Lecture 4 - Genetic Variation Flashcards
What is CF?
Impaired function of organs with secretory function - affects ion trabnsport
mutation in a single gene
RECESSIVE
over 1,500 gene mutations in CTFR
What structual changes occur in patients with CF?
Bronchial wall thickening
Bronchiectasis
Pneumothorax
huge neutrophil infiltration in airways
inflammatory damage to airway tissue
decline in lung function from epithelial damage
The CTFR is regulated through 2 different mechanisms
1) regulated domain
2) nuclear binding domain
How is ion transport affected in CF?
blocked transport of sperm
nasal polyps in the nose
cysts in the pancreas - lack of pancreatic enzyme secretion - unable to be transported out into the stomach
digestive system - thick black tarr substance - first signs a baby has CF
Name the CFTR modulators
Suppressors
correctors
potentiators
amplifiers
How is CF screened?
Immunoreactive trypsinogen (IRT)
IRT positive for most common mutations
sweat test - defect in the ion transport, elevated skin chloride skin levels
Name the typical lung infections in CF
Psuedomonas aeruginosa
stapylococcus auerus
Haemophilus influenza
burkholderia cepacia
What are the current established therapies?
early recognition - neonatal screening
antibiotics against pathogens
beta-adrenoceptor agonists
anti-inflammatory osmotic agents - hypertonic saline, mannitol
mucolytics - break down mucus
How is nutrition managed in CF?
pancreatic insufficiency - lack of pancreatic protease, lipase, amylase
managed by diet and enzyme supplements e.g. pancreatin (Creon, Pancrex)
Describe ion transport in the lung
chloride ions move OUT of the cell into luminal space, enables sodium to MOVE and water moves with it
enables lungs to be hydrated in the body - don’t want too much water to be present
ENaC channel - responsible for the reuptake of sodium as well as water and chloride back into the cell
actions of ENaC and the CFTR - small amount of fluid is maintained on the surface of the cell
What happens if not enough chloride passes through the membrane?
sodium and water cannot pass through the membrane - reducing hydration of the epithelial cells
mucus is sticky and the cilia cannot function properly
CFTR does not function properly -> level of hydration is decreased
cilia cannot move properly - growth environment for bacteria
How can ion transport issues be corrected?
Hypertonic saline - partial correction
Name the new therapies for the treatment of
Trikafta/ Kaftrio - combination of 2 correctors and potentiators, CFTR modulator
CACC activator - Denfusol - activates alternative chloride channels
ENaC blockers - amiloride - blocking sodium reabsorption
