Flashcards in Hemodynamic disorders and thromboembolic disease Deck (26):
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.
How can abnormal blood flow causes thrombosis?
Abnormal blood flow
Turbulence contributes to arterial and cardiac thrombosis by causing endothelial injury or dysfunction, as well as by forming countercurrent and local pocket of stasis. Under normal laminar blood flow, platelets are found mainly in the center of the vessel lumen, separated from the endothelium. Stasis and turbulence effects:
- Both promote endothelial cell activation and enhance procoagulant activity, through flow-induced changes in endothelial gene expression.
- Stasis allows platelets and leukocytes to come into contact with the endothelium.
- Stasis slows the washout of activated clotting factors.
What causes primary hypercoagulability?
Primary hypercoagulability caused by mutations in the factor V and prothrombin genes:
- Deep venous thrombosis (DVT) alters an amino acid residue in factor V and renders it resistant to proteolysis by protein C.
- A single-nucleotide substitution (G to A) in the 3’-untranslated region of prothrombin gene. This variant results in increased prothrombin transcription and is associated with an early three-fold increased risk for venous thromboses.
- Elevated levels of homocysteine contribute to arterial and venous thrombosis.
- Inherited deficiencies of anti-coagulant such as thrombin III, protein C, or protein S.
What causes secondary hypercoagulability?
Secondary hypercoagulability - Hyperestrogenic state of pregnancy may be related to increased hepatic synthesis of coagulation factors and reduced synthesis of anti-thrombin III. In disseminated cancers, release of procoagulant tumor products (e.g., mucin from adenocarcinoma) predisposes to thrombosis. The hypercoagulability with advancing age is attributed to increased platelet aggregation and reduced release of PGI2 from endothelium.
- Heparin-induced thrombocytopenia (HIT) syndrome. Development of autoantibodies that bind complexes of heparin and platelet membrane protein. This result in a pro-thrombotic state.
- Anti-phospholipid antibody syndrome has protean clinical manifestations, including recurrent thromboses, repeated miscarriages, cardiac valve vegetations, and thrombocytopenia. Depending on the vascular bed involved, the clinical presentations can include pulmonary embolism, pulmonary hypertension, stroke.
what are the morphology of arterial thrombi, venous thrombi, postmortem clots and vegetations!
Arterial thrombi are rich in platelets, as the processes underlying their development lead to platelet activation.
Venous thrombi propagate some distance toward the heart, forming along cast within the vessel lumen that is prone to give rise to emboli.
Postmortem clots are gelatinous and because of red cell settling they have a dark red dependent portion and yellow upper portion.
Vegetations (thrombi on heart valves) – bacterial or fungal blood borne infections can cause valve damage, leading to the development of large thrombotic masses.
What is systemic thromboembolism?
Most systemic emboli arise from intracardiac mural thrombi and from aortic aneuryms, thrombi overlying ulcerated atherosclerotic plaques, fragmented valvular vegetations, or the venous system.
Arterial emboli can travel virtually anywhere; their final resting place depends on their point of origin and the relative flow rates of blood to the downstream tissues.
What is fat embolism?
Fat and marrow emboli are common incidental findings after vigorous cardiopulmonary resuscitation. Symptomatic fat embolism syndrome characterized by pulmonary insufficiency, neurologic symptoms, anemia, thrombocytopenia, and a diffuse petechial rash that is fatal in 10% of cases. Clinical signs and symptoms appear 1 to 3 days after injury as the sudden onset of tachypnea, dyspnea, tachycardia, irritability, and restlessness, which can progress rapidly to delirium or coma.
Fat microemboli occlude pulmonary and cerebral microvasculature, both directly and by triggering platelet aggregation.
What is amniotic fluid embolism?
Amniotic fluid embolism characterized by sudden severe dyspnea, cyanosis, and hypotensive shock, followed by seizures and coma. If the patient survives the initial crisis, pulmonary edema typically develops, along with (in about half the patients) disseminated intravascular coagulation secondary to release of thrombogenic substances from amniotic fluid.
The cause is the entry of amniotic fluid into the maternal circulation via tears in the placental membrane and/or uterine vein rupture.
What is air embolism?
Air embolism - Gas bubbles within the circulation can coalesce and obstruct vascular flow and cause distal ischemic injury.
Gas bubbles in the pulmonary vasculature cause edema, hemorrhages, and focal atelectasis or emphysema, leading to respiratory distress. Bubbles in the central nervous system can cause mental impairment and even sudden onset of coma. Placing affected persons in a high-pressure chamber, to force the gas back into solution, treats acute decompression sickness.
When do red infarcts occur?
Red infarcts occur (1) as a result of venous occlusions; (2) in loose tissue (lung) where blood can collect in infarcted zone; (3) in tissue with dual circulations such as lung and small intestine; (4) in previously congested tissue; and (5) when flow is reestablished after infarction has occurred.
When do white infarcts occur?
White infarcts occur with arterial occlusions in solid organs with end-arterial circulations (e.g., heart, spleen, and kidney), and where tissue density limits the seepage of blood from adjoining patent vascular beds