5070: Acid Disorders

the stomach lining has millions of _____ that lead to the gastric _____ that produce gastric juice

pits

glands

what are the type of cells in the gastric glands that secrete gastrin

G cells

what do parietal cells secrete? x 2 things

what do chief cells secrete? x2 things

HCl acid and intrinsic factor

pepsinogen and gastric lipase

how is gastric acid normally secreted?

gastric acid secretion increases in response to what stimuli? x 4 things

at a basal rate

1. distention of the stomach

2. peptides

3. rising pH

4. ingestion of proteins

what is another unique feature of parietal cell?

H+-K+ pump, aka proton pump

what does the proton pump do in the body?

how is the proton pump powered?

moves one H+ ion out of the parietal cell (into lumen) and one K+ ion back into the parietal cell

with ATP, works against the concentration gradients of H+ and K+

as H+ ions are being pumped into the stomach, what moves into the stomach lumen to form HCL?

how does this happen?

Cl-

the alkaline tide of bicarbonate

what 3 hormones stimulate acid secretion?

1. gastrin

2. acetylcholine

3. histamine

where is the histamine receptor located?

what is the receptor called that is used to reduce gastric acid?

on the surface of the parietal cells

H2 receptors

what is the process that occurs when histamine binds with H2 receptor on parietal cell? x 3 things

1. protein kinases phosphorylate a protein

2. translocation of proton pumps to the plasma membrane

3. decreased pH in stomach lumen

what type of receptor is H2?

GPCR

what is the general cellular response from histamine binding to H2 receptor?

translocation of H+/K+ ATPase from cytoplasm to plasma membrane of parietal cell

what does the binding of histamine to H2 receptor dramatically increase?

the # of proton pumps on the surface of the cell

stimulated H+ secretion

what is the overall pH result in the stomach after histamine binds to H2 receptor?

decreased stomach pH

acid disorders result from an imbalance of what 2 things?

an imbalance of aggressive/damaging factors and mucosal defense/protective factors

what needs to be maintained in the body to avoid damage from acid?

gastric mucosal barrier

what is the pH at the surface of the mucosa?

vs pH of 1-2 in into the stomach?

pH of 7

pH of 2

what cellular feature of the stomach epithelial cells prevents HCl from leaking into underlying tissue?

tight junctions

what does mucus contain that plays a critical role in maintaining the gastric mucosal barrier function?

what does mucin form close to the lumen?

mucin proteins

forms a gel closest to the lumen

what is the def of GERD?

sx condition of histologic change associated with retrograde movement of gastric contents to esophagus

what is PUD? what does it require?

where do most ulcers form?

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

in the stomach or duodenum (most common)

what is the most common cause of GERD?

what change to the structure causes this?

incompetent lower esophagus sphincter (LES) which allows acid reflux

pressure of LES is reduced

what is the lower esophageal sphincter?

what is the normal function of it

a high-pressure zone of thickened muscle

to prevent reflux of gastric contents

what is the pressure of the LES in normal resting conditions?

15-30 mm Hg above intragastric pressures

what are two other causes of GERD?

1. anything altering normal fx +/ tone of the LES

   1. anything that incr abdominal pressure

what is a hiatal hernia?

the stomach bulging into the chest through opening in diaphragm

what are the 2 types of hiatal hernias?

which is the most dangerous?

1. sliding (most common)

2. paraoesophageal

paraesophageal are more dangerous, due to risk of stomach incarceration/halted blood supply

what are carminatives?

how do they worsen GERD sx?

herbal remedy used for gas, indigestion, bloating

decrease LES pressure

what is a carminative that pts should avoid with GERD?

peppermint

what 5 foods also decrease LES pressure?

1. fatty meal

2. chocolate

3. coffee/tea/cola

what medications/other drugs decr LES pressure? x 2 things

ethanol and nicotine

what 4 foods are direct esophageal irritants?

1. coffee

2. orange juice

3. spicy foods

4. tomato juice

what meds/drugs are direct esophageal irritants? x 3 things

1. aspirin

2. other NSAIDs

3. cigarette smoke

what are the 4 typical s/sx of GERD?

when are these often worse?

1. “heartburn” felt in sternum

2. water brash (hypersalivation)

3. belching

4. regurgitation w/w/o nausea

worse when supine

what are 7 more severe s/sx of GERD?

1. continual pain

2. dysphagia, odynophagia

3. vomiting acid in sleep

4. choking, bleeding

5. unexplained weight loss

what are some atypical s/sx of GERD? x 6 things

1. non-allergic asthma

2. chronic cough

3. hoarseness

4. laryngitis

5. chest pain

   1. dental erosions

what can chronic GERD cause ? x 5 things

1. reflux espohagitis

2. erosive esophagitis

3. esophageal strictures

4. barrett’s esophagus

5. adenocarcinoma

what is Barrett’s esophagus?

what kinds of new cells are there?

what could this develop into?

metaplasia due to chronic exposure to gastric acid

replaced goblet/mucous cells are more tolerant of acid, but more likely to develop into adenocarcinoma

what do we need to monitor pts with Barrett’s esophagus for ?

no development of esophageal cancer

what is peptic ulcer disease? PUD

how severe is this?

injury to the mucosa of the stomach, duodenum, espohagus

slight mucosal injury to severe ulceration w/ bleeding

what is PUD caused by?

increase in aggressive factors that injure the mucosa relative to defense factors protecting it

what is the most common cause of PUD?

what are other common causes ? x 3 things

H. pylori infection

1. NSAIDS

2. corticosteroids

3. increased risk by smoking

what helps H. pylori move below the mucosal surface to colonize the gastric epithelium and lead to PUD?

flagella

how does H. pylori infection lead to PUD? x 4 steps

1. disrupts mucus layer

2. neuralizes pH, mucin de-gels

3. releases enzymes and toxins

4. adheres to gastric epithelium

what enzyme does H. pylori release and what does it do?

what is the effect on the body?

urease enzyme

converts urea to CO2 and ammonia

this neutralizes stomach acid and irritates/injures the mucosa

H. pylori also promotes an _____ reaction which causes further tissue injury

inflammatory reaction

mucosal disruption and tissue injury by H. pylori is the eventual site of _____ and then ______.

erosion and ulcer formation

in what ways are H. pylori associated with gastric cancer? x 3 things

1. inhibits apoptosis of its gastric pit cells- inhibits cell turnover and healing

2. chronic inflammation → incr risk of cancer

3. some produce CagA that degrade p53 proteins (tumor suppressors)

what process does H. pylori require in order to move through the mucus layer to get to epithelial cells?

under what pH conditions does this occur?

mucin de-gels

increased pH

in the case of gel + low/acid pH, what is the movement pattern of H. pylori?

they cannot move

what are 3 ways H. pylori infection is dx?

which is the gold standard?

1. biopsy via endoscopy

2. breath test → non-invasive and reliable

3. serum antibody → not recommended

biopsy via endoscopy is gold standard

what does H. pylori breath test take advantage of ?

1. release of urease

2. carbon 12 and 13 are stable isotopes

what is the process of the breath test for H. pylori?

1. if H. pylori is present, 13 C-urea is broken into 13CO2 and NH3

2. the 13CO2 is absorbed and travels to lungs/breathed out

3. pre and post ratios of 13CO2 to 12CO2 is compared

4. if there is more 13 CO2 than 12CO2, the test is POSITIVE for H. pylori (ratio is increased)

with what types of NSAID use/therapy is PUD more likely?

long-term and/or high-dose therapy

what are 3 ways that NSAIDs can cause PUD?

1. cause topical injury to gastric mucosa

2. promote incr neutrophil adherence to vascular endothelium → ROS/protease damage

3. inhibiting beneficial prostaglandins

NSAIDs inhibit beneficial prostaglandins that can cause what 4 things associated with PUD?

1. decr submucosal blood flow- ischemia

2. decr mucosal proliferation

3. decr production of mucus and HCO3-/bicarb

   1. incr secretion of gastric acid and pepsin

what are 2 major risk factors for NSAID induced PUD?

corticosteroids and cigarette smoking

do all hospitalized pts need stress ulcer prophylaxis?

no, no evidence to support this

what is the def of populations who shouldn’t receive stress ulcer prophylaxis?

hemodynamically stable patients admitted to general-care floors

what are some presentation sx of PUD? x 4 things

1. epigastric pain

2. nausea

3. asymptomatic

4. GI bleed

what is gastric pain?

pain aggravated or precipitated by food

what is duodenal pain?

pain occuring 1-3 hrs after a meal, and relieved by food

what are 3 PUD ‘alarm sx’?

1. bleeding shown as black stools or hematemesis

2. perforation → upper abdominal pain w radiation to back

3. obstruction → N/V, abdominal distension

what are alarm sx an indication for?

emergency medical care