Pathophysiology of Acid Disorders: GERD & PUD

Question 1

What is the proton pump?

Answer 1

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

Question 2

What three hormones stimulate acid secretion?

Answer 2

Gastrin

Acetylcholine

Histamine

Question 3

Describe what happens when H2 receptors on parietal cells are activated

Answer 3

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

Question 4

Acid disorders are a result of:

Answer 4

An imbalance of aggressive/damaging factors and mucosal defenses/protective factors

Question 5

What are examples of aggressive factors?

Answer 5

Gastric acid

Pepsin

Bile acids

Pancreatic enzymes

Question 6

What are examples of mucosal defense factors?

Answer 6

LES normal tone

Esophageal clearance

Mucosal resistance

Tight junctions

Gastric emptying

Epidermal growth factor

Salivary Buffering (HCO3-)

Prostaglandins

Question 7

How is the integrity of the gastric mucosal barrier maintained?

Answer 7

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

Question 8

What is GERD?

Answer 8

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

Question 9

What is PUD?

Answer 9

Peptic Ulcer Disease

Gastritis, erosions, and ulcers of the GI tract that require gastric acid for their formation

Question 10

Where do ulcers form?

Answer 10

Most ulcers form in the stomach or duodenum

Duodenal ulcers are more common than stomach ulcers

Question 11

What is the most common cause of GERD?

Answer 11

“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

Question 12

What are some causes of GERD other than an incompetent LES?

Answer 12

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

Question 13

What is a hiatal hernia?

Answer 13

When the stomach bulges up into the chest through the hiatus

Question 14

Describe the two types of Hiatal hernias

Answer 14

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)

Question 15

What are typical S/Sx of GERD?

Answer 15

Heartburn

Water brash (hypersalivation)

Belching

Regurgitation w/w/o nausea

Question 16

What are severe s/sx of GERD?

Answer 16

Continual pain

Dysphagia

Bleeding

Odynophagia (painful swallowing)

Vomiting acid in sleep

Unexplained weight loss

Choking

Question 17

What are atypical s/sx of GERD?

Answer 17

Non-allergic asthma

Chronic cough

Hoarseness

Laryngitis

Chest pain

Dental erosions

Question 18

What is Barret’s esophagus?

Answer 18

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

Question 19

What are some common causes of PUD?

Answer 19

H. pylori

NSAIDs

Smoking

Question 20

How does H. pylori’s structure lead to PUD?

Answer 20

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

Question 21

How does H. pylori form ulcers?

Answer 21

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

Question 22

Describe H. pylori’s association with gastric cancer

Answer 22

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

Question 23

How can you diagnose an H. pylori infection?

Answer 23

Biopsy via endoscopy (gold standard)

Breath test (non-invasive)

Question 24

How does the H. pylori breath test work?

Answer 24

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

Question 25

How can NSAIDs cause PUD?

Answer 25

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

Question 26

PUD Symptoms

Answer 26

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

Question 27

Gastric vs. Duodenal epigastric pain

Answer 27

Gastric: pain aggravated or precipitated by food

Duodenal: Pain occurs 1-3 hours after a meal, and is relieved by food

Question 28

What are alarm symptoms in PUD?

Answer 28

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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