case 1: peptic ulcer

Question 1

chief complaints

Answer 1

hematemesis

Question 2

history

Answer 2

• dyspepsia and epigastric pain
• stress
• Spicy food, coffee and fatty food elicit pain
  ** these are myth risk factors for peptic ulcers
• ibuprofen (Advil, 400 mg q.i.d for 6 months)
  for rheumatoid arthritis
  ** NSAIDs is an aggressive factor of peptic ulcer disease

Question 3

physical exam

Answer 3

• pallor
• reclining position BP – 110/70, pulse rate – 100; on standing position BP – 90/50, pulse rate – 130
• heart: regular rhythm with tachycardia

Question 4

Why and how might change of positions affect
his BP and pulse rate?

Answer 4

heart rate and blood pressure are higher in standing and sitting positions due to gravity?

Question 5

clinical tests

Answer 5

CBC – hematocrit (38), WBC (9,800) and platelets (300,000) are all within normal range

Question 6

how peptic ulcer was diagnosed

Answer 6

endoscopy

Question 7

treatment at ER

Answer 7

• insertion of nasogastric tube
• IV infusion normal saline

Question 8

hematocrit

Answer 8

– a.k.a. packed cell volume (PCV)
or erythrocyte volume fraction (EVF), is the volume percentage (%) of RBC in blood
– Normal value – (♂) 41-53%, (♀) 36-46
– Anemia vs. polycythemia (Males with hemoglobin values less than 13 g/dL were classified as anemic, and those with values greater than 16.5 g/dL or hematocrit greater than 49 percent were categorized as having polycythemia)

Question 9

why was hematocrit normal?

Question 10

endoscopy

Answer 10

• A nonsurgical procedure used to
  examine a person’s digestive tract
  – Use an endoscope, a flexible
  tube with a light and camera attached to it

Question 11

other method to diagnose peptic ulcer

Answer 11

Barium X-ray of upper GI tract
– Barium is an X-ray contrast medium
– To study the appearance and
function of the parts of the gastrointestinal tract

Question 12

describe the general structure of the stomach

Answer 12

• most distensible part of GI tract
  – Cardia, fundus, body, antrum, pylorus, pyloric sphincter
  – Mucosa, submucosa, muscle (circular & longitudinal), and serosa
  – Gastric glands – deeper in the mucosa

Question 13

what is the function of gastric glands?

Answer 13

secrete gastric juice

Question 14

what do the gastric glands contain?

Answer 14

• mucus (goblet cells)
• Parietal cells – HCl & intrinsic factor
  (exocrine)
• Intrinsic factor – a polypeptide that
  promotes absorption of vit B12 in the
  small intestine (ileum) → helps
  prevent pernicious anemia; the only
  essential function in stomach
  – Chief cells – secrete pepsinogen
  – Enterochromaffin-like cells (ECL) –
  histamine & serotonin (paracrine)
  – G cells secrete gastrin (endocrine,
  hormone)
  – D cells – secrete somatostatin

Question 15

what secretes HCl?

Answer 15

parietal cells, containing H+-K+-ATPase (proton
pump)

Question 16

describe the pathway of food in the stomach to secrete HCl

Answer 16

• Food in stomach →
  – Activation of parietal cell → increases
  insertion of H+-K+-ATPase in the apical membrane
  – Net effect – transporting H+ & Cl- into the gastric lumen; HCO3- into blood
• CA – carbonic anhydrase

Question 17

composition of luminal fluid

Answer 17

isotonic H+, Cl-, K+ & Na+ (hydrochloric acid, gastric acid)
Why is the secretion isotonic?
- similar concentration of dissolved particles as blood

Question 18

Gastric Endocrine Secretion – Gastrin

Answer 18

• The gastroenteropancreatic (GEP) endocrine cells – some GI epithelial cells secrete hormones (blood-borne & ductless)
• Stomach G cells – gastrin-producing cells in gastric antrum, duodenum & pancreas → blood circulation → parietal cells in fundus
  – Peptide of 17 a.a.; secretion stimulated by food (esp. protein); secretion of gastrin is inhibited by a decline in pH in stomach (acidic chyme). Why?
• sodium bicarbonate from the isotonic secretion?

Question 19

functions of gastrin

Answer 19

• Gastrin – help process food in stomach & duodenum by:
  – Enhances parietal cell secretion of acid
  – ↑ Histamine secretion from ECL cells → ↑ acid secretion
  – GI trophic action – proliferation of mucosal epithelial cells. Why? to expand stomach when filled with food?
  – Control of GI motility – ↑ contraction of stomach （ major)
• Also ↑ contraction duodenum, ileum & lower esophageal sphincter tone
• Relaxation of ileocecal sphincter (why would that help process food?)
• Induces mass movement in colon
  – ↑ Secretion of pancreatic enzymes

Question 20

regulation of HCl secretion

Answer 20

• 3 Limbs regulation -> increase acid secretion
  – Neural – acetylcholine (parasympathetic NS)-M3 receptor
  – Hormonal – gastrin (G cells)-CCK2 receptor
  – Paracrine – histamine (ECL cells)-H2 receptor
• Histamine from ECL cells is the most potent stimulus
  – Acetylcholine (parasympathetic NS) acts on G, ECL & parietal cells
  – Gastrin acts on ECL & parietal cells

Question 21

vagus nerve (acetylcholine)

Question 22

Gastric Mucosal Barrier

Answer 22

• Mucosal barrier enables stomach to contain acid without injuring itself
• Structural protection – luminal membrane (1) & tight junctions (2)
• Chemical protection – alkaline mucus (3)
  – Mucus gel layer slows diffusion of H+
  – HCO3- neutralizes H+ before reaching epithelium
• Cytological protection – surface epithelial cells replaced every 4-7 days, due to endogenous prostaglandins (PGE2), gastrin & growth factors

Question 23

Functions of The Stomach

Answer 23

• Storage of food (HCl), minimizing growth of bacteria
  – Along with salivary lysozymes and pepsin, killing most of the microorganisms ingested with food
• Denaturation and partial digestion of proteins
  – Activation of pepsinogen to active pepsin (positive feedback)
  – Providing acid medium optimal for pepsin activity
  – Aiding in breakdown of connective tissue, muscle fibers and other proteins for faster pancreatic enzymatic digestion
• Regulation the rate of food emptying into the small intestine
  – Digestion occurs at much slower rate than consumption
  – Allowing maximal intestinal digestion and absorption
• Secretion of intrinsic factor (the only essential function)
• Question – What would happen if the production of HCl is
  reduced?

Question 24

define Hypochlorhydria

Answer 24

deficiency of hydrochloric acid production in
the stomach

Question 25

risk factors of hypochlorhydria

Answer 25

– Age – people over the age of 65 have the highest risk
– Medications – proton pump inhibitors, antacids or heart burn medications
– Helicobacter pylori infection

Question 26

hypochlorhydria symptoms

Answer 26

– Gastrointestinal infections, bloating, burping, gas, diarrhea
– Undigested food in the stool
– Nutrient deficiencies

Question 27

erosion

Answer 27

mucosal layer is damaged

Question 28

Ulceration

Answer 28

mucosal, submucosal and/or muscle layers are damaged

Question 29

Perforation

Answer 29

all four layers are damaged → stomach contents leak into abdominal cavity →peritonitis

Question 30

types of ulcers

Answer 30

gastric, duodenal, esophageal

Question 31

Peptic Ulcer Disease (PUD)

Answer 31

• Imbalance between the aggressive and defensive factors in the gastroduodenal mucosa
  – Aggressive factors – gastric acid, pepsin, Helicobacter pylori infection & NSAIDs
  – Protective factors – mucin, HCO3-, prostaglandins (epithelial cell replenishment)
  – PUD patients → ↑ gastric emptying rate → ↑ duodenum acidification → gastric metaplasia → ↑ H. pylori colonization in duodenum

Question 32

Some Facts about Peptic Ulcer

Answer 32

• Epidemiology – lifetime prevalence – 5-10%
• Helicobactor pylori infection (~85%)
  – Only infects gastric mucosa
  – Found in 80-95% of duodenal ulcers, due to
  gastric metaplasia (change in duodenal
  mucosa to gastric mucosa → decreases HCO3-
  production → decreases acid neutralization
  – Found in 70-90% of gastric ulcer
• Non-steroidal anti-inflammatory drug (NSAIDs) (10-15%)
• Overproduction of gastrin (Zollinger-Ellison syndrome) – 0.1%
• “Myth” risk factors (not an initiator)
  – Cigarette smoking, stress, personality & occupation
  – Diet (spicy food, neutral fats), alcohol consumption

Question 33

Helicobacter pylori Infection

Answer 33

– Gram-negative, curved, with 4-6 flagella, rod
– Resides in gastric-type epithelium within mucosal layer (protects the bacteria from acid)
– Is the main cause of peptic ulcers (85%)
– Can also cause gastritis and stomach cancer

Question 34

The Finding of H. pylori Pathogenesis

Answer 34

• The causative role of H. pylori infection in
  PUD was first elucidated by Barry J.
  Marshall and J. Robin Warren in 1984.
• To prove the causative role, Marshall
  ingested inoculum of H. pylori and
  confirmed the presence of its infection.
• Marshall and Warren received Nobel Prize
  for Medicine and Physiology in 2005.
• H. pylori is now classed by WHO as a
  class 1 carcinogen.
• H. pylori uses its flagella to penetrate
  gastric mucus layer to reach gastric
  epithelial cells (more neutral pH)

Question 35

Mechanisms for H. pylori-induced GI injury

Answer 35

• H. pylori harm gastric epithelium
  by:
  – Producing urease to convert urea
  into ammonia
• (NH2)2CO + H2O → CO2 + 2 NH3
• NH3 + H+ → NH4+
  – NH3 is toxic to gastric epithelium
  – Produce proteases and other chemicals disrupts tight junctions and causes apoptosis
• Mode of transmission
  – Likely oral-oral/fecal-oral
  – Age of acquirement – childhood

Question 36

NSAIDs

Answer 36

• Function of cyclooxygenase (COX)
  – COX-1 – constitutively active, catalyzes
  production of gastric prostaglandins
• Support blood flow in stomach wall
• Enhance mucus and HCO3- production
• Mediate somatostatin (from gastric D cells)
  suppression of acid secretion
  – COX-2 – induced as part of an immune
  response, inflammatory prostaglandins
  contribute to pain, heat, swelling
• NSAIDs (non-steroidal anti-inflammatory
  drugs) – most widely used classes of
  drugs, non-selective
  – Ibuprofen (Advil), naproxen (Alleve),
  sulindac (Clinoril), aspirin, indomethacin
  (Indocin)
  – Baby aspirin (81 mg daily) → decrease gastric
  mucosal PGE2 → gastric lesions

Question 37

NSAIDs and Peptic Ulcer

Answer 37

• NSAIDs → decrease gastric prostaglandins secretion → decrease mucin secretion
  → weaken the mucosal barrier → acid can directly injure the
  mucosa → causes gastric ulcers
• Risk of NSAID-induced ulceration
  – Age > 60; increasing duration & dose of therapy
  – Concurrent steroid or anticoagulant use
• Symptoms (quite variable)
  – Asymptomatic
  – Vague abdominal discomfort
  – Classical symptom – dyspepsia
• Pain centered in the upper abdomen
• Discomfort in the form of fullness, bloating, distention or nausea
• 1-3 hr post-meal or midnight; relieved by food or antacid

Question 38

Stress Ulcers

Answer 38

• Severe physiologic stress →
  (fight or flight) → splanchnic
  hypoperfusion → ischemic → a
  cascade of inflammatory
  responses are the key causes
  – In this sense, stress does
  cause stress ulcers
  – Acid alone does not cause
  stress ulcers
• Splanchnic circulation – the
  blood flow to abdominal GI
  organs ( stomach, liver,
  spleen, pancreas, small
  intestine & large intestine
• Cushing ulcer – ↑ intracranial
  pressure → vagus nerve → ↑
  parietal cells → increase acid secretion
• Curling ulcer – severe burn
  (>35%) → decrease gastric ischemia

Question 39

Zollinger-Ellison Syndrome

Answer 39

• Caused by tumors
• Most often found in the head of the pancreas and the upper small
  intestine
• Produce the hormone gastrin and are called gastrinomas
• Stimulates the parietal cells to secrete gastrin
• → HCl secretion to maximal activity
• → Gastrointestinal mucosal ulceration

Question 40

Peptic Ulcer – Diagnosis

Answer 40

• Immediate endoscopy, X-ray or CT scan
• Noninvasive test for H. pylori
  – Serological testing for IgG, can remain
  “+” for 3 yr after therapy
  – Urea breath test – use C13 or C14 labeled
  urea
• (NH2)2CO + H2O → HCO3- + 2 NH3 →
  CO2 + 2 NH3
• Detect level of CO2
  – Stool H. pylori antigen test
• Invasive test for H. pylori
  – Biopsy for H. pylori culture or histology
  – Rapid urease test

Question 41

Peptic Ulcer – Treatment

Answer 41

1. • decrease HCl secretion by parietal cells
     – Proton pump inhibitors (PPI, most
     effective)
     * Drugs ending in “prazole“ –
     omeprazole, esomeprazole
     – Histamine (H2) blockers (very safe)
     * Competitive antagonists
     at H2 receptors, e.g. ranitidine,
     cimetidine
     * decrease Basal & meal-stimulated HCl
     * H1 antagonists – anti-allergy, anti- vomiting, motion sickness
     – Anticholinergic drugs
     * Eradicate H. pylori – antibiotics (clarithromycin, amoxicillin, or
     metronidazole)
     * Mucosal protectants such as sucralfate require acidic environment for activation.
     As such, does not work with H2 blockers or antacids (decrease acidity)
2. • Mucosal protectants (protect mucosa)
     – Sucralfate (disaccharide-SO3-Al)
     * The negatively charged sucrose sulfate binds to positively charged proteins
     in the base of ulcers or erosions
     * → form a cross-linking, viscous, paste-like material
     * → physical barrier that restricts further caustic damage
     – Bismuth subsalicylate – like sucralfate, bismuth coats ulcers and
     erosions, creating a protective layer against acid and pepsin
     – Side effects – constipation & black stool
     * Re-establish mucosal barrier – prostaglandins (PGE & PGI)
     * Acidity – buffering acid & decrease acid secretion
     – Antacids – aluminum or magnesium hydroxide
     * Al(OH)3 + 3 HCl <–> AlCl3 + 3 H2O

Question 42

Acute Gastritis

Answer 42

• Acute gastritis – submucosa inflammation
• Causes
  – Non-steroidal anti-inflammatory drugs (NSAIDs)
  – Mast cells tumor (most common skin tumor in dogs) → ↑ histamine
  production → ↑ H+ production from parietal cells
  – Helicobacter pylori – humans, rare in cats, not in dogs

Question 43

Gastroesophageal Reflux Disease (GERD)

Answer 43

• Normally lower esophageal sphincter (LES) closes to prevent acidic
  chyme from reflux
• Reflux occurs when the LES is weak or relaxes inappropriately → GERD
  (heart burn)
• Treatment – Antacids (neutralize HCl), mucosal protectants, reducing HCl
  production
  Gastroesophageal Reflux Disease (GERD)