Lecture PSL302: 68-69, by French!
Mon-Wed. Apr. 4-6, 2011
Digestion Control & Diseases
Outline - What happens during the cephalic phase of digestion? - Case #1: Victor - What happens during the gastric phase? - Case #2: Rahul - What happens during the intestinal phase? - Case #3: Johanne Textbook reading: 708-718 + running problem in ch. 21
Review
Figure 21.22
Control of GI activities: represents continuum of activities in GI tract - Cephalic phase: neural processing of food pathways activate stomach & intestines - Sensory receptors & thoughts of food initiate reflexes = salivation, pdc of gastric juice & gastric contractions - Mediated by vagus nerve: prepare GI system for arrival of food - Gastric phase: regulation of stomach, while digesting food - Stomach contents & volume initiate reflexes = gastric secretions gastric motility - Intestinal phase: chyme enters intestines inhibit gastric activity (slow gastric emptying) & stimulate secretions into intestines - Intestinal contents & volumes initiate reflexes = secretion of bicarbonate, digestive enzymes & bile; segmental contractions; slow gastric emptying - Chyme is neutralized, digested & absorbed
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PSL302: Lecture 68-69, by French!
Mon-Wed. Apr. 4-6, 2011
- Phases of control occur in seqce only at beginning of meal Cephalic phase - Once a meal is underway, the phases are smelling, tasting, i.e.thinking aboutintestines work Seeing, simultaneous: or stomach & food back and forth to digest contents of meal What happens during the cephalic phase of digestion? - In brain: seeing, smelling tasting, or thinking about food - Effects: salivation, pdc of gastric juice & gastric contractions - Salivary center (medulla) CN VII (facial nerve) & CN IX (glossopharyngeal nerve) - Secretion of saliva under parasympathetic (watery secretion) & sympathetic nervous control (thick secretion)
salivary center CN VII CN IX
Swallowing Reflex (1) Two components: voluntary & involuntary - Voluntary: you decide when to swallow = use tongue to push Figure from Interactive Physiology, Pearson back bolus - Involuntary: tongue pushes bolus against soft palate & back of mouth = reflex - Food CN IX, X swallowing center CN V, VII, IX, X, XII = swallowing (2) Upper esophageal sphincter (guards esophagus) relaxes Swallowing - Epiglottis closes = keeps bolus out of airways Swallowing (3) Bolus moves down esophagus via peristalsis & gravity
Swallowing
Swallowing
Figure stomach Cephalic phase--control of from Interactive Physiology, Pearson
from Interactive Figure Interactive Food F d CN IX X Figureswallowing center IX, fromPearson Pearson i t Physiology, ll Physiology, Cephalic phase: control of stomach nerves to CN Figure (1) Perception of food Figure 21 24 21 24 medulla CNCNX IX VII,ll IX, ll vagus t swallowing CN21.24 21.24 nerves Food Food IX V, swallowing i t center F d F CN nerves, mainly center i X, XII d IX, IX, X swallowing CN
Figure 21 24 21.24
medulla pancreatic XII swallowing CN CN V, VII, secretion swallowing - PNS: Vagus stimulates stomach & V, VII, IX, X,IX, X, XII (2) Signals that food is on its way = pdc of gastric juices & contractions vagus stimulates - Vagus stomach: synapse on post-ganglionic neurons & ENS (submucosal plexus) stomach and - Neurotransmitter released: ACh acts on ENS cells & from Interactive Figure glands pancreatic (3) Innervate G cells (release gastrin into bloodstream) Physiology, Pearson secretion Cephalic Figure 21Innervate parietalstomach acid): also affected by gastrin phase--control of cells (secrete 21.24 24 - Innervate mucous d Food (secrete X swallowing center F cells CN IX mucous) & chief icells (secrete pepsin) IX, ll t
details swallowing CN V, VII, IX, X, XII
erves to lla s stimulates ach and eatic tion
details
Figure from Martini (2006) Fundamentals of Anatomy and Physiology
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PSL302: Lecture 68-69, by French!
Mon-Wed. Apr. 4-6, 2011
Cephalic phase--control of small intestine
Cephalic phase: control of small intestine - Vagus nerve also innervates pancreas (also affected by gastrin) - Acinar cells secrete enzymes - Ductal cells secrete bicarbonate - Cephalic phase is relatively short: quickly merges w/ gastric phase ! Case #1: Victor Victor, a 55-year old male, has gone out with his wife to celebrate their 25th wedding anniversary. They order steak with a cream sauce, chocolate cake and a bottle of wine. When they get home, Victor goes to bed immediately. He awakens with a burning sensation in his lower chest that spreads towards his neck. The pain is alleviated with antacids. 1) What is he suffering from? Gastroesophageal reflex Dx (GERD) or heartburn 2) How would you treat him? Lifestyle changes & drugs 3) Are there any long-term risks if this condition persists? - Esophagus walls change morphology & properties look like intestinal epithelial cells = Barrett's esophagus Gastroesophageal reflux disease (GERD) - Predisposes to esophageal cancer
No reflux Reflux
Gastroesophageal reflux disease (GERD)
-Normally: lower esophageal sphincter (LES) closes off stomach from esophagus -If GERD: acid reflux into lower esophagus Barrett's esophagus Measurement o p in t e esop agus easu e e t of pH the esophagus Measurement of pH in the esophagus
Esophageal pH
-During meal: pH drops & reaches low at end of meal = heartburn -When lie down: greater chance for acid to move into esophagus = pH drops = heartburn
GERD: causes & treatment - Causes: Fatty meal, alcohol, caffeine, peppermint, chocolate, smoking all relaxation of LES - Treatment: - Lifestyle changes: weight, eat small meals, eat earlier in evening, stop smoking - Drugs: acid secretion or stomach emptying - Antacids: acid pH - Proton pump inhibitors, histamine receptor (H2) inhibitor: acid secretion Review: Which of the following is a fxn of gastrin? acid secretion from parietal cells
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PSL302: Lecture 68-69, by French!
Mon-Wed. Apr. 4-6, 2011
Cephalic phase review and intro to gastric ph
Cephalic phase review & Intro to gastric phase
Initiation of gastric phase - Stimulus: food in stomach = distension, presence peptides & aas = initiate short reflexes astric phase - In gastric mucosa: sensory input - Short reflex: Enteric plexus post-ganglionic PS & intrinsic enteric effectors ers local neural and endocrineneurons - Effect: secretion & motility What happens during the gastricFood in the stomach triggers local neural and endocrine effectors phase? - Short reflex: food in stomach triggers local neural & endocrine effectors - Trigger release of: - Gastrin from G cells - Acid from parietal cells
details
Gastric phase
Figure 21.23
details
Effects in stomach (1)Distension stretch receptors myenteric plexus Figure from Martini (2006) Fundamentals Anatomy and Physiology ! = contractions (mixingofwaves) (2)Elevated pH chemoreceptors ENS ! = mucous, chief, parietal & G cells (3)Peptides G cells = release of gastrin ! = gastrin chief & parietal cells = motility
Details: regulation of stomach secretions
re from Martini (2006) Fundamentals of Anatomy and Physiology
Details: regulation of stomach secretions (1) Food/cephalic reflexes = gastric secretion - Food: enteric sensory neurons detect aas or peptides - Effect: G cells - Cephalic reflex: input via vagus nerves Effect: - G cells, parietal cells & enterochromaffin-like (ECL) cells (2) Effects of secretions: - Gastrin directly parietal cells = acid - Indirectly via ECL cells = histamine (3) Acid short reflex = pepsinogen - Acts on enteric sensory neurons ! chief cells = pepsinogen - Also activates pepsinogen pepsin (4) Negative feedback: acid acts on D cells = somatostatin - Inhibits: G cells, parietal cells, ECL cells, & chief cells - Modulates acid & pepsin release
Figure 21.26
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PSL302: Lecture 68-69, by French!
Mon-Wed. Apr. 4-6, 2011
! ! Case #2: Rahul Rahul is a 35-year old male stockbroker immigrated to Brazil when he was a teenager. Lately, he has started feeling nauseated following meals. He has a burning sensation in his stomach that is worse a few hours after a meal and in the middle of the night. His appetite is poor and he feels weak. 1) What is he suffering from? Gastric (or peptic) ulcer 2) How would you treat him? Treatment for H. pylori infection What are ulcers? - Perforations into mucosa or further into mucosal layers = exposure of nerves - White blood cells & inflammation = lesion Causes - Previously thought ulcers were caused by anxiety = excess acid production - BUT actually caused by bacterial infection! - Primary: Helicobacter pylori - Secondary - Drugs: i.e. NSAIDs (non-steroidal anti-inflammatory drugs, i.e. aspirin) pdc of prostaglandins (protect stomach lining) = risk for ulcer - Excess acid: i.e. Zollinger Ellison (G cell hyperplasia) - Stress, other: i.e. head injury H. pylori H. pylori H. pylori
Prevalence pylori infection Prevalence of H. of H. pylori infection H. pylori infection strongly H. pylori infection stronglyyou infected with H. -Even if associated with disease pylori, associated with disease may not develop ulcers (data from USA)
(data from USA)
-HP-: not infected (green) -HP+: infected (purple)
-HP+ risk of developing many urease gastric conditions+(i.e. duodenal C=O(NH2)2 + H + 2H2O & gastric ulcers also risk for gastric cancer, gastric lymphoma)
How H. pylori survives in the stoma
HCO3- + NH
How H. pylori survives in the stomach - Pbm: Stomach acid has pH = 2 no way bacteria could survive in stomach! - Strategy: bacteria resides in mucous gel layer on surface of stomach = pH http://www.helico.com/h_epidemiology.html http://www.helico.com/h epidemiology.html more neutral - Enzyme urease takes urea bicarbonate & ammonia = both How H. pylori survives in the stomach neutralize acid
urease
http://www.helico.com/h_epidemiology.html http://www.helico.com/h epidemiology.html
HCO3- NH4+
C=O(NH2)2 + H+ + 2H2O
HCO3- + NH4+
- Scientists used knowledge of metabolism to create a test to detect infection - Then treat w/ antibiotics = cure ulcer!
http://www.helico.co
HCO3- NH4+
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Breath test for H. pylori infection
PSL302: Lecture 68-69, by French!
drink urea containing with 14C isotope4-6, 2011 Mon-Wed. Apr.
Breath test for H. pylori infection (1) Take pill w/ radioactive urea (contain 14C isotope) - If H. pylori present: metabolized into bicarbonate & ammonia - If not present: excreted in urine (2) Bicarbonate is reabsorbed into stomach or small intestine blood - CO2 transported in blood as bicarbonate expelled at lungs (3) Measure 14C in breath
Treatment
Check f H. l i infection Ch k for H pylori i f ti
Treatment - Check for H. pylori infection, then treat w/ measure 14CO2 long drug regime H+/K+ pump H2 inhibitors - Drugs: histamine receptor antagonists - Proton pump inhibitors: acid Figure from http://www.helico.com/diag_breath.html pdc by inhibiting H+/K+ pumps - Histamine (H2) antagonists: ECL antibiotics cells act on parietal cells = acid H. pylori - Antibiotics to fight infection
in breath
Intestinal D cells Intestinal Review: What directly stimulates the release of somatostatin from phasein the stomach? Acid
Modified from Figure 21.26
phase
Chyme in/distension of the small intestine What happens during the intestinal phase? - Stimulus: Chyme enters distension of the small intestine - Acid, protein/peptides, secretin from S cells fats stimulate secretion of hormones from intestinal cells stimulates fluid and HCO3- Effects: secretion - Secretin from S cells: - Respond to acid & fat CCK from I cells stimulates - Act on pancreatic ductal cells secretion of pancreatic - Secretion of fluid & HCO3- secretion enzymes - Cholecystokinin (CCK) from I cells details - Respond to acid & peptides - Act on pancreatic acinar cells - Secretion of pancreatic enzymes - Two desired overall effects - digestion gastric emptying
- CCK & secretin act on stomach cells via circulation (blue arrows) inhibit: - Chief cells: pepsinogen - Parietal cells: acid - Peristalsis: motility - Enterogastric reflex - Duodenal stretch & chemoreceptors myenteric plexus = contraction
Chyme in/distension of the small intestine secretin from S cells stimulates fluid and HCO3secretion CCK from I cells stimulates secretion of pancreatic enzymes
Figure from Martini (2006) Fundamentals of Anatomy and Physiology
details
Figure from Martini (2006) Fundame
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PSL302: Lecture 68-69, by French!
Mon-Wed. Apr. 4-6, 2011
Intestinal phase -- details
Intestinal phase: details - The contents of chyme initiate gastric phase - Acid secretin ! = pancreatic bicarbonate - Fats, proteins CCK ! ! ! = pancreatic enzymes - Carbs gastric inhibitory enzyme (GIP) ! ! glucagon-like peptide (GLP-1) ! ! = insulin - Negative feedback to the stomach: - Acid pdc via GIP, GLP-1, CCK, secretin - Gastric motility via GLP-1, CCK, secretin Review: What is NOT a direct effect of CCK? A. Stimulating gallbladder contraction ! CCK: "bile" - "bladder" - "move" B. Stimulating the release of insulin C. Stimulating the secretion of pancreatic enzymes D. Inhibiting gastric motility E. Inhibiting gastric acid secretion ! Case #3: Johanne Johanne is a 4-year old Haitian girl who lives in the Artibonite Departmente, approx. 50 miles north of Port-au-Prince. She ate food contaminated with Vibrio cholerae and has developed cholera. V. cholerae produces a toxin that results in the following changes: - CT (toxin) permanently activates Gs = excess pdc of cAMP in intestinal epithelial cells - Activates PKA phosphorylation of channels - NaCl co-transporter = inhibited - CFTR (transport of Cl- out) = activated
Cholera toxin (LT)
NaCl N Cl ClCl
Figure 21.28
(-) () (+)
CFTR CT
Protein phosphorylation A-kinase
(+)
cAMP
1) How do these changes influence water & electrolyte absorption? - NaCl absorption creates osmotic gradient = allows water absorption - W/ cholera: NaCl absorption water absorption - Compounding this pbm: excess transport of Cl- draws solutes into lumen - In pancreas, CFTR aids in creating watery secretions - W/ cholera: Cl- secretion = water loss - Effect: Severe dehydration & diarrhea 2) Oral rehydration therapy is used to treat this condition. How does it help? * Note: solution contains Na+, glucose, KCl, & citrate (osmolarity = 245 mmol/L) - Idea: Load system w/ more Na, Cl & water - AND osmolarity is a bit lower = helps draw water into cells - Sol'n has glucose: Na+/glucose transporter still working = Na+ absorbed - AND water is co-transported = water absorbed - Also forms basis for sports drink & rehydrating after exercising
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