ders path Flashcards
guaiac test
tests for occult blood in stool(turns blue)
-ulcerative colitits, chrons, colorectal cancer
how to get leukoplakia
HPV, friction(ill fitting dentures), pipe smoking tobacco
-same risk factors for oral SCC, and erythroplakia
Red velvety eroded area
* Poorly circumscribed
* Typically marked dysplasia,
and intense inflammation
with vascular dilation
Erythroplakia
hairy oral leukoplakia microscopic features
Hyperkeratosis and acanthosis seen microscopically
plummer vinson syndrom sx
iron def anemia, esophageal webs, glossitits
plumber vinson syndrom ->
SCC
-partial obstruction causes progressive dysphagia
pseudoalchesia
secondary:
Chagas disease (Trypanosoma cruzi)
* Diabetic autonomic neuropathy
* Infiltrative disorders: malignancy, amyloidosis, sarcoidosis
what conditions are associated with esophageal varicies
decompensated cirrhosis and hepatocellular carcinoma (HCC)
-significant cuase of death in cirrhosis
via vericeal hemmorage
what changes morphologically under go with GERD
Hyperemia(so much blood flow), basal zone hyperplasia, and elongation of lamina propria all happen reactively
-will also see eosinophils NOT neutrophils
risk factors that cause scc of esophagus
achlasia, hot beverages/spicy foods, HPV, diet deficient in fruit and veggies, alochol and tobacco, plumber vinson
esophageal SCC metastisis
direct stread to mediastinal trachea and heart
lymphatic spread to Cervical, Mediastinal Paratracheal; Tracheobronchial; Gastric and celiac nodes
how to get congenital vs aquires pyloric stenosis
congential: trisomy 18, turner syndroms, esophageal atresia
aquired: peptic ulcer, chronic antral gastritis, malignency (inflammatoion and fibrosis cuases closing of opening)
acute erosive gastritis vs chronic non erosive gastritis
both non neoplastic, irritation to stomach from not enough protection to too much irritant
acute: NSAIDS, alcohol, iron, ulcers, AI
chronic: H pyloir, AI/pernicious anemia, systemic diseases
H Pylori associations
Diffuse antral gastritis(+- increase acid productin) and
Multifocal atrophic gastritis, both chronic gastritis(not neccesarily pernicious anemia).
Also Peptic Ulcers, Gastric carcinomas, and a MALToma/gastric lymphoma
-if inflammation is limited to antrium there will be inc gastrin. inc in parietal cells and inc acid
-if inflammation spreads to body, fundus will more likely be gastric carcinoma because will be gastric atrophy, dec parietal cells, dec acid
test to diagnose H Pylori
non invasive: urea breath, saliva or fecal PCR
invase: rapid urease test
AI gastritis complications
gastric carcinoma(gland destruction and atrophy, dec acid, dec intrinstic factor)
carcinoid tumor (causes endocrine hyperplasia)
what are risk factors that cause peptic ulcers
- Helicobacter pylori infection
- NSAIDs (potentiated by corticosteroids and inhibition of prostaglandins, besides that it is also a direct irritant!)
- Zollinger-Ellison syndrome (PUD of stomach, duodenum, and jejunum bc of pancreatic tumor and too much gastric acid)
what are the differences between two types of gastric adenocarcinoma
intestinal: from chronic gastritis and intestinal metaplasia, H pylori, atrophy
diffuse:E-cadherin (CDH1) germline mutation. Signet ring cells, no gland formation, hard and plasticy = Linitis plastica
Krukenberg tumor
bilateral ovarian
spread of adenocarcinoma of stomach
Virchow node
active in adenocarcinoma of stomach
Blumer shelf
palpable mass on digital rectal exam suggesting stomach adenocardinoma metastasis to rectouterine pouch (pouch of Douglas)
Sister Mary Joseph nodule
subcutaneous periumbilical metastasis of stomach adenocarcinoma
Most common mesenchymal tumor of the abdomen
origin?
morphology?
mutation?
Gastrointestinal Stromal Tumor (GIST), most commonly in the stomach
-arise from the interstitial cells of Cajal, or pacemaker cells, of the
gastrointestinal muscularis propria
-solitary, well-circumscribed, fleshy, submucosal mass composed of thin, elongated spindle cells or plumper epithelioid cells
-Ckit (tyrosine kinase) gain of function mutations
Congenital anomaly due to incomplete involution of vitelline duct
other features:
meckles diverticulum
-in the right lower quadrent
-rule of 2s
-true diverticulum
meckles diverticulum complications
hemmorage and peptic ulcer
intersusseption and internal blockage
diverticulitis and fistule
HLA DQ2 (majority) and HLA DQ8
also…
celiac
also Anti gliadin antibodies
2. Antiendomysial antibodies(antibodies actually target tTG-2 enzyme
within endomysium).
3. Anti-tissue transglutaminase2 (tTG2)antibodies
Reduced villous : crypt ratio
* Villous blunting and crypt
hyperplasia
* Crypt elongation
* Lymphoplasmacytic infiltrate in
lamina propria
* Increased intraepithelial
lymphocytes (CD8+)
celiac
celiac disease complications
t cell lymphoma, iga nephropathy, dermititis herpetiformis
Whipple Disease
Multi-visceral chronic disease involving the small intestine, joints, heart and CNS
> malabsorptive diarrhea due to impaired villous absorption and lymphatic drainage.
triad: diahreah, weight loss, and arthritis. extra intestinal sx continue years after malasbortive, also cardiac neurologic, adn pulmonary problmes
mucosa laden with distended macrophages in lamina propria- contain PAS positive granules; Partially digested bacilli. This infects the intestines absorptive ability
whipple
-mycobacterium can also present like this(both PAS posi) so use zeil nelson to differntiate
PAS positive a1AT def
what can cause intestinal obstructions
- Hernias
- Intestinal adhesions
- Intussusception(most common in young children- if they get rota there is a hypertrophy of peyer patches and then there is drag )
- Volvulus
or paryltyic mucosa like hirchspurg
acute appendicitis etiology
Stasis of luminal contents by a fecalith/fecal block→increase in intraluminal pressure→
impaired venous outflow plus bacterial proliferation → ischemia and inflammation.
Neutrophilic infiltration of the muscularis propria
acute appendicitos
complication include peritonitis, pyelephlebitis(infalmmed thrombosis of the portal vein), portal venous thrombosis, liver abscess, and bacteremia
acute appendicitis
tumors of the appendix
-carcinoid is most common and is begign
-begnin mucinous cystadenomas
-malignent mucin producing cystadenocarcinoma
both Characterized by mucinous epithelial proliferation, extracellular mucin (mucin can dissect through and cause rupture–> PSEUDOMYXOMA PERITONEI
PSEUDOMYXOMA PERITONEI
from a ruptured appendix mucin neoplasm
-Tenacious, semisolid mucin fills the abdomen
- spreads to: Adenocarcinoma of ovary, colon, pancreas
Associated with RET mutation in most inherited cases
Hirschsprung
-causes failure of neuroblasts from the neural crest to migrate to the end of gastrointestinal tract causing a loss of smooth muscle relaxation(via NO) in the rectum and causes obstruction
aganglionosis
Distal intestinal segment lacks both the Meissner submucosal plexus and the Auerbach myenteric plexus)Enteric Nervous System absent (no meissner or myenteric plexus of nerves)
seen in hirschpurng
complication of hirschpung dx
perforation and peritonitits
Acquired pseudo-diverticular (all layers not involved) flask-like outpouchings of the colonic mucosa and submucosa through the colonic wall
diverticular disease
-at the sight of the signoid colon
-form contispation
extraintestinal sx of IBD
more prevelant in UC
-migratory polyarthritis, alkylating spondylosis, erythma nodulosum, PSC, clubbing
intraintestinal = malabsorption more related to chrons
string sign
chrons strictures
backwash ileitis
aka toxic mega colon from ulcerative colitis
inflammatory infiltrates, crypt abscesses, crypt distortion, PSC
associatiations of both UC and Chrons
pseudopolyps
UC
infective agents of infective enterocolytis
bacteria: *salmonella, *mycobacterium, shigella, ecoli, yersinia, campylobacter
viral: CMV
parasite: Entamoeba histolytica
infective form and tansmission of amebic colitis
cystic form
feacal oral transmission
mimics pancreatitis
Entamoeba histolytica, amebic colitis
moa of Entamoeba histolytica
- Attatch to colonic epithelium via adhesin
2 .Epithelial breakdown via protease*** - invade lamina propria into submucosa
- recuit neutrophils**
- lateral submucosal breakdown
- flash shaped ulcer
- bloody diahrea*
complication of Entamoeba histolytica
amebic liver abcess
erythrophagocytosis diagnostic for what
dignostic for active amebic enterocolitis
-Stool analysis shows presence of ingested red blood cells within
trophozoites which is pathognomonic
-Stool analysis can also show cysts with multiple nuclei, if seen alone it is
not specific for active disease (can be seen in carrier state)
what cuases typhoid fever
-transmission?
Salmonella enterica, and its two subtypes, typhi and paratyphi
-fecal oral, food, water
MOA of S. typhi
- Bacteria endocytized (brough in) by the endothelila cells and the Microfold M cells via T3SS to go into submucosa
- evade immune system via Capsular Vi antigen which inhibits phagocytosis and inflammation
- Engulfed in the submucosa by macrophages. can survive in macrophage and not phagocytize by T3SS.
- Macrophages take to other lymphoid tissue and causes enlargement of primary and secondary lymphnode tissues…Peyer patches enlarge into sharply delineated, longitudinal plateau-like elevations (may be longitdinal formation of ulcerations from inflammation above the peyer patch)
salmonella
typhoid nodules (aggregates of macrophages) in liver and spleen (hepatosplenomegaly) as well as other tissue such as peyer patches and mesenteric lymph nodes
progression of typ[hoid fever> step ladder fever
-ulcer above the submucosa of peyer patch is oval shape in longitudinal orientation
typhoid fever diagnosis
culture from bone marrow!
PSEUDOMEMBRANOUS COLITIS aka
Antibiotic-associated colitis/ diahreah
-predominently from clostridium diff
-also associated with PPI and immuno comprimose
Superficially damaged crypts distended by mucopurulent exudate which erupt in pseudomembranous colitis
mushroom cloud
sx for acute ischemic colitis vs chronic ischemic colitis
maybe from a thrombo embolysm
sudden onset pain, bloody diahreah, desire to deficate, coagulative necrosis of the musclar propia, exudate and fibrosis on serosa
-chronic from atherosclerosis or hypoperfusion(splenic flexture) cuases intestinal angina, strictures and can mimic inflammatory bowel disease
Mucosal epithelial hyperplasia projecting as a mass in the lumen in the left colon
Hyperplastic Polyps
-piling up of epithelium
non malignent polyps
hyperplastic
Nodular protrusions of the mucosa with a serrated surface
Hyperplastic Polyps
-right side colon cancer (MSI,HPNCC, nonconventional)
Typically pedunculated, smooth-surfaced, reddish lesions
* Focal disorganization of the epithelium and lamina propria with cystically dilated
glands/ tubules filled with mucin and inflammatory infultrate in the lamina propria
juvinile polyp
-Large and pedunculated with a lobulated contour
-Arborizing (branch-like) network of smooth muscle in lamina propria.
PEUTZ JEGHER SYNDROME
mucocutaneous
hyperpigmentation
PEUTZ JEGHER SYNDROME
-dark blue to brown macules on the lips, nostrils, buccal mucosa, palmar surfaces of the hands, genitalia, and perianal region
complications of peutz jegher
intussuspetion,
inc risk of malignencies(colonies, pancreatic, breast
convential vs non convential adenomas
- Conventional adenomas - tubular, villous, tubulovillous (
- Non-conventional - Sessile serrated adenomas. (right)
-Presence of epithelial dysplasia (risk of malignancy) with no invasion-tall, hyperchromatic crowded nuclei
clinical features of adenomas
asymtomatic, anemia from occult blood loss, intercusseption
villous adenoma can cause hypokalemia
APC tumor suppressor gene on chr. 5q
Familial Adenomatous Polyposis
-needs two hits
-causes 1000+ polyps
Gardner Syndrome
FAP + osteomas of the mandible, skull, and long bones + epidermal cysts + desmoid and thyroid tumors + dental abnormalities
Turcot Syndrome
FAP + CNS tumors
MSH2, MLH1
mismatch repair mutation causes HNPCC
Mucinous and signet ring cell
Hereditary Non-Polyposis Colon Cancer
neoplasm that Usually arise at sites of chronic inflammation
MALT (b cell ) lymphoma
ex. peyers patch
from H pylori chronic gastritis
acute liver failure association
encephalopathy
acetometaphen damage
heptitis virus infectin
autoimmune hepitits
Liver is small and shrunken due to loss of parenchyma → can lead to decline in
serum transaminases
acute liver failure
large zones of hepatocyte loss with areas flooded with RBCs
interspersed by occasional islands of surviving/ regenerating hepatocytes
acute liver failure
what causes cronic liver failure
hep b/c, NAFLD, AFLD, AI hepatitis
Condition marked by the diffuse transformation of the entire liver into regenerative
parenchymal nodules surrounded by fibrous bands with variable degrees of vascular shunting
cirrhosis
cirrosis pathogenesis, what cells
Activation of Hepatic stellate cells (Ito) responsible for hepatic fibrosis
Pruritis due to persistent cholestasis
* Hyperestrogenemia due to impaired metabolism
➢ Palmar erythema, Spider Angioma
➢ Hypogonadism and Gynecomastia in males
* Hypogonadism in women can occur due to disruption of hypothalamic
pituitary axis function
cirrhosis
cirrhosis complications
Hepatic encephalopathy
* Bleeding from esophageal varices
* Bacterial infections (resulting from damage to gut mucosal barrier and
Kupffer cell dysfunction)
* Development of hepatocellular carcinoma
Chronic, progressive hepatitis, presence of autoantibodies, and therapeutic response to immunosuppression
AI hepetitis
Interface hepatitis, lymphoplasmacytic activity in portal tract and lobule, Regenerating hepatic rosettes
AI hepetitis
Steatosis
* Steatohepatitis (NASH): ballooning, Mallory hyaline (Mallory-Denk bodies)
* Fibrosis around central vein
ALD, NAFLD, Wilsons disease(with central fat necrosis)
Autoimmune disease characterized by progressive nonsuppurative, inflammatory destruction of small and medium sized intrahepatic bile duct
PBC
-resulting from T lymphocyte–mediated destruction
PBC diagnosis
Antimitochondrial antibodies. Elevated serum alkaline phosphatase and γ-glutamyl transferase→both are markers of cholestasis(flow bile blockage from liver to duodenum)
PBC features morphological and clinical
*Lymphocytic and/or granulomatous bile duct destruction (florid duct lesion)
* Profound cholestasis→feathery degeneration; Mallory Denk bodies(also seen in Wilson disease)
* May progress to cirrhosis
Clinical features: Fatigue, pruritus and jaundice.
Chronic cholestatic liver disease with segmental inflammation and obliterative fibrosis of intrahepatic and extrahepatic bile ducts with dilation of preserved segment
PSC
Excess iron deposited in parenchymal organs such as the liver and pancreas → followed by
heart, joints, and endocrine organs
hemochromatosis
Hemochromatosis mutation,or can be caused by?
autosomal recessive mutations in HFE gene most commonly (excessive iron absorption)
can also be causes by transfusions, alcohol, HEPETITIS C
hemosiderosis
Excess iron in cells (no symptoms)
Autosomal recessive disorder that affects copper metabolism in body.
wilson dz
wilson dz mutation
mutations in the ATP7B gene on chromosome 13, which is responsible for encoding a protein that helps transport copper out of the liver.
wilson dz morphology
Liver: non-specific changes including
* Fatty change with focal hepatocyte necrosis
and Mallory Denk bodies
* Acute fulminant hepatitis, chronic hepatitis, cirrhosis
-deposition in the neuronal gangia causes CNS sx
-deposition in eye causes sunflower cataracs
Periodic acid–Schiff (PAS) stain of the liver, highlights the characteristic magenta cytoplasmic granules→round-to-oval cytoplasmic globular inclusions of misfolded protein
alpha 1 AT
Long term use of oral contraceptives and anabolic steroids are associated with the development in some patients
hepatic adenoma
hepatoblastoma spreads to
Spreads to lungs, lymph nodes and peritoneum
types of hepatoblastoms
- Epithelial type: composed of small polygonal fetal cells or embryonal cells forming
acini, tubules, or papillary structures vaguely recapitulating liver development - Mixed epithelial and mesenchymal type: contains foci of mesenchymal
differentiation that may consist of primitive mesenchyme, osteoid, cartilage, or striated muscle
Strong propensity for invading vascular channels (portal vein, Inferior Vena Cava)
hepatocellular carcinoma
Variant of hepatocellular carcinoma
* Younger age
* No association with HBV or cirrhosis
* AFP normal
* Outcome similar to HCC in non-cirrhotic live
Fibrolamellar Carcinoma
-AFP also normal in cholangiocarcinoma
- Usually, single hard tumor with fibrous bands traversing through it (scirrhous)
- Well differentiated polygonal cells in cords or nests, separated by fibrous septa
Fibrolamellar Carcinoma
Malignancy of the biliary tree, arise from intra and extra hepatic bile ducts
how does it present?
Cholangiocarcinoma
-presents as multifocial liver lesions)
risk factors for cholangiocarcinoma
PSC, gallstones, benzidine, nitrosamines
parasitic infections: Clonorchis sinensis and Opisthorchis viverini
what neoplasms metastitize to the liver
-adenocarcinomas of the colon, stomach, pancreas
-breast
-lung
-neuroendocrine tumors
-melanoma
-neuroblastoma
-Wilms tumor
-leukemia
Risk factors: advancing age, female gender, oral contraceptives, obesity, rapid weight reduction
Cholelithiasis (cholesterol stones)
Primarily in the setting of bacterial infections of the biliary tree and parasitic
infestations
* Risk factors: chronic hemolysis, biliary infection
pigmented biliary stones- cholelithiasis
Primary complication of gallstones
Acute calculous cholecystitis(inflammation of the gallbladder)
-from flow obstruction
Results from gall bladder stasis and ischemia→cystic artery is an end artery with no collateral circulation
Acute acalculous cholecystitis
-bc of hypotension sepsis, immunosupression, infection
Mucosal phospholipase converts lecithin to lysolecithin
→Damage to glycoprotein layer of mucosa →Further release of prostaglandins from mucosa
→ Cumulatively leads to mucosal & mural inflammation
→Increased intraluminal pressure will can cause ischemia
→Superimposed bacterial contamination
pathogenesis of cholecystisis due to obstruction of flow
PORCELAIN GALL BLADDER
extensive dystrophic calcification from multiple acute cholecytisis attacks causes chronic cholecystitis
-Bluish discoloration and brittle consistency of gallbladder(inc risk of cancer)
Mirizzi syndrome
gallstone impacted in the cystic duct causing compression of
common hepatic duct and obstructive jaundice
type of Choledocholithiasis (bile duct stone)
agents that cause CHOLANGITIS (bile duct inflammation)
E.coli, S.faecalis,
Enterobacter
sx for cholangitis
charcots triad (fever, right upper quadrant pain and jaundice)
An autosomal recessive systemic disorder of exocrine glands characterized by:
* Chronic pulmonary disease
* Deficient exocrine pancreatic function
* Other complications of inspissated mucus in a number of organs, including the small intestine, liver and the reproductive tract
cystic fibrosis
cystic fibrosis mutation
Gene on chromosome 7 (7q31.2) encodes for a protein called the CF transmembrane conductance regulator (= CFTR)
* Major function of the CFTR protein in the sweat gland ducts → reabsorb luminal chloride ions and augment sodium reabsorption through the epithelial sodium channel (ENaC)
with defective Cl transport: high sweat salt concentration, thick luminal secretions
Bronchiectasis
* Pancreatitis
* Diabetes
* Neonatal intestinal obstruction * Azoospermia, infertility
cystic fibrosis
acute pancreatitis laboratory findings
- Raised amylase levels in first 24 hours
- Followed by lipase within 72-96 hours
- Hypocalcemia (calcium used in fat necrosis)
acute pancreatitis complications
- Acute Respiratory Distress Syndrome (ARDS)
- Acute Tubular Necrosis (ATN)
- Pancreatic abscess – later in the course of the disease
- Pseudocysts
pancreatic adenocarcinoma accosiation
smoking
KRAS mutation
-usually in the head, then body, then tail
Features of obstructive jaundice – tumor in the head of pancreas
* Trousseau’s syndrome (migratory thrombophlebitis) may be present.
* Release of platelet activating factors and procoagulants from tumor
* No single specific marker but sometimes raised CA 19-9
pancreatic adenocarcinoma
what vaccines are available for food borne pathogens
type?
- rotavirus given at 2 months(2 live attenuated oral- common AE is intussusseption)
- cholera (attenuated with ctxA delected). give to travelers or for outbreaks
- typhoid (2- Vi capsular polysachoride, and Ty21a live attenuated oral
- Hepetitis A
common food poisoning organisms
bacteria: staph aureus, Clostridium botulism
marine/algae: Ciguatera, Scombroid, Shellfish, Pufferfish
Associated foods: sliced meat, ham, poultry, *puddings, *potato or egg salad, *mayonnaise, *cream pastries
staph aureus
what makes you stick with staph aureus food poisoning
enterotoxin ST:heat stable and activate guanylate cyclast
-also used in B.cereus
Large, G +ve, motile, rods, anaerobic, spores forming,
neurotoxin
clostridium botulism
-spores germinate when at low O2 concentrations and they are heat resistant but the toxin is heat liable
-Disease often starts with nausea,vomiting,abdominal pain,diarrhea,and dry mouth with sore throat.
– Eventually CNS symptoms develop:
* Cranial nerve palsies-doubl evision,blurred vision,drooping eyelids, slurred speech, difficulty swallowing, dry mouth and muscle weakness ***Symmetric descending flaccid paralysis, respiratory failure, death
clostridium botulism
moa of botulism toxin
Binding presynaptically to high-affinity recognition sites on the *cholinergic nerve terminals and decreasing the release of acetylcholine, causing a neuromuscular blocking effect.
toxin activates voltage dependent sodium channels
where to be found
Ciguatoxin
found in barracuda, black grouper & amberjacks
Ciguatera Fish Poisoning presentation
GI (3-6 hrs post ingestion) - diarrhea, nausea, vomiting, abdominal pain/cramps
– CNS (3-72 hrs post ingestion) - peri-oral paresthesias, pruritus without urticaria, a metallic taste in the mouth, painful dentition, painful urination, blurred vision, and temperature- related dysesthesias
– CVS (within hours) - bradycardia, heart block, hypotension
Scombroid poisoning
-how does it happen and from where
from tuna, mackerel, mahi mahi, swiss cheese
pimproper storage allows bacterial overgrowth causing build up of histidine > histamine
major agents causing esophagitis
- candida spp, 2. HSV, 3. CMV,
also can be caused from immunosupresion (cancer, transplant, HIV, diabetes)
Multinucleated giant cells with ground-glass nuclei and eosinophilic inclusions
HSV
intranuclear or intracytoplasmic inclusion bodies (Owl’s eye inclusions)
CMV
- Gram negative
- Curved to spiral (1-3 turns)
- Motile: 5-6 polar flagella
- Microaerophilic: 2-5% O2, 5-10% CO2
- Oxidase positive
- Urease positive
H Pylori
Helicobacter pylori: Virulence Factors
-colonization
-immune escape
-disease induction
Colonization:
* Adhesins: BabA and SabA
* Outer membrane proteins
* Flagella: Bacterial movement to epithelial surface
* Urease: Neutralize gastric acid
Immune escape:
* Lipopolysaccharides
* Exotoxins: Suppress phagocytosis, Block effector T cell response
Disease induction:
* Type IV secretion system :Injection of effectors
* Secretory enzymes
* Exotoxins-Caga+, Vaca
* Effectors
Cytotoxin associated gene A+(CagA+) strains have inc risk of:
from H pylori
inc risk of peptic ulcers and oncogenesis (facilitates malignent transformation of gastric epithelial cells)
Forms anion-selective channels in vacuole membranes➔swelling * Inserts in mitochondrial membranes➔mitochondrial death➔
induction of apoptosis
VacA toxin from H pylori
Production of ammonia increases pH
principle of urease invasive test for H pylori (urease produces ammonia)
agents of appendicitis and pseudoappendicits
E coli, B. fragilis, Peptostreptococci, Pseudomonas
Pseudoappendicitis by Yersinia
enterocolitica
Grey Turner sign
Cullen sign
pancreatitis
GT sign is flank ecchymosis
Cullen is perumbilical ecchymosis
what mirobe causes intrabdonimal access
Bacteroides fragilis- GNAR
-cna really cause abcess anywhere
can also include resident GI microbes(E coli, klebsiella)
bacteriodes fragilis virulence factors
-adhesive surface pilli
-antiphagocytic capsule
-penicillin resistant bc beta lactamase production
LPS endotoxin is less toxic than other gram -
major nosocomial pathogen
Clostridium difficle
-primary cause of anti biotic associated diahreah in the hospital
G+ bacillus
anaerobe
endospore formation
motile
oppertunistic
toxin produces
risk factors?
clostridium difficile
-only the toxin forming stains thrive with antibiotic otherwise there are non toxic versions in the normal GI. A and B toxin.
- risks to C diff is antibiotic use, hospitalization, PPI, older, exposure to health care worker(may cause initial endospore formation, then add antibiotic and get full sx)
toxic mega colon
complication of:
ulcerative colitis
C difficile
C diff toxin and virulence factor
A and B toxin. TcdA-enterotoxin binds to brush border. TcdB-cytotoxin(depolymerized actin and disrupts cytoskeleton)
flagella and adhesin
toxin leads to an inflammatory cascade
C difficile
pseudomembranes
adherent white yellow plaques
somewhere inbetween mild diahrea sx and severe toxic megacolon sx.
diagnosis for C diff
(GDH)EIA for Glutamate Dehydragenase
EIA for toxin A or B
-no culture
tests for diagnosing inflammatory diahrea
only preformed in certain situations:
-stool lactoferrin tests for WBC(inflammatory diahrea)
-stool RBC
-ova and parasite stool test(done under special circumstance)
in US stool culture will be for
camylobacter(with CAMPY micro-aerobic conditions), shigella, and salmonella
e coli needs special request
macconkey will have ecoli fermenting lactose and shigella and salmonella not fermenting(clear)
shigella -salmonella agar has salmonella black H2S produced. and shigella green/cleart H2S not produced
Enterobacteriaceae members
similarities
Escherichia** Shigella** Salmonella** Yersinia**
Klebsiella* Proteus*
all facultative anaerobes
Gram -ve, non-spore forming, rod shaped bacteria. all motile except shigella and klebsiella
Gram -ve bacilli (Rods)
Facultative anaerobes
Motile
* Rapid Fermenter of Lactose
* Catalase Positive
* Oxidase Negative
e coli
grow pink on mc conkey agar
ETEC virulence factor
Mucosal adherence with pili/fimbrae(CFA- colonization factor antigens).
Exotoxin/enterotoxin production: Heat-labile and stable toxin ( LT and ST). Both 1A 5B(acitve and binding)
LT-similar to cholera and inc Camp
ST- inc guanilate cyclase(in staph aureus poisoning)
both of these virulence factors are plasma encoded
1o cause of “Traveller’s Diarrhoea”
pathogenesis?
ETEC
-injest contaminasted foos, strong attatchment to SI and release of LT and ST to cause electrolyte disturbance, no invasion
infintile diahrea
pathogenesis?
EPEC
-no LT, ST, CFA like seen in ETEC
-plasmid encodes for adherence factor Bundle Forming Pilli(BFP)
-also does not invade like ETEC but will cause attatchment-effacement lesion and will cover the whole top surface area to a dec in absorption leading to diahrea (food borne illness)
Single curved Gram-ve rods, 2 - 4μm long
– (May be linked end to end) forming “S” shapes – Motile (single polar flagellum)
– Non-spore forming
– Facultative anaerobes
– Oxidase +ve
vibrio cholera
oxidase is key test done for diagnosis
ferments sucrose and mannose
acid sensitive
halo tolerant
vibrio cholera
Bacteriophage encoded AB toxin
cholera toxin CtxA
-very similar effect to LT toxin of ETEC and will cause electrolyte imbalance via inc in camp
causes rice water stool
-food borne illness
Thiosulphate-citrate-bile salts-sucrose (TCBS) agar
sucrose acts as a differentiating agent for Vibrio CHOLERA(not another type of vibrio)
sucrose+ yellow dots
Gram-positive
* Large anaerobes
* Non-motile rods
* Spore-forming
*Members of the intestinal microflora of humans and most other animals
clostridium perforingens
type A causes the food borne infection
clostridium perforingens pathogenesis
injestion from food source, sporulation in SI(conditions are perfect) and will release CPE (an LT type toxin which causes *cytotoxic acitivty and *alters membrane permeability, causing electrolyte imbalance and diahrea
can see enterotoxin in feces
Gram +ve rods
Arranged in chains
Aerobic
Spore former
Emetic toxin & Enterotoxin
bacillus cereus
emetic is if injesting preformed toxin(resemble Staph aureus and injest ST NEUROtoxin found in rice/grains)
entereotoxin if ingesting pathogen-acts identically to C-perforingens with LT toxin inc camp
Non-enveloped
Icosahedral nucleocapsid
ss +ve sense RN
norovirus -
winter vomitting disease
pathogenesis
norovirus
-transmitted fecal oral, food, water
SI is perfect conditions for multiplication, transient lesions produced- microvilli shortened and intrercellular spaces wider, no damage to large intestine and no fecal leukocytes, shed in feces
Wheel-shape,
Non-enveloped
double-capsid structure (3 layers counting core)
ds RNA
whats in core and whats on capsid
rotavirus
core has rna dep rna polymerase
capsid has VP4- P antigen for Protease sensitive ATTATCHMENT and VP7-G antigen for Glycoprotein
rota virus pathogenesis
kinda similar to noro
- ingest fecal oral or water and multiply in the SI. Causes SI microvilli dmaage and atrophy(decreasing surface area of SI and dec production of disaccharides). Normal columnar epithelium at the villus tips is replaced by irregular cuboidal, cryptlike cells, leading to multiple defects in fluid and electrolyte regulation in the affected intestinal mucosa. NSP4 protein acts like a toxin and inc net fluid excretion, shed in the faeces
Non-enveloped,
icosahedral symmetry
* Smooth or slightly indented outer shell
* ss +ve sense RNA
Astroviruses
like noro also peaks in winter
like rota virus pathogenesis with infection there is villi shortening and decreased intestinal enzyme activity(sx are milder here than rota)
Icosahedral protein shell capsomeres
ds DNA
Pentons
adenovirus
main taget is the respiratory system, but can also infect small intestine
Coccidian Protozoan that causes chronic diahrea
Cryptosporidium
-especially in AIDS pts
called persistent diahrea in children of endemic countried
-can cause some mild villopus blunting
which oocytes resist disinfectant including chlorination
cryptosporidium
acid fast thick walled oocyte is shed in feaces (diagnostic and infective stage)
Gram-positive, facultatively intracellular,
Non-spore forming, halophilic, beta-hemolytic (beta hemolysin), coccobacilli (short rods).tumbling motibily
Listeria
-tumbling motility
-readily multiplies in the fridge(putting unpasturized milk and raw cheeses(soft)/meat in the fridge aint gunna cut its)
-Only Gram-positive organism that has an endotoxin
motile at 30°C and below
Transplacental vertical transmission
Vaginal transmission- during birth of neonate
listeria
effects pregnant women and neonates
listeria pathogenesis
-Invades epithelium via InlA and InlB
-will go in a vacuole
-vacuole rupture via pore forming toxin LLO +PlcA and PlcB
-now an replicate freely in the cytoplasm
-when it is time to spread to the next cell. ActA expression forces host to polymerize actin. rocket propell
-into the next with a double vacuole which will just get taken care of by LLO…
listeria diagnosis
with blood culture!
No known animal reservoir
* Non-motile
* Non-encapsulated
* Gram –ve rods
Acid stable
***Intracellular
(does not ferment lactose
H2S negative)
shigella
-similar to EIEC with toxin and has a low infectious dose
-H2S negative, does not ferment lactose
Food, Flies, Feaces, Fingers…not animal
-exposure risk at day care! day care exposure also to yersinia
shigella virulence factors and pathogenesis
Endocytosis the M cell: attatch and T3SS
Phagosome lysis, and macropahge apoptosis, IL 1 release : T3SS
Endotoxin: O
Exotoxin: shigella toxin only in shigella D
-Stays intracellular to avoid humoral immunity
-actin rockets
NAD glycohydrolase: destroys NAD causing cell death
does not invade into the blood stream
Bacillary dysentery
causes inhibition of?
from the shigella toxin(only in shigella dysteneria)
-enterotoxic(adheres to SI and blocks absorption), neurotoxic(abdonimal cramping), cytotoxic(1A 5 B structure…B bing to glycolipid, A active causes irreversible inhibition of 60 S ribsomoal subunit
reactive arthritis
conjuctivitis, urethritis, arthritis
cant see, cant pee, cant climb a tree
Shigella, Salmonella, Yersinia, (1% c. jejuni)
Gram-negative, rod-shaped
* Motile
* Facultative anaerobic
* Non spore-forming
Lactose fermenter
major surface antigens?
E coli
major surface antigens: K=capsule, H=flaHgella, O: LipOPS
EIEC pathogenesis
no virulence factors given
similar to Shigella
-Endocytosis into M cell. Invades the LI where macrophage will eat it.
-Lysis of phagolysosome
-replicates in cytoplasm
-actin rocket
destroys colonic cells , does not invade the system.
Characterized by the presence of aggregative adherence fimbriae (AAF
EAEC
-helps with attatchment to intestinal mucosa and triggests host immune responce with enhanced mucus biofilm production**
-there is no intracellular jouney like EPEC and ETEC
AAF binds to MUC1
O157:H7
resoviour?
SLT- shigela like toxin of EHEC, STEC, VTEC
-resovior in cattle and sheep
STEC presentation
- Hemoragic colitis( 3 days after injestion) = bloody diahrea,,,started as watery
- About one week after the diahrea there is HUS(microangio anemia with shistocytes, thrombocytopenia, and acute renal failure)
- if elder can develpoe TTP which is HUS with mental presentation
STEC pathogenesis
-injestion (cattle and sheep resoviour)
-attatchment similar to EPEC(Bundle Forming Pilli(BFP))
-phage encoded toxin-cytotoxin/verotoxin(Stx-1 is similar to shigella, also Stx-2…both are AB toxins and blocks rRNA)
-this causes the hemoragic colitis
-toxin enters the blood! and binds to glomerular epithelium cuasing the HUS
Gram negative rods
* Do not ferment lactose
* Motile
acid labile
H2S positive
major surface antigens?
Salmonella
surface manigens: O-LPS cell wall
H= flaHgella
Capsular Vi
colorless on mac conkey agar(doesn ferment lactose)
pathogenesis of salmonella
- Attatchment and invasion of eplithelial via SPI-1and T3SS
- Invade M cells/macrophage of Peyer patch
- Intracellular survival via SPI-2 and T3SS
- replicate INSIDE vacule
- macropahge disseminatesto different organs…this is when it becomes typhoid fever
transport to liver, spleen, bone marrow in macrophage, colonization in gallbladder, bacteremia and replication in bile. bile renters intestines
macular rash on trunk
salmonella typhi
-other dx for salmonella is blood(amenia, leukopenia, NO eosinophils)
curved-spiral rods
* Gram -ve
* Motile (single polar flagellum)
* Microaerophilic
* Oxidase +ve
resovior?
toxin?
campylobacter jejunilarge animal
-resovior: esp kittens and puppies, also commercial poltery, cows, sheep
-toxin: endotoxin, enterotoxin(watery diahrea),cytotoxin(bloody diarrhea)
oxidase catalase test is the definitive diagnosis
Symptoms appear 3-5 days after ingestion
* Vomiting – slight
* Diarrhea - often profuse
* Abdominal pain - often severe
* Prostration – often severe
* Pyrexia – often present
* Other symptoms – blood-stained feces
campylobacter jejuni
similar clinical presentation for salmonella and shigella
Guillain-Barré syndrome
paralysis starting form the feet
c. jejuni
-antibodies against c. jejuni cross react with GM1 ganglioside in the myelin sheaths bc they look similar and leads to their destruction
pseudoappendicitis
toxin and effect?
yersinia
ST enterotoxin(inc cGMP)
Psychrotroph
resovior?
Yersinia
resovior: pigs*, any farm animalor rodent. fish and shellfish. risk with unpasturized milk, cheese
-ink risk if you have iron overload!
Gram -ve,
Glucose +ve
Sucrose +ve
Catalase +ve
Oxidase -ve
Yersinia
bipolar-staining,
coccobacilli
Yersinia
Not agglutinated by anti O1 sera
non cholera vibrio
and halophilic(likes salt, vibrio cholera is halo tolerant)
enterotoxin & haemolysin
Vibrio parahaemolyticus
Vibrio vulnificus is concern for
sx?
Patient with underlying liver conditions
-acute gastroenteritis, necrostizing skin, invasive sepsis
Capsule
* Heme receptors, siderophores (iron acquisition)
* Fibronectin binding protein, pili (adherence)
* Metalloprotease, hemolysin, cytolysin, phospholipase (extracellular products)
* Endotoxin
* Flagellum
Vibrio vulnificus virulence
Vibrio vulnificus diagnosis
Screening of stool samples
oxidase activity
TCBS) agar - for both vuln and parahaemocyticus
sucrose test - for both vuln and parahaemocyticus
