1. Volumes of Body Fluid Compartments
Relationship between the volumes of major fluid
compartments. The actual
are calculated for a 70 kg man.
TBW = 0.6 x Body Weight
2. Measurements of Body Fluid Compartments
if 25 mg of glucose are added to an unknown volume of distilled water and the
concentration of glucose after mixing is 0.05 mg/ml, then the volume of solvent is ???
Markers for measurement must share following qualities:
1. They are measurable
2. They remain in the compartment being measured
3. They do not alter water distribution
4. They are not toxic
1. TBW is measured by triated water (tritium oxide)
2. ECF volume is measured by inulin that is proportionally distributed between plasma volume and interstitial volume
3. Plasma volume can be measured either by radioactive albumin or by Evans blue. These substances neither leave the vascular system nor penetrate the erythocytes.
4. Interstitial volume cannot be measured directly, because no substance is distributed exclusively within this compartment. Therefore, the interstitial fluid volume is determined as the difference between ECF volume and plasma volume.
5. ICF volume cannot be measured directly by dilution because no substance is confined exclusively to this compartment. The ICF volume is obtained by subtracting the ECF volume from the TBW.
3. Composition of Body Fluid Compartments
|Ion Plasma (mmol/L) ICF (mmol/L)|
Disturbances of Volume and Concentration of Body Fluids.
The general clinical terms for volume abnormalities are dehydration and overhydration. Both conditions are associated with a change in ECF volume.
Osmolarity – refers to the number of solute particles per liter of solution
Osmolality – refers to the number of solute particles per kg of water
Tonicity of a solution is related to the effect of the concentration of the solution on the volume of a cell (e.g. erythrocytes)
Isotonic – it means that the solution does not change the volume of the cell
Hypotonic – it means that the solution causes a cell to swell
Hypertonic – it means that the solution causes a cell to shrink
Isosmotic, Hyperosmotic, and Hyposmotic refer to the osmolar concentrations of the ECF.
Definition. Dehydration is an ambiguous term that does not distinguish between simple water loss and loss of Na+. Both water loss and Na+ loss are associated with a decrease in the ECF volume, which is determined by the amount of Na+ in the body and not by the Na+ concentration in the plasma.
1. Isosmotic dehydration.
Causes of isosmotic dehydration include hemorrhage, plasma exudation through burned skin, and gastrointestinal fluid loss (e.g. vomiting, diarrhea). Initially, fluid is lost from the plasma and then is repleted from the interstitial space. No major change occurs in the osmolality of ECF; therefore any fluid shifts into or out the ICF compartment.
2. Hyperosmotic dehydration.
Causes of hyperosmotic dehydration include water deficits caused by decreased intake, diabetes insipidus, diabetes mellitus, fever (through excessive evaporation of the sweat from the skin – sweat is hypotonic). Initially, fluid is lost from the plasma, which becomes hyperosmotic, causing a fluid shift from the interstitial fluid to the plasma. The rise in interstitial fluid osmolality causes fluid shift from the ICF to the ECF. Finally, both the ECF and ICF compartments are decreased and the osmolality is increased.
3. Hyposmotic dehydration
Causes of hyposmotic dehydration include renal loss of NaCl because of adrenal insufficiency (e.g. primary hypoadrenocorticalism – Addison’s disease).
1. Isosmotic overhydration
Causes of isosmotic overhydration are oral or parenteral administration of a large volume of isotonic NaCl. This type of overhydration is characterized by an overall expansion of the ECF without any change in the osmolality of the ECF and ICF compartments.
2. Hyperosmotic overhydration
Causes are oral or parenteral intake of large amounts of hypertonic fluid. Intravenous infusion of a hypertonic saline solution leads to an increase in the plasma osmolality. The rise in plasma osmolality causes water to shift from the interstitium into the plasma, thereby initially increasing plasma volume. The increase in the osmolality of the ECF causes water to flow out of the ICF, which eventually decreases the volume of the ICF and increases the volume of the ECF. The osmolality of both compartments is increased.
3. Hyposmotic overhydration
There are usually two reasons: 1/ ingestion of a large volume of water and 2/ renal retention of water due to syndrome of inappropriate antidiuretic hormone secretion (SIADH). Initially, water enters the plasma, causing a decline in the plasma osmolality and a shift of water into interstitial space and a decrease in the interstitial fluid osmolality. The decrease in the interstitial osmolality causes water shift to the ICF (from ECF). Finally, both ECF and ICF compartments are increased and the osmolality of both compartments are decreased.
Hypernatremia refers to serum sodium concentration that is above normal. Clinically significant are serum sodium levels greater than 155 mmol/L. Hypernatremia always implies hypertonicity of all body fluids.
1. Extrarenal causes
a. Decreased fluid intake. In cool environment at least the intake of 700ml/day is required.
b. Increased skin losses. Profuse sweating may lead to excess water losses.
c. Increased gastrointestinal losses.
2. Renal causes
a. Osmotic diuresis.
Decreased ADH effect.
b. Central diabetes insipidus (i.e. failure of ADH synthesis or release) (tumor, sarcoidosis, trauma)
c. Nephrogenic diabetes insipidus (renal diseases, hypercalcemia, hypokalemia, lithium ingestions, urinary tract obstruction)
a. CNS disorders
b. Extracellular volume depletion
c. Abnormal urine output
a. Free water may be administrated orally, which is the preferred route, or intravenously as a 5% dextrose solution. Infusion of a fluid with a tonicity less than 150 mOsm/L is a dangerous and may lead to acute hemolysis.
c. Thiazide diuretics and other drugs, such as clofibrate, chlorpropramide enhance the renal tubular effects of ADH and also contribute to the stimulation of ADH release.
Hyponatremia refers to serum sodium concentration of less than 135 mmol/L. The name, however, is somewhat misleading, because hyponatremia is usually a problem of too much water, not too little sodium
a. Pseudohyponatremia is a laboratory artifact that occurs in the setting of extreme hyperlipidemia or hyperproteinemia.
b. Hypertonic hyponatremia results from the shift of water from ICF to ECF, which is caused by the presence of osmotically active particles (e.g. glucose) in the ECF space. Serum sodium concentration is reduced, but the osmolality of the ECF is normal or even above normal.
c. True hyponatremia (hypotonic hyponatremia) is clinically significant when the serum sodium concentration is less than 125 mmol/L and the serum osmolality is less than 250 mOsm/kg.
1. Decreased glomerular filtration rate.
2. Increased proximal tubular reabsorption. Decreased renal perfusion pressure in diseases such as congestive heart failure, cirrhosis, nephrotic syndrome stimulates proximal tubular reabsorption.
3. Increased collecting tubular reabsorption of water is induced by nonosmotically stimulated ADH secretion, so called syndrome of inappropriate ADH secretion (SIADH). This syndrom is associated with the following disorders:
b. CNS diseases
c. Pulmonary diseases. The mechanism is believed to be stimulation of the so-called J receptors in the pulmonary circulation.
d. Drug-induced SIADH (chlorpropramide, clofibrate).
1. Fluid restriction. All patients who are severely hyponatremic should reduce free water intake to approximately 700ml/day
2. Inhibition of water reabsorption (furosemide)
3. Hypertonic infusion. Infusion of 3% sodium chloride rapidly raises the tonicity of ECF. The amount of Na+ needed to raise the serum sodium is calculated using the following equation:
(normal serum Na+ ) – (current serum Na+ ) x total body water
Hyperkalemia is defined as serum potassium concentration greater than 5,5 mmol/L.
Pseudohyperkalemia may be caused by release of potassium from red cells
True hyperkalemia may result from extrarenal and renal causes.
1. Extrarenal causes
a. Acidosis may be associated with an acute shift of potassium from ICF to ECF as hydrogen ions and chloride ions enter cells.
b. Insulin deficiency. Hyperkalemia in diabetic patients may be due to a lack of insulin.
c. Hyperosmolality. Acute increases in ECF osmotic activity may produce a transcellular shift of potassium and following hyperkalemia.
2. Renal causes
a. Severe renal failure. When GFR is below 10 ml/min, hyperkalemia may occur, even with normal diet.
b. Aldosterone insufficiency.
1. Acquired aldosterone deficiency (obstructive uropathy, diabetic nephropathy, interstitial renal disease etc.)
2. Inherited aldosterone deficiency. Several adrenal enzyme defects are associated with aldosterone deficiency.
3. Drug-induced aldosterone deficiency. NSAIDs act to reduce renin secretion and may produce hyperkalemia through aldosterone deficiency.
c. Aldosterone resistance. Some diseases are associated with tubular defects of actions of aldosterone, even if the aldosterone levels are high (amyloidosis, obstructive nephropathy, lupus erythomatodes)
1. Cardiac arrhytmias may occur and especially when level exceeds 6 mmol/L
2. Neuromuscular disorders. Hyperkalemia may alter muscle function, neuromuscular transmission, leading to severe weakness or paralysis.
a. Calcium chloride, i.v. administration antagonize the cardiac effects of hyperkalemia
b. Glucose and insulin, i.v. infusion lowers potassium level within 10 minutes.
c. Sodium bicarbonate, i.v. infusion stimulates cellular uptake of potassium.
d. Diuretics (furosemide), increase potassium excretion
e. Cation exchange resins, administration of polystyrene sulfonate binds potassium in the gastrointestinal tract.
Hypokalemia is defined as serum potassium concentration of less than 3.5 mmol/L
3. Potassium redistribution
a. insulin administration
b. epinephrine infusions, acute hypokalemia can be produced by activation of ß2 – receptors.
c. Acute alkalemia
d. Folic acid and vitamin B12 therapy for patients with megaloblastic anemia stimulates cell proliferation and produces acute hypokalemia as potassium is used in cell synthesis.
3. Amphotericin B
4. Primary hyperaldosteronism (primary adrenal adenoma, diffuse bilateral adrenal hyperplasia)
5. Secondary hyperaldosteronism (renin-secreting tumor, in congestive heart failure and cirrhosis)
6. Potassium loss due to primary renal tubular disorders (renal tubular acidosis, Bartter’s syndrom)