The development of edema contributes to the development of
E. Braunwald (Eugene Braunwald)
Swelling is an increase in extravascular(interstitial) component of the extracellular fluid volume, which can reach several liters before the disease manifests itself clinically. This is why an increase in body weight over several sig- nograms usually precedes the apparent clinical manifestations of edema and, conversely, weight loss by stimulation of diuresis is possible in moderately edematous patients before "dry weight" is achieved. Ascites (see Chapter 39) and hydrothorax signify the accumulation of excess fluid in the abdominal and pleural cavities, respectively. These conditions are considered as specific forms of edema. The term "anasarka" means massive, generalized swelling. Depending on the causes and mechanisms of development, edema can be localized or spread. The common edema is manifested by the puffiness of the face, which is most clearly seen in the periorbital areas, and the preservation of the pits on the skin after pressing. This form is known as "pressed edema." Its easiest manifestation can be detected by an impression that leaves the stethoscope's circumference on the skin of the chest, which persists for several minutes. One of the earliest symptoms that a patient can indicate is the difficulty that occurs when putting a ring on a finger or while training, especially in the evenings.
Pathogenesis (see also Chapter 41)
About 1/3 of the body's fluid is inextracellular space. This volume in turn consists of the volume of plasma and interstitial space. Under normal conditions, the plasma volume is about 25% of the extracellular space, and the rest is occupied by the interstitial fluid. It is often believed that the forces that regulate fluid distribution between these two components of the extracellular volume are the powers of Starling. In general terms, the hydrostatic pressure in the vascular system and the colloidal-oncotic pressure in the interstitial space tend to provide fluid from the vascular to the extravascular space. On the contrary, the colloid-oncotic pressure produced by plasma proteins and the hydrostatic pressure of the interstitial fluid, commonly called tissue pressure, facilitate the movement of fluid into the vascular bed. Due to these forces, water and soluble substances leave the vascular space in the arteriolar end of the capillaries. Through the lymphatic fluid, fluid returns from the interstitial space to the vascular bed. And in the absence of obstruction, the lymph flow increases, if there is a pronounced movement of the intravascular fluid into the interstitium. Usually, these forces are in equilibrium, so that the values of intravascular and interstitial volumes are kept constant, despite the fact that there is a fluid exchange between them. However, as soon as one of the forces changes significantly, there is an immediate movement of fluid from one part of the extracellular space to another.
The increase in capillary pressure may bethe result of an increase in venous pressure due to local venous outflow, congestive heart failure or, which is rare, due to a simple increase in vascular volume when large amounts of liquid are administered at a rate exceeding the ability of the kidneys to withdraw it. Colloid-oncotic plasma pressure can be reduced by any factor that causes hypoalbuminemia (malnutrition, liver disease, loss of protein in the urine or through the gastrointestinal tract), as well as in severe catabolic conditions.
Swelling can be the result of damageendothelium of capillaries, in which their permeability rises and the barrier for moving to the interstitial space of a liquid containing a large amount of protein disappears. Damage to the capillary wall can be caused by chemical, bacterial, thermal or mechanical agents. The increase in permeability of capillaries can also be a consequence of the hypersensitivity reaction, being a characteristic feature of immune damage. Damage to the endothelium of the capillaries, apparently, is the main cause of inflammatory edema, which differs in density, usually a limited inflammation, a combination with other signs of inflammation - redness, local fever and pain.
Fig. 28.1. The consequences of the pathological process, leading to a delay in the body of water and minerals and the development of edema. PNP, atrial natriuretic factor; dotted arrow - suppression of renal vasoconstriction.
In order to formulate the hypothesis ofpathogenesis of edema, it is important to draw a line between primary changes, such as obstruction of the venous or lymphatic ducts, reduction of cardiac output, hypoalbuminemia, fluid sequestration, for example in the abdominal cavity, or increased capillary permeability, and the most likely secondary changes that occur in kidney water retention and salts. There are situations in which a pathological positive balance of salts and water can be really primary. At the same time edema develops again, reflecting the generalized increase in the volume of extracellular fluid. These special cases are usually associated with conditions characterized by a sharp decrease in kidney function, such as tubular necrosis or acute glomerulonephritis (Figure 28-1).
Discarding these circumstances aside, you cancontinue to develop a hypothesis that, although incomplete, can contribute to an understanding of the pathophysiology of the changes that are taking place. The fundamental premise is that the primary disorder affects primarily one or more Starling forces, resulting in a clear movement of fluid from the vascular system into the interstitium, or "third space", or from the arterial part of the vasculature in the heart cavity or directly into the venous system. Effective volume of arterial blood - a parameter that reflects the filling of the arterial system and is difficult to determine by modern methods - is reduced. As a consequence, a whole series of physiological reactions are set in motion, aimed at restoring this index to normal values. The key element. These reactions are the retention of excess salt, and consequently, of water. In many cases, this compensates for the deficit of an effective volume of arterial blood and the resulting disorder is not accompanied by the development of obvious edema. If, however, delays in salts and water are not enough to restore and maintain an effective volume of arterial blood, then pathological stimulation continues. This leads to further accumulation in the body of minerals and water and ultimately to the development of edema. Such a sequence. changes occur with dehydration and bleeding. Despite the fact that under these conditions there is a decrease in the effective volume of arterial blood and activation of the whole chain of reactions presented in the right part of Fig. 28-1, including a decrease in the excretion of salts and water, edema does not occur, since there is a pronounced negative balance of sodium and water ions. In most states leading to the formation of edema, the mechanisms responsible for maintaining normal effective osmolarity of body fluids operate quite effectively, so that the retention of sodium ions leads to a feeling of thirst and secretion of the antidiuretic hormone, which in turn stimulates consumption and retention in the body at about 1 liter of water for every 140 mmol of sodium ions. Similarly, measures that promote the removal of sodium in the urine, such as the administration of diuretics, are accompanied by parallel excretion from the body of an equivalent volume of water.
Reduction of cardiac output irrespective ofcauses is accompanied by a decrease in the effective volume of arterial blood, as well as renal, blood flow and increased filtration fraction, i.e., the ratio of glomerular filtration rate to renal plasmacy. In severe heart failure, especially the blood flow of the outer layers of the cortical substance of the kidneys decreases, the blood flow of the central parts is less inhibited. This leads to a slowing down of the glomerular filtration rate. The developing narrowing of the vessels of the cortical substance of the kidneys plays an important role in the retention of salt and water and the formation of edema in heart failure. At various stages of heart failure, renal vasoconstriction results in the activation of either the sympathetic nervous system or the renin-angiotensin system. Activation of the first of these can be prevented by the introduction of β-adrenoblockers. This indicates that an increase in renal vascular resistance in heart failure is at least partially mediated through sympathetic stimulation. Increased renal blood flow and copious diuresis; caused by the appointment of angiotensin-converting enzyme inhibitors, indicate the involvement of the renin-angiotensin system in salt and water retention in heart failure.
Reinforcement of tubular reabsorption of the glomerularThe filtrate plays a fundamental role in the retention of salt and water in heart failure. However, the exact location of the kidney tubule section (s) (Henle loop or collecting ducts), which is () responsible for this, is unknown, as well as the probable mechanisms of this phenomenon are not established. It is believed that a significant role here is played by the change in intracenal hemodynamics. Heart failure, increasing the restriction of potechnyh arterioles, reduces hydrostatic pressure and raises colloid osmotic pressure in the circumcircular capillaries, thereby stimulating the reabsorption of salt and water in the proximal tubule. The above redistribution of the intrarenal blood flow, characteristic of heart failure, can lead to an increase in the reabsorption of sodium ions in the ascending knee of the Henle loop.
In addition, a decrease in renal blood flow,which is a characteristic feature of all conditions under which the effective volume of arterial blood decreases, is perceived by juxtaglomerular kidney cells as a signal to enhance the release of renin (see Chapter 325). The specific nature of this signal is complex. One of the participating factors is the baroreceptor mechanism, which consists in that reduced renal perfusion leads to incomplete filling of renal arterioles and insufficient extension of juxtaglomerular cells. This signals the need for the production and (or) release of renin. The second mechanism involves the participation of a dense spot. Due to a decrease in glomerular filtration, the amount of sodium ions reaching the distal renal tubules decreases. This is perceived by a dense patch and, in an unknown manner so far, causes adjacent juxtaglomerular cells to secrete renin. The third mechanism includes the sympathetic nervous system and circulating catecholamines. Activation of α-adrenergic receptors of juxtaglomerular cells stimulates the release of renin. All three mechanisms usually work together.
Renin, an enzyme with a molecular weight of about 40,000,acts on the substrate, angiotensinogen -? 2-globulin, synthesized in the liver with the formation of angiotensin I, which is a decapeptide, which in turn decomposes to form angiotensin II, an octapeptide that has vasoconstrictive properties. Intra-cellular production of angiotensin II can also lead to narrowing of the kidney vessels and to salt and water retention in heart failure. Angiotensin II, in addition, enters the bloodstream and stimulates the synthesis of the glomerular zone of the adrenal cortex of aldosterone. In patients with heart failure, not only the increased secretion of aldosterone occurs, but the half-life also increases, which leads to an even higher increase in the level of this hormone in the plasma. Inhibition of renal blood flow, especially during exercise, as a consequence of a decrease in cardiac output leads to a decrease in hepatic catabolism of aldosterone.
Despite the fact that with heart failureand other conditions accompanied by edema, the amount of secreted aldosterone increases and in spite of the fact that blockade of aldosterone action by spironolactone often causes a moderate increase in diuresis in the presence of edema, elevated levels of aldosterone and other mineralocorticoids do not always contribute to the formation of edema, which is confirmed by the absence of appreciable fluid retention in most cases primary aldosteronism (see Chapter 325). Moreover, although healthy individuals experience partial retention of salts and water under the influence of such powerful mineralocorticoids as deoxycorticosterone acetate or fludrocortisone, it is self-regulating, regardless of the continued intake of electrolytes and water. The lack of accumulation of large amounts of fluid in the body in healthy people is probably due to the intensification of glomerular filtration, other hemodynamical reactions and, most importantly, the increase in the volume of the circulating fluid, which stimulates the excretion of salts regardless of the filtered amount of sodium ions, i.e., through action natriuretic substances. The role of aldosterone in the accumulation of fluid in edematous states can increase, since these patients lack the ability to compensate for the deficit of effective arterial blood volume.
Stretching of the atrial cavity and (or) enlargementthe intake of sodium ions causes the release into the bloodstream of the atrial natriuretic factor (PNP), a polypeptide whose active fraction includes 21 to 33 amino acids. The PFN precursor, which has a high molecular weight, is stored in secretory granules within the atrial myocytes. The release of PNP leads to the excretion of sodium and water ions due to an increase in the rate of glomerular filtration and inhibition of the intake of renin and aldosterone in the blood, as well as the expansion of arterioles and veins. Thus, PNP has the ability to counteract the delay in the body of sodium ions and increase blood pressure in conditions characterized by hypervolemia. There are also separate reports indicating the existence of another, completely different from the first, natriuretic factor, which is a low-molecular compound. It is activated or enters the bloodstream due to an increase in the volume of extracellular fluid and causes sodium nares, suppressing the reabsorption of sodium ions in the kidneys by inhibiting ouabain-sensitive Na, K-ATPase. The role of this factor and PNP in normal and pathophysiological conditions requires specification.
Obstruction of venous and lymphatic fluid outflow from the extremity.
In this case, the hydrostatic pressure inthe capillary bed above the obstruction site increases, so that more fluid than under normal conditions passes from the vascular to the interstitial space. Since an alternative way of fluid outflow (through the lymphatic vessels) is also impossible, there is an accumulation of the interstitial fluid in the affected limb (as in the trap), naturally, due to the volume of blood of the whole organism. As a consequence, the effective volume of arterial blood decreases, which leads to the consequences indicated in Fig. 28-1.
As the fluid accumulates in the interstitialthe limb space, the venous and lymphatic outflow from which is difficult, there is an increase in tissue pressure until it compensates for the primary change in Starling's forces. After that, the accumulation of fluid in the limb is stopped. Additional intake into the body at this point in the fluid compensates for the deficiency of the plasma volume and interrupts the stimulation of mechanisms for salt and water retention. Thus, a violation of the outflow of fluid from any area leads to a local increase in the volume of the interstitial fluid, and the secondary compensatory mechanisms that are developing compensate for the resulting deficiency of the plasma volume.
Similar changes occur with ascites andhydrothorax, when fluid is retained or accumulated in the interstitial space, reducing the volume of intravascular fluid and leading to secondary retention of salts and water, as described above.
Congestive heart failure (see also Ch. 182). With this violation, incomplete emptying of the heart cavities in the systole leads to accumulation of blood in them and in the venous system to the detriment of the arterial volume. After that, the mechanisms described above are included (see Figure 28-1). In many cases with moderate heart failure, a small increase in volume can restore the existing deficit and lead to a stable state, because, according to Starling's law for the heart, an increase in the volume of blood in the heart cavities causes a stronger contraction of it, which can increase cardiac output (cm (see Figure 181-4). However, if the cardiac disorder is more severe, an increase in fluid volume can not compensate for the deficiency of effective arterial blood volume. Additional fluid accumulates in the venous system and, by increasing hydrostatic pressure, promotes the formation of edema. The appearance of edema in the lung tissue (see Chapter 26) disrupts gas exchange and can lead to hypoxia, which further weakens the function of the heart.
In addition to the changes that arethe right-hand side of Fig. 28-1, incomplete ventricular liberation leads to an increase in diastolic pressure in the ventricles. If the pathological process affects the work of the right ventricle, then its incomplete emptying leads to an increase in the diastolic volume and pressure in it. As a result, the pressure in the venous system and capillaries increases, which entails an increase in the fluid's transudation into the interstitial space. This creates the prerequisites for the development of peripheral edema. Increased systemic venous pressure is transmitted to the chest lymphatic duct, reducing the outflow of lymph, which further contributes to the formation of edema. If the pathological process affects the left ventricle, then the pressure in the pulmonary veins and capillaries increases (in some cases this leads to pulmonary edema, Chapter 26), as well as pressure in the pulmonary artery. This in turn hinders the emptying of the right ventricle, leading to an increase in diastolic pressure in it, as well as an increase in central and systemic venous pressure, increasing the risk of developing systemic edema.
Nephrotic syndrome and othershypoalbuminemic conditions (see also Chapter 223). The primary disorder in this condition is a decrease in colloid-oncotic pressure due to massive protein losses in the urine. In response, the fluid passes into the interstitial space, causes hypovolemia, followed by the chain of changes described above. In the case of prolonged severe hypoalbuminemia, the electrolytes and water retained in the body can not remain in the vascular bed, and consequently, impulses aimed at delaying their excretion are not weakened. A similar chain of events occurs in other conditions in which severe hypoalbuminemia arises, including reduced nutrition, enteropathy accompanied by loss of protein, congenital hypoalbuminemia, and severe chronic liver disease.
Cirrhosis of the liver (see also Chapters 39 and 249). The total volume of blood in cirrhosis is usually increased when the disease reaches the stage at which the venous network expands and numerous arteriovenous anastomoses open. However, effective systemic perfusion, effective arterial blood volume and intrathoracic blood volume are reduced, possibly due to blood circulation through these anastomoses, development of portal hypertension, and impaired lymphatic drainage from the liver. These changes are often complicated by a decrease in the level of albumin in the serum, which further reduces the effective volume of arterial blood, leading to the activation of the renin-angiotensin-aldosterone system and other salt and water retention mechanisms. Initially, the excess of interstitial fluid is localized mainly in the region of stagnant portal venous and occluded lymphatic systems of the liver, namely in the peritoneal cavity. In the late stages of the disease, especially in the presence of hypoalbuminemia, the development of peripheral edema becomes noticeable.
Idiopathic edema. This syndrome occurs almost exclusively in women, who often have psychosocial problems, and is characterized by episodes of periodic onset of edema, often in combination with stretching of the anterior abdominal wall. During the day there are quite significant fluctuations in body weight, so after staying for several hours in an upright position, it can increase by 1-2 kg. Such pronounced daily changes in body weight allow one to suspect the presence of increased capillary permeability, the extent of which, apparently, can vary. The condition is aggravated in hot weather. The fact that this syndrome occurs mainly in women and is most pronounced in the pre-menstrual period, and that the condition may improve after the administration of progesterone, indicates that the permeability of the vessels varies under the influence of hormones. In the vertical position, plasma loss to the interstitial space occurs, which in turn leads to a decrease in the plasma volume and subsequent retention of electrolytes and water.
Treatment of idiopathic cyclic edemais to reduce salt intake, daily rest in a horizontal position for several hours, use elastic stockings that should be worn in the morning before getting out of bed, and also whenever possible a quick solution to any emerging emotional problems. There are reports that if these simple measures do not have the desired effect, the condition can be facilitated by taking an angiotensin-converting enzyme inhibitor captopril, a dopamine receptor agonist bromocriptine, and a sympathomimetic amine dextroamphetamine. Providing initially a positive effect, diuretic medications can lose their effectiveness with prolonged administration. Therefore, they should be appointed carefully, if at all, to be appointed.
As a rule, localized edema occursit is easy to distinguish from generalized edema. In the overwhelming majority of patients with non-inflammatory generalized edema of considerable severity, the functions of the heart, kidneys, liver, and digestive tract, which go far beyond the limits, suffer. Therefore, the differential diagnosis of generalized otkov should be aimed at identifying or eliminating these serious diseases.
Localized edema. Edemas resulting from inflammation or hypersensitivity reactions can usually be recognized without difficulty. Localized edema due to venous or lymphatic obstruction can be caused by thrombophlebitis, chronic lymphangitis, resection of regional lymph nodes, filariasis, etc. Lymphatic edema is usually very poorly displaced, as limiting lymph outflow is accompanied by an increase in protein concentration in the interstitial fluid. It is this circumstance that makes it very difficult to remove the accumulated liquid.
Edema with heart failure. Edema in heart failure is usually combined with such manifestations of heart disease as an increase in heart size and gallop rhythm, as well as signs of lowering the pumping function of the heart, such as dyspnea, wheezing in the lower parts of the lungs, swelling of the veins and hepatomegaly. Clinical examination, such non-invasive studies as echocardiography and radioisotope angiography, can facilitate the diagnosis of heart failure and the identification of pathogenesis factors for the formation of edema (see also Chapters 179 and 182).
Edema with nephrotic syndrome. In this case, there is massive proteinuria (more than 3.5 g / day), severe hypoalbuminemia, and in some cases, hypercholesterolemia. This syndrome can occur during the progression of a number of kidney diseases - glomerulonephritis, diabetic glomerulosclerosis, as well as allergic reactions of immediate type. Some patients have a history of kidney disease (see also Chapter 233).
Edema in acute glomerulonephritis. A characteristic feature of edema developing in the acute phase of glomerulonephritis is their combination with hematuria, proteinuria and arterial hypertension. Despite the fact that there are indications that fluid retention is a consequence of increased capillary permeability, in most cases edema in this disease occurs as a result of primary retention of sodium and water ions by kidneys whose function is reduced. This condition, unlike congestive heart failure, is characterized by normal or increased cardiac output, normal or shorter blood circulation time, a decrease in hematocrit and the usual values of the arteriovenous oxygen difference. These patients with chest radiography usually show signs of fluid stagnation in the lungs, which appear before the increase in the size of the heart. However, orthopnea does not develop (see also Chapter 223).
Edema with cirrhosis of the liver. For edema of hepatic origin is characterized by a combination of ascites with such signs of liver disease as the development of venous collaterals, jaundice and arachnid angiomas. Ascites are rarely treatable, because accumulated fluid is the result of a combination of obstruction of the lymph drainage from the liver, portal hypertension and hypoalbuminemia. Moreover, a significant accumulation of ascitic fluid can increase intra-abdominal pressure and prevent venous return from the lower extremities. Naturally, this also contributes to the formation of edema in this area (see also Chapter 249).
Edema of alimentary origin. Inadequate nutrition for a long time causes hypoproteinemia and swelling, which can be aggravated by heart disease as a result of beriberi disease. At the same time, numerous peripheral arteriovenous anastomoses are opened, leading to a decrease in effective systemic perfusion and an effective volume of arterial blood, thereby stimulating the formation of edema (see Chapter 193). The swelling becomes even more severe when exhausted people begin to receive adequate food. Consuming more foods increases the intake of salts, which then linger, dragging water behind them. In addition to hypoalbuminemia, hypokalemia and caloric insufficiency also contribute to the appearance of edema, when fasting.
Other causes of edema. These include hypothyroidism, in which the myxedema in typical cases is localized in the prebiotic area, combined with periorbital edema. Exogenous hyperadrenocorticism, pregnancy, treatment with estrogens and vasodilators can also cause the appearance of edema.
Distribution. Distribution of edema is an important diagnostic feature. Thus, swelling of one leg or one or both arms is usually the result of venous and (or) lymphatic obstruction. Edema due to hypoproteinemia, as a rule, is generalized in nature, but most clearly they appear in the soft tissue of the eyelids and face, especially in the mornings after staying throughout the night in a horizontal position. Edema associated with heart failure, on the contrary, is most noticeable on the lower limbs and mainly in the evening, which is also primarily related to the position of the body. With rare heart diseases such as stenosis of the tricuspid valve and constrictive pericarditis, in which orthopnea is absent and patients prefer to occupy a horizontal position, the gravitational factor is leveled and the edema is located in the face area. Less frequent causes of edema of the face are trichinosis, allergic reactions and myxedema. Unilateral edema in a number of cases can be the result of a lesion of the CNS affecting the vasomotor fibers of one side of the body. Paralysis also reduces the outflow of lymph and venous blood from the side of the lesion.
Additional diagnostic factors. The color, thickness, density and sensitivity of the skin are also important. Local increase in sensitivity and temperature suggests the presence of inflammation. Local cyanosis can indicate a violation of venous outflow. In persons with repeated episodes of long-lasting edema, the skin above the affected area can be thickened, compacted, and often its redness is noted.
When examining a patient with edema is importantthe element is the measurement of venous pressure. Its elevation in one area of the body usually reflects local venous obstruction. A generalized rise in systemic venous pressure usually indicates the presence of congestive heart failure, although this can also be observed with hypervolemia that accompanies acute renal failure. As a rule, a significant increase in venous pressure can be recognized by determining the level of the head lift at which the cervical veins collapse. In doubtful cases, and to obtain more accurate data, the central venous pressure should be measured. In patients with obstruction of the superior vena cava, edema is localized mainly in the face, neck and upper extremities, since venous pressure is higher here than in the lower extremities. Measuring the venous pressure of the upper limbs is also useful in patients with massive edema of the lower extremities and ascites. With edema of cardiac origin, for example, with constrictive pericarditis or tricuspid stenosis, it is elevated, but it remains normal if edema is caused by cirrhosis of the liver.
Determination of protein concentration in serum,especially albumin, allows to identify those patients whose edema, at least in part, is a consequence of a decrease in intravascular colloid-oncotic pressure. Proteinuria is a valuable diagnostic feature. The complete absence of protein in the urine allows you to reject kidney disease as the cause of edema. Light or moderate proteinuria is a natural finding in patients with heart failure, while prolonged massive proteinuria is usually characteristic of nephrotic syndrome.
Diagnostic approach to a patient with edema
First of all it is necessary to find out which swelling -localized or generalized - are available to the patient. If localized, then attention should be concentrated on the relevant states. In this context, localized edema should include hydrothorax, ascites or both in the absence of congestive heart failure or hypoalbuminemia. Any of these can be a consequence of local venous or lymphatic obstruction, as well as an inflammatory disease or carcinoma.
If swelling is generalized, thenFirst of all, the degree of hypoalbuminemia should be assessed. Expressed hypoalbuminemia is considered a decrease in the albumin level below 25 g / l. If there is indeed hypoalbuminemia, then on the basis of the history, physical examination, urinalysis results and other laboratory studies should determine its cause: cirrhosis, severe eating disorders, gastroenteropathy with protein loss or nephrotic syndrome. If hypoalbuminemia is not present, it should be determined whether there are signs of congestive heart failure of the degree of severity that could cause generalized edema. In conclusion, you should make sure that the patient has an adequate diuresis or, conversely, there is a pronounced oliguria or even anuria. These disorders are discussed in Ch. 40, 219, 220. In this case, a differential diagnosis should be made between primary renal salt and water retention and congestive heart failure