CF Case

Description:	CF Case
Category:	USMLE
Created by:	Kelly Murphy on 2009-10-20

Question	Answer
What chromosome band is the CFTR gene located on?	7q.31.2
What is bronchial cuffing?	surround a structure w/ fluid or cells, as w/ a cuff; bronchial wall thickening on CXR
What is bronchiectasis?	chronic dilation of bronchi or bronchioles c/b inflammatory disease or obstruction often associated w/ heavy sputum produxn (Greek: “ectasis” = “stretching”)
What are the most common bugs seen in CF?	S. aureus & H. flu early; P. aeruginosa later
What is CF?	CF is a disorder in EPITHELIAL TRANSPORT t/o the body affecting the FLUID SECRETION in exocrine glands, & GI, respiratory, & reproductive epithelial lining. Thick mucus clogs organ passages.
What are the most prominent clinical features of CF?	Malnutrition, Recurrent lung infections, CLD, Hepatic cirrhosis, Pancreatic insufficiency, Intestinal obstruction, Steatorrhea, Infertility.
What percent of whites are CF carriers?	4% (1/25)
What chromosome is the CFTR gene on?	7
What is the most common mutation that causes CF?	∆F508: accounts for 60-70% of mutations
What does the CFTR gene code for?	The CF Transmembrane Conductance Regulator (CFTR) gene encodes plasma Cl- channels of ductal epithelia. CFTR mutation is the 1o defect of CF.
What does a normally functioning CFTR do?	A normally functioning CFTR will inhibit ENaC!!! Located on the apical surface of exocrine epithelial cells, CFTR regulates intracytoplasmic transport of Na+. Its main function is to make sure the luminal fluid stays hypotonic.
Where is CFTR found?	pancreas, liver, lungs, digestive tract, reproductive tract & skin sweat glands
What are the 3 main types of epithelia affected by CFTR mutations?	Volume-absorbing (airways & distal intestinal epithelia). Salt-absorbing but not volume-absorbing (sweat duct). Volume-secretory (proximal intestine & pancreas)
What is the pathophysiology of lung disease in CF?	H2O follows Na+ back into cells when it should stay in mucus. (ENaC is not inhibited by CFTR so Na+ reabsorbed by cells).
What is the pathophysiology of pancreatic disease in CF?	CFTR mutation causes low bicarbonate, Na+, & water secretion -> low release of pancreatic enzymes.
What is the pathophysiology of CF in the intestines?	Intestinal epithelium – no Cl- secretion, so Na+ & H2O don’t follow -> secreted mucins & other macromolecs not flushed from crypts -> obstruction.
What is the pathophysiology of CF in the sweat glands?	Sweat Glands: normal CFTR reabsorbs luminal Cl- ions & augments Na+ reabsorption via ENaC. CF pts secrete normal volumes of sweat, but they can't absorb Na+ as it moves thru the sweat duct, so sweat stays salty.
What is the pathophysiology of CF in the bones?	Can't absorb fat-soluble vitamins like Vit D, so bone & jt pain may occur. Pts also suffer from ↑ed bone reabsorption (osteoclast activity). Arthropathy (12%) & osteoporosis (38-77%) are common.
What are the PFTs of restrictive lung disease?	Decreased: TLC, RV, DLCO, FVC. Normal or decreased: RV/TLC ratio, FEV1. Normal or increased: FEV1/FVC ratio
What are the PFTs of obstructive lung disease?	Increased: TLC, RV, DLCO, RV/TLC ratio. Decreased: FVC, FEV1, FVC/FEV1 ratio.
What are the PFTs for combined obstructive & restrictive lung disease?	Decreased: TLC, FVC, FEV1. Increased: RV/TLC ratio (means air trapping). Normal or increased: RV. Variable: DLCO
What is hypoxIA?	↓ed O2 delivery to, or utilization by, the TISSUES. Hypoxemia is one (but not the only) cause of tissue hypoxia.
What is hypoxIA?	↓ed O2 delivery to, or utilization by, the TISSUES. Hypoxemia is one (but not the only) cause of tissue hypoxia.
What is hypoxIA?	↓ed O2 delivery to, or utilization by, the TISSUES. Hypoxemia is one (but not the only) cause of tissue hypoxia.
What is hypoxIA?	↓ed O2 delivery to, or utilization by, the TISSUES. Hypoxemia is one (but not the only) cause of tissue hypoxia.
What is hypoxEMIA?	↓ed arterial pO2. N > 60mmHg – anything below = hypoxemia.
What is a ventilation/perfusion (V/Q) mismatch?	Always causes hypoxemia & ↑ed A-a gradient. Ventilation of lungs that aren’t perfused (not enough blood Q). Or perfusion of lungs (lots of blood Q) that aren’t ventilated.A-a gradient = (P alveolar O2) – (P arterial O2)
What is the source of DNA in CF sputum?	Leukocytes: specifically neutrophils. Sputum viscosity further ↑ed by excess extracellular DNA from chronic inflammation & neutrophil autolysis.
What is decreased bacterial killing in the lungs of CF pts due to?	↓ed pathogen uptake by airway epithelia. Altered airway surface liquid composition. Impaired innate immune factors (NO, defensins). Decreased antibiotic penetration.
What are biofilms?	Bacterial virulence factors that interfere w/ phagocytosis & can allow bacteria to be up to 1000x more antibiotic resistant -> bacteria recovers, persists, spreads.
How does the innate immune response contribute to chronic lung infections in CF?	Chronic infexn & inflamm impair innate immunity. PMNs in airway survive longer d/t ++ produxn of stimulating factor->high # PMNs in airway. PMNs release O2 FRs that damage airway & elastase->too much protease activity.
What is alginate?	The biofilm of P. aeruginosa. It allows mucoid Pseudomonas to form microcolonies safe from antibodies & antibiotics.
Describe the treatment for acute pulmonary exacerbations in CF.	Antibiotics, Mucolytic agents, Bronchodilators
Describe lung development at week 4 gestation.	Lower respiratory organs begin developing.
When do the tertiary (segmental) bronchi develop?	Week 7
What happens to terminal bronchioles at week 24 gestation?	They give rise to 2+ respiratory bronchioles.
What does each respiratory bronchiole divide into?	3-6 tubular passages called alveolar ducts.
From what do the visceral pleura & parietal pleura form?	Visceral: splanchnic mesoderm; Parietal: somatic mesoderm
From what does the pulmonary circulation form?	6th pharyngeal arch artery.
What are the 4 periods of lung development?	Pseudoglandular (6-16wks), Canalicular (16-26wks), Terminal saccular (26wks-birth), Alveolar (32wks-8yrs).
What are terminal saccules?	Terminal saccules arise from the ALVEOLAR DUCTS at the end of the RESPIRATORY BRONCHIOLES to allow respiration. They begin to form in the CANALICULAR PERIOD.
When do type I & II pneumocytes form & what do they do?	By the end of week 26. Type I: gas exchange occurs across these cells; Type II: secrete surfactant.
During what time frame does surfactant production occur?	24-28 weeks it starts to be secreted & reaches adequate levels 2 weeks before birth.
Name 3 important factors in lung development.	Adequate thoracic space for lung growth, Fetal breathing movements, Adequate amniotic fluid volume.
How does the concentration of elastic fibers relate to the size of the conducting tube in the lungs?	It's inversely proportional.
What kind of epithelium is found in the majority of the conducting portion of the lungs?	Ciliated pseudostratified columnar epithelium with goblet cells.
What are the terminal bronchioles lined by?	Simple cuboidal epithelium with Clara cells that secrete granules that protect the bronchiolar lining.
List in descending order the structures from terminal bronchioles to alveoli.	Terminal bronchioles => Respiratory bronchioles => atria => alveolar sacs => alveoli
Describe the epithelial histology of the trachea & the primary bronchi.	CILIATED PSEUDOSTRATIFIED COLUMNAR with goblet cells, brush cells, neuro-endocrine cells, small granule cells, & short cells.
Describe the non-epithelial histology of the trachea & the primary bronchi.	Hyaline cartilage rings w/ sm. muscle in gaps; elastic/reticular adventitia.
Describe the histology of the intrapulmonary bronchi.	CILIATED PSEUDOSTRATIFIED COLUMNAR w/ goblet cells. Submucosal glands & plates of hyaline cartilage.
Describe the histology of the bronchioles.	CILIATED SIMPLE COLUMNAR w/ goblet cells; no cartilage or glands but sm. muscle.
Desrcibe the histology of the terminal bronchioles.	CILIATED CUBOIDAL - Clara cells (bulge into lumen) secrete protease inhibitors, oxidase, immunosuppressive pts, & neuroepithelial bodies.
Describe the histology of the respiratory bronchioles.	CILIATED CUBOIDAL - more Claras & less goblets – 1st gas exchange; few alveoli
Describe the histology of the alveolar ducts.	Type I pneumo’s (squame), type II pneumo’s (cube – secrete surfactant), alveolar MΦs, & capillary endothelial cells – reticular & elastic fibers.
Desribe the alveolar sacs.	Alveoli clusters forming alveolar duct ends
Describe the histology of the blood/air barrier (alveoli).	Type I pneumocytes – pneumocyte BM – capillary BM (may be fused w/ pneumo BM) – capillary endothelium.
What is clubbing?	Enlargement of distal tips of digits d/t connective tissue (CT) proliferation. Angle btn the nail bed & cuticle >160o (no diamond shape when you put fingers together).
What is the most accepted theory as to the cause of clubbing?	The Platelet Theory: Plt fragments lodge in sm vessels of fingertips &/or Plt-filled megakaryocytes travel to finger tips -> get stuck & occlude sm vessels. Then plts secrete PDGF which ↑es sm muscle & fibroblast proliferation.