Blood Detail Flashcards
Clotting factors are made where?
in the liver, except VIII (vascular endothelium)
intrinsic pathway
contact activation. blood contacts collagen. slower, forms larger clots
intrinsic pathway sequence
exposed collagen, XII, XI, IX, X
extrinsic pathway
tissue factor initiated. faster (15s), less thrombin, smaller clot
extrinsic pathway sequence
trauma, III, VII, X
exposed collagen–>
XII
XIIa–>
XI
XIa (or VII/TF)–>
IX/VIII/platelets
IX/VIII/platelets–>
V/X/platelets
X (prothrobin activator), V (from platelets)
damaged tissue–>
VII/TF
VII/TF–>
V/X/platelets (prothrombin activator)
V/X/platelets
FII (prothrombin)–> thrombin–>
FI (fibronogen) to fibrin
coagulation cascade is
secondary hemostatis
fibrin is
a woven rope of 3 chains (2 alpha, 2beta, 2 gamma) , acts as glue for platelets
fibrin ropes are crosslinked by
a transglutaminase, FXIIIa
Which CFs and anticoagulants depend on vitamin K?
FII, FVII, FIX, FX, Protein C and S
for binding Ca
Warfarin and Coumadin block
vitamin K, prevent clotting factors from attachment to platelets
Tenase complex
allows FX activation. IXa, VIIIa
IXa linked to
hemophilia B
VIIIa linked to
hemophilia A
circulating VII adheres to
non-endothelial cells that express Tissue Factor
which have become exposed to the blood due to damage. VII is then autoactivated
tertiary hemostatis: XII–>XIIa
cleaves kallirein, activating plasminogen to plasmin,
tertiary hemostatis: urokinase and tPA
also generate plasmin
plasmin
binds and deactivates V, VIII, fibrin to dissolve clots
detect clotting and clot reabsorption
fibrin degradation products (FDPs or d-dimers)
Protein C and S (with thrombomodulin)
inactivate FV and FVIII
platelets 150,000
normal
platelets 100,000
bleeding in surgery
platelets 20,000
bleeding in acute illness
platelets 10,000
spontaneous injury
WASp syndrome
X-linked disease (mainly males) thrombocytopenia, eczema, recurrent infections, and small-sized platelets
Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT)
both caused by WASp mutation: thrombocytopenia and small platelets are the only consistent features of WAS and XLT
thrombocytopenia
relative decrease in platelets
GATA 1 and megakaryocytes
combines with RUNX1, drives gene expression. if defective, megakaryocytes do not mature
Thrombopoetin
from liver, tells megakaryocytes to make platelets (via TPO receptor intereaction)
congenital amegakaryocytic thrombocytopenia
defect in c-Mp1, Megakaryocyte’s Thrombopoetin receptor
vWF A1 domain interacts where on platelet?
GpIba
ADAMTS13
inhibits vWF clot size by cleaving at A2
thrombotic thrombocytopenia purpura (TTP)
clots-low platelets-bleeing in skin. caused by ADAMTS13 mutations
fibrin clots in TTP
shear RBCs into fragments called schistocytes
platelet activation due to
Receptors for: TxA2, thrombin, ADP, and collagen integrin receptor
TxA2 receptor
TxA2 receptor!
PAR1
Thrombin receptor
P2Y12
ADP receptor
alpha2beta1, GPVI-FcR gamma
Collagen integrin recptor
Aspirin
inhibits thromboxane sythesis.
limits platelet activation
Plavix
irreversibly blocks P2Y12 receptor:
limits platelet activation
P2Y12
ADP receptor on platelets, blocked by plavix (clopidogrel)
Hermansky-Pudlak
platelets lack ADP granules. defective coat protein!
bleeding disorder, also comes with albinism
alphaIIbB3
last step in activation. alphaIIbB3 integrin is activated, binds circulating fibrin/fibrinogen to stabilize clot.
NO and prostaglandin PGI2
inhibit clotting.
bind plt., increase cAMP to decrease cytosolic Ca.
Generated by endothelium.
In atherosclerosis, there is less
PGI2, thus more platelet activation
LDL lipids activate
platelet thromboxane.
atherosclerosis is thrombogenic!
platelet granules
serotonin, ADP, TxA2
heme comes from
succinyl CoA. seven steps
lead blocks
last step in heme formation
RDS in heme formation
aminolevulinic acid step
porphyria
heme abnormalities cause skin photosensitivity and psychiatric neural-visceral symptoms
a2g2 or z2g2 or apha epsilon
embryonic hemoglobin
ALPHA2GAMMA2, alpha2delta2
fetal hemoglobin
ALPHA2BETA2, alpha2gamma2
adult hemoglobin
thalassemia
defects in heme gene expression cause compensations that distort cell shape and half life of RBCs in circulation
1 alpha mutation, aa/a-
asymptomatic
2 alpha deletion aa/– or a-/a-
mild microcytic anemia
microcytic anemia
characterized by small RBCs
3 alpha deletion a-/–
anemia, hemolysis, jaundice. “hemoglobin H disease” beta tetramers precipitate and kill the cell
4 alpha defects –/–
anemia, hydrops fetalis, death of fetus
beta thal nomenclature
+ partial synthesis of beta chain
0 no synthesis of beta chain
b/b0 or b/b+
asymptomatic
b+/b0
intermediate thal trait
b0/b0
severe thal
thal traits
hypoxia, extramedullary hematopoesis, skull bone changes, iron overload. high output heart failure
haptoglobin
captured heme released by lysed cells
hemoglobinopathy
chains (not amounts) of hemoglobin defective
SS disease
2 copies of beta6glu–>valine
C disease
2 copies of beta6glu–>lysine
SS and C disease results
polymerization of hemoglobin (exposed hydrophobic regions) short half-life, RBC destruction, bilirubin production causing gallstones, then anemia, hypoxia
haptoglobin measure of
hemolysis
blood maximum O2 load
20.4 ml/dl
blood maximum O2 delivery
1020ml/min
right shift on O2 curve
lower affinity, takes more O2 to saturate, thus more to deliver
left shift on O2 curve
higher affinity, less delivery to tissue
fetal hemoglobin has
higher affinity for O2 (duh, how else would it get O2)
leftward shift
muscle O2 curve
even lefter than fetal!