Hemodynamic disorders and thromboembolic disease Flashcards
What is the difference between hyperermia and congestion?
Hyperemia and congestion
Hyperemia and congestion is an increase in blood volume. Hyperemia is an active process resulting from arteriolar dilation and increased blood inflow. Congestion is a passive process resulting from impaired outflow of venous blood from a tissue. In long-standing chronic congestion, hypoxia may lead to parenchymal cell death and secondary tissue fibrosis, and the elevated intravascular pressure may cause edema.
What is effusion?
Effusion is extravascular fluid accumulation in body cavities.
What is anasarca?
Anasarca is severe edema marked by profound swelling of subcutaneous tissues and accumulation of fluid in body cavity.
Explain the process of edema when the heart fails!
Increases in hydrostatic pressure are caused by disorders that impair venous return. The reduced cardiac output lead to systemic venous congestion and resultant increase in capillary hydrostatic pressure. Reduction in cardiac output results in hypoperfusion of the kidneys, triggering the renin-angiotensin-aldosterone axis and inducing sodium and water retention. The failing heart often can’t increase its cardiac output in response to the compensatory increases in blood volume. Instead, it increases venous hydrostatic pressure, and worsen the edema. Secondary hyperaldosteronism is a common feature of generalized edema, salt restriction, diuretics, and aldosterone antagonists are of value in the management of generalized edema resulting from non-cardiac causes.
How does reduced plasma osmotic pressure leads to edema?
Reduced plasma osmotic pressure
Reduction of plasma albumin concentration leads to decreased colloid osmotic pressure of the blood and loss of fluid from the circulation. Condition in which albumin is lost from the circulation or synthesized in inadequate amounts; such as the glomerular capillaries become leaky, leading to the loss of albumin. Reduced albumin synthesis occurs in the setting of severe liver disease.
What is hematoma?
- Hemorrhage may be external or accumulate within tissue as a hematoma.
What is petechiae?
- Petechiae are minute hemorrhage into skin, mucous membrane, or serosal surface; causes include low platelet count, defective platelet function, and loss of vascular wall support, as in vitamin C deficiency.
What is purpura?
- Purpura are larger hemorrhages that can be caused by trauma, vascular inflammation, and increased vascular fragility.
What is ecchymoses?
- Ecchymoses are larger subcutaneous hematomas. Red cells are phagocytosed and degraded by macrophages; the characteristic color changes of a bruise result from the enzymatic conversion of hemoglobin to bilirubin and hemosiderin.
What are the events that leads to hemostasis
Event leading to hemostasis:
Arteriolar vasoconstriction which reduces the blood flow. It is mediated by reflex neurogenic mechanisms and augmented by the local secretion of factors such as endothelin.
Primary hemostasis: the formation of the platelet plug. Disruption of the endothelium exposes subendothelial von Willebrand factor (vWF) and collagen, which promote platelet adherence and activation. Activation of platelets results in shape change and the release of secretory granules that recruit additional platelets, which undergo aggregation to form a primary hemostatic plug.
Secondary hemostasis: deposition of fibrin. Tissue factor is a membrane-bound procoagulant glycoprotein expressed by subendothelial cells in the vessel wall. Tissue factor binds and activates factor VII, setting in motion a cascade of reactions that culiminates in thrombin generation. Thrombin cleaves circulating fibrinogen into insoluble fibrin, creating a fibrin meshwork, and also is a potent activator of platelets.
Clot stabilization and resorption. Polymerized fibrin and platelet aggregates contract to form a solid, permanent plug that prevent further hemorrhage. At this stage, counterregulatory mechanisms (tissue plasminogen activator, t-PA) are set into motion that limit clotting to the site of injury
Endothelial cells are central regulatory of hemostasis. Normal endothelial cells express a variety of anticoagulant factors that inhibit platelet aggregation and coagulation and promote fibrinolysis. After injury, endothelial cells acquire numerous procoagulant activities. Endothelium can be activated by microbial pathogens, hemodynamic forces, and a number of pro-inflammatory mediators.
What are platelets function in hemostas? What does their function depends on?
Platelets form the primary plug and provide a surface that binds and concentrates activated coagulation factors. Their function depends on glycoprotein receptors, a contractile cytoskeleton, and two types of cytoplasmic granules. α-Granules have the adhesion molecule P-selectin on their membranes and contain proteins involved in coagulation, such as fibrinogen, coagulation factor V, and vWF, and protein factors that may be involved in wound healing, such as fibronectin, platelet factor 4 (a heparin-binding chemokine), platelet-derived growth factor (PDGF), and transforming growth factor-β. δ granules contain ADP and ATP, ionized calcium, serotonin, and adrenaline.
What are the reactions that culminate in the formation of a platelet plug?
Reactions that culminate in the formation of a platelet plug:
- Platelet adhesion is mediated via interactions with vWF, which acts as a bridge between the platelet surface receptor glycoprotein Ib (GpIb) and exposed collagen.
- Platelet rapidly change shape following adhesion, accompanied by alternation in glycoprotein IIb/IIIa that increases its affinity for fibrinogen, and by the translocation of negatively charged phospholipids to the platelet surface. These phospholipids bind calcium and serve as nucleation sites for the assembly of coagulation factory complex.
- Platelet activation trigged by coagulation factor thrombin (through protease-activated receptor) and ADP. Activated platelets produce the prostaglandin thromboxane A2 (TXA2), a potent inducer of platelet aggregation. Aspirin inhibits platelet aggregation and produces a mild bleeding defect by inhibiting cyclooxygenase (enzyme required for TXA2 synthesis)
- Platelet aggregation – conformational change in glycoprotein IIb/IIIa allows binding of fibrinogen which forms bridges between adjacent platelets, leading to their aggregation. Thrombin converts fibrinogen into insoluble fibrin. Red cells and leukocytes adhere to P-selectin expressed on activated platelets.
How does fibrin amplified coagulation cascade?
Thrombin converts soluble fibrinogen into fibrin monomers that polymerize into an insoluble fibril and amplifies the coagulation process by activating factor XI and two critical factors: factors V and VIII. It stabilizes the secondary hemostatic plug by activating factor XIII, which covalently crosslinks fibrin.
What are the factors that limit coagulation?
Factors that limit coagulation
- Blood flowing past the site of injury washes out activate coagulation factors, which are removed by liver.
- Requirement for negatively charged phospholipids provided by platelets that have been activated by contact with subendothelial matrix at site of vascular injury.
- Activation of the coagulation cascade sets a fibrinolytic cascade that limits the size of the clot and contribute to its later dissolution. Fibrinolysis is accomplished through the enzymatic activity of plasmin, which breaks down fibrin and interferes with its polymerization. Breakdown products of fibrinogen are useful clinical markets of several thrombotic state. Plasmin is generated by catabolism of the inactive circulating precursor plasminogen, either by a factor XII-dependent pathway or plasminogen activator. Plasmin is controlled by counterregulatory factors such as 2-plasmin inhibitor.
What are the major pro-thrombotic alternations that occur to the endothelial?
Major pro-thrombotic alternation:
- Procoagulant changes - endothelial cells activated by cytokines downregulate the expression of thrombomodulin. This may result in sustained activation of thrombin, which can in turn stimulate platelets and augment inflammation through PARs expressed on platelets and inflammatory cells. Inflamed endothelium downregulates the expression of other anti-coagulants, such as protein C and tissue factor protein inhibitor.
- Anti-fibrinolytic effects – Activated endothelial cells secrete plasminogen activator inhibitors (PAI), which limit fibrinolysis and downregulate the expression of t-PA that favor the development of thrombi.
