Robbins 7th ed - Chapter 4 - Haemostasis (1)

Question 1

Name 5 different pathologic mechanisms causing oedema.

Answer 1

1. Increased hydrostatic pressure
2. Reduced plasma oncotic pressure.
3. Lymphatic obstruction
4. Increased renal Na+ retention
5. Inflammation (increased vascular permeability, yielding exudative oedema)

Question 2

What is the difference between hyperaemia and congestion?

Answer 2

Hyperaemia is an active process involving arteriolar dilatation and subsequent increased bloodflow to an area. Congestion is a passive process caused by impaired outflow from a tissue due to venous obstruction.

Question 3

Describe some of the disease processes that cause oedema due to reduced plasma oncotic pressure.

Answer 3

Reduced albumin production: Liver cirrhosis, Protein malnutrition.
Increased protein losses: Nephrotic syndrome

Question 4

What are “heart failure cells”

Answer 4

Haemosiderin-laden macrophages that are found in the alveoli of patients with heart failure.

Question 5

Describe the four processes that occur immediately after vascular injury, in order.

Answer 5

1. Reflex vasoconstriction
2. Primary haemostasis
3. Secondary haemostasis
4. Clot stabilization

Question 6

What is endothelin?

Answer 6

A potent endothelium-derived vasoconstrictor.

Question 7

Describe what happens during primary haemostasis, after vascular injury.

Answer 7

vWF from exposed subendothelial ECM triggers platelet adherence and activation. Activated platelets release contents from their granules (ADP, TXA2), causing recruitment of other platelets, aggregation, and formation of haemostatic plug.

Question 8

What is tissue factor, and how is it relevant in vascular injury? What is another name for tissue factor?

Answer 8

Also called thromboplastin, tissue factor is a membrane-bound procoagulant glycoprotein, found on the cell surface of subendothelial cells such as fibroblasts and smooth muscle cells. In vascular injury, tissue factor is exposed, and triggers secondary haemostasis, by binding and activating factor VII. This triggers the coagulation cascade, resulting in fibrin meshworks.

Question 9

What happens during the 4th phase of haemostasis after vascular injury?

Answer 9

Activation of counter-regulatory mechanisms, e.g. the release of t-PA, restriction of the haemostatic plug, eventually there is clot resorption.

Question 10

What is the most important structural factor allowing for platelet adhesion, and how does it work?

Answer 10

Von-Willebrand Factor. It acts as a bridge between platelet surface Glycoprotein Ib (GpIb) and exposed collagen.

Question 11

What is the GpIIb-IIIa complex?

Answer 11

This is the surface complex on platelets that binds to fibrinogen allowing platelets to adhere to each other.

Question 12

Describe some of the functions of thrombin.

Answer 12

• Conversion of fibrinogen into cross-linked fibrin
• Platelet activation
• Proinflammatory effects
• Anticoagulant effects at exposure to normal endothelium (preventing the clot from extending beyond the site of injury)

Question 13

What is Virchow’s Triad?

Answer 13

Virchow’s Triad describes the three abnormalities that cause thrombosis:

• Endothelial Injury
• Stasis of blood
• Hypercoagulable state (aka thrombophilia)

Question 14

Describe four possible outcomes that occur to a thrombus in the days - weeks after it is formed.

Answer 14

• Propagation (grows bigger)
• Embolisation
• Dissolution (fibrinolysis)
• Organization and recanalization (capillary channels can form inside older thrombi, re-establishing the original lumen)

Question 15

Describe some of the ways that the endothelium can become injured, leading to thrombus formation.

Answer 15

• Toxins (e.g. cigarette smoke)
• Trauma
• Inflammation
• Hypertension
• Metabolic products (e.g. hypercholesterolaemia or homocysteinaemia)

Question 16

Describe some of the ways that stasis/turbulence of bloodflow can be created, leading to thrombus formation.

Answer 16

• Aneurysm
• Atherosclerotic plaque
• Atrial fibrillation
• Ventricular infarct causing disorganized contraction

Question 17

What are some of the Primary causes of hypercoagulable states?

Answer 17

• Factor V Leiden
• Antithrombin III deficiency
• Increased prothrombin synthesis

Question 18

What are some of the Secondary causes of hypercoagulable states?

Answer 18

• Bed rest
• Tissue damage
• Malignancy
• Development of antiphospholipid antibodies
• HIT syndrome (heparin-induced thrombocytopaenia, caused by antibodies)

Question 19

What is the difference between primary and secondary antiphospholipid syndrome?

Answer 19

SLE (systemic lupus erythematosus) and other autoimmune diseases involve secondary antiphospholipid syndrome, in addition to multiple other symptoms.
Primary antiphospholipid syndrome is in individuals that show no evidence of any other autoimmune disease.

Question 20

What are some of the clinical manifestations of antiphospholipid syndrome?

Answer 20

Recurrent venous or arterial thrombi, Repeated miscarriages, Cardiac valvular vegetations, Thrombocytopaenia.

Question 21

What is meant by the term “systemic thromboembolism”, and what are most cases caused by?

Answer 21

As opposed to pulmonary thromboembolism, systemic thromboembolism refers to emboli traveling within the arterial circulation. Most (80%) arise from intracardiac mural thrombi, which may be caused by disorders such as left ventricular wall infarcts or atrial fibrillation.

Question 22

What are four factors that will influence whether or not a tissue will infarct if its blood supply is cut off?

Answer 22

• Nature of the vascular supply (end-organs like kidney and spleen do not have readily available collateral circulation)
• Rate of development of occlusion (if a coronary artery is occluded very slowly, there may be time for collateral circulation to develop around the occlusion)
• Vulnerability to hypoxia (neurons undergo irreversible damage when deprived of a blood supply for only 3-4 minutes, myocardial cells can last 25 minutes, fibroblasts can last hours)
• Oxygen content of blood (patients with anaemia and/or low PaO2 may suffer infarction even in otherwise insignificant blockages)

Question 23

What is LPS, and how does it arise in the circulation?

Answer 23

Lipopolysaccharides. They are a type of endotoxin, released from gram-negative bacilli bacteria as their cell walls are degraded. LPS is an important mediator of septic shock, and there are analogous molecules on fungi and gram-positive bacteria.

Question 24

Which two receptors does LPS bind to, and on which cells?

Answer 24

LPS binds to CD14 molecules on leukoctyes, and then this complex binds to nearby Toll-like receptor 4 on the same cell. This leads to leukocyte activation, production of cytokines and reactive oxygen species.

Question 25

Give an overview of how LPS acts in sepsis.

Answer 25

• At low doses, LPS mainly activates complement and monocyte/macrophages.
• At high doses, LPS causes high levels of cytokine activity, causing systemic vasodilation, diminished myocardial contractility, and activation of the coagulation system and DIC. All of these are part of Septic Shock.

Question 26

What happens during platelet activation?

Answer 26

Platelets release their granular contents (ADP and TXA2), and they change their shape.

Question 27

What are the three stages of shock?

Answer 27

1. Non-progressive (vital organ perfusion is maintained by reflex compensatory mechanisms)
2. Progressive (compensatory mechanisms becoming overwhelmed, development of lactic acidosis)
3. Irreversible (even if vital organ perfusion is restored, death is inevitable)