Materiały źródłowe

• #1 Pulmonary Embolism (PE) – Pulmonary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pulmonary-disorders/pulmonary-embolism/pulmonary-embolism-pe

  Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are conditions that impair venous return, conditions that cause endothelial injury or dysfunction, and underlying hypercoagulable states. […] Nearly all pulmonary emboli arise from thrombi in the veins of the legs or pelvis (deep venous thrombosis). Risk of embolization is higher with thrombi that reach the popliteal vein or above. Thromboemboli can also originate in arm veins or central veins of the chest (caused by central venous catheters or resulting from thoracic outlet syndromes). […] Pulmonary embolism can also arise from nonthrombotic sources (eg, embolism of air, amniotic fluid, fat, infected material, orthopedic cement, foreign body, tumor). […] Once deep venous thrombosis develops, clots may dislodge and travel through the venous system and the right side of the heart to lodge in the pulmonary arteries, where they partially or completely occlude one or more vessels. The consequences depend on the size and number of emboli, the underlying condition of the lungs, how well the right ventricle (RV) is functioning, and the ability of the body’s intrinsic thrombolytic system to dissolve the clots. Death, when it does occur, is often due to right ventricular failure.

• #1 Epidemiology, Pathophysiology, and Natural History of Pulmonary Embolism

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5986574/

  Most PEs originate as thrombi in the deep veins of the lower extremities. The site of thrombosis is most frequently in the calf veins, then femoropopliteal veins, and less frequently in the iliac veins. Thrombosis begins in areas of decreased flow such as valve cusps and bifurcations and then propagates due to local hypercoagulability caused by hypoxia and hemoconcentration. A smaller percentage of emboli arises from upper extremity veins and are typically associated with central venous catheters, intracardiac devices such as pacemakers and defibrillators, and malignancy or activity-related venous trauma. Pelvic vein DVTs can also cause pulmonary emboli, but they are generally associated with a predisposing factor such as pelvic infection, pelvic surgery, or pregnancy. Lower extremity central DVTs are most likely to embolize and cause PE (15-32% of the time), whereas upper extremity DVTs cause PE only 6% of the time. Calf vein DVTs rarely embolize to the lungs, but one-third can extend into the central veins and subsequently have the potential to embolize.

• #1 Deep Vein Thrombosis and Pulmonary Embolism | Yellow Book | CDC

  https://www.cdc.gov/yellow-book/hcp/travel-air-sea/deep-vein-thrombosis-and-pulmonary-embolism.html

  Virchow’s classic triad for thrombus formation is venous stasis, vessel wall damage, and a hypercoagulable state. Prolonged, cramped sitting during long-distance travel interferes with venous flow in the legs, creating venous stasis. […] Coagulation activation can result from an interaction between air cabin conditions (e.g., hypobaric hypoxia) and individual risk factors for VTE. Studies of the pathophysiologic mechanisms for the increased risk of VTE after long-distance travel have not produced consistent results, but venous stasis appears to play a major role. Other factors specific to air travel might increase coagulation activation, particularly in travelers with preexisting risk factors for VTE.

• #1 Pulmonary Embolism – Pulmonary Pathophysiology for Pre-Clinical Students

  https://pressbooks.lib.vt.edu/pulmonarypathophysiology/chapter/pulmonary-embolism/

  Like any other embolism, an embolus affecting the lung tissue can be made of fat, amniotic fluid, tumor, tissue fragment, or foreign body, but by far the most common cause of pulmonary emboli are blood clots. […] About 90 percent of PEs are caused by deep vein thrombi, but at least one of three main predisposing factors (Virchows triad) are present in a case of PE: Abnormal vessel walls, Stagnation of blood, and Increased coagulability. […] Damage to the inner wall of veins causes adherence of blood platelets and activation of clotting factors. […] Venous stasis appears to be the most important factor in thrombus formation, and cases of PE are often preceded by periods of immobility. […] Any condition that increases coagulability elevates the risk of PE, and most are due to trauma of some form or another or an elevated inflammatory state such as cancer or the postsurgery state.

• #1 Venous Thrombosis: Pathogenesis and Potential for Embolism

  https://www.uspharmacist.com/article/venous-thrombosis-pathogenesis-and-potential-for-embolism

  Endothelial injury causes subendothelial collagen exposure and platelet adherence, among other changes; many factors can contribute to the injury, including hypertension, vasculitis, scarred valves, bacterial endotoxins, cholesterolemia, and chemicals from cigarette smoke. […] […] Stasis and turbulence are alterations in normal blood flow, which can cause endothelial injury. Aneurisms (aortic and arterial dilations) cause local turbulence; a dilated atrium in the presence of atrial fibrillation is a site of significant stasis that may provoke thrombus development. Additional conditions are associated with stasis, such as sickle cell anemia and polycythemia, both of which may predispose a patient to thrombosis. […] […] Hypercoagulability can be described as any alteration of the coagulation pathway that places the patient at risk for thrombosis. There are two types of hypercoagulability states; primary disorders are genetically inherited (e.g., mutations in factor V, allelic variations in prothrombin levels) and secondary disorders are acquired (e.g., tissue damage such as surgery, fractures, burns; myocardial infarction; cancer; heparin-induced thrombocytopenia [HIT]). Hypercoagulability associated with advancing age is thought to be due to an increase in platelet aggregation and a reduction in prostacyclin, a potent vasodilator and inhibitor of platelet aggregation that is released by the endothelium. […]

• #1 Acute pulmonary embolism 1: pathophysiology, clinical presentation, and diagnosis | Heart

  https://heart.bmj.com/content/85/2/229

  As pulmonary embolism is preceded by DVT, the factors predisposing to the two conditions are the same and broadly fit Virchow’s triad of venous stasis, injury to the vein wall and enhanced coagulability of the blood. The identification of risk factors not only aids clinical diagnosis of venous thromboembolism, but also guides decisions about prophylactic measures and repeat testing in borderline cases. […] Primary thrombophilic abnormalities are usually discovered after the thromboembolic event. Therefore, the risk of venous thromboembolism is best assessed by recognising the presence of known clinical risk factors. However, investigations for thrombophilic disorders at follow up should be considered in those without another apparent explanation. In many patients, multiple risk factors are present, and the risks are cumulative.

• #1 Mechanism of Pulmonary Embolism – TrialQuest Inc.

  https://www.trialexhibitsinc.com/library/library-item/mechanism-of-pulmonary-embolism-1

  Mechanism of Pulmonary Embolism A pulmonary embolism occurs when emboli form in the veins of the leg (DVT) and travel up to the heart, where they are pumped into the pulmonary arteries and become lodged in the lungs, blocking blood flow.

• #1 Epidemiology, Pathophysiology, and Natural History of Pulmonary Embolism

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5986574/

  Emboli detach from their point of origin and travel through the systemic venous system, through the right sided chambers of the heart, and lodge in the pulmonary arterial system. The physiologic and clinical consequences of PE vary ranging from asymptomatic to hemodynamic collapse and death. PE contributes to gas exchange abnormalities and hypoxemia, but it is predominantly the hemodynamic consequences of PE that are responsible for increased morbidity and mortality. An understanding of the pulmonary pathophysiology of PE is important in risk-stratifying patients to determine treatment with anticoagulation alone or consideration for catheter-directed therapies (thrombolytics or mechanical thrombectomy), systemic thrombolytics, or surgical intervention. […] The cardiac and hemodynamic effects relate to the size and location of emboli and the presence or absence of underlying cardiopulmonary disease (CPD). As opposed to clot burden, acute PEs are categorized according to hemodynamic effect, with a focus on the effects of right ventricular (RV) physiology. Nonmassive PE patients are those who are normotensive with normal RV function. Massive PE implies hemodynamic instability from RV failure and submassive PE patients may clinically be normotensive but have evidence of RV dysfunction by echocardiography or CT imaging. These categories have risk implications with regard to morbidity and mortality and treatment choices.

• #1 Epidemiology, Pathophysiology, and Natural History of Pulmonary Embolism

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5986574/

  When thrombus embolizes from the extremities and lodges in the pulmonary arterial vasculature, pulmonary vascular resistance (PVR) increases due to both mechanical obstruction and release of vasoconstrictive substances from platelets (serotonin and thromboxane-A2), plasma (thrombin), and tissue (histamine and endothelin). The thin walled RV is accustomed to low pressure and cannot easily adapt to this increased afterload, which has effects on both RV and left ventricular (LV) function. If obstruction is mild, PVR and pulmonary artery pressure remain normal by recruiting and distending pulmonary vessels. At moderate levels of obstruction, pulmonary artery pressure and right atrial pressure increase. Initially, RV stroke volume and cardiac output are maintained by an increase in heart rate and contractility. In patients without prior CPD, the maximal mean pulmonary artery pressure that can be generated even with 50% obstruction is 40mm Hg. Obstruction much beyond this will precipitate RV failure. When the degree of obstruction exceeds 50 to 60%, the right heart dilates, RV wall tension increases, coronary perfusion pressure drops, RV ischemia and RV dysfunction develops, and cardiac output falls, leading to hypotension. Furthermore, the dilated RV impinges on the intraventricular septum and via interventricular dependences causes decreased LV diastolic filling and decreased LV cardiac output. In patients without prior CPD, the degree of obstruction has a hyperbolic relationship to PVR and the hemodynamic manifestations of PE are related to embolism size. Patients with preexisting CPD have diminished pulmonary vascular reserve and a smaller degree of obstruction can lead to disproportionate increase in pulmonary artery pressure and hemodynamic instability.

• #1 Pulmonary embolism pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Pulmonary_embolism_pathophysiology

  After its formation, a thrombus might dislodge from the site of origin and circulate through the inferior vena cava, into the right ventricle, and into the pulmonary vasculature. […] PE results in the elevation of the pulmonary vessel resistance as a consequence of not only mechanical obstruction of the capillary by the embolism, but also due to pulmonary vasoconstriction. Pulmonary vasoconstriction can be either biochemically mediated, hypoxia induced, or reflex-induced. […] Several mediators are involved the pulmonary vasoconstriction that occurs in the setting of acute PE, such as: Thromboxane A2 (end product of arachidonic acid metabolism), Serotonin (vasoconstrictor in the pulmonary circulation and vasodilator in the systemic circulation), Endothelin 1, Prostaglandin F2, Thrombin, Histamine.

• #1 Acute pulmonary embolism with loss of consciousness as the first manifestation: a case report

  https://atm.amegroups.org/article/view/112839/html

  Acute pulmonary embolism can lead to increased pulmonary circulation resistance, increased pulmonary artery pressure, and decreased pulmonary vascular bed area. When the pulmonary vascular bed area is reduced by 30% to 40%, the mean pulmonary artery pressure can reach more than 30 mmHg; when the pulmonary vascular bed area is reduced by 40% to 50%, the mean pulmonary artery pressure can reach 40 mmHg; when the pulmonary vascular bed area is reduced by 50% to 70%, persistent pulmonary hypertension can occur; when the pulmonary vascular bed area is reduced by more than 85%, sudden death can occur. […] As pulmonary vascular resistance increases, the pressure and volume of the right ventricle increase, the right ventricle dilates, and wall tension increases to maintain blood flow in the blocked pulmonary vascular bed, while systemic vascular constriction stabilizes systemic blood pressure. However, the degree of this immediate compensation is limited, and right cardiac insufficiency eventually occurs, resulting in reduced left cardiac return blood volume and thus reduced cardiac output. The cerebral cortex is unable to meet the demand for blood supply, and hypoxemia caused by the imbalance of the ventilation: blood flow ratio in the clogged capillary bed also affects the oxygen demand of the cerebral cortex. The normal functioning of the higher nervous system mainly in the cerebral cortex depends on the continuous provision of a sufficiently large blood supply and oxygen demand. As the demand for adequate blood and oxygen supply cannot be met during acute pulmonary embolism, amaurosis, fainting, and loss of consciousness may result, which explains the patients clinical symptoms.

• #1 Pulmonary embolism pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Pulmonary_embolism_pathophysiology

  When pulmonary vascular resistance occurs following an acute PE, the rapid increase in the right ventricular afterload might lead to the dilatation of the right ventricular wall and subsequent right heart failure. In addition, the elevated pulmonary vascular resistance causes a decrease in the left ventricular preload and consequently leads to systemic hypotension. […] Right heart failure, as well as systemic hypotension, can attenuate coronary perfusion and contribute to subsequent coronary ischemia. […] In summary, the hemodynamic consequences of PE include: Pulmonary hypertension, Right ventricular strain, Right heart failure, Systemic hypotension. […] In PE, hypoxemia occurs mainly due to the ventilation perfusion mismatch. In fact, in the setting of an acute PE, the ventilation to perfusion ratio (V/Q) increases and the dead space enlarges. […] In addition, the occurrence of right to left shunt also contributes to the hypoxemia among patients with PE. When right to left shunt occurs, the administration of oxygen to the patient fails to correct the hypoxemia.

• #1 Pulmonary Embolism (PE) – Pulmonary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pulmonary-disorders/pulmonary-embolism/pulmonary-embolism-pe

  Small emboli may have no acute physiologic effects and may begin to lyse immediately and resolve within hours or days. Larger emboli can cause reflex increase in ventilation (tachypnea), hypoxemia due to ventilation/perfusion (V/Q) mismatch, low mixed venous oxygen content as a result of low cardiac output, atelectasis due to alveolar hypocapnia and abnormalities in surfactant, and increase in pulmonary vascular resistance caused by mechanical obstruction and vasoconstriction resulting in tachycardia and hypotension. […] Endogenous lysis reduces most emboli, even those of moderate size, and physiologic alterations decrease over hours or days. Some emboli resist lysis and may organize and persist and sometimes cause chronic thromboembolic pulmonary hypertension (CTEPH). […] Pulmonary emboli may be classified according to the physiologic effects as described by the European Society of Cardiology/American Heart Association into high risk (massive), intermediate risk (submassive), and low risk. […] When a large embolus acutely occludes major pulmonary arteries or when many smaller emboli combine to occlude a significant proportion of the more distal vessels, RV pressure increases, which may lead to acute RV failure, shock, or sudden death. The risk of death depends on the degree and rate of rise of right-sided pressures and on the patient’s underlying cardiopulmonary status.

• #1 Pulmonary Embolism – Pulmonary Pathophysiology for Pre-Clinical Students

  https://pressbooks.lib.vt.edu/pulmonarypathophysiology/chapter/pulmonary-embolism/

  The pathophysiology and clinical severity of PE depend on the number and size of the emboli, so clinical manifestations can be highly variable. […] Small emboli that can travel further into the vasculature may cause occlusion of relatively small areas of the lung, but with these areas receiving no perfusion and still being ventilated V/Q becomes inappropriately high. […] Depending on the size and number of emboli, these V/Q mismatches can produce a widening alveolararterial PO2 difference and lead to hypoxemia. […] With larger emboli that occlude larger vessels there will not only be a larger impact on gas exchange, but also a more increase in pulmonary vascular resistance. […] Pulmonary infarction, however, is rare, occurring in only 10 percent of PE cases.

• #1 Pulmonary Embolism Video – Trial Image Inc.

  https://trialimage.com/home-page/stock-medical-animation/pulmonary-animation-library/pulmonary-embolism-video/

  Its important to note here that the reduction in pulmonary arterial flow is directly related to the number and size of emboli which enter the arterial system. […] In addition, emboli lodged within pulmonary arteries cause localized inflammation, resulting in dysfunction of surfactant. […] If the amount of clot lodged in the pulmonary arterial system is sufficient, it may result in a critical impairment of blood oxygenation, leading to multiple organ failure, shock, and death. […] Another physiological consequence of pulmonary emboli is an increase in pulmonary vascular resistance, also known as PVR. […] The key point to take away from this analysis of heparins activity in the coagulation cascade, and this applies to both the unfractionated and low molecular weight forms, is that heparin interferes with the formation of clots, and it has no activity whatsoever in dissolving clots which have already formed.

• #1 Pulmonary Infarction: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/908045-overview

  An increase in effective alveolar dead space is a direct result of the V/Q mismatch. Ventilation (carbon dioxide removal) is usually compensated for by tachypnea. […] In cases in which the pulmonary embolus is large, a sudden increase in pulmonary artery pressure may lead to right ventricular strain and right heart failure. A sudden rise in the right ventricular pressure may cause a leftward shift of the intraventricular septum, which may impair left ventricular filling and output (classic obstructive shock). […] Reflex bronchoconstriction is often associated with pulmonary embolism. This increases the work of breathing and decreases pulmonary compliance. Pulmonary infarction is also associated with diminished surfactant levels, which may contribute to the increased work of breathing and diminished oxygenation.

• #1

  https://step2.medbullets.com/pulmonary/120673/pulmonary-embolism

  Pulmonary embolism is mechanical obstruction of the pulmonary vasculature secondary to a blood clot. […] occlusion of the pulmonary vasculature commonly from a dislodge DVT results in hypoxemia and subsequent pulmonary vasoconstriction. […] the increased pulmonary constriction causes an increase in pulmonary vascular resistance, which decreases right ventricular stroke volume leading to increased ventricular oxygen demand, right ventricular dilatation, decreased left ventricular preload, and poor blood flow to the lung, leading to a ventilation-perfusion mismatch. […] hypoxemia leads to compensatory tachypnea, hyperventilation, and a respiratory alkalosis.

• #1 Pulmonary Embolism (PE) – Pulmonary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pulmonary-disorders/pulmonary-embolism/pulmonary-embolism-pe

  Patients with preexisting cardiopulmonary disease are at higher risk of death, but young and/or otherwise healthy patients may survive a PE that occludes 50% of the pulmonary bed. […] Pulmonary infarction due to PE is sometimes represented by a pleural-based wedge-shaped pattern on chest radiograph or other imaging modalities. This low rate has been attributed to the dual blood supply to the lung (ie, bronchial and pulmonary). Generally, pulmonary infarction is due to smaller emboli that become lodged in more distal pulmonary arteries and is nearly always completely reversible; pulmonary infarction is recognized early, often before necrosis occurs.

• #1 Decoding Pulmonary Embolism: Pathophysiology, Diagnosis, and Treatment

  https://www.mdpi.com/2227-9059/12/9/1936

  Pulmonary Embolism (PE) is a life-threatening condition initiated by the presence of blood clots in the pulmonary arteries, leading to severe morbidity and mortality. Underlying mechanisms involve endothelial dysfunction, including impaired blood flow regulation, a pro-thrombotic state, inflammation, heightened oxidative stress, and altered vascular remodeling. […] These mechanisms contribute to vascular diseases stemming from PE, such as recurrent thromboembolism, chronic thromboembolic pulmonary hypertension, post-thrombotic syndrome, right heart failure, and cardiogenic shock. […] The endothelium can undergo structural or functional changes due to various clinical risk factors, including genetic predisposition, recent surgery, prior thromboembolic events, and hemoptysis, among others. Additionally, cellular risk factors such as oxidative stress, metabolic alterations, and inflammation can trigger decreased endothelial vasodilator capacity, pro-thrombotic responses, and abnormal modulation of vascular growth, potentially leading to pulmonary embolism (PE).

• #1 Decoding Pulmonary Embolism: Pathophysiology, Diagnosis, and Treatment

  https://www.mdpi.com/2227-9059/12/9/1936

  ED disrupts the endothelium’s anticoagulant properties, characterized by reduced synthesis and release of anticoagulant molecules such as tissue factor pathway inhibitor (TFPI) and heparin sulfate (HS), coupled with an increase in procoagulant factors, including tissue factor (TF) and von Willebrand Factor (vWF). This imbalance in the coagulation cascade favors clot formation, heightening the risk of thrombus development in the pulmonary vasculature, a hallmark of PE. […] PE can also potentially disrupt the normal function of ECs, leading to endothelial injury. This can be attributed to multiple factors, including the presence of a blood clot in the pulmonary arteries and the release of inflammatory mediators. The impaired vasodilator capacity of the endothelium in PE patients can contribute to increased pulmonary vascular resistance, potentially leading to RV dysfunction.

• #1 Advanced Research in the Pathophysiology of Venous Thromboembolism–Acute Pulmonary Embolism

  https://www.mdpi.com/2227-9059/13/4/906

  In general, in the early hours and days after an APE episode, the components of innate immunity, such as macrophages, monocytes, and neutrophils, play a major role in the pathophysiology of the inflammatory reaction. […] The upregulation of chemokines, cytokines, and transcriptional changes in both the pulmonary vasculature and right ventricular (RV) muscle further highlights the profound immunological and inflammatory shifts associated with APE. […] Overall, these findings suggest that targeting innate immune pathways could be a promising therapeutic approach for mitigating inflammatory damage, preventing RV dysfunction, and improving thrombus resolution in APE. Future research should focus on refining anti-inflammatory strategies, such as selective chemokine inhibitors or immune cell modulation, to optimize clinical outcomes in APE patients.

• #1 Advanced Research in the Pathophysiology of Venous Thromboembolism–Acute Pulmonary Embolism

  https://www.mdpi.com/2227-9059/13/4/906

  According to the literature, cardiovascular diseases (CVDs)—including myocardial infarction, stroke, and venous thromboembolism (VTE)—are among the leading causes of mortality and morbidity worldwide. Evidence suggests that CVDs share common risk factors and pathophysiological mechanisms. […] Our previous research introduced a revised Mosaic Theory of Acute Pulmonary Embolism (APE), highlighting immunity as a crucial risk factor for APE. Inflammation plays a central role in the complex crosstalk among the coagulation cascade, platelets, endothelium, reactive oxygen species (ROS), and genetic factors. […] The aim of this review is to focus on the interplay between immunity and thrombosis in APE. In addition, it aims to elucidate the roles of the immune cells, NETs, cytokines, endothelium, and miRNAs in the pathophysiology of APE and to provide new insights into potential therapeutic targets.

• #1 Analysis on the Pathogenesis of Symptomatic Pulmonary Embolism with Human Genomics

  https://www.medsci.org/v09p0380.htm

  BACKGROUND: In the present study, the whole human genome oligo microarray was employed to investigate the gene expression profile in symptomatic pulmonary embolism (PE). […] Genomic data showed no damage to vascular endothelial cells in PE patients. Genomic data only found increased mRNA expression of a small amount of coagulation factors in PE patients. In the PE group, anticoagulant proteins, Fibrinolytic system and proteins related to platelet functions only played partial roles in the pathogenesis of PE. In addition, the mRNA expressions of a fraction of adhesion molecules were markedly up-regulated. Gene Ontology analysis showed the genes with down-regulated expressions mainly explain the compromised T cell immunity. Symptomatic VTE patients have compromised T cell immunity. […] The damage to vascular endothelial cells is not necessary in the pathogenesis of VTE, and only a fraction of factors involved in the shared coagulation cascade are activated.

• #1 Analysis on the Pathogenesis of Symptomatic Pulmonary Embolism with Human Genomics

  https://www.medsci.org/v09p0380.htm

  Additionally, the high mRNA expression of L-selectin, ITGAL and ICAM-1 in PE patients revealed the elevated adhesion of vascular endothelial cells, white blood cells and platelets which indicated that the adhesion molecules play an important role in the pathogenesis of VTE. […] Comparisons between PE patients and controls revealed the mRNA expressions of only a few proteins in the coagulation system, anti-coagulation system and fibrinolysis system were markedly up-regulated and only 3 factors or receptors in the shared coagulation cascade were activated, which was inconsistent with traditional theory that coagulation factors are comprehensively activated. […] In the present study, we apply the unitarian theory to explain the pathogenesis of symptomatic VTE: the occurrence of symptomatic VTE is closely related to the compromised immune function as well as the viral infection. This also explains why VTE is frequently found in patients with advanced age, trauma, surgery, malignant tumors, heart failure, immobilization, pregnancy and other risk factors. Our findings provide new knowledge on the etiology and pathophysiology of VTE and novel clue for the clinical diagnosis, treatment and prevention of VTE.

• #1 Associations and Outcomes of Septic Pulmonary Embolism

  https://openrespiratorymedicinejournal.com/VOLUME/8/PAGE/28/FULLTEXT/

  Septic pulmonary embolism (SPE) is an uncommon syndrome characterized by embolization of infected thrombi from a primary infectious site into the venous circulation with implantation into pulmonary vasculature resulting in parenchymal infection. […] Infections with contiguous septic thrombophlebitis leading to SPE have been well established in pediatric populations but have only recently been emphasized in adults by Brenes et al. […] An extrapulmonary site of infection can allow extravasation or translocation of an organism, most commonly bacterial, into the systemic venous circulation. Once in the bloodstream, the pathogen can produce damage directly through toxins and indirectly via inflammatory mediators, which may occasionally promote local thrombosis, which serves as an additional nidus for proliferation of the bacteria.

• #1 Associations and Outcomes of Septic Pulmonary Embolism

  https://openrespiratorymedicinejournal.com/VOLUME/8/PAGE/28/FULLTEXT/

  Embolization of these thrombi into the pulmonary circulation allows for metastatic parenchymal infection of the lungs, even in the absence of cardiac valvular involvement. […] Special attention should be given to Staphylococcus aureus, which can provoke an intense inflammatory reaction, with direct endothelial damage via cytotoxins and enzymatic mechanisms, culminating in septic pulmonary emboli, with concomitant septic thrombophlebitis in a minority of the cases. […] The diagnosis of SPE should be suspected in a febrile bacteremic patient, with an identified extrapulmonary source of infection who develops secondary pulmonary symptoms such as pleuritic chest pain, dyspnea and cough. […] The diagnosis of septic pulmonary embolism is strongly supported by characteristic findings including multiple bilateral peripheral nodules, often pleural based, with or without cavitary changes.

• #1 Chronic thromboembolic pulmonary hypertension: the magic of pathophysiology – Simonneau- Annals of Cardiothoracic Surgery

  https://www.annalscts.com/article/view/16872/html

  Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and underdiagnosed complication of acute pulmonary embolism (APE). […] Initially, PH in chronic thromboembolic pulmonary disease (CTEPD) was thought to be due exclusively to the intravascular obstruction of pulmonary arteries by unresolved fibrotic clots. However, it is now well accepted that pulmonary vascular remodelling can include significant pulmonary microvasculopathy, which plays a role in the development of CTEPH. […] The histological description and clinical consequences of CTEPH microvasculopathy are now better understood. These lesions may involve not only small muscular pulmonary arteries 500 m, but also pulmonary capillaries and veins. […] In addition, enlargement and proliferation of systemic bronchial arteries as well as anastomoses between the systemic and pulmonary circulations contribute to the development of microvasculopathy.

• #1 Chronic thromboembolic pulmonary hypertension: the magic of pathophysiology – Simonneau- Annals of Cardiothoracic Surgery

  https://www.annalscts.com/article/view/16872/html

  The natural history of CTEPH is complex. Initially it was considered that PH in CTEPD was exclusively due to the intravascular obstruction of pulmonary arteries by unresolved fibrotic clots. However, it is now well accepted that pulmonary vascular remodelling can lead to significant pulmonary microvasculopathy, which plays a role in the development of CTEPH. […] In CTEPH, pulmonary microvasculopathy was first described by Kenneth Moser and Colin Bloor in lung tissues obtained by biopsy or at autopsy. These lesions are characterized by a major remodelling of the wall of muscular pulmonary arteries (50500 m), with a full range of PH lesions similar to those observed in idiopathic PAH, including eccentric intimal fibrosis and intimal fibromuscular proliferation. […] More recently, another form of microvasculopathy has been described in CTEPH, characterized by a remodelling of small pre-capillary vessels, capillaries (with pulmonary hemangiomatosis-like remodelling) and pulmonary venules (pulmonary veno-occlusive disease like).

• #1 Pulmonary embolism | Nature Reviews Disease Primers

  https://www.nature.com/articles/nrdp201828

  Pulmonary embolism (PE) is caused by emboli, which have originated from venous thrombi, travelling to and occluding the arteries of the lung. […] Acute PE is associated with right ventricular dysfunction, which can lead to arrhythmia, haemodynamic collapse and shock. […] Furthermore, individuals who survive PE can develop post-PE syndrome, which is characterized by chronic thrombotic remains in the pulmonary arteries, persistent right ventricular dysfunction, decreased quality of life and/or chronic functional limitations. […] Several important improvements have been made in the diagnostic and therapeutic management of acute PE in recent years, such as the introduction of a simplified diagnostic algorithm for suspected PE as well as phase III trials demonstrating the value of direct oral anticoagulants in acute and extended treatment of venous thromboembolism. […] Future research should aim to address novel treatment options (for example, fibrinolysis enhancers) and improved methods for predicting long-term complications and defining optimal anticoagulant therapy parameters in individual patients, and to gain a greater understanding of post-PE syndrome.

• #1 Pathophysiology of right ventricular failure in acute pulmonary embolism and chronic thromboembolic pulmonary hypertension: a pictorial essay for the interventional radiologist | Insights into Imaging | Full Text

  https://insightsimaging.springeropen.com/articles/10.1186/s13244-019-0695-9

  When afterload has reached the critical level, the RV dilates, the LV underfills, and decreases supply to the coronary arteries. […] As the right ventricle becomes ischemic, its contractility further suffers, further decreasing right ventricular output, increasing right ventricular dilatation, and decreasing left ventricular output, resulting in a downward hemodynamic spiral that augments itself and leads to cardiogenic shock. […] In CTEPH, to accommodate the RV afterload and wall stress to the RV, adaptive remodeling occurs with RV wall hypertrophy, through the addition of sarcomeres, the functional unit of striated muscle, in a process called adaptive hypertrophy. […] However, the ill-equipped RV is not capable of sustaining the long-term progressively increased afterload and remodeling becomes maladaptive.

• #1 Pathophysiology of right ventricular failure in acute pulmonary embolism and chronic thromboembolic pulmonary hypertension: a pictorial essay for the interventional radiologist | Insights into Imaging | Full Text

  https://insightsimaging.springeropen.com/articles/10.1186/s13244-019-0695-9

  RV dilatation and wall hypertrophy increase oxygen demand to a level which the coronary artery blood flow cannot meet, resulting in ischemia, necrosis, and fibrosis of the RV wall, worsening contractility of the right ventricle, and right ventricular failure. […] Right ventricular failure leads to further RV dilatation impinging on the LV, worsening LV filling, decreased LV stroke volume, increased heart rate to compensate for the decrease in the LV stroke volume (SV), and decreased output to the coronary arteries. […] The compromise of the coronary arteries is accentuated as the coronary arteries already cannot meet the demand of the hypertrophied dilated RV. […] The chronic RV dysfunction creates a progressive downward spiral leading to severe heart failure.

• #1 pulmonary embolism | Calgary Guide

  https://calgaryguide.ucalgary.ca/?s=pulmonary+embolism

  Pulmonary Embolism: Pathogenesis and Clinical Findings Virchows Triad Body attempts to break down clot Fibrinogen breakdown products in blood Lab: Positive D-Dimer D-Dimer only performed if clinical suspicion of PE low (Wells Criteria) […] Hypercoagulable State Blood clot develops (commonly in deep veins of legs) Venous stasis = Deep Vein Thrombus (95% of PE) Vessel injury Ultrasound: Presence of Clot in Deep Vein of Leg Clot dislodges migrates to inferior vena cava (IVC) right atrium of heart right ventricle lodges in pulmonary arteries/arterioles Pulmonary Embolism (PE) Thromboembolic blockage of pulmonary vasculature perfusion to lung parenchyma Clot occludes pulmonary arteries/ arterioles dead space ventilation and V/Q mismatching Blood pumped from RV to pulmonary arteries cannot pass clot pulmonary and right ventricle (RV) pressure RV Strain RV workload, right coronary artery perfusion Computed Tomography- Pulmonary Angiogram (CTPA): Filling Defect (*see Radiology slide for CTPA findings)

• #2 Epidemiology, Pathophysiology, and Natural History of Pulmonary Embolism

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5986574/

  Most PEs originate as thrombi in the deep veins of the lower extremities. The site of thrombosis is most frequently in the calf veins, then femoropopliteal veins, and less frequently in the iliac veins. Thrombosis begins in areas of decreased flow such as valve cusps and bifurcations and then propagates due to local hypercoagulability caused by hypoxia and hemoconcentration. A smaller percentage of emboli arises from upper extremity veins and are typically associated with central venous catheters, intracardiac devices such as pacemakers and defibrillators, and malignancy or activity-related venous trauma. Pelvic vein DVTs can also cause pulmonary emboli, but they are generally associated with a predisposing factor such as pelvic infection, pelvic surgery, or pregnancy. Lower extremity central DVTs are most likely to embolize and cause PE (15-32% of the time), whereas upper extremity DVTs cause PE only 6% of the time. Calf vein DVTs rarely embolize to the lungs, but one-third can extend into the central veins and subsequently have the potential to embolize.

• #2 Acute pulmonary embolism 1: pathophysiology, clinical presentation, and diagnosis | Heart

  https://heart.bmj.com/content/85/2/229

  Thrombotic pulmonary embolism is not an isolated disease of the chest but a complication of venous thrombosis. Deep venous thrombosis (DVT) and pulmonary embolism are therefore parts of the same process, venous thromboembolism. Evidence of leg DVT is found in about 70% of patients who have sustained a pulmonary embolism; in most of the remainder, it is assumed that the whole thrombus has already become detached and embolised. Conversely, pulmonary embolism occurs in up to 50% of patients with proximal DVT of the legs (involving the popliteal and/or more proximal veins), and is less likely when the thrombus is confined to the calf veins. Rarely, the source of emboli are the iliac veins, renal veins, right heart, or upper extremity veins; the clinical circumstances usually point to these unusual sites.

• #2 Pulmonary embolism – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/pulmonary-embolism/symptoms-causes/syc-20354647

  A pulmonary embolism (PE) occurs when a blood clot gets stuck in an artery in the lung, blocking blood flow to part of the lung. Blood clots most often start in the legs and travel up through the right side of the heart and into the lungs. This is called deep vein thrombosis (DVT). […] A pulmonary embolism is a blood clot that blocks and stops blood flow to an artery in the lung. In most cases, the blood clot starts in a deep vein in the leg and travels to the lung. Rarely, the clot forms in a vein in another part of the body. When a blood clot forms in one or more of the deep veins in the body, it’s called a deep vein thrombosis (DVT). […] Because one or more clots block blood flow to the lungs, pulmonary embolism can be life-threatening. However, prompt treatment greatly reduces the risk of death. Taking measures to prevent blood clots in your legs will help protect you against pulmonary embolism.

• #2 Pulmonary embolism – Symptoms and causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/pulmonary-embolism/symptoms-causes/syc-20354647

  A pulmonary embolism occurs when a clump of material, most often a blood clot, gets stuck in an artery in the lungs, blocking the flow of blood. Blood clots most commonly come from the deep veins of your legs, a condition known as deep vein thrombosis. […] In many cases, multiple clots are involved. The portions of lung served by each blocked artery can’t get blood and may die. This is known as a pulmonary infarction. This makes it more difficult for your lungs to provide oxygen to the rest of your body. […] Occasionally, blockages in the blood vessels are caused by substances other than blood clots, such as fat from the inside of a broken long bone, part of a tumor, or air bubbles.

• #2 Pulmonary Embolism | Concise Medical Knowledge

  https://www.lecturio.com/concepts/pulmonary-embolism/

  Pulmonary embolism (PE) is a potentially fatal condition that occurs as a result of intraluminal obstruction of the main pulmonary artery or its branches. The causative factors include thrombi, air, amniotic fluid, and fat. In PE, gas exchange is impaired due to the decreased return of deoxygenated blood to the lungs. More than 90% of PEs are complications of a deep vein thrombosis (DVT) of the lower extremity. […] The 3 primary factors that contribute to VTE (known as Virchows triad) include venous stasis, hypercoagulability, and vascular endothelial damage. Any condition that worsens 1 (or more) of the 3 factors increases the risk of DVT formation and, thus, PE. […] Virchows triad: Circulatory stasis, endothelial injury or dysfunction, and hypercoagulability are the primary etiologic factors that cause venous thromboembolic disease.

• #2 7.1: Pulmonary Embolism – Medicine LibreTexts

  https://med.libretexts.org/Courses/Virginia_Tech_Carilion_School_of_Medicine/Pulmonary_Pathophysiology_for_Pre-Clinical_Students_(Binks)/07%3A_Pulmonary_Embolism/7.01%3A_PATHOLOGY_OF_PULMONARY_EMBOLISM_(PE)

  Venous stasis appears to be the most important factor in thrombus formation, and cases of PE are often preceded by periods of immobility. […] Any condition that increases coagulability elevates the risk of PE, and most are due to trauma of some form or another or an elevated inflammatory state such as cancer or the postsurgery state. […] The pathophysiology and clinical severity of PE depend on the number and size of the emboli, so clinical manifestations can be highly variable. […] Small emboli that can travel further into the vasculature may cause occlusion of relatively small areas of the lung, but with these areas receiving no perfusion and still being ventilated V/Q becomes inappropriately high. […] Depending on the size and number of emboli, these V/Q mismatches can produce a widening alveolararterial PO2 difference and lead to hypoxemia. […] With larger emboli that occlude larger vessels there will not only be a larger impact on gas exchange, but also a more increase in pulmonary vascular resistance. […] Pulmonary infarction, however, is rare, occurring in only 10 percent of PE cases.

• #2

  https://www.alliedacademies.org/articles/exploring-the-multifaceted-etiology-pathogenesis-and-management-strategies-for-pulmonary-embolism-a-comprehensive-review-24166.html

  Pulmonary Embolism (PE) is a potentially life-threatening condition that occurs when a blood clot, usually from the legs or pelvis, travels to the lungs and blocks one or more pulmonary arteries. […] The pathogenesis of PE involves the formation and migration of a blood clot from the deep veins in the legs or pelvis to the lungs, where it blocks one or more pulmonary arteries. The formation of a blood clot involves three components: Virchow’s triad. This triad includes endothelial injury, blood stasis, and hypercoagulability. […] Endothelial injury can be caused by various factors, including trauma, surgery, inflammation, and infections. This injury exposes the underlying tissue and activates platelets and the coagulation cascade. Blood stasis can occur due to immobility, obesity, and venous insufficiency. This can lead to a pooling of blood in the veins, which increases the risk of blood clots forming. Hypercoagulability can be caused by various factors, including cancer, hormone therapy, pregnancy, and genetic factors. These factors increase the activity of blood clotting factors, making it more likely for blood clots to form. Once a blood clot forms in the deep veins of the legs or pelvis, it can migrate to the lungs through the venous system. The size and location of the blood clot determine the severity of the PE. Small clots may cause no symptoms, while large clots can be life-threatening.

• #2 Acute pulmonary embolism 1: pathophysiology, clinical presentation, and diagnosis | Heart

  https://heart.bmj.com/content/85/2/229

  As pulmonary embolism is preceded by DVT, the factors predisposing to the two conditions are the same and broadly fit Virchow’s triad of venous stasis, injury to the vein wall and enhanced coagulability of the blood. The identification of risk factors not only aids clinical diagnosis of venous thromboembolism, but also guides decisions about prophylactic measures and repeat testing in borderline cases. […] Primary thrombophilic abnormalities are usually discovered after the thromboembolic event. Therefore, the risk of venous thromboembolism is best assessed by recognising the presence of known clinical risk factors. However, investigations for thrombophilic disorders at follow up should be considered in those without another apparent explanation. In many patients, multiple risk factors are present, and the risks are cumulative.

• #2 Pulmonary Embolism Video – Trial Image Inc.

  https://trialimage.com/home-page/stock-medical-animation/pulmonary-animation-library/pulmonary-embolism-video/

  This is Dr. Cal Shipley with a review of pulmonary embolism. […] In order to understand the mechanism and significance of a pulmonary embolism, it is critical to be familiar with the physiology of respiration and blood oxygenation in the body. […] Most pulmonary emboli originate as clots which are formed in the venous system of one of the lower limbs. […] Once the initial DVT has formed it may extend in length by several inches in a matter of seconds. […] The DVT has now become an embolus, a traveling clot. […] These fragments will flow throughout the pulmonary arterial system until they reach vessels whose caliber is smaller than their own, at which point they will become lodged within the vessel, obstructing local blood flow and interfering with the oxygenation process previously reviewed.

• #2 Basic Science and Pathophysiology – RCEMLearning India

  https://www.rcemlearning.org/modules/pulmonary-embolism/lessons/basic-science-and-pathophysiology-4/

  PE should be regarded as a complication of underlying venous thrombosis. In the normal situation, tiny microthrombi are continually formed and lysed in equal measure within the venous circulatory system i.e. there is a balance between the thrombotic and fibrinolytic systems. In some pathological situations, microthrombi escape the fibrinolytic system and are allowed to propagate into larger thrombi. […] Most pulmonary emboli occur when fragments of a thrombus break free from the deep venous system, typically in the pelvis and lower limb, travel up the vena cava, through the right atrium and into the pulmonary vasculature. […] The lungs act as a filter for all blood returning to the heart so all but the smallest clots will get stuck there rather than travelling to the arterial circulation.

• #2 Pulmonary Embolism (PE): Practice Essentials, Background, Anatomy

  https://emedicine.medscape.com/article/300901-overview

  Pulmonary embolism reduces the cross-sectional area of the pulmonary vascular bed, resulting in an increment in pulmonary vascular resistance, which, in turn, increases the right ventricular afterload. If the afterload is increased severely, right ventricular failure may ensue. In addition, the humoral and reflex mechanisms contribute to the pulmonary arterial constriction. Following the initiation of anticoagulant therapy, the resolution of emboli usually occurs rapidly during the first 2 weeks of therapy; however, it can persist on chest imaging studies for months to years. Chronic pulmonary hypertension may occur with failure of the initial embolus to undergo lyses or in the setting of recurrent thromboemboli.

• #2 Epidemiology, Pathophysiology, and Natural History of Pulmonary Embolism

  https://pmc.ncbi.nlm.nih.gov/articles/PMC5986574/

  When thrombus embolizes from the extremities and lodges in the pulmonary arterial vasculature, pulmonary vascular resistance (PVR) increases due to both mechanical obstruction and release of vasoconstrictive substances from platelets (serotonin and thromboxane-A2), plasma (thrombin), and tissue (histamine and endothelin). The thin walled RV is accustomed to low pressure and cannot easily adapt to this increased afterload, which has effects on both RV and left ventricular (LV) function. If obstruction is mild, PVR and pulmonary artery pressure remain normal by recruiting and distending pulmonary vessels. At moderate levels of obstruction, pulmonary artery pressure and right atrial pressure increase. Initially, RV stroke volume and cardiac output are maintained by an increase in heart rate and contractility. In patients without prior CPD, the maximal mean pulmonary artery pressure that can be generated even with 50% obstruction is 40mm Hg. Obstruction much beyond this will precipitate RV failure. When the degree of obstruction exceeds 50 to 60%, the right heart dilates, RV wall tension increases, coronary perfusion pressure drops, RV ischemia and RV dysfunction develops, and cardiac output falls, leading to hypotension. Furthermore, the dilated RV impinges on the intraventricular septum and via interventricular dependences causes decreased LV diastolic filling and decreased LV cardiac output. In patients without prior CPD, the degree of obstruction has a hyperbolic relationship to PVR and the hemodynamic manifestations of PE are related to embolism size. Patients with preexisting CPD have diminished pulmonary vascular reserve and a smaller degree of obstruction can lead to disproportionate increase in pulmonary artery pressure and hemodynamic instability.

• #2 Basic Science and Pathophysiology – RCEMLearning India

  https://www.rcemlearning.org/modules/pulmonary-embolism/lessons/basic-science-and-pathophysiology-4/

  In massive PE (i.e. more than 50% obstruction of the pulmonary vascular bed) the most immediate problem is usually circulatory collapse due to a fall in cardiac output as the right heart fails to pump an adequate volume of blood through the reduced pulmonary vasculature to the left side of the heart. […] However, in patients with underlying lung pathology such as COPD a non-massive PE may present major problems with maintaining oxygenation despite the absence of haemodynamic compromise, as the function of the lung unaffected by the PE is already impaired.

• #2 Pulmonary Thromboembolism and Thrombolytics – Manual of Medicine

  https://manualofmedicine.com/topics/emergency-acute-medicine/massive-pulmonary-thromboembolism-and-thrombolytics/

  Venous thromboembolism (VTE), which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is responsible for more than 250,000 annual hospitalizations in the United States, with significant risk for morbidity and mortality. The most serious clinical presentation of VTE is acute PE. […] Acute PE interferes with the circulation in the pulmonary bed. If more than 30% to 50% of the total cross-sectional area of the pulmonary arterial bed is occluded by thromboemboli, the pulmonary artery pressure (PAP) increases. […] Additionally, local hypoxia induces vasoconstriction in the vascular bed, leading to a further increase in the pulmonary vascular resistance. As such, the abrupt increase in pulmonary vascular resistance results in RV dilation, with resultant increase in RV pressure and volume. […] The sudden increase in wall tension prevents the RV from overcoming the PAP, leading to leftward bowing of the interventricular septum. This impedes LV filling in early diastole, eventually reducing the cardiac output and contributing to hemodynamic instability and obstructive shock.

• #2 Pulmonary Embolism | Concise Medical Knowledge

  https://www.lecturio.com/concepts/pulmonary-embolism/

  Obstruction of vascular flow results in dead space (ventilation without perfusion). […] Inflammatory response, which leads to: Vasoconstriction and bronchoconstriction in unaffected nearby areas further decreases blood flow and air flow (Q) and worsens V/Q mismatch. […] Abnormal gas exchange (due to dead space and shunting), resulting in: Hypoxemia. […] Right-sided heart failure: Increased pulmonary vascular resistance (PVR) and decreased ejection from the right ventricle (RV) with subsequent increase in central venous pressure. […] Ultimately leads to prolonged RV strain, distention, and decreased contractility. […] Pulmonary infarction: Occurs in about 10% of patients. Associated with small emboli in the segmental and subsegmental branches, causing ischemia of lung tissue.

• #2 Pulmonary Infarction: Background, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/908045-overview

  An increase in effective alveolar dead space is a direct result of the V/Q mismatch. Ventilation (carbon dioxide removal) is usually compensated for by tachypnea. […] In cases in which the pulmonary embolus is large, a sudden increase in pulmonary artery pressure may lead to right ventricular strain and right heart failure. A sudden rise in the right ventricular pressure may cause a leftward shift of the intraventricular septum, which may impair left ventricular filling and output (classic obstructive shock). […] Reflex bronchoconstriction is often associated with pulmonary embolism. This increases the work of breathing and decreases pulmonary compliance. Pulmonary infarction is also associated with diminished surfactant levels, which may contribute to the increased work of breathing and diminished oxygenation.

• #2 pulmonary embolism | Calgary Guide

  https://calgaryguide.ucalgary.ca/?s=pulmonary+embolism

  Pulmonary Embolism (PE): Thromboembolic blockage of pulmonary vasculature Clot occludes pulmonary artery/ arterioles D-Dimer is only performed if clinical suspicion of PE low (Wells Criteria) CT-PA is the current diagnostic test for PE V/Q Scan is performed when CT contrast is contraindicated X-Ray is usually normal in PE (Except Hamptons Hump, a rare but specific sign of PE) Ischemia of lung tissue distal to clot X-Ray: Hamptons Hump pleural based area of opacity Air flow/ ventilation to lungs unaffected Pleuritic Chest Pain + Dyspnea VQ Scan: V/Q Mismatch dead space ventilation and V/Q mismatching Chemoreceptors detect CO2 and O2 Signal brain to breathing rate Tachypnea Arterial O2 Blood pumped from RV to pulmonary arteries cannot pass clot pulmonary and RV pressure RV Strain CT-PA: Filling Defect Echo: RV size + RV Function ECG: S1Q3T3 Pattern Lab: BNP Chest Pain Tachycardia RV work load, right coronary artery perfusion

• #2 Pulmonary Embolism (PE) – Pulmonary Disorders – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/pulmonary-disorders/pulmonary-embolism/pulmonary-embolism-pe

  Small emboli may have no acute physiologic effects and may begin to lyse immediately and resolve within hours or days. Larger emboli can cause reflex increase in ventilation (tachypnea), hypoxemia due to ventilation/perfusion (V/Q) mismatch, low mixed venous oxygen content as a result of low cardiac output, atelectasis due to alveolar hypocapnia and abnormalities in surfactant, and increase in pulmonary vascular resistance caused by mechanical obstruction and vasoconstriction resulting in tachycardia and hypotension. […] Endogenous lysis reduces most emboli, even those of moderate size, and physiologic alterations decrease over hours or days. Some emboli resist lysis and may organize and persist and sometimes cause chronic thromboembolic pulmonary hypertension (CTEPH). […] Pulmonary emboli may be classified according to the physiologic effects as described by the European Society of Cardiology/American Heart Association into high risk (massive), intermediate risk (submassive), and low risk. […] When a large embolus acutely occludes major pulmonary arteries or when many smaller emboli combine to occlude a significant proportion of the more distal vessels, RV pressure increases, which may lead to acute RV failure, shock, or sudden death. The risk of death depends on the degree and rate of rise of right-sided pressures and on the patient’s underlying cardiopulmonary status.

• #2 Pulmonary Embolism – Pulmonary Pathophysiology for Pre-Clinical Students

  https://pressbooks.lib.vt.edu/pulmonarypathophysiology/chapter/pulmonary-embolism/

  The pathophysiology and clinical severity of PE depend on the number and size of the emboli, so clinical manifestations can be highly variable. […] Small emboli that can travel further into the vasculature may cause occlusion of relatively small areas of the lung, but with these areas receiving no perfusion and still being ventilated V/Q becomes inappropriately high. […] Depending on the size and number of emboli, these V/Q mismatches can produce a widening alveolararterial PO2 difference and lead to hypoxemia. […] With larger emboli that occlude larger vessels there will not only be a larger impact on gas exchange, but also a more increase in pulmonary vascular resistance. […] Pulmonary infarction, however, is rare, occurring in only 10 percent of PE cases.

• #2 Pathophysiology of right ventricular failure in acute pulmonary embolism and chronic thromboembolic pulmonary hypertension: a pictorial essay for the interventional radiologist | Insights into Imaging | Full Text

  https://insightsimaging.springeropen.com/articles/10.1186/s13244-019-0695-9

  Pulmonary embolus (PE) is the third most common cause of cardiovascular death with more than 600,000 cases occurring in the USA per year. About 45% of patients with acute PE will have acute right ventricular failure, and up to 3.8% of patients will develop chronic thromboembolic pulmonary hypertension (CTEPH) with progressive, severe, chronic heart failure. The right ventricle (RV) is constructed to accommodate a low-resistance afterload. Increases in afterload from acute massive and submassive PE and CTEPH may markedly compromise the RV function leading to hemodynamic collapse and death. […] Understanding the pathophysiology of RV heart failure in these diseases formulates the rationale for therapeutic intervention by the interventional radiologist. […] In chronic thromboembolic pulmonary hypertension (CTEPH), RV dilatation and wall hypertrophy increase oxygen demand to which the coronary artery blood flow cannot meet, resulting in ischemia, necrosis, and fibrosis of the RV wall.

• #2 Advanced Research in the Pathophysiology of Venous Thromboembolism–Acute Pulmonary Embolism

  https://www.mdpi.com/2227-9059/13/4/906

  According to the literature, cardiovascular diseases (CVDs)—including myocardial infarction, stroke, and venous thromboembolism (VTE)—are among the leading causes of mortality and morbidity worldwide. Evidence suggests that CVDs share common risk factors and pathophysiological mechanisms. […] Our previous research introduced a revised Mosaic Theory of Acute Pulmonary Embolism (APE), highlighting immunity as a crucial risk factor for APE. Inflammation plays a central role in the complex crosstalk among the coagulation cascade, platelets, endothelium, reactive oxygen species (ROS), and genetic factors. […] The aim of this review is to focus on the interplay between immunity and thrombosis in APE. In addition, it aims to elucidate the roles of the immune cells, NETs, cytokines, endothelium, and miRNAs in the pathophysiology of APE and to provide new insights into potential therapeutic targets.

• #2 Analysis on the Pathogenesis of Symptomatic Pulmonary Embolism with Human Genomics

  https://www.medsci.org/v09p0380.htm

  Additionally, the high mRNA expression of L-selectin, ITGAL and ICAM-1 in PE patients revealed the elevated adhesion of vascular endothelial cells, white blood cells and platelets which indicated that the adhesion molecules play an important role in the pathogenesis of VTE. […] Comparisons between PE patients and controls revealed the mRNA expressions of only a few proteins in the coagulation system, anti-coagulation system and fibrinolysis system were markedly up-regulated and only 3 factors or receptors in the shared coagulation cascade were activated, which was inconsistent with traditional theory that coagulation factors are comprehensively activated. […] In the present study, we apply the unitarian theory to explain the pathogenesis of symptomatic VTE: the occurrence of symptomatic VTE is closely related to the compromised immune function as well as the viral infection. This also explains why VTE is frequently found in patients with advanced age, trauma, surgery, malignant tumors, heart failure, immobilization, pregnancy and other risk factors. Our findings provide new knowledge on the etiology and pathophysiology of VTE and novel clue for the clinical diagnosis, treatment and prevention of VTE.

• #2 Advanced Research in the Pathophysiology of Venous Thromboembolism–Acute Pulmonary Embolism

  https://www.mdpi.com/2227-9059/13/4/906

  In general, in the early hours and days after an APE episode, the components of innate immunity, such as macrophages, monocytes, and neutrophils, play a major role in the pathophysiology of the inflammatory reaction. […] The upregulation of chemokines, cytokines, and transcriptional changes in both the pulmonary vasculature and right ventricular (RV) muscle further highlights the profound immunological and inflammatory shifts associated with APE. […] Overall, these findings suggest that targeting innate immune pathways could be a promising therapeutic approach for mitigating inflammatory damage, preventing RV dysfunction, and improving thrombus resolution in APE. Future research should focus on refining anti-inflammatory strategies, such as selective chemokine inhibitors or immune cell modulation, to optimize clinical outcomes in APE patients.

• #2 Associations and Outcomes of Septic Pulmonary Embolism

  https://openrespiratorymedicinejournal.com/VOLUME/8/PAGE/28/FULLTEXT/

  Embolization of these thrombi into the pulmonary circulation allows for metastatic parenchymal infection of the lungs, even in the absence of cardiac valvular involvement. […] Special attention should be given to Staphylococcus aureus, which can provoke an intense inflammatory reaction, with direct endothelial damage via cytotoxins and enzymatic mechanisms, culminating in septic pulmonary emboli, with concomitant septic thrombophlebitis in a minority of the cases. […] The diagnosis of SPE should be suspected in a febrile bacteremic patient, with an identified extrapulmonary source of infection who develops secondary pulmonary symptoms such as pleuritic chest pain, dyspnea and cough. […] The diagnosis of septic pulmonary embolism is strongly supported by characteristic findings including multiple bilateral peripheral nodules, often pleural based, with or without cavitary changes.

• #2 Chronic thromboembolic pulmonary hypertension: the magic of pathophysiology – Simonneau- Annals of Cardiothoracic Surgery

  https://www.annalscts.com/article/view/16872/html

  The natural history of CTEPH is complex. Initially it was considered that PH in CTEPD was exclusively due to the intravascular obstruction of pulmonary arteries by unresolved fibrotic clots. However, it is now well accepted that pulmonary vascular remodelling can lead to significant pulmonary microvasculopathy, which plays a role in the development of CTEPH. […] In CTEPH, pulmonary microvasculopathy was first described by Kenneth Moser and Colin Bloor in lung tissues obtained by biopsy or at autopsy. These lesions are characterized by a major remodelling of the wall of muscular pulmonary arteries (50500 m), with a full range of PH lesions similar to those observed in idiopathic PAH, including eccentric intimal fibrosis and intimal fibromuscular proliferation. […] More recently, another form of microvasculopathy has been described in CTEPH, characterized by a remodelling of small pre-capillary vessels, capillaries (with pulmonary hemangiomatosis-like remodelling) and pulmonary venules (pulmonary veno-occlusive disease like).

• #2 Pathophysiology of right ventricular failure in acute pulmonary embolism and chronic thromboembolic pulmonary hypertension: a pictorial essay for the interventional radiologist | Insights into Imaging | Full Text

  https://insightsimaging.springeropen.com/articles/10.1186/s13244-019-0695-9

  RV dilatation and wall hypertrophy increase oxygen demand to a level which the coronary artery blood flow cannot meet, resulting in ischemia, necrosis, and fibrosis of the RV wall, worsening contractility of the right ventricle, and right ventricular failure. […] Right ventricular failure leads to further RV dilatation impinging on the LV, worsening LV filling, decreased LV stroke volume, increased heart rate to compensate for the decrease in the LV stroke volume (SV), and decreased output to the coronary arteries. […] The compromise of the coronary arteries is accentuated as the coronary arteries already cannot meet the demand of the hypertrophied dilated RV. […] The chronic RV dysfunction creates a progressive downward spiral leading to severe heart failure.

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