cystic fibrosis cystic fibrosis cystic fibrosis (cf) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. other signs and symptoms may include sinus infections, poor growth, fatty stool, clubbing of the fingers and toes, and infertility in most males. different people may have different degrees of symptoms. cystic fibrosisother namesmucoviscidosisspecialtymedical genetics, pulmonologysymptomsdifficulty breathing, coughing up mucus, poor growth, fatty stoolusual onsetsymptoms recognizable ~6 monthdurationlife longcausesgenetic (autosomal recessive)risk factorsgeneticdiagnostic methodsweat test, genetic testingtreatmentantibiotics, pancreatic enzyme replacement, lung transplantationprognosislife expectancy between 42 and 50 years (developed world)frequency1 out of 3,000 (northern european) cystic fibrosis is inherited in an autosomal recessive manner. it is caused by the presence of mutations in both copies of the gene for the cystic fibrosis transmembrane conductance regulator (cftr) protein. those with a single working copy are carriers and otherwise mostly healthy. cftr is involved in the production of sweat, digestive fluids, and mucus. when the cftr is not functional, secretions which are usually thin instead become thick. the condition is diagnosed by a sweat test and genetic testing. screening of infants at birth takes place in some areas of the world. there is no known cure for cystic fibrosis. lung infections are treated with antibiotics which may be given intravenously, inhaled, or by mouth. sometimes, the antibiotic azithromycin is used long term. inhaled hypertonic saline and salbutamol may also be useful. lung transplantation may be an option if lung function continues to worsen. pancreatic enzyme replacement and fat-soluble vitamin supplementation are important, especially in the young. airway clearance techniques such as chest physiotherapy may have some short-term benefit, but long-term effects are unclear. the average life expectancy is between 42 and 50 years in the developed world. lung problems are responsible for death in 80% of people with cystic fibrosis. cf is most common among people of northern european ancestry, for whom it affects about 1 out of 3,000 newborns, and among which around 1 out of 25 people is a carrier. it is least common in africans and asians, though it does occur in all races. it was first recognized as a specific disease by dorothy andersen in 1938, with descriptions that fit the condition occurring at least as far back as 1595. the name "cystic fibrosis" refers to the characteristic fibrosis and cysts that form within the pancreas. signs and symptoms health problems associated with cystic fibrosis cystic fibrosis typically manifests early in life. newborns and infants with cystic fibrosis tend to have frequent, large, greasy stools (a result of malabsorption) and are underweight for their age. 15–20% of newborns have their small intestine blocked by meconium, often requiring surgery to correct. newborns occasionally have neonatal jaundice due to blockage of the bile ducts. children with cystic fibrosis lose excessive salt in their sweat, and parents often notice salt crystallizing on the skin, or a salty taste when they kiss their child. the primary cause of morbidity and death in people with cystic fibrosis is progressive lung disease, which eventually leads to respiratory failure. this typically begins as a prolonged respiratory infection that continues until treated with antibiotics. chronic infection of the respiratory tract is nearly universal in people with cystic fibrosis, with pseudomonas aeruginosa, fungi, and mycobacteria all increasingly common over time. inflammation of the upper airway results in frequent runny nose and nasal obstruction. nasal polyps are common, particularly in children and teenagers. as the disease progresses, people tend to have shortness of breath, and a chronic cough that produces sputum. breathing problems make it increasingly challenging to exercise, and prolonged illness causes those affected to be underweight for their age. in late adolescence or adulthood, people begin to develop severe signs of lung disease: wheezing, digital clubbing, cyanosis, coughing up blood, pulmonary heart disease, and collapsed lung (atelectasis or pneumothorax). in rare cases, cystic fibrosis can manifest itself as a coagulation disorder. vitamin k is normally absorbed from breast milk, formula, and later, solid foods. this absorption is impaired in some cf patients. young children are especially sensitive to vitamin k malabsorptive disorders because only a very small amount of vitamin k crosses the placenta, leaving the child with very low reserves and limited ability to absorb vitamin k from dietary sources after birth. because clotting factors ii, vii, ix, and x are vitamin k–dependent, low levels of vitamin k can result in coagulation problems. consequently, when a child presents with unexplained bruising, a coagulation evaluation may be warranted to determine whether an underlying disease is present. 'comorbidities' and intracellular electrolytes. persons with cf show an extraordinary number of "comorbidities" affecting almost every organ in the body. these have in the past been viewed as incidental and not caused directly by the faulty cftr gene but that should be reconsidered. if chloride is not being pumped out of cells because of the faulty cftr channel, then the levels within the cells will be high and will need be balanced by increased cations (potassium and calcium in particular). high calcium in the parathyroid cells may be expected to affect the function of that gland and so too the bones, causing hypoporosis. high intracellular potassium may be expected to affect adrenal function causing hypokalaemia. muscle activity may be affected by these electrolyte abnormalities including cardiomyopathy of the heart. nerve function is affected by electrolytes esp. potassium. the endocrine cells of the pancreas that produce insulin, in the islets of lanaghans, may be affected too. our personal experience is that the response to treatment of hypoglycemia is better if glucose is given in an electrolyte drink. more research is needed into intracellular electrolytes in pwcf. we may well find the cftr gene affects every cell in the body not just those producing mucous. lungs and sinuses respiratory infections in cf vary according to age.green = pseudomonas aeruginosabrown = staphylococcus aureusblue = haemophilus influenzaered = burkholderia cepacia complex lung disease results from clogging of the airways due to mucus build-up, decreased mucociliary clearance, and resulting inflammation. in later stages, changes in the architecture of the lung, such as pathology in the major airways (bronchiectasis), further exacerbate difficulties in breathing. other signs include high blood pressure in the lung (pulmonary hypertension), heart failure, difficulties getting enough oxygen to the body (hypoxia), and respiratory failure requiring support with breathing masks, such as bilevel positive airway pressure machines or ventilators. staphylococcus aureus, haemophilus influenzae, and pseudomonas aeruginosa are the three most common organisms causing lung infections in cf patients.: 1254 in addition, opportunistic infection due to burkholderia cepacia complex can occur, especially through transmission from patient to patient. in addition to typical bacterial infections, people with cf more commonly develop other types of lung diseases. among these is allergic bronchopulmonary aspergillosis, in which the body's response to the common fungus aspergillus fumigatus causes worsening of breathing problems. another is infection with mycobacterium avium complex, a group of bacteria related to tuberculosis, which can cause lung damage and do not respond to common antibiotics. mucus in the paranasal sinuses is equally thick and may also cause blockage of the sinus passages, leading to infection. this may cause facial pain, fever, nasal drainage, and headaches. individuals with cf may develop overgrowth of the nasal tissue (nasal polyps) due to inflammation from chronic sinus infections. recurrent sinonasal polyps can occur in 10% to 25% of cf patients.: 1254 these polyps can block the nasal passages and increase breathing difficulties. cardiorespiratory complications are the most common causes of death (about 80%) in patients at most cf centers in the united states.: 1254 gastrointestinal in addition, protrusion of internal rectal membranes (rectal prolapse) is more common, occurring in as many as 10% of children with cf, and it is caused by increased fecal volume, malnutrition, and increased intra–abdominal pressure due to coughing. the thick mucus seen in the lungs has a counterpart in thickened secretions from the pancreas, an organ responsible for providing digestive juices that help break down food. these secretions block the exocrine movement of the digestive enzymes into the duodenum and result in irreversible damage to the pancreas, often with painful inflammation (pancreatitis). the pancreatic ducts are totally plugged in more advanced cases, usually seen in older children or adolescents. this causes atrophy of the exocrine glands and progressive fibrosis. individuals with cf also have difficulties absorbing the fat-soluble vitamins a, d, e, and k. in addition to the pancreas problems, people with cf experience more heartburn, intestinal blockage by intussusception, and constipation. older individuals with cf may develop distal intestinal obstruction syndrome, which occurs when feces becomes thick with mucus (inspissated) and can cause bloating, pain, and incomplete or complete bowel obstruction. exocrine pancreatic insufficiency occurs in the majority (85–90%) of patients with cf.: 1253 it is mainly associated with "severe" cftr mutations, where both alleles are completely nonfunctional (e.g. δf508/δf508).: 1253 it occurs in 10–15% of patients with one "severe" and one "mild" cftr mutation where little cftr activity still occurs, or where two "mild" cftr mutations exist.: 1253 in these milder cases, sufficient pancreatic exocrine function is still present so that enzyme supplementation is not required.: 1253 usually, no other gi complications occur in pancreas-sufficient phenotypes, and in general, such individuals usually have excellent growth and development.: 1254 despite this, idiopathic chronic pancreatitis can occur in a subset of pancreas-sufficient individuals with cf, and is associated with recurrent abdominal pain and life-threatening complications. thickened secretions also may cause liver problems in patients with cf. bile secreted by the liver to aid in digestion may block the bile ducts, leading to liver damage. impaired digestion or absorption of lipids can result in steatorrhea. over time, this can lead to scarring and nodularity (cirrhosis). the liver fails to rid the blood of toxins and does not make important proteins, such as those responsible for blood clotting. liver disease is the third-most common cause of death associated with cf. around 5–7% of people experience liver damage severe enough to cause symptoms: typically gallstones causing biliary colic. endocrine the pancreas contains the islets of langerhans, which are responsible for making insulin, a hormone that helps regulate blood glucose. damage to the pancreas can lead to loss of the islet cells, leading to a type of diabetes unique to those with the disease. this cystic fibrosis-related diabetes shares characteristics of type 1 and type 2 diabetes, and is one of the principal nonpulmonary complications of cf. vitamin d is involved in calcium and phosphate regulation. poor uptake of vitamin d from the diet because of malabsorption can lead to the bone disease osteoporosis in which weakened bones are more susceptible to fractures. infertility infertility affects both men and women. at least 97% of men with cystic fibrosis are infertile, but not sterile, and can have children with assisted reproductive techniques. the main cause of infertility in men with cystic fibrosis is congenital absence of the vas deferens (which normally connects the testes to the ejaculatory ducts of the penis), but potentially also by other mechanisms such as causing no sperm, abnormally shaped sperm, and few sperm with poor motility. many men found to have congenital absence of the vas deferens during evaluation for infertility have a mild, previously undiagnosed form of cf. around 20% of women with cf have fertility difficulties due to thickened cervical mucus or malnutrition. in severe cases, malnutrition disrupts ovulation and causes a lack of menstruation. causes cystic fibrosis has an autosomal recessive pattern of inheritance. cf is caused by a mutation in the gene cystic fibrosis transmembrane conductance regulator (cftr). the most common mutation, δf508, is a deletion (δ signifying deletion) of three nucleotides that results in a loss of the amino acid phenylalanine (f) at the 508th position on the protein. this mutation accounts for 70% of cf cases worldwide and 90% of cases in the united states; however, over 700 other mutations can produce cf. although most people have two working copies (alleles) of the cftr gene, only one is needed to prevent cystic fibrosis. cf develops when neither allele can produce a functional cftr protein. thus, cf is considered an autosomal recessive disease. the cftr gene, found at the q31.2 locus of chromosome 7, is 230,000 base pairs