case 1: peptic ulcer Flashcards
chief complaints
hematemesis
history
- 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
physical exam
- pallor
- reclining position BP – 110/70, pulse rate – 100; on standing position BP – 90/50, pulse rate – 130
- heart: regular rhythm with tachycardia
Why and how might change of positions affect
his BP and pulse rate?
heart rate and blood pressure are higher in standing and sitting positions due to gravity?
clinical tests
CBC – hematocrit (38), WBC (9,800) and platelets (300,000) are all within normal range
how peptic ulcer was diagnosed
endoscopy
treatment at ER
- insertion of nasogastric tube
- IV infusion normal saline
hematocrit
– 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)
why was hematocrit normal?
endoscopy
- 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
other method to diagnose peptic ulcer
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
describe the general structure of the stomach
- 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
what is the function of gastric glands?
secrete gastric juice
what do the gastric glands contain?
- 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
what secretes HCl?
parietal cells, containing H+-K+-ATPase (proton
pump)
describe the pathway of food in the stomach to secrete HCl
- 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
composition of luminal fluid
isotonic H+, Cl-, K+ & Na+ (hydrochloric acid, gastric acid)
Why is the secretion isotonic?
- similar concentration of dissolved particles as blood
Gastric Endocrine Secretion – Gastrin
- 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?
functions of gastrin
- 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
regulation of HCl secretion
- 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
vagus nerve (acetylcholine)
Gastric Mucosal Barrier
- 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
Functions of The Stomach
- 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?
define Hypochlorhydria
deficiency of hydrochloric acid production in
the stomach
risk factors of hypochlorhydria
– Age – people over the age of 65 have the highest risk
– Medications – proton pump inhibitors, antacids or heart burn medications
– Helicobacter pylori infection
hypochlorhydria symptoms
– Gastrointestinal infections, bloating, burping, gas, diarrhea
– Undigested food in the stool
– Nutrient deficiencies
erosion
mucosal layer is damaged
Ulceration
mucosal, submucosal and/or muscle layers are damaged
Perforation
all four layers are damaged → stomach contents leak into abdominal cavity →peritonitis
types of ulcers
gastric, duodenal, esophageal
Peptic Ulcer Disease (PUD)
- 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
Some Facts about Peptic Ulcer
- 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
Helicobacter pylori Infection
– 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
The Finding of H. pylori Pathogenesis
- 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)
Mechanisms for H. pylori-induced GI injury
- 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
NSAIDs
- 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
NSAIDs and Peptic Ulcer
- 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
Stress Ulcers
- 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
Zollinger-Ellison Syndrome
- 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
Peptic Ulcer – Diagnosis
- 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
Peptic Ulcer – Treatment
- 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)
- decrease HCl secretion by parietal cells
- 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
- Mucosal protectants (protect mucosa)
Acute Gastritis
- 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
Gastroesophageal Reflux Disease (GERD)
- 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)
