Cystic fibrosis

Pulmonology MSN 605 SPRING 2021

Pulmonology MSN 605 SPRING 2021

Choanal atresia
Laryngomalacia
Allergic rhinitis
Nasal polyps
Upper respiratory tract infection
Sinusitis
Laryngitis
Retropharyngeal and peritonsillar abscesses
Bacterial epiglottitis
Nasopharyngeal carcinoma
Tracheoesophageal fistula
Congenital pulmonary airway malformation
Pulmonary hypoplasia
Neonatal respiratory distress syndrome
Transient tachypnea of the newborn
Meconium aspiration syndrome
Apnea of prematurity
Sudden infant death syndrome
Acute respiratory distress syndrome
Decompression sickness
Cyanide poisoning
Methemoglobinemia
Emphysema
Chronic bronchitis
Asthma
Cystic fibrosis
Bronchiectasis
Alpha 1-antitrypsin deficiency
Restrictive lung diseases
Sarcoidosis
Idiopathic pulmonary fibrosis
Pneumonia
Croup
Bacterial tracheitis
Lung cancer
Pancoast tumor
Superior vena cava syndrome
Pneumothorax
Pleural effusion
Mesothelioma
Pulmonary embolism
Pulmonary edema
Pulmonary hypertension
Sleep apnea
Respiratory distress syndrome: Pathology review
Cystic fibrosis: Pathology review
Pneumonia: Pathology review
Tuberculosis: Pathology review
Deep vein thrombosis and pulmonary embolism: Pathology review
Pleural effusion, pneumothorax, hemothorax and atelectasis: Pathology review
Obstructive lung diseases: Pathology review
Restrictive lung diseases: Pathology review
Apnea, hypoventilation and pulmonary hypertension: Pathology review
Lung cancer and mesothelioma: Pathology review
Renal agenesis
Horseshoe kidney
Potter sequence
Hyperphosphatemia
Hypophosphatemia
Hypernatremia
Hyponatremia
Hypermagnesemia
Hypomagnesemia
Hyperkalemia
Hypokalemia
Hypercalcemia
Hypocalcemia
Renal tubular acidosis
Minimal change disease
Diabetic nephropathy
Focal segmental glomerulosclerosis (NORD)
Amyloidosis
Membranous nephropathy
Lupus nephritis
Poststreptococcal glomerulonephritis
Rapidly progressive glomerulonephritis
IgA nephropathy (NORD)
Lupus nephritis
Alport syndrome
Kidney stones
Hydronephrosis
Acute pyelonephritis
Chronic pyelonephritis
Prerenal azotemia
Renal azotemia
Acute tubular necrosis
Postrenal azotemia
Renal papillary necrosis
Renal cortical necrosis
Chronic kidney disease
Polycystic kidney disease
Multicystic dysplastic kidney
Medullary cystic kidney disease
Medullary sponge kidney
Renal artery stenosis
Renal cell carcinoma
Angiomyolipoma
Nephroblastoma (Wilms tumor)
WAGR syndrome
Beckwith-Wiedemann syndrome

Transcript

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You’re probably aware that cystic fibrosis, or CF, is a genetic disorder that affects the lungs, but that’s only part of the story.

In fact, the name “cystic fibrosis,” refers to the disease’s effects on the pancreas, where it can lead to cysts, which are fluid-filled sacs wrapped in a membrane and fibrosis—excess deposition of connective tissue that can replace or infiltrate normal tissue in an organ.

CF is an autosomal recessive disorder involving the CFTR gene, which stands for “cystic fibrosis transmembrane conductance regulator,” and this gene codes for the CFTR protein.

CF develops when there’s a mutation in the CFTR gene, but because it’s autosomal recessive, you need to inherit two mutated CFTR genes, one from mom and one from dad.

Now if mom and dad both have one copy of the mutated gene and one normal gene, they’re considered carriers and don’t have the disease.

Inheriting CF is more common in people of European descent.

The CFTR protein is a channel protein that pumps chloride ions into various secretions, those chloride ions help draw water into the secretions, which ends up thinning them out.

The most common mutation is the “∆F508” mutation.

Delta means a deletion, and the F (which can also be written as “Phe”) is short for phenylalanine, and the 508 is the five hundred and 8th amino acid in the CFTR protein.

So, the ∆F508 mutation is where the 508th amino acid out of 1480, phenylalanine, is deleted and missing.

This CFTR protein with the ∆F508 mutation gets misfolded and can’t migrate from the endoplasmic reticulum to the cell membrane, meaning there’s a lack of CFTR protein on the epithelial surface, and this means that it can’t pump chloride ions out, which means water doesn’t get drawn in, and the secretions are left overly thick.

In a newborn, thick secretions can affect the baby’s meconium, or first stool, or, which can get so thick and sticky that it might get stuck in the baby’s intestines and not come out, and this is called a meconium ileus and is a surgical emergency.

In early childhood, pancreatic insufficiency is the most prominent effect of CF.

This happens because thick secretions jam up the pancreatic ducts, not allowing digestive enzymes to make it to the small intestine.

Without those pancreatic enzymes, protein and fat aren’t absorbed.

And over time this can lead to poor weight gain and failure to thrive.

Fat malabsorption can lead to steatorrhea, or fat-containing stools.

Eventually the pancreas gets damaged, because backed-up digestive enzymes degrade the cells lining the pancreatic ducts, causing local inflammation.

This can lead to acute pancreatitis and—with repeated episodes—chronic pancreatitis, with the development of cysts and fibrosis like we talked about, giving the disease it’s name.

Finally, the destruction of pancreatic tissue can also compromise of the endocrine function of the pancreas, causing insulin-dependent diabetes.

It’s usually not until later in childhood that lung problems start to crop up.

Normally the cilia, these hair-like projections lining the airways, do a pretty good job of keep the them clean by moving mucus, which catches things like debris and bacteria, toward the pharynx, called mucociliary action.

With thick mucus, though, it gets a lot harder to clear and the mucociliary action becomes defective, which means bacteria is allowed to chronically colonize the lungs.

If the bacterial load suddenly increases, it causes symptoms like cough and fever, a decrease in lung function, and sometimes changes on a chest X-ray, and this is called a CF exacerbation and usually prompts a round of antibiotics.

Pneumonia is one example of a CF exacerbation which requires antibiotic treatment.

Sources

  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
  4. "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
  5. "Cystic Fibrosis: Lessons from the Sweat Gland" Physiology (2007)
  6. "Infection Control in Cystic Fibrosis" Clinical Microbiology Reviews (2004)
  7. "Pharmacological approaches for targeting cystic fibrosis nonsense mutations" European Journal of Medicinal Chemistry (2020)