GI, Pancreas liver & colon

How does the enteric nervous system coordinate GI function?

WHAT: Intrinsic neural plexuses of the gut. HOW: Sensory neurons, interneurons and motor neurons coordinate smooth muscle and glands. WHY: Local digestion and motility can continue without constant cortical commands.

How do Auerbach and Meissner plexuses differ?

WHAT: Auerbach=myenteric; Meissner=submucosal. HOW: Myenteric between muscle layers controls motility; submucosal regulates secretion, absorption and blood flow. WHY: Specialized neural circuits control distinct gut functions.

How do parasympathetic and sympathetic signals affect the gut?

WHAT: Extrinsic autonomic modulation. HOW: Vagal ACh generally increases enteric activity; sympathetic NE often inhibits secretion/motility. WHY: GI function adjusts with feeding versus stress.

What is the difference between endocrine and paracrine GI signaling?

WHAT: Endocrine acts via blood; paracrine acts nearby. HOW: Gastrin travels in blood; ECL histamine diffuses to neighboring parietal cells. WHY: Local and systemic signals coordinate digestion.

How does gastrin stimulate gastric acid secretion?

WHAT: G-cell hormone in gastric antrum. HOW: Peptides and vagal GRP stimulate G cells; gastrin activates CCK-B pathways on ECL/parietal cells. WHY: Promotes protein digestion and mucosal growth.

Why does low gastric pH inhibit gastrin?

WHAT: Negative feedback for acid secretion. HOW: Acid increases D-cell somatostatin, inhibiting gastrin and acid pathways. WHY: Prevents uncontrolled gastric acidity.

Why can Zollinger–Ellison syndrome cause steatorrhea?

WHAT: Gastrin-secreting tumor. HOW: Excess gastrin → excess acid → low duodenal pH → pancreatic lipase inactivation. WHY: Fat becomes poorly digested and absorbed.

How does CCK coordinate digestion?

WHAT: Hormone from duodenal/jejunal I cells. HOW: Fatty acids and peptides → CCK → pancreatic enzymes, gallbladder contraction and slower gastric emptying. WHY: Provides time and digestive components for fats/proteins.

Why does CCK slow gastric emptying?

WHAT: Duodenal brake on gastric delivery. HOW: Nutrient sensing triggers CCK and neural reflexes, reducing stomach outflow. WHY: Fat digestion/absorption needs additional time.

How does secretin respond to acid in duodenum?

WHAT: S-cell hormone. HOW: Luminal H⁺ → secretin → pancreatic/biliary HCO₃⁻ secretion and reduced gastric acid drive. WHY: Neutralizes chyme to preserve enzyme function.

What does GIP do after a meal?

WHAT: Incretin from intestinal K cells. HOW: Luminal nutrients stimulate GIP; enhances glucose-dependent β-cell insulin secretion. WHY: Coordinates insulin release with nutrient absorption.

How does motilin regulate motility?

WHAT: Fasting gut hormone. HOW: Motilin cycles promote migrating motor complexes between meals. WHY: Clears residual food and bacteria during fasting.

What do circular and longitudinal GI muscles do?

WHAT: Two smooth-muscle layers. HOW: Circular contraction narrows lumen; longitudinal contraction shortens gut segment. WHY: Together create propulsion and mixing.

How are segmentation and peristalsis different?

WHAT: Mixing versus propulsion. HOW: Segmentation alternates local contractions; peristalsis coordinates contraction behind bolus with relaxation ahead. WHY: Allows nutrient contact and forward transit.

What is the physiological role of GI slow waves?

WHAT: Rhythmic membrane-potential oscillations. HOW: Interstitial cells of Cajal generate pacemaker oscillations; spikes/contraction occur if threshold reached. WHY: Coordinates possible contractions without each wave automatically contracting.

Why does chewing facilitate digestion?

WHAT: Mastication. HOW: Breaks particles, mixes saliva and forms bolus. WHY: Improves swallowing and increases digestive surface area.

How do the three stages of swallowing differ?

WHAT: Oral, pharyngeal and esophageal phases. HOW: Oral phase largely voluntary; pharyngeal reflex protects airway; esophageal peristalsis moves bolus. WHY: Food reaches stomach without aspiration.

How does secondary esophageal peristalsis start?

WHAT: Clearance reflex after an incomplete swallow. HOW: Residual bolus distends esophagus → local/vagovagal reflexes → new wave. WHY: Removes material remaining after primary peristalsis.

Why does receptive relaxation occur in the proximal stomach?

WHAT: Accommodative response. HOW: Swallowing/distension induces vagovagal inhibitory pathways and smooth-muscle relaxation. WHY: Stores a meal with modest pressure rise.

How does the distal stomach mix food?

WHAT: Antral grinding and retropulsion. HOW: Strong contractions drive chyme toward partially closed pylorus and back. WHY: Breaks solids into particles appropriate for emptying.

Why does duodenal acid slow gastric emptying?

WHAT: Enterogastric feedback. HOW: Duodenal H⁺ triggers secretin and neural inhibitory signaling. WHY: Avoids overwhelming neutralizing capacity.

Why does fluid exit the stomach faster than solids?

WHAT: Different emptying requirements. HOW: Solids need antral grinding and pyloric sieving; liquids flow more readily. WHY: Limits large particles reaching small intestine.

How does the GI tract handle liters of secreted fluid daily?

WHAT: Bulk fluid recycling. HOW: Digestive fluids enter lumen and most are reabsorbed along intestines. WHY: Avoids large net fluid losses.

How are primary and final saliva different?

WHAT: Acinar versus duct-modified saliva. HOW: Acini make near-isotonic primary fluid; ducts reabsorb NaCl with little water reabsorption. WHY: Final saliva becomes hypotonic.

Why does high salivary flow make saliva less hypotonic?

WHAT: Reduced ductal modification time. HOW: Fluid passes ducts faster, allowing less NaCl reabsorption. WHY: Final ionic composition approaches primary secretion.

How does acetylcholine stimulate saliva?

WHAT: Parasympathetic secretomotor signal. HOW: ACh activates M3 → intracellular Ca²⁺ increases → glandular fluid secretion. WHY: Supports chewing, swallowing and oral protection.

What cells make HCl, intrinsic factor and pepsinogen?

WHAT: Parietal: HCl and intrinsic factor; chief: pepsinogen. HOW: Different gastric gland cells have specialized secretory pathways. WHY: Acid digestion and B12 handling require distinct products.

How does a parietal cell secrete HCl?

WHAT: H⁺/K⁺ ATPase is final acid pump. HOW: Carbonic anhydrase forms H⁺ and HCO₃⁻; apical H⁺/K⁺ pump exports H⁺; Cl⁻ exits lumen. WHY: Generates acidic gastric juice and alkaline tide.

How do ACh, gastrin and histamine stimulate parietal cells?

WHAT: Three acid secretagogues. HOW: ACh→M3/Ca²⁺; gastrin→CCK-B/Ca²⁺; histamine→H₂/cAMP. WHY: Different signals synergize to activate acid secretion.

How does somatostatin reduce gastric acid secretion?

WHAT: Inhibitory D-cell signal. HOW: Somatostatin suppresses G/ECL/parietal activity. WHY: Protects gastric mucosa from excess acidity.

How does the gastric mucosal barrier resist acid?

WHAT: Mucus-bicarbonate-epithelial protection. HOW: Surface mucus traps HCO₃⁻; tight junctions and perfusion maintain barrier. WHY: Prevents H⁺ back-diffusion and peptic injury.

Why can loss of intrinsic factor cause B12 deficiency?

WHAT: Loss of parietal-cell protein necessary for ileal absorption. HOW: B12 must bind intrinsic factor to be taken up by specific terminal-ileal receptors. WHY: Deficiency risks megaloblastic anemia and neurologic dysfunction.

How do emetic inputs trigger vomiting?

WHAT: Brainstem-coordinated motor reflex. HOW: GI afferents, area postrema CTZ, vestibular input and higher centers activate medullary networks. WHY: Expels potentially harmful gastric contents.

Why does the area postrema sense circulating emetics?

WHAT: Chemoreceptor trigger zone with relatively weak BBB. HOW: Bloodborne chemicals can stimulate D₂/5-HT₃-related pathways. WHY: Links toxins/drugs in blood to vomiting.

Which receptors link motion sickness to vomiting?

WHAT: Vestibular emetic signals. HOW: Vestibular H₁ and muscarinic pathways communicate with brainstem emetic networks. WHY: Explains benefit of selected antihistamines/antimuscarinics.

How do 5-HT3 blockers reduce chemotherapy nausea?

WHAT: Antiemetic receptor antagonism. HOW: Block serotonin signaling in vagal/GI and brainstem emetic pathways. WHY: Less emetic transmission reaches vomiting network.

Why does the liver have dual blood supply?

WHAT: Portal venous and hepatic arterial inflow. HOW: Portal vein delivers GI blood; artery supplies oxygenated blood; both mix in sinusoids. WHY: Supports nutrient processing and tissue oxygen needs.

What is the direction of blood and bile in a liver lobule?

WHAT: Opposed flows. HOW: Blood travels from portal triads through sinusoids to central vein; bile travels canaliculi toward portal bile ducts. WHY: Allows hepatocytes to extract from blood and excrete into bile.

Why are hepatic sinusoids well suited for exchange?

WHAT: Low-resistance fenestrated exchange network. HOW: Slow blood flow and sinusoidal structure allow blood-hepatocyte transfer. WHY: Improves metabolism, detoxification and nutrient handling.

What is the role of Kupffer cells?

WHAT: Resident hepatic macrophages. HOW: Sample sinusoidal blood and remove debris/pathogens. WHY: Provides immune surveillance of gut-draining blood.

How does cirrhosis cause portal hypertension?

WHAT: Fibrosis and regenerative nodules distort liver. HOW: Stellate-cell activation → collagen deposition → intrahepatic vascular resistance ↑. WHY: Portal venous pressure rises and collaterals form.

Why can portal hypertension lead to ascites?

WHAT: Splanchnic hydrostatic/renal retention effects. HOW: Portal pressure rises, splanchnic vasodilation and RAAS activation promote sodium/water retention. WHY: Fluid accumulates in peritoneal cavity.

Why do portosystemic collaterals develop?

WHAT: Alternative venous paths around high-resistance liver. HOW: Elevated portal pressure recruits esophageal, rectal and paraumbilical anastomoses. WHY: Diverts portal blood but may produce varices.

What are the main functions of the large intestine?

WHAT: Electrolyte/water recovery, mucus secretion and stool storage. HOW: Colonic transport reabsorbs fluid and muscular circuits move feces. WHY: Maintains fluid balance and continence.

How does the colon absorb Na⁺ and water?

WHAT: Electrolyte-coupled absorption. HOW: Apical Na⁺ entry and basolateral pumping promote osmotic water absorption. WHY: Conserves body fluid.

How does secretory diarrhea occur?

WHAT: Excess luminal anion/fluid secretion. HOW: Enterotoxins → cAMP increases → CFTR-mediated Cl⁻ secretion; Na⁺/water follow. WHY: Produces high-volume watery stool.

Why can gut microbes supply energy to colonocytes?

WHAT: Fermentation yields short-chain fatty acids. HOW: Bacterial metabolism creates butyrate, acetate and propionate; colon absorbs them. WHY: SCFAs support mucosal metabolism; butyrate fuels colonocytes.

How does rectal distension trigger defecation?

WHAT: Defecation reflex. HOW: Rectal stretch activates enteric/spinal pathways → rectal contraction and internal anal relaxation. WHY: Supports fecal evacuation.

How do internal and external anal sphincters differ?

WHAT: Internal = smooth involuntary; external = striated voluntary. HOW: Autonomic reflexes regulate internal tone; somatic pudendal activity controls external sphincter. WHY: Balances defecation with continence.

What is the role of hypothalamic arcuate nucleus in feeding?

WHAT: Integrates peripheral energy signals. HOW: NPY/AgRP neurons promote feeding; POMC/CART neurons promote satiety. WHY: Matches eating behavior with energy stores.

How does NPY/AgRP signaling increase hunger?

WHAT: Orexigenic arcuate pathway. HOW: NPY promotes feeding; AgRP antagonizes melanocortin receptor signaling. WHY: Mobilizes behavior to restore low energy availability.

How does POMC signaling promote satiety?

WHAT: Anorexigenic melanocortin pathway. HOW: POMC processed to α-MSH → activates MC4R and decreases food intake. WHY: Counters overeating.

How does leptin signal body fat stores?

WHAT: Adipocyte-derived long-term adiposity signal. HOW: Higher fat mass → leptin rises → suppresses NPY/AgRP and promotes anorexigenic circuits. WHY: Signals adequacy of stored energy.

Why do ob/ob and db/db mice differ in leptin response?

WHAT: Leptin deficiency vs receptor deficiency. HOW: ob/ob lacks leptin and can respond to hormone; db/db has defective receptor signaling. WHY: Shows ligand and receptor are both required.

How does ghrelin increase food intake?

WHAT: Stomach-derived hunger hormone. HOW: Fasting increases ghrelin; activates hypothalamic orexigenic circuits. WHY: Promotes seeking and eating food.

How do CCK, PYY and GLP-1 reduce food intake?

WHAT: Meal-associated satiety signals. HOW: Gut hormones act through vagal/central pathways; PYY acts on Y₂; GLP-1 stimulates satiety pathways. WHY: Limits meal size after nutrient delivery.

How do GLP-1 receptor agonists affect appetite?

WHAT: Pharmacologic incretin signaling. HOW: Activate GLP-1 receptors in satiety/metabolic circuits, often slowing gastric emptying. WHY: Reduce intake while supporting glucose homeostasis.

Why does MC4R deficiency cause hyperphagia?

WHAT: Impaired central melanocortin satiety pathway. HOW: α-MSH cannot effectively activate MC4R signaling. WHY: Reduced anorexigenic output promotes excessive eating.

How do acinar and ductal pancreatic secretions differ?

WHAT: Acini secrete enzymes; centroacinar/duct cells secrete HCO₃⁻ fluid. HOW: CCK/ACh favor enzymes; secretin favors aqueous bicarbonate. WHY: Enzymes digest food while bicarbonate neutralizes acid.

How does secretin trigger pancreatic bicarbonate secretion?

WHAT: Duodenal acid-to-pancreas response. HOW: H⁺ stimulates S cells → secretin → ductal cAMP signaling → apical HCO₃⁻ secretion. WHY: Creates pH suitable for digestive enzymes.

Why do pancreatic bicarbonate and chloride change inversely with flow?

WHAT: Variable ductal electrolyte composition. HOW: Higher stimulated flow increases HCO₃⁻ secretion and lowers Cl⁻; Na⁺ and K⁺ vary little. WHY: Allows large alkaline secretion while juice stays isotonic.

How does pancreatic ductal bicarbonate move into lumen?

WHAT: Apical anion transport. HOW: Carbonic anhydrase/basolateral entry supply HCO₃⁻; CFTR-supported Cl⁻ recycling and Cl⁻/HCO₃⁻ exchange drive secretion. WHY: Neutralizes gastric acid.

What controls the intestinal phase of pancreatic secretion?

WHAT: Major phase after food reaches duodenum. HOW: Peptides/fats → I cells → CCK → acini; acid → S cells → secretin → ducts. WHY: Matches enzymes and alkalinity to meal contents.

Why does vagal ACh increase pancreatic enzyme secretion?

WHAT: Parasympathetic support of acini. HOW: ACh binds muscarinic receptors and boosts intracellular Ca²⁺ signaling. WHY: Potentiates nutrient-triggered CCK effects.

Why are pancreatic proteases secreted as zymogens?

WHAT: Proteolytic enzymes stored in inactive precursors. HOW: Trypsinogen and other precursors become active mainly in intestinal lumen. WHY: Prevents premature digestion of pancreatic tissue.

How is trypsinogen activated?

WHAT: Inactive precursor of trypsin. HOW: Brush-border enteropeptidase activates trypsinogen; trypsin activates further zymogens. WHY: Starts coordinated pancreatic protein digestion.

Which pancreatic enzymes digest carbs, proteins and fat?

WHAT: Amylase; trypsin/chymotrypsin/elastase/carboxypeptidases; lipase-colipase. HOW: Enzyme classes hydrolyze different nutrient bonds. WHY: Produce absorbable molecules.

How do bile salts help lipid absorption?

WHAT: Amphipathic derivatives of cholesterol. HOW: Emulsify fat and form mixed micelles with digestion products. WHY: Allow hydrophobic lipids to reach intestinal surface.

Why is colipase needed for pancreatic lipase?

WHAT: Lipase cofactor. HOW: Anchors lipase at lipid-water interface despite bile salts. WHY: Permits triglyceride hydrolysis in intestinal lumen.

How does enterohepatic bile salt circulation work?

WHAT: Bile-salt recycling loop. HOW: Liver → bile → intestine → terminal ileum uptake → portal vein → liver. WHY: Conserves bile salts for repeated meals.

Why does terminal ileum disease impair fat absorption?

WHAT: Bile salts are mainly reabsorbed there. HOW: Reduced recycling depletes bile-salt pool → weaker micellar solubilization. WHY: Can cause steatorrhea and fat-soluble vitamin deficiency.

How do villi and microvilli enhance absorption?

WHAT: Surface-area amplification of small intestine. HOW: Folds, villi and brush border increase membrane contact with chyme. WHY: Maximize nutrient uptake.

How are glucose and galactose absorbed from intestine?

WHAT: Apical SGLT1 transport. HOW: Na⁺ electrochemical gradient powers secondary-active uptake; basolateral GLUT2 exports to blood. WHY: Allows sugar absorption even against concentration gradients.

Why is fructose uptake different from glucose uptake?

WHAT: Apical GLUT5-mediated facilitated diffusion. HOW: Fructose moves through transporter without Na⁺ cotransport and exits via GLUT2. WHY: Different monosaccharides use distinct mechanisms.

How does Na⁺/K⁺ ATPase indirectly power SGLT1?

WHAT: Basolateral primary-active pump. HOW: ATP-driven Na⁺ extrusion maintains low intracellular Na⁺; inward Na⁺ drives SGLT1. WHY: Secondary active absorption depends on a primary pump.

How do brush-border enzymes complete carbohydrate digestion?

WHAT: Disaccharidases and oligosaccharidases. HOW: Sucrase, lactase, maltase and related enzymes release monosaccharides. WHY: Only small sugars can be absorbed efficiently.

How does gastric pepsin begin protein digestion?

WHAT: Chief-cell pepsinogen activated in acid. HOW: HCl promotes pepsin formation and protein denaturation. WHY: Starts proteolysis before pancreatic digestion.

How are amino acids and small peptides absorbed?

WHAT: Apical amino-acid and peptide transport systems. HOW: Many amino acids use Na⁺ cotransport; PepT1 carries di-/tripeptides with H⁺. WHY: Enables uptake of both free and peptide-bound amino acids.

What is the correct general order of lipid assimilation?

WHAT: Emulsification → lipase digestion/micelles → enterocyte uptake → chylomicrons. HOW: Bile salts disperse fat; micelles deliver products; enterocytes repackage long-chain lipids. WHY: Makes water-insoluble fat transportable.

Why do micelles not enter enterocytes intact?

WHAT: Micelles are extracellular delivery vehicles. HOW: Lipid products leave micelles and enter membrane; bile salts remain in lumen for recycling. WHY: Delivery is distinct from cellular absorption.

How are long-chain lipids transported after absorption?

WHAT: Chylomicron-dependent lymphatic route. HOW: Enterocytes re-esterify fatty acids → triglycerides → apoprotein-coated chylomicrons → lacteals. WHY: Allows hydrophobic fat transport.

How are short-chain fatty acids handled differently?

WHAT: More water-soluble lipids. HOW: They can enter portal blood without obligatory chylomicron packaging. WHY: Their solubility permits more direct transport.

Why does lack of pancreatic lipase cause steatorrhea?

WHAT: Failure of triglyceride hydrolysis. HOW: Triglycerides cannot yield sufficient absorbable monoglycerides/fatty acids. WHY: Undigested fat stays in stool.