Round 2 Flashcards
Initial upper GI bleed management
Remember ABC’s
Airway?
CPR?
IV access
At least 2 large bore IVs
Infusion
Crystalloid
Blood products
Varices
Presentation: Dramatic bleeding, usually hematemesis
Causes: Portal hypertension
Associated with: Liver disease/cirrhosis
Treatment: Octreotide or Vasopressin Proton Pump inhibitor Non-selective Beta-blocker Variceal band ligation
Responsible for tolerance
Treg cells
NSAIDs and Peptic Ulcer Disease
Direct injury effects
Systemic effects
COX inhibition and prostaglandin production
Prostaglandins in the gut regulate mucus secretion and basal bicarbonate secretion
Prostaglandins are trophic for gastric epithelia and play role in feedback inhibition of gastric acid secretion
COX-2 selective inhibitors still pose risk for PUD
Intraepithelial Barrier
Intraepithelial Lymphocytes (IEL) promote barrier repair and are rapidly recruited Majority of IELs express CD8 (recognize MHC class I Ag) Two types of TCR αβ, thymus derived γδ, non-thymic derived 15% of small intestine IEL 40% of colonic IEL Produce keratinocyte growth factor
Lamina Propria
Reservoir to 70-80% total lymphocytes Predominate T cells are CD4, recognize MHC class II Ag
M Cells
Some bacteria and viruses cross the epithelial barrier via M Cells
α-Defensin
Neutrophils, NK cells, Paneth cells
β-Defensin
Leukocytes and Epithelial cells
Paneth Cells
Small intestine is lined with villi interspersed with Crypts.
Paneth cells harbor pro-defensin 5
Degranulation occurs following bacteria penetration
Type 1 Interferons
(IFN-α/β)
Induces MHC Class I expression
Kill Infected Host Cell
Natural resistance-associated macrophage proteins
remove mn to starve bacteria
Calprotectin
Broad spectrum scavenger of divalent cations is Calprotectin, S100 protein that sequesters Ca, Fe, Zn and Mn
Lipocalin
remove lipids to starve bacteria
indoleamine 2,3-dioxygenase
Tryptophan removal to starve bacteria
anti-inflammatory mediators
IL-10, IL-1ra
pro-inflammatory mediators
IFN-gamma, TNF-alpha, IL-12
TH1 Lymphocytes
Acute Inflammation
IFN-γ
Acute Inflammation
M-1 Macrophage
Acute Inflammation
IgG
Acute Inflammation
sIgA
Acute Inflammation
CTL cells
Acute Inflammation
NK cells
Acute Inflammation
TH2
Chronic Inflammation
TH17 Lymphocytes
Chronic Inflammation
IL-4
Chronic Inflammation
IL-17
Chronic Inflammation
M-2 Macrophage
Chronic Inflammation
IgE
Chronic Inflammation
Eosinophils
Chronic Inflammation
Basophils
Chronic Inflammation
secretory diarrhea
characterized as an infection of the proximal small bowel marked by watery diarrhea that does NOT contain fecal leukocytes. Viruses that cause gastroenteritis do not infect the colon
Rotavirus Clinical presentation:
gastroenteritis
Norwalk Virus (Norovirus) Clinical presentation:
gastroenteritis
Adenovirus Clinical presentation:
gastroenteritis (do not confuse with other serotypes of adenoviruses that cause respiratory tract infections)
Rotavirus Pathology:
transmitted via the fecal to oral route. After ingestion of the virus it travels in the GI tract (the virus particle is stable within the low pH of the gastrointestinal system) to eventually infect the villus cells of the proximal small intestine. Here the virus replicates within these cells eventually lysing these cells which leads to the impaired adsorption of carbohydrates and other nutrients. This can lead to vomiting followed by watery diarrhea.
Norwalk Virus (Norovirus) Pathology:
fecal to oral transmission usually through direct contact or through contaminated food and water. Causes a local infection and inflammation in the proximal small intestine.
Adenovirus Pathology:
fecal to oral transmission. Causes a local infection and inflammation in the proximal small intestine. If inhaled into the lungs some respiratory symptoms can be present.
Rotavirus Diagnosis:
stool specimen, serology for the virus. Electron microscopy and RT-PCR also possible.
Norwalk Virus (Norovirus) Diagnosis:
not typically done. When done it is through visualization of the virus in stool specimens or PCR/serology of stool and/or vomit specimens.
Adenovirus Diagnosis:
PCR detection of the viral genome within a stool sample
Rotavirus Treatment:
rehydration (supportive). There is a rotavirus vaccine (live oral attenuated).
Norwalk Virus (Norovirus) Treatment:
usually not required because it is self-limited. When done, treatment consists of rehydration (supportive) if there is severe fluid loss. Outbreaks can be minimized through proper food handling, clean water supplies, and hand washing.
Adenovirus Treatment:
self-limiting infection in immunocompetent individuals. Supportive care only.
Rotavirus
because rotaviruses cause no inflammation, diarrhea has no blood. Infection before 6 months of age is uncommon due to passive IgA immunity from the mother’s colostrum. However, by age 3, almost every individual worldwide (~95%) has been infected and develops lifelong immunity. Virus particle contains a double-layered capsid.
Norwalk Virus (Norovirus)
this virus is a major cause of group-related or institutional diarrhea.
Adenovirus
major cause of acute infantile gastroenteritis. These serotypes of adenoviruses rarely cause fever or respiratory tract symptoms.
bifidobacteria
are among the first colonizers in breast-fed infants
Staphylococcus aureus
Gram +CocciCatalase +Coagulase +Also a common infectious agent of surgical wounds and cause of scalded skin syndromein food that sits around for a whileno need for antibiotics for a food borne infection
Bacillus cereus
Gram +Large Bacilliendospore-formingFacultative anaerobeMostly motileβ hemolytic Box-car shaped Also frequently found on skin and is a threat in hospitals as it produces biofilms that adhere easily to invasive devices. This produces chronic persistent infection, as the biofilm can periodically release B. cereus into the bloodstreamB. Cereus spores are commonly found in the soil and sometimes in plant foods that are grown close to the ground – such legumes, cereals, spices etc..Spores can survive rice cooking processDuration for both only about 24 hrsBecause of its ubiquity, B. cereus often is ignored or dismissed as a contaminant when found in a culture specimen. B. cereus in food and vomitus or feces of same serotype Large numbers of B. cereus of serotype known to produce endotoxinOnly necessary when tracking outbreaks
Clostridium botulinum
Gram +BacilliSpore-formingObligate anaerobeMotileSpores or toxin are the important issues for transmission of botulism
Staphylococcus aureus Symptoms:
Symptoms:nausea, vomiting, stomach cramps, and diarrhea for 1-3 daysAppear 1-7 hrs following ingestion of foodSelf-limiting, once toxin is gone, illness is gone
Staphylococcus aureus diagnosis
Positive diagnosis:Toxin-producing S. aureus can be identified in stool or vomitMost conclusive test is the linking of an illness with a specific food, or in cases in which multiple vehicles exist, detection of pre-formed enterotoxin in food sample(s).Only necessary when tracking outbreaks
Bacillus cereus infection
Infection takes two forms:Emetic (vomiting):Diarrheal:Duration for both only about 24 hrs
Bacillus cereus Emetic infection
Emetic (vomiting):1 to 6 hours incubationNausea and vomitingresembles the vomiting illness caused by Staphylococcus aureus enterotoxinsCaused by preformed enterotoxin that forms holes in membranesSelf limiting
Bacillus cereus Diarrheal infection
Diarrheal:6-15 hours incubationclinically similar to the symptoms of Clostridium perfringens infectionWatery diarrhea and abdominal crampsMechanism: Caused by large molecular weight enterotoxin that causes intestinal fluid secretion, probably by several mechanismsThis toxin is not likely pre-formed!Ingestion of large amounts of bacteria cause it to generate the toxin in the small intestineVulnerable populations might get sicker and require antibioticsPoor outcomes for systemic infection
Bacillus cereus diagnosis
Because of its ubiquity, B. cereus often is ignored or dismissed as a contaminant when found in a culture specimen. B. cereus in food and vomitus or feces of same serotype Large numbers of B. cereus of serotype known to produce endotoxinOnly necessary when tracking outbreaks
Botulism
Food borne botulism: ingesting toxinWound botulism: producing toxin Infant botulism: ingested sporesNot really a GI illness, diarrhea not prominent
Botulism Diagnosis
Symptoms and history, results of physical exam indicate botulismTests to exclude other causes of the illnessOrganism or toxin in stool sample only indirect evidence
Treatment for foodborne botulism
Ventilator if respiratory failure and paralysisAntitoxin if paralysis is not yet completeRemove contaminated food if still likely in gut
Botulism toxin
neurotoxinirreversibly blocks the release of acetylcholine from the motoric end plate which results in muscle weakness and paralysisToxin is absorbed from GI tract to bloodstream
Symptoms, botulism
Toxin already produced, symptoms can begin when toxin hits GI tractdouble vision, blurred vision, drooping eyelids, slurred speech, difficulty swallowing, dry mouth, and muscle weakness
Symptoms, infant botulism
Incubation period, spores have to produce toxin-forming bacterialethargic, feed poorly, are constipated, and have a weak cry and poor muscle toneCan lead to paralysis of respiratory system and other muscles
Clostridium perfringens
Gram +BacilliSpore-formingObligate anaerobeNon-motileEnterotoxin binds to receptors in endothelial cell junctions, then generates pores in host mucosa cells.“C. perfringens infection often occurs when foods are prepared in large quantities and kept warm for a long time before serving”
Clostridium perfringens Symptoms
Symptoms:Diarrhea and abdominal crampsIncubation 6 to 24 hours (typically 8-12)Symptoms last for less than 24 hoursUsually NO fever or vomitingThe illness is not passed from one person to another
Clostridium perfringens Positive diagnosis
Positive diagnosis:Detection of toxin or high amounts of bacteria in fecesC. perfringens normally present in the GI tract, the problem is when you ingest a C. perfringens load high enough to produce enough toxin to generate symptoms
Clostridium perfringens Treatment
Treatment:Usually self-limiting, but more serious, longer-lasting cases in immunocompromised individuals should be treated to avoid complications
Campylobacter jejuni
Gram -Bacilli (Spirilli)microaerophilicMotileCold sensitive (often leads to false negatives)get it from poultryOne unique feature is that campylobacter cannot usually multiply in food.Symptoms:diarrhea, cramping, abdominal pain, and fever2-5 day incubationSymptoms can last a weekCan have vomiting, diarrhea can be bloodyMechanism: Symptoms are an inflammatory response to cell invasionPositive Diagnosis: stool culturePossible complication: Guillain-Barré syndrome
Salmonella enterica
Gram -BacilliNon spore formingH2S positive & lactose negativeMotile, flagellated
Salmonellosis
Symptoms:diarrhea, fever, and abdominal cramps 12 hr to 3 day incubationSymptoms typically last 4 to 7 daysMost persons recover without treatmentRemember: reactive arthritis as a possible complicationDiagnosis: we know for sure with a stool cultureTreatment: Hydration. Antibiotics only necessary if infection spreads beyond gut
Vibrio parahaemolyticus
Gram (-)Vibrio (curved rod)facultative anaerobesFlagellated, motileOxidase +water lovingDiagnosis: Vibrio may be isolated from cultures of stool, wound, or blood. Form pores in red blood cells but also in epithelial cells, disrupting gut homeostasissushi and shellfish
Vibrio parahaemolyticus Symptoms
Fairly mild bloody diarrhea, stomach cramps, fever, nausea, and/or vomiting, Symptoms last less than a week. In the immunocompromised, it can spread to the blood and cause serious or deadly infections in other parts of the body
Listeria monocytogenes
Gram positive rod-shaped bacteriaAlthough a rare illness, a leading cause of death by foodborne illnessGram (+)BacillusNon-fastidious!!!Flagellated, motileNon spore formingOxidase -Diagnosis: Stool sample ID inappropriatePositive ID is the bacterium found in a normally sterile siteImmune cells spread Listeria to other organsTrojan horseLiver is a major targetmilk, cheese, seafood, deli
Listeriosis
Mild GI infection for mostMore vulnerable are older adults, pregnant women, newborns, and adults with weakened immune systems OPPORTUNISTICFever and muscle aches or stiff neck, or if you develop while pregnant: fever and chillsMeningitis and sepsis in vulnerable populations
Shigella
Gram (-)BacillusFacultative anaerobenonmotile (distinguishes from e. coli)Non spore formingMainly lactose negative, H2S (-) (distinguishes from e. coli)Shigella sonnei: most Shigella-caused GI illnessesShigella flexnori: causes bacillary dysenteryShigella dysenteriae: rarest but most severe dysenteryinvade through m cellsSince Shigella is invasive, if not treated it can spread beyond the GI tract and cause complicationsAntibiotics for more severe cases, most usually resolve without antibioticsPossible complication: hemolytic uremic syndrome (HUS)
What is dysentery
Frequent, small bowel movements with blood and mucus, accompanied by rectal pain and spasms (tenesmus)
Shigella Transmission
Transmission: Mostly bacterium passing from stools or soiled fingers of one person to the mouth of another person.
Shigella Symptoms:
Symptoms: diarrhea (often bloody)feverstomach crampsSymptoms start 1-2 days following exposureUsually resolves in 5 to 7 days.
E. coli
Gram (-)BacillusFacultative anaerobemotileNon spore formingMainly lactose positiveDiarrheaUrinary tract infectionNeonatal sepsisGram-negative sepsisETECSTECTreatment: antibiotics generally not recommended (decaying bacteria release toxins)Tracking outbreaks: commercial PCR and antibody-based kits.
ETEC
Traveler’s Diarrhea, diarrhea in childrenactivates adenylate cyclase, end result water into lumen, NO bacterial penetration.
STEC
penetrates like Shigilla toxin. hemorrhagic colitis (HC) and/or HUS can result as a complication; children more vulnerable
E. coli Symptoms:
profuse watery diarrhea and abdominal crampingCan progress to bloody diarrhea for STECFever, chillsNausea with or without vomiting, loss of appetiteLess common: headache, muscle aches and bloatingIncubation:1-3 days ETEC, 3-8 for STEC Illness typically lasts 3-4 days, less than 10.
cholera toxin
Activates adenylate cyclase cAMP → Na+ absorption, Cl- excretionWater moves into lumen
typhoid fever
Only fecal-oral contaminant, no other host, so water is a big source of contaminatonDrinking water, unwashed fruits/veggiesTravelers are vulnerableVaccine availableLife-threatening illnessIn GI tract and then to bloodstreamHigh fevers (103-104 °F)Weakness and headacheStomach pains, loss of appetite, diarrhea or constipation Sometimes, a rash of flat, rose-colored spotsAfter symptoms clear, person could become a carrierAntibiotic treatment is recommended
High inoculum organisms
Tens of thousands or more neededExamples: Vibrio cholerae, C. perfringens
Clostridium difficile
Gram +BacilliSpore-formingObligate anaerobeMotileMakes exotoxinsantibiotic diarrhea
Giardia lamblia
Also most common intestinal parasite in USGiardiasis (aka Beaver Fever) is the foe of backpackers/hikersSymptoms for 1-2 weeks or more, may seem to resolve and then come backMechanism: presence of parasite causes loss of epithelial absorptive surface area. Trophozoites: Attachment but not penetrationFoul-smelling diarrheaFilter water in areas where Giardia cysts are likely to exist. Water does not need to be contaminated with human sewage. Wildlife can deposit cysts.
Cryptosporidium parvum
Often seen when a sanitation system failsPool/waterpark chlorination/UV treatmentStorms or issues with drinking waterDiarrhea symptoms for 1-2 weeks to ~30 days, may seem to resolve and then come backMechanism: Absorption impaired and secretion enhanced when intestinal epithelial cells are infected by Cryptosporidium“Crypto” is opportunisticHIV/Immunocompromised individualsChronic Diarrhea/fluid lossCan be fatalWatery, frequent, non-bloody stoolDisrupts epithelial microvilli, slides into host cells, enveloping itself in the host cell membraneOocysts to sporozoites and backCoccidia subclass
Entamoeba histolytica
AmebiasisMore prevalent in tropical/subtropical climatesOnly 10-20% of infected individuals will become ill (CDC)Of US population, male homosexuals most vulnerableBloody, mucus-ey loose stoolRelatively mild symptoms butCan invade the liver and form an abcessX-ray/ultrasound to detect abscess or tissue damageCysts in stool sample. Must differentiate from non-pathogenic entamoeba, takes a specialist.cytotoxic
Metronidazole, Tinidazole
Tissue antiparasitic- low concentration in intestine, oral dose almost completely absorbed with high bioavailabilityDespite this, it is the drug of choice to treat symptomatic Giardia infection, even though organism that does not penetrate the epithelium!!Reminder: all about metronidazole/Tinidazole in lectures relating to treatment of H. pyloriDisulfiram reaction, avoid alcoholDisturb normal GI florabreaks down into toxic metabolites, damages DNA
Nitazoxanide
Mechanism: Interferes with pyruvate::ferredoxin oxidoreductase enzyme dependent electron transfer, essential to anaerobic energy metabolism protein Selectivity: Species difference in electron transferDistribution: Rapidly metabolized to tizoxanide. Parent compound is not detected in plasma. Moderately absorbed (33%), primarily luminal. For Crypto, used in combination with retroviral therapy for AIDS patients if at all, because of ineffectiveness
Iodoquinol
Mechanism: UnknownToxicity: loss of visual acuityUse with caution in patients with thyroid disease – its use interferes with certain thyroid testsDistribution: only 10% of the drug is absorbed so it works locally on the protozoa including cysts in the GI tract, luminal antiparasitic (amebicide)
Paromomycin
Mechanism: Aminoglycoside- targets 30S subunit ribosomeToxicity: Diarrhea, other GI effects including issues with intestinal flora because it has activity against some bacteria.Distribution: Luminal antiparasitic- Minimal absorption after oral administrationOtotoxicity, nephrotoxicity
TMP-SMX
Spectrum: Broad spectrum, many bacteria, but also effective against apicomplexans including Toxoplasma and Cystoisospora (formerly Isospora), and Cyclosporahits folic acid system
Enterobius vermicularis
Staple-sized wormspinwormsWorldwide distribution, most common helminth infection in USPrevalence can reach 50% in children, caregivers of infected children, and institutionalized individuals.Symptom: perianal pruritisAcquired by ingestion of pinworm eggsEggs can remain viable on surfaces for 2-3 weeks
Necator americanus/Ancylostoma duodenale
Pruritic Papular Erythematous RashHookworms are bloodsuckers…Major symptom is iron-deficiency anemia¼ ml/day/worm
Strongolides stercoralis
Autoinfection possible, especially with Immunosuppressed individualsStomach and GI complaintsRespiratorydry coughthroat irritationSkinan itchy, red rash that occurs where the worm entered the skinrecurrent raised red rash typically along the thighs and buttocks.
