Hemodynamics and Clotting Flashcards
Where is the capillary endothelium continuous? Why is it continuous?
Brain, muscle, lung, bone; Junctional complexes (occluding)
Where is the capillary endothelium fenestrated? Why?
Glomeruli, intestines, endocrine, choroid plexus, ciliary processes; small pores allow transfer of small molecules
Where is the capillary endothelium discontinuous? Why?
Spleen, liver, bone marrow, LN; large gaps for free transfer of proteins, cells, etc.
Difference between arteries and veins?
Arteries have internal and external elastic lamina
What molecules move freely across plasma membrane
Lipophilic, uncharged/unpolar, O2, CO2, urea, H2O, fatty acids
What molecules do not move freely across plasma membrane
Lipophobic, polar, electrolytes, Ca, glucose, amino acids
What determines osmolality? Serum osmolality is equivalent to _______
Glucose, electrolytes, urea; ECF
What determines osmolarity?
Large proteins (albumin) that can’t between plasma and interstitium
What three types of granules do platelets have, and what is in them?
Alpha- vWF, fibrinogen (factor I), factor V, XI, XII, integrins, P selectin, chemokines, TGFbeta, VEGF
Delta- Serotonin, histamine, epi/norepi, ADP, ATP, Ca, Mg
Lysosomes
What causes vasoconstriction at sites of injury?
Endothelin
What forms the platelet plug of primary hemostasis?
Platelets bound to ECM
GpIb on platelets bound to vWF on collagen
GpIIb-IIIa on platelets bound to fibrinogen
What does a deficiency in GpIb cause?
Bernard-Soulier syndrome
What does a deficiency in vWF cause?
von Willebrand disease
What does a deficiency in GpIIb-IIIa cause? Who is predisposed?
Glanzmann thrombasthenia; Otterhound and great pyrenees
What causes platelet activation? What causes GpIIb-IIIa to change conformation, giving it a high affinity for fibrinogen?
ADP, thrombin
What does thrombin cleaving PAR on platelets do?
Activates platelets and inflammatory cells, stimulates TXA2 production
What on the platelet becomes site of coag factor complexes?
Phosphatidylserine flipped out and bound to Ca
Who get signal transduction disorders (abnormal aggregation/granule release)?
Simmental cattle, Spitz, Basset hound
What is prolonged with hemophilia A and B? What factors are deficienct?
PTTs; A- VIII, B- IX
What factor deficiency causes the most severe bleeding?
Factor X
Which factor deficiency results in no bleeding?
Factor XII
Most comon cause of secondary coagulation defect
Inflammation- use
How does DIC cause a coagulation? Anticoagulation?
There is systemic activation of thrombin due to lots of tissue factorr
What factors require Vitamin K?(6) What factors require Ca?
X, IX, VII, II, C, and S; X, IX, VII, II
How does uremia cause coagulation defect? Aspirin?
Inhibits platelet activation/aggregation; Inhibits COX, so no TXA2
Virchow’s triad
Abnormal flow
Hypercoagulability
Endothelial injury (most important)
In septic shock, how does coagulation happen?
LPS directly activates factor XII (intrinsic pathway)
What causes platelet inhibition in normal vessels?
ADPase
NO
Prostacyclin
What does antithrombin do? What does it need to do so?
Binds and inactivates thrombin*, factors IXa, Xa; Heparin-like molecule
What does the protein C pathway do? What does it need to do so?
Destroys factors Va and VIIIa; Thrombomodulin bound to thrombin to cleave protein C, bind to protein S on phospholipid surface, vitamin K
What else does protein C pathway do?
Inactivates PAIs and factor Xa
What does Tissue Factor Pathway Inhibitor (TFPI) do? What does it need?
Inhibits extrinsic pathway; protein S as cofactor
What does tPA do? What inhibits it?
Converts plasminogen to plasmin, which inhibits fibrin formation; PAIs
What does endothelium release when damaged?
PAIs
vWF from dense granules
TF on surface
PARs on surface
Role of inflammation in injured endothelium?
Decreases activity of protein C, thrombomodulin, antithrombin, TFPI
Effect of thrombin on endothelial cells
Binds PAR-1, increases intracellular Ca, which activates MLCK to cause actin-myosin contraction, AND activates annexin A2, which disassembles VE-Cadherin
What is thrombin’s role in the clotting cascade?
Converts fibrinogen (I) to fibrin (Ia)
Converts XIII to XIIIa (which then crosslinks fibrin)
Activates V, VII, VIII, XI (amplifier)
GpIIb-IIIa conformational change to bind fibrinogen
Most important initiator of coagulation IN VIVO
Factor III (tissue factor)
Clotting factor with shortest half life?
Factor VII
Most important clotting factor?
Factor II (thrombin)
What requires a phospholipid surface?
Activation of X, conversion of prothrombin to thrombin by Xa and Va, Protein C pathway
Most important in fibrinolysis; most important activator of this; other activator
Plasmin; t-PA; kallikrein (via XII)
What else does plasmin do?
Cleaves C5 (along with kallikrein)
What are D dimers? What do D dimers do?
Fibrin degradation products; Inhibit thrombin, coat platelets, interfere with fibrin polymerization
What do alpha2 antiplasmins do? What else do they inhibit?
Bind plasmin; Protein C
Where is vWF made?
Endothelial cells and megakaryocytes
