Cystic Fibrosis In Child
Cystic fibrosis (also known as CF, mucovoidosis, or mucoviscidosis) is a genetic disorder known to be an inherited disease of the secretory glands, including the glands that make mucus and sweat.
The hallmarks of cystic fibrosis are salty tasting skin, appetite but poor growth and poor weight gain, excess mucus production, and coughing/shortness of breath. Males can be infertile due to the condition congenital bilateral absence of the vas deferens. Often, symptoms of CF appear in infancy and childhood. Meconium ileus is a typical finding in newborn babies with CF.
Although technically a rare disease, cystic fibrosis is ranked as one of the most widespread life-shortening genetic diseases. It is most common among nations in the Western world; one in twenty-two people of Mediterranean descent is a carrier of one gene for CF, making it the most common genetic disease in these populations. An exception is Finland, where only one in 80 people carry a CF mutation. In the United States, 1 in 4,000 children are born with CF. In 1997, about 1 in 3,300 caucasian children in the United States was born with cystic fibrosis. In contrast, only 1 in 15,000 African American children suffered from cystic fibrosis, and in Asian Americans the rate was even lower at 1 in 32,000.
Signs and symptoms
Lung and sinus disease
Lung disease results from clogging the airways due to mucosa buildup and resulting inflammation. Inflammation and infection cause injury to the lungs and structural changes that lead to a variety of symptoms. In the early stages, incessant coughing, copious phlegm production, and decreased ability to exercise are common. Many of these symptoms occur when bacteria that normally inhabit the thick mucus grow out of control and cause pneumonia. In later stages of CF, changes in the architecture of the lung further exacerbate chronic difficulties in breathing. Other symptoms include coughing up blood (hemoptysis), changes in the major airways in the lungs (bronchiectasis), 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. In addition to typical bacterial infections, people with CF more commonly develop other types of lung disease. 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 (MAC), a group of bacteria related to tuberculosis, which can cause further lung damage and does 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. These polyps can block the nasal passages and increase breathing difficulties.
Gastrointestinal, liver and pancreatic disease
Prior to prenatal and newborn screening, cystic fibrosis was often diagnosed when a newborn infant failed to pass feces (meconium). Meconium may completely block the intestines and cause serious illness. This condition, called meconium ileus, occurs in 10% of newborns with CF. In addition, protrusion of internal rectal membranes (rectal prolapse) is more common in CF because of 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 which help break down food. These secretions block the movement of the digestive enzymes into the duodenum and result in irreversible damage to the pancreas, often with painful inflammation (pancreatitis). The lack of digestive enzymes leads to difficulty absorbing nutrients with their subsequent excretion in the faeces, a disorder known as malabsorption. Malabsorption leads to malnutrition and poor growth and development because of calorie loss. Individuals with CF also have difficulties absorbing the fat-soluble vitamins A, D, E, and K. In addition to the pancreas problems, people with cystic fibrosis experience more heartburn, intestinal blockage by intussusception, and constipation. Older individuals with CF may also develop distal intestinal obstruction syndrome when thickened feces cause intestinal blockage.
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. Over time, this can lead to cirrhosis, in which the liver fails to rid the blood of toxins and does not make important proteins such as those responsible for blood clotting.
Endocrine disease and growth
The pancreas contains the islets of Langerhans, which are responsible for making insulin, a hormone that helps regulate blood glucose. Damage of the pancreas can lead to loss of the islet cells, leading to diabetes that is unique to those with the disease. Cystic Fibrosis Related Diabetes (CFRD), as it is known as, shares characteristics that can be found in Type 1 and Type 2 diabetics and is one of the principal non-pulmonary complications of CF. Vitamin D is involved in calcium and phosphorus regulation. Poor uptake of vitamin D from the diet because of malabsorption leads to the bone disease osteoporosis in which weakened bones are more susceptible to fractures. In addition, people with CF often develop clubbing of their fingers and toes due to the effects of chronic illness and low oxygen in their tissues.
Poor growth is a hallmark of CF. Children with CF typically do not gain weight or height at the same rate as their peers, and occasionally are not diagnosed until investigation is initiated for poor growth. The causes of growth failure are multi–factorial and include chronic lung infection, poor absorption of nutrients through the gastrointestinal tract, and increased metabolic demand due to chronic illness.
Infertility
Infertility affects both men and women. At least 97 percent of men with cystic fibrosis are infertile but are not sterile and can have children with assisted reproductive techniques. These men make normal sperm but are missing the tube (vas deferens), which connects the testes to the ejaculatory ducts of the penis. Many men found to have congenital absence of the vas deferens during evaluation for infertility have a mild, previously undiagnosed form of CF. Some women have fertility difficulties due to thickened cervical mucus or malnutrition. In severe cases, malnutrition disrupts ovulation and causes amenorrhea.
Cause
CF is caused by a mutation in the gene cystic fibrosis transmembrane conductance regulator (CFTR). The product of this gene is a chloride ion channel important in creating sweat, digestive juices and mucus. Although most people without CF 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. Therefore, CF is considered an autosomal recessive disease.
Pathophysiology
Cystic fibrosis occurs when there is a mutation in the CFTR gene. The protein created by this gene is anchored to the outer membrane of cells in the sweat glands, lungs, pancreas, and other affected organs. The protein spans this membrane and acts as a channel connecting the inner part of the cell (cytoplasm) to the surrounding fluid. This channel is primarily responsible for controlling the movement of chloride from inside to outside of the cell; however, in the sweat ducts it facilitates the movement of chloride from the sweat into the cytoplasm. When the CFTR protein does not work, chloride is trapped inside the cells in the airway and outside in the skin. Because chloride is negatively charged, positively charged ions cross into the cell because they are affected by the electrical attraction of the chloride ions. Sodium is the most common ion in the extracellular space and the combination of sodium and chloride creates the salt, which is lost in high amounts in the sweat of individuals with CF. This lost salt forms the basis for the sweat test.
How this malfunction of cells in cystic fibrosis causes the clinical manifestations of CF is not well understood. One theory suggests that the lack of chloride exodus through the CFTR protein leads to the accumulation of more viscous, nutrient-rich mucus in the lungs that allows bacteria to hide from the body's immune system. Another theory proposes that the CFTR protein failure leads to a paradoxical increase in sodium and chloride uptake, which, by leading to increased
