Cystic Fibrosis Flashcards Preview

CRRAB II-- Wk 8 > Cystic Fibrosis > Flashcards

Flashcards in Cystic Fibrosis Deck (24)
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1
Q

Inheritence pattern in CF

A

autosomal recessive

2
Q

Channel defect in CF

A

CFTR

ATP-gated Cl- channel

3
Q

Membrane spanning of CFTR

A

12 membrane-spanning domains

4
Q

Regulation modalities of CFTR protein

A

NBD: nucleotide binding domain

–> ATP binds, must have 2 sites occupied to open

R domain: phophorylated via PKA

–> protein kinase A

5
Q

What activates phosphorylation of R domain?

A

cAMP buildup

cAMP activates PKA

PKA phosphorylates R domain

6
Q

CFTR chromosome

A

chromosome 7 long arm

7
Q

Most common CFTR mutation

A

F508del (deletion of Phe508)

mutation in NBD

(binding site of ATP)

⇒ gating defect

⇒ protein folding defect

8
Q

Polarity of CFTR in

lung

pancreas

liver

A

lung: Cl- outward movement
pancreas: Cl- outward movement
liver: Cl- outward movement
skin: Cl- inward movement

9
Q

CFTR mutation

lung manifestation

pathophysiology

A

Cl- and HCO3- not secreted into airway

→ decreased airway surface liquid volume

→ expansion of mucin not completed by HCO3-

10
Q

Airway damage in CF

A

inflammation due to inability to clear secretions/bacteria

activation of inflammatory pathways

LPS → TLR4 → MyD88 → NF-kB

inflammatory mediators: TNF-α

neutrophil recruitment

11
Q

Neutrophil airway damage mechanism

A

elastase release

damage of CFTR

DAMPs → furthur damage

12
Q

Common infection in CF patients

A

Pseudomonas aeruginosa

13
Q

Long-term pulmonary damage in CF

A

bronchiectasis

14
Q

Tx of CF classically

A

N-acetylcysteine

⇒ cleaves disulfide bonds in mucus

dornase alfa

⇒ DNAse, clears leukocytic debris

15
Q

Pancreatic duct CFTR mutation

A

HCO3- not secreted by epithelial cells lining pancreatic duct

blockage of pancreatic duct by secreted protein plugs

leakage of proteolytic enzymes

inflammatory damage

16
Q

Pancreatic damange manifestations

A

inability to absorb lipids, fat-soluble vitamins

CF-associated diabetes

⇒ from collateral inflammatory damage

17
Q

Intestine CFTR mutation manifestations

A

crypt cells of intestinal epithelium

cannot secrete H2O that follows Cl-

⇒ obstruction

⇒ inability to absorb proteins, fats

18
Q

Long-term GI risk in CF

A

colon cancer

more colonoscopies for screening

19
Q

Liver CF manifestations

A

HCO3- normally neutalizes bile acids

retention of bile acids

→ MCP1 synthesis

→ hepatic stellate cell and fibrogenic myofibroblast acitvation

→ collagen, fibrogenesis

⇒ cirrhosis or portal HTN

20
Q

CF and fertility

A

vas deferens absent in almost all males

absorbed in featus or infancy

21
Q

Sweat glands CF

A

opposite polarity of other areas

Cl- brought in from interstitium

→ high Cl- in sweat

→ basis for sweat test

22
Q

Ivacaftor

MOA

TU

A

MOA: keeps CFTR channel in open position longer

TU: G551D and F508del mutation, NBD mutation

23
Q

Ataluren

MOA

TU

A

MOA: allows ribosome to read through stop codons

TU: G542X mutation, premature stop codon

24
Q

Lumacaftor

MOA

TU

A

MOA: promotes trafficing of CFTR to membrane instead of degradation

TU: F508del mutation