21. ACUTE LIVER DISEASES IN DOGS. ACUTE HEPATIC FAILURE Flashcards
Clinical signs of acute liver failure
- Sudden onset
- Good general condition
- (Ø oedema, ascites, kachexia)
Mild-middle
- Anorexia, depression, dehydration
- Vomitus, (diarrhoea), pd
- Icterus (usually no anaemia)
- Fever (infection)
- Coagulopathy (acute cases)
- Hemorrhagia, petechia, hematemesis, melena, hematochezia
- He
- Abdominal pain
- Liver: normal size, pain - acute liver cell distension
Intrinsic effect
- reproducible
- dose-dependent, over dose limit
- Direct toxic effect
- like paracetamol, xylitol
Idiosyncratic effect
- Unique, can not calculate, not reproducible, unique effect
- In therapeutic dose also, not dose-dependent
- rare, only in few cases
- phenobarbital, lomustin, itraconazole
Influenced by:
- Age, condition, general health, immune system, unique sensitivity, other drugs parallel
- Genetics?
- Breed predisposition:
o Dobermann: sulfonamide, amiodaron
o Labrador: carprofen (cause more chronic hepatitis) - Toxin: type, dose, exposure time
- Glutathione role (detoxification of toxic metabolits) – cats are very sensitive
- Drugs/toxin no signs, acute, fulminant, chronic
- NECROSIS (zone3), centrolobular +- cholestasis, steatosis (fatty), (inflammation)
Main groups of causes of acute hepatic failure:
Infections, other( trauma, heat), systemic or metabolic
Infectious causes:
Vírus Bacterium Fungus Protozoon Parasites
Oher causes:
Trauma
Heat stroke
hypoxia
Systemic or metabolic causes
IHL
Acute pancreatitis
Acute hemolytic anaemia
aim of treatment of AHF:
stabilization, support of liver function:
- Stop the indicial cause, antidote
- Fluid and electrolyte, acid base therapy
- Treat the Brain oedema, HE, bleeding
Hepatotoxicosis - drugs:
- Diazepam C
- Phenobarbital D ,phenitoin, primidon D
- Sulfonamide D
- Trimetoprim-sulfa
- Paracetamol (acetaminofen) D,C
- Amanita mushroom (Amanita phalloides) D,C (very dangerous)
- Xylitol (sugar – did you use any substitutions)
Short about paracetamol poisoning:
Quck depletion of glutathion stores, methaemoglobinaemia, hepatic necrosis (centrolobular hepatic necrosis)
Signs of paracet poison:
- Cyanosis
- dyspnoe (lung edema)
- tachycardia
- tachypnoea
- brown blood
- (looks similar to heart failure)
Lab work of paracet:
- Hemolytic anaemia, with methemoglobinaemia,
- brown blood, nucleated rbc, schistocyta, acanthocyta, heinz body,
- ALT increased
- Br increased
- Hb uria
Treatment of Hepatotoxins in general:
N-Acetylcystein NAC
SAMe (Hepapet, Samyilin, Denosyl) -additional treatment after stabilization!
Sylimarin
C-vitamin, E-vit
Cimetidine (Histodyl inj)
- Inhibit the P450 enzyme system – it worsen the condition so we must stop!
Fluid, electrolyte, oxigen, mannit..
- Stop the toxic drugs, toxins
- Antidote (if exist……)
- Gastric lavage, charcoal < within 2 hours
- Stabilization (fluid-electrolite therapy, oxygen…)
- Antioxidant treatment
o N-acetilcystein, SAMe, E vitamin, syilimarine - Refilling the glutathion stores
o NAC, SAMe
Phenobarbital poisoning:
Normal: liver enzyme induction common
- cytochrome P450 enzyme induction,
- Mild-middle↑: ALP, ALT, GGT, Normal albumin, Br, BA!
o 3-4 times higher liver enzymes but liver function tests are still normal
- Swallowed ER→ enlarged hepatocytes→ ↑liver, smooth
- Always check liver parameters before administering this drug for epileptic patient
Hepatotoxicity rare
- Acute necrosis or chronic hepatitis, cirrhosis
- Idiosyncratic reaction
- Minimum 5-12 month in high dose (upper range of therapeutic dose)
- ALP, ALT (>5x), GGT ~ acute / chronic hepatitis
- Abnormal liver function tests: ↓albumin, ↑Br, BA !
- Enlarged liver (acute) or smaller, irregular (chronic toxicity)
Treatment:
- Dose (decrease or stop) + (KBr, or Levatiracetam)
- Supportive therapy (SAMe!!)
- Rutin labor 4-6 months in case of chronic Pb treatment
PHENYTOIN poison
Hepatotoxicosis - very hepatotoxic (especially + Phe) - Acute or chronic hepatitis / fatal intrahepatic cholestasis - In dogs short half life time - Do not use as antiepileptic drugs !!! Primidone - Metabolits of Phe - Very hepatotoxic - Liver necrosis, lipidosis, cholestasis - Never use in cats
Primidone poison
Primidone
- Metabolits of Phe
- Very hepatotoxic
- Liver necrosis, lipidosis, cholestasis
- Never use in cats
PotSA poisoning:
- Idiosyncratic effect (also dose-dependent)
- Quite common
- Especially in dogs
- In Dobermann mostly Poly arthropathy, not the liver form
Sulphonamide hypersensitivity - Missing the gene that codes the important enzyme which detoxifying the reactive metabolites
- Oxidative sulphonamide metabolite indicate the T-cell mediated immune response
- Thrombocytopenia, fever, Poly arthropathy
- Common in dobbermann
acute hepatopathy - Acute hepatic necrosis + cholestasis / ly, pl inflammation
DESTRUCTIVE CHOLANGITIS – new disease - Idiosyncratic hypersensitivity
- Destruction of bile ducts in portal region + inflammation (macrophage, ngr, eo) + portal fibrosis
- Severe intrahepatic cholestasis → acholic faeces
Infectious diseases: viral
- Rubarth CAV-1 (canine adenovirus)
- Canine, feline herpesvirus
- FIP (feline infectious peritonitis)
- Suspected other viruses in the pathomechanism of hepatitis!!!
Infectious diseases: BACTERIAL
BACTERIAL
- Leptospirosis - Clostridium piliformis (Tyzzer’ diseases) - Helicobacter canis - Extrahepatic infection, liver abscess (sepsis) - Acute bacterial cholangiohepatitis
Infectious diseases: FUNGUS
FUNGUS
- Histoplasmosis - Coccidiomycosis
Infectious diseases: PROTOSOON
PROTOSOON - Toxoplasmosis
Infectious diseases: PARASITES
PARASITES - Dirofilaria immitis
HEPATITIS CONTAGIOSA CANIS (RUBARTH)
HEPATITIS CONTAGIOSA CANIS (RUBARTH)
Exposure → viraemia → lymphoid/other tissues → cytotoxic injury
- Canine adenovirus 1 (CAV-1) - vaccination against it, rarely seen these days
- Acute hepatic necrosis, GB-edema, dark, mottled appearance of liver
- Tropism: vascular endothel cell, hepatocyte (cytotoxic injury)
o 1: 500 → ø clinical signs
o 1: 4 → centrilobular to bridging hepatic necrosis
o 1:16-500 → chronic hepatitis , cirrhosis
- Complication: HE, DIC, G, GN (ic), GI, vasculitis, tonsillitis „blue eye disease”: uveitis, cornea edema, glaucoma, keratopathy
- Diagnosis: inclusion bodies, direct fluorescent antibody, biopsy
- Treatment: widespread use of vaccine (cross-reacting CAV-1, 2)
- atropine → anterior uveitis, - iv fluid therapy, blood transfusion
- topical corticosteroid →minimize inflammation in acute stage
CANINE HERPESVIRUS
- Acute, afebrile, rapidly fatal in neonatal puppies (die within 1 -3 weeks)
- Older dogs: mild upper respiratory signs
- Multiorgan necrosis? (liver, kidney, lung, other organs)
- Acute, systemic necrosis and hemorrhage
- Liver necrosis, necrotizing vasculitis, petechia, vesicles, sc edema
- Eosinophilic intranuclear inclusion bodies in hepatocytes, bile duct epithelium
Leptospirosis
Acute disease, primarily ARF + cholestatic hepatic disease
Leptospira interrogans / gryppotyphosa
- L. icterohaemorraghie → icterus, hepatic damage
- L. grippotyphosa → chronic hepatitis, fibrosis
- L. canicola → renal failure
o (L. pomona, L. bratislava, australis)
- Cats are relatively resistant
o Reservoir of spirochetas in stagnant water, contact with nondomestic maintenance hosts (skunk, rats, racoons). Shedding via urine
- Toxin: lysis of tight junctions between hepatocytes (dissociation, separation of hepatocytes); intrahepatic cholestasis; vascular damage,
- Laboratory findings: Br increased ,ALP increased ,ALT increased ,BA increased
- Clinical signs:
- fever, myalgia, jaundice, vomiting, vascular injury, uveitis, DIC, edema, oliguria, anuria, uremia
- Hematemesis, hematochezia, melena, epistaxis
- Fever of unknown origin + unexplained renal dysfunction: serology!
Diagnosis:
- Silver (Wartin-Starry)- /Giemsa-stain (stain and cut in lumen!)
- Serology: igg and igm response. Serology titer may be negative during first week, (repeat in 2 weeks) antibody paired serum titers microscopic agglutination test MAT
- PCR: identification of L. DNA
- Isolation from fresh urine (dark-field microscopy)
TYZZER’S DISEASE RARE
- Clostridium piliformis (Bacillus p.) Gr - fusiform bacteria + immunsuppression!
- multifocal hepatic necrosis, necrotizing ileitis
Clin: dogs, cats - acute onset: anorexia, lethargy, abdominal discomfort
- rapidly fatal, 24-48 h dying. No treatment
Dg: - Biopsy: multifocal periportal hepatic necrosis, C.p within hepatocytes
- surrounding areas of necrosis and intestinal epithelial cells
- Routine culture techniques are not effective for isolation
- Wartin Starry or Giemsa stain
HELICOBACTER CANIS
HELICOBACTER CANIS
- Multifocal hepatic necrosis
- Mostly in young dogs
- It presents at periphery of the lesions, located in bile canaliculi
- Suggesting ascending infection along bile duct
MYCOSIS
MYCOSIS
- systemic mycosis→mononuclear phagocytosis→liver signs (no acute)
- Clin: hepatomegaly, ascites, icterus. inhalation: cough, dyspnoe
- Liver: granulomatous or pyogranulomatous inflamm.(Giant cell, ly, pl)
HISTOPLASMOSIS
- Bone marrow, lymph nodes, GI
COCCIDIOMYCOSIS
- Bones, joints, lymph nodes, abdominal organs
- Labor: enzymes are slightly elevated or normal
PROTOZOAL
PROTOZOAL
Toxoplasma gondhii + immunosuppression
- Widespread multifocal necrosis, AHF (rapid multiplication of tachyzoites)
- Lungs, eye, lymphoid tissue, spleen, CNS, heart
- Clin: icterus, abdominal pain, fever, uveitis, concomitant lung involvement
- Cats: FeLV/FIV/CCH + Dogs: Fc+
- Treat: clindamycin
PARASITE
PARASITE
- post caval syndrome or vena caval syndrome (heartworm disease)
DIROFILARIA IMMITIS
- D.i.→right atrium or v.cava or v.hepatica →acute, passive congestion of the liver
Clin: acute onset:
- anorexia/weekness/dyspnoe/Hburia/anaemia/icterus
- Abrupt loss of venous blood flow→ infarction→ necrosis
- Intravascular hemolysis
- No history of cardiopulmonary signs
