Week 3/4 - H - Cystic Fibrosis (abnormal secretions), Kartageners and Young's syndrome (abnormal cilia) Flashcards
Cystic fibrosis (CF) is a genetic disorder that affects mostly the lungs, but also the intestines, pancreatic ducts, sweat glands, and reproductive organs What is the inheritance pattern of cystic fibrosis and when are people screened for this disease?
CY is autosomal recessive and is screened for in the newborn heel prick test along with other disease
What is the incidence of people carrying the CF mutation in the UK? What is the average age expectancy in the condition?
1in25 people in the UK carry a copy of the gene (need 2 copies as it is recessive) Average age expectancy in CF is 40 years old
What is cystic fibrosis caused by and what is the most common mutation?
Cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) The most common mutation in the CFTR is delta F 508 deletion - * delta signifies a deletion, in the three nulceotides that result in the loss of the amino acid phenylalanine (F) at the 508th position of the protein (deletion of a single codon)
What chromsome is the CFTR located? Most common mutation causing CF is delta F 508 deletion
Cystic fibrosis transmembrane conductance regulator is located on chromomse 7
What does the mutation in the CFTR actually cause?
The CFTR is an anion channel found in the apical membrane of epithelial cells important in creating sweat, digestive juices and mucus A defect in this ion channel transport results in a combination of defective chloride secretion and increased sodium absorption across airway epithelium. Most of the damage in CF is due to blockage of the narrow passages of affected organs with thickened secretions
What are the clinical features of cystic fibrosis? Talk about lung and intestine features on this card (remember affects lungs, intestines, pancreatic ducts, sweat glands and reproductive organs)
* Lungs - cough, wheeze, recurrent infections, bonchiectasis (presents with persistent mucuopurulent cough, recurrent infections), chronic sinusitis * Intestines - distal intestinal obstruction syndrome (DIOS) (meconium ileus equivalent), gallstones
What are the clinical features of cystic fibrosis? Talk about pancreatic, sweat glands and reproducitve organs on this card
Pancrease - pancreatic insufficiency - endocrine pancrease doesnt produce insulin resulting in diabetes Exocrine pancreas doesnt produce digestive enzymes or bile salts resulting in eg steatorrhea Sweat glands - salty sweat Reproductive organs - in males infertility
Why is there infertility in males? How does cystic fibrosis affect a patients stools?
There is infertility in some males with cystic fibrosis due to bilateral absence of the vas deferens - nothing to transport sperm form epididymis to prostatic urethra Cystic fibrosis can cause fatty stools steathorrea - these stools are often pale, fouling smelling and bulku
What are features of CF in neonates? How is distal inestinal obstruction caused in cystic fibrosis?
Features in neonates eg * Failure to thrive as they cant breakdown fatty foods for energy * Meconium ileus * Always hungry Distal intestinal obstruction (in neonates meconium ileus) is caused by thick mucous blocking up small & large intestine
How is cystic fibrosis diagnosed? In a patient with cystic fibrosis there will be other things that can be diagnosed eg bronchiectasis using CXR and HRCT
Cystic fibrosis diagnosis * Diagnosis can be based on positive test results in people with no symptoms ie newborn blood spot test followed by sweat test or gene tests for confirmation * Diagnosis based on clinical manifestations, supported by sweat or gene test results for confirmation
What is looked for on the newborn blood spot test for CF? ( Infants with an abnormal newborn screen need a sweat test or gene test to confirm the CF diagnosis) What is measured in the sweat test? What is looked for in gene testing?
Newborn blood spot test measures for raised immunoreactive trypsinogen which indicates CF Sweat test measures sweat sodium and chloride levels >60mmol/L Gene testing looks for abnormalities in the cystic fibrosis transmembrane conductance regulator (CFTR)
What is a simple and useful screening tests that assesses if there is exocrine pancreatic dysfunction?
Exocrine pancreatic dysfunction means there is failure to produce the digestive enzymes Elastase is a protein secreted by the exocrine pancreatic cells and is not degraded during transit and is found in the faeces Measuring faecal elastase is a non-invasive test technique that tests for exocrine pancreatic insufficiency if levels are low
How is diagnosis of cystic fbroris related diabetes carried out?
Diagnose cystic-fibrosis-related diabetes using one of the following: Annual oral glucose tolerance testing (OGTT) – if OGTT is abnormal perform CGM or serial glucose testing over several days to confirm the diagnosis. continuous glucose monitoring (CGM) - usually 7 days serial glucose testing over several days
TREATMENT FOR CF - multidisciplinary management What is given to treat the pancreatic insufficiency in cystic fibrosis?
Offer oral pancreatic enzyme replacement therapy to people with exocrine pancreatic insufficiency. - eg creon If a patient is diagnosed with cystic fibrosis related diabetes usually insulin is required as they have insulin production failure
As said before, the thick mucus build up in the GI tract can cause bowel obstruction (distal intestinal obstruction syndrome) How is this treated?
Treatment is similar to constipation - lactulose and hydration
What is Young’s syndrome and how does it present?
Young’s syndrome is a rare condition caused by a defect in cilia - presents as bronchiectasis, sinusitis and obstructive azoospermia Presentation of CF, Kartagener’s and Young’s all seem similar affffff - investigations needed for diagnosis
