Flashcards in Disorders of the equine liver READING Deck (78):
How is the liver involved in protein metabolism? 3
-synthesises 90% plasma proteins
-transamination to produce new amino acid and a new keto acid
What makes urea?
2 ammonia molecules + carbon dioxide
How is the liver involved in carbohydrate metabolism? 4
--synthesis/storage/release of glucose
-G6P used to synthesise FAs and cholesterol
-release glucose into systemic circulation
Role of liver in lipd metabolism?
-esterify FAs into Tgs which are packaged with protein, carbohydrates and cholestero to from VLDL and HDL
-use of FFAs for energy
Role of liver in bile secretion?
-bile released from hepatocytes. major component is bile acids, into duodenum, >95% reabsorbed (enterohepatic circulation)
-bilirubin is a breakdown product
-liver conjugates bilirubin
What is the mononuclear phagocyte system?
-hepatic macrophages = Kuppffer cells. These produce many inflammatory mediators and have an important role in filtering portal blood
Clinical signs of hepatic dysfunction
vary greatly, non-specific, depend on extent and duration of hepatic disease, usually >80% hepatic function must be lost.
COMMON = depression, anorexia, colic, HE, weight loss, icterus
LESS COMMON = photosensitisation, diarrhoea, bilateral laryngeal paralysis, haemorrhagic diathesis, ascites, dependent oedema
What might the colic be due to?
acute hepatocellular swelling or biliary obstruction (cholelithisais)
Clinical signs of HE
vary from mild depression, to manic behaviour, head pressing, stupor
Pathogenesis of HE? 3
Likely to be multi-factorial:
-reduced clearance of ammonia
-imbalance between AAA and BCAA may result in increased concentration of false NT produced in brain
-other theories exist too
When does weight loss occur?
most likely with chronic liver disease. due to decreased intake + loss of normal hepatic metabolic activities
3 broad causes of icterus
hyperbilirubinaemia caused by:
-impaired hepatic uptake or conjugation
-impaired excretion of bilirubin
How do you diagnose increased bilirubin production/haemolysis? 2
usually increased unconjugated +/- conjugated if liver capacity exceeded
Diagnosis - impaired hepatic uptake or conjugation
increased unconjugated, possible cause is acute hepatocellular disease, also anorexia
Most common type of icterus in horses = ?
impaired hepatic uptake or conjugation
Cause of increased excretion of bilirubin
cholangitis, colangiohepatitis etc. if conjugated bilirubin concentration is greater than 30% total, indicates H
What is phylloerythrin?
photodynamic agent formed by bacteria in gut, absorbed conjugated and excreted by liver
How does phylloerythrin cause photosensitisation?
UV light exposure causes activation of electrons within the molecule to an excited state, leading to free radical formation --> cell membrane damage and necrosis. Lesions in non-pigmented skin (UV light absorbed more efficiently).
Why might diarrhoea be seen? 3
alterations in intestinal microflora, portal hypertension, deficiency of bile acids
What is haemorrhagic diathesis? When might it be seen?
predisposition to bleeding. Subclinical coagulopathy common, rare to see clinical signs
3 specific indicators of liver dyfunction
increased bile acids, increased sorbitol dehydrogenase (SDH) and increased gamma-glutamyl transferase.
Why do hepatic ultrasonography?
determines size, changes in hepatic parenchyma, dilated bile ducts, choleliths, can only image 20% liver
Why liver biopsy? 3 Where?
diagnosis, prognosis, treatment, 12-14th ICS, submit for histopathologic evaluation +/- culture, poor prognosis if bridging fibrosis
What is essential to do before taking a liver biopsy?
Evaluate coagulation parameters
General treatment principles - icterus 8
-maintain animal until liver regenerates sufficiently
-sedation if HE present (xylazine, detomidine)
-correct fluid deficits and acid-base imbalances
Treatment of HE 5
-liquid paraffin, magnesium sulfate (reduce toxin absorption)
-mannitol (cerebral oedema)
-oral neomycin (decrease bacterial production of ammonia)
-oral lactulose (limit ammonia absorption)
-oral BCAA (no evidence)
high carbohydrate, limit protein (but not too much, more important to ensure quality protein to ensure malnutrition doesn't occur)
What is DMSO
dimethyl sulfoxide - may help dissolve intrabiliary sludge or small stones
Suggest some anti-inflammatories 3
-pentoxifylline - shown to reduce hepatic fibrosis in humans
Another name for pyrrolizidine-alkaloid toxicity
Why might horses ingest ragwort?
Accidental (usually unpalatable), contaminated pasture or hay. problems if chronic ingestion (e.g 4-12 weeks)
Clinical signs - ragwort poisoning 2
HE and photosensitisation (classically)
other signs of chronic liver disease (weight loss etc)
diagnosis - ragwort poisoning 2
presumptive (history of ingestion and clinical signs of liver disease)
definitive - liver biopsy (megalocytosis, biliary hyperplasia, fibrosis)
Treatment of ragwort poisoning
no specific but treat for general liver disease. poor prognosis
Causes of acute hepatitis
Bacterial - tyzzer's, infectious necrotic hepatitis
viral (EHV in foals, EIA, EVA)
parasites (migration of parascaris equorum , strongylus edentatus/equines/vulgaris
Other names for acute hepatitis
serum sickness, acute necrotic hepatitis, serum-associated hepatitis
Pathogenesis - acute hepatitis
small liver, moderate to severe centrilobular to midzonal hepatocellular necrosis with haemorrhage
Diagnosis - acute hepatitis 2
hisotry+abrupt onset, evidence of hepatic insufficiency
Aetiology of Tyzzer's disease
Infectious hepatitis caused by Clostridium piliformis
Clinical signs - tyzzer's disease
foals (7-42 days), may be found dead, non-specific
Epidemiology and pathogenesis of tyzzer's disease
organism excreted in faeces of normal horses, bacteria replicate in GIT and reach liver and heart (via blood and lymphatics), causes acute multifocal hepatitis and enteritis
Diagnosis - tyzzer's diesae
difficult antemortem and often found dead, otherwise non-specific of liver failure, definitive = by post mortem. ID organism using silver stains
Treatment of tyzzer's disease
organism sensitive to penicillin, TCs, and erythromycin
poor prognosis - highly fatal
stones in bile ducts
stones in common bile duct, most common cause of biliary obstruction in horse
stones in intrahepatic bile ducts (variation of cholelithiasis
Cause of stone formation
uncertain - perhaps ascariasis, ascending biliary infection or inflammation, biliary staasis, changes in bile composition, presence of FB. Bacteria - salmonella, e coli, aeromonas hav ebeen cultured from stones
Triad of clinical signs associated with cholelithiasis/choledocholithiasis/hepatolithiasis
Diagnosis - cholelithiasis/choledocholithiasis/hepatolithiasis
-increased liver enzyme activity (GGT, SDH, AST)
-ultrasound (dilated bile ducts, evidence of cholelith)
-biopsy (histopathology and culture)
Treatment - cholelithiasis/choledocholithiasis/hepatolithiasis
long term antimicrobials, general supportive care, surgery?, prognosis variable depending on fibrosis extent, number/location of choleliths, severity of clinical signs
Horses likely to get hyperlipaemia and hepatic lipidosis
shetlands, miniature horses, other pony breeds and donkeys (especially if obese).increased risk during pregnancy, lactation or if a primary disease entity exists
What happens in hyperlipaemia and hepatic lipidosis?
metabolism of fatty acids in peripheral tissues (via action of hormone sensitive lipase), converted to Tg in liver, released into circulation, taken up by peripheral tissues (by lipoprotein lipase).
In animals with hyperliapemia, disease occurs due to overporduction of Tg in liver - lipoprotein lipase activity is high
Clinical signs - hyperlipaemia and hepatic lipidosis
icterus, anorexia, weakness, severe depression, ataxia, mm weakness, recumbency, diarrhoea, mild colic, fever, oedema. If severe fatty infiltratin of liver, signs of hepatic failure may occur
Diagnosis - hyperlipaemia and hepatic lipidosis 3
breed, clinical signs,
measurement of Tg in serum
liver biopsy (usually not necessary)
Treatment - hyperlipaemia and hepatic lipidosis
reverse NEB (encourage to eat, enteral nutrition, parenteral nutrition)
-eliminate stress/treat concurrent disease
-inhibit furhter fat mobilisation from adipose tissue (restore positive energy balance, insulin inhibits hormone sensitive lipase)
-increase Tg uptake by peripheral tissues (heparin increases activity of lipoprotein lipase - but already maximised in hyperlipaemic ponies)
Prognosis - hyperlipaemia and hepatic lipidosis
poo r- motality in 60-100%
Prevention - hyperlipaemia and hepatic lipidosis 2
-avoid obesity and stress
-monitor Tg levels in sick ponies (early attention to nutritional needs in sick animals)
Main cause of pre-hepatic icterus
haemolysis (-->increased bilirubin production)
Causes of haemolysis in horses 5
-Infectious (e.g. EIA)
-Toxins (onions --> HA)
-autoimmune HA - relatively rate in horses, Dx by exclusion
What % of normal horses show icterus?
10-15% of normal horses will look mildly ictericq
What is the most common cause of icterus in the horse?
anorexia (thus nothing actually wrong with the liver)
What is ligandin? When is it released?
a protein responsible for uptake of unconjugated bilirubin into liver. its release is stimulated by eating?
Causes of post-hepatic icterus? 4
cholangitis, cholangiohepatitis, cholestasis, shunts (v rare)
What should you ask when you have an icteric horse?
If no __> think liver disease
Functions of liver
4 methods of diagnosing liver disease
clinical signs, blood work, ultrasonogaphy, biopsy
What might you see on hepatic ultrasonography?
general size, changes in echogenicity, dilated bile ducts, choleliths, abscesses, neoplasia, can only image about 20% liver.
When is liver regeneration unlikely?
if severe fibrosis
beet pulp, cracked corn (=maize), molasses, sorghum/bran/milo (instead of beet pulp), oat hay (discourage lucerne/alfalfa)
Which anti-inflammatories might you give?
NSAIDs - flunixin meglumine
corticosteroids - dexamethasone and prednisolone (to prevent progression of inflammation as this leads to fibrosis)
Why should you be careful when you give hroses corticosteroids?
they cause an increased risk of laminitis
What is the result of the fact that the liver has minimal ways of respondign to insult?
aetiologic agent often not seen on biopsy
biopsy chagnes are often not definitive (non-specific lymphocytic/lymphoplasmacytic changes for examples)
What law requires land owners to limit ragowrt?
Ragwort control act 2003
How do pyrroles cause damage?
they are anti-mitotic = crosslink DNA and bind to nucleic acid and proteins within hepatocyte. this means cells cannot divide --> megalocyte porduction --> megalocyte death --> fibrosis
Why don't horses get gall stones?
The have no gallbladder! Instead bile duct stones form
What is the difference between hyperlipidaemia and hyperlipaemia?
Hyperlipaemia treatment 5
-treat the hepatic disease
-eliminate stress/treat concurrent disease
-inhibit further fat mobilisation (insulin inhibits hormone sensitive lipase)
-increase Tg uptake by peripheral tissues (heparin)