Pathology of Bacterial Infections Inflammatory in GI System Flashcards
what is the main function of the GI system (4)
- selectively permeable barrier
- transit, digestion and absorption of nutrients, electrolytes and fluids
- prevent entry of pathogens and toxis
- immune function (extensively developed mucosal associated lymphoid tissue MALT)
what are the cell types in the intestine (6)
- globet cell
- enterocyte
- paneth cell
- M cell
- neuroendocrine cell
- stem cells
what are the functions of globlet cell
mucus layer production
what are the functions of enterocytes
absorption
what are the functions of paneth cell
antimicrobial proteins/peptides
- lysozyme
- phospholipase
- DNAse
- ribonuclease
- alpha-defensins
what are the functions of M cells
microorganisms, particles and macromolecules uptake and transfer
what are the functions of neuroendocrine cell
serotonin
somatostatin
cholecystokinin
peptide UU
glucagon-like peptide
secretin regulation of: intestinal motility, secretions, visceral sensations, appetite
what are the functions of stem cells
intestinal epithelium renewal compartment reside in the lower half portion of the crypts
what are the mechanisms of diarrhea
- secretory
- osmotic/malabsorptive
- inflammatory
what is the mechanism of secretory diarrhea induced by bacterial toxins (11)
- ingestion of bacteria
- colonization of mucosa
- release of toxin
- heat labile or heat stable entertoxin
- pass through intestinal lumen through receptor
- causes increase in adenylyl or guanylate cyclase activity
- increase in cAMP or cGMP
- causes of activation of ion/H2O pumps
- causes water, K+, Cl-, Na+, HCO3- to pass through intestinal lumen
- causes severe dehydration/electrolyte imbalances
- leads to secretory diarrhea
what is the net effect of secretory diarrhea induced by bacterial toxins
net increase in electrolytes and water passing through small intestine to colon
what other factors stimulate secretory diarrhea (2)
- prostaglandins and other arachidonic acid derived inflammatory mediators
- histamine, kinins, cytokines
what factors cause increase in bacterial overgrowth (8)
- increased entry of bacteria
- abnormality of intestinal loops
- reduced clearance of bacteria
- reduced gastric acidity increased pH
- motility disturbance
- obstruction of intestine
- immunodeficiency
- cachexia (wasting syndrome)
what is the mechanism of malabsorption diarrhea due to bacterial overgrowth
multiple factors lead to bacterial overgrowth leading to:
- bile salt conjugation –> bile salt deficiency –> malabsorption
- toxins –> intestinal epithelial cell injury –> malabsorption
- consumption of nutrients –> malapsorbtion
what is the mechanism of inflammatory diarrhea (5)
- ingestion of bacteria
- cytotoxin release
- villous enterocytes release IL-8 –> activation of local macrophages which release histamine, serotonin, adenosine –> leukocytes recruitment
- these local factors cause increased intestinal Cl-, H2O secretion + inhibit absorption, promote secretory diarrhea
- acute inflammation –> prostaglandins/leukotrines, PAF, cytokines
- promote diarrhea
what are the consequences of diarrhea
- dehydration
- electrolyte depletion
- metabolic acidosis
what are the factors that influence gastroenteritis and diarrhea in domestic animals
- age
- immunity (colostrum?)
- environmental/seasonal factors
- management conditions
what are the issues that interfere with pathology diagnosis of diarrhea in swine and ruminants (2)
- causal agents can be transiently present
- causal agents produce lesions such as villus atrophy which are easily obscured by autolysis
how do you overcome the diagnostic issues in diarrhea in ruminants and swines
- evaluate one or more untreated animals representative of the herd problem
- preferably in the early phase of the disease and with symptoms (not in advanced condition if possible)
how would you collect samples in pathology diagnosis in ruminants and swine
euthanasia immediately followed by post mortem
PM procedure modified to prioritize collection of specimens from intestine
samples are formalin fixed within a few minutes of death and then timely collection of appropriate samples for additional testing (parasitology, bacterial culture, virology, PCR)
what are patterns of intestinal injury and some examples in horses, dogs, swine, calves, goats, bovine
- catarrheal enteritis and intestinal impaction: ascarids in horses
- hemorrhagic enteritis: dogs hookworms
- necrotizing colitis (‘swine dysentry’): pig brachyspira hydodysenteriae
- proliferative enteritis: goat coccidiosis
- granulomatous enteritis: bovine johne’s disease
- necrotizing-hemorrhagic enteritis: calf coccidiosis
what are the effects of bacterial virulence factors (5)
- production of bacterial toxins that kill phagocytes
- synthesis of bacterial proteins that prevent phagocytosis by blocking the interaction of opsonins with phagosomes
- bacterial capsule –> block contact with microbe –> prevent phagocytosis
- facilitate escape of the microbe into the cytoplasm before the microbe is killed in the phagolysomes
- production of bacterial antioxidants (ex. catalase) that block killing in phagolysosomes
what do E. coli (ETEC) adhere to
microvilli on intestinal epithelium
what effect do heat labile toxins from E. coli have
LT-I and LT-II
Cl- secretion from enterocytes which cause diarrhea
what effect do the heat stable toxins from E.coli have
inhibit Na+/Cl- cotransport in surface enterocytes which indice Cl- and water secretion from crypt enterocytes
what does verotoxin ETEC cause
porcine edema disease
shiga toxin –> systemic vascular endothelial damage –> leakage –> edema
brain and spinal cord vessels also affected –> neurological manifestations
what do enteropathogenic/attaching effacing E. coli (EPEC/AEEC) cause
attachment + translocation into enterocytes –> loss of microvillus brush border
what are enteroinvasive E. coli (EIC) cause
internalized by surface enterocytes –> disseminate through the body –> septicemic colibacillosis
what do the shiga toxin produce E.coli cause
protein synthesis inhibition + apoptosis
what are the gross signs of porcine edema disease
subcutaneous edema of snout, eyelids, angle of the mandible
edema of gastric wall
edema of mesocolon
what are the common serovars of salmonella
S. typhimurium
S. dublin
S choleraesuis
what type of bacteria is salmonella
gram negative
is salmonella an aerobe or anaerobic bacteria
aerobe/faculative anerobic
is salmonella motile or non motile
motile
how is salmonellosis transmitted
oro-fecal –> penetrate through M cells
what does salmonella invade
enterocytes
what is the virulence factor of salmonella
neutralization of macrophage nitric oxide (NO) production
bacteria survive within macrophage phagolysosomes
additional virulence factors: fimbriae (adhesions), lipopolysaccharide (LPS)
what affect do the salmonella toxins have (5)
- damage to the enterocytes –> interfere with closure of chloride channels –> secretory diarrhea
- interaction with toll like receptor (TLRs)
- cytokines/chemokines upregulation
- inflammation with neutrophil influx
- inflammatory cells-derived PGE-2–> further chloride hypersecretion
these all amplify inflammation that promote further chloride secretion and diarrhea
what is the pathogenesis of infection of salmonella
- salmonella invade M cells in intestinal epithelium
- macrophages in lamina propria and Peyer’s patches which are able to resist killing from macrophages
- transferred to mesenteric lymph nodes
- via portal circulation to liver
what is peracute septicemic salmonellosis
disease of calves, foals and pigs
younger animals most sensitive
usually fatal in animals 1-6 months of age
what is the pathogenesis of peracute septicemic salmonellosis
multisystemic vascular lesions with fibrinoid change, thrombosis and necrosis
- petechiation and blue discoloration (cyanosis) of ventral abdomen, extremities (ears commonly affected)
- death caused by disseminated intravascular coagulation (DIC)
how does salmonellosis classically present in swine
congestion/cyanosis of the ear pinna with ischemic necrosis of the tip
how does horse peracute salmonellosis present
colon have areas of hemorrhage and necrosis from vascular thrombosis and subsequent ischemia
hemorrhagic necrosis –> vascular thrombosis with subsequent ischemia
what bacteria causes acute enteric salmonellosis
salmonella typhimurium
how does acute enteric salmonellosis adhere
surface fimbrial antigens (pilus adhesion) mediate invasion
receptor mediated endocyte within enterocytes
membrane bound vacuoles –> translocate bacteria to lamina propria macrophages
what are the pathogenic affects of acute enteric salmonellosis
- interference with chloride channels –> secretory diarrhea
- induction of enterocyte apoptosis + recruitment of neutrophils
- endotoxins –> vascular thrombosis
what type of intestinal lesions does acute enteric salmonellosis cause
fibrino necrotic enterocolitis
malodourous intestinal contents with mucus, fibrin and occasionally blood
what extra intestinal lesions can be found with acute enteric salmonellosis (3)
- mesenteric lymph nodes: reactive lymphadenopathy
- liver: foci of hepatocellular necrosis
- gallbladder: fibrinous cholecystitis (distinctive sign in calves)
what lesion is shown here in a foal
acute salmonellosis, colitis with prominent fibrino necrotic membranes
what strain of salmonella causes chronic enteric salmonellosis
salmonella typhimurium
what species does chronic enteric salmonellosis occur in
pigs, cattle, horses
lesions most commonly observed in pigs
what lesions are seen in chronic enteric salmonellosis and where
multiple discrete areas of necrosis and ulceration mostly in the cecum and colon
what lesions are shown here in the horse
chronic enteric salmonellosis
colon, nodular ulcerative lesions
what type of bacteria is lawsonia intracellularis (gram - or +)
-ve
what species are susceptible to Lawsonia intracellularis
swine, horses, hamster, rabbit, ferret, sheep, deer, fox
what are the clinicopathological presentations of lawsonia intracellularis in swine
porcine intestinal adenomatosis (PIA)
necrotic enteritis
proliferative hemorrhagic enteropathy (PHE)
–> porcine proliferative enteropathy (PPE)
what causes equine proliferative enteropathy (EPE)
lawsonia intracellularis
when does equine proliferative enteropathy typically occur
in post weaning foals (2-8 months)
occasionally in adult animals
what lesions are shown in this pig
lawsonia intracellularis infection
PPE intestinal adenomatosis
what are the clinical signs in horses with Lawsonia intracellularis (8)
- rapidly deteriorating body condition
- anorexia
- hypoproteinemia (hypoalbuminemia)
- peripheral edema
- fever
- lethargy
- colic and diarrhea
- secondary bacteremia
what do the virulence factors that lawsonia intracellularis produce cause
inhibition of enterocyte differentation –> impaired absorption –> osmotic/malabsorptive diarrhea
induction of enterocyte proliferation
how is equine proliferative enteropathy (EPE) diagnosed
- ELISA (serum)
- PCR on feces
- distinctive gross PM findings
- immunohistochemistry
what does Rhodococcus equi cause
enterocolitis in foals
where Rhodococcus equi found
in the soil and as part of normal intestinal flora
what does R. equi cause in foals
suppurative bronchopneumonia and about 50% of pneumonic foals also have ulcerative colitis
where are the lesions associated with R. equi
in small and large intestine
most severe in peyer’s patches in SI, cecum, large colon, and related lymph nodes
what are the ulcers covered in in R. equi infection
purulent/necrotic debris
what occurs in the mesenteric LNs in R. equi
mesenteric LNs –> enlarged –> pyogranulomatous inflammation/abscesses
what is shown here
foal with R. equi infection
ulcerative colititis
what is shown here
suppurative/pyogranulomatous mesenteric lymphadenitis
R. equi infection
is clostridia a gram negative or positive bacteria
gram + spore forming anaerobic bacillary bacteria
what does clostridia perfringens cause
enterotoxemias
what does clostridia difficile cause
entero-typhlo-colitis
what does clostridia piliforme cause
tyzzer’s disease (necrotizing colitis, hepatitis and myocarditis)
what changes in the enteric microenvironment favour expansion of enteric populations of clostridia (5)
- change in feed, abnormally nutrient rich digesta
- antibiotic therapy
- altered pancreatic exocrine function or trypsin inhibitors
- reduced intestinal motility
- primary infections (CPV-2 or coccidia in piglents and chickens)
what are 3 mechanisms of clostridial disease (3)
- local effects of toxins on mucosa –> hemorrhage, fibrinous, or necrotic enteritis
- secretory effects of locally acting enterotoxin –> diarrhea and minor lesions
- systemic absorption of entero toxins –> effects at sites distant from gut
what does Cl. perfringens type D enterotoxemia cause
focal symmetrical encephalomalacia
what toxin does Cl. perfringens type D enterotoxemia produce
ε toxin which causes vascular endothelial damage –> vascular leakage
what does ε toxin in Cl. perfringens cause
generalized brain edema
ischemia and degeneration/necrosis (malacia) in different areas of the brain
what does clostridium perfringens type A cause in foals
necrotizing hemorrhagic enteritis
what does clostridium perfringens type A cause in adult horses
enterocolitis
what does what does clostridium perfringens type A cause in piglets
necrotizing enterocolitis
what does clostridium perfringens type A cause in lambs and calves
enterotoxemia and hemorrhagic enteritis
what does clostridium perfringens type A cause in chickens
necrotizing enteritis
what does clostridium perfringens type A cause in canines
hemorrhagic canine gastroenteritis
bloody diarrhea
peracute syndrome with enteritis and colitis (occasionally hemorrhagic gastritis)
what is the pathology of clostridial perfringens type C enterotoxemia in horses
serosal and mucosal congestion/hemorrhage
thickening with gelatinous clear transmural edema
mucosal necrosis/hemorrhage
brown to red foul smelling fluid intestinal contents
what lesions can clostridium perfringens type C enterotoxemia in horses cause in the lungs (3)
- congestion
- hemorrhage
- thrombosis
what lesions can clostridium perfringens type C enterotoxemia in horses cause in the heart
subepicardial and subendocardial hemorrhage
what lesions can clostridium perfringens type C enterotoxemia in horses cause in the visceral organs and serosal surfaces (2)
- congestion
- hemorrhage
what lesions can clostridium perfringens type C enterotoxemia in horses cause in the mesenteric lymph nodes (3)
- edema
- congestion
- hemorrhage
what lesions can clostridium perfringens type C enterotoxemia in horses cause in the kidney (2)
- tubular degeneration
- necrosis
where is clostridial difficile found
spores common in environment and intestinal tract of many mammals
what does clostridium difficile cause in foals
hemorrhagic enterocolitis
what does clostridium difficile cause in adult horses
necrotizing typhlocolitis
what does clostridial difficile cause in suckling piglets
mesocolonic edema and typhlocolitis
what do clostridium difficile exotoxins cause (3)
- damage to intestinal epithelium
- trigger inflammatory reaction
- stimulation of the enteric nervous system
what are predisposing factors of clostridium difficile enteric infection in horses (8)
- antibiotic therapy
- hospitilization
- stress
- change of diet
- transportation
- starvation
- nasogastric intubation
- surgical or medical treatment
what is the age related distribution of lesions in horses with clostridium difficile
- <1 mo: small intestine involvement
- 1mo- 1 y: colon (no small intestine or cecum)
- >1y: colon/cecum (no small intestines)
what gross lesions can be found in horses with clostridium infections
left ventral colon: diffuse mucosal congestion/hemorrhage
large colon distended with abundant, turbid, green fluid (with grass particles and seeds in suspension)
large colon: transmural gelatinous edema
necrotizing or necro-hemorrhagic enteritis, colititis and/or typhlitis
how is clostridium diagnosed
ELISA based detection of toxins
what pathogen causes potomac horse fever (equine monocytic ehrlichiosis)
neorickettsia risticii
where is neorickettsia risticii found
river valleys in NE usa but now throughout US and south america
when is neorickettsia risticii disease most commonly observed in
summer
what type of bacteria is neorickettsia risticii
obligate intracellular bacterial pathogen
how is potomac horse fever transmitted
accidental ingestion of trematode larvae infected with N. risticii
what disease does potomac horse fever cause (7)
- fever
- leukopenia
- depression
- inappetance
- diarrhea
- abortion in pregnant mares
- fibrino-necrotic to ulcerative colitis
what is the disease expression of potomac horse fever cause
- colic
- subcutaneous edema
- laminitis
- shock
- mortality in up to 30% of untreated cases
what are the differentials to the disease expression of potomac horse fever
salmonella
clostridium
what is GCB
granulomatous colitis of boxer dogs
what are the clinical signs of GCB (4)
- frequent bloody mucoid stools
- anemia
- hypoalbuminemia
- weight loss
what is the gross pathology found with GCB (2)
- thickening and folding of the colon
- possible dilation and shortening with some segmental or focal areas of scarring and stricture
what are the mucosal lesions of GCB (2)
- patchy punctate red ulcers
- more extensive irregular circular or linear lesions that may coalesce
what disease are these lesions associated with
GCB of boxer dogs
what histopathology changes can be seen here in GCB
lamina propria expanded by macrophages (containing PAS positive material)
what histopathological changes can occur with GCB
- loss of colonic epithelium and goblet cells/microerosions
- neutrophilic infiltration and neutrophil efflux into the gut lumen
- glandular crypts displacement, with possible hyperplasia
what can occur in the mucosa with GCB
E.coli isolates from GCB have an adherent/invasive phenotype similar to Crohn’s disease
there are clusters of bacteria within the mucosa
what changes occur due to idiopathic inflammatory bowel disease (IBD) (4)
- villus blunting (and possible alteration of superficial epithelium)
- variable crypt dilation (filled with mucus and cellular debris)
- possible crypt epithelial hyperplasia
- inflammatory cell infiltration in lamina propria (and variably intraepithelial)
–> mostly small lymphocytes and plasmacells
–> variable numbers of neutrophils/eosinophils
what is an important ddx with IBD
intestinal lymphoma because in IBD there can be small lymphocytes and plasma cells and variable number of neutrophils/eosinophils
what are the genetic predispositions to IBD (4)
- Basenji
- german shepherds
- boxer (GCB)
- irish setter: enteritis associated with familial sensitivity to wheat protein
what factors can contribute to IBD (4)
- perturbation of balance mucosal immunity/intestinal microbiota
- shifts in intestinal microbiome gram + –> gram - proteobacteria –> dysbiosis possible trigger and drive to persistent inflammation
- diet (food allergy/adverse food reaction)
- loss of tolerance to dietary and/or intestinal microflora antigens: innate immune response dysregulation as possible trigger
what are the histological parameters in the stomach in IBD (3)
- fibrosis
- intraepithelial lymphocytes
- lamina propria inflammatory infiltrates
what are the histological parameters in the duodenum and ileum in IBD (5)
- villus stunting
- crypt dilation
- lacteal dilation
- surface epithelial injury
- lamina propria inflammatory infiltrates
what are the histological parameters of the colon in IBD (5)
- crypt dilation
- fibrosis
- goblet cell number
- surface epithelial injury
- lamina propria inflammatory infiltrates
in calves <3 weeks what are the pathogens that can cause gastroenteritis (9)
- enterotoxigenic E.coli
- enterohemorrhagic E.coli (Shiga toxin)
- rotavirus
- cornnavirus
- bovine viral diarrhea (BVDV pestivirus)
- bvine herpesvirus
- clostridium perfringens type C
- GI parasites
- cryptosporidium
in cattle >3 weeks what are the pathogens that can cause gastroenteritis
in small ruminants <3 weeks what are the pathogens that can cause gastroenteritis
in small ruminants >3 weeks what are the pathogens that can cause gastroenteritis
in piglets <3 weeks what are the pathogens that can cause gastroenteritis
in pigs >3 weeks what are the pathogens that can cause gastroenteritis
in foals what are the pathogens that can cause gastroenteritis
in adult horses what are the pathogens that can cause gastroenteritis
in dogs what are the pathogens that can cause gastroenteritis
in cats what are the pathogens that can cause gastroenteritis
how do you differentiate lymphoma from IBD
histopathology, immunochemistry and PARR
- inraepithelial nests (>5 clustered lymphocytes) and intraepithelial plaques (lymphocytes obliterating >5 adjacent enterocytes) are both strong indicators for intestinal T-cell lymphoma
