Small Intestine and Colon Flashcards
What are the main causes of mechanical bowel obstruction?
(epi)
major causes:
- hernia (most common globally)
- adhesions (most common US)
- intussuseption (most common in children)
- volvulus
- tumors (most common LBO)
less common:
-infarction
What is paralytic ileus?
What are the main causes?
Functional bowel obstruction:
-interupted passage of bowel contents due to imparied peristalsis
Causes:
- post-operative ileus (most common)
- hypokalemia
- hypothyroidism
- drugs (opioids, anticholinergics)
- infections
What are common symptoms of GI obstruction?
- abdominal pain
- distension
- constipation (w/ inability to pass gas)
- vomting
How does vomiting in GI obstruciton change with location of obstruction?
- non-bilious at pylorus
- bilious in SBO
- feculent in LBO (late)
What exam and imaging findings are associated with mechanical GI obstruction?
Exam:
- colicky pain
- distention
- high-pitched BS (early) -> absent BS (late)
Imaging:
- dilated loops of bowel proximally
- air-fluid levels
- collapsed bowel distally
- no air in rectum
What are hernias?
protrusions of portion of GI tract through a weakness/deformity in muscular wall of abdomen
most common casue of obstruction worldwide
What complications can occur with hernias?
- obstruction
- imapired venous drainage -> edema -> incarceration (can’t be manually reduced) -> strangulation (vascular compromise)
- > infarction (necrosis)
What is an adhesion?
fibrous bridge connecting connecting parts of GI tract with itself or to the abdominal wall
most common cause of obstruction in US
What are cause of adhesions?
Acquired:
- surgery/trauma (hence prominence in US)
- peritonitis
- endometirosis
Congenital:
-rare, but can still occur
What are complications of adhesions?
- obstruction
- formation of closed loops of bowel -> internal herniation (complications similar to external herniation)
What is a volvulus?
Where does it most commonly occur?
twisted loop of bowel on mesentary -> obstruction and strangulation/ischemia
- occurs in redundant loops of bowel
- sigmoid colon >>> cecum > midgut/SI
- can be caused by congenital intestinal malrotation
What is intussusecption?
(mechanism)
“telescoping” of bowel in on itself
-occurs at a lead point (anomoly in GI wall that restricts motion) during peristalsis; lead point does not dilate during peristalsis and collsapses into proximally dilated portion
- highly associated with immune reactions in Peyer’s patches of children (viral infections and rotovirus vaccine)
- can be associated with tumor/polyps in older groups
What are complications of intussusception?
- obstruction
- ischemia (mesentary trapped as well) -> infarction
What are the sources of blood supply of the GI tract?
- celiac artery
- superior mesenteric artery
- inferior mesenteric artery
What are the main causes of chronic and acute bowel ischemia?
Chronic (hypoperfusion related):
- cardiac failure
- shock
- dehydration
- vasoconstrictors
Acute (obstruction related):
- atherosclerosis
- AAA
- embolized cardiac vegetations
- venous thrombosis
How does the bowel respond to chronic and actue vascular compromise?
Chronic/progressive:
-numerous collaterals allow for adaptation
Acute:
-can cause large portions of bowel to become ischemic
How does acute bowel ischemia present?
What symptoms indicate surgery?
- periumbilical pain disproportionate to exam findings
- bloody diarrhea
- thumbprinting (ABD XR)
peritoneal signs/infarction indicate surgery:
- absent BS
- cessation of stools
- guarding/rebound
- shock
How does chronic bowel ischemia present?
“Abdominal angina”
- dull periumbilical pain
- worse with with increased GI activity -> worse following meals
- “food fear”
- weight loss
What factors affect severity of injury in ischemic bowel disease?
What causes the most damage in acute bowel ischemia?
- severity of compromise
- time of compromise
- vessel affected (more proximal or larger area supplied = worse)
- reperfusion injury: toxic substances from hypoxic injury and potentially the intenstial lumen enter blood stream causing systemic effects
What is angiodysplasia?
Where does it most commonly occur and what is is associated with?
abnormal tortuous, dilated blood vessels (typically veins) in the mucosa and submucosa
most common in cecum and ascending colon
associated with episodic GI bleeding later in life
What is diarrhea?
increase in one of the following:
-frequency (>3/day)
-water content (>75%)
-mass (>200mg/day) of stool
What are the types of diarrhea?
Exudative diarrhea:
- due to inflammation
- bloody, purulent stool
- persists with fasting
Secretory diarrhea:
- increased cAMP -> active secretion of water
- persists with fasting
Osmotic diarrhea:
- water drawn into stool by unabsorbed solutes in the lumen
- abates with fasting
Malabsorptive diarrhea:
- general malabsorption -> increased fat in stool; steatorrhea
- abates with fasting
What is malabsorption?
Mechanisms:
- impaired intraluminal digestion of macromolecules
- impaired terminal digestion of oligosaccharides/pepetides at intestinal surface
- impaired epithelial transport
- imparied lymph transport of lipids
failure of absorption of (one or multiple):
- fat
- fat/water soluble vitamins
- proteins
- carbohydrates,
- electrolytes/minerals
- water
What conditions cause malabsorption and associated diarrhea?
Maldigestion:
- pancreatitis/exocirne pancreatic insufficiency
- bile acid deficiency
- cystic fibrosis
- hypo/achlorhydria
Malabsorbtion:
- IDB (CD/UC)
- lactase deficiency/lactose intolerance
- abetalipoproteinemia
- environmental/autoimmune enteropathy
- infectious gastroenteritis
- Whipple
How do conditions of malabsorption typically present?
General malabsorptions:
- diarrhea, particularly steatorrhea
- weight loss (if chronic)
- distension
- flatulence
- associated deficiencies
Specific malabsorptions:
-varies, dependent on what is not absorbed or associated deficiency
What is cystic fibrosis?
genetic defect in Cl ion transporter, CFTR, found in exocrine glands as well as respiratory, GI, and reproductive epithelium -> imparied water transport and thickened secretions
What mechanism of malabsorbtion occurs in cystic fibrosis and how does it present?
Failed intraluminal digestion:
- pancreatic duct obstruction due to thickend secretions -> pancreatitis/exocrine pancreatic insufficiency -> carbs, lipids, and proteins not digested
- general malabsorption due to lack of digestive enzymes -> steatorrhea and malnutrition
- impaired water secretion into GI lumen -> viscid mucous -> obstruction
What is the mechanism of celiac disease?
gluten-sensitive, immune-mediated enteropathy:
- autoimmune reaction triggered by gluten leading to damage of intestinal epithelium
- gliadin trigger epithelial cells to release IL-15 -> activates CD8+ T cells expressing NKG2D
- NKG2D binds MIC-A expressed on stressed enterocytes -> cell-mediated damage of epithelium -> malabsorption
- gliadin also binds HLA-DQ2 and HLA-DQ8 on APCs -> activate CD4+ T cells -> activate B cells -> production of anti-gliadin, anit-tTG, and anti-endomysial abs
What characteristics of celiac disease are used in its diagnosis?
(lab and histology)
Lab:
- anti-tTG IgA (gold standard)
- anti-endomysial IgA
- both high sens. and spec.
Histo:
- villous atrophy (loss of villi)
- crypt hyperplasia (elogation of crypts
- increased intraepithelial CD8+ T cells
- none are unique to celiac disease
What is the epidemiology of celiac disease?
Bimodal
Children:
- onset with introduciton of wheat products to diet ~6-24 months
- M=F
Adults:
- 30-40
- F>M
What are the clinical features of celiac disease in adults?
Classical:
- chronic diarrhea
- bloating/cramping
- malabsorption -> iron/vitamin deficiency -> anemia -> -chronic fatigue
What non-GI condition is associated with celiac disease?
dermatitis herpatiformis:
-autoimmune blistering disease associated with anti-tTG produced in celiac disease
What are the clinical features of celiac disease in children?
Often onsets at young age and pt may not be able to describe symptoms.
GI:
- chronic diarrhea/steatorrhea
- abdominal distension/pain -> irritability
- malabsorption -> failure to thrive/weight loss
Extraintestinal (impact of malabsorption on growth):
- arthritis
- growth restriction -> short
- delayed puberty
What causes many cases of celiac disease to go undetected/delay detection?
Most cases are atypical in their presentation, delaying testing for celiac disease
many cases are asymptomatic and go undetected
How is celiac disease treated?
No treatment available -> gluten-free diet to prevent symptoms
What is environmental enteropathy?
Environmental sprue/non-tropical sprue
similar to celiac disease (which is alternatively called non-tropical sprue) in presentation/appearance but:
-cause is unknown
- associated with poor sanitation/hygiene -> responds to antibiotics
- endemic to the tropics (***visiting or from there***)
Presentation:
- chronic diarrhea/steatorrhea
- bloating/cramping
- malabsorption -> iron/vitamin deficiency -> anemia -> chronic fatigue
Biopsy:
-villous atrophy
-cryptic hyperplasia
How is environmental enteropathy treated?
antibiotics
What are helpful factors in distinguishing between celiac sprue and environmental sprue?
- celiac predominates in the duodenum; environmental predominates in the ileum and jejunum (B12/folate deficiency)
- environmetal responds to Abx
- environmental is typically preceeded by infectious diarrhea
What is autoimmune enteropathy?
(etiology and presentation)
IPEX - Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked
- X-linked autoimmune disorder associated with mutation in FOXP3 -> loss of Treg cells
- presents early in life
Presentation:
- eczema
- T1DM
- malabsorption -> chronic diarrhea -> failure to thrive
What antibodies are found in autoimmue entropathy?
- anti-enterocyte
- anti-goblet cell
- anti-parietal cell
- anti-islet cell (-> T1DM)
How is autoimmune enteropathy treated?
immune supression:
-cyclosporine
What is lactase deficiency?
Lactase: brush-border enzyme, breaks down lactose -> galactose and glucose
-when deficient, lactose remains in lumen and exerts osmotic force, pulling water into stool -> osmotic diarrhea
What is the etiology/epidemiology of lactase deficiency?
Congenital:
- mutation in lactase gene
- very rare
Acquired:
- downregulation of lactase gene
- common in Native American, Africian American, and Chinese
- can be acquired following gastroeneteritis and gradually improve over time
What is the presentation of lactase deficiency?
Following consumption of milk:
- watery, frothy diarrhea (osmotic)
- cramping
- flatulence
Symptoms are more variable in aquired due to variance in active lactase
What is abetalipoproteinemia?
(presentation and findings)
autosomal recessive disorder associated with microsomal triglyceride transfer protein, MTP
- blood has no lipoprotein B
- body is unable to transport fats and fat soluble vitamins from the intestine
- diarrhea/steatorrhea
- failure to thrive
- lipid accumulation in enterocytes
- membrane defects -> acanthocytes/spur RBCs
What is IBS?
(presentation and cause)
Irritable bowel syndrome:
chronic, relapsing:
- abdominal pain
- bloating
- change in bowel habits
It has no known cause:
- diagnosed using Rome criteria
- diagnosed by elimination of DDx’s
What changes are associated with IBS?
NONE; GI tract has a normal macroscopic and microscopic appearance
What is the epidemiology of IBS?
- women
- 20-40 years
What is diversion colitis?
blind ending segment of colon resulting from surgery that produced an ostomy
What is microscopic colitis?
What are the types?
Normal gross appearing colon but with microscopic abnormalities
Symptoms:
-chronic diarrhea (non-bloody)
- weight loss
- abdominal pain
Collagenous colitis: increased subepithelial collagen
Lymphcytic colitis: intraepithelial lymphocyte infiltrate; commonly in setting of celiac dz or autoimmune dz
How does GVHD most commoly present in the GI tract?
SI and colon involved in most cases of GVHD
- watery diarrhea
- apoptosis of crypt cells
What are colonic diverticula?
false divertiucla/outpouchings of the mucosa and submucosa of the colon through discontinuities in the muscular layer
What is the epidemiology of colon diverticular disease?
How does this relate to likley location of the diverticula?
Epi:
- rare <30
- prevalence increases with age -> 50% by age 60
- more common in Western countries (left-sided diverticula)
- less common in Asia and Africa (right sided diverticula)
How do diverticula present?
most are asymptomatic
Those that are symptomatic (20%):
- painless lower GI bleed/hematochezia
- lower abdominal pain/cramping
- constipation
- sensation of not being able to empty the rectum
What is diverticulitis?
What complications can be associated with it?
inflammation of diverticula
Complicaitons:
- abscess
- fistula formation
- perforation
Where are polyp most commonly found?
colo-rectal, but can be found throughout GI tract
What are the morphological appearances of polyps?
Sessile polyps:
-small elevations of mucosa w/o stalks
Pedunculated polyps:
- protrusions of mucosa w/ stalks
- typcially preceded by a sessile precursor
What are the non-neoplastic polyp variants?
- hyperplastic
- inflammatory
- hamartomatous
What are hyperplastic polyps?
(description and location)
Benign epithelial proliferation:
- decreased epithelial turnover and decreased sheding leading to “piling up” of NORMAL cells (no dysplasia)
- small (<5 cm) sessile polyp
-serrated crypts
-tufting of surface due to crowding
-left/descending colon
What is significant about hyperplastic polyps?
very similar in presentation to serrated, sessile adenoma which is malignant, and must be ruled out
What are inflammatory polyps?
(description and location)
Benign polyp:
- caused by repeated injury and healing of the mucosa
- typcially assocaiated with solitary rectal ulcer sundrome (SRUS) where anorectal sphincter fails to relax -> recurrent abrasion/ulceration
Appearance:
- mixed inflammatory infiltrates
- erosion
- epithelial hyperplasia w/ fibromuscular hyperplasia
What are hamartomatous polyps?
(etiology)
disorganized growth of mature cells native to local tissue
- autosomal dominant inheritance (if genetic etiology)
- involved genes tend to be tumor supressors or protooncogenes -> increased risk of malignancy
- the polyps themselves tend to be benign
What are the main hamartomatous syndromes?
- juvenile polyposis syndrome
- Peutz-Jeghers syndrome
- Cowden syndrome
- Cronkhite-Canada syndrome
What is juvenile polyposis?
(symptoms/complications and cancer risk)
Autosomal dominant syndrome (SMAD4)
- presents <5 years
- >10 polyps (mostly colon, can involve stomach and SI)
- high risk of bleeding -> rectal bleeding -> anemia
- risk of intussusception and obstruction
Increased risk of gastric, SI, and colon adenocarcinoma
What is Peutz-Jeghers syndrome?
(symptoms and cancer risk)
Autosomal dominant syndrome (STK11):
- mucocutaneous hyperpigmentation, especially oral (mucosal “freckles”)
- arborizing polyps (most commonly SI, can occur in colon, stomach, bladder and lungs)
- can cause intussusception
Increased risk of colorectal, breast, lung, and pancreatic cancer
What are adenomatous polyps?
pre-malignant lessions that have a high risk becoming adneocarcinomas
-typcially distinguished from other, more benign polyps by the pressence of a stalk and dysplasia
What adenoma does not fit the typical description/classification of adenoma?
(why is this significant)
Sessile serrated adenomas:
- still a pre-malingnant lesion
- lack a stalk -> sessile
- lack dysplasia -> hyperplastic
Very similar in appearance to benign hyperplastic polyps, but can become malignant:
- crypts are serrated to their base; more common in right colon (adenoma)
- crypts are only serrated partway down; more common in left colon (hyperplastic)
What is the most significant prognostic factor of colorectal adenomas progressing to colorectal adenocarcinoma?
size:
- <1cm -> minimal risk
- >4cm -> 40%
What are the two genetic pathways associated with development of colonic adenocarcinoma?
(compare)
Classic, adenoma-carncinoma sequence:
- associated with FAP or sporadic mutations in APC/WNT pathway (growth supression) (APC-> K-RAS -> P53)
- 70-80% of sporadic CRC
- polypoid precursor -> non-mucinous adneocarcinoma
- typcially left-sided (sporadic only; FAP has no preference)
MMR sequence:
- associated with NHPCC or sporadic mutations in mismatch repair pathway (MLH1/MSH2)
- 10-15% of sporadic CRC
- most common inherited CRC (HNPCC)
- non-polypoid, serrated sessile precursor -> mucinous adneocarcinoma
- typcially right-sided
What drug impedes classic, adneoma-carcinoma sequence progression?
Aspirin/NSAIDs
-increased COX expression is part of transformation so COX inhibitors impede progression
What is familial adenomatous polyposis (FAP)?
(extra-GI manifestations and cancer risk)
autosomal dominant syndrome:
- development of >100, potentially 1000’s of adenomatous polyps
- mutation in Adenomatous Polyposis Coli (APC) gene
- associated with congenital retinal pigmented epithelium hypertrophy (can be deceted at birth)
100% risk of developing adenocarcinoma by age 45
What is MYH-associated polyposis?
Very similar to FAP but is more mild (<100 polyps) and slower progression (CRC around 50 y/o)
-MYH gene is affected instead of APC
How is FAP treated?
-prophylactic proctocolectomy w/ ileoanal anastamosis (prior to age of 20) otherwise colorectal cancer is inevitable
What is Gardner syndrome?
variant of FAP (APC mutation):
-additional risk of osteoma and soft tissue tumors
What is Turcot syndrome?
variant of FAP (APC mutation):
-additional risk of brain tumors
What is Lynch syndrome?
Hereitary nonpolyposis colorectal cancer (HNPCC):
- autosomal dominant mutations in mismatch repair genes (MSH2/MLH1)
- atypical adenomas (sessile instead of pedunculated) with high rate of prgression to CRC
- most common inherited cause of CRC
What cancers have an increased risk in Lynch syndrome?
- colon (HNPCC)
- endometrium
- stomach
- ovary
What is the difference in appearance and presentation colon cancer based on location?
Right-sided/proximal:
- flat, exophytic masses; “inverted mushroom”
- LIGB -> anemia
- rarely casue obstruction
Left-sided/distal:
- annular, “napkin-ring” constrictions
- blood streaked stools
- change in bowel habits
- may lead to obstruction
Where are colon adneocarcinomas most likely to metastasize to?
- LNs
- liver
What are the most important prognostic factors for colorectal adenocarcinoma?
- depth of invasion
- metastasis to LNs
less important but still prognostic:
- mucinous (MMR/sessile serrated)
- poorly differentiated
What findings should always trigger investigation for possible GI cancer?
- fatigue/weakness from IDA in older men or postmenopausal women (anemia of unknown origin)
- GI bleed
- most common presenting complaint in colon cancer and frequent with others
Where are carconoid tumors most likley to be found in the lower GI tract?
What do they secrete? (symptoms?)
most found in jejunum/ileum (most common site of carcinoid tumors in whole GI tract)
Secrete serotonin
- serotonin is mostly release into portal circulation -> metabolisim in liver (first-pass effect)
- if high tumor burden or directly secreted into systemic circulation -> carcinoid syndrome
Cacinoid syndrome:
- flushing, sweating
- bronchospasm
- colicky abdominal pain, diarrhea
- right-sided cardiac valve fibrosis (pulmonary system metabolizes 5HT preventing it from reaching L heart)
What infection is associated with colorectal carcinoma?
Streptococcus gallolyticus/bovis endocarditis
What tumor marker is associated with CRC?
CEA
- not reliable in screening as it is not always present
- can be used to monitor CRC known to produce CEA or similarly look for relapse
What genes are associated with juvenile polyposis?
SMAD4
What genes are associated with Puetz-Jeghers syndrome?
STK11
What genes are associated with adenomatous polyps?
APC (chromosome 5)
Adenomatous Polyposis Coli gene
What genes are associated with the classical sequence of CRC (stalked polyps)?
APC -> β-catenin -> K-RAS -> TP53, DCC, COX-2
What genes are associated with the MMR sequence of CRC (sessile polyp)?
MLH1, MSH2
