Intrinisic innervation by enteric nervous system
Within the wall of the GI:
Myenteric Plexus (Auerbach’s)
Submucosal Plexus (Meissner’s)
Myenteric Plexus (Auerbach’s)
*Located between layers of muscularis externa
*Regulates motility/muscular contraction
Submucosal Plexus (Meissner’s)
*Located in the submucosa
*Regulates secretion and absorption
Extrinisic Innervation of GI
Outside the wall of the GI.
*Sympathetic
*Parasympathetic
*Neurotrasmitters (acetylcholine, serotonin, dopamine, norepi)
Sympathetic Innervation of GI
*Via celiac, superior mesenteric, inferior mesenteric ganglion
*Decreased motility and secretion
*Increased sphincter ctx
*Increased vasoconstriction
Parasympathetic Innervation of GI
*Via vagus nerve (mouth to transverse colon), pelvic nerve (distal colon, rectum, anus)
*Increased motility and secretion
*Sphincter relaxation
Gastrin
*Released @ gastric antrum and duodenum
*Stimulated by peptides, amino acids, distention, vagal stimulation
*Stinulates acid secretion
CCK
*Released in duodenum and jejunum
*In response to peptides, amino acids, fatty acids
*Stimulates gallbladder ctx, bicarb secretion
Secretin
*Released by duodenum
*In the presnece of acid (fat)
*Stimulates bicarb secretion. Inhibits gastric acid secretion
Motilin
*Released in duodenum ad jejunim
*Stimulates gastric and duodenal motility
Pancreatic polypeptide
*Released at islets of Langerhans in reponse to proteins (fat and glucose)
*Inhibits pacreatic bicarb and ezyme secretion
Somatostatin
Released in response to acid. Vagal inhibits release
Inhibits release of most other peptide hormones
Prostaglandins (GI)
Promotes blood flow, increases mucous and bicarb secretion from gastric mucosa
Histamine (GI)
Stimulates gastric acid secretion
VIP
Relaxes spincters and gut circular muscle; stimulates intestinal and pancreatic secretion
Intrinisic factor
Released by parietal cells in the stomach to bind vit b12 and facilitate its absorption
Mucin
Goblet cells. Lubrication and protection
Acid
Parietal cells of stomach.
Prevents infection; initiates digestion; activates enzyme pepsinogen; release b12 from food
H+ ion secretion process by parietal cells
*Secreted by parietal cells in gastric body
*H+ formed within parietal cells is pumped via H+ -K+ ATPase (proton pump) against a high H+ concentration gradient.
*Cl- transported across the parietal cells to the GI lumen –> HCl
*Acid secretion by stomach – pH 1 to 2
*HCO3 elimination from the parietal cells creates alkaline tide that helps prevent mucosal injury
Acid secretion – stimulated by
Histamine, Gastrin, Acetylcholine, eating
Acid secretion – Inhibited by
Somatostatin, GIP, secretin
3 phases of acid secretion stimulated by eating
*Cephalic (sight, smell taste): activates parasympathetic system to secrete gastrin, histamine, acetylcholine
*Gastric: distention of food. Stimulates parasympathetic system
*Intestinal: nutrients reach duodenum; gastric secretion modulated by duodenal contents
Gastroparesis – Definition
Delayed gastric emptying due to partial or incomplete paralysis of the stomach motility
Gastroparesis – Etiology
Common complication of poorly controlled diabetes mellitus with autonomic neuropathy
Gastroparesis – Pathogenesis
*Impairment of neural control of gastric motility by enteric nervous system and autonomic nervous system.
*Poor glucose control leads to neuropathy and impaired gastric motility
*Results in partial to complete gastric outlet obstruction, delayed emptying, release of large boluses of chyme
Characteristics of H. pylori
*Flagella – motility
*Elaborates urease which helps to increase local gastric pH and protect itself from the gastric acid
*Adhesins –> enhances bacterial adherence to surface foveolar cells
*Secretes toxins encoded by cytotoxin-associated gene A (CagA)
H. pylori – increased risk of ulcers patho
Increased gastric acid production and impairment of duodenal bicarb production
H pylori – risk for carcinoma patho
Damage to mucosa permits leakage of tissue nutrients to the surface and also permits back leakage of acid to epithelium –> injury of cells leads to intestinal metaplasia
H pylori has a role in:
*Acute/chronic gastritis
*H pylori gastritis
*PUD
*gastric tumors
Esophageal varices – Etiology
Portal HTN
Hepatic schistosomiasis
Esophageal varices – patho
*Collateral bypass channels develop in lower esophagus when portal HTN diverts blood flow through coronary veins of stomach into esophageal subepithelial and submucosal veins
*Vessels become dilated and turtorous
Esophageal varices – clinical manifestations
Often asymptomatic. May rupture leading to massive hematemesis and death. >50% mortality rate.
Osmotic Diarrhea
*Due to malabsorbed nutrients or poorly absorbed electrolytes that retain water in lumen
*High osmolality of solutes draws water into lumen
*Stops when fasting
*Mannitol, lactulose, defective fat solubilization, pancreatic enzyme deficiency
Secretory Diarrhea
*Excessive mucosal secretion of F&E that is greater than absorptive capacity of GI lumen
*Does not stop when fasting
*Enterotoxins, tumors that stimulate secretion, laxatives that stimulate secretion, Infectious agents that injure enterocytes and alter absorptive function, bile acids, fatty acids
Exudative Diarrhea
*Purulent, bloody stools that are frequent (may be large or small in volume)
*Does not stop when fasting
*Infections (Salmonella), inflammatory bowel disease
Inflammatory Bowel Disease – Definition
Characterized by recurrent episodes of mucopurulent, bloody diarrhea, but lack of positive cultures for infectious organisms and fails to respond to abx alone
Types: Crohn’s, Ulcerative Colitis
Crohn’s Disease – Definition
AKA regional enteritis.
*May involve any area of the GI tract.
Is frequently transmural. Discontious lesion patterns (skip lesions).
*Fissures and noncaseating granulomas
Crohn’s Disease – Clinical Manifestations
*Intermittent attack of mild diarrhea
*Malabsorption/malnutrition –> hypoproteinemia
*Other inflammatory dieases (arthritis, uveitis, ankylosing spondylitis)
Ulcerative Colitis – Definition
*Chronic inflammatory disease linited to colon and rectum
*Only involves superficial mucosa and submucosa
*Nongranulomatous
*Continuous lesion pattern
Ulcerative Colitis – Clinical Manifestations
*Periods of remission and exacerbation
*Bloody diarrhea
*Complications of toxic megacolon.
*Increased risk of ca (higher than Crohn’s)
Colorectal Carcinoma (Adenoma-Carcinoma Sequence)
*Mutation in tumor suppressor genes – APC (signal transduction)
*Protooncogene mutation – most commonly K-ras
Colorectal Carcinoma (Microsatellite Instability)
*No detectable antecedent lesions or the tumors may develop from sessile serrated adenomas
*Mutation to DNA mismatch repair gene (MSH2) leads to the accumulation of mutations (because defective cells are not repaired) culminating in the emergence of colorectal carcinomas
Chronic gastritis – definition
Chronic mucosal inflammation and injury that leads to eventual epithelial metaplasia or mucosal atrophy and loss of glands
Types of chronic gastritis
*H pylori gastritis (90%)
*Autoimmune gastritis (10%)
H pylori gastritis – clinical manifestations and dx tests
*N/V, epigastric pain
Dx Tests:
*positive serologic test for anti-h pylori antibodies
*positive urea breath test
*fecal bacterial detection
*gastric biopsy to test for urease, bacterial culture
H pylori gastritis – patho
*modulation of immune system to allow colonization of gastric cells
*urease damages mucosa and causes inflammation
*increased gastric acid secretion and impaired duodenal bicarb production
*increased risk for carcinoma r/t damage causing metaplasia
Autoimmune gastritis – patho
*Antibody to parietal cells–> loss of parietal cells
*Defective acid secretion (achlorydia) –> stimulates gastrin –> hypergastrinemia and hyperplasia of G cells
*Decreased intrinsic factor –> pernicious anemia
Esophageal achalasia – definition
A motor DO of the esophagus in which the lower esophageal sphincter fails to relax properly during swallowing leading to a functional obstruction
Esophageal achalasia – patho
Primary:
*Loss of intrinisic inhibitory innervation of LES
*Loss of normal peristalsis
Secondary:
*Myenteric plexus damage from disease
*Incomplete LES relaxation
*Increased LES tone
*Aperistalsis
*Progressive dilation of esophagus
*botulinum toxin to LES can ameriloriate s/s
Esophageal achalasia – clinical manifestations
*Dysphasia
*Diffuse esophageal spasm
*Noncardiac chest pain
*Regurg and aspiration of undigested food through UES
*Risk of esophageal carcinoma 2-7%
Malabsorption syndrome – Definition
Defective ability to digest or absorb nutrients that produce voluminous bulky stools
Malabsorption syndrome – Patho/Etiology
*Defective intraluminal digestion
*Mucosal cell abnormalities
*Reduced small intestinal surface area
*Infection
*Lymphatic obstruction
*Lactase deficiency
*Gluten deficiency/Celiac Disease
Lactase deficiency – patho
*Lactase enzyme usually present in brush border of the enterocytes in the small intestine
*Deficiency of lactase –> prevents lactose absorption and undigested lactose is present in GI lumen
*Increases osmotic gradient in intestines –> diarrhea
Celiac Disease – patho
*Immune mediated that is triggered by gluten ingestion
*Cell mediated response (CD4 T-cell) to glutens.
*CD8 T-cell and inflammatory response
Celiac Disease – clinical manifestations
Anemia, diarrhea, bloating, fatigue
*presence of IgA antibodies to tissue transglutaminase
*Presence of IgA or IgG antibodies to deamidated gliadin
Irritable bowel syndrome – definition
Altered bowel function (constipation/diarrhea) with abd pain or discomfort that it NOT explained by strutural or biochemical abnormalities
Irritable bowel syndrome – etiology
*Gut microbiota (type and # of bacteria)
*Immune reactivity/inflammation
*Genetics
Irritable bowel syndrome – patho
*Dysfunction of extrinsic and intrinsic nervous system
*Altered bowel motility (exagerated intestinal motor response to stress and food intake. Altered frequency of peristaltic contractions.)
*Visceral hypersensitivity (normal distention to be felt as discomfort)
Irritable bowel syndrome – clinical manifestations
*Alterations in bowel habits between diarrhea and constipation
*Abd pain
*Bloating , perceived abd distention
*High health care costs, impacts quality of life
GERD – definition
Reflux of gastric acid and pepsin through LES into esophagus
GERD – Etiology (5 factors)
*Inefficient/slowed gastric emptying
*Increased frequency of transient LES relaxations
*Increased acidity
*Loss of secondary peristalsis
*Decreased LES tone/incompetent LES
GERD – patho
*Persistent and repeitive acid to the esophageal mucosa –> esophagitis
*Epithelial hyperplasia and ulcertions
*Esophageal stricture/perforation
*Chronic GERD –> intestinal metaplasia –> Barrett’s Esophagus
*Barrett’s Esophagus occurs in 10%. Increased risk of esophageal adenocarcinoma
GERD – clinical manifestations
*Heartburn worse when lying prone
*Stricture of esophagus –> dysphagia
*Hoarseness, coughing, wheezing, pneumonia
*Reddened mucosa under endoscopy
Acute gastritis – definition
Acute inflammation of gastric mucosa and usually transient with relief from etiological stimulus
Acute gastritis – etiology
NSAIDs
Excessive alcohol use
Heavy smoking
Tx for ca, uremia, infection
Stress
Mechanical trauma
H pylori infection
Acute gastritis – Patho
*Increased acid production –> injury to gastric cells –> acute inflammation with mucosal edema and infiltrate of neutrophils
*Possible errosion and hemorrhage (particularly those who take NSAIDs and alcoholics)
Acute gastritis – clinical manifestations
Variable epigastric pain, N/V, bleeding
NSAID-induced gastric ulceration
NSAIDs suppress mucosal prostaglandin synthesis –> increased secretion of HCl and decreased bicarb and mucin production
Peptic ulcer disease occurs most frequently in:
gastric antrum and first portion of the duodenum
Most common cause of duodenal ulcers
H pylori infection
Most common cause of gastric ulcers
NSAID use
PUD – patho
*Gastric hyperacidity (parietal cell hyperplasia, excessive secretory response)
*Impaired defensive mechanisns
*Increased depth of damage to the submucosa at least and is possible into the muscularis mucosa
Zollinger-Ellison Syndrome
Uncontrolled release of gastrin
PUD – clinical manifestations
*Pain 1 to 3 hours after meals
*Worse at night
*Relieved by alkali or food
*N/V, bloating
Acute appendicitis – patho
*Progressive increase in intraluminal pressure –> impaired venous outflow
*Overt obstruction by stool (most often), gallstone, tumor, or mass, worm
*Ischemic injury and stasis of luminal contents –> inflammatory response –> tissue edema
Acute appendicitis – Clinical manifestations
*Periumbilical pain localized to right lower quad
*Low grade fever
*Mildly elevated WBC
*McBurney’s sign: deep tenderness at location 2/3 of the distance from the umbilicus to the right anterior superior iliac spine
A manifestation of liver dysfunction is impaired protein synthesis. What are the three phenomenons related to that?
- clotting factor deficiency: bleeding, elevated PT (vitamin K related anemia).
- hypoalbuminemia: edema, ascites.
- inadequate antibody production. (immunoglobulin = protein)
What is indirect bilirubin?
= unconjugated bilirubin
- elevated with increased RBC breakdown or impaired liver uptake
- bound by albumin so not found in urine
(Bilirubin, the end product of heme catabolism, is transported to the liver to be conjugated and excreted via the bile. Most of the bilirubin in blood is in transit from the tissues to the liver, in the unconjugated form, bound to albumin. Only small amounts of conjugated bilirubin are normally found in blood, and it is believed that the usual analytical methods tend to overestimate it in the low reference range. Bilirubin determinations are reported in two fractions, the “conjugated” and the “total.”)
What is direct bilirubin?
= conjugated bilirubin
- elevated with impaired excretion of bilirubin from liver
- water soluble, so is found in urine
How is bilirubin transported?
unconjugated bilirubin –> liver –> conjugated bilirubin –> gall bladder –> bile production in the gallbladder to digest fat in the GI tract
How is bilirubin excreted?
- Bile
- some excreted in the stool (brown)
- Some reabsorbed into the blood stream
- very small amount, if any, excreted in the urine
(Bilirubin is excreted in bile and urine.
- the yellow color of bruises
- the yellow color of urine (via its reduced breakdown product, urobilin)
- the brown color of faeces (via its conversion to stercobilin)
- the yellow discoloration in jaundice.)
If the liver gets fibrotic and not working well which bilirubin level would be elevated?
conjugated bilirubin (hepatitis, fibrosis, and cirrhosis) . In hepatitis, fibrosis, and cirrhosis, high amounts of unconjugated bilirubin means the liver cells are not conjugating bilirubin normally, causing it to build up in the blood (abnormal RBC breakdown).
If we have a plug so bile can’t get out of the liver (e.g. cholelithiasia), what happened to bilirubin?
increased conjugated bilirubin. –> Jaundice
(The liver converts ammonia to urea for excretion in the urine.)
What are the three causes for jaundice?
- prehapatic: increased indirect (unconjugated) bilirubin.
- hepatocellular: e.g. ETOH, hepatitis that increase direct bilirubin
- cholestatis/obstructive: increase direct bilirubin
When patient has cholelithiasia, what color of stool and urine would he have?
- Stool: pale, white, clay because no bilirubin in the stool.
- dark urine because elevated direct bilirubin goes to the nephrons and excrete in the urine.
In a liver dysfunction, urea synthesis is inadequate. What happens?
increased blood ammonia level (NH3). –> hepatic encephalopathy
What is the normal amino acid breakdown process?
amino acid breakdown –> ammonia –> urea, excreted in urine. On standing, urea in urine reverts to ammonia.
What are the correct precipitating factors of hepatic encephalopathy?
- decreased potassium, sodium, and oxygen (O2).
- increased Co2.
- alkalosis, infection, hemorrhage, increased protein intake, renal failure, constipation
- sedatives
What does Lactulose (Cephulac) do?
Decreases pH of colon.
- decreased production of ammonia (NH3).
- reduced diffusion of NH3 from colon into blood.
- cathartic excretion of NH3.
Due to liver dysfunction, toxins and hormones are accumulated. What are the three outcomes from it?
- Accumulation of toxins and hormones
- feminization (excess estrogens)
- poor metabolism of drugs
- spider nevi (estrogen)
What happened to AST and ALT levels in a patient with liver dysfuction?
Release of marker enzymes into body: elevated AST and ALT
Explain the portal circulation system?
All blood from the GI tract goes to the liver to metabolize and absorb nutrition, then goes out through the hepatic vein to vena cava. If the liver is not working then blood backs up in the portal vein which leads to portal hypertension.
What causes portal hypertension and what are its complications?
Liver fibrosis and degeneration causes backup of blood into portal circulation. Increased pressure (hydrostatic pressure) causes varices, ascites, anorexia, hemorrhoids.
What are the three medication treatments for esophageal varices?
- vasopressin (Pitressin) = ADH has a vasoconstriction effect. Side effect: MI (Give NTG), hyponatremia. (ADH: holds on to water)
- Octreotide: reduce portal blood flow.
- metoclopramide (Reglan): esophageal muscle constriction. neuromuscular disorder side effect.
What other medical treatments are there for esophageal varices?
EGD- sclerosis, ligation/banding, Balloon tamponade.
transjugular intrahepatic portosystemic shunting. (shunt between portal vein and hepatic vein)
What are the two major causes of ascites?
Ascites is accumulation of fluid in the peritoneal space.
Portal hypertension (increased hydrostatic pressure) + hypoalbuminemia (decreased oncotic pressure).
What are the two major complications with hepatic ascities?
peritonitis and esophageal varices.
Why do you give albumin for paracentesis?
to prevent hypotension.
What are the two medications causing GERD?
tricyclics and anticholinergics
What are the complications of GERD?
- . Barrett’s esophagus (esophageal lining replaced with columnar epithelium, premalignant) 2. aspiration pneumonia.
- bronchospasms (45-65% w asthma have GERD).
- strictures of esophagus.
What are the medication options for GERD?
- antiacids, H2 blockers, proton pump inhibitors (PPI).
- Gaviscon: breaks down gas bubbles
- Metoclopramide (reglan): increases GI motality –> increases gastric emptying
- Bethanecol (Urecholine) = cholinergic drugs increases GI motality –> increases gastric emptying; increases lower esophageal sphincter (LES) tone.
What is a surgical option for GERD?
Nissen fundoplication.
What is the difference between sliding hiatal hernia and rolling hital hernia?
Sliding hiatal hernia is that fundus moves up through and rolling (paraesophageal) hernia is that part of stomach slips up. Both increases a chance of stomach contents getting up in the esophagus.
What are the two surgical repairs for hital hernia?
laparoscopic fundoplication and endoscopic fundoplication.
What are the contributing factors of gastritis?
ETOH, caffeine, smoking, ASA, steroids, reflux of duodenal contents, bacterial endotoxins (H. pylori, e. coli), radiation
what condition does a specific hyperacidity test for?
Zollinger-Ellison Syndrome
What are the medication choices for gastritis?
PPI, H2 blockers, Cytotec = misoprostol (acts as prostaglandin protecting the lining of the stomach)
What are three kinds of peptic ulcers?
gastric, duodenal, stress (in ICU setting stress ulcer means it’s from a HPTN epicode).
What are the surgical options for peptic ulcers?
Billroth I, Billroth II, vagotomy
What is the major cause of pancreatitis?
autodigestion of pancreas
What are the symptoms of pancreatitis?
epigastric tenderness and pain, abdominal distention, peritoneal fluid accumulation, stool changes, jaundice, high fever, tachycardia, cullen’s sign, and turner’s sign, hypocalcemia.
Which lab tests are monitored for pancreatitis?
elevated serum lipase and amylase
Others: increased bilirubin, alk phos, LFT, WBC, and glucose
What is the difference between ulcerative colitis and crohn’s disease?
ulcerative colitis is an inflammatory process only in the colon mucosal layer whereas crohn’s diease is anywhere in the GI tract.
What are the drug choices for ulcerative colitis?
- anti-inflammatories: sulfasalazine, corticosteroids, dipentium.
- immunosuppressants: cyclosporine.
- Rowasa (decreased prostaglandin production).
- antidiarrheal drugs.
What is the main mechanism of IBS?
Not inflammatory changes (means not an autoimmune) but change in motility and functional disorder.
What are three main changes caused by portal hypertension?
- increased pressure in peritoneal capillaries: ascites.
- portosystemic shunting of blood: caput medusae, hemorrhoids, varices, encephalopathy.
- spelnomegaly: anemia, thrombocytopenia, leukopenia.
Three stages of alcoholic liver disease?
- fatty liver (steatosis): enlarged liver with fat deposits.
- Alcoholic hepatitis: inflammation and cell failure (necrosis).
- cirrhosis: scar tissue partially blocks sinusoids and bile canaliculi.
What kind of cellular injury does viral hepatitis cause?
direct cellular injury
Which function of Kupffer’s cells is to remove harmful substances or cells from the portal blood as it moves through the venous sinusoids?
phagocytes (macrophages: A large phagocytic cell found in stationary form in the tissues or as a mobile white blood cell, esp. at sites of infection.)
Both prehepatic and posthepatic causes of portal hypertension include the formation of?
venous thrombosis
What are the prehepatic, intrahepatic, and posthepatic causes of portal hypertention?
- Prehepatic obstruction: portal vein thrombosis or congenital atresia (Narrowing of the ear canal).
- Intrahepatic: liver cirrhosis, and hepatic fibrosis (e.g. due to Wilson’s disease, hemochromatosis, or congenital fibrosis).
- Posthepatic: (occurs at any level between liver and right heart) e.g. hepatic vein thrombosis, inferior vena cava thrombosis, inferior vena cava congenital malformation, and constrictive pericarditis.
What are the two late signs of cirrhosis?
liver failure and portal hypertension.
What is caused when patient has an acute pancreatitis, activated pancreatic enzymes that escape into surrounding tissues in the abdominal cavity?
fatty deposits
How much of fluid does the bode secret into the gastrointestinal tract?
7000ml
What is the movements that are rhythmic propulsive movements that occur when the smooth muscle layer constricts, forming a contractile band that forces the intraluminal contents forward?
Peristaltic movement (peristalsis)
Does the mesentery contain the intestine’s blood supply?
An extension of the visceral peritoneum, the mesentery contains blood vessels that supply oxygen and nutrients to (arteries) and eliminate CO2 and waste from (veins) the intestines.
what is Ghrelin?
An enzyme produced by stomach lining cells that stimulates appetite
What is ghrelin level in Prader-Willi Syndrome?
very high
what is Gastrin?
A hormone that stimulates secretion of gastric juice, and is secreted into the bloodstream by the stomach wall in response to the presence of food
What is the largest serous membrane in the body, the outer wall of the intestine, and contains a serous fluid between its two layers?
Peritoneum
Which neuron is innervated by for motility along the length of the gut, control of function, and communication of each segment?
intramural neurons
The stomach is the source of two hormones produced by the gastrointestinal tract: gastrin and ghrelin. Ghrelin is a peptide hormone produced in the mucosal layer that has an important role in regulation of __ secretion.
growth hormone
In addition to mucus, the intestinal mucosa produces two other types of secretions. Copious amounts of the serous type fluid are secreted to act as a(n)
vehicle for absorption
The intestinal absorption of glucose and amino acids is facilitated by a __ transport system.
sodium-dependent
As food enters the esophagus, which nerve initiates peristaltic waves controlled by the swallowing center?
vagus nerve