Ch.3 Hemodynamic Disorder Pt.2

Question 1

Vasodialator, increases vascular permeability, modulator of pain

Answer 1

Bradykinin

Question 2

Bradkykinin is degraded by what enzyme?

Answer 2

Angiotensen Converting Enzyme (ACE)

Vasoconstrictor! Opposite effect of bradykinn

Question 3

Use of _____ raise the bodys level of bradykinin

Answer 3

ACE inhibitors. No enzymes secreted= no degredation of Bradykinin.

Question 4

If levels of bradykinin in the body get to high, this can leave to a dangerous side effect; swelling of deep layers of skin

Answer 4

Angioedema

Question 5

Bradykinin can also be degraded by ____ inhibitors from the complement system.

Answer 5

C1 Inhibitor

Question 6

A deficiency in C1 inhibitor can cause what?

Answer 6

Hereditary Angioedema

Question 7

What is the coagulation factor that activates coagulation cascade, and also activates the pathway that forms bradykinin?

Link between the coagulation & inflammation

Answer 7

Hagman factor XII

Question 8

• Rare condition
• Markedly **prolonged PTT **(intrinsic pathway)
• **XII cannot **acitvate normally
• Coagulation deficiency

Answer 8

Prekallikrein deffinceny (PK deficiency)

Question 9

Hagman factor XII requires what two things to generate bradykiin?

Answer 9

1. Prekallikrein (PK)
2. Hime molecular weight Kinogen (HMWK)

Question 10

Prekallikrein deffinceny (PK deficiency) causes what to go up?

Answer 10

PTT

Question 11

Thrombin does what ?

Answer 11

Fibrogen to cross linked fibrogen, amplifying generation of fibrin.

Activates Factor 5, 8, 11, stabalize clot activates 13

Question 12

. Thrombin is a potent inducer of what?

Answer 12

Patlet activation

Question 13

Features of what?

• Can mediate effects & contibute to tissue repair
• Anticoagulant effect; prevents clot from extending from site of injury

Answer 13

Thrombin

Question 14

What factor that limits coagulation?

blood flowing past the site of injury washes out activated coagulation factors, which are rapidly removed by the liver

Answer 14

Simple Dilution

Question 15

What factor that limits coagulation?

____ which are provided mainly by activated platelets, which are not present away from the site of injury.

Answer 15

negatively charged phospholipids

Question 16

limits the size of the clot and contributes to itslater dissolution

Answer 16

fibrinolytic cascade

Question 17

Fibrinolysis is accomplished largely through the enzymatic activity of _____ which breaks down fibrin and interferes with its polymerization.

Answer 17

plasmin,

Question 18

Fibrin derived breakdown product of fibrogens,

good clinical marker for diffrent thrombotic states and to see if thrombosis was resolbed

Answer 18

D-Dimers

Question 19

an inactive circulating precursor, by enzymatic cleavage that forms plasmin.

Answer 19

plasminogen

Question 20

Where is tissue plasminogen activator t-PA? When is it most active?

Answer 20

t-PA is synthezised by endothelium and most active when bound to fibrin

Question 21

Explain thromosis and antithrombotic properties of the endothelium.

Answer 21

There is a balance between anticoagulant and procoagulant activities of the endothelium

• Normal endothelial cells express factors that inhibit procoagulant activity of platelets and coagulation factors that augment firbinolysis= prevent thrombosis and limit vasucular damage
• If damaged, endothelial cells Lose their antithrombotic properties

Question 22

WHat are the 3 effects of difrrent antithrombotic agents?

Answer 22

1. Platlet inhibtion
2. Anticoagulant effects
3. Fibrinolytic effects

Question 23

Release of:
* Prostacyclin (PGI2)
* Nitric Oxide (NO)
* Adenosin
* Binding of thrombin

By the endothelium all do what?

Answer 23

inhibit platlet aggregation

Adenosine degrades ADP and PGL2 & NO are vasodialators thus promoting

washout of coagulation factors. Thrombin bound inhibits ability to actiavtes platlets

Question 24

What do
* Thrombomodulin
* Endotehlial C-Receptors
* Heprin Like molecules
on endothelium surface do?

Answer 24

bind
* thrombin
and
* protein C
respectively, in complexes on the endothelial cell surface.

Antitrhombosis

Question 25

# Anticoagulation effect What occurs when thrombomoduline binds thrombin on the endothelial surface?

Answer 25

When thrombin is bound it loses the abilit to activate coagulation factors & platlets, **instead it cleaves & activates protein C (with cofactor protien S)** | protein C/S complex is a **potent inhibitor of coagulation factors**

Question 26

# Anticoagulant Effect What do heprin like molecules on the surface of endothelum do?

Answer 26

Inactivate thrombin and other coagulationf actros by binding and activating **Antithrombin III**

Question 27

What is the clincial utility of heprin and related durgs based on?

Answer 27

Their ability to stimulate antithrombin activity

Question 28

Another anticoagulant effect, like protein C, requires protein S as a cofactor and, as the name implies, **binds and inhibits tissue factor/factor VIIa complexes.**

Answer 28

Tissure Factor Pathway Inhibitor

Question 29

Normal endothelial cells synthesize t-PA, already discussed as a key component of the fibrinolytic pathway.

Answer 29

Fibronolytic effects, T-PA

Question 30

Explain Virchow traid

Answer 30

3 Things leading to Thrombosis= 1. Endothelial Injury 2. Stasis or turbulant blood flow 3. Hypercoagulability of blood

Question 31

**Endothelial injury** leading to platelet activation almost inevitably underlies thrombus formation ____ and ____ , where the **high rates of blood flow otherwise impede clot formation.** These kinds of clots are rich in what?

Answer 31

1. heart 2. arterial circulation **rich in platlets**

Question 32

A shift in pattern of gene expression in the endothelium to one that is **prothrombotic** produced by physical injury, infectious agets, abnormal blod low, cytokienes, and metaboic abnormalities.

Answer 32

Endothelial Activation or dysfunction

Question 33

what are 2 major prothrombic alterations in endothelial dysfunction?

Answer 33

1. **Procoagulant changes** (downregulation of expression of coagulation inhiibitors) 2. **Antifibronolytic effects** (increased secretion of plasminogen activator inhibitors which limit fibrynolysis by anatagonizig t-PA and urokinase)

Question 34

____ contributes to arterial and cardiac thrombosis by causing endothelial injury or dysfunction, as well as by forming countercurrents and local pockets of stasis.

Answer 34

Turbulant blood flow

Question 35

What 3 things does stasis and turbulant blood flow result in?

Answer 35

1. **Promote** endothelial cell acitavted and enhanced **pro-coagulant activity** 2. **Stasis** allows platlets and leukocytes to contact endothelium 3. **Stasis** slows washout of activated clotting faactors, imbeating inflow of clotting factor inhibitors.

Question 36

____ refers to an abnormally **high tendency of the blood to clot** and is usually caused by alterations in coagulation factors.

Answer 36

Hypercoagulability

Question 37

**Primary (inherited) hypercoagulability** is most often caused by | Gentic

Answer 37

mutations in the factor V and prothrombin genes | Factor V, prothrombin mutation, increased levels Factor 8, 9, 11, fibrog

Question 38

What form of **hypercoaggubility is secondary**?

Answer 38

Aquired; results in high or elevated risk of thrombosis

Question 39

# What specific hypercoaguable state? Marked by the **development of autoantibodies that bind complexes of heparin and platelet factor-4 (PF4)** * Occurs in 5% of pt treated with unfraction heprin * Net result is prothrombotic state even with heprin administattion, clot still forms.

Answer 39

Heparin-induced thrombocytopenia (HIT) syndrome.

Question 40

Where can arterial or cardiac thrombi arise? What about in veins?

Answer 40

* At sites of endotheliali injury or blood turbulance * At sutes if stasis

Question 41

How do venous vs arterial thrombi propogate and what can both result in?

Answer 41

**Arterial thrombi**= grows away from point of attachment **Venous thrombi**= grow in direction of blood flow. **propogating portion is porly attached and prone to fragment & migrate to the heart as an embolus**

Question 42

Where are thrombi more common?

Answer 42

**Veins** because less blood flow! **most comonly embolized** | **veins off lower extremetuies most commonly affected**

Question 43

Thrombi occurring in heart chambers or in the aortic lumen

Answer 43

Mural Thrombi | Proimoted by Arrythmias, MI, myocarditis

Question 44

# What thrombus? **typically rich in platelets**, as the processes underlying their development (e.g., endothelial injury) lead to platelet activation

Answer 44

Arterial Thrombus **obstruct vessles and cause infarction locally** | ruptured atherosclerotic plaque (e.g., vasculitis, traum also trigger

Question 45

What are the 4 events that come after a thrombolytic event?

Answer 45

1. **Propagation**: thrombus enlages 2. **Embolization**: Part of thrombus dislodge and travels elswhere 3. **Dissolution**: (newer thrombus) fibronylitic factors lead to shrinkage and dissolution of thrombus. (older) harder to get rid of. 4. **Organization & Recanalization**: older thronbi have ingrowht of cells

Question 46

Where do **superficial venous thrombi** usually arise?

Answer 46

**saphenous system (legs), particularly in the setting of varicosities**; these rarely embolize but they may cause pain, local congestion, and swelling fro

Question 47

Where do **Deep venous thrombi** usually arise? | DVTs

Answer 47

Larger leg veins at or above knee joint. **more serious and more prone to emolize**

Question 48

Lower-extremity DVTs are associated with ____ and ____ states

Answer 48

Lower DVTs are assoociated with **stasis and hypercoaguability states** | Conjestive heart falure, bed rest, imobalization, pregnancy

Question 49

widespread thrombosis within the microcirculation that may be of sudden or insidious onset.

Answer 49

Disseminated Intravascular Coagulation (DIC) | Excessive clotting, excessive bleeding.

Question 50

A detached intravascular solid, liquid, or gaseous mass that is carried by the blood from its point of origin to a distant site, where it often causes tissue dysfunction or infarction

Answer 50

Embolisim | mostly derived from dislodged thromi; thromboembolism

Question 51

Originate from deep venous thrombi and are responsible for the most common form of thromboembolic disease.

Answer 51

Pulmonary Thromboembolism * Most are small * Large embolus block major pulmonary arterys causing sudden death. | Mostly originating from deep leg vein thrombois

Question 52

Most **airse from intercardiac mural thrombi,** usually arterial and can **travel virtually anywhere** , consequence depend on caliber of oluded vessles and presence or absence of colateral blood supply.

Answer 52

Systemic Thromboembolism

Question 53

Soft tissue crush injury or rupture of marrow vascular sinusoids (e.g., resulting from a long bone fracture) **release microscopic fat globules** and associated marrow elements into the circulation.

Answer 53

Fat Embolism

Question 54

Attributed to **platelet adhesion to fat globules and subsequent aggregation or splenic sequestration** ; anemia may result from red cell aggregation and/or hemolysis.

Answer 54

Thrombocytopenia

Question 55

an uncommon, grave complication of labor and the immediate postpartum period that is caused by the **entry of amniotic fluid (and its contents) into the maternal circulation** via tears in the placental membranes and/or uterine vein

Answer 55

Αmniotic embolism

Question 56

Gas bubbles that enter the circulation can coalesce and obstruct vascular flow and cause distal ischemic injury

Answer 56

Air embolism

Question 57

What form of air embolism occurs in divers?

Answer 57

decompression sickness is caused by sudden changes in atmospheric pressure. "the bends"

Question 58

**an area of ischemic necrosis caused by occlusion of the vascular supply of the affected tissue**. In the Heart and the brain are common, important causes of illness.

Answer 58

Infarction | Can be red (venous occlsuons( or white (arterial occlusions)

Question 59

What 3 things affect infaract development?

Answer 59

1. **Anatomy of vascular supply ** 2. **Rate of occlusion** (how quick blood is being blocked, slow is less likley to become infarcted because allows time for collateral blood supply to kick in 3. **Tissue vaulnerability to hypoxia** (how long can cell withstand lack of blood, ex. skeletal msucles cell vs neuron)

Question 60

A state in which diminished cardiac output or reduced effective circulating blood volume impairs tissue perfusion and leads to cellular hypoxia

Answer 60

Shock | Prolonged shock leads to irreversible injury

Question 61

results from **low cardiac output as a result of myocardial pump failure.** It may be caused by * myocardial damage (infarction) * ventricular arrhythmia * extrinsic compression (cardiac tamponade) * Ouflow obstruction

Answer 61

Cardiogenic Shock

Question 62

Results from **low cardiac output due to loss of blood or plasma volume** resulting from * hemorrhage * fluid loss from severe burn * Diarreah & vomiting

Answer 62

Hypovolemic shock

Question 63

Triggered by **microbial infections and is associated with severe systemic inflammatory response syndrome (SIRS)**. In addition to microbes, SIRS may be triggered by burns, trauma, and/or pancreatitis **Mast cell degranulation, vasodialation, venous blood pooling,

Answer 63

Septic Shock | Mortalilty rate 20-30%, gram + bacterial infections

Question 64

results from **systemic vasodilation** and increased vascular permeability and is triggered by **IgE–mediated hypersensitivity reactions**

Answer 64

Anaphylactic shock

Question 65

The pathophysiology of Septic shock involves what?

Answer 65

1. endothelial cell activation and injury 2. vasodilation 3. edema in many tissues 4. disseminated intravascular coagulation 5. Metabolic derangements.