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Flashcards in GI Path Deck (154):

Common signs and symptoms of GI problems

-Pay attention to the pattern of bleeding for clues to origin


Usual locations for severe upper GI bleeding (in descending order of frequency)

-duodenal ulcer
-gastric ulcer
-esophageal varices
Note that all of these are above the ligament of Treitz. They make up 90% of major GI bleeds.


Signs of bleed

Hemoglobin converted to hematin by stomach acid



bright red blood in the stool
sign of distal small bowel (10%) or bleeding originating below the ileocecal valve (90%)
-most commonly the colon (usually diverticulosis)


Guaiac Tests

based on detection of endogenous peroxidase in RBCs

 false positives: foods (rare red meat, cruciferous veggies, horseradish), myoglobin
false negatives: ascorbic acid or other reducing agents


Apt test

used to evaluate newborns with blood in stool or vomit
-fetal hemoglobin is resistant to acid and alkaline denaturation
positive test = blood is derived from newborn


Diseases of the esophagus

Heartburn (pyrosis)
-Pay attention to location of dysfunction and food type for clues to origin
*Just solid food = obstruction
*Solids and liquids = motility disorder
+Upper esophagus involved = skeletal muscle problem
e.g., myasthenia gravis, stroke
+Lower esophagus involved = smooth muscle problem
e.g., CREST syndrome


Atresias and Fistulas

developmental defects that must be corrected early because incompatible with life
-starvation, aspiration and pneumonia, paroxysmal suffocation from food


Atresias and Fistulas when discovered

usually discovered soon after birth
-regurgitation after first feed
-impossible to pass nasogastric catheter to stomach
may be identified before birth by ultrasound
-association with other congenital anomalies


VATER Syndrome

Vertebral abnormalities
Anal atresia
TE fistula
Renal disease and radial agenesis

cause unknown


Esophageal Webs and Rings

main symptom: dysphagia with solid food
most common in women >40 yoa


Esophageal Mucosal Webs

uncommon ledgelike protrusions of mucosa into esophageal lumen
usually in upper esophagus and semicircumferential
congenital, or in association with long-standing reflux esophagitis, GVHD, or blistering skin diseases


Plummer-Vinson Syndrome (Paterson-Brown-Kelly Syndrome)

web accompanied by Fe-deficiency anemia, glossitis, leukoplakia in oral cavity and esophagus, cheilosis
risk for postcricoid esophageal squamous cell carcinoma


Esophageal Rings

plates of tissue protruding into lumen
in lower esophagus and concentric
-A ring = above squamocolumnar junction of esophagus and stomach
-B ring (Schatzki ring) = at this junction


Esophageal Stenosis

main symptom: progressive dysphagia (starts with solids, then liquids)
fibrous thickening of the esophageal wall, usually due to inflammatory scarring after injury
-gastroesophageal reflux, radiation, scleroderma, caustic injury



progressive dilation of the esophagus above the lower esophageal sphincter (LES), due to
-partial or incomplete relaxation of the LES with swallowing
-increased resting tone of the LES


primary achalasia

uncertain (may be autoimmune in origin)
dysfunction of inhibitory neurons containing NO and VIP?
degenerative changes in neural innervation of distal esophagus?


secondary achalasia

Chagas disease
Trypanasoma cruzi infection destroys myenteric plexus of esophagus, duodenum, colon, and ureter, with resulting dilation


Achalasia: Clinical Features

main symptom: progressive dysphagia (first solids, then liquids)
nocturnal regurgitation and aspiration of undigested food
frequent hiccups, difficulty belching
primary form usually occurs in adulthood in bimodal distribution
-20s-40s, and after age 60


Manometry Test

detects aperistalsis and failure of LES to relax
An esophageal manometry test measures the motility and function of the esophagus and esophageal sphincter. A tube is usually inserted through the nose and passed into the esophagus. The pressure of the sphincter muscle is recorded and also the contraction waves of swallowing are recorded. The manometry test is a tool used to help evaluate swallowing disorders.


Hiatal Hernia

protrusion of a portion of the stomach above the diaphragm due to separation of the diaphragmatic crura and widening of the space between the muscular crura and esophageal wall (etiology unknown)
most common is sliding hernia


Hiatal Hernia: Clinical Features

bowel sounds heard over left lung base
usually asymptomatic
heartburn or nocturnal epigastric distress (only ~9% of patients)
much less commonly, ulceration, hematemesis, dysphagia due to stenosis



outpouchings of the alimentary tract that contain all visceral layers (mucosa, submucosa, muscularis propria, and adventitia)
-a false diverticulum (pulsion diverticulum) does not have all four layers
*outpouching of mucosa and submucosa into area of weakness in the wall
any diverticula can undergo inflammation (diverticulitis), ulceration, bleeding, and perforation


Zenker Diverticulum

pulsion diverticulum located in upper esophagus, just above UES
-cricopharyngeus muscle is area of weakness
clinical findings:
-odynophagia, halitosis (due to food entrapped in the diverticulum), regurgitation


Midesophageal Diverticulum

pulsion diverticulum located near midpoint of esophagus (near tracheal bifurcation)
-usually due to motor dysfunction (e.g., PSS) or congenital
-Can see these as true diverticula in the setting of tuberculosis
Usually asymptomatic


Epiphrenic Diverticulum

immediately above the LES
clinical findings: nocturnal regurgitation of massive amounts of liquid


Lacerations: Mallory-Weiss Syndrome

longitudinal tears at the esophagogastric junction or gastric cardia
-usually due to retching in alcoholics and bulimics
*hiatal hernia is a predisposing factor in those without this history
produces hematemesis
-usually stops without surgical intervention, but supportive therapy might be required (vasoconstrictive meds, transfusions, balloon tamponade)


Lacerations: Boerhaave Syndrome

rupture of distal esophagus
-Endoscopy causes ~75% of cases (but not Boerhaave)
-retching, bulimia
*air dissects subcutaneously into the anterior mediastinum
*crunching sound (Hamman’s crunch) on auscultation
-pleural effusion containing food, acid, amylase


Esophageal Varices

portal hypertension induces formation of collateral bypass channels where the portal and caval systems communicate
develop in 90% of cirrhotic patients, most often those with alcoholic cirrhosis
-most common cause of death in this group


Esophageal Varices: Clinical Findings

asymptomatic until rupture, then massive hematemesis
~50% die during first bleed; of remainder, 50% will have another bleed within the year (with similar mortality rate)
can monitor at-risk patients with endoscopy and treat varices when found (sclerotherapy



most important cause of esophagitis
usually limited to adults, but sometimes in infants and children
due to reflux of gastric contents into lower esophagus


GERD causes

decreased LES tone
CNS depressants, pregnancy, hypothyroidism, sclerosing disorders, tobacco or alcohol exposure, nasogastric tube, etc
sliding hiatal hernia
present in ~70% of people with GERD
inadequate or slowed esophageal clearance of refluxed material
delayed gastric emptying and increased gastric volume
reduction in reparative capacity of esophageal mucosa


GERD morphology

inflammatory cells (particularly eosinophils) in the squamous epithelium
basal zone hyperplasia
elongation of lamina propria papillae and capillary congestion


GERD Clinical Features

heartburn, indigestion
nocturnal cough and/or asthma
-GERD is most common cause of this symptom
early satiety, abdominal fullness
bloating with belching
when severe: hematemesis or melena


GERD labs

Esophageal pH monitoring
-LES pressure < 10 mm Hg

Esophageal pH monitoring is a test that measures how often and how long stomach acid is entering the esophagus. A small thin tube is introduced through the nose or mouth and into the stomach, which is then drawn back up into the esophagus. The tube is attached to a monitor which records the level of acidity in the esophagus. The patient records symptoms and activity while the tube is left in place for the next 24 hours. The information from the monitor is compared to the diary the patient provides. This test is helpful in determining the amount of stomach acid entering the esophagus.


Eosinophilic Esophagitis

increasing incidence, for unknown reasons (more common in those with atopic history)
-children = feeding intolerance, GERD-like symptoms
-adults = dysphagia, fodd impaction
hallmarks: abundant eosinophils at sites away from gastroesophageal junction; absence of acid reflux/no response to high-dose proton pump inhibitor treatment


Infectious Esophagitis

most commonly caused by viruses and fungi, and the most common cause of odynophagia
usually limited to immunosuppressed patients


HSV Esophagitis

most common in patients with leukemia and lymphoma
produces “punched out” lesions on endoscopy; biopsy confirms nuclear inclusions of herpesvirus


CMV Esophagitis

most common in AIDS patients
-AIDS patients can have ulcers in esophagus that mimic CMV without infection
linear ulcerations; biopsy confirms basophilic nuclear and cytoplasmic inclusions


Candida esophagitis

immunocompromised and diabetes mellitus
entire esophagus covered with patches of gray-white fungal hyphae


Chemical Esophagitis

ingestion of mucosal irritants
-alcohol, corrosive acids or alkali, excessively hot fluids, heavy smoking, cytotoxic anticancer therapy
pill-induced esophagitis
-Taking meds without water or lying down increases risk
-NSAIDS, antibiotics, iron tablets, Vit. C, potassium, quinidine, etc


Barrett Esophagus

distal squamous mucosa is replaced by metaplastic columnar epithelium
-complication of long-standing GERD (seen in 10% of symptomatic patients)
Single most important factor predisposing to esophageal adenocarcinoma


Barrett Esophagus diagnosed by

endoscopic evidence of columnar epithelium above the gastroesophageal junction
-appears as red, velvety mucosa
intestinal metaplasia in biopsy specimens



Older African-American men
Developing countries
Dietary & environmental link-strong
no association w barrets
anywhere in esophagus involved- middle & upper most common



Older Caucasian men
More common in the US
No dietary & environmental factors
Association w Barretts
Lower esophagus involved


Signs and Symptoms of Stomach Disease

-most commonly due to peptic ulcer disease (PUD)
-usually as melenemisis
Gastric analysis
includes measurement of
-BAO (basal acid output)
*output of gastric juice collected in 1 h via nasogastric tube on empty stomach
-MAO (maximal acid output)
*same as BAO, but this time stimulate with pentagastrin
-BAO:MAO ratio
normally ~0.20:1


Pyloric Stenosis

progressive hypertrophy of the circular muscles in the pyloric sphincter
treatment: myotomy


Congenital Pyloric Stenosis Epidemiology

likely genetic: affected parents have increased risk of child with CPS, and high rate of concurrence with monozygotic twins
associated with Turner and Edward’s syndrome, esophageal atresia


Congenital Pyloric Stenosis path & clinical features

Pathogenesis: recent evidence implicates NO synthase deficiency
Clinical features:
-NOT present at birth, but shows up within 2-5 weeks
-projectile vomiting of non-bile-stained fluid
-the hypertrophied pylorus (“olive”) is commonly palpated



inflammation of the gastric mucosa
is a histologic diagnosis, but clinically is applied to any gastric complaint without doing a confirmatory biopsy.
-Often a missed diagnosis, bc most patients with chronic gastritis are asymptomatic
types of inflammation
-neutrophils: acute gastritis
-lymphocytes and/or plasma cells: chronic gastritis


Acute Gastritis

acute (usually transient) inflammation of the mucosa, sometimes with hemorrhage
unifying features of factors known to incite acute gastritis:
-increased acid secretion with back-diffusion
-decreased production of bicarbonate buffer
-direct damage to the epithelium


Acute Gastritis morphology

can range from mild neutrophilic invasion of the epithelial layer to erosion of the epithelial layer with hemorrhage (note there is no breach of muscularis mucosa)


Acute Gastritis clinical

asymptomatic, or epigastric pain, nausea, vomiting
may present with overt hemorrhage, massive hematemesis, melena, or fatal blood loss


Acute Gastric Ulceration (Stress Ulcers)

differ from PUD in timing is acute, there are multiple lesions (mainly in the stomach), and there is no association with H. pylori infection
-these are NOT precursors to chronic PUD


Acute Gastric Ulceration (Stress Ulcers)

follow severe physiologic stress, usually in patients with
-shock, extensive burns, sepsis, or severe trauma
*gastric cells hypoxic due to stress-induced splanchnic vasoconstriction
-intracranial injury
*hypersecretion of gastrin due to stimulation of vagal nuclei by increased intracranial pressure


Ulcers types

Curling ulcers:
arise in proximal duodenum
associated with severe burns, trauma

Cushing ulcers:
arise in stomach, duodenum, and esophagus
associated with intracranial injury, operations, or tumors
high incidence of perforation


Acute Gastric Ulceration (Stress Ulcers) morphology & clinical

-usually multiple, small (<1 cm) ulcers, frequently stained dark brown by acid digestion of extruded blood
clinical features:
-1-4% of critically ill patients will require transfusion due to bleeding


Chronic Gastritis

chronic mucosal inflammation that leads to mucosal atrophy and intestinal metaplasia
-metaplasia can develop into dysplasia, creating a background for cancer
in contrast to acute gastritis, erosions rarely occur


Chronic Gastritis: Helicobacter pylori Infection

THE most important association
most infected adults have associated gastritis but are asymptomatic
-Estimated 50% of American adults >50 yoa are infected
gastritis results from combination of bacterial enzymes and toxins, and chemicals released from recruited neutrophils


gastritis develops in two patterns

antral type
-high acid production
-high risk of duodenal ulcer

pangastric type
-multifocal mucosal atrophy
-increased risk of gastric carcinoma and lymphoma


Autoimmune Gastritis and Pernicious Anemia

<10% of chronic gastritis cases
due to autoantibodies against components of gastric gland parietal cells (e.g., H+,K+- ATPase, gastrin receptor, intrinsic factor)
-loss of acid production, intrinsic factor no longer produced
leads to atrophy and dysplasia
increased risk of gastric carcinoma and carcinoid tumors


Chronic Gastritis

usually asymptomatic, but can cause nausea, vomiting, upper abdominal discomfort
-in setting of H. pylori infection
*May be hypochlorhydric due to parietal cell damage (but not achlorhydric)
*not enough damage to induce pernicious anemia
-in setting of autoimmune gastritis
*hypochlorhydria or achlorhydria (↓BAO, MAO)


Peptic Ulcer Disease

ulcers are breaches in the mucosa of the alimentary tract that extend through the muscularis mucosa into the submucosa or deeper, most commonly in duodenum and stomach
peptic ulcers are usually solitary lesions < 4 cm, located in any site exposed to peptic juices
-first portion of the duodenum
-stomach (usually antrum)


Peptic Ulcer Disease who affected

most commonly diagnosed in middle-age to older life, but may first become evident in young adulthood
-relapsing lesions that develop suddenly and without cause, are active from weeks to months, and then spontaneously heal
*although ulcers heal, infection with H. pylori is persistent, so they tend to recur


tests to identify H. pylori (>90% sensitivity and specificity)

Urea breath test
-documents active infection
Stool antigen test
-positive when active infection only
tests to detect urease in a gastric biopsy (e.g., CLOtest- campylobacter like organism)
-gold standard, but invasive
serologic tests
-cannot distinguish current from past infection


H. pylori

H. pylori does not invade tissues
-induces intense inflammatory and immune response
Several bacterial gene products promote inflammation
H. pylori enhances gastric acid secretion and impairs duodenal bicarbonate production
Only 10-20% of infections result in ulcers


PUD locations

98% of all peptic ulcers are found in
-first part of duodenum
*usually within few cm of pyloric ring on anterior wall
*no association with cancer development
*usually along lesser curvature
*1-4% will already be malignant, so must biopsy these


the vast majority of ulcers are single

-10-20% of gastric ulcers will also be accompanied by duodenal ulcer
-suspect Zollinger-Ellison syndrome if multiples in unusual locations
*ZE is due to excess gastrin secretion by a tumor
+causes excess gastric acid production
+↑BAO, MAO; ↑ serum gastrin level
*multiple ulcers in stomach, duodenum, and even jejunum
+ulcers resistant to typical therapy (directed at H. pylori)


ulcer description

ulcers usually round to oval, with relatively straight walls
-heaped up margins are rare in benign lesions but characteristic for malignant
-ulcer size and location can’t predict malignancy
-bases of ulcers usually smooth and clean, as any exudates are digested by peptic juices


PUD clinical

main symptoms: epigastric gnawing, burning, or aching pain
-pain worse at night
-pain either caused by eating (gastric) or relieved by eating (duodenal)
significant minority first come to clinical attention due to Fe-deficiency anemia, frank hemorrhage, or perforation
sometimes nausea, vomiting, bloating, belching, weight loss
perforated ulcers: referred pain to the back, left upper quadrant, or chest


Hypertrophic Gastrophy

includes group of uncommon conditions all characterized by giant cerebriform enlargement of the rugal folds of the gastric mucosa, due to hyperplasia without inflammation


Hypertrophic Gastrophy clinically important bc...

they may mimic infiltrative carcinoma or lymphoma of the stomach
with exception of Ménétrier disease, increased risk of peptic ulceration due to enormous increase in gastric acid secretion


Hypertrophic Gastrophy 3 variants

Ménétrier Disease
-hyperplasia of the surface mucous cells
Hypertrophic-hypersecretory gastropathy
-hyperplasia of the parietal and chief cells within gastric glands
Excessive gastrin secretion in the setting of a gastrinoma
-promotes gastric gland hyperplasia
-e.g., Zollinger-Ellison syndrome


Ménétrier Disease

most often in males 30-50 yoa
unknown cause; may be growth factor overexpression
-may involve entire stomach or just body-fundus or antrum
gastric secretions contain excessive mucus; hypochlorydria or achlorhydria
-may produce hypoalbuminemia and peripheral edema due to sufficient protein loss in the gastric secretions (protein-losing enteropathy)
usually produces epigastric discomfort, diarrhea, weight loss, and occasionally bleeding



any nodule or mass that arises from the mucosa and projects above the surrounding mucosa (polypoid lesions arise from submucosa, such as a lipoma or leiomyoma)
-uncommon in the stomach
-seen most frequently in context of chronic gastritis
-found incidentally, or when pursuing dyspepsia or Fe-deficiency anemia cause
most (>90%) are not neoplasms, but simply hyperplastic epithelial tissue


Neoplasms: Malignant

carcinoma (90-95%)
lymphomas (4%)
carcinoids (3%)
mesenchymal tumors (2%)


Gastric Carcincoma

2nd most common tumor in the world
-incidence varies by geographic area (similar to esophageal cancer)
*used to be most common cause of cancer death in US until endoscopy
more common in men in lower socioeconomic groups


Gastric Carcincoma: Classification

intestinal-type adenocarcinoma
diffuse carcinoma


intestinal-type adenocarcinoma

bulky tumors composed of glandular structures
predominates in high-risk areas
develops from precursor lesions
more common in men; mean age 55 yo


diffuse carcinoma

infiltrative growth of poorly differentiated discohesive cells
-signet ring cells characteristic
*mucin pushes nucleus to periphery
no difference in incidence by area
no precursor lesions
equal prevalence in men and women; mean age 48 yo


Gastric Carcinoma location & clinical

most in pylorus and antrum (50-60%) along the lesser curvature (40%)
-although less common, ulcerative lesions on the greater curvature or more likely to be malignant
asymptomatic until late in course, then weight loss, abdominal pain, anorexia, vomiting, altered bowel habits


Gastric Carcinoma: Skin markers

acanthosis nigricans
sign of Leser-Trélat
supraclavicular sentinel (Virchow) node
less commonly, periumbilical region as Sister Mary Joseph nodule


Gastric Carcinoma: Invasion and Metastases

local invasion into duodenum, pancreas, retroperitoneum; peritoneal seeding
-Krukenberg tumor = metastasis to one or both ovaries


Gastric Lymphoma

stomach is most common site for extranodal lymphoma (20%) and almost all are B-cell lymphomas of mucosa-associated lymphoid tissue (MALT lymphomas)
->80% associated with chronic gastritis and H. pylori infection
*50% of these tumors regress with antibiotic treatment for H. pylori
+ones that don’t usually have genetic abnormalities, like trisomy 3 or t(11;18) translocation


Gastrointestinal Stromal Tumor (GIST)

stromal tumors thought to arise from interstitial cells of Cajal that control GI peristalsis
-have mutations in c-KIT (a receptor for stem cell growth factor) or PDGFRA (a receptor for platelet-derived growth factor)
*both of the gene products have tyrosine kinase activity, and mutation results in their constitutive activation (so cell proliferation is promoted)


Carcinoid Tumors

called “carcinoid” because slower growing than carcinomas
arise from neuroendocrine organs and neuroendocrine-differentiated gastrointestinal epithelia
-most are found in GI tract, and >40% in small intestine
-in stomach, usually arise in setting of hypergastrinemia that promotes ECL hyperplasia, such as multiple endocrine neoplasia type 1 and Zollinger-Ellison syndrome


Carcinoid Tumors symptoms & location

symptoms determined by hormones produced
-vasoactive substances cause flushing, sweating, bronchospasm, diarrhea, etc
-if confined to intestine, “first-pass” effect similar to an oral drug (liver metabolizes)
Most important prognostic factor for gastrointestinal carcinoid tumors is LOCATION:
-foregut (proximal to ligament of Treitz) = rarely metastasize; resection curative
-midgut (tumors in jejunum and ileum) = aggressive, larger, often multiple, deeply invasive  poor outcome
-hindgut (appendix and colorectum) = incidental finding, rarely metastasize


Signs and Symptoms of Small Bowel Disease

Colicky pain (pain that comes and goes)
-accompanied by constipation and inability to pass gas
-symptom of bowel obstruction
-sign of infection, malabsorption, or osmotic diarrhea
-if bloody, consider infarction, volvulus, dysentery
-sign of malabsorption (iron, folate, Vit. B12)


Signs and Symptoms of Large Bowel Disease

-sign of infection, laxative abuse, inflammatory bowel disease
-if bloody, consider infarction or dysentery
-bloody diarrhea with mucus
-painful, ineffective straining at stool
-common in ulcerative colitis
Iron Deficiency Anemia
-consider polyps, colorectal cancer
-sigmoid diverticulosis (most common)


Congenital Anomalies: Omphalocele

abdominal musculature fails to form
abdominal contents herniate into ventral membranous sac


Congenital Anomalies: Gastroschisis

extrusion of the intestines due to failure of a portion of the abdominal wall to form


Congenital Anomalies: Meckel Diverticulum

a true diverticulum that is due to failure of involution of the vitelline duct (connects lumen of developing gut to the yolk sac)
in newborn with MD, may sometimes find fecal material in umbilical area due to persistence of vitelline duct
usually on antimesenteric side of the bowel
Remember 2’s:
-usually within 2 feet of the ileocecal valve and 2 inches long
-present in ~2% of the normal population, of which 2% are symptomatic


Congenital Anomalies: Congenital Aganglionic Megacolon (Hirschsprung Disease)

characterized by absence of ganglion cells and ganglia in a portion of the intestinal tract
-absence of staining for acetylcholinesterase
-the migration of neural crest cells arrests prematurely before reaching the anus, OR the ganglion cells undergo premature death
proximal to the aganglionic segment, the colon undergoes massive dilation and hypertrophy
-colonic wall becomes thinned and can rupture (usually near cecum)


Congenital Anomalies: Congenital Aganglionic Megacolon (Hirschsprung Disease) cells

since the neural crest cells migrate in a cephalad to caudad direction during development, the rectum is ALWAYS affected, but involvement spreading to the proximal colon varies from patient to patient and depends when migration ceased
-short-segment disease = rectum and sigmoid only (most cases)
-long-segment disease = rectum and entire colon (very rare)
-~1/5th of cases are intermediate to these


Congenital Anomalies: Congenital Aganglionic Megacolon (Hirschsprung Disease) clinical

failure to pass meconium in the immediate neonatal period, followed by obstructive constipation
-if only a few cm affected, build-up of pressure allows stool passage
major threats:
-superimposed enterocolitis with fluid/electrolyte imbalances
-perforation of the colon or appendix  peritonitis


Acquired Megacolon

occurs at any age and results from
Chagas disease (only acquired form due to loss of mural ganglia)
bowel obstruction (neoplasm or inflammatory stricture)
toxic megacolon complicating ulcerative colitis
functional psychosomatic disorder



diarrhea = increase in stool mass, stool frequency, and/or stool fluidity
-daily stool production in excess of 250 gm, containing 70-95% water
-over 14 L/day of fluid can be lost in severe cases
-usually accompanied with pain, urgency, perianal discomfort, incontinence
dysentery = low-volume, painful, bloody diarrhea mixed with mucus


Enterocolitis: Types of Diarrhea

Secretory diarrhea
Osmotic diarrhea
Exudative (invasive) diseases
Deranged motility



defined as increased fecal excretion of fat (steatorrhea) with concurrent deficiencies of vitamins, minerals, carbohydrates, and proteins


Clinical Features of Malabsorption

steatorrhea (the hallmark of malabsorption)
-passage of excessive amounts of greasy stools (bulky, frothy, yellow, or gray)
-a result of maldigestion of fats by pancreatic lipase, or malassimilation of fat in the small bowel
weight loss, diarrhea, and malnutrition


Consequences of Malabsorption

Alimentary tract: diarrhea, flatus, abdominal pain, borborygmi, weight loss, mucositis resulting from vitamin deficiencies; steatorrhea is the hallmark of malabsorption
Hematopoietic: anemia from deficiencies in iron, pyridoxine, vit. B12, folate; bleeding from vit. K deficiency
Musculoskeletal: osteopenia and tetany from calcium, magnesium, and vit. D deficiency
Endocrine: amenorrhea, impotence, infertility; hyperparathyroidism from protracted calcium and vit. D deficiency
Epidermis: purpura and petechiae from vit. K deficiency; edema from protein deficiency; dermatitis and hyperkeratosis from deficiencies in vit. A, zinc, niacin, and essential fatty acids
Nervous system: peripheral neuropathy from vit. B12 and A deficiencies


Laboratories for Stool Fat

Quantitative stool for fat
-THE test to use
-stool collected over 72 hour period
*positive test > 7 g of fat/24 hours
Qualitative stool for fat
-use stains (e.g., Sudan III) to identify fat in stool
-lacks sensitivity
Serum beta carotene
-precursor for fat-soluble vit. A
-decreased levels (<20 µg/dL) indicates malabsorption


Celiac Disease

aka, celiac sprue or gluten-sensitive enteropathy
chronic autoimmune disease producing diffuse enteritis, with marked atrophy or total loss of villi, that improves on withdrawal of wheat gliadins and related grain proteins from the diet


Celiac disease: Epidemiology

most often in Caucasians of European descent (rare to non-existent among native Africans, Chinese, Japanese)
almost all individuals share MHC class II HLA-DQ2 or HLA-DQ8 haplotype
heterogeneity in symptoms of celiac disease make recognition difficult; may be diagnosed as early as infancy or not until 40s or 50s
when diagnosed in adults, more likely women (2-3x)
association with other diseases (Down syndrome, Turner syndrome, type 1 diabetes); increased risk of having other autoimmune disorder


Celiac disease: Environmental Factors

most of what is known concerns factors influencing symptomatic celiac disease in infancy and childhood, and include:
-conditions that increase epithelial permeability to gliadin
*e.g., rotaviral infections
formula feeding
the timing of introduction of gluten to the infant diet


Celiac disease: Clinical Features

vary by age group (only most common presented):
children: diarrhea, abdominal distention, failure to thrive
older children: short stature, neurologic symptoms, anemia
adults: diarrhea, iron-deficiency anemia, osteoporosis


Celiac disease: Diagnosis

clinical documentation of malabsorption
characteristic intestinal lesions in biopsy:
-atrophy and loss of villi with an increased number of epithelial lymphocytes
-elongated, hyperplastic crypts


Inflammatory Bowel Disease

a set of chronic inflammatory conditions resulting from inappropriate and persistent activation of the mucosal immune system by normal gut flora
encompasses two disorders: Crohn disease (CD) and ulcerative colitis (UC)


IBD: Common Features

chronic and relapsing disease
immune in origin, but considered idiopathic because basis is unknown
-mainly an exaggerated CD4+ T-cell response
-although considered “autoimmune”, unknown if antigens are self or microbial


IBD epidemiology

more common in developed countries, usually in Caucasians, and specifically people of Northern European descent
most common in teenagers through mid-30s
no sex prediliction
develops in genetically susceptible individuals, but multigenic trait (almost all associations to date [e.g., NOD2] are not shared by a large percentage of patients)


IBD: extraintestinal inflammatory manifestations are common

primary sclerosing cholangitis (UC > CD)
erythema nodosum
iritis/uveitis (CD > UC)
pyoderma gangrenosum
sacroiliitis (due to association with HLA-B27)


IBD: Common Features

similar pathogenic abnormalities:
-there is a strong immune response against normal flora
*disease disappears in mouse models of IBD that have been made germ-free
there are defects in epithelial barrier function


IBD: Common Features

association with cancer (UC > CD)
highest risk in UC patients with pancolitis of >10 years duration
the distinction between CD and UC are dependent on clinical history, radiographic exam, lab findings, and biopsy… there is no single test that can distinguish between the two


UC vs CD

the colonic wall in Crohn's disease is considerably thicker than that in chronic ulcerative colitis.  This is for a number of reasons.  First of all, the inflammation in Crohn's disease is transmural; that is, it involves all coats of the colonic wall whereas the inflammation in ulcerative colitis is usually limited to the mucosa and submucosa.  The collections of chronic inflammatory cells in all levels of the colonic wall, as well as the inflammatory edema and subsequent fibrosis of the submucosa and serosa in Crohn's disease, account for the increased thickness of the colonic wall.  Linear ulcers are present in Crohn's disease as well as in ulcerative colitis, and you can see one in the center of the colonic mucosa in the Crohn's disease below.  Whereas the ulcers in ulcerative colitis are usually shallow, the ulcers in Crohn's disease are often fissuring, knife-like ulcers that penetrate deep into the colonic wall.  Pseudopolyps are much more common in ulcerative colitis than in Crohn's disease.



Perianal Fistula
"String Sign”


Malabsorption Syndromes: Whipple Disease

Incredibly rare (only ~1000 documented cases to date), but you need to know about it because of recent hype with culture of causal organism (Tropheryma whipplei) in 2000 followed by the sequencing of its genome
-most common in middle-aged men


Whipple Disease 2 stages

development of chronic, non-specific findings
-mainly arthritis and arthralgias
*intermittent, usually in large joints
much later development (avg. 6 years) of weight loss and diarrhea (due to malabsorption)
-development occurs more rapidly in patients undergoing immunosuppressive therapy for chronic arthritis, so this could be a big clue


Whipple Disease signs

pathognomonic neurologic sign: oculomasticatory myorhythmia
neurologic involvement indicates worse prognosis


Ischemic Bowel Disease

may affect small or large intestine, or both, depending on vessel affected
-occlusion of any of the major supply trunks (celiac, superior mesenteric [SMA], or inferior mesenteric arteries) produces more extensive infarctions
-small bowel more likely to have ischemic damage
-bc of anastomosing network of smaller vessels, occlusion may not result in infarction
ischemic injury is not only due to initial hypoxia, but more importantly, due to reperfusion
-review reperfusion injury if necessary


Ischemic Bowel Disease: Most Common Causes

thrombosis over an atherosclerotic plaque or embolization from left side of heart (50%)
-most commonly occludes SMA in both cases
nonocclusive ischemia (25%)
-hypotension secondary to heart failure, shock
mesenteric vein thrombosis (25%)
-thrombosis states, such as polycythemia vera or antiphospholipid syndrome


Ischemic Bowel Disease: Clinical Features

although uncommon, high death rate (50-75%)
tends to occur in elderly (when cardiac and vascular disease is greater)
findings in small bowel infarction:
*sudden and severe abdominal pain and tenderness
+sometimes with nausea, vomiting, bloody diarrhea or melena
*absent bowel sounds; abdominal wall rigidity later in course
-mucosal or mural
*nonspecific abdominal complaints, intermittent bloody diarrhea or guaiac-positive stool


Ischemic Bowel Disease: Ischemic Colitis

usually pain in splenic flexure shortly after eating
-patient may lose weight for fear of pain
barium study shows “thumb-printing” of colon due to edema of the mucosa


Vascular Disorders: Angiodysplasia

dilation of mucosal and submucosal blood vessels in the cecum and right colon
typically not seen until after age 40
pathogenesis speculative, but thought cecum (because largest diameter), is subject to increased wall stress that stretches the venules
-some individuals may be more predisposed than others, as there is an association with aortic stenosis and Meckel diverticulum
although not incredibly common lesions (<1% of population has them), they account for 20% of significant lower intestinal bleeds


Intestinal Obstruction

occurs at any level, but most common in small intestine due to smaller lumen
tumors account for 10-15% of small-bowel obstructions
-although there are many other causes, almost all other obstructions (80%) are due to one of four conditions: hernias, adhesions, volvulus, and intussusceptions



weakness or wall defects in peritoneal cavity allow pouch-like, serosa-lined sac of peritoneum to protrude
usual sites: anterior at the inguinal and femoral canals, umbilicus, and in surgical scars
main concern: external herniations



a segment of intestine telescopes into the immediately distal segment of bowel, then is propelled farther into the segment by peristalsis, pulling -mesentery along with it
mesenteric vessels can become trapped and infarct


Intussusception causes

infants and children: otherwise healthy, although association with rotavirus infection (enlarged Peyer’s patches or areas of inflammation serve as traction point)
adults: usually an intraluminal mass or tumor serves as traction



complete twisting of a loop of bowel about its mesenteric base, producing obstruction and infarction
occurs most often in large redundant loops of sigmoid, followed by cecum, small bowel, stomach, or (rarely) transverse colon



fibrous bridges between bowel segments or abdominal wall create closed loops through which other viscera can slide and become trapped (internal herniation)
risk factors: surgery, infections, endometriosis


Diverticular Disease

like diverticula of the esophagus, these are blind pouches lined by mucosa that communicate with the lumen of the gut
-true diverticula involve all three layers of the bowel wall
*congenital diverticula, such as Meckel diverticulum
-acquired diverticula have attenuated muscularis propria
*most common site: left colon, particularly sigmoid colon
*may also see in duodenum in context of PUD


Diverticular Disease: Pathogenesis 2 factors

focal weakness in wall
-in colon, between the taeniae coli where nerves and blood vessels penetrate the wall
increased intraluminal pressure
-exaggerated peristaltic contractions with spasmodic sequestration of bowel segments


Diverticular Disease: Clinical Features

only 20% of those affected will ever be symptomatic
-intermittent cramping, constipation, distention, continuous lower abdominal discomfort
-sensation of incompletely emptying the rectum
diverticula may become a site for bacterial overgrowth, and lead to Vitamin B12 or bile salt deficiency


Diverticular Disease: Complications

perforation with peritonitis
fistula formation
-most commonly, bowel to bladder (colovesicular)



inflammatory changes brought about by obstruction and/or perforation
-obstruction may result from stool trapped in the diverticulum, which subsequently hardens to form a fecalith
-dissects into pericolic fat
-may lead to fibrosis in and about colonic wall
symptoms similar to acute appendicitis (fever, rebound tenderness, constant pain) but in left lower quadrant


Tumors of the small and large intestine: Trends to Remember

the small intestine is an uncommon site for tumors (even though it makes up 75% of length of GI tract!)
unlike elsewhere in the body, adenomas in the small and large intestine are considered premalignant lesions
most cancers are adenocarcinomas and occur in the colon



any mass that protrudes into the lumen of the gut = polyp
-may be sessile or pedunculated (stalked)
polyps that form as result of inflammation or abnormal maturation/architecture are NOT neoplastic
polyps that arise from proliferation and dysplasia = adenomatous polyps
-true neoplasms and are precursors to cancer


Non-Neoplastic Tumors: Hyperplastic Polyps

usually multiple nipple-like protrusions on tops of mucosal folds in the rectosigmoid colon
probably due to decreased cell turnover and accumulation of mature cells
found incidentally in 50% of adults >60 yoa


Non-Neoplastic Tumors: Hamartomatous Polyps

malformations of the glands and stroma
although these are non-neoplastic lesions and do not progress to cancer, you do need to know about some exceptions to this rule:
-Juvenile polyposis syndrome
-Peutz-Jeghers syndrome
-Cowden syndrome
-Cronkhite-Canada syndrome


Peutz-Jeghers Syndrome

hamartomatous polyps + melanotic mucosal and cutaneous pigmentation around the lips, oral mucosa, face, genitalia, palms
-most polyps are large and pedunculated and in small bowel
common cause of mortality = intussusceptions
although polyps don’t have malignant potential, these patients have increased risk of developing cancer of pancreas, lung, ovary, and uterus
autosomal dominant (STK11) mutation


Tumors of Colon and Rectum: Adenomas

adenomas grow up from (tubular adenomas) or across (villous adenomas) the mucosa, or a mix of the two (tubulovillous adenomas)


Tumors of Colon and Rectum: Trends to Remember for Adenomas

the greater the % of villous architecture in the adenoma, the more likely it will progress to cancer
size and severity of dysplasia in an adenomatous polyp also predict cancer risk
tubular adenomas are more likely in the colon; villous adenomas are more likely in the rectum and rectosigmoid colon
villous adenomas are more likely to be symptomatic
-usually rectal bleeding
-hypoproteinemia or hypokalemia (secreting lots of mucus rich in protein and potassium)


Colorectal Carcinoma: Epidemiology

peak incidence: 60-80 yoa
no gender difference, except men slightly more likely to have rectal cancer
dietary factors play large role
-factors most implicated: diet that is high in calories, refined carbs, red meat, and low in fiber and micronutrients
use of aspirin and NSAIDS appears protective (COX-2 overexpressed in CC)


Colorectal Carcinoma: Morphology

most common in rectum and sigmoid colon (55%), followed by cecum/ascending colon (22%), transverse colon, and descending colon
different morphology depending on site


cecum/ascending colon

polypoid exophytic masses extending along one wall
obstruction uncommon
generally behave less aggressively and arise from microsatellite instability pathway (discussed below)


distal colon

“napkin ring” lesions (encircle and constrict the bowel)
generally more aggressive and arise from APC/β-catenin pathway


right vs left sided cancers

right-sided cancers:
-fatigue, weakness, Fe-deficiency anemia
left-sided cancers:
-occult bleeding, changes in bowel habit, crampy discomfort in lower left quadrant
don’t forget: Fe-deficiency anemia in older men in the US means GI cancer until proven otherwise!


Colorectal Carcinoma: Invasion and Spread

because lymphatic channels are largely absent in the colonic mucosa, even if there is invasion of the lamina propria, these are regarded as having little or no metastatic potential
spread by extension into adjacent structures
metastasize via lymphatics and blood vessels to (in order of preference): regional lymph nodes, liver, lungs, bone


Colorectal Carcinoma: Staging & Path

the most important prognostic indicator = stage, which is based on depth of tumor invasion
there are two pathogenetically distinct pathways:
-APC/β-catenin Pathway
-Microsatellite Instability Pathway


Colorectal Carcinoma: Familial Syndromes

underlie 1-3% of colorectal cancers
Two distinct types:
-Familial Adenomatous Polyposis (FAP) syndrome
*Hundreds to thousands of adenomatous polyps in the colon that will progress to cancer (100%)
-Hereditary Nonpolyposis Colorectal Cancer (HNPCC) syndrome
*Multiple adenomatous polyps (although cancer occurs, doesn’t arise from them) and extraintestinal cancers


Acute Appendicitis

inflammation of the appendix
-primarily occurs in adolescents and young adults, males slightly more often
-most commonly due to obstruction (fecalith, gallstone, tumor, etc) that leads to increased intraluminal pressure, causing collapse of draining veins and subsequent ischemia and bacterial proliferation


Acute Appendicitis clinical

“classic presentation”
periumbilical pain that later localizes to right lower quadrant
nausea and/or vomiting
abdominal tenderness
mild fever
elevation of peripheral WBC count up to 20,000 cells/µl


Disorders of the Appendix: Tumors

most common = carcinoid (rarely symptomatic)
-most frequently distal tip; soild bulbous swelling (2-3 cm)
-distant spread rare (even though local invasion may be present)

-dilated appendix filled with mucin
-due to obstruction, or a mucin-secreting adenoma or adenocarcinoma


Anal Fissures

are painful longitudinal defects in the mucosa that extend down from the dentate line
rectal pain on defecation (sharp, knife-like) associated with bleeding (blood coats the stool or appears on TP)
sentinel pile (fibroepithelial tag) located below the fissure


Disorders of Anal Canal: Tumors

Basaloid (cloacogenic) carcinoma
-most common type
-in transitional zone above the dentate line
-more common in women

Squamous cell carcinoma
-associated with HPV types 16 and 18
-most common in MSM