Lecture 8 Flashcards
What is saliva production stimulated by?
Sight, smell of food, inhibition during sleep, stimulated by acid in oes
What are the contents of saliva?
Electrolytes, high HCO3-, mucins, salivary enzymes, lactoferrin, lysozyme
What is xerostomia?
Loss of saliva.
What are the symptoms of xerostomia?
Drying of mouth, oral infections, dental decay, loss of taste (saliva irrigates taste buds)
What can lead to decrease of salivary secretion?
Sjogrens disease, which causes loss of salivary secretion because of chronic inflammation of salivary glands. Also decreased by anticholenergic drugs.
What are the major roles of the stomach?
- Acts as a reservoir for food during initial digestion, allowing food to pass through in controlled amounts of semi-liquid paste
- Adjusts the osmolality of contents before they enter the small intestine
- Antrum acts as a grinding mill, pylorus regulates size of particles that can pass through to the duodenum
- Secretion of acid
- Other secretions: intrinsic factor, pepsinogen, mucus, prostaglandins, HCO3-
What does the control of gastric emptying require?
Intact antrum, pylorus, and duodenum for normal function
Normal vagal function to coordinate activity
Normal hormonal function
What are the 4 steps that occur in the stomach during food digestion?
1) Relaxation of fundus (vagovagal reflex)
2) Contraction of body and antrum
3) Pylorus contracts
4) Mixing by retropulsion
Define neurotransmitter
Molecules that transmits a signal from one neuron to another
Define autocrine
Molecule released by a cell that targets itself
Define paracrine
Molecule released by a cell that targets adjacent cells
Define endocrine
Molecule released by endocrine cells into circulation to target distant cells
What are the two types of abnormal gastric emptying?
Rapid and delayed
What can cause rapid gastric emptying?
- After gastric surgery, dumping syndrome can occur.
- Drugs that speed up gastric emptying - prokinetics
Give an example of a prokinetic drug
Metoclopramide - release of ACh at myenteric plexus
What are the symptoms of dumping syndrome?
Nausea, vomiting, cramping, diarrhoea
What happens in dumping syndrome?
Food moves too quickly from stomach into duodenum and so are not completely digested as the antrum and pylorus are removed. Undigested food particles result in a hyperosmolar chyme in small bowel. Rapid fluid shift into gut causes intestinal distension which leads to pain. Osmotic effect results in diarrhoea.
What can cause delayed gastric emptying?
Diabetic gastroparesis, drugs that delay gastric emptying
What is diabetic gastroparesis due to? What does it lead to?
Due to autonomic neuropathy. Leads to variable rate of glucose absorption. Upper abdominal discomfort.
Give an example of a drug that delays gastric emptying
Anticholinergic drugs
What is the role of gastric acid?
Sterilise the stomach
Limited role in digestion (denatures proteins)
Helps in absorption of B12 and Fe
What is the only bacteria living in the stomach?
H. pylori
What does achlorydia mean?
Absent or low gastric acid.
- May be some bacterial overgrowth
- Absorption of Fe slightly decreased
- Increased risk of enteric infections
Describe the ion exchange occurring within parietal cells.
- H+K+ATPase actively pumps H+ out of cell and into stomach and K+ leaks into the cell.
- HCO3- is formed from action of carbonic anhydrase (H2O + CO2 H+ + HCO3-)
- Cl- enters the cell in exchange for HCO3-, which moves out to the bloodstream. The Cl- then diffuses across the cell into the stomach
What is the pH of HCl? What is the pH of the lumen of the stomach? What accounts for this difference?
pH of HCl: 0.8
pH of stomach: 1.5-2.0
Dilution with other secretions and buffering with HCO3-
Describe the general features of the 24 hour profile of stomach pH
Buffering with meals to 5-6 for 1/2 to 1 hour. pH gradually falling during night (often 1.5 from 2am to 6am)
What features are present to protect the gastric mucosa from acid?
Mucous layer
Bicarbonate secretion
This protection is unique to the stomach
Why is ATP needed for exchange of H+ and K+?
H+ is moved against its concentration gradient
How do canaliculi of the parietal cell aid in ion exchange?
At rest, parietal cell has canaliculi, which when acitvated, bind with the tubulovesicles and H+/K+ ATPase pumps release H+ into lumen
What is another name for H+K+ATPase?
Proton pump
What are the three phases of gastric digestion?
Cephalic phase
Gastric phase
Intestinal phase
What is involved in the cephalic phase of gastric activity?
Thought, sight, smell of food
Mediated via vagus nerve through ACh, which directly stimulates parietal cells to release HCl, stimulates ECL cells to release histamine (stimulates parietal cells), stimulates G cells to release gastrin (stimulates parietal and ECL cells)
What is ACh released by?
Vagus nerve and enteric neurones
What occurs in the gastric phase of gastric activity?
Distension of both body and antrum causes acid secretion mediated largely by the vagus nerve. Protein in the antrum (amino acids and peptides) stimulates G-cells leading to gastrin release.
What occurs during the intestinal phase of gastric activity?
Inhibition of acid secretion
How does inhibition of acid secretion and gastric emptying become initiated?
- Low pH in antrum causes release of somatostatin from D cells, which inhibit gastrin.
- Acid in duodenum stimulates secretin, which inhibits gastric acid and gastric emptying and stimulates pancreatic and bile duct HCO3- secretion
- Partially digested fats and proteins in duodenum stimulate CCK, which inhibits gastric acid and gastric emptying. Slows down stomach as duodenum is full of fat and acid. Also stimulates release of pancreatic enzymes and gallbladder contraction to release bile for absorption of fats
What are the two types of abnormal gastric acid secretion?
Increased
Decreased
What causes increased gastric acid secretion?
H. pylori gastritis
Tumours of gastrin (gastrinoma)
What leads to decreased gastric acid secretion?
- Loss of parietal cell - atrophy and inflammation - pernicious anaemia
- Vagotomy (division of vagus nerve)
- Drugs: proton pump inhibitors and histamine antagonists
- Gastric surgery
What are the other gastric secretions?
Pepsinogen
Intrinsic factor
Prostaglandins
What is pepsinogen? What happens to it in the stomach? What functions does it perform?
Pro-enzyme of pepsin secreted from gastric chief cells. Cleaved in acid to form pepsin. Pepsin hydrolyses proteins at aspartic amino acids. Roles in early digestion of collagen. Hydrolysed proteins more active stimulus for gastrin.
When is the pepsinogen not activated? How is this useful for preventing rebleeding from ulcers?
pH>4
Acute inhibition of acid secretion helps prevent rebleeding from ulcers perhaps because the adherent clot is not dissolved by pepsin if pH>4
What are prostaglandins?
Lipid molecules that protect and repair the gastric mucosa
What does ECL cell stand for?
Enterochromaffin-like
What type of activity do histamine, gastrin, and somatostatin display?
Histamine: Paracrine
Gastrin: Endocrine
Somatostatin: Endo and paracrine
Describe the mode of infection of H.pylori
Only infects humans. Person to person transmission must happen.
What region of the stomach does H. pylori prefer?
Antrum
What happens after H. pylori infection?
Child is infected by H. pylori, which sits in the antrum. Invades mucosa and causes inflammation. Occurs over a long period of time. Most people who present with complications from peptic ulcer disease are adults. Inflammation of stomach leads to gastritis.
When is the infection by H. pylori acquired? What does it lead to?
Acquired in childhood and leads to life-long infection and chronic gastritis in all infected individuals
What are the 4 diseases that H. pylori can cause?
Gastritis
Peptic ulcer disease
Gastric cancer
Gastric MALToma
What is gastritis?
Non-specific inflammatory response in the mucosa