Hepatobiliary diseases II

Question 1

Describe Destructive cholangitis

Answer 1

Rare in companion animals. 9 cases in dogs reported in the last 20 years. In cats not reported.

Is 1of the 4 subtypes of cholangitis.

Destruction and loss of the bile ducts in the portal region with inflammation and eventual fibrosis.

Pathogenesis in dogs is unknown and often idiopathic.

Potential to be Idiosyncratic drug reaction (e.g., sulphonamides, amoxicillin-clavulanate),
or related to viral infections and/or immune-mediated.

Question 2

Destructive cholangitis
Presentation, clinical signs, diagnosis

Answer 2

Vomiting, lethargy, weight loss, diarrhea, decreased appetite, and jaundice.

Only known cause of intrahepatic cholestasis that can result in acholic (without bile) feces.

The length of time clinical signs before diagnosis varies from days-to-months due to the variety of diseases that can cause destructive cholangitis.

Abdominal imaging results nonspecific or unremarkable. Injury is directed at small bile ducts.

Histology obtained from multiple lobes is required for a diagnosis.

Question 3

Destructive cholangitis treatment, prognosis

Answer 3

Treatment: discontinuing all possible causal drugs.

In humans high-dose Ursodeoxycholic acid and immunosuppression. This strategy was used in a single case report of a dog with success.

Prognosis in dogs cannot be ascertained from limited reports, but recovery is possible.

Ursodeoxycholic acid is also known as ursodiol.

Question 4

Acute liver injury (ALI)
vs
Acute liver failure (ALF)

Answer 4

Acute liver injury (ALI) is defined as an acute hepatic injury with sustained hepatic function and normal conventional coagulation times.

Acute liver failure (ALF ) is defined as development of acute clinical signs of severe hepatocellular injury with concurrent hyperbilirubinemia and coagulopathy.

Question 5

Acute Liver Failure (ALF) Patophysiology

Answer 5

Clinical signs and biochemical manifestations develop when >70% of functional hepatic mass is lost.

• Sudden massive hepatocyte necrosis or apoptosis (cell death).
• Release of dead material-> production of inflammatory mediators-> development of SIRS (systemic inflammatory response syndrome).

Question 6

Acute Liver Failure (ALF) Etiology

Answer 6

In a retrospective study of 49 dogs with ALF, an etiology was determined in 18/49 (37%) dogs:
* Neoplasia (13/49; 27%)
* Leptospirosis (4/49; 8%)
* Ischemia (1/49; 2%)

Thirty-one of forty-nine (63%) had no identifiable cause, although 15 had exposure to potential hepatotoxins.

Question 7

Potential Acute Liver failure (ALF) Consequences (6)

Answer 7

MODS (multiorgan dysfunction syndrome)

Cardiovascular dysfunction
* Tachycardia, hypotension

AKI (acute kidney injury)
* Due to disseminated intravascular coagulation (DIC), sepsis, dehydration, hypovolemia, or direct nephrotoxicosis (hepatotoxins or leptospirosis).

Respiratory involvement
* Due to leptospiral pulmonary hemorrhage syndrome, acute respiratory distress syndrome (ARDS), atelectasis due to recumbency, pulmonary thromboembolism (PTE), aspiration pneumonia as a result of hepatic encephalopathy (HE).

Pleural effusion
* Secondary to low oncotic pressure

Aquired portosytemic shunts
* Development of acute intrahepatic portal hypertension.

Question 8

Acute liver disease (ALD) patient History should include: (5)

Answer 8

Careful review of:
* Toxin exposure
* Medication history (including exposure to recognized hepatotoxic drugs, nutritional and herbal supplements)
* Travel history
* Vaccination status
* Diet history, including snacks

Question 9

Acute liver disease (ALD) Clinical signs

Answer 9

Ranges from subclinical increases in liver enzymes to hepatic encephalopathy, seizures, and death.

Acute history of vomiting, diarrhea, polyuria/ polydipsia (PU/PD), anorexia, lethargy, abdominal pain, and/or jaundice.

May be evidence of a bleeding diathesis (petechiae, hematemesis, melena).

Signs of hepatic encephalopathy may manifest as:
* Behavioral changes
* Apathy, dull mentation, obtundation, circling, head pressing, acting blind, tremors, ataxia, ptyalism.
* Delayed menace and pupillary light reflexes, anisocoria, conscious proprioceptive deficits, stupor, seizures, and coma etc.

Question 10

Acute liver disease (ALD)
Potential physical examination findings:

Answer 10

Dehydrated or signs of hypovolemic or distributive/ vasodilatory shock.

Jaundice
Uremic oral ulceration

Tachypnea and dyspnea

Cranial abdominal pain and/or alterations in palpable liver size and/or ascites (portal hypertension, hypoalbuminemia, peritonitis, vasculitis, SIRS).

Pyrexia when an infectious disease.

Mentation changes suggestive of hepatic encephalopathy.

Mydriasis, decerebrate posturing, seizures or clinical signs of Cushing reflex (indicative of Cerebral edema and ICH (intracranial hypertension))

Decerebrate rigidity is characterized by opisthotonus and extension of all limbs.

Question 11

explain Cushing reflex

Answer 11

is a physiological response to increased intracranial pressure (ICP) and is characterized by a classic triad: bradycardia, hypertension, and irregular or altered respiration.

This reflex occurs as a compensatory mechanism to preserve cerebral perfusion in the face of rising ICP, which can result from trauma, tumors, hemorrhage, or other intracranial pathology.

As ICP increases, it compresses cerebral vessels, reducing blood flow to the brain. In response, the body increases systemic blood pressure to maintain cerebral perfusion, which then triggers baroreceptors that slow the heart rate.

Recognizing this reflex in small animals is critical, as it indicates potentially life-threatening intracranial pathology requiring immediate intervention.

indicative of Cerebral edema and ICH (intracranial hypertension)

Question 12

Acute liver disease (ALD)
Serum biochemistry findings (6)

Answer 12

Marked increases of hepatocellular leakage enzymes ALT and AST.
* Can be >100 folds

Variable increases of cholestatic markers ALP and GGT.
* Up to 2-5 folds

May show evidence of hepatic dysfunction.
* Low BUN, cholesterol, albumin and glycose

Hyperbilirubinemia
* Hepatocyte dysfunction and intrahepatic cholestasis.

Electrolyte ja Phos derangements
* PU/PD, reduced intake, GI loss, metabolic acidosis.

Increased creatinine
* Prerenal vs renal

Question 13

Acute liver disease (ALD)
Complete blood count findings (3)

Answer 13

Anemia
* Inflammatory disease, acute hemorrhage (GI, lungs) or DIC.

Leukocytosis or leukopenia
* Infectious disease or sepsis

Thrombocytopenia may be due to
* impaired thrombopoietin production by the liver.
* Decreased platelet survival (increased platelet clearance due to SIRS).
* Immune-mediated destruction
* Splenic sequestration (a consequence of portal hypertension)
* Consumption (hemorrhage, thrombosis, DIC)
* Direct result of the causative agent (leptospirosis, xylitol, cycads, aflatoxins)

Thrombocytopenia in up to 92% of dogs with ALF and less commonly in cats with ALF and suspected DIC.

Question 14

Acute liver disease (ALD)
Urinalysis findings (4)

Answer 14

Decreased urine specific gravity
* PU/PD (secondary to inflammation) or concurrent AKI

Bilirubinuria
* Small amount Can be normal finding in male dogs

Glucosuria
* Leptospirosis, lomustine (chemotherapy med), carprofen, cycads, blue-green algae, Amanita (mushrooms) and copper toxicosis – can all cause renal proximal tubular damage.

Ammonium biurate crystals
* Liver fails to process ammonia and fails to convert uric acid into allantoin.

Question 15

Explain Ammonium biurate crystals due to failure of the liver to process what? and why.

Answer 15

ammonium biurate crystals commonly form in the urine when the liver fails to properly metabolize ammonia and uric acid, typically due to congenital or acquired liver dysfunction such as a portosystemic shunt.

Normally, the liver converts ammonia into urea. and uric acid into allantoin, both of which are more easily excreted by the kidneys.

When liver function is impaired, ammonia and uric acid accumulate in the bloodstream, leading to the formation of ammonium biurate crystals, which can be seen in urine sediment and may be associated with urinary tract issues or systemic signs of hepatic encephalopathy.

Question 16

Acute liver disease (ALD)
potential Coagulation profile findings (3)

Answer 16

Liver is responsible for the clearance of activated pro- and anticoagulants. Liver also produces all coagulation factors.

Bleeding tendencies
* Thrombocytopenia, thrombocytopathia (dysfunctional platelets), hypofibrinogenemia and hyperfibrinolysis, vitamin K and clotting factor deficiencies.
* Spontaneous hemorrhage, including GI in >50% of dogs with ALF

Hypercoaculability
* Increased factor VIII and von Willebrand factor

Sinusoidal endothelial dysfunction as a result of SIRS
* Decrease in anticoagulant factors
* Production of pro-thrombotic microparticles

sinusoidal epithelium produces some coagulation factors

Question 17

Acute liver disease (ALD)
Imaging other than U/S

Answer 17

Thoracic radiographs
* Pleural effusion, metastasis
* Alveolar pattern such as in
ARDS, aspiration pneumonia, atelectasis, hemorrhage, PTE

Abdominal radiographs
* Liver size and serosal detail estimations

CT and MRI
* May show evidence of cerebral edema
* To exclude other intracranial disease processes (hemorrhage)
* Under-utilized due to the risk of sedating or anesthetizing a critically ill pet.

Question 18

Acute liver disease (ALD)
Imaging with U/S

Answer 18

Abdominal ultrasound for Assessment of the liver parenchyma.
* Decreased liver volume (massive hepatocyte loss)
* Hepatomegaly (malignant infiltration, ischemic hepatitis)
* Variable diffuse echogenicity changes, and ascites

Other findings that we may see:
* GI ulceration
* Acute pancreatitis
* Evidence of thrombosis
* Renal changes (increased renal cortical echogenicity, renomegaly, renal pelvic dilation, peri-renal fluid) (consider Leptospirosis vs AKI)

NB! US has poor accuracy in diagnosing diffuse hepatic parenchymal disease and can be normal even in the presence of severe ALD!

Question 19

Acute liver disease (ALD)
Cytology

Answer 19

Utility in diagnosing vacuolar hepatopathy, infiltrative neoplasia and even parasitic infections.

Low sensitivity for inflammatory diseases and fibrosis.

Advantages:
* Low cost
* Ability to sample multiple regions using only mild sedation e.g. tissue sampling (and potentially exclusion of infiltrative disease and lipidosis) in pets unstable for a general anesthesia.

Limitations:
* Risk of hemorrhage
* Small sample size
* Hemodilution, so when you only get blood cells when you try to FNA (challenging to ascertain inflammatory hepatitis).
* Inability to assess hepatic parenchymal architecture.

Question 20

Acute liver disease (ALD)
Biopsy

Answer 20

Indications for establishing cause, severity, reversibility, and/or prognosis. Indicators of chronicity include fibrosis, biliary hyperplasia, and cirrhosis.

Advantages and Disadvantages
* Greater risk of hemorrhage, Prior coagulation profile is needed.

Needle samples do not always correlate with biopsies obtained surgically due to smaller size but Shorter anesthetic times and limited tissue trauma compared to surgical and laparoscopic methods.

Surgical and laparoscopic biopsies more invasive but
allow direct visualization for hemorrhage and obtainment of larger tissue samples.

Question 21

Acute liver disease (ALD)
Potential histological findings:

Answer 21

In acute liver dz, you usually find Centrilobular, periportal or panlobular (massive) hepatic necrosis.

Results do not often confirm a specific etiology.
* Aside from neoplasia

Predominant findings
* Necrosis 47% (diffuse 47%, centrilobular 20%, multifocal 33%)
* Neoplasia 40%
* Degenerative (lipidosis 40%, vacuolar 19%)
* Inflammation 21% (lymphoplasmacytic/ pyogranulomatous)
* Biliary proliferation 8%
* Bile duct necrosis 2% and gallbladder inflammation 2%

Inclusion bodies
* Viral causes, e.g., herpesvirus and canine adenovirus-1 (CAV-1)

Tachyzoites and bradyzoites (life stages)
* Toxoplasma

Question 22

Acute liver disease (ALD)
3 Common causes

Answer 22

Bacterial hepatitis
Infectious Canine Hepatitis (CAV-1)
Leptospirosis

Question 23

Describe bacterial hepatitis.

Answer 23

Common cause of Acute liver disease (ALD)

Can be diagnosed by liver and bile culture, histopathology, PCR, and fluorescence in-situ hybridisation (FISH).

Bile cultures more often positive than liver culture.
* Escherichia coli spp., Enterococcus, Bacteroides spp. and Clostridium spp. infections are most commonly isolated.

Salmonella, Leptospirosis association of hepatitis have been more frequently reported since development of FISH.

Question 24

Describe Infectious Canine Hepatitis (CAV-1)

Answer 24

Causes Acute liver disease (ALD), Significant cause in unvaccinated dogs. Usually affects young dogs.

Red foxes in Europe are subclinical reservoir.

Non-hepatic clinical signs include anterior uveitis, bronchopneumonia, and lymphadenopathy.

• Mortality can reach 30%
• No specific treatment

Complications
* Corneal edema (“blue eye”)
* Interstitial nephritis (immune-complex deposition and viral persistence in the kidneys)

Histopathologic findings: centri- to panlobular hepatic necrosis with large basophilic intranuclear inclusion bodies.

Diagnosis on histological sections: immunohistochemistry, viral isolation, and PCR.

Detection of virus also on ocular swabs, feces, and urine with PCR.

Question 25

Describe Leptospirosis.

Answer 25

Common cause of acute liver disease. * Spirochete bacteria * Systemic zoonotic disease * Reservoir subclinically affected wild and domestic mammalians. Causes Renal and hepatic dysfunction, pulmonary manifestations, and reproductive failure. Causes systemic Vasculitis: * Endothelial damage -> bleeding tendency and pulmonary hemorrhage syndrome. Liver damage * Hepatocellular necrosis and cholestasis Kidney damage * Leptospires localize in the proximal renal tubules. Thus, can also cause glucosuria. Clinical leptospirosis rare in cats!

Question 26

Diagnosis of Leptospirosis.

Answer 26

Presence of concurrent ALI, AKI, thrombocytopenia, and evidence of proximal tubular damage (glucosuria) warrant further testing regardless of vaccination status due to lack of vaccinal cross protection. Microscopic agglutination test (MAT) serologic testing * Antibody titer * Paired sera over a 2-4 week interval * 4-fold increase in titers consistent with a diagnosis * Single high titer -> suspicion of leptospirosis, but does not confirm the diagnosis especially in vaccinated dogs. PCR * Detect leptospiral DNA in blood and urine * Utility in the diagnosis of seropositive vaccinated animals. * Affected by antibiotic treatment. Histopathology * Mild vacuolar hepatopathy in subclinical cases * Diffuse mild to moderate hepatic necrosis, neutrophilic periportal hepatitis and intrahepatic cholestasis in severe cases.

Question 27

Tx of lepto.

Answer 27

Antibiotics * first with Parenteral potentiated amoxicillin During initial hospitalization. * Then, 2-week course of 10 mg/kg PO q24h doxycycline at home To prevent a long-term carrier state. Other dogs in the home also need to be treated.

Question 28

Describe neoplasia as a common cause of acute liver disease.

Answer 28

Malignant intrahepatic biliary infiltration-> obstruction of hepatic venules-> ischemic injury and necrosis, and rapid replacement by malignant cells-> critical mass of hepatocyte destruction. Mainly: * Round cell malignancies (lymphoma, poorly differentiated round cell tumors, mast cell tumors) * Also carcinomas are represented.

Question 29

Describe copper storage disease as a common cause of Acute liver disease (ALD).

Answer 29

Copper storage disease is suspected to cause * Acute hepatic necrosis in dogs * Because Increased centrilobular copper staining with acute hepatitis as been found. The above Suggests a role of excess copper in the pathogenesis of ALD, but the role of copper toxicosis in the pathophysiology of ALD warrants further evaluation. Treatment * Chelation therapy (binding particles of metal) * Dietary copper restriction * Antioxidant treatment

Question 30

Describe Drug-Induced Liver Injury (DILI)

Answer 30

Direct causes * Are Predictable * Hepatocellular and dose-dependent (high or supra-therapeutic doses) so can sorta prepare if you know you have to give a high dose. * Short latency period * Typically responds to a reduction dose * Cessation is rarely required Idiosyncratic * Agents with minimal or no intrinsic toxicity. * Result of reactive metabolite formation. * Variable latency period (usually within 4 weeks) and can occur after drug discontinuation. * Are difficult to predict and only lead to toxicosis in a small percentage of patients at therapeutic doses. * Drug discontinuation is recommended.

Question 31

Diagnosis of Drug-Induced Liver Injury (DILI)

Answer 31

Diagnosis of exclusion. * May be accompanied by hypersensitivity reactions (pyrexia, rash, joint pain, eosinophilic leukocytosis). Establishing diagnosis technically with; * Response to drug withdrawal and positive re-challenge, but ethical implications to this as repeat exposure may be associated with a more rapid and severe return of ALD due to adaptive immune responses; therefore, the diagnosis is usually presumptive. Histology: acute hepatic necrosis with minimal inflammation (cytotoxic); bile duct injury and cholestasis (cholestatic). ## Footnote Treatment of DILI: Drug withdrawal of all but essential medications. Serial monitoring of liver enzymes until normalized.

Question 32

Describe Drug-Induced Liver Injury (DILI) specifically with acetaminophen / paracetamol.

Answer 32

Clinical signs * Brown/cyanotic mucous membranes (methemoglobinemia), facial and paw edema. Doses of * 100 mg/kg can lead to hepatotoxicosis * 200 mg/kg can lead to methemoglobinemia NB There is no safe dosage for cats! Treatment: * Emesis and activated charcoal Up to 4 hours after ingestion. * IV N-acetylcysteine up to 48 hours after ingestion. Later, can switch to oral. * S-adenosyl methionine (SAMe) * Oral Silymarin * IV/PO Vit C / Ascorbic acid to reduce methemoglobin to hemoglobin. ## Footnote (In moderate to severe methemoglobinemia, methylene blue IV (1–2 mg/kg) is often the first-line antidote in dogs.)

Question 33

Describe Drug-Induced Liver Injury (DILI) specifically with phenobarbital.

Answer 33

Can cause Development of Increased liver enzyme activities without hepatocellular damage. * Dose-dependent ALD * Or chronic hepatopathy Clinical signs (when apparent): * After >1 year of cumulative treatment Extent of hepatic injury associated with duration of administration. Improvement seen after dose reduction -> Suggest dose-dependent toxicity. Histopathology * Portal fibrosis, nodular regeneration and biliary hyperplasia.

Question 34

Describe Drug-Induced Liver Injury (DILI) specifically with azathioprine.

Answer 34

Azathioprine (immunosupressant) can cause reversible dose-dependent drug induced liver injury. * Mild, asymptomatic, self-limiting increases in liver enzyme * Less commonly clinical hepatotoxicosis and jaundice Hepatotoxicosis reported in 15% of dogs after a median of 2 weeks of treatment. Recommended monitoring of liver enzymes in the first 4 weeks of treatment. SAMe or N-acetylcysteine supplementation may be useful for duration of treatment.

Question 35

Describe Drug-Induced Liver Injury (DILI) specifically with antifungals.

Answer 35

Antifungal drugs such as Ketoconazole, itraconazole, and fluconazole. * Subclinical liver enzyme increases * Uncommonly clinical hepatotoxicosis * Ketoconazole usage in cats is controversial because of high risk of side effects. * Fluconazole is the least hepatotoxic drug. May be utilized in transitioning in patients that develop hepatotoxicosis with the former drugs.

Question 36

Describe Drug-Induced Liver Injury (DILI) specifically with amiodarone.

Answer 36

Amiodarone (class-III antiarrhythmic) for tx of ventricular tachyarrhythmias in dogs. Dose-dependent toxicosis * Vomiting, anorexia, and increased liver enzyme activities seen in up to 45% of dogs after 6 days to 8 months of treatment. Toxicosis resolves after drug discontinuation, but time to liver enzyme normalization can be protracted.

Question 37

Describe Drug-Induced Liver Injury (DILI) specifically with Antibiotics: Potentiated sulphonamides.

Answer 37

Idiosyncratic hepatotoxicosis mainly in dogs; uncommonly in cats. Clinical signs * 5-36 days after exposure * Fever, polyarthropathy, dermatologic lesions, keratoconjunctivitis sicca, hematologic dyscrasias (thrombocytopenia, neutropenia, hemolytic anemia, eosinophilia), hepatotoxicosis and uveitis. Hepatotoxicosis * Acute parenchymal damage * Moderate to severe increases in ALT * Acute cholestasis with jaundice Histopathology * Diffuse hepatic necrosis * Severe cholestasis and lymphoplasmacytic inflammation Drug discontinuation usually leads to resolution. ## Footnote e.g. Trimethoprim-sulfadiazine

Question 38

Describe Drug-Induced Liver Injury (DILI) specifically with Antibiotics (tetracyclines).

Answer 38

Doxycycline * Subclinical increases in ALT and ALP in 40% of treated dogs. Clinical significance of this is unknown. Associated with clinical hepatotoxicosis in a cat.

Question 39

Describe Drug-Induced Liver Injury (DILI) specifically with Lomustine (antineoplastic).

Answer 39

Increased liver enzyme activities in up to 86% of dogs. Clinical hepatotoxicosis occurs in 3-6% of dogs. * Higher cumulative doses and number of doses. * Median of 4 doses with a median of 11 weeks duration. * Reversible in most dogs after discontinuation of treatment but some can develop a chronic hepatopathy 3 months to over 3 years after diagnosis. * Can be lethal due to progressive hepatotoxicosis. Combination of SAMe and silymarin decrease the incidence and severity of hepatotoxicosis and should be administered concurrently.

Question 40

silymarin mechanism of action in liver support

Answer 40

Silymarin (the active extract from milk thistle) is a hepatoprotective agent. given orally. * Silymarin scavenges free radicals and increases glutathione levels in hepatocytes. * reduces oxidative stress * stabilizes hepatocyte membranes, preventing toxins (like drugs, mycotoxins, or other chemicals) from entering liver cells. * inhibits the NF-κB pathway and reduces production of inflammatory cytokines (e.g., TNF-α, IL-1). * stimulates RNA polymerase I activity in the nucleolus, enhancing ribosomal RNA synthesis. This promotes hepatocyte regeneration. * inhibits the activation of hepatic stellate cells, which are key players in liver fibrosis. ## Footnote Epato 1500 Plus tablets

Question 41

Describe Drug-Induced Liver Injury (DILI) specifically with Diazepam (anxiolytic, muscle relaxant, sedative, anticonvulsant, and appetite-stimulating).

Answer 41

Clinical toxicosis reported in cats. * Not reported with parenteral formulations * Idiosyncratic hepatotoxicosis * Repeated oral administration -> clinical signs such as: Anorexia, lethargy, jaundice, HE within 4-11 days. Prognosis is poor: * 16 out of 18 reported cats dying/being euthanized within 15 days of initial drug administration. Histopathology * Centrilobular-to-panlobular hepatic necrosis, biliary hyperplasia and suppurative cholangitis.

Question 42

Describe Drug-Induced Liver Injury (DILI) specifically with Methimazole (antithyroid).

Answer 42

Within the first month 2% of cats develop a reversible idiosyncratic cholestatic hepatopathy. Resolves with discontinuation and you CANNOT retrial as subsequent signs will be worse. Mechanism of toxicity in cats is unknown. Increased liver enzymes and bilirubin. Should be differentiated from increased liver enzymes with untreated hyperthyroidism which resolve with establishment of euthyroidism.

Question 43

Describe Drug-Induced Liver Injury (DILI) specifically with carprofen.

Answer 43

NSAID that can cause Idiosyncratic hepatocellular hepatotoxicosis of Variable severity in dogs. Usually within the first month of treatment. Improves within a few weeks of discontinuation. Histopathology: hepatic necrosis Its Unclear whether pre-existing liver disease is a risk factor for toxicosis or does chronic inflammatory liver disease develop as a consequence.

Question 44

Treatment of neutrophilic cholangitis vs lymphocytic vs chronic vs destructive. Explain super shortly, 1-2 words.

Answer 44

neutrophilic cholangitis tx long course AB lymphocytic tx Immunosuppressive doses of steroids chronic cholangitis with praziquantel, surgery if obstructed destructive tx surgery, ursochol life-long basically

Question 45

Describe Environmental toxins as causes of Acute liver disease (ALD).

Answer 45

More in dog than cats due to scavenging nature. Confirmation of exposure difficult. No pathognomonic clinical features. Only few veterinary labaratories worldwide offer testing. Decontamination is main treatment. * Emesis, gastric lavage, activated charcoal

Question 46

Describe aflatoxins as a cause of Acute liver disease (ALD).

Answer 46

Aflatoxins produced by Aspergillus spp., found in cereal ingredients contained in contaminated pet food formulations or mouldy foodstuffs. Toxicosis occurs after a median of 45 days. * Detailed dietary history needed. * Some dogs exhibit aversion to contaminated food. Clinical signs * Subclinical * Anorexia, lethargy, vomiting/hematemesis, jaundice, diarrhea, ascites, peripheral edema, bleeding diathesis, HE and sudden death. Histopathology * Diffuse cytoplasmic lipid vacuolation, biliary duct hyperplasia, scattered individual hepatocyte necrosis and varying degrees of fibrosis (subacute). * Marked diffuse bridging portal fibrosis with regenerative nodules and aPSS (chronic low grade exposure). Mortality ranges from 64-100%!

Question 47

Describe Sago Palm (ornamental cycad plants) as a cause of Acute liver disease (ALD).

Answer 47

All parts of the plant contain toxins. The responsible toxin is cycasin. Hepatotoxic, carcinogenic, GI and teratogenic effects. * GI signs, with hepatic damage occurring within 24-48 hours of ingestion. * Neurological signs are seen in >50% of dogs. Histopathology * Centrilobular necrosis, degeneration due to inflow of water and sinusoidal congestion. Mortality is seen in 32-50% of dogs.

Question 48

Describe Xylitol (sweetener) as a cause of Acute liver disease (ALD).

Answer 48

Dosages over 100 mg/kg in dogs lead to profound hypoglycemia due to insulin release followed by hepatotoxicosis. * ↓GLU may be delayed due to gradual depletion of hepatic glycogen stores following acute liver failure development. Acute hepatic necrosis with increased liver enzyme activities 9-72h after ingestion. * Development of ALF is idiosyncratic and not dose dependent. Clinical signs: * Onset variable, can start within 30 minutes after ingestion. * Vomiting, lethargy, weakness, ataxia and seizures. Diagnosis based on history. Treatment * Emesis & activated charcoal if too much time hasn't pasted from ingestion yet. * IV Dextrose/glucose, SAMe, IV N-AcetylCysteine Histopathology * Severe acute centrilobular and midzonal hepatic necrosis. Experimentally, cats do not develop xylitol hepatotoxicosis.

Question 49

Describe Blue-Green Algae (Cyanobacteria) as a cause of Acute liver disease (ALD).

Answer 49

Cyanotoxins released as algae cells die and the bloom appears as a blue-green scum floating on the water surface. Hepatotoxicity * Ingestion of contaminated water by drinking, swimming, or licking contaminated fur. * Hepatic necrosis and accumulation of blood in the sinusoids. Signs can occur within 6-12 hours. Often begins with GI tract signs.

Question 50

Describe Amanita phalloides („death cap” mushrooms) as a cause of Acute liver disease (ALD).

Answer 50

Species of mushroom toxic to people, dogs and cats. * Contains 2 toxins: phallotoxin damages cell membranes of intestinal epithelium and amatoxin is hepatotoxic. 4 phases of toxicosis: * Subclinical lag phase * GI phase 6-12 hours post-consumption with nausea, vomiting, diarrhea, and abdominal cramping. * Apparent recovery (lasting 12-24h) whilst subclinical increases in liver enzyme activities. * Acute liver failure and acute kidney injury 36-84 hours post-consumption. Penicillin and silymarin accepted antidotes in people to inhibit hepatocyte amatoxin uptake. Reported: Silymarin in dogs at higher doses (50 mg/kg IV administered at 5 hours and 24 hours after intoxication). Survival approximately 26%, high mortality.

Question 51

Acute liver disease (ALD) Treatment – General supportive care:

Answer 51

Support liver function until recovery. * SAMe, silymarin, NAC etc. IV fluid therapy * Preferably 0.9% NaCl or ringer's acetate (because there is already metabolic acidosis happening). * If no metabolic acidosis (check blood gases), Ringer's lactate okay. Colloids * In hypoalbuminemic pets to maintain oncotic pressure Vasopressors * For refractory hypotension Dextrose Antiemetics

Question 52

Acute liver disease (ALD) Prognosis

Answer 52

After surviving the acute phase of ALD/ALF complete recovery without permanent hepatic injury is possible. Often chronic hepatic disease develops though. Approximately 14% survive to discharge when all causes' statistics pooled. Negative prognostic markers: * Hyperbilirubinemia, hypoalbuminemia, hypocholesterolemia, hypoglycemia – indication of liver dysfunction. * Evidence of a bleeding diathesis (spontaneous bleeding, altered clotting profile). * Development of ascites Good prognostic indicators: * High serum ALT at presentation and >50% decrease over several days because it shows you you have more viable hepatocytes with subsequent greater ALT leakage. * Toxic etiologies that inhibit ALT were more likely in non-survivors (aflatoxins, cyanotoxins).