Gastrointestinal Pathology

Question 1

What is the Major Functions of the GI

Answer 1

• Ingest and prepare food for digestion
• Mechanical and chemical digestion
• Regulated absorption of nutrients
• Metabolism of endogenous and exogenous chemicals
• Immune surveillance
• Regulated secretion of hormones, enzymes, lubricants and water
• Microbiome functions
• Propulsion of waste
• Regulated defecation

Question 2

Regions of the GI

Answer 2

• Upper GI tract: mouth, esophagus,
  stomach
• Middle GI tract: (small bowel) duodenum (9”), jejunum (2.5 m), ileum (3 m)
• Lower GI tract: (large bowel) cecum, colon (ascending, transverse, descending), rectum
• Accessory structures: salivary glands, liver, pancreas

Question 3

Mesentery, Serosa, Muxosa, Muscularis

Answer 3

Mesentery: Connection of fats, vessels, and. verves that hold the bowel in place
Serosa: Areolar connective tissue; Epithelium
Mucosa: Epithelium; Lamina propria, Muscularis mucosae
Muscularis: Circular muscle, Longitudinal muscle

Question 4

Mechanics of Digestion

Mouth

Answer 4

Mastication breaks food into smaller segments
- Food mixes with salive that is released from three pairs of salivary glands
– Sublingual (under tongue), Submandibular (corner fo jaw), Parotid (angle of jaw; largest)

Question 5

What do Saliva contain and it’s pH?

Answer 5

Saliva Contain:
- Amylase (begin carbohydrates digestion)
- Lingual Lipase (triglycerides to partial glycerides and FFA)

Saliva has a pH of 7.4
- Inhibit bacterial growth in the oral cavity
- Neutralizes acid from the stomach (hence the need to rinse the mouth after vomiting to prevent erosion of the teeth)

Question 6

Mechanics of Digestion

Esophagus

Answer 6

Esophagus is a muscular tube that is 20-30 cm long
- Swallowing begin by expansion of the upper esophageal sphincter and peristaltic movement mediated by smooth muscle
- Upper 1/3 of esophagus is skeletal muscle and is voluntary. The rest is smooth muscle and is autonomic control
- Food takes 5-7 seconds to traverse the esophagus; this is why it is important to take pills with water
- Relaxation of lower esophageal sphincter permits movement of food into stomach; Contraction prevents reflux of gastric content

Question 7

Mechanics of Digestion

Stomach

Answer 7

Function of the stomach is to mix the food (chyme;1.2pH) with acid and digestive enzymes
- HCI is formed by parietal cells (kills unwanted bacteria) and aids in digestion
– Provides optimal pH for pepsin, and kills organisms consumed with food
- Parietal cells also produce intrinsic factors (essential for RBC formation) and is essential for absorption of vitamin B12
- Pepsin is produced by Chief Cells as pepsinogens; it require low pH (around 2) for optimal activity
- Gastrin produced in the stomach stimulates production of HCI and pepsinogen
- Gastric digestion is inhibited by sympatheitc innervation (in response to fear, pain, aggression, unpleasant taste or smell)
- Digestion is enhanced under vagal control (para)
- Mucosa of stomach protected by mucus, production of which is stimulated by prostaglandins.
- Prostaglandin Inhibitors (eg. NSAIDs) may induce gastic erosion

Question 8

Mechanics of Digestion

Stomach II

Answer 8

Muscle of stomach provide thorough mixing with acid and enzymes, progessiviely liquefying the content
- Peristaltic contractions around 3/min, gain forces as they approach the pyloric sphincter
- Chyme enter the duodenum through the pyloric sphincter, relaxation of which is coordinated with the stomach peristaltic waves

Excessive loss of gastric fluids may increase loss of sodium and potassium ==> hyponatremia and hypokalemia

Question 9

Mechanics of Digestion

Small Intestine

Answer 9

Chyme enter the duodenum, where it is neutralized by mixing with bile, pancreatic juice and intestinal enzymes (maltase, lactase, sucrase, trypsin, and chymotrypsin) and bicarbonate from Brunner’s glands
- Rate of digestion is regulated by secretin, cholecystokinin, motilin, and gastric inhibitory peptide
- Bile and pancreatic fluid enter the duodenum via common duct through the ampulla of Vater, which is regulated by the sphincter of Oddi (has to dilate)
- The mucosal surface of the small intestine is modified to enchance absorption of nutrients, mineral, vitamins, etc
- Movement of chyme is the result of coordinated HAUSTRAL SEGMENTALl contraction of inner smooth muscle and longitudinal peristaltic movements
- These movements are controlled by both the autonomic and regional NS, and peptide producing paraneurons
- Movement of intestine in place is facilitated by the serosal secretion; limited by omentum
- Majority of nutrient absorption occurs in small intestine

Content of small intestine pass through liver via the portal system before entering systemic circulation, hence 1st-pass metabolism of drugs taken by mouth

Question 10

Where do the majority of nutrient absorption happen?

Answer 10

It occurs in small intestine

Question 11

What is the first pass metabolism of drugs

Answer 11

Liver

Question 12

What happens if the small intestine do not neutralize the acidic chyme?

Answer 12

Ulcers occurs

Question 13

What is rate of digestion regulated by?

Answer 13

Secretin, Cholecystokinin, Motilin, and Gastric inhibitory peptide

Question 14

Bile and pancreatic fluid enter the duodenum through?

Answer 14

Common duct, through the ampulla of Vater which is regulated by sphincter of Oddi

Question 15

Movement of chyme is result of?

Answer 15

coordinated haustral segmental contraction of inner smooth muscle and longitudinal peristaltic movements.
- Controlled by both the autonomic and regional NS, and peptide-producing paraneurons

Question 16

Movement of intestine in place is facilitated by

Answer 16

the serosal secretion;
limited by the omentum

Question 17

Mechanics of Digestion

Large Intestine

Answer 17

Chyme enters the cecum via the ileocecal valve
- Some digestion happen in the proximal large intestine, but primary function is to recover water and control the fluidity of the feces
- Defecation is signaled by the distention of the distal sigmoid colon and rectum
- Defecation require the coordinated relaxation of two sphincters;
– The internal anal sphincter (autonomic control)
– External anal sphincter (more or less voluntary control)
- 30% of fecal mass is bacteria
- Internal ecology of GI bacteria (microbiome) is critical for health
- Rectal blood does not return via the liver

Question 18

Chyme enter the cecum via?

Answer 18

The ileocecal Valve

Question 19

What happens in the proximal large intestine

Answer 19

Some digestion happen but primary function is to recover water
and control the fluidity of the feces

Question 20

Defecation is signaled by

Answer 20

distention of the distal sigmoid colon and rectum

Question 21

Defection requires the…

Answer 21

coordinated relaxation of two sphincters: the internal anal sphincter (autonomic control) and external anal sphincter
(more or less voluntary control)

Question 22

Rectal blood

Answer 22

does not return via the liver

Question 23

Gastrointestinal Microbiome

Answer 23

Microbiome: aggregate of all microbiota residing on or within tissues
- May be bacteria, fungi or viruses (majority are bacteria)
- Organisms may be commensal, mutualist or pathogenic
- GI tract has the broadest diversity of organisms
- Composition of microbiome changes with age, diet, and health
- Reconstitution of ‘normal’ microbiome by fecal microbiome transplants has high efficacy in some diseases

Question 24

Composition of microbiome established at?

Answer 24

Established at birth
- vaginal delivery results in largely non-pathogenic microbiota resembling mother’s.
- Caesarian delivery results in more pathogenic organisms and delays the establishment of a normal GI microbiome

Mutualistic organisms contribute to normal GI function through cooperative synthesis (eg. Vit K) and metabolism

Question 25

Changes in microbiome cause?

Answer 25

It Implicated in diseases ranging from diabetes, obesity, IBD, neurological diseases (eg. Parkinson’s), antibiotic-mediated colitis to colon cancer

Question 26

Major Diseases of the GI Tract

Answer 26

- Dysregulation of movement and fluid balance -- obstruction, diarrhea, constipation - Inflammation - Ulceration - Infection - Neoplasia

Question 27

Oral Disease

Answer 27

Infections (bacterial, fungal, viral), frequent in immunosuppressed hosts Cancers (95% squamous cell Ca) - Oral squamous cancer has poor prognosis <50% 5-year survival - Up to 70% of oral cancer are result of HPV infections, particularly HPV 16 & 18 -- National Cancer institute recommends HPV vaccination of children as young as 9 years - HPV- related cancer in tonsil or tongue - Other risk factors (smoking, alcohol, poor oral care, excessive dryness)

Question 28

Clinical Effects of Esophageal Disease

Answer 28

- Retrosternal pain unassociated with swallowing. May be confused with MI - Hematemesis (bright red blood) - Dysphagia/obstruction -- Patients may subconsciously change diet to reduce problems with swallowing

Question 29

Principal Diseases of the Esophagus

Answer 29

- Reflux esophagitis (GERD): Increase in abdominal pressure; lower esophageal sphincter doesn't fully close - Infections: common in AIDS patients (Herpes, Candida) or following chemotherapy-associated immunosuppression - Inflammatory erosion: Chemicals (may cause achalasia-the failure of muscle relaxation) - Barrett's esophagus (Squamous to glandular metaplasia): GERD - Esophageal varices (from portal hypertension); develop in 50% of patients with hepatic cirrhosis - Cancer: 50% in lower 1/3, primarily adenocarcinoma (most common form in US). Upper/mid 1/3 are squamous carcinoma

Question 30

Esophageal Cancer

Answer 30

Primarily carcinoma; sarcoma very rare - Squamous cell carcinoma: M:F ratio 4:1; after 45 years of age - Adenocarcinoma incidence is increasing rapidly; particularly in distal 1/3, as result of Barrett esophagus. -- AdenoCa is 7:1 (M:F); whites - Risk Factors: alcohol, smoking, GERD - Prognosis bleak: ~65% mortality in 1 year - 9% 5-year survival squamous, ~25% adenoCa - Metastasis early to local lymph nodes Most patients present with dysphagia, generally indicating an nonresectible lesion. Most patients display cachexia

Question 31

Clinical Manifestations of Gastric Disease

Answer 31

- Pain and dyspepsia - Loss of appetite - Bloating and distention - Bleeding and vomiting -- if slow, black; coffee ground; emesis -- If rapid, Brightt red blood - Mass effect mimicking satiety - Outlet obstruction (pyloric stenosis) with profuse vomiting -- Hypokalemic alkalosis

Question 32

Gastric Inflammations

Answer 32

Gastritis (acute and chronic) - Associated with enhanced gastric secretion and/or impaired gastric defenses -- Alcohol, smoking, infections (Helicobacter pylori, Herpes, Salmonella), corticosteroids and NSAIDS, stress, CNS trauma, shock, serious illnesses Chronic gastritis associated with anemia; common in elderly patients -- H. pylori is most common cause; 90% of patients with chronic gastritis are infected -- Autoimmunity

Question 33

Peptic Ulcer Disease

Answer 33

Occurs anywhere mucosa is exposed to acid gastric juice (esophagus, stomach, duodenum) - Often chronic, frequently recurrent - Most common site is duodenum (70%); M:F ratio ~3:1 ‘true’ gastric ulcers occur in older individuals (~60+) - Extremely common (lifetime incidence up to 10%) Duodenal ulcers most common age 20-40 years - Most common in patients with blood type O Signs/symptoms: - ‘burning or gnawing’ epigastric pain with transient reduction of pain upon eating, bleeding, belching, Pain worse 1-3 hours after eating; at night INFECTION WITH HELICOBACTOR in >65% of patients with gastric ulcer; 85-100% of patients with duodenal ulcers - Genetic and systemic factors can contribute - Gastric ulcers resemble carcinomas; all should be biopsied - Gastric ulcer erosions may cause peritonitis or catastrophic hemorrhage

Question 34

Peptic Ulcer Disease: occurs where?

Answer 34

Occurs anywhere mucosa is exposed to acid gastric juice (esophagus, stomach, duodenum) - Often chronic, frequently recurrent - Most common site is duodenum (70%); M:F ratio ~3:1

Question 35

‘true’ gastric ulcers occur in?

Answer 35

Older individuals (~60+) - Extremely common (lifetime incidence up to 10%)

Question 36

Duodenal ulcers most common in?

Answer 36

In age 20-40 years - Most common in patients with blood type O

Question 37

H. pylori

Answer 37

H. pylori produces urease; increasing ammonia production - this is the basis of the urea breath test - H. pylori toxic to mucosal cells; hides in mucous layer - Stimulates gastric emptying, thus overwhelming bicarbonate buffering

Question 38

Stress-Induced Mucosal Disease | Stress, Curling, Cushing ulcer

Answer 38

Stress ulcers: - Affect critically ill patients with shock, sepsis or sever trauma. - Associated with ischemia and/or hypersecretion of acid Cushing ulcer: - Arises in stomach, duodenum or esophagus in patients with CNS disease - Thought to arise from vagal stimulation leading to acid hypersecretion - Often perforates Curling ulcer: - Occur in proximal duodenum - Associated with sever burns *Stress-induced gastric injury occurs in >75% of patients with critical illnesses within 3 days of their onset.* - The etiology is often systemic or localized ischemia due to hypotension or blood redistribution

Question 39

Stress Ulcers affect?

Answer 39

Affect critically ill patients with shock, sepsis or severe trauma. - Associated with ischemia and/or hypersecretion of acid

Question 40

Cushing ulcer: Arises in?

Answer 40

arise in stomach, duodenum or esophagus in patients with CNS disease. - Thought to arise from vagal stimulation leading to acid hypersecretion. - Often perforates

Question 41

Curling ulcer: occurs in?

Answer 41

- occur in proximal duodenum and are associated with severe burns

Question 42

Gastric Cancer

Answer 42

Shows geographical variance; incidence has decreased 85% in US over last 70 years - Usually diagnosed late as it's asymptomatic early in development. - Mean age at presentation is 55 years - Most commonly adenocarcinoma (90%); 2:1 (M:F) - Prognosis depend on stage: > stage II prognosis is poor - Metastasis usually at presentation -- To ovaries (Krukenberg tumor) -- To left supercalvicular node (Virchow's node) - 5-year survival <30% - Clinical Signs: -- Rare or nonspecific early signs (eg., dysphagia, dyspepsia) -- Late signs include anorexia, anemia, and weight loss

Question 43

Why is Gastric Cancer usually diagnosed late? | Also most common presentation?

Answer 43

it’s asymptomatic early in development. Mean age at presentation 55 yrs - Most commonly adenocarcinoma (~90%); 2:1 M/F

Question 44

Gastric Cancer Metastasis?

Answer 44

Metastasis usually present at diagnosis - Metastasis to ovaries (Krukenberg tumor) - left supraclavicular node (Virchow’s node). 5-year survival <30%

Question 45

Clinical Manifestations of Intestinal Disease

Answer 45

- Malaobsorption - Obstruction/Constipation - Paralytic bowel - Ischemia - Perforation - Hemorrhage - Diarrhea-rapid movement, often high vol; extremely dangerous in yound and old - Dysentery-blood and mucous - Steatorrhea

Question 46

Infections

Answer 46

Viruses: - Noroviruses - Rotoviruses Bacteria - Typhoid - Salmonella - Cholera - Campylobacter Helminths - Ascaris - Echinococcus - Hookworm

Question 47

Appendicitis

Answer 47

Difficult to diagnosis - 20% missed dx; 15-40% over dx'ed - Peak incidence 10-12 years - CT scans good dx if available - Start as diffuse pain => becomes localized; Rebound tenderness classic, with guarding Treatment is surgery BEFORE rupture

Question 48

Appendicitis: Signs

Answer 48

- WBC>10,000 mL - Fever >99.5F - Pain in right lower quadrant with rebound tenderness - Danger is rupture with peritonitis; this occurs in ~90% <3 years old Treatment is surgery BEFORE rupture

Question 49

Inflammatory Bowel Disease | IBD

Answer 49

Types: - Idiopathic colitis - Crohn disease - Ulcerative colitis IBDs are usually idopathic with multi-factorial origins - Most arise from mucosal immune activation and interaction between gut MICROBIOME - Both Chohn and IC are more common in females; often in teens and 20s - Both Crohn and UC have increased long-term risk of Ca

Question 50

Crohn Disease

Answer 50

F>M; Rare in youn children. Common in Whites - Etiology unknown; can be triggered by stress - Common in US and Western Europe Clinical Signs: Highly Variable, - Acute: Pain, Diarrhea, Fever - Chronic: Relapse and remission, weight loss, obstruction, malabsorption - Anatomic: Full thickness inflammation, Skip lesions, luminal narrowing (lead-pipe bowel, string-sign on X-ray) - Lesion may occur anywhere (mouth to anus) but are MOST COMMON in TERMINAL ILEUM Multiple surgeries often required leading to short bowel syndrome - Suppression of inflammatory response used but has side effect; particularly activation of Herpes virus

Question 51

Crohn Disease

Answer 51

F>M; Rare in youn children. Common in Whites - Etiology unknown; can be triggered by stress - Common in US and Western Europe Clinical Signs: Highly Variable, - Acute: Pain, Diarrhea, Fever - Chronic: Relapse and remission, weight loss, obstruction, malabsorption - Anatomic: Full thickness inflammation, Skip lesions, luminal narrowing (lead-pipe bowel, string-sign on X-ray) - Lesion may occur anywhere (mouth to anus) but are MOST COMMON in TERMINAL ILEUM Multiple surgeries often required leading to short bowel syndrome - Suppression of inflammatory response used but has side effect; particularly activation of Herpes virus

Question 52

Crohn Disease; Common in?

Answer 52

F>M; rare in young children. Most common in whites - Common in US and Western Europe

Question 53

Crohn Disease: Clinical signs?

Answer 53

They are highly variable - acute: pain, diarrhea, fever - chronic: relapse and remission, weight loss, obstruction, malabsorption

Question 54

Crohn Disease: Anatomics

Answer 54

Full thickness inflammation, ‘skip’ lesions, luminal narrowing (‘lead-pipe’ bowel, string-sign on X-ray - Lesions may occure anywhere (mouth to anus) but are most common in Terminal Ileum

Question 55

Chrohn Disease: Treatment?

Answer 55

Multiple surgeries often required leading to ‘short bowel syndrome’ * Suppression of inflammatory response used but has side-effects, particularly activation of Herpes virus

Question 56

Ulcerative Colitis

Answer 56

Most common in the 20-30s year old group; F>M - Most common in US and Western Europe - Etiology unknown: episodes may be precipitated by psychological stress - Disease involves primarily rectum; Inflammation involves ONLY MUCOSA - Sloughing of contiguous sheets of mucosa with bleeding Clinical Signs - Pain - Bloody diarrhea - Pain and fever - Exacerbation - Remissions Increased risk of aggressive rectal adenocarcinoma after 8-10 years of disease

Question 57

Ulcerative Colitis; Most common in?

Answer 57

Most common in 20-30 year old group - F>M - Most common in US and Western Europe

Question 58

Ulcerative Colitis: Mainly involves

Answer 58

Disease involves primarily rectum; inflammation involves only the mucosa - ‘Sloughing’ of contiguous sheets of mucosa, with bleeding

Question 59

Ulcerative Colitis for 8-10 years?

Answer 59

Increased risk of aggressive rectal adenocarcinoma

Question 60

Colorectal Cancer

Answer 60

Most common in the >60 age group - Strong correlation to diet - Frequently arises from adenoma (benign) precursors - Second only to lung cancer for total death - Common in Males and females -- Rectal cancer is more common in males -- Colon cancer F:M 2:1 - Recto-sigmoid ~50% - If iron-deficiency anemia presents in postmenopausal female or older male, expect right-side GI cancer - Clinical: blood in stool, anemia, obstruction - Prognosis: excellent if caught early, poor if Stage III or IV - Metastasis to liver, extension through bowel wall - Importance of digital exam, colonoscopy, family history Multiple mutational events: - Mutation of p53 tumor suppressor gene - Lose of DCC (deleted in colon cancer gene)

Question 61

If iron-deficiency anemia presents in postmenopausal female or older male, expect?

Answer 61

right-side GI cancer

Question 62

Colorectal Cancer got a strong correlation to? and most common in what age group

Answer 62

Diet; >60 age group

Question 63

Colorectal Cancer: Mutations

Answer 63

Mutation of p53 tumor suppressor gene, loss of DCC (‘deleted in colon cancer’ gene)

Question 64

Colorectal Cancer frequently arises from?

Answer 64

adenoma (benign) precursors Second only to lung cancer for total death

Question 65

Colorectal cancer; Male and female

Answer 65

Rectal cancer slightly more common in M Colon cancer F:M 2:1

Question 66

Colorectal cancer; Metastasis to? What exams are important

Answer 66

Metastasis to liver, extension through bowel wall - Importance of digital exam, colonoscopy, family history

Question 67

Crohn Disease: Anatomics

Answer 67

Full thickness inflammation, ‘skip’ lesions, luminal narrowing (‘lead-pipe’ bowel, string-sign on X-ray - Lesions may occure anywhere (mouth to anus) but are most common in Terminal Ileum

Question 68

Crohn Disease: Anatomics

Answer 68

Full thickness inflammation, ‘skip’ lesions, luminal narrowing (‘lead-pipe’ bowel, string-sign on X-ray - Lesions may occure anywhere (mouth to anus) but are most common in Terminal Ileum