Equine liver diseases

Question 1

Two routes of blood flow to the equine liver.
Also name what percentage goes through each.

Answer 1

Portal vein
* 70% of blood (comes from digestive tract +
spleen + pancreas)

Hepatic artery
* 30% of blood

Question 2

Describe the horse gallbladder.

Answer 2

Psyche! Horses don’t have gallbladders you dummy!

Question 3

What vitamins/elements does the liver store? (8)

Answer 3

iron, copper, selenium

vit A, D, E, K, B12

ADEK = fat soluble vitamins

Question 4

When is the liver a haematopoietic organ?

Answer 4

In the fetus.

Question 5

Clinical signs of liver disease in horses appear when about ?% of liver function is lost.

Answer 5

Clinical signs of liver disease in horses appear when about 80% of liver function is lost.

• Signs reflect loss of various liver functions
• Most of them are nonspecific
• Not all of them are always present

less common signs include photosensitization and bilat. laryngeal paralysis

Question 6

Explain how heme leaves the body, in what forms. (4-5)

Answer 6

Erythrocyte dies, heme is taken up by macrophages (in bonemarrow, spleen, liver) and turned into biliverdin.

Macrophages convert biliverdin into insoluble,
unconjugated bilirubin. Albumin transports this
to the liver.

Liver conjugates bilirubin into water-soluble form. Excreted into bile.

Question 7

When does unconjugated bilirubin increase and when does conjugated?

Answer 7

Decreased hepatic uptake due to anorexia: usually
complete anorexia lasting more than 2 days: increase in unconjugated bilirubin.

Severe liver disease: liver does not conjugate bilirubin
or conjugated bilirubin escapes to circulation.

Question 8

Icterus does not indicate liver disease, it indicates

Answer 8

excess bilirubin which can be due to a variety of causes.

Question 9

Normal liver enzymes but >90% unconjugated (indirect) bilirubin may be seen in (2)

Answer 9

Fasting horses! Up to 11 mg/dl.

or

Increased erythrocyte destruction so look for anemia, hemoglobinuria, pos. Coombs test, other hemolysis signs.

Increased liver enzymes and an increase in both unconjugated
and conjugated (direct) bilirubin indicates liver disease. Check NH3, bile acids, urine for bilirubinuria, urea for a decrease (cause liver not doing its job producing it).

Question 10

Hepatic encephalopathy is caused by

Answer 10

 Hyperammonemia (NH3)
 which causes cerebral oedema
 which increases glutamate levels (excitatory neurotransmitter)
 then it, augments GABA and serotonin systems (inhibitory neurotransmitters)

Other gut-derived neurotoxins may play a role too.

Aromatic amino acids from the gut (tryptophan, tyrosine, phenylalanine) may alter the balance of neurotransmitters.

There’s more theories too…

Question 11

Clinical signs of hepatic encephalopathy. (10+)

Answer 11

Clinical signs vary but e.g. anorexia, yawning, drowsiness, disorientation, ataxia, blindness, circling,
head-pressing, somnolence, occasional aggressiveness, coma etc.

Based on clinical signs alone you cannot differentiate
between something primarily intracranial and
something caused by liver dysfunction.

Question 12

Further diagnostics when suspecting hepatic encephalopathy: blood samples.

Answer 12

Hematology + Serum/plasma biochemistry: test for presence of disease presence and test for liver function.

Specific indicators that INCREASE:
 SDH (sorbitol dehydrogenase) from hepatocytes
 Glutamate dehydrogenase (GLDH) from hepatocytes
 Gamma-glutamyl transferase (GGT)
 Serum bile acids
 Ammonia

Non-specific indicators that INCREASE:
 Aspartate aminotransferase (AST) from hepatocytes
 Alanine aminotransferase (ALT) from hepatocytes
 Alkaline phosphatase (ALP/ALKP) from biliary epithelium
 Lactate dehydrogenase-5 (LDH-5)
 Total bilirubin
 Indirect (unconjugated) bilirubin
 Triglycerides

Nonspecific, DECREASE:
Albumin
Glucose
Blood urea nitrogen (BUN)

Question 13

Name two biochemical parameters that tell you about the biliary epithelium.

Answer 13

Gamma-glutamyl transferase (GGT)
Alkaline phosphatase (ALP/ALKP/AFOS)

NB ALP is naturally higher in growing horses cause its released from bones.

Question 14

Name two biochemical parameters that tell you about hepatocyte damage.

Answer 14

 Aspartate aminotransferase (AST) from hepatocytes
 Alanine aminotransferase (ALT) from hepatocytes

Bonus two:
 SDH (sorbitol dehydrogenase) from hepatocytes
 Glutamate dehydrogenase (GLDH) from hepatocytes

Question 15

Name three biochemical parameters that decrease in liver disease.

Answer 15

Non-specific, DECREASE:
Albumin
Glucose
Blood urea nitrogen (BUN)

Question 16

If you want to take a minimum biochemical liver database, what 6-7 parameters would you measure with priority?

Answer 16

As a rule:
* GGT
* GLDH (SDH if you can cause comes from mitochondria and indicates a greater cellular damage)
* Bile acids
* Triglycerides

Plus the non-specific:
 AST
 ALT
So: compare with kidney values (creatinine) and
muscle values (CK).

When signs of more severe liver disease is present, add:
 Triglycerides
 Total and conjugated bilirubin
 Glucose
 Ammonia
 Coagulation factors

 SDH (sorbitol dehydrogenase) from hepatocytes
 Glutamate dehydrogenase (GLDH) from hepatocytes

Question 17

GGT tells you about:

Answer 17

• Is a hepatobiliary enzyme
• Indicates cholestasis, but also hepatocellular necrosis.
• Half-life 3 days

NB GGT is naturally slightly higher (2-3 times) in
* Neonatal foals
* Horses in heavy training
* Sometimes during certain colics

Question 18

Describe GLDH.

Answer 18

glutamate dehydrogenase is a hepatocellular enzyme.

• Increases during acute liver disease
• Half life 14 hrs
• Unstable in serum, needs to be analysed fast

Question 19

AST is present where? (3)

Answer 19

AST: present in all cells, but most is in liver and skeletal muscle.

Question 20

Who conjugates bile acids?
If elevated, indicates?

Answer 20

Liver should conjugate them.

If elevated: hepatic insufficiency.

Question 21

Bilirubin is elevated in liver disease. In what 2 physiological instances is it also elevated?

Answer 21

• Higher in anorexia (long fast counts)
• Slightly higher in neonatal foals (reduced liver uptake of it)
• A significant elevation is still indicative of disease though.

Question 22

Ultrasound when suspecting liver disease.

Answer 22

 3-5 MHz linear or sector array probe

 In right and left side 9th to 14th intercostal spaces.

 Look for changes in echogenicity (side by
side with spleen it’s less echogenic); masses, abscesses, choleliths etc.

Question 23

Complications of U/S guided liver biopsy: (4)

Answer 23

• Pneumothorax
• Colon penetration, peritonitis
• hemorrhage

Question 24

Aims of the tx of liver disease.

Answer 24

• Treatment is largely supportive to give the liver time to regenerate.

Aims
* Electrolyte correction and diuresis
* Reduce ammonia loading
* Decrease discomfort and inflammation
* Nutritional support

You will learn how sometimes you just have to
* Disrupt large intestinal microflora
* Feed fat ponies pure sugar

Question 25

Fluid therapy in tx of liver disease.

Answer 25

Maintenance iv fluids: * Ringer acetate/ lactate 65-80 ml/kg/d * Helps kidneys clear ammonia * Hydrates, corrects electrolyte imbalances Add 5% glucose if hypoglycemia and anorexia. Add K if hypokalemia. IVFT Not always needed * If mild hepatic encephalopathy? signs * No hyperammonemia * Is the horse eating and drinking?

Question 26

Managing hyperammonemia (4)

Answer 26

Lactulose (Duphalac) * Lactose syrup, aims to reduce colonic pH * Bacteria produce less ammonia and assimilate it more. * 0.3-0.5 ml/kg every 8 hours PO Antibiotics aimed at changing the gut flora * Metronidazole, neomycin * Metronidazole is mainly metabolized in the liver! (Both reduced colonic pH and changing gut flora is generally considered a bad thing and may lead to colitis, but needs to be done.) Probiotics * Lactobacilli, enterococci Low protein diet

Question 27

Anti-inflammatories that can be used in liver disease tx. (5)

Answer 27

Flunixin meglumine 0.25-1.1 mg/kg every 12h IV * NSAID * Anti-inflammatory, antipyretic * Lower dose safer Pentoxifylline 10 mg/kg every 8-12 hrs PO * Reduces hepatic fibrosis in humans DMSO (dimethyl sulfoxide) * An industrial solvent (really) * 0.5-1 mg/kg DILUTED to 10%, given iv for 3-5 days * May flush out biliary sludge. Ursodiol (bile salt ursodeoxycholic acid) * Increases bile flow * Anti-inflammatory SAMe (S-adenosylmethionine) * Supplement * Converted into glutathione (anti-oxidant) * Anti-inflammatory, cell membrane stabilizer * No studies in horses

Question 28

Caution with drugs during liver disease because The liver’s capacity to metabolize them is compromised. Thus, Avoid what drugs?

Answer 28

Erythromycin, florfenicol, corticosteroids Benzodiazepines (diazepam, midazolam): affect GABA receptors, worsen HE Avoid sedation if possible: * Xylazine and detomidine are relatively safe, but use low dosages and don’t sedate so that the head falls low.

Question 29

Main goals of feeding during liver disease.

Answer 29

 Get the horse to eat  Give the horse easily digestible energy (high carb, low protein),  Reduce ammonia loading

Question 30

Feeding a liver disease horse: what if completely anorexic?

Answer 30

* Find ANYthing the horse wants to eat * Give molasses syrup orally * Place a small bore feeding tube and give molasses-electrolyte water (simplest) and/or Very liquid gruel (specific feeding mixtures). * Total parenteral nutrition via iv catheter is Inaccessible and Very expensive in horses but there are Special hepatic disease formulas in existence. AVOID: passing a larger nasogastric tube unless absolutely necessary as it may cause severe bleeding and coag factors may be poor due to the liver disease.

Question 31

Why Keep the horse out of sunlight while liver enzymes high?

Answer 31

The liver enzymes induce Photosensitivity, painful skin lesions.

Question 32

Primary and secondary liver diseases.

Answer 32

Primarily: a myriad of causes Secondarily: anything that causes biliary obstruction * Gastroduodenal obstruction * Severe duodenitis * Colon displacement (right dorsal displacement) Parasitic migration of Parascaris equorum Also, Pelvic flexure displaced to the right and wrapped around cecum sometimes obstructs duodenum (see pic).

Question 33

Name 8 causes of Acute hepatitis in horses.

Answer 33

 Hyperlipemia  Cholangiohepatitis (bacterial)  Tyzzer’s disease (bacterial)  Acute biliary obstruction  Toxic hepatopathy  Theiler’s disease (viral)  Viral  Parasitic

Question 34

Name 6 causes of chronic hepatitis in horses.

Answer 34

 Pyrrolizidine alkaloid toxicity  Cholangiohepatitis (bacterial)  Cholelithiasis (bacterial)  Abscess  Neoplasia  Amyloidosis

Question 35

Describe Hyperlipemia and hepatic lipidosis.

Answer 35

A cause of acute hepatitis in horses. You will probably see this most often. * Mini horses, donkeys, fat ponies Beware of the fat pony that stops eating! Anything that increases energy expenditure and mobilizes fatty acids can be involved: * Primary systemic illness * Anorexia for whatever reason * Late term pregnancy, lactation: high energy demand * Stress

Question 36

What happens physiologically when the horse needs more energy?

Answer 36

Question 37

Clinical signs of Hyperlipemia. (7)

Answer 37

* Depression * Anorexia * Ventral edema * Icterus * Vascular thrombosis * Enlarged liver, may even rupture * Azotemia In plasma * High triglycerides * Moderately high hepatocellular enzymes * Plasma looks white

Question 38

Treatment and prognosis of hyperlipemia/hepatic lipidosis in horses.

Answer 38

Without aggressive, adequate nutritional support: prognosis guarded at best. Nutritional support * Indwelling NG tube with specific powdered mixes. * Need to be low-fat! * Can be protein rich (add whey powder) * If nothing else then molasses water. Total parenteral nutrition but No lipids please. * Allow the horse to eat whatever it wants. * + iv fluids (+ glucose) * + iv insulin if persistent hyperglycemia * In a lactating mare: remove foal and give milk replacer to it.

Question 39

How can you prevent hyperlipemia and hepatic lipidosis in horses?

Answer 39

* Keep late term and early lactating mares on a good nutritional plane. You can actually give them fats at this point. * Know your at-risk patients * If sick: monitor triglycerides routinely! If TG starts to rise or if anorexic: * Molasses orally or glucose iv * (+ insulin) Treat primary disease best you can.

Question 40

Describe these Obstructive diseases: Cholangiohepatitis (CH) and Cholelithiasis (CL) when seen in horses.

Answer 40

Cholangiohepatitis is inflammation of the biliary system and the liver. * Probably retrograde bacterial infection from duodenum * E.coli, Streptococcus, Enterococcus, Bacteroides, Clostridium spp etc Cholelithiasis: biliary stones * Stones form as a result of inflammation Acute and chronic courses of disease.

Question 41

Cholangiohepatitis (CH) and Cholelithiasis (CL) diagnosis, tx and prognosis in horses:

Answer 41

Biopsy is ideal, and culture if possible. Specific treatment: * Antibiotics: combine to achieve gram+ and gram- spectrum * Penicillin-gentamicin or penicillin-enrofloxacin * 3rd generation cephalosporins * Trimetoprim sulfadiazine * Metronidazole might be considered? And add DMSO, ursodiol, pentoxifylline; surgery (for stones). Treatment is LONG, 50 days on AVERAGE. Clinical signs improve faster, liver enzymes decrease slower. Expect weeks, but there needs to be a downward trend. Prognosis: fair to guarded if no hepatic fibrosis. * Even with fibrosis, may live for years with dietary management.

Question 42

Name 3 Hepatotoxic drugs used in horses.

Answer 42

Phenothiazines (acepromazine) Macrolide antibiotics (erythromycin, azithromycin) * Increased hepatocellular activity but no significant damage seen with : Corticosteroids, phenylbutazone, benzimidazole anthelminthics (like fenbendazole) ## Footnote Idiosyncratic reactions seen with: rifampin, sulphonamides, tetracyclines; diazepam, phenobarbital, aspirin.

Question 43

Describe Theiler’s disease (“serum hepatitis”).

Answer 43

Acute hepatic necrosis Seen In adult horses Usually occurs after administering equine-origin biological antiserum. * 4-10 weeks after receiving the biological product * Sometimes no history even Several newly discovered viruses (equine hepacivirus, equine parvovirus) may be behind this but its not 100% confirmed yet.

Question 44

Presentation/clinical signs/findings in Theiler's disease.

Answer 44

* Presents with acute hepatopathy, HE, icterus * Hepatocellular enzymes: marked increase * Hepatobiliary enzymes: moderate increase * Liver anechoic and smaller * No specific treatment * Aggressive supportive care * Prognosis: good to grave depending on severity of signs.

Question 45

Name 2 clostridial disease seen in horses.

Answer 45

Tyzzer’s disease caused by Clostridium piliforme & Infectious necrotic hepatitis (Black liver disease) caused by Clostridium novyi

Question 46

Describe Tyzzer’s disease.

Answer 46

* Caused by clostridium piliforme * 6-42 day old foals in pasture * Peracute or acute hepatitis * Severe clinical signs * Treat aggressively with Penicillin, Anti-shock care, Anticonvulsants * Prognosis is grave though

Question 47

Describe Infectious necrotic hepatitis (Black liver disease)

Answer 47

* Caused by Clostridium novyi * Usually if pastured close to sheep or cattle (liver fluke) cause seems to affect animals that also have liver flukes. * Peracute or acute * Causes acute toxemia, icterus, sudden death * Can attempt aggressive treatment * Usually fatal Peracute: the horse is found dead or dies rapidly without any specific clinical signs.

Question 48

Describe Toxic plants and horses. E.g. What's the most common plant origin compound to cause toxicity in horses?

Answer 48

The most common: pyrrolizidine alkaloid toxicity which causes cumulative injury, chronic liver failure. * Most commonly called “ragwort toxicity”. Also, Senecio jacobaea, Senecio vulgaris, Cynoglossum officinale, Amsinckia intermedia, Crotalaria Eaten directly in pasture or in contaminated hay. Usually clinical signs when liver damage is widespread and irreversible. If responds to treatment and no reoccurrence in 6 months – prognosis is good. ## Footnote All of these toxic plants are found in Estonia and Finland too but most clinical cases occur in the UK and the US.

Question 49

When a horse from a non-cultivated pasture develops liver failure, what should you consider as a top ddx?

Answer 49

toxic plant ingestion

Question 50

Describe iron toxicity in horses.

Answer 50

* Suspected mechanism is free radical damage. * The horse is possibly the only known domesticated species that has physiological iron deficiency anemia as a foal. * Mare’s milk low in iron. * Do not need to be supplemented though! Newborn foals supplemented with iron (before colostrum) develop acute hepatopathy! Adult horses get iron toxicity rarely. * Anemia is almost NEVER true iron deficiency. * Instead Systemic inflammation anemia: Hepacidin (acute phase protein) inhibits iron absorption from gut AND its release from the liver. * About 4 times the daily recommended dose of iron is needed over a length of time to develop liver damage.