W1.1_Gut Physiology Flashcards
Contrast pharmacokinetics and pharmacodynamics.
- Pharmacokinetics (PK): what body does to drug (dose regimen <-> plasma concentration)
- Pharmacodynamics (PD): what drug does to the body (site of action <-> effects)
Define ADME and give the most related organ(s) in each process.
Absorption (GI tract), Distribution (circulatory), Metabolism (liver), Excretion (kidneys)
What are the functions of GI system (3)?
- Digestion of food (through mechanical and chemical breakdown of food into small molecules)
- Absorption of nutrients and drugs (absorbed into circulatory system for distribution throughout the body, similar principles apply for drugs)
- Elimination
What are the functions of mouth (2) and tongue (1)? Relate them to the absorption of buccal/sublingual tablets.
- Physical breakdown of food particles through mastication in teeth
- Chemical breakdown through salivary amylase in saliva, secreted in salivary glands (break down starch into maltose)
- Tongue rolls food into bolus and facilitates swallowing
- Transmucosal tablets (buccal/sublingual): possible through epithelial mucosa in sublingual and buccal mucosa
What are the functions of oesophagus (2) and epiglottis (1)? How does food enter the stomach?
- Transport of food to stomach
- Conduct peristalsis (waves of muscle contraction that move food forward, can be seen throughout the whole GI tract)
- Epiglottis: folds backwards to cover entrance of larynx while swallowing to prevent food to enter the trachea
- Entry to stomach via sphincter
What are the functions/processes of stomach (5)? How does food move into the small intestine? Define and relate gastric emptying to drug absorption.
- Secretion of gastric juices for chemical digestion
- Mechanical breakdown of food
- Mixing of food and gastric juices (digestive enzymes + HCl controlled by vagus nerve and hormone gastrin) to form chyme
- Initiates digestion of proteins (pepsinogen converted into pepsin by HCl to convert protein chains into peptones, chymosin converts caseinogen to casein) and digestion of triglycerides
- Mucus coating lubricates and protects epithelial surface against pepsin
- Moving food to small intestine via sphincter
- Gastric emptying: great variability in time depending on meal properties and population
- Presence of food in stomach delays gastric emptying -> lowers drug absorption rate
What are the four types of cells present in gastric gland? What are their functions?
- Surface mucous cells + neck cells: secrete bicarbonate and gastric mucus
- Parietal cells: produce HCl (activate digestive enzymes by achieving pH≈2) and intrinsic factor (necessary for absorption of vitamin B12)
- Chief cells: secrete pepsinogen and gastric lipase (converts triglycerides into fatty acids and diglycerides)
What are the three sections of small intestine? What are the different processes/functions of small intestine (6)?
- Duodenum, jejunum, ileum
- Completes digestion of nutrients in chyme
–> Digestion of carbohydrates (pancreatic amylase, maltase (maltose to glucose), lactase (lactose to glucose and galactose), sucrase (sucrose to glucose and fructose)
–> Digestion of lipids (pancreatic lipase, intestinal lipase (lipids into fatty acids and glycerol), bile (emulsification of fat into small lipid droplets) -> micelle formation for transport of lipids
–> Digestion of proteins (pancreatic trypsin (peptones into peptides), intestinal peptidase (peptides into amino acids)) - Major site of absorption of different nutrients (large surface area and high perfusion, exposure to enzymes and solubilisers, receives secretion from liver and pancreas)
–> Water-soluble nutrients: through epithelial cells into the capillaries and carried through hepatic portal vein
–> Lipid-soluble nutrients: through epithelial cells into lacteals to the lymphatic vessels - Major site of absorption of orally administered drugs
–> Acidic drugs: epithelial cells of stomach as it remains unionised
–> Alkaline drugs: pass through sphincter to small intestine and be absorbed - Absorption of water: most absorbed in small intestine and remaining ones in large intestine (through osmosis after absorption of Na+ ions to create an osmotic gradient)
- Site of first-pass metabolism of drugs via CYP3A4
- Movement of food residues to large intestine
Give the basic structure of a villi. How does the nature of small intestine favour absorption? Describe the absorption process of oral drugs in small intestine.
- Structure: mucosa (epithelium + connective tissue + blood capillaries + lacteal) + submucosa + serosa
- Villi: extend from luminal surface of small intestine
- Microvilli: brush border
∴ Highly convoluted, circular folds, villi, microvilli -> increase surface area for absorption - Oral drugs: dissolved drug is absorbed across gut wall mainly via passive diffusion (other routes: paracellular/transport-facilitated) -> enterocytes contain metabolic enzymes for intestinal first-pass -> blood perfusing intestine goes into liver via hepatic portal vein -> goes into systemic circulation
Briefly explain how coeliac disease can reduce absorption in small intestine.
chronic autoimmune disorder of small intestine (inflammation triggered by consumption of gluten -> atrophy of villi in small intestinal epithelium)
What does the liver do? What does it secrete?
- Main site of metabolism of xenobiotics (any drugs/toxins)
- Secretes bile (important for digestion of lipids), enters duodenum via hepatic duct, stored in gallbladder between meals
Explain the three components in pancreatic juice.
- Secretes proteolytic enzymes (trypsin/chymotrypsin) for protein digestion
- Lipase for digestion of lipids
- HCO3- (bicarbonate) for neutralising stomach acid
What happens in the large intestine (3)? How are faecal waste eliminated?
- Reabsorption of remaining water and salts from chyme
- Absorption of remaining minimal drug molecules
- Mixing and propulsion of contents
- Indigestible residue and liquid are eliminated as faecal waste (stool pushes against muscular walls of rectum -> muscular action of sphincter forces it out)
Explain the colonic microbiota and the gut-brain axis.
- Colonic microbiota: distal intestine populated by large number of bacteria that contribute to normal digestion (ferment carbohydrate and protein escaping digestion into absorbable energy) and metabolise some drugs/other xenobiotics
- Gut-Brain Axis (brain influencing GI physiology/motility/mucin production, GI influencing brain/behaviour/mood)
