Pathophysiology of the stomach- exam 3

What can cause loss of intrinsic factor (leading to pernicious anemia)?

1) Gastric resection. 2) autoimmune gastritis, antibodies against parietal cells which produces gastric intrinsic factor. 3) Chronic gastritic atrohpy, immune reaction against parietal cells. Lose ability to secrete acids and make intrinsic factors.

What factors contribute to activating the parietal cells to secrete protons/intrinsic factor?

Acetylcholamine, Histamines, Gastrin hormone.

What is intrinsic factor?

Also known as gastric intrinsic factor, is a glycoprotein produced by the parietal cells of the stomach and is necessary for absorption of vitamin B12. Important for DNA synthesis and production of red blood cells. Travels down the small intestines for vitamin B12 absorption.

Anticholenergic definition

An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. Vagus nerve controls stomach motility and acetycholine is a major contributer to vagus control.

Pernicious anemia

Anemia related to insufficient intrinsic factor, leading to insufficient absorption of vitamin B12 and thus insufficient formation of red blood cells, and resulting in anemia.

Causes of gastroperesis

Anti cholenergic drugs- atropine, psychotropic drugs. Narcotic analgesics (opiods)-morphine, demoral. Constipation. Constipation causes blockage (gastroperesis) and increase in pressure that can lead to distention in parts of GI tract and cause diverticula from pressure increase and blockage.

Treatments of Ulcer

Antibiotics to eradicate H pylori. Neutralize acid with magnesium or calcium salts, NaHCO3. Decrease acid production using H2 receptor blockers, H/K pump inhibitors. Increase mucous production- increases protection. Replace mucous barrier with sucralfate- gel coating, or introduce synthetic prostaglandin.

Dumping syndrome?

Back up contents, pyloric sphincter is constricted but relaxes periodically, and opens extremely wide, and stomach contents dump into the small intestines (including excess acid) and causes problems in the small intestines ( irritation of lining, ulceration, may flush through small intestines very quickly leading to diarrhea.

What does H plyori cause?

Bacterial cause-root cause of number of forms of acid-peptic disease, including duodenal ulcer, gastric ulcer, and gastritis.

Inhibiting proton secretion of parietal cells

Block proton pumps ( proton pump inhibitor) and histamine or histamine type 2 receptor blockers. Could also result in autoimmune destruction of parietal cells, which would reduce proton secretion.

Acetocholine

Can directly bind to aceytocholamine recepter on parietal cell to stimulate secretion of protons. This is a neuronal input via neurocrine. Indirectly stimulates ECL to release histamine and cause increase in proton secretion in parietal cell.

Gastric obstruction

Can occur from the inside (tumor, or foreign body) GI tumors are fairly present due to the highly mitotic nature of GI. Can also occur from the outside pushing in, including tumors (anything growing in abdomen pushing on the GI). Pyloric sphincter is under neuro control ( parasympathetic control) and opens/closes when needed. Loss of vagal tone or diabetes can lead to obstruction of pyloric sphincter. Pylorus can be scarred by acid or have a congenital defect causing stenosis or constriction.

Stages in Digestion process

Cephalic phase-neural control, increases salivation through thought of food, Gastric phase-acidify, intestinal phase- digestion. Intestinal compartment will determine how much chyme is allowed to enter through pyloric sphincter from stomach.

Zollinger-Ellison syndrome

Condition of a gastrin secreting tumor. Results in elevated plasma gastrin levels. We can diagnose this by the secretin test.

Duodenal response to increased acidity

During intestinal phase, S cells in intestines release secretin and are stimulated by increased acidity in the small intestines. This decreases proton secretion and motility of stomach, to slow things down by providing feedback.

ECL cell

Enterochromaffin-like cell, Directly stimulates proton secretion from parietal cells through secretion of histamine (which stimulates proton secretion) in response to Acetocholine (neuronal control) and gastrin (hormonal control). Indirect control

Things that increase acid secretion- which can cause ulcers

Ethanol, caffeine, gastrin secreting tumor (gastrinoma),

Gastric phase

Food contents start stimulating parietal cells and G cells, more release of protons, positive feedback.

As food enters the stomach

Food undergoes mechanical as well as chemical changes to render it suitable for absorption and assimilation. Beginning of protein digestion due to acidic environment and pepsin that is activated by acidity.

Loss of intrinsic factor

Gastric intrinsic factor from parietal cells in stomach is important for uptake of vitamin B12. Lack of intrinsic factor leads to lack of red blood cell production- pernicious anemia.

G cell

Gastrin secreting cell- releases gastrin into circulation and binds directly to gastrin receptor on parietal cells to cause proton secretion. This is a hormonal input via endocrine system. Can also indirectly stimulate ECL to release histamine and cause increase in proton secretion in parietal cell.

Most common cause of stomach gastric disorders leading to ulcers

Helicobacter pylori, which damages the mucosal protective layer and causes inflammation that increases acid secretion.

What happens to the negative feedback of the G cell if there are no parietal cells (or low number)?

If there are low numbers of parietal cells, proton secretion is lowered, which will not stimulate D cells to produce somatostatin to turn off G cells. Therefore, there will be no negative feedback and gastrin will constantly be produced, resulting in an increase of gastrin.

Causes of ulcer formation in stomach

Increased gastrin, which results in an increase in acid. H pylori, which increases acidity while simultaneously decreasing mucosal protection of stomach. NSAIDS and stress, which both decrease the mucosal protection of the stomach.

What is gastritis and what causes it?

Inflammation of the stomach- H pylori, NSAIDs, stress. Alcohol, caffeine, radiation, Chron's disease, reflux of bile and/or pancreatic secretions, chronic excessive vomiting (bulemia).

Sphincters surrounding stomach

LES between esophagus and beginning of stomach. and pyloric sphincter between bottom of stomach to intestines.

GI problems commonly lead to

Lethargy, fatigue, failure to thrive in congenital issues

Motility of stomach

Many muscular layers and innervation.

Gastric cancer

Most common in people of asian descent (some genetic descents more susceptible). Caused by H pylori, constant gastric irritants including alcohol, caffeine, smoked fish, capsaicin, radiation.

Timing of ulcer symptoms if duodenal ulcer

Pain occurs much later after eating, when chyme and acid enters duodenum. Pain occurs about several hours after eating.

Signs and symptoms of Peptic ulcer disease

Pain, Nausea, Hematemesis -Vomiting red blood if acute or digested blood if chronic. Dark Tarry stools (Melana) due to blood in stools (brighter blood-fresher blood, closer to point of exit, and vice versa) changes in appetite, perforation of gastric or duodenal wall: air in peritoneal cavity visible on xray.

Gastroperesis

Paralysis of stomach, vagus nerve dysfunction- problems with acetycholine release or CNS control (since one of the primary regulators of gastric motility is the ability to squeeze/macerate the food as a result of vagus nerve stimulation) Diabetes and other nervous.

Secretions of stomach

Parietal cells secrete protons- HCL and intrinsic factor. Chief cells secrete pepsinogen, which is the inactive form of pepsin. Pepsin is activated by the acidic environment of the stomach. Pepsin is an enzyme that chews up proteins. G cells secrete gastrin to control the ability of the parietal cells to secrete HCL.

Decreased mucosal protection

Prostaglandins increase mucous secretion in the stomach. Prostaglandins also cause inflammation and pain in muscles and joints for various reasons. NSAIDs work by reducing the production of prostaglandins, thus decreasing the mucosal protective layer. This causes ulcers. Alcohol and tobacco also decrease mucous secretion.

Intrinsic factor of stomach

Released by parietal cells, travels down to the small intestine and enables vitamin B12 to be uptaken by the from the small intestines. Vitamin B12 is necessary for DNA replication and red blood cell production. Can live without the mechanical functions of the stomach, but not without the intrinsic factor- must supplement vitamin B12.

Parietal cell

Secretes protons in stomach through H/K pump, and makes intrinsic factors.

Turning the G cell off

Somatostatin (d cell) secreting cell. This needs to be off for gastrin secretion. Low pH is a major stimulator for somatostatin release. Negative feedback of proton production. More protons= produce somatostatin= turn off G cell.

What are inhibitory factors to the parietal cells?

Somatostatin, prostaglandins, secretin and VIP vasointestinal peptide (from intestines, telling stomach to slow down.)

Gastric obstruction effects on stomach

Stresses underlying muscle layers, can lead to loss of motility and gastric paralysis.

Responsibility of Secretin in intestines

Tells pancreas to release bicarbonate to neutralize acid in the intestines. We do not want such a low pH in intestines. Secretin also activates liver to release bicarbonate to neutralize. Lack of secretin can lead to ulcerations in the intestines.

Gastric pathologies

Ulcer- caused by a loss or disruption of mucosal protection (mucus barrier is very important for protection) and/or excess acid secretion. Loss of intrinsic factor- causing pernicious anemia. Outlet obstruction- pyloric stenosis (can be caused by congenital problems, loss of neuronal control, cause pyloric sphincter to be constricted). Loss of gastric churning-gastric paresis. Gastritis. Gastric carcinoma. H plyori

What is the secretin test?

Used to diagnose gastrin secreting tumors. Works by testing the feedback of secretin. Give secretin- normally, this should tell pancreas to release bicarbonate and neutralize acid and slightly decrease or no change in gastrin. If you give secretin to someone with a gastrin secreting tumor (Such as in Zollinger-ellison syndrome) there will be a large paradoxical INCREASE in gastrin.

Turning the G cell on

Vagus nerve can stimulate gastrin cell directly to release gastrin (cephalic phase). Protein digestion (during gastric phase)

Timing of ulcer symptoms if gastric ulcer

When food arrives in stomach, (few seconds after eating) acid is secreted leading to pain at the time of eating. ( Usually tells us gastric, maybe esophageal)

Stress ulcers

caused by severe physiological stress-burns, shock, sepsis, trauma. ANY Decreases in gastric blood flow decreases mucous protection. Stressed patients are given anti ulcer medications prophylactically. (Ex. Proton pump inhibitors- want to decrease acidity since mucous is decreased)