Flashcards in GI Physiology Deck (41):
GI physiology in order
Mouth -> Pharynx (back of throat) -> Oesophagus -> Stomach -> Small intestine (split into 3 regions, duodenum, jejunum, ileum) -> Large intestine (colon) -> Rectum -> Anus
- Salivary glands
- Secrete amylase and lipase
Produce mucin (glycoprotein) for lubrication
- 3 sets of glands = sublingual, submandibular and parotid glands (secrete amylase)
Nerves involved in swallowing
Trigeminal, facia, glossopharyngeal, vagus, spinal accessory, and hypoglossal nerves
Oesophageal sphincter is unable to prevent acid reflux which damages cells and turns them into cancerous, columnar cells, so we say Barrett's disease can progress to adenocarcinoma
Gastric cell types
- Mucous cells = secrete mucus
- Chief cells
- Parietal cells
- Found in the antrum in the stomach
- Secrete gastrin which is used in acid production
- Found in fundus in the body
- Secretes pepsinogen and lipase
- Also known as oxyntic cells
- Found in fundus in the body
- Pump out HCl
- Inactive from of pepsin
- Also known as a zymogen
How is pepsinogen converted to pepsin?
- Acid cleaves pepsinogen to produce pepsin
- So, pepsinogen is activated by HCl
- Pepsin is a protease which means when more pepsinogen is produced, pepsin acts on it to produce more pepsin via positive feedback
- This is achieved by removing 44 amino acids to activate pepsinogen into pepsin
Converts short chain triglycerides into monoglycerides
How do we secrete acid?
1. Via the parietal (oxyntic) cells = triggers (e.g. smell) release ACh which binds to parietal cells and releases HCl
2. G-cells produce gastrin which binds to parietal cells and also releases HCl
3. When food enters the stomach, there is stretching/distension which releases histamine which triggers the release of acid
H2 receptor antagonists
These drugs bind to the H2 receptor so that histamine cannot bind and this releases acid secretion
- Cimetidine and Ranitidine
Proton pump inhibitors
- Irreversibly bind to -SH groups in proton pump
- Unable to pump out H+
- Stop acid production
How do we get H+?
- Enzyme carbonic anhydrase combines CO2 and H2O into carbonic acid and then splits that into bicarbonate and protons
- This reaction happens inside parietal cells
What prevents the stomach from digesting itself?
Protease is secreted as a zymogen (inactivated form) known as pepsinogen
Why does the stomach not suffer from 1st or 2nd degree burns?
1. Mucus in foveolar cells = mucus is alkaline so it neutralises HCl
2. Tight junctions = lock epithelial cells together so acid cannot penetrate
3. High cell turnover = cells are replaced from gastric pits every 2-3 days
What would happen if there was a breakdown in mucus barrier?
- Stomach cells are exposed to HCl = ulcers
- May progress to perforated ulcer if there is complete erosion though the GIT wall
- Allows food and bacteria to move into peritoneal cavity = may cause peritonitis or sepsis
What is Helicobacter pylori
Bacterium that infects the gastric mucosa and causes a breakdown in barrier efficiency, causing more ulcers
Treatment of Helicobacter pylori
2 antibiotics + 1 PPI
- Clarithromycin + Amoxicillin + Omeprazole
- Clarithromycin + Metronidazole + Omeprazole
Procedures to reduce food intake
1. Gastric sleeve = 70-80% of stomach removed
2. Gastric band = Limits food capacity + reduces calorie intake
3. Roux en Y bypass = allows food to bypass stomach and go straight to small intestine
How does food move along the small intestine?
- Circular muscles = contract to prevent movement backwards into small intestine
- Longitudinal muscles = contract to push food bolus along GIT
What is diarrhoea?
Diarrhoea is the excessive loss of fluid and ions
How do medicines work to prevent diarrhoea?
- Reduce function of longitudinal muscles so food is pushed along GIT very slowly and remains in small intestine for longer, so there is more opportunity for water and ions to be reabsorbed and so reduce diarrhoea.
- These drugs e.g. loperamide target the MP
Myenteric plexus (MP)
Layer containing nerves within intestine sandwiched between circular and longitudinal muscles
Bile acid synthesis
What are the different adaptations of the small intestine?
1. Large SA = plicae > villi > microvilli = absorption
2. Thin epithelium = 1 cell thick for easier absorption
3. Digestive enzymes than convert non-absorbable macromolecules into absorbable smaller molecules
Cells of the small intestine
How is glucose transported into SI?
Via the SGLT1 transporter which is:
- Na+ dependent as Na+ absorbs glucose
- Glucose is polar and cannot penetrate lipid bilayer so a transporter is needed
How is fructose transported into SI?
Via the GLUT5 transporter
- No need for Na+
How is protein transported into SI?
Proteins are macromolecules that cannot be absorbed so they must be digested into smaller peptides and amino acids
- Peptides are transported by PepT1
- Amino acids are transported by several different systems
Carbohydrate digestion by sucrase
Sucrose = glucose + fructose
Carbohydrate digestion by lactase
Lactose = glucose + galactose
Carbohydrate digestion by maltase
Maltose = glucose + glucose
List of drugs absorbed by the PepT1 transporter
Cephalosporins; Penicillins; Enalapril; α-Methlydopa-phenylalanine; Val-acyclovir
These have the opposite effect pf uptake transporters, and pump out molecules back into gut lumen
- P-glycoprotein (P-gp)
- Breast cancer resistance protein (BCRP)
Efflux transporters are the reason why anti-cancer drugs are not given orally
List of drugs pumped out by P-gp
- HIV PI (Indinavir)
- Immunosupressants (CsA; Tacrolimus)
- Antibiotics (Erythromycin)
- Cardiotonics (Digoxin; Quinidine)
- Anti-cancer agents (Verapamil; Quinidine; Imatinib)
What happens when you give oral anti-caner drugs and efflux blockers at the same time?
Increases AUC but also increases toxicity
Examples of efflux blockers
Valspodar and VX-710