Gastrointestinal Pathology Flashcards
What is the Major Functions of the GI
- 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
Regions of the GI
- 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
Mesentery, Serosa, Muxosa, Muscularis
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
Mechanics of Digestion
Mouth
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)
What do Saliva contain and it’s pH?
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)
Mechanics of Digestion
Esophagus
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
Mechanics of Digestion
Stomach
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
Mechanics of Digestion
Stomach II
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
Mechanics of Digestion
Small Intestine
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
Where do the majority of nutrient absorption happen?
It occurs in small intestine
What is the first pass metabolism of drugs
Liver
What happens if the small intestine do not neutralize the acidic chyme?
Ulcers occurs
What is rate of digestion regulated by?
Secretin, Cholecystokinin, Motilin, and Gastric inhibitory peptide
Bile and pancreatic fluid enter the duodenum through?
Common duct, through the ampulla of Vater which is regulated by sphincter of Oddi
Movement of chyme is result of?
coordinated haustral segmental contraction of inner smooth muscle and longitudinal peristaltic movements.
- 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 the omentum
Mechanics of Digestion
Large Intestine
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
Chyme enter the cecum via?
The ileocecal Valve
What happens in the proximal large intestine
Some digestion happen but primary function is to recover water
and control the fluidity of the feces
Defecation is signaled by
distention of the distal sigmoid colon and rectum
Defection requires the…
coordinated relaxation of two sphincters: the internal anal sphincter (autonomic control) and external anal sphincter
(more or less voluntary control)
Rectal blood
does not return via the liver
Gastrointestinal Microbiome
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
Composition of microbiome established at?
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
Changes in microbiome cause?
It Implicated in diseases ranging from diabetes, obesity, IBD, neurological diseases (eg. Parkinson’s), antibiotic-mediated
colitis to colon cancer
Major Diseases of the GI Tract
- Dysregulation of movement and fluid balance
– obstruction, diarrhea, constipation - Inflammation
- Ulceration
- Infection
- Neoplasia
Oral Disease
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)
Clinical Effects of Esophageal Disease
- 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
Principal Diseases of the Esophagus
- 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
Esophageal Cancer
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
Clinical Manifestations of Gastric Disease
- 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
Gastric Inflammations
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
Peptic Ulcer Disease
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
Peptic Ulcer Disease: occurs where?
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 in?
In age 20-40 years
- Most common in patients with blood type O
H. pylori
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
Stress-Induced Mucosal Disease
Stress, Curling, Cushing ulcer
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
Stress Ulcers affect?
Affect critically ill patients with shock, sepsis or severe trauma.
- Associated with ischemia and/or hypersecretion of acid
Cushing ulcer: Arises in?
arise in stomach, duodenum or esophagus in patients with CNS disease.
- Thought to arise from vagal stimulation leading to acid hypersecretion.
- Often perforates
Curling ulcer: occurs in?
- occur in proximal duodenum and are associated with severe burns
Gastric Cancer
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
Why is Gastric Cancer usually diagnosed late?
Also most common presentation?
it’s asymptomatic early in development. Mean age at presentation 55 yrs
- Most commonly adenocarcinoma (~90%); 2:1 M/F
Gastric Cancer Metastasis?
Metastasis usually present at diagnosis
- Metastasis to ovaries (Krukenberg tumor)
- left supraclavicular node (Virchow’s node).
5-year survival <30%
Clinical Manifestations of Intestinal Disease
- 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
Infections
Viruses:
- Noroviruses
- Rotoviruses
Bacteria
- Typhoid
- Salmonella
- Cholera
- Campylobacter
Helminths
- Ascaris
- Echinococcus
- Hookworm
Appendicitis
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
Appendicitis: Signs
- 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
Inflammatory Bowel Disease
IBD
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
Crohn Disease
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
Crohn Disease
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
Crohn Disease; Common in?
F>M; rare in young children. Most common in whites
- Common in US and Western Europe
Crohn Disease: Clinical signs?
They are highly variable
- acute: pain, diarrhea, fever
- chronic: relapse and remission, weight loss, obstruction, malabsorption
Crohn Disease: Anatomics
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
Chrohn Disease: Treatment?
Multiple surgeries often required leading to ‘short bowel
syndrome’
* Suppression of inflammatory response used but has
side-effects, particularly activation of Herpes virus
Ulcerative Colitis
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
Ulcerative Colitis; Most common in?
Most common in 20-30 year old group
- F>M
- Most common in US and Western Europe
Ulcerative Colitis: Mainly involves
Disease involves primarily rectum; inflammation involves only the mucosa
- ‘Sloughing’ of contiguous sheets of mucosa, with bleeding
Ulcerative Colitis for 8-10 years?
Increased risk of aggressive rectal adenocarcinoma
Colorectal Cancer
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)
If iron-deficiency anemia presents in postmenopausal female or older male, expect?
right-side GI cancer
Colorectal Cancer got a strong correlation to? and most common in what age group
Diet; >60 age group
Colorectal Cancer: Mutations
Mutation of p53 tumor suppressor gene, loss of DCC (‘deleted in colon cancer’ gene)
Colorectal Cancer frequently arises from?
adenoma (benign) precursors
Second only to lung cancer for total death
Colorectal cancer; Male and female
Rectal cancer slightly more common in M
Colon cancer F:M 2:1
Colorectal cancer; Metastasis to? What exams are important
Metastasis to liver, extension through bowel wall
- Importance of digital exam, colonoscopy, family history
Crohn Disease: Anatomics
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
Crohn Disease: Anatomics
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
