Gastrointestinal Anatomy and Physiology Underpinning Pathology and Therapeutics 2 Flashcards
How are proteins digested/absorbed (Acidic liquefaction of meal) (8)
- Starts in the stomach, and continues in the small intestine.
- zymogenic chief cells of the stomach mucosa release the pro-enzyme pepsinogen
- pepsinogen > active Pepsin (enzyme).
- Pepsin (enzyme) has an acid pH optimum of 1.8 – 3.5; digests proteins to peptides.
- Peptides induce pyloric antrum to secrete gastrin (hormone).
6.Gastrin (from G-cells) evokes Histamine release from ECL-cells, which stimulates Parietal cells (acid-producing) - Gastrin (from G-cells) evokes Bicarbonate-laden mucus secretion from superficial epithelial cells to protect against digestive acid/proteolysis.
8.(Secretion is also mediated by prostaglandins).
How are carbohydrates digested/absorbed (4)
- Starts in the mouth with salivary amylase until stopped by gastric pH
- Bulk carb digestion occurs in the upper small intestine by pancreatic amylase and finally by intestinal disaccharidases (maltase, sucrase, lactase etc).
- probiotics ferment un-digested starch (fibre) forming short-chain fatty acids, e.g. butyrate:
- Benefits colonocytes; is anti-inflammatory & anti-cancerous.
What is the acute availability of glucose for direct absorption to buccal vasculature relevant to
relevant to emergency hypoglycaemic treatment.
What do congenital or temporary deficiencies in disaccharidases (M, S, L) cause (3)
- accumulation of undigested disaccharides
- pass unabsorbed into the colon
- causing osmotic diarrhoea.
What happens when one lacks lactase (3)
- unable to split lactose into β-glucose and galactose
- lactose intolerance due to bacterial ferment
- causing wind (flatus) and diarrhoea.
How are fats digested/absorbed (6)
- Dietary lipids are primarily triglycerides (TG); cholesterol, its esters; and phospholipids.
- In the Small Intestine by pancreatic lipase, emulsification by bile salts is essential to increase SA for lipase activity and fat-soluble vitamin absorption (A D E K).
- Monoglycerides (MG) and free Fatty acids (FFA) readily partitioned into lipid plasma membrane of microvilli (brush border) of Small Intestine (SI);
- Bile salts also resorbed, recycled to liver via distal ileum to hepatic portal vein (HPV) for reuse (enterohepatic circulation).
- Cholesterol esterase hydrolysis and bile emulsification required for cholesterol uptake.
- Gut cells create lipoprotein micelles (chylomicrons) from absorbed fats; these are transported via lacteals (lymphatics) to general circulation at the subclavian vein and via HPV to liver.
What is the lipase inhibitor orlestat used for (2)
- used to treat obesity.
- Need to be combined with low-fat diet to avoid undigested fat, wind (flatus), diarrhoea and (if long term) deficiencies in fat-sol vitamin absorption (A D E K).
How may ileal diseases such as Crohn’s disease lead to malabsorption (3)
- failed resorption of bile
- leading to irritation of colon
- creating a laxative action (diarrhoea).
What may diseases of the gall bladder/pancreas reduce fat absorption do (2)
- reduce fat absorption by 50-70% (to 30-50%);
- resulting fatty stools are pale, soft, particularly foul-smelling (steatorrhea).
How are nutrients absorbed (4)
- 90% of substances (incl water) are absorbed at the small intestine.
- LI (colon) important site for absorption of water, electrolytes & bacterial metabolites (Vitamin B12; short chain fatty acids from fibre fermentation).
- There are active or facilitated transporters for amino acids, mono-saccharides and electrolytes.
- Sodium-dependent transport (AA & sugars) promotes the passive movement of water.
How are drugs absorbed (4)
- Gastic mucosa which for drugs like aspirin that ionises inside the cell leading to toxic concentration
- Mesenteric blood from SI (carries ionisable substances and small chylomicrons); feeds hepatic portal vein (HPV); ensures pre-systemic (first-pass) metabolism by liver.
- IN CONTRAST: Pro-drugs typically require first-pass metabolism to release active form.
- Alternative drug administration routes (to oral/ingestion): Buccal/sublingual (eg GTN); Transdermal (eg Glyceryl Trinitrate, GTN, hyoscine (scopolamine), sex hormones), Parenteral (iv, im, sc)
How are disorders associates with the small/large intestine associated with malnutrition (2)
- 90% of substances (incl water) are absorbed at the small intestine.
- LI (colon) important site for absorption of water, electrolytes & bacterial metabolites (Vitamin B12; short chain fatty acids from fibre fermentation).
What is pharmacological therapies are used for passive movement of water by sodium transport
Oral rehydration therapy salts including glucose to promote water replacement.
What happens when Aspirin is absorbed by the gut mucosa (4)
- Aspirin: Is unionised (lipophilic) in gastric juice
- is readily absorbed by gastric mucosa
- ionises once inside cell; “ion-trapping” leads to toxic concentration.
- Contributes to ulcerogenic properties; because inhibits prostaglandin functions that sustain gut integrity.
What happens to first-pass metabolism in the elderly & those with liver disease (2)
- reduced
- You may have to reduce the dose to avoid toxicity.
How is the absorption of drugs managed in patients with stomas (3)
- Ileal discharge (SI) is always fluid (has digestive secretions).
- Colonic discharge is normally low fluid (paste).
- The management of patients with stomas needs to consider enhanced fluid discharge of ileostomas & reduced water resorption
What are the mouth digestive enzymes/hormones/factors (4)
- Amylase (Carbohydrate)
- Lipase
- IgA
- Lysozyme (defence)
What are the stomach digestive enzymes, hormones & factors: Sites of production & functions (6)
- Pepsinogen (zymogen) → Pepsin (Proteolytic “endopeptidase”)
- HCl (hydrolytic)
- Mucus (self defence against acid)
- Intrinsic factor (IF): Formed by acid producing parietal cells:
- IF Binds “extrinsic factor”, B12, a hematinic factor synth’ by intestinal microbes.
- B12-IF binds / absorbed by enterocytes of terminal ileum & colon.
What is the Liver (hepatocytes)/Gall bladder digestive enzymes/hormones/factors
Bile (Lipid sol)
What is the small intestine digestive enzyme/hormone/factor (1) sites of production & functions (1)
- Cholecystokinin / Pancreozyme (CCK-PZ)
- from I-cells
- stimulate gall bladder (bile) emptying
- stimulate pancreatic juice (digestive enzymes) secretion
What are the pancreas digestive enzymes, hormones & factors: Sites of production & functions (5)
- HCO3- bicarbonate (neutralize acid)
- Amylase (Carbs)
- Lipase (Lipids)
- Nuclease (Nucleotides)
- Zymogens (inactive) e.g. Trypsinogen (+HCl) → Trypsin (Peptidase)
What are the three phases regulating gastric acid secretion from Parietal cell
CEPHALIC PHASE - Sight, sound, smell, taste initiate digestive reflex
GASTRIC PHASE - Presence of food promotes digestive reflex
INTESTINAL PHASE - Negative feedback turns off gastric acid production
What is the function of gastric acid (7)
- Stimulation translocates Proton Pumps (H+/K+-ATPase) to Parietal cell membrane.
- 2-2.5L gastric acid solution produced per day.
- Kills bacteria.
- Aid in digestion/liquefaction of meal.
- Promotes protein digestion enzyme activation / pH optimum.
- Mucosal surfaces require protective bicarbonate and mucus.
- Ulceration injury; therapy aims to reduce erosive gastric acid secretions.
How is gastric acid secreted
HCl is released from Parietal cells by insertion of H/K-ATPase (Proton Pump) and K/Cl- exchangers in cell membrane
What chemical stimuli evoke Parietal cell HCl release (3) and what inhibits it (1)
- Histamine from Enterochromaffin cell (ECL) - stim Parietal cell HCl release via H2-Rs.
- Gastrin from G-cells via G-Rs - stim Parietal cell HCl release - directly and indirectly via ECL histamine (H2-Rs).
- Ach from Vagus (PsNS) via M-Rs - stim Parietal cell HCl release - directly and indirectly via ECL histamine (H2-Rs)
- Somatostatin from D-cells (stimulated by HCl and Vagus) inhibits Parietal cell activation.
What are the protective actions of prostaglandins (4)
- Prostaglandins PGE2 & PGI2 derived from AA by COX enzyme
- Inhibit Parietal cell HCL release
- Activate Goblet cell bicarbonate/mucus release - neutralise acid.
- Hence injurious effect of NSAIDs on gastric/duodenal mucosal integrity.
What does heartburn suggest (5)
- Upper GIT disorder
- GORD / GERD (Gastro (O)Esophageal Reflux Disease)
- Peptic Ulcer Disease (secondary to Helicobacter pylori or NSAID injury)
- Peptic ulcers - eroded area of mucosa - digested by gastric acid and enzymes - Common to Stomach & duodenum. May bleed if perforated.
- Possible sign of cancer.
What are the possible causes of peptic ulcers (5)
- Infection by Helicobacter Pylori
- Imbalance of HCl and mucus/bicarbonate - can damage mucosal layer.
- Stress – inhibitory to mucus/bicarbonate secretion.
- Smoking
- NSAIDs - inhibit protective effects of PGs
What is the danger of Helicobacter Pylori (H. Pylori) in peptic ulcers (4)
- typically asymptomatic
- increased ulcer risk
- disrupts mucin layer
- promotes gastrin-induced HCl secretion.
What are the treatments for peptic ulcers (4)
- Ant-acids: Mg or Al OH, (Gaviscon) - short-acting; neutralise HCl; raise pH to ~3
- PPIs: Omeprazole - well tolerated effective long-lasting
- H2 blockers (Cimetidine, Ranitidine) - now largely replaced by the PPI
- Potassium-competitive acid blockers - not currently licensed in UK (a new generation of PPIs)
How is exocrine pancreas digestive secretion into the lumen/duct achieved (2)
- Digestive juices - amylase, lipase, peptidase
- Protective - mucus and bicarbonate (secretory response to duodenal Secretin & CCK)
How is endocrine pancreas coordination of hormones into the blood achieved (4)
- Insulin – drives hypoglycaemic homeostasic response
- Glucagon – drives hyperglycaemic homeostasic response
- Gastrin - stim gut motility
- Somatostatin – from pancreas inhibits gastric secretions; also inhibits pancreatic secretions (insulin & glucagon).
How is control of Pancreatic Secretions achieved (3)
- Acid in duodenum → Secretin → Release of watery bicarb secretions from pancreas (that carries/washes pancreatic enzymes to duodenum).
- Fats in duodenum → CCK-PZ → Gall bladder (bile) & Pancreatic enzyme release.
- Duodenal distention → Vagal afferent → efferents (Ach) stim Pancreatic enzymes
