hydrostatic and osmotic forces are normally balanced so there is little net #51 | | |
movement of fluid into the interstitium. However, increased hydrostatic #52 | | |
pressure or diminished plasma osmotic pressure leads to extravascular fluid #53 | | |
accumulation (edema). Tissue lymphatics drain much of the excess fluid back #54 | | |
to the circulation by way of the thoracic duct; however, if the capacity for #55 | | |
lymphatic drainage is exceeded, tissue edema results. #56 | | |
Increased Hydrostatic Pressure #57 | | |
Increases in hydrostatic pressure are mainly caused by disorders that impair venous return. Local increases in intravascular pressure caused, for example, by deep venous thrombosis in the lower extremity can cause edema restricted to the distal portion of the affected leg. General- ized increases in venous pressure, with resultant systemic edema, occur most commonly in congestive heart failure (Chapter 11). Fig. 4.3 illustrates the interlocking mecha- nisms that underlie generalized edema resulting from cardiac, renal, and hepatic failure. Several factors increase venous hydrostatic pressure in patients with congestive heart failure (Fig. 4.3). The reduced cardiac output leads to systemic venous congestion and resultant increase in capil- lary hydrostatic pressure. At the same time reduction in cardiac output results in hypoperfusion of the kidneys, trig- gering the renin-angiotensin-aldosterone axis and inducing sodium and water retention (secondary hyperaldosteron- ism). In patients with normal heart function, this adapta- tion increases cardiac filling and cardiac output, thereby improving renal perfusion. However, the failing heart often cannot increase its cardiac output in response to the com- pensatory increases in blood volume. Instead, a vicious cycle of fluid retention, increased venous hydrostatic pres- sures, and worsening edema ensues. Unless cardiac output is restored or renal water retention is reduced (e.g., by salt restriction or treatment with diuretics or aldosterone antagonists), this downward spiral continues. Because sec- #58 | | |
ondary hyperaldosteronism is a common feature of generalized edema, salt restriction, diuretics, and aldosterone antagonists also are of value in the management of generalized edema resulting from non-cardiac causes. #59 | | |
Reduced Plasma Osmotic Pressure #60 | | |
Reduction of plasma albumin concentrations leads to decreased colloid osmotic pressure of the blood and loss of fluid from the circulation. Under normal circumstances, albumin accounts for almost half of the total plasma protein. Therefore, conditions in which albumin is either lost from the circulation or synthesized in inadequate amounts are common causes of reduced plasma osmotic pressure. Nephrotic syndrome is the most important cause of albumin loss from the blood. In diseases that are character- ized by nephrotic syndrome (Chapter 14), the glomerular capillaries become leaky, leading to the loss of albumin (and other plasma proteins) in the urine and the develop- ment of generalized edema. Reduced albumin synthesis occurs in the setting of severe liver disease (e.g., cirrhosis) (Chapter 16) and protein malnutrition (Chapter 8). Regard- less of cause, low albumin levels lead in a stepwise fashion to edema, reduced intravascular volume, renal hypo- perfusion, and secondary hyperaldosteronism. Unfortu- nately, increased salt and water retention by the kidney not only fails to correct the plasma volume deficit but also exacerbates the edema, because the primary defect—low serum protein—persists. #61 | | |
| | |
Edema may result from lymphatic obstruction that com- promises resorption of fluid from interstitial spaces. Impaired lymphatic drainage and consequent lymph- edema 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”) by producing inguinal lymphatic and #63 | | |
lymph node fibrosis. Infiltration and obstruction of super- ficial 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 also may occur as a complica- tion of therapy. One relatively common setting for this clinical entity is in women with breast cancer who undergo axillary lymph node resection and/or irradiation, both of which can disrupt and obstruct lymphatic drainage, result- ing in severe lymphedema of the arm. #64 | | |
Sodium and Water Retention #65 | | |
Excessive retention of salt (and its obligate associated water) can lead to edema by increasing hydrostatic pres- sure (because of expansion of the intravascular volume) and reducing plasma osmotic pressure. Excessive salt and water retention are seen in a wide variety of diseases that compromise renal function, including poststreptococcal glomerulonephritis and acute renal failure (Chapter 14). #66 | | |
MORPHOLOGY Edema is easily recognized on gross inspection; microscopic exam- #67 | | |
ination shows clearing and separation of the extracellular matrix (ECM) elements. Although any tissue can be involved, edema most commonly is encountered in subcutaneous tissues, lungs, and brain. #68 | | |
Subcutaneous edema can be diffuse but usually accumu- lates preferentially in parts of the body positioned the greatest distance below the heart, where hydrostatic pressures are highest. Thus, edema typically is most pronounced in the legs with standing and the sacrum with recumbency, a relationship termed dependent edema. Finger pressure over edematous subcuta- neous tissue displaces the interstitial fluid, leaving a finger-shaped depression; this appearance is called pitting edema. Edema resulting from renal dysfunction or nephrotic syndrome often manifests first in loose connective tissues (e.g., the eyelids, causing periorbital edema). With pulmonary edema, the lungs often are two to three times their normal weight, and sectioning shows frothy, sometimes blood-tinged fluid consisting of a mixture of air, edema fluid, and extravasated red cells. Brain edema (Chapter 23) can be localized (e.g., because of abscess or tumor) or generalized, depending on the nature and extent of the pathologic process or injury. With generalized edema, the sulci are narrowed as the gyri swell and become flattened against the skull. #69 | | |
| | |
The effects of edema vary, ranging from merely annoying #71 | | |
to rapidly fatal. Subcutaneous edema is important to rec- ognize primarily because it signals potential underlying cardiac or renal disease; however, when significant, it also can impair wound healing and the clearance of infections. Pulmonary edema is a common clinical problem. It is seen most frequently in the setting of left ventricular failure, but also may occur in renal failure, acute respiratory distress syndrome (Chapter 11), and inflammatory and infectious disorders of the lung. It can cause death by interfering with normal ventilatory function; besides impeding oxygen dif- #72 | | |
fusion, alveolar edema fluid also creates a favorable envi- ronment for infections. Brain edema is life threatening; if the swelling is severe, the brain can herniate (extrude) through the foramen magnum. With increased intracranial pressure, the brain stem vascular supply can be com- pressed, leading to death due to injury to the medullary centers controlling respiration and other vital functions (Chapter 23). #73 | | |
| | |
| | |
• Edema results from the movement of fluid from the vascula- #76 | | |
ture into the interstitial spaces; the fluid may be protein poor #77 | | |
(transudate) or protein rich (exudate). #78 | | |
• Edema may be caused by: #79 | | |
• Increased hydrostatic pressure (e.g., heart failure) #80 | | |
• Increased vascular permeability (e.g., inflammation) #81 | | |
• Decreased colloid osmotic pressure resulting from reduced #82 | | |
| | |
• Decreased synthesis (e.g., liver disease, protein #84 | | |
| | |
• Increased loss (e.g., nephrotic syndrome) #86 | | |
• Lymphatic obstruction (e.g., inflammation or neoplasia) #87 | | |
• Sodium retention (e.g., renal failure) #88 | | |
| | |
Hemorrhage, defined as the extravasation of blood from vessels, is most often the result of damage to blood vessels or defective clot formation. As described earlier, capillary bleeding can occur in chronically congested tissues. Trauma, atherosclerosis, or inflammatory or neo- plastic erosion of a vessel wall also may lead to hemor- rhage, which may be extensive if the affected vessel is a large vein or artery. #90 | | |
The risk of hemorrhage (often after a seemingly insignifi- cant injury) is increased in a wide variety of clinical disor- ders 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 homeostasis. These are discussed in the next section. Here we focus on clinical fea- tures of hemorrhages, regardless of the cause. #91 | | |
Hemorrhage may be manifested by different appear- ances and clinical consequences. #92 | | |
Hemorrhage may be external or accumulate within a tissue as a hematoma, which ranges in significance from trivial (e.g., a bruise) to fatal (e.g., a massive retroperi- toneal hematoma resulting from rupture of a dissecting aortic aneurysm) (Chapter 10). Large bleeds into body cavities are described variously according to location— hemothorax, hemopericardium, hemoperitoneum, or hemar- throsis (in joints). Extensive hemorrhages can occasionally result in jaundice from the massive breakdown of red cells and hemoglobin. #93 | | |
Petechiae are minute (1 to 2 mm in diameter) hemor- rhages into skin, mucous membranes, or serosal sur- faces (Fig. 4.4A); causes include low platelet counts (thrombocytopenia), defective platelet function, and loss of vascular wall support, as in vitamin C deficiency (Chapter 8). #94 | | |
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. #95 | | |
Ecchymoses are larger (1 to 2 cm) subcutaneous hemato- mas (colloquially called 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). #96 | | |
The clinical significance of any particular hemorrhage depends on the volume of blood that is lost and the rate of bleeding. Rapid loss of up to 20% of the blood volume, or slow losses of even larger amounts, may have little impact in healthy adults; greater losses, however, can cause hem- orrhagic (hypovolemic) shock (discussed later). The site of hemorrhage also is important; bleeding that would be trivial in the subcutaneous tissues can cause death if located in the brain (Fig. 4.4B). Finally, chronic or recurrent external blood loss (e.g., due to peptic ulcer or menstrual bleeding) frequently culminates in iron deficiency anemia as a consequence of a loss of iron in hemoglobin. By contrast, iron is efficiently recycled from #97 | | |
hagocytosed red cells, so internal bleeding (e.g., a hematoma) does not lead to iron deficiency. #98 | | |
HEMOSTASIS AND THROMBOSIS #99 | | |
Normal hemostasis comprises a series of regulated pro- cesses that culminate in the formation of a blood clot that limits bleeding from an injured vessel. The pathologic counterpart of hemostasis is thrombosis, the formation of blood clot (thrombus) within non-traumatized, intact vessels. This discussion begins with normal hemostasis and its regulation, to be followed by causes and conse- quences of thrombosis. #100 | | |
