Cystic Fibrosis: Diagnosis and Management

00:00 All right, let's discuss now the clinical presentation of cystic fibrosis.

00:05 We'll begin with the pulmonary findings.

00:07 Here you see a gross specimen of bronchiectatic lung.

00:11 Those honeycomb cavities tracing the airways are the hallmark of longstanding obstruction and infection.

00:17 In cystic fibrosis, viscous mucus plugs the bronchioles and invites a host of bacteria and in particular, Pseudomonas aeruginosa to set up permanent shop, igniting cycles of infection and inflammation that end up with dilated flabby airways.

00:33 There will be persistent wheezing and a barrel chest on exam, digital clubbing in the fingers due to hypertrophic pulmonary osteoarthropathy from chronic hypoxia and exertional dyspnea as lung function steadily declines.

00:48 In the sinuses, where the drainage is likewise dependent on normal mucus viscosity, this translates into chronic sinus infections and nasal polyps.

00:58 Shifting gears to the gastrointestinal tract, imagine the small intestine now clogged by thick secretions.

01:05 Newborns can present with meconium ileus when that first stool won't budge.

01:10 In older children, pancreatic insufficiency becomes a bigger issue.

01:14 Kids struggle with malabsorption, steatorrhea, and constipation as pancreatic enzymes can't reach the duodenum.

01:21 In most cases, premature pancreatic enzyme activation and clogged pancreatic ducts also leads to autodestruction of the pancreas.

01:30 Loss of pancreatic function leads not only to fat-soluble vitamin deficiencies and malabsorption, but with loss of islets due to the pancreatic autodigestion, CF patients can develop an interesting variant of diabetes with a hybrid picture blending both insulin deficiency and resistance.

01:50 Beyond the lungs and gut, cystic fibrosis leaves its signature in other corners of the body.

01:57 Sweat glands deprived of CFTR-mediated chloride reabsorption pour out salt and put patients at risk for dehydration, especially in hot weather.

02:07 In the reproductive tract, the CFTR mutations lead to maldevelopment of the vas deferens, rendering most males infertile.

02:16 Males may also face reduced fertility or irregular cycles.

02:21 Even the urinary system can be affected.

02:24 Patients with CF can have an increased risk of kidney stones, specifically calcium oxalate, due to GI-related hyperoxaluria caused by the pancreatic insufficiency and malabsorption.

02:34 Okay, and with that, we can move on to the diagnosis of this disease.

02:39 First, think of newborn screening as our molecular tripwire.

02:43 A few drops of blood from a baby's heel let us measure immunoreactive trypsinogen.

02:48 That's the precursor protein to trypsin.

02:51 When it's elevated, that says that normal pancreatic digestive enzyme processing is not happening and is essentially the pancreas waving a distress flag when its ducts are clogged.

03:01 If that immunoreactive trypsinogen is high, we move on to a CFTR mutation panel, hunting for those DNA glitches.

03:10 And when the genetic picture still leaves room for doubt, we circle back at two weeks of age.

03:16 Once the infant weighs in at around 2 kilos, we run the sweat chloride test.

03:20 Shifting to imaging, remember that plain films often miss the early damage.

03:24 A sinus CT can expose polyp-filled, fluid-laden cavities long before a physical exam picks them up.

03:31 Down in the chest, high-resolution CT is even more telling.

03:34 In CF lungs, you'll see bronchiectasis, especially in the upper lobes.

03:39 Over time, those patterns may become apparent on a standard chest X-ray, but it's the CT that first lights up the roadmap of chronic injury.

03:47 Finally, let's discuss the management of cystic fibrosis.

03:50 Here, the targeted therapies meet time-tested support to keep patients breathing easier.

03:56 At the heart of our modern approach are CFTR modulators, small molecules that act like locksmiths to open the misfolded channel.

04:04 Together, these modulators form a multi-tiered rescue team.

04:09 Gene therapy and RNA repair work at the blueprint level to correct or patch faulty CFTR transcripts.

04:16 Read-through compounds coax ribosomes past premature stop signals.

04:21 Correctors then shepherd misfolded protein out of the ER and through the Golgi.

04:27 Potentiators boost the gate-opening probability of any channel that reaches the surface.

04:32 And proteostasis inhibitors slow down the rapid degradation of rescued CFTR, giving each channel more time to ferric chloride.

04:41 Beyond fixing the channel itself, we still rely on classic airway clearance tactics, DNases to chop up viscous DNA nets released in the mucus plugs by recruited neutrophils, hypertonic saline to draw fluid into the lumen, and chest physiotherapy to mobilize plugs plus aggressive antibiotic regimens to keep pseudomonas and friends off-balance.

05:04 Immunizations and prophylaxis remain key.

05:07 Yearly influenza and pneumococcal vaccines, RSV prevention, and strict contact precautions in healthcare settings.

05:16 We also add bronchodilators, beta-2 agonists to ease airflow, and high-dose ibuprofen as an anti-inflammatory to reduce chronic airway damage.

05:25 Meanwhile, fluid and electrolyte balance demands constant attention.

05:30 It's really important to maintain adequate hydration and liberal salt intake, especially during fevers, vomiting, or hot weather, to prevent dehydration and cramping.

05:40 In the gut, pancreatic exocrine insufficiency calls for enzyme rescue at every meal.

05:47 Lipase and protease capsules provide digestive enzymes and help mitigate steatorrhea and nutrient loss.

05:54 Internal support builds on that foundation.

05:57 A high-calorie, high-fat diet supplemented by fat-soluble vitamins, minerals, and trace elements with enteral feeding as needed.

06:06 When CF-related diabetes arises, a hybrid of insulin deficiency and resistance, we step in with insulin therapy, tailoring doses to each patient's evolving needs.

06:16 Lastly, the prognosis slide underscores both progress and perseverance.

06:20 With optimal therapy, median survival now stretches into the mid-40s, a testament to decades of targeted advances.

06:28 Yet the sobering reality that half of all deaths still occur before age 18 from respiratory failure drives home why our work continues.

06:36 Every intervention, from gene-level correction to the simplest salt supplement, is a lifeline in the ongoing effort to turn cystic fibrosis into a chronic, manageable condition rather than a fatal one.

06:49 And with that, we have covered cystic fibrosis.

06:51 Thanks for watching.