Small and Large Intestines Flashcards
(106 cards)
1
Q
Meckel diverticulum
A
Outpouching of all three layers of the bowel wall (true diverticulum) on antimesenteric side of the small bowel (small intestine)
2
Q
Meckel diverticulum - Cause
A
Arises due to failure of the vitelline duct to involute
Vitelline duct = embryological remnant through which fetus received nutrients from yolk sac
3
Q
Meckel diverticulum - Rule of 2’s
A
- Seen in 2% of the population (most common congenital anomaly of the GI tract)
- 2 inches long and located in the small bowel within 2 feet of the ileocecal valve
- Can present during the first 2 years of life
4
Q
Meckel diverticulum - Presentation
A
ASx (most cases) OR with bleeding (due to heterotopic gastric mucosa b/c it produces acid), volvulus, intussusception, or obstruction (mimics appendicitis)
5
Q
Hirschsprung disease (AKA congenital aganglionic megacolon)
A
Defective relaxation and peristalsis of rectum and distal sigmoid colon
6
Q
Hirschsprung disease - Associated w/
A
Down syndrome
7
Q
Congenital defect of Hirschsprung disease is
A
Congenital failure of ganglion cells (neural crest-derived) to descend into myenteric (Auerbach) plexus (b/w IC and OL muscle of muscularis propria/externa; regulates motility) and submucosal (Meissner) plexus (b/w submucosa and IC muscle; regulates blood flow, secretions, and absorption)
MORE SPECIFICALLY = premature arrest of migration of vagal NC cells in the hindgut –> total lack of parasympathetic ganglion in these ENS plexuses
8
Q
Clinical features of Hirschsprung disease
A
Based on obstruction due to functional loss of peristalsis:
- Failure to pass meconium
- Full rectal vault on digital rectal exam
- Massive dilatation (megacolon) of bowel proximal to obstruction with risk for rupture
- Constipation, emesis or diarrhea after newborn period
- Must be recognized before becomes fatal
9
Q
Dx of Hirschsprung disease
A
Rectal suction biopsy reveals lack of ganglion cells
10
Q
Tx of Hirschsprung disease
A
Resection of the involved bowel; ganglion cells are present in the bowel proximal to the diseased segment.
11
Q
Genetics of Hirschsprung disease
A
- Incomplete penetrance and sex-linked (preferential and more penetrance for males)
- Heterozygous loss-of-function mutations in receptor tyrosine kinase RET at 10q11.2 = majority of familial cases and ~ 15% of sporadic cases
- Long segment (from IAS to proximal splenic flexure) = AD w/low penetrance
- Short segment (from IAS to distal to splenic flexure; most common form) = AR or multigenic inheritance
- Inheritance seems to be multifactorial
12
Q
Necrotizing enterocolitis (NEC) - most common in
A
Premature infants
Associated w/ enteral feeding ad high perinatal mortality
13
Q
NEC - Cause
A
No specific bacterial pathogen, but ultimately bacteria enter mucosa and cause inflammation, mucosal necrosis –> sepsis and shock –> intestinal perforation and peritonitis
Important inflammatory mediator = platelet activating factor (PAF) –> ↑ mucosal permeability by ↑ enterocyte apoptosis and compromising intercellular tight junctions
14
Q
NEC - Clinical features (4)
A
- Onset of bloody stools, abdominal distention, and development of circulatory collapse
- X ray = gas within the intestinal wall (pneumatosis intestinalis)
- Involves terminal ileum, cecum, and right colon
- Involved segment = distended, friable, and congested, or gangrenous
15
Q
NEC - microscopic features
A
Mucosal or transmural coagulative necrosis, ulceration, bacterial colonization, and submucosal gas bubbles
16
Q
NEC - prognosis/tx
A
If detected early –> resection of necrotic segments of bowel; survivors have post-NEC strictures from fibrosis caused by the healing process.
17
Q
Hernias - Definition
A
Weakness/defect in wall of the peritoneal cavity –> protrusion of a serosa-lined pouch of peritoneum (hernia sac)
18
Q
Acquired hernias
A
Most commonly occur anteriorly, via the inguinal and femoral canals or umbilicus, or at sites of surgical scars
19
Q
Concerns w/hernias
A
Visceral protrusion (external herniation) a problem b/c bowel loops/omentum may protrude and can become entrapped –> impaired venous drainage –> stasis and edema –> permanent entrapment (incarceration) –> arterial and venous compromise (strangulation) –> infarction
20
Q
Adhesions - Definition
A
Inflammation of some kind (e.g. infection, peritonitis, surgery) or congenital (rare) –> development of adhesions (fibrous bridges) b/w bowel segments, abdominal wall, and operative sites
21
Q
Adhesions - Problems
A
Can cause closed loops through which other viscera may slide and become entrapped (internal herniation) –> obstruction and strangulation (like in external hernias)
22
Q
Volvulus - Definition
A
Twisting of bowel along its mesentery –> most commonly in sigmoid colon (elderly) and cecum (young adults)
23
Q
Volvulus - Problems
A
Results in obstruction and disruption of the blood supply with infarction
24
Q
Intussusception - Definition
A
Telescoping of proximal segment of bowel forward into distal segment
25
Intussusception - Problems
Telescoped segment is pulled forward by peristalsis, resulting in obstruction and disruption of blood supply with infarction --> gives current jelly stools
26
Intussusception - Associated w/
A leading edge (focus of traction)
| In adults, the most common cause is tumor.
27
Ischemic Bowel Disease (IsBD) - locations
Can occur at any level of gut, but small bowel is highly susceptible to ischemic injury.
28
IsBD - Transmural vs. Mucosal infarction
1. Transmural infarction occurs with thrombosis/embolism of the superior
mesenteric artery or thrombosis of the mesenteric vein.
2. Mucosal infarction occurs with marked hypotension/hypoperfusion (e.g. shock)
29
IsBD - Intestinal responses to ischemia (2 phases)
1. Initial hypoxic injury
2. Reperfusion injury (greatest damage) --> ROS, neutrophil infiltration, complement proteins + TNF --> can trigger multiorgan failure
30
How anatomy contributes to IsBD
Intestinal segments at the end of their respective arterial supplies are particularly susceptible to ischemia
1. E.g. splenic flexure (where the superior and inferior mesenteric arterial circulations terminate) --> watershed area of SMAJ due to atherosclerosis (most common cause)
2. E.g. sigmoid colon and rectum (where inferior mesenteric, pudendal, and iliac arterial circulations end)
31
Why the epithelium more vulnerable to ischemic injury?
Intestinal capillaries run in glands (from crypt to surface before making a hairpin turn at the surface to empty into the post-capillary venules) so this means that crypts are protected (which contain epithelial stem cells) and receive oxygenated blood while the epithelium is vulnerable to ischemic injury
32
IsBD - Clinical features
Older w/coexisting cardiac or vascular disease
Acute = sudden, severe abdominal pain and tenderness, w/sometimes N/V, bloody diarrhea and melena
Prolonged = absence of bowel sounds and boardlike rigidity of abdominal wall b/c muscular spasm
33
IsBD is missed/delayed b/c
Sx overlap w/acute appendicitis, perforated ulcer, and acute cholecystitis
Chronic IsBD looks like IBD w/episodes of bloody diarrhea interspersed w/periods of healing
34
IBD has high/low morality
High b/c these infarctions can become more extensive if vascular supply not restored via correction or collateral blood
35
Angiodysplasia - definition
Malformed submucosal and mucosal blood vessels in cecum or R colon
36
Angiodysplasia - Clinical features
Rupture classically presents as hematochezia in an older adult (60's)
Pathogenesis uncertain, may be due to vascular changes due to age + cecum has largest diameter and highest wall tension)
Occurs in <1% of adult pop/n, but causes 20% of major lower GI bleeds
37
Hemorrhoids (aka anal varices) - Development
Develop 2nd to persistently elevated venous pressure w/in the hemorrhoidal plexus
38
Hemorrhoids - Predisposing factors
Straining at stool b/c constipation and venous stasis of pregnancy
Can develope b/c of portal HTN
39
Hemorrhoids - Pathogenesis
Like esophageal varices, but less serious
Anal and perianal venous plexuses dilate and form collaterals that connect portal and caval venous systems --> less venous HTN.
40
Hemorrhoids - Clinical features
1. Present w/ pain and rectal bleeding (bright red blood on TP)
2. Not an emergency
3. Rare for under 30
4. 5% of pop/n
41
Hemorrhoids - Tx
Sclerotherapy, rubber band ligation, infrared coagulation, or hemorrhoidectomy.
42
Hemorrhoids - Morphology
1. External hemorrhoids = collateral vessels w/in inferior hemorrhoidal plexus are located below the anorectal line
2. Internal hemorrhoids = dilation of superior hemorrhoidal plexus w/in distal rectum
3. Histologically = thin-walled, dilated, submucosal vessels that protrude beneath the anal or rectal mucosa (and thus can become inflamed/thrombosed/recanalized)
43
Malabsorption - Main Sx
1. Presents most commonly as chronic diarrhea (from nutrient malabsorption + excessive intestinal secretion)
2. Characterized by defective absorption of fats, fat- and water-soluble vitamins, proteins, carbohydrates, electrolytes and minerals, and water
44
Classifications of diarrhea (4)
1. Secretory (isotonic stool, persists w/fasting)
2. Osmotic (w/lactase deficiency, concentrated, abates w/fasting)
3. Malabsorptive (steatorrhea, abates w/fasting)
4. Exudative (w/inflammatory disease, purulent/bloody stools, persists w/fasting)
45
Other Sx of Malabsorption (7)
1. Flatus
2. Abdominal pain
3. Anemia and mucositis due to pyridoxine (B6), folate, or vit B12 deficiency
4. Bleeding, due to vitamin K deficiency
5. Osteopenia and tetany due to calcium, magnesium, or vitamin D deficiencies
6. Peripheral neuropathy due to vitamin A or B12 deficiencies
7, If chronic --> weight loss, anorexia, abdominal distention, borborygmi, and muscle wasting
46
Most common chronic malabsorptive disorders (3)
1. Pancreatic insufficiency
2. Celiac disease
3. Crohn disease
47
Stages of nutrient absorption (4)
1. Intraluminal digestion = proteins, carbohydrates, and fats are broken down into forms suitable for absorption
2. Terminal digestion = hydrolysis of carbohydrates and peptides by disaccharidases and peptidases, respectively, in the brush border of the small intestinal mucosa
3. Transepithelial transport = nutrients, fluid, and electrolytes are transported across and processed within the small intestinal epithelium
4. Lymphatic transport of absorbed lipid
48
What is steatorrhea?
Excess fecal fat and bulky, frothy, greasy, yellow or clay-colored stools
49
What is dysentery?
Painful, bloody, small volume diarrhea
50
Lactase (disaccharidase) deficiency - cause
Decreased function of the lactase enzyme found in the brush border of enterocytes
--> Lactase normally breaks down lactose into glucose and galactose.
51
Lactase (disaccharidase) deficiency - presentation
Abdominal distension and diarrhea upon consumption of milk products; undigested lactose is osmotically active.
Congential form presents w/explosive diarrhea w/watery/frothy stools + abdominal distension
52
Lactase (disaccharidase) deficiency - Congenital vs. acquired
1. Congenital (rare autosomal recessive disorder)
2. Acquired (often develops in late childhood, seen in Native Americans, AA's, and Chinese) --> note that temporary deficiency is seen after small bowel infection b/c lactase is highly susceptible to injury
N
53
Tropical sprue - Cause
Damage to small bowel villi due to an unknown organism resulting in malabsorption
54
Tropical sprue - Presentation
1. Like celiac disease except occurs in tropical regions (e.g. Caribbean) and arises after infectious diarrhea and responds to antibiotics
2. Damage most prominent in jejunum and ileum (2nd vit B12 or folate deficiency may ensue; duodenum less involved)
55
Abetalipoproteinemia - Cause
1. Rare AR deficiency of apolipoprotein B (although gene is OK) and caused by mutation in microsomal triglyceride transfer protein (MTP) that catalyzes transport of triglycerides, cholesterol esters, and phospholipids
2. MTP-deficient enterocytes can’t export lipoproteins and free fatty acids --> monoglycerides cannot be assembled into chylomicrons and triglycerides accumulate within the epithelial cells --> liquid vacuolization
56
Abetalipoproteinemia - Presents
1. In infancy w/a failure to thrive, diarrhea, and steatorrhea
2. Can’t absorb essential FA’s --> deficiency of fat-soluble vitamins + lipid membrane defects
3. Blood smears --> acanthocytic red cells (burr cells)
4. Absent plasma VLDL and LDL. (require Apolipoprotein B-100)
57
Celiac disease (celiac sprue; gluten-sensitive enteropathy) - Cause
Immune-mediated damage of small bowel villi (LOSS OF VILLI) due to gluten exposure; associated with HLA-DQ2 and DQ8
58
Process of gluten absorption and how this is messed up in Celiac Disease
1. Gluten is present in wheat and grains; its most pathogenic component is gliadin b/c it is resistant to degradation by gastric, pancreatic, and s.i. proteases
2. Gliadin can induce expression of IL-15 (--> activation/proliferation of CD8+ T cells) and NKG2D (NK cell marker) so that T cells become cytotoxic and kill enterocytes w/surface MIC-A (HLA-Class I that show w/stress).
2. Once absorbed by epithelium, gliadin is deamidated by tissue transglutaminase (tTG).
3. Deamidated gliadin is then presented by antigen presenting cells via MHC class II to CD4+ T cells
4. Helper T cells mediate tissue damage via cytokine secretion
59
Celiac disease - Presentation (5)
1. Children classically present with abdominal distension, diarrhea, and failure to
thrive.
2. Adults (b/w 30-60) classically present with chronic diarrhea and bloating.
3. Detected in >W b/c of increased iron demand from menstruation so enhances effects of impaired absorption
4. Small, herpes-like vesicles may arise on skin (dermatitis herpetiformis) due to IgA deposition on lips of dermal papillae
5. Complications = small bowel carcinoma and T cell lymphoma (present during refractory disease despite diet)
60
Celiac Disease - Lab findings
1. IgA antibodies against endomysium, tTG, or gliadin; IgG antibodies are also
present and are useful for diagnosis in individuals with IgA deficiency (increased incidence of IgA deficiency is seen in celiac disease)
61
Celiac Disease - Biopsy findings
1. Duodenal biopsy reveals flattening of villi, hyperplasia of crypts, and increased
intraepithelial lymphocytes --> Might confuse with colon if not told that biopsy came from duodenum or jejunum.
2. Damage is most prominent in the
duodenum; jejunum and ileum are less involved.
62
Celiac Disease - Tx
Resolve with gluten-free diet
| On withdrawal of gluten, the inflammation dies out and the mucosa is able to reconstitute the villi.
63
Pseudomembranous colitis (AKA antibiotic-associated colitis or antibiotic-associated diarrhea) - Transmission/Geography/Reservoir
```
Geography = Developing countries
Reservoir = Humans, hospitals
Transmission = Antibiotics (usually 3rd generation cephalosporins) allow emergence b/c disrupt normal colonic flora --> allowing bacterial overgrowth
```
64
Pseudomembranous colitis - Epidemiology
Advanced age, hospitalized, immunosuppressed, antibiotic-treated (afterwards, can be caused by C. difficile, Salmonella, C. perfringens type A, or Staph aureus), usually caused by Clostridium difficile)
65
Pseudomembranous colitis - C. difficile
C. difficile have toxins that cause ribosylation of small GTPases (e.g. Rho) --> disruption of epithelial cytoskeleton, tight junction barrier loss, cytokine release, and apoptosis
--> 30% of hospitalized adults have C. diff colonization, but most are free of disease
66
Pseudomembranous colitis - Morphology
Pseudomembrane = layer of inflammatory cells + debris at sites of colonic mucosal injury Microscopically from crypt damage --> mucopurulent exudate eruption like a volcano, which form the pseudomembrane
67
Pseudomembranous colitis - Sx
Watery diarrhea, fever, leukocytosis, abdominal pain, cramps, Hypoalbuminemia, dehydration
Complications = relapse
68
Pseudomembranous colitis - Dx and Tx
```
Dx = C. difficile toxin + histopathology
Tx = Metronidazole or vancomycin
```
69
Whipple disease - Cause
Systemic tissue damage characterized by distended pale macrophages loaded with Tropheryma whippelii organisms in lamina propria, which are positive for PAS, NOT acid-fast, gram positive actinomycete
70
Whipple disease - Site of involvement
Classic site of involvement is the small bowel lamina propria
71
Whipple disease - Sx
Uncertain how mxn --> fat malabsorption, steatorrhea, and wt loss
Other common sites of involvement include synovium of joints (arthritis), cardiac valves, lymph nodes, and CNS.
72
Amebiasis (Entamoeba histolytica, a protozoan) - Transmission, Geography, and Epidemiology
```
Epidemiology = E. histolytica cysts that are resistant to gastric acid so they can colonize epithelial surface of colon (esp. cecum and ascending colon) and release trophozoites
Transmission = fecal-oral
Geography = developing countries (e.g. India)
```
73
Amebiasis - Cause
Causes dysentery (once amebae attaches to colonic epithelium --> apoptosis --> crypt invasion --> neutrophils --> tissue damage --> flask-shaped ulcer w/narrow neck and broad base) and liver abscess (parasites have penetrated splanchnic vessels), which persist
74
Amebiasis - Histology
Looks like macrophages so difficult
75
Amebiasis - Sx
Abdominal pain, bloody diarrhea, or weight loss
| More rare: NEC and megacolon --> significant mortality
76
Amebiasis - Tx
Metronidazole (inhibits enzyme pyruvate oxidoreductase that is required for fermentation)
77
Giardiasis (Giardia lamblia, G. duodenalis, G. intestinalis, are flagellated protozoans) - Transmission/Cause/Epidemiology
```
Cause = Most common pathogenic parasitic infection in humans
Transmission = Fecally contaminated water or food or fecal-oral route
Epidemiology = B/c cysts are resistant to chlorine, Giardia are endemic in unfiltered public water supplies (e.g. rural streams, seen in campers) or swallowed when swimming in contaminated water
```
78
Giardiasis - Pathophys
1. Cause ↓ expression of brush-border enzymes, microvillous damage; and apoptosis of small intestinal epithelial cells.
2. Does not invade --> surface protein toxin and presence damage BB
3. Found in duodenum and proximal jejunum
4. Secretory IgA and mucosal IL-6 responses --> clearance of Giardia infections
79
Giardiasis - Presentation
1. Immunosuppressed, agammaglobulinemic, or malnourished individuals are often severely affected
2. Can persist for months to years while causing intermittent Sx
3. Acute or chronic diarrhea, malabsorption, and weight loss
80
Giardiasis - Dx /Tx
```
Dx = Duodenal biopsies w/pear shape + 2 equal nuclei and immunofluorescent detection of cysts in stool (cyts form w/decreasing cholesterol availability)
Tx = oral antimicrobial therapy; recurrence is common.
```
81
Inflammatory Bowel Disease (InBD) - 2 subtypes
1. Ulcerative colitis
| 2. Crohn disease
82
InBD - Definition
Chronic, relapsing inflammation of bowel possibly due to abnormal immune response to enteric flora and classically presents in young women (teens to 30s) as recurrent bouts of bloody diarrhea and abdominal pain
83
InBD - Who gets it?
More prevalent in the West, particularly in Caucasians and Eastern European
Jews
84
InBD - Dx
Dx of exclusion; Sx mimic other causes of bowel inflammation (e.g., infection).
85
InBD - distinction b/c ulcerative colitis and Crohn disease
Based on (1) the distribution of affected sites and (2) the morphologic expression of disease at those sites.
86
Ulcerative colitis (UC) - Location
Colon only (begins in rectum and can extend up to cecum) - NO SKIP LESIONS
87
Crohn disease - Location
Anywhere from mouth to anus with skip lesions;
terminal ileum is the most common site, rectum is
least common.
88
Ulcerative colitis (UC) - Sx
LLQ pain (rectum) with bloody diarrhea
89
Crohn disease - Sx
```
RLQ pain (ileum) with fever and nonbloody diarrhea (usually)
Can present w/RLQ pain, bloody diarrhea, fever, mimicking acute appendicitis
```
90
Ulcerative colitis (UC) - Ulcers
Mucosal and submucosal ulcers
91
Crohn disease - Ulcers
Full-thickness inflammation with knife-Iike fissures
92
Ulcerative colitis (UC) - Inflammation
Crypt abscesses with neutrophils
93
Crohn disease - Inflammation
Lymphoid aggregates with granulomas (35% of
| cases)
94
Ulcerative colitis (UC) - Gross Appearance
Pseudopolyps; loss of haustra ('lead pipe' sign on
| imaging); thin wall; no recurrence after surgery
95
Crohn disease - Gross Appearance
```
Cobblestone mucosa, creeping fat,
fibrosing strictures ('string-sign' on imaging), thick wall; recurrence after surgery
```
96
Ulcerative colitis (UC) - Complications
Toxic megacolon and carcinoma (risk is based
on extent of colonic involvement and duration of
disease; generally not a concern until > 10 years of
disease)
97
Crohn disease - Complications
Malabsorption with nutritional deficiency,
calcium oxalate nephrolithiasis, fistula formation,
and carcinoma, if colonic disease is present
98
Ulcerative colitis (UC) - Associations
Primary sclerosing cholangitis and p-ANCA
| positivity
99
Crohn disease - Associations
Ankylosing spondylitis, sacroiliitis, migratory
| polyarthritis, erythema nodosum, and uveitis
100
Ulcerative colitis (UC) - Smoking
Protects against UC
101
Crohn disease - Smoking
Increases risk for Crohn disease
102
Microscopic appearance of small intestine
Mucosal villi confirm small intestine
Segment identification: 1. Duodenum – Brunner’s glands 2. Ileum – Peyer’s patches 3. Jejunum – neither of the above
103
Colonic Diverticula - Definition
Outpouchings of mucosa and submucosa through the muscularis propria (false diverticulum)
104
Colonic Diverticula - Cause
Related to wall stress
1. Associated with constipation, straining, and low-fiber diet; commonly seen in older adults (risk increases with age)
2. Arise where the vasa recta traverse the muscularis propria (weak point in colonic
wall) ; sigmoid colon is the most common location.
105
Colonic Diverticula - Presentation
Usually ASx; complications include
1. Rectal bleeding (hematochezial)
2. Diverticulitis—due to obstructing fecal material; presents with appendicitis-like Sx in LLQ
3. Fistula—Inflamed diverticulum ruptures and attaches to a local structure. Colovesicular fistula presents with air (or stool) in urine.
106
Microscopic morphology for large intestine (3)
Uniform flat mucosa - no villi
Uniform side-by-side straight tubular crypts
Crypt lining cells predominantly goblet cells
