Causes and Pathogenesis of Major Diseases

Learning Objectives

• Causes of major diseases presented will be named and their pathogenesis outlined.
• Gross and microscopic lesions will be recognized.
• Differential diagnoses can be provided.
• The most likely diagnosis based on signalment and gross/microscopic findings will be reached.

Age-Related Susceptibility to Pathogens

• Neonates are especially susceptible.
• Due to an immature mucosal barrier
• Decreased gastric acid
• Decreased proteolytic activity
• Decreased mucus production
• Decreased IgA production
• Enteric pathogens to which neonates are more susceptible include:
• Rotavirus
• E. coli
• Coronavirus
• Cryptosporidium
• Clostridium perfringens type C
• C. difficile
• Salmonella
• Prioritizing differential diagnoses depends on the age and lifestyle stage of the animals.

Infectious Diarrheas

• Intestinal viruses create disease by infecting certain cells and destroying them.
• Bacteria cause disease via several mechanisms.
• Some invade cells directly
• Others produce exotoxins or secretory toxins
• Diarrhea is more dangerous for young animals.
• Younger animals have slower cell turnover, so they lose fluids for a longer time.

General Themes for Clinical Signs, Diarrhea, and Pathology

• Enterotoxigenic E. coli causes diarrhea only because there are no growth or microscopic lesions.
• ETEC attaches to the surface of epithelial cells.
• This stimulates the epithelial cells to secrete chloride into the lumen.
• It has a functional lesion.
• Parvovirus, BVD/MD, Salmonella, Clostridia, and Coccidia (in cattle and swine) cause necrohemorrhagic/fibrinonecrotic enteritis/enterocolitis.
• Leads to exudative or effusive diarrhea with blood, mucus, cellular debris, and protein.
• Rotavirus, Coronavirus, and Cryptosporidium cause villi atrophy, with mild inflammation and growth changes.
• Mycobacterium, Pythiosis, and Histoplasma cause granulomatous enteritis.
• Lawsonia intracellularis in pigs causes proliferation of the crypts in the ileum.
• Coccidiosis in goats causes nodules in the mucosa due to crypt and villi proliferation.

Causes of Infectious Diarrhea in Calves (<3 weeks)

• Enterotoxigenic E. coli typically affects calves less than 3 days old.
• Rotavirus typically affects calves 5-15 days old.
• Coronavirus typically affects calves 5-20 days old.
• Cryptosporidium typically affects calves 1-4 weeks old.
• Salmonellosis typically affects calves 1-2 months old.
• Cryptosporidium and ETEC can look similar
• Cryptosporidium is acid-fast positive, which aids differentiation.
• ETEC stimulates epithelial cells to secrete chloride, while Cryptosporidium effaces the brush border.

Causes of Infectious Diarrhea in Cattle (>3 weeks)

• Acute to subacute causes:
• BVD/MD, MCF can cause ulcers
• Coronavirus can cause Winter Dysentery, usually in dairy cattle and is self-limiting.
• Salmonella
• Coccidia
• Nematodes require sufficient burden
• Subacute to chronic causes:
• Johne's
• Ostertagia - Abomasal disease causing chronic diarrhea
• Salmonella
• Coccidia
• Nematodes require sufficient burden
• Hemorrhagic fluid leakage and necrosis is caused by Clostridium.
• Ulcers mean there is a loss of epithelium.
• Salmonella, BVD, and Clostridium all cause bloody diarrhea.
• ETEC causes secretory and watery diarrhea with no mucosal damage.

Diarrhea Chart for Pigs

• Disease causing Diarrhea in Pigs and the common age groups
• Enterotoxigenic E. coli - Farrowing (3 w), Nursery (6-8w), Grower/Finisher (16w) and Adult
• Rotaviral infection - Farrowing (3 w), Nursery (6-8w), Grower/Finisher (16w) for early growers
• Transmissible gastroenteritis virus - Farrowing (3 w), Nursery (6-8w), Grower/Finisher (16w) and Adult
• Clostridium difficile - Farrowing (3 w)
• Clostridium perfringens Type A - Farrowing (3 w)
• Clostridium perfringens Type C - Farrowing (3 w)
• Isospora suis (Coccidia) - Nursery (6-8w)
• Porcine epidemic diarrhea virus - Nursery (6-8w), Grower/Finisher (16w) and Adult
• Salmonellosis - Grower/Finisher (16w)
• Swine dysentery - Grower/Finisher (16w) and Adult
• Proliferative enteropathies - Nursery (6-8w) and Adult
• In adult pigs, consider Salmonellosis, Swine dysentery, Proliferative enteritis, and Porcine epidemic diarrhea virus
• Clostridium and Isospora suis usually cause bloody diarrhea due to severe mucosal damage.

Clinical Application: 1 Week Old Piglets Found Dead in Winter

• Surviving piglets are non-febrile, with yellow diarrhea.
• The farmer reports some vomiting.
• Necropsy of the dead piglets reveals an empty stomach, thin-walled intestine with green contents.
• Histopath evaluation reveals blunted villi with virus at the villus tips/lateral surface by IHC.
• Differential diagnoses include:
• E. coli
• coccidia
• clostridium
• rotavirus (low mortality)

Rankings for piglet watery diarrhea

• Rotavirus ranks as the first disease
• Transmissible Gastroenteritis, Coronavirus as the second
• Coronavirus can cause a more severe disease than Rotavirus and mortality tends to be higher.
• ETEC ranked third
• Clostridium, Isospora suis, Coccidiosis listed

Causes of Infectious Diarrhea in Foals

• Causes include:
• Rotavirus
• Coronavirus
• Clostridium perfringens A or C, colostrum (trypsin inhibitor)
• Clostridium difficile
• Salmonellosis
• Lawsonia intracellularis
• Rhodococcus equi
• Parasites
• Colostrum has trypsin inhibitors, increasing susceptibility to Clostridium perfringens.
• Clostridium perfringens causes severe mucosal necrosis due to the production of isotoxins.

Rhodococcus Equi

• Causes pulmonary pyogranulomas.
• Bacteria can resist the intracellular environment of macrophages.
• Bacteria enters intestinal M cells overlying the GALT when coughed up and swallowed.
• This results in ulcerative pyogranulomas over the GALT and in mesenteric lymph nodes.
• The three main lesions from Rhodococcus equi are pyogranulomatous pneumonia, ulcerative enterocolitis, and pyogranulomatous lymphadenitis of the mesenteric lymph nodes.

Causes of Infectious Diarrhea in Adult Horses

• Salmonella
• Clostridium difficile
• Coronavirus
• Potomac Horse Fever

Potomac Horse Fever

• Causes equine monocytic ehrlichiosis.
• The causative agent is Neorickettsia risticii, an intracytoplasmic bacteria of epithelial cells, macrophages, and monocytes.
• Potomac Horse Fever is a seasonal disease occurring in summer and early fall.
• Equids become exposed by consuming infected snails or aquatic insects, most commonly mayflies and caddis flies, (horses near slow-moving bodies of water).
• Ingestion of the dead fly leads to bacteria traveling to the intestines causing the disease.
• This can cause congestion, petechiae, and edema in the cecum and colon with mild mucosal erosions/ulcerations.
• Gross appearance can look like Salmonella and Clostridium difficile. Diagnosis confirmed by PCR.
• Main ddx is salmonella and C. difficile.

Equine Proliferative Enteropathy

• As with most species infected with Lawsonia causes proliferation of crypts.
• Disruption of villi structure> Malabsorption> Osmotic diarrhea
• Horses experience rapid weight loss
• Results in marked hypoproteinemia clinically
• Symptoms: Colic, lethargy, PLE, subcutaneous edema
• Most common in Weanling foals (4-6 months most common)
• Replicates in enterocytes of the crypts, intracellular pathogen

Important Information related to Equine Proliferative Enteropathy

• Infection with Lawsonia intracellularis causes proliferative enteropathy.
• This results in outbreaks of diarrhea, rapid weight loss, colic, lethargy, subcutaneous edema, and protein-losing enteropathy in weanling foals.
• Marked hypoproteinemia (<4 mg/dL) with hypoalbuminemia (<1.5 g/dL) are the most common laboratory findings. The WBC (White Blood Cell) count and fibrinogen concentrations tend to be normal to moderately increased.
• Anemia, hyponatremia, hypochloremia, and hypocalcemia may be seen.
• CK concentration is often mildly increased.
• Differential diagnoses include salmonellosis, clostridiosis, Neorickettsia risticii, R equi, parasitic infections, and any cause of infiltrative/inflammatory bowel disease.
• The failure of that response within 7-10 days should lead to reassessment the diagnosis.

Lawsonial Enteritis in Pigs

• Lawsonia can also cause fibrinonecrotic or hemorrhagic enteritis, resulting in either osmotic or effusive diarrhea.
• The nonhemorrhagic form affects 40- to 80-lb (18- to 36-kg) pigs and is characterized by a sudden onset of diarrhea. The feces are watery to pasty, brownish, or faintly blood stained.
• After ~2 days, pigs may pass yellow fibrinonecrotic casts that have formed in the ileum. Most affected pigs recover spontaneously, but a significant number develop chronic necrotic enteritis with progressive emaciation.
• Lesions may be seen anywhere in the lower half of the small intestine, cecum, or colon but are most frequent and obvious in the ileum. The wall of the intestine is thickened, and the mesentery may be edematous.
• The mesenteric lymph nodes are enlarged. The intestinal mucosa appears thickened and rugose.
• May be covered with a brownish or yellow fibrinonecrotic membrane, and sometimes has petechial hemorrhages. Yellow necrotic casts may be found in the ileum or passing through the colon.
• Diffuse, complete mucosal necrosis in chronic cases causes the intestine to be rigid, resembling a garden hose.
• Proliferative mucosal lesions often are in the colon but are detected only by careful inspection at necropsy. In the profusely hemorrhagic form, there are red or black, tarry feces in the colon and clotted blood in the ileum.

Infectious Diarrhea in Puppies/Dogs

• Canine parvovirus-2
• Rota/corona
• Distemper
• Parasites, specifically:
• Nematodes
• Giardia
• Coccidia
• Pythium
• Histoplasma
• Prototheca
• Salmonella
• Clostridium

Clostridial Enteritis in Dogs

• Clostridial enteritis in dogs = Acute Hemorrhagic Diarrhea Syndrome.
• It's most likely caused by C. perfringens type A.
• Due to stress or dietary indiscretion.
• It mostly appears in toy and miniature breeds, younger than 2 years.
• Dogs experience bloody diarrhea, vomiting, and hemoconcentration.
• The GI mucosa necrotizes hemorrhagically which can occur anywhere from the stomach caudally.
• Acute Hemorrhagic Diarrhea Syndrome is characterized by massive leakage of blood into the stomach and intestines.

Causes of Infectious Diarrhea in Kittens/Cats:

• Feline parvovirus "panleukopenia" virus (major)
• Feline Enteric Coronavirus
• Bacterial enteritis is uncommon

Feline Panleukopenia Virus

• Primarily affects kittens
• Resilient and persistent environmental pathogen (can survive up to 1 yr at room temperature)
• Targets/infects rapidly dividing cells:
• GIT (crypts)
• Bone marrow
• Cerebellum
• Be aware of cerebellar hypoplasia"
• It infects and destroys actively dividing cells of bone marrow, lymphoid tissues, intestinal epithelium, affects cerebellum and retina in very young animals.
• Transplacentally, in pregnant queens, the virus may spread and cause embryonic resorption, fetal mummification, abortion, or stillbirth.
• Can also destroy the germinal epithelium of the cerebellum, perinatal period-infection of kittens, (cerebellar hypoplasia, incoordination, and tremor).
• The classic microscopic lesion of Parvo is necrosis. Necrosis can appear like a loss of crypts with collapse of the lamina propria and V-line.