Gastrointestinal Tract

Gastrointestinal Tract:

• a continuous “tube” from the mouth to the anus, along with associated glands (liver, gall bladder, pancreas) needed for digestion

GI tube is divided into:

• Upper GI Tract: Oropharynx, Esophagus, Stomach

• Lower GI Tract: Intestines, Colon, Rectum

Peristalsis:

• Coordinated symmetrical contraction and relaxation of muscles that propagates in a wave down the GI tube

Major GI functions:

• Digestion and movement of food

• Absorption of nutrients

• Elimination of wastes

• Mucosal immunity

Basic Structure of the GI Tube:

• Mucosa

• Submucosa

• Muscularis

• Serosa

Mucosa:

• Inside of the tube Epithelium, Basement Membrane, Lamina Propria (connective tissue, small blood vessels, nerves and lymphatics), thin muscle layer

Submucosa:

• Connective tissue, blood vessels, nerves, lymphatics, secretory glands

Muscularis:

• 2 layers of Smooth Muscle (circular inner layer, lengthwise outer layer)

Serosa:

• Outside of the tube

• Connective tissue with larger blood vessels, nerves and lymphatics

Regions of the GI tube:

• Each organ of the GI Tube is divided into anatomical and functional regions

• Esophagus

• Stomach

• Intestine

• Colon

• Diseases tend to occur in specific regions of each organ

Esophagus:

• Cervical, Upper Thoracic, Mid Thoracic, Lower Thoracic

Stomach:

• Cardia, Fundus, Body (Corpus), Antrum, Pylorus

Intestine:

• Duodenum, Jejunum, Ileum

Colon:

• Cecum, Ascending, Transverse, Descending, Sigmoid, Rectum

Dysphagia:

• Difficulty swallowing

Dyspepsia:

• Indegestion (upper abdomen discomfort with bloating & gas)

Reflux:

• Regurgitation of stomach (gastric) fluids into the esophagus

GERD:

• Gastroesophageal reflux disease, can injure the esophagus

Pyrosis:

• Burning chest pain (heartburn), can mimic cardiac pain

Hematemesis:

• Vomiting up blood

• Significant upper GI hemorrhage (ruptured vessel) has fresh (red) blood

• Slow bleed causes blood to be degraded by stomach acid, vomit has a “coffee ground” appearance

Melena:

• Black tar-like stool caused by an upper GI bleed (need significant

  and protracted GI bleed), term is specific for blood causing a dark stool. Many foods and medications can cause a black stool but are not melena

Fecal occult blood test:

• Detects blood in stool samples, also called the Stool Guaiac test. Fresh blood (bright red) in the stool indicates a rectal or anal bleed (often hemorrhoids)

Esophagus: Congenital Defects:

• Esophageal Atresia

• Tracheo-Esophageal Fistula

• Esophageal Stenosis

Esophageal Atresia:

• Failure to develop and results in a “dead- end” pouch, results in vomiting

Tracheo-Esophageal Fistula:

• Abnormal connection between lungs and GI tract, results in either food in the lungs (causes aspiration pneumonia) or bloating due to air in the stomach

Esophageal Stenosis:

• Narrowing of the tube, results in Dysphagia (difficulty swallowing)

Acquired/Congenital Defect:

• Lower Esophageal Sphincter (LES)

• Hiatal Hernia

Lower Esophageal Sphincter (LES):

• a thickening of esophageal wall and diaphragm muscles, prevents

  stomach contents from entering esophagus. Relaxation of the LES can cause Reflux of gastric fluids. Many substances (alcohol, caffeine, tobacco, certain foods) can relax the normal muscle tone of the LES

Hiatal Hernia:

• Defect in the opening of the diaphragm, causes part of the cardia region of stomach to protrude into the thoracic cavity. Can interfere with normal LES function and cause reflux

Esophageal Varices:

• Dilation of veins in the distal (lower thoracic) esophagus

• Caused by high pressure in the veins due to portal hypertension (caused by liver cirrhosis)

• Rupture can cause massive bleeding and death, common cause of death in cirrhosis

• Treated by Band Ligation: tie off the vessel with a surgical band

  to stop blood flow, causes varices to regress

Esophagitis:

• Inflammation of the Esophagus

Causes:

• GERD (common cause) and infections (viral and fungal)

Symptoms

• Dsyphagia and Pyrosis

GERD:

• caused by chronic reflux due to LES dysfunction

• Reflux of stomach acid damages and inflames the squamous epithelium of the esophagus, can cause fibrosis and narrowing

• Long-term GERD causes metaplasia of the distal (lower thoracic) region from squamous to gastric epithelium: Barrett Esophagus

Esophagitis: Infections:

• Often in immunocompromised

• Viruses: Herpes, Cytomegalovirus (CMV)

• Fungus: Candida albicans

Barrett Esophagus:

• Metaplasia of the distal (lower thoracic) region from squamous

  to glandular gastric epithelium

• Caused by chronic reflux of gastric fluids that damage the

  esophagus (GERD)

• Chronic GERD can predispose to develop adenocarcinoma of esophagus

Esophageal Carcinoma: Two major types:

• Squamous Cell Carcinoma (SCC), Adenocarcinoma (AC)

• Both are uncommon cancers in the U.S.

• Adenocarcinoma is more common type (> 60%)

• Usually found in males >50 years old (4:1 M/F ratio)

• Common in China, Iran, Russia, parts of Africa

  • Squamous Cell Carcinoma is more common globally

  • Male/Female ratio is almost equal

• Symptoms: Dysphagia, weight loss, hematemesis, pain (but symptoms often non-specific and mild)

• Risk factors: Diet & Environment

  • Nitrosamines in food (smoked & pickled foods): SCC

  • Excessive or long-term alcohol & tobacco use: AC, SCC

  • Possible environmental/occupational causes: SCC

  • Long-standing GERD: AC

• Diagnosis & Prognosis:

• Imaging, Endoscopy with biopsy

• No effective treatment. Very poor 5-year survival, but

  has improved (from 5% to 20%) by earlier detection 13

Squamous Cell Carcinoma:

• Most in mid-upper (75%) part of esophagus (25% in lower)

• Uncommon in the U.S.

• Develops from squamous epithelium

• Associated with diet & environment

Adenocarcinoma:

• Found in the lower part of esophagus, near LES

• More common in the U.S.

• Develops from gastric glands in regions of Barrett esophagus

• Associated with long-standing GERD

Stomach Regions:

• Cardia

• Fundus

• Body (Corpus)

• Antrum

• Pylorus

Cardia:

• region below the LES where the stomach begins

Fundus:

• upper region that stores gas and undigested food

Body (Corpus):

• largest part where the main digestion occurs

Antrum:

• largest part where the main digestion occurs

Pylorus:

• derived from the Greek word for ”gatekeeper”, it controls movement of food into the duodenum

Stomach Histology: Gastric Mucosa:

• Folded into Gastric Pits that contain multiple cell types

Stomach Cell Types: Parietal Cells:

• Also secrete Intrinsic Factor, needed to absorb vitamin B12 (required for RBC production)

Protection of Gastric Mucosa: Required for protection:

• Normal, intact blood flow to the stomach

• Intact mucus layer and normal mucus production

• Normal acid and bicarbonate (neutralizes acid) production

• Normal hormone secretion (gastrin and somatostatin)

Protection of Gastric Mucosa: Damage can be caused by:

• Infection with Helicobacter pylori

• Increased acid production (often caused by certain foods)

• Aspirin and other NSAIDs (Ibuprofen, Naproxen, etc.)

• Smoking and excessive alcohol use

• Ischemia and/or trauma

Acute Gastritis:

• Relatively short duration, but can be severe

• Usually caused by irritant exposure (high amount alcohol or NSAIDs) or trauma (burns, stroke, injuries)

• Often results in pain, vomiting (possibly hematemesis), dyspepsia

• Irritants often produce erosions of the mucosa (superficial ulcers)

• Trauma often results in stress ulcers (multiple small ulcers)

  • Both usually self-limiting, resolves after irritant/trauma is removed

• Severe acute gastritis can cause significant blood loss

Chronic Gastritis:

• Long duration and often produce ulcers

• Infection with Helicobacter pylori is the most common cause

Autoimmune Atrophic Gastritis:

• destruction of the mucosa results in gastric atrophy. Most often occurs in the elderly, caused by autoantibodies to parietal cells, this can result in Pernicious Anemia:

  • Decreased intrinsic factor due to death of parietal cells, which leads to decreased vitamin B12 absorption in the gut, results in anemia

Peptic Ulcers:

• The “umbrella” term for this chronic condition

• Gastric ulcer: peptic ulcer in the stomach (20% of ulcers)

• Duodenal ulcer: peptic ulcer in the duodenum (80% of ulcers)

• Very common condition that affects about 10% of U.S. population

• Most often seen in men over 50 years old

• Smoking, alcohol and NSAID use are major risk factors

• Helicobacter pylori is associated with >90% of cases (2005 Nobel Prize in Medicine was awarded for discovering this link between infection and ulcers)

• H. pylori is a gram-negative bacterium that does not directly damage the mucosa, it alters the gastric mucosa to allow acid to produce an ulcer at infection site

• Symptoms will vary depending on location of the ulcer

• Gastric ulcers: epigastric pain 0.5 to 1 hour after a meal

• Duodenal ulcers: epigastric pain 2 to 4 hours after a meal

Pathology of peptic ulcers:

• Round (often solitary) with sharp “punched- out” appearance that can extend deep into submucosa

Peptic ulcers complications:

• significant bleeding if ulcer erodes a blood vessel, or peritonitis if ulcer erodes stomach wall (perforation) into peritoneal cavity

Gastric cancer: Adenocarcinoma:

• Accounts for 90-95% of all stomach cancers

• Uncommon cancer in the U.S., Canada and western Europe, and

  incidence is declining

• Very common cancer world-wide, particularly in Latin America, China, Japan, Russia

• Symptoms are vague: dyspepsia, vomiting, weight loss, pain

• Risk factors: Nitrosamines in food, cigarette smoking, chronic H. pylori infection

• Diagnosis: Imaging, Endoscopy with biopsy

• Prognosis: No effective treatment, very poor 5-year survival

Gastric Cancer: Tumor Pathology:

• Several different tumor growth patterns, small tumors may resemble a peptic ulcer:

• Fungating tumor: Grows and fills the stomach lumen

• Diffuse tumor: Infiltrates the stomach wall and encases it with cancer, producing a rigid, thick “leather bottle” appearance

• Tumors often invade into the peritoneal cavity

Intestine:

• Largest digestive organ: about 3.5x body length (average length of 22 feet)

Intestine major functions:

• Food absorption, Ileum has extensive lymphoid tissue (Peyer’s Patches) that make large amounts of IgA (mucosal immunity)

• Enterocytes have a very large surface area for absorption

Intestine Cell Types: Anoikis:

• Epithelial enterocytes die by apoptosis, shed into lumen

Intestinal Pathology: Tumors:

• Very rare, <5% of all GI tumors are intestinal, and most are benign!

Intestinal Pathology: Gastroenteritis:

• Infections, usually viral or bacterial, are extremely common and result in cramping, gas and diarrhea. Severe bacterial infections (cholera and salmonella) can be fatal if not treated promptly.

Celiac disease:

• Immune reaction against the wheat protein Gliadin.

• NOT a classic autoimmune disease (but has some characteristics)

• T-cytotoxic cells responding to gliadin kill enterocytes and destroy villi

• Most often occurs in the duodenum and jejunum

• Results in decreased absorption and malnutrition

• Treatment is to avoid gluten!

Intussusception:

• A serious medical emergency in which part of the intestine slides into an adjacent part of the intestine/colon. Blocks food or fluid from passing, also can stop the blood supply to that part of the intestine.

• Usually affects infants and young children, more often in males

• In adults this can be caused by tumors, polyps or scar tissue

• Treatment is surgery ASAP!

• Colon & Rectum

Acute Appendicitis:

• Very common, particularly those under 20 years old

• Develops from an obstruction, primarily caused by:

• Fecalith (hardened stool blocking lumen)

• Hyperplasia of lymphoid tissue (Appendix is a lymphoid organ)

• Obstruction leads to ischemia and overgrowth of gut bacteria

• Classic symptoms: Pain in the right lower quadrant, fever, abdominal tenderness, nausea, leukocytosis (elevated white blood cell count)

• Surgical treatment is required since rupture can cause peritonitis

• Interval appendectomy: if appendix already ruptured, some people will be treated with antibiotics, followed for several weeks/months, then surgery when inflammation has subsided

• Before modern surgery and antibiotics, this was almost always fatal

Inflammatory Bowel Disease (IBD):

• Broad category that contains two distinct diseases: Crohn’s Disease (Regional Enteritis) and Ulcerative Colitis

Common features of BOTH Crohn’s Disease and Ulcerative Colitis:

• Idiopathic diseases with both genetic and autoimmune components

• Chronic relapsing diseases (cycles of remission then relapse)

• Affects women more than men

• Can affect almost any age from pre-teen to elderly, but peak incidence in people in their 20’s

• Both cause intermittent diarrhea, but severity is variable ranging from mild to chronic severe disease

• Medical treatment includes steroids, antibiotics and new targeted biologics (anti-cytokine drugs), response to therapy is also variable

• NOTE: Don’t confuse IBD with Irritable Bowel Syndrome (IBS), IBS is very common and is defined by symptoms, it does not have the severity or tissue pathology of IBD

Crohn’s Disease (CD):

• Also known as Regional Enteritis

• Less common than Ulcerative Colitis

• Usually presents with more severe symptoms and pathology

• About 30% have lesions outside the GI tract (skin, eyes, joints)

Ulcerative Colitis (UC):

• 3-fold more common than CD

• Disease usually starts with relatively mild symptoms

• Excessive diarrhea is the classic manifestation of UC

• Severe cases have bloody diarrhea, often with abdominal pain and fever

• Comparison of CD & UC Pathology

Diverticulosis:

• an abnormal outpouching in the wall of the colon

• Very common, increases with age: 20% at age 40, >60% at age 60

• Thought to be caused by increased pressures in the colon wall (hard dry feces due to diet) and/or weak spots in colon wall

• Occur most often in distal colon (descending, sigmoid), can have just one or many diverticula

Diverticulitis:

• Inflammation of diverticula, due to obstruction with hard feces. Symptoms are very similar to appendicitis but usually on the left side, Complications include

• Rupture → peritonitis

• Scarring → stricture and obstruction

• Fistulas

• Massive bleeding from erosion into a blood vessel

• Treatment: Surgical removal if antibiotics fail

Colon Polyps:

• Very common, incidence increases with age: 1% at age 25, >50% at age 70

Hyperplastic polyp:

• most common non-cancerous polyp, small and flat

• Polyps can be Sessile (flat) or Pedunculated (a stalk)

Adenomatous polyp:

• most common pre-neoplastic polyp, polyps start as benign growths, but some can transform into cancer.

• Nearly all colon cases develop from adenomatous polyps

Tubular Adenoma:

• Pedunculated, about 80% of colonic adenomas are benign, but about 10-20% may develop into adenocarcinoma

Villous Adenoma:

• Sessile, about 15% of colonic adenomas, but about 50% may develop into adenocarcinoma

Adenocarcinoma of the Colon:

• accounts for > 95% of all colon cancers

• 3rd most common (non-skin) cancer in both men and women in U.S.

• 2nd leading cause of cancer deaths in both men and women in U.S.

• Associated with a diet high in animal fat and low in fiber

• Most cases (~65%) occur in distal colon (descending, sigmoid, rectum)

• Most cases are diagnosed in older adults (60’s and 70’s)

• Lynch Syndrome (Hereditary non-polyposis colorectal cancer) is an inherited early onset form (<1% cases) that develops in 30’s to 40’s

• Symptoms are usually vague and non-specific:

  1) Changes in bowel habits, constipation (more common) or diarrhea

  2) Mild anemia (causes fatigue) due to slow blood loss around the tumor

  3) Abdominal pain, can be diffuse or sharp

  4) Unexplained weight loss

  5) Blood in stool

Colon cancer staging:

• based on depth of tumor invasion & number of cancer positive lymph nodes

TNM Cancer Staging: Tumor:

• Size of tumor and if it has invaded nearby tissue

TNM Cancer staging: Nodes:

• Number of lymph nodes positive for cancer cells

TNM Cancer staging: Metastasis:

• Spread of cancer to another part of the body (often the liver)

Endoscopy:

• Colonoscopy has helped greatly in the diagnosis and management of diseases of colon: Easier access = more biopsies = diagnosis

• Prognosis is good if colon cancers are detected in Stage I or II, and screening colonoscopy has greatly reduced incidence (removal of pre-cancerous polyps) and improved survival by earlier detection