case 1: peptic ulcer Flashcards
(43 cards)
1
Q
chief complaints
A
hematemesis
2
Q
history
A
- 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
3
Q
physical exam
A
- pallor
- reclining position BP – 110/70, pulse rate – 100; on standing position BP – 90/50, pulse rate – 130
- heart: regular rhythm with tachycardia
4
Q
Why and how might change of positions affect
his BP and pulse rate?
A
heart rate and blood pressure are higher in standing and sitting positions due to gravity?
5
Q
clinical tests
A
CBC – hematocrit (38), WBC (9,800) and platelets (300,000) are all within normal range
6
Q
how peptic ulcer was diagnosed
A
endoscopy
7
Q
treatment at ER
A
- insertion of nasogastric tube
- IV infusion normal saline
8
Q
hematocrit
A
– 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)
9
Q
why was hematocrit normal?
A
10
Q
endoscopy
A
- 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
11
Q
other method to diagnose peptic ulcer
A
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
12
Q
describe the general structure of the stomach
A
- 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
13
Q
what is the function of gastric glands?
A
secrete gastric juice
14
Q
what do the gastric glands contain?
A
- 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
15
Q
what secretes HCl?
A
parietal cells, containing H+-K+-ATPase (proton
pump)
16
Q
describe the pathway of food in the stomach to secrete HCl
A
- 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
17
Q
composition of luminal fluid
A
isotonic H+, Cl-, K+ & Na+ (hydrochloric acid, gastric acid)
Why is the secretion isotonic?
- similar concentration of dissolved particles as blood
18
Q
Gastric Endocrine Secretion – Gastrin
A
- 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?
19
Q
functions of gastrin
A
- 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
20
Q
regulation of HCl secretion
A
- 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
21
Q
vagus nerve (acetylcholine)
A
22
Q
Gastric Mucosal Barrier
A
- 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
23
Q
Functions of The Stomach
A
- 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?
24
Q
define Hypochlorhydria
A
deficiency of hydrochloric acid production in
the stomach
25
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
26
hypochlorhydria symptoms
– Gastrointestinal infections, bloating, burping, gas, diarrhea
– Undigested food in the stool
– Nutrient deficiencies
27
erosion
mucosal layer is damaged
28
Ulceration
mucosal, submucosal and/or muscle layers are damaged
29
Perforation
all four layers are damaged → stomach contents leak into abdominal cavity →peritonitis
30
types of ulcers
gastric, duodenal, esophageal
31
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
32
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
33
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
34
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)
35
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
36
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
37
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
38
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
39
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
40
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
41
Peptic Ulcer – Treatment
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
42
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
43
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)
