Fluid & Hemodynamic Derangements PDF

Fluid & Hemodynamic Derangements Dr. Henry Sánchez, M.D. 1  Hemostasis To thoracic duct and eventually to left subclavian vein Increased interstit...

Fluid & Hemodynamic Derangements Dr. Henry Sánchez, M.D. 1  Hemostasis To thoracic duct and eventually to left subclavian vein Increased interstitial Hydrostatic pressure fluid pressure Shock Edema Congestion Thrombus Plasma colloid osmotic pressure Embolus Arterial end CAPILLARY BED Venous end Hemorrhage Infarct 2  Edema Injury to endothelial cells/blood vessel wall Increase hydrostatic pressure Increase interstitial sodium Decrease colloid osmotic pressure (albumin) Lymphatic obstruction 3  Edema Formation To thoracic duct and eventually to left subclavian vein 5 Increased interstitial + Hydrostatic pressure H 2O Na fluid pressure Na+ H2 O + Na+ H2O H2O Na Na+ 3 Na+ Na + Na+ H 2O H 2O 1 H 2O H 2O H 2O H2O Na+ + Na Plasma colloid 2 Na+ Na+ osmotic pressure Hydrostatic pressure Albumin 4 Albumin Arterial end CAPILLARY BED Venous end 4  Edema Local Acute inflammation, urticaria, venous thrombosis, left-sided heart failure Systemic (anasarca) Heart - congestive heart failure Liver - cirrhosis Kidney - nephrotic syndrome Iatrogenic - fluid resuscitation 5  Anasarca MALNUTRITION, HEPATIC SYNTHESIS, NEPHROTIC SYNDROME HEART FAILURE Plasma oncotic pressure Central venous Cardiac output Blood volume pressure Effective arterial blood volume ASCITES, Capillary OTHER EFFUSIONS pressure Renal vasoconstriction Renin Aldosterone Tubular GFR reabsorption of Na+ + H2O Angiotensin II Renal Na+ ADH reabsorption Renal retention Renal retention of Na+ + H2O of water PRIMARY RENAL FAILURE Plasma volume Transudation EDEMA 6 Congestive Heart Failure Pitting Edema 7  Circulation Pathology Effusion: fluid within the body cavities Transudate versus exudate Transudate - edema fluid with low protein content Specific gravity 1.020 Types of exudates Purulent (pus) Fibrinous Eosinophilic Hemorrhagic 8  Congestion Definition: Dilated blood vessel Passive congestion (e.g., mechanical effect - congestive heart failure, venous thrombosis) Active congestion (hyperemia) - acute inflammation, hypersensitivity reaction type I 9  NORMAL Venule Arteriole HYPEREMIA erythema Increased inflow Congestion (e.g., exercise, inflamation) CONGESTION cyanosis/hypoxia Decreased outflow (e.g., local obstruction, congestive heart failure) 10 Nutmeg 11 Chronic Passive Congestion “Nutmeg liver” 12 Chronic Passive Congestion 13  Hemostasis Definition: sequence of events leading to the cessation of bleeding by the formation of a stable fibrin-platelet hemostatic plug Vascular Wall Platelets Coagulation cascade 14  Hemostasis Vascular Wall Endothelial lining - endothelial cells contain: Potent thrombogenic tissue factor (tissue thromboplastin), decreased blood flow, von Willebrand factor, thromboxane A2 Anti-thrombogenic substances (tissue plasminogen activator, anti-platelet aggregating prostaglandins - prostacyclin, nitric oxide, thrombomodulin) 15  FAVOR THROMBOSIS INHIBIT THROMBOSIS Inactivates thrombin and factors Xa and IXa Extrinsic coagulation sequence Proteolysis of factors Va and VIIIa Active protein C Protein C Fibrinolytic cascade Thrombin Exposure of Inactivates tissue Inhibit platelet membrane-bound factors VIIa and Xa aggregation tissue factor Platelet adhesion: Antithrombin III Thrombin Held together vWF PGI2, NO, and by fibrinogen adenosine diphosphate t-PA Endothelial effects Thrombomodulin Heparin-like Thrombin Endothelium Collagen molecule receptor Tissue factor pathway inhibitor 16  Hemostasis Vascular wall Subendothelial connective tissue Promotes platelet adherence and release reactions 17  Hemostasis Vascular wall Muscular layer Constriction of blood vessels induced by pain reflexes and vasoactive amines (histamine and serotonin) Dependent upon the amount of muscular tissue composing the vascular wall 18  Hemostasis Platelets Circulating platelets = 150k to 400k per mm3 Derived from megakaryocytes in the bone marrow Thrombocytopenia = decreased number of platelets Decreased production Increased destruction 19  Platelets Derived from megakaryocytes in the bone marrow Step 1: platelet adhesion First vWF adheres to subendothelial collagen Platelets then adhere to vWF by glycoprotein Ib Step 2: platelet activation Platelets undergo a shape change and degranulation occurs Platelet synthesis of thromboxane A2 Membrane expression of the phospholipid complex, which is an important platform for the coagulation cascade Step 3: platelet aggregation Additional platelets are recruited from the blood stream ADP and thromboxane A2 are potent mediators of aggregation Platelets bind to each other by binding to fibrinogen using Gp IIb-IIIa 20 21 Fibrin-platelet thrombus 22 Peripheral Blood Smear: Schistocyte Microangiopathic Hemolytic Anemia 23 Laboratory Tests for Platelets Platelet count (normal 150 to 400K/mm3) Bleeding time test (normal 2 to 7 minutes) Platelet aggregometry 24 25  Deficiency: Bernard-Soulier syndrome Deficiency: GpIb Glanzmann thrombasthenia Platelet GpIIb-IIIa Fibrinogen complex GpIb Endothelium ADP induces conformational change von Willebrand factor Deficiency: von Willebrand Subendothelium disease 26 Immune Thrombocytopenia Purpura (ITP) Etiology Antiplatelet antibodies against platelet antigens such as Gp IIb-IIIa and Gp Ib-IX Antibodies are made in the spleen Platelets are destroyed peripherally in the spleen by macrophages, which have Fc receptors that bind IgG- coated platelets 27 Purpura (“purple”) 28 Immune Thrombocytopenia Purpura (ITP) Forms of ITP Acute ITP Seen in children following a viral infection Self-limited disorder Chronic ITP Usually seen in women in their childbearing years May be the first manifestation of systemic lupus erythematosus (SLE) and AIDS Petechiae, ecchymoses, menorrhagia, and nosebleeds 29 Immune Thrombocytopenia Purpura (ITP) Lab Decreased platelet count and prolonged bleeding time Normal prothrombin time (PT) and partial thromboplastin time (PTT) Peripheral blood smear shows thrombocytopenia with enlarged immature platelets (megathrombocytes) Bone marrow biopsy shows increased numbers of megakaryocytes with immature forms 30 Immune Thrombocytopenia Purpura (ITP) Treatment Corticosteroids, which decrease antibody production Immunoglobulin therapy, which binds Fc receptors on splenic macrophages Splenectomy, which removes the site of platelet destruction and antibody production 31 Thrombotic Thrombocytopenic Purpura (TTP) Pathology Widespread formation of fibrin-platelet thrombi (hyaline thrombi) Deficiency of a plasma metalloprotease (ADAMTS13) Clinical presentation Most often affects adult women Pentad of characteristic signs Fever Thrombocytopenia Microangiopathic hemolytic anemia Neurologic symptoms Renal failure 32 Thrombotic Thrombocytopenic Purpura (TTP) Labs Decreased platelet count and prolonged bleeding time Normal PT and PTT Peripheral blood smear shows thrombocytopenia and schistocytes, and reticulocytosis 33 Hemolytic Uremic Syndrome (HUS) Example of thrombotic microangiopathy Occurs most commonly in children Follows a gastroenteritis with bloody diarrhea Organism: verotoxin-producing E. coli 0157:H7 Similar clinical pentad 34 Kidney: Thrombotic Microangiopathy 35  Hemostasis Coagulation Intravascular transformation of fluid blood into a gel matrix entrapping cellular constituents (red blood cells and white blood cells) Coagulation factors Majority of the clotting factors are synthesized by the liver Pro-enzymes that must be converted to the active form Some conversions occur on a phospholipid surface Some conversions require calcium 36  Hemostasis Coagulation Intrinsic system All substrates necessary for clotting are present within the circulating blood Activated by contact with a foreign surface - usually collagen, Ag-Ab complexes, glass, etc. Contact-sensitive protein is Hageman factor (factor XII) 37  Hemostasis Coagulation Extrinsic system After tissue injury, phospholipid protein complex (tissue thromboplastin) is released into the circulating blood Activating the extrinsic pathway (inactive factor VII to active factor VII) 38  COAGULATION CASCADE Endothelial Cell Injury INTRINSIC PATHWAY (Hageman Factor) XII EXTRINSIC PATHWAY or Collagen, etc. Cofactor: HMWK ct Fa e su s Kallikrein Ti XIIa VII Prekallikrein Kallikrein XI IX X VIIa XIa or ct Fa Thrombin Ca2+ e su s Ti IIa IXa VIII VIIIa Ca2+ Xa IIa Phospholipid Bilayer V Va Ca2+ Surface XIII Prothrombin Thrombin II IIa Ca2+ Ca2+ XIIIa I Ia Fibrinogen Fibrin Cross-linked Fibrin COMMON PATHWAY © HCS 2018 39  Coagulation Active coagulation factor (enzyme) Phospholipid Inactive coagulation surface factor (substrate) Cofactor VIIIa Ca2+ ions Activated factor X (Xa) Cofactor Va 40  Fibrinolysis 2 -antiplasmin 2 -antiplasmin/plasmin complexes Plasminogen Activator Inhibitors (PAI) Free plasmin Thrombin Fibrin degradation Tissue Plasminogen Fibrin products Activator (tPA) clot and Urokinase Plasminogen Platelets Plasmin Endothelium 41  Laboratory Tests for Coagulation Prothrombin time (PT) - (normal range: 10-15 seconds) Tests the extrinsic and common coagulation pathways - VII, X,V, prothrombin, fibrinogen Partial thromboplastin time (PTT) - (normal range: 25-35 seconds) Tests the intrinsic and common coagulation pathways - XII, XI, IX,VIII, X,V, prothrombin, fibrinogen Thrombin time (TT) tests for adequate fibrinogen levels - (normal range: 9-13 seconds) Fibrin degradation products (FDP) tests the fibrinolytic system (increased with DIC) 42 VASOCONSTRICTION Endothelium Basement membrane Arteriole smooth muscle Site of injury Endothelin release Reflex ECM (collagen) causes vasoconstriction vasoconstriction 43 PRIMARY HEMOSTASIS 2 Shape change 4 Recruitment 3 Granule release 1 Platelet adhesion (ADP, TXA2) Aggregation (hemostatic vWF 5 plug) Endothelium Basement membrane Collagen 44 SECONDARY HEMOSTASIS 2 Phospholipid complex expression 3 Thrombin activation 4 Fibrin polymerization 1 Tissue factor Tissue factor 1 Fibrin 45 THROMBUS AND ANTITHROMBOTIC EVENTS Release of: Trapped neutrophil t-PA (fibrinolysis) Trapped red thrombomodulin blood cells (blocks coagulation cascade) Polymerized fibrin 46  Hemophilia A (classic hemophilia) Deficiency of factor VIII X-linked recessive Clinical features Predominately affects males and symptoms are variable dependent on the degree of deficiency Spontaneous hemorrhages into joints (hemarthrosis) Easy bruising and hematoma formation after minor trauma Severe prolonged bleeding after surgery or lacerations Petechiae or ecchymoses can occur 47  Hemophilia A Labs Normal platelet count and bleeding time Normal PT and prolonged PTT Treatment: factor VIII concentrate 48 Hemophilia B (Christmas disease) Deficiency of factor IX X-linked recessive Clinically identical to hemophilia A 49  Acquired Coagulopathies Vitamin K deficiency: decreased synthesis of factors II,VII, IX, X, and protein C & S Liver disease: decreased synthesis of virtually all clotting factors 50  von Willebrand Disease Definition: inherited bleeding disorder characterized by either a deficiency or qualitative defect in von Willebrand factor vWF is normally produced by endothelial cells and megakaryocytes Clinical features Spontaneous bleeding from mucous membranes Prolonged bleeding from wounds Menorrhagia in young females Bleeding into joints is uncommon 51  von Willebrand Factor Endothelium Collagen Factor VIII X Xa Clotting vWF Activated, aggregated Circulating vWF cascade platelets with Factor VIII Platelet Fibrinogen GpIIb/IIIa GpIb Platelet Subendothelial vWF Endothelial defect 52  von Willebrand Disease Labs Normal platelet count and a prolonged bleeding time Normal PT with often a prolonged PTT Abnormal platelet response to ristocetin (adhesion defect) is an important diagnostic test Treatment: treat mild cases (type I) with desmopressin (an anti-diuretic hormone [ADH] analogue), which releases vWF from Weibel-Palade bodies of endothelial cells 53 Disseminated Intravascular Coagulation (DIC) DIC is always secondary to another disorder Causes Obstetric complications (placental tissue factor activates clotting) Gram-negative sepsis (tumor necrosis factor [TNF] activates clotting) Micro-organisms (especially, meningococcus and rickettsia) AML M3 (cytoplasmic granules in neoplastic promyelocytes activate clotting) Adenocarcinomas (mucin activates clotting) 54 Fibrin-Platelet Thrombus 55 Peripheral Blood Smear: Schistocyte 56 Pathogenesis of Disseminated Intravascular Coagulation Sepsis Massive Tissue Injury Endothelial Cell Injury Release of Tissue Factor Platelet Aggregation Extensive Microvascular Consumption of Clotting Activation of Plasmin Thromboses Factors & Platelets Vascular Occlusion Microangiopathic Hemolytic Anemia Proteolysis of Fibrinolysis Ischemic Tissue Injury Clotting Factors Fibrin Split Products Inhibition of thrombin, platelet activation & Bleeding Diathesis fibrin polymerization Hypoxic Injury 57 58 59 Bleeding Diathesis: DIC 60 Bleeding Diathesis: DIC 61 Pathogenesis of Meningococcemia 62 Pathology of Meningococcemia 63 Pathology of Meningococcemia 64 Pathology of Meningococcemia 65 Pathology of Meningococcemia 66 Pathology of Meningococcemia 67 Pathology of Meningococcemia 68 Disseminated Intravascular Coagulation (DIC) Pathology Results in widespread fibrin-platelet thrombi Consumption of platelets and clotting factors leads to a bleeding diathesis Labs Platelet count is decreased Prolonged PT/PTT Decreased fibrinogen Elevated fibrin split products (D-dimers) Treatment: treat the underlying disorder 69  Thromboembolism Three Predisposing Factors Leading to Abnormal Thrombosis Injury to vascular endothelium - atherosclerosis Changes in laminar flow of blood - increased viscosity (polycythemia), stasis of blood (deep leg veins), and turbulence (aneurysms) Hypercoagulability - increased level of platelets or clotting factors, decreased fibrinolytic activity (pregnancy) 70 Laminar Flow of Blood 71 72  Hypercoagulable States Primary (Genetic) Common - Factor V mutation (factor V Leiden), Prothrombin mutation (increased prothrombin levels, Increased levels of factors VIII, IX, XI, or fibrinogen Rare - Antithrombin III deficiency, Protein C deficiency, Protein S deficiency Very Rare - Fibrinolysis defects, Homozygous homocystinuria (deficiency of cystathione beta-synthetase Secondary (Acquired) High Risk for Thrombosis - Prolonged bed rest or immobilization, Myocardial infarction, Atrial fibrillation, Tissue injury (surgery, fracture, burn), Cancer, Prosthetic cardiac valves, Disseminated intravascular coagulation, Heparin-induced thrombocytopenia, Anti-phospholipid antibody syndrome Low Risk for Thrombosis - Cardiomyopathy, Nephrotic syndrome, Hyperestrogenic states (pregnancy and postpartum), Oral contraceptive use, Sickle cell anemia, Smoking 73  ENDOTHELIAL INJURY THROMBOSIS ABNORMAL BLOOD FLOW HYPERCOAGULABILITY 74 Thrombus 75 Thrombus (“Lines of Zahn”) 76 77 78  Thromboembolism Evolution of a Thrombus Enlarge and cause obstruction with the formation of Lines of Zahn (early) Give rise to an embolus Be removed by fibrinolytic action (small thrombi) or Become organized leading to recanalization (large thrombi) 79 Inferior vena cava Thrombosed vein Iliac vein Propagation towards heart Resolution Embolization to lungs Organized and Organized and incorporated into wall recanalized 80 Organizing Thrombosed Hemorroids 81 Organizing Thrombosed Hemorroids 82  Thromboembolism Thrombus vs Blood Clot Thrombus only occurs within the intravascular space while a blood clot can occur in either intravascular (postmortem), or extravascular compartments Blood clot does not have Lines of Zahn Blood clot contains minimal number of platelets 83 Blood Clot 84 85  Thromboembolism Embolus Definition - a detached intravascular mass (solid, liquid, or gas) that is carried to a site distant from point of origin Embolus vs Thrombus Embolus can be composed of "foreign" material (amniotic fluid, bacteria, tumor cells) Embolus may not conform to the shape of a blood vessel Arterial thrombus is usually associated with underlying atherosclerosis, while an embolus is typically found overlying a normal vessel until organization occurs 86 Thromboembolism Types of Emboli Thrombus Bone marrow Atheromatous debris Fat Bacteria Tumor cells Amniotic fluid Air - acute and chronic 87 Bone Marrow Embolus 88 Amniotic Fluid Embolus 89 Fat Emboli 90  Thromboembolism Epidemiology of Pulmonary Embolus Often clinically silent Most commonly missed diagnosis in hospitalized patients 91  Thromboembolism Pulmonary Embolus Origin - deep leg veins, & prostatic and uterine venous plexus Outcome Resolution in 70 to 80% Infarction in 10 to 15% Chronic pulmonary hypertension in 3-5% Sudden death in 5% 92  Recent Pulmonary Emboli Right Main Pulmonary Artery Left Main Pulmonary Artery 93 Pulmonary Saddle Embolus 94 Recent Pulmonary Embolus: Lines of Zahn 95 Normal Prostate Prostatic Venous Thromboses 96 Prostatic Organizing Thrombosis 97 Prostatic Organizing Thrombosis 98 Prostatic Organizing Thrombosis 99  Paradoxical Embolus Definition: any venous embolus that gains access to the systemic circulation by crossing over from the right to the left side of the heart through a septal defect 100  Infarct Definition - A localized area of necrosis resulting from circulatory insufficiency/ischemia Infarcts of the heart, brain, and lungs collectively account for more deaths than all forms of cancer and infectious disease put together in the United States 101  Infarct Etiology Thrombus Embolus Low-output state 102  Infarct Whether or not an infarct occurs depends on several factors Degree of obstruction Rate of occlusion - acuteness Vulnerability of tissue to ischemia Presence or absence of collateral circulation Pre-existing disease Oxygen-carrying capacity of the blood 103  Infarct Gross Pathology Wedge-shaped Apex of wedge points to the occlusion 104  Infarct Anemic infarcts (pale or white color) Occur in solid organs with a single blood supply such as the spleen, kidney, and heart Hemorrhagic infarcts (red color) Occur in organs with a dual blood supply or collateral circulation, such as the lung and intestines Also occur with venous occlusion (e.g., testicular torsion) 105  Infarct Gross Pathology Heart (usually anemic) - thrombus secondary to underlying atherosclerotic coronary artery Brain (hemorrhagic or anemic) - thrombotic occlusions are usually anemic while embolic occlusions are usually hemorrhagic Lung (hemorrhagic) - usually due to embolism rather than thrombus Intestine (hemorrhagic) - thrombotic or embolic Spleen (anemic) - thrombotic or embolic 106 Hemorrhagic Infarct 107 Acute Hemorrhagic Infarct 108 Acute Hemorrhagic Infarct 109 Acute Pale Infarcts 110 Acute Pale Infarcts 111 Acute Pale Infarcts 112  Infarcts Microscopic Pathology Ischemic coagulative necrosis Brain is the exception with liquefaction necrosis Inflammatory response Granulation tissue (proliferation of blood vessels and fibroblasts) surrounds the infarcted area Fibrosis Brain will become cystic surrounded by a glial scar 113 3-5 days Post-myocardial Infarction 114 14 days Post-myocardial Infarction 115 Remote Infarct 116  Hemorrhage Terminology Petechie Ecchymosis Purpura Epistaxis - bleeding from the nose Hematemesis - vomiting blood 117  Hemorrhage Terminology Hemoptysis - coughing blood Melena - partially digested blood in the stools Hematochezia - passage of bloody stools Hematuria - blood in the urine Hemothorax, hemopericardium, hemoperitoneum - bleeding into the various cavities Hematoma - localized hemorrhage into the tissues or tissue spaces 118  Shock Definition: shock is characterized by vascular collapse and widespread hypoperfusion of cells and tissue due to reduced blood volume, cardiac output, or vascular tone Cellular injury is initially reversible If the hypoxia persists, the cellular injury becomes irreversible, leading to the death of cells and the patient 119  Factors Affecting Blood Pressure Angiotensin II Prostaglandins Sodium Catecholamines Kinins Mineralocorticoids Thromboxane NO Atriopeptin Leukotrienes Endothelin BP = CARDIAC X PERIPHERAL OUTPUT RESISTANCE Autoregulation Ionic (pH, hypoxia) Heart rate Contractility -adrenergic -adrenergic 120  Shock Causes of shock Cardiogenic shock (pump failure) Myocardial infarction Cardiac arrhythmia Cardiac tamponade Hypovolemic shock (reduced blood volume) Hemorrhage Fluid loss secondary to severe burns Severe dehydration 121  Shock Obstructive Pulmonary embolus Septic shock (bacterial infection) Gram-negative septicemia Release of endotoxins (bacterial wall lipopolysaccharides) into the circulation High levels of endotoxin results in: Production of cytokines TNF, IL-1, IL-6, and IL-8 122  Shock Septic Shock Vasodilatation and hypotension Acute respiratory distress syndrome (ARDS) DIC Multisystem organ failure Mortality rate: 50% 123  Pathogenesis of Endotoxic Septic Shock LPS TNF IL-1 IL-6/IL-8 NO, PAF other mediators LOW QUANTITIES MODERATE QUANTITIES HIGH QUANTITIES Monocyte/ Fever Low cardiac output macrophage/ neutrophil Low peripheral resistance activation Brain Blood vessel injury, Acute-phase thrombosis, Endothelial cell DIC activation reactants Liver ARDS C3a, C5a Complement activation Bone Leukocytes LOCAL INFLAMMATION SYSTEMIC EFFECTS SEPTIC SHOCK 124  Shock Major causes of shock Neurogenic shock (generalized vasodilatation) Anesthesia Brain or spinal cord injury Anaphylactic shock (generalized vasodilatation) - type I hypersensitivity reaction 125 Causes of Shock N eurogenic Anaphylactic C ardiogenic Hypovolemic Obstructive Sepsis 126  Shock Stages of shock Stage I: compensation, in which perfusion to vital organs is maintained by reflex mechanisms Increased sympathetic tone Release of catecholamines Activation of the renin-angiotensin system Stage II: decompensation Progressive decrease in tissue perfusion Potentially reversible tissue injury occurs Development of a metabolic acidosis, electrolyte imbalances, and renal insufficiency 127  Shock Stage III: irreversible Irreversible tissue injury and organ failure Ultimately resulting in death 128  Shock Pathology Kidneys Acute tubular necrosis (”shock kidney”) Lungs undergo diffuse alveolar damage ("shock lung") Intestines Superficial mucosal ischemic necrosis and hemorrhages Prolonged injury may lead to sepsis with bowel flora Liver undergoes centrilobular necrosis ("shock liver") Adrenals undergo Waterhouse-Friderichsen syndrome Commonly associated with meningococcal septic shock Bilateral hemorrhagic infarction Acute adrenal insufficiency 129  Hemostasis To thoracic duct and eventually to left subclavian vein Increased interstitial Hydrostatic pressure fluid pressure Shock Edema Congestion Thrombus Plasma colloid osmotic pressure Embolus Arterial end CAPILLARY BED Venous end Hemorrhage Infarct 130