9. Lung Defence I Flashcards
What does the MUCOCILIARY ESCALATOR consist of
- CILIATED airway Epithelial Cells
- AIRWAY SURFACE LIQUID (over cilia)
layers in the AIRWAY SURFACE LIQUID
upper: GEL / MUCOUS
below: PERI-CILIARY SOL LAYER - LIQUID
what does MUCOCILIARY ESCALATOR do
SELF-CLEARING Mechanism of the AIRWAYS (DEFENCE)
as CILIA BEAT they CARRY/PULL MUCOUS away
MOVE PARTICLES to top of Trachea (SWALLOWED) to PREVENT them ENTERING LUNGS (from distal to apical airway)
- all beat in same direction (coordinated)
SPEED at which CILIA BEAT Per Second
10-15 BEATS PER SECOND
how much time does the MUCOCILIARY CLEARANCE mechanism have/give (before entering lungs)
15 minutes
passage time length so 15 min time zone of mucociliary escalator to clear pathogens
MAINTENANCE of …. is CRITICAL - key physiological mechanism to achieve MUCOCILIARY CLEARANCE of the airways
AIRWAY SURFACE LIQUID (ASL) HEIGHT
- PERI-CILIARY LIQUID (PCL) at 7 μm
ASL is made in the LUNGS and PULLED UP into Trachea (like a FUNNEL)
- what prevents ‘DROWNING’ of airways
VOLUME ABSORPTION
- LIQUID PULLED OUT of the ASL as it moves up
- by NA TRANSPORT
what is VOLUME/LIQUID ABSORPTION of the ASL DRIVEN by
NA+ TRANSPORT
- as Na+ travels through ENaC (Epithelial NA CHANNEL)
it PULLS WATER WITH IT (osmosis)
(TRANSEPITHELIAL ION TRANSPORT)
how do we have a shift from fluid absorption to FLUID PRODUCTION ie if airways are dry
CFTR
- DOWNREGULATES NA+ ABSORPTION
- causes CHLORIDE SECRETION (CL- CHANNEL)
how do we have a shift from fluid absorption to FLUID PRODUCTION ie if airways are dry
CFTR
- DOWNREGULATES NA+ ABSORPTION
- CHLORIDE SECRETION (CFTR CL- CHANNEL)
Cl- outside cells attracts layer of WATER
INNATE DEFENCE factors in AIRWAYS
in ASL:
DEFENSINS & OPSONINS
scavenging cells (engulf & digest):
- ALVEOLAR MACROPHAGES
- NEUTROPHILS
- CHRONIC INFLAMMATORY CELLS
INNATE DEFENCE MOLECULES present/made in ASL
DEFENSINS
OPSONINS
a significant component of AIRWAY DEFENCE is the PHYSICAL BARRIER provided by the…
AIRWAY SURFACE LIQUID
what is the CFTR GENE
makes CFTR protein:
CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR
- MUTATIONS in this gene cause CYSTIC FIBROSIS (CF)
what does the CFTR PROTEIN do when switched on
- NA+ DOWN REGULATOR
- acts as CHLORIDE CHANNEL for Cl- SECRETION outside cell (attracts water)
what is the name of the MOST COMMON GENE VARIENT that can AFFECT CF GENE
F508del
what 2 mechanisms does AIRWAY HEALTH depend on
- MUCOCILIARY ESCALATOR
- INATE DEFENCE
what many things happen WITHOUT CFTR
- HYPERABSORPTION of NA+
- HYPERABSORPTION of FLUID from ASL
- ASL becomes very SMALL and Crushes down on CILIA
- CILIA CANNOT FUNCTION PROPERLY (need peri-sol layer)
BODY RESPONSE: MORE MUCOUS SECRETION
(more mucous layer, less sol layer)
in CF: more PRONE to AIRWAY INFECTION
NEUTROPHILS come in and explore causing INFLAMMATION etc.
how does the BODY RESPOND when CILIA CANNOT FUNCTION PROPERLY due to LOW LIQUID in ASL
SECRETE MORE MUCOUS (mucosal glands)
example of a BACTERIA that causes characteristic LONG TERM AIRWAY INFECTION if appears in CF
PSEUDOMONAS AERUGINOSA
what TYPE of BACTERIA is PSEUDOMONAS AERUGINOSA (+/-)
GRAM NEGATIVE
what happens to the PHENOTYPE of PSEUDOMONAS AERUGINOSA when present in CF and how does it lead to ANTIBIOTIC RESISTANCE
CHANGING PHENOTYPE
- QUORUM SENSING
(when bacteria change phenotype in presence of other bacteria)
- leads to ALGINATE PRODUCTION
-> INCREASED ANTIBIOTIC RESISTANCE
what does the MUCUS BUILD UP in CF mean for BACTERIA
PROVIDE IDEAL ENVIRONMENT
- more inclined to BACTERIAL ADAPTATION
what are the SHORT TERM CONSQUENCES for a person with CF
INTENSE NEUTROPHIL MEDIATED INFLAMMATION
- LOCALISED in AIRWAYS
Downward spiral of Airway Destruction:
- Proteases, Cytokines/Chemokines, Chondrolysis (loss of articular cartilage)
-> REMODELLING OF LUNGS
