GI Path Flashcards
Common signs and symptoms of GI problems
Pain
Malabsorption
Bleeding
-Pay attention to the pattern of bleeding for clues to origin
Usual locations for severe upper GI bleeding (in descending order of frequency)
Duodenum -duodenal ulcer Stomach -gastric ulcer Esophagus -esophageal varices Note that all of these are above the ligament of Treitz. They make up 90% of major GI bleeds.
Signs of bleed
hematemesis
melenemesis
melena
Hemoglobin converted to hematin by stomach acid
Hematochezia
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)
Dysphagia
-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
Odynophagia
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
-polyhydramnios
-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
Achalasia
progressive dilation of the esophagus above the lower esophageal sphincter (LES), due to
- aperistalsis
- 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
Diverticula
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
complications:
-pneumomediastinum
*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
GERD
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
Endoscopy
Manometry
-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)
symptoms
-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
SCC
Older African-American men Developing countries Dietary & environmental link-strong no association w barrets anywhere in esophagus involved- middle & upper most common
Adenocarcinoma
Older Caucasian men More common in the US No dietary & environmental factors Association w Barretts Lower esophagus involved
Signs and Symptoms of Stomach Disease
Hematemesis -most commonly due to peptic ulcer disease (PUD) -usually as melenemisis Melena 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
males>females
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
Gastritis
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
Morphology:
-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)
- hypergastrinemia
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
- stomach
- 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
polyp
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
Epidemiology:
-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)
pathogenesis:
->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
pathogenesis:
-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
Diarrhea
-sign of infection, malabsorption, or osmotic diarrhea
-if bloody, consider infarction, volvulus, dysentery
Anemia
-sign of malabsorption (iron, folate, Vit. B12)
Signs and Symptoms of Large Bowel Disease
Diarrhea -sign of infection, laxative abuse, inflammatory bowel disease -if bloody, consider infarction or dysentery Dysentery -bloody diarrhea with mucus -infection Tenesmus -painful, ineffective straining at stool -common in ulcerative colitis Iron Deficiency Anemia -consider polyps, colorectal cancer Hematochezia -sigmoid diverticulosis (most common) -angiodysplasia
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
pathogenesis:
-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
Enterocolitis
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 Malabsorption
Malabsorption
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.
CD
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:
-transmural:
*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
Hernias
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
Intussusception
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
Volvulus
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
Adhesions
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) hematochezia diverticulitis
Diverticulitis
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
polyps
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
epidemiology:
-primarily occurs in adolescents and young adults, males slightly more often
pathogenesis:
-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)
mucocele
- 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
