Hemodynamics PDF

 EMBOLISM An embolus is a detached intravascular solid, liquid, or gaseous mass that is carried by the blood from its point of origin to a distant site, where it often causes tissue dysfunction or infarction. The vast majority of emboli are dislodged thrombi...

 EMBOLISM An embolus is a detached intravascular solid, liquid, or gaseous mass that is carried by the blood from its point of origin to a distant site, where it often causes tissue dysfunction or infarction. The vast majority of emboli are dislodged thrombi, hence the term thromboembolism. Other rare emboli are composed of fat droplets, nitrogen bubbles, atherosclerotic debris (cholesterol emboli), tumor fragments, bone marrow, or even foreign bodies. Emboli travel through the blood until they encounter vessels too small to permit further passage, causing partial or complete vascular occlusion. Pulmonary Embolism (PE) Pulmonary emboli originate from DVT and are the most common form of thromboembolic disease. Fragmented thrombi from DVT are carried through progressively larger veins and the right side of the heart before slamming into the pulmonary arterial vasculature. Depending on the size of the embolus, it can occlude the main pulmonary artery, straddle the pulmonary artery bifurcation (saddle embolus), or pass out into the smaller, branching arteries.  Pulmonary Embolism (PE) Sudden death, acute right heart failure (cor pulmonale), or cardiovascular collapse occurs when emboli obstruct 60% or more of the pulmonary circulation. Embolic obstruction of medium-sized arteries with subsequent vascular rupture can result in pulmonary hemorrhage but usually does not cause pulmonary infarction. This is because the lung is supplied by both the pulmonary arteries and the bronchial arteries, and the intact bronchial circulation is usually sufficient to perfuse the affected area. Understandably, if the bronchial arterial flow is compromised (e.g.,by left-sided cardiac failure), infarction may occur. Embolic obstruction of small end-arteriolar pulmonary branches often does produce hemorrhage or infarction. Multiple emboli over time may cause pulmonary hypertension and right ventricular failure.  Systemic Thromboembolism Most systemic emboli (80%) arise from intracardiac mural thrombi, two-thirds of which are associated with left ventricular wall infarcts and another one-fourth with left atrial dilation and fibrillation. The remainder originates from aortic aneurysms, atherosclerotic plaques, valvular vegetations, or venous thrombi (paradoxical emboli); 10% to 15% are of unknown origin. In contrast to venous emboli, the vast majority of which lodge in the lung, arterial emboli can travel to a wide variety of sites; the point of arrest depends on the source and the relative amount of blood flow that downstream tissues receive.  Systemic Thromboembolism Most come to rest in the lower extremities (75%) or the brain (10%), but other tissues, including the intestines, kidneys, spleen, and upper extremities, may be involved. The consequences of systemic emboli depend on the vulnerability of the affected tissues to ischemia, the caliber of the occluded vessel, and whether a collateral blood supply exists; in general, however, the outcome is tissue infarction.  Fat Embolism Trauma Vascular Fat globules After fracture of long Rupture vascular sinusoid Fat travel to the lung bones, soft tissue trauma, in the marrow allowing burns marrow or adipose tissue to herniate into the vascular space  Fat Embolism syndrom tacypneu Pulmonary Insufficiency dyspneu Tachycardia Irritability Neurologic symptom Restlessness Delirium or coma Anemia and Diffuse petechial rasht Thrombocytopenia Fatal in 5%-15% cases t Fat Embolism Fat microemboli and associated red cell and platelet aggregates and occlude and the pulmonary and cerebral microvasculature. release of free fatty acids from the fat globules exacerbates the situation by causing local toxic injury to endothelium, and platelet activation and granulocyte recruitment (with free radical, protease, and eicosanoid release) complete the vascular assault. Air Embolism Gas bubbles within the circulation can coalesce to form frothy masses that obstruct vascular flow and cause distal ischemic injury Mechanism → intense inflammatory response with release of cytokines that may injure the alveoli 300-500 ml of air 100 ml at 100 mL/ sec Bubbles in the central nervous system can cause mental impairment/ sudden onset of coma. Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.132-134​ Decompression Sickness Bends, chokes, air is breathed at high pressure stagger increased amounts of gas dissolved in the blood and tissues ascends too rapidly Caisson disease nitrogen comes out of solution in the tissues and the blood Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.132-134​ Amniotic Fluid Embolism Amniotic fluid and its content enters the uterine veins and embolize 5th cause of maternal mortality worldwide Characterized: Severe dyspnea Cyanosis Shock Neurologic impairment → headache to seizures and coma Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.132-134​  Tear in the placental membranes or rupture of uterine veins Biochemical activation of coagulation factors, components of the innate immune system, and release of vasoactive substances Acute pulmonary hypertension and right heart failure, which causes hypoxia, left heart failure, pulmonary edema, and diffuse alveolar damage Autopsy and microscopic examination may show hair, mucin, and fetal squames in maternal pulmonary microvasculature Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.132-134​ INFARCTION → an area of ischemic necrois caused by occlusion of either the arterial supply or the venous drainage. Red Infarction White Infarct Venous occlusions Arterial occlusions in solid organs with end-arterial circulation Loose, spongy tissues Tissue density limits the seepage of blood from adjoining capillary beds into Tissues with dual circulations the necrotic area. Tissues previously congested by sluggish venous outflow Flow is reestablished to a site of previous arterial occlusion and necrosis Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.132-134​ Kidney – Infarct – NUS Pathweb :: NUS Pathweb Factors That Influence Development of an Infarct Anatomy of the vascular supply Rate of occlusion (alternative blood supply) Meier, P., Schirmer, S.H., Lansky, A.J. et al. The collateral circulation of the heart. BMC Med 11, 143 (2013). https://doi.org/10.1186/1741-7015-11-143 Tissue vulnerability to hypoxia Hypoxemia (low blood oxygen content) Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.132-134​  Normal Hemostasis Essential for life. Orchestrated process involving platelets, clotting factors, and endothelium that occurs at the site of vascular injury and culminates in the formation of a blood clot, which serves to prevent or limit the extent of bleeding. Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.118-120​ General sequence of hemostasis Arteriolar vasoconstriction. Reduces blood flow to the injured area Mediated by reflex neurogenic mechanism may be augmented by the local secretion of factors such as endothelin Having transient effect. Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.118-120​ General sequence of hemostasis The formation of the platelet plug. Disruption of the endothelium 🡪 exposes subendothelial von Willebrand factor (vWF) and collagen🡪 platelet adherence and activation. Activation of platelet results in a dramatic shape change, as well as the release of secretory granules. Within a few minutes, the secreted products recruit additional platelets Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic that Basis of Disease. undergo 10th ed. Philadelphia: Elsevier; 2021. aggregation to form a primary p.118-120​ General sequence of hemostasis 2. Deposition of fibrin. Vascular injury 🡪 exposes tissue factor 🡪 Tissue factor binds and activates factor VII 🡪 cascade of reactions that culminates in thrombin generation. Thrombin cleaves circulating fibrinogen into insoluble fibrin, creating a fibrin meshwork, and also is a potent activator of platelets, leading to additional platelet aggregation at the site of injury. Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.118-120​ General sequence of hemostasis Clot stabilization and resorption Polymerized fibrin and platelet aggregates form a solid, permanent plug that prevents further hemorrhage. Counterregulatory mechanisms (e.g., tissue plasminogen activator [t-PA] made by endothelial cells) are set into motion that limit clotting to the site of injury and lead to clot resorption and tissue repair. Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.118-120​ Normal Hemostasis Endothelial cells are central regulators of hemostasis → the balance between the antithrombic and prothrombotic activities of endothelium determines whether thrombus formation, propagation, or dissolution occur. Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.118-120​ Platelets - Disc-shaped anucleate cell fragments from megakaryocytes in the bone marrow into the bloodstream. - Critical role in hemostasis by forming the primary plug that initially seals vascular defects and by providing a surface that binds and concentrates activated coagulation factors. - Their function depends on several glycoprotein receptors, a contractile cytoskeleton, and two types of cytoplasmic granules. Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.118-120​ Platelets adhesion and aggregation Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.118-120​ Coagulation Cascade Coagulation Cascade Definition: A series of amplifying enzymatic reactions that lead to the deposition of an insoluble fibrin clot. Part of secondary hemostasis. Leads to deposition of fibrin & consolidates the initial platelet plug. Based on assay performed in clinical laboratories: divided into extrinsic and intrinsic pathway. Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.120-124​  Clotting in Laboratory vs In Vivo Prothrombin time (PT) assay: assesses the function of the proteins in the extrinsic pathway (factors VII, X, V, II (prothrombin), and fibrinogen). Partial thromboplastin time (PTT) assay: * vit. K-dependent screens the function of the proteins in the intrinsic pathway (factors XII, XI, IX, VIII, X, V, II, and fibrinogen). Coagulation Cascade Important initiator → tissue factor. Most important anticoagulant factor → thrombin. Its most important activities are the following: ○ Conversion of fibrinogen into cross- linked fibrin ○ Platelet activation ○ Pro-inflammatory effects → to mediate pro-inflammatory effects that contribute to tissue repair and angiogenesis. ○ Anticoagulant effects (reversal in function prevents clots from extending beyond the site of the vascular injury. Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.120-124​  Factors that Limit Coagulation Coagulation must be restricted to the Expression of thrombomodulin on site of vascular injury to prevent normal endothelial cells, which binds & convert thrombin to an deleterious consequences. anticoagulant. Coagulation normally is restricted to Activation of fibrinolytic pathways sites of vascular injury by: (by association of tissue Limiting enzymatic activation to plasminogen activator [t-PA] with fibrin). phospholipid surfaces provided by activated platelets or endothelium. Circulating inhibitors of coagulation factors, such as antithrombin III, whose activity is augmented by heparin-like molecules expressed on endothelial cells. Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. p.120-124​ Endothelium Antithrombotic properties of endothelium: Anticoagulan Platelet inhibitory effects Procoagulant t As a barrier of platelets from subendothelial vWF and collagen. Release factors → prostacyclin (PGI2), nitric oxide (NO), and adenosine diphosphatase → inhibit platelet activation and aggregation. The balance often determines → clot formation / Anticoagulant effects propagation / dissolution. Shields coagulation factors from tissue Normal endothelial cells express: factor → in vessel walls. Anticoagulant factors (inhibit the platelet Expresses multiple factors → aggregation & coagulation process) → prevent thrombomodulin, endothelial protein C thrombosis, limit clotting to sites of vascular receptor, heparin-like molecules, tissue factor pathway inhibitor → bind thrombin → damage. thrombin lose its procoagulation function. In injury or exposed to pro-inflammatory factors: Fibrinolytic effects Endothelium lose many of their antithrombotic Synthesize t-PA (a key component of properties. fibrinolytic pathway). Endothelium Anticoagulant activities of normal endothelium Procoagulant properties of injured or activated endothelium Kumar V, Abbas AK, Aster JC, Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th ed. Philadelphia: Elsevier; 2021. Endothelial Injury Alterations in Hypercoagulabilit Fate of the Normal Blood y Thrombus Flow Endothelial injury leading to Turbulence contributes to Hypercoagulability refers to Thrombus development platelet activation almost arterial and cardiac an abnormally high tendency usually is related to one or more components of the inevitably underlies thrombus thrombosis by causing of the blood to clot, and is Virchow triad formation in the heart and the endothelial injury or typically caused by arterial circulation, where the dysfunction as well as by alterations in coagulation high rates of blood flow forming countercurrents that factors impede clot formation contribute to local pockets of stasis, whereas stasis is a major contributor to the development of venous thrombi Here it suffices to mention Turbulence and stasis Hypercoagulability has a If a patient survives the initial several of the major therefore: particularly important role in thrombosis, in the ensuing prothrombotic alterations: Promote endothelial venous thrombosis and can days to weeks thrombi Procoagulant changes. activation be divided into primary undergo some combination of Antifibrinolytic effects. Disrupt laminar flow (genetic) and secondary the following four events: Prevent washout and (acquired) disorders. Propagation dilution of activated clotting Embolization. factors Dissolution. Organization and Morphology of Thrombosis 1. Arterial Thrombosis - Turbulence / Endothelial Injury - Grow retrograde - Frequently Occlusive - These are usually happened on a ruptured atherosclerotic plaque / Source picts: Thrombosis (An Over other vascular injuries view): Causes, Symptoms & Diagno 1. Venous Thrombosis sis (myhematology.com) - Stasis - Extend in direction of blood flow - Occlusive - Consist of lines of Zahn - 90% involved at lower extremities Kumar V,Abbas AK,Aster JC,Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th.ed. Philadelphia: Elsevier;2021. p.128-129 Kumar V,Abbas AK,Aster JC,Turner JR. Robbins & Cotran Pathologic Basis of Disease. 10th.ed. Lines of Zahn: Philadelphia: Elsevier;2021. p.128-129 - Platelet, fibrin (pucat) - Tumpukan sel darah merah (merah gelap) Source pict: JaypeeDigital | Obstructive Circulatory Dis Dissaminated Intravascular Coagulation (DIC) Gando, S., Levi, M. & Toh, CH. Disseminated intravascular coagulation. Nat Rev Dis Primers 2, 16037 (2016). https://doi.org/10.1038/nrdp.2016.37 Dissaminated Intravascular Coagulation (DIC) Merupakan suatu keadaan dimana terjadinya trombosis yang tersebar pada seluruh pembuluh darah kecil Secara bersamaan terjadi proses fibrinolisis Menyebabkan penyumbatan pada pembuluh darah kecil dan berkurangnya faktor pembekuan yang diperlukan untuk mengendalikan perdarahan DIC bukanlah suatu penyakit primer, melainkan suatu komplikasi berbahaya dari berbagai keadaan yang berkaitan dengan aktivasi trombin Akibat yang Ditimbulkan oleh DIC Terjadi pengendapan fibrin yang tersebar luas dalam Terjadi diatesis perdarahan mikrosirkulasi Contoh Kondisi yang Memicu DIC Komplikasi Sepsis Trauma Kanker Kehamilan Infeksi berat, Cedera berat dapat Sel-sel tumor, Emboli cairan terutama yang menyebabkan terutama kanker ketuban, solusio disebabkan oleh pelepasan zat-zat pankreas dan plasenta, atau bakteri gram prokoagulan dari leukimia eklampsia, di negatif dan gram jaringan yang promyelositik mana produk- positif rusak akut, dapat produk janin atau melepaskan faktor plasenta masuk jaringan (TF) dan ke sirkulasi ibu zat prokoagulan dan memicu DIC lainnya SHOCK What is shock? Shock is a state of circulatory failure that impairs tissue perfusion and leads to cellular hypoxia.  3 General Categories of shock Cardiogenic: Myocardial pump Hypovolemic Sepsis. Septic failure🡪low shock: shock, and the cardiac output. Low blood volume🡪 inflammatory low cardiac output. response syndrome. Et causa: intrinsic myocardial damage Et causa: massive (infarction), hemorrhage, fluid ventricular loss from severe arrhytmias, extrinsic burns. compression. Septic shocks🡪 a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities🡪 greater risk of mortality. Systemic inflammatory response syndrome (SIRS)🡪 sepsis-like condition associated with systemic inflammation that may be triggered by variety of nonmicrobial insults🡪 burn, trauma. Sepsis🡪 life-threatening organ dysfunction et causa a dysregulated host response to infection. Major factors contributing to the pathophysiology of septic shock are following : 1. Inflammatory mediators. 2. Endothelial cell activation and injury. -Has 3 major sequele-thrombosis,increase vascular permiability,vasodilation 3. Metabolic abnormalities. -Septis patient exhibit insulin resistance and hyperglycemia. -Cytokines such as TNF & IL-1,stress induced hormone(glucagon,catecholamines)🡪gluconeogenesis. -At the same time the pro-inflammatory cytokines🡪suppress insulin 🡪resistance in the liver & other tissue🡪Hyperglycemia🡪reduced neutrophil function & bactericidal activity. 4. Organ disfunction. -Systemic hypotension, interstitialedema, microvascular dysfunction, and small vessel thrombosis🡪 the delivery of oxygen and nutrients to the tissues that, because of cellular hypoxia, fail to properly use those nutrients that are delivered🡪 failure of multiple organs.  STAGES OF SHOCK An initial non progressive stage In this phage a varieties of neuro-hormonal & haemostatic mechanism helps to maintain cardiac out- put & blood pressure. A progressive stage tissue hypoperfusion and onset of worsening circulatory and metabolic derangement, including acidosis. An irreversible stage in which cellular and tissue injury is so severe that even if the hemodynamic defects are corrected, survival is not possible. CLINICAL PRESENTATION OF SHOCK ⚫ Altered mental status-Restless,confusion,stupor,coma,agitation ⚫ Patient may unconscious or semi-conscious ⚫ Pallor ⚫ Increase sweating ⚫ Cold clammy skin. Warm in septic shock ⚫ Pulse-Tachycardia, rapid weak thready pulse ⚫ Respiration-Tachypnia, slow and regular ⚫ Blood pressure-low blood pressure ⚫ Temperature may or may not be raised ⚫ Dehydration ⚫ Reduce urine output