G.I. Tract Test II

Question 1

GI System

Answer 1

Consumes, digests, and eliminates food

Made of;

Upper division (Oral cavity, Pharynx, Esophagus, and Stomach)

Lower division (Small intestine, Large intestine, and anus)

Hepatobiliary system (Liver, gallbladder, and pancreas)

Question 2

GI System tissues

Answer 2

Four Layers - Muscosa, Submucosa, Muscle, Serosa

Peritoneum - Parietal (lines the cavity), Visceral (Lines the organs), Cavity (space between the two).

Mesentary - double layer peritoneum containing blood vessels and nerves that supply the intestinal wall.

Question 3

GI wall

Answer 3

Question 4

GI Wall part 2

Answer 4

Epithelium - Most exposed part of the mucosa - composed of simple columnar epithelium or stratified squamous epithelium, also present ar Goblet cells (secrete mucus that protects the epithelium from digestion) and endocrine cells (secrete hormones into the blood).

Under the epithelium is the lamina propria, which contains myofibroblasts, blood vessels, nerves and several different immune cells, and the muscularis mucosa which is a layer of smooth muscle that aids in the action of continued peristalsis along the gut.

The submucosa contains nerves including the submucosal plexus (Meissner’s plexus), blood vessels and elastic fibers with collagen, that stretches with increased capacity but maintains the shape of the intestine.

Surrounding this is the muscular layer, which comprises both longitudinal, and circular smooth muscle that also helps with continued peristalsis and the movement of digested material out of and along the gut. In between the two layers of muscle lies the myenteric plexus (Auerbach’s plexus).

The serosa is a serous membrane that covers the muscularis externa of the digestive tract in the peritoneal cavity.

Question 5

Upper GI tract

Answer 5

Food enters mouth to begin mechanical/chemical digestion.

Swallowing coordinated by the swallowing center in the medulla and cranial nerves V, IX, X, and XII.

Question 6

Digestive juices and actions

Answer 6

From the Salivary Glands

Bicarbonate - Moistens food

Salivary Lipase - Digests Fat

From the Stomach

Hydrochloric acid - Kills Bacteria

Pepsin - Digests Protein

Gastric Lipase - Digests Fat

Intrinsic Factor - Aids in B12 absorption

Mucus - Protects stomach lining.

Question 7

Congenital abnormalities of the GI

Atresia, Fistulae, and Duplications

Answer 7

Atresia - Incomplete development of the Esophagus.

Most commonly occurs at the tracheal bifurcation and is usually associated with a Fistula (Adhesion of the esophagus to the trachea ). Discovered shortly after birth - Regurgitation during feeding. Leads to Aspiration, suffocation, pneumonia, and severe fluid/electrolyte imbalances. (associated with congenital heart defects, genitourinary malformations, and neurologic disease)

Acquired Stenosis - inflammatory scarring eg. GERD, irradiation, systemic sclerosis, or caustic injury.

Question 8

Congenital abnormalities of the GI

Diaphragmatic Hernia & Omphalocele

Answer 8

Diaphragmatic Hernia - Incomplete formation of the diaphragm allows the abdominal viscera to herniate into the thoracic cavity

Omphalocele - occurs when the closure of the abdominal musculature is incomplete and the abdominal viscera herniate into a ventral membranous sac.

Question 9

Congenital abnormalities of the GI

Meckel’s Diverticulum

Answer 9

A true diverticulum - blind outpouring of the alimentary tract that communicates with the Lumen.

Failed involution of the Vitelline duct.

Rule of 2

Occurs in 25 of the population present within 2 feet of the ileocecal valve, approx 2 inches long, 2 times as common in males, most often symptomatic by 2 y/o. (only 4% symptomatic)

Ectopic pancreatic or gastric tissue may also be present giving the ability to Secrete acid causing peptic ulceration of adjacent small intestinal mucosa.

May present with occult bleeding (painless BRBPR) or abdominal pain resembling acute appendicitis or obstruction.

Question 10

Congenital abnormalities of the GI

Pyloric Stenosis

Answer 10

3-5 times more common in males and occurs 1 in 300-900 live births.

Increased risk in monozygotic twins, dizygotic twins, siblings, Turner syndrome, and trisomy 18, erythromycin or Azithromycin exposure.

Presents between 3-6 weeks as new onset Regurgitation, projectile, non-bilious vomiting after feeding, and frequent demands for re-feeding.

Hyperplasia of the pyloric muscularis externa, which obstructs the gastric outflow tract.

Edema and inflammatory changes in the mucosa and submucosa may aggravate the narrowing.

Acquired - antral gastritis or peptic ulcers close to the pylorus, ca. stomach.

Question 11

Congenital Abnormalities of the GI

Hirschsprung Disease

Answer 11

1 in 5000 live births, ~ 10% in Down Syndrome

Presents with failure to pass meconium in the immediate postnatal period.

Obstruction or constipation follows, often with visible ineffective peristalsis, and may progress to abnormal distension and bilious vomiting (congenital aganglionic megacolon).

Major Threats - enterocolitis, fluid/electrolyte disturbances, perforation, and peritonitis

Question 12

Congenital Abnormalities of the GI

Achalasia

Answer 12

Increased amounts of Ach at the Lower Esophageal Sphincter (LES) prevents it from opening all the way which then leads to a back-up in the esophagus.

Symptoms - Dysphagia for solids/liquids, difficulty in belching, regurgitation, chest pain, and weight loss.

Primary- ganglion cell degeneration

Secondary- Chagas disease, diabetic neuropathy, infiltrative disorders such as malignancy, amyloidosis, lesions of the dorsal motor nuclei of vagus, polio or surgical ablation, in association with Down syndrome; alacrima and adrenal insufficiency.

Question 13

Esophageal conditions

Relux Esophagus

Answer 13

Reflux of gastric contents into the lower esophagus.

SSE - sensetive to acid

Submucosal glands - protection by secreting mucin and HCO3.

Alcohol/tobacco, obesity, CNS depressants, pregnancy, hiatal hernia, decreased gastric emptying leads to Less Tone of LES and Inc abdominal pressure.

Most Frequent Clinical Features - Heartburn, dysphagia, regurgitation, sour-tasting gastric contents.

Complications - ulceration, hematemesis, melena, stricture development, and Barret’s esophagus.

Question 14

Esophageal conditions

Esophageal Varacies

Answer 14

Abnormal dilation of the junction between the portal and systemic venous systems.

Important cause of massive and frequent life-threatening bleeding.

Portal HTN -> Esophageal Varacies -> Bleeding

Portal HTN forces Portal blood into alternate channels.

Presents in nearly half of the PTs with cirrhosis - as many as half the PTs die from the first bleeding episode.

Question 15

Esophageal conditions

Barrett Esophagus

Answer 15

Complication of the chronic GERD characterized by intestinal metaplasia

Characterized by the replacement of the normal stratified squamous epithelial lining -> simple columnar epithelium with goblet cells (which are mostly found lower in the GI tract)

Most commonly found in white males 40-60 y/o

Increased risk of esophageal adenocarcinoma

Barrett esophagus can only be identified through endoscopy and biopsy, which are usually prompted by GERD symptoms.

Question 16

Esophageal conditions

Esophageal Tumors

Answer 16

7th leading cause of cancer death.

Incidence increases with age: peak -> 6th -7th decade.

Sq. Cell carcinoma (middle 3rd) / Adenocarcinoma (Lower 3rd)

Worldwide: SCC - most common

Adenocarcinoma >50% in the USA due to its association with GERD, Barrett esophagus and obesity.

Question 17

Sq. Cell Carcinoma Risk Factors

Answer 17

Alcohol/Tobacco use (90%)

Caustic esophageal injury

Achalasia, Tylosis

Plummer - Vinson syndrome

Diet deficient in fruits or Vegetables

Very hot beverages

Generic Abnormalities - p53, EGFR

Question 18

Adenocarcinoma Risk Factors

Answer 18

Barret Esophagus, Gerd, hiatal hernia

Obesity

Smoking

Increased acid exposure eg., Zollinger-Ellison Syndrome

Question 19

Esophageal tumors clinical features

Answer 19

Present with dysphagia (90%), odynophagia (pain on swallowing), or progressively increasing obstruction.

Prominent weight loss and debilitation result from both impaired nutrition and the effects of the tumor itself.

Hemorrhage and sepsis may accompany tumor ulceration, and symptoms of iron deficiency are often present.

Lymph node metastases - poor prognosis

5-year survival rate <25%

Question 20

Stomach anatomy

Answer 20

4 major regions - Cardia (the neck), Fundus (top of the body) Body (The main portion of the stomach) Antrum (beginning of the Pyloric canal)

Cardia and Antrum lined mainly with mucin-secreting foveolar cells that form small glands.

The Antral glands are similar but also contain endocrine cells, such as G-cells, that release gastrin to stimulate luminal acid secretion by parietal cells within the gastric fundus and body.

The well-developed glands of the body and fundus also contain chief cells that produce and secrete digestive enzymes such as pepsin.

Question 21

Stomach - Acute gastritis

Answer 21

Includes a diverse set of disorders marked by mucosal injury or dysfunction.

Causes: NSAIDs, alcohol, bile, and stress-induced injury, acute mucosal erosion or hemorrhage, such as Curling ulcers or portal HTN.

Symptoms: Asymptomatic -> variable degrees of epigastric pain, nausea, and vomiting. Severe cases -> mucosal erosion, ulceration, hemorrhage, hematemesis, melena, or, rarely, massive blood loss.

Question 22

Pathogenesis of Acute gastritis

Answer 22

Loss of protective mechanism i.e. NSAID, infection, Hypoxemia, chemicals.

NSAID -> DEC COX -> DEC PGE2/I2 ->DEC Mucosal Protection

H. pylori -> DEC HCO3

Hypoxemia and DEC O2 delivery may account for an increased incidence of gastropathy and acute gastritis at high altitudes.

Ingestion of harsh chemicals (accidentally or in a suicide attempt) -> severe gastric mucosal damage.

Chemicals, alcohol, radiation -> direct epithelial injury

Chemotherapy -> epithelial regeneration

Question 23

Stomach - Chronic Gastritis

Answer 23

Most common - H. pylori (90%), autoimmune gastritis (<10%), Chronic NSAID use.

Less Common - Radiation injury, chronic bile reflux, mechanical injury (e.g. an indwelling nasogastric tube), and systemic diseases such as Crohn disease, amyloidosis, or graft-versus-host disease (GVHD)

Presents as antral gastritis with normal or increased acid production -> PUD.

Question 24

Chronic Gastritis

Answer 24

H. Pylori enters body through the mouth, moves through the digestive system, and infects the stomach or the first part of the small intestine. The spiral-shaped bacterium uses its tail-like flagella to move around and burrow into the stomach lining, which causes inflammation.

Unlike other bacteria, H. Pylori bacteria can survive in the Harsh acidic environment of the stomach because they produce urease that neutralizes stomach acid. Urease reacts with urea to form ammonia, which is toxic to human cells. H. Pylori can also cause overproduction of stomach acid.

Question 25

Virulence Factors of Chronic Gastritis

Answer 25

**Flagella -** mobility, chemotaxis, and colonization of the mucosa **Urease -** Neutralizes gastric acid; mucosal injury (by ammonia) **LPS and Outer Proteins** **-** Adhere to host cells and inflammation **Exotoxins - (vacA) -** Gastric mucosal injury **Secretory enzymes -** mucinase, protease, lipase - mucosal injury **Effectors -** Host cell growth and apoptosis inhibition **Type IV secretion system -** injection of effectors

Question 26

Peptic Ulcer Disease (PUD)

Answer 26

**Complication of chronic gastritis** - chronic mucosal ulceration affecting duodenum or stomach. Associated with **H.Pylori infection, NSAIDs, smoking.** **Clinical Features** Epigastric burning, iron deficiency anemia, hemorrhage, or perforation. Pain tends to occur 1-3 hours after meals during the day, is worse at night and is relieved by alkali or food. Nausea, vomiting, bloating, belching, and significant weight loss. **Complication:** Bleeding, perforation, obstruction.

Question 27

Gastric Polyps

Answer 27

**Inflammatory and Hyperplastic Polyps (75%)** **Polyp \>1.5 cm - should be resected and examined histologically.** Fundic Gland Polyps In individuals with familial adenomatous polyposis (FAP). Increased prevalence - use of PPI therapy. •Asymptomatic or associated with nausea, vomiting, or epigastric pain.

Question 28

Gastric Adenocarcinoma

Answer 28

**Most common malignancy of the stomach ~ 90%** Morphologically - **Intestinal type and diffuse type.** Early symptoms - similar to chronic gastritis and PUD. Advanced - weight loss, anorexia, early satiety (primarily in diffuse cancers), anemia, and hemorrhage. Overall 5-year survival rate \<30%. Precursors - Gastric dysplasia, adenomas. Overall reduction - linked to decreases in H. Pylori prevalence, decreased consumption of dietary carcinogens. Age~55 years and the male-female ratio is 2:1

Question 29

Mutations leading to Gastric Adenocarcinomas

Answer 29

CDH1 BRCA2 TP53 APC TGFB BAX CDKN2A

Question 30

Intestinal obstruction

Answer 30

Most common cause **Adhesions** **Hernia** - any weakness or defect in the abdominal wall permits protrusion of a serosa-lined pouch of peritoneum called a hernia sac. **Volvulus** - twisting of the bowel **Intussusception -** Segment of the intestine, constricted by a wave of peristalsis, telescopes into the immediately distal segment Most common in children \<2

Question 31

Ischemic Bowel Disease

Answer 31

The Majority of the GI tract is supplied by the celiac, superior mesenteric, and inferior mesenteric arteries. Severe atherosclerosis, Aortic Aneurysm, Hypercoagulable states, Oral contraceptive use, Embolization, or Hypoperfusion -\> **Infarction of mucosal/Mural/Transmural layer** -\> Causes **Ischemia** 2 Phase injury **Hypoxic Injury** followed by **reperfusion injury** Most common ~ 70 y/o Sudden onset cramping, left lower abdominal pain, a desire to defecate and bloody diarrhea-\> shock and vascular collapse.

Question 32

Infectious Enterocolitis

Answer 32

Diarrhea, abdominal pain. urgency, perianal discomfort, incontinence, and hemorrhage. \>2000 deaths/day among children in developing countries and greater than 10% of all deaths before age 5 worldwide. Bacterial infections eg. **enterotoxigenic E. coli** are frequently responsible, but etiology varies with age, nutrition, and host immune status as well as environmental influences. **Vibrio** **cholerae** **-\> Contaminated food and water -\> Cholera**

Question 33

Infectious Enterocolitis pathogenesis.

Answer 33

**Non-invasive -** Causes diseases by producing a toxin that interferes with the absorptive function of enterocytes. Asymptomatic or mild diarrhea Sever disease - watery diarrhea **(rice water stools; rate - 1 i/hr)** and vomiting following an incubation period 1-5 days Leads to dehydration, hypotension, muscular cramping, anuria, shock, loss of consciousness, and death. Cholera Toxin -\> INC cAMP -\> Diarrhea

Question 34

Campylobacter Enterocolitis

Answer 34

**Campylobacter jejuni - Most common bacterial enteric pathogen in developed countries.** Important cause of traveler's diarrhea. Associated with ingestion of improperly cooked chicken, unpasteurized milk or contaminated water - an important cause of food poisoning. **Virulence factors:** Motility, adherence, toxin production, and invasion. Enteric fever occurs when bacteria proliferate within the lamina propria and mesenteric lymph nodes. Watery diarrhea, dysentery - can result in **reactive arthritis, erythema nodosum, and Guillain Barre Syndrome.**

Question 35

Campylobacter Enterocolitis Virulence

Answer 35

Ingestion of as few as 500 C. jejuni organisms can cause disease after 8 day incubation period Pathogenesis of Campylobacter infection remains poorly defined. 4 major virulence properties: **Motility, adherence, colonization, and toxin production** **Flagella -** motility adherence & colonization -\> mucosal invasion **Cytotoxins** -\> cause epithelial damage. Dysentery or bloody diarrhea -\> associated with invasion Extraintestinal complications -\> Guillan-Barre syndrome

Question 36

Shigellosis

Answer 36

Shigella flexneri - Gram negative unencapsulated, non-motile facultative anaerobes. Secretes **Shiga toxin (Stx)** -\> DEX protein synthesis **One of the most common causes of bloddy diarrhea (dysentery).** Highly transmissible by the fecal-oral route or via contaminated water and food. Most infectious deaths - children \<5 y/o **Clin Features** 1 week incubation period Diarrhea (watery-\>dystentery), fever, and abdominal pain

Question 37

Shigellosis - Invasion and inflammation caused by Shigella

Answer 37

Shigella organisms are resistant to the harsh acidic environment of the stomach which partially explains the very low infective dose. Shigella species cross the epithelial barrier through M-cells (microfold cells) where they encounter macrophages. Binding of lipoprotein to TLR2 in macrophages results in the production of chemoattractant IL-1B and IL-8. IL-8 is a potent chemoattractant for PMNs which are the destructive force in Shigella infection. PMNs cause CI-secretion through generation of a precursor to the secretagogue adenosine and can also cause ulceration of the epithelium, which results in a decrease in the absorptive surface but also maximizes permeability and allows easy access of Gut flora to the basolateral surface of the cells further driving inflammation

Question 38

Salmonella

Answer 38

S. typhi - Typhoid fever; non-typhoid salmonella **(S.enteritidis, Typhimurium)** - salmonellosis \>1M cases each year in the United States - can cause food poisoning Most common in young children and older adults with peak incidence in the summer and fall Possesses virulence genes that encode a **Type III secretion system** capable of transferring bacterial **proteins into M cells and enterocytes**.

Question 39

Salmonella Clinical Features

Answer 39

Clinically indistinguishable from those caused by other enteric pathogens. Causes **inflammatory diarrhea** Fever often resolves within 2 days, but diarrhea can persist for a week and organisms can be shed in the stool for several weeks after resolution.

Question 40

Typhoid Fever

Answer 40

Two subtypes, Typhi and paratyphi **Clinical Features** Anorexia, abdominal pain, bloating, nausea, vomiting, and bloody diarrhea followed by a short asymptomatic phase. **Rose spots** - small erythematous maculopapular lesions. Extraintestinal complications - encephalopathy, meningitis, seizures, endocarditis, myocarditis, pneumonia, and cholecystitis

Question 41

Escherichia Coli, Enterohemorrhagic and Enterogenic

Answer 41

**Gram-Negative Bacilli** that colonizes the healthy GI tract Most are non-pathogenic, but a subset cause human disease. **Enterohemorrhagic (non-penetrating)** Secretes shigella like toxin that inactivates ribosomes Associated with consumption of undercooked ground beef Hemolytic uremic syndrome can cause cytokine release and lysis of RBCs leading to renal failure and thrombocytopenia. **Enterotoxigenic (non-penetrating)** Travelers Diarrhea Heat-stable toxin (ST) and heat-labile toxin (LT) INC Adenylate cyclase -\> INC cAMP -\> INC secretions Secretory, non-inflammatory diarrhea, dehydration, and in sever cases shock.

Question 42

Escherichia Coli, Enteroinvasive and Enteropathogenic

Answer 42

**Enteroinvasive (penetrating)** Transmitted via food, water, or by person to person contact Do not produce toxins, they invade epithelial cells -\> dysentery **Enteropathogenic (non-penetrating)** Important cause of endemic diarrhea particularly in children \<2 y/o Attachment to epithelium -\> loss of microvilli -\> mucus diarrhea

Question 43

Pseudomembranous Colitis

Answer 43

Caused by **C. difficile**, also referred to as antibiotic-associated colitis. Disruption of bacterial flora -\> Colonization of C. diff -\> Mucosal damage and inflammation **Clin Features** **Risk factors** - advanced age, hospitalization, and antibiotic treatment Fever, leukocytosis, abdominal pain, cramps, watery diarrhea, and dehydration. Protein loss-\> hypoalbuminemia **Major challenge -** Recurrent infection (40%)

Question 44

Viral Gastroenteritis

Answer 44

C - Corona Virus A - Adenovirus N - **Novovirus** C - Calicivirus A - Astrovitus R - **Rotacvirus** Children between 6 and 24 months are most vulnerable **Rotavirus outbreaks** in hospitals and daycare centers are common, and infection spreads easily. Estimated minimal infective inoculum is only **10 viral particles.**

Question 45

Viral Gastroenteritis Pathogenesis

Answer 45

During the first cycle of rotavirus replication in mucosal epithelial cells, the synthesis of rotaviral proteins in the cell cytoplasm leads to an **increase in the** **plasma-membrane** **permeability to Ca2+,** to activation of regulatory mechanisms and to an increase in the concentration of Ca2+ in the endoplasmic reticulum (ER) The increased concentration of cytosolic Ca2+ in infected cells promotes the activation of Ca2+ dependent enzymes, which in turn induces cell lysis and the release of viral proteins and viral progeny **Non-structural protein (NSP)-4** might act as a viral enterotoxin on as-yet-uninfected cells to induce secratory diarrhea through (i) Ca2+- dependent secretion by intestinal cells, (ii) Ca2+- dependent secretion of peptides and amines to stimulate the enteric nervous system (ENS), and (iii) further activation of epithelial-cell chloride (Cl-) secretion by the ENS. In parallel, released virus infects downstream absorptive cells. This will lead to a massive cell death and, as a consequence, **reduction of the absorptive surface of the intestinal epithelium and an osmotic component of diarrhea.**

Question 46

Parasitic Enterocolitis

Answer 46

Entamoeba histolytica Giardia lamblia Ascaris lumbricoides - **Giant Roundworm** Strongyloides - **Threadworm** Necator duodenale and Ancylostoma duodenale - **Hookworms** Enterobius vermicularis - **Pinworms** Tichuris trichura - **Whipworm** Cryptosporidium

Question 47

Inflammatory Bowel Disease

Answer 47

Chronic Condition -\> inappropriate muscosal immune activation 2 types Crohn Disease Ulcerative colitis Pathogenesis NOD2, ATG16L1, and IRGM

Question 48

Crohn Disease Clinical Features

Answer 48

Extremely variable - intermittent mild diarrhea, fever, and abdominal pain Iron-deficiency anemia, serum protein loss and hypoalbuminemia, malabsorption of Vitamin B12 and bile salts Fibrosing structures of the terminal ileum - surgical resection **Fistulae develop** between loops of bowel and may also involve urinary bladder, vagina, and abdominal or perianal skin.

Question 49

Ulcerative colitis Clinical Features

Answer 49

Bloody diarrhea with stringy, mucoid material, lower abdominal pain, adn cramps that are temporarily relieved by defecation. ~ 30% require colectomy because of uncontrollable symptoms. Trigger factors - infectious enteritis, stress

Question 50

Primary Crohn disease and Ulcerative Colitis differences

Answer 50

Crohn Disease - Ulcerative Colitis Ileum +- Colon - Colon Skip lesion Distrobution - Diffuse Distrobution Transmural inflammation - Mucosa inflammation only Deep knife-like ulcers - Superficial broad-based ulcers Fistulae/sinuses - None Perianal fistula in Colonic disease - None Fat/Vit malabsorption - None