CF, Sleep, Respiratory Control Flashcards
How does CFTR function in the lungs? in the periphery?
Lungs: CFTR secretes Cl, and suppresses ENaC (Cl secreted, less Na reabsorption, less water reabsorption -> watery mucus)
Periphery/sweat glands: CFTR reabsorbs Cl, and activates ENAC
(Cl absorbed, more Na reabsorption, more water reabsorption –> dilute saltless sweat)
What happens in a patient with CF?
CFTR is mutated, and therefore in the
Lungs: there is no CFTR-mediated suppression of ENaC, thus Na is reabsorbed and water follows. RESULT: thick mucus + dehydration of airway surfaces, leading to defective ciliary transport
Periphery/sweat glands: no CFTR-mediated activation of ENaC, and therefore less Na is reabsorbed and therefore less water is reabsorbed. RESULT: salty sweat.
What is the pathophysiology of CF in the lungs?
since there is increased reabsorption of ions and fluids, the mucus membranes becomes dehydrated and results in:
1) shrinkage of the precapillary layer layer of air-liquid interface and subsequent impaired cilia action to remove mucus
2) colonization of mucus by the bacteria, which leads to an inflammatory response, which stimulates even more mucus secretion
both of these result in mucus plugging, thereby resulting in an OBSTRUCTIVE lung defect (air can’t get Out)
There are 6 classes of CFTR mutations, which one is the most common one among the Ashkenazi Jewish populations? greater population?
What is common among these two mutations?
Ashkenazi - Class I - defective protein production
Population - Class II - defective protein processing
Class I/II mutations result in decreased lung function and pancreatic insufficiency.
How is CF screened/diagnosed? (3)
1) Serum reactivity to trypsin and trypsinogen (IRT) - trypsinogen is made in the pancreas and blockage of the pancreatic ducts, resulting in elevated trypsinogen levels in the newborns with CF
2) sweat Cl- test - sweating stimulated with pilocarpine (non-selective muscarinic receptor alkaloid)
3) genetic testing of newborns and mothers/couples
What are some of the pulmonary complications in a patient with CF?
1) Obstructive lung disease + bronchiectasis (widening of the bronchioles)
2) bacterial colonization - pseudomonas aeroginosa (resistant to many antibiotics), staph. aureus, non-TB mycobacterium
3) fungal colonization - aspergillosis
4) hemoptysis - typically secondary to progressive bronchiectasis, which erodes into blood vessels and cause bleeding
Why do CF patients have a failure to thrive? Why do some CF patients develop diabetes?
1) malabsorption of nutrients and glucose as a result of pancreatic insufficiency (caused by thick exocrine pancreatic secretions); can lead to malnutrition and DIABETES
2) increased metabolic demand because the body is constantly trying to fight off infections
What are CF correctors and potentiators?
correctors - compounds that increase CFTR production
potentiators - compounds that increase CFTR function
What are some CF therapies (4) that target the lungs?
What other supplemental drugs must you give a CF patient?
1) bronchodilators - improve pulmonary function
2) mucolytics - DNAse that causes partial liquefaction
3) corticosteroids - improve lung function
4) antibiotics - decrease CFU to reduce lung inflammation
Supplemental:
- insulin supplement
- vitamins DEAK
- salt relacement
- anti-depressants
There are 3 neural stages of sleep: wakefulness, N-REM, and REM. What characterizes each one of these states?
1) wakefulness: control of breathing mediated by
a) behavioral responses - voluntary control of breathing
b) metabolic responses (response to changes in CO2)
2) N-REM: control of breathing mediated purely by metabolic processes
3) REM: control of breathing mediated purely by
a) behavioral responses related to dream content
b) metabolic control (though this is less responsive)
What happens to sleep respiration in patients with lung disease? Why do these patients become hypoxemic?
Patients with lung disease often have VQ mismatch w. varying degrees of hypoxemia + hypercapnia and this this becomes amplified especially during REM sleep since there is:
1) loss of accessory muscles of inspiration
2) decreased mechanical efficiency of the chest wall
What are the consequences of hypoventilation syndromes during sleep? (4 biggies)
1) sleep deprivation
2) hypercapnia (respiratory acidosis)
3) hypoxemia -> vasoconstriction -> chronic pulmonary HTN -> RV enlargement/failure
4) CVD - likely due to chronic activation of the nervous system that is associated with chronic obstructive sleep apnea.
Sleep apnea can be of obstructive or central etiology. What’s the difference?
Obstructive “can’t breathe” due to narrowing/collapse of pharyngeal airway during sleep; results in abrupt arousal
Central “won’t breathe” due to inability of the brain to send proper signals to the respiratory muscles
What are some of the risk factors for obstructive sleep apnea?
What are factors that exacerbate obstructive sleep apnea?
risk factors: obese patients male gender aging alcohol
exacerbating factors:
benzodiazepines
barbiturates
supine position
What are some of the structural causes for obstructive sleep apnea?
large size/fat content of uvula
soft palate
large posterior lying tongue
vascular congestion/edema of pharyngeal mucosa
