Edema

Body Fluid Compartments

Intracellular fluid compartment

• Accounts for ⅔ of total body water
• The total volume contained by all cells in the body
• Calculated by subtracting the total body water from extracellular fluid volume

Extracellular fluid compartment

• Accounts for ⅓ of total body water
• Can be measured using inulin, mannitol, or radioactive sodium
• Subdivided into:
  • Interstitial fluid:
    • Accounts for ⅔ of the extracellular fluid compartment
    • Calculated by subtracting the extracellular fluid volume from plasma volume
  • Blood plasma 
    • Accounts for ⅓ of the extracellular fluid compartment
    • Can be measured using radioiodinated serum albumin or Evans blue dye

Osmolarity and Osmolality

• Osmolarity: number of solute molecules per liter of solvent
• Osmolality: number of solute molecules per kilogram of solvent
• The difference between both is insignificant for solutions.
• Estimated osmolality:
  • Posm = (2 x Na) + (glucose/18) + (BUN/2.8)
• Direct measurement of osmolality: freeze point depression/vapor pressure
• Hematocrit: blood concentration:
  • Indirectly relates to osmolality
  • ↑ In a hypo-osmotic solution (cells swell)
  • ↓ In a hyperosmotic solution (cells shrink)
• Serum proteins (oncotic pressure): serum albumin and globulins:
  • Indirectly related to osmolality
• Physiological level of blood osmolality is approximately 300 mOsm.

Starling Forces

• When arteriolar hydrostatic pressure > arterial oncotic pressure, fluid flows from arteriolar side → interstitium
• 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 out.
  • 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.
• Causes of edema by Starling forces:
  • ↑ Capillary hydrostatic fluid pressure (e.g., heart failure)
  • ↓ Plasma oncotic pressure (e.g., protein loss in nephrotic syndrome)
  • ↑ Capillary permeability (e.g., burns)
  • ↑ Interstitial fluid colloid osmotic pressure (e.g., lymph vessel blockage)

Types of Edema

Peripheral edema

Peripheral edema is the swelling of the lower extremities, namely, legs, feet, and ankles. Although peripheral edema is typically painless, it can cause discomfort from swelling 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

Internal edema

• Ascites: accumulation of fluid in the abdomen
• Hydrothorax: accumulation of fluid in the pleural cavity (also known as pleural effusion) 
• Anasarca: generalized edema

Clinical Relevance

The following conditions commonly lead to edema:

• Heart failure: a condition in which the heart is unable to pump 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 causes peripheral edema of the legs, whereas left-sided heart failure causes pulmonary edema. Treatment is with diuretics and vasodilators.
• Nephrotic syndrome: a group of conditions characterized by proteinuria (approximately 3–3.5 grams of protein in a 24-hour period). The loss of protein leads to lower blood albumin levels and subsequent edema due to a loss of capillary oncotic pressure. Nephrotic syndrome causes anasarca (diffuse edema). 
• Liver cirrhosis: a chronic fibrotic liver disease associated with liver failure. Fibrotic liver tissue leads to portal hypertension, which can result in ascites. Transudative ascites leads to fluid build-up in the abdominal cavity. Liver failure occurs when albumin and protein levels in the blood are low, and results in swelling of the lower extremities. Management includes targeting the underlying liver disease and paracentesis for removal of abdominal fluid.
• Distributive shock: an abnormal distribution of blood flow resulting in inadequate blood supply to tissues and organs. Increased capillary permeability and vasodilation result in a serious condition characterized by low systemic vascular resistance and high cardiac output that causes flushing, low BP, and syncope. Septic shock is the most common type of distributive shock.
• Lymphedema: 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 of the soft tissues. The increase in extravascular protein stimulates fibroblast proliferation, fluid organization, and non-pitting swelling of the affected extremity.