Hemodynamic Disorders - PDF

Hemodynamic Disorders. Morphological indicators: thromboembolic disease, shock, and disseminated intravascular coagulation (DIC). Jakub Jóźwicki, MD PhD  Introduction to Circulatory Health Key Functions of Circulation: Delivers oxygen and nutrients. Removes metabolic...

Hemodynamic Disorders. Morphological indicators: thromboembolic disease, shock, and disseminated intravascular coagulation (DIC). Jakub Jóźwicki, MD PhD  Introduction to Circulatory Health Key Functions of Circulation: Delivers oxygen and nutrients. Removes metabolic waste products. Normal Capillary Dynamics: Minimal net movement of water/electrolytes into tissues. Pathologic Disruptions: Altered endothelial function. Increased vascular hydrostatic pressure. Decreased plasma protein content. Edema – Definition and Implications What is Edema? Accumulation of fluid in tissues. Caused by water movement into extravascular spaces. Impact of Edema: Mild: Swelling in lower extremities after prolonged inactivity. Severe: Pulmonary edema causing alveolar fluid accumulation → Life-threatening hypoxia. Hemostasis and Vascular Integrity Role of Hemostasis: Blood clotting process post vascular damage. Consequences of Inadequate Hemostasis: Hemorrhage (Excessive bleeding): ○ Tissue perfusion compromise. ○ Potential for hypotension, shock, and death. Thrombosis (Inappropriate clotting): ○ Formation of obstructive clots in blood vessels. Embolism (Clot migration): ○ Potential for ischemic cell death (infarction). Clinical Relevance of Thromboembolism Major Outcomes of Thromboembolism: Myocardial infarction. Pulmonary embolism. Cerebrovascular accident (stroke). Significance: Among the leading causes of morbidity and mortality worldwide. Hemodynamic Disorders Overview Focus Areas: Conditions increasing blood volumes. Impact on local and systemic circulatory systems. Next Steps in Discussion: Pathophysiological mechanisms. Clinical presentations and implications. Hyperemia and Congestion – Overview Definition: Both refer to increased blood volume in tissue but differ in mechanisms. Hyperemia (Active Process): Caused by arteriolar dilation → increased blood inflow. Common during inflammation or in exercising skeletal muscle. Appearance: Bright red due to oxygenated blood. Congestion (Passive Process): Caused by impaired venous outflow. Common in systemic cardiac failure or localized venous obstruction. Appearance: Blue-red (cyanotic) due to deoxygenated hemoglobin. Clinical Consequences of Congestion Acute vs. Chronic Congestion: Acute: ○ Impaired venous drainage → capillary rupture and edema. Chronic: ○ Persistent hypoxia → parenchymal cell death, fibrosis. ○ Elevated pressures → capillary rupture → focal hemorrhages. Systemic Effects: Chronic congestion may affect the lungs and liver, causing tissue remodeling and functional impairment. Morphology of Hyperemia and Congestion General Characteristics: Wet cut surfaces, oozing blood. Microscopically: Variable edema and hemorrhage. Acute Pulmonary Congestion: Blood-engorged alveolar capillaries. Alveolar septal edema and intraalveolar hemorrhage. Chronic Pulmonary Congestion: Thickened and fibrotic alveolar septa. Presence of “heart failure cells” (macrophages with hemosiderin). Chronic Hepatic Congestion Acute Hepatic Congestion: Distension of central vein and sinusoids. Central hepatocyte necrosis; fatty changes in periportal hepatocytes. Chronic Passive Liver Congestion: "Nutmeg Liver": ○ Central regions: Red-brown and depressed (necrosis, cell loss). ○ Periportal regions: Tan, may exhibit fatty changes. Morphological Highlights: Contrast between congested and non-congested areas is prominent. Key Histological Features “Heart Failure Cells”: ○ Hemosiderin-laden macrophages in alveolar spaces. ○ Derived from phagocytosed red cells leaking from congested capillaries. Liver Morphology: ○ Red-brown congested zones vs. tan periportal hepatocytes. ○ Reflects chronic venous congestion and ischemia. Overview of Edema Definition: Accumulation of interstitial fluid within tissues. Distribution: Interstitial fluid → Edema. Body cavities → Effusion: ○ Hydrothorax: Pleural cavity. ○ Hydropericardium: Pericardial cavity. ○ Ascites (Hydroperitoneum): Peritoneal cavity. Severe Cases: Anasarca: Generalized edema with profound swelling and fluid accumulation. Causes of Edema Increased Hydrostatic Pressure Impaired venous return: ○ Systemic: Congestive heart failure, constrictive pericarditis, liver cirrhosis. ○ Localized: Venous obstruction (thrombosis, external pressure). Arteriolar dilation: Heat, neurohumoral dysregulation. 2. Reduced Plasma Osmotic Pressure (Hypoproteinemia) Causes: ○ Protein loss (nephrotic syndrome, gastroenteropathy). ○ Reduced synthesis (liver disease, malnutrition). 3. Lymphatic Obstruction Causes: Inflammation, neoplasia, postsurgical/irradiation effects. 4. Sodium and Water Retention Mechanism: Renal hypoperfusion, increased renin-angiotensin-aldosterone activation. 5. Inflammation Acute, chronic, or due to angiogenesis. Mechanisms of Edema Formation Fluid Movement Regulation: Hydrostatic Pressure: Drives fluid out of capillaries. Colloid Osmotic Pressure: Pulls fluid into capillaries. Normal balance → Minimal interstitial fluid. Edema Formation: Increased hydrostatic pressure or reduced osmotic pressure. Lymphatic drainage overwhelmed → Fluid accumulates. Types of Edema Fluid: Transudate: Protein-poor (e.g., from hydrostatic imbalance). Exudate: Protein-rich (e.g., from inflammation). Clinical Types of Edema Subcutaneous Edema: Most pronounced in dependent areas (legs/sacrum). Pitting Edema: Finger pressure leaves a depression. Indicates underlying cardiac/renal disease. 2. Pulmonary Edema: Causes: Left ventricular failure, renal failure, acute lung injury. Morphology: ○ Frothy, blood-tinged fluid. Clinical Effects: ○ Impaired ventilation, increased risk of infection. 3. Brain Edema: Causes: Localized (abscess/tumor) or generalized injury. Morphology: ○ Narrowed sulci, flattened gyri. Clinical Effects: ○ Increased intracranial pressure, risk of herniation, and brain stem vascular compromise. Pathophysiology in Specific Conditions 1. Congestive Heart Failure: Pathway: ○ Reduced cardiac output → Venous pooling → Increased hydrostatic pressure. ○ Kidney hypoperfusion → Renin-angiotensin-aldosterone activation → Sodium/water retention → Worsening edema. Management: ○ Salt restriction, diuretics, aldosterone antagonists. 2. Reduced Plasma Osmotic Pressure: Causes: ○ Albumin loss (nephrotic syndrome). ○ Decreased synthesis (liver cirrhosis, malnutrition). Consequences: ○ Edema, hypoperfusion, secondary hyperaldosteronism. 3. Lymphatic Obstruction: Examples: ○ Elephantiasis: Fibrosis of lymphatics from filariasis. ○ Peau d’orange: Breast cancer obstruction. Morphological Features of Edema Gross Inspection: Subcutaneous swelling, dependent regions. Frothy fluid in lungs, narrowed sulci in brain. Microscopic Features: Separation of extracellular matrix. Presence of transudate or exudate. Clinical Implications Subcutaneous Edema: Indicator of systemic diseases (cardiac, renal). Impaired wound healing. Pulmonary Edema: Life-threatening, predisposes to infections. Brain Edema: Risk of herniation, vital function compromise, death. Overview of Hemorrhage Definition: Extravasation of blood from vessels. Causes: Trauma. Atherosclerosis. Inflammatory or neoplastic vessel wall erosion. Chronic capillary bleeding in congested tissues. Exacerbating Factors: Hemorrhagic diatheses: Defects in vessel walls, platelets, or coagulation factors. Forms of Hemorrhage External Bleeding vs. Internal Accumulation: Hematoma: ○ Trivial: Bruises. ○ Fatal: Retroperitoneal hematoma (e.g., aortic aneurysm rupture). Large Cavity Hemorrhages: ○ Hemothorax: Thoracic cavity. ○ Hemopericardium: Pericardial cavity. ○ Hemoperitoneum: Peritoneal cavity. ○ Hemarthrosis: Joints. Jaundice: Large hemorrhages → Hemoglobin breakdown → Bilirubin accumulation. Types of Hemorrhages 1. Petechiae: Minute hemorrhages (1–2 mm). Causes: ○ Thrombocytopenia. ○ Defective platelet function. ○ Vitamin C deficiency (scurvy). 2. Purpura: Slightly larger hemorrhages (3–5 mm). Causes: ○ Same as petechiae, plus trauma, vasculitis, and vascular fragility. 3. Ecchymoses: Large subcutaneous hematomas (1–2 cm, "bruises"). Color Progression: ○ Hemoglobin (red-blue) → Bilirubin (blue-green) → Hemosiderin (golden-brown). Clinical Impact of Hemorrhage Factors Affecting Severity: Volume and rate of blood loss. Bleed location. Individual health status. Tolerated Loss: Healthy adults: Up to 20% blood volume. Greater losses: Risk of hemorrhagic (hypovolemic) shock. Location-Specific Effects: Subcutaneous: Often trivial. Brain: Potentially fatal (e.g., intracerebral hemorrhage). Chronic vs. Acute Blood Loss Chronic/Recurrent Blood Loss: Examples: Peptic ulcers, menstrual bleeding. Consequence: Iron deficiency anemia (loss of hemoglobin iron). Internal Bleeding: Example: Hematomas. No iron deficiency: Efficient iron recycling from phagocytosed red cells. Morphological Examples Petechial Hemorrhages: Example: Colonic mucosa in thrombocytopenia (Fig. 3.4A). Intracerebral Hemorrhage: Fatal outcomes due to pressure on vital brain structures (Fig. 3.4B). Overview of Hemostasis and Thrombosis Hemostasis: ○ Normal process to prevent blood loss after vascular injury. ○ Involves platelets, clotting factors, and endothelium. Thrombosis: ○ Pathologic formation of a clot (thrombus) within vessels. ○ Occurs in vessels damaged by disease processes. Steps in Hemostasis Arteriolar Vasoconstriction Immediate response to vascular injury. Mechanism: ○ Neurogenic reflexes. ○ Local release of endothelin (vasoconstrictor). Effect: ○ Reduces blood flow transiently; requires further hemostatic activation. 2. Primary Hemostasis: Platelet Plug Formation Initiation: ○ Endothelial disruption → Exposure of subendothelial collagen. ○ von Willebrand factor (vWF) binds collagen and promotes platelet adhesion. Platelet Activation: ○ Shape change (flat plates with spiky protrusions). ○ Granule release (e.g., ADP, thromboxane A2). Aggregation: ○ Platelets recruited and adhere via fibrinogen and GpIIb-IIIa receptors. ○ Formation of a primary hemostatic plug. Secondary Hemostasis: Fibrin Deposition Tissue Factor Activation: Exposed at injury site (on smooth muscle cells and fibroblasts). Activates Factor VII → Initiates coagulation cascade. Thrombin Generation: Cleaves fibrinogen → Insoluble fibrin. Promotes further platelet aggregation. Result: Formation of a fibrin meshwork. Consolidates the platelet plug into a stable structure. Clot Stabilization Processes: ○ Fibrin Crosslinking: Covalent bonds formed by Factor XIII. ○ Platelet Contraction: Solidifies the clot structure. Outcome: ○ Formation of a permanent hemostatic plug. ○ Prevents further bleeding. Regulation: ○ Counterregulatory mechanisms: Restrict clotting to injury site. Promote clot resorption and tissue repair. Role of Endothelium in Hemostasis Anticoagulant Functions (Healthy Endothelium): Inhibits platelet aggregation. Prevents coagulation. Promotes fibrinolysis. Procoagulant Functions (Injury/Activation): Shifts balance to favor clot formation. Triggers for Activation: Microbial pathogens. Hemodynamic forces. Proinflammatory mediators. Clinical Relevance Hemostasis: Essential to prevent excessive bleeding after injury. Thrombosis: Risk of obstruction, ischemia, and tissue damage. Common in conditions with endothelial dysfunction (e.g., inflammation, atherosclerosis). Overview of Platelets in Hemostasis Role of Platelets: Form primary plug sealing vascular defects. Provide a surface for activated coagulation factors. Origin: Anucleate cell fragments derived from megakaryocytes. Key Components: Glycoprotein receptors. Contractile cytoskeleton. Two granule types: ○ α-Granules: Adhesion molecules (e.g., P-selectin), coagulation factors (fibrinogen, factor V, vWF), and wound healing proteins (PDGF, TGF-β). ○ Dense Granules: ADP, ATP, calcium, serotonin, epinephrine. Platelet Activation Sequence Platelet Adhesion: Mediated by vWF acting as a bridge between: ○ GpIb receptor on platelets. ○ Exposed collagen in subendothelial connective tissue. Genetic Defects: ○ Von Willebrand Disease: Deficiency of vWF. ○ Bernard-Soulier Syndrome: Deficiency of GpIb receptor. 2. Shape Change: Platelets become spiky, increasing surface area. GpIIb/IIIa receptors increase affinity for fibrinogen. Negatively charged phospholipids (e.g., phosphatidylserine) translocate to the surface: ○ Bind calcium. ○ Nucleation sites for coagulation factor complexes. Platelet Activation Triggered by: Thrombin: Activates via protease-activated receptor (PAR). ADP: Released from dense granules, recruits more platelets. Granule Secretion: Release of ADP, calcium, and thromboxane A2 (TxA2). TxA2: Potent inducer of platelet aggregation. Aspirin Mechanism: ○ Inhibits cyclooxygenase → Prevents TxA2 synthesis → Reduces aggregation. Growth Factor Contribution: PDGF promotes vessel wall repair. Platelet Aggregation Mechanism: Activated GpIIb/IIIa binds fibrinogen: ○ Forms bridges between platelets. Initial aggregation is reversible. Stabilization: Thrombin: ○ Promotes irreversible aggregation. ○ Converts fibrinogen → Insoluble fibrin. Fibrin crosslinking (via Factor XIIIa) consolidates the plug. Cytoskeleton: Platelet contraction strengthens aggregated platelets. Hemostatic Plug Components: Platelets. Fibrin mesh. Entrapped red cells and leukocytes: ○ Leukocytes adhere to P-selectin on activated platelets. Result: Definitive secondary hemostatic plug. Clinical Correlations Disorders of Platelet Function: ○ Von Willebrand Disease: Impaired adhesion. ○ Bernard-Soulier Syndrome: Defective GpIb receptor. ○ Glanzmann Thrombasthenia: Deficiency of GpIIb/IIIa receptor → Aggregation failure. Therapeutic Interventions: ○ Aspirin: Reduces aggregation by inhibiting TxA2 synthesis. ○ Platelet-related therapies in bleeding disorders. Overview of Coagulation Factors Role in Hemostasis: Series of enzymatic reactions leading to fibrin clot deposition. Components of Each Reaction: Enzyme: Activated coagulation factor. Substrate: Inactive proenzyme. Cofactor: Reaction accelerator. Assembly: On negatively charged phospholipid surfaces (platelets). Requires calcium and γ-carboxylated glutamic acid (Vitamin K-dependent). Coagulation Pathways Extrinsic Pathway: Test: Prothrombin Time (PT). Factors Assessed: X, VII, V, II (prothrombin), fibrinogen. Initiation: Tissue factor, phospholipids, and calcium. 2. Intrinsic Pathway: Test: Partial Thromboplastin Time (PTT). Factors Assessed: XII, XI, IX, VIII, X, V, II, fibrinogen. Initiation: Negatively charged particles (e.g., glass), phospholipids, and calcium. In Vivo vs. In Vitro Coagulation 1. In Vitro: Cascade driven by either intrinsic or extrinsic factors. 2. In Vivo: Tissue Factor-Factor VIIa Complex: Key activator of Factor IX. Factor IXa/VIIIa Complex: Activates Factor X. Thrombin Feedback: ○ Amplifies cascade by activating Factors V, VIII, XI. ○ Converts fibrinogen into fibrin. Key Coagulation Factor – Thrombin Central Role in Hemostasis: Fibrin Formation: Converts fibrinogen to crosslinked fibrin. Platelet Activation: Induces activation, aggregation, and contraction via PARs. Cascade Amplification: Activates Factors V, VIII, XI. Fibrin Stabilization: Activates Factor XIII for fibrin crosslinking. Broader Effects: Inflammation and Repair: PARs on inflammatory and endothelial cells. Anticoagulant Effects: ○ On normal endothelium, thrombin limits clot extension. Clinical Implications 1. Coagulation Factor Deficiencies: Severe Bleeding: ○ Deficiency in Factors V, VII, VIII, IX, X, or prothrombin. Mild Bleeding: ○ Factor XI deficiency. No Bleeding Disorder: ○ Factor XII deficiency (but may cause angioedema via bradykinin generation). 2. Vitamin K Dependency: Factors II, VII, IX, X depend on γ-carboxylation (Vitamin K). Warfarin Therapy: ○ Antagonizes Vitamin K → Reduces clotting. 3. Laboratory Assays: PT: Evaluates extrinsic pathway. PTT: Evaluates intrinsic pathway. Both essential for assessing coagulation function. Coagulation Cascade Summary Sequential Activation: ○ Factor IXa/Factor VIIIa Complex: Activates Factor X. ○ Factor Xa/Factor Va Complex: Converts prothrombin to thrombin. Essential Components: ○ Phospholipid surfaces, calcium, and cofactors. Factors That Limit Coagulation Importance of Regulation: Prevent coagulation from spreading beyond the injury site. Key Mechanisms: Dilution: ○ Blood flow washes away activated coagulation factors. ○ Factors removed by the liver. Requirement for Phospholipids: ○ Provided by activated platelets only at the injury site. Endothelial Counterregulation: ○ Intact endothelium adjacent to the injury inhibits coagulation. Fibrinolytic Cascade Role: Limits clot size and facilitates clot dissolution. Key Enzyme: Plasmin: ○ Breaks down fibrin. ○ Prevents fibrin polymerization. Clinical Marker: D-dimers: Breakdown products of fibrin; indicate thrombotic activity. Activation and Control of Plasmin Plasminogen Activation: Plasminogen: Inactive precursor circulating in blood. Activators: ○ Tissue Plasminogen Activator (t-PA): Synthesized by endothelium. Most active when bound to fibrin → Localized fibrinolysis. ○ Urokinase. Control of Plasmin: α2-Plasmin Inhibitor: ○ Rapidly inactivates free plasmin in circulation. Endothelial Regulation of Fibrinolysis Endothelial-Derived Regulators: Plasminogen Activator Inhibitors (PAIs): ○ Negative regulators of plasmin activity. ○ Prevent excessive fibrinolysis. Therapeutic Applications: t-PA as a Drug: ○ Targets clots due to fibrin specificity. ○ Used for thrombolytic therapy. Thrombin’s Role in Regulation Procoagulant Effects: Cleaves fibrinogen → Fibrin. Activates Factor XIII → Fibrin crosslinking. Cellular Activation via PARs: Platelets: ○ TxA2 secretion, aggregation, and degranulation. Endothelium: ○ Generates adhesion molecules. Leukocytes: ○ Enhances adhesion to endothelium. Anticoagulant Effects: On intact endothelium, thrombin prevents clot extension. Clinical Significance Diagnostic Marker: D-dimer Testing: ○ Elevated levels signal active thrombosis or fibrinolysis. Therapeutic Implications: t-PA and Fibrinolytics: ○ Effective for localized thrombus dissolution. Plasmin Control: ○ Balance between clot stability and dissolution. Overview of Endothelium in Hemostasis Key Role: ○ Balance between anticoagulant and procoagulant activities determines clot formation, propagation, or dissolution. Antithrombotic Activities: ○ Directed toward: Platelets: Inhibition of activation and aggregation. Coagulation Factors: Prevention of clotting. Fibrinolysis: Promotion of clot dissolution. Platelet Inhibitory Effects Physical Barrier: Shields platelets from subendothelial vWF and collagen. Key Inhibitors: Prostacyclin (PGI2) and Nitric Oxide (NO): ○ Inhibit platelet activation and aggregation. ○ Promote vasodilation and washout of coagulation factors. Adenosine Diphosphatase: ○ Degrades ADP, preventing platelet activation. Thrombin Binding: Endothelial cells inhibit thrombin’s platelet-activating ability. Anticoagulant Effects Protection Against Coagulation: Shields coagulation factors from tissue factor in vessel walls. Key Anticoagulant Molecules: Thrombomodulin: ○ Binds thrombin → Converts thrombin to an anticoagulant enzyme. ○ Activates protein C → Inhibits Factors Va and VIIIa (requires Protein S). Endothelial Protein C Receptor: ○ Enhances activation of Protein C. Heparin-Like Molecules: ○ Activate antithrombin III → Inhibits thrombin and Factors IXa, Xa, XIa, XIIa. Tissue Factor Pathway Inhibitor (TFPI): ○ Requires Protein S. ○ Inhibits Tissue Factor/Factor VIIa complexes. Fibrinolytic Effects Key Enzyme: Tissue Plasminogen Activator (t-PA): ○ Synthesized by endothelial cells. ○ Activates plasminogen → Plasmin. ○ Localized fibrinolysis at the clot site. Antithrombotic Effects Clinical Relevance Therapeutic Implications: Heparin: Enhances antithrombin activity. t-PA: Fibrinolytic agent targeting clots. Pathological Considerations: Loss of endothelial antithrombotic properties → Increased risk of thrombosis Virchow’s Triad and Endothelial Integrity Virchow’s Triad: Endothelial Integrity: Most critical factor in thrombosis. Abnormal Blood Flow: ○ Stasis or turbulence → Endothelial dysfunction. Hypercoagulability: Induced by procoagulant shifts. Key Takeaway: Endothelial health is pivotal in preventing thrombosis. Overview of Thrombosis Definition: Formation of a blood clot (thrombus) within the vascular system. Key Underlying Abnormalities (Virchow’s Triad, Fig. 3.12): Endothelial injury. Abnormal blood flow (stasis or turbulence). Hypercoagulability of the blood. Endothelial Injury and Thrombosis Role of Endothelial Injury: Triggers platelet activation and thrombus formation. Particularly important in arterial and cardiac thrombi. Mechanisms: Severe injury → Exposure of vWF and tissue factor. Endothelial activation/dysfunction from: ○ Physical injury. ○ Infections. ○ Cytokines and inflammatory mediators. ○ Metabolic abnormalities (e.g., hypercholesterolemia, homocystinemia). ○ Toxins (e.g., cigarette smoke). Prothrombotic Changes: Downregulation of thrombomodulin, endothelial protein C receptor, and tissue factor pathway inhibitor. Increased secretion of plasminogen activator inhibitors (PAIs). Abnormal Blood Flow Mechanisms: ○ Turbulence: Causes endothelial injury and dysfunction. Forms countercurrents and pockets of stasis. ○ Stasis: Slows washout of clotting factors. Allows platelet-endothelium interaction. Examples of Abnormal Blood Flow: ○ Atherosclerotic plaques: Expose ECM and cause turbulence. ○ Aneurysms: Local stasis promotes thrombosis. ○ Atrial fibrillation: Combines stasis and turbulence. ○ Hyperviscosity (e.g., polycythemia vera): Increases resistance and stasis. Hypercoagulability Definition: ○ Increased tendency of blood to clot due to altered coagulation factors. Types: ○ Primary (Genetic): Factor V Leiden (Arg506Glu mutation): Resistant to protein C cleavage. Increased venous thrombosis risk (3-50x). Prothrombin G20210A mutation: Increased prothrombin expression. 3x increased venous thrombosis risk. Rare Deficiencies: Antithrombin, Protein C, Protein S. Homozygous homocystinuria. ○ Secondary (Acquired): High-risk states (e.g., surgery, cancer, immobilization). Moderate-risk states (e.g., pregnancy, oral contraceptives, smoking). Clinical Syndromes of Hypercoagulability 1. Heparin-Induced Thrombocytopenia (HIT): Mechanism: ○ Antibodies against heparin-PF4 complexes activate platelets. ○ Paradoxical prothrombotic state despite low platelet count. Associated with: ○ Unfractionated heparin > Low molecular weight heparins. 2. Antiphospholipid Antibody Syndrome: Clinical Features: ○ Recurrent thrombosis, pregnancy loss, cardiac valve vegetations. ○ Renal microangiopathy → Renal failure. Mechanism: ○ Antibodies target β2-glycoprotein I or other proteins bound to phospholipids. Types: ○ Primary: Hypercoagulable state without autoimmune disease. ○ Secondary: Associated with systemic lupus erythematosus. Therapy: ○ Anticoagulation and immunosuppression. Genetic Testing and Thrombosis Factor V Leiden and Prothrombin Mutation Testing: Indicated in: ○ Young patients (90% survival with proper treatment. Septic/Cardiogenic Shock: Poorer outcomes. Management: 1. Immediate Interventions: ○ Restore circulation: IV fluids, vasopressors. ○ Treat underlying cause: Antibiotics for sepsis, surgery for hemorrhage. 2. Supportive Care: ○ Oxygenation, electrolyte management, DIC treatment. 3. Long-Term Care: ○ Monitor for organ dysfunction and systemic complications. Summary Shock is a life-threatening condition requiring early recognition and rapid intervention. Key Takeaways: Understanding pathogenesis and clinical stages guides effective treatment. Prevention and management of complications (e.g., sepsis, DIC) are critical to improve outcomes.