral invasions
B cells –> become plasma cells, secrete Ab (w/ help from T cells)
NK cells –> attack cancer cells & infectious microbes
lymphocytes, innate vs adaptive immune system
B/T cells are adaptive
NK cells are innate
how long can WBCs live?
in healthy body –> several months/years
however
–> most only live a few days due to being destroyed during immune activity
E.g.
During infection phagocytic WBCs may live only a few hours
WBC functions –> when pathogens enter body
WBCs combat pathogens
–> via phagocytosis
–> via immune response
which leukocytes never return to bloodstream?
Granular Leukocytes (neutrophils, eosinophils, basophils)
& macrophages
which leukocytes constantly recirculate?
Lymphocytes
constantly recirculate
I.e.
blood –> ISF –> Lymph –> blood
what percentage of lymphocytes are circulating at a given time?
about 2% circulate
rest are in lymphatic fluid or organs (esp lymphoid organs)
E.g.
thymus, lymph nodes, spleen, and appendix
some terms related to WBC functions
a) Emigration (Diapedesis)
b) Phagocytosis
c) Chemotaxis
a) Emigration (Diapedesis)
how WBCs leave bloodstream
roll along endothelium
–> attach and squeeze out between endothelial cells
AKA Diapedesis
OR
“LEUKOCYTE EXTRAVASATION”
extra = out
vas = related to vessel
ADHESION MOLECULES during diapedesis (emigration/ leukocyte extravasation)
adhesion molecules include
–> Selectins, Integrins
these help WBCs stick to endothelium
b) Phagocytosis
eating/engulfing cell/microbe
c) Chemotaxis
“the process by which chemicals released by toxins or damaged/inflamed tissue attract phagocytes”
WBC movement up concentration gradient to site of infection/inflammation/injury etc.
other common terms related to WBCs
Leukocytosis
Leukopenia
Leukemia
Leukocytolysis
leukocytosis
“increase in the number of WBCs”
“Normal, protective response to stresses such as invading microbes, strenuous exercise, anethesia and surgery”
can also be pathological
Leukopenia
“An abnormally low level of WBC”
“May be caused by radiation, shock or chemotherapeutic agents”
Leukemia
Cancer of WBCs
“WBCs differentiate and divide uncontrollably, producing non-functional WBCs”
Leukocytolysis
WBC death
“Due to trauma, disease or chemicals”
Platelets
Aka thrombocyte
“Cell fragments, have no nucleus”
“Short life span of 5 to 9 days”
“Aged and dead platelets are
–> removed by:
fixed macrophages in the spleen and liver”
platelet function
“Platelets function primarily in the formation of plugs and release of other chemicals to assist in blood clot formation”
thrombopoiesis
myeloid stem cells
–> progenitor CFU-Meg cells
–> Megakaryoblast
–> Megakaryocyte
–> Platelet
how do megakaryocytes become platelets?
“megakaryocytes splinter into 2000-3000 cell fragments called a platelet”
Thrombopoietin (TPO)
From liver
stimulates platelet production
hemostasis
stop blood loss from damaged BV
quick, localized to damaged area
three phases of hemostasis
1) vascular phase
2) platelet phase
3) coagulation phase
hemorrhage define
loss of large amount of blood
thrombosis define
clotting @ undamaged vessel
“local coagulation or clotting of the blood in a part of the circulatory system.”
1) vascular phase of hemostasis
lasts about 30 minutes
endothelial response + vascular spasm
–> smooth muscle contracts
reduces blood loss @ damage vessel until next step
what causes the spasm/contraction during 1) vascular phase of hemostasis?
a) Endothelial chemical release via damaged BV
b) platelet chemical release
c) nociceptor reflexes
One of the substances that endothelial cells release
Endothelins
which cause:
a) smooth muscle contractions (vascular spasms)
b) division of cells (endothelial, smooth muscle)
c) division of fibroblasts
Note endothelial plasma membranes become “sticky”
2) platelet phase of hemostasis
note that platelets always present
however when tissue damaged:
–> causes platelet adhesion
–> platelets stick to area of damaged BV
why do platelets stick to area of damaged BV?
platelets bind to exposed collagen fibres of CT beyond damaged endothelial cells
what happens after platelets adhere @ site of damage?
platelets are activated
interact with one another
release contents of vesicles
others platelets are attracted via contents (CHEMOTAXIS)
which substances are released by platelets
ADP, thromboxane A2, setotonin
what does each substance do?
ADP/thromboxane A2 attract other platelets
serotonin/ thromboxane A2 stimulate vasoconstriction
thromboxane A2 = both
what happens after platelets release contents of vesicles?
more platelets attracted
area becomes sticky
arriving platelets adhere to existing platelets
PLATELET PLUG forms
–> later tightened by fibrin threads during clotting
3) Coagulation phase of hemostasis
involves clotting cascade
via substances called “CLOTTING FACTORS”
ultimately involves formation of FIBRIN via FIBRINOGEN
& blood cells + platelets are trapped in “Fibrin Network” (Blood Clot)
it is an example of positive feedback system
quick note about blood outside body
outside body blood thickens to:
–> Serum = blood plasma w/o clotting factors
–> Clot = gel-like, network of Fibrin (Insoluble protein fibres) + trapped formed elements
what are Clotting factors (Procoagulants)
Ca2+
& 11 different proteins
many are “proenzymes” (I.e. inactive)
activated enzymes lead to “chain reaction” –> “Clotting Cascade”
proenzymes define
“any of a group of proteins that are converted to active enzymes by partial breakdown”
two different pathways that lead to same common pathway for blood clotting (coagulation step of hemostasis)
1) extrinsic pathway
2) intrinsic pathway
1) extrinsic pathway to clotting
quicker than intrinsic pathway
extrinsic b/c involves factor from outside blood
steps of extrinsic pathway to (Common pathway) blood clotting
1) broken tissue releases TF (tissue factor)
–> AKA thromboplastin, or factor iii
2) TF + Ca2+ = FACTOR X activated
detailed steps:
Factor iii + [Ca2+] + Factor vii –> Tissue factor complex
—> FACTOR X activated
1) intrinsic pathway to clotting
takes few minutes to begin (slower than extrinsic pathway
called “intrinsic” b/c all factors are found directly inside blood
steps of intrinsic pathway to blood clotting (Common Pathway)
1) factor xii activated via damaged platelets/endothelium
PF-3 (platelet factor)
+
Ca2+
+
Factor viii + ix
—>
Factor X activator complex
—> Activated Factor X (Common pathway)
can both extrinsic and intrinsic pathways be active at once
yes
both tissue trauma and blood vessel trauma
for simplified purposes (extrinsic/intrinsic pathways steps)
extrinsic
–> Factor iii + Ca2+ = Factor X activated
intrinsic
–> Factor xii + Ca2+ = Factor X activated
extrinsic factor ii
–> via tissue damage
intrinsic factor xii
–> via BV damage
common pathway (of coagulation phase of hemostasis)
factor X activates “Prothrombinase”
what does prothrombinase do
converts Prothrombin to thrombin
via Ca2+
what is prothrombin
proenzyme
formed by liver
what is thrombin
enzyme
what does thrombin do
converts Fibrinogen to Fibrin (enzyme)
what about Factor xiii
factor xiii + thrombin
–> Activates factor xiii
–> which strengthens Fibrin threads
vitamin K
not directly responsible for clotting
contributes to production of some clotting factors
fibrinolysis
dissolving of small/unneeded clots after repair
via “Fibrinolytic system”
–> Lysis of fibrin
which enzyme/protein is responsible for fibrinolysis
plasminogen
–> inactive plasma protein
–> component
plasminogen converts to Plasmin
–> active plasma enzyme
plasmin breaks down fibrinogen in blood clots
anticoagulants (hemostatic control mechanisms)
anticoagulant (substances that prevent unnecessary coagulation)
E.g.
Warfarin
Anti-thrombin
Heparin
APC (Activated Protein C)
Warfarin
“aka Coumadin ® blocks Vit K, therefore production of clotting factors”
Anti-thrombin
blocks thrombin formation
which blocks fibrinogen –> fibrin conversion
Heparin
produced by Mast Cells & Basophils
–> helps activate anti-thrombin
note mast cell vs basophil
structurally/functionally similar
APC (Activated protein C)
blocks clotting factors
enhances plasminogen activation
thrombolytic agents
note “thrombolysis”
thrombolytic agents:
–> synthetic/artificial chemicals
–> injected to dissolve clots
E.g.
Tissue plasminogen activator –> activates plasmin
Streptokinase –> produced by streptococcus bacteria –> helps dissolve clots
Aspirin
–> inhibits vasoconstriction (opens vessels)
–> prevents platelet aggregation (blocks thromboxane A2)
intravascular clotting (thrombus)
thrombus
–> a clot in an unbroken or undamaged blood vessel
–> “usually self dissolves, happens in cases of minute traumas”
intravascular clotting (embolus)
embolus:
“broken off piece of thrombus that travels the bloods stream”
“can have serious consequences if it lodges itself in small arteries”
“leads to arterial blockage”
“Can be blood clot, air bubble, fat or debris”
embolism
“obstruction of an artery, typically by a clot of blood or an air bubble.”
blood types
..
what is blood type
determined by presence/absence of specific surface antigens on RBCs
antigen? “substance eliciting immune response”
antigens on cells
“surface antigens embedded in plasma membranes”
“recognized as normal, or self, by immune system”
what are antigens on surface of RBC composed of?
composed of:
–> glycoproteins
–> glycolipids
called “Agglutinogens”
–> “substance that acts as an antigen to stimulate production of specific agglutinin”
agglutinogens, agglutin, agglutination
called “Agglutinogens”
–> “substance that acts as an antigen to stimulate production of specific agglutinin”
“AGGLUTININ is a substance (such as an antibody) producing agglutination.”
“Agglutination is a reaction in which particles suspended in a liquid collect into clumps usually as a response to a specific antibody”
E.g. of antigens (agglutinogens) on RBCs
A antigen
B antigen
agglutinin
“Agglutinins are substances that make particles (such as bacteria or cells) stick together to form a clump or a mass.”
“Antibodies can be agglutinins”
E.g. of Agglutinins
anti-A antibody
anti-B antibody
blood types E.g.
determined genetically
via which surface antigens are on RBC membrane
> 50 blood cell antigens
three most important:
A
B
Rh (or D)
blood type A
surface antigen A
anti-B antibodies (in plasma)
blood type B
surface antigen B
anti-A antibodies (in plasma)
blood type AB (universal recipient)
surface antigens A & B
neither antibody in plasma
blood type O (universal donor)
neither surface antigen
both antibodies in plasma
ABO blood group
consists of four types:
A
B
AB
O
reiterate blood types with different terms
type A
A agglutinogens (Ag)
B agglutinins (Ab)
type B
B agglutinogens (Ag)
A agglutinins (Ab)
type AB
A + B agglutinogens
no agglutinins
type O
no agglutinogens
A + B agglutinins
Rh blood group
Named because the antigen was discovered in the blood of the Rhesus monkey
Rh+
RBCs have Rh antigen
Rh-
RBCs lack Rh antigen
Rh blood type & anti-Rh antibodies
“Normally blood plasma does not contain anti-RH antibodies”
“If an Rh- person receives Rh+ blood the immune system will start to make anti-Rh antibodies”
Will cause agglutination/hemolysis in event of SECOND exposure to blood
E.g. blood of fetus Rh+, mother Rh-
genetics of blood type
genetically determined
foreign exposure not needed to produce Ab (agglutinins)
–> Ab naturally present in plasma
Exception:
“Anti-Rh antibodies are not automatically present”
–>
“Rh-negative person will not have any anti-Rh antibodies until exposed to Rh-positive RBCs (sensitized); then develops anti-Rh antibodies”
Blood transfusion
“transfer of whole blood or blood components into the bloodstream or directly into the red bone marrow”
for:
“Anemia, increase blood volume, improve immunity”
incompatible blood transfusion
“Antibodies in the recipients plasma bind to the antigens on the donated RBCs and cause agglutination, or clumping of the RBCs”
–> Ab attack RBCs (?)
hemolytic disease of newborn (Rh factor)
common problem with Rh incompatibility
“Normally there is no direct contact of fetal and maternal blood”
“Small amount can leak from the fetus through the placenta or @ delivery”
“If mother is Rh- and baby is Rh+, mother may create anti-Rh antibodies”
hemolytic disease of newborn (Rh factor) 2
First pregnancy – mother creates antibodies
“Second pregnancy – the anti-Rh antibodies can cross the placenta and cause agglutination and hemolysis”
treatment to prevent hemolysis of Rh+ fetus by (Rh-) mother’s Rh-antibodies
“Treatment – injection of … anti-Rh gamma globulin”
“bind to and inactivate the fetal Rh antigens before the mother’s immune system can respond”
erythroblastosis
“abnormal presence of erythroblasts in the circulating blood”
“erythroblastosis fetalis”
“erythroblastosis fetalis, type of anemia in which the red blood cells (erythrocytes) of a fetus are destroyed in a maternal immune reaction resulting from a blood group incompatibility between the fetus and its mother.”
blood type test
“Drops of person’s blood are mixed with solutions containing antibodies to surface antigens A, B, and Rh”
“Clumping (agglutination) occurs where sample contains the corresponding antigen”
“Typing is necessary to avoid transfusion reactions (cross-reactions occurring from transfusing mismatched blood)”
“Donor and recipient blood types must be compatible (will not cross-react)”
transfusion reaction
cross-reactions occurring from transfusing mismatched blood
blood pathologies
..
anemia
“problem of not having enough healthy RBC or hemoglobin to carry oxygen’
“oxygen-carrying capacity of blood is reduced”
symptoms:
Fatigue
Intolerant of cold
Skin appears pale
Dyspnea with mild exertion
dyspnea
difficult or labored breathing.
iron-deficiency anemia
a) Inadequate absorption of iron
b) Excessive loss of iron (menstruation)
c) Increased iron requirement
d) Insufficient intake of iron
hypermenorrhea, polymenorrhea, oligomenorrhea
Heavy menstrual bleeding (hypermenorrhea)
more frequently than 21 days is considered abnormal (polymenorrhea)
less frequently than every 37 days is considered abnormal (oligomenorrhea).
menstruation, meno, month
word “menstruation” is etymologically related to “moon”
meno = month
rrhea = flow
monthly flow
megaloblastic anemia
Inadequate Vit B12 or folic acid (Vit B9) levels
Red bone marrow produces large, abnormal RBCs
Ineffective at carrying oxygen
megaloblast
“large erythroblast that appears in the blood especially in pernicious anemia”
megaloblastic
pernicious anemia define
“Pernicious anemia is a relatively rare autoimmune disorder that causes diminishment in dietary vitamin B12 (cobalamin) absorption, resulting in B12 deficiency and subsequent megaloblastic anemia.”
megalo
prefix meaning “large, great, grand, abnormally large.”
pernicious anemia
A type of megaloblastic anemia
“Vit B12 deficiency resulting from an inability of the stomach to produce intrinsic factor which is needed for absorption of vit B12”
autoimmune disorder:
“immune system attacks the actual intrinsic factor protein or the cells in the lining of your stomach that make it”
hemorrhagic anemia
Excessive loss of RBCs
“bleeding from large wounds, ulcers or heavy menstruation”
heavy menstrual bleeding
aka
hypermenorrhea, menorrhagia
acute blood loss
“Recovery enhanced by increase in EPO levels” (kidneys)
“marrow response is marked by reticulocytosis “
reticulocytosis
“increase in reticulocytes, immature red blood cells”
“commonly seen in anemia”
“bone marrow is highly active in an attempt to replace red blood cell loss such as in haemolytic anaemia or haemorrhage”
chronic blood loss
Iron stores eventually depleted, hemoglobin ends up low
hemolytic anemia
premature RBC plasma membrane rupture
“inherited defects, parasites, toxins or antibodies”
“possibly see jaundice with hemolytic anemia”
–> Note Heme-ring pigment structure
–> Bilirubin
jaundice (hemolytic anemia)
“when too much bilirubin builds up in the body. Jaundice can occur if: Too many red blood cells are dying or breaking down and going to the liver.”
Can also occur with liver dysfunction
hemolytic anemias E.g.
Thalassemia
Sickle cell disease
Infections: malaria, HIV
Medications
thalassemia
deficient synthesis of hemoglobin (one globin chain)
Autosomal recessive blood disorder
“RBCs are small, pale and short-lived”
“reduced rate of synthesis or no synthesis of one globin chain”
autosomal recessive define
“Autosomal recessive is a pattern of inheritance characteristic of some genetic disorders.”
“‘Autosomal’ means that the gene in question is located on one of the numbered, or non-sex, chromosomes.”
“‘Recessive’ means that two copies of the mutated gene (one from each parent) are required to cause the disorder”
thalassemia most common in which ethnicities
populations from countries bordering the Mediterranean Sea
“South Asian, Italian, Greek, Middle Eastern, and African descent.”
thalassemia (continued)
“reduced rate of synthesis or no synthesis of one globin chain”
“β-Thalassemias or α-Thalassemias”
(depending on which chain is affected?)
thalassemia prognosis
Can be fatal early in life depending on severity
Some forms are mild and present as mild anemia
thalassemia treatment
“If severe, may require regular blood transfusions”
sickle cell disease
an abnormal hemoglobin
–> Hb-S
when O2 released
–> “forms long, stiff, rodlike structures that bend the RBC into a sickle shape”
“sickled cells rupture easily”
sickle cell anemia vs sickle cell trait
Sickle Cell Anemia
–> Two copies of gene (one from each parent)
–> Rapid breakdown of RBCs
Sickle Cell Trait
–> One copy of gene
–> usually no symptoms
more about sickle cell disease
inherited
found in populations that live in “malaria belt”
–> “Mediterranean Europe, sub-Saharan Africa, tropical Asia”
sickle cell disease and malaria
“Sickle cell trait gives protection against malarial infection”
“cells that obtain malaria parasite sickle and are removed from circulation”
HOWEVER:
“Sickle cell anemia is worse during malarial infection (not advantageous)”
sickle cell disease symptoms
Degree of anemia
Mild jaundice
Joint or bone pain
Breathlessness
Rapid heart rate
Abdominal pain
fatigue
sickle cell disease treatment
Pain medication
Fluid therapy for hydration
Oxygen
Antibiotics
Blood transfusions
aplastic anemia
destruction of red bone marrow
toxins, gamma radiation, viral hepatitis, medications
aplastic anemia signs/symptoms
“Slowly progressive anemia”
“causes insidious development of weakness, pallor, and dyspnea”
thrombocytopenia
–> petechiae
–> ecchymoses
Granulocytopenia
–> frequent minor infections
–> sudden onset of chills, fever
thrombocytopenia
deficiency of platelets in the blood
“bleeding into the tissues, bruising”
“slow blood clotting after injury”
petechiae
“a small red or purple spot caused by bleeding into the skin.”
“tiny spots of bleeding under the skin or in the mucous membranes. The pinpoint-sized purple, red or brown dots are not a rash”
ecchymosis
“a discoloration of the skin resulting from bleeding underneath, typically caused by bruising.”
aplastic
“characterized by the failure of an organ or tissue to develop or to function normally.”
aplastos = unshaped
“aplastic” anemia
“Stem cells in the bone marrow produce blood cells”
“In aplastic anemia, stem cells are damaged.”
As a result, the bone marrow is either empty (aplastic) or contains few blood cells (hypoplastic).
granulocytes
neutrophil
eosinophils
basophil
splenmegaly & aplastic anemia
absent in aplastic anemia
“you’re just not making any blood cells. The spleen has nothing to recognize as abnormal, which means your spleen isn’t going to enlarge.”
leukemia
“group of red bone marrow cancers in which abnormal WBCs multiply uncontrollably”
“Interferes with normal processes and causes”
–>Reduced oxygen-carrying capacity
–> Increase susceptibility to infection
–> Abnormal blood clotting
“Spread to lymph nodes, liver and spleen”
leukemia symptoms
Anemia
Weight loss
Fever
Night sweats
Excessive bleeding
Recurrent infections
leukemia risk factors
Genetics (ie. Down syndrome)
Family Hx
Smoking
Radiation, chemotherapy (previous cancer treatment)
leukemia treatment
Chemotherapy
Radiation
Stem cell transplant
Antibodies
Blood transfusions
hemophilia
“inherited deficiency of clotting in which bleeding may occur spontaneously or after only minor trauma”
“Usually affects males”
“Different types of hemophilia are due to deficiencies of different blood clotting factors”
hemophilia treatment
Transfusions, clotting factors
hemochromatosis
Primary
Inherited
Secondary
Caused by anemia, alcoholism or other disorders
hemochromatosis etymology
chromato- (“color”) + -osis (“condition, disease”)
about hemochromatosis
causes body to absorb and store too much iron
“Extra iron builds up in the body’s organs and without treatment can cause them to fail”
normal iron absorption vs iron absorption with hemochromatosis
“Normally we absorb 10% of the iron in our food”
“Someone with hemochromatosis absorbs up to 30%”
hemochromatosis symptoms
Arthritis
Liver disease
Damage to pancreas
Heart abnormalities
Thyroid deficiency
Abnormal pigmentation of skin – gray/bronze
hemochromatosis treatment
take blood
Monitor ferritin levels
jaundice
“abnormal yellowish discoloration of the sclerae of the eyes, skin and mucous membranes due to excessive bilirubin in the blood”
3 categories of jaundice
Prehepatic –>
Due to excessive production of bilirubin
Hepatic –>
Abnormal bilirubin processing by the liver
Extrahepatic –>
Due to blockage of bile drainage by gallstones or cancer of bowel or pancreas
excess breakdown of RBC
prehepatic jaundice (?)
excess breakdown = “excessive production of bilirubin” (??)
