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Flashcards in Intestinal Pathology Deck (58):

Where does intestinal obstruction most commonly occur? Why?

- the small intestine
- because it is relatively narrow


What is Hirschprung Disease? What area of the intestines does it always affect? What morphology might result? What is it associated with?

- a congenital defect in colonic innervation (ganglion cells fail to migrate into the bowel wall here), resulting in intestinal obstruction due to non-functional intrinsic plexuses (inability to relax)
- ALWAYS affects the rectum (rectal constriction); may result in a dilated sigmoid colon as a result of the pressure build-up
- associated with Down syndrome


How do patients with Hirschprung Disease present?

- as neonates who are unable to pass meconium (the earliest stool of an infant) and who develop obstructive constipation
- upon DRE, patients will also have an empty rectal vault (because no feces is entering this area due to the contraction)


What is a hernia? What may permit it to happen in the abdomen?

- hernia: protrusion of peritoneum
- weakness/defect in the peritoneal wall may permit this to happen


Name three vascular disorders of the bowel.

- ischemic bowel disease, angiodysplasia, and hemorrhoids


What is the range of damage in Ischemic Bowel Disease? What is each usually due to? What are the 2 phases? How can patients present?

- damage can range from mucosal infarction (mucosa) --> mural infarction (mucosa + submucosa) --> transmural infarction (all 3 layers)
- the first two are usually due to hypoperfusion/hypotension; the third is due to acute vascular obstruction (of SMA)
- two phases: initial hypoxic phase + reperfusion injury phase (this one causes the most damage)
- severe abdominal pain, bloody diarrhea, and decreased bowel sounds


What are some predispositions to Hemorrhoids?

- constipation w/ heavy straining, pregnancy, and portal HTN


What are the top 3 causes of malabsorptive diarrhea in the US? What is another common cause?

- pancreatic insufficiency, celiac disease, Crohn disease
- irritable bowel syndrome (IBS)


What occurs in malabsorptive diarrhea? What is the hallmark sign?

- chronic diarrhea results from defective absorption of fats, vitamins, proteins, carbohydrates, electrolytes, and (therefore) water
- the hallmark sign is steatorrhea


What is Celiac Disease also known as? What is the pathology involved? What do we use to diagnose it?

- also known as gluten-sensitive enteropathy
- it involves a T-cell immune-mediated enteropathy triggered by the ingestion of gluten that results in the blunting of villi (mainly in the terminal duodenum or proximal jejunum), leading to malabsorption and steatorrhea
- diagnose with serology: antibodies against gliadin and tTG will be present (tTG antibodies are more specific for celiac than gliadin antibodies); in addition, serum levels may reflect micronutrient deficiencies due to malabsorption


What is Celiac Disease highly associated with? 10% of patients with Celiac Disease have what characteristic symptom/clinical sign? What are some other symptoms?

- complete association with HLA-DQ2 and HLA-DQ8; 95% of patients have the former, the remaining 5% have the latter
- dermatitis herpetiformis: a pruritic, blistering skin lesion due to IgA deposition at the tips of dermal papillae; also due to malabsorption of vit A
- weight loss, weakness, chronic diarrhea, anemia, osteoporosis, osteomalacia, hormonal disorders (all due to malabsorption)


What is Irritable Bowel Syndrome (IBS)? How do we diagnose it? Is it more common in women or men?

- chronic and relapsing abdominal pain, bloating, diarrhea, and constipation (changing bowel habits)
- the diagnosis depends on these clinical symptoms, and all other pathology must be ruled out
- (more common in females)


What intestinal disease is responsible for 1/2 of all worldwide deaths in children younger than 5?

- infectious enterocolitis


Name 5 common bacterial causes of Infectious Enterocolotis and 2 viral causes.

- bacteria: Cholera, Campylobacter enterocolitis, E. coli, Salmonellosis (and typhoid fever), Pseudomembranous Colitis
- viral: norovirus and rotavirus (we have a rotavirus vaccine, but no norovirus vaccine)


What organism is responsible for Cholera? How is it transmitted? What is the pathologic mechanism? What percentage of untreated patients will die? How do we treat it?

- Vibrio cholerae
- transmitted mainly via contaminated drinking water (poor sanitation, natural disasters, etc.)
- the cholera toxin causes Cl- release in the lumen, creating a large osmotic gradient that draws in water = diarrhea
- 50-70% of untreated cases are fatal!
- treating with simple fluid replacement save 99% of patients


What is the most common bacterial enteric pathogen of the developed world? What does it cause?

- Campylobacter jejuni --> causes Campylobacter enterocolitis
- patients usually present with water diarrhea (up to 50% of patients may present with dysentery)


There are two organisms responsible for Typhoid Fever - what are they? What is each associated with? What clinical sign may patients develop?

- Salmonella typhi and Salmonella paratyphi
- S. typhi: children and endemic areas
- S. paratyphi: developed world and travelers
- patients may develop "rose spots" (small, erythematous papular lesions on the chest and abdomen)


What is the most common organism involved with antibiotic-associated diarrhea? Which pathogen causes the most severe cases? What do we treat these patients with?

- most times, the pathogen is unable to be identified
- most severe: Clostridium dificile --> causes pseudomembranous colitis
- treat C. dificile with metronidazole (mild to moderate cases) or vancomycin (severe cases); use both for complicated cases (shock, ileus, toxic colon, etc.)


How does the rotavirus cause diarrhea?

- the virus destroys mature enterocytes, causing the villi surfaces to be replaced with immature secretory cells, leading to a loss of absorptive function = diarrhea


What is Inflammatory Bowel Disease (IBD)? What are the two major types?

- a chronic condition resulting from inappropriate mucosal immune activation
- two types: Chron disease and ulcerative colitis


Compare Chron Disease and Ulcerative Colitis.

- Chron disease: can involve any area of the GIT (usually the terminal ileum and spares the rectum); transmural; ulcers are deep and linear; characterized by skip lesions; cobblestone appearance; creeping fat; bowel wall thickening ("string sign"; presence of fibrosing strictures and granulomas
- ulcerative colitis: limited to the colon and rectum; extends only into the mucosa and submucosa; ulcers are superficial and broad; diffuse in nature; bloody diarrhea; loss of haustra ("lead pipe"); no strictures or granulomas


Chron Disease can occur anywhere along the GIT, but where is it most commonly found? As for Ulcerative Colitis, which part of the tract is always involved?

- Chron disease is most common in the terminal ileum, the ileocecal valve, and the cecum
- ulcerative colitis always involves the rectum, and may progress to some or all of the colon (full colon involvement = pancolitis)


What is Duodenal Atresia highly associated with? What are 3 of its clinical features?

- highly associated with Down Syndrome
- polyhydramnios (too much amniotic fluid because the baby is unable to digest the swallowed fluid = build up)
- bilious vomiting (bile is present at this point)
- "double-bubble" sign (distention of the stomach and of the duodenal blind loop w/ the pyloric sphincter in between yields a "double bubble")
- (meconium IS passed, but bowel movements do stop afterwards)


What is a diverticulum in the small bowel known as? Is it a true or false diverticulum? What is it due to?

- Meckel's diverticulum; it is a true diverticulum (out pouching of all 3 layers of the wall)
- it is due the persistence of the vitelline duct, which is how the midgut gets its nutrients during embryogenesis
- rule of 2's: 2% of population, 2 inches long, w/in 2 feet of the ileocecal valve, presents w/in first 2 years of life, may contain 2 types of epithelia (gastric or pancreatic)


What is a volvulus? What two things result from one? What is the most common site in a child? In an elderly patient? Whom is it more common in?

- a volvulus is a twisting of the bowel along its mesentery
- two things that result: infarction (due to the blood supply being cut off) and obstruction
- child: cecum; elderly patient: sigmoid colon
- classic patients: elderly; bedridden; constipation; patients on anti-cholinergics


Intussusception is the telescoping of a proximal segment of bowel into a distal segment and requires a "leading edge" - what is meant by a leading edge? How do patients typically present?

- it's basically something that is protruding from the wall, allowing the wall to be "grabbed" by the movements along the tract, resulting in the telescoping effect
- in children (most common), this is most commonly due to lymphoid hyperplasia
- in adults (rare), it is most commonly due to cancer/tumor
- patients are usually children with intermittent abdominal pain and "currant jelly" stool


Which genotypes are genetically predisposed to Celiac Disease?

- HLA-DQ2 (95%) and HLA-DQ8 (5%)


What is the pathogenic component of gluten? In what form is is presented to the APCs?

- gliadin is the pathogenic component
- it is presented in its deamidated form (it gets deamidated by tissue transglutaminase/tTG)


Celiac Disease is similar to Tropical Sprue - how can we tell them apart?

- celiac disease: doesn't respond to antibiotics and the damage is mainly in the duodenum
- tropical sprue: does respond to antibiotics (its due to an infectious agent), occurs only in tropical regions, and the damage is more in the jejunum and ileum


Damage to the jejunum results in decreased absorption of what nutrient? What about damage to the ileum?

- jejunum: folic acid
- ileum: vitamin B12 and bile salts (also some folic acid)
- (also, iron is mainly absorbed in the duodenum)


What does the diagnosis of Hirschprung Disease require?

- a rectal suction biopsy
- (normal biopsy is just of the mucosa, but we need to check for the absence of the ganglia, so suction is required to get a biopsy of the submucosa)


What happens in a colonic diverticula? Is it a true or false diverticulum? Where is it most commonly found?

- outpouchings of mucosa and submucosa through the muscularis externa/propria
- it is a false diverticulum
- most common location = the sigmoid colon (left colon)


3 possible complications of a colonic diverticula? How common is complicated diverticular disease?

- rectal bleeding from rupture of adjacent vasa recta, diverticulitis, fistula (w/ bladder, ureter, vagina, uterus, abdominal wall, etc.)
- complications are relatively uncommon; 90% of cases of diverticulosis are uncomplicated


What is hematochezia?

- the passage of fresh (bright red) blood through the anus
- associated with ruptured diverticula and angiodysplasia (among other things)


What is Angiodysplasia? Where does it most commonly occur?

- an acquired malformation of the mucosal and submucosal vessels due to high wall tension (occurs in elderly patients)
- usually occurs in the cecum/right colon
- hematochezia results


Dilated, thin-walled blood vessels in the nasopharynx and the GIT due to a genetic defect is known as:

- hereditary hemorrhagic telangiectasia
- (it's autosomal dominant)


What is the most common cause of ischemic colitis?

- atherosclerosis of the superior mesenteric artery
- (most commonly occurs at the splenic flexure because this is the last thing fed by the SMA)


Colonic polyps are raised protrusion of the colonic _______; what are the two most common types? Are either pre-cancerous?

- protrusions of the colonic mucosa
- most common types = hyperplastic polyps followed by adenomatous polyps; both are benign, but adenomatous polyps have the potential to become malignany


Describe the Adenoma-Carcinoma Sequence.

- this is the sequence involved in an adenomatous polyp becoming a carcinoma
- APC loss-of-function mutations result in an increased risk for polyp formation --> KRAS mutation results in polyp formation and an increased risk for mutations --> p53 loss-of-function and an increase in COX results in carcinoma


Which chromosome is the APC gene found on?

- it's a TSG on chromosome 5q
- APC = adenomatous polyposis coli


What can act as a prophylaxis against colorectal carcinoma? Why?

- aspirin; because it inhibits COX (and an increase in COX is associated with progression from adenomatous polyp to carcinoma)


What is FAP? In a patient with FAP, what prophylaxis is given to reduce the risk of developing colorectal carcinoma?

- familial adenomatous polyposis; an inherited genetic knockout of APC leading to 100's and 1000's of adenomatous polyps
- nearly all patients with FAP have their colons and rectums removed as prophylaxis (without this, nearly all patients develop carcinoma by 40)


Gardener Syndrome

- FAP + osteomas (benign tumors in the bone - usually the skull) + fibromatosis (non-neoplastic proliferation of fibroblasts)


Turcot Syndrome

- FAP + CNS tumors (medulla blastomas)


Peutz-Jeghers Syndrome

- hamartomatous polyps throughout the GIT + hyperpigmentation of the lips, oral mucosa, and genital skin
- results in an increased risk for colorectal, breast, and gynecologic cancers


What are some of the more common extraintestinal manifestations and complications of IBD?

- (these are all largely immune-mediated)
- skin: erythema nodosum (painful red nodes), pyoderma gangrenosum (large, gangrenous skin ulcers that are amazingly NOT painful)
- joints: seronegative arthritis, ankylosing spondylitis (inflammation of the spine and large joints)
- eyes: episcleritis (most common), uveitis
- CD: calcium oxalate nephrolithiasis (inflammation increases oxalate absorption), migratory polyarthritis; strictures, fistulas
- UC: primary sclerosing cholangitis; toxic megacolon, CRC


What is toxic megacolon? What disease is it a potential complication of?

- a dilated, paralyzed colon that can be infected, necrotic, and is prone to rupture
- a complication of ulcerative colitis (especially when attempting to treat with antispasmodics)


Which two types of tissue can be found in a Meckel diverticulum? What can each result in?

- gastric tissue and/or pancreatic tissue
- the gastric tissue may be acid-secreting and result in ulceration


What organism is responsible in Whipple disease? What is the pathophysiology? What symptoms can patients present with?

- Tropheryma whipplei gets ingested by macrophages, which are unable to completely clear them and become foamy macrophages that classically accumulate in the lamina propria
- this results in an inability to absorb fats (due to physical blockage), leading to fat malabsorption and steatorrhea
- accumulation in mainly small bowel (diarrhea), heart (Cardiac symptoms), joints (Arthralgias) and CNS (Neurologic symptoms)
- "foamy whipped cream in a C.A.N."


Which polyps have the greatest risk of becoming malignant?

- polyps larger than 2 cm
- polyps that are sessile (not pedunculated)
- polyps with a villous histology (rather than tubular)


Risk Factors for CRC

- FAP, Peutz-Jeghers, juvenile poplyposis syndrome, IBD (especially ulcerative colitis), HNPCC, tobacco use, large villous sessile adenomas


Where does colorectal cancer most likely hit? Compare CRC of the left colon to that of the right colon.

- rectosigmoid > ascending > descending
- left colon: tendency for obstruction, "napkin-ring" / "apple-core" lesion, associated with adenoma-carcinoma sequence and FAP
- right colon: tendency to bleed, iron deficiency anemia, associated with microsatellite instability and HNPCC


What can colorectal cancer rarely present as? Men with what clinical finding are deemed to have CRC until proven otherwise?

- can rarely present as Strep. bovis bacteremia and endocarditis (make sure to check these patients for CRC!)
- men (over 50) with iron deficiency anemia have CRC until proven otherwise


What are the two pathways of colorectal carcinoma development?

- 1) adenoma-carcinoma sequence (most common; 85%)
- 2) microsatellite instability pathway (15%): mutation in microsatellite segments suggests mutations in other genes due to mutations in DNA mismatch repair genes; associated with HNPCC


Hereditary Nonpolyposis Colorectal Carcinoma

- HNPCC (AKA Lynch syndrome)
- associated with microsatellite instability; increases risk for colorectal, ovarian, and endometrial carcinomas
- right sided CRC
- "nonpolyposis" = no polyp precursor to the carcinoma


What are the two broad causes of bowel obstruction? Which is more common? Which is more serious? How can we tell them apart clinically?

- 1) mechanical obstruction: less common; a medical emergency; increased bowel sounds, diffuse
- 2) adynamic ileus: more common; usually self-limiting; decreased/absent bowel sounds, more localized


What is the most common cause of small bowel obstruction? What about large bowel obstruction? What are other causes?

- SBO: adhesions after abdominal surgery; incarcerated hernias
- LBO: neoplasms; diverticular disease, sigmoid volvulus (rarely caused by adhesions and hernias)


What can ulcerative colitis present as? In terms of general IBD, what marker can we use to help rule in/rule out this disease?

- UC can present as acute severe colitis: at least 6 bloody stool motions a day + fever + inflammatory markers + anemia
- to help diagnose IBD, the patient's FC (fecal calprotectin) levels can be looked; calprotectin is a neutrophil protein and a patient with IBD will have elevated FC levels