Small and Large Intestinal Disease Flashcards
1
Q
Describe the locations of the most severe lesions in DPJ
A
- duodenum and proximal jejunum
- may extend proximally to gastric mucosa and aborally to LI mucosa and submucosa
2
Q
Describe the microscopic lesions associated with DPJ
A
- varying degrees of mucosal and submucosal hyperaemia with oedema
- more severe lesions include villous degeneration with necrosis and more severely, sloughing of villous epithelium
- lamina propria, mucosa and submucosa may have varying degrees of granulocyte infiltration (predominantly neutrophils)
- muscular layers and serosal surfaces contain small haemorrhages
- proximal SI serosal fibrinopurulent exudate is common finding in more severe cases
- can have evidence of multiple organ involvement - can have hepatic changes including hepatocellular vacuolization, cholestasis, inflammatory infiltrate and biliary hyperplasia
3
Q
Describe the possible mechanisms of development of hepatic disease in DPJ?
A
- ascending infection by way of the common bile duct
- local absorption of endotoxin via portal circulation
- systemic consequences of endotoxin absorption
- metabolic imbalances such as acidaemia
- hypoperfusion or hypovolaemia
4
Q
Which infectious agents have been proposed to play a role in DPJ?
A
- Salmonella spp. (although Salmonellosis not consistently identified in majority of cases)
- Clostridium spp.
- Fusarium spp.
5
Q
List possible predisposing factors for DPJ
A
- recent dietary change with abrupt increase in dietary concentrate - may cause intraluminal microbial imbalances
6
Q
Name the two intracellular processes that control intestinal secretion.
A
- cyclic nucleotide (cAMP & CGMP) system
- calcium system
7
Q
List the common clinical pathology findings in peritoneal fluid of horses with DPJ
A
- protein concentration higher than in horses with SI obstruction (often > 3.5g/dL)
- mild to moderate increase in WCC (usually < 10000/microliter)
- disproportionate increase in total protein concentration relative to TNCC - probably by leakage of blood or plasma into peritoneal cavity without significant stimulus for leukocyte chemotaxis
- usually yellow and turbid - in severe cases, diapedesis can occur, resulting in serosanguinous colour
8
Q
Discuss the suggested mechanisms for increased abdominal fluid protein concentration in DPJ
A
- serositis associated with inflamed intestine
- SI distension causing passive congestion and increased capillary hydrostatic pressure of visceral peritoneal vessels
9
Q
Discuss the pathophysiology and predisposing factors for development of ileus in DPJ
A
- involves primary and secondary dysfunction of the central, autonomic and enteric nervous systems
- peritoneal inflammation
- inflammatory cell migration/activation within the muscularis
- SI mechanical distension
- endotoxin absorption
10
Q
Describe the difference in clinical signs between DPJ and SI obstructive lesions
A
- signs of acute abdominal pain typically subside after gastric decompression - then display lethargy, general malaise
- degree of SI distension on rectal exam is less, particularly following gastric decompression
- colour and odour of gastric reflux can be similar but horses with DPJ tend to have larger volume (>4-20L with each decompressive effort)
- temperature often 38.6 - 39.1
- brick-red mm, lethargy, decreased to absent gut sounds, prolonged CRT, tachycardia, tachypnoea
11
Q
Describe the haematology and biochemical abnormalities in horses with DPJ
A
- normal, decreased or increased WCC
- abnormalities in leukogram more common than in horses with SI obstructive lesions
- increased PCV and TPP reflective of volume depletion
- biochemical changes: hyponatraemia, hypochloraemia, hypokalaemia, prerenal azotaemia, elevated liver enzymes (GGT, AST, ALP)
- metabolic acidosis with high anion gap - loss of enteric bicarbonate through evacuation of gastric reflux and hyperlactataemia from poor tissue perfusion and hypovolaemia
12
Q
Describe the ultrasonographic findings in DPJ
A
- gastric distension
- duodenal distension
- segments of SI containing hypoechoic to anechoic fluid
- wall of SI can be normal or thickened with time
- peristalsis decreased, normal or increased
13
Q
Define malabsoprtion
A
The impairment of digestive and absorptive processes arising from functional or structural disorders of the SI and related organs, including the pancreas, liver and biliary tract
14
Q
List the carbohydrate absorption tests used for the diagnosis of IBD in horses
A
1) oral glucose tolerance test - 1g/kg glucose administered as 20% solution via NGT following overnight fast (14-16hrs)
- blood glucose measured at 30min intervals for 180mins; then at 60min intervals until 360mins
- max plasma glucose level (> 85% baseline) reached by 120mins in healthy horses
- 15-85% baseline = partial malabsorption
- < 15% baseline = total malabsorption
- abnormal OGTT result and weight loss can occur in horse as a transient event and without significant morphologic changes in SI
- immediate dietary history, gastric emptying rate, intestinal transit, age and hormonal effects influence glucose peak and curve shape
- prolonged fasting results in delayed and slightly lower peak
- also affected by content of NSC and fat in diet and other disorders such as PSSM
2) D-Xylose absorption test
- 0.5g/kg D-xylose administered as 10% solution via NGT
- same fasting and blood collection as OGTT
- peak plasma D-xylose b/w 20-25mg/dL b/w 60-90 mins
- not confounded by hormonal effects or mucosal metabolism
- altered by diet, length of fasting and age, gastric emptying rate, intestinal motility, intraluminal bacterial overgrowth and renal clearance
- abnormal tests likely indicates abnormal mucosal SA or permeability
15
Q
Discuss the features of lactase deficiency in foals
A
- secondary lactase deficiency can occur when a SI disorder damages epithelial cells, resulting in decreased brush border disaccharidase activity
- typically rotavirus
- also reported secondary to clostridial enteritis in foals
- can perform oral lactose tolerance test - 1g/kg lactose monohydrate as 20% solution via NGT; same blood sampling as OGTT; plasma glucose typically peaks 1hr after lactose administration (range 30-90mins) with mean increase of 77mg/dL
16
Q
Discuss the findings on diagnostic workup in horses with alimentary lymphosarcoma
A
- anaemia, thrombocytopenia, neutrophilia or neutropenia, hypoalbuminaemia with hyperglobulinaemia with normal or elevated serum protein
- rectal palpation may reveal intra-abdominal masses, mainly enlarged mesenteric lymph nodes
- abdominocentesis and rectal biopsy not sensitive indicators of disease
- carbohydrate absorption tests: partial to total malabsorption indicative of the severely reduced SA resulting from significant villous atrophy and extensive mucosal or transmural infiltration
- early confirmation necessitates ex lap to obtain multiple intestinal and LN biopises
17
Q
List the disorders associated with MEED (multisystemic eosinophilic epitheliotropic disease)
A
- chronic eosinophilic gastroenteritis
- eosinophilic granulomatosis
- chronic eosinophilic dermatitis
- basophilic enterocolitis
- MEED encompasses disorders characterised by predominant eosinophilic infiltrate in the GIT, associated LN, liver, pancreas, skin and other structures
- accompanied by some degree of malabsorption and enteric protein loss (diarrhoea common)
- liver and pancreatic involvement —–> maldigestion may contribute to wasting disease
18
Q
Describe the skin lesions commonly seen in horses with MEED
A
Exudative dermatitis and ulcerative coronitis
19
Q
List the diagnostic workup findings in MEED
A
- systemic eosinophilia RARE
- hypoalbuminaemia
- elevations in GGT and ALP
- carbohydrate absorption tests: reduced or normal peak concentration delayed to at least 180mins
- morphologic changes less pronounced in SI than LI - severe segmental or multifocal granulomatous lesions with mucosal and transmural thickening and extensive ulceration (likely cause of diarrhoea)
- SI lesions predominate segmentally in proximal duodenum and distal ileum
- significant hyperkeratosis of fundic region may contribute to gastric muscle contractile disruption
- biopsies of rectal mucosa or skin, liver, intestinal tract and LN may assist diagnosis
20
Q
Discuss the causes of MEED
A
- cause is unknown
- could represent chronic, ongoing, immediate hypersensitivity reaction against undefined antigens ingested or excreted into lumen from parasitic, bacterial or dietary sources
- infectious agents have not been identified
21
Q
What is the causative organism of proliferative enteropathy (PE)?
A
Lawsonia intracellularis
- obligate, intracellular, gram negative bacteria
- found in cytoplasm of proliferative crypt epithelial cells of jejunum and ileum
22
Q
What are the diagnostic tests for PE?
A
- may suspect based on clinical signs and severe hypoalbuminaemia in a weanling
- faecal PCR for bacterial DNA
- serum immunofluorescence assay or immunoperoxidase monolayer assay (IMPA) for antibodies against the organism
- IMPA may be more sensitive - titers > or equal to 1:60 considered positive
- submission of both tests (PCR + IMPA) recommended; both tests lack sensitivity esp early in course of disease (serology) or with prior antimicrobial therapy (faecal PCR)
- not typically associated with abnormal carbohydrate absorption tests
- PM diagnosis: characteristic mural thickening and intracellular bacteria within apical cytoplasm of proliferating crypt epithelial cells using silver stains, PCR or immunohistochemical testing
23
Q
What is the common treatment for PE?
A
- IV oxytetracycline
- may follow with oral doxycycline
- duration of tx usually 2-4 weeks
24
Q
Which species of Salmonella are most frequently isolated from horses
A
- gram negative facultatively anaerobic bacteria
- S.enterica serovar group B commonly infect horses
- S. enterica var. typhimurium and S. enterica var. agona
- s. enterica var. typhimurium is most pathogenic serotype in horses and is associated with higher case fatality rate
25
What environmental factors or stresses may increase susceptibility to S. enterica infection?
- high ambient temperature ----> peak incidence in late summer and autumn
- transportation
- antibiotic administration before or during hospitalisation
- gastrointestinal or abdominal sx
- general anaesthesia
- pre-existing GIT disease (eg. colic, diarrhoea)
- presence of leukopenia or laminitis during hospitalisation
- prolonged hospital stay
- change in diet
- immunosuppression
- foals with gastrointestinal dz more likely to shed S. enterica organisms than are adult horses with GIT dz
26
What host factors restrict gastrointestinal colonisation and invasion by pathogens?
- gastric pH
- commensal GIT flora - secrete bacteriocins, SCFAs and other substances; compete for nutrients and space esp. on mucosa
- GIT motility
- mucosal barrier
- mucosal immunity - mucosal antibody secretion and enterocyte-derived cationic peptides
27
What are the features of S.enterica that allow it to invade and survive?
- capable or surviving and multiplying within macrophages, rendering humoral (non cellular) immune systems ineffective
- ability of S. enterica to cause enterocolitis depends on ability to invade GIT mucosa
- invasion of GIT mucosa occurs preferentially through specialised enterocytes called M cells that overlay intestinal lymphoid tissue
- ----> self induced uptake via apical membrane of M cell, often killing the cell in the process
- S. enterica then invades neighbouring cells via basolateral membrane
- virulent S. enterica have invasion mechanism involving generation of a Type III secretory system that enables virulence gene products to be injected directly into enterocytes
- virulence proteins injected into enterocyte ----> induce cell to engulf bacteria by macropinocytosis
- virulence gene products also induce enterocyte chloride and fluid secretion and upregulate enterocyte transcription of inflammatory cytokines and chemokines that trigger mucosal infl. response
28
What are the important defense mechanisms against dissemination and systemic infection by S.enterica?
- specific cellular immunity
- protective immunity may be induced by oral inoculation with small numbers of virulent organisms but duration of immunity not known
- oral and parenteral vaccines using killed or attenuated organisms and bacterial products effective only against homologous organisms
29
What are the causes of diarrhoea associated with virulent S. enterica.
- a S. enterica cytotoxin inhibits protein synthesis in mucosal cells, causing morphologic damage and altered permeability
- produce an enterotoxin that increases secretion of chloride and water by colonic mucosal cells (by increasing cAMP concentrations)
- ability to invade enterocytes and trigger infl. reaction - infl. cytokine and chemokine production ---> recruitment of leukocytes esp neutrophils and activation of resident macrophages and mast cells
- products of activated leukocytes include prostaglandins, leukotrienes, reactive O2 metabolites and histamine ----> potent stimulators of chloride secretion in colon
- enteric nervous system integrates the diverse processes of pathogen recognition, triggering of infl. response and induction of enterocyte fluid secretion
30
What are the four clinical syndromes of S. enterica infection in horses?
1) inapparent infections with latent or active carrier states
- can be activated to clinical dz in compromised horses
- latent infections can become active infections under certain conditions (transportation stress, AB tx)
2) depression, fever, anorexia and neutropenia without diarrhoea or colic
- good px and usually recover in several days without specific tx
3) fulminant or peracute enterocolitis with diarrhoea
4) septicaemia (enteric fever) with or without diarrhoea
- mostly restricted to neonatal foals and is uncommon in adult horses
31
How is S. enterica infection diagnosed?
- analysis of five daily faecal cultures using enrichment techniques - sensitivity can be as low as 30-50%; concurrent culture of rectal biopsy specimens may increase sensitivity to 60-75%
- Faecal PCR is most sensitive and rapid detection method esp. if early in dz - up to 100% sensitivity and 98% specificity
- detection of organisms not necessarily proof of dx but PPV of either positive PCR or culture is high in horses with compatible clinical signs
32
What are possible complications of S. enterica infection?
- MODS
- vascular leak syndrome with peripheral and organ oedema
- laminitis
- ARF
- venous thrombosis and septic phlebitis
- irreversible PLE or chronic malabsorption
- pulmonary aspergillosis
- gastrointestinal infarction
33
List the factors which may increase clostridial numbers in the GIT
- dietary factors
- colic
- antibiotics esp those administered orally or recycled via enterohepatic system
- ----> C. difficile likely to be most important cause of antibiotic-induced enterocolitis in the horse
34
Describe the roles of Clostridium difficile toxins A and B in enterocolitis in horses
- Toxin B: potent cytotoxin in vitro but role in enterocolitis is less clear thatthat of toxin A
- Toxin A: enterotoxin that induces an infl. response with hypersecretory diarrhoea; induces neutrophil influx into intestinal tissue, mast cell degranulation and secretion of prostaglandins, histamine, cytokines and 5-HT by these activated leukocytes; products of neutrophils and mast cells have significant role in vasodilatory and secretory responses in intestine
35
Describe the role of the enteric nervous system in C. difficile enterocolitis
- ENS is central to the induction of intestinal inflammation and mucosal secretion by toxin A
- toxin A stimulates substance P-containing afferent sensory nerve fibres ----> in turn stimulate mast cell degranulation, recruitment and activation of PMN and vasodilation
- Toxin A-induced stimulation of enterocyte secretion can occur via secretomotor neuronal stimulation by substance P-containing sensory neurons or products of mast cells and PMN
- mast cell degranulation, PMN influx and enterocyte secretion are all abolished by neural blockade or depletion of substance P
- toxin A induced necrosis of enterocytes likely exposes afferent neurons to the noxious milieu of the intestinal contents
36
Describe the aetiology of equine coronavirus
- Coronaviruses: members of Coronaviridae family - single-stranded, positive-sense, nonsegmented, enveloped RNA viruses
- Coronaviridae subdivided into two subfamilies - Torovirinae and Coronavirinae
- Coronavirinae contains 4 genera defined on basis of serological cross-reactivity and genetic differences: Alpha-, Beta-, Delta- and Gamma-coronavirus
- Equine coronavirus classified within the Betacoronavirus genus
37
Describe the important epidemiology of Equine coronavirus
- sporadic or epizootic
- case number higher during colder months but cases occur year around
- widespread across lower 48 states of USA
- predominantly reported in adult horses
- more common in riding, racing and show horses than in breeding animals
- frequent circulation of ECoV b/w asymptomatic young animals and adult resident horses, conferring protection against clinical disease in adult horses
- suspected faeco-oral transmission
- variable morbidity rate; low mortality rate
- incubation time: 2-3 days
- outbreak duration: 2-3 weeks
- period of illness: few days - 1 week
- faecal shedding can range between 3 and 25 days
- not known how long it can survive in environment and potentially act as source of infection
- ECoV can occur in one or more horses on a farm with no recent exposure to new horses - could be explained by indirect ECoV transmission by nonequine animal species or colder weather may allow increased faecal replication of virus from chronically infected horse
38
What clinical signs are associated with ECoV
- anorexia
- lethargy
- fever
- diarrhoea (less frequent)
- colic
- GIT signs generally preceded by systemic signs of anorexia and fever
- neurological signs - circling, head pressing, ataxia, proprioceptive deficits, nystagmus, recumbency and seizure
- clinical disease apparent in 10-83% of ECoV infected horses but some horses remain asymptomatic after infection
39
How is ECoV diagnosed?
- clinical signs compatible with ECoV infection
+
- neutropenia and/or lymphopenia (not a classical viral CBC)
+
- exclusion of other infectious causes
+
- molecular detection of ECoV in faeces
40
List the biochemical abnormalities which may occur in ECoV infection
- may be unremarkable
- elevation of total and indirect bilirubin due to partial or complete anorexia
- electrolyte changes consistent with enterocolitis
- transient elevation of liver enzymes and renal parameters (suggestive of prerenal azotaemia)
- measure blood ammonia concentratons if concurrent signs of encephalopathy - hyperammonaemia likely due to increased ammonia production within or absorption from GIT due to gastrointestinal barrier breakdown
41
Describe the molecular techniques for diagnosis of ECoV
- faecal quantitative PCR (qPCR)
- 90% accuracy b/w clinical status and PCR detection
- may be negative in peracute stages of infection or in horses with ileus and colic - retest in a suspected index case at later time point or collect multiple samples for pooled sampling
- usually shed in faeces 3-4 days post infection and continue shedding for 12-14 days post infection
- PM diagnosis: qPCR of faeces, SI tissue, GIT content; can also collect formalin fixed intestinal tissue samples for immunohistochemistry and direct fluorescent antibody testing using BCoV reagents
42
Discuss the differences in ECoV infection in foals and adult horses
- high and similar frequency of ECoV shedding detected in healthy foals and foals with GIT diseases
- ECoV likely commonly circulates among young horses with subclinical dz
- all ECoV infections in foals with GIT dz associated with coinfections whereas healthy foals infected with ECoV displayed moninfection
- in foals, pre-existing ECoV infection may predispose to opportunistic secondary viral, bacterial or protozoal infections
- vast majority of adults: ECoV is a monoinfection
43
Describe the pathology associated with ECoV infection in adult horses
- severe, diffuse, necrotising enteritis
- marked villous attenuation
- epithelial cell necrosis in tips of villi
- neutrophilic and fibrin extravasation into SI lumen (pseudomembrane formation)
- crypt necrosis
- microthrombosis
- haemorrhage
44
Discuss the important biosecurity recommendation in outbreaks of ECoV infection.
- routine management practices should be aimed at reducing likelihood of introducing and disseminating ECoV at any horse-based premises
- horses developing or presenting with fever, anorexia and lethargy with or without enteric signs should be strictly isolated until dx is secured
- once ECoV infection confirmed, strict isolation procedures (footbaths, PPE) and secondary quarantine of source stable of particular horse should be employed
- infected horses may need to be isolated for > 14 days after cessation of clinical signs
- post infection testing of clinical cases to prevent viral spread to other horses
- all newly arrived horses on a farm should be isolated for at least 3 weeks
- separate equipment for care of infected animals
- vans and trailers thoroughly cleaned and disinfected (susceptible to common disinfectants)
- examination of at risk horses for clinical signs of dz - twice daily rectal temp
- importance of retesting in horses that are negative initially, particularly if not passing normal amounts of faeces
