SM 170 Cystic Fibrosis Flashcards by Ashwin Sunderraj

Where does the F508 mutation affect the CFTR protein?

It alters the Nucleotide Binding componenet

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How does CF cause female sexual dysfunction?

It doesn’t; only males are effected

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What are the mucolytics and how do they treat CF?

Pulmozyme = DNAse that makes mucous less thick
Hypertonic Saline = promotes water secretion into mucous
Mannitol = promotes water secretion into mucous

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What are the major treatment categories for CF?

Mucolytics, CPT/Postural Drainage, HFCWO, Exercise

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Does CF genotype predict severity?

Yes, double mutants fare worse that heterozygotes, but genotype does not predict prognosis

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What anti-inflammatory agents are used to treat CF and why?

Anti-inflammatory agents lessen the damage to lung epithelium from constant infection

MIC; Macrolides, Ibuprofen, and Corticosteroids

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What can be seen on gross anatomy in end stage bronchiectasis driven by CF?

Red areas of the lung = hemoptosis

Yellow areas of the lung = mucus filled lumen

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Does CF genotype predict prognosis?

No, it predicts severity

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What are the major ways CF manifests, with respect to organ systems?

Chronic sino-pulmonary infections
GI Abnormalities
Male Infertility

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How do H2O channels contribute to sweat gland function?

There are no H2O channels in sweat glands

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What is used as a diagnostic test for CF in newborns?

Sweat chloride test

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What type of CF mutation is Class VI?

Rapid degradation/turnover due to mutation

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What are the 3 ways to diagnose CF?

Sweat Testing, Genotyping, and Nasal Potential Difference

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What is HFCWO and how does it treat CF?

High Frequency Chest Wall Oscillations; vibrates the chest to break up mucous and help clear the lungs

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What is the role of Mucociliary clearance of the airway?

Mediated by cilia on epithelial cells, helps move mucus out of the airways and down the esophagus to clear pathogens

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What type of CF mutation is Class I?

Premature stop codon

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What molecule can activate sweat glands?

Pilocarpine

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What does nutritional support in CF entail?

Pancreatic enzymes, vitamins, nutritional supplements, and nocturnal feeds via tubes

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What do antibiotics in CF target?

Pseudomonas, typically with Ciprofloxacin

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What do CPT and Postural drainage do?

Help clear the lungs

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What organ does CF treatment focus on?

The lungs

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How does the Nasal Potential test diagnose CF?

First, a baseline potential is taken. Then, Amiloride is administered to block Nav channels and depolarize the cells. Low Cl is added to hyperpolarize, and Isuprel is added to further hyperpolarize

Normal cells start hyperpolarized and respond mildly, in CF cells start depolarized and respond strongly to Amiloride

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How are sweat glands altered by CF?

In CF, the loss of function of CFTR results in the failure to reabsorb Cl and Na, leading to the production of hypertonic sweat

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Which race is most effected by CF?

Caucasians

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How is Pilocarpine used to diagnose CF?

Pilocarpine activates sweat glands, allowing for measurement of sweat chloride concentration Sweat chloride > 60 = CF diagnosis

Which pathogen effects adults most often in CF?

Pseudomonas Aeruginosa

What is the mode of inheritance of CF?

Autosomal Recessive

How do potentiators work?

They are chaperones that alter the gating function of existing CFTR to increase ion flow through the channel

Are combination therapies viable in CF?

Absolutely

What 4 types of drugs are used to treat CF?

BAAM Bronchodilators (b2 agonists) Antibiotics Anti-inflammatory agents Mucolytics

What type of channel is the CFTR?

A cAMP gated Cl channel

What can be seen on lung histology in CF?

Bronchiectasis, due to constant infection of the airways producing inflammation that pathologically dilates airways Absent lumen as well

What type of CF mutation is Class III?

Protein reaches membrane but has defective gating due to the mutation

What type of CF mutation is Class V?

Splice abnormality due to the mutation

Describe the physiology of sweat production?

In a sweat gland, towards the base, blood is used to form sweat with high Na and Cl concentrations As the sweat progresses towards the surface, Cl is removed via the CFTR protein, ultimately releasing hypotonic sweat

What is Lumacaftor?

A corrector chaperone that can treat F508 CF

What type of cells express CFTR?

Epithelial cells; therefore, CF effects Epithelial organs

How is eNaC effected by the loss of CFTR function?

eNaC is normally inhibited by the Chloride influx of CFTR, so losing the CFTR channel potentiates eNaC

What is the basic principle behind new CF treatments?

Maximize use of existing protein instead of fixing CFTR gene

What are the 3 infections CF causes?

Sino-pulmonary infections Bronchiectasis Nasal Polyposis

How do correctors work?

They are chaperons that increase delivery of CFTR proteins to the cell surface

What is Azithromycin?

A macrolide commonly used to treat CF

How does exercise treat CF?

Helps open up the airways

How does CF cause a vicious cycle of infections?

CFTR dysfunction results in altered airway secretions that predispose infections, which lead to tissue damage and inflammation (bronchiectasis), in turn further altering airway secretions and predisposing more infection

How does bronchiectasis show up on HRCT?

The inflamed airway will appear larger than the corresponding vessel

Which states mandate Newborn screening for CF?

All of them, required nationwide

What is Ibuprofen?

A NSAID that inhibits Neutrophil migration at high conc. in treating CF

What is Ivacaftor?

A potentiator that can treat G551D CF

What factors effect CF prognosis?

CFTR mutation, genetic background, and the environment

Which pathogen effects children most often in CF?

S. Aureus

What type of CF mutation is Class II?

Misfolding due to mutation that leads to degradation (processing mutant)

How does CF alter Mucociliary clearance?

CF is due to dysfunction of the CFTR, leading to lower Cl influx and disinhibition of the eNaC sodium channel; Sodium then flows into the cell, bringing water with it and desiccating the mucous on epithelial cells, making it harder to clear the mucous

What is the strongest predictor of morbidity and mortality in CF?

Lung function

What type of novel CF therapy may be effective against F508?

Chemical chaperones such as Lumacaftor

What type of CF mutation is Class IV?

Mutation effects the channel itself and it's ability to conduct ions across the membrane

What sexual dysfunction does CF cause?

Male infertility due to loss of Vas Deferens

What does the Nucleotide Binding component of the CFTR gene do?

The Nucleotide Binding component regulates opening and closure of the channel

How is CF care managed?

With a multi-disciplinary team

What GI abnormalities does CF cause?

Pancreatic insufficiency Cirrhosis of the Liver Meconium Ileus in the Small Bowel

What regulates the eNaC channel?

Cl negatively regulates eNaC, and the Cl is able to enter the cell via CFTR

Which mutations are screened for in CF genotyping?

All of them

What sweat chloride level rules out CF?

Chloride < 40

What composes a CF multidisciplinary team?

MD's, Nurse, Respiratory therapist, Dietitian, social worker, physical therapist

What are the 3 components of the CFTR gene?

Transmembrane, Nucleotide Binding, and R Domain

What ion does eNaC conduct?

Sodium, into the cell

What gene is mutated in CF?

CFTR, which leads to defective ion transport in epithelial cells

What channels are regulated by the CFTR?

HCO3, eNaC (negatively), and Outward-Rectifying Chloride Channels (positively)

What does the TM component of the CFTR gene do?

The TM component allows for Cl flow through the channel

How is CF induced pancreatic insufficiency treated?

Enzyme replacements to digest food

If a child is born with CF, what can be inferred about their parents?

Both parents are carriers

What is used as a screening test for CF in newborns?

IRT, a pancreatic function test

What are the two types of chaperones?

Correctors and Potentiators

What does the R domain of the CFTR gene do?

The R domain is phosphorylated and leads to permanent closure

What bronchidilators are used in treating CF?

b2 agonists, Anti-cholinergics, Anti-Leukotrienes

How does CF worsen lung function?

CF results in more frequent infections as well as an inability to eradicate bacteria from the lungs, which damages the lungs