Cystic Fibrosis

By Kristina Eriksen, Miles Johnson, Courteny Cox, and McKenzie McPherson

What is cystic fibrosis?

What Happens in Cystic Fibrosis?

Pathogenesis of CF


Lung: Cystic Fibrosis (CF) patients have lost the function of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. This protein is a membrane protein and chloride channel encoded by the CFTR gene. This membrane protein is found in airways, bile ducts, the pancreas, and sweat ducts. In CF, the gene is either blocked or completely missing from the membrane of epithelial cells. In a healthy patient, chloride is transported across the cell membrane via the CFTR protein. Sodium follows chloride to the extracellular fluid, which means water also follows. Water help keeps the surface of the lungs moist.

In CF, chloride cannot travel across the membrane, which leads to water reabsorption in the cells. The extracellular fluid becomes more viscous without water. Mucous buildup causes plugging in the bronchioles and into the alveoli. The goblet cells increase in size and number, secreting more mucous in the airway. More mucous in the airway promotes bacterial colonization. Chronic infection is common in CF patients, primarily with Pseudomonaa aeruginosa and Staphylococcus aureus infections. These infections may lead to pneumonia, or developing cysts, and even hemoptysis. Chronic inflammation is another common manifestation, due to chronic infections. Neutrophils are constantly being released to phagocytize bacteria, however, the great number of neutrophils present cause a release of toxic neutrophil elastase, which causes the inflammation and damage to the host tissue. The structural damage of lung proteins by neutrophil elastase induces airway cells to produce interleukin 8. Interleukin 8 produces more neutrophils, which stimulate more mucous secretion. This destroys IgG, important for opsonization and phagocytosis of pathogens. Opsonization refers to a process that tells the immune cells which pathogenic cells to target for destruction. This leads back to neutrophils being present in excess and releases toxic neutrophil elastase. This is an example of a positive feedback loop. Ultimately, this effect leads to bronchiectasis, which causes the airway to widen and become scarred. Bronchiectasis makes it difficult to clear mucous out of the airways.

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Pancreas: The pancreas contains pancreatic ducts that are lined with pancreatic epithelial cells. The primary objective of the epithelial cells provides the correct viscosity of the pancreatic juice outside of the epithelial membrane. The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein can be found along this epithelial membrane, separating the cells from the pancreatic juice. The CFTR protein is a chloride channel that pumps chloride out of the cell and into the pancreatic juice. The negative charge from the chloride attracts positively charged sodium and water into the pancreatic juice. The pancreatic juice becomes more dilute and greater in volume. Bicarbonate is also secreted by the pancreatic epithelial cells into the pancreatic juice, which creates a pH friendly environment for digestion. If too much volume of pancreatic juice is secreted, epithelial cells will secrete sodium outside the cell through the basal membrane. This creates a concentration gradient from the pancreatic juice to the epithelial cell, where sodium will be pumped back into the cell. Chloride will follow into the cell or between cells.

In Cystic Fibrosis (CF) patients, the CFTR protein is either missing or dysfunctional, not allowing chloride to cross the epithelial membrane. The chloride becomes trapped in the cell. This prevents sodium or water from moving into the pancreatic juice. The pancreatic juice becomes more viscous without water. Sodium channels are still active, pumping sodium from the pancreatic juice back into the cell. This causes the pancreatic juice to become even more viscous. The pancreatic juice becomes so viscous that it causes pancreatic duct blockage. The blockage prevents pancreatic enzymes to be released into the small intestine. The pancreatic enzymes that are blocked are amylase, lipase, chymotrypsin, trypsin, and pancreatic bicarbonate. The result is maldigestion and malabsorption of important nutrients. The blockage of pancreatic bicarbonate also causes the pH in the small intestine to be more acidic than necessary. Without lipase, CF patients commonly have steatorrhea, or fatty stool. The blockage of the pancreatic ducts also cause the enzymes to become activated within the pancreas, leading to autodigestion of the pancreas.

Pancreas & Cystic Fibrosis [HD Animation]

How is CF Diagnosed?

There are two primary methods for diagnosis of cystic fibrosis: sweat test and genotyping. The sweat test measures the amount of chloride and sodium in the patients sweat. The procedure is done by applying a drug solution called pilocarpine to the patients skin. Normally, pilocarpine is applied to gauze, which is placed beneath and electrode. A second electrode is placed on the arm without pilocarpine. When activated, the electrodes will draw the pilocarpine into the skin and activate the sweat glands. Afterwards, the electrodes are removed and a piece of gauze is wrapped around the arm to collect sweat. At the same time, the electrodes may be placed on the other arm for an additional sample. The gauze is then removed after 30 minutes and sent to the lab for inspection. A chloride level of over 60 mmol/L typically leads to a diagnosis of CF.

Cystic Fibrosis Foundation: Sweat Test

The genetic test looks for the CFTR gene and whether it has been mutated. Everyone has two copies of this gene. If one is mutated, they are a carrier for the disease. If both are mutated, they have Cystic Fibrosis. “There are more than 1,500 different CFTR mutations known to cause CF, and new mutations are being discovered as research on the gene continues” (Alma). To determine if the CFTR gene is mutated, there must be at least 23 mutations on the gene. This is the standard that the American College of Medical Genetics developed. There are also more advanced genetic testing that may test for rarer mutation of the CFTR gene.

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Who is At Risk for CF?

Family History


Family history is the primary risk factor for Cystic Fibrosis. Because Cystic Fibrosis is an autosomal recessive genetic disorder, it is passed down through families through the inheritance of a mutation on the CFTR gene. A person cannot contract the disease unless both of their parents are carriers for the gene. If someone in a person's family has cystic fibrosis, they are at higher risk of being born with CF or of being a carrier for the mutated CFTR gene and passing it on to their own offspring.


At Risk Populations


Cystic Fibrosis is more common among certain races than others, particularly Caucasians of Northern European descent. For whites of Northern European descent, for every 3,200-3,500 people there is 1 case of Cystic Fibrosis, more than any other ethnic group (Sharma, 2015).

Signs and Symptoms of CF

Newborns in all 50 states in the U.S. are now screened for cystic fibrosis, and can be diagnosed within the first month of birth. However, there are many people who may have been born before the screenings and go undiagnosed until symptoms appear, which may not happen until adolescence or adulthood.


Signs and symptoms of cystic fibrosis can vary widely, depending on the severity of the disease and the age of the affected person. For instance, adults with cystic fibrosis are more likely to present with atypical symptoms of CF such as pancreatitis, diabetes, and infertility. Symptoms can also vary widely from person to person - symptoms can become better or worse as time goes on, depending on the individual.


People with CF have high levels of salt in their sweat, and children can taste salty when their parents kiss them. However, cystic fibrosis affects the respiratory and digestive systems primarily, which is where most of the symptoms manifest.

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Respiratory Manifestations



  • Thick mucous production in lungs and airways
  • Persistent productive cough (thick sputum)
  • Exercise intolerance - difficult or labored breathing (dyspnea) upon exertion
  • Breathlessness
  • Recurrent pneumonia and bacterial infections
  • Inflamed nasal passages/stuffy nose
  • Chest pain



As CF progresses, difficulty breathing can cause other pulmonary problems, such as cyanosis (bluish skin discoloration due to poor circulation or inadequate oxygenation), clubbing (hand and finger deformity due to poor oxygenation), and barrel chest.

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Digestive Manifestations



  • Meconium ileus: intestinal blockage in newborns due to thicker than normal meconium (substance in intestines of fetus)
  • Greasy, smelly stools
  • Recurrent abdominal pain
  • Under weight/poor growth, which can cause failure-to-thrive
  • Jaundice (yellow appearance of skin and eye sclera)
  • Fat-soluble vitamin (vitamin A, D, E, and/or K) deficiency
  • Malabsorption of fats and proteins



Many digestive issues are caused by pancreatic insufficiency, where the increased thick mucous blocks the ducts where the pancreas releases digestive enzymes. These digestive enzymes help the small intestine absorb nutrients, so patients with CF have many symptoms related to malabsorption of nutrients.

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How is CF Treated?

Treatment plans are individualized for each patient. The treatments for cystic fibrosis are done to better the health of the patient and prolong their life. This is done by airway clearance techniques, oral, inhaled and nebulized medications, nutrition therapies and fitness plans. Airway clearance techniques are used to clear out thick mucus from the lungs and allow for the patient to breath better.


Airway Clearance Techniques (ACT's)


  • Coughing and huffing: This can be used while other ACT's are being done also. Coughing helps move mucous from larger airways out of the lungs.


  • Chest physical therapy: This can be done by laying in different positions so that each of the lobes of the lungs can face downward while being percussed. The vibrations and gravity help break up and loosen the mucus in the lungs.


  • Active cycle of breathing technique: This can be done in three phases. In the first one, the breathing is relaxed. The second phase uses chest expansion exercises. In the last phase the patient will cough and huff to loosen mucus and clear it from the lungs.


  • Autogenic drainage: This is done by changing breathing rates to clear mucus.


  • Positive expiratory pressure: This gets more air into the lungs and behind the mucus to clear it.


  • High frequency chest wall oscillation: This is a vest used to administer vibrations to lungs with intervals of the patient coughing to clear the mucus.



Medication Treatments used are: antibiotics to fight and control infection-causing bacteria; mucolytics, which are inhaled medications that help thin the mucus; and nebulizers, which can be used to administer moistened medication to the lungs to help clear out the mucus.


Nutrition Therapies include taking different vitamins, medications, and high calorie diets to manage a healthy nutritional status. Most patients need to take pancreatic enzymes with meals due to the decrease or lack of pancreatic enzymes being released naturally into the small intestine. Cystic fibrosis patients usually need to consume a high calorie and high fat diet to make up for the fat and other minerals and vitamins they are unable to absorb from their small intestine as easily. Physical activity is also helpful in cystic fibrosis patients to keep them active as it helps in the aid of loosening of mucus and increase their health.

References

Alma, L. (2014, June 15). Genetic Testing for Cystic Fibrosis. Retrieved December 2, 2015, from http://cysticfibrosis.about.com/od/diagnosis/a/basic_DNA_test.htm


Cystic fibrosis. (2015, July 7). Retrieved December 2, 2015, from http://www.mayoclinic.org/diseases-conditions/cystic-fibrosis/basics/definition/con-20013731


Sharma, MD, G. (2015, July 8). Cystic Fibrosis (M. Bye, MD, Ed.). Retrieved December 2, 2015, from http://emedicine.medscape.com/article/1001602-overview


Treatments and Therapies. (n.d.). Retrieved December 2, 2015, from https://www.cff.org/Living-with-CF/Treatments-and-Therapies/