Hemodynamics and Clotting

Question 1

Where is the capillary endothelium continuous? Why is it continuous?

Answer 1

Brain, muscle, lung, bone; Junctional complexes (occluding)

Question 2

Where is the capillary endothelium fenestrated? Why?

Answer 2

Glomeruli, intestines, endocrine, choroid plexus, ciliary processes; small pores allow transfer of small molecules

Question 3

Where is the capillary endothelium discontinuous? Why?

Answer 3

Spleen, liver, bone marrow, LN; large gaps for free transfer of proteins, cells, etc.

Question 4

Difference between arteries and veins?

Answer 4

Arteries have internal and external elastic lamina

Question 5

What molecules move freely across plasma membrane

Answer 5

Lipophilic, uncharged/unpolar, O2, CO2, urea, H2O, fatty acids

Question 6

What molecules do not move freely across plasma membrane

Answer 6

Lipophobic, polar, electrolytes, Ca, glucose, amino acids

Question 7

What determines osmolality? Serum osmolality is equivalent to _______

Answer 7

Glucose, electrolytes, urea; ECF

Question 8

What determines osmolarity?

Answer 8

Large proteins (albumin) that can’t between plasma and interstitium

Question 9

What three types of granules do platelets have, and what is in them?

Answer 9

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

Question 10

What causes vasoconstriction at sites of injury?

Answer 10

Endothelin

Question 11

What forms the platelet plug of primary hemostasis?

Answer 11

Platelets bound to ECM
GpIb on platelets bound to vWF on collagen
GpIIb-IIIa on platelets bound to fibrinogen

Question 12

What does a deficiency in GpIb cause?

Answer 12

Bernard-Soulier syndrome

Question 13

What does a deficiency in vWF cause?

Answer 13

von Willebrand disease

Question 14

What does a deficiency in GpIIb-IIIa cause? Who is predisposed?

Answer 14

Glanzmann thrombasthenia; Otterhound and great pyrenees

Question 15

What causes platelet activation? What causes GpIIb-IIIa to change conformation, giving it a high affinity for fibrinogen?

Answer 15

ADP, thrombin

Question 16

What does thrombin cleaving PAR on platelets do?

Answer 16

Activates platelets and inflammatory cells, stimulates TXA2 production

Question 17

What on the platelet becomes site of coag factor complexes?

Answer 17

Phosphatidylserine flipped out and bound to Ca

Question 18

Who get signal transduction disorders (abnormal aggregation/granule release)?

Answer 18

Simmental cattle, Spitz, Basset hound

Question 19

What is prolonged with hemophilia A and B? What factors are deficienct?

Answer 19

PTTs; A- VIII, B- IX

Question 20

What factor deficiency causes the most severe bleeding?

Answer 20

Factor X

Question 21

Which factor deficiency results in no bleeding?

Answer 21

Factor XII

Question 22

Most comon cause of secondary coagulation defect

Answer 22

Inflammation- use

Question 23

How does DIC cause a coagulation? Anticoagulation?

Answer 23

There is systemic activation of thrombin due to lots of tissue factorr

Question 24

What factors require Vitamin K?(6) What factors require Ca?

Answer 24

X, IX, VII, II, C, and S; X, IX, VII, II

Question 25

How does uremia cause coagulation defect? Aspirin?

Answer 25

Inhibits platelet activation/aggregation; Inhibits COX, so no TXA2

Question 26

Virchow's triad

Answer 26

Abnormal flow Hypercoagulability Endothelial injury (most important)

Question 27

In septic shock, how does coagulation happen?

Answer 27

LPS directly activates factor XII (intrinsic pathway)

Question 28

What causes platelet inhibition in normal vessels?

Answer 28

ADPase NO Prostacyclin

Question 29

What does antithrombin do? What does it need to do so?

Answer 29

Binds and inactivates thrombin*, factors IXa, Xa; Heparin-like molecule

Question 30

What does the protein C pathway do? What does it need to do so?

Answer 30

Destroys factors Va and VIIIa; Thrombomodulin bound to thrombin to cleave protein C, bind to protein S on phospholipid surface, vitamin K

Question 31

What else does protein C pathway do?

Answer 31

Inactivates PAIs and factor Xa

Question 32

What does Tissue Factor Pathway Inhibitor (TFPI) do? What does it need?

Answer 32

Inhibits extrinsic pathway; protein S as cofactor

Question 33

What does tPA do? What inhibits it?

Answer 33

Converts plasminogen to plasmin, which inhibits fibrin formation; PAIs

Question 34

What does endothelium release when damaged?

Answer 34

PAIs vWF from dense granules TF on surface PARs on surface

Question 35

Role of inflammation in injured endothelium?

Answer 35

Decreases activity of protein C, thrombomodulin, antithrombin, TFPI

Question 36

Effect of thrombin on endothelial cells

Answer 36

Binds PAR-1, increases intracellular Ca, which activates MLCK to cause actin-myosin contraction, AND activates annexin A2, which disassembles VE-Cadherin

Question 37

What is thrombin's role in the clotting cascade?

Answer 37

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

Question 38

Most important initiator of coagulation IN VIVO

Answer 38

Factor III (tissue factor)

Question 39

Clotting factor with shortest half life?

Answer 39

Factor VII

Question 40

Most important clotting factor?

Answer 40

Factor II (thrombin)

Question 41

What requires a phospholipid surface?

Answer 41

Activation of X, conversion of prothrombin to thrombin by Xa and Va, Protein C pathway

Question 42

Most important in fibrinolysis; most important activator of this; other activator

Answer 42

Plasmin; t-PA; kallikrein (via XII)

Question 43

What else does plasmin do?

Answer 43

Cleaves C5 (along with kallikrein)

Question 44

What are D dimers? What do D dimers do?

Answer 44

Fibrin degradation products; Inhibit thrombin, coat platelets, interfere with fibrin polymerization

Question 45

What do alpha2 antiplasmins do? What else do they inhibit?

Answer 45

Bind plasmin; Protein C

Question 46

Where is vWF made?

Answer 46

Endothelial cells and megakaryocytes