week 9 cystic fibrosis and pandemic Flashcards
(41 cards)
What is cystic fibrosis (CF)?
CF is a genetic disorder caused by mutations in the CFTR gene, leading to thick, sticky mucus in the lungs and other organs, resulting in respiratory infections and organ dysfunction.
What gastrointestinal symptoms are common in CF?
Pancreatic insufficiency
Bulky/smelly stools
Poor weight gain despite excessive appetite
What causes breathing difficulties in people with CF
The mucus in CF is thick and sticky, impairing clearance, trapping bacteria, and leading to inflammation and infections.
What is the relationship between P. aeruginosa and CF?
P. aeruginosa thrives in thick mucus
Forms biofilms that protect it from immune cells and antibiotics
Leads to chronic infection, often starting in childhood
What is the epidemiology of CF?
Most common in white populations
~100,000–180,000 affected globally
Average life expectancy: ~40 years (mutation-dependent)
Treatment cost: $250,000–$350,000/year
How does P. aeruginosa impair neutrophil function?
Produces toxins that kill neutrophils
Causes release of proteases (e.g. neutrophil elastase)
These cleave CXCR1 receptors, impairing chemotaxis
Triggers TLR2 activation → IL-8 release → recruits more neutrophils
→ perpetuates a vicious inflammatory cycle
What does the CFTR gene do?
Encodes a Cl⁻ and bicarbonate ion channel, regulating mucus hydration and epithelial transport
Summarise the vicious cycle of inflammation in CF lungs.
Dead neutrophils → protease release → CXCR1 cleavage → neutrophil dysfunction → TLR2 activation → IL-8 release → more neutrophils → cycle repeats
What is the inheritance pattern of CF?
Autosomal recessive – both parents must be carriers for a child to inherit CF (25% chance if both are carriers)
How is CF diagnosed?
Sweat test: measures Na⁺ and Cl⁻ in sweat
Chest X-rays and FEV1 tests: assess lung function
What types of mutations can affect the CFTR gene?
Deletion
Missense
Frameshift
Nonsense
Splicing
What is the mechanism of Levofloxacin?
Targets DNA gyrase (Topoisomerase II) → inhibits DNA replication in bacteria
How does Tobramycin work?
Inhaled aminoglycoside
Binds 30S & 50S ribosomes → inhibits 70S complex formation → no protein synthesis
Effective against P. aeruginosa
How does Dornase alfa work?
Inhaled therapy that thins mucus by breaking down DNA → improves cough clearance
What is the role of Mannitol in CF?
nhaled dry powder that increases osmolarity
Stimulates mediator release → enhances mucus clearance via coughing
What does Ivacaftor do?
Increases probability of CFTR channel opening → improves Cl⁻ transport
What is the role of Ivacaftor + Lumacaftor or Tezacaftor?
Corrector drugs: help traffic CFTR to the membrane so it can function properly
What is Trikafta (Ivacaftor + Tezacaftor + Elexacaftor)?
Triple combination therapy
Binds multiple sites on CFTR → improves trafficking and function
Increases lung function and life expectancy
Why does pancreatic insufficiency occur in CF and what are the consequences?
Insufficient enzyme secretion → malabsorption of fats/proteins
Leads to cachexia and worsened infection risk
What enzymes are supplemented in pancreatic therapy for CF?
Amylase: starch breakdown
Lipase: lipid breakdown
Protease: protein breakdown
Delivered via pH-sensitive, enteric-coated preparations
What supportive therapies are used in CF?
Exercise
Chest physiotherapy to stimulate coughing
Lung transplantation (less common now with advanced therapies)
What is the key difference between the innate and adaptive immune responses?
Innate: Rapid, stereotyped, no memory
Adaptive: Slower, highly specific, has memory and recall
What are PAMPs and how are they detected?
PAMPs (pathogen-associated molecular patterns) are microbial markers detected by pattern recognition receptors (PRRs) such as TLRs, NLRs, RLRs, and CLRs.
What is the role of the mucociliary escalator in lung defence?
It sweeps mucus and trapped pathogens upward at 1–2 cm/min using cilia. Viscosity or toxic exposures (e.g., smoke) can impair its function.
