proteins. Circulate in blood as proenzymes (zymogens) (roman numerals, inactivated enzymes that must be activated to function).
An a is added to the roman numeral if activated.
#s 1-13, not 4 or 6.
vascular endothelium and anticoagulants
when squamous endothelium in vessels is damaged, platelets and factor 8 attach to basement membrane (collagen and fibronectin) to form clot. Only if broken or activated.
Models of hemostasis
Y cascade (older, easier to understand but wrong)
Cell-based model (physiological, in vivo model. Right but more complicated).
Sequence of events in vascular injury
primary hemostasis (unstable platelet plug)
secondary hemostasis (stable platelet plug. Activation of coagulation factors, mesh of fibrin)
anticoagulent events (keeps clots localized)
fibrinolysis (repair of damage, dissolution of clot)
both hyper and hypo coagulation at the same time. Makes microclots that are ineffective, so still bleeds.
Difference between extrinsic and intrinsic traditional model of hemostasis
Extrinsic is started by a damaged tissue, simple process, tissue factor, Calcium to common pathway
Intrinsic is started with damaged vessel, MANY STEPS and factors but get to common pathway. Then same
Common pathway in traditional model of hemostasis
Factor X to activated X, Factor V, Ca2+, Prothrombinase, Prothrombin to thrombin, thrombin activates XIII and fibrinogen. Fibrinogen plus Ca2+ to loose fibrin plus activated XIII to strenghtened fibrin (strengthened clot)
breakdown of RBC inside a macrophage.
Major steps of cell-based hemolysis
Initiation (injury, tissue factor exposed, small thrombin)
Amplification (thrombin activates platelets, cleaves von Willebrand factor from VIII, platelet aggregation and adhesion)
Propagation (Coagulation propagated on activated platelet, LOTS OF THROMBIN)
Initiation of cell-based model of hemostasis
injury, cells bearing Tissue Factor exposed, generate small amount of thrombin.
Amplification of cell-based model of hemostasis
(small amount of) thrombin activates platelet, cleaves von Willebrand factor from Factor VIII leading to platelet aggregation and adhesion to exposed subendothelial collagen
Propagation of cell-based model of hemostasis
coagulation propagated on activated platelet surface, LARGE amount of thrombin formed.
Cell-based model steps
Vascular injury (collagen exposed, release of molecules from endothelium and nocioceptors)
Vascular constriction (to prevent blood loss)
Platelet adhesion and aggregation (swell, get sticky and develop pseudopods)
formation of platelet plug (release granules, recruitment of more platelets)
Thrombin formation in clotting
Prothrombin (Factor II)
proenzyme continuously form in liver
requires vitamin K for synthesis
makes thrombin (factor IIa)
Plasma protein formed in liver
thrombin converts to fibrin, held together by hydrogen bonds
FVa + FXa = prothrombin complex
Prothrombin (II) + prothrombin complex = thrombin (IIa)
Fibrinogen + thrombin = Fibrin
FXIII + thrombin = FXIIIa
Fibrin + FXIIIa = crosslinked fibrin clot
Von willebrand factor
makes platelets stick together (platelet aggregation) and stick to subendothelial collagen.
a dense network of fibrin fibers that enmesh platelets, blood cells and plasma
Why doesn't the whole body coagulate?
constant blood flow (active factors float away, need activated platelet and damaged endothelium)
removal of activated factors by hepatocytes
removal of particulate matter by mononuclear cells
Restriction of the clotting process to activated membrane
within minutes of formation, expresses serum, pulls edges of broken blood vessels together
Platelet-derived growth factor is released to stimulate smooth muscle and fibroblast to divide and repair
Vascular endothelial growth factor causes endothelial cells to multiply and restore BV lining
Plasminogen is activated into plasmin (clot-buster), digests fibrin fibers into fibrin degredation products (covalent bonds break to create D dimers)
Lower Calcium levels: sodium or potassium citrate
Heparin: inactivates FIIa, IXa, Xa and XIa
Dicoumarol: Found in mouldy sweet clover and rodenticide. Inhibits vitamin K clotting factors (II, VII, IX and X)
What was wrong with Butch? Blood in urine, dark stool, pale gums, weak, cold, epistaxis. Outside dog on farm.
ate rodenticide or poisoned rat. Blocks epoxide reductase, vitamin K can't be reused, inhibits clotting factors.
Induce vomiting if just ate
Give vitamin K and transfusion if bleeding.
Vitamin K and coagulation factors
Vitamin K (quinon). Vitamin K reductase makes reduce vitK, gamma carboxylase (activates II, VII, IX, X, proteins C, S, Z), Oxidized vitamin K, Epoxide reductase (warfarin inhibits)
returns oxidized vitamin K to useable vitamin K. Rodent poison (warfarin) inhibits.
abnormal clot that develops in a blood vessel and STAYS at the site of its formation.
abnormal clot that has broken away from its attachment and flowed away with current. MOVES. Can obstuct a blood vessel. Could be a plug of other material too.