Path: Hemodynamics 2

Question 1

________ is inappropriate formation of blood clot in a blood vessel, usually occlusive.

Answer 1

Thrombosis

Question 2

There are three predisposing factors to thrombosis:

referred to as Virchow’s triad by elderly pathologists

Answer 2

(1) Endothelial injury, (2) Abnormal blood flow, and (3) Hypercoagulability.

Question 3

__________ is the most important factor predisposing to thrombosis.

Answer 3

Endothelial injury

Question 4

The hemodynamic stress of hypertension or toxicity of hypercholesterolemia or products absorbed from smoking can create these pro-thrombotic events:

Answer 4

increase endothelial procoagulant factors or decrease their anticoagulant factors enough to cause thrombosis

Question 5

T/F: Abnormal blood flow, either turbulence or stasis, and turbulent blood flow over ulcerated atherosclerotic plaques does NOT predispose to thrombosis.

Answer 5

False. They do predispose one to thrombosis.

Question 6

T/F: thrombosis is more common in veins and more serious in arteries.

Answer 6

True

Question 7

Thrombosis due to endothelial injury is mediated by:

Answer 7

endothelial cell activation or dysfunction

Question 8

T/F: Activated or dysfunctional (messed up) endothelial cells express more thrombomodulin, tissue factor protein inhibitor and other anti-coagulant factors.

Answer 8

False. Less of each

Question 9

Describe the effect of activated or dysfunctional endothelial cells on secretion of plasminogen activator inhibitors and up/down regulation of expression of t-PA.

Answer 9

Activated or dysfunctional endothelial cells also secrete plasminogen activator inhibitors and downregulate the expression of tissue plasminogen activator (t-PA).

Question 10

Does the presence of plasminogen activator inhibitors and the downregulation of t-PA cause clotting? Explain.

Answer 10

No, but it is more likely to fail to stop a clot from occluding the entire vessel when platelets clot out of control.

Question 11

Stasis promotes thrombosis by allowing platelets to spend more time sitting on ________ .

Answer 11

Endothelial cells

Question 12

Normal blood flow is laminar and the platelets (and other cells) are concentrated in the central, more rapidly flowing bloodstream, while there is a peripheral layer of _______, moving more slowly, spending more time in contact with the blood vessel lining.

Answer 12

plasma

Question 13

Describe the cellular presentation of polycythemia vera.

Answer 13

abnormally large number of erythrocytes, an autonomous proliferation of erythroid line bone marrow cells

Question 14

Describe the condition Waldenstrom macroglobulinemia as it relates to viscosity and Ab load in the plasma.

Answer 14

abnormally thick hyperviscuous plasma loaded with excess IgM. Due to an autonomous proliferation of B lymphocytes making IgM.

Question 15

How does turbulent blood flow promote thrombosis?

Answer 15

By activating, sometimes even injuring endothelial cells, and by creating countercurrents (eddies) creating local pockets of stasis.

Question 16

What is the medical, super-sciency YAY! term for a hypercoagulable state?

Answer 16

thrombophilia

Question 17

Hypercoagulable states can be congenital. List 6.

Answer 17

Factor V Leiden mutation
Prothrombin gene mutation
Methyl-tetra-hydro-folate reductase gene mutation
Anti-thrombin 3 deficiency 
Protein C deficiency
Protein S deficiency

Question 18

Hypercoagulable states can be caused by acquired circumstances such as surgery or trauma. Name 5 other potential causes.

Answer 18

Cancer
Bed-ridden state
DIC
Heparine-induced thrombocytopenia 
Antiphospholipid syndrome

Question 19

_____________ is the most common inherited hypercoagulable state (5% of whites).

Answer 19

Factor V Leiden mutation

Question 20

Describe the elevated risk (e.g. two-fold…) of venous thrombosis associated with Factor V Leiden mutation for heterozygotes and homozygotes.

Answer 20

Heterozygotes have a 5-fold higher risk of venous thrombosis and homozygotes have a 50-fold increased risk

Question 21

In Factor V Leiden mutation, mutation in clotting factor V makes it resistant to activated __________, resulting in the loss of an important clot-limiting counter-regulatory mechanism.

Answer 21

protein C (activated form of which plays an important role in regulating anticoagulation) 
-Proteolytically inactivating proteins Factor Va and Factor VIIIa

Question 22

_____________ is the second most common inherited hypercoagulable state (2% of whites) and it confers a 3-fold increased risk of venous thrombosis.

Answer 22

Prothrombin G20210A mutation

Question 23

T/F: many pts with heterozygous mutations for hypercoagulable states or mutations causing less hypercoagulability live a normal lifespan without suffering venous thrombosis, and others get a deep venous thrombosis (typically in a leg) only when their congenital hypercoagulability is combined with an acquired hypercoagulability.

Answer 23

True

Question 24

Patients under the age of ____ , who present with thrombosis, should be worked up for inherited hypercoagulability.

Answer 24

50

Question 25

Why are patients hypercoagulable post-surgery?

Answer 25

surgery cuts blood vessels. Clotting factors inevitably spread beyond surgical site and can initiate clotting at other locations in the body.

Question 26

Why does cancer, especially malignant tumors that outgrow their blood supplies, cause a hypercoagulable state?

Answer 26

This is partly due to the inflammatory response to malignant tumors. Also, very often malignant tumors outgrow their blood supply and have some necrosis, which releases highly thrombogenic necrotic debris into the general circulation. Malignant tumors frequently compress veins or invade them, partially or completely obstructing blood flow in them, creating turbulent flow or stasis, either of which predisposes to thrombosis. Malignant glandular tumors that produce mucin, which gets into the bloodstream, are particularly likely to cause thrombosis, because mucin is thrombogenic.

Question 27

Describe migratory thrombophlebitis.

Answer 27

Metastatic cancers can cause simultaneous venous thrombi and inflammation to pop up at one subcutaneous site after another. This is called migratory thrombophlebitis

Question 28

What makes antiphospholipid antibody syndrome life-threatening?

Answer 28

causes arterial thrombosis

Question 29

Describe the laboratory findings in the serum of pts with antiphospholipid antibody syndrome.

Answer 29

These patients have autoantibodies against phospholipids (actually against plasma protein antigens unveiled by binding to phospholipids).

Question 30

Describe the clinical presentation of pts with antiphospholipid antibody syndrome.

Answer 30

The patients present with recurrent miscarriages, deep vein thromboses in their legs, cerebral infarctions, migraine headaches, cardiac vegetations, ischemic hands or feet, thrombocytopenia and various other manifestations.

Question 31

Describe, in vivid, colorful detail, DIC.

Answer 31

Disseminated intravascular coagulation is a condition of thrombus formation in small blood vessels all over the body.

Question 32

How does DIC often first manifest itself?

Answer 32

brain malfunction (altered behavior, then confusion progressing to lethargy and coma)

Question 33

What is often the secondary manifestation of DIC?

Answer 33

lung probs: dyspnea, hypoxemia

Question 34

In DIC, will you see high levels of clotting factors in the blood?

Answer 34

No, low bc all the factors are being used up in the systemic clotting.

Question 35

What are hemoglobin levels going to look like in a pt with DIC?

Answer 35

Reduced levels due to RBCs getting fragmented as they push through the microvascular thrombi

Question 36

What is consumptive coagulopathy?

Answer 36

Coagulopathy caused by all the clotting factors being used up by something like DIC.

Question 37

What are the 3 (congenital or acquired) most common causes of hypercoagulability?

Answer 37

Surgery, then cancer, then factor V Leiden mutation.

Question 38

Name the 3 types of thrombi and their characteristic locations.

Answer 38

Arterial thrombi tend to be rich in platelets (and be “white thrombi”). Venous thrombi tend to be rich in erythrocytes (and be “red thrombi”). “Mural thrombi” are located on the wall of the heart.

Question 39

______ thrombi are usually at sites of endothelial injury, most often an atherosclerotic plaque that has ulcerated or ruptured.

Answer 39

Arterial

Question 40

______ thrombi are most commonly at sites of stasis such as on the venous valves in the legs, especially in sedentary individuals.

Answer 40

Venous

Question 41

______ thrombi are generally on sites of myocardial infarction or areas of heart chamber dilatation (creating a combination of turbulent flow and stasis).

Answer 41

Mural

Question 42

Are the newest or oldest parts of a thrombus more likely to break off and be carried with the bloodstream as an embolus?

Answer 42

Newest

Question 43

Why are DVTs asymptomatic in half of pts who have them?

Answer 43

because collateral venous channels compensate for the DVT

Question 44

What is the most standard modality for diagnosing DVT in the legs?

Answer 44

ultrasound

Question 45

Can someone with elephant legs (fat legs) complicate an ultrasound for a DVT and give a false negative?

Answer 45

Yes.

Question 46

Where is it believed that greatest risk for emboli that will lodge in lungs derive from in DVT in the leg?

Answer 46

thrombosis at or ABOVE the knee (iliac, femoral, or popliteal veins)

Question 47

Thrombi on the heart valves are called “__________”

Answer 47

vegetations

Question 48

Libman-Sacks endocarditis in systemic lupus erythematosus is a vegetative, infective, or autoimmune endocarditis?

Answer 48

autoimmune

Question 49

What is marantic endocarditis?

Answer 49

Non-bacterial thrombotic endocarditis

Question 50

Which is more likely to become occlusive and totally block off the lumen of a vessel, an arterial thrombus or a venous thrombus and why?

Answer 50

Arterial. Veins are more stretchy and can better accommodate the thrombus and more importantly, arterial thrombi often occur on atherosclerotic plaques that have already narrowed the lumen.

Question 51

What are lines of Zahn?

Answer 51

Thrombi frequently have layering, with layers rich in platelets interspersed with layers rich in erythrocytes. These layers can be visible grossly, microscopically or both, and are called lines of Zahn.

Question 52

List, in order of clinical importance, the venous thromboses including arms, pelvis and legs.

Answer 52

Venous thrombosis is clinically most important in the legs, the arms and the pelvis

Question 53

List, in order of importance, the arterial thromboses including those found in the femoral artery, cerebral arteries, coronary arteries.

Answer 53

coronary arteries, cerebral arteries and femoral arteries

Question 54

List the 4 fates of a thrombus.

Answer 54

(1) dissolution, (2) propagation, (3) embolization, (4) organization (and recanalization)

Question 55

Describe dissolution of a thrombus.

Answer 55

Dissolution is the dissolving of the thrombus by fibrinolysis, either the body’s own (primary) fibrinolysis or the therapeutic administration of fibrinolytic agents.

Question 56

T/F: Fibrinolytic therapy is best delivered orally and is generally effective only when given several hours after the thrombosis.

Answer 56

False. best delivered by intravascular catheter at the site of thrombosis and is generally effective only when given during the first few hours of the thrombosis

Question 57

T/F: peripherally inserted central catheters (slang jargon “PICC lines”) in arm veins is leading to an explosive increase in deep venous thrombosis in the arms of American patients.

Answer 57

True

Question 58

What happens in organization/recanalization of a thrombus?

Answer 58

Organization is ingrowth by fibroblasts, who convert thrombus to fibrous tissue, with ingrowth of new capillaries, which can coalesce to recanalize a thrombosed blood vessel.

Question 59

What is a mycotic aneurysm?

Answer 59

A localized outpouching of an artery, especially the biggest one, the aorta, containing infected thrombus. Rarely due to a fungal infection, usually bacterial, so "mycotic" is a misnomer.

Question 60

T/F: All emboli are due to a thrombus.

Answer 60

False. Can be due to thrombus, atheromatous debris, fat, air, amniotic fluid, and fragments of tumor.

Question 61

T/F: most pulmonary emboli present as a clinical pulmonary embolism that causes life-threatening symptoms.

Answer 61

False, most (up to 80%) are clinically silent.

Question 62

What is the major symptom of pulmonary embolism?

Answer 62

Dyspnea

Question 63

It is thought that emboli must block ___% or more of the pulmonary circulation to cause right heart failure.

Answer 63

60%

Question 64

"Saddle emboli" are found where during autopsy?

Answer 64

pulmonary trunk

Question 65

What are paradoxical emboli?

Answer 65

emboli that pass through a patent foramen ovale or atrial septal defect to go to organs besides the lungs; this is rare.

Question 66

Systemic thromboembolism is thromboembolism to any organ but _____, and are most commonly from the ______ (80%) and most commonly land in the _______ (75%) and ______(10%).

Answer 66

lung; heart; legs; brain

Question 67

Fat embolism is most commonly from ________ and usually occur __ to ___ days following trauma.

Answer 67

long bone fractures; 1 to 3 days following trauma

Question 68

In the case of air embolism, generally more than _____ mL of air is needed to cause any clinical effect.

Answer 68

100 mL

Question 69

________ embolism can be caused by tears in the placental membranes during the course of labor and delivery.

Answer 69

Amniotic fluid embolism

Question 70

So, like, there are fetal cells and fragments of material from the placenta in the maternal circulation all the time in every pregnancy, so why doesn't that cause the symptoms of a pulmonary embolism?

Answer 70

The difference in the patients who get the amniotic fluid embolism syndrome is apparently in the mother’s immune reaction to a bolus (single large amount) during labor and delivery.

Question 71

Let's play "Do You Remember from Block 1?" | Describe the character of a "white anemic" infarct. (what organs, what does it look like?)

Answer 71

“White anemic” infarcts are typical of solid organs with end-arterial circulation (heart, spleen, kidney).

Question 72

Let's play "Do You Remember from Block 1?" | Describe the character of a "red hemorrhagic" infarct. (what organs, what does it look like?)

Answer 72

“Red hemorrhagic” infarcts are typical with venous occlusion (as in ovarian torsion), dual or anastomosing blood supply (in lung or intestines) or with reperfusion.

Question 73

Let's play "Do You Remember from Block 1?" | The likelihood of an infarction is determined by 4 things:

Answer 73

(1) an organ’s vulnerability to hypoxia (neurons die after 4 minutes of ischemia, cardiac myocytes after 20 minutes), (2) the rate of development of vascular occlusion (if slow, it allows collateral circulation to develop) (3) the nature of an organ’s blood supply (a dual blood supply is protective, for example, in the liver) (4) oxygen content of the blood.