Cystic Fibrosis Flashcards
Where has the highest incidence of CF?
Ireland -1,300 - 34 cases a year
What organs are affected by CF & why?
Lungs, pancreas, kidneys, & intestines - due to their mucous lining
What causes CF?
Genetics:
~mutation in CF transmembrane conductance regulator (CFTR) gene
~CFTR regulates the passage of Na+ & CL- ions across epithelial cells - dysfunction causes build up of thick mucous
~F508del causes 70% cases (2000 genes located)
How is CF inherited?
It is autosomal recessive - must receive a copy of the allele from both parents
A quick note on all 6 types of CF
~T1: Lack of CFTR synthesis - no Cl- channels
~T2: Defective CFTR protein processing - destroyed in cell, does not reach cell surface
~T3: Defective channel protein - CFTR reaches cell surface but doesn’t open for Cl-
~T4: Defective Cl- conduction - CFTR functions poorly - minimal Cl- conduction
~T5: Reduced amount of CFTR
~T6: Increased turnover of CFTR at cell surface - functional but unstable at cell surface - destroyed
Role of CFTR gene
~Encodes CF transmembrane conductance regulator protein
~regulates flow of Na+ & Cl- ions
~found in the membrane of epithelial cells in pancreas and lungs
~ion imbalance > more viscous fluid secretion > blocks secretary glands
CF Diagnosis - Heel Prick Test
~>99% newborns tested
~Blood sample taken on Guthrie cars and sent to Temple Street - stored for 10 years
~CF, congenital hypothyroidism, phenylketonuria, homocystinuria
CF Diagnosis - Sweat Test
~Sweat stimulated (chemically for children)
~increased sweat Cl- & sweat conductivity = CF
CF symptoms
~recurring chest infections
~difficulty breathing
~Failure to thrive (children)
~Jaundice & gastric problems
~Bowel obstruction in babies (meconium ileus - first stool sample of baby - gelly substance)
Pathogenesis of CF
~viscous secretion due to ion imbalance
~named after fibrotic lesions in pancreas
~Lungs & pancreas affected
CF: Pancreatic pathogenesis
~T1-4 & T6 pancreatic insufficient due to lack or non-functioning CFTR protein - lose exocrine function - require intake of pancreatic enzymes
~T5 & some T4 - Pancreatic sufficient - prone to acute & chronic pancreatitis
~Dysfunction of endocrine function - destruction of beta & islet cells - 50% CF patients develop DM - impaired oral glucose tolerance test before development
~ 2 types of development - beta cell dysfunction & reduction in islet cell mass
~Steatorrhea, Vit A deficiency, failure to thrive, meconium ileus (15% babies), decreased pH (failure to activate proenzymes)
CF & GI Complications
~Malnutrition - fats & proteins not absorbed
~DM
~Liver diseases due to blockage of bile ducts (Cirrhosis, jaundice, fatty liver)
~Intesusception- segment of intestine slides into the next segment
CF: Pulmonary pathogenesis
~CF lung disease - infection & severe inflammation - damages lung structure
~Failure of immune system against inhaled pathogens - inability to clear mucous
~Abnormal volume & composition of airway surface liquid impairs ciliary function, mucociliary clearance, & antimicrobial properties
~Repeated chronic infections - scarring that comes with repeated inflammation
CF: Respiratory system complications
~Bronchiectasis - chronic abnormal largening & widening of bronchi, increased difficulty of air passage & mucous clearing
~Chronic Infections - Thick stationary mucous ideal for bacterial and fungal growth (sugars) - block antimicrobial passage
~Nasal polyps- growth in the nasal cavity - repeated inflammation in nasal mucosa
~Haemoptysis - scarring in bronchi adjacent to blood vessels - blood coughed up
~Pneumothorax - collapsed lung - air leaks out of lungs into surrounding cavity - pressure on lungs
~Respiratory failure - fibrosis
CF Treatments
NO CURE
~antibiotics for infections & anti-inflammatories
~Hypotonic saline & High frequency chest wall oscillation vest - lossens mucous
~Bronchodilators
~Oral pancreatic enzymes
~CRISPR - target defective CFTR genes
~Triple therapy - 2 correctors & 1 potentiator - elexacaftor- tzacaftor-ivacaftor
~Orkambi
