HPRS Discussion 3

Discussion on Cystic Fibrosis

Cystic fibrosis (CF) is the most common inherited disease among whites, particularly in the UK. CF is a disease that affects many organs but majorly the lungs, pancreas and the small intestines and requires a multidisciplinary approach in its management, in conjunction with a specialist center for CF tailoring the treatment to the individual. The mainstay of control is the proactive treatment of infections in the airway and encouragement of proper nutrition and a lifestyle that is active (Garry, 2014). Conventional therapies have shown much improvement in the disease, but newer approaches like small molecule and gene-based treatments may have the potential to stop disease progression.

The discovery of patient with cystic fibrosis was first diagnosed a few centuries ago as early as 1595 references were found in medical textbooks that was relating salty skin and pancreas damage with infant’s death. Frederick Chopin who died in 1849 as a result of respiratory arrest after a long duration of lung infection and malabsorption syndrome was suspected of having a mild form of cystic fibrosis. Dr. Dorothy Anderson, an American pathologist, provided the first literature review of cystic fibrosis of the pancreas in the year 1938 basing her findings from postmortem results of children who had died of malnutrition. Dr. Paul di Sant also analysis sweats of dehydrated children and noted that sweats of children with cystic fibrosis had a higher concentration of salt (Garry, 2014). The responsible gene for cystic fibrosis was discovered in 1989.

Cystic fibrosis is an autosomal recessive genetic disorder caused by a mutation in the protein cystic fibrosis transmembrane conductance regulator gene that is responsible for regulation of chloride ions in the epithelium. The disease affects cell membranes. The affected areas are the lungs and gastrointestinal tract. With cystic fibrosis, there is a disruption in the movement of water and salt in and out of the cells (Wang et al., 2014).

Cystic fibrosis affects the lungs, liver, large intestines, small intestines, and pancreas. Lungs are air sac filled organs located on both sides of the chest walls. Lungs are designed to exchange oxygen and carbon dioxide when breathing air in and out. The right lung has three lobes, and the left lung has two lobes. Both lungs have alveoli that aids in gaseous exchange. The alveolus is covered with capillaries where gaseous exchange takes place. The lungs are lined with epithelial cells that produce mucus which trap germs and mucus. Cystic fibrosis leads to build up of more thick mucus in the lungs thus decreasing the surface area of the lungs leading to dyspnea and frequent lung bacterial infections.

The pancreas is a small organ approximately 6 inches located behind the stomach and sits across the back of the abdomen. The pancreas is both an exocrine and endocrine gland in that being an exocrine gland pancreas secretes pancreatic enzymes that are important for the breakdown of lipids, carbohydrates, proteins, and nucleic acid. As an endocrine gland, the pancreas secretes both insulin and glucagon hormone necessary for blood sugar control and balance. The pancreas plays a significant role in food digestion where it secretes pancreatic juice that has bicarbonate ion that insulates and provides protection to intestinal walls. The pancreas is the most affected organ in a patient with cystic fibrosis. Pancreatic epithelial cells absorb chlorides and secretes bicarbonates. In cystic fibrosis, there is an altered composition of pancreatic fluids leading to accumulation of mucus from epithelium cells. With a modified structure of pancreatic fluid there will be a problem with the breakdown of fat, malabsorption and also causes inflammation of the pancreas. Cystic fibrosis of endocrine pancreas leads to diabetes mellitus.

The small intestine is found between the stomach and large intestine and plays a significant role in the absorption of nutrients and minerals. The small intestine is divided into three regions namely duodenum, jejunum, and ileum. Duodenum secretes bicarbonate that neutralizes stomach acid in gastric chyme. Jejunum has villi that absorb final products of digestion including amino acids, glucose, and fatty acids. Ileum which is the last part of the small intestine also has villi that absorb mainly vitamin B12 and bile acid as well as other final nutrients. Cystic fibrosis affects small intestine altering absorption of fat by the inability of the ileum to absorb bile salt. Absorption of fat-soluble vitamin also diminishes causing malnutrition (De Lisle and Borowitz, 2013). The small intestine of a cystic fibrosis patient is often unable to neutralize excess acidity from the stomach leading to peptic or duodenal ulcer disease.

Cystic fibrosis causes constipation due to indigestion by decreasing water and electrolyte content in fecal matter. With chronic constipation, a patient may suffer from intussusception and rectal prolapse. Male patients with cystic fibrosis usually have delayed puberty due to impaired sex hormones production. Men also suffer testicular function while women may experience prolonged amenorrhea in the absence of any family planning use. Cystic fibrosis also leads to urine incontinence and accumulation of kidney stones.Old adults have osteoporosis making them prone to fractures.

The large intestine is the terminal part of the alimentary canal which runs from the appendix to the anus and frames the small intestines on three sides. The large intestine starts from the pelvis iliac region just at the right waist. The organ contains the least lymphoid tissues and is part of mucosa-associated lymphoid tissue with an essential role in immunity. It is divided into the cecum, colon, rectum and the anus. Effects of CF to the large intestine is an obstruction in the proximal part, which can result in sepsis and rupture if untreated. The liver is the second largest gland in the human body and the most massive visceral structure in the abdominal cavity. The organ is predominantly situated in the right hypochondrium region and extends into the left hypochondrium. The liver has two surfaces, the diaphragmatic and the visceral and has two lobes. The effect of CF to the liver is that it causes loss of bile acids through feces which leads to poor micelle formation causing malabsorption of fats and vitamins (Kobelska-Dubiel,  Klincewicz, and Cichy, 2014).

Cystic fibrosis is caused by gene mutation which is autosomal recessive. The gene is inherited. Signs and symptoms of cystic fibrosis depend on the organ involved ranging from dyspnea, hemoptysis, cough, weight loss, constipation, melena, foul-smelling diarrhea, abdominal pain, and intestinal obstruction. Diagnosis of cystic fibrosis includes physical examination, signs and symptoms and tests. Signs and symptoms include respiratory problems to include sinuses and lung infection, inflammation and obstruction, gastrointestinal issues such as constipation, intestinal obstruction and other unusual presentations along with an elevation in sweat chloride concentration of more than 60mM. Sonographic tests reveal echogenic bowel, dilated bowel, and nonvisualization of the gall bladder. Testing includes prenatal screening for careers, newborn screening, gene mutation analysis, sweat test, and imaging studies.

Complications that may arise from cystic fibrosis include colon cancer, diabetes mellitus, infertility, liver failure, pancreatitis, malnutrition, nasal polyps, intestinal obstruction, rectal prolapse, respiratory arrest, chronic rhinosinusitis, and chronic bacterial infections. Colon cancer may be as a result of prolonged intestinal obstruction which occurs due to poor water and electrolyte reabsorption in the large intestines. Diabetes mellitus occurs following the effects of cystic fibrosis to the pancreas, whose function of secreting Insulin from the Beta cells in the Islets of Langerhans is interfered with, causing abnormally high blood glucose levels. With time as the damage continues, the patient develops Diabetes mellitus type I due to blockage of ducts and destruction of Beta cells.

Infertility in females may be due to amenorrhea and delayed puberty as a result of malnutrition. Mutations of CFTR have also been associated with the absence of the vagina and uterus congenitally. Besides, they have thicker cervical mucus, which makes it more difficult for the sperms to penetrate the cervix, causing a woman to take more time to conceive. In men, infertility may occur due to the absence of the sperm canal totally or a blockage of the same. The liver failure which is also a complication of cystic fibrosis is usually a result of the effects of cystic fibrosis to the liver where an abnormal cystic fibrosis transmembrane regulator (CFTR) protein in the biliary system leads to impaired secretion and deposition of thick, viscous bile that has reduced alkalinity. Bile with unusual features causes increased activity of free radicals and susceptibility to infectious agents and other toxic substances secreted with bile which may directly damage a hepatocyte leading to liver failure.

Intestinal obstruction occurs due to the poor absorption of water and electrolytes in the large intestines which results from a decrease in fluid and anion transport caused by loss of (CFTR) function (Somerset and Lili, 2014). Respiratory arrest occurs due to the effects of cystic fibrosis to the lungs, whereby the mucus that accumulates in the lungs causes the airway to become constricted therefore limiting airflow to and out of the lungs. Chronic bacterial infections occur mostly in the respiratory tract are due to the accumulated thick mucus which acts as a reservoir for micro-organisms since they inhibit an active cough reflex.

Treatment of cystic fibrosis depends on the organ or system affected. The standard regimen treatment includes administration of antibiotics for bacterial infections, medication to thin sticky mucus, anti-inflammatory drugs, nutritional advice, chest physiotherapy, oral pancreatic enzymes, lung transplant and use of disease-modifying therapies and surgery. Replacement of pancreatic enzymes is also used since the pancreas is one of the organs that CF mostly affects thus interfering with its secretion of various hormones (Flume and Van Devanter, 2012). This replacement has resulted in progressive improvement in children born with CF with survival to an average age of 37 years. Another therapy is increasing the activity of the chloride channel of mutant forms of CFTR. Side effects of cystic fibrosis treatment include becoming antibiotic resistance due to prolonged use of antibiotics and effects from inflammatory medication such as lowered body immune system.

Research on new drugs development by cystic fibrosis foundation will significantly improve the impact on the disease and dramatically reduces morbidity and mortality associated with the disease. Sponsoring cystic fibrosis centers and also the researches on new drug development will help to standardize medical treatment across the world. The Food and Drug Administration (FDA) is currently reviewing some drugs to include Tobramycin inhalation powder, Levofloxacin inhalation solution, and Mannitol which will be excellent weapons in fighting CF in the near future. CFTR modulators are other drugs that have generated much excitement. Though the CFTR modulators are not a cure, they are a sign of first successes in treating early events in the pathophysiology of lung disease CF, which means they have a high potential of being indeed disease-modifying. Lung transplantation may also be an option with lung disease CF. Use of ivacaftor has also been recently approved though it offers treatment to a minority of patients its approval has given hope to the persons with CF.

There is need to develop new medications for every type of mutation, and with already two new drugs under active investigation for F508del, which is the most common CFTR mutation, it brings us closer to making a big difference in the lives of patients with CF.

The focus should be put more on obstructive lung disease resulting from CF since it is the primary cause of morbidity with up to 80% of mortality. It is also significant to screen parents who intend to conceive and even newborns for CF so that early interventions can be put into place to avoid the manifestations and complications of the disease. A greater understanding of the environmental and genetic modifiers of cystic fibrosis will enable medical professionals to target individual risk factors.  Unfortunately, the disease cannot be prevented, but genetic screening can help identify children who are at risk early enough.





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