Snf Test 4 - Coronary Circulation

Front 1

From what is coronary circulation derived from?

Back 1

The right and left coronary arteries

Front 2

What does the right coronary artery principally supply?

Back 2

The right ventricle and atrium

Front 3

What does the left coronary artery branch into and principally supply?

Back 3

Divides near its origin into the anterior descending and the circumflex branches

Mainly supplies the left ventricle and atrium

Front 4

In humans which artery is most commonly dominant (supplying most of the myocardium)?

Back 4

-Right coronary artery in about 50% of individuals
-Left coronary artery is dominant in another 20%
-Flow delivered by each main artery is about equal in the remaining 30%

Front 5

What is the venous return for the coronary circulation?

Back 5

Coronary veins flow into the great coronary vein that empties into the right atrium via the coronary sinus. Some veins empty directly into the atria. These are thebesian veins.

Front 6

What are thebesian veins?

Back 6

Veins that empty directly into the atria

Front 7

Is coronary blood flow high or low during systole and why?

Back 7

Coronary blood flow is low during systole, despite the increase in aortic pressure. This is because during systole the ventricle muscle contracts and compresses the coronary blood vessels. During the early diastole, aortic pressure is maintained because of elastic recoil and the ventricles relax so blood flow can increase.

Front 8

How is coronary blood flow regulated?

Back 8

By sympathetic and parasympathetic innervation in addition to local metabolic factors

Front 9

How do the sympathetic nerve receptors affect systolic compression?

Back 9

Alpha-receptors increase resistance
Beta-receptors decrease resistance

Front 10

How do the vagus nerves affect coronary blood flow?

Back 10

Decrease resistance and increase blood flow

Front 11

How does adenosine affect coronary blood flow?

Back 11

Decreases resistance and increases blood flow

Front 12

How does systolic compression affect coronary blood flow?

Back 12

Increases resistance and thus decreases blood flow

Front 13

How does vascular smooth muscle relax?

Back 13

Acetylcholine stimulation of GPCRs (muscarinic) is seen in blood vessel endothelial cells of some tissues. This activates the PLC pathway to elevate Ca2+ which binds to calmodulin and activates nitric oxide synthase stimulating the production of NO which is rapidly diffusing neurotransmitter that stimulates guanylate cyclase. This catalyzes the formation of cGMP which activates protein kinase G which relaxes smooth muscle.

Front 14

What is nitroglycerin a substrate for?

Back 14

Nitroglycerin is a substrate for NO synthesis to relax coronary arteries

Front 15

How is cGMP broken down to GMP and what drug inhibits this process?

Back 15

By phosphodiesterase-5

Silendafil (Viagra) and its variations inhibit PDE-5 to prolong the effect of elevated cGMP levels

Front 16

What are the effects of nitrates on circulation?

Back 16

The primary effect of nitrates is the dilation of the major veins which will reduce venous return and thus pre-load (filling). With a reduced venous return, cardiac output and thus workload for the heart will decrease. Nitrates also reduce systemic arterial pressure and afterload which also reduces the work required of the heart

Front 17

What can atherosclerotic plaque build up result in?

Back 17

Blood vessels in the heart may become occluded. These narrowings may create turbulence and are susceptible to blockage by thromboemboli (coronary thrombosis).

Front 18

What allows for compensation when a blockage occurs on one side?

Back 18

Anastomoses between right and left coronary artery branches are able to compensate to a degree. Generally, they develop slowly and compensate for longer term impairment of coronary blood flow.

Front 19

What can unwanted clot formation result in?

Back 19

Thrombus that can block blood flow.

Front 20

What is a saddle embolism?

Back 20

When a clot blocks the branch point for the pulmonary arteries leading to the lungs. Dehydration and inactivity can concentrate and plasma proteins in pooled venous blood and lead to unwanted thrombus formation.

Front 21

What are the major causes of morbidity and mortality in developed countries?

Back 21

Failure to maintain normal fluid status

Front 22

What are the three most important causes of pathologic lesions in Western society?

Back 22

Myocardial infarction
Pulmonary embolism
Cerebrovascular accident (stroke)

Front 23

What occurs when a blood vessel is damaged?

Back 23

Factors in the blood contact proteins in the basal lamina and initiate a complex series of reactions that lead to a platelet aggregation and clot formation.
-Vasoconstriction
-Platelet Aggregation
-Coagulation (soluble fibrinogen polymerizes to form fibrin)

Front 24

What is the general sequence of events in primary hemostasis at a site of vascular injury?

Back 24

1. Platelet adhesion
2. Shape change
3. Granule release
4. Recruitment
5. Aggregation (hemostatic plug)

Front 25

What is the brief period of arteriolar vasoconstriction that occurs shortly after injury largely attributable to?

Back 25

Reflex neurogenic mechanisms and augmented by the local secretion of factors such as endothelin (a potent endothelium-derived vasoconstrictor). The effect is transient, however, and bleeding would resume were it not for activation of the platelet and coagulation systems

Front 26

What does endothelial injury expose?

Back 26

Endothelial injury also exposes highly thrombogenic subendothelial extracellular matrix (ECM), which allows platelets to adhere and become activated, that is, undergo a shape change and release secretory granules. Within minutes, the secreted products have recruited additional platelets (aggregation) to form a hemostatic plug; this is the process of primary hemostasis.

Front 27

What is von Willebrand's factor (vWF) and what role does it play in platelet aggregation?

Back 27

A plasma protein

Binds to collagen and other ECM proteins in the sub-endothelium. vWF also has binding sites to a glycoprotein lb in the platelet membrane.

Front 28

What do platelets release when they aggregate and what effects does it have?

Back 28

ADP and thromboxane A2

Activate a glycoprotein (integrin) that can bind the plasma protein, fibrinogen. At the same time, a complex series of reactions is initiated to cause fibrinogen to polymerize and form a clot to stabilize the platelet plug and stop blood loss

Front 29

What do normal, undamaged endothelial cells secrete to prevent platelet aggregation in addition to thrombomodulin that binds to thrombin to prevent fibrin formation?

Back 29

Prostacyclin (PGI2) and NO

Front 30

What is an example of a cyclooxygenase inhibitor and what does it do?

Back 30

Aspirin

Inhibit the formation of PGH2 which is a precursor for thromboxane A2

Front 31

What is hemostasis?

Back 31

Balance between normal flow and thrombus formation

Front 32

During platelet aggregation what two molecules bind to receptors on the platelet membrane and activate a signaling pathway that modifies GpIIb-IIIa so it can bind fibrinogen, linking platelets together?

Back 32

ADP and Thromboxane A2 (TXA2)

Front 33

During coagulation what is fibrinogen converted to and why?

Back 33

Fibrin
To create the fibrous clot

Front 34

When does a thromboembolism occur?

Back 34

In pooled venous blood and trubulent flow around atherosclerotic plaques where local concentration of clotting factors can occur.

Front 35

What does platelet activation by thromboxane A2 and ADP result in?

Back 35

Activate fibrinogen binding receptors and also cause platelets to become flattened and extend pseudopodia to increase the membrane area exposed for greater aggregation and facilitation of clot formation.

Front 36

What can occur if platelet aggregations form in the absence of vessel damage?

Back 36

Platelet aggregations can circulate and form a thromboembolism that can block blood flow to the heart ("heart attack") or brain (stroke).

Front 37

What do people at risk for platelet aggregation take?

Back 37

Aspirin
Plavix

Front 38

How does aspirin act?

Back 38

Blocks COX to inhibit TXA2 synthesis

Front 39

How does plavix act?

Back 39

Irreversible inhibitor of ADP binding to purinergic receptor on platelet

Front 40

What is tissue factor and how does it work?

Back 40

A membrane-bound procoagulant factor synthesized by endothelium and released at the site of injury.

It acts in conjunction with the secreted platelet factors to activate the coagulation cascade, culminating in activation of thrombin.

Front 41

What does thrombin do when vessel damage occurs?

Back 41

Cleaves circulating fibrinogen into soluble fibrin creating a fibrin meshwork deposition. Thrombin also induces further platelet recruitment and granule release.

Front 42

Which takes longer, secondary hemostasis or the formation of the initial platelet plug?

Back 42

Secondary hemostasis

Front 43

What do polymerized fibrin and platelet aggregates form?

Back 43

A solid, permanent plug to prevent any further hemorrhage.

Counter-regulatory mechanisms are set into motion to limit the hemostatic plug to the site of injury

Front 44

What is the intrinsic pathway of thrombin formation?

Back 44

A protein (factor XII = Hageman factor) in the blood itself binds to negatively charged surfaces, such as exposed collagen, to initiate the pathway that converts prothrombin to thrombin.
Longer

Front 45

What is the extrinsic pathway of thrombin formation?

Back 45

Protein (tissue factor) released from endothelial cells, outside the blood, activate pathway to convert prothrombin to thrombin
Shorter

Front 46

What is short form of secondary hemostasis?

Back 46

Prothrombin is converted to thrombin. Thrombin converts fibrinogen, a soluble plasma protein into fibrin that is able to cross link and polymerize.

Front 47

What are factors VII, XII, XI, IX, X and II (prothrombin), where are they made and how are they activated?

Back 47

Serine proteases

Made in the liver in an inactive form (zymogen)

Become activated when a peptide sequence is cleaved

Front 48

What is the advantage to having such a complex activation system for thrombin?

Back 48

Each protease molecule can activate many molecules of the next protein in the pathway. Thus, a single XII can activate many XI molecules that can activate many more IX molecules. Thus, many prothrombin molecules can be activated to thrombin very rapidly to form a clot.

Front 49

What two factors initiate the intrinsic and extrinsic pathways?

Back 49

Intrinsic: Collagen exposure of an intrinsic factor (XII)

Extrinsic: Release of tissue thromboplastin (tissue factor)

Front 50

What accelerates the activation of factor X?

Back 50

Factor VIIIa that holds factor X in close proximity with factor IXa.

Front 51

The binding of factors IX and X to the platelet membrane requires what ion?

Back 51

Ca2+

Front 52

What stabilizes factor VIII and what results from a defect in stabilization?

Back 52

Von Willibrand's factor

Von Willibrand's disease results from defective vWF

Front 53

What symptoms may von Willibrand's disease show?

Back 53

Hemophilia - results from a defective factor VIII

Front 54

What brings together activated Xa with prothrombin (factor II) and where does this occur?

Back 54

Va

On the surface of the platelet membrane

Front 55

What is required for binding to the membrane where catalysis occurs?

Back 55

Ca2+

Front 56

What are factors VIII and V referred to as since they facilitate reactions where the enzymatic factors X and II become activated?

Back 56

Cofactors

Front 57

Which clotting factors bind to phospholipid bilayers platelets and why?

Back 57

II, VII, IX, X

Increase the rates of reactions in the clotting pathways and also confine the clot formation to the vicinity of the platelet plug.

Front 58

What must occur on membrane phospholipids in order for clotting factors to bind?

Back 58

Glutamic acid residues must be carboxylated to form carboxyglutamate.

Front 59

Where are glutamic acid residues carboxylated to form carboxyglutamate?

Back 59

Liver, as a post translational step

Front 60

What is a cofactor in the carboxylation reaction and thus in blood clotting?

Back 60

Vitamin K

Front 61

How is vitamin K deficiency seen?

Back 61

As Impaired formation of prothorombin and factor VII (of the extrinsic pathway)

Front 62

What are two examples of anticlotting agents and how do they work?

Back 62

Coumadin and warfarin

Inhibit vitamin K action

Front 63

How is blood stored?

Back 63

With chelating agents to bind Ca2+

Front 64

Where do the activations of factor x and prothrombin occur?

Back 64

On reactions on platelet membranes

Front 65

Where is it essential that the clots form?

Back 65

Where there is a break in the vessel wall

Front 66

What factors do endothelial cells release to (1) break up clots and block the (2) coagulation cascade?

Back 66

(1) tissue plasminogen activator
(2) thrombomodulin

Front 67

What is antithrombin III, how is it activated, and what does it do?

Back 67

Most potent of the endogenous inhibitors of clot formation

Activated by heparin

Inactivates thrombin, factors Xa and IXa

Front 68

What is heparin used as clinically?

Back 68

Anticoagulant, especially in patients undergoing dialysis or thoracic surgery

Front 69

What does plasmin do and how is it made?

Back 69

Proteolytic enzyme that dissolves clots

Active plasmin is made when plasminogen is subject to proteolytic cleavage by plasminogen activators. Tissue plasminogen activator (t-PA) and streptokinase are used to break up clots that block coronary arteries and cause a "myocardial infarction"