Chaptr 17 Part 2 Flashcards
Symptoms and signs of general obstruction of the small intestine and colon
Abdominal distention, vomiting, pain, constipation, tympanic by percussion
What causes 80% of SI and colon obstruction
Hernias, adhesions, intussusceptions, and volvulus
What causes 10-15% of SI and colon obstruction
Tumors, infarction, and other causes of structures
Hernias
Protrusion of a serosa lined pouch of peritoneum that can trap bowel segments externally, usually small bowel
What is the most frequent cause of intestinal obstruction worldwide and 3rd most common USA
Hernia
Acquired hernia
Occur anteriorly via inguinal and femoral canals, umbilicus or surgical scars
(External herniation)
Incarceration hernia
Permanent entrapment due to venous stasis+edema
Hernia strangulation
Due to arterial and venous compromise due to pressure at the neck of the pouch
Infarction and hernia
Sure
What is the most common cause of obstruction in USA
Adhesions
What is an adhesion
Localized inflammation due to surgery, trauma, infection, endometriosis or radiation;rarely congenital
How does adhesion form
Healing of inflammation-leads to fibrous bridges creating closed loop through which viscera may slide and become entrapped -internal herniation
Obstruction and strangulation from adhesion
Yup as viscera slide and become trapped
Volvulus
Complete twisting of a bowel loop about its mesenteric vascular base
What happens when volvulus compromise vascular and luminal
Infarction and obstruction
Where is volvulus most common
In redundant loops of sigmoid colon
What is the biggest concern with colculus
Can lead to toxic megacolon
Intussusception
Intestinal segment telescopes into the immediately distal segment
Peristalsis propels th invaginated segment with its attached mesentery
Obstruction, vessel compression and infarction
Intussusception is the most common cause of what
Intestinal obstruction in children <2 yrs
Causes of intussusception in young kids
Spontaneous or associated with viral infection, rotavirus vaccine
-get reactive hyperplasia of peyer patches and other lymphoid tissue acting as a leading edge
Intussusception older children
Due to intraluminal mass or tumor
-surgical intervention is necessary
Diagnosis intussusception
Via contrast enemas
Treat intussusception children
Contrast enema, air enema
Treat intussusception older
Surgery
Ischemic bowel disease
Collateral blood supple allows slow, progressive loss of blood supply to be tolerated
Abrupt compromise of a vessel leads to infarction of several meters of intestine
What areas are at risk for ischemic bowel disease
Mucosal infarction to transmural
Watershed zones=most vulnerable
Epithelial cells at tips of villi(bc end of capillary network)
What are watershed regions of bowel
Splenic flexure
Sigmoid colon and rectum
Splenic flexure
Between superior and inferior mesenteric arteries
Marginal artery of Drummond
Sigmoid colon and rectum
Where inferior mesenteric, pudendal and iliac arterial circulations end
Acute causes of ischemic bowel disease-vascular etiology
Severe atherosclerosis (at origin of mesenteric vessels)
AAA
Hypercoagulatioble states
Embolization due to cardiac vegetation’s or aortic atheromas
Hypoperfusion due to cardiac failure, shock, dehydration or wegener granulomatosis
Morphology ischemic bowel disease
Patchy
Mucosa is hemorrhagic and ulcerated
Bowel wall is thickened with edema
Transmural infarction: large portions of bowel are affected and there is a sharp line between infarct and healthy tissue
Coagulation necrosis: 1-4 DAYS AFTER, MAY LEAD TO PERFORATION, SEROSTITIS WITH PURLUENT EXUDATES AND FIBRIN DEPOSIT
Epithelial surface sloughs off(CHARACTERISTIC), HYPERPROLIFERATION IN CRYPTS
Chronic ischemic bowel disease
Fibrous scarring of lamina propria
Who gets ischemic bowel disease
70 or older
Ischemic bowel disease
Can be caused by cocaine (___)or from CMV/E-coli (O157-H7) or trauma (___)
Vasoconstrictor use
Epithelial damage
Prognosis ischemic bowel disease
Unlikely fatal
Presentation of ischemic bowel disease
Acute: sudden onset of cramping, LLQ pain, desire to defecate, passage of blood or bloody diarrhea
Progresses to school and vascular collapse in hours if severe
Prognosis infarct ischemic bowel disease
10% of transmural infarct die first 30 days
Death fro ischemic bowel disease in doubled in who
Patients with right sided colonic disease
-right side of colon is supplied by superior mesenteric artery, which also supplies small intestine
Worse prognosis ischemic bowel disease
COPD or signs and symptoms lasting longer than 2 weeks
Does ischemic bowel disease recur
No
Treatment ischemic bowel disease
Surgery if bowel sounds are absent (paralytic ileus) or if guarding, rebound develop
Chronic ischemia
Can masquerade IBD
Episodes of bloody diarrhea interspersed with periods of healing
__ infection causes ischemic GI disease due to viral tropism for endothelial cells
CMV
Radiation enterocolitis and ischemic bowel disease
Epithelial damage+vascular injury
Radiation fibroblasts in stroma
Acute radiation enterocolitis: ischemic bowel disease
Anorexia, abdominal cramps, malabsorption diarrhea
Chronic radiation enterocolitis ischemic bowel disease
More indolent, may present as inflammatory enterocolitis
Ischemic bowel disease : necrotizing enterocolitis
Most common acquired GI emergency of neonate*
Prematureinfants or low birth weight babies are at high risk
Present when oral feeding is initiated
Acute disorder ofsmall and large intestines leading to transmural necrosis
Angiodysplasia
Malformed tortuous, ectatic dilation of veins, venues and capillaries in mucosa and submucosa
Where is angiodysplasia most common
In cecum or ascending colon
What percent of adult population patients older than 60 have angiodysplasia
1%
Angiodysplasia causes _% of major lower GI bleeds
20
Morphology angiodysplasia
Only vascular wall and a layer of attenuated epithelial cells separate vascular channels from the intestinal lumen, limited injury=significant bleeding
Diagnose angiodysplasia
Diagnosis of exclusion
Malabsorption
Defective absorption of fats, proteins, carbohydrates, electrolytes, minerals, water, and vitamin (fat and water soluble)
Presentation of malabsorption
Chronic diarrhea
Hallmark=steatorrhea*
Accompanying symptoms malabsorption
Weight loss, anorexia, abdominal distention, borborygmi(gurgling), muscle wasting
More common causes malabsorption
Pancreatic insuffiency, celiac disease, Crohn’s disease and intestinal GVHD following allogenic hematopoietic stem cell transplantation
What are the 4 processes of nutrient absorption
Interruption of intraluminal digestion
Terminal digestion
Transepithelial transport
Lymphatic transport of absorbed lipids
Interruption of intraluminal digestion
Emulsification and break down of nutrients into absorbable forms
Terminal digestion
Hydrolysis of carbs and proteins in enterocyte brush border
Transepithelial transport
Nutrients, fluid, electrolytes transported across and processed in the small intestinal epithelium
Consequences of malabsorption
Anemia, mucositis
Pyridoxine (B6) folate, b12 defiency
Bleeding
Vitamin k defiency
Osteopenia and tetany
Ca, mg or vit d defiency
Endocrine or skin disturbances
What are main categories of diarrhea
Secretory
Osmotic
Malabsorptive
Exudative
Secretory diarrhea
Isotonic (to plasma) stool
Persists during fasting
Osmotic diarrhea
Due to excessive osmotic forces exerted by unabsorbed luminal solutes
Fluid is >50 mosm more concentrated than plasma
Seen with lactase defiency
Abates with fasting
Malabsorptive diarrhea
Generalized failure of nutrient absorption
Associated with steatorrhea
Relieved by fasting
Exudative diarrhea
Due to inflammatory disease
Purple NT, bloody stools
Persists during fasting
What aer the 2 diseases that only have issues with intraluminal digestion
Chronic pancreatitis
Cystic fibrosis (->pancreatitis)
What is the diseases that only has a problem with terminal digestion
Disaccharidase defiency
What is the only disease that only has a problem with the lymphatic transport
Whipple disease
What is the only disease that only has a problem with transepithelial transport
Abetalipoproteinemia
Cystic fibrosis
Formation of pancreatic intraductal concretions leads to duct obstruction, low grease chronic autodigestion of pancreas, and exocrine pancreatic insuffiency
Absorption and CF
Failure of intraluminal nutrient absorption
Treat absorption i CF
Supplemental oral enzymes
Genes cf
CFTR absence
Celiac disease
Celiac sprue
Immune mediated diarrheal disorder due to ingestion of gluten-containing foods
Wheat, rye, barley
Genetics celiac disease
Class II HLADQ2, HLAD!8
Gluten and celiac disease
Usually broken down by brush borer into a-gliadin (alcohol soluble fraction): disease producing component. Resistant to degradation by protease
Gliadin induced damage
Il15 activation of cd8 lymphocytes that express NKGD2 which attack MIC-A on enterocytes (apoptosis) leading to enhanced gliadin transport into cells
Deamination by transglutaminase
De-aminated peptide bind MHC of susceptible patients (specific HLA) activating CD4 cells and leads to more tissue damage
Where is celiac disease anatomically
2nd part of the duodenum to the proximal jejunum
Villi in celiac disease
Diffusely flattened(atrophic)
Crypts celiac disease
Elongated regenerative crypts associated with intraepithelial CD8 T cells
Villa us atrophy celiac
Loss of mucosal and brush border surface
Lamina propria celiac
Exuberant lamina propria chronic inflammation
How diagnose celiac disease
Biopsy of second part of duodenum or proximal jejunum increased numbers of CD8 T cells, crypt hyperplasia and villous atrophy
Increase in the number of intraepithelial lymphocytes, particularly within the villus, is a sensitive marker of celiac disease, even in the absence of epithelial damage and villous atrophy
Lymphocytosis and villous atrophy are not specific; may be present in viral enteritis
Need histology and serology
IgA antibodies to tissue transglutimnase or anti endomysial
May also be detected in IgA defiency
HLADQ2/8 absence is highly predictive ; presence is not diagnostic
Dermatitis hepetiformis is found in 10% of celiac
Micro abscess: papillae
Subepidermal-blister
Granular IgA deposits
Extremely pruritis small vesicles
Why get dermatitis herpetiformic with celiac
Anti-gluten antibodies cross reacting with BM proteins
Adult celiac disease
30-60
Can be clinically silent or symptomatic
Chronic diarrhea, bloating, chronic fatigue, anemia (iron and vitamin malabsorption)
Dermatitis herpetiformis: itchy, blistering skin lesion(10%)
Females 2:1 may be due to monthly menstrual bleeding impairing absorption
Pediatric celiac disease classic
6-24 months
-irritability, abdominal distention, anorexia, chronic diarrhea, failure to thrive, weight loss, msucle wasting
Pediatric celiac non classic
Later onset
Abdominal pain, nausea, vomiting, bloating, constipation, arthritis, aphthous stomatitis, iron deficient anemia, deflated puberty, short
No gender preference
Treat celiac
Gluten free
Decrease risk of long term complications: anemia, female infertility, osteoporosis, and cancer
Considerations is symptoms return
Adhering to diet
Development of enteropathy associated T cell lymphoma or small intestine adenocarcinoma
Environmental enteropathy/tropical sprue
Prevelance in areas and populations with poor sanitation and hygiene
Distal bowel is most severely affected (young)
Malabsorption, malnutrition, stunted growth, and defective intestinal mucosal immune function
Defective intestinal barrier function, chronic exposure to fecal pathogens, and othe microbial contaminants and repeated bouts of diarrhea within the first 2-3 years of life are likely involved
Environmental enteropathy and oral antibiotics or nutritional supplementation
Not correlated
Environmental enteropathy cognitive
Associated uncorrectable cognitive effects
Autoimmune enteropathy
Severe, persistent diarrhea and autoimmune disease affecting young kids
IPEX
Immune dysregulaion, polyendocrinopathy, enteropathy, X linked
IPEX genetic
FOXP3 mutation=defective CD4
Treg cells
In autoimmune enteropathy, what are there autoantibodies to
Enterocyte and goblet cells
What else do we see with autoimmune enteropathy
Neutrophils and intraepithelial lymphocytes
Treatment autoimmune enteropathy
Immunosuppression (cyclosporine) and HSC transplant in rare cases
Lactase defiency
Enzyme located in brush borer of villus absorptive epithelial cells
Biopsy is unremarkable bc the defect is biochemical
Congenital lactase defiency
Explosive diarrhea with water, frothy stools and abdominal distention following dairy ingestion
Rare AR mutation in lactase gene
Acquired lactase defiency
Abdominal fullness, diarrhea, flatulence, following ingestion of lactose products
Due to fermentation of unabsorbed surgery by colonic bacteria
Downregulation of lactase gene expression often following a viral or bacterial infection
May resolve over time
Who gets acquired lactase defiency
Common in Native American, african American, and Chinese populations
Abetalipoproteinemia
Inability to secrete triglyceride rich lipoproteins
AR mutation of microcomal triglyceride transfer protein (MTP) that presents in infancy
What happens when u don’t have TMP
Enterocyte cant assemble or export lipoproteins —>intracellular lipid accumulations
Pathogenesis abetalipoproteinemia
Microsomal TG transfer protein normally transfers lipids to rough ER, promoting TG production
Complete absence of all plasma lipoproteins containing APO B (though gene is not affected)=inability to assemble and export lipoproteins causing intracellular accumulation
Vacuolization of intestinal epithelial cells seen with oil red-O stain, espicially after fatty meal
Clinical abetalipoprotenemia
Failure to thrive, diarrhea, steatorrhea
Acanthocytic red cells (burr cells) in peripheral blood smears due to inability to absorb essential FA
Defiency of fat soluble vitamins ADEK
Lipid membrane defects
Infectious enterocolitis symptoms
Diarrhea, abdominal pain, urgency, perinatal discomfort, incontinence, hemorrhage
What causes 10% of all death in children <5 worldwide
Infectious entercolitis
Infectious entercolitis: enteric viruses commonly cause pediatric infectious diarrhea leading to what
Severe dehydration and metabolic acidosis
Vibrio cholera
Comma-shaped
Gram -ve
Epidemiology vibrio cholera
Endemic to Ganges valley (India) and Bangladesh
Seasonal variation , rapid growth in warm temperatures
Primarily transmitted in contaminated drinking H2O (fecal-oral)
Rampant in areas of natural disasters where supplies may be compromised
Clinical vibrio cholera symptoms
Most asymptomatic or mild diarrhea
Severe-rice water diarrhea fishy odor
Incubation period vibrio cholera
1-5 days
Severe vibrio cholera
Dehydration, hypotension, muscle cramping, anuria, shock, loss of consciousness, and death in 24 hours
Treat vibrio cholera
Oral rehydration=99% success
If don’t treat vibrio cholera
50% mortality
Campylobacter enterocolitis cause
Campylobacter jejuni
Improperly cooked chicken, unpasteurized milk, or contaminated water
What is the most common bacterial enteric pathogen in developed countries
Campylobacter
Travels diarrhea and food poisoning
Campylobacter enterocolitis
Campylobacter
Gram -, comma shaped, flagellated
Morphology campylobacter enterocolitis
Neutrophils in the submucosa and cryptos may cause crypt abscess
Crypt architecture is preserved
Sequelae campylobacter
HLAB27=reactive arthritis
Erythema nodosum
Guillain-Barré syndrome-ascending flaccid paralysis due to immune mediated inflammation of peripheral nerves due to molecular mimicry due to LOPS cross reactivity
Clinical campylobacter
Acute watery diarrhea or may follow influenza-like prodrome
Dysentery in 15% adults, 50% kids
Only 500 organisms necessary for NF1 toon
Incubation campylobacter
8 days
How long after campylobacter enterocolitis do u shed bacteria
1 month after resolution
Diagnosis campylobacter enterocolitis
Stool culture
Treatment campylobacter
Antibiotics are not usually necessary
Shigella
Non encapsulated, non motile, facultative anaerobe
Closely related to the enteroinvasive strain of E. coli
Resistant to acidic environment of stomach-> low infective dose
Taken up by M cells in the intestine
What is the most common cause of bloody diarrhea
Shigella
How get shigella
Fecal oral transmission or contaminated food.water
Kids and shigella USA
Children in daycare, migrant workers, travelers to developing countries, nursing home population
Virluence of shigella
Infective dose,several hundred organisms
Who dies rom shigella
Kids <5
Shigella is responsible for _% of all pediatric deaths and _% of all diarrheal deaths
10
75
Morphology shigella
Most common in the left colon
Hemorrhagic and ulcerated mucosa
Often with pseudomembranes
Incubation shigella
1 week
Treat shigella
Self limited diarrhea, fever, abdominal pain
Dysenteric phase shigella
50%, up to a month
Subacute shigella phase
Patients have waxing and waning diarrhea
Children shigella
Shorter duration, more severe
Complication triad of shigella
Sterile reactivation arthritis, urethritis, conjunctivitis in HLAB27 + males 20-40
Shigella serotype 1 complication
Leads to toxin causing hemolytic uremic syndrome
Complication shigella
Toxic megacolon and intestinal obstruction are uncommon
Diagnosis shigella
Confirm via stool culture
Treat shigella
Antibiotics shorten duration of signs and symptoms
Anti diarrheal medications are CONTRAINDICATED because they delay clearance
Salmonella enteritidis
Gram - bacillus
Member of the enterobacteriaceae family
-TLR=LPS
TLR5=flagellin
Who is at risk for salmonella
Small$ necessary, even less in patients on acid suppression therapy
Incidence peaks in summer and fall
Commonly in young children and older adults
Food poisoning due to ingestion of contaminated food (raw/undercooked meat, poultry, eggs milk)
Large outbreaks in centralized food processing
TH17 genetic defect=increased susceptibility
Vaccination salmonella
Got human and farm animals
Clinical salmonella
Signs and symptoms similar to other enteric pathogens
Range from loose stool to profuse diarrhea to dysentery
Stool cultures essential for diagnosis
Complications salmonella
Severe illness more likely in patients with malignancy, immunosuppression, alcoholism, CV, dysfunction, sickle cell disease, and hemolytic anemia
Diagnose salmonella
Stool
Treat salmonella enteritidis
Most infections are self limited and last 1 week
Antibiotics are not recommended, prolong airier state, no effect on duration fo diarrhea
Typhoid fever (enteric fever)
Salmonella enterica (typhi and paratyphi)
Endemic areas typhoid fever-who gets it
(Typhi) Children and adolescents most affected
Developed counties-who gets typhoid fever
No age preference
Typhoid fever associated with
Travel (paratyphi0: India, Mexico, Philippines, Pakistan, El Salvador, haiti
-travelers most likely to be vaccinated
Transmission typhoid fever
Transmitted human human or via food/contaminated H2O
Taken up by M cells
Morphology typhoid fever
Infection causes plateau-like elevations of Peters patches in terminal ileum
Enlargement of draining mesenteric lymph nodes
Acute and chronic inflammatory cell recruitment to the lamina proporia leads to necrotic debris’s and overlying mucosal ulcers that orient along the axis of the ileum (may perforate)
Spleen is enlarged and soft with uniform pale red pulp and obliterated follicular markings
Typhoid nodules: focal hepatocyte necrosis int he liver with macrophage aggregates
Typhoid fever symptoms
Anorexia, abdominal pain, bloating, nausea, vomiting, bloody diarrhea
Followed by asymptomatic phase that leads to bacteremia and fever with flu like symptoms
90% of typhoid fever patients have + blood cultures during __ phase
Febrile
-antibiotics can prevent further disease progression
Gallbladder typhoid fever
Colonization can be associated with gallstones and the chronic carrier state
Rose spots typhoid fever
Small erythematous maculopapular lesion on chest and abdomen
Typhoid fever extra intestinal
Osteomyelitis (espicially in sickle cell), encephalopathy, meningitis, seizures, endocarditis, myocarditis, pneumonia, cholecystitis
Treat typhoid fever
Antibiotics to prevent progression
What is no antibiotics with typhoid fever
Initial febrile phase lasts 2 weeks have sustained high fever and abdominal tenderness mimicking appendicitis
Symptoms abate after several weeks in surviving patients
Can get relapse
How get yer Sinai enterocolitica
Ingestion of pork, raw milk and contaminated H2O
Yersinia enterocolitica mimics appendicitis?
Tropism for ileum, appendix and right colon
In yersinia enterocolitica where do organisms proliferate
Extracellularly in lymphoid tissue leading to lymph node and peyer patch hyperplasia
Morphology yersinia enterocolitica-mimic crohns
Bowel was thicking
Overlying mucosa can become hemorrhagic and ulcerated with neutrophilic infiltrates and granulomas
Yersinia enterocolitica clinical
Abdominal pain +/- fever, diarrhea, nausea, vomiting
Teens/young adults: mimic appendicitis
Younger children: enteritis and colitis predominate
Extra-intestinal: pharyngitis, arthralgia, erythema nodosum
Lymph node or blood cultures may be +
How detect yersinia enterocolitica
Stool
Iron enhances yersinia enterocolitica virluence
Stimulates systemic dissemination
-individuals with increased non heme iron (chronic forms of anemia o hemochromatosis) are at increased risk to develop sepsis and die
Post infectious complications yersinia enterocolitica
Reactive arthritis, urethritis, conjunctivitis, myocarditis, erythema nodosum, and kidney disease
E. coli
Gram - bacilli that colonize healthy GI tract
Most onpathogenic
Some can cause human disease
Anterotoxigenic E. coli
Travelers diarrhea (could also be campylobacter)
Symptoms diarrhea with enterotoxigenic E. coli
Secretory, non inflammatory diarhea, dehydration and if severe, shock
How does enterotoxigenic E. coli spread
Contaminated food or water
Who is particularly susceptible to enterotoxigenic E. coli
Children less than 2
What does enterotoxigenic E. coli cause
Cl and H2O secretion and inhibit absorption
Enterotoxigenic E. coli heat label toxin
Similar to cholera toxin
Activates AC=increased cAMP, increased Cl secretion
Enterotoxigenic E. coli heat stable toxin
Increased cGMP
Enteropathy E. coli
Causes endemic diarrhea and diarrheal outbreaks in patients less than 2 years old
Enteropathy E. coli Tir
A receptor for intimin allows detection and diagnosis of infection by EPEC
Enteropathy E. coli produce attaching and effacing lesions
In which bacteria attach tightly to the enterocyte apical membranes and cause local loss (effacement of the microvilli)
-proteins (Tir) necessary for creating A/E lesions are all encoded in the locus of enterocyte effacement (LEE) which is also present in many EHEC strains
In enteropathy E. coli, bacteria attach to enterocyte __ membrane, cause local loss of microvilli (effacement)
Apical
Tir and other proteins are necessary for what (enteropathy E. coli)
Creating A/E lesions all encoded int he locus of enterocyte effacement which is also present in many ehec strains
When enteropathy E. coli attach to enterocyte apical membrane, what happens
Cause loss of microvilli (effacement)
Do enteropathy E. coli produce shiga toxin
NO
Enterohemorrhagic E. coli
O157:H7 and non-O157:H7
From consumption of undercooked need (cows are reservoir), milk and vegetables
Do enterohemorrhagic E. coli produce shiga like toxins
Yup and clinically resemble shigella dysenteriae
O157:H7
More likely to produce outbreaks, bloody diarrhea, hemolytic uremic syndrome (HUS) and ischemic colitis
Why are antibiotics contraindicated in patients with enterohemorrhagic E. coli
Killing bacteria increases the amount of toxin released and enhances HUS
Espicially in kids
Enteroinvasive E. coli
Do not produce toxins
Invade epithelial cells causing nonspecific, acute self limited colitis
Transmitted via food, water or human contact
Where is enteroinvasive E. coli most common
Infects young children in developing countries
Enteroaggregative E. coli
Can also cause travelers diarrhea
Describe enteroaggregative E. coli diarrhea
Non bloody diarrhea that is prolonged in AIDS patients
How does enteroaggregative E. coli cause diarrhea
Attach to epithelial via fimbriae and are aided by dispersion, bacterial protein which neutralizes the - surface of LPS
Enteroaggregative E. coli and shiga
Do make shiga like toxin but causes minimal histologic damage
Enteroaggregative E. coli characteristic
Adherence lesions only visible with electron microscope
Pseudomembranous collitis
Caused by overgrowth of clostridium difficult due to antibiotic use
Formation of adherent inflammatory pseudomembranes overlying sites of mucosal injury
Also due to immunosuppression
Describe the pseudomembrane
Made up of an adherent layer of inflammatory cells and debris at sites of colonic mucosal injury
Are pseudomembranes specific for pseudomembranous colitis
No may occur with ischemia of necrotizing infections
Morphology pseudomembranous colitis
Surface epithelial is denuded and the lamina propria contains a dense infiltrate of neutrophils and occasional fibrin thrombi within capillaries
Damaged crypts pseudomembranous colitis
Distended by a mucopurluent exudate that form an eruption like a volcano that leads to the formation of the membrane
-histology is pathognomonic
Risk factors pseudomembranous colitis
Advanced age, hospitalization and antibiotic use
Clinical presentation pseudomembranous colitis
Fever, leukocytes, abdominal pain, cramps, watery diarrhea, dehydration
But most are asymptomatic
Peripheral edema
Fecal leukocytes and occult blood , but grossly bloody diarrhea uncommon
Pseudomembranous colitis why peripheral edema
Protein loss leads to hypoalbuminemia
Diagnosis pseudomembranous colitis
Detect toxin in stool
Treat pseudomembranous colitis
Metronidazole, oral vancomycin (stays in GIT, is not absorbed)
Recurrence in up to _% of patients with pseudomembranous colitis
40
Whipple disease
Rare, systemic condition due to actinomycete tropheryma whippelii
Accumulation of organism laden macrophages accumulate in laminae propria of small intestine and in mesenteric lymph nodes leading to lymphatic obstruction
Who gest whipple disease
Caucasian males (farmers, occupational exposure)
Characteristics of whipple
Gram+ bacillus
Who gest whipple disease
Caucasian males, particularly farmers and others with occupational exposure to soil or animals
Morphology whipple disease
Dense accumulation of distended foamy macrophages in small intestine lamina propria
Stuffed with PAS positive bacteria in lysosomes
Also seen in lymphatics, lymph nodes, synovial membranes of joints, cardiac valves, and brain
Marked villous expansion in small intestine
Lymphatic dilation and mucosal lipid deposition lead to shaggy white yellow mucosal plaques
Triad of whipple disease
Diarrhea, weight loss, arthralgia
Why get malabsorptive diarrhea with whipple disease
Impaired lymphatic transport
Complications of whipple disease
Malabsorption, arthritis, fever, LAD, neurological, cardiovascular, or pulmonary disease
What causes 1/2 of all gastroenteritis outbreaks worldwide, is a common cause of sporadic gastroenteritis in developed nations, most common cause of acute gastroenteritis requiring medical attention, and 2nd most common cause of severe diarrhea in infants and young kids
Norovirus
Cruise ship virus
Norovirus
What is the most common virus causing diarrhea in kids and infants
Rotavirus
But norovirus will become one as toravirus vaccination becomes widespread
Characteristics norovirus
Icosahedral, ssRNA virus
Calciviridae family
-the cruise ship departing from California
Transmission norovirus outbreaks
Transmission via contaminated food or H2O
Treanmission sporadic cases norovirus
Human human transmission
Transmission norovirus places
Schools, nursing homes, cruise ships
How is norovirus spread
Airborne droplets, environmental surfaces and forties
Incubation period norovirus
Short
Symptoms norovirus
Nausea, vomiting, watery diarrhea, abdominal pain—nonspecific abdominal complaints
Treat norovirus
Self limited in immunocompetend
Morphology norovirus
Villous shortening, loss of brush border, crypt hypertrophy, lymphocytic infiltration
Immunocompromised norovirus
Persists up to 9 months, patients experience intermittent diarrhea, malnutrition and dehydration that can exacerbate their underlying disease
Rotavirus characteristics
Encapsulated virus with segmented dsRNA
What is the most common cause of severe childhood diarrhea and diarrheal mortality worldwide
Rotavirus
Who is most susceptible to rotavirus
Children 6-24 months —-daycare
Do children 0-6 months get rotavirus
No passive immunity from mom , but less effective in India
Rotavirus 2 year olds and on
Immunity that develops following the first or second infection
Where are rotavirus outbreaks
Hospitals and daycare centers
Infective load rotavirus
<10 particles and has short incubation time
Vaccine rotavirus
Associated with intussusception
Rotavirus pathogenesis
Net secretion of H2O/electrolytes, malabsorption, osmotic diarrhea
Adenovirus
Nonspecific signs and symptoms after 1 week incubation period
Symptoms adenovirus
Diarrhea, vomiting, abdominal pain maybe fever and weight loss
Adenovirus is the _ leading cause of pediatric diarrhea
3rd
Who besides children is effected by adenovirus
Immunocompromised patients
Epithelium adenovirus
Epithelial degeneration
Villi adenovirus
Villous atrophy and compensatory crypt hyperplasia
Ascaris lumbricoidrs
Ingested eggs hatch in intestint->larvae penetrate the intestinal mucosa->migrate from splanchnic to systemic circulation->enter the lungs to grow within the alveoli ->coughed up swallowed ->larvae mature into worms->eosinophilic rich inflammatory reaction->physical obstruction or the intestine or biliary tree
How does ascaris lumbricoides spread
Fecal oral
Diagnose ascaris lumbricoides
Eggs in stool
Strongyloides
Larvae penetrate unbroken skin ->migrate through the lungs->induce inflammatory infiltrates->reside in the intestines maturing into adult worms
Strongyloides autoinfection
Eggs of strongyloides can hatch within the intestine and release larvase that penetrate the mucosa
Infection can persist for life
Strongyloides larva stage inside or outside the human host
Outside
Tissue reaction to strongyloides
Strong and induce peripheral eosinophilia
Nectar dupdenale and ancylostoma dupdenale
Hookworms—larvae penetrate through he skin, develop int he lungs, migrate up the trachea and are swallowed
What do necator dupdenale and ancylostoma duodenale do in the duodenum
Suck blood and reproduce-multiple superficial erosions, focal hemorrhage and inflammatory infiltrates
Chronic infection of necator dupdenale and ancylostoma dupdenale is associated with
Iron defiency anemia
Enterobius vermicularis
Pinworm/parasites
Do enterobius vermicularis invade host tissue
No
Where do enterobius vermicularis live life cycle
In intestinal lumen
Symptoms enterobius
Rarely
Transmission enterobius vermicularis
Fecal oral
Diagnose enterobius vermicularis
Scotch tape test
Trichuris trichiura
Whipworms
Who gets trichuris trichiura
Young kids
Heavy infections of trichuris trichiura
Can lead to bloody diarrhea and rectal prolapse
Trichuris trichiura does _ penetrate intestinal mucosa and rarely causes serious disease
Not
Schistosomiasis
Adult worms residing within mesenteric veins
Symptoms schistosomiasis
Trapping of eggs within the mucosa and submucosa
Schistosomiasis causes a __- immune reaction that can cause bleeding and obstruction
Granulomatous
Intestinal cestodes
Tapeworms that reside in the intestinal lumen but do not penetrate the intestinal mucosa==peripheral eosinophilia does not occue
Treanmission intestinal cestodes (tapeworm)
Raw meat that contains encrypted larvae
-proglottids and eggs are shed in the feces
Symptoms intestinal cestodes
Diarrhea, abdominal pain, nausea
What are the three primary species of intestinal cestodes
Diphyllobothrium latum (fish tapeworm)=causes B12 defiency and megaloblastic anemis because it competes with the host for dietary B12
Taenia solium (pork)
Hymenolepis nana (dwarf tapeworm)
Entamoeba histolytica treanmission
Fecal oral
Symptoms of entamoeba histolytica
Abdominal pain, bloody diarrhea, or weight loss causes liver abscesses and dysentery
What can entamoeba histolytica cause that is associated with significant mortality
Acute necrotizing colitis and megacolon
Describe entamoeba cysts
Have chitin wall and 4 nuclei and resistant to gastric acid
Describe entamoeba histolytica
Flask shaped upcer with a narrow neck and broad base
Pathogenesis entamoeba histolytica
Penetrate splanchnic vessels and embolism to liver producing abscesses
Entamoeba histolytica __ mitochondria or Karen’s cycles enzymes=obligate fermenters of glucose.
Lack
Treat entamoeba histolytica
Metronidazole takes advantage of this and is an effective treatment (lacking mitochondria)
Giardia lamblia
Most common parasitic pathogen in human and spread recalls contaminated water or food
Giardia lamblia form ___ that are resistant to ___
Cysts
Chlorine
Describe giardia lamblia
Flagellate protozoan that decrease expression of brush border enzymes, including lactase
How do clear giardia lamblia
IgA and mucosal IL-6
Giardia
Continuous modification of the major surface antigen
How get giardia lamblia
Ingested from fecally contaminated for or H2O
Trophozites giardia lamblia
Characteristics pear shape with two equal size nuclei
Does giardia lamblia invade tissue
No
How does giardia work
Secretes products that damage crush border=malabsorption
Cryptospordium
Chronic diarrhea in AIDS patients
Oocytes are resistant to chlorine-need to freeze or filter
Entire life cycle in a single host
Cryptospordium malabsorption of what
Na, Cl secretion, an increased tight junction permeability-nonbloody watery diarrhea
Where is cryptosporidium concentrated
In terminal ileum and proximal colon
Present through the GIT, biliary tree and even the respiratory tract of immunodeficiency hosts
How diagnose cryptosporidium
Oocytes in stool
IBS
Non pathological , chronic relapsing abdominal pain, bloating and changes in bowel habits representing multiple illnesses
Who gets IBS
20-40 years old, significant female
Causes of IBS
Psychological stressors, diet ,abnormal GI motility, disrupted brain gut axis, immune activation or altered gut microbiome
Diagnose IBS
Clinical criteria: gross and microscopic evaluation is normal in most patients
Symptoms IBS
Abdominal pain 3 days/month over three months
When does pain from IBS improve
Following defecation
What does longer duration of IBS mean
Decreased likelihood of improvement
Issues with IBS
No serious long term sequelae
May undergo unnecessary abdominal surgery due to chronic pain
Ability to function may be compromised
Treat IBS
Depends on signs and symptoms: 5HT2 antagonists, opoids, anticholinergics or fecal transplant
IBD
Chronic condition due to inappropriate mucosal immune responses to normal gut flora
Classified as either crohn disease or ulcerative colitis
Who gets IBD
Teens-early 20s
Caucasions
Ashkenazi jews
Hygiene hypothesis
Hygiene hypothesis
Increasing incidence is due to improved food storage condition, decreased food contamination, and changes in gut microbiome composition
Why do people with IBD have reduced frequency of enteric infection
Inadequate development of mucosal immune regulation
IBD helminth
Helminth infections may prevent development
Pathogenesis IBD
Altered host integration with intestinal microbiota
Intestinal epithelial dysfunction
Aberrant mucosal responses
Altered composition of gut microbiome
Genetic influences are stronger in Crohn’s disease than in ulcerative colitis
IBD mucosal immune response
T helper cells polarized to TH1 types
TH17 cells with IL23 receptor polymorphisms have a reduced risk of crohns and ulcerative colitis
Mutations or proinflammatory cytokines: TNF, IFNy, IL13
Mutations of immunoregulatory molecules leads to severe, early onset of disease: IL10, TGFb
Antibodies against flagellin==Crohn’s disease
-uncommon in ulcerative colitis
Crohn’s disease
Transmural inflammation that involves any area of the GI tract
With intermittent signs and symptoms that may be brought on by social or environmental factors (smoking)
Genetics crohns
Genes related tot he response of mycobacterium
NOD2 polymorphism: NFKB activation affected
ATG23l2 and IRGM can also be involved
Epithelial defects crohns
Epithelial tight junction Barriers are defective due to NOD2 polymorphism
Crohn’s disease: _% involve small intestine, _% colon, _% both
40
30
30
Skip lesions crohns
Separate, sharply delineated disease areas with granular and inflamed serose and adherent creeping mesenteric fat
Bowel crohns
Wall is thick and rubbery
Crohns strictures
Present in crohns and not in ulcerative colitis
Crohns punched out aphthous ulcers
That coalesce into axilla oriented serpentine ulcers
Crohns cobblestone appearance
Sparing of interspersed mucosa with disease tissue that is depressed
Fissures and fistula crohns
Yup
Microscopic morphology crohns
Mucosal inflammation and ulceration with intraepithelial neutrophils and crypt abscesses
Creeping fat
Chronic mucosal damage with villus blunting , atrophy, pseudo-pyloric or paneth cell metaplasia and architectural disarray
-paneth cell metaplasia may occur in the left colon where paneth cells are normally absent
Transmural inflammation with lymphoid aggregates in submucosa, muscle wall and subserosal fat
Noncaseating granulomas throughout the gut, even in uninvolved segments
Cutaneous granulomas misnamed metastatic crohns
Presentation crohns
Present with intermittent attacks of diarrhea, fever, and abdominal pain (may be rlQ like appendix)
With asymptomatic periods that may last weeks-months
Malabsorption, malnutrition, hypoalbuminemia, iron deficient anemia, +/- B12 defiency may occur
Disease onset of Crohns is associated with initiation
Smoking
With Crohns, __ _ are common and need to be respected
Fibrosis strictures
Crohns extra intestinal
Migratory polyarthritis, sacrolitis, ankylosis spondylitis, erythema nodosum, uveitis, cholangitis, amyloidosis, finger clubbing
Crohns have increased risk of developing what
Adenocarcinoma in patients with longstanding colon involvement
Why can crohns lead to obstruction
From strictures
Crohns have antibodies to what
Saccharomyces cerevisiae***
Treat crohns
Immunosuppression
Surgical resection of fibrotic strictures/fistulae to adjacent viscera, abdominal or perineal skin, bladder or vagina and can recur at site of anastomsis
Ulcerative colitis
Inflammatory disease limited to the colon and rectum
Affects only the mucosa and submucosa
Epithelial defects in ulcerative colitis
ECM1 normally inhibits MMP9 to reduce severity of disease
HNFA associated with reduced intestinala barrier function
Skip lesions ulcerative colitis
No
What does ulcerative colitis involve
Left colon and rectum (retrograde involvement: pancoliitis)
Distal ileum may show some inflammation (backwash ileitis)
In ulcerative colitis, extensive broad based ulcers that are aligned along the long axis of the ___
Colon
Mucosa in ulcerative colitis
Reddened, granular, and friable with inflammatory pseudopolyps and easy bleeding
Ulcerative colitis pseudopolyp
Isolated islands of regenerating mucosa that often bulge into the lumen
Tips can touch each other and create mucosal bridges
Ulcerative colitis morphology
Crypt abscess, ulceration, chronic mucosal damage, glandular architectural distortion and atrophy
No thickening, strictures, fissures, or granulomas
Complication ulcerative colitis
Inflammation can lead to damage in the muscularis propria and disturb neuromuscular function which leads to colonic dilation and toxic megacolon (high risk perforation)
-
30% ulcerative colitis require __ within 3 years which cures intestinal disease but extra GI symptoms remain
Colectomy
Ulcerative colitis have increased risk of what
Colonic adenocarcinoma
Clinical presentation ulcerative colitis
Intermittent attacks of bloody diarrhea with stringy, mu oil material and abdominal pain that persists days-months before subsiding
What may trigger initial onset of ulcerative colitis
Infectious enteritis, psychological stress,or cessation of smoking
___ may partially relieve symptoms ofof UC
Smoking
Extra-intestinal UC
Migratory polyarthritis, sacrolitis, ankylosis spondylitis, uveitis, skin lesions, primary sclerosis cholangitis
Indeterminate colitis diagnosis
Definitive diagnosis is not possible in 10% of patients due to clinical overlap
-used for cases of IBD without definitive features of either ulcerative colitis or crohn disease
Indeterminate colitis do not involve the small bowel and have colonic disease in a continuous pattern (__)
UC
Risk of interminate colitis
Patchy histologic disease, fissures, family history of crohns, perinatal lesions, onset after initiating use of cigarettes
Peri-nuclear anti-neutrophil cytoplasmic antibodies
75% of individuals with ulcerative colitis
11% with crohns
Overlap of clinical management of UC vs crohns is __ therefore these people will be just fine
Minimal
Colitis associated neoplasia (carcinoma)
Long term complication of IBD that depend on
Duration>8-10 yrs
Extend of disease: pancolitis>those with only left sided disease
Greater frequency and severity of active infalmmation (presence of neutrophils)
Surveillance colitis associated neoplasia
8 years after diagnosis, immediately if co diagnosed with primary sclerosing cholangitis
Colitis associated neoplasia classification
Low or high grade
High grade colitis associated neoplasia
Prompt colectomy because associated with invasive carcinoma at the same site or elsewhere in the colon
Low grade colitis associated neoplasia
May be treated with colectomy of closely followed based on age, foci
Diversion colitis
Complication of ostomy and blind distal segment of colon from which normal fecal flow is diverted
Develops in the diverted segment , particularly in UC patients
Morphology diversion colitis
Development of numerous mucosal lymphoid follicles
Diversion colitis treat
Enemas containing short chain fatty acids (product of bacterial digestion int he colon and an important energy source for colonic epithelial cells) promotes mucosal recovery
Cure diversion colitis
Re-anastomosis
Microscopic colitis
Chronic, nonbloody, watery diarrhea without weight loss
What are the two types of microscopic colitis
Collagenous colitis
Lymphocytic collitis
Demographic and characteristic of collagenous colitis
Middle aged and older women
Dense, subepithelial collagen layer, increased numbers of intraepithelial lymphocytes and mixed inflammatory infiltrate within the lamina propria
Lymphocytic colitis characteristic and associated
Subepithelial layer is of normal thickness and the increase in intraepithelial lymphocytes is greater, frequently exceeding ont T cell per five colonocytes
Celiac disease and autoimmune disease (graves, RA, autoimmune or lymphocytic gastritis
GVHD occurs after what
Following hematopoietic stem cell transplantation
Why does GVHD occur
Why does GVHD occur
Donor T cells targeting antigens on the recipients GI epithelial cells
GVHD lamina propria lamina propria lymphocytic infiltrate is sparse
Ok
What is the most common histological feature of GVHD
Epithelial apoptosis of crypts cells
GVHD most common symptoms
Watery diarrhea but also may be bloods
Sigmoid diverticulum disease
Refers to small acquired
Sigmoid diverticulum disease
Small, acquired pseudo-diverticulum, flask like outpouchings of the colonic mucosa and submucosa
Where does sigmoid diverticula occur
Along taeniae coli
Most common in the sigmoid colon
Colonic diverticula are often multiple and the condition of having them is called ___
Diverticulosis
Diverticulitis
When they become inflamed and irritated
Where are sigmoid diverticulum uncommon
Japan and developing coutnries due to diet
Where do sigmoid diverticula occur
Western coutnries
Pathogenesis sigmoid diverticula
Inherent structure of colonic muscularis propria+elevated intraluminal pressure in the sigmoid colon
-most often, the muscularis proporia is absent
Increased intraluminal pressure due to exaggerated peristaltic contractions, with spasmodic sequesteration of bowel segments
Manage sigmoid diverticula
Eat more fiber->increased stool bulk
Resolves spontaneously and few patients require intervention
Clinical sigmoid diverticula
Intermittent cramping
Continuous lower abdominal discomfort
Constipation
Distention
Sensation of never being able to completely empty rectum
Alternating constipation and diarrhea that can mimic IBS
Treat sigmoid diverticula
High fiber
Polyps
Masses that protrude into the colorectal region (or esophagus, stomach, SI)
How do polyps begin
As elevationsof mucosa
Sessile
Lacking a stalk
Pedunculated
Has a stalk
Non neoplastic
Inflammatory, hamartin atoms, hyperplastic
Most common polyp
Neoplastic adenoma
Hyperplastic polyps
Bening epithelial proliferation’s with no malignant potential
Why get hyperplastic polyps
Piling up of goblet and absorptive cells due to decreased epithelial cell turnover and delayed shedding
Can also occur adjacent to or overlying other lesions tat may be clinically important
When get hyperplastic polyps
6th-7th decade
Hyperplastic polyps are histologically similar to __ __ __ but are not potentially malignant
Sessile serrated adenomas
Morphology hyperplastic polyps
Most common left colon
Multiple
Smooth, nodular protraction often on crests of mucosal folds
Mature goblet+absorptive cells
Serrated surface architecture typically restricted to the upper 1/3 of the crypt
Inflammatory polyps triad
Rectal bleeding, mucus discharge, inflammatory lesion on the anterior rectal wall
Inflammatory polys are from
Chronic injury and healing
Inflammatory polys: how damage rectal mucosa
Sharp angle of the anterior rectal shelf with impaired relaxation of the anorectal sphincter
Mucosal prolapse : inflammatory polyps
Entrapment by fecal stream
Morphology inflammatory polyps
Mixed inflammatory infiltrates, erosiona nd epithelial hyperplasia+lamina propria fibromuscular hyperplasia
Hamartomatous polyps
Occur sporadically or as a component of a genetic syndrome
Many are due to germline mutation in tumor suppressor genes or Porto oncogenes
Risk of what with hamartomatous polyps
Cancer, so many are considered precancerous lesions
Symptoms hamartomatous polyps
Extra intestinal symptoms
Genetics hamartomatous polyps
Yea family members effected
Juvenile polyps
Focal hamartomatous malformations of small intestine and colon mucosa
Who gets juvenile polyps
Children <5 who present with rectal bleeding
Where are most juvenile polyps
Rectum
Genetics juvenile polyps
Sporadic:solitary lesion
AD-3-100 polyps may require colectomy to limit hemorrhage
Juvenile polyps sequelae
Polyps in stomach and small bowel that can undergo malignant transformation which may lead to clubbing
Morphology juvenile polyps
Pedunculated, smooth surfaced, reading lesions with cystic spaces
Cysts are dilated and filled with mucin and inflammatory debris
Mucosal hyperplasia may be initiating event
Most common mutation is in SMAD4 which affects TGFb signaling
30-50% develop colonic adenocarcinoma by age 45 if they have juvenile polyposis syndrome
What is juveniles polyposis syndrome
Dysplasia is present -extremely rare if sporadic
What are people with juvenile polyposis syndrome at risk for
30-50% get colonic adenocarcinoma by 45
Peutz-jeghers syndrome inheritance
Rare AD pattern of inheritance is common between peutz jeghers syndrome and familial adenomatous polyposis
What is peutz jeghers syndrome
Multiple GI hamartomatous polyps and mucocutansous hyperpigmentation
Dark blue brown macules onthe lips, nostrils, buccal mucosa, palmar hand, genitalia and perinatal region
-similar to freckles but no freckles on buccal mucosa
Age peutz jeghers syndrome
11
Risk of peutz jeghers syndrome
Several malignancies
Sequelae peutz jeghers syndrome
40% increased lifetime risk of malignancies
-100% guarantee to get malignancy in FAP-prophylactic colectomy
Screen neonates for sex cord tumors of testes
Screen in late childhood for gastric and small intestine cancers
Screen in 2-3 decades for colon, pancreatic, breast, lung, ovarian and uterine cancers
May initiate intussusception
Morphology peutz jeghers syndrome
50% have heterozygous STK11 loss of function mutation
-lack of STK11 mutations does not exclude the diagnosis of peutz jeghers syndrome
Arborizing polyps:small bowel.colon, stomach
Polyps are large, pedunculated and lobulated with arborizing smooth msucle, CT, glands and lamina propria lined by normal epithelium
Diagnosis peutz
Multiple polyps in small intestine, mucocutaneous hyperpigmentation, and a positive family history
Detection of STK11 mutations can be helpful in patients without mucocutaneous hyperpigmentation
The pigment is melanin
Neoplastic polyps
Any cancer in he GI tract can produce a polyp
Most common neoplastic polyps
Colonic adenomas which are precursors to colorectal adenomas which are precursor to colorectal adenocarcinomas
Name some other neoplastic polyps
Adenocarcinoma, neuroendocrine, stromal, lymphomas, etastatic
Adenomas
Intraepithelial neoplasm ranging from small, pedunculated polyps to large, sessile lesions
Adenomas are found in 30% of adults at age ___ in western world
60
Symptoms adenoma
Usually silent
Adenomas are associated with __ diet
Western
Characterization colorectal adenoma
Presence of epithelial dysplasia
Adenoma: what is epithelial dysplasia
Benign precursor lesions
Do adenomas always progress to adenocarcinoma
No
How can you tell whether an adenoma will progress to adenocarcinoma
No markers to tell
What are large adenomas associated with
Occult bleeding and anemia
What are villous adenomas associated with
Cause hypo proteinemic hypokalemia due to secretion of protein and potassium
Morphology adenoma
Pedunculated or sessile with a velvet or raspberry surface
Hallmark of epithelial dysplasia=hyperplasia, nuclear hyper-chromasia, loss of polarity-epithelial cells fail to mature as they migrate from crypt to surface
Tubular, tubulovillous, villous
Adenomas are connected to submucosa by what
Thin vascular wall
What is the most important characteristic correlating with risk of malignancy of adenomas
Larger size=cancer
Higher degree of dysplasia=cancer
Sessile serrated adenomas
Full length exhibits serrated architecture, with crypt dilation and lateral growth
Despite malignant potential, typical dysplastic changes seen in other adenomas is absent-similar to hyperplastic polyps
Found more commonly in the right colon
Where are sessile serrated adenomas most commonly found
Right colon
Intramucosal carcinoma
Occurs when dysplastic cells invade the lamina proporia or muscularis mucosa
Little or no metastatic potential due to lack of lymphatic channels in colonic mucosa
Complete polpectomy==curative
Invasive adenocarcinoma
Crosses into the submucosa and accesses lymphatics
Risk of metastases is
Familial adematous polyposis (FAP)
Autosomal dominant , APC mutation (negative regulator of WNT)
Numerous colorectal adenomas develop as a teenager
-morphologically indistinguishable from sporadic adenomas except in terms of number
Colorectal adenocarcinomas develop in __% of untreated FAP patients, often at <30 years and always by 50
100
Prophylactics FAP
Prophylactic colectomy to prevent colorectal cancer
FAP associated with what
Increased risk of neoplasia at other sites (ampulla of vater, stomach)
Gardner and turcot syndromes
FAP is morphologically indistinguishable from __ __
Sporadic adenomas
FAP extra intestinal
Congenital hypertrophy of retinal pigment epithelium (detected at birth)
FAP with no APC mutation
Biallelic mutations of MYH( base excision repair gene)-MYH associated polyposis:polyps develop later, have <100 adenomas and acquire colonic aner at <50 years
Serrated polyps with KRAS mutations are often present
Which characteristic of an adenoma is the most oimportant that correlated with risk of malignancy
Polyp size -4cm is thresholds
Hereditary non polyposis colorectal cancer
AD
Most common syndromic form of colon cancer
Get clusters of cancer that develop at different sites throughout the body
-colorectal, endometrium, stomach, ovary, ureters, brain, small bowel, hepatobiliary tract, pancreas and skin
Age hereditary polyposis
Under 50
Location of hereditary non polyposis colorectal cancer
Right colon
Genetics HNPCC
Inherited mutation in genes that encode proteins responsible for the detection, excision and repair of errors that occur during DNA replication
Mutations in MSH2 or MLH1 (mismatch repair)
Colonic adenocarcinoma
Most common malignancy of the GI tract
Colonic adenocarcinoma is responsible fo r_% of all cancer deaths
10
In the USA colonic adenocarcinoma is the _ most common cause of cancer death
2nd
Age colonic adenocarcinoma
60-70
Younger in HNPCC and FAP
Risk factors colonic adenocarcinoma
Diet: change of GI flora and synthesis of carcinogenic byproducts which have prolonged contact with intestinal mucosa due to decreased stool bulk
Decreased vegetable fiber
Increased refined carb diet
NSAIDS: protective effect via COX2
Colonic adenocarcinoma COX2
COX2 is overexpressed in 90% of colorectal carcinomas and 40-90% of adenomas
COX2 expression is regulated by TLR4; TLR4 is also overexpressed in adenomas and carcinomas
Genetics colonic adenocarcinoma genetics
APC/B catenin pathway
Microsatellite instability due to defects in DNA mismatch repair
CpG island hypermethylation phenotype
Increased CpG is all methylation int he absence of microsatellite instability
APC/B catenin pathway
80% sporadic colon tumors
Key - regulator of B catenin, a component of WNT signaling
Loss of APC-> B catenin accumulates->translocates to the nucleus->does gene transcription (MYC and cyclin D1)->cell proliferation->cancer
Can still have cancer in the presence of wild type APC when B catenin is constituitively active
Chromosomal instability is a hallmark of APC/B catenin pathways
Colonic adenocarcinoma microsatellite instability due to defects in DNA mismatch repair
TGF-B:inhibits colonic epithelial cell proliferation
BAX: pro apoptotic
Colonic adenocarcinoma CpG island hypermethylation phenotype
Microsatellite instability
MLH1 is hypermethylated
Activating mutations of BRAF oncogene
KRAS and TP53 are not mutated
Colonic adenocarcinoma increased CpG island methylation in the sbsence of microsatellite instability
KRAS is mutated
TP53 and BRAF mutations are uncommon
Colonic adenocarcinoma __ distribution throughout colon
Equal
Colonic adenocarcinoma proximal colon
Polypoid, exophytic masses that rarely cause obstruction
Colonic adenocarcinoma distal colon
Annular masses with napkin ring obstruction, lumen narrows , often to the point of obstruction
Morphology colonic adenocarcinoma
Tall, columnar cells resembling adenomatous neoplastic epithelium with invasion into usubmucosa, muscularis propria or beyond
Strong desmoplastic response which makes them firm
Penetrate the bowel wall over the course of many years
Glands may be scarce or abundant, producing excess mucin
(Worse prognosis)
Tumors may have signet ring cells or show neuroendocrine differentiation
Prognosis colonic adenocarcinoma
Depth of invasion==histological feature that most significantly affects prognosis w
Righ sided colonic adenocarcinoma presentation
Fatigue and weakness due to iron deficient anemia
Older males or postmenopausal females with iron deficient anemia have this diagnosis until proven otherwise
Left sided colorectal adenocarcinoma presentation
Can produce occult bleeding, changes in bowel habits or cramping and LLQ discomfort
What is the most important prognostic factor of colonic adenocarcinoma
Depth of invasion and presence of lymph node metastases
Colonic adenocarcinoma and muscularis proporia invasion
Decreased survival
With colonic adenocarcinoma, metastases is most common to where
Liver, then lymph nodes ,lung, bone
Not rectum which does not drain via portal circulation
Prognosis colonic adenocarcinoma
5 year survival 65%
Patient with what presentation have colorectal cancer until proven otherwise
Older populations with blood loss/anemia and unintentional weight loss
Anal canal: upper 1/3
Columnar rectal epithelium
Glandular carcinoma
Anal canal: middle 1/3
Transitional epithelium
Cloacogenic carcinoma=basaloid tumors populated with immature cells from the basal layer of transitional epithelium
-basaloid pattern may be mixed with squamous or mucinous differentiation
Anal canal lower 1/3
Stratified squamous epithelium
Squamous carcinoma
Pure squamous cell carcinoma of this region is often associated with HPV infection which can cause precursor lesions (condylomata acuminatum ‘anal warts’)
Hemorrhoids
Not a medical emergency
Varices dilation of anal canal and perinatal submucosal venous plexuses
Associated with constipation (straining), venous stasis in pregnancy and cirrhosis (portal HTN)
Secondary thrombosis (with recanalization), strangulation or ulceration with fissure formation can occur
Treat hemorrhoids
Sclerotherapy, rubber band ligation, infrared coagulation, surgery
External hemorrhoids
Occur with ectasia of the inferior hemorrhoids plexus below the anorectal line
Extremely painful
These are portal-canal anastomoses, indicative of hepatic pathology
Internal hemorrhoids
Occur with actasia of superior hemorrhoids plexus above the anorectal line
Generally painless
These are from staining
Acute appendicitis
Initiated by progressive increases in intraluminal pressure that compromise venous outflow
Usually due to obstruction of the lumen by stool, tumor, or worms that increase intraluminal pressure
What does acute appendicitis cause
Bacterial proliferation, ischemia, and inflammatory response leads to tissue edema and neutrophilic infiltration of the lumen , muscle wall and peri-appendiceal soft tissues
Morphology acute appendicitis
Serosa is dull, granular and red neutrophilic infiltration of the muscularis propria-suppurative
Severe neutrophilic infiltration: fibrniopurulent esrosal exudate, luminal abscess formation, ulceration and suppuratove necrosis
Can progress to acute gangrenous appendicitis followed by perforation (suppurative peritonitis)
Clinical acute appendicitis
Periumbilical pain migrating to RLQ , nausea, vomiting, abdominal tenderness (Mcburney), mild fever, leukocytosis
Children and elderly more likely to have abnormal presentation
Complications acute appendicitis
Pyelophlebitis, portal vein thrombosis, liver abscess, bacteremia
Perforation has high morbidity
Carcinoid tumor
Well differented neuroendocrine tumor
Most common tumor of the appendix
Usually benign often incidental finding
Morphology carcinoid tumor
Solid bulbous swelling at the distal tip of the appendix that can reach 2-3 cm in diameter
Nodal metastases are infrequent
Distal spread is extremely rare
Mucocele
Dilated appendix filled with mucin
Mucocele presntation
May simply represent an obstructed appendix containing inpissaated mucin or be a consequence of:
Mucinous cystadenoma
Mucinous cystadenocarcinoma->invasion through appendices wall->intraperitoneal seeding->pseudomyxoma peritonei
Peritonitis
Inflammation of the membrane lining the abdominal wall and covering the abdominal organs
May be due to bacterial infection or chemical irritation or perforation of abdominal viscera
Sterile peritonitis
Irritation of the peritoneum due to leakage of bile or pancreatic enzymes
Perforation or rupture leads to highly irritating peritonitis that is often complicated by bacterial superinfection
Acute hemorrhagic pancreatitis-peritonitis
Leakage of pancreatic enzymes and fat necrosis allows bacterial to spread to the peritoneal cavity
Foreign material-peritonitis
Irritation of the peritoneum due to objects introduced surgically (talc, sutures, watches) that can induce a foreign body type granuloma and fibrous scarring
Endometriosis-peritonitis
Irritation of the peritoneum due o hemorrhage into the peritoneal cavity
Ruptured dermoid cyst-peritonitis
Irritation of the peritoneum due to release of keratinize which induce an intense granulomatous reaction
Peritoneal infection
Perforation of GI structures releases bacteria into the peritoneal cavity
Spontaneous bacterial peritonitis develops in the absence of an obvious source of contamination
- seen most often in patients with cirrhosis and ascites
- seen less frequently in children with nephrotic syndrome
Common bugs of peritoneal infection
E. coli Streptococci Staph aureus Enterococci Clostridium perfringens
Morphology peritoneal infection
Peritoneal membranes become dull and grey, followed by exudative and frank suppurations
Localized abscesses can develop
Inflammation tends to remain superficial
Sclerosing retroperitonitis (idiopathic retroperitoneal fibrosis, or Mongolian disease)
Characterized by dense fibrosis that may extend to involve the mesentery
Cause is unknown (idiopathic)
Frequently compresses the ureters
Peritoneal tumors
Primary are rare
Meothelioma
Asbestos exposure
Desmoplastic round cell tumor
Kids and young adults
-aggressive tumor
-bears resemblance o Ewing sarcoma and other small found cell tumors
Characterized by a reciprocal translocation t(11;220(p13;q12) resulting in fusion gene EWS-WT1
Secondary peritoneal tumor
Secondary from direct spread or seeding leads to peritoneal carcinomatosis
Mucinous carcinoma (of appendix)
Can cause pseudomyxoma peritonei
All peritoneal tumors prognosis
All malignant and have poor prognosis
