Blood Flashcards
1
Q
Facts about blood
A
- 7-8% of body weight
- present in blood vessels but also in tissues
- thicker than water
- blood cells sediment in tube due to gravity or in a centrifuge
2
Q
functions of blood
A
transport - exchange, O2, CO2, nutrients, waste products, ions, hormones, and heat (maintain body temp)
regulation - ion and pH balance
defence - immune protection
hemostasis
3
Q
hemostasis
A
process of forming blood clots in the walls of damaged blood vessels and preventing blood loss while maintaining blood in a fluid state within the vascular system
natural mechanism
prevention of blood loss
4
Q
hematocrit
A
% of total blood volume occupied by packed red blood cells
males have greater hematocrit than females (~47%, ~42%)
5
Q
separation of blood cells and plasma
A
components of whole blood are separated by centrifuge
plasma ~55%, buffy coat - white blood cells + platelets <1%, red blood cells ~45%
6
Q
anemia
A
low hematocrit
symptoms: tiredness, out of breath, paleness, brittle nails
7
Q
polycythemia
A
high hematocrit
blood is more viscous = slower (can strain circulatory system)
an adaptational change when moved from sea level to higher elevation where <O2 sat in air → advantage to carry more O2
8
Q
blood doping
A
in athletes
boost red blood cells to increase O2 delivery to muscles
adverse consequences
9
Q
intracellular fluid
A
ICF
fluid inside of cells
10
Q
extracellular fluid
A
ECF
fluid outside of cell membranes
= plasma + interstitial fluid
11
Q
interstitial fluid
A
outside blood vessels
interstitial space
12
Q
plasma
A
non-cellular portion of blood - liquid portion
> 90% water
electrolytes, organic molecules, trace elements, gases
transport (CO2)
13
Q
plasma proteins
A
albumins, globulins, fibrinogen, tranferrin
made in the liver
functions: distribution of body water, buffering, transport, defence, hemostasis
14
Q
albumins
A
major contributors to colloid osmotic pressure of plasma; carriers of various substances
15
Q
globulins
A
clotting factors, enzymes, antibodies, carriers for various substances
16
Q
fibrinogen
A
forms fibrin threads essential to blood clotting
17
Q
transferrin
A
iron transport
18
Q
distribution of body water
A
capillary walls are impermeable to plasma proteins → exert osmotic force across wall that pulls water into the blood
19
Q
serum
A
plasma contains clotting factors that are used up to form a blood clot → remaining clear portion is serum
= plasma - clotting factors
20
Q
blood cell types
A
red blood cells (erythrocytes)
white blood cells (leukocytes)
platelets (thrombocytes)
identification based on staining (hematoxylin-eosin) characteristics
21
Q
red blood cells
A
normal count = ~5 million cells/microL
transport of oxygen
22
Q
white blood cells
A
normal count = ~6 thousand cells/microL
neutrophils, eosinophils, basophils, monocytes, lymphocytes
23
Q
platelets
A
normal count = ~2 hundred thousand cells/microL
hemostasis
24
Q
polymorphonuclear granulocytes
A
neutrophils, eosinophils, and basophils
variation in the nucleus but all have granules in the cytoplasm
25
neutrophils
neutrophilic granules (only nuclei are stained)
40-60% of leukocytes
phagocytes
26
eosinophils
contain granules that stain with acidic dyes
1-4% of leukocytes
defence against parasites
27
basophils
have basophilic granules
<1% of leukocytes
inflammation
28
monocytes
have abundant agranular cytoplasm and large kidney-shaped nuclei
2-8% of leukocytes
phagocyte + immune defence
29
lymphocytes
large round nuclei and little cytoplasm
20-40% of leukocytes
B cells and T cells
immune defence
30
B cells
antibody production
humoral immunity
31
T cells
cellular immunity
32
hematopoiesis
process of formation of blood cells
prenatal hematopoiesis occurs in the yolk sac (early embryo), the fetal liver, and the fetal spleen
postnatal hematopoiesis occurs in the bone marrow
33
multipotent hemtopoietic stem cell
differentiates into progenitor cells: lymphoid stem cell or myeloid stem cell
bone marrow cells with capacity to synthesize any cell
34
lymphoid stem cell
in process of hematopoiesis, form lymphocytes
35
myeloid stem cell
in process of hematopoiesis, can form any other blood cell type
need cytokines to differentiate
36
stages of hematopoiesis
all stem cells begin in the bone marrow
stem cells that become T cells will migrate to the thymus gland before differentiating in the blood
red blood cells, platelets, monocytes, granulocytes, and B cells will differentiate in the blood
B cells and T cells will migrate between the blood and tissues depending on need
monocytes will differentiate to macrophages when move to the tissues
granulocytes can also migrate to the tissues
37
cytokines
(hematopoietins)
small proteins that regulate hemtopoiesis
hormone-like in their mechanism of action
act as growth factors
38
erythropoietin
cytokines that regulate hematopoiesis of erythrocytes (red blood cells
39
thrombopoietin
cytokines that regulate hematopoiesis of thrombocytes (platelets)
40
erythrocytes (red blood cells)
7-8 µm diameter
2-3 µm thickness
~ 5 million/µL
120 day lifespan (short without nucleus)
function in O2 transport
lose nucleus and other organelles during development - small shape, only contains Hb
full of hemoglobin molecules
41
shape of red blood cells
biconcave shape - thicker on outside and thinner in middle = greater surface area:volume ratio → allows greater diffusion - transport of O2
shape makes the cells flexible - can more through blood vessels and capillaries
42
hemoglobin
heme (non-protein) + globin (protein)
responsible for ~99% of total oxygen transport
43
Hemoglobin A
HbA - hemoglobin A
alpha2beta2 form = 2 alpha globin chains + 2 beta globin chains
heme = iron-containing non-protein group
max of 4 ferrous iron molecules contained by heme per hemoglobin molecule
44
O2 transport
hemoglobin binds to oxygen in loose and reversible manner
each ferrous iron (Fe++) combines with one molecule of O2 by process of oxygenation
picked up in lungs and delivered to tissues by blood
45
oxygen binding and unloading
oxyhaemoglobin = relaxed binding structure; open pockets so O2 can bind quickly
deoxyhaemoglobin = tight binding structure; changed conformation of globin chains to prevent other gases binding once O2 has been released
46
CO inhalation
= fatal
hemoglobin can bind to other gases - 200x more affinity for CO than O2
high affinity = tight binding and stays bound
colourless + odourless gas
47
red blood cell production
cytokine erythropoietin
dietary factors
intrinsic factor
48
erythropoietin
produced by cells in kidneys
testosterone helps release and regulation of EPO synthesis = difference in hematocrit between males and females
other hematopoietins also play a role
49
dietary factors of RBC production
iron
folic acid
vitamin B12
50
erythropoietin regulation of RBC production
low O2 delivery to kidneys triggers EPO synthesis
kidneys increase EPO secretion, elevating plasma EPO
circulates in blood to increase production of erythrocytes in bone marrow
increases blood hemoglobin concentration → increased blood O2 carrying capacity
= restoration of O2 delivery
51
factors that decrease oxygenation
1. low blood volume
2. anemia (decreased red blood cells)
3. low hemoglobin synthesis
4. poor blood flow - decreased heart pumping function
5. pulmonary disease
52
decreased tissue oxygenation
decreased erythropoietin in kidneys causes increased release
trigger hematopoietic stem cells → proerythroblasts → red blood cells → increased hemoglobin = tissue oxygenation
53
uptake of iron
regulation of iron levels
dietary absorption based on sensors in the small intestine
circulates through blood vessels:
i. plasma iron circulates to all other cells
ii. loss of iron through urine, skin cells, sweat, and menstrual blood
iii. storage in liver: fixed deposit bound to ferritin protein
54
iron recirculation
through blood vessels → bone marrow → erythrocytes → spleen and liver → blood
new erythrocytes released from the blood marrow
old erythrocyte removal in spleen - extract iron from hemoglobin
55
body iron reserve
50%: hemoglobin - broken down from old red blood cells
25%: other iron containing proteins
25%: bound with ferritin in liver
56
recycling iron from old/damaged red blood cells
in spleen
old red blood cells taken up into macrophage by phagocytosis
hemoglobin is braken down into heme and globin
globin → protein broken down into amino acids that are released and either used in metabolism of form new proteins
heme → i. iron moves into blood bound to transferrin - sent either to bone marrow to make new hemoglobin or liver for storage (bound to ferritin) ii. biliverdin (green) → bilirubin (yellow) → moves to liver and forms bile → small intestine - excreted as feces or through blood as urine
57
folic acid
needed for synthesis of thymine (essential for DNA)
58
Vitamin B12
essential for folic acid to work
59
intrinsic factor
protein factor released from cells in lining of stomach
60
absorption of vitamin B12
vitamin B12 from diet is moved to the stomach where it binds with intrinsic factor and forms a complex to be transported to the small intestine
in the ileum (lower small instestine), the complex comes apart and transporters move the B12 out into the blood
61
anemia
decreased oxygen-carrying capacity of the blood due to a deficiency of red blood cells and/or hemoglobin contained in the cells
62
causes of anemia
decreased production of rbc in the bone marrow
hemolytic anemia
hemorrhagic anemia
abnormal hemoglobin production
63
hemolytic anemia
increased destruction of the red blood cells in the body
64
hemorrhagic anemia
increased blood loss leading to loss of red blood cells
65
factors leading to anemia
lack of iron
pernicious anemia
aplastic anemia
chronic kidney disease (reduced levels of EPO)
hemolytic anemia due to abnormal shape of RBC or immune reactions during transfusion
hemorrhagic anemia due to injury, bleeding ulcers, or chronic menstruation
abnormal structure of hemoglobin
66
pernicious anemia
lack of vitamin B12
damage can result in decreased intrinsic factor
autoimmune/inflammatory disease can affect transporters so B12 can't be absorbed
67
aplastic anemia
damage of bone marrow due to radiation/drugs
not making enough red blood cells
68
Sickle cell disease
abnormal structure of hemoglobin beta globin chain
HbS = a2B*2
single amino acid mutation in B chain
cell membranes of sickle-shaped red blood cells are hard and non-flexible, affecting passage through capillaries → damaged cells = hemolytic anemia
autosomal recessive disease
69
sickle cell adaptation
gene is prominent in regions common to malaria infections
carriers of sickle-cell (heterozygotes) have some sickled cells but are more resistant to malaria
70
immunity
defence: body's capacity to defend itself
self vs non-self
protect from internal damage signals
71
non-specific defenses
innate immunity
born with
physical barrier + chemicals
- intact skin, enzymes in saliva, tears, mucous
- acidic gastric secretion
- granulocytes and macrophages
72
specific defenses
acquired/adaptive immunity
develop by infections
lymphocytes
73
white blood cell hematopoiesis
development in bone marrow
stem cells → WBC precursors → granulocytes; monocytes; B-cells; (T cell precursors move to thymus + finish development)
emerge from bone marrow to blood vessels
granulocytes
monocytes
B-cells + T-cells = lymphocytes
when needed, move from blood vessels to tissues
granulocytes
monocytes → macrophages
lymphocytes
lymphatic system
lymphocytes can recirculate to blood
74
innate immunity
non-specific; no memory; fast
involve phagocytes: granulocytes and macrophages
complement system
75
acquired immunity
specific; memory; slow
involve lymphocytes
antibodies and cytotoxic molecules
76
appropriate role of immune system
defence against foreign invaders
removal of own old damaged abnormal cells
identify/destroy abnormal/mutant cells
77
inappropriate role of immune system
allergies
autoimmune reaction
78
allergies
exaggerated response to harmless substances
heightened sensitivity
79
autoimmune reaction
attacking own immune system
self vs self
80
inflammation
non-specific innate response to tissue injury
compromised physical barrier - cut, wound, burns, infections
81
purpose of inflammation
destruction of non-self →fibrosis (clotting/scar tissue) → healing
inducers → sensors → mediators
82
physical characteristics of inflammation
redness
swelling
heat
pain
loss of function
83
redness
rubor
increased blood flow
histamine
84
swelling/edema
tumor
increased blood flow
histamine
85
heat
calor
increased blood flow
histamine
86
pain
dolor
pressure on nerve endings
bradykinin and prostaglandin
87
mast cell
in tissues
similar to basophils
granules filled with histamine
88
vascular events
release of inflammatory mediators
increased blood flow
increased permeability of small blood vessels
89
inflamed vasculature
1. increased blood flow
2. edema expands extracellular matrix
3. neutrophil emigration
arteriole and venule dilation
deposition of fibrin and other plasma proteins
90
1. increased blood flow
causes capillaries to enlarge → both venule and arteriole dilation
91
2. edema expands extracellular matrix
the single layer of endothelial cells expands = leaky
allows plasma proteins out of plasma = increases osmotic force → swelling
92
3. neutrophil emigration
neutrophils and monocytes move into the infected area
93
vascular events - acute inflammation
release of histamine
local blood vessels dilate
blood vessels become leaky
accumulation of protein + fluid in extracellular spaces
additional inflammatory mediators are released: bradykinin, prostaglandings, complement proteins
94
cellular events - acute inflammation
resident macrophages entrap and kill pathogens - release chemical signals
increased movement of WBCs (neutrophils and monocytes) into infected area
phagocytosis and destruction of foreign non-self
95
goal of cellular events - inflammation
accumulate leukocytes or WBCs in the inflamed tissue and kill non-self
96
sequence of cellular events - inflammation
1. margination of WBCs
2. tethering and rolling of WBCs inside blood vessel
3. activation of WBCs and endothelial cells
4. arrest/firm attachment of WBCs to endothelial cells
5. emigration/diapedesis
6. chemotaxis of WBCs
7. recognition of non-self by WBCs
8. phagocytosis of non-self pathogen by WBCs
97
phagocyte movement
rolling adhesion
tight binding
diapedesis
migration
98
chemotaxis
ability of WBCs to move against a concentration gradient in response to chemical (chemotactic) factors
chemicals are more concentrated at the site of the pathogen
99
chemotactic factors
complement products
chemokines
bacterial products
damaged membrane products - arachidonic acid metabolites
100
role of phagocytes at the site of infection
recognition of foreign body
attachment to foreign body
internalization destruction of the 'non-self- pathogen
101
Pattern Recognition Receptors
Toll-like receptors
non-specific
proteins expressed on surface of macrophages
recognition of common patterns
102
opsonization
process of opsonin addition to bacteria to enhance attachment and engulfment of pathogen
103
opsonins
host factors added to non self
speed up the process of phagocytosis
two types: antibodies and complement proteins
104
engulfment
injurious agent surrounded by pseudopods and internalized in a membrane-bound phagocytic vacuole
105
killing by neutrophils
3 processes could occur based on what is available
1. oxygen dependent killing
2. oxygen independent enzymatic killing
3. suicidal killing
106
oxygen-dependent killing
inside neutrophils
production of oxygen free radicals → oxidative burst
107
oxygen free radicals
superoxide anion O2-
hydrogen peroxide H2O2
myeloperoxidase → produces HOCl
108
oxygen-independent killing
use enzymes
could be in addition to O2 dependent killing
bactericidal proteins and enzymes
- lysozyme
- lactoferrin
- defensins
109
lysozyme
action inside the cell
breakdown contents
110
lactoferrin
act in the extracellular space
released outside of neutrophil
binds to iron found in the extracellular space → use up iron so that bacteria cannot grow
111
defensins
act outside of cell
poke holes in membrane = bacteria can't survive
112
suicidal killing
outside the neutrophils
NETs - neutrophil extracellular traps
113
NETs
neutrophils throw out their DNA to trap particles
once entangled, enzymes are used to destroy it
neutrophils do not survive = suicide killing
114
is inflammation beneficial?
yes - short-term
no - long-term
too much killing is bad
neutrophilic killing = destructive and indiscriminate
products produced during phagocytosis are released extracellularly - lysosomal enzymes, oxygen-derived active metabolites
115
complement proteins
inactive plasma proteins
involved in innate defence
plasma-derived mediators
116
complement activation
3 possible ways to activate system: classical pathway, lectin pathway, alternative pathway
OIL: opsonization of pathogens, inflammatory cell recruitment, lysis of pathogens
117
lysis - killing by MAC formation
MAC pokes hole in membrane
activated complement proteins insert into surface of membrane
fluid flows inside = compromise bacterial survival
118
MAC
membrane attack complex
collection of activated complement proteins
119
innate defense
vascular events result in cellular events
bacteria trigger macrophages to release cytokines and chemokines →
vasodilation and increased vascular permeability cause redness, heat, and swelling →
inflammatory cells migrate into tissue, releasing inflammatory mediators that cause pain
large reserves of neutrophils are stored in the bone marrow and are released when needed to fight infection →
neutrophils travel to and enter the infected tissue where they engulf and kill bacteria - neutrophils die in the tissue and are engulfed and degraded by macrophages
120
primary lymphoid tissues
sites of lymphocyte differentiation and education
where lymphocyte synthesis begins
bone marrow
thymus
121
lymphocyte education
before the lymphocytes emerge from the bone marrow or thymus, they are educated as to what is foreign
122
secondary lymphoid tissues
sites where lymphocytes encounter antigen and become activated
lymph nodes
spleen
123
role of lymphocytes in acquired immunity
recognize antigens as foreign
respond to antigens
remember the first encounter with an antigen - memory
124
antigen
structure to which specific antibody binds to form a complex
125
antibody
globulin class of protein
y shape
recognition molecule on B cells - B cell receptor
2 light chains
2 heavy chains
top of 'y' = antigen binding site
bottom of 'y' = effector cell binding site - where macrophage binds
126
role of B cells
B cells in lymphocytes travel through blood to recognize foreign body
antibodies on cell surface bind to antigens if they match
mitosis of B cells
clonal expansion of match receptor in response to antigen
maturation of B cells into plasma cells → produce antibodies
some B cells become memory cells
127
humoral immunity
defence against bacterial infections
antibodies bind to antigens → form complex
opsonization
complement activation
'direct effects' →neutralization of toxins
128
antibody neutralization
toxic molecules bind to receptors on cell surface → physiological changes = symptoms of illness
antibodies prevent antigens from binding = neutralization
ingestion and destruction by phagocyte of bound antigen
129
cellular immunity - acquired immunity
major defence against viruses, cancer, transplants
T lymphocytes: helper T cells, cytotoxic T cells, memory T cells
130
antigen presentation
processing:
antigen presenting cell (usually a macrophage) engulfs the antigen and processes it - broken down and loaded into MHC → moved to membrane surface
presentation:
MHC protein attaches to helper T cell receptor - presents the antigen
131
3 signals to trigger immune response
1. APC presents antigen on MHC
2. expression of co-stimulatory molecules on APC → activate process
3. cytokine secretion by APC
132
Major Histocompatibility Complex
MHC
proteins are present on the membrane of most cells
two types: MHC I and MHC II
133
MHC I proteins
present on all nucleated cells
134
MHC II proteins
present on specialized antigen-presenting cells (macrophages, dendritic cells)
135
helper T cells
antigen presented to helper T cells
produce cytokines that activate cytotoxic T cells and B cells
136
cytotoxic T cells
activated by cytokines
clones are carried to all parts of the body via blood
toxic molecules released attack antigen-bearing cells (when bound)
perforin + granzymes
137
perforin
facilitates entry of cytotoxic granzymes into cell → induces apoptosis
138
immunological memory
measure of antibodies in the body
primary response to antigen = small and slow
decline over time
secondary response to antigen = large and fast
vaccination
139
B cell memory
naive cells are first exposed to antigen → small number of activated plasma cells, + memory cells (in lymphnodes)
secondary exposure to antigen causes memory cells to divide → more memory cells + large number of activated cells = lots of antibodies
140
active immunity
acquired by exposure to disease or vaccination
self-generated antibodies
acquired in weeks (primary) or days (secondary)
lasts months to years
purpose: combat future infection
141
passive immunity
acquired by ingestion of antibodies across placenta or through mother's breast milk
pre-formed antibodies (in the mother)
acquired immediately
lasts a few weeks
purpose: to combat existing infection
142
necessity of hemostasis
balance between pro-hemostatic and anti-hemostatic factors
143
pro-hemostatic factors
pro-coagulant factors
prevent blood loss
144
anti-hemostatic factors
anti-coagulant factors
keep blood fluid
145
steps of hemostasis
1. vasoconstriction (constrict to prevent blood loss - blood flows to site of injury)
2. primary hemostasis
3. secondary hemostasis
146
primary hemostasis
platelet plug formation
white thrombus
seal area with collected platelets
147
secondary hemostasis
blood clotting/coagulation
red thrombus
gel-like clot
148
platelet origin
bone marrow stem cells → megakaryocyte (intermediate cell) → blood
149
megakaryocyte
giant cells in the bone marrow
form platelets by pinching off bits of cytoplasm and extruding them into the circulation
150
platelet structure
non-nucleated (short life-span)
alpha granules
dense granules
glycogen = energy
actin and myosin
phospholipids
151
alpha granules
contain relatively large molecules
- adhesion molecules - von Willebrand factor
- growth factors
- some clotting factors
- cytokines
152
dense granules
contain relatively small molecules
- ADP and ATP
- serotonin
- Ca2+
153
Von Willebrand Factor
vWF
most important protein
adhesion molecule - has sticky properties
154
platelet plug formation
occurs with damage to smaller blood vessels
1. adhesion of platelets - stick to damaged vessel wall
2. activation of platelets - change shape, express various receptors, and secrete various substances
3. aggregation of platelets - attract other platelets; stick to each other to form a plug
155
mechanism of platelet plug formation
rupture of blood vessel → collagen is exposed to platelets → adhesion (vWF)
platelets release thromboxane, ADP
fibrinogen binds platelets together
156
receptor expression on platelets
expression of fibrinogen receptors → fibrinogen binds to platelets and anchors them together
expression of vWF receptors → vWF polymerizes to collagen and binds to receptors on platelets
157
activated platelets
5HT - serotonin
TXA2 - thromboxane A2
ADP - adenosine diphosphate
PL - phospholipid
158
5HT role
target blood vessels
vasoconstriction → reduce blood flow = limit damage
159
Thromboxin A2
vasoconstriction of blood vessels
further platelet aggregation
160
ADP role
further platelet aggregation
161
phospholipid - exposed on platelet surface
targets thrombin
162
damage to endothelial cells
exposed collagen at site of damage
163
reactions involved in hemostasis
injury to a blood vessel exposes collagen and thromboplastin → recruitment of platelets to site of injury
platelets releast 5-HT → smooth muscle contraction + vasoconstriction
collagen activates clotting cascade → activation of thrombin by thromboplastin - converts circulating fibrinogen to fibrin monomers → polymerize and cross link; accumulate with platelets to form clot
164
signaling - mediation of response to blood damage
adjacent endothelial cells secrete chemical signals (NO and PGI2)
→ influence platelet aggregation and alter blood flow and clot formation at the affected site
= platelet plug does not continuously expand
165
effects of arachidonic acid metabolites
arachidonic acid is generated from phospholipids by phospholipase A2
generation of enzymes in 2 pathways:
1. lipoxygenase pathway
2. cyclooxygenase pathway
166
lipooxygenase pathway
initiates inflammation
formation of leukotrienes
occurs before COX pathway
167
cyclooxygenase pathway
hemostasis
formation of prostoglandins
COX 1 and 2
168
COX 1
enzyme carried in platelets (→ non-nucleated = cannot synthesize new machinery)
generation of thromboxane A2
169
COX 2
enzyme carried in endothelial cells (→ nucleated; can synthesize new parts after temporary inhibition)
generation of prostacyclin
170
thromboxane A2
pro-hemostatic effect:
vasoconstriction
increased platelet aggregation
171
prostacyclin
prostaglandin
anti-hemostatic effect:
vasodilation
decreased platelet aggregation
172
effect of aspirin on hemostasis
aspirin causes irreversible inhibition of both COX 1 and COX 2
at low doses of aspirin, COX 2 is favoured
endothelial cells can resume synthesis after temporary inhibition by aspirin
173
secondary hemostasis
occurs following a platelet plug formation
cascade of enzyme activation → by proteolutic cleavage
formation of gel-like fibrin clot
174
clotting/coagulation factors
plasma proteins
mostly made in the liver
175
factor I
fibrinogen
176
factor II
prothrombin
need vitamin K for synthesis
177
factor III
tissue factor
178
factor IV
calcium
not made in the liver
179
factors that need vitamin K for synthesis
factor II, IX, and X
180
co-factors
help other factors
factor V and VIII
181
key step of blood clotting
prothrombin is broken down into thrombin by prothrombinase
thrombin converts fibrinogen to fibrin (insoluble plasma protein)
182
activation of thrombin
intrinsic pathway and extrinsic pathway come together to activate a "common activated factor"
→ prothrombinase converts prothrombin to thrombin
vessel damage → exposure of blood to subendothelial tissue → activation of plasma factors by enzymes
183
cascade of plasma enzyme activations
requires activated platelets, plasma cofactors, and Ca2+
184
mechanism of blood clotting
intrinsic pathway + extrinsic pathway
→ activation of factor Xa
→ common pathway
185
intrinsic pathway
"contact activation"
XII → XIIa
activates XIa
+ (Ca2+) → activates IXa
+ VIIIa + (Ca2+) + PL → activates Xa
186
extrinsic pathway
tissue damage
activates VIIa and TF
+ (Ca2+) + PL → activates Xa
187
common pathway
Xa + Va + (Ca2+) + PL
= prothrombin to thrombin
→ fibrinogen to fibrin
fibrin stabilized by XIIIa + (Ca2+)
188
factor deficiencies: VII
severe bleeding
extrinsic pathway = cannot initiate
189
factor deficiencies: VIII
severe bleeding
no homeostasis
intrinsic pathway = cannot activate factor X
190
factor deficiencies: XI
moderate bleeding
intrinsic pathway = cannot activate factor IX
191
factor deficiencies: XII
not involved in initiating intrinsic pathway
= no bleeding problem in vivo
(in vitro = failure to clot)
VII can activate IX (bypass if XII deficient)
192
in vivo blood clotting
initiation happens at extrinsic pathway → small amounts of thrombin amplify intrinsic pathway to form large clot
thrombin creates positive feedback in intrinsic pathway
- activation of XI, X, prothrombin → thrombin, and stabilizing fibrin
193
role of thrombin in clotting pathway
1. activation of platelets
2. conversion of soluble fibrinogen to insoluble fibrin
3. activation of other clotting factors: V, VIII, XI, XIII
4. activation of protein C → anticoagulant activity
194
hemophilia B
X-linked recessive gene
deficiency of factor IX
less common than hemophilia A
195
hemophilia A
deficiency of factor VIII
196
regulation of blood clotting
1. prevention of clot formation where and when it is not required
2. breakdown of clot as tissue repair occurs (fibrinolytic system)
197
prevention of clot formation
natural anticoagulants
thrombin
clinical anticoagulants
198
TFPI
tissue factor pathway inhibitor
(extrinsic pathway)
inhibits X a and VII a
natural
199
antithrombin 3
inhibits thrombin
natural
200
thrombomodulin
changes thrombin activity
activates protein C and S
natural
201
protein C and S
inhibit V a and VIII a
natural
202
thrombin as an anticoagulant
thrombin bound to thrombomodulin has anti-coagulant activity
activates protein C → inhibition of factor VIIIa and factor Va = inhibit coagulation
203
calcium chelators
ex. Na citrate
remove ionized calcium (by binding) = no clotting
works in vitro
clinical
204
heparin
increases effect of antithrombin 3 (blocks actions of thrombin)
works in vitro and in vivo
clinical
205
antagonists of vitamin K
inhibit synthesis of II, VII, IX, and X in liver
works in vivo
clinical
206
fibrinolysis
plasminogen activators
plasminogen → plasmin = in presence of clot, turn insoluble fibrin into soluble fibrin degradation products
207
natural plasminogen activators
tissue plasminogen activator
released from endothelial cells
release increased by exercise
208
clinical clot busters / thrombolytic drugs
plasminogen activator
used to treat patients with heart attacks
209
tenectaplase
thrombolytic drug
210
abnormal hemostasis
imbalance of pro and anti hemostatic factors
excessive bleeding/hemorrhage
thrombosis
211
excessive bleeding/hemorrhage
failure of hemostatic mechanisms when they are required
1. problems with platelets
2. problems with clotting factors
212
thrombocytopenia
damaged bone marrow = not enough platelets
excessive bleeding
213
abnormal platelet function
ex. vWF deficiency
excessive bleeding
214
problems with clotting factors
hereditary deficiencies (ex. hemophilias)
acquired deficiencies (ex. vit K deficiency)
215
thrombosis
formation of blood clot when not required
1. hereditary disorders
2. acquired disorders
216
anti X
antibody that binds to X antigen (A, B, or D)
217
antigens of the ABO system
present on surface of red blood cells
determine blood types
carbohydrate molecules
218
antibodies of the ABO system
usually of the IgM class
naturally occurring antibodies
large molecules
219
RBC type A
A antigens and anti B antibodies present in blood
220
RBC type B
B antigens and anti A antibodies present in blood
221
RBC type AB
A and B antigens present in blood
no antibodies
222
RBC type O
anti A and anti B antibodies present in blood
no antigens
223
expression of ABO antigens on RBCs
ABO genes code for enzymes of the ABO system
enzymes add on the specific terminal carbohydrate molecules to the surface of RBC
= carbohydrate ABO antigen molecules
224
ex. O gene (ABO system)
codes no functional enzyme
RBC does not carry CHO antigen
225
AA or AO genotype
blood type = A
A antigens on RBC
anti B antibodies in plasma
226
BB or BO genotype
blood type = B
B antigens on RBC
anti A antibodies in plasma
227
AB genotype
blood type = AB
A and B antigens on RBC
no antibodies in plasma
228
OO genotype
blood type = O
no antigens on RBC
anti A and B antibodies in plasma
229
determining ABO blood type
separate blood sample into RBC and plasma fractions
RBCs are mixed with known solution of either anti-A or anti-B antibodies
mixture is observed for RBC agglutination or clumping
O will not agglutinate (no antigens for antibodies to recognize)
230
agglutination
surface antigens + opposing antibodies (recognize antigens + bind) → clumping + hemolysis
231
cross-match
sample donor blood - RBC antigens are matched to sample recipient blood plasma antibodies
match = no recognition, no binding
232
blood transfusion matches
ideally, donor and recipient should match ABO blood type
in emergency, O is a universal donor (but cannot receive from anybody but O); AB is a universal recipient
233
Rhesus system antigens
protein molecules
form integral part of RBC membrane
IgG class
D gene codes for D antigen on surface of RBC
234
Rh+
D antigen present
235
Rh-
absence of D antigen (D gene deletion)
236
mismatched blood transfusion (Rh)
Rh- is exposed to Rh+ → develops anti-D antibodies
second exposure → anti-D antibodies will bind to Rh+ RBC and cause clumping + hemolysis
237
rhesus mismatch in pregnancy
Rh- mother + Rh+ father
1st child: if Rh+ → born healthy but Rh+ crosses into mother's blood = anti-D antibodies develop
2nd child: if Rh+ → anti-D crosses placenta and binds to Rh+ antigen in child = HDN
238
hemolytic disease of newborn
caused by rhesus mismatch in pregnancy if mother is Rh- and child is Rh+
Rh hemolytic disease
fever, chills, nausea
clotting within blood vessels
hemoglobin in urine
239
