CH10 - Gastrointestinal Pathology Flashcards
What are some diseases that affect the oral cavity?
1) cleft up and palate 2) aphthous ulcer 3) Behcet syndrome 4) Oral herpes 5) squamous cell carcinoma
What is cleft up and palate?
Full-thickness defect of lip or palate
What is cleft up and palate due to?
failure of facial prominences to fuse
How is face formed?
During early pregnancy, facial prominences (one from superior, two from the sides, and two from inferior) grow and fuse together to form the face
Does the cleft lip and palate usually occur together or separate?
Usually together, isolated cleft lip or palate is less common.
What is aphthous ulcer?
Painful, superficial ulceration of the oral mucosa
When does aphthous ulcer arise?
in relation to stress and resolves spontaneously, but often recurs
What is aphthous ulcer characterized by?
a grayish base surrounded by erythema
What is behcet syndrome?
Recurrent aphthous ulcers, genital ulcers, and uveitis
What is behcet syndrome due to?
immune complex vasculitis involving small vessels
When might you see behcet syndrome?
after viral infection, but etiology is unknown
What is oral herpes?
Vesicles involving oral mucosa that rupture, resulting in shallow, painful, red ulcers
What is oral herpes usually due to?
HSV-1
For oral herpes when does the primary infection occur?
in childhood; lesions heal, but virus remains dormant in ganglia of the trigeminal nerve.
For oral herpes what might cause reactivation of the virus?
Stress and sunlight, leading to vesicles that often arise on the lips (cold sore)
What is squamous cell carcinoma of the oral cavity?
Malignant neoplasm of squamous cells lining the oral mucosa
For oral squamous cell carcinoma what are the major risk factors?
Tobacco and alcohol
What is the most common location for oral squamous cell carcinoma?
Floor of mouth
Regarding oral squamous cell carcinoma what are the precursor lesions
Oral leukoplakia and erythroplakia
What is leukoplakia?
It is a white plaque that cannot be scraped away; often represents squamous cell dysplasia
What is oral candidiasis?
it is a white deposit on the tongue, which is easily scraped away; usually seen in immunocompromised states
What is hairy leukoplakia?
it is a white, rough (hairy) patch that arises on the lateral tongue. It is usually seen in immunocompromised individuals (AIDS) and is due to EBV-induced squamous cell hyperplasia; not pre-malignant
What is erythroplakia?
(red plaque) represents vascularized leukoplakia and is highly suggestive of squamous cell dysplasia,
Would you biopsy erythroplakia and leukoplakia?
they are often biopsied to rule out carcinoma
What are salivary glands?
they are exocrine glands that secrete saliva.
What are salivary glands divided into?
major (parotid, submandibular, and sublingual glands and minor glands (hundreds of microscopic glands distributed throughout the oral mucosa)
What is the mumps?
Infection with mumps virus resulting in bilateral inflamed parotid glands
In mumps, what other infections in addition to the mumps virus may be present?
Orchitis, pancreatitis, and aseptic meningitis may also be present.
Why is serum amylase increased?
due to salivary gland or pancreatic involvement
What is there a risk of with orchitis?
carries risk of sterility, especially in teenagers.
What is sialadenitis?
Inflammation of the salivary gland
What is sialadenitis most commonly due to?
an obstructing stone (sialolithiasis) leading to Staphylococcus aureus infection; usually unilateral
What is pleomorphic adenoma?
Benign tumor composed of stromal (e.g., cartilage) and epithelial tissue;
What is the most common tumor of the salivary gland?
Pleomorphic adenoma
Where does pleomorphic adenoma usually arise?
in parotid
What does pleomorphic adenoma present as?
a mobile, painless, circumscribed mass at the angle of the jaw
What is the rate of recurrence in pleomorphic adenoma?
High rate of recurrence;
In pleomorphic adenoma what often leads to incomplete resection?
extension of small islands of tumor through tumor capsule
What does pleomorphic adenoma present as?
Rarely may transform into carcinoma, which presents with signs of facial nerve damage (facial nerve runs through parotid gland)
What is a warthin tumor?
Benign cystic tumor with abundant lymphocytes and germinal centers (lymph node-like stroma);
What is the 2nd most common tumor of the salivary gland?
Warthin tumor
Where deos the warthin tumor almost always arise?
in the parotid
What is a mucoepidermoid carcinoma?
Malignant tumor composed of mucinous and squamous cells
What is the most common malignant tumor of the salivary gland?
Mucoepidermoid carcinoma
Where does mucoepidermoid carcinoma usually arise?
in the parotid
What does mucoepidermoid carcinoma commonly involve?
the facial nerve
What is a tracheoesophageal fistula?
Congenital detect resulting in a connection between the esophagus and trachea
What is the most common variant of tracheoesophageal fistula?
consists of proximal esophageal atresia with the distal esophagus arising from the trachea
How does a tracheoesophageal fistula present?
with vomiting, polyhydramnios, abdominal distension, and aspiration
What is esophageal web?
Thin protrusion of esophageal mucosa, most often in the upper esophagus
What does esophageal web present with?
dysphagia for poorly chewed food
What is there an increased risk for with esophageal web?
esophageal squamous cell carcinoma
What is Plummer-Vinson syndrome characterized by?
severe iron deficiency anemia, esophageal web, and beefy-red tongue due to atrophic glossitis.
What is zenker diverticulum?
An outpouching of pharyngeal mucosa through an acquired defect in the muscular wall (false diverticulum)
Where does the zenker diverticulum arise?
above the upper esophageal sphincter at the junction of the esophagus and pharynx
What does Zenker Diverticulum present with?
dysphagia, obstruction, and halitosis (bad breath)
What is Mallory weiss syndrome?
Longitudinal laceration of mucosa at the gastroesophageal (GE) junction
What is Mallory weiss syndrome caused by?
severe vomiting, usually due to alcoholism or bulimia
What does Mallory weiss syndrome present with?
painful hematemesis
With Mallory weiss syndrome, what is there a risk of?
Boerhaave syndrome
What is Boerhaave syndrome?
rupture of esophagus leading to air in the mediastinum and subcutaneous emphysema
What is esophageal varices?
Dilated submucosal veins in the lower esophagus
What does esophageal varices arise with?
It arises secondary to portal hypertension
What does the distal esophageal vein normally drain into?
the portal vein via the left gastric vein
What is seen in portal hypertension?
the left gastric vein backs up into the esophageal vein, resulting in dilation (varices)
What are the symptoms for esophageal varices?
Asymptomatic, but risk of rupture exists
What does esophageal varices present with?
painless hematemesis
What is the most common cause of death in cirrhosis?
Esophageal varices
What is achalasia?
Disordered esophageal motility with inability to relax the lower esophageal sphincter (LES)
What is achalasia due to?
damaged ganglion cells in the myenteric plexus
Where are the ganglion cells of the myenteric plexus located?
between the inner circular and outer longitudinal layers of the muscularis propria
What are the ganglion cells of the myenteric plexus important for?
regulating bowel motility and relaxing the LES.
What causes damage to ganglion cells [of the myenteric plexus]?
can be idiopathic or secondary to a known insult (e.g., Trypanosoma cruzi infection in Chagas disease)
What are the clinical features for achalasia?
- Dysphagia for solids and liquids 2. Putrid breath 3. High LES pressure on esophageal manometry 4. Bird-beak sign on barium swallow study 5. Increased risk for esophageal squamous cell carcinoma
What is there an increased risk for with achalsia?
Esophageal squamous cell carcinoma
What is GERD?
Gastroesophageal reflux disease - Reflux of acid from the stomach due to reduced LES tone
What are the risk factors for GERD?
include alcohol, tobacco, obesity, fat-rich diet, caffeine, and hiatal hernia.
What are the clinical features for GERD?
- Heartburn (mimics cardiac chest pain) 2. Asthma (adult-onset) and cough 3. Damage to enamel of teeth 4. Ulceration with stricture and Barrett esophagus are late complications.
What is barrett esophagus?
Metaplasia of the lower esophageal mucosa from stratified squamous epithelium to nonciliated columnar epithelium with goblet cells seen in
What % of patients with GERD present with Barrett Esophagus?
10%
Barrett Esophagus is a response of what to what stimuli?
Response of lower esophageal stem cells to acidic stress
What might Barrett Esophagus progress to?
May progress to dysplasia and adenocarcinoma
What is esophageal carcinoma?
Subclassified as adenocarcinoma or squamous cell carcinoma
What is adenocarcinoma?
a malignant proliferation of glands;
What is the most common type of esophageal carcinoma in the West?
Adenocarcinoma
From what does adenocarcinoma arise?
from preexisting Barrett esophagus; usually involves the lower one-third of the esophagus
What is squamous cell carcinoma?
it is a malignant proliferation of squamous cells
What is the most common esophageal cancer worldwide?
Squamous cell carcinoma
Where does squamous cell carcinoma usually arise?
in upper or middle third of the esophagus;
What are the major risk factors for squamous cell carcinoma?
1) Alcohol and tobacco (most common causes) 2) Very hot tea 3). Achalasia 4) Esophageal web (e.g., Plummer-Vinson syndrome) 5) Esophageal injury (e.g., lye ingestion)
What is the prognosis for esophageal carcinoma?
Poor prognosis due to late presentation
What are the symptoms for esophageal carcinoma?
progressive dysphagia (solids to liquids), weight loss, pain, and hematemesis.
In addition to the symptoms for esophageal carcinoma what may squamous cell carcinoma additionally present with?
hoarse voice (recurrent laryngeal nerve involvement) and cough (tracheal involvement).
In esophageal carcinoma what determines the location of lymph node spread?
it depends on the level of the esophagus that is involved
For esophageal carcinoma involvement of the upper 1/3 of the esophagus results in what lymph node spread?
cervical nodes
For esophageal carcinoma involvement of the middle 1/3 of the esophagus results in what lymph node spread?
mediastinal or tracheobronchial nodes
For esophageal carcinoma involvement of the lower 1/3 of the esophagus results in what lymph node spread?
celiac and gastric nodes
What is gastroschisis?
congenital malformation of the anterior abdominal wall leading to exposure of abdominal contents
What is omphalocele?
Persistent herniation of bowel into umbilical cord
What is omphalocele due to?
failure of herniated intestines to return to the body cavity during development, the contents are covered by peritoneum and amnion of the umbilical cord
What is pyloric stenosis?
congenital hypertrophy of pyloric smooth muscle; more common in males
How does pyloric stenosis classically present?
two weeks after birth as; 1. Projectile nonbilious vomiting 2. Visible peristalsis 3. Olive-like mass in the abdomen
What is the treatment for pyloric stenosis?
myotomy
What is acute gastritis?
Acidic damage to the stomach mucosa
What is acute gastritis due to?
imbalance between mucosal defenses and acidic environment
What do the defenses of acute gastritis include?
mucin layer produced by foveolar cells, bicarbonate secretion by surface epithelium, and normal blood supply (provides nutrients and picks up leaked acid).
How is a severe burn a risk factor for acute gastritis?
(Curling ulcer) Hypovolemia leads to decreased blood supply.
How are NSAIDs a risk factor for acute gastritis?
decreased PGE
How is increased intracranial pressure a risk factor for acute gastritis?
(Cushing ulcer) Increased stimulation of vagus nerve leads to increased acid production
What is the relationship between shock and acute gastritis?
Multiple (stress) ulcers may be seen in ICU patients
What are the risk factors for acute gastritis?
- Severe burn 2. NSAIDs 3. Heavy alcohol consumption 4. Chemotherapy 5. Increased intracranial pressure 6. Shock.
In acute gastritis what does acid damage result in?
superficial inflammation, erosion (loss of superficial epithelium), or ulcer (loss of mucosal layer)
What is chronic gastritis?
Chronic Inflammation of stomach mucosa
What is chronic gastritis divided into?
two types based on underlying etiology: chronic autoimmune gastritis and chronic H pylori gastritis
What is chronic autoimmune gastritis due to?
autoimmune destruction of gastric parietal cells
Where are the gastric parietal cells located?
in the stomach body and fundus.
What is chronic autoimmune gastritis associated with?
antibodies against parietal cells and/or intrinsic factor; useful for diagnosis, but pathogenesis is mediated by T cells (type IV hypersensitivity)
What are the clinical features for chronic autoimmune gastritis?
1) Atrophy of mucosa with intestinal metaplasia 2) Achlorhydria with increased gastrin levels and antral G-cell hyperplasia 3) Megaloblastic (pernicious) anemia due to lack of intrinsic factor 4) Increased risk tor gastric adenocarcinoma (intestinal type)
What is chronic H pylori gastritis due to?
H pylori-induced acute and chronic inflammation
What is the most common form of gastritis?
(90%) chronic H pylori gastritis
How does H pylori lead to gastritis?
H pylori ureases and proteases along with inflammation weaken mucosal defenses; antrum is the most common site
How does H. Pylori gastritis present?
with epigastric abdominal pain; increased risk for ulceration (peptic ulcer disease), gastric adenocarcinoma (intestinal type), and MALT lymphoma
What is the treatment for H Pylori gastritis?
involves triple therapy.
What is triple therapy?
Proton pump inhibitors and antibiotics
What does triple therapy treatment for H pylori gastritis result in?
1) Resolves gastritis/ulcer and reverses intestinal metaplasia 2) Negative urea breath test and lack of stool antigen confirm eradication of H pylori.
What is peptic ulcer disease?
Solitary mucosal ulcer involving proximal duodenum (90%) or distal stomach (10%)
What is the duodenal ulcer due to?
almost always due to H pylori (> 95%); rarely, may be due to Zollinger Ellison (ZE) syndrome
What does a duodenal ulcer present with?
epigastric pain that improves with meals
What does biopsy of a duodenal ulcer show?
Diagnostic endoscopic biopsy shows ulcer with hypertrophy of Brunner glands.
What might happen to a duodenal ulcer?
May rupture leading to bleeding from the gastroduodenal artery (anterior ulcer) or acute pancreatitis (posterior ulcer)
What is gastric ulcer usually due to?
H pylori (75%); other causes include NSAlDs and bile reflux.
What doses gastric ulcer present with?
epigastric pain that worsens with meals
Where is the gastric ulcer usually located?
on the lesser curvature of the antrum.
What does rupture of gastric ulcer result in?
carries a risk of bleeding from left gastric artery
What is the differential diagnosis of ulcers?
includes carcinoma.
Might duodenal ulcers lead to carcinoma?
Duodenal ulcers are almost never malignant (duodenal carcinoma is extremely rare).
Is there a relationship between gastric ulcers and carcinoma?
Gastric ulcers can be caused by gastric carcinoma (intestinal subtype)
How do benign peptic ulcers usually appear?
small (< 3 cm), sharply demarcated (punched-out), and surrounded by radiating folds of mucosa
How do malignant ulcers appear?
they are large and irregular with heaped up margins
What is required for definitive diagnosis regarding gastric ulcers?
biopsy
What is gastric carcinoma?
Malignant proliferation of surface epithelial cells (adenocarcinoma)
How is gastric carcinoma subclassified?
into intestinal and diffuse types
Which subclassification of gastric carcinoma is more common?
Intestinal type
How does the intestinal type of gastric carcinoma present?
presents as a large, irregular ulcer with heaped up margins;
What does the intestinal type of gastric carcinoma most commonly?
involves the lesser curvature of the antrum
How is gastric carcinoma similar to gastric ulcer?
They both involve the lesser curvature of the antrum
What are risk factor for the intestinal type of gastric carcinoma?
they include intestinal metaplasia (e.g., due to H pylori and autoimmune gastritis), nitrosamines in smoked foods (Japan), and blood type A.
How is the diffuse type of gastric carcinoma characterized?
by signet ring cells that diffusely infiltrate the gastric wall, desmoplasia resulting in thickening of stomach wall (linitis plasties)
What is the diffuse type of gastric carcinoma not associated with
its not associated with H pylori, intestinal metaplasia, or nitrosamines
What does gastric carcinoma present with?
It presents late with weight loss, abdominal pain, anemia, and early satiety; rarely presents as acanthosis nigricans or Leser-Trelat sign
What might gastric carcinoma spread to?
lymph nodes can involve the left supraclavicular node (Virchow node).
For gastric carcinoma what does distant metastasis most commonly involve?
Liver
For the intestinal type of gastric carcinoma what does distant metastasis involve?
Periumbilical region (Sister Mary Joseph nodule)
For the diffuse type of gastric carcinoma what does distant metastasis involve?
Bilateral ovaries (Krukenberg tumor)
What is duodenal atresia?
Congenital failure of duodenum to canalize;
What is duodenal atresia associated with?
Down syndrome
What are the clinical features for duodenal atresia?
- Polyhydramnios 2. Distension of stomach and blind loop of duodenum (double bubble) 3. Bilious vomiting
What is meckel diverticulum?
Outpouching of all three layers of the bowel wall (true diverticulum)
Why does meckel diverticulum arise?
due to failure of the vitelline duct to involute
For meckel diverticulum what is the rule of 2s?
1) Seen in 2% of the population 2) 2 inches long and located in the small bowel within 2 feet of the ileocecal valve 3) during the first 2 years of life with bleeding, volvulus, intussusception, or obstruction (mimics appendicitis); however, most cases are asymptomatic
What is the most common congenital anomaly of the GI tract?
Meckel diverticulum
How long is the meckel diverticulum?
2 inches long
Where is the meckel diverticulum located?
in the small bowel within 2 feet of the ileocecal valve
How can meckel diverticulum present?
during the first 2 years of life with bleeding, volvulus, intussusception, or obstruction (mimics appendicitis); however, most cases are asymptomatic
Why is there bleeding during the presentation of meckel diverticulum?
Its due to heterotopic gastric mucosa
What is volvulus?
Twisting of bowel along its mesentery
What does volvulus result in?
obstruction and disruption of the blood supply with infarction
What are the most common locations for a volvulus?
sigmoid colon in the elderly and cecum in young adults
What is intussusception?
Telescoping of proximal segment of bowel forward into distal segment
How does intussusception work?
Telescoped segment is pulled forward by peristalsis, resulting in obstruction and disruption of blood supply with infarction.
What is intussusception associated with?
a leading edge (focus of traction)
What is the most common cause of intussusception in children?
lymphoid hyperplasia (e.g., due to rotavirus) which usually arises in the terminal ileum, leading to intussusception into the cecum
What is the most common cause of intussusception in adults?
tumor.
What is small bowel infarction?
Small bowel is highly susceptible to ischemic injury.
When does transmural infarction occur?
with thrombosis/embolism of the superior mesenteric artery or thrombosis of the mesenteric vein.
When does mucosal infarction occur?
with marked hypotension
What are the clinical features for small bowel infarction?
they include abdominal pain, bloody diarrhea, and decreased bowel sounds,
What is lactose intolerance?
Decreased function of the lactase enzyme found in the brush border of enterocytes
What is the normal function of lactase?
It normally breaks down lactose into glucose and galactose.
How does lactose intolerance present?
with abdominal distension and diarrhea upon consumption of milk products; undigested lactose is osmotically active.
How does lactose deficiency develop?
it may be congenital (rare autosomal recessive disorder) or acquired (often develops in late childhood);
How is lactose deficiency related to small bowel infarction?
temporary deficiency is seen after small bowel infection (lactase is highly susceptible to injury).
What is celiac disease?
Immune-mediated damage of small bowel villi due to gluten exposure
What is celiac disease associated with?
HLA-DQ2 and DQ8
In what is gluten present?
in wheat and grains
What is the most pathogenic component of gluten?
gliadin
What happens to gliadin once absorbed?
gliadin is deamidated by tissue transglutaminase (tTG).
What happens to deamidated gliadin?
it is presented by antigen presenting cells via MHC class II where the helper T cells mediate tissue damage.
What is the clinical presentation for celiac disease in herpes?
Children classically present with abdominal distension, diarrhea, and failure to thrive
What is the clinical presentation for celiac disease in adults?
It classically presents with chronic diarrhea and bloating
What is seen on the skin in celiac disease?
Small, herpes-like vesicles may arise on skin (dermatitis herpetiformis).
What is dermatitis herpetiformis in celiac diseae due to and how does it resolve?
IgA deposition at the lips of dermal papillae it resolves with gluten-free diet
What are the laboratory findings for celiac disease?
1) IgA antibodies against endomysium, tTG (tissue transglutaminase), or gliadin
What lab finding for celiac disease is also used in IgA deficiency?
IgG antibodies are also present and are useful for diagnosis in individuals with IgA deficiency
What is the relationship between IgA deficiency and celiac disease?
increased incidence of IgA deficiency is seen in celiac disease
What does duodenal biopsy reveal in celiac disease?
flattening of villi, hyperplasia of crypts, and increased intraepithelial lymphocyte
In celiac disease where is damage most prominent?
in the duodenum (jejunum and ileum are less involved)
When would the symptoms of celiac disease resolve?
with gluten-free diet.
What are late complications that present as refractory disease despite good dietary control?
Small bowel carcinoma and T-cell lymphoma
What is tropical sprue?
Damage to small bowel villi due to an unknown organism resulting in malabsorption
How does tropical spure compare to celiac disease?
Its similar to celiac disease except 1. Occurs in tropical regions (e.g., Caribbean) 2. Arises after infectious diarrhea and responds to antibiotics
In tropical spure, where is damage most prominent?
in jejunum and ileum (secondary vitamin B12 or folate deficiency may ensue); duodenum is less commonly involved.
What is whipple disease?
Systemic tissue damage characterized by macrophages loaded with Tropheryma whippelii organisms; partially destroyed organisms are present in macrophage lysosomes (positive for PAS).
What is the classic site of involvement in whipple disease?
the small bowel lamina propria
What happens in whipple disease?
- Macrophages compress lacteals. 2. Chylomicrons cannot be transferred from enterocytes to lymphatics. 3. Results in fat malabsorption and steatorrhea
What are the other common sites of involvement for whipple disease?
they include synovium of joints (arthritis), cardiac valves, lymph nodes, and CNS.
What is abetalipoproteinemia?
Autosomal recessive deficiency of apolipoprotein B-48 and B-100
What are the clinical features for abetalipoproteinemia?
Malabsorption due to defective chylomicron formation (requires B-48), Absent plasma VLDL and LDL (requires B-100)
What is carcinoid tumor?
Malignant proliferation of neuroendocrine cells; low-grade malignancy
What do the tumor cells in carcinoid tumor contain?
neurosecretory granules that are positive for chromogranin
Where can carcinoid tumor cells arise?
Can arise anywhere along the gut; small bowel is the most common site
What does carcinoid tumor grow as?
It grows as a submucosal polyp-like nodule
What is the relation between carcinoid tumor and serotonin?
The neurosecretory granules often secrete serotonin
What is serotonin released into?
the portal circulation
Where is serotonin metabolized?
Its metabolized by liver monoamine oxidase (MAO) into 5-HIAA (5-hydroxyindoleacetic acid)
What happens to 5-HIAA?
it is excreted in the urine.
What does metastasis of carcinoid tumor to the liver result in?
it allows serotonin to bypass liver metabolism.
What is carcinoid syndrome / heart disease?
Serotonin is released into the hepatic vein and leaks into systemic circulation via hepato-systemic shunts, resulting in carcinoid syndrome and carcinoid heart disease.
What is carcinoid syndrome characterized by?
bronchospasm, diarrhea, and Hushing of skin;
What might trigger symptoms of carcinoid syndrome?
it can be triggered by alcohol or emotional stress, which stimulate serotonin release from the tumor,
What characterizes carcinoid heart disease?
It is characterized by right-sided valvular fibrosis
In carcinoid heart disease why is there right sided valvular fibrosis?
increased collagen
What does the right sided valvular fibrosis seen in carcinoid heart disease lead to?
tricuspid regurgitation and pulmonary valve stenosis
In carcinoid heart diseae are there left-sided valvular lesions?
No, they are not seen due to presence of monoamine oxidase which metabolizes serotonin in the lung,
What is acute appendicitis?
Acute inflammation of the appendix; most common cause of acute abdomen
What is the most common cause of acute abdomen?
Acute appendicitis
What is acute appendicitis related to?
obstruction of the appendix by lymphoid hyperplasia (children) or a tecalith (adults)
What is McBurney point?
It is where the pain for acute appendicitis localizes to lower right quadrant
What are the clinical features in acute appendicitis?
- Periumbilical pain, fever, and nausea; pain eventually localizes to right lower quadrant (McBurney point). 2. Rupture results in peritonitis that presents with guarding and rebound tenderness.
What is a common complication for acute appendicitis?
Periappendiceal abscess is a common complication
What is inflammatory bowel disease?
Chronic, relapsing inflammation of bowel
What is inflammatory bowel disease possibly due to?
abnormal immune response to enteric flora
How does inflammatory bowel disease classically present?
in young women (teens to 30s) as recurrent bouts of bloody diarrhea and abdominal pain
Where is inflammatory bowel disease more prevalent?
in the West, particularly in Caucasians and Eastern European Jews
How do you diagnose inflammatory bowel disease?
It?s a diagnosis of exclusion whose symptoms mimic other causes of bowel inflammation
What is inflammatory bowel disease subclassified as?
ulcerative colitis or Crohn?s disease
What is the wall involvement for ulcerative colitis?
Mucosal or submucosal ulcers
Where does ulcerative colitis begin?
In the rectum
What does ulcerative colitis involve after the rectum?
It can extend proximally up to the cecum, the remainder of the GI tract is unaffected
What are the symptoms of ulcerative colitis?
Left lower quadrant pain (rectum) with bloody diarrhea
What is involved in inflammation with ulcerative colitis?
Crypt abscesses with neutrophils
What is the gross appearance of ulcerative colitis?
Pseudopolyps, loss of haustra ? lead pipe sign on imaging
What are the complications for ulcerative colitis?
Toxic megacolon and carcinoma
For ulcerative colitis what is the risk based on?
Its based on extent of colonic involvement and duration of disease (generally not a concern until >10 years of disease)
What are the associations for ulcerative colitis?
Primary sclerosing cholangitis and p-ANCA positivity
What is the effect of smoking on ulcerative colitis?
Smoking protects against it
What is the wall involvement for crohns disease?
Full thickness inflammation with knife like fissures
What is the location for Chrons disease?
Anywhere from mouth to anus with skip lesions
What is the most common and least common site for chrons disease?
Most common is the terminal ileum and the least common is the rectum
What are the symptoms for chron?s disease?
Right lower quadrant pain (ileum) with non bloody diarrhea
What is involved with the inflammation in Crohn?s disease?
Lymphoid aggregates with granulomas (40% of cases)
What is the gross appearance of Crohn Disease?
Cobblestone mucosa, creeping fat, and strictures (string sign on imaging)
What are the complications for Crohns Disease?
Malabsorption with nutritional deficiency, calcium oxalate nephrolithiasis, fistula formation, and carcinoma if colonic disease is present
What are the associations for Crohns disease?
Ankylosing spondylitis, sacroiliitis, migratory polyarthritis, erythema nodosum and uveitis
What effect does smoking have on Crohns disease?
It increases the risk for developing Crohns disease
What is hirschsprung disease?
Defective relaxation and peristalsis of rectum and distal sigmoid colon
What is hirschsprung disease associated with?
Down syndrome
What is hirschsprung disease due to?
congenital failure of ganglion cells which are neural crest-derived, to descend into myenteric and submucosal plexus
Where is the myenteric (Auerbach) plexus located?
between the inner circular and outer longitudinal muscle layers of the muscularis propria and regulates motility
Where is the submucosal (Meissner) plexus located?
in the submucosa and regulates blood flow, secretions, and absorption.
What are the clinical features for hirschsprung disease based on?
Obstruction
What are the clinical features for hirschsprung disease?
- Failure to pass meconium 2. Empty rectal vault on digital rectal exam 3. Massive dilatation (megacolon) of bowel proximal to obstruction with risk for rupture
In hirschsprung disease what does rectal suction biopsy reveal?
lack of ganglion cells.
What is the treatment for hirschsprung disease?
involves resection of the involved bowel; ganglion cells are present in the bowel proximal to the diseased segment.
What is colonic diverticula?
Outpouchings of mucosa and submucosa through the muscularis propria (false diverticulum)
What is colonic diverticula related to?
wall stress
What is colonic diverticula associated with?
constipation, straining, and low-fiber diet; commonly seen in older adults (risk increases with age)
From where does the colonic diverticula arise?
where the vasa recta traverse the muscularis propria (weak point in colonic wall)
What is the most common location for colonic diverticula?
sigmoid colon
What are usually the symptoms for colonic diverticula?
Its usually asymptomatic
What are the complications for colonic diverticula?
- Rectal bleeding (hematochezia) 2. Diverticulitis 3. Fistula
What is diverticulitis due to?
obstructing fecal material
How does diverticulitis present?
with appendicitis-like symptoms in the left lower quadrant
What is the relationship between colonic diverticula and a fistula?
Inflamed diverticulum ruptures and attaches to a local structure.
What does the colovesicular fistula present with?
air (or stool) in urine
What is angiodysplasia?
Acquired malformation of mucosal and submucosal capillary beds
How does angiodysplasia usually arise?
in the cecum and right colon due to high wall tension
How does rupture in angiodysplasia classically present?
as hematochezia in an older adult.
What is hereditary hemorrhagic telangiectasia?
Autosomal dominant disorder resulting in thin-walled blood vessels, especially in the mouth and GI tract
What does rupture in hereditary hemorrhagic telangiectasia present as?
presents as bleeding.
What is ischemic colitis?
Ischemic damage to the colon, usually at the splenic flexure, watershed area of superior mesenteric artery (SMA)
What does ischemic cholitis present with?
postprandial pain and weight loss; infarction results in pain and bloody diarrhea.
What is irritable bowel syndrome?
Relapsing abdominal pain with bloating, flatulence, and change in bowel habits (diarrhea or constipation) that improves with defecation
What is irritable bowel syndrome classically seen in?
middleaged females
What is irritable bowel syndrome related to?
disturbed intestinal motility; no identifiable pathologic changes
What may improve the symptoms of irritable bowel syndrome?
Increased dietary fiber may improve symptoms.
What are colonic polyps?
Raised protrusions of colonic mucosa
What are the most common types of colonic polyps?
hyperplastic and adenomatous polyps
What are hyperplastic polyps due to?
hyperplasia of glands; classically show a serrated appearance on microscopy
What is the most common type of polyp and where does it usually arise?
Hyperplastic polyps and it usually arises in the left colon (rectosigmoid)
Can hyperplastic polyps result in cancer?
No its benign, with no malignant potential
What are adenomatous polyps due to?
neoplastic proliferation of glands
What is the 2nd most common type of colonic polyp?
Adenomatous polyps
Can andenomatous polyps lead to cancer?
Benign, but premalignant, it may progress to adenocarcinoma via the adenoma-carcinoma sequence
What is the adenoma-carcinoma sequence?
it describes the molecular progression from normal colonic mucosa to adenomatous polyp to carcinoma.
What is APC?
APC (adenomatous polyposis coli gene)
What do mutations in the APC lead to?
either sporadic or germline mutations increase risk for the formation of polyp.
Mutations of what leads to increased risk for polyp progression to carcinoma?
APC, k-ras and p53
How does k-ras mutation affect polyps?
leads to formation of polyp
What is the effect of p53 mutation and polyps?
p53 mutation and increased expression of COX allow for progression to carcinoma; aspirin impedes progression from adenoma to carcinoma.
How is screening for polyps performed?
by colonoscopy and testing for fecal occult blood
How do polyps present clinically?
they are usually clinically silent, but can bleed.
What is the goal in term of polyps?
it is to remove adenomatous polyps before progression to carcinoma
On colonoscopy can you tell the difference between hyperplastic and adenomatous polyps?
No they look identical. Hence, all polyps are removed and examined microscopically
With polyps what is the risk for progression from adenoma to carcinoma related to?
size > 2 cm, sessile growth, and villous histology.
What is familial adenomatous polyposis?
(FAP)Autosomal dominant disorder characterized by 100s to 1000s of adenomatous colonic polyps
What is familial adenomatous polyposis (FAP) due to?
inherited APC mutation (chromosome 5); increases propensity to develop adenomatous polyps throughout colon and rectum
How is familial adenomatous polyposis treated?
Colon and rectum are removed prophylacticly ; otherwise, almost all patients develop carcinoma by 40 years of age.
What is gardner syndrome?
it is FAP with fibromatosis and osteomas
What is fibromatosis?
it is a non-neoplastic proliferation of fibroblasts
Where does fibromatosis arise?
in retroperitoneum (desmoid) and locally destroys tissue
What is Osteoma?
it is a benign tumor of bone that usually arises in the skull
What is Turcot syndrome?
it is FAP with CNS tumors (medulloblastoma and glial tumors)
What is a juvenile polyp?
Sporadic, hamartomatous (benign) polyp that arises in children (< 5 years)
How does juvenile polyp usually present?
as a solitary rectal polyp that prolapses and bleeds
What is juvenile polyposis characterized by?
multiple juvenile polyps in the stomach and colon; large numbers of juvenile polyps increase the risk of progression to carcinoma.
What is peutz-jeghers syndrome?
Hamartomatous (benign) polyp throughout GI tract and mucocutaneous hyperpigmentation (freckle-like spots) on lips, oral mucosa, and genital skin; autosomal dominant disorder
In Peutz-Jeghers Syndrome what is there an increased risk for?
colorectal, breast, and gynecologic cancer
What is colorectoal carcinoma?
Carcinoma arising from colonic or rectal mucosa
What is the 3rd most common site of cancer?
Colorectal carcinoma
What is the 3rd most common cause of cancer-related death?
Colorectal carcinoma
What is the peak incidence for colorectal carcinoma?
it is 60-70 years of age
What does colorectal carcinoma most commonly arise from?
adenoma-carcinoma sequence
For colorectal carcinoma what is a second important molecular pathway?
the microsatellite instability (MSI) pathway
What are microsatellites in the MSI pathway?
they are repeating sequences of noncoding DNA; integrity of the sequence (stability) is maintained during cell division.
What does instability in the microsatellite instability pathway indicate?
defective DNA copy mechanisms (eg. DNA mismatch repair enzymes).
What is HNPCC
Hereditary non polyposis colorectal carcinoma
What is HNPCC due to?
Inherited mutations in DNA mismatch repair enzymes.
With HNPCC what is there an increased risk for?
colorectal, ovarian, and endometrial carcinoma
Where does colorectal carcinoma arise?
de novo (not from adenomatous polyps) at a relatively early age; usually right-sided
How does the screening for colorectal carcinoma occur?
via endoscopy and fecal occult blood testing
When does screening for colorectal carcinoma begin?
at 50 years of age
What is the goal for screening for colorectal carcinoma?
To remove adenomatous polyps before carcinoma develops and to detect cancer early (before clinical symptoms arise).
In colorectal carcinoma where can carcinoma develop?
anywhere along entire the length of the colon
In colorectal carcinoma how does left-sided carcinoma usually grow?
as a napkin-ring lesion;
In colorectal carcinoma how does left-sided carcinoma present?
With decreased stool caliber, left lower quadrant pain, and blood-streaked stool
In colorectal carcinoma how does right-sided carcinoma usually grow?
as a raised lesion;
In colorectal carcinoma how does right-sided carcinoma usually present?
with iron deficiency anemia (occult bleeding) and vague pain. All older adults with iron deficiency anemia has colorectal carcinoma until proven otherwise.
What infection is colonic carcinoma associated with?
an increased risk for Streptococcus bovis endocarditis.
What is the T stage for colorectal carcinoma based on?
depth of invasion;
Do tumors limited to the mucosa generally spread?
No they do not spread due to lack of lymphatics in the mucosa
What does the N stage for colorectal carcinoma represent?
spread to regional lymph nodes
What does the M stage for colorectal carcinoma represent?
distant spread
What does the M stage for colorectal carcinoma most commonly involve?
the liver
What is CEA?
it is a serum tumor marker that is useful for assessing treatment response and detecting recurrence; not useful for screening
