Cell membranes are selectively permeable. This means that they allow the movement of some molecules freely across them, but do not allow the free passage of others. In broad terms, there are three ways in which molecules move across membranes. These processes are diffusion, osmosis and active transport.
In this article, we will describe the process of diffusion, discuss the different types of diffusion, and consider the clinical relevance of this process.
Mechanism of Diffusion
Diffusion is the movement of a molecule down a concentration gradient, from an area of its high concentration to an area of its low concentration. This process is passive, i.e. it requires no input of additional energy; the concentration gradient alone is enough to drive the process.
Types of Diffusion
Diffusion across the cell membrane is either simple or facilitated.
|Simple diffusion||Facilitated diffusion|
|Mechanism||Molecules move directly across the membrane without the aid of a carrier protein||Movement occurs passively down a concentration gradient, however, the molecules require the help of carrier proteins to allow them to cross the lipid bilayer|
|Examples of molecules using this process||
An example of a membrane transport protein involved in facilitated diffusion is the GLUT-2 protein, which is the primary protein involved in the transfer of glucose from the liver into the blood.
Rate of Diffusion
Fick’s laws describe the factors affecting the rate of diffusion. Simplified, this states that:
“the rate of diffusion is proportional to the concentration gradient, the length of the diffusion pathway and the surface area available for diffusion.”
This can be written as follows:
Rate of diffusion ∝ (surface area x concentration gradient)/(length of diffusion pathway)
N.B. Fick’s laws of diffusion are in truth more complex, but beyond the scope of this article.
The effect of these factors is summarised in Table 1:
|Factor||Increased rate of diffusion||Reduced rate of diffusion|
|Concentration gradient||Large gradient||Small gradient|
|Length of pathway||Short pathway||Long pathway|
|Surface area||Greater surface area||Reduced surface area|
Clinical Relevance – Drug Targets
The channel proteins that allow facilitated diffusion can be exploited as pharmacological targets, particularly in the kidney. Some examples include:
- SGLT-2 inhibitors: Reduce the reabsorption of glucose in the proximal tubule, and are used in the management of type 2 diabetes.
- Loop diuretics: Reduce water reabsorption in the Loop of Henle by blocking the sodium/potassium/chloride co-transporter (NKCC2). They are used in conditions such as congestive cardiac failure.
- Thiazide diuretics: Reduce water reabsorption in the distal convoluted tubule by blocking the sodium/chloride symporter (NCCT). These are primarily used in the management of hypertension.
Clinical Relevance – Cystic Fibrosis
The Cystic Fibrosis Transmembrane Conduction Regulator (CFTR) protein is a ligand-gated chloride channel found in the cell membranes of epithelial cells of many organs such as the lungs, pancreas and reproductive tracts.
In healthy people, it allows chloride ions to flow freely out of cells. These chloride ions are followed passively by sodium ions to maintain electrochemical balance, and then water follows via osmosis. This keeps secretions in these organs thin and watery.
Cystic fibrosis results from various mutations that lead to either absent or dysfunctional CFTR proteins. This means that chloride ions cannot flow out of cells, and thus neither does sodium or water. This results in mucus which is thick and sticky, which is especially problematic in the lungs, pancreas and reproductive tract.
However, in the sweat glands, the CFTR protein’s role is slightly different. Rather than allowing chloride ions to flow out of the cells, in sweat glands the CFTR protein is involved in the reabsorption of chloride, and subsequently sodium, from the sweat. In cystic fibrosis, this cannot occur, thus sodium and chloride remain in the sweat, giving rise to the classically “salty” sweat seen in CF.