Body Fluid Composition and Balance

• In a 70 kg man, body fluid is 60% of body weight
• Average total body water is 42 liters
• Intracellular fluid is 28 liters
• Extracellular fluid (plasma and interstitial) is 14 liters
• Daily intake of water is 2100ml
• An additional 200ml of water comes from carbohydrate metabolism
• A total daily water intake is 2300ml
• Daily insensible water loss via skin is 300-400ml
• Daily insensible water loss via lungs is 300-400ml
• Sweat glands excretion is 100ml/day, but it may increase to 1-2 L/Hr
• 100ml of water is lost in feces each day
• Daily water loss by kidneys is 0.5-20 liters
• As a person ages, the percentage of total body weight that is fluid gradually decreases because the body fat percentage increases, leading to a decrease in water percentage
• Total body water in women averages 50% of body weight
• Total body water in premature and newborn babies is 70-75% of body weight
• Normal fluid intake is 2100ml
• Fluid intake from metabolism is 200ml
• Total fluid intake is 2300ml
• Insensible fluid loss via skin is 350ml
• Fluid loss via lungs is 350ml
• Fluid loss via sweat is 100ml
• Fluid loss via feces is 100ml
• Fluid loss via urine is 1400ml
• Total fluid output is 2300ml
• Fluid intake during prolonged exercise is unknown
• Fluid loss from metabolism is 200ml
• Total fluid loss is unknown
• Insensible fluid loss via skin is 350ml
• Insensible fluid loss via lungs is 650ml
• Fluid loss via sweat is 5000ml
• Fluid loss via feces is 100ml
• Fluid loss via urine is 500ml
• Total fluid output is 6600ml

Hematocrit

• Hematocrit is the percentage of blood volume that is composed of red blood cells
• Hematocrit values range from 40-50% in men and 36-46% in women
• Hematocrit decreases in severe anemia
• Hematocrit increases in polycythemia

Ion Composition of Plasma and Interstitial Fluid

• Plasma and interstitial fluid are separated only by highly permeable capillary membranes, and they have a similar ionic composition
• A major difference between plasma and interstitial fluid is a higher concentration of protein in the plasma
• The concentration of positively charged ions (cations) is slightly greater (about 2%) in the plasma than in the interstitial fluid due to the Donnan effect

Osmosis Principles

• Osmosis is the net diffusion of water across a selectively permeable membrane from an area of high water concentration to an area of low water concentration
• Osmotic pressure is the precise amount of pressure required to prevent osmosis
• A solution containing 1 mole of glucose in each liter has a concentration of 1 osm/L
• A molecule dissociates into two ions like sodium chloride, then a solution containing 1 mol/L will have an osmolar concentration of 2 osm/L

Body Fluid Osmolarity

• The total osmolarity of each of the three compartments is about 300 mOsm/L (280 mosm/L)
• Plasma has 1 mOsm/L greater osmolarity than interstitial and intracellular fluids
• Plasma proteins maintain about 20 mm Hg greater pressure in the capillaries than in the surrounding interstitial spaces
• To calculate osmolarity of a 0.9% NaCl solution
• 0.9% NaCl = 0.9g/100ml = 9g/l
• 58.5 g = 1 mol
• 9g = 9/58.5 = 0.154 moles
• 1 mol of NaCl = 2 osmol
• 0.154 mol = 2 X 0.154 = 0.308 osmoles or 308 mOsm
• 1 mosmole exerts = 19.3 mm of mercury Osmotic Pressure
• 308 mosmol = 308 X 19.3 = 5944mmHg
• Actual osmolarity = 308 X0.93 (osmotic coefficient) = 286 mosm/l
• Plasma osmolarity can be estimated via the following formula: Plasma osmolarity = 2 x Plasma Na+ + Glucose/18 + BUN/2.8
• ECF and plasma's major solutes are plasma sodium concentration, plasma glucose concentration, and blood urea nitrogen (BUN).
• Plasma osmolarity refers to the total osmolar concentration in mOsm/L
• Plasma Na+ concentration is expressed in mEq/L
• Plasma glucose concentration is expressed in mg/dL
• Blood urea nitrogen concentration is expressed in mg/dL

Isotonic/Hypotonic/Hypertonic Solutions

• Effects of solutions on cell volume:
  • Isotonic: No change at 280 mOsm/L.
  • Hypotonic: Cell swells at 200 mOsm/L.
  • Hypertonic: Cell shrinks at 360 mOsm/L.
• Osmolarity considers all solutes in a solution, regardless of whether they can cross the cell membrane
• Tonicity (hypotonic, isotonic, hypertonic) only depends on impermeable solutes that dictate water movement.
• Hypo, iso, or hypertonic fluids focus on water movement into or out of cells, where the solute is impermeable
• An Iso-osmotic fluid can be hypotonic
• Normal saline (or 0.9% NaCl) and D-5-W [or 5% dextrose (glucose)] in water is a commonly used IV fluid
• These fluids measure 278 mOsmol/l if concentration is measured making them isosmotic
• Normal saline is isotonic, while D-5-W is hypotonic when administered

Example: 5% Dextrose in Water (D5W)

• Initially, D5W is iso osmotic in the IV bag (~278 mOsm/L), meaning it does not cause immediate water shifts
• Dextrose gets metabolized by cells
• Water remains once dextrose is metabolized, making the solution effectively hypotonic to cells
• Free water moves into cells, which leads to cell swelling over time
• NaCl does not enter cells, whereas D-5-W is hypotonic because glucose enters cells
• Isosmotic is not isotonic in this example
• A 5% glucose solution, which is nearly isosmotic, is often used to treat dehydration
• Because the solution is isosmotic, it can be infused intravenously without causing red blood cell swelling, as would occur with an infusion of pure water
• Glucose in the solution is rapidly transported into the cells and metabolized
• Infusion of a 5% glucose solution reduces extracellular fluid osmolarity and therefore helps correct the increase in extracellular fluid osmolarity associated with dehydration

Volume Changes of ECF

• Adding isotonic saline solution to the ECF expands the ECF with no change in osmolarity
• Adding hypertonic solution to the ECF increases its osmolarity and expands its volume, shrinking the ICF
• Adding hypotonic solution to the ECF decreases its osmolarity and expands both the ECF and ICF compartments

Fluid Volume Regulation

• Hyponatremia occurs when plasma sodium concentration is reduced to below normal (142mEq/L)
• Hypernatremia occurs when plasma sodium concentration is elevated above normal

Hyponatremia

• Plasma sodium levels are lower than normal
• Potential causes: loss of sodium chloride from the extracellular fluid (hyponatremia dehydration), diarrhea, Addison's disease and an addition of excess water to the extracellular fluid (hyponatremia overhydration), excess ADH (SIADH)

Hypernatremia

• Plasma sodium levels are higher than normal
• Water loss (hypernatremic dehydration) occurs with sweating and diabetes insipidus
• Excess sodium (hypernatremic overhydration) occurs with Cushing's disease and primary aldosteronism

Osmolarity and Fluid Movements

• Intracellular osmolarity is equal to extracellular osmolarity in the steady state
• Osmolarity is the same throughout the body fluids
• Water shifts freely across cell membranes to maintain osmolarity equality
• Changes in ECF osmolarity will shift water across cell membranes to make the ICF osmolarity equal to the new ECF osmolarity
• Solutes such as NaCl, NaHCO3, and mannitol are confined to the ECF compartment since they do not readily cross cell membranes
• NaCl will be added only to the ECF compartment and the total solute content of the ECF increases if a person ingests a large quantity of it

Fluid Volume

• Volume contraction: decrease in ECF volume
• Volume expansion: increase in ECF volume
• Isosmotic, hyperosmotic, and hyposmotic: refer to the osmolarity of the ECF
• Isosmotic disturbance: there is no change in ECF osmolarity
• Hyperosmotic disturbance: there has been an increase in ECF osmolarity
• Hyposmotic disturbance: there has been a decrease in ECF osmolarity
• To understand these disturbances take a stepwise approach: identify any change occurring in the ECF, and decide whether that change will produce an increase, a decrease, or no change in ECF osmolarity is occuring. If ECF changes determine which directions that water shifts in order to reestablish ECF and ICF equality

Causes of Dehydration and Overhydration

• Hyponatremia-dehydration: Decrease in plasma sodium concentration and extracellular fluid volume
• Hyponatremia-overhydration: Decrease in plasma sodium concentration and expansion of extracellular fluid volume
• Hypernatremia-dehydration: Increase in plasma sodium concentration and decrease in extracellular fluid volume
• Hypernatremia-overhydration: Increase in plasma sodium concentration and expansion of extracellular fluid volume

Health Risks of Abnormal Fluid Volumes

• Brain cell edema and neurological symptoms, including headache, nausea, lethargy, and disorientation, may result from a rapid reduction in plasma sodium concentration
• Seizures, coma, permanent brain damage, and death may occur, if plasma sodium concentration rapidly falls below 115 to 120 mmol/L, leading to brain swelling
• Because the skull is rigid, the brain can only increase its volume by 10%
• Brain herniation down the neck can result in permanent brain injury and death
• The brain and other tissues transport sodium, chloride, potassium, and organic solutes such as glutamate from the cells into the extracellular compartment for chronic hyponatremia to attenuate osmotic flow of water into cells and swelling of the tissues
• Osmosis-mediated demyelination of neurons is avoided by limiting the correction of chronic hyponatremia to less than 10-12 mmol/L in 24 hours and less than 18 mmol/L in 48 hours
• A slow correction rate permits the brain to recover the osmoles that were lost from the cells due to adaptation to chronic hyponatremia slow correction is achieved with hypertonic solutions because they are added too rapidly to correct hyponatremia
• If intervention outpaces the brain's ability to recapture the solutes lost from the cells, osmotic injury of the neurons occurs
• Severe symptoms usually occur only with rapid and large increases in the plasma sodium concentration above 158 to 160 mmol/L with hypernatremia
• Intense thirst is stimulated and ADH secretion is promoted with hypernatremia
• Hypothalamic lesions may impair one's sense of thirst
• Infants and older patients may not be able to access water, and may have altered mental status or diabetes insipidus

Edema

• Edema is the excess fluid in tissues and tissue spaces
• Intracellular edema conditions occur with a depression of the metabolic systems of the tissues, lack of adequate nutrition to cells, and hyponatremia
• Extracellular edema is caused by increased capillary filtration and defects in lymphatic drainage
• Factors that increase capillary filtration include where Kf is the capillary filtration coefficient (product of the permeability and surface area of the capillaries
• Pc is the capillary hydrostatic pressure, Pif is the interstitial fluid hydrostatic pressure, πρ is the capillary plasma colloid osmotic pressure, and πif is the interstitial fluid colloid osmotic pressure
• Increased capillary hydrostatic pressure, decreased plasma colloid osmotic pressure, and increased capillary filtration coefficient increase capillary filtration rate

Causes of Increased Hydrostatic Pressure

• Excessive kidney retention of salt and water occurs in acute or chronic kidney failure and mineralocorticoid excess
• High venous pressure and venous constriction occur in heart failure, venous obstruction, and failure of venous pumps
• Decreased arteriolar resistance occurs with excessive body heat, insufficiency of the sympathetic nervous system and vasodilator drugs
• Decreased oncotic pressure happens with loss of proteins in urine (nephrotic syndrome), loss of protein from denuded skin areas like burns and wounds, and failure to produce proteins like liver disease (cirrhosis) and serious protein or caloric malnutrition
• Nephrotic syndrome involves damage to the glomeruli of kidneys, resulting in proteinuria and swelling of feet
• Cirrhosis of the liver is the replacement of liver parenchymal cells with fibrous tissue and protein concentration of less than 2.5 g/100 ml
• Increased capillary permeability occurs in immune reactions that cause release of histamine and other immune products, toxins, bacterial infections, vitamin deficiency, prolonged ischemia and burns
• Blockage of lymph return occurs in cancer, infections (e.g., filaria nematodes), surgery, and congenital absence or abnormality of lymphatic vessels
• Safety factors that prevent edema are: a safety factor due to low tissue compliance in the negative pressure range being about 3 mm Hg, the safety factor caused by increased lymph flow being about 7 mm Hg, and the safety factor by wash down of proteins from the interstitial spaces being about 7 mm Hg
• Edema fluid in the potential spaces is called "effusion"
• Potential spaces include ascites (peritoneal cavity), pleural effusion, and pericardial effusion

Kidney Function Summary:

• Excretion of metabolic waste products and foreign substances (e.g., drugs)
• Regulation of water and electrolyte balances and body fluid osmolality
• Maintaining plasma volume
• Regulation of arterial pressure and acid-base balance
• Secretion of hormones
• Gluconeogenesis