The effect of a solution on a cell's volume is determined by its tonicity. Isotonic solutions do not change the volume of a cell. A hypotonic solution causes a cell to swell, while a hypertonic solution causes a cell to shrink. Tonicity takes into account the ability of molecules in the solution to cross the cell membrane.

Let's consider two solutions: a 300-mmol/L solution of sucrose and a 300-mmol/L solution of urea. Both solutions have an osmolality of 300 mOsm/kg H2O, making them isosmotic. When red blood cells, which also have an intracellular fluid osmolality of 300 mOsm/kg H2O, are placed in these solutions, the cells in the sucrose solution maintain their normal volume, while the cells in the urea solution swell and eventually burst. This demonstrates that the sucrose solution is isotonic and the urea solution is hypotonic. The differential effect on red blood cell volume is due to the permeability of the red blood cell plasma membrane to sucrose and urea. The red blood cell membrane contains uniporters for urea, allowing urea to easily cross the cell membrane driven by the concentration gradient. In contrast, the red blood cell membrane does not have sucrose transporters, preventing sucrose from entering the cell.

For a molecule to exert osmotic pressure across a membrane, it must not be able to cross the membrane. Since the red blood cell membrane is impermeable to sucrose, it exerts an osmotic pressure equal and opposite to the osmotic pressure generated by the contents within the red blood cell. On the other hand, urea can readily cross the red blood cell membrane and cannot exert an osmotic pressure to balance that generated by the intracellular solutes. Therefore, sucrose is considered an effective osmole, while urea is an ineffective osmole.

To account for a molecule's ability to permeate the membrane and its effect on osmotic pressure, we need to modify equation 1.7 as follows: Πe = ˙(nCRT), where σ represents the reflection coefficient or osmotic coefficient. The reflection coefficient measures the relative ability of the molecule to cross the cell membrane, and Πe is the "effective osmotic pressure."

In the previous example, urea, which freely crosses the cell membrane, has a σ value of 0 and does not exert an effective osmotic pressure. Sucrose, on the other hand, has a σ value of 1 as it cannot cross the cell membrane, making it an effective osmole. Many molecules have a σ value between 0 and 1, indicating that they can partially cross cell membranes and generate an osmotic pressure that is a fraction of what would be expected based on their concentration in solution.

Oncotic pressure refers to the osmotic pressure generated by large molecules, particularly proteins, in a solution. The relationship between protein concentration and osmotic pressure does not strictly follow van't Hoff's law, as illustrated in Fig. 1.9. The exact cause of this deviation is not fully understood, but it appears to be influenced by the size and shape of the protein molecule. Small, globular proteins show a more precise correlation to van't Hoff's law compared to larger protein molecules.
The tonicity of a solution is related to the effect of the solution on the volume of a cell. Solutions that do not change the volume of a cell are said to be isotonic. A hypotonic solution causes a cell to swell, whereas a hypertonic solution causes a cell to shrink. Although related to osmolality, tonicity also accounts for the ability of the molecules in solution to cross the cell membrane.
Consider two solutions: a 300-mmol/L solution of sucrose and a 300-mmol/L solution of urea. Both solutions have an osmolality of 300 mOsm/kg H2O and therefore are said to be isosmotic (i.e., they have the same osmolality). When red blood cells—which for the purpose of this illustration also have an intracellular fluid osmolality of 300 mOsm/kg H2O—are placed in the two solutions, those in the sucrose solution maintain their normal volume, whereas those placed in urea swell and eventually burst. Thus the sucrose solution is isotonic and the urea solution is hypotonic. The differential effect of these solutions on
CHAPTER 1 Principles of Cell and Membrane Function red blood cell volume is related to the permeability of the red blood cell plasma membrane to sucrose and urea. The red blood cell membrane contains uniporters for urea. Thus urea easily crosses the cell membrane (i.e., the cell is permeable by urea), driven by the concentration gradient (i.e., extracellular urea concentration > intracellular urea concentration). In contrast, the red blood cell membrane does not contain sucrose transporters, and sucrose cannot enter the cell (i.e., the cell is impermeable by sucrose).
To exert an osmotic pressure across a membrane, a molecule must not cross the membrane. Because the red blood cell membrane is impermeable by sucrose, it exerts an osmotic pressure equal and opposite to the osmotic pressure generated by the contents within the red blood cell (in this case, 300 mOsm/kg H2O). In contrast, urea is readily able to cross the red blood cell membrane, and it cannot exert an osmotic pressure to balance that generated by the intracellular solutes of the red blood cell. Consequently, sucrose is termed an effective osmole, whereas urea is an ineffective osmole.
To take into account the effect of a molecule’s ability to permeate the membrane on osmotic pressure, it is necessary to rewrite eq. 1.7 as follows:
Equation 1.9 ˜e = ˙(nCRT), where σ is the reflection coefficient (or osmotic coefficient) and is a measure of the relative ability of the molecule to cross the cell membrane, and Πe is the “effective osmotic pressure.”
For a molecule that can freely cross the cell membrane, such as urea in the preceding example, σ= 0, and no effective osmotic pressure is exerted (e.g., urea is an ineffective osmole for red blood cells). In contrast, σ= 1 for a solute that cannot cross the cell membrane (in the preceding example, sucrose). Such a substance is said to be an effective osmole. Many molecules are neither completely able nor completely unable to cross cell membranes (i.e., 0 <σ< 1) and generate an osmotic pressure that is only a fraction of what is expected from the molecules’ concentration in solution.
Oncotic pressure is the osmotic pressure generated by large molecules (especially proteins) in solution. As illustrated in
Fig. 1.9 , the magnitude of the osmotic pressure generated by a solution of protein does not conform to van’t Hoff’s law. The cause of this anomalous relationship between protein concentration and osmotic pressure is not completely understood, but it appears to be related to the size and shape of the protein molecule. For example, the correlation to van’t Hoff’s law is more precise with small, globular proteins than with larger protein molecules.