Equine Hepatic Diseases Flashcards
metabolic functions of the liver
– Gluconeogenesis
– Conversion of amino acids to glucose or glycogen
– Urea-cycle enzymes
> Conversion of ammonia to urea
– Phylloerythrin metabolism
how often does the equine liver renew itself
Liver undergoes constant repair.
– Renewed in horses every 50-70 days.
synthetic functions of the liver
– Albumin
- cholesterol
- glucose
- urea
– Clotting proteins
* Fibrinogen (Factor I)
* Prothrombin (Factor II)
* Factors VII, IX, X
- amino acids
Excretory functions of the liver
- horse gall bladder?
– Conjugation of bilirubin
– Production of bile
– NO gall bladder in the horse
liver detocification
- endogenous and exogenous compounds
– Endogenous compounds
* Endotoxins
* Bilirubin
* Ammonia
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– Exogenous compounds
* Drugs
* Planttoxins
how much liver functional capacity can be lost before liver failure
- Liver failure occurs after loss of 75-80% of functional capacity
- Tremendous functional reserve and regenerative capacity
Primary liver diseases we are concerned about in the horse:
– Serum-associated acute hepatitis
(Theiler’s disease)
– Chronic active hepatitis
– Pyrrolizidine alkaloid toxicosis
– Obstructive cholelithiasis (gallstones)
– Cholangio-hepatitis/cholangitis
– Tyzzer’s disease (foals 7-42 days)
– Toxic hepatopathies
– Hepatic neoplasia (RARE)
– Portosystemic vascular shunts (RARE)
secondary liver disease
- what are these?
- which are we worried about in the horse?
- Affects liver as part of a more generalized
disorder - Metabolic disorders
<><><><> - Hyperlipemia (“fatty liver”)
–Ponies, minis, donkeys, “cold” blooded horses - Hyperadrenocorticism (pituitary tumor PIPD)
- Neoplastic metastases
Pyrrolizidine poisoning
- what plant?
- pathogenesis?
- Tansy Ragwort (Senecio jacobaea)
– contains at least six pyrrolizidine alkaloids (not toxic)
– combined with liver enzymes after ingestion
> they are converted to pyrroles > liver dysfunction
– Antimitotic effect on DNA > hepatocytes cannot divide > die + replaced by fibrosis
Pyrrolizidine poisoning
- diagnosis and prognosis
– Liver biopsy
* Triad of fibrosis, bile duct proliferation, and megalocytes
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* Prognosis
– horses are most seriously affected followed by goats
– >600 alkaloids identified
cholelithiasis
- what is this, how common
- pathogenesis
- stone composition
- Choledo-cholelithiasis (common bile duct) is the most common biliary obstruction in the horse (occurs more frequently in the horse than in other domestic animals)
<><> - Pathogenesis
– Unknown: ascending infection, parasites, foreign body etc)
<><> - Composition of stones: mixed
– Bilirubin, CaPO4, cholesterol esters, bile pigments, etc
cholelithiasis
- signalment
- risk factors
- clinical signs
- Dx labwork
- Signalment: ADULTS, no breed or sex predilection
<><> - Risk factors: enteric Gram – infection from SI
<><> - Clinical Signs
– Intermittent abdominal pain w pyrexia and icterus – Less commonly HE, photosensitization, weight loss
<><> - Lab evaluation
– Increased liver enzymes (GGT, ALP, bile acids)
– Suspect cholestasis if direct is >30% of total bilirubin
what do we see on US in cholelithiasis
– Hepatomegaly and bile duct dilation
– Generally multiple choleliths seen
cholelithiasis Tx options, prognosis
– Medical:
* long term broad spectrum AB’s (enrofloxacin/ ceftiofur)
* Fluid therapy
* DMSO: helps dissolve Ca glucoronidate calculi??
* Bile salt therapy: contraindicated in horses
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– Surgical: relief of obstruction
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– Guarded prognosis
cholelithiasis monitoring
– Repeat US, sequential GGT/ALP
Tyzzers disease
- pathogen
- signalment
- risk factors
- Etiology: Clostridium piliformis
- Signalment: 7-40 days of age
- Risk factors: parturition
Tyzzers disease pathophysiology
- transmission
- carriers
- contagiousness
– Fecal-oral route of transmission
– Carrier state may exist ????
– Not a highly contagious disease
Tyzzers disease clinical signs
– Often found dead w no history of signs
– Fever, depression and anorexia
– Icterus, hypoxia, coma, seizures etc
Tyzzers disease diagnosis
– Lab evaluation
> elevated enzymes, severe hypoglycemia
– Definitive only at post-mortem
– Organism difficult to identify in routine stains
Tyzzers disease Tx
– No reports of successful treatments (1 report)
– Antimicrobial therapy (pen, tetracyclines, erythromycin)
primary liver tumour in horses - how common?
rare
Equine Hyperlipemia
- who is susceptible
- what is this?
- risk factors?
– Small, fat-obese, female Pony or Miniature Horse
– Metabolic disease
– Negative-energy balance
– Fatty infiltration of liver
– Hepatic failure
– Anorexia / Starvation
– Late-pregnancy / Lactation
– Parasitism
– Transportation
Equine Hyperlipemia
- Dx
- Equine Hyperlipemia
– Opaque, fatty appearance to
plasma
–increased serum triglycerides > 500 mg/dL
<><> - increased liver enzymes
> SDH, GGT, AST
<><> - Liver biopsy: fatty infiltration
Causes of hepatitis
* Viral:
– Equine parvovirus-hepatitis (EqPV-H)
– Non-primate hepacivirus (NPHV)
– Equine genus Pegivirus
– Theiler’s Disease Associated Virus (TDAV)
Theiler’s disease
- what is it?
- lesions/ severity
an acute hepatitis frequently occurring several weeks after administration of a biological substance of equine origin
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- can lead to hepatic necrosis (4-18%) which can be fatal (2%), several weeks (4-24 weeks) after the vaccination
> ie. related to the vaccine protocol
equine biologic products associated with Theiler’s disease, or other hepatic diseases
- Tetanus antitoxin
- Botulinum antitoxin
- Antiserum against Streptoccocus equi
- Pregnant mare’s serum
- Equine plasma
- Allogeneic stem cells
Equine parvovirus-hepatitis
- prevalence
- transmission
- Virus prevalence: 13% (serum PCR)
- Sero-prevalence: 15%
<><><><> - Transmission:
– Iatrogenic through biologic products, otherwise unknown
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– Viral DNA in nasal secretions and feces at peak viremia - Transmission routes remains to be determined
are clinical signs of liver disease pathognomonic?
no
– Signs secondary to failure of a specific liver function
does icterus mean liver disease? is it always present with liver disease? where should we look?
– Icterus may be present in horses with diseases NOT directly involving liver (Fasting)
– Sclera: best mucous membrane to assess !!
– Examine in direct sunlight
– May NOT see icterus in chronic hepatic failure
non-liver disease issue that can produce icterus in the horse?
– Anorexia and fasting can produce icterus in the horse
Anorexia and fasting can produce icterus in the horse
- how?
– Failure of hepatic uptake of free bilirubin
– Failure of transport of free bilirubin
If conjugated bilirubin >25% of total serum
bilirubin, indicates….
- conjugated bilirubin has an affinity for…
> consequence
– If conjugated bilirubin >25% of total serum bilirubin indicates biliary obstruction
– Conjugated bilirubin has a much greater affinity for connective tissue
– Greater degree of icterus in cholestatic liver disease
Hepatic encephalopathy signs
- Generalized muscle weakness
- Truncal ataxia, weakness, dysphagia
- Behavioural abnormalities
– Yawning, head pressing, compulsive walking
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– Severe depression: - head drooped
- Sleepy
- yawning (excessive)
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– Defective vision: - sluggish PLR
- sluggish menace
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– Ataxia, incoordination, circling
– Compulsive walking
– Head pressing (terminal sign)
liver disease physical findings, in general
– Anorexia, depression, dullness, weight loss
– Behavioural abnormalities
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* Normal TPR
* Anorexia
* Depression/lethargy
* Weight loss (chronic)
* Icterus
– Hepatic encephalopathy signs
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– ± Colic
– ± Photosensitization
* Dysfunctional liver NOT capable of metabolizing phylloerythrin (photodynamic agent)
– Constipation
* pass small, hard fecal balls
- Clinical Pathology: Serum enzymes in liver disease
- where they are from
- properties
– Gamma-glutamyl transpeptidase (GGT)
* bile duct and hepatic cellular damage (t/2 14-26 d)
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– Glutamate dehydrogenase (GLDH)
* cytoplasmic (mitochondrial)
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– Sorbitol dehydrogenase (SDH)
* cytoplasmic ( very short half life)
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– Alkaline phosphatase (AP)
* High in foals (bone metabolism), associated with biliary S
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– Aspartate aminotransferase (AST, GOT)
* Mostly in hepatocytes (t/22 h or more d in LA)
- Clin Path: Serum biochemistry
- bile acids for liver disease
- normal variation?
- sensitive or no? other metrics?
– Elevated total serum bile acids (SBA) (0-6 normal)
* >20 μmol/L
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– No significant diurnal variation
– No post-prandial rise in bile acids as horses do NOT have a gall bladder
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– Sensitive indicator especially in chronic cases
* Total serum bilirubin/conjugated bilirubin increased
- Clin Path: Serum biochemistry
- non-bile acids tests
- increased blood ammonia (in HE)
<><> - ± decreased serum [Urea]
> NOT a consistent finding in hepatic failure
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– ± Hypoglycemia - terminal event
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– Hypoproteinemia/hypoalbuminemia - terminal event
- Albumin t/2 3 weeks
urinalysis results for liver disease
– ± Bilirubinuria
– ± Hemoglobinuria
– ± Urobilinogenuria
Liver biopsy:
what should we do before performing a liver biopsy? what tests? what needle? how to get the right site?
– Perform blood coagulation tests before
* Prothrombin time (PT)
– Activated partial thromboplastin
time (APTT)
– “Tru-Cut” biopsy needle
– Site: via ultrasound guidance or percutaneous over right 12th intercostal space
liver disease Ddx
– Other causes of progressive weight loss
– Other causes of acute neurologic dysfunction
* Rabies, EPM, WNV, EEE, WEE
– Other causes of icterus
– Other causes of colic
Liver disease therapy, general goals
– Support liver functions
– Reduce hepatic workload
– Allow sufficient time for hepatic regeneration
liver disease therapy - glucose considerations, reasoning
- Maintain blood [glucose]:
– Hypoglycemia occurs in liver failure
– 50 g dextrose IV/hour for 48 hours
– Decreases hepatic workload
– Oral glucose by stomach tube
liver disease therapy - water and electrolytes, reason
– Maintain hydration
– Preserve hepatic microcirculation
– Aid renal excretion of hepatotoxins
what IV fluid therapy to give for liver disease
– Balanced Electrolyte Solution IV (LRS)
– ± Add KCl (20 mEq/L) to fluids
– Correct acid-base imbalances SLOWLY
– Avoid IV HCO3 unless severe acidosis
Liver disease therapy - how do we combat hepatic encephalopathy?
Decrease absorption and production of
NH3 from gastrointestinal tract
– Lactulose
– Mineral oil
– Dioctyl sodium sulfosuccinate (DSS)
– Oral antibiotics (neomycin) ??
– Metronidazole
exercise vs rest for liver disease
- Stall rest:
- Keep out of direct sunlight
- Risk of photosensitization
liver disease diet, vitamins
Diet:
* Low protein & readily digestible CHOs
* Attempting to decrease production of NH3 by gut bacteria
* Avoid legume hays (too high protein)
* Avoid wheat, soya beans, oats
* Feed diet high in BCAAs
> Sorghum grains, beet pulp (soaked)
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Vitamins:
– Vitamin B complex and K1 parenteral
when would we give antibiotics for liver disease?
– Suppurative cholangitis/cholangiohepatitis
how to control abnormal behaviour due to liver disease
- when to act?
- what to use?
- cautions?
– Sedation/anti-convulsants
– Only administer if having seizures
– Care: drugs are slowly metabolized
– Use LOW doses of sedatives/tranquilizers NOT diazepam
Poor prognosis for liver disease with:
- Chronic hepatic failure
- Severe encephalopathy
- Hemoglobinemia/hemoglobinuria
- Pyrexia
Prevention of liver disease - what can clients avoid?
– Limit use of equine anti-sera
– Avoid hay or pellets that may contain pyrrolizidine alkaloid-containing plants
