Lecture 2 Hemodynamics

Question 1

What do heparin like molecules do?

Answer 1

Bind to anti thrombin 3, therefore inhibiting anti thrombin activity

Question 2

What does t-PA do?

Answer 2

Break fibrin, therefore dissolves clots.

Question 3

What is vWF do?

Answer 3

It makes the surface of the injured endothelial site sticky and adhesive. Therefore, causing increased platelet adhesion.

Question 4

What is a platelet?

Answer 4

Cell fragments derived from megakaryocytes in bone marrow.

Question 5

What do platelets do upon contact with extracellular matrix?

Answer 5

• Adhesion: bind to extracellular matrix. Basement membrane is very sticky sticky from collagen
• Activation: change shape, release granule contents and other factors ex. Ca2+, ADP, thromboxane A2
• Aggregation: platelets fuse together to form platelet plug

Question 6

What is the coagulation cascade?

Answer 6

Series of enzymatic reactions

Key event us activation of thrombin (factor 2a), which converts fibrinogen (factor 1) -> fibrin (factor 1a)

Question 7

What are the different pathways in the coagulation cascade?

Answer 7

Intrinsic: activated by contact with collagen
Extrinsic: activated by contact with tissue factor
Common pathway: both pathways converge to this pathway

Question 8

What is prothrombin time (PT)?

Answer 8

Asses the function of proteins in extrinsic and common pathways

Question 9

What is international normalized ratio (INR)?

Answer 9

Same as PT

Standardized by WHO

Question 10

What is activated partial thromboplastin time (aPTT)?

Answer 10

Assesses the function of the proteins in the intrinsic and common pathways.

Question 11

What is thrombin time (TT)?

Answer 11

Assesses the function/ level of fibrinogen

Question 12

When do the two pathways converge?

Answer 12

Clotting factor Xa (10a)

Question 13

What is the term for low platelets?

Answer 13

Thrombocytopenia

Question 14

What is the term for high platelets?

Answer 14

Thrombocytosis

Question 15

What are different platelet tests?

Answer 15

• Platelet count from CBC
• Peripheral blood smear: gross morphological characteristics of platelet function
• Aggregation assays

Question 16

What are the three factors to Virchow’s triad?

Answer 16

Endothelial injury, abnormal blood flow, hypercoagulability

Question 17

What are examples endothelial injury in Virchow’s triangle?

Answer 17

• loss of endothelial cells
• disruption of balance between pro and anti coagulation factors
• damage to vessel lining

Question 18

What are examples of abnormal flow in Virchow’s triangle?

Answer 18

• stasis
• turbulence: bounces into endothelial cells and can cause damage

Question 19

What are the examples of hypercoagulability in Virchow’s triangle?

Answer 19

• Primary ex. genetic disorder
• Secondary ex. Cancer, smoking, pregnancy, oral contraceptives, HRT, obesity

Question 20

What is thrombosis?

Answer 20

It is the pathological formation of blood clot

Question 21

What is a thrombi?

Answer 21

Composed of platelets, erythrocytes, leukocytes, and fibrin

Attached to underlying vascular surface but prone to fragmentation and embolism

Question 22

What are the two thrombi locations?

Answer 22

Arterial and Venous

Question 23

What is an arterial thrombi?

Answer 23

Forms under high flow conditions, and are rich in platelets and tightly packed fibrin

Most commonly found in aorta and its major branches

Question 24

What is a venous thrombi?

Answer 24

Forms under low flow conditions, and are rich on erythrocytes and fibrin.

Most commonly found in the legs

Question 25

What can cause arterial thrombi?

Answer 25

Damage to endothelium (ex. Ruptured atherosclerosis plaques) <—- most common cause Turbulence or slowing of blood flow (ex. Aneurysm) Hypercoagulability (ex. Polycythemia) Can cause decreased blood flow to tissues (ischemia)

Question 26

What causes venous thrombi?

Answer 26

Surgery or trauma Reduced venous return (ex. Lack of exercise, heart failure, defective venous valves, age, bed rest) Hypercoagulability

Question 27

What is superficial venous thrombosis

Answer 27

Usually displays as traditional signs of inflammation. Treatments: - analgesics, anti-inflammatories - may progress to DVT

Question 28

What is deep vein thrombosis (DVT)?

Answer 28

Is very dangerous - most commonly found in popliteal, femoral or iliac veins - pain and swelling may be present, but many patients are asymptomatic, due to collateral vessels - possibility of embolism - especially pulmonary b/c its the first contact of a capillary bed

Question 29

What are the different fates if a thrombus?

Answer 29

1) Dissolution: clot may dissolve due to fibrinolysis 2) Propagation: continued growth 3) Embolization: breaks of entirely or in pieces (can get lodged somewhere else) 4) organization and recanalization: connective tissue and all cells grow into thrombus and establish channels for blood flow

Question 30

Treatments and prevention of thrombus

Answer 30

Anticoagulants (blood thinners) Anti platelet drugs Thrombolytic drugs

Question 31

What is coumarins

Answer 31

Anticoagulant - blocks liver enzyme required for vit K activation ex. Warfarin

Question 32

What is heparin?

Answer 32

Anticoagulant - activates anti thrombin -> block thrombin from converting fibrinogen into fibrin

Question 33

What is direct oral anticoagulants (DOACs)?

Answer 33

Anticoagulant - binds directly to factors - thrombin inhibitor (dabigatran) - factor Xa inhibitors (ex. Rivaoxaban, apixaban, edoxaban) Xa is in name of all drugs

Question 34

What are examples of antiplatelet drugs?

Answer 34

Aspirin, thromboxane inhibitors

Question 35

What are examples of thrombolytic drugs?

Answer 35

Streptokinase, tissue plasminogen activator (tPA)

Question 36

When are these drugs used?

Answer 36

Patient at risk for developing clots: - a fib, coronary artery disease, hypercoagulability disorders Patients who have clots: - DVT, stroke, MI, pulmonary embolism

Question 37

What are the risks of treatment?

Answer 37

Bleeding Thrombolytic drugs can increase embolization by breaking big clots into pieces that can get stuck in smaller vessels

Question 38

What is an embolism?

Answer 38

Anything that travels through circulation that gets stuck and obstructs blood flow Blockages can lead to infarction Thromboemboli are most common

Question 39

What is a pulmonary embolism?

Answer 39

Embolism in the pulmonary circuit (lungs)

Question 40

How does pulmonary embolisms develop?

Answer 40

- from DVT - can develop in surgery patients over 40 1-2% (risk increases with many factors age, obesity, length surgery etc.) - prolonged period of inactivity

Question 41

What are some clinical manifestations of pulmonary embolism?

Answer 41

Small can be asymptomatic Moderate can cause dyspnea, tachycardia, and hemoptysis Large can cause chest pain, heart failure, and shock (ded)

Question 42

What are some treatments of pulmonary embolism?

Answer 42

- anticoagulants - inferior vena cava filters - thrombolytics - embolectomy

Question 43

Other forms of emboli

Answer 43

Fat embolism Air embolism Amniotic fluid embolism (rare but bad, often ded) - amniotic fluid containing fetal epithelial cells and lanugo enters maternal circulation through open veins - cause systematic inflammatory response, HF, disseminated intravascular coagulation

Question 44

What is disseminated intravascular coagulation (DIC)?

Answer 44

- complications of many conditions - widespread formation of thrombi -> organ failure - Platelet and coagulation protein consumption -> spontaneous hemorrhage We love DIC :0

Question 45

What is infarction?

Answer 45

Blocking of blood to an area causing it to be starved with oxygen Infarct is ischemic necrosis Can be classified as colour, red vs pale And presence of infection, septic vs bland

Question 46

Red infarcts

Answer 46

Occurs in organs with rich blood supply - affected tissue turns necrotic and fills with blood from surrounding non blocked vessels - must be loose enough blood to accumulate

Question 47

Pale infarct

Answer 47

Solid organs supplied by terminal arteries - blockage occurs in only artery that feeds the tissue