Diseases of the Colon

Colitis associated Carcinoma vs Sporadic Carcinoma

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Colorectal Cancer

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Intestinal Malrotation

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Features that impact the malignant potential of adenomatous polyps

* * *Histological appearance (Villous = higher risk) *Size (<1cm)= small risk; >4 cm (40% risk)

Hereditary Hemorrhagic Telangiectasia

*AD *Also known as Osler-Weber-Rendu Syndrome *hyperemic vessels that *blanch with pressure* *Characterized by arteriovenous malformation (AMVs) in small vessels of the skin and mucous membranes *clinically presents as recurrent epistaxis *Often, there are mucocutaneous telangiectasias characteristically found on the lips, oral cavity, fingers, and nose. *HHT can also result in a catastrophic events such as sudden death, stroke, or pulmonary hemorrhage, depending on the location of AVMs. * Identified typically by the triad of telangiectasia, recurrent epistaxis, and a positive family history for the disorder.* *GI bleeding and Hematuria Characteristic Lip Telangiectases in the image

Hirschprung Disease

*AD *Congenital megacolon due to absence of ganglion cells in the myenteric and submucosal plexus **99% of cases are localized in the rectum* AD transmission *Majority of patients are male *Most cases are diagnosed after birth or early in childhood* *Defective relaxation and peristalsis of rectum and sigmoid colon* *Associated with mutations in RET gene *Clinical features are based on obstruction: -failure to pass meconium -empty rectal vault on distal rectal exam -massive dilation (megacolon) of bowel proximal to obstruction with risk for rupture Dx: Rectal *suction* biopsy reveals lack of ganglion cells; (suction is required to obtain tissue from the *submucosa* which contains the ganglion cells) *Tx: Resection of involved bowel; ganglion cells are present in the bowel proximal to the disease segment

What is the most common cause of colovesical fistulas? What are 2 presenting signs/symptoms of colovesical fistulas?

*Diverticulitis* is the most common cause of colovesical fistulas: communications between the lumen of the colon and the bladder. Colovesical fistulas can present with recurrent urinary tract infections and pneumaturia, or passage of air in the urine.

What effect does aspirin have on the progression of colorectal adenomas to carcinomas?

*Increased expression of COX has been linked to the progression of colorectal adenomas to carcinomas.* Aspirin can impede the progression from adenoma to carcinoma.

Ischemic Colitis

*Ischemia of the colon secondary to atherosclerosis of SMA or systemic hypotension *MCC is atherosclerosis of SMA* *tends to occur in older patients with concomitant cardiac or valvular disease. *most commonly involves splenic flexure* * *Barium enema shows "thumbprinting" of affected colon* * *seen in approximately 1-7% of patients following aortoiliac surgery* (you may hear that patient had repair on aortic/or mesenteric artery IMA) *Increased serum lactate* *increased WBC* May have decreased or absent bowel sounds Presents with *postprandial pain* and weight loss (w/ just ischemia) infarction results in *pain and bloody diarrhea*

Necrotizing Enterocolitis

*More common AND more severe in premature and low birth weight infants (due to decreased immunity) *Age of onset is inversely related with gestation age (later onset for preterm) **Frequently presents when formula feeding is initiated* *Most commonly identified organisms = E. Coli, Klebsiella Pneumo, C. Perfringens **Increased risk in patients with PDA treated with indomethacin (causes splanchic vasoconstriction => reduction in mesenteric blood flow) *Ileocecal region is most commonly involved *Variable damage to the intestinal tract, ranging from mucosal injury to full-thickness necrosis and perforation **Platelet counts may fall rapidly* *Presentation: Vomiting, feeding intolerance, abdominal distention, circulatory collapse/shock *Abdominal radiographs often demonstrate gas within the intestinal wall (pneumatosis intestinalis) or portal venous gas *Those who survive often develop fibrotic strictures due to healing of necrotic areas *Tx:

Angiodysplasia

*Tortuous dilation of venules in the mucosa and submucosa *Degenerative lesion of previously healthy blood vessels *More common in elderly *Extremely common cause of otherwise unexplained lower bowel bleeding (2nd MC after diverticulosis) *Most often involving the cecum or ascending colon (77%) (location of highest wall stress) **Associated with aortic valve disease (aortic stenosis)and often presents after aortic valve replacement *The link with Aortic stenosis is due to increased proteolysis of von Willebrand Factor due to high shear stress in the highly turbulent blood flow around the aortic valve *Lesions are multiple *Diagnosed/Identified by colonoscopy. Confirmed by angiography. *Colonoscopy reveals characteristic vascular spots which are reminiscent of spider nevi (cherry red fern-like pattern of blood vessels that appear to radiate from a central feeding vesse) *Most bleeding angiodysplasias will cease spontaneously. Often recur *Tx:

Irritable Bowel Syndrome

*chronic abdominal pain and altered bowel habits in the absence of any known physiological cause. * bloating, flatulence, and change in bowel habits (diarrhea or constipation) that *improves with defecation;* *classically seen in middle-aged females* Related to disturbed intestinal motility no identifiable pathologic changes *Increased dietary fiber may improve symptioms*

Describe the clinical presentation of Hirschprung Disease

- failure to pass meconium - Empty rectal vault on DRE - massive dilation of bowel proximal to obstruction with risk of rupture => (may lead to enterocolitis) - rectal suction biopsy reveals lack of ganglion cells Symptoms -yellow-green/bilious vomiting -failure to thrive -chronic constipation later in life Physical exam *abdominal distention

Symptoms of Diverticulosis

-usually asymptomatic (only about 20% develop symptoms) -painless rectal bleeding (hematochezia) -cramping, abdominal discomfort Most individuals with diverticular disease remain asymptomatic throughout their lives-the lesions are most often discovered incidentally. 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.

A 71-year-old Caucasian male presents to your office with bloody diarrhea and epigastric pain that occurs 30 minutes after eating. He has lost 15 pounds in 1 month, which he attributes to fear that the pain will return following a meal. He has a history of hyperlipidemia and myocardial infarction. Physical exam and esophagogastroduodenoscopy are unremarkable. What is the most likely cause of this patient's pain? 1. Atherosclerosis 2. Peptic ulcer disease 3. Crohn's disease 4. Amyloid deposition 5. Diverticulosis

1. Atherosclerosis This patient's presentation is consistent with ischemic colitis secondary to an atherosclerotic process. Ischemic colitis is caused by changes in systemic circulation, narrowing of blood vessels, or a blood clot that results in a loss of blood flow to the bowel. Most commonly, ischemic colitis occurs at the splenic flexure, a "watershed" area supplied by both the superior and inferior mesenteric arteries. Patients often have a history of hyperlipidemia and cardiovascular disease, and may present with mesenteric angina with meals, secondary to athersclerotic lesions of superior mesenteric artery.

A 65-year-old man with a past medical history of aortic stenosis presents to your office complaining of decreased energy and weakness for the past three years. Exam is notable for conjunctival and nail bed pallor, as well as a 3/5 crescendo-decrescendo murmur over the upper right sternal border. Laboratory workup reveals a hemoglobin of 9.1 g/dL. A colonoscopy is performed and reveals the finding on Figure A. What is the most likely source of this patient's anemia? 1. Vascular malformation 2. Cancerous growth 3. Ischemia of the bowel wall 4. Outpocketing of the mucosa 5. Inflammation of the mucosa

1. Vascular Malformtaion This patient presents with symptomatic anemia due to occult gastrointestinal bleeding caused by angiodysplasia, a vascular malformation of the GI tract. Angiodysplasia is a common condition due to vascular degeneration and, in those over the age of 60 years, is the second leading cause of lower gastrointestinal bleeding. They are most often located in either the cecum or ascending colon, but jejunal and ileal lesions are also seen. Angiodysplasias typically present with hematochezia and melena, with a frequency of 60% and 26%, respectively. Aortic stenosis is often seen in conjunction with angiosyplasias and this association is referred to as Heyde's syndrome.

What is the average time required for malignant transformation of an adenoma?

10 years

A 20-year-old Caucasian male presents with recurrent nosebleeds. Complete history reveals his father died in his 40's after an intracranial hemorrhage and two of his father's five siblings have also had recurrent nosebleeds. Which of the following would you expect to find in this patient? Topic Review Topic 1. Retinal hemangioblastoma 2. Renal cell carcinoma 3. Mucosal arteriovenous malformations 4. Vestibular schwannoma 5. Cafe-au-lait spots

3. Mucosal arteriovenous malformations The clinical picture of recurrent bleeding with a strong family history suggestive of an autosomal dominant inheritance pattern is consistent with Osler-Weber-Rendu syndrome. Otherwise known as hereditary hemorrhagic telangiectasia (HHT), Osler-Weber-Rendu is characterized by arteriovenous malformations (AVMs) of the skin and mucous membranes. HHT is an autosomal dominant disorder that results in abnormal blood vessel formation. Clinically, it presents often as recurrent epistaxis. Often, there are mucocutaneous telangiectasias characteristically found on the lips, oral cavity, fingers, and nose. HHT can also result in a catastrophic events such as sudden death, stroke, or pulmonary hemorrhage, depending on the location of AVMs. As discussed by Olitsky et al., the symptoms of HHT can often go unrecognized, even in patients with affected family members. The diagnosis of HHT is clinical, based on the presence of 3 of 4 criteria: epistaxis, telangiectasias, visceral AVMs, or family history of the disease.

A 75-year-old male is hospitalized for bloody diarrhea and abdominal pain after meals. Endoscopic work-up and CT scan lead the attending physician to diagnose ischemic colitis at the splenic flexure. Which of the following would most likely predispose this patient to ischemic colitis: 1. Increased splanchnic blood flow following a large meal 2. Essential hypertension 3. Obstruction of the abdominal aorta following surgery 4. Hyperreninemic hyperaldosteronism secondary to type II diabetes mellitus 5. Juxtaglomerular cell tumor

3. Obstruction of the abdominal aorta following surgery Ischemic colitis results from low perfusion of the bowel, most often from atherosclerosis of the superior mesenteric artery (SMA) or systemic hypotension. A partial obstruction of the abdominal aorta would reduce blood flow to the SMA and the inferior mesenteric artery (IMA) and could prompt ischemic colitis when physiologic demand increased post-prandially. Ischemic colitis is most common in elderly patients. It often occurs in watershed areas between the blood supply of two different arteries. Ischemic colitis most frequently occurs at the splenic fixture (the border area between the blood supply of the SMA and IMA) and the distal colon. Symptoms include abdominal pain, bloody diarrhea, and weight loss.

A 68-year-old male presents to the emergency department with left lower quadrant pain and fever for 1 day. Laboratory results show: WBC 14.8 cells/mm^3 Hb 12.0 g/dL Hct 38% Na 138 mEq/L K 4.0 mEq/L Creatinine 1.0 mg/dL Which of the following studies is contraindicated in the workup of this patient? 1. MRI 2. Ultrasound 3. Contrast CT 4. Colonoscopy 5. Abdominal radiograph

4. Colonoscopy This patient's presentation is consistent with acute diverticulitis. Colonoscopy is contraindicated in acute diverticulitis due to the risk of bowel perforation. CT is the preferred diagnostic modality. Acute diverticulitis typically presents with constipation or diarrhea along with LLQ tenderness. Age and low-fiber diet are the most important risk factors. CT is the preferred diagnostic imaging in suspected acute diverticulitis.

A three-week-old boy presents to general pediatrics clinic with constipation. His mother reports that he has not had a bowel movement for over 10 days and is quite concerned. On further examination, you discover that the boy is in the 5th percentile for weight. Physical examination shows a distended abdomen. Rectal examination shows an absence of stool in the rectal vault. A contrast enema reveals the following seen in Figure A. A rectal biopsy is performed (Figure B). Which of the following is true regarding this illness? 1. The disease more commonly affects females than males 2. Trisomy 18 is a risk factor for this disease 3. The vast majority of the cases of this illness affect the entire length of the bowel 4. MEN I is a risk factor for this disease 5. The mainstay of treatment is surgical

5 Treatment is surgical and if the disease affects the entire colon, it requires diverting ileostomy. Image A depicts the classic appearance of a transition point found in short segment Hirschsprung's disease.

A 5-day-old male is brought to your office by his mother. The infant is experiencing bilious vomiting, abdominal distension, and overall failure to thrive. A contrast enema shows a transition point at the transverse colon between dilated ascending colon and non-distended distal portion of the colon. Which of the following is the most likely etiology of this patient's disease? Topic Review Topic 1. Muscle hypertrophy 2. Mechanical bowel obstruction 3. CFTR gene mutation 4. Meiotic nondisjunction 5. Failure of neural crest cell migration

5. Failure of neural crest cell migration The patient presented in this question is suffering from Hirschprung's disease (HD). Hirschprung's is caused by failure of neural crest cell migration. In normal fetal development, neural crest cells migrate caudally through the intestine and form Meissner's and Auerbach's plexi in the wall of the bowel. *Hirschsprung's disease results when this migration fails. Without ganglion cells, the bowel cannot relax and consequently, the lumen remains narrow.* Passage of intestinal contents is compromised, resulting in abdominal distension, vomiting, and sometimes failure to pass meconium. The disease ranges in severity depending on how much of the colon is affected, but the rectum is always involved due to the direction of cell migration. The disease is treated with resection of aganglionic colon segments.

A premature neonate is found at birth to have a machinery-like heart murmur, and an echocardiogram is diagnostic for patent ductus arteriosus. The infant was not in heart failure when diagnosed, and he is successfully treated with indomethacin. Oral intake is started on the third day of life, and shortly thereafter the infant develops feeding intolerance and abdominal distention. By day 4 he is noted to have a rapidly dropping platelet count. X-rays show distended loops of bowel throughout the abdomen, and there is intramural air in some of the loops. He does not have air in the biliary tree or pneumoperitoneum. Which of the following is the most likely diagnosis? 1.Intussusception 2.Malrotation with Ladd bands 3.Meconium ileus 4.Mesenteric embolus 5.Necrotizing enterocolitis

5.Necrotizing enterocolitis *More common AND more severe in premature and low birth weight infants **Frequently presents when oral feeding is initiated* **Platelet counts may fall rapidly* **Increased risk in patients with PDA treated with indomethacin* *Abdominal radiographs often demonstrate gas within the intestinal wall (pneumatosis intestinalis)

Normally, 90% of babies pass their first meconium within ____ hours, and 99% within ___ hours

90% within 24 hours 99% within 48 hours

Adenomatous polyps involve mutations in what two genes?

Adenomatous polyps contain neoplastic proliferation of glands due to chromosomal instability pathway involving mutations in *APC and KRAS.*

A 77-year-old woman is brought to the emergency department after collapsing at home. Six hours ago, she had the sudden onset of massive bright red rectal bleeding. On arrival, her blood pressure is 90/60 mm Hg, and pulse is 120/min. Abdominal examination shows no abnormalities. Insertion of a nasogastric tube yields clear aspirate. Her hematocrit is 28%. Which of the following is the most likely diagnosis? A ) Colon cancer B ) Diverticulosis C ) Duodenal ulcer D ) Hemorrhoids E ) Inflammatory bowel disease

B ) Diverticulosis

A 68-year-old man comes to the physician because of a 1-month history of light-headedness and tightness in his chest with exertion. He adds that the pain is worse after arguing with his wife, and the symptoms resolve with rest. He has a past history of lower gastrointestinal bleeding; evaluation at that time was negative on upper endoscopy and colonoscopy. His temperature is 37°C (98.6°F), pulse is 85/min, respirations are 15/min, and blood pressure is 110/75 mm Hg. Physical examination shows no abnormalities. His hemoglobin concentration is 8.2 g/dL, and hematocrit is 24%. Test of the stool for occult blood is positive. An ECG shows no abnormalities. Repeat colonoscopy shows no abnormalities. Which of the following is the most likely cause of this patient's gastrointestinal symptoms? A) Adenocarcinoma of the colon B) Angiodysplasia C) Diverticulitis D) Peutz-Jeghers syndrome E) Ulcerative Colitis

B) Angiodysplasia

What procedures are contraindicated in the diagnosis of acute diverticulitis? What is the preferred diagnostic imaging?

Barium Enema and Colonoscopy are contraindicated in the setting of suspected acute diverticulitis due to an increased chance of perforation CT is the preferred diagnostic imaging in suspected acute diverticulitis.

What is hematochezia

Bright red stools, usually lower GI bleeding

A 55 year old woman presents with a history of chronic bloody stools. She denies massive amount of blood per rectum. Physical examination of the heart reveal a murmur that starts immediately after the first heart sound, gradually rises in pitch and gradually decreases before the second heart sound. She denies shortness of breath and abdominal pain. This combination of findings is most consistent with which of the following? A. Colon carcinoma B. Congestive heart failure C. Coagulation abnormality D. Rheumatic disease E. Ischemic colitis

C. Coagulation abnormality This patient has Heyde's syndrome, a condition involving aortic valve stenosis associated with gastrointestinal bleeding from colonic angiodysplasia. The latter causes painless bleeding that may manifest as melena(brownish, tarry, foul smelling stools), hematemesis (vomiting blood), or hematochezia (fresh blood in stools). Von willebrand factor is a protein involved in blood coagulation, as it binds factor VIII. In Heyde's syndrome, von Willebrand factor (vWF) is proteolysed due to high shear stress in the highly turbulent blood flow around the aortic valve. Angiodysplasia is a vascular anomaly characterized by dilated, tortuous submucosal blood vessels lined with endothelial cells, but no smooth muscle cells. Because the bleeding tend to occur in the veins, it is usually not massive, which would be the case for arterial bleed. Colonic angiodysplasia most often originate in the asending colon or cecum. vWF is most active in vascular beds with high shear stress, such as angiodysplasias, and deficiency of vWF increases the bleeding risk from such lesions. In mild cases, patients are treated with desmopressin, which promotes the release of vWF.

What is the most common location of Angiodysplasias? Why?

Cecum and ascending colon These are the locations of highest wall stress. (Recall that the cecum has the largest diameter of any colonic segment and according to law of laplace, inc diameter => inc wall stress)

Acquired Hirschsprung disease can occur in_______________ where amastigotes destroys ganglion cells.

Chagas Disease

Most common type of fistula formed due to diverticulitis? How does this present?

Colovesical Fistula (fistula between colon and bladder) presents with air or stool in the urine, or maybe even urine in the stool -recurrent UTIs

Complications of Diverticulosis?

Complications include diverticular bleeding (painless hematochezia) diverticulitis.

What are complications of an untreated colonic infarction?

Complications of ischemic colitis include: Bowel tissue death Perforation Bowel inflammation Bowel obstruction (strictures) Ischemic areas may progress to gangrene if the ischemia is sufficiently severe; if ischemia is milder, the areas may heal, often with strictures.

A 52 year old woman presents to her primary care physician complaining of vomiting and abdominal pain that occurs following meals. She notes that the symptoms are improved if she lies supine following meals. Imaging studies show that she has an obstruction of the duodenum proximal to the ligament of Treitz. What is the most likely cause of her symptoms? A) Compression of the duodenum by the inferior mesenteric artery B) Compression of the duodenum by the inferior mesenteric vein C) Compression of the duodenum by the superior mesenteric vein D) Compression of the duodenum by the superior mesenteric artery E) Pyloric stenosis F) Zenker diverticulum

D) Compression of the duodenum by the superior mesenteric artery Explanation: The superior mesenteric artery passes anterior to the distal duodenum, and can compress the duodenum, leading to obstruction, inability to eat, vomiting and weight loss. This is known as Superior Mesenteric Artery Syndrome (aka SMA syndrome). Patients are encouraged to lie supine following meals, since this moves the duodenum more posterior, thereby relieving the obstruction. Definitive treatment is surgery.

Diverticulosis and vasa recta

Diverticula tend to occur around the vasa recta. The vasa recta penetrates the muscle wall and creates an area of weakness. The associated vasa recta are then protected only by the overlying mucosa and are at risk for bleeding => hematochezia

What 3 diseases are associated with diverticulosis?

Diverticulosis has been associated with Marfan syndrome Ehlers-Danlos syndrome (connective tissue disordres may cause weakness in the colonic wall) Adult polycystic kidney disease (ADPKD)

What is the most common cause of hematochezia?

Diverticulosis often causes painless bleeding and is the most common cause of hematochezia.

Most common cause of lower GI tract bleeding in the US?

Diverticulosis/ Diverticular bleeding (upper GI tract bleeding is fairly uncommon) *(2nd most common cause is angiodysplasia)

Describe the pathophysiology of Hirschsprung Disease

Embryologically the enteric neurons arise from neural crest cells and must travel from the caudal hindbrain to the gut. In Hirschsprung disease, these ganglion cells fail to migrate to the bowel, especially the colon

Most feared complications of Hirschsprung Disease?

Enterocolitis and colonic rupture are the most serious complications associated with the disease and are the most common causes of Hirschsprung's-related mortality

Which two conditions are associated with hamartomatous polyps?

Hamartomatous polyps are associated with Peutz-Jeghers syndrome and juvenile polyposis.

What is the malignant potential of hamartomatous polyps?

Hamartomatous polyps are solitary *non-neoplastic lesions* that do not have a significant risk for malignant transformation.

If the question mentions a 6-day-old boy who has not had a stool since birth, who has a distented abdomen, and who has a dilated distal colon on abdominal radiograph, think?

Hirschsprung Disease

What are the 4 types of colonic polyps based on histology?

Histologically they are categorized into *Hyperplastic *Hamartomatous *Adenomatous *Serrated

What is the malignant potential of hyperplastic polyps? What area of the colon do they often occur?

Hyperplastic polyps are small *non-neoplastic polyps* usually located in the *rectosigmoid area*.

What is a non-pharmacologic treatment for irritable bowel syndrome?

IBS can be treated non-pharmacologically by an increased intake in fiber and avoidance of aggravating foods.

What structural/histological findings are associated with irritable bowel syndrome (IBS)?

IBS most commonly presents with no structural or histological findings.

Diverticulitis causes RLQ or LLQ Pain? What is Diverticulitis caused by? What are the complications of Diverticulitis?

LLQ pain ("left-sided appendicitis" usually caused by stool impacted (fecalith) in diverticulum sac abscess, fistula, obstruction (inflammatory stenosis), perforation => leading to peritonitis

What are the two watershed areas of the colon that are most susceptible to ischemic damage during hypotensive states?

MC: Splenic flexure (area of perfusion between IMA and SMA) 2nd MC: Rectosigmoid junction

Which has a higher malignant potential, villous or tubular adenomatous polyps?

Malignant potential in adenomatous polyps from highest to least: 1. *Villous* 2. Sessile and over 2 cm 3. Tubulovillous 4. Tubular "Villous is the Villain"

Colonic Diverticula

Outpouchings of mucosa and submucosa through the muscularis propria (false diverticulum) - related to wall stress - increased intraluminal pressure - associated with constipation *- low fiber diets* -seen in old adults Image shows a colonoscopic view of diverticulosis

Describe the appearance of the colonic mucosa on colonoscopy within the first 48 hours after ischemia?

Pale mucosa and petechial hemorrhages

HIrschsprung Disease is associated with mutations in which gene?

RET

Which part of the colon is most commonly affected in Hirschsprung Disease?

Recto-sigmoid colon

How do the appearance of

Right sided: Commonly appear as fungating exophytic masses Left sided: Commonly appear annular (napkin ring/apple core appearance)

How do the signs and symptoms of proximal (right-sided) colorectal cancer classically differ from distal (left-sided) colorectal cancer?

Right sided: More prone to bleed => iron deficiency anemia Left sided: More commonly produce obstructive symptoms (change in bowel habits (constipation), nausea/vomiting, bowel obstruction and abdominal distention)

Serrated polyps are benign, premalignant or malignant? What is the molecular pathogenesis behind serrated polyps?

Serrated polyps are *premalignant* via the CpG hypermethylation phenotype pathway with microsatellite instability and mutations in BRAF.

Most common location of Diverticula in the entire GI tract?

Sigmoid Colon seen in ~ 50% of people > 60 years

Diverticulosis vs Diverticulitis

Single = diverticulum Diverticulosis: presence of multiple acquired diverticula Diverticulitis: infection and macroperforation (a complication of diverticulosis) Diverticulosis = non-inflammatory condition (no fever, no increased WBC count --> just painless bleeding out of the ass. Diverticulitis = inflammation of a diverticulum --> fever, increased WBC, pain (bleeding is optional).

Adenoma-Carcinoma Sequence

The adenoma-carcinoma sequence describes the molecular progression from normal colonic mucosa to adenomatous polyp, and to carcinoma: *APC mutations decrease intercellular adhesion and increases proliferation *Normal mucosa => small adenomatous polyps **KRAS mutation allows for unregulated intracellular signal transduction and uncontrolled cell proliferation **Increase in size of an adenoma.* *p53 mutation (tumor suppressor gene) and increased expression of COX allows for increased tumorigenesis. **Malignant transformation of adenoma to carcinoma.* Mnemonic: *AK53*

What two factors determine the extent of damage in ischemic colitis?

The key features determining the extent of damage are severity and duration of compromise and vessels affected.

What are some risk factors that make one more susceptible to irritable bowel syndrome?

The pathophysiology of IBS is multifaceted. Risk factors include: History of childhood sexual abuse Domestic abuse in women Presence of stress, depression, or a personality disorder

What are the three degrees of bowel infarction?

There are 3 degrees of infarction: Mucosal infarction Mural (submucosal infarction) Transmural infarction

Are diverticulum more common on right or left side? Why?

Three times more common on left than the right Diverticulitis can occur on the right side but is much less common as most diverticuli are located in the descending and sigmoid colon

What is the goal of screening for colorectal polyps?

To remove adenomatous polyps before progression to carcinoma

Transition Zone and Hirschsprung Disease

Transition between the constricted aganglionic portion of the colon and the dilated "normal" portion

Treatment of Hirschsprung Disease

Treatment is purely surgical and involves resection of the affected bowel segments and there is no medical management for the disease.

20% of cases of sporadic colorectal cancer is due to what type of colonic polyp?

Up to 20% of cases of sporadic colorectal cancer are due to *serrated polyps.*

Angiodysplasia vs Diverticulosis

both due to high stress both lead to hematochezia Angiodysplasia = due to RLQ stress Diverticulosis = due to LLQ stress Angiodysplasia = typically low volume venous bleeding Diverticulosis = high volume arterial bleeding

A 55-year-old man with hypertension and end-stage renal disease requiring hemodialysis presents with 2 days of painless hematochezia. He reports similar episodes of bleeding in the past, which were attributed to angiodysplasia. He denies abdominal pain, nausea, vomiting, diarrhea, and fever. His vitals include HR of 90 beats per minute, BP of 145/95 mm Hg, RR of 18 breaths per minute, and temperature of 98°F. His abdomen is soft and nontender and his stool is grossly positive for blood. Which of the following statements are true regarding angiodysplasia? a. They are responsible for over 50% of acute lower GI bleeding. b. They are more common in younger patients. c. Angiography is the most sensitive method for identifying angiodysplasias. d. They are less common in patients with end-stage renal disease. e. The majority of angiodysplasias are located on the right side of the colon

e. The majority of angiodysplasias are located on the right side of the colon Angiodysplasia most commonly affects the cecum and the ascending colon

What laboratory values are helpful in the diagnosis of ischemic colitis?

elevated white blood cell count and serum lactate level

The adenoma-carcinoma sequence describes the molecular progression from __________ to ___________, and to ________

normal colonic mucosa => adenomatous polyp => carcinoma