Exam 3 - Digestive System

Esophageal Sphincter

- Maintains specific pressure to prevent ulcers from happening o Acidic environment prevents stomach from self digesting o Esophagus doesn't have as good protection mechanisms - ulcers more likely

Acid Secretion Inhibited By...

- Prostaglandin E2 and somatostatin o Both Gi coupled o Opposite of what histamine is doing

Why does the GI Smooth Muscle Contract Spontaneously

- Serves two purposes: o 1. Moving food along o 2. Mixes food and breaks it down to prepare it for digestion (motility in GI tract) -Influenced by chemical output

Sphincters

- closing points; separate each portion of the GI tract so food cannot move so freely from one portion to another

Intraperitoneal Organs; examples

- housed in front of parietal peritoneum (inside of abdominal cavity) -stomach, large intestine, most of small intestine

Myentric Plexus

-AKA Auerbach's Plexus -In Muscularis Externa o Located between two muscle layers o Nerve supply to muscularis externa

Gastric Emptying

-Basically content moving from stomach to small intestine • Strong peristaltic waves in gastric pump - ready to push it along in small intestine • Increased tone in gastric reservoir (gastric body) - tonic contractions push contents to posterior parts of the stomach • Opening of pylorus (needs to relax) • Inhibition of duodenal segmental contractions

Muscularis Externa

-Composed of two layers of smooth muscle o 1. Inner layer = circular/ring shape • Contraction causes lumen to close and become smaller o 2. Outer Layer = Longitudinal • Contraction causes GI Tract to shorten; helps food moves shorter distances to go to a location much faster

Dumping Syndrome

-Could happen after gastrectomy • Partly digested food draws excess fluid into intestine - food doesn't have enough time to get digested o So then they might develop vomiting, diarrhea • Also may have malabsorption - B12 deficiency and anemia o Cut away big portion of stomach - remove parietal cells responsible for absorption

Blocking the fusion of tubulovesicular membrane and intracellular canaliculus in parietal cells would result in...

-Decreasing secretion so it will result in decreased somatostatin production -Also could be increased production of pepsinogen by chief cells -This is a tough question, so don't necessarily worry so much

Brush Border Enzymes

-Enzymes bound to apical membranes of intestinal cells o Kind of just hang out in cell membranes o Bind to digestive products coming in o These enzymes break them down more so they can be absorbed inside the cell

GI Tract Surface Area

-Large surface area (like a tennis court) to be able to do the job -Most of this area is in the small intestine (speed is really important)

Acid Secreted by

-Parietal Cells in the Gastric Glands

Fundus and Body: Secretion and Motility

-Secretion for LES+Cardia and Antrum/Pylorus are the same, so anything that isn't mucous or bicarb is the middle region secretions Motility: Reservoir -Tonic force during emptying

What creates spontaneous movement (i.e contraction frequency)

-Set by Basic Electric Rhythm (BER) o Slow waves (3-20s) o Set by pacemaker cells (interstitial cells of Cajal)

Zymogens

-This sort of secretion is a mechanism to protect yourself against auto-digestion -Inactive form of the enzyme

Question: What neurotransmitters are involved in opening the pyloric sphincter?

-VIP and Nitric Oxide (NO) -Things that open the pyloric sphincter relax it, so they're smooth muscle relaxers

Small Intestine Peristalsis Waves

-Weak in the small intestine -You don't want them to be strong, because the peristalsis waves will move the chyme too fast, which doesn't give the time much time to respond and digest/absorb

Retroperitoneal Organs; examples

-housed behind parietal peritoneum (outside of abdominal cavity) -kidneys, duodenum, parts of pancreas

Salivary Secretion: Explain the Two epithelial Transport Steps

1. Acinar Cells: resembles extracellular fluid o 2. Ductal Cells: • 1. Absorb Na+ and Cl- • 2. Secrete K+ and HCO3- • 3. Net removal of solute • 4. Impermeable to water

Posterior (distal) Portion of the Stomach Includes Function(s) of this regions

1. Antrum (Pyloric Region) 2. Pyloric Sphincter A. Pump/Grinder -Strong peristaltic waves help mix content inside -Gastric juice mixed with food you injested

Anterior (Proximal) Portion of the Stomach includes Function(s) of this region?

1. Cardia 2. Fundus 3. Body A. Reservoir: food enters here, stays here, waits to be processed

Structures Unique to Support Its Unique Functioning

1. Circular folds or plicae • Do not disappear if you fill with content (permanent), unlike rugae 2. Villi (in plicae) • Increase surface area 3. Microvilli • Furthermore increase surface area

Anatomy of the Small Intestine: 1. Duodenum 2. Jejunum 3. Illium

1. Duodenum: common bile duct + pancreatic duct joining here 2. Jejunum: most absorption 3. Illeum: Peyer's patches or lymph nodules, ileocecal valve

Paracrine Secretion: Three Kinds

1. Histamine o Secreted by ECL cells o Stimulated by gastrin and Ach 2. Intrinsic Factor o Important for parietal cells o Critical for B12 absorption 3. Somatostatin o Secreted by D cells o Slows down everything o Primary feedback signal

6 Digestive Functions of the Alimentary Canal

1. Ingestion 2. Mechanical Processing 3. Digestion 4. Secretion 5. Absorption 6. Excretion

Gastric Motility Primarily Controlled By...

1. Neural control (vasovagal reflexes) o Mechanical stimulation (i.e distension) o Chemical stimulation (i.e presence of products of protein digestion)

Enzyme Secretions

1. Pepsin (effective on collagen) o Secreted by chief cells as pepsinogen o Activated by acid and existing pepsin 2. Gastric lipase: co-secreted with pepsin

Relaxations in Storage Phases of the Stomach

1. Receptive Relaxation • Relaxation of stomach muscles as food moves through esophagus and enters stomach 2. Adaptive Relaxation • Relaxation of stomach muscles when filled

Structures to Support its unique functions

1. Rugae - will disappear when food enters and stomach expands 2. Oblique layer - Antrum part so strong because there's lots of motion

Gastrin Secretions; 1. Secreted by? 2. Stimulated by? 3. Functions?

1. Secreted by G cells (found deep in the pits) 2. Stimulated by: o 1. Gastrin releasing peptide o 2. Vagus nerve stimulation (parasympathetic) 3. Functions: • Act on parietal and ECL cells o Stimulate acid release - Mucosa growth

CCK (Cholecystokinin) 1. Secreted by? 2. Triggered by? 3. Inhibited when?

1. Secreted by I cells in the small intestine (mucosa of upper small intestine) 2. Triggered by: o Amino acids o Peptides o Fatty Acids 3. Inhibited when products of digestion move to the lower portion of the small intestine and large intestine

Secretin: 1. Secreted by? 2. Triggered by

1. Secreted by: S cells (mucosa of upper small intestine) 2. Triggered by: o 1. Acid found in small intestine o 2. Products of protein digestion - amino acids, peptides, etc

Motor Functions of Stomach

1. Storage: Proximal portion (Fundus + Body) 2. Mixing o Distal Portion (Antrum) o Peristalsis

Regional Differences in GI Contractions: Different kinds of contraction

1. Tonic Concentrations o Constant contractions - lasting hours and stuff o Sphincters o Anterior portion of the stomach 2. Phasic Contractions o Seconds to minutes o Peristaltic waves o Posterior portion of the stomach o Small intestine

Resting Pressure in Gastroesophageal Junction = Substances that Reduce This Pressure?

30 mmHg 1. Alcohol 2. Caffeine 3. Cigarette Smoke 4. Chocolate

Trace the pathway of food moving through the Alimentary Canal (another name for alimentary canal is...)

AKA GI tract o Mouth > Esophagus > Stomach > Small Intestine > Large Intestine

Submucosal Plexus

AKA Meissner's Plexus -Provides nerve supply to the MUSCULARIS MUCOSAE

Salivary Secretion Under the Direction of what?

Autonomic nervous system... Specifically, Parasympathetic (ANS) increases flow of saliva -Sympathetic makes more proteins and mucous but not increase volume of saliva -When you're nervous, dry mouth because the saliva production isn't there

Products of fat digestion (what are they) enter _________

Chylomicrons enter lacteal o Big, so they don't fit into the vessels o End of the lymph system, bypass liver, inferior vena cava, joins general circulation later

Pacemaker Cells

Interstitial cells of Cajal) • Modified smooth muscle cells that lie between muscle and nerve plexus • Certain threshold for these waves. Past this threshold = AP • More AP's = stronger and longer contraction • Waves close to the threshold = smaller waves generated

Products of carbohydrates and proteins are absorbed ______

Into the hepatic portal system o So things like monosaccharides and amino acids since they're small o To the liver then the blood

Speed of AP Waves for GI tract depends on what

It depends on the region of the GI -Example: Duodenum contracts faster; distal portions of small intestine contract slower

Submandibular Glands

Mixed secretion

Enteric Nervous System: Motility Excitatory and Inhibitory NT's

Motility Excitatory NT's 1. AcH (Gi coupled - inhibiting the inhibition) 2. Substance P (Gq coupled) - increases calcium binding to calmodulin - formation of MLCK Motility Inhibitory NT's 1. Nitric Oxide 2. Vasoactive Intestinal Polypeptide -Smooth muscle relaxation

What Two Contractions Do You See After a Meal?

Phasic Contracitons: Peristalsis and Segmentation.. Peristalsis: Moves the food down o Involves both longitudinal (contracts) and circular smooth muscle layers o Proximal end of smooth muscle contracts plus distal relaxation o Seen primarily in: • 1. Esophagus • 2. Stomach (mixes food) • 3. Intestinal Segmentation: Circular layers contract alternatively o Content in GI Tract is mixed (enzymes, mucous, food, etc) o Contractile rings o Seen predominantly in small and large intestine

Sublingual Glands

Rich in mucous

Antrum and Pylorus Secretion and Motility

Secretion: mucous and bicarb Motility: mixing/grinding -Sieving -Regulation of emptying

Lower Esophageal Sphincter and Cardia Region Secretion and Motility

Secretions: Mucous and bicarb (to protect lining of esophagus) Motility: Prevention of reflux -Entry of food -Regulation of bleching

What does most of the digesting and absorbing in the digestive system?

The small intestine

True or False: Responses vary depending on the region in the stomach

True... o Proximal portion o Distal portion

Lamina Propria

Under mucosal epithelium o Connective tissue that contains nerve fibers, vessels, and lymph nodes • Supporting structures help prevent bacteria coming in o Wandering Immune Cells (i.e. Peyer's Patch)

Parotid Glands

Watery Solution

GI Peptides: Secretin =

hormone secreted by small intestine

GI Peptides: Gastrin =

hormone secreted by stomach

Control of Gastric Emptying: Decrease gastric emptying

o 1. Distension plus acid in duodenum (enterogastric reflex) o 2. Hormonal: GIP, CCK, Secretin

During Salivary Stimulation...

o 1. Ductal modification reduces o 2. HCO3- remains high by action of secretagogues o So K+ decreases

Control of Gastric Emptying: Increase emptying

o 1. Gastric volume o 2. Neural: vagus nerve activation o 3. Hormonal: Gastrin • 1. increased peristaltic wave in gastric pump • 2. increased tonic contracton in gastric reservoir • 3. increased action of VIP in the pyloric sphincter

Secretin: Functions?

o 1. Stimulating pancreatic bicarbonate secretion; augment CCK functions - this means that they help each other amplify function • Neutralizes acidic environment you just got from the stomach o 2. Inhibit gastric emptying and gastric secretion (very similar to CCK) • BOTH secretin and CCK Stops secretion when chyme has moved into lower portion of small intestine and large intestine

CCK (Cholecystokinin): 1. Functions?

o 1. Stimulating pancreatic enzyme secretion (augment secretin functions) o 2. Contraction of gallbladder (moves bile out of the gallbladder) • Need this mechanism to release content of the gallbladder o 3. Relaxation of sphincter of Oddi • Connects duct that moves bile in pancreatic secretions from accessory organs to small intestine • Relaxation = secretions from pancreas and liver can come out o 4. Inhibit gastric emptying and gastric secretion • Slows down movement of content from stomach into small intestine

Two ways to stop gastrin release

o 1. When the lumen in stomach becomes too acidic - negative feedback on gastrin - decreased gastrin stimulation o 2. Somatostatin - breaker to the whole gastric secretion - everything starts to quiet down

Peritoneal Fluid

o Between the two layers o Produced by serous membrane lining o Provides lubrication which allows sliding without friction or irritation

Mucosal Epithelium

o Depends on esophagus or in small intestine • Stratified Squamous or Simple Columnar • Most variable feature in GI tract

3 Types of Mucosal Epithelial Cells

o Enterocytes - Absorptive - absorb nutrients o Endocrine - Release hormones into blood o Exocrine - Out into the lumen, has enzymes of mucous

What happens when too much peritoneal fluid is secreted?

o Gets into abdominal cavity; swollen stomach

Control of Gastric Emptying: ingestion of food and liquids

o Ingest big meal: faster because you have more pressure coming from stomach o Liquid meal = even faster

Enteric Nervous System: How is it similar to the CNS?

o Intrinsic neurons (dendrites, cell bodies, etc) o Respond to many NT's -Glial cells -Diffusion Barrier -Integrating Center Primarily via motility and secretion

Cell-to Cell Junction.. In stomach and small intestine

o Lots of variety o In stomach: tight junctions - acidic environment - leaky acid is painful o In small intestine: cell cell junctions become more leaky • Can be controlled by neuron peptides around them

Absorption

o Mostly takes place in small intestine o Water and ions in the large intestine

Two forms of peristalsis during the swallowing reflex

o Primary Peristalsis • Normal - initiated by swallowing reflex o Secondary (repetitive) peristalsis • When food is stuck somewhere in the middle (not in the stomach) • Generating strong waves to push food from higher pressure to lower pressure (esophagus to stomach)

Digestion

o Process by which we break down macromolecules into absorbable units • Examples: Proteins -> Amino Acids, Starches -> Monosaccharides

Accessory Organs of the Digestive System and What They Do

o Salivary Organs - Secrete saliva o Gallbladder - Store bile that comes from the liver o Liver - secretes bile for digesting fat o Pancreas - secreting enzymes for digestion

Case Study: A 31 year old man has been diagnosed with a peptic ulcer. He also suffers from heart burn. What kind of treatments would you propose for his gastritis?

o Solution 1: Antacids to help heart burn o Solution 2: H+ pump blocker (like omeprazole) • Proton pump blocker because rate limiting factor • Make it less acidic o Solution 3: H2-blocking durgs (like cimetidine) - Release somatostatin

Folds... What are they in stomach and small intestine

o Stomach: Rugae: can't expand after a meal; can completely disappear if you eat a huge meal o Small Intestine: Plicae: does not disappear when you eat

Small Intestine Motility: Segmentation

o Strongest in small intestine (compared to peristalsis) o Mixes stuff inside small intestine o Slow propulsion possible due to frequent gradient o Segmentation in the small intestine is fastest in beginning of small intestine, slowest at the end of the small intestine o Different frequency rate in different portion due to pacemaker cells

Muscularis Mucosae

o Thin layer of smooth muscle o Shape intestinal folds (plicae), moves the villi when layers contract

Gastric Secretion Control

• 1. Food or cephalic reflexes initiate gastric secretion • 2. Gastrin stimulates acid secretion by direct action on parietal cells or indirectly through histamine • 3. Acid stimulates short reflex secretion of pepsinogen • 4. Somatostatin released by H+ is the negative feedback signal that modulates acid and pepsin release

Two Things That Secrete Digestive Enzymes (locations and types)

• 1. Secreted by exocrine glands o A. Salivary glands - lipase/amylase - start digestion in mouth o B. Pancreas - protease/lipase/amylase - digestion in small intestine • 2. Epithelial cells o A. Stomach o B. Small Intestine

Absorption by the stomach

• Aspirin, other weak acids • EtOH and other alcohols • Stomach wall is NOT specialized for absorption

Long Reflexes

• Can originate anywhere • Integrated in the CNS • HAS TO involve neurons outside ENS (specifically involve the CNS) • Cephalic reflexes - initiated from a sensory stimuli

Serosa

• Consists of connective tissue • Outer covering of the GI tract • Replaced by fibrous adventitia in the oral cavity, pharynx, esophagus, and rectum

Increasing Smooth Muscle Contraction

• Do so by activating Myosin Light Chain Kinase • We do NOT have troponin in smooth muscle • Phosphotase works against myosin light chain kinase - RELAXES smooth muscle • cAMP acts as inhibition to MLCK - functions the same way as phosphatase • Gi inhibits cAMP - inhibiting inhibition leading to positive effect on myosin light chain kinase - smooth muscle contraction • M2 is Gi coupled - inhibiting this would relax smooth muscle because Gi usually decreases cAMP

Gastrectomy

• Gastrectomy may lead to loss of feedback control of emptying o Cutting big portion of your stomach, in order to decrease absorption, reduced feedback loop, decrease time food is in your stomach o People who get this are usually overweight (gastric bypass surgery, overweight)

Parietal Cells are stimulated by... H+/K+ ATPase Pump: Why

• Gastrin, AcH, and Histamine • H+/K+ ATPase: rate limiting factor; keep increasing to drive the rest of the process

GI Peptides

• Hormones, neuropeptides, cytokines • Secreted by isolated endocrine cells in mucosa • Have functions not limited to the GI

What primarily influences digestion and absorption?

• Influenced primarily by motility and secretion in the GI

Invaginations... What are they in stomach and small intestine

• Invaginations: going into mucosa regions o Stomach: Gastric Glands o Small Intestine: Crypts

Submucosa

• Larger areas of loose connective tissue containing large blood and lymph vessels • Macrophages, b cells here -> readily protect yourself

Explain the contraction that occurs between meals

• Migrating Motor Complex (why you hear gurgling when you're hungry) o Strong peristalsis that starts at proximal end to distal end of small intestine. o Wave series pushes food down small intestine o "Housekeeping" -> making room for the next meal

Histological Organization of the GI Tract

• Mucosa: most inner facing the lumen • Submucosa: connective tissue layer • Muscularis: layers of smooth muscle • Serosa: covering connective tissue

Short Reflexes

• Originated within the ENS • Integrated in the ENS • Cells in lumen pick up chemicals, and they'll be able to tell secretion or motility of neighboring cells • KEY: Short reflexes don't involved anything outside ENS

Achalasia

• Peristaltic waves are under lower pressure (smaller waves, weaker waves) • Hard to move food down • Opening is really pinched • Elevated resting pressure to begin with

Ulcers: Primary Causes

• Primary Causes: 1. NSAID (inhibits mucus production) like aspirin - Mucous alkaline lining protection is so important - Lumen has pH of 2. But by the time you reach stomach lining it is neutralized 2. Infections (Helicobacter Pylori = main course of your ulcer) • Rarely due to over-secretion of gastric acid

Mucous Secretion; Primary Function; Stimulated by...

• Secreted by exocrine cells (mucous cells, salivary glands, goblet cells in small intestine) • Primary Function: o 1. Protect GI mucosa o 2. Lubricate the contents • Stimulated by: o 1. Parasympathetic o 2. Neuropeptides o 3. Cytokines • Example: inflammation in your lungs or upper airway -> mucous production promoted

Gastric Phase

• Series of short reflexes that are initiated when food enters the stomach • Main topics for this phase are Secretion and motility

Function of Saliva

• Softens and lubricates food • Chemical digestion o Secretion of salivary amylase (carbohydrates) and some lipase (fats) • Taste - because of moisture for food • Protection mechanisms o Secretion of lysozyme, immunoglobulins, fluoride (teeth), HCO3- (neutralizes content in esophagus)

Acid Secretion stimulated by... CCK-B?

• Stimulate by gastrin, Ach, and histamine (much bigger effect than the other two) o Gq coupled o CCK-B: used by gastrin to increase intracellular calcium increase... Activation of parietal cell

Protection of the Stomach Wall

• Thick, alkaline mucus (important for protection of stomach) • Tight junctions between epithelial cells • Rapid replacement of GI mucosa layer (around 5 days) by GI stem cells

Explain the mechanism that governs the swallowing reflex

• Tongue pushes bolus against soft palate and back of mouth, triggering the swallowing reflex • Upper esophageal sphincter opens/relaxes while the epiglottis closes to keep swallowed materials out of the airway • Food moves downward into the esophagus propelled by peristaltic waves and aided by gravity

Gastroesophageal Reflux

• Very common • Lower esophageal sphincter becomes too loose • So there's acidic stuff coming into esophagus, causing corruption of lower esophagus • Heart burn, cessation, ulcer in esophagus