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Edema Edema Edema is defined as an increase in the extravascular (interstitial) component of the extracellular fluid volume, which may expand by several liters before the abnormality is recognized. Edema The blood volume that is detected by the volume sensors located in the arterial side of the circulation is sometimes referred to as the effective arterial blood volume (EABV). EABV is the amount of arterial blood volume required to adequately ‘fill’ the capacity of arterial circulation. ECF volume and EABV can be independent of each other. Edema For example, some edematous states can be associated with an increase in total ECF volume and decreased EABV. Also, postural changes may cause fluid shifts that influence the EABV without affecting the total blood volume. Volume changes in various disease states Renal Compartment Volume Nephrosis Congestive A-V fistule with congestive artery depletion heart failure state stenosis Total ECF ↓ ↑ ↑ ↑ ↑ volume Total blood ↓ ↓ ↑ ↑ ↑ volume Arterial blood ↓ ↓ ↓ ↑ ↑ volume EABV ↓ ↓ ↓ ↓ ↑ Renal blood ↓ ↓ ↓ ↓ ↓ flow Edema The characteristic feature of the body fluid homeostatic mechanism is that the composition of the body fluid compartments remains remarkably constant despite wide daily variations in solute and water intake. Edema The integrated homeostatic response involves two key components: an afferent limb that contains sensors that detect changes in the effective circulating volume and an efferent limb that regulates the rate of sodium excretion by the kidney Major efferent mechanisms regulating ECF volume I. Glomerular filtration rate II. Physical factors: at the level of the proximal tubule beyond the proximal tubule III. Humoral effector mechanisms Renin-angiotensin-aldosteron system, Vasopressin, Catecholamines, Prostaglandins, Kinin-kalikrein system, Atrial natriuretic peptide, Endothelium-derived factors IV. Renal sympathetic nerves Hormones regulating renal sodium excretion – Vasoconstrictors Mediators Angiotensin II Site of production Circulating/local generation Site of action Glomerular arterioles, proximal tubule Tubular actions Na retention Aldosterone Vasopressin Adrenal glands, Hypothalamus Na retention Water retention Na retention Catecholamines Adrenal glands Distal tubule Thick ascending limb of loop of Henle (TAL), distal tubule Glomerular arterioles, proximal tubule Glomerular arterioles, proximal tubule Glomerular arterioles Inner medullary collecting duct (IMCD) Tubular Na/K ATPase Kidneys Renal sympathetics Endothelium Endothelin 1 Adrenal glands Na/K ATPase inhibitors Na retention Na retention Natriuresis Natriuresis Hormones regulating renal sodium excretion – Vasodilators Mediators Atrial natriuretic peptide Brain natriuretic prptide C-type natriuretic peptide Urodilatin Nitric oxide Site of production Cardiac atria Tubular actions Natriuresis Brain Site of action Cortical collectin duct(CCD) CCD/IMCD Endothelium CCD/IMCD Natriuresis Renal tubules Endithelium CCD/IMCD Glomerular arterioles, distal nephron Glomerular arterioles, TAL, CCD, IMCD Glomerular arterioles, IMCD Natriuresis Natriuresis Prostaglandins E2 and I2 Bradykinine-kalikrein Kidneys Distal nephron Natriuresis Natriuresis Natriuresis Classification of disorders associated with extracellular fluid volume excess on the type of physiologic derangement I. Disturbed Starling forces: reduced effective circulating volume, edema formation -Systemic venous pressure increases: right heart failure, constrictive pericarditis -Local venous pressure increases: left heart failure, vena cava obstruction, portal vein obstruction -Reduced oncotic pressure: nephrotic syndrome -Combined disorders: cirrhosis Classification of disorders associated with extracellular fluid volume excess on the type of physiologic derangement. II. Primary hormones excess: increased effective circulating volume Primary aldosteronism Cushing’s syndrome Syndrome of inappropriate secretion of vasopressin (SIADH) III. Primary renal sodium retention: increased effective circulating volume Acute glomerulonephritis Edema Depending on its cause and mechanism, edema may be localized or have a generalized distribution; it is recognized in its generalized form by puffiness of the face, which is most readily apparent in the periorbital areas, and by the persistence of an indentation of the skin following pressure; this is known as "pitting" edema. Edema Therefore, the weight gain of several kilogrames usually precedes overt manifestations of edema, and a similar weight loss from diuresis can be induced in a slightly edematous patient before „dry weight” is achieved. Edema In its more subtle form, it may be detected by noting that after the stethoscope is removed from the chest wall, the rim of the bell leaves an indentation on the skin of the chest for a few minutes. Edema An early symptom a patient may note is the ring on the finger fitting more snugly than in the past, or difficulty in putting on shoes, particularly in the evening Ascites and hydrothorax refer to accumulation of excess fluid in the peritoneal and pleural cavities, respectivly, and are considered to be special forms of edema. Anasarca refers to gross, generalized edema. Congestive heart failure Clinical manifestation Patient with congestive heart failure usually present with history of dyspnea on exertion, weakness, decrease exercise tolerance, orthopnea, paroxysmal nocturnal dyspnea, sometimes nocturia Patient with congestive heart failure Physical examination reveals increased weight gain distention of the jugular veins pulmonary rales tachycardia, third heart sound ankle edema (pretibial and ankle edema is frequently seen in the evening in ambulatory patients, and presacral edema is features of individuals at bed rest) Nephrotic syndrome The edema of nephrotic syndrome is usually diffuse and manifests itself as anasarca. Periorbital edema is a characteristics feature of nephrotic syndrome. Some patients may present with pleural effusions or ascites. SODIUM HOMEOSTASIS AND EDEMA FORMATION The presence and severity of edema are related in a general way to the extent of depression of albumin concentration; however, notable exceptions may occur. Initially a drop in interstitial oncotic pressure concomitant with the decline in plasma oncotic pressure tends to preserve the transcapillary oncotic pressure gradient and retard the development of edema. The limited ability of the interstitial oncotic pressure to fall further despite worsening of plasma albumin concentration and plasma oncotic pressure (below about 8 mm Hg) ultimately leads to enhanced flow of fluid into the interstitial space at rates that cannot be accommodated by a further increase in lymphatic flow, so edema fluid accumulates. SODIUM HOMEOSTASIS AND EDEMA FORMATION It seems likely that the Na+ retention in nephrotic states is related to intrarenal events and is not dependent on a change in activity of the reninangiotensin-aldosterone system. Indeed, values for plasma volume, plasma renin, and plasma aldosterone are highly variable in nephrotic subjects with edema. In general, expanded plasma volume and suppressed plasma renin are more often observed in patients with proliferative glomerular lesions, especially with reduced GFR. SODIUM HOMEOSTASIS AND EDEMA FORMATION Lowered plasma volume and enhanced plasma renin are more often observed in patients with minimal glomerular lesions and the acute onset of severe proteinuria. Water immersion of nephrotic subjects with edema will result in a diuresis, natriuresis (albeit blunted compared with normal subjects), phosphaturia, and calciuria. These effects can occur without major change in plasma aldosterone concentration, and the intensity of the augmented excretion of Na+ is related directly to the preimmersion plasma volume. Complications and General Management EDEMA The edema of nephrotic syndrome is in many instances a bothersome but not debilitating clinical feature, but it can occasionally be severe and associated with accumulation of peritoneal or pleural fluid. Pericardial effusions are rare in uncomplicated nephrotic syndrome. In the periphery, edema is characteristically soft and easily pitting and accumulates in areas of low interstitial tissue pressure and high compliance, such as the periorbital areas. It is usually worse about the face on arising and increases in dependent areas with activity and upright posture. Complications and General Management EDEMA Treatment of edema consists of mild sodium restriction and, in selected cases, the judicious use of diuretics. Many patients experience spontaneous diuresis during recumbency. Potent loop diuretics such as furosemide, bumetanide, or ethacrynic acid have become popular, although thiazide diuretics (hydrochlorothiazide or chlorthalidone) may suffice in many cases. Metolazone may be effective when used alone or in combination with furosemide in severe or refractory nephrotic edema. Complications and General Management EDEMA Because marked kaliuresis may occur with the use of these diuretics, a K+ sparing diuretic such as spironolactone, amiloride, or triamterene may be employed concomitantly to prevent hypokalemia. However, these agents should not be used when GFR is substantially decreased because of the danger of precipitating hyperkalemia. Diuretics should be used cautiously in patients with profound hypoalbuminemia. Hyperoncotic salt-poor albumin infusions should be reserved for patients for whom orthostatic hypotension and hypovolemia are a significant problem or in cases of severe and refractory edema. Complications and General Management EDEMA Albumin infusions transiently increase plasma volume and oncotic pressure and may restore diuretic responsiveness, but most of the infused albumin is excreted in the urine 24 to 48 hours after completion of the infusion. When plasma oncotic pressure is profoundly depressed (less than 8 mm Hg), as in the case of severe hypoalbuminemia, there may be a tendency for accumulation of interstitial fluid even in the lowpressure pulmonary circuit. Even minor increases in left atrial filling pressure may induce florid pulmonary edema in such patients. Complications and General Management EDEMA Treatment for this complication is similar to that for the pulmonary edema of left ventricular failure, with the addition of measures to increase plasma oncotic pressure, while at the same time ensuring that left atrial (pulmonary wedge) pressure is not further increased. The combination of intravenous furosemide and hyperoncotic albumin infusion would seem to be a reasonable therapeutic approach to this uncommon problem. Extracorporeal ultrafiltration is rarely, if ever, required unless GFR is markedly reduced. Hepatic cirrhosis Hepatic cirrhosis presents clinically as ascites and lower-extremity edema as a result of portal hypertension and hypoalbuminemia. Other signs of liver disease include: jaudice, spider angiomas palmar erythema gynecomastia TREATMENT The management of ECF volume-expanded states is dependent on the accurate diagnosis and treatment of the underlying disorder The cornerstones of therapy in these patients is 1) salt restriction patients with mild volume expansion – 4g/day (172 mmol/day) patients with moderate-to-severe ECF volume expansion – 2g/day (86 mmol/day) 2) diuretics 3) restriction of daily fluid intake (the intake should be adjusted to equal urinary losses and insensible loss THE MANAGEMENT OF VOLUME – EXPANDED STATES SHOULD AIM TO CORRECT THE UNDERLUING PRIMARY DISORDER Drugs that predispose to salt retention or alter the effect of diuretics need to be discontinued Classification of diuretics Site of action Proximal diuretics Loop diuretics Distal convoluted tubule diuretics Collecting duct diuretics Acetozolamide Metolazone Furosemide Bumetanide Torsemide Ethacrynic acid Thiazides Metolazone Amiloride Triamterene Spironolactone Classification of diuretics based on predominant site of action Type of diuretic Site of action Carbonic anhydrase inhibitor Acetozolamid Proximal tubule Potency Primary Secondary Complications effect effect ↑ K loss ↑ HCO 3 loss +++ +++ ↓ Na + /K + /2Cl absorption ↑ K + loss ↑H+ secretion Hypokalemic alkalosis ++ ++ ++ ↓ Na + absorption ↑ K + loss ↑H+ secretion Hypokalemic alkalosis + + + ↓ Na + absorption ↓ K + loss ↓H+ secretion Hyperkalemic acidosis + Loop Furosemide Etacrynic acid Loop of Henle Thiazide Chlorthiazide Distal tubule Hydrochlorothiazide M etolazone Potassium sparing Collecting Triamterene duct Amiloride Spironolocatone Hypokalemic hyperchloremic acidosis ↓ Na /K exchange + + + Idiopathic edema This syndrome occurs almost exclusivly in women often with psychosocial difficulties, is characterized by periodic episodes of edema, frequently accompanied by abdominal distention Fairly large, diurnal alterations in weigh occur, so that the patient may weigh several pounds more after having been in the upright posture for several hour. This fact suggest an increase in capillary permeability which appears to fluctuate in severity and is aggrevated by hot weather. Edema; Anasarca Swelling involves the enlargement of organs, skin, or other body structures caused by excessive buildup of fluid in the tissues. This buildup can lead to a rapid increase in weight over a short period of time (days to weeks). Swelling can occur throughout the body (generalized) or it may be limited to a specific part of the body (localized). Edema; Anasarca Slight edema of the lower legs commonly occurs in warm summer months, especially if a person has been standing or walking a lot. Generalized swelling, or massive edema (also called anasarca), is a common sign in severely ill people. Although slight edema may be difficult to detect, especially in an overweight person, massive edema is very obvious. Edema can indicate a chronic and progressive medical illness. Edema; Anasarca Edema may be generally described in one of two ways: Pitting edema -- When you press a finger against a swollen area for 5 seconds and then quickly remove it, an indentation is left that fills slowly. Nonpitting edema -- When you press a finger against a swollen area for 5 seconds and then quickly remove it, no indentation is left in the skin. Edema; Anasarca Common Causes Too much salt or sodium intake Burns Sunburn Too little albumin in the blood (hypoalbuminemia) Malnutrition Pregnancy Drugs Androgenic and anabolic steroids Antihypertensives Corticosteroids such as prednisone (causes sodium retention) Estrogens Nonsteroidal anti-inflammatory drugs (see NSAIDs) Calcium channel blockers Nephrotic syndrome Acute glomerulonephritis Chronic kidney disease Heart failure Liver failure from cirrhosis Thyroid disease Edema; Anasarca Medical history Time pattern When did you first notice this? Is it present all the time? Does it come and go? Quality How much swelling is there? When you poke the area with a finger, does the dent remain? Location Is it overall or in a specific area (localized)? If swelling is in a specific area, what is that area? Other What seems to make the swelling better? What seems to make the swelling worse? What other symptoms are also present? Edema; Anasarca Diagnostic tests that may be performed include the following: Albumin levels ECG Echocardiography Serum electrolyte tests Urinalysis X-rays Liver function tests Kidney function tests Edema; Anasarca Treatment may include fluid and sodium restriction, diuretics, or water pills. fluid intake and output should be monitored, and patient should be weighed daily. „Avoid alcohol if liver disease (such as cirrhosis or hepatitis) is causing the problem.” Vascular support hose may be advised. Localized edema due to venous or lymphatic obstruction may be caused by thrombophlebitis, chronic lymphangitis resection of regional lymph nodes, filariaris etc. Lymphedema is particularly intractable because restriction of lymphatic flow results in increased protein concentration in the interstitial fluid, a circumstance which aggravates retention of fluid Edema – peripheral Swelling of the ankles - feet - legs; Ankle swelling; Foot swelling; Leg swelling; Peripheral edema is an abnormal buildup of fluids in ankle and leg tissues. Painless swelling of the feet and ankles is a common problem, particularly in older people. It may affect both legs and may include the calves or even the thighs. Because of the effect of gravity, swelling is particularly noticeable in the lower legs. When the swollen area is squeezed, the fluid will move out of the affected area and may leave a deep impression for a few moments. Swelling of the legs is many times related to systemic causes (for example, heart failure, renal failure, or liver failure). Edema – peripheral Common Causes Long airplane flights or automobile rides Menstrual periods (for some women) Sunburn Generalized allergy Prolonged standing Injury or trauma to the ankle or foot Venous insufficiency (varicose veins) Pregnancy (mild to severe swelling) Environmental Burns Insect bite or sting Starvation or malnutrition Edema – peripheral Common Causes Medical treatments Body fluid overload Infiltration of an IV site Extremity surgery Medications Estrogens and progestin oral contraceptives Blood pressure-lowering drugs Certain antidepressants (such as Nardil) Estrogen - oral Long-term corticosteroid therapy Nifedipine Testosterone Diagnostic tests Venogram Congestive heart failure Glomerulonephritis or other kinds of kidney disorders Edema – peripheral Home Care Elevate the legs above the heart while lying down. Avoid sitting or standing without moving for prolonged periods of time. Avoid putting anything directly under the knees when lying down, and don't wear constricting clothing or garters on the upper legs. Exercising the legs causes the fluid to work back into the veins and lymphatic channels so that the swelling goes down. Elastic bandages or support stockings can provide pressure to help reduce ankle swelling. Edema – peripheral Medical history questions documenting ankle, feet, and leg swelling in detail include the following: Location What specific body part(s) swell? Is there ankle swelling? Is the whole foot swollen? Is there swelling over the small bones of the feet? Is there swelling of the toes? Is the knee swollen? Is the whole leg swollen? Time pattern Is the swelling always present? Is it worse in the morning or the evening? Edema – peripheral Medical history questions documenting ankle, feet, and leg swelling in detail include the following: Aggravating and relieving factors What makes it better? Does the swelling go down when the legs are elevated? What makes it worse? What other symptoms are also present? The physical examination may include emphasis on the heart, lungs, kidneys, and legs. Edema – peripheral Diagnostic tests that may be performed include the following: Blood tests such as a CBC or blood chemistry (Chem-20) ECG Chest X-ray or extremity X-ray Edema – peripheral The specific treatment will be directed at whatever underlying cause is found. Diuretics may be prescribed. These are effective in reducing the swelling but have some side effects. Home treatment for benign causes of leg swelling should be tried before drug therapy under medical supervision. Facial swelling Edema, central on the face Puffy face; Swelling of the face; Moon face; Facial edema Facial swelling involves an accumulation of fluid in the face, which may extend to the neck and upper arms. Facial swelling If the facial swelling is mild, it may be hard to detect. it is important to note the following: Whether there is pain The duration of the swelling What makes it better or worse Any other symptoms that accompany the swelling Facial swelling Common Causes Obesity Allergic reaction (such as allergic rhinitis, hay fever, or a bee sting) Conjunctivitis with swelling around the eye(s) Stye with swelling around the infected eye Malnutrition (when severe) Sinusitis Facial trauma or injury (such as burns) Drugs including prolonged use or allergic reaction to aspirin, antipyretics, penicillin, sulfa, glucocorticoids, or other drugs Blood transfusion reaction Head, nose, or jaw surgery Angioedema from any cause including reaction to contrast media from radiologic tests Cellulitis Tooth abscess Facial swelling If facial swelling is caused by burns and/or respiratory distress is present, emergency measures must be taken first. Then the medical history will be obtained and a physical examination performed. Medical history questions documenting facial swelling in detail may include the following: Time pattern • How long has the facial swelling lasted? • When did it begin? What makes it worse? What makes it better? General health • What is your height and weight? • How is your diet? Facial swelling Other • Has there been exposure to something to which the person may be allergic (an antigen)? • What medication(s) are you taking? • Have you had recent facial injury? • Have you had a recent test or surgical procedure? • What other symptoms are also present? Especially, is there: – Facial pain – Sneezing – Difficulty breathing – Hives or rash – Eye redness – Fever Diagnostic tests will be determined by other accompanying symptoms and results of the physical examination. Joint swelling Swelling of a joint; Knee swelling; Toe swelling; Finger swelling; Hip swelling Swelling occurs in the joints when fluid accumulates in the soft tissue, such as "water on the knee." Joint swelling may occur along with joint pain. Joint swelling Common Causes Acute gouty arthritis (gout) Chronic gouty arthritis Rheumatoid arthritis Trauma Ankylosing spondylitis Enteropathic arthropathy Infection Pseudogout Psoriatic arthritis Reiter's syndrome Systemic lupus erythematosus Hemarthrosis Joint swelling Medical history questions Location Which joint is swollen? Is it the big toe? Is the jaw or neck swollen? Are multiple joints swollen? Time pattern When did the joint swelling develop? Is it always present or off and on? Is this the first time you have had swollen joints? Quality How swollen is the area? If you press over the swollen area with a finger, does it leave a dent after you take the finger away? Joint swelling Medical history Aggravating factors What makes the swelling worse? Is it any worse in the morning or at night? Does exercise make it worse? Relieving factors What make the swelling better? Does elevating the affected body part make the swelling go down? Is it better if you use an elastic wrap? What home treatment have you tried? How effective was it? Other What other symptoms are also present? Is there joint pain? Is there fever? Is there a rash? The physical examination will include a detailed examination of the affected joint(s). Joint swelling Diagnostic tests that may be performed include the following: Blood studies (such as a CBC or blood differential) Joint X-rays Physical therapy for muscle and joint rehabilitation may be recommended. Angioedema Angioneurotic edema; Swelling - eyes The development of large welts below the surface of the skin, especially around the eyes and lips. The welts may also affect the hands, feet, and throat. The condition is associated with allergies and histamine release. Angioedema Common allergens include: medications foods (such as berries, shellfish, fish, nuts, eggs, milk, and others) pollen animal dander (scales of shed skin) insect bites exposure to water, sunlight, cold or heat emotional stress Hives and angioedema may also occur after infections or illness (including autoimmune disorders, leukemia, and others). Angioedema Symptoms sudden development of wheals or welts usually located on the eyes and mouth, but may also occur on the hands and feet or in the throat red itching or painful blanch and swell if irritated deep localized edema (eyes and mouth appear swollen) abdominal cramping difficulty breathing chemosis (swollen conjunctiva) Angioedema Signs and tests The diagnosis is primarily based on the appearance of the skin and a history of exposure to an irritant/allergen. There may be stridor (crowing sound when inhaling) if the throat is affected. Rarely, allergy testing may be performed to determine the causative allergen. Angioedema Treatment Mild symptoms may not need treatment. Moderate to severe symptoms may need treatment. Difficulty breathing or stridor indicates an emergency condition. Self-care includes cool compresses or soaks to the area to provide pain relief and reduce symptoms. Medications to reduce the allergic response and associated symptoms include antihistamines, adrenaline (epinephrine), terbutaline, cimetidine, corticosteroids, sedatives, and tranquilizers. For an emergency condition, protect the airway. At the hospital, there may be a need for intubation (placement of a tube in the throat to keep the airway open). To prevent recurrence of angioedema avoid irritating the affected area, avoid known allergens, and avoid temperature extremes. Angioedema Complications Angioedema that does not affect the breathing may be uncomfortable, but it generally is harmless and resolves itself in a few days. life-threatening airway obstruction (if swelling occurs in the throat) anaphylactic reaction Edema of Nutritional Origin A diet grossly deficient in protein over a prolonged period may produce hypoproteinemia and edema. The latter may be intensified by the development of beriberi heart disease, also of nutritional origin, in which multiple peripheral arteriovenous fistulas result in reduced effective systemic perfusion and effective arterial blood volume, thereby enhancing edema formation. Edema may actually become intensified when these famished subjects are first provided with an adequate diet. The ingestion of more food may increase the quantity of salt ingested, which is then retained along with water. Edema of Nutritional Origin So-called "refeeding edema" may also be linked to increased release of insulin, which directly increases tubular sodium reabsorption. In addition to hypoalbuminemia, hypokalemia and caloric deficits may be involved in the edema of starvation. Other Causes of Edema These include hypothyroidism, in which the edema (myxedema) may be located typically in the pretibial region and which may also be associated with periorbital puffiness. Exogenous hyperadrenocortism, pregnancy, and administration of estrogens and vasodilators, particularly the calcium antagonist nifedipine, may also all cause edema. Effect of hemodynamic changes on proximal tubule solute transport: a summary. Hemodynamic mechanisms by which a reduction of effective arterial volume causes salt and water retention and thereby contributes to the formation of edema Sequence of events leading to the formation and retention of salt and water and the development of edema. ANP, atrial natriuretic peptide; RPF, renal plasma flow; GFR, glomerular filtration rate. Inhibitory influences are shown by broken lines. ADH, antidiuretic hormone.