Pathology of Bacterial Infections Inflammatory in GI System

Question 1

what is the main function of the GI system (4)

Answer 1

1. selectively permeable barrier
2. transit, digestion and absorption of nutrients, electrolytes and fluids
3. prevent entry of pathogens and toxis
4. immune function (extensively developed mucosal associated lymphoid tissue MALT)

Question 2

what are the cell types in the intestine (6)

Answer 2

1. globet cell
2. enterocyte
3. paneth cell
4. M cell
5. neuroendocrine cell
6. stem cells

Question 3

what are the functions of globlet cell

Answer 3

mucus layer production

Question 4

what are the functions of enterocytes

Answer 4

absorption

Question 5

what are the functions of paneth cell

Answer 5

antimicrobial proteins/peptides

• lysozyme
• phospholipase
• DNAse
• ribonuclease
• alpha-defensins

Question 6

what are the functions of M cells

Answer 6

microorganisms, particles and macromolecules uptake and transfer

Question 7

what are the functions of neuroendocrine cell

Answer 7

serotonin

somatostatin

cholecystokinin

peptide UU

glucagon-like peptide

secretin regulation of: intestinal motility, secretions, visceral sensations, appetite

Question 8

what are the functions of stem cells

Answer 8

intestinal epithelium renewal compartment reside in the lower half portion of the crypts

Question 9

what are the mechanisms of diarrhea

Answer 9

1. secretory
2. osmotic/malabsorptive
3. inflammatory

Question 10

what is the mechanism of secretory diarrhea induced by bacterial toxins (11)

Answer 10

1. ingestion of bacteria
2. colonization of mucosa
3. release of toxin
4. heat labile or heat stable entertoxin
5. pass through intestinal lumen through receptor
6. causes increase in adenylyl or guanylate cyclase activity
7. increase in cAMP or cGMP
8. causes of activation of ion/H2O pumps
9. causes water, K+, Cl-, Na+, HCO3- to pass through intestinal lumen
10. causes severe dehydration/electrolyte imbalances
11. leads to secretory diarrhea

Question 11

what is the net effect of secretory diarrhea induced by bacterial toxins

Answer 11

net increase in electrolytes and water passing through small intestine to colon

Question 12

what other factors stimulate secretory diarrhea (2)

Answer 12

1. prostaglandins and other arachidonic acid derived inflammatory mediators
2. histamine, kinins, cytokines

Question 13

what factors cause increase in bacterial overgrowth (8)

Answer 13

1. increased entry of bacteria
2. abnormality of intestinal loops
3. reduced clearance of bacteria
4. reduced gastric acidity increased pH
5. motility disturbance
6. obstruction of intestine
7. immunodeficiency
8. cachexia (wasting syndrome)

Question 14

what is the mechanism of malabsorption diarrhea due to bacterial overgrowth

Answer 14

multiple factors lead to bacterial overgrowth leading to:

1. bile salt conjugation –> bile salt deficiency –> malabsorption
2. toxins –> intestinal epithelial cell injury –> malabsorption
3. consumption of nutrients –> malapsorbtion

Question 15

what is the mechanism of inflammatory diarrhea (5)

Answer 15

1. ingestion of bacteria
2. cytotoxin release
3. villous enterocytes release IL-8 –> activation of local macrophages which release histamine, serotonin, adenosine –> leukocytes recruitment
4. these local factors cause increased intestinal Cl-, H2O secretion + inhibit absorption, promote secretory diarrhea
5. acute inflammation –> prostaglandins/leukotrines, PAF, cytokines
6. promote diarrhea

Question 16

what are the consequences of diarrhea

Answer 16

1. dehydration
2. electrolyte depletion
3. metabolic acidosis

Question 17

what are the factors that influence gastroenteritis and diarrhea in domestic animals

Answer 17

1. age
2. immunity (colostrum?)
3. environmental/seasonal factors
4. management conditions

Question 18

what are the issues that interfere with pathology diagnosis of diarrhea in swine and ruminants (2)

Answer 18

1. causal agents can be transiently present
2. causal agents produce lesions such as villus atrophy which are easily obscured by autolysis

Question 19

how do you overcome the diagnostic issues in diarrhea in ruminants and swines

Answer 19

1. evaluate one or more untreated animals representative of the herd problem
2. preferably in the early phase of the disease and with symptoms (not in advanced condition if possible)

Question 20

how would you collect samples in pathology diagnosis in ruminants and swine

Answer 20

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)

Question 21

what are patterns of intestinal injury and some examples in horses, dogs, swine, calves, goats, bovine

Answer 21

1. catarrheal enteritis and intestinal impaction: ascarids in horses
2. hemorrhagic enteritis: dogs hookworms
3. necrotizing colitis (‘swine dysentry’): pig brachyspira hydodysenteriae
4. proliferative enteritis: goat coccidiosis
5. granulomatous enteritis: bovine johne’s disease
6. necrotizing-hemorrhagic enteritis: calf coccidiosis

Question 22

what are the effects of bacterial virulence factors (5)

Answer 22

1. production of bacterial toxins that kill phagocytes
2. synthesis of bacterial proteins that prevent phagocytosis by blocking the interaction of opsonins with phagosomes
3. bacterial capsule –> block contact with microbe –> prevent phagocytosis
4. facilitate escape of the microbe into the cytoplasm before the microbe is killed in the phagolysomes
5. production of bacterial antioxidants (ex. catalase) that block killing in phagolysosomes

Question 23

what do E. coli (ETEC) adhere to

Answer 23

microvilli on intestinal epithelium

Question 24

what effect do heat labile toxins from E. coli have

Answer 24

LT-I and LT-II

Cl- secretion from enterocytes which cause diarrhea

Question 25

what effect do the heat stable toxins from E.coli have

Answer 25

inhibit Na+/Cl- cotransport in surface enterocytes which indice Cl- and water secretion from crypt enterocytes

Question 26

what does verotoxin ETEC cause

Answer 26

porcine edema disease shiga toxin --\> systemic vascular endothelial damage --\> leakage --\> edema brain and spinal cord vessels also affected --\> neurological manifestations

Question 27

what do enteropathogenic/attaching effacing E. coli (EPEC/AEEC) cause

Answer 27

attachment + translocation into enterocytes --\> loss of microvillus brush border

Question 28

what are enteroinvasive E. coli (EIC) cause

Answer 28

internalized by surface enterocytes --\> disseminate through the body --\> septicemic colibacillosis

Question 29

what do the shiga toxin produce E.coli cause

Answer 29

protein synthesis inhibition + apoptosis

Question 30

what are the gross signs of porcine edema disease

Answer 30

subcutaneous edema of snout, eyelids, angle of the mandible edema of gastric wall edema of mesocolon

Question 31

what are the common serovars of salmonella

Answer 31

S. typhimurium S. dublin S choleraesuis

Question 32

what type of bacteria is salmonella

Answer 32

gram negative

Question 33

is salmonella an aerobe or anaerobic bacteria

Answer 33

aerobe/faculative anerobic

Question 34

is salmonella motile or non motile

Answer 34

motile

Question 35

how is salmonellosis transmitted

Answer 35

oro-fecal --\> penetrate through M cells

Question 36

what does salmonella invade

Answer 36

enterocytes

Question 37

what is the virulence factor of salmonella

Answer 37

neutralization of macrophage nitric oxide (NO) production bacteria survive within macrophage phagolysosomes additional virulence factors: fimbriae (adhesions), lipopolysaccharide (LPS)

Question 38

what affect do the salmonella toxins have (5)

Answer 38

1. damage to the enterocytes --\> interfere with closure of chloride channels --\> secretory diarrhea 2. interaction with toll like receptor (TLRs) 3. cytokines/chemokines upregulation 4. inflammation with neutrophil influx 5. inflammatory cells-derived PGE-2--\> further chloride hypersecretion these all amplify inflammation that promote further chloride secretion and diarrhea

Question 39

what is the pathogenesis of infection of salmonella

Answer 39

1. salmonella invade M cells in intestinal epithelium 2. macrophages in lamina propria and Peyer's patches which are able to resist killing from macrophages 3. transferred to mesenteric lymph nodes 4. via portal circulation to liver

Question 40

what is peracute septicemic salmonellosis

Answer 40

disease of calves, foals and pigs younger animals most sensitive usually fatal in animals 1-6 months of age

Question 41

what is the pathogenesis of peracute septicemic salmonellosis

Answer 41

multisystemic vascular lesions with fibrinoid change, thrombosis and necrosis 2. petechiation and blue discoloration (cyanosis) of ventral abdomen, extremities (ears commonly affected) 3. death caused by disseminated intravascular coagulation (DIC)

Question 42

how does salmonellosis classically present in swine

Answer 42

congestion/cyanosis of the ear pinna with ischemic necrosis of the tip

Question 43

how does horse peracute salmonellosis present

Answer 43

colon have areas of hemorrhage and necrosis from vascular thrombosis and subsequent ischemia hemorrhagic necrosis --\> vascular thrombosis with subsequent ischemia

Question 44

what bacteria causes acute enteric salmonellosis

Answer 44

salmonella typhimurium

Question 45

how does acute enteric salmonellosis adhere

Answer 45

surface fimbrial antigens (pilus adhesion) mediate invasion receptor mediated endocyte within enterocytes membrane bound vacuoles --\> translocate bacteria to lamina propria macrophages

Question 46

what are the pathogenic affects of acute enteric salmonellosis

Answer 46

1. interference with chloride channels --\> secretory diarrhea 2. induction of enterocyte apoptosis + recruitment of neutrophils 3. endotoxins --\> vascular thrombosis

Question 47

what type of intestinal lesions does acute enteric salmonellosis cause

Answer 47

fibrino necrotic enterocolitis malodourous intestinal contents with mucus, fibrin and occasionally blood

Question 48

what extra intestinal lesions can be found with acute enteric salmonellosis (3)

Answer 48

1. mesenteric lymph nodes: reactive lymphadenopathy 2. liver: foci of hepatocellular necrosis 3. gallbladder: fibrinous cholecystitis (distinctive sign in calves)

Question 49

what lesion is shown here in a foal

Answer 49

acute salmonellosis, colitis with prominent fibrino necrotic membranes

Question 50

what strain of salmonella causes chronic enteric salmonellosis

Answer 50

salmonella typhimurium

Question 51

what species does chronic enteric salmonellosis occur in

Answer 51

pigs, cattle, horses lesions most commonly observed in pigs

Question 52

what lesions are seen in chronic enteric salmonellosis and where

Answer 52

multiple discrete areas of necrosis and ulceration mostly in the cecum and colon

Question 53

what lesions are shown here in the horse

Answer 53

chronic enteric salmonellosis colon, nodular ulcerative lesions

Question 54

what type of bacteria is lawsonia intracellularis (gram - or +)

Answer 54

-ve

Question 55

what species are susceptible to Lawsonia intracellularis

Answer 55

swine, horses, hamster, rabbit, ferret, sheep, deer, fox

Question 56

what are the clinicopathological presentations of lawsonia intracellularis in swine

Answer 56

porcine intestinal adenomatosis (PIA) necrotic enteritis proliferative hemorrhagic enteropathy (PHE) **--\> porcine proliferative enteropathy (PPE)**

Question 57

what causes equine proliferative enteropathy (EPE)

Answer 57

lawsonia intracellularis

Question 58

when does equine proliferative enteropathy typically occur

Answer 58

in post weaning foals (2-8 months) occasionally in adult animals

Question 59

what lesions are shown in this pig

Answer 59

lawsonia intracellularis infection PPE intestinal adenomatosis

Question 60

what are the clinical signs in horses with Lawsonia intracellularis (8)

Answer 60

1. rapidly deteriorating body condition 2. anorexia 3. hypoproteinemia (hypoalbuminemia) 4. peripheral edema 5. fever 6. lethargy 7. colic and diarrhea 8. secondary bacteremia

Question 61

what do the virulence factors that lawsonia intracellularis produce cause

Answer 61

inhibition of enterocyte differentation --\> impaired absorption --\> osmotic/malabsorptive diarrhea induction of enterocyte proliferation

Question 62

how is equine proliferative enteropathy (EPE) diagnosed

Answer 62

1. ELISA (serum) 2. PCR on feces 3. distinctive gross PM findings 4. immunohistochemistry

Question 63

what does Rhodococcus equi cause

Answer 63

enterocolitis in foals

Question 64

where Rhodococcus equi found

Answer 64

in the soil and as part of normal intestinal flora

Question 65

what does R. equi cause in foals

Answer 65

suppurative bronchopneumonia and about 50% of pneumonic foals also have ulcerative colitis

Question 66

where are the lesions associated with R. equi

Answer 66

in small and large intestine **most severe in peyer's patches in SI, cecum, large colon, and related lymph nodes**

Question 67

what are the ulcers covered in in R. equi infection

Answer 67

purulent/necrotic debris

Question 68

what occurs in the mesenteric LNs in R. equi

Answer 68

mesenteric LNs --\> enlarged --\> pyogranulomatous inflammation/abscesses

Question 69

what is shown here

Answer 69

foal with R. equi infection ulcerative colititis

Question 70

what is shown here

Answer 70

suppurative/pyogranulomatous mesenteric lymphadenitis R. equi infection

Question 71

is clostridia a gram negative or positive bacteria

Answer 71

gram + spore forming anaerobic bacillary bacteria

Question 72

what does clostridia perfringens cause

Answer 72

enterotoxemias

Question 73

what does clostridia difficile cause

Answer 73

entero-typhlo-colitis

Question 74

what does clostridia piliforme cause

Answer 74

tyzzer's disease (necrotizing colitis, hepatitis and myocarditis)

Question 75

what changes in the enteric microenvironment favour expansion of enteric populations of clostridia (5)

Answer 75

1. change in feed, abnormally nutrient rich digesta 2. antibiotic therapy 3. altered pancreatic exocrine function or trypsin inhibitors 4. reduced intestinal motility 5. primary infections (CPV-2 or coccidia in piglents and chickens)

Question 76

what are 3 mechanisms of clostridial disease (3)

Answer 76

1. local effects of toxins on mucosa --\> hemorrhage, fibrinous, or necrotic enteritis 2. secretory effects of locally acting enterotoxin --\> diarrhea and minor lesions 3. systemic absorption of entero toxins --\> effects at sites distant from gut

Question 77

what does Cl. perfringens type D enterotoxemia cause

Answer 77

focal symmetrical encephalomalacia

Question 78

what toxin does Cl. perfringens type D enterotoxemia produce

Answer 78

ε toxin which causes vascular endothelial damage --\> vascular leakage

Question 79

what does ε toxin in Cl. perfringens cause

Answer 79

generalized brain edema ischemia and degeneration/necrosis (malacia) in different areas of the brain

Question 80

what does clostridium perfringens type A cause in foals

Answer 80

necrotizing hemorrhagic enteritis

Question 81

what does clostridium perfringens type A cause in adult horses

Answer 81

enterocolitis

Question 82

what does what does clostridium perfringens type A cause in piglets

Answer 82

necrotizing enterocolitis

Question 83

what does clostridium perfringens type A cause in lambs and calves

Answer 83

enterotoxemia and hemorrhagic enteritis

Question 84

what does clostridium perfringens type A cause in chickens

Answer 84

necrotizing enteritis

Question 85

what does clostridium perfringens type A cause in canines

Answer 85

hemorrhagic canine gastroenteritis bloody diarrhea peracute syndrome with enteritis and colitis (occasionally hemorrhagic gastritis)

Question 86

what is the pathology of clostridial perfringens type C enterotoxemia in horses

Answer 86

serosal and mucosal congestion/hemorrhage thickening with gelatinous clear transmural edema mucosal necrosis/hemorrhage brown to red foul smelling fluid intestinal contents

Question 87

what lesions can clostridium perfringens type C enterotoxemia in horses cause in the lungs (3)

Answer 87

1. congestion 2. hemorrhage 3. thrombosis

Question 88

what lesions can clostridium perfringens type C enterotoxemia in horses cause in the heart

Answer 88

subepicardial and subendocardial hemorrhage

Question 89

what lesions can clostridium perfringens type C enterotoxemia in horses cause in the visceral organs and serosal surfaces (2)

Answer 89

1. congestion 2. hemorrhage

Question 90

what lesions can clostridium perfringens type C enterotoxemia in horses cause in the mesenteric lymph nodes (3)

Answer 90

1. edema 2. congestion 3. hemorrhage

Question 91

what lesions can clostridium perfringens type C enterotoxemia in horses cause in the kidney (2)

Answer 91

1. tubular degeneration 2. necrosis

Question 92

where is clostridial difficile found

Answer 92

spores common in environment and intestinal tract of many mammals

Question 93

what does clostridium difficile cause in foals

Answer 93

hemorrhagic enterocolitis

Question 94

what does clostridium difficile cause in adult horses

Answer 94

necrotizing typhlocolitis

Question 95

what does clostridial difficile cause in suckling piglets

Answer 95

mesocolonic edema and typhlocolitis

Question 96

what do clostridium difficile exotoxins cause (3)

Answer 96

1. damage to intestinal epithelium 2. trigger inflammatory reaction 3. stimulation of the enteric nervous system

Question 97

what are predisposing factors of clostridium difficile enteric infection in horses (8)

Answer 97

1. antibiotic therapy 2. hospitilization 3. stress 4. change of diet 5. transportation 6. starvation 7. nasogastric intubation 8. surgical or medical treatment

Question 98

what is the age related distribution of lesions in horses with clostridium difficile

Answer 98

1. \<1 mo: small intestine involvement 2. 1mo- 1 y: colon (no small intestine or cecum) 3. \>1y: colon/cecum (no small intestines)

Question 99

what gross lesions can be found in horses with clostridium infections

Answer 99

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**

Question 100

how is clostridium diagnosed

Answer 100

ELISA based detection of toxins

Question 101

what pathogen causes potomac horse fever (equine monocytic ehrlichiosis)

Answer 101

neorickettsia risticii

Question 102

where is neorickettsia risticii found

Answer 102

river valleys in NE usa but now throughout US and south america

Question 103

when is neorickettsia risticii disease most commonly observed in

Answer 103

summer

Question 104

what type of bacteria is neorickettsia risticii

Answer 104

obligate intracellular bacterial pathogen

Question 105

how is potomac horse fever transmitted

Answer 105

accidental ingestion of trematode larvae infected with N. risticii

Question 106

what disease does potomac horse fever cause (7)

Answer 106

1. fever 2. leukopenia 3. depression 4. inappetance 5. diarrhea 6. abortion in pregnant mares 7. fibrino-necrotic to ulcerative colitis

Question 107

what is the disease expression of potomac horse fever cause

Answer 107

1. colic 2. subcutaneous edema 3. laminitis 4. shock 5. mortality in up to 30% of untreated cases

Question 108

what are the differentials to the disease expression of potomac horse fever

Answer 108

salmonella clostridium

Question 109

what is GCB

Answer 109

granulomatous colitis of boxer dogs

Question 110

what are the clinical signs of GCB (4)

Answer 110

1. frequent bloody mucoid stools 2. anemia 3. hypoalbuminemia 4. weight loss

Question 111

what is the gross pathology found with GCB (2)

Answer 111

1. thickening and folding of the colon 2. possible dilation and shortening with some segmental or focal areas of scarring and stricture

Question 112

what are the mucosal lesions of GCB (2)

Answer 112

1. patchy punctate red ulcers 2. more extensive irregular circular or linear lesions that may coalesce

Question 113

what disease are these lesions associated with

Answer 113

GCB of boxer dogs

Question 114

what histopathology changes can be seen here in GCB

Answer 114

lamina propria expanded by macrophages (containing PAS positive material)

Question 115

what histopathological changes can occur with GCB

Answer 115

1. loss of colonic epithelium and goblet cells/microerosions 2. neutrophilic infiltration and neutrophil efflux into the gut lumen 3. glandular crypts displacement, with possible hyperplasia

Question 116

what can occur in the mucosa with GCB

Answer 116

E.coli isolates from GCB have an adherent/invasive phenotype similar to Crohn's disease there are clusters of bacteria within the mucosa

Question 117

what changes occur due to idiopathic inflammatory bowel disease (IBD) (4)

Answer 117

1. villus blunting (and possible alteration of superficial epithelium) 2. variable crypt dilation (filled with mucus and cellular debris) 3. possible crypt epithelial hyperplasia 4. inflammatory cell infiltration in lamina propria (and variably intraepithelial) **--\> mostly small lymphocytes and plasmacells** **--\> variable numbers of neutrophils/eosinophils**

Question 118

what is an important ddx with IBD

Answer 118

intestinal lymphoma because in IBD there can be small lymphocytes and plasma cells and variable number of neutrophils/eosinophils

Question 119

what are the genetic predispositions to IBD (4)

Answer 119

1. Basenji 2. german shepherds 3. boxer (GCB) 4. irish setter: enteritis associated with familial sensitivity to wheat protein

Question 120

what factors can contribute to IBD (4)

Answer 120

1. perturbation of balance mucosal immunity/intestinal microbiota 2. shifts in intestinal microbiome gram + --\> gram - proteobacteria --\> dysbiosis possible trigger and drive to persistent inflammation 3. diet (food allergy/adverse food reaction) 4. loss of tolerance to dietary and/or intestinal microflora antigens: innate immune response dysregulation as possible trigger

Question 121

what are the histological parameters in the stomach in IBD (3)

Answer 121

1. fibrosis 2. intraepithelial lymphocytes 3. lamina propria inflammatory infiltrates

Question 122

what are the histological parameters in the duodenum and ileum in IBD (5)

Answer 122

1. villus stunting 2. crypt dilation 3. lacteal dilation 4. surface epithelial injury 5. lamina propria inflammatory infiltrates

Question 123

what are the histological parameters of the colon in IBD (5)

Answer 123

1. crypt dilation 2. fibrosis 3. goblet cell number 4. surface epithelial injury 5. lamina propria inflammatory infiltrates

Question 124

in calves \<3 weeks what are the pathogens that can cause gastroenteritis (9)

Answer 124

1. enterotoxigenic E.coli 2. enterohemorrhagic E.coli (Shiga toxin) 3. rotavirus 4. cornnavirus 5. bovine viral diarrhea (BVDV pestivirus) 6. bvine herpesvirus 7. clostridium perfringens type C 8. GI parasites 9. cryptosporidium

Question 125

in cattle \>3 weeks what are the pathogens that can cause gastroenteritis

Answer 125

Question 126

in small ruminants \<3 weeks what are the pathogens that can cause gastroenteritis

Answer 126

Question 127

in small ruminants \>3 weeks what are the pathogens that can cause gastroenteritis

Answer 127

Question 128

in piglets \<3 weeks what are the pathogens that can cause gastroenteritis

Answer 128

Question 129

in pigs \>3 weeks what are the pathogens that can cause gastroenteritis

Answer 129

Question 130

in foals what are the pathogens that can cause gastroenteritis

Answer 130

Question 131

in adult horses what are the pathogens that can cause gastroenteritis

Answer 131

Question 132

in dogs what are the pathogens that can cause gastroenteritis

Answer 132

Question 133

in cats what are the pathogens that can cause gastroenteritis

Answer 133

Question 134

how do you differentiate lymphoma from IBD

Answer 134

histopathology, immunochemistry and PARR 1. inraepithelial nests (\>5 clustered lymphocytes) and intraepithelial plaques (lymphocytes obliterating \>5 adjacent enterocytes) are both strong indicators for intestinal T-cell lymphoma