Cystic Fibrosis

The purpose of this paper is to define what cystic fibrosis is and the aetiology and/ or predisposing factors involved with CF. I will then describe the diagnostic process involved with CF. Furthermore, I will discuss two clinical manifestations arising from CF as well as the pathophysiology behind these clinical manifestations.  The two clinical manifestations I will be discussing in detail are cystic fibrosis related diabetes and meconium ileus.

According to Cystic Fibrosis Australia (n.d.), Cystic fibrosis (CF) is an inherited disease.  It is inherited from both parents and occurs equally in females and males, otherwise known as an autosomal recessive disease. Genetics play a specific role in determining the makeup of a person’s body and its functioning. How the gene works is determined by its individual DNA code. There are four building blocks referred to as bases within the DNA. The four bases join in a specific order for each gene and if they don’t join in a specific order then this is when there are changes to the gene thus preventing it from working properly.  Genetic disorders occur when there is a change to the structure of the gene and these can lead to birth defects. It is referred to as a mutation of the gene. A child inherits one gene from each parent thus making the pair that is required.  When both genes have a mutation, cystic fibrosis can occur (Stanford Medicine, 2018).

Approximately four percent of the population carry the CF gene, the majority of whom are unaware they are carriers as they are not actually affected by the disease.  One in every 2,500 babies are born with CF in Australia (Cystic Fibrosis Australia, n.d.) CF mainly affects the respiratory and digestive systems due to a defect in the exocrine system which is predominately responsible for the production of saliva, sweat, tears and mucus. Cystic fibrosis patients have an alteration in genetics that sees changes in the production of the cystic fibrosis transmembrane conductance regulator (CTFR). CFTR regulates the secretion of chloride and fluids in the exocrine glands, intestine, biliary and reproductive systems, pancreatic duct and bronchial glands (Cystic Fibrosis Australia, n.d.). In cystic fibrosis patients the function of the cell protein cystic fibrosis transmembrane regulator (CFTR) has abnormalities. The CFTR gene is a protein that functions as a chloride channel, it is responsible for the control of water and salt balance in and out of the body’s cells (Stanford Medicine, 2018). There are varying classes of cystic fibrosis defined by how damaged the CFTR protein function is. Classes I, II, and III are the more severe cases of CF and are referred to as the “classic CF”. Whereas classes IV and V present as being milder with less severe symptoms.  Genes known as the modifier genes can also play a role in a CF patient’s symptoms and outcome. (Terlizzi et al., 2018; American Lung Association 2018) Unfortunately to date there is no cure for cystic fibrosis.

There are various methods used for diagnosing CF including pathology, genetic testing and the sweat test. All newborns are subject to a heel prick test which is used to screen for numerous conditions, including cystic fibrosis. The sample is tested for high levels of immunoreactive trysinogen (IRT) which is a chemical released by the pancreas. This test however has proven to not be one hundred percent reliable as high levels of IRT can also be present due to a premature birth or a traumatic delivery. Genetic testing can be utilised in conjunction with the blood test to test for specific defects on the CFTR gene responsible for CF.  The more definitive of tests for CF is the sweat test. It is known that high levels of salt in sweat is a key indicator for CF.  Sweat testing is used for older children and adults who were not screened at birth and present with symptoms of CF which include recurring bouts of pancreatitis, chronic sinus, lung infections, bronchiectasis, nasal polyps and infertility. Infants as young as 2 weeks old can also be tested using the sweat test. The sweat test is conducted by placing a “sweat-producing” chemical to a small patch of skin and then collecting the sweat to be analysed for cystic fibrosis (Huether & McCance, 2014).

There are numerous clinical manifestations associated with cystic fibrosis. The two main systems that cystic fibrosis has the largest impact on are the respiratory system and the digestive system. Within the digestive system CF mainly affects the pancreas (Stanford Children’s Health, n.d. -a). The pancreas is an organ that is located behind the stomach, between the spleen and duodenum (Huether & McCance, 2014).  It is responsible for the secretion of substances that aid with the process of digestion as well as controlling the body’s blood sugar levels (Stanford Children’s Health, n.d. -a). Located on the surface of the pancreas are the islets of Langerhans which are related to the endocrine functions of the pancreas. These “small islands”, as they are referred to, include three major types of cells: alpha, beta and delta cells. Alpha cells are known to be responsible for the secretion of the hormone glucagon which elevates blood sugar levels.

The secretion of insulin is performed by beta cells which in turn affects the metabolism of carbohydrates, fats and proteins (Da Silva Xavier, 2018). Delta cells secrete a substance known as somatostatin also known as growth hormone inhibiting hormone (GHIH). Somatostatin in the pancreas inhibits the secretion of pancreatic hormones, including glucagon and insulin (Corleto, 2010). Cystic fibrosis is characterized by a deficiency in the secretion of pancreatic juices as well as an increase in its viscosity, the thickness and stickiness. Due to the pancreatic secretions being more viscous and tackier they can cause the ducts the pancreas to become blocked. A blockage within these causes a significant decrease in the volume of digestive enzymes secreted, resulting in a person with cystic fibrosis having difficulties absorbing fat, as well as fat-soluble vitamins A, D, E and K, and some proteins (Stanford Children’s Health, n.d. -a).

Cystic Fibrosis Related Diabetes (CFRD) occurs in approximately 20% of adolescents with cystic fibrosis and approximately 40-60% of adults (Norman, n.d.). According to Smyth, endocrine pancreatic insufficiency increases after the age of 10yrs old.  Although CFRD can have similar features as type 1 and type 2 diabetes it is seen as a completely different condition. One task of the pancreas is to produce the hormones insulin and glucagon (CFWA, n.d.). Insulin, as stated above, is secreted by the beta cell of the pancreas.

There is always a low level of insulin being secreted from the pancreas but as the blood glucose rises more insulin is secreted to maintain a balance within the body.  Glucagon, on the other hand, does the exact opposite. It is secreted by the alpha cells however if the blood glucose is too high then no glucagon will be secreted (Norman, n.d). CFRD is more commonly diagnosed with the glucose tolerance tests as blood glucose, urinalysis and glycosylated haemoglobin measurements do not reliably identify CFRD. Very rarely does one see ketosis in CFRD (CFWA, n.d.). Ketoacidosis is a serious condition that is associated with either extreme hyperglycaemia or illness.  Insufficient insulin in the body leads to ketoacidosis. When there is insufficient amounts of insulin present in the body the body’s cells have no glucose to utilise for energy.  The body then turns to the fat stores and burn fat for energy instead. Ketones, which are a dangerous chemical substance, then accumulate in the blood and urine (Diabetes Australia, 2015) CFRD patients are often advised not to change their diet to a diabetic diet.  Instead it has been proven that insulin is the treatment for CFRD. Insulin aids in the control of the correct amount of glucose in the blood. It is recommended that CFRD patients continue with the recommended CF nutritional guidelines which is a healthy high fat and high energy diet. They should also ensure carbohydrates are also included (CFWA, n.d.).

According to Sathe and Howen (2017), one of the first manifestations of cystic fibrosis is meconium ileus. In approximately twenty percent of CF patients Meconium ileus (MI) occurs. MI is more so associated with class I-III CFTR mutations. There are two forms of meconium ileus and they are defined as simple MI and complex MI. Simple MI is a result of when viscid meconium obstructs the terminal ileum and the small intestine proximal to the obstruction. When the obstruction occurs in the ileum dilation is seen due to a build-up of meconium, gas and fluids. The more severe of the two is known as complex MI this is because as the meconium distended areas can lead to prenatal volvulus, intestinal atresia, ischemic necrosis as well as perforation that can lead to meconium leaking in to the peritoneum. CFTR is responsible for bicarbonate and chloride excretion patients with abnormal CFTR results in abnormal bicarbonate secretion which in turn decreases the luminal PH. This then goes on to create an acidic and dehydrated environment which results in thick, dehydrated mucus and leads to viscid meconium physically obstructing the terminal ileum.

MI is usually diagnosed prenatally during prenatal ultrasounds however if it is not diagnosed prenatally it will present with clinical indications within hours of birth. With feeds bilious emesis will occur however this may or may not present with abdominal distension. Clinical infants with MI will also present with tenderness of the abdomen on palpation, fevers and clinical signs of shock. If bilious emesis is present it is assumed that there is an obstruction and the neonate should be nursed in the Neonatal Intensive Care Unit and stabilised as soon as possible. The neonate should have feeds ceased and IV therapy commenced to allow for adequate perfusion. Bloods and urine should be obtained and tested. Intravenous antibiotics should be commenced immediately if white blood cell count is high, or the neonate is febrile. A nasogastric tube should be inserted and left open to vent or regular aspirates done to allow for decompression of the stomach and small bowel as well as a means of expelling the bilious bile to avoid the neonate from aspirating on the bilious emesis.  Abdominal x-rays should be done to confirm the obstruction. If the neonate is unstable and presents with clinical signs of perforation leading to peritonitis, then immediate surgery is warranted (Sathe. & Houwen, 2017).

In summary Cystic Fibrosis is a life limiting disease characterised by the build-up of thick, sticky mucus that damages multiple organs of the body. There are varying degrees of CF however CF patients will spend a considerable amount of time in hospital and at medical appointments.  Patients routinely find themselves as inpatients whilst undergoing a CF tune-up. The more common issues with cystic fibrosis include progressive damage to the respiratory system as well as chronic gastrointestinal issues. Cystic fibrosis is more likely to be the cause of meconium ileus in neonates with ninety percent of meconium ileus cases being diagnosed with cystic fibrosis. The endocrine system is also affected as the build-up of thick, sticky mucus blocks the ducts of the pancreas, impairing its ability to produce insulin resulting in CFRD. Cystic fibrosis patients have a shortened life span which are usually due to reoccurring lung infections. Cystic fibrosis patients require ongoing medical and multidisciplinary team involvement, with physiotherapy playing a major role in patients’ day to day activities.

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