IUHS Student-2-Student USMLE Step 1 Recall

                                                    GI Tract

                                        Small and Large Intestine

Volvulus of the Small Intestine

twisting of a segment of a bowel on its vascular mesentery, resulting in intestinal obstruction and infarction...

 Intussusception of the Small Intestine

telescoping of a proximal segment of the bowel into the distal segment...

 most commonly in infants and children...

 in adults it may be associated with a mass or tumor...

 presentation: intestinal obstruction, abdominal pain, and "currant-jelly" stools...

 complication: infarction of the intussuscepted segment...

 Atresia and Stenosis of the Small & Large Intestines

usually, projectile vomiting within the first week of life...

 congenital intestinal obstuction is an uncommon but dramatic lesion that may affect any level of the intestines...

 duodenal atresia is most common; the jejunum and ileum are equally involved and the colon virtually never...

 the obstruction may be complete (atresia) or incomplete (stenosis)...

 atresia may take the form of an imperforate mucosal diaphragm or a string like segment of bowel connecting intact proximal and distal intestine...

 stenosis is less common and is due to a narrowed intestinal segment or a diaphragm with a narrow central opening...

 single or multiple lesions appear to arise from developmental failure, intrauterine vascular accidents, or intussusceptions (telescoping of one intestinal segment within another) occurring after the intestine has developed...failure of the cloacal diaphragm to rupture leads to an imperforate anus...

Meckel Diverticulum

failure of involution of the vitelline dut (omphalomesenteric duct), which connects the lumen of the developing gut to the yolk sac, produces a meckel diverticulum...this solitary diverticulum lies on the antimesenteric side of the bowel, usually within 2 feet (85cm) of the ileocecal valve...

 this is a true diverticulum in that it contains all three layers of the normal bowel wall: mucosa, submucosa, and muscularis propria...

 meckel diverticula may take the form of only a small pouch or a blind segment having a lumen greater in diameter than that of the ileum and a length of up to 6cm...although the mucosal lining may be that of normal small intestine, heterotopic rests of gastric mucosa (or pancreatic tissue) are found in about one half of these anomalies...

 meckel diverticula are present in an estimated 2% of the normal population, but most remain asymptomatic or are discovered incidentally...when peptic ulceration occurs in the small intestinal mucosa adjacent to the gastric mucosa, mysterious intestinal bleeding or symptoms resembling those of an acute appendicitis may result...alternatively, presenting symptoms may be altered to intussusception, incarceration, or perforation...

Congenital Aganglionic Megacolon - Hirschsprung Disease

this disorder is characterized by the absence of ganglion cells in the large bowel, leading to functional obstruction and colonic dilatation proximal to the affected segment...

 most cases are sporadic, but familiar forms occur...it should be recalled that the intestinal neuronal plexus develops from neural crest cell that migrate into the bowel during development...

 studies of familial forms and mouse models have traced the aganlioinosis to heterogenous defects in genes regulating migration and survival of neuroblasts (endothelin 3 and its receptor), neurogenesis (glial cell - derived growth factor, GDNF), and receptor tyrosine kinase activity...

 failure of neural crest cells to migrate into the coloic wall...

 there is absence of ganglion cells in the muscle wall (myenteric auerbach plexus) and submucosa (meissner) of the affected segment...

 myenteric plexus is located in the muscularis externa...

 the rectum is always affected, with involvement of more proximal colon to variable extents...most cases involve the rectum and sigmoid only, with longer segments in a fifth of cases and rarely the entire colon...

 this is sometimes accompanied by thickening and hypertrophy of nonmyelinated nerve fibers...

 proximal to the aganglionic segment, the colon undergoes progressive dilation and hypertrophy, beginning with the descending colon...with time, the proximal innervated colon may become massively distended, sometimes achieving a diameter of 15-20 cm (megacolon)...

 males predominate 4:1...short segments aganglionosis with megacolon is more common in boys, whereas long affected segments are more common in girls...

 hirschsprung disease usually manifests itself in the immediate neonatal period by failure to pass meconium followed by obstructive constipation...

 in those instances when only a few centimeters of the rectum are affected, the build up of pressure may permit occasional passage of stools or even intermittent bouts of diarrhea...

 abdominal distention develops if a sufficiently large segment of colon is involved...

 Acquired Megacolon

acquired megacolon is a condition of any age and may result from

 (1) chagas disease, in which the trypanosomes directly invade the bowel wall to destroy the enteric plexuses;

 (2) organic obstrution of the bowel as by a neoplasm or inflammatory stricture;

 (3) toxic megacolon complicating ulcerative colitis or crohn disease; or

 (4) a functional psychosomatic disorder...

 except for chagas disease, in which inflammatory involvement of the ganglia is evident, the remaining forms of megacolon are not associated with any deficiency of mural ganglia...

 Celiac Sprue

celiac sprue is a relatively rare chronic disease, in which there is a characteristic mucosal lesion of the small intestine and impaired nutrient absorption, which improves on withdrawal of wheat gliadins and related grain proteins from the diet...

 this condition is known by a variety of names - gluten-sensitive enteropathy, nontropical sprue, celiac disease...

 celiac sprue occurs largely in whites and is rare or nonexistent among native africans, japanese, and chinese...

 Anti-endomysial antibody...

 involved the proximal small bowel...

 the fundamental disorder in celiac sprue is a sensitivity to gluten, which is the alcohol-soluble, water insoluble protein component (gliadin) of wheat and closely related grains (oat, barley, and rye)...

 cell mediated immunity appears to be important in the pathogenesis of the disease...the small intestinal mucosa, when exposed to gluten, accumulates intrepithelial cytotoxic T cells and large numbers of lamina propria T helper cells that are sensitized to gliadin...

 cytokine release by the T cells is thought to damage the intestinal enterocytes...

 although the genetic trends in this disease are variable, a specific HLA DQ alpha/beta heterodimer appears to confer susceptibility through its interaction with gliadin...90-95% of patients express the DQw2 histocompatibility antigen on chromosome 6, particularly a DQ alpha/beta heterodimer, and familial clustering is well known in this disease...

 DR3...

 b/c the DQ locus is lined with HLA B8, as many as 80% of patients express this latter antigen as welll...an intriguing hypothesis invokes cross-reactivity of gliadin with a fragment of the E1b protein of type 12 adenovirus, raising the possibility that celiac disease results, in part, from environmental exposure to this virus...

 Anti-endomysial antibody...

 the mucosa appears flat or scallped or may be visually normal...biopsy specimens demonstrate a diffuse enteritis, with marked atrophy or total loss of villi...the surface epithelium shows vacuolar degeneration, loss of the microvillus brush border, and an increased number of intraepithelial lymphocytes...

 the crypts exhibit increased mitotic activity and are elongated, hyperplastic, and turtuous, so that the overall mucosal thickness remains the same...

 the lamina propria has an overall increase in plasma cells, lymphocytes, macrophages, eosinophils, and mast cells...

 the symptoms of celiac sprue vary tremendously from patient to patient...symptomatic diarrhea and failure to thrive may be evident during infancy, yet adults may seek attention only in their forties...the classic presentation includes diarrhea, flatulence, weight loss, and fatigue...

 extraintestinal manifestation of malabsorption may overshadow the intestinal symptoms..

 detection of circulating antigliadin or anti-endomesial antibodies stongly favors the diagnosis...

 definitive diagnosis rests on (1) clinical documentation of malabsorption, (2) demonstration of the intestinal lesion by small bowel biopsy, and (3) unequivocal improvement in both symptoms and mucosal histology of gluten withdrawal from the diet...if there is doubt about the diagnosis, gluten challenge followed by rebiospy has been advocted...

 patients with celiac sprue are prone to the development of

dermatitis herpetiformis, the dermatologic diagnosis in this patient...

 most patients with celiac sprue who adhere to a gluten free diet remain well indefinetly and ultimately die of unrelated causes...there is a long term risk of malignant disease, although it may be les than a two fold increase over the usual rate...more than half of these malignancies are intestinal lymphomas, including a disproportionately high number of T-cell lymphomas, other malignancies include GI and breast carcinomas...

 Whipple Disease

whipple disease is a rare, systemic condition , which may involve any organ of the body but principally affects the intestine, CNS, and joints...

 the casual organism is a gram positive actinomycete, now named tropheryma whippelii, on the basis of recent molecular phylogenetic analysis...

 the hallmark of whipple disease is a small intestinal mucosa laden with distended macrophages in the lamina propria - the macrophages contain periodic acid schiff (PAS) - positive granules and rod shapaed bacilli by electron microscopy...

 in untreated cases, bacilli can be seen in neutrophils, the extracellular space of the lamina propria, and even in epithelial cells...expansion of the villi imparts a shaggy gross appearance to the intestinal mucosal surface; edema of the mucosa thickens the intestinal wall...

accompanying these changes is involvement of mesenteric lymph nodes by the same process and lymphatic dilation, suggesting lymphatic obstruction...

 bacilli-laden macrophages also can be found in the synovial membranes of affected joints, the brain, cardiac valves, and elsewhere...at each of these sites, inflammation is essentially absent...

 whipple disease is principally encountered in whites in their thirties to forties, with a strong male predominace of 10:1...

 it usually presents as a form of malabsorption with diarrhea and weight loss, sometimes of years duration...

 atypical presentations, with polyarthritis, obscure central nervous system complaints, and other symptom complexes, are common...

 lymphadenopathy and hyperpigmentation are present in more than half of patients...

 the diagnosis rests on light microscopic changes of PAS positive macrophages, which contain rod shaped organism by electron microscopy...

 response to antibiotic therapy is usually prompt, although some patients have a protracted course...

 Abetalipoproteinemia

inability to synthesize apolipoprotien B is a rare inborn error of metablism that is transmitted by autosomal recessive inheritance...

 it is characterized by a defect in the synthesis and export of lipoproteins from intestinal mucosal cells...

 free fatty acids and monoglycerides resulting from hydrolysis of dietary fat enter the absorptive epithelial cells and are re-esterfied in the normal fashion but cannot be assembled into chylomicrons...

 as a consequence, triglycerides are stored within the cells, creating lipid vacuolation, which is readily evident under the light microscope, particularly with special fat stains...concomitantly, there is complete absence in plasma of all lipoproteins containing apolipoprotien B (chylomicrons, very low density lipoproteins, and low-density lipoproteins)...

 the failure to absorb certain essential fatty acids leads to systemic abnormalities, including lipid membrane abnormalities, readily evident in the characteristic acanthocytic erythrocytes (burr cells)...

 the disease becomes manifest in infancey and is dominated by failure to thrive, diarrhea, and steatorrhea...

 Crohn Disease (Regional Enteritis)

crohn disease is characterized pathologically by (1) sharply delimited and typically transmural involvement of the bowel by an inflammatory process with mucosal damage, (2) the presence of noncaseating granulomas, and (3) fissuring with formation of fistulas...

 there is gross involvement of the small intestine alone in about 40% of cases, of small intestine and colon in 30%, and of the colon alone in about 30%...crohn disease may involve the duodenum, stomach, esophagus, and even mouth, but these sites are distinctly uncommon...in diseased bowel segments, the serosa is granular and dull gray, and often the mesenteric fat wraps around the bowel surface (creeping fat)...the mesentary of the involved segment is also thickened, edematous, and sometimes fibrotic...

 the intestinal wall is rubbery and thick, the result of edema, inflammation, fibrosis, and hypertrophy of the muscularis propria...

 as a result, the lumen is also always narrowed; in the small intestine, this is evidenced on x-ray as the string sign, a thin stream of barium passing through the diseased segment...strictures may occur in the colon but are usually less severe...a classic feature of crohn disease is the sharp demarcation of diseased bowel segments from adjacent uninvolved bowel...when multiple bowel segments are involved, the intervening bowel is essentially normal (skip lesions)...

 focal mucosal ulcers resembling canker sores (aphthous ulcers), edema, and loss of the normal mucosal texture...with progressive disease, mucosal ulcers coalesce into long, serpentine linear ulcers, which tend to be oriented along the axis of the bowel...

 as the intervening mucosa tend to be relatively spared, the mucosa acquires a coarsely textured, cobblestone appearance...narrow fissures develop between the folds of the mucosa, often penetrating deeply through the bowel wall and leading to bowel adhesions...

 further extension of fissures leads to fistual or sinus tract formation, to an adherent viscus, to the outside skin, or into a blind cavity...free perforation or localized abscesses may also develop....

 colon revelas characteristic "string sign"...

 Mucosal Inflammation - the earliest histologic lesion in crohn disease appears to be focal neutrophilic infiltration into the epithelial layer, particularly overlying mucosal lymphoid aggregates...as the disease becomes more established, neutrophils infiltrate isolated crypts; when a sufficient number of neutrophils have traversed the epithelium of a crypt (both in the small and large intestine), a crypt abscess is formed, usually with ultimate destruction of the crypt...

 Chronic Mucosal Damage - the hallmark of inflammatory bowel disease, both crohn disease and ulcerative colitis, is chronic mucosal damage...architectural distortion is manifest in the small intestine as variable villus blunting; in the colon, crypts exhibit irregularity and branching...crypt destruction leads to progressive atrophy, particularly in the colon...the mucosa may undergo metaplasia; this may take the form of gastric antral type glands (pyloric metaplasia) or as the development of paneth cells in the distal colon, where they are normally absent (paneth cell metaplasia)...

 Ulceration - ulceration may be superficial, may undermine adjacent mucosa in a lateral fashion, or may penetrate deeply into underlying tissue layers...there is often an abrupt transition between ulcerated and adjacent normal mucosa...

 Transmural Inflammation Affecting all Layers - chronic inflammatory cells suffuse the affected mucosa and, to a lesser extent, all underlying tissue layers...lymphoid aggregates are usually scattered throughout the bowel wall..

 Noncaseating Granulomas - present in about half of cases, sarcoid like granulomas may be present in all tissue layers, both  within areas of active disease and in uninvolved regions of the bowel...granulomas have been documented throughout the alimentary tract, from mouth to rectum, in patients with crohn disease limited to one bowel segment...conversely the absence of granulomas does not preclude the diagnosis of crohn disease...

 Other Mural Changes - in diseased segments, the muscularis mucosa usually exhibits reduplication, thickening , and irregularity...fibrosis of the submucosa, muscularis propria, and mucosa eventually leads to stricture formation...

in about one fifth of patients, the onset is more abrupt, with acute right-lower-quadrant pain, fever, and diarrhea sometimes suggesting acute appendicitis or an acute bowel perforation...

during the lengthy, chronic disease, complication may arise form fibrosing strictures, particularly of the terminal ileum, and fistulas to other loops of bowel, the urinary bladder, vagina, or perianal skin or into a peritoneal abscess...

 extensive involvement of the small bowel, including the terminal ileum, may cause marked loss of albumin (protein losing enteropathy), generalized malabsorption, specific malabsorption of vit B12 (with consequential pernicious anemia) or malabsorption of bile salts, leading to steatorrhea...

 hepatic primary sclerosing cholangitis occurs, but the association is not as strong as in ulcerative colitis...

 Ulcerative Colitis

ulcerative colitis is an inflammatory disease limited to the colon and affecting only the mucosa and submucosa except in the most severe cases...

 in contrast to crohn disease, ulcerative colitis is a systemic disorder associated in some patients with migratory polyarthritis, sacroiliitis, akylosing spondylitis, uveitis, hepatic involvement (

precholangitis and primary sclerosing cholangitis), and skin lesions...

pseudopolyps are inflammatory polyps found in ulcerative colitis and not in chrons disease...

ulcerative colitis involves the rectum and extends proximally in a retrograde fashion to involve the entire colon (pancolitis) in the more severe cases...it is a disease of continuity, and skip lesions such as occur in crohn disease are no found...in 10% of patients with severe pancolitis, the distal ileum may develop mild mucosal inflammation (backwash ileitis)...the appendix may be involved with both crohn disease and ulcerative colitis...

 in the course of colonic involvement with ulcerative colitis, the mucosa may exhibit slight reddening and granularity with friability and easy bleeding...with fully developed severe, active inflammation, there may be extensive, broadbased ulceration of the mucosa in the distal colon or throughout its length...

 isolated islands of regenerating mucosa bulge upward to create pseudopolyps...as with crohn disease, the ulcers of ulcerative colitis are frequently aligned along the axis of the colon, but rarely do they replicate the linear serpentine ulcers of crohn disease, with indolent chronic disease or with healing of active disease, progressive mucosal atrophy leads to a flattened and attenuated mucosal surface...

 in contrast to crohn disease, mural thickening does not occur in ulcerative colitis, and the serosal surface is usually completely normal...

 the mucosal features of ulcerative colitis are similar to those of colonic crohn disease, with mucosal inflammation, chronic mucosal damage, and ulceration (friable mucosa)...

 a key feature of ulcerative colitis is that the mucosal damage is continuous from the rectum and extending proximally...in crohn disease, mucosal damge in the colon may be continuous but is just as likely to exhibit skip areas....

 ulcerative colitis typically presents as a relapsing disorder by attacks of bloody mucoid diarrhea that may persist for days, weeks, or months, then subside, only to recur after an asymptomatic interval of months to years to even decades...

 in the fortunate patient, the first attack is the last...at the other end of the spectrum, the explosive initial attack may lead to such serious bleeding and fluid and electrolyte imbalance as to constitute a medical emergency...in most patients, bloody diarrhea containing stringy mucus, accompanied by lower abdominal pain and cramps usually relieved by defecation, is the first manifestation of the disease...in a small number of patients, constipation may appear paradoxically, owing to disruption of normal peristalsis...

 associated with rheumatology diseases such as ankylosing spondylysis (HLA-B27)...

often the first attack is preceded by  stressful period in the patient's life...spontaneously, or more often after appropriate therapy, these symptoms abate in the course of days to weeks...flare ups, when they do occur, may be precipitated by emotional or physical stress and rarely concurrent intraluminal growth of enterotoxin forming C. difficile...sudden cessation of bowel function with toxic dilation (toxic megacolon) rarely develops with severe acute attacks; perforation is a potentially lethal event...

 Elevated serum alkaline phosphatase...

the most feared long term complication of ulcerative colitis is cancer...there is a tendency for dysplasia to arise in multiple site, and the underlying inflammatory disease may mask the symptoms and signs of carcinoma...

 historically the risk of caner is highest in patients with pancolitis of 10 or more years duration, in whom it exceeds by 20-30 fold risk in that control population, equivalent to an absolute risk of colorectal cancer 35 years after diagnosis of 30%...

 Ischemic Bowel Disease

ischemic lesions may be restricted to the small or large intestine or may affect both, depending on the particular vessel affected...acute occlusion of one of the three major supply trunks of the intestines - celiac, superior and inferior mesenteric arteries - may lead to infarction of several meters of intestine...

insidious loss of one vessel may be without effect, owing to the risk anastomotic interconnections...

lesions within the end arteries, which penetrate the gut wall, produce small, focal ischemic lesions...

the severity of injury ranges from (1) transmural infarction of the gut, involving all visceral layers; to (2) mural infarction of the mucosa and submucosa; to (3) mucosal infarction, if the lesion extends no deeper than the muscularis mucosae...

almost always, transmural infarction implies mechanical compromise of the major mesenteric blood vessels...mucosal or mural infarction more often results from hypoperfusion, either acute or chronic...

splenic flexure is most common...

Angiodysplasia

less than 1% in the adult population, they account for 20% of significant lower intestinal bleeding; intestinal hemorrhage may be chronic and intermittent or acute and massive...

most angiodysplasias span the mucosa and submucosa and contain a small amount of smooth muscle, suggesting that they are ectatic nests of preesisting veins, venules, and capillaries...

the vascular channels may be separated from the intestinal lumen by only the vascular wall and a layer of attenuated epithelial cells, explaining the propensity toward bleeding...

the pathogenesis of angiodysplasia remains speculative but is attributed to mechanical factors operative in the colonic wall...normal distention and contraction may intermittently occlude the submucosal veins that penetrate through the muscle wall...this occlusion then leads to focal dilation and tortuosity of overlying submucosal and mucosal vessels...accoring to LaPlace's Law, tension in the wall of a cylinder is a function of intraluminal pressure and diameter...b/c the cecum has the widest diameter of the colon, it develops the greatest wall tension, perhaps explaining the distribution of these lesions...vascular degenerative changes related to aging may also play some role...

Hemorrhoids

most often, long term heroin addicts develop hemorrhoids...

hemorrhoids are variceal dilations of the anal and perianal venous plexuses...these extremely common lesions affect about 5% of the general population and develop secondary to persistently elevated venous pressure within the hemorrhoidal plexus...

the most frequent predisposing influences are constipation with straining at stool and the venous stasis of pregnancy...except for pregnanct women, they are rarely encountered in persons under the age of 30...more rarely but much more importantly, hemorrhoids may reflect collateral anastomotic channels that develop as a result of portal hypertension...

Diverticular Disease

often due to a lack of dietary fiber...

a diverticulum is a blind pouch leading off the alimentary tract, lined by mucosa that communicates with the lumen of the gut...congenital diverticula have all three layers of the bowel wall; the prototype is Meckel diverticulum...

virtually, all other diverticula are acquired and either lack or have an attenuated muscularis propria...acquired diverticula may occur in the esophagus, stomach, and duodenum; duodenal diverticula occur in more than 1% of adults, possible reflecting defects from healed peptic ulcer disease...

multiple diverticula of the jejunum and ileum are rare, occurring in the setting of abnormalities in the muscle wall or myenteric plexus...

unless otherwise specified, however, diverticular disease refers to acquired outpouching of the colonic mucosa and submucosa...colonic diverticula are rare in persons under age 30, but in western adult populations over the age of 60 the prevalence approaches 50%...they generally occur multiply and are referred to as diverticulosis...they are much less frequent in nonindustrialized tropical countries and in japan...

There can be ectopic tissue in the Meckel's diverticulum, most likely pancreas, but sometimes gastric mucosa, which can cause ulceration and bleeding.

histologically, colonic diverticula have a thin wall composed of a flattened or atrophic mucosa, compressed submucosa, and attenuated or totally absent muscularis propria...

it has been proposed that diets low in fiber reduce stool bulk which, in turn. leads to increased peristaltic activity, particularly in the sigmoid colon...exaggerated contractions sequester segments of bowel (segmentation); this deranged motility can lead to symptoms in the absence of inflammation...

only about 20% of those affected ever develop manifestations: intermittent cramping or continuous lower abdominal discomfort, constipation, distention, and a sensation of never being able to empty the rectum completely...

patients sometimes experience

alternating constipation and diarrhea...occasionally, there may be minimal chronic or intermittent blood loss or, rarely, massive hemorrhages...

longitudinal studies have shown that diverticula can regress early in their development or may become more numerous and prominent with time...whether a high fiber diet prevents such progression or protects against superimposed diverticulitis is still unclear...

relatively few patients require surgical intervention for obstructive or inflammatory complications...

fever, leukocytosis, and  left sided abdominal pain...with refereal to the back...

Meckel Diverticulum

congenital small bowel diverticulum...

remnant of vitelline (omphalomesenteric) duct...

rule of 2s -> 2% of the population, 2 ft from the ileocecal valve, 2cm in length, 2 years old or younger at the time of diagnosis, 2% of carcinoid tumors occur ina meckel diverticulum...

most are asymptomatic...may contain rests of ectopic gastric mucosa and present with intestinal bleeding...

most common complication is bleeding or inflammed diverticulum leading to diverticulitis...

Adenocarcinoma of the Small Intestine

the large majority of small intestinal adenocarcinomas occur in the duodenum and jejunum, with a presenting age usually between 40-70 years of age...these tumors grow in a napkin ring encircling pattern or as polypoid fungating masses, in a manner similar to colonic cancers...

tumors in the duodenum, particularly involving the ampulla of vater, may present with obstructive jaundice early in their course...more typically, cramping pain, nausea, vomiting, and weight loss are the presenting signs and symptoms, resulting from intestinal obstruction...as with adenomas, fatigue from occult blood loss may be the only sign...rarely the tumorous mass is a lead point for intussusception...

Non-Neoplastic Polyps of the Colon and Rectum

non-neoplastic polyps (mostly hyperplastic) represent about 90% of all epithelial polyps in the large intestine and are found in more than half of all persons age 60 years or older...often have "saw tooth" appearance or "dewdrop" appearance...

inflammatory (pseudo) polyps, representing islands of inflamed regenerating mucosa surrounded by ulceration, are seen in patients with longstanding inflammatory bowel disease (ulcerative colitis or crohn disease)...

lymphoid polyps are an essentially normal variant of the mucosal bumps containing intramucosal lymphoid tissue...three forms of non-neoplastic polyps deserve separate mention...

most often in sigmoid colon...

Adenomas of the Colon and Rectum

adenomatous polyps are segregated into three subtypes on the basis of the epithelial architecture: tubular adenomas, tubular glands; villous adenomas: villous projections; tubulovillous adenoma: a mixture of the previous two...

there is considerable overlap among these categories, so by convention, tubular adenomas exhibit greater than 75% tubular architecture, villous adenomas contain greater than 50% villous architecture, and tubulovillous adenomas contain 25-50% villous architecture...tubular adenomas are by far the most common; about 5-10% of adenomas are tubulovillous, and only 1% are villous...

all adenomas lesions arise as the result of epithelial proliferative dysplasia, which may range from mild to so severe as to constitute carcinoma in situ...furthermore, there is strong evidence that adenomas are a precursor lesion for invasive colorectal adenocarcinomas...

the period required for an adenoma to double in size is estimated at about 10 years...thus, they are slow growing and must certainly have been present for many years before detection...the following concepts are pertinent: most tubular adenomas are small and pedunculated; conversely, most pedunculated polyps are tubular...villous adenomas tend to be large and sessile, and sessile polyps usually exhibit villous features...

Tubular Adenomas

microsatellite instability...

most (90%) are found in the colon, but they can occur in the stomach and small intestine...in about half of the instances, they occur singly; in the remainder, two or more lesions are distributed at random...

crowded, tubular, atypical colonic-type glands...the polyp is covered with normal colonic epithelium...

the smallest tubular adenomas are smooth contoured and sessile; larger ones tend to be coarsely lobulated and have slender stalks...

uncommonly, they exceed 2.5cm in diameter...histologically the stalk is composed of fibromuscular tissue and prominent blood vessels (derived from the submucosa), and it is usually covered by normal, non-neoplastic mucosa...adenomatous epithelium, however, may extend down the stalk and into adjacent regions of the mucosa, particularly in the stomach...

Villous and Tubulovillous Adenomas

Villous Adenomas - elongated colonic glands lined by crowded columnar cells with hyperchromatic nuclei. This process is above the basement membrane...villous adenomas are the larger and more ominous of the epithelial polyps...they tend to occur in older persons, most commonly in the rectum and rectosigmoid, but they may be located elsewhere...

they generally are sessile, up to 10cm in diameter, velvety or cauliflower-like masses projecting 1-3cm above the surrounding normal mucosa...

their histology is that of frondlike villiform extensions of the mucosa, covered by dysplastic, somewhat disordered columnar epithelium...

all degrees of dysplasia may be encountered...when invasive carcinoma occurs, there is no stalk as a buffer zone, and invasion is directly into the wall of the colon (submucosa or deeper)...

Tubulovillous Adenomas - tubulovillous adenomas are typically intermediate between the tubular and villous lesions in terms of their frequency of having a stalk or being sessile, their size, and the general level of dysplasia found in such lesions...the risk of harboring in situ or invasive carcinoma generally correlates with the proportion of the lesion that is villous...

Colorectal Carcinoma

virtually 98% of all cancers in the large intestine are adenocarcinomas...

they represent one of the prime challenges to the medical profession b/c they arise in polyps and prodcue symptoms relatively early and at a stage generally curable by resection...

with an estimated 134,000 new cases per year and about 55,000 deaths, this disease acounts for 10% of all cancer related deaths in the U.S...

The glandular epithelial surface of the colon gives rise to adenocarcinomas...

the dietary factors receiving the most attention as predisposing to a higher incidence of cancer are (1) excess energy intake relative to requirements, (2) a low content of unabsorbably vegetable fiber, (3) a corresponding high content of refined carbohydrates, (4) intake of red meat, and (5) decreased intake of protective micronutrients...

colorectal cancers remain asymptomatic for years; symptoms develop insidiously and frequently have been present for months, sometimes years, before diagnosis...

cecal and right colonic cancers are most often called to clinical attention by the appearance of fatigue, weakness, and iron deficiency anemia...these bulky lesions bleed readily and may be discovered at an early stage, provided that the colon is examined thoroughly radiographically and during colonoscopy...

left sided lesions come to attention by producing occult bleeding, changes in bowel habit, or crampy left lower quadrant discomfort...

in theory, the chance for early discovery and successful removal should be greater with lesions on the left side because these patients usually have prominant disturbances in bowel function, such as melena, diarrhea, and constipation...

cancer of the rectum and sigmoid, however, tend to be more infiltrative at the time of diagnosis than proximal lesions and therefore have a somewhat poorer prognosis...it is a clinical maxim that iron deficiency anemia in an older man means GI cancer until proven otherwise...

Carcinoid Tumors

neuroendocine tumor often producing serotonin...

locations: appendix (most common) and terminal ileum...

terminal ileum is associated with carcinoid sydrome but not appendix b/c the tumor will not be big enough...

metastasis to the liver may result in carcinoid heart disease...

carcinoid syndrome: diarrhea, cutaneous flushing, bronchospasm and wheezing, and fibrosis...

diagnosis is via urinary 5-HIAA (5-hydroxyindoleacetic acid)...

all carcinoid tumors are malignant...with low potential...

Familial Adenomatous Polyposis (FAP)

FAP exhibits innumerable adenomatous polyps and has a frequency of progression to colon adenocarcinoma approaching 100%...autosomal dominant condition...

FAP is the archetype of the adenomatous polyposis syndromes...the genetic defect is in the APC gene on chromosome 5q21...patients typically develop 500-2500 colonic adenomas that carpet the mucosal surface...occasionally, as few as 150 polyps are present; a minimum of 100 polyps is necessary for a diagnosis of FAP...

multiple adenomas may also be present elsewhere in the alimentary tract, including the region of polyps are tubular adenomas; occasional polyps may have villous features...some patients already have cancer of the colon or rectum at the time of diagnosis...

cancer preventative measures include a prophylactic colectomy as soon as possible and the early detection of the disease in siblings and first degree relatives at risk...

Turcot Syndrome

turcot syndrome is a rare variant marked by the combination of adenomatous colonic polyposis and

tumors of the central nervous system, mostly gliomas...

the average age of onset of polyps in each of these adenomatous polyp syndromes is the teens to twenties, followed by cancer within 10-15 years unless surgical resections interrupt the natural progression...

turcot tumors go around your head...

Hereditary Nonpolyposis Colorectal Cancer (HNPCC) - Lynch Syndrome

HNPCC is an autosomal dominant familial syndrome (extensively described by henry lynch, hence the alternative name of lynch syndrome) characterized by an increased risk of colorectal cancer and extraintestinal cancer, particularly of the endometrium in women...

adenomas do occur in low numbers but considerably earlier than in the general adult population...

the colonic malignancies often are multple and are not always asociated with preesisitng adenomas...

the genetic defect involves

mismatch repair genes...

accounts for 1-3% of colon cancer...

Mismatch repair Defects...

a gene involving this DNA repair defect has been found and maps to chromosome 2p...this gene, called hMSH2 (human mutS homologue 2), is homologous to the bacterial gene mutS, which is responsible for strand specific mismatch repair...