Term
A 28 year old man presents with a sputum-producing cough (significant amounts) and dyspnea.
What innate immune defenses must have been overcome to produce this condition? |
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Definition
Presentation fits non-resolving infection/inflammation from bronchiectasis.
Mucociliary escalator and Ion transport throughout the airway. Proximally, in bronchus, goblet cells and ciliated cells defend, while more distally, in bronchioles, Clara cells take over.
s
1) Secreted proteins with anti-microbial activity
2) Mucus blanket (gel layer)
3) PLC layer
4) Synchronous ciliary action
5) Alveolar macrophages |
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Term
| What adaptive immune responses are overcome in bronchiectasis to produce persistent inflammation and airway surface remodeling? |
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Definition
Airway becomes floppy and dilated because leukocyte end products overcome native anti-protease activity (alpha-1 anti-trypsin) to produce remodeling.
1) recruitment of inflammatory cells that have intrinsic anti-microbial properties,
2) secretion of mucus and fluid that promotes clearance of airway pathogens and inflammatory cells
3) an increase in ciliary beat frequency that promotes mucociliary clearance. |
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Term
| What 2 major pathophysiological processes lead to obstructive lung disease in Bronchiectasis? |
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Definition
1) Mucus/inflammatory cell plug of airway
2) Airway collapse (bronchial cartilage damage and chronic inflammation) |
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Term
| What are 5 major categories of disease that can produce bronchiectasis? |
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Definition
1) Acute bronchopulmonary infection
- Pertussis or measles in childhood
- Staph, Klebsiella, TB, Histoplasma, Hemophilus
2) Bronchial obstruction
- Foreign body aspiration
- Neoplasm
- Alpha-1-anti-trypsin deficiency
3) Disorder of airway defense
- Ciliary abnormalities
- CF
- Immunodeficiency
4) Congenital/Acquired anatomic
- Cartilage deficiency
- Amyloidosis
5) Miscellaneous
- Irritant inhalation
- Transplant rejection |
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Term
| What is the basic pathophysiological basis of Cystic Fibrosis? |
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Definition
AR disease of epithelial organs due to mutations in CFTR.
1) CFTR is a chloride/HCO3- channel regulated by cAMP and ATP that down-regulates activity of ENaC
2) In CF, excessive ENaC activity results in excess sodium absorption, reducing liquid in the airway (dehydration) and preventing mucociliary clearance.
3) CF mutations also affect processing of glycoconjugates, leading to abnormal surface glycolipids of glycosylated mucins that affect bacterial adhesion and reduce clearance. |
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Term
| How do the 5 different classes of CFTR mutations seen in CF differentially affect ionic transport? |
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Definition
1) Class 1 mutations are stop mutation that produces short, non-functional protein
2) Class 2 mutations are F508 mutation (70%) which causes misfolding
3) Class 3/4 produce full-length with defective channel regulation (less severe)
4) Class 5 causes reduced mRNA and production (Deficiency) |
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Term
What is the affect of CFTR in each of the following epithelial organs?
1) Sweat gland
2) Pancreas
3) Vas deferens |
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Definition
1) Excessively salty sweat, since salt cannot be absorbed from sweat duct lumen into interstitium
2) Bicarbonate secretion is impeded, causing mucus inspissation in pancreatic ducts, and proteolysis that leads to fibrosis and/or pancreatitis
3) Congenital bilateral absence (CBAVD) and infertility. |
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Term
A young boy presents with a recurrent cough that produces high volumes of purulent, green, foul-smelling mucus (especially in the mornings). He is also wheezing a bit with some chest tightness.
You notice some "clubbing" of his digits and nasal polyps on PE. You also hear mid-inspiratory crackles.
How should you manage this condition? |
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Definition
Sounds like bronchectasis from CF.
- Cough and sputum production are classic
- Mid-inspiratory crackles also fit, as opposed to "Late-inspiratory crackles" in pulmonary edema or other causes of alveolar fluid accumulation.
- "Clubbing" rarely is seen in COPD or Asthma.
1) Abnormal CFTR: gene therapy
2) Decrease Cl- secretion/Na absorption: ion channel modulation
3) Airway obstruction: airway clearance and mucin drugs
4) Infection: antibiotics
5) Inflammation: Steroids, CXCR2 receptor antagonist
6) Airway destruction: Lung transplant |
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Term
| What is the most useful radiological test to run for CF diagnosis and what do you find? |
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Definition
CT
1) Dilation and thickening of conduction airways
2) Tree and bud appearance to distal airway
3) Nodular opacities (dilated airways filled with mucus)
4) Thick wall cysts, with or w/o fluid. |
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Term
| What is the basic diagnostic algorithm for bronchiectasis? |
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Definition
1) Clinical suspicion (cough and sputum?)
2) Sputum culture (Pseudomonas aeroginosa is diagnostic)
3) CXR and chest CT
4) If bronchiectasis present
- quantitative IgG analysis
- nasal scrap for ciliary structure
- mycobacterial culture
- CF evaluation
- IgE/aspergilus precipitans
- Bronchoscopy with lavage/biopsy |
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Term
| What is the specific diagnostic algorithm for CF? |
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Definition
1) Clinical suspicion leads you to get a sweat test (2x)
2) If sweat is hypotonic, CF is unlikely, but still get genotype analysis. 1 mutation suggests CF or carrier, while 2 or more means CF
3) Get a nasal potential difference to look for Cl- secretion.
4) IF NPD is negative, CF is ruled out, otherwise, CF is indicated. |
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Term
What do each of the following clinical findings indicate about etiology of Bronchiectasis?
1) Sweat chloride >60 mEq 2X with lack of chloride secretion on nasal potential difference
2) Decreased clearance of saccharin and radionucleide mucus, with lack of dynein arms on ciliary microtubules from EM analysis
3) Decreased IgA, IgG or IgG sub-class
4) Elevated IgE
5) Reduced serum level of anti-protease |
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Definition
1) CF
2) Immotile Cilia Syndrome
3) Immunodeficiency
4) Aspergillus fungal infection
5) Alpha-1 antitripsin deficiency. |
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