Hemodynamic Disorders PDF

Hemodynamic Disorders, Thromboembolism, and Shock Hyperemia and Congestion Hyperemia and congestion both refer to an increase in blood volume within a tissue but have different underlying mechanisms. Hyperemia is an active process resulting from arteriolar dilation and increased bloo...

Hemodynamic Disorders, Thromboembolism, and Shock Hyperemia and Congestion Hyperemia and congestion both refer to an increase in blood volume within a tissue but have different underlying mechanisms. Hyperemia is an active process resulting from arteriolar dilation and increased blood inflow; it occurs at sites of inflammation and in exercising skeletal muscle. Hyperemic tissues are redder than normal because they are engorged with oxygenated blood. In long-standing chronic congestion, inadequate tissue perfusion and persistent hypoxia may lead to parenchymal cell death and secondary tissue fibrosis, and the elevated intravascular pressures may cause edema or rupture capillaries, producing focal hemorrhages. Edema Approximately 60% of lean body weight is water, two-thirds of which is intracellular. Most of the remaining water is found in tissues in the form of interstitial fluid; only 5% of the body’s water is in blood plasma. Edema is an accumulation of interstitial fluid within tissues. Extravascular fluid can also collect in body cavities, where it is often referred to as an effusion. Examples include effusions in the pleural cavity (hydrothorax), the pericardial cavity (hydropericardium), and the peritoneal cavity (hydroperitoneum, or ascites). Anasarca is severe, generalized edema marked by profound swelling of subcutaneous tissues and accumulation of fluid in body cavities. Fluid Movement Fluid movement between the vascular and interstitial spaces is governed mainly by two opposing forces: Vascular hydrostatic pressure. Colloid osmotic pressure produced by plasma proteins. Normally, the outflow of fluid produced by hydrostatic pressure at the arteriolar end of the microcirculation is nearly balanced by inflow at the venular end owing to osmotic pressure. The small net outflow of fluid into the interstitial space is drained by lymphatic vessels to the bloodstream by way of the thoracic duct, keeping the tissues “dry.” Either increased hydrostatic pressure or diminished colloid osmotic pressure will result in increased movement of water into the interstitium, and if the drainage capacity of the lymphatics is exceeded, edema results. FLUIDS and ELECTROLYTES BODY FLUIDS Distribution of Body Fluids – 50-70% of total body weight; infant [70-80%], elderly [45-50%] ICF ECF 60-kg man TBW = 0.6 x 60 kg = 36 L P I ICF = 0.4 x 60 kg ECF S = 24 L = 12 L 3L 9L 40% TBW 20% TBW 5 Fluids and Electrolytes Isotonic solution Hypotonic solution Hypertonic solution Increased Hydrostatic Pressure Increases in hydrostatic pressure are mainly caused by disorders that impair venous return. For example, deep venous thrombosis in the lower extremity may cause edema restricted to the distal portion of the affected leg, whereas congestive heart failure leads to a systemic increase in venous pressure and, often, widespread edema. Reduced Plasma Osmotic Pressure Reduced plasma albumin is a common feature of disorders in which edema is caused by decreases in colloid osmotic pressure. Normally, albumin accounts for almost half of the total plasma protein and is the biggest contributor to colloid osmotic pressure. Albumin levels fall if urinary loss increases or hepatic synthesis decreases. Nephrotic syndrome is the most important cause of albuminuria. In diseases associated with nephrotic syndrome, damage to glomeruli allows albumin (and other plasma proteins) to pass into the urine. Reduced albumin synthesis is seen in the setting of severe liver disease (e.g., cirrhosis) and protein malnutrition. Lymphatic Obstruction Edema may result from lymphatic obstruction that compromises resorption of fluid from interstitial spaces. Impaired lymphatic drainage and consequent lymphedema usually results from a localized obstruction caused by an inflammatory or neoplastic condition. For example, the parasitic infection filariasis can cause massive edema of the lower extremity and external genitalia (so- called “elephantiasis”) secondary to fibrosis of the inguinal lymphatics and lymph nodes. Infiltration and obstruction of superficial lymphatics by breast cancer may cause edema of the overlying skin; the characteristic finely pitted appearance of the skin of the affected breast is called peau d’orange (orange peel). Lymphedema may also occur as a complication of therapy, as in Edema Edema represents the accumulation of fluid volume in the interstitial spaces of the ECF resulting from: (1) an increase in capillary filtration pressure, (2) a decrease capillary colloidal osmotic pressure, (3) an increase in capillary permeability, or (4) obstructed lymphatic flow. The effect that edema exerts on body function is determined by its location, with edema of the brain, larynx, or lungs representing an acute life-threatening situation. Common Causes of Edema Increased Capillary Pressure: Increased vascular volume (e.g., heart failure, kidney disease) Venous obstruction (e. g., thrombophlebitis) Liver disease with portal vein obstruction Acute pulmonary edema Decreased Colloidal Osmotic Pressure: Increased loss o f plasma proteins (e.g., protein-losing kidney diseases, extensive burns) Decreased production of plasma proteins (liver disease, malnutrition) Increased Capillary Permeability: Water Regulation The main determinant of water and sodium balance is the effective circulating blood volume, which is monitored by stretch receptors in the vascular system that exert their effects through thirst, which controls water intake, and the antidiuretic hormone (ADH), which controls urine concentration. The sympathetic nervous system and the renin-angiotensin-aldosterone system contribute to fluid balance through the regulation of sodium balance. Water Regulation Isotonic fluid disorders result from contraction or expansion of ECF volume brought about by proportionate changes in sodium and water. Isotonic fluid volume deficit (hypovolemia), which is characterized by a decrease in ECF volume, causes thirst, signs of decreased vascular volume, and a decrease in urine output along with an increase in urine specific gravity. Isotonic fluid volume excess (hypervolemia), which is characterized by an increase in ECF volume, is manifested by signs of increased vascular volume and edema. Sodium and Water Retention Excessive retention of salt (and associated water) can lead to edema by increasing hydrostatic pressure (owing to expansion of the intravascular volume) and reducing plasma osmotic pressure (because of decreased plasma protein concentration). Excessive salt and water retention are seen in a wide variety of diseases that compromise renal function, including poststreptococcal glomerulonephritis and acute renal failure. Hemorrhage Hemorrhage, defined as the extravasation of blood from vessels, results from damage to blood vessels and may be exacerbated by defects in blood clotting. Capillary bleeding can occur in chronically congested tissues. Trauma, atherosclerosis, or inflammatory or neoplastic erosion of a vessel wall also may lead to hemorrhage, which may be massive if the affected vessel is a large vein or artery. Hemorrhage The risk of hemorrhage is increased in a wide variety of disorders collectively called hemorrhagic diatheses. These have diverse causes, including inherited or acquired defects in vessel walls, platelets, or coagulation factors, all of which must function properly to ensure hemostasis. Hemorrhage Hemorrhage may take the form of external bleeding or may accumulate within a tissue as a hematoma. These range in significance from trivial (e.g., a bruise) to fatal (e.g., a massive retroperitoneal hematoma caused by rupture of a dissecting aortic aneurysm). Large bleeds into body cavities are described according to their location; hemothorax, hemopericardium, hemoperitoneum, or hemarthrosis (in joints). Large hemorrhages can occasionally result in jaundice as red cells and hemoglobin are broken down by macrophages. Petechiae Petechiae are minute (1 to 2 mm in diameter) hemorrhages into skin, mucous membranes, or serosal surfaces. Causes include low platelet counts (thrombocytopenia), defective platelet function, and loss of vascular wall support, as in vitamin C deficiency. Purpura Purpura are slightly larger (3 to 5 mm) hemorrhages. Purpura can result from the same disorders that cause petechiae, as well as trauma, vascular inflammation (vasculitis), and increased vascular fragility. Ecchymoses Ecchymoses are larger (1 to 2 cm) subcutaneous hematomas (bruises). Extravasated red cells are phagocytosed and degraded by macrophages; the characteristic color changes of a bruise result from the enzymatic conversion of hemoglobin (red-blue color) to bilirubin (blue-green color) and eventually hemosiderin (golden-brown). Hemorrhage The clinical impact of a hemorrhage depends on the volume of blood that is lost, the rate of bleeding, the location of the bleed, and the health of the individual affected. Rapid loss of up to 20% of the blood volume may be well tolerated in healthy adults yet cause cardiovascular decompensation in individuals with underlying heart or lung disease. Greater losses may cause hemorrhagic (hypovolemic) shock even in those who are healthy. A bleed that is relatively trivial in the subcutaneous tissues may cause death if located in the brain. Chronic or recurrent external blood loss (e.g., due to peptic ulcer or menstrual bleeding) frequently leads to iron deficiency anemia owing to loss of the iron in hemoglobin. Hemostasis and Thrombosis Hemostasis is a process initiated by a traumatic vascular injury that leads to the formation of a blood clot. Hemostasis is a precisely orchestrated process involving platelets, clotting factors, and endothelium that occurs at the site of vascular injury and leads to the formation of a blood clot, which serves to prevent or limit the extent of bleeding. Hemostasis Arteriolar vasoconstriction occurs immediately and markedly reduces blood flow to the injured area. It is mediated by neurogenic reflexes and augmented by the local secretion of factors such as endothelin, a potent endothelium-derived vasoconstrictor. This effect is transient, however, and bleeding resumes without the activation of platelets and coagulation factors. Hemostasis Primary hemostasis: the formation of the platelet plug. Disruption of the endothelium exposes subendothelial collagen, which binds von Willebrand factor, a molecule that promotes platelet adherence and activation. Activated platelets undergo a dramatic shape change (from small, rounded discs to flat plates with spiky protrusions that markedly increase surface area) and release their secretory granules. Within minutes the secreted products recruit additional platelets, which aggregate to form a primary hemostatic plug. Hemostasis Secondary hemostasis: deposition of fibrin. Vascular injury exposes tissue factor at the site of injury. Tissue factor is a membrane-bound procoagulant glycoprotein that is normally expressed by subendothelial cells in the vessel wall, such as smooth muscle cells and fibroblasts. Tissue factor binds and activates factor VII, setting in motion a cascade of reactions that lead to thrombin generation. Thrombin cleaves circulating fibrinogen into insoluble fibrin, creating a fibrin meshwork, and is a potent activator of platelets, leading to additional platelet aggregation at the site of injury. This sequence, referred to as secondary hemostasis, consolidates the platelet plug. Hemostasis Clot stabilization. Polymerized fibrin is crosslinked covalently by factor XIII and platelet aggregates contract, both of which contribute to the formation a solid permanent plug that prevents further bleeding. The size of the clot is limited by counterregulatory mechanisms that restrict clotting to the site of injury and eventually lead to clot resorption and tissue repair. Hemostasis The integrity and function of endothelial cells determine whether clots form, propagate, or dissolve. Healthy endothelial cells express a variety of anticoagulant factors that inhibit platelet aggregation and coagulation and promote fibrinolysis; after endothelial injury or activation, however, this balance shifts to favor clotting. Endothelium can be activated by microbial pathogens, hemodynamic forces, and a number of proinflammatory mediators, all of which may increase the risk of thrombosis. Thrombosis The primary abnormalities that lead to intravascular thrombosis are the so-called “Virchow triad”: (1) endothelial injury; (2) stasis or turbulent blood flow; and (3) hypercoagulability of the blood. Abnormal Blood Flow Turbulence (chaotic blood flow) contributes to arterial and cardiac thrombosis by causing endothelial injury or dysfunction, as well as by forming countercurrents and local pockets of stasis. Stasis is a major factor in the development of venous thrombi. Under conditions of normal laminar blood flow, platelets (and other blood cells) are found mainly in the center of the vessel lumen, separated from the endothelium by a slower-moving layer of plasma. By contrast, stasis and turbulence have the following deleterious effects: Both promote endothelial cell activation and enhanced procoagulant activity, in part through flow-induced changes in endothelial gene expression. Stasis allows platelets and leukocytes to come into contact with the endothelium. Hypercoagulability Hypercoagulability refers to an abnormally high tendency of the blood to clot and is usually caused by alterations in coagulation factors. It is an important risk factor for venous thrombosis and occasionally contributes to arterial or intracardiac thrombosis. Alterations that lead to hypercoagulability can be divided into primary (genetic) and secondary (acquired) disorders. Hypercoagulability Primary (inherited) hypercoagulability is most often caused by mutations in the factor V and prothrombin genes: A factor V mutation, called the Leiden mutation after the Dutch city where it was first described, causes an amino acid substitution in factor V that renders it resistant to proteolysis by protein C. Thus, an important antithrombotic counterregulatory mechanism is lost. Factor V Leiden heterozygotes have a 3- to 4-fold increased risk for venous thrombosis, while homozygotes have a 25- to 50- fold increased risk. Among those with recurrent deep venous thrombosis (DVT), the frequency of factor V Leiden approaches 60%. This mutation is seen in approximately 2% to 15% of individuals of European ancestry and is present to varying degrees in other American groups, largely due to population admixture. Disseminated Intravascular Coagulation (DIC) DIC is widespread thrombosis within the microcirculation that may be of sudden or insidious onset. It may be seen in disorders ranging from obstetric complications to advanced malignancy. To complicate matters, the widespread microvascular thrombosis consumes platelets and coagulation proteins (hence the synonym consumptive coagulopathy), and, at the same time, fibrinolytic mechanisms are activated. The net result is that excessive clotting and bleeding may coexist in the same patient. Shock Shock is a state in which diminished cardiac output or reduced effective circulating blood volume impairs tissue perfusion and leads to cellular hypoxia. At the outset, the cellular injury is reversible; however, prolonged shock eventually leads to irreversible tissue injury and is often fatal. Shock causes fall into three general categories: Cardiogenic shock results from low cardiac output as a result of myocardial pump failure. It may be caused by myocardial damage (infarction), ventricular arrhythmia, extrinsic compression (cardiac tamponade), or outflow obstruction (e.g., pulmonary embolism). Hypovolemic shock results from low cardiac output due to loss of blood or plasma volume (e.g., resulting from hemorrhage or fluid loss from severe burns). Septic shock is triggered by microbial infections and is associated with Shock Less commonly, shock may result from a loss of vascular tone associated with anesthesia or secondary to a spinal cord injury (neurogenic shock). Anaphylactic shock results from systemic vasodilation and increased vascular permeability and is triggered by IgEe mediated hypersensitivity reactions. Stages of Shock Shock is a progressive disorder that leads to death if the underlying problems are not corrected. The stages of shock have been documented most clearly in hypovolemic shock but are common to other forms as well: An initial nonprogressive stage during which reflex compensatory mechanisms are activated and vital organ perfusion is maintained. A progressive stage characterized by 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. Stages of Shock In the early nonprogressive phase of shock, various neurohumoral mechanisms maintain cardiac output and blood pressure. These mechanisms include baroreceptor reflexes, release of catecholamines and antidiuretic hormone, activation of the renin- angiotensinaldosterone axis, and generalized sympathetic stimulation. The net effect is tachycardia, peripheral vasoconstriction, and renal fluid conservation. Cutaneous vasoconstriction causes the characteristic “shocky” skin coolness and pallor (notably, septic shock can initially cause cutaneous vasodilation, so the patient may present with warm, flushed skin). Coronary and cerebral vessels are less sensitive to sympathetic signals and maintain relatively normal caliber, blood flow, and oxygen delivery. Thus, blood is shunted away from the skin to the vital organs Stages of Shock If the underlying causes are not corrected, this cause widespread tissue hypoxia. In the setting of persistent oxygen deficit, intracellular aerobic respiration is replaced by anaerobic glycolysis with excessive production of lactic acid. The resultant lactic acidosis lowers the tissue pH, blunting the vasomotor response of arterioles, which dilate, leading to the pooling of blood in the microcirculation. Peripheral pooling of blood not only lowers cardiac output but also puts endothelial cells at risk for the development of ischemic injury and subsequent DIC. With widespread tissue hypoxia, vital organs begin to fail. Stages of Shock In the absence of intervention, or in severe cases, the process eventually enters an irreversible stage. Widespread cell injury is reflected in lysosomal enzyme leakage, further aggravating cell injury. Myocardial contractile function worsens and the ischemic bowel may allow intestinal flora to enter the circulation; thus, bacteremic shock may be superimposed. Commonly, renal failure occurs as a consequence of ischemic injury of the kidney. Despite therapeutic interventions, this downward spiral often ends in death. Clinical Features. The clinical manifestations of shock depend on the precipitating insult. In hypovolemic and cardiogenic shock, patients exhibit hypotension, a weak rapid pulse, tachypnea, and cool, clammy, cyanotic skin. In septic shock, the skin may be warm and flushed owing to peripheral vasodilation. The primary threat to life is the underlying initiating event (e.g., myocardial infarction, severe hemorrhage, bacterial infection). However, the cardiac, cerebral, and pulmonary changes rapidly aggravate the situation. If patients survive the initial period, worsening renal function can provoke a phase dominated by progressive oliguria, acidosis, and electrolyte imbalances. Prognosis Prognosis varies with the origin of shock and its duration. Thus, more than 90% of young, otherwise healthy patients with hypovolemic shock survive with appropriate management; by comparison, septic or cardiogenic shock is associated with substantially worse outcomes, even with state-of-the-art care. Acid–base balance Normal body function depends on the precise regulation of acid–base balance. Metabolic processes produce the volatile carbonic acid (H2CO3) in equilibrium with dissolved carbon dioxide (PCO2), which is eliminated through the lungs, and nonvolatile acids, which are excreted by the kidneys. Acid–base balance (Con’t) Because of its low concentration in body fluids, the hydrogen (H+) concentration is expressed as pH, or the negative log of the H+ ion concentration. It is the ratio of the bicarbonate (HCO3) concentration to H2CO3 (PCO2), normally 20:1, that determines body pH. Acid–base balance (Con’t) The ability of the body to maintain pH within the normal range depends on intracellular and extracellular buffers, as well as respiratory and renal compensatory mechanisms. The respiratory regulation of pH, which relies on pulmonary ventilation for release of CO2 into the environment, is rapid but does not return the pH completely to normal. Renal mechanisms, which rely on the elimination of H+ ions and conservation of HCO3 – ions, take longer but return pH to normal or near-normal levels. Metabolic Metabolic acid and base disorders reflect a decrease or increase in HCO3. Metabolic acidosis, which reflects a decrease in pH due to a decrease in HCO3, is caused by conditions that prompt an excessive production and accumulation of metabolic acids or excessive loss of HCO3. Metabolic alkalosis, which reflects an increase in pH due to an increase in HCO3, is caused by conditions that produce a gain in HCO3 or a decrease in H+. Respiratory Respiratory acid–base disorders reflect an increase or decrease in PCO2 levels due to altered pulmonary ventilation. Respiratory acidosis, which reflects a decrease in pH due an increase in PCO2 levels, is caused by conditions that produce hypoventilation. Respiratory alkalosis, which reflects an increase in pH due to a decrease in PCO2 levels, is caused by conditions that produce hyperventilation.