4. Hemodynamic Disorders, Thromboembolism, and Shock

Question 1

Edema

Answer 1

Edema results form the movement of fluid from the vasculature into the interstitial spaces; the fluid may be protein poor (transudate) or protein rich (exudate)

Question 2

Edema causes

Answer 2

• Increased hydrostatic pressure (e.g., heart failure)
• Increased vascular permeability (e.g., inflammation)
• Decreased colloid osmostic pressure resulting from reduced plasma albumin
  
  • Decreased synthesis (e.g., liver disease, protein malnutrition)
  • Increased loss (e.g., nephrotic syndrome)
• Lymphatic obstruction (e.g., inflammation or neoplasia)
• Sodium retention (e.g., renal failure)

Question 3

Platelet adhesion, activation, and aggregation

Answer 3

• Endothelial injury exposes the underlying basement membrane ECM; platelets adhere to the ECM primarily through the binding of platelet Gplb receptors to VWF.
• Adhesion leads to platelet activation, an event associated with secretion of platelet granule contents, including calcium (a cofactor for severe coagulation proteins) and APD (a mediator of further platelet activation); dramatic changes in shape and membrane composition; and activation of GpIIb/IIIa receptors.
• The Gpllb/IIIa receptors on activated platelets form bridging crosslinks with fibrinogen, leading to platelet aggregation.
• Concomitant activation of thrombin promotes fibrin deposition, cementing the platelet plug in place.

Question 4

Coagulation factors

Answer 4

• Coagulation occurs via the sequential enzymatic conversion of a cascade of circulating and locally synthesized proteins.
• Tissue factor elaborated at sites of injury is the most important initiator of the coagulation cascade in vivo.
• At the final stage of coagulation, thrombin converts fibrinogen into insoluble fibrin that contributes to formation of the definitive hemostatic plug.

Question 5

Coagulation normally is restricted to sites of vascular injury by:

Answer 5

• Limiting enzymatic activation to phospholipid surfaces provided by activated platelets or endothelium
• Circulating inhibitors of coagulation factors, such as anti-thrombin III, whose activity is augmented by heparin-like molecules expressed on endothelial cells
• Expression of thrombomodulin on ormal endothelial cells, which bind thrombin and convert it into an anti-coagulant
• Activation of fibrinolytic pathways (e.g., by association of tissue plasminogen activator with fibrin).

Question 6

Thrombosis

Answer 6

Thrombus development is usually related to one or more components of Virchow’s triad
Thrombi may propagate, resolve, become organized, or embolize.
Thrombosis causes tissue injury by local vascular occlusion or distal embolization.

Question 7

Virchow’s Triad

Answer 7

• Endothelial injury (e.g., by toxins, hypertension, inflammation, or metabolic products)
• Abnormal blood flow, stasis, or turbulence (e.g., resulting from aneurysms, atherosclerotic plaque)
• Hypercoagulability: either primary (e.g., factor V Leiden, increased prothrombin synthesis, anti-thrombin III deficiency) or secondary (e.g., bed rest, tissue damage, malignancy)

Question 8

Embolism

Answer 8

• An embolus is a solid, liquid, or gaseous mass carried by the blood to a site distant from its origin; most are dislodged in thrombi.
• Pulmonary emboli derive primarily from lower-extremity deep vein thrombi. Their effects depend mainly on the size of the embolus and the location in which it lodges. Consequences may include right-sided heart failure, pulmonary hemorrhage, pulmonary infarction, or sudden death.
• Systemic emboli derive primarily from cardiac mural or valvular thrombi, aortic aneurysms, or atherosclerotic plaques; whether an embolus causes tissue infarction depends on the site of embolization and the presence or absence of collateral circulation.
• Fat embolism can occur after crushing injuries to the bones; symptoms include pulmonary insufficiency and neurological damage. Amniotic fluid embolism may follow childbirth and can give rise to fatal pulmonary and cerebral manifestations. Air embolism can occur upon rapid decompression, most commonly divers; it results from sudden bubbling of nitrogen dissolved in blood at higher pressures.

Question 9

Infarction

Answer 9

• Infarcts are areas of ischemic necrosis most commonly caused by arterial occulsion (typically resulting from thrombosis or embolization)l venous outflow obstruction is a less frequent cause.
• Infarcts caused by venous occlusion or occurring in spongy tissues typically are hemorrhagic (red); those caused by arterial occlusion in compact tissues typically are pale (white).
• Whether or not vascular occlusion causes tissue infarction is influenced by collateral blood supplies, the rate at which an obstruction develops, intrinsic tissue susceptibility to ischemic injury, and blood oxygenation.

Question 10

Shock

Answer 10

• Shock is defined as a state of systemic tissue hypoperfusion resulting from reduced cardiac output and/or reduced effective circulating blood volume.
• The major types of shock are cardiogenic (e.g., myocardial infarction), hypovolemic (e.g., blood loss), and septic (e.g., infections).
• Shock of any form can lead to hypoxic tissue injury if not corrected.
• Septic shock is caused by the host response to bacterial or fungal infections; it is characterized by endothelial cell activation, vasodilation, edema, disseminated intravascular coagulation, and metabolic derangements.