GI Mod 1 Flashcards
Digestive System Structures
- GI tract (alimentary canal): mouth, esophagus, stomach, SI, LI rectum and anus
- Accessory organs of digestive system: liver, gallbladder, exocrine pancreas
4 Layers of GI Tract
- mucosa
- submucosa– glands and associated ducts
- muscularis
- adventitious (serosa)– connective tissue
Mucosa Layer of the GI Tract is made up of? (3)
a. mucosa epithelium
b. lamina propria
c. muscularis mucosae
Muscularis Layer of GI Tract is made up of? (2)
a. circular layer
b. longitudinal layer
Enteric nervous system: intrinsic nervous system of GI tract
- Enteric nervous system is considered part of the ANS
2. Functions autonomously and influenced extrinsically via parasympathetic/sympathetic nervous systems
Three Enteric Plexuses
a. Submucosal plexus (Meissner plexus)
• located in submucosa (text describes location within muscularis mucosae)
b. Myenteric plexus (Auerbach plexus)
• located between circular and longitudinal layers of muscularis
c. Subserosal plexus
Three general “functional components” of enteric plexuses
a. Sensory neurons monitor:
• distension and the “chemical status” of GI tract
b. Motor neurons control:
• motility of the gut wall
• smooth muscle of GI vasculature
• secretions of the muscosa/submucosa
c. Interneurons communication between sensory and motor
Regulation of appetite and satiety
- appetite = hunger
2. satiety = sensation of fullness/satisfied
Two centers (nuclei) located in hypothalamus control appetite & satiety
Lateral center
(appetite center)
Medial center
(satiety center)
Function and Stimuli Lateral Center
a. Function:
• Stimulate appetite
• Excitatory to hunger contractions in stomach
b. Stimuli:
• Smell (CN 1), Visual, Taste (CN 7, 9), Hearing (CN 8)
• Physiological depletion of nutrient/energy stores
• Memory/fantasy – limbic/insular lobes
• Gastric hormone: Ghrelin
(i) “Hunger Hormone”
(ii) Released from stomach
Function and Stimuli Medial center (satiety center)
a. Function:
• suppress appetite
• inhibitory to hunger contractions in stomach
b. Stimuli:
• Hormones:
(i) GI hormones released during food ingestion (CCK, GLP-1, etc…) – short term action
(ii) Leptin - released by fat cells and chief cells
(iii) PYY (peptide YY) - released by SI after meal
(iv) Insulin - released by pancreas after increase blood glucose after meal
Sympathetic system for Extrinsic Regulation: ANS & Enteric Nervous System
• Pathway: (i) nerves of sympathetic tract in thoracic and upper lumbar regions • Function: (i) Inhibitory to GI tract 1. decrease peristalsis and secretions 2. inhibit blood flow to GI tract
Obesity Hormone Levels
Leptin (satiety hormone)
increased levels in obesity
Obesity: “leptin resistance”
effectiveness of leptin to produce sensation of satiety may be blunted
Ghrelin (hunger hormone)
decreased levels in obesity
physiological strategy to signal feeding is adequate
Ghrelin
“fast acting”
meal initiation - levels rise just before meals
most circulating levels are produced in stomach
“other” roles: memory, sleep
Leptin
Leptin:
“long term” role in energy balance and suppressing food intake
released from fat cells
PYY (peptide YY) –
“fast acting” counteraction to ghrelin post feeding
released from SI
Insulin
“fast-acting” post feeding
released from pancreas
Parasympathetic Extrinsic Regulation: ANS & Enteric Nervous System
• Pathway:
(i) Vagus nerve (esophagus to transverse colon) and pelvic nerves of sacral plexus
• Function:
(i) Excitatory to GI tract
1. increase peristalsis and secretions,
2. relax involuntary sphincters of GI tract
3. facilitate blood flow to GI tract
Intrinsic regulation: enteric nervous system
a. Two neural networks located within the multiple layers of the intestinal walls as described above
b. Intrinsic system can feedback on itself and function autonomously
brain in the gut
General function of each plexus during intrinsic regulation
• Myenteric plexus (Auerbach’s)
(i) controls motility
• Submucosal plexus (Meissner’s)
(i) controls secretions and absorption
Specific functions of enteric nervous system
• Controls motility
(i) Peristalsis, sphincter control, etc…
• Regulation of fluid exchange and local GI blood flow
• Regulation of gastric and pancreatic secretion
• Regulation of gastrointestinal endocrine cells
• Defense reactions
• Entero-enteric reflexes
• ENS and CNS interaction
Regulation of fluid exchange and local GI blood flow
(i) Regulates permeability to ions thus influence fluid
(ii) Influences vasodilation of BV
(iii) Influences fluid secretion
Regulation of gastrointestinal endocrine cells
(i) Intrinsic system can signal release of GI hormones
(ii) Example: excessive serotonin released from GI walls = nausea/vomit
Entero-enteric reflexes
(i) Signaling system between regions of GI tract
1. Examples:
a. Gastric activity stimulates SI motility and relaxation of ileocecal valve
b. Small intestine activity signals release of enzymes from pancreas
Defense reactions
(i) Vomit, diarrhea and exaggerated propulsive motility reflexes
Intrinsic (enteric nervous system) Summary
- Myenteric plexus (Auerbach’s) = located in muscular layers so control motility
- Submeucosal (Meissner’s) = located within/beneath mucosal layers so control secretions
Extrinsic Summary
• Directly influences intrinsic system
(i) parasympathetic = excitatory to GI motility and secretions
(ii) sympathetic = inhibiatory to GI motility and secretions
Saliva Contains (3)
• Water with mucus, sodium, bicarbonate, chloride, potassium
(i) Bicarbonates in saliva maintain pH in mouth to neutralize bacteria (tooth decay)
• Salivary amylase
(i) digestion initiated in mouth
(ii) amylase begins first steps to break down (digests) carbohydrates
• Immunoglobulin A (IgA)
(i) prevents infection (“dogs/animals lick their wounds”)
Secretion of Saliva
a. Three salivary glands
• submandibular, sublingual & parotid
b. Autonomic control of saliva
• Both parasympathetic and sympathetic systems stimulate salivary glands
(i) NOTE: secretion of saliva IS NOT controlled by hormones
Esophagus Musculature
a. Upper third – striated (voluntary) muscle
b. Middle third – mixed
c. Lower third – smooth (involuntary) muscle
Location and Function of Upper Esophageal Sphincter (cricopharyngeus muscle)
a. Location of UES:
• junction of lower pharynx and esophagus
• approximately at the level of cricoid cartilage
b. Function of UES:
• Prevent air from entering esophagus during ventilation
Location and Function of Lower Esophageal Sphincter
a. Location of LES:
• narrowing of the esophagus proximal to the junction of esophagus and stomach
b. Function of LES:
• Barrier to the reflux (regurgitation) of the acidic content of the stomach
• The LES is maintained by increased smooth muscle tone
Swallowing and Resting Tone
Resting Tone and Swallowing
(i) Resting tone:
1. LES smooth muscle tone increased to 20 mmHg
2. Fun facts: “belching” – air pressure in stomach exceeds LES pressure
(ii) Swallowing:
1. LES smooth muscle to tone is relaxed
2. peristaltic wave relaxes smooth muscle of LES
a. Control centers located in brainstem (reticular formation)
• Complex function requiring coordination between digestive tract and respiratory system
Voluntary Phase of Swallowing
(i) Food broken down & tongue pushes bolus posteriorly
1. Soft palate (superior constrictor muscles) contract to close of nasopharynx
2. Epiglotis closes off larynx/trachea
(ii) Food pushed into esophagus within 1-2 seconds
Involuntary Phase of Swallowing
(i) Begins as bolus enters esophagus and ends as bolus enters stomach
1. esophageal phase of swallowing food takes approximately 5-10 seconds
Peristalsis
a. coordinated contraction/relaxation of longitudinal/circular muscles
b. esophageal muscular pressures range from 35 to 80 mmHg
i. upper and lower esophagus tend to be higher (60-80 mmHg)
ii. mid esophagus tend to be lower (30-45 mmHg)
iii. peristaltic contractions of < 30 mmHg may leave food residue within esophagus
c. tension (distension of esophagus) increases force of contractions
i. intense contractions = substernal pain similar to angina/heartburn
Control of peristalsis
requires complex coordinated activities of
a. Parallel vagal inhibitory and excitatory pathways
i. Vagus nerve has both excitatory and inhibitory pathways to coordinate contraction/relaxation of esophageal peristalsis
Primary Peristalsis
a. “normal” peristaltic wave as bolus descends in esophagus
b. coordinated muscular activity of all phases of swallowing
i. oral phase, pharyngeal peristalsis, UES relaxation, esophageal peristalsis, and LES relaxation
Secondary Peristalsis
a. food residue from ineffective primary peristalsis or a bolus that is “stuck” will cause addition or second peristaltic wave
b. esophageal peristaltic wave only – DOES NOT include swallowing reflex
c. bolus/food residue distention causes intrinsic feedback to:
i. constrict esophagus above the distention
ii. relax esophagus below distention
iii. which pushes residue/bolus along
Swallowing Food
- A single swallow will initiate esophageal peristaltic contraction that lasts about 5-10 seconds short refractory period also follows peristaltic contraction
a. Inhibits ability to swallow a second bite of food - in general: attempting to swallow food more frequently than 10-15 seconds is difficult because of inhibitory mechanisms
Swallowing Liquid
- Normal drinking – swallow every 1-2 seconds
- The quick subsequent swallows create an inhibitory reflex (deglutitive inhibition) that prevents the esophagus from ongoing contraction
a. This inhibitory reflex causes esophagus to stay relaxed to allow more liquid to descend - This inhibitory reflex will continue until the last swallow in a series of swallows – after which a full peristaltic contraction will occur
Basal tone of LES is net result of 3 factors:
- Myogenic tone that is independent of any neural input
- Excitatory vagal tone (cholinergic)
- Inhibitory vagal tone (nitrergic – nitric oxide)
Factors that increase LES pressure
• Vagus nerve influence
(i) Excitatory pathways of vagus nerve
1. cholinergic post ganglionic neurons – release Ach
• Gastrin
(i) In stomach gastrin promotes acid secretion/motility so need to keep LES closed
Factors that decrease LES pressure
(i) Inhibitory pathways of vagus nerve
1. non-cholinergic post ganglionic neurons: stimulate NO and VIP (vasoactive intestinal peptide) release
• Hormones: progesterone, secretin, glucagon
(i) Progesterone levels elevated during pregnancy and second half of menstrual cycle – transient reflux may occur
• Common foods/substances suggested to relax LES (varying levels of evidence or clinical significance)
(i) Fried fatty foods, tomatoes, citrus, high protein diet, chocolate, peppermint, etc..
(ii) Tobacco, alcohol, caffeine
GERD (gastroesophageal reflux disease)
• Decreased LES pressure and ineffective clearance mechanism of secondary peristaltic waves
• Chronic acid reflux results in inflammation/pain and eventual destruction of esophageal wall (esophagitis)
• Medications
(i) Antacids – neutralize stomach acids
(ii) Histamine (H2) receptor blockers – decrease acid secretion histamine receptors
(iii) Proton pump inhibitors – stop acid secretion
(iv) Parasympathetic drugs – to increase LES tone
Achalasia
(i) “failure to relax”
(ii) Relatively rare disease in which LES fails to relax…pain w/eat and drinking
(iii) Aka…”cardiospasm” (discuss DDx with cardiac signs/symptoms) , urgent clinical priority is to rule out cardio first…then determine GI pathology
• Etiology – unknown thought to be defect of intrinsic esophagus plexus
Treatment Strategies of Achalasia
(i) Pneumatic dilation (literally stretch LES to relax)
(ii) Medications to relax LES
Esophageal varices
• severely dilated sub-mucosal veins in the esophagus
• most often a consequence of portal hypertension (common with cirrhosis)
• patients with esophageal varices have a strong tendency to develop bleeding
(i) chronic long term GI bleed can progress to severe systemic consequences
Barrett’s esophagus (BE)
• Barrett’s esophagus is a condition in which normal mature cells lining the esophagus are replaced with abnormal cells due to exposure to stomach acids
(i) normal esophageal squamous epithelium is replaced by a spectrum of metaplastic columnar mucosa
(ii) metaplasia:
1. in which one mature adult cell type is replaced by another type of mature cell
Symptoms of Barretts Esophagus
(i) the metaplasia itself does not cause physical “heartburn” symptoms but is histological reflection of the chronic exposure to acid
1. the stomach acid is the physical stimulus for “heartburn” symptoms
Barrett’s esophagus and GERD
(i) Chronic esophagitis or reflux disease
(ii) NOT all patients with GERD will develop Barrett’s esophagus
Barrett’s esophagus and cancer
(i) In some individuals these cells develop into a type of cancer of the esophagus called adenocarcinoma.
(ii) NOT all patients with Barrett’s esophagus will develop cancer
1. Risk reported as 1:300
2. Amount of dysplasia present increases risk of cancer
3. dysplasia:
a. Abnormal development/maturation of cells
b. Delay/abnormal differentiation of cells results in number of immature cells
c. Often an indication of early neoplastic process
Gastric Function of Digestion
• secretion of gastric juices
• continues to digest food into chyme (partially digested food)
• no absorption takes place except:
(i) aspirin, NSAIDs
(ii) alcohol (ethanol)
1. 20% of drink absorbed in stomach and 80% in SI
2. carbonated drink and empty stomach – absorb faster
Gastric Function of Motility
• After initial digestive processes the stomach propels food into duodenum
a. Relaxation of stomach musculature
• Swallowing – stimulates relaxation of stomach to prepare for bolus
Motility of the Stomach- Stimulus and Sequence
• Stimulus:
(i) Vagus (cholinergic)
(ii) Hormones: gastrin and motilin
• Sequence:
(i) series of alternating small waves traveling towards the pylorus
(ii) 4or 5 sequential peristaltic waves push chyme back and forth (“churn”)
(iii) The last wave “forces” pyloric sphincter to open and chyme is pushed into duodenum
1. pylorus normally is open just a small amount 1-2 cm
2. opening not enough to have duodenum regurgitate back into antrum (pylorus)
Gastric Emptying
• Average total time to empty stomach?
(i) 50% empties after 2-3 hours
(ii) Total emptying after 4-5 hours
• Rate of gastric emptying is dependent on volume, osmotic pressure and type of food ingested
Factors that increase rate of gastric emptying
Larger food volume increases rate of gastric emptying
Factors that decrease rate of gastric emptying
- Hyper/hypotonic fluid
a. receptors in stomach wall detect osmotic pressure
b. this allows time to create/facilitate an isoosmotic environment for duodenum - Fatty foods
a. CCK (cholecystokinin) synthesized and released by duodenum/SI will inhibit gastric motility (and decrease acid production)
b. Fats are digested in the duodenum – if too much fat enters SI then feedback loop slows down rate to allow time to properly digest fats - Increased rate of acids entering the duodenum
a. acid is neutralized in duodenum so if too much entering then feedback is to inhibit gastric emptying to decrease acid entering duodenum
Gastric Secretions
a. Specialized cells of gastric mucosa produce and secrete necessary substances for digestion/gastric homeostasis
• Gastric juice = acid, mucus and pepsinogen
b. Major secretions of stomach (mucus, acid, proteases, hormones, intrinsic factor)
Function of Mucus
- Protection of mucosal layer from acid and pepsin (protease)
a. The acid in the stomach has a pH of approximately 1.5
b. The mucous provides a “transitional layer” to protect the epithelium of the stomach
i. This layer has a neutral pH (approximately 7.0) at the epithelial surface
ii. The mucous contains high levels of bicarbonate (HCO3-) to neutralize the H+
Stimulus of Mucus Secretion
- Prostaglandins
2. Nitric oxide
Disruption of mucus barrier (inflammation/ulceration)
- Aspirin, NSAIDs and alcohol
- bile salts – regurgitated from SI
- Helicobacter pylori (H pylori)
Function of Acid Secretion
- Dissolve food
- Inactivation of digested bacteria/microorganisms
- Convert pepsinogen to pepsin
Acid Secretion from parietal cells:
- Acid formation/secretion occurs in “exchange” for bicarbonate
a. Increased gastric acid secretion will increase bicarbonate entering plasma
Stimulus of acid secretion
- Ach (acetylcholine) – via vagus nerve (parasympathetic)
- Gastrin
- Histamine
Inhibition of acid secretion
- Gastric inhibitory peptide (GIP)
- Somatostatin
- Secretin
- Prostaglandins
Pepsin (protease) secretion
(i) Pepsinogen is produced and secreted by chief cells
(ii) Pepsinogen is converted to pepsin in an acidic environment (pH < 2)
(iii) Function: Proteolytic enzyme that breaks down proteins in the stomach
(iv) Pepsin is inactivated as chyme passes into alkaline conditions of duodenum
4 Gastric Hormones
(i) Gastrin
(ii) Motilin
(iii) GIP (gastric inhibitory emptying peptide)
(iv) Grehlin
Gastrin
- promotes gastric juice (acid) secretion and gastric motility
- secreted from G cells of stomach (located in antrum
Motilin
- promotes stomach/SI motility
2. secreted from endocrine cells located in small intestine
GIP (gastric inhibitory emptying peptide)
- inhibits gastric juice (acid) secretion and gastric motility
- secreted from endocrine cells located in small intestine
Grehlin
- “hunger hormone” - plays role in appetite sensation/feeding behavior
- Fast acting - stimulates the sensation of hunger
a. Levels rise just before meals - secreted from endocrine cells mostly located in stomach
a. also secreted from: kidneys, hypothalamus, pituitary, placenta
Intrinsic Factor for Gastric Hormones
(i) Secreted by parietal cells of stomach
(ii) Necessary for Vitamin B12 absorption in small intestine
1. B12 – plays role in maturation of erythrocytes
2. Deficiency of B12 absorption will develop pernicious anemia
Surface epithelial cells of the folds (Cells of the Stomach)
- Mucous cells
- Function:
a. produce thick mucous (protection from abrasion of food and from acidic pH levels in stomach)
4 Types of cells in the Body or fundus regions
- Mucous cells
a. Located in “neck” of gastric glands
b. Secrete thin, watery mucus to liquefy stomach contents - Parietal cells
a. secrete acid (HCl) and intrinsic factor - Chief cells
a. secrete pepsinogen (promote protein digestion) - Enterochromaffin-like cells
a. Secrete histamine (promotes acid secretion)
1 Type of Cell in the Cardiac Region
- Mucous cells
a. Secrete thin, watery mucus to liquefy stomach contents
2 Types of Cells in the Pyloric (antrum) regions
- Mucous cells
a. Secrete thin, watery mucus to liquefy stomach contents - G cells
a. Secrete gastrin (promotes acid secretion/motility)
Adjustable gastric band (LAP BAND)
(i) placement of a band creates a small pouch at the top of the stomach
(ii) small pouch ‘fills’ with food quickly and the passage of food from the top to the bottom of the stomach is slowed
(iii) upper part of the stomach experiences a sensation of fullness
Vertical Banded Gastroplasty (VBG) - “stomach stapling with lap band”
(i) MC restrictive operation for weight control.
(ii) Both a band and staples are used to create a small stomach pouch.
(iii) Small opening in bottom of the pouch through which food can pass into the remainder of the stomach
(iv) Smaller pouch
1. sense of fullness occurs with less food intake
2. if continue to eat then individual will experience pain, nausea, or possible vomit
3. helps the person to eat smaller portions and lose weight over time
Outcomes of VBG (meaningful lifestyle changes important for success)
- Initial outcomes of VBG
a. will vary from “complete” wt loss (30%), some wt loss (50%) to poor - Long term outcomes of VBG
a. many patients may regain wt by gradually stretching the small pouch
Gastric bypass procedures
- reduces stomach size by creating small pouch (similar to above)
a. staples or lap ring (mimics pyloric valve) - physically redirects anatomy of GI tract
a. bypass created so chyme bypasses proximal small intestine
i. different procedures vary how much of the small intestine is bypassed
b. purpose of bypass:
i. limit absorption of calories (and nutrients) in small intestine
Complications of Gastric Bypass Procedure
- nutritional deficiencies: long term supplementation plan necessary to compensate for bypass
- Dumping syndrome (“rapid gastric emptying”)
a. occurs when jejunum rapidly fills with undigested food from the stomach
b. results in cramping, bloating, nausea, vomiting, diarrhea, and shortness of breath - direct complications to GI tract: bleeding, infections, etc…
Gastritis
• Gastritis commonly refers to inflammation of the gastric mucosa (lining of the stomach)
(i) Not referring to peptic ulcer disease
• The term is often used to cover a variety of symptoms resulting from the inflammation and ulceration of gastric mucosa.
Acute Gastritis
(i) Injury to the gastric mucosa
(ii) Causes of acute gastritis
1. Drugs or chemicals
a. Ex: NSAIDs - inhibit PGs which normally promote mucus secretion
2. H pylori (helicobacter pylori) infection
3. Alcohol and smoking
(iii) Healing
1. can be within in few days if remove offending factor ASAP
Chronic Gastritis
(i) Degenerative gastritis that is more common in elderly
(ii) Results in chronic inflammation, mucosal atrophy and epithelial metaplasia
(iii) Two types of chronic gastritis
1. Type A: chronic fundal gastritis
2. Type B: chronic antral gastritis
Type A Chronic Fundal Gastritis
a. Less common vs Type B
b. Suggested to be a result of autoimmune disorder
i. Antibodies attack parietal, chief cells and intrinsic factor
c. Mucosa degenerates – loss of parietal cells & chief cells lead to decreased gastric acid, pepsinogen and intrinsic factor (pernicious anemia)
Type B Chronic Antral Gastritis
a. 4x’s more common than Type A
b. NOT considered an autoimmune dysfunction
i. No loss of acid secretion, parietal cells, intrinsic factor
c. Extrinsic environmental causes:
i. H pylori, alcohol, tobacco, NSAIDs
Location and Patho/phys of a Gastric Ulcer
• Location
(i) More common in antrum
• Pathophsyiology
(i) Chronic exposure to various substances result in break down of protective mucosal lining of the stomach
(ii) Mucosal lining becomes permeable to H+ ions
(iii) Submucosal area exposed to digestive acids and secretions
(iv) Damaged mucosa releases histamine which increases release of acids/pepsinogen, capillary permeability
• Misc comments
(i) Gastric ulcers possess higher risk of cancer
Risk Factors for Gastric Ulcers
- Chronic use of aspirin, NSAIDs
- Helicobacter pylori (H. pylori) infection
a. present in 60 – 80% individuals with gastric ulcer
i. Note: H pyloric present 95-100% in duodenal ulcers
(ii) Other risk factors
1. Chronic gastritis
2. Chronic alcohol use
3. Smoking
4. Increasing age
5. Reflux of bile salts from duodenum
Clinical Signs and Symptoms of Gastric Ulcers
(i) Food provoking pain pattern (pain immediately after eating)
1. different pattern for duodenal ulcer (relief with eating and pain 2-3 hrs post eating)
(ii) Gastric ulcers – more chronic in nature vs exacerbation/remission with duodenal ulcer
