Equine Liver Disease Flashcards
Hepatic Insufficiency
~80% of liver must be affected for function to be impaired
CS variable and non-specific; depend on distribution and extent of damage as well as duration of disease or insult
Chronic conditions may appear acutely as “threshold” is crossed
Hepatic disease can be present without hepatic failure
CS of Hepatic Insufficiency
Icterus Weight loss Anorexia Colic Depression Pyrexia Hepatoencephalopathy Photosensitization Coagulopathy, hemolysis Ascites, edema Diarrhea, steatorrhea Endotoxic shock Hypoglycemia Hypoproteinemia Electrolyte abnormalities
Icterus
Hyperbilirubinemia with deposition of pigment in tissues (total serum bilirubin = indirect + direct bilirubin)
Yellow discoloration of sclera, mm, and non-pigmented skin
Normal in 10-15% of horses
Increased bilirubin production or impaired hepatic uptake, conjugation, or excretion
Conjugated (direct) and unconjugated (indirect) bilirubin increased in hepatic disease
Increased unconjugated bilirubin and icterus seen with hemolysis, anorexia, GI disease
- Hemolysis: increased indirect bilirubin
- Hepatic disease: direct and indirect increased
- Post-hepatic (biliary outflow obstruction): marked increases in direct bilirubin (>30% of total)
Hepatic encephalopathy
Abnormal mentation accompanied by hepatic disease
CS: depression, head-pressing, circling, hyperactivity, aimless walking, persistent yawning, ataxia, disorientation, central blindness, proprioceptive deficits; progression to unpredictable aggressive or violent behavior interspersed with somnolence
Dx: Neuro signs consistent with cerebral dysfunction, PE and clin chem findings of hepatic dz
Hepatic encephalopathy associations
Severity correlates with degree of hepatocellular damage; does not predict disease reversibility
Pathophysiology is elusive
- Characteristically associated with hyperammonemia (increased CSF and serum ammonia)
- False NT, inflammation, neurosteroids, oxidative stress
Alzheimer Type II astrocytes on postmortem
Hepatogenic Photosensitization
Secondary photosensitization
Decreased clearance of phylloerythrin
-Accumulates in skin where UV light causes free-radical production and cell damage
Most prominent in non-pigmented areas
Laboratory abnormalities
Liver specific: Sorbitol dehydrogenase (SDH), Glutamate dehydrogenase (GLDH), Gamma-glutamyl transferase (GGT)
Tests of liver function: bile acids
Nonspecific: Bilirubin, Alkaline phosphatase (ALP), aspartate aminotransferase (AST), lactate dehydrogenase, ammonia, plasma proteins, hemostatic function, BUN
GLutamate dehydrogenase (GLDH)
Hepatocellular mitochondrial enzyme
Marker of acute or ongoing hepatocellular necrosis/damage
Short half life, more stable than SDH
Sorbitol dehydrogenase (SDH)
Hepatocellular necrosis
Highly specific
Short half life, acute and ongoing damage
Gamma-glutamyl transferase (GGT)
Biliary epithelium, marker of cholestasis (biliary disease)
Longer half life (17-96h) compared to SDH and GLDH
Baseline values higher in neonatal foals (2-4 weeks old) and donkeys
Other sources: renal, pancreatic GGT
Bile acids
Functional reserve of liver - excellent screen of liver failure
Increases: hepatocellular damage, biliary obstruction, portosystemic shunts
Specific for presence of liver disease but not specific for type of disease
Bilirubin
Can be normal in hepatic disease
Indirect (unconjugated): Acute hepatocellular disease, not specific, R?O hemolysis, anorexia, GI disease
Direct (conjugated): More reliable indicator of liver disease (values >25% of total bilirubin), cholestasis >30% total bilirubin; urine positive
Alkaline phosphatase (ALP)
Chronic or cholestatic liver disease
Pregnancy, hemolysis, GI disease, normal foals
Lactate dehydrogenase (LDH)
Isoenzyme (LDH-5) - acute hepatocellular disease
Aspartate aminotransferase (AST)
Hepatocellular damage, increases mostly secondary to muscle damage
Hyperammonemia
Secondary to other causes (GI disease) can present as hepatoencephalopathy
- Ammonia: byproduct of metabolism of nitrogen-containing compounds; neurotoxic at elevated concentrations = astrocyte dysfunction
- Liver clears majority of ammonia
- Tx: aimed at reducing production of ammonia; lactulose or antimicrobials (metronidazole)
Liver US
May be WNL
- Visualization limited by size and depth of liver and overlying structures (ribs, diaphragm, lungs)
Most useful for:
- Size, shape, and position of liver
- Parenchymal changes (abscesses, cysts, masses)
- Dilated bile ducts, choleliths (biliary system not normally visible)
- Liver biopsy
Liver Biopsy
Histopathology and microbiology
Coagulation profile performed PRIOR to biopsy
US guidance
R side, 12-14th intercostal space
Most useful diagnostics for liver disease
GLDH (or SDH) GGT Total and direct bilirubin Bile acids Liver US and biopsy - ALP, AST, plasma proteins, ammonia may be useful in specific cases of hepatic disease
Treatment of liver disease
Goal: provide supportive care until adequate liver regeneration
- Correct fluid deficits, acid-base and electrolyte imbalances, coagulopathy
- Mineral oil by NGT (bind toxins)
- Lactulose (hyperammonemia)
- Nutritional support (high CHO, low protein)
Severe hepatic impairment carries poor prognosis (fibrosis, etc.)
Equine hyperlipidemia
Increased triglyceride concentration
Associated with negative energy balance
- Ponies, miniature horses, donkeys
- Stress: illness, late gestation, early lactation
Clinical manifestation
- Signs often nonspecific or masked by primary disease
- Common: reduced water and feed intake, depression
- Severe: diarrhea, colic, fever, ventral edema, cachexia
Definitive diagnosis: increased serum triglycerides
Mild hypertriglyceridemia
All breeds: TG 100-500mg/dL
Not associated with lipemia, fatty infiltrates, CS
Severe hypertriglyceridemia
Adult horses: TG >500mg/dL
Lipemia absent
Rare CS and fatty infiltrates
Hyperlipemia with severe hypertriglyceridemia
Ponies, mini horses, donkeys
TG >500mg/dL
Lipemia, fatty infiltrates, CS
Normal energy metabolism
Glucose - Primary energy source - Stored in liver as glycogen - Stored in adipose tissue as TG (glycerol, FA) 2 key hormones
What are the 2 key hormones in normal energy metabolism and what do they do?
Hormone sensitive lipase: TG metabolism (adipose)
Lipoprotein lipase: TG (VLDL) tissue uptake
Negative energy balance
Decreased glucose utilization
Promotes gluconeogenesis, glycogenolysis, lipolysis
Primary energy reserve is FA stores in adipose tissue
Increased activity of hormone sensitive lipase
Hyperlipemia
Physiologic stress exacerbates normal response to negative energy balance
- Hormone sensitive lipase further upregulated
Insulin resistance
Obesity = excessive FA mobilization
Excessive TG & VLDL production and accumulation in blood
Treatment
Correct primary disease
Correct negative energy balance
- Enteral nutrition (palatable feed, enteral feeding tube)
- Parenteral nutrition
- 5% dextrose supplementation
- IVF (balanced electrolytes
Inhibit fat mobilization and improve TG uptake by peripheral tissues
- Exogenous insulin: suppress hormone sensitive lipase and activate lipoprotein lipase
- Exogenous heparin: stimulate lipoprotein lipase and promote TG metabolism
Chronic Megalocytic Hepatopathy
Pyrrolizidine alkaloid-containing plants (Senecio, Crotolaria)
4 weeks-6mo after exposure
Toxicity: cross-link DNA
- Altered cell division and protein synthesis
- Cell necrosis
Histology of chronic megalocytic hepatopathy
Megalocytosis
Biliary hyperplasia
Fibrosis
Death usually soon after onset of CS
Cholelithiasis
Biliary calculi
Bacterial infection may precipitate
Triad of CS:
- Icterus, fever, colic
Dx: Increased GGT, bilirubin (direct >30% of total), bile acids, bilirubinuria, US (dilated bile ducts +/- hyperechoic foci)
Tx: Long-term antimicrobial therapy (until GGT normal), Sx (choledocholithotripsy, choledochotomy)
Tyzzers disease
Bacterial hepatitis - Clostridium piliforme
Acute, necrotizin hepatitis in foals 7-42d old
Nonspecific signs of severe hepatic compromise
Sporadic outbreaks in foals ingesting contaminated feces or soil
Definitive Dx: organism ID at PM
Highly fatal, grave prognosis in foals
Theiler’s disease Hx and risk factors
Acute serum hepatitis, post-vaccination hepatitis, idiopathic acute hepatic disease
First described in 1919: African horse sickness vaccine
CS appear 4-10wk after administration of biologic of equine origin
- Tetanus antitoxin
- Hyper-immune plasma or antiserum/antitoxin: botulism, anthrax, strangles, WEE, influenza
- Vaccinations
- Plasma for colloid support
Theiler’s disease CS
Variable and nonspecific
- Acute onset, rapidly progressive
- Lethargy, anorexia, icterus, fever, encephalopathy
- Marked increase in liver enzymes
Mortality 50-90% in clinically affected horses
Histopath of Theiler’s disease
Severe hepatocellular necrosis and degeneration
T/F: Theiler’s disease has a potential bacterial association
False; viral (Flaviviridae)
Toxic Hepatopathy (acute)
Centrilobular (lowest O2 tension) or periportal (site of 1st exposure): diagnosis of exclusion, history of exposure, or detection of toxin
Drugs - hypersensitivity, intrinsic toxicity, or idiosyncratic: Erythromycin, tetracycline, diazepam, corticosteroids
Iron toxicity (ferrous fumarate): oral admin to foals before ingest colostrum
Mycotoxins (aflatoxin, fumonisin)
Plants (ryegrass, lupine, etc)
Chronic, active hepatitis
Idiopathic, chronic, progressive hepatopathy
- Causes: autoimmune, hypersensitivity, bacterial
Insidious onset of progressive liver failure
Dx: Liver enzymes, systemic inflammation, histopathology
Tx: Supportive care, corticosteroid therapy, antimicrobial therapy
Prognosis depends on cause, severity, and duration
