Pathophysiology of Acid Disorders: GERD & PUD Flashcards
What is the proton pump?
An active transport protein H+/K+ -ATPase
It moves one H+ ion OUT of the parietal cell and one K+ IN to the cell
Cl also moves into the stomach lumen –> forms HCl
What three hormones stimulate acid secretion?
Gastrin
Acetylcholine
Histamine
Describe what happens when H2 receptors on parietal cells are activated
The H2 receptor is a G Protein-Coupled Receptor
Causes translocation of the proton pump from the cytoplasm to the plasma membrane of the parietal cell
It dramatically increases the number of proton pumps on the surface of the cell and stimulates H+ secretion –> decreased pH in the stomach lumen
Acid disorders are a result of:
An imbalance of aggressive/damaging factors and mucosal defenses/protective factors
What are examples of aggressive factors?
Gastric acid
Pepsin
Bile acids
Pancreatic enzymes
What are examples of mucosal defense factors?
LES normal tone
Esophageal clearance
Mucosal resistance
Tight junctions
Gastric emptying
Epidermal growth factor
Salivary Buffering (HCO3-)
Prostaglandins
How is the integrity of the gastric mucosal barrier maintained?
HCO3-
pH of 7 on the surface // pH of 2 in the stomach lumen
Tight junctions prevent HCL from leaking
Physical barrier of mucous cells –> trap bicarb-rich fluid
Mucus contains mucin proteins (maintain barrier function)
Mucin forms a gel closest to the lumen
What is GERD?
Gastroesophageal Reflux Disease
Symptomatic condition or the histologic change associated with retrograde movement of gastric contents to the esophagus
Backwards movement fro, stomach to the esophagus
What is PUD?
Peptic Ulcer Disease
Gastritis, erosions, and ulcers of the GI tract that require gastric acid for their formation
Where do ulcers form?
Most ulcers form in the stomach or duodenum
Duodenal ulcers are more common than stomach ulcers
What is the most common cause of GERD?
“Incompetent” LES –> allows acid reflux
The normally high pressure of the LES is reduced if the LES is incompetent –> permits the reflux of gastric contents every time the pressure in the stomach exceeds the pressure in the LES
What are some causes of GERD other than an incompetent LES?
Anything that alters the normal function and/or tone of the LES or increases the abdominal pressure
- Certain foods and meds
- Smoking
- Obesity
- Hiatal Hernia
- Pregnancy
- Sleeping positions
What is a hiatal hernia?
When the stomach bulges up into the chest through the hiatus
Describe the two types of Hiatal hernias
Sliding - stomach is protruding out
Paraesophageal - stomach is squeezed next to the esophagus, more dangerous due to the risk of the stomach becoming incarcerated (blood flow cut off)
What are typical S/Sx of GERD?
Heartburn
Water brash (hypersalivation)
Belching
Regurgitation w/w/o nausea
What are severe s/sx of GERD?
Continual pain
Dysphagia
Bleeding
Odynophagia (painful swallowing)
Vomiting acid in sleep
Unexplained weight loss
Choking
What are atypical s/sx of GERD?
Non-allergic asthma
Chronic cough
Hoarseness
Laryngitis
Chest pain
Dental erosions
What is Barret’s esophagus?
A sequela of chronic GERD
Involves metaplasia of stratified squamous cell –> columnar cell with goblet cells and mucous cells
They are more tolerant of an acid environment BUT are also more likely to develop into adenocarcinoma
What are some common causes of PUD?
H. pylori
NSAIDs
Smoking
How does H. pylori’s structure lead to PUD?
Helical (corkscrew shape) aids mobility
Flagella help it move below the mucosal surface to colonize the gastric epithelium
Well-adapted to gastric environments (low pH)
Neutralizes pH in the mucous layer –> releases urease enzyme
Promotes an inflammatory reaction –> further tissue injury
How does H. pylori form ulcers?
Tissue injury gives H. pylori an opportunity to move below the surface of the mucosal layer
Can then be the site of an erosion
Eventually becomes an ulcer
Describe H. pylori’s association with gastric cancer
Inhibits apoptosis of gastric pit cells (lack of cell turnover and healing)
Chronic inflammation –> increased risk of cancer
Some strains produce a toxin that can degrade proteins that are normally tumor suppressors
How can you diagnose an H. pylori infection?
Biopsy via endoscopy (gold standard)
Breath test (non-invasive)
How does the H. pylori breath test work?
Takes advantage of the fact that H. pylori bacteria releases urease that breaks down urea into CO2 and ammonia
Comparison of the ratio of Carbon-12 and Carbon-13
An increase in Carbon-13 indicates an H. pylori infection
How can NSAIDs cause PUD?
Direct topical injury to the gastric mucosa
Promote increased neutrophil adherence to vascular epithelium –> ROS and proteases –> damage to the mucosal layer
Inhibit beneficial prostaglandins
Decrease submucosal blood flow –> slows healing down
PUD Symptoms
Epigastric pain (gnawing, dull, aching, burning)
Nausea
Some ulcers may be asymptomatic until the pt. suffers from a more serious event such as a GI bleed
If bleeding is present –> labs may show anemia
Gastric vs. Duodenal epigastric pain
Gastric: pain aggravated or precipitated by food
Duodenal: Pain occurs 1-3 hours after a meal, and is relieved by food
What are alarm symptoms in PUD?
Bleeding (melena - black or tarry appearing stools // hematemesis - coffee ground emesis)
Perforation – upper abdominal pain with radiation to the back
Obstruction – nausea, vomiting, abdominal distention
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