EIM 12-14 GI/Liver/Urinary Flashcards
hepatic changes with DPJ
hepatocellular vacuolization
cholestasis
inflammatory infiltrate
biliary hyperplasia
suspected causative agent of DPJ
Salmonella spp or Clostridium spp
—can be isolated from culture of gastric reflux.
—Fusarium spp (causative agent of bovine interdigital necrobacillosis) also suspected
alimentary lymphosarcoma primarily affects horses aged
2-4
alimentary lymphosarcoma
lymphocytosis is rare
prognosis is poor
granulomatous enteritis
Standardbreds are overrepresented
Affected horses are 1-6 years, majority <3
+/- scurfy skin, severe lesions rare
Clinical signs include severe wasting, edema, variable appetite, depression, and occasional slight fever
Diarrhea is infrequent
proliferative enteropathy
L. intracellularis has a tropism for crypt epithelium
Infected cells proliferate far more rapidly than uninfected cells
L. intracellularis enters cell in membrane-bound vacuole, but eventually escapes vacuole and found free in cytoplasm
Lesions are most commonly found in ileum and terminal jejunum, but may be found in duodenum
Which serovar of Salmonella is the most pathogenic in horses?
Group B Salmonella enterica var. Typhimurium
What is the most common isolate type of Clostridium perfringens from healthy and diarrheic horses of all ages?
C. perfringens type A is the most common clostridial isolate from healthy and diarrheic horses of all ages.
C. perfringens types A, B, C, and D have all been associated with hemorrhagic enteritis in foals younger than 10 days of age, with type C being the most common cause in North America.
The primary toxin produced by C. perfringens type A is α-toxin (phospholipase C), virulent strains of type A may also produce enterotoxin
What are the more common toxins produced by Clostridium difficile?
Toxin A (enterotoxin) and Toxin B (cytotoxin), Toxin A’s role in the pathophys is more clear than Toxin B (in terms of equine diarrhea)
C. difficile toxin A is an enterotoxin that induces an inflammatory response with hypersecretory diarrhea
Preliminary diagnosis of equine intestinal clostridiosis caused by C. perfringens is based on the isolation of greater than what # of colony forming units (CFU) of C. perfringens type A per gram of feces (in horses with consistent Hx and CS)
> 100
Which life stage of Strongylus vulgaris is primarily responsible for the parasite’s pathogenicity in the equine abdomen?
L4
Fourth-stage larvae migrate through the mucosa and submucosa into the large intestinal vasculature - causing mural edema, hemorrhage, and infiltration of inflammatory cells of the bowel, and possible ischemia or acute infarction
arsenic toxicosis: CS
Acute hemorrhagic colitis with severe mural edema and mucosal ulceration.
Profuse hemorrhagic diarrhea and abdominal pain.
Later, cardiac arrhythmias, pulmonary edema, acute renal failure, and neurologic deficits (ataxia and stupor) may develop.
arsenic toxicosis: DX
measuring blood and urine arsenic concentration, but these tests may not be diagnostic. Post-mortem diagnosis is confirmed by measuring arsenic concentrations in liver and kidney samples. History of exposure and clinical signs remain the primary means of diagnosis.
hydrolyzed by colonic bacteria to SCFAs, such as butyrate, which represent a major energy source for colonocytes
Psyllium
PGE2
Increases Cl secretion, decreases neutral NaCl absorption
Vasoactive Intestinal Peptide
Increases cAMP-mediated NaCl secretion
Endotoxin
Increases Na absorption, Increases cell membrane permeability
Interferon-gamma
Decreases tight junctions and causes increase in cell membrane permeability
IL-1
Increase PGE2
H1
Increases Cl secretion via Ca-mediated pathways
endotoxin and prostaglandins affect large intestinal motility by:
creating less coordinated contractions.
the most important lps receptors are:
CD14 and TLR4
Which two intracellular processes control colonic secretion?
Cyclic nucleotide (cAMP, CGMP) and calcium system
The proximal 2/3 of the esophagus is
skeletal muscle
Why are horses are risk of gastric rupture
The mechanical and vagal mechanisms that promote lower esophageal sphincter tone prevent spontaneous decompression of the stomach, which along with a lack of a vomiting reflex in the horse, increases the risk of gastric rupture during episodes of severe distention.
Common site for esophageal obstruction in the horse
Esophageal obstruction occurs most commonly at sites of natural narrowing of the esophageal lumen, such as the cervical esophagus, the thoracic inlet, base of the heart, or the terminal esophagus
food should be withheld for what amount of time following esophageal obstruction?
24-48 hrs
The rate of re-obstruction may be as high as 37%.
Depending on the duration of the obstruction and the degree of trauma or dilation, the risk of re-obstruction is high for 24 to 48 hours or longer.
Esophageal disorders including megaesophagus, esophageal diverticulum, and esophageal rupture appear to be more common in
young Friesian horses, suggesting the possibility of a genetic predisposition in this breed.
Esophageal strictures may resolve with conservative management within
60 days
A foal presents with salivation, esophageal dysphagia, and swelling of the cervical esophagus. What can cause this presentation?
A: congenital stenosis B: persistent right aortic arch C: esophageal duplication cysts D: intramural inclusion cysts E: idiopathic megaesophagus
Isolated equine parietal cells respond maximally to which stimuli:
Histamine - released by mast cells and ECL-like cells in the gastric gland.
Gastric acid secretion by parietal cells is primarily inhibited by
somatostatin, which is released by fundic and antral D cells.
actions of sucralfate
A: adherence to ulcerated mucosa
B: enhanced PGE synthesis
C: stimulation of mucous secretion
D: promotes healing via concentration of growth factor at affected sites
The most common clinical sign of horses with intestinal neoplasia
Weight loss
primary caecal impactions
typically consist of impacted, relatively dry faecal material and there is a gradual onset of abdominal pain over a number of days reminiscent of the development of a large colon impaction
secondary caecal impactions
develop when a horse is being treated for a separate problem, and tend to have very fluid contents
caecal impaction - DX
based on rectal palpation of a firm, impacted or fluid-filled caecum. The hand will be unable to move completely dorsal to the impacted viscus due to the caecum’s attachment to the dorsal body wall
Just like urolithiasis in small ruminants, feeding alfalfa hay and decreased dietary proportions of pasture grass have been consistently identified as risk factors in horses with ____
enterolithiasis
Enteroliths are usually found in the
RIGHT DORSAL and TRANSVERSE colons
Enteroliths are mineralised masses typically composed of
ammonium magnesium phosphate
STRUVITE
alfalfa hay contains 6X the daily requirement of ____
Mg
The ascending colon is freely moveable except for the
RVC AND RDC
Development of large colon displacement
- feeding of large concentrate meals contributes to initiation by increasing the rate of passage of ingesta, allowing a greater percentage of soluble CHO to reach the large intestine
- increased rate of fermentation and amount of gas and VFAs produced
- production of large amounts of VFAs stimulates the secretion of large volumes of fluid into the colon
pelvic flexure usually not palpable
Ileocolonic aganglionosis
lethal white foal syndrome
aganglionosis of the distal portion of the ileum and large intestine
foals appear normal at birth but develop signs of intestinal ileus and colic within 12 to 24 hours
LWFS
Occurs in foals from Overo-Overo paint horse matings, parents are heterozygous for EDNRB
Affected foals may be completely white, or have very little pigmented hair around the muzzle, base of the tail, or hooves. These babies have blue eyes and pink skin, like a human baby
Foals are homozygous for the endothelin receptor B (EDNRB) gene, resulting in altered neural crest cell migration or survival, affecting progenitor cells for melanocytes and intestinal ganglia
Slaframine toxicosis
Slaframine is a toxic alkaloid produced by the fungus Rhizoctonia leguminocola
Ingestion of slaframine causes hypersalivation in horses and ruminants
Slaframine, which causes black patch disease in red clover, is a parasympathomimetic, it stimulates exocrine secretion in the parotid
Most common in spring or early summer
Rarely requires treatment other than removal from pasture
Differentials in large animals may include bluetongue, vesicular stomatitis, vesicular exanthema, and foot-and-mouth disease
the most important growth factor in early mucosal repair events is
TGF-Beta
a potent stimulus of epithelial restitution and modulator of the ECM.
Neutralization of TGF-β retards epithelial migration in vitro, and it appears that TGF-β may serve as a point of convergence for mediators of restitution, because neutralizing TGF-β also inhibits the effects of other peptides. However, TGF-β paradoxically inhibits epithelial proliferation, reducing the supply of new enterocytes for mucosal repair.
The principal metabolic fuel of enterocytes is
glutamine
The principal metabolic fuel of colonocytes is
butyrate
What is ileus
The inhibition of propulsive bowel activity
“MMC”s: small intestinal and colonic migrating motility (or myoelectric) complexes
originate where?
The colonic complex usually originates in the right ventral colon and variably traverses the ascending and descending colons.
Many of these complexes are related temporally to a specialized motility event of the ileum, the migrating action potential complex
detomidine can reduce large intestinal myoelectric activity for
up to 3 hours in a dose dependent fashion
generally, horses in which more than ____ small intestine is devitalized are considered to have a grave prognosis
50% of the SI
in a 360 degree volvulus, the colon becomes irreversibly damaged in:
3-4 hours
Congenital rents may result from incomplete fusion of any of the four embryonic components of the diaphragm.
Those are:
- pleuroperitoneal membrane
- transverse septum
- body wall
- esophageal mesentery
large congenital hernias are typically present at
The ventral-most aspect of the diaphragm
HOW DO TYPE I AND II RECTAL PROLAPSES DIFFER FROM TYPE III AND IV?
Involvement of small colon as well as rectum
Which is the most common manifestation of peritonitis?
Acute, Diffuse, Septic
Typically following inflammation, vascular insult, perforation, or surgical manipulation
cell count in peritoneal sepsis
> 500,000/ul
hyperlipemia
- serum triglyceride concentration in excess of 500 mg/dL
- grossly discolored plasma or serum (lipemia)
- occurs primarily in ponies, Miniature Horses, and donkeys
- may lead to fatty infiltration of the liver
- often accompanied by clinical signs of liver disease and a guarded prognosis.
Clinical signs also include: icterus, anorexia, weakness, severe depression, ataxia, muscular weakness, recumbency, diarrhea, mild colic, fever, and dependent edema
hyperLIPIDemia
- increase in serum triglyceride concentration (generally less than 500 mg/dL)
- without grossly lactescent blood or fatty infiltration of the liver
What is the histopathological hallmark of chronic hepatic disease
hepatic fibrosis
Regardless of the cause or site of injury, histopathologic evidence of fibrosis develops after chronic injury
A horse ingests Crotalaria sp.
When will clinical signs develop and what clinical signs would you expect to see?
Up to 12 months after consumption; signs of HE & photosensitivity.
Crotalaria spp. Is a pyrrolizidine alkaloid–containing plant.
Crotalaria spp
PA
Delayed onset of chronic, progressive liver failure
Clinical signs of liver disease is usually delayed 4 weeks to 12 months after the consumption of pyrrolizidine alkaloid–containing plants.
Individual differences in susceptibility occur (not all horses consuming the plants develop clinical signs)
Obvious hepatic failure, characterized by HE and photosensitization (usually abrupt)
Premonitory signs of insidious onset may include anorexia, weight loss, exercise intolerance, mild to moderate icterus, diarrhea, edema, polydipsia, pruritus, laryngeal hemiparalysis
Megalocytes may not start to appear on liver histopath samples until after how many days following consumption of pyrrolizidine alkaloids?
Megalocytes may not be seen in the liver on microscopic examination until 30 days or more after exposure to the pyrrolizidine alkaloid
Ingested pyrrolizidine alkaloids are carried to the liver via the portal circulation and are metabolized by the microsomal enzymes in zone 3 to toxic pyrrole derivatives
The pyrroles are chemically highly reactive and capable of alkylating nucleic acids and protein; consequently the pyrroles inhibit cellular replication and protein synthesis.
Cells cannot divide, hepatocytes enlarge, forming megalocytes.
When the megalocytes die, fibrosis ensues. When fibrosis becomes extensive, the liver shrinks, develops a firm texture, and failure is inevitable
How could you differentiate PA toxicity from clover poisoning on histopath?
they have similar features (biliary hyperplasia and periportal fibrosis)
–but megalocytosis is unique to PA
–and clover is much more rare
Chronic Active Hepatitis CS
moist exfoliative coronary dermatitis
depression, exercise intolerance, weight loss, anorexia, icterus, colic, fever
chronic, progressive onset, insidious
uncommon and idiopathic etiology
Chronic Active Hepatitis DX: Histopath
Characterized by: biliary hyperplasia, periportal or biliary inflammation
- associated hepatocellular damage (areas of necrosis and fibrosis)
- ‘bridging necrosis’, often mononuclear predominance
Chronic Active Hepatitis DX: Clinpath
mildly increased SDH and AST
markedly increased GGT and ALP
Increased bile acids, increased TP, increased bilirubin (high direct %)
Hepatoliths
Suspect they start with ascending infection from small intestine
- -Gram negative, enteric bacteria usually implicated
- -Microscopically often have concentric biliary fibrosis
- -If obstructive, cause colic and icterus
Most common equine hepatic neoplasm
Primary = cholangiocarcinoma
–originates from the bile duct epithelium and is distinguished from hepatocellular carcinoma by its tendency to form multiple foci, its firm texture, and a whitish color produced by abundant fibrous stroma.
OR likely to be a met from somewhere else
Portosystemic Shunts in Foals
- age of presentation 2-6mos
- majority extra hepatic
- Present for vague signs of HE – ataxia, depression, blindness
- Most significant lab abnormalities low BUN and markedly high NH3
- diagnostic demonstration is to perform an ultrasound-guided percutaneous trans-splenic injection of 10 mL of agitated saline (bubble gram) or trans-rectal scintigraphy
- tx options similar to SA
Theiler’s disease
For the last 40 years, tetanus antitoxin has been the most common blood product associated with this disease in the US
Equine parvovirus has experimentally induced liver disease in horses
Both unconjugated and conjugated bilirubin levels are increased, however the conjugated portion generally remains less than 25% of the total
Theiler’s disease not associated with blood products appears to be most common in late summer through autumn
Findings on histopathology consistently include widespread centrilobular to midzonal hepatocellular necrosis and apoptosis with haemorrhage
Tyzzer’s Disease
Acute necrotising hepatitis first described by Tyzzer in 1917 in a colony of waltzing mice
Non specific findings, including hyperfibrinogenaemia, and increased liver enzymes
Acute multifocal hepatitis, myocarditis, and enteritis
Limited to foals 7-42 days of age (average 20 days)
- Often affected foals, especially the younger ones, are found dead without premonitory signs
Definitive diagnosis at necropsy by demonstration of organism intracytoplasmically using silver stains or by PCR analysis
Caused by Clostridium piliforme, bacterium excreted in the faeces of clinically healthy horses, can survive in the soil for at least 1 year
Black Disease
Clostridium novyi type B
Liver enzymes and bilirubin are mildly to moderately increased
Most reported cases in horses have been fatal
Known as black disease, as the carcass blackens rapidly after death from engorgement of subcutaneous blood vessels
Peracute signs include sudden death, whereas acute signs are progressive over 24 to 72 hours and include depression, reluctance to move, recumbency, fever, icterus, ataxia, colic, petechiae, tachycardia and tachypnoea. Despite this some affected horses remain standing until a short time before death
Some horses w infectious necrotic hepatitis have had parasitic infestations, although migrating parasites in the liver at the time of necropsy were not evident
Onset of disease in one case occurred 48 h after administration of mebendazole
Iron Toxicity in Horses
Acute toxic hepatopathy in foals is reproducible if foals are administered ferrous fumarate orally prior to administering colostrum
–Colostrum contains abundant vitamin E and essential cofactors for glutathione. Glutathione protects against free radical damage, a proposed mechanism for iron toxicity
—Supportive therapy may prolong life, but most clinically affected foals die
Adult horses are less susceptible to iron toxicity than many other species
Foals are normally born with high serum iron levels and high percent saturation of transferrin
CS: Calves with iron toxicosis
exhibit trembling, vocalising, bruxism, colic and convulsions
CS: Foals with iron toxicosis
HE, icterus and peracute death
The cause of HE is
insufficient hepatocellular function
Hepatogenic Photosensitization
In the case of hepatogenic photosensitization, the photodynamic agent is phylloerythrin.
Phylloerythrin is normally formed in the gastrointestinal tract as a result of bacterial degradation of chlorophyll and is absorbed into the general circulation, conjugated, and excreted by the liver. During hepatic insufficiency, the blood concentrations of this photodynamic agent are increased.
Subsequent exposure of phylloerythrin to ultraviolet light causes activation of electrons within the molecule to an excited state, with resultant free radical formation. The local production of free radicals causes cell membrane damage and necrosis.
Unpigmented areas most efficiently absorb ultraviolet light; thus the lesions of photosensitization are restricted to white skin.
The skin first appears erythematous and edematous. Pruritus, pain, vesiculation, ulceration, necrosis, and sloughing may ensue. Mucous membranes may also be affected.
An increase in the _____ bilirubin fraction in horses more reliably is indicative of hepatic disease.
conjugated
If the conjugated bilirubin concentration is less than 25% of the total bilirubin value, ________ should be suspected.
hepatocellular disease
If the conjugated bilirubin concentration is greater than 30% of the total value, ____ should be suspected
cholestasis
Which of the following acinus lobule zones is most susceptible to toxins and hypoxic damage?
Zone III (adjacent to central veins)
This zone is highest in CyP450 and has the least oxygen content (takes in venous blood from sinusoids only). Some toxins most affect Zone II, though. Zone 1 hepatocytes are responsible for oxidative liver activity, including gluconeogenesis and Beta-oxidation of fats. Also site of hemosiderin deposition.
Exclusively produced by the liver
albumin
fibrinogen
c-reactive protein
The majority of absorbed fatty acids are transported as
Most short fatty acids are carried directly as phospholipids or triglycerides and are not packed into chylomicrons (which go through the lymphatics)
Bilirubin is converted to urobilinogen and stercobilin (yellow), so why is adult horse manure brown-green?
Chlorophyll pigments mask the yellow coloration
Some urobilinogen is also excreted in urine.
Intrinsic renal disease is most common at what site?
tubules
most common causes of equine ATN
ischemia, especially when associated with microvascular coagulation (which often leads to irreversible cortical necrosis), and nephrotoxins probably are the most common causes of equine ATN.
postrenal failure in horses most often results from
intraluminal blockage by uroliths, which can cause obstruction anywhere in the urinary outflow tract.
Other possible intraluminal causes include neoplasia or stricture formation. Extraluminal obstructive lesions such as retroperitoneal tumors, adhesions, or bladder displacements also occasionally are associated with the development of postrenal failure.
__ is considered the hallmark of ARF.
oliguria
the most frequently reported clinical sign that is related directly to urinary tract dysfunction.
oliguria
main indication for kidney biopsy
To differentiate between types of intrinsic renal diseases when one thinks that this distinction will have therapeutic and prognostic relevance.
how do you differentiate ARF caused by acute glomerulonephritis from that caused by hypoperfusion?
Significant proteinuria and red blood cell numbers = acute gn
Therefore although urinary indexes should make possible differentiation of acute glomerulonephritis from other parenchymal and postrenal diseases, they overlap much with those associated with prerenal ARF. One is going to differentiate ARF caused by acute glomerulonephritis from that caused by hypoperfusion based on the significant proteinuria and red blood cell numbers usually associated with the former disease. Erythrocyte casts are more common with glomerulonephritis than with other intrinsic causes of ARF. Some causes of postrenal ARF also may manifest red blood cell casts, but the proteinuria is not normally as great in those situations.
when treating ARF, one should correct initial fluid deficits over :
6-12 hrs
glomerulonephritis
immune-mediated glomerular damage is suspected to be the initiating factor in the development of renal failure
glomerulosclerosis
end stage of progressive, irreversible glomerular injury
replacement of glomerular components with hyaline material is visible on histologic examination
defined most strictly by clinical signs of renal disease associated with histologic changes of tubular damage and an interstitial inflammatory cell infiltrate.
Chronic interstitial nephritis
what are common sites of deposition in amyloidosis?
Amyloid deposition in the kidney is most common in dogs and cattle, and renal amyloidosis is a significant cause of CKD in dogs.
In horses, localized amyloidosis of the upper airway (around the nares or nasal septum) or skin is more common than systemic amyloidosis.
Systemic amyloidosis has been recognized most often in horses hyperimmunized for antiserum production, and hepatic and splenic involvement may be more common than renal involvement in these horses
What Is The Most Common Presenting Complaint For Horses With CKD?
chronic weight loss
What is the target of furosemide?
Na+/K+/2Cl- cotransporter in the ascending loop of Henle
What regulates potassium and acid excretion by sodium exchange in the distal tubule?
Aldosterone
Once >75% of nephrons are nonfunctional
Doubling of creatinine represents a 50% decrease in remaining renal function
BUN and creatinine increase above reference ranges
Which class of antimicrobials can spuriously increase creatinine?
Cephalosporins
Kidney Innervation
it’s obviously preganglionic fibers that originate from the spinal segments L1-L4 and synapse at the caudal mesenteric ganglion. DUH!
Parasympathetic innervation is provided via the sacral segments of the spinal cord that comes together to form the pelvic nerve
renal agenesis
Unilateral or bilateral failure of the metanephric duct to fuse with the metanephrogenic mesodermal tissue (bonus point if you know which is more common, unilateral or bilateral)
renal hypoplasia
One kidney is 50% smaller than normal or the total renal mass is decreased by a third
renal dysplasia
Disorganized development of renal tissue caused by anomalous differentiation, teratogens, in utero viral infections, or intrauterine ureteral obstruction
water balance
equids tolerate water deprivation well
Increased plasma osmolality and hypovolemia are stimuli for thirst
Vasopressin is a stress hormone in equids, and have higher concentrations after placement of a twitch
Most of a horse’s water intake happens periprandially
