CF 201: Know Thyself
The following is an intermediate-level course in the pathophysiology of cystic fibrosis. If you need a basic overview of the disease before you continue with CF201, check out the info here. There are many things about CF that every patient needs to know in order to embark on a path of self-healing. The more informed you are about your disease, the more empowered you will become to make your own health decisions. So I have put together some info below as a kind of intermediate course on your health. At a certain point, you'll be educating your doctors!
Genetic Mutation
At the cellular level, the fundamental problem is that a protein embedded in the membranes of our body's epithelial cells (i.e. lungs, skin, digestive tract, etc.)--the CFTR (cystic fibrosis transmembrane conductance regulator) protein--is mutated and thus does not function properly. A healthy, unmutated CFTR channel transports sodium and chloride ions across the cell membrane efficiently to maintain the correct balance of electrolytes inside and outside of the cell. This is a very important function in epithelial cells that ensures our mucus has enough water in it, and is not too thick and sticky. A normal CFTR protein moves chloride and thiocyanate ions (both with a negative charge) out of the cell and into the mucus covering the cell. Positively charged sodium ions follow these anions out of the cell to maintain the electrical balance, or gradient. This increases the total electrolyte concentration in the mucus and results in the movement of water out of cell and into the mucus via osmosis, thus thinning the mucus out.
A mutated CFTR protein (coded for by a number of different mutations of the CFTR genes on chromosome 7) does not allow these ions to flow across the cell membrane effectively, and this results in water retention in the cell. When water is retained in the cell, it means the mucus is not getting enough water and it becomes thick and sticky. The mucus is so thick and so sticky that the cilia (cute little hairs on the outside of the cell that move mucus in the respiratory tract) cannot move. That means the mucus cannot be effectively moved out of the airways and can attract pathogens (viruses, bacteria, fungi) that just sit there and proliferate.
The purpose of mucus is to catch pathogens in the body, neutralize them, and carry them out via your orifices (think of a runny nose when you've got a cold). But when the mucus can't move, the pathogens don't move either, and soon you've got an infection. There are new drugs available and in development that correct this defect in the CFTR protein in certain mutations (e.g. Kalydeco in G551D mutations; Orkambi, Symdeko, and Trikafta in deltaF508 mutations). Each CF genetic mutation causes a different problem for the CFTR protein in the cell membrane (either a lack or absence of them, or change in their functions) so CFTR-correcting drugs have to be targeted to specific mutations. Their first drug was able to correct the "easiest" of the CF mutations (i.e. CFTR proteins are present but have a "gating" problem = the G551D mutation), and the next drugs in development are targeted at fixing the more difficult mutations, which cause a lack of enough CFTR proteins (i.e. the deltaF508 and G542X mutations).
So at the roots of it all, we've got a mucus problem due to improper ion transport through faulty CFTR proteins. One way to treat this mucus problem in the lungs is through the use of osmotic drugs, i.e. inhaled hypertonic saline or a sugar called mannitol. The point of both of these drugs is to artificially increase the electrolyte load in your mucus so that water is drawn out of the cells via osmosis into the mucus, thinning it and allowing us to cough it up and out of our lungs. Simple, safe, and effective! Our digestive tissue also has this problem with mucus thickening, and so the use of miralax (an osmotic laxative used in CF-related constipation) also uses this concept to induce bowel movements in CFers with constipation. Natural alternatives to pharmaceutical laxatives may also be effect for this issue.
There are many other things that we can expose ourselves to that can exacerbate this mucus problem, primarily foods, food-like substances (i.e. junk food), and digestive deficiency. I am particularly concerned with what foods and food-like substances can make our mucus problems worse, setting us up for more serious infections and worsened symptoms overall.
Explore the sections under the Cystic Fibrosis heading on the menu bar for more info on particular topics. It will be most beneficial to you to read these sections in sequential order, as I explain concepts that build upon each other. This is an outline of what I discuss:
I. Inflammation and Infection
II. Bronchiectasis and Inflammation
III. The Microbiome: Your Gut and Immunity
IV. Carbohydrate Malabsorption and Gut Flora
V. CF-Related Diabetes and Impaired Glucose Tolerance
************************
Sources:
CFTR Mutations: A Guide. <https://www.cftrscience.com/a_guide.php>
Genetic Mutation
At the cellular level, the fundamental problem is that a protein embedded in the membranes of our body's epithelial cells (i.e. lungs, skin, digestive tract, etc.)--the CFTR (cystic fibrosis transmembrane conductance regulator) protein--is mutated and thus does not function properly. A healthy, unmutated CFTR channel transports sodium and chloride ions across the cell membrane efficiently to maintain the correct balance of electrolytes inside and outside of the cell. This is a very important function in epithelial cells that ensures our mucus has enough water in it, and is not too thick and sticky. A normal CFTR protein moves chloride and thiocyanate ions (both with a negative charge) out of the cell and into the mucus covering the cell. Positively charged sodium ions follow these anions out of the cell to maintain the electrical balance, or gradient. This increases the total electrolyte concentration in the mucus and results in the movement of water out of cell and into the mucus via osmosis, thus thinning the mucus out.
A mutated CFTR protein (coded for by a number of different mutations of the CFTR genes on chromosome 7) does not allow these ions to flow across the cell membrane effectively, and this results in water retention in the cell. When water is retained in the cell, it means the mucus is not getting enough water and it becomes thick and sticky. The mucus is so thick and so sticky that the cilia (cute little hairs on the outside of the cell that move mucus in the respiratory tract) cannot move. That means the mucus cannot be effectively moved out of the airways and can attract pathogens (viruses, bacteria, fungi) that just sit there and proliferate.
The purpose of mucus is to catch pathogens in the body, neutralize them, and carry them out via your orifices (think of a runny nose when you've got a cold). But when the mucus can't move, the pathogens don't move either, and soon you've got an infection. There are new drugs available and in development that correct this defect in the CFTR protein in certain mutations (e.g. Kalydeco in G551D mutations; Orkambi, Symdeko, and Trikafta in deltaF508 mutations). Each CF genetic mutation causes a different problem for the CFTR protein in the cell membrane (either a lack or absence of them, or change in their functions) so CFTR-correcting drugs have to be targeted to specific mutations. Their first drug was able to correct the "easiest" of the CF mutations (i.e. CFTR proteins are present but have a "gating" problem = the G551D mutation), and the next drugs in development are targeted at fixing the more difficult mutations, which cause a lack of enough CFTR proteins (i.e. the deltaF508 and G542X mutations).
So at the roots of it all, we've got a mucus problem due to improper ion transport through faulty CFTR proteins. One way to treat this mucus problem in the lungs is through the use of osmotic drugs, i.e. inhaled hypertonic saline or a sugar called mannitol. The point of both of these drugs is to artificially increase the electrolyte load in your mucus so that water is drawn out of the cells via osmosis into the mucus, thinning it and allowing us to cough it up and out of our lungs. Simple, safe, and effective! Our digestive tissue also has this problem with mucus thickening, and so the use of miralax (an osmotic laxative used in CF-related constipation) also uses this concept to induce bowel movements in CFers with constipation. Natural alternatives to pharmaceutical laxatives may also be effect for this issue.
There are many other things that we can expose ourselves to that can exacerbate this mucus problem, primarily foods, food-like substances (i.e. junk food), and digestive deficiency. I am particularly concerned with what foods and food-like substances can make our mucus problems worse, setting us up for more serious infections and worsened symptoms overall.
Explore the sections under the Cystic Fibrosis heading on the menu bar for more info on particular topics. It will be most beneficial to you to read these sections in sequential order, as I explain concepts that build upon each other. This is an outline of what I discuss:
I. Inflammation and Infection
II. Bronchiectasis and Inflammation
III. The Microbiome: Your Gut and Immunity
IV. Carbohydrate Malabsorption and Gut Flora
V. CF-Related Diabetes and Impaired Glucose Tolerance
************************
Sources:
CFTR Mutations: A Guide. <https://www.cftrscience.com/a_guide.php>
