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Edema

Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a sign observed in several medical conditions. Fluid dynamics in the body depend on body fluid compartments Body fluid compartments The adult human body is made up of 60% water and is divided into extracellular and intracellular fluid compartments. Extracellular fluid is present outside the cells and makes up two-thirds of the total body water. Intracellular fluid is present inside the cells and makes up two-thirds of the total body water. Body Fluid Compartments, fluid osmolarity Osmolarity The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per liter of solution. Osmolality is expressed in terms of osmoles of solute per kilogram of solvent. Hypernatremia, and Starling forces Starling Forces Capillaries: Histology. Edema can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Symptoms vary depending on location of the edema.

Last updated: Aug 18, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Body Fluid Compartments

Intracellular fluid Intracellular fluid The fluid inside cells. Body Fluid Compartments compartment

Extracellular fluid Extracellular fluid The fluid of the body that is outside of cells. It is the external environment for the cells. Body Fluid Compartments compartment

  • Accounts for ⅓ of total body water Total body water Body Fluid Compartments
  • Can be measured using:
    • Inulin Inulin A starch found in the tubers and roots of many plants. Since it is hydrolyzable to fructose, it is classified as a fructosan. It has been used in physiologic investigation for determination of the rate of glomerular function. Glomerular Filtration
    • Mannitol Mannitol A diuretic and renal diagnostic aid related to sorbitol. It has little significant energy value as it is largely eliminated from the body before any metabolism can take place. It can be used to treat oliguria associated with kidney failure or other manifestations of inadequate renal function and has been used for determination of glomerular filtration rate. Mannitol is also commonly used as a research tool in cell biological studies, usually to control osmolarity. Osmotic Diuretics
    • Radioactive sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia
  • Subdivided into:
Body fluid compartments

Image demonstrating body fluid compartments Body fluid compartments The adult human body is made up of 60% water and is divided into extracellular and intracellular fluid compartments. Extracellular fluid is present outside the cells and makes up two-thirds of the total body water. Intracellular fluid is present inside the cells and makes up two-thirds of the total body water. Body Fluid Compartments and the division by intracellular and extracellular fluid Extracellular fluid The fluid of the body that is outside of cells. It is the external environment for the cells. Body Fluid Compartments

Image by Lecturio.

Osmolarity and Osmolality

  • Osmolarity Osmolarity The concentration of osmotically active particles in solution expressed in terms of osmoles of solute per liter of solution. Osmolality is expressed in terms of osmoles of solute per kilogram of solvent. Hypernatremia: number of solute molecules per liter of solvent
  • Osmolality Osmolality Plasma osmolality refers to the combined concentration of all solutes in the blood. Renal Sodium and Water Regulation: number of solute molecules per kilogram of solvent
  • The difference between both is insignificant for solutions.
  • Estimated osmolality Osmolality Plasma osmolality refers to the combined concentration of all solutes in the blood. Renal Sodium and Water Regulation:
    • Posm = (2 x Na) + ( glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance/18) + (BUN/2.8)
  • Direct measurement of osmolality Osmolality Plasma osmolality refers to the combined concentration of all solutes in the blood. Renal Sodium and Water Regulation: freeze point depression/vapor pressure
  • Hematocrit Hematocrit The volume of packed red blood cells in a blood specimen. The volume is measured by centrifugation in a tube with graduated markings, or with automated blood cell counters. It is an indicator of erythrocyte status in disease. For example, anemia shows a low value; polycythemia, a high value. Neonatal Polycythemia (blood concentration):
    • Indirectly relates to osmolality Osmolality Plasma osmolality refers to the combined concentration of all solutes in the blood. Renal Sodium and Water Regulation
    • ↑ In a hypo-osmotic solution (cells swell)
    • ↓ In a hyperosmotic solution (cells shrink)
  • Serum proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis (oncotic pressure):
    • Serum albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests and globulins
  • Physiological level of blood osmolality Osmolality Plasma osmolality refers to the combined concentration of all solutes in the blood. Renal Sodium and Water Regulation is approximately 300 mOsm.
Fluid distribution and their respective cations and anions

Diagram and chart showing fluid distribution and their respective cations Cations Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. Electrolytes and anions Anions Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. Electrolytes:
Notice that K+ levels are the highest in cells and Na+ levels are the highest in the plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products.

Image by Lecturio. License: CC BY-NC-SA 4.0

Starling Forces

  • When arteriolar hydrostatic pressure > arterial oncotic pressure, fluid flows from arteriolar lumen → interstitial space
  • On the venular side, the opposite occurs: 
    • Venular oncotic pressure > venular hydrostatic pressure
    • Compels fluid to move into the capillary lumen
  • Balance of pressure:
    • Arteriolar hydrostatic and venular oncotic pressures are not completely balanced.
    • Arteriolar hydrostatic pressure is slightly ↑, meaning more fluid is deposited in the tissues than that being reabsorbed
    • Leftover fluid is collected by the lymphatic vessels Lymphatic Vessels Tubular vessels that are involved in the transport of lymph and lymphocytes. Lymphatic Drainage System: Anatomy.
  • Causes of edema by Starling forces Starling Forces Capillaries: Histology:
    • ↑ Capillary hydrostatic fluid pressure (e.g., heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR))
    • Plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products oncotic pressure (e.g., protein loss in nephrotic syndrome Nephrotic syndrome Nephrotic syndrome is characterized by severe proteinuria, hypoalbuminemia, and peripheral edema. In contrast, the nephritic syndromes present with hematuria, variable loss of renal function, and hypertension, although there is sometimes overlap of > 1 glomerular disease in the same individual. Nephrotic Syndrome)
    • ↑ Capillary permeability (e.g., sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock, burns Burns A burn is a type of injury to the skin and deeper tissues caused by exposure to heat, electricity, chemicals, friction, or radiation. Burns are classified according to their depth as superficial (1st-degree), partial-thickness (2nd-degree), full-thickness (3rd-degree), and 4th-degree burns. Burns)
    • Interstitial fluid Interstitial fluid Body Fluid Compartments colloid Colloid Colloid solutions include large proteins or cells that do not readily cross capillary membranes. They remain in the ecf and do not distribute into the icf (similar to crystalloids). Intravenous Fluids osmotic pressure Osmotic pressure The pressure required to prevent the passage of solvent through a semipermeable membrane that separates a pure solvent from a solution of the solvent and solute or that separates different concentrations of a solution. It is proportional to the osmolality of the solution. Intravenous Fluids (e.g., lymph Lymph The interstitial fluid that is in the lymphatic system. Secondary Lymphatic Organs vessel blockage)
Starlings law diagram

Diagram of Starling’s Law in a systemic capillary:
Shows the location and computation of intra and extraluminal forces to calculate pressures of filtration and of absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption.
HP: hydrostatic pressure
OP: oncotic pressure

Image by Lecturio. License: CC BY-NC-SA 4.0

Types of Edema

Peripheral edema

Peripheral edema is the swelling Swelling Inflammation of the gravity-dependent extremities (more common in the lower limbs, distal > proximal). Although peripheral edema is typically painless, it can cause discomfort from swelling Swelling Inflammation and pose difficulty in walking.

Subtypes:

  • Pitting edema:
    • Edema caused by excess fluid without excess colloid
    • Leaves “pits” due to fluid displacement when pressure is applied to the area
  • Non-pitting edema
    • Edema caused by excess colloid without excess fluid:
      • Lymphedema: problems in lymphatic drainage, proteins accumulate in the interstitium
      • Myxedema: accumulation of hydrophilic mucopolysaccharides in the tissue, leading to fluid retention
    • Does not cause pitting because fluid is “held” in place by proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis

Internal edema

  • Ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites: accumulation of fluid in the abdomen
  • Hydrothorax: accumulation of fluid in the pleural cavity Pleural cavity Paired but separate cavity within the thoracic cavity. It consists of the space between the parietal and visceral pleura and normally contains a capillary layer of serous fluid that lubricates the pleural surfaces. Pleura: Anatomy (also known as pleural effusion Pleural Effusion Pleural effusion refers to the accumulation of fluid between the layers of the parietal and visceral pleura. Common causes of this condition include infection, malignancy, autoimmune disorders, or volume overload. Clinical manifestations include chest pain, cough, and dyspnea. Pleural Effusion
  • Anasarca Anasarca Hookworm Infections: generalized edema
Photograph showing marked pitting edema and erythema with poorly demarcated borders due to cellulitis

Abdominal wall Abdominal wall The outer margins of the abdomen, extending from the osteocartilaginous thoracic cage to the pelvis. Though its major part is muscular, the abdominal wall consists of at least seven layers: the skin, subcutaneous fat, deep fascia; abdominal muscles, transversalis fascia, extraperitoneal fat, and the parietal peritoneum. Surgical Anatomy of the Abdomen cellulitis Cellulitis Cellulitis is a common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. It is frequently caused by Staphylococcus aureus and Streptococcus pyogenes. The skin infection presents as an erythematous and edematous area with warmth and tenderness. Cellulitis:
Image showing marked pitting edema and erythema Erythema Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes. Chalazion with poorly demarcated borders due to cellulitis Cellulitis Cellulitis is a common infection caused by bacteria that affects the dermis and subcutaneous tissue of the skin. It is frequently caused by Staphylococcus aureus and Streptococcus pyogenes. The skin infection presents as an erythematous and edematous area with warmth and tenderness. Cellulitis

Image: “How 40 kilograms of fluid retention can be overlooked: two case reports” by Ong HS HS Hypertrophic scars and keloids are raised, red, and rigid (3 rs) scars that develop during cutaneous wound healing and are characterized by a local abnormal proliferation of fibroblasts with over-production of collagen. Over-expression of growth factors and decreased production of molecules that promote matrix breakdown appear to be involved in the etiology. Hypertrophic and Keloid Scars, Sze CW, Koh TW, Coppack SW. License: CC BY 2.0

Clinical Relevance

The following conditions commonly lead to edema:

  • Heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR): a condition in which the heart is unable to pump Pump ACES and RUSH: Resuscitation Ultrasound Protocols enough blood to the rest of the body, leading to fluid build-up that ultimately results in edema. The location of edema depends on which side of the heart is affected. Right-sided heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) causes peripheral edema of the legs, whereas left-sided heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) causes pulmonary edema Pulmonary edema Pulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure. Pulmonary Edema. Treatment is with diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication and vasodilators Vasodilators Drugs used to cause dilation of the blood vessels. Thromboangiitis Obliterans (Buerger’s Disease).
  • Nephrotic syndrome Nephrotic syndrome Nephrotic syndrome is characterized by severe proteinuria, hypoalbuminemia, and peripheral edema. In contrast, the nephritic syndromes present with hematuria, variable loss of renal function, and hypertension, although there is sometimes overlap of > 1 glomerular disease in the same individual. Nephrotic Syndrome: a group of conditions characterized by proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children (approximately 3–3.5 grams of protein in a 24-hour period). The loss of protein leads to lower blood albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests levels and subsequent edema due to a loss of capillary oncotic pressure. Nephrotic syndrome Nephrotic syndrome Nephrotic syndrome is characterized by severe proteinuria, hypoalbuminemia, and peripheral edema. In contrast, the nephritic syndromes present with hematuria, variable loss of renal function, and hypertension, although there is sometimes overlap of > 1 glomerular disease in the same individual. Nephrotic Syndrome causes anasarca Anasarca Hookworm Infections (diffuse edema). 
  • Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis: a chronic fibrotic liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease associated with liver failure Liver failure Severe inability of the liver to perform its normal metabolic functions, as evidenced by severe jaundice and abnormal serum levels of ammonia; bilirubin; alkaline phosphatase; aspartate aminotransferase; lactate dehydrogenases; and albumin/globulin ratio. Autoimmune Hepatitis. Fibrotic liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy tissue leads to portal hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, which can result in ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites. Transudative ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites leads to fluid build-up in the abdominal cavity. Liver failure Liver failure Severe inability of the liver to perform its normal metabolic functions, as evidenced by severe jaundice and abnormal serum levels of ammonia; bilirubin; alkaline phosphatase; aspartate aminotransferase; lactate dehydrogenases; and albumin/globulin ratio. Autoimmune Hepatitis occurs and leads to low levels of albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests and protein in the blood, resulting in swelling Swelling Inflammation of the lower extremities. Management includes targeting the underlying liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease and paracentesis Paracentesis A procedure in which fluid is withdrawn from a body cavity or organ via a trocar and cannula, needle, or other hollow instrument. Portal Hypertension for removal of abdominal fluid.
  • Distributive shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock: an abnormal distribution of blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure resulting in inadequate blood supply to tissues and organs. Increased capillary permeability and vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs result in a serious condition characterized by low systemic vascular resistance Systemic vascular resistance Afterload is the resistance in the aorta that prevents blood from leaving the heart. Afterload represents the pressure the LV needs to overcome to eject blood into the aorta. Cardiac Mechanics and high cardiac output Cardiac output The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). Cardiac Mechanics that causes flushing, low BP, and syncope Syncope Syncope is a short-term loss of consciousness and loss of postural stability followed by spontaneous return of consciousness to the previous neurologic baseline without the need for resuscitation. The condition is caused by transient interruption of cerebral blood flow that may be benign or related to a underlying life-threatening condition. Syncope. Septic shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock is the most common type of distributive shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock.
  • Lymphedema Lymphedema Edema due to obstruction of lymph vessels or disorders of the lymph nodes. Lymphatic Filariasis (Elephantiasis): an abnormal collection of protein-rich fluid in the interstitium resulting from an obstruction in lymphatic drainage. An increase in the protein content of the extravascular tissue causes water retention and swelling Swelling Inflammation of the soft tissues. The increase in extravascular protein stimulates fibroblast proliferation, fluid organization, and non-pitting swelling Swelling Inflammation of the affected extremity.

References

  1. Koeppen, B.M., Stanton, B.A. (2013). 1 – Physiology of Body Fluids, Editor(s): Renal Physiology (5th Edition), Mosby, Pages 1–14. https://www.sciencedirect.com/science/article/pii/B9780323086912000016
  2. Whiting, E., McCready, M.E. (2016). Pitting and non-pitting oedema. The Medical Journal of Australia, 205(4), 157–158. https://doi.org/10.5694/mja16.00416
  3. Hou, W., Sanyal, A.J. (2009). Ascites: Diagnosis and management. The Medical Clinics of North America, 93(4), 801–817. https://doi.org/10.1016/j.mcna.2009.03.007

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