Liver Disease

5/28/2019

Primary vs Secondary Liver Disease Practical • One of the most difficult tasks of dealing with liver Gastroenterology disease is to distinguish one from another • Primary Liver disease must be treated at it’s cause, if Liver Disease we are to do anything but palliate Wendy Blount, DVM • Secondary Liver Disease just distracts us from the primary problem, whether liver disease, and/or something else • Secondary Liver Disease = Reactive Hepatopathy • However, as the liver acts as an innocent bystander, it can suffer collateral damage, which we should mediate

Primary vs Secondary Liver Disease Primary vs Secondary Liver Disease Signs of Primary Liver Disease – The Liver Is Sick! Signs of Primary Liver Disease – The Liver Is Sick! • Change in liver size or shape • Acholic feces – Hepatomegaly • Superficial necrolytic hyperkeratosis – aka – Microhepatia hepatocutaneous syndrome – Liver mass – Irregular liver margins – Radiographs the best test for liver size – Ultrasound the best test for liver shape and to find masses • Icterus without anemia • Hepatic encephalopathy

Primary vs Secondary Liver Disease Primary vs Secondary Liver Disease Signs of Primary Liver Disease Signs of Primary Liver Disease • Coagulopathy – The Liver Is Very Sick!! • Coagulopathy – The Liver Is Very Sick!! – GI hemorrhage death spiral – GI hemorrhage death spiral 1. Increased stomach acidity 4. Cholestasis Vit K absorption – Decreased hepatic clearance of gastrin, decreased – Vit K needed to make factors 2,7,9,10 mucus, mucosal ischemia – Long term antimicrobial Tx inhibits Vit K production – Increased bile acids further stimulate HCl secretion 2. Clotting factor’s, AT3 not produced adequately by – Hemorrhage elsewhere only when near death failing liver • Petechiae, bruising, bleeding into cavities – Poor clotting and thromboembolic disease 3. DIC – more AT3 consumption – more thrombosis • Positive Feedback Loop #1 - GI Bleeding exacerbates hepatic encephalopathy • Positive Feedback Loop #2 - Large bleed can cause depletion coagulopathy

1 5/28/2019

Normal Liver Size Hepatomegaly • Look at the gastric axis!! (fundus to pylorus) • Look at the gastric axis!! (fundus to pylorus) • Normal gastric axis range: • Gastric axis more acute angle with the spine • From: perpendicular to the spine; To: parallel to the ribs.

Hepatomegaly Hepatomegaly • Focal hepatomegaly is often, but not always neoplasia • Focal hepatomegaly is often, but not always neoplasia • Gallbladder mass can be mistaken for liver mass or even • Gallbladder mass can be mistaken for liver mass or even normal liver if filled with amorphous sludge normal liver if filled with amorphous sludge • Glycogen vacuolar hepatopathy can be focal • Nodular hyperplasia is a benign process causing liver masses • Generalized hepatomegaly • Primary or secondary liver disease • Toxic exposure and swelling of the liver – hypoechoic large liver with smooth borders and rounded margins • Steroid hepatopathy – hyperechoic large liver with smooth borders and normal margins • Any generally large liver with rounded margins can be neoplastic, regardless of echotexture and relative echogenicity – LSA, MCT, hepatocellular carcinoma

2 5/28/2019

Microhepatia - Microhepatica Microhepatia - Microhepatica • Look at the gastric axis!! (fundus to pylorus) Differential Diagnosis: • Gastric axis more obtuse angle with the spine 1. Atrophy • Portasystemic shunt – any age, chronic disease • AV fistula – usually less than 2 yrs old (rare) • Often normal panel, but elevated bile acids + ammonias

Microhepatiacirrhosis - Microhepatica Microhepatia - Microhepatica scites Differential Diagnosis: iver Differential Diagnosis: 1. Atrophy – Small, maybe hyperechoic liver 3. Congenital small size – diagnosis of exclusion • Portasystemic shunt – any age, chronic disease • Imaging – no lumps, normal appearing margins, • AV fistula – usually less than 2 yrs old (rare) normal echotexture (just small) • Often normal panel, but elevated bile acids + ammonias • All liver blood tests normal, except changes due to 2. Cirrhosis secondary liver disease • history of chronic inflammatory disease • Liver biopsy normal • History of massive hepatic necrosis • Splenic portagram normal • History of untreated PSS for years • Usually middle aged to older patients • Liver enzymes usually but not always elevated, bile acids elevated, albumin may be low • Ascites is common

Problems Causing Diagnostics for Liver Disease Reactive Hepatopathy First Tier Tests: • CBC, panel, urinalysis • Any systemic infection or inflammation – Occult - urinary tract, metritis, prostatitis, dental disease, etc. • Fecal flotation, direct smear, cytology • Disease of organ drained by portal vein • HWAg in the dog, FeLV/FIV in the cat – Gut, spleen, pancreas (ultrasound the best test) Second Tier Tests: • Hyperthyroidism in cats • Bile Acids • Severe muscle disease • Complete Abdominal Ultrasound (not focused liver/GB • Untreated Cushing’s Disease or diabetes mellitus and not GlobalFAST®) • Hypoxia, passive congestion • Liver sampling & spleen FNA – after BMBT – heart failure, respiratory disease, severe anemia • FNA – 25-50% diagnostic – hypotension • Ultrasound guided biopsy – 50% diagnostic • Drugs causing liver enzyme induction • Wedge biopsy – more likely to be diagnostic • VARYING DEGREES OF COLLATERAL DAMAGE

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Diagnostics for Liver Disease Pattern Recognition - Liver Disease Third Tier Tests: • High liver enzymes • if Bile Acids are equivocal and PSS is suspected – ALT – hepatocellular disease (hepatocellular membrane) – Ammonia tolerance test – ALKP, GGT – more sensitive indicator of – Splenic portagram cholestasis than bilirubin (from biliary epithelium) • Coagulation tests if significantly systemically ill, severe • Low albumin liver disease is suspected, or liver sampling will be done – low alb indicates severe disease (90% loss of hepatic • Hunt for causes of secondary liver disease function) • Imaging – thoracic rads and ultrasound – Beware human labs (falsely low values) - Abaxxis • Testing for infectious disease and Cushing’s Disease • Low fasting glucose (70% loss of hepatic function) • Diagnostic surgery, MRI/CT • High prost-prandial glucose • Low BUN • Abnormal cholesterol, triglycerides

ALT Gems ALKP Gems The enzyme formerly known as SGPT • Bone disease can also cause ALKP elevation • RBC & skeletal muscle contain small amts of ALT – Neoplasia, osteomyelitis, hyperPTH, growth & – Hemolysis and muscle damage cause moderate elevations in healing ALT (2-3x) • DDx cholestasis: • ALT - t1/2 – 1-2 days – the first to improve – Starts improving within 1-2 weeks of liver disease resolution – Gallbladder disease – remains elevated during hepatic regeneration • Intramural - Gallbladder sludge, mucocoele, stones, infection • DDx hepatocellular turnover • Mural - Gallbladder wall polyps, masses, infection • Extramural – Pancreatitis, abdominal mass, duodenal foreign – Hepatocellular disease body, diaphragmatic hernia – Poor perfusion – hypotension, passive congestion, anemia • Gallbladder trauma or rupture • Marker for anaphylaxis, along with increased PTT and AFAST sonogram – Trauma – surgery, trauma, peritonitis – Liver Disease – Toxicity • microscopic cholestatic disease (infectious, inflammatory, toxic), liver trauma, neoplasia, lipidosis

ALKP Gems GGT Gems • DDx cholestasis: • less influenced by secondary liver disease or – Systemic cholestatic disease acute hepatic necrosis than ALKP • Endocrine – diabetes mellitus, hyperadrenocorticism, chronic • Not confounded by bone disease as ALKP stress, hyperthyroidism • Passive congestion – RHF, pericardial disease • more useful in cats to identify fatty liver • Systemic infection/inflammation – especially sepsis, • More useful in dogs to identify biliary disease rickettsial disease, protozoal disease, fungal disease • Otherwise, follows ALKP

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Hepatotoxic Drugs

• Drug induced ALKP does not necessarily indicate hepatic pathology – Assess with bile acids if concerned – Phenobarbital can also cause hepatotoxicity, but glucocorticoids almost never do • GGT increases markedly with corticosteroid enzyme induction in dogs • Drug induced ALKP takes weeks to months to resolve after stopping the drug • Glucocorticoids almost always elevate ALKP (and ALT) in dogs, but almost never in cats

Elevated Liver Enzymes in the Cat Hepatotoxic Drugs Cats are not little dogs – Thumb Rules • Drugs that increase ALT are more likely to • Cats with persistently elevated enzymes should be cause hepatic damage if continued worked up

• At a marked increase in ALT, the offending drug – T1/2 of liver enzymes is hours in the cat, not days as in the dog should ideally be stopped, and ALT rechecked – cats have 1/3 the liver ALKP compared to dogs in 30 days • Cats with significant cholangiohepatitis can have normal liver enzymes, though that problem often • Lomustine - missing from the chart, but can causes very high ALT cause potentially life threatening hepatotoxicity • GGT in cats has higher sensitivity but lower indicated first by increased ALT and then specificity for biliary disease decreased albumin • If a cat has biliary disease, GGT is likely high • Use of any drug on either chart indicates • If cat does not have biliary disease, GGT can still monitoring of liver nz + bile acids, albumin sometimes be high

Elevated Liver Enzymes in the Cat Elevated Liver Enzymes in Well Dogs Cats are not little dogs – Thumb Rules Grrrr… Reactive Hepatopathy or Liver Disease? • ALKP elevation significantly exceeds GGT 1. Expect ALKP to be high in growing dogs (2x) elevation only in hepatic lipidosis 2. Explore the history & exam for untreated problems • High bile acids in the cat indicate liver disease that might cause reactive hepatopathy  treat nearly 100% of the time 3. Treat empirically for common things first • Most common causes of ALKP elevation in the cat • Treat subclinical cholangiohepatitis – Cholangiohepatitis, cholangitis – Amoxicillin 10 mg/lb PO BID x 3 weeks – Hyperthyroidism • Supplement to curtail hepatic inflammation – Fatty liver, diabetes mellitus (not hyperadrenocorticism alone) – Denosyl®, Denamarin® – dosage chart in package – (Lymphoma, Pancreatitis) • Now available in chewables (Denosyl®, Denamarin®) – Be careful of SAMe supplements not in foil packages – Milk thistle (Marin®) – Combination antioxidants (VetriScience Cell Advance®)

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Elevated Liver Enzymes in the Well Pet Elevated Liver Enzymes in Well Dogs 4. Recheck Liver enzymes in 30 days Milk Thistle 5. Proceed with further diagnostics for liver • Dried herb: 15-20mg/lb SID (1.5-3% silymarin) disease if still significantly elevated (2-3x), • Standardized Concentrated Extract: 2-5 or trending up mg/lb BID (70-80% silymarin) – Assess liver function with bile acids • Alcohol concentrated extract: 2-5 mg/lb BID- – Abdominal ultrasound and liver/spleen cytology TID (70-80% silymarin) – ACTH stim or Low Dose Dex if signs of Cushing’s 6. If Step 4 reveals no significant problems, Proceed to 3 Tier Liver Diagnostics NOTE: some extracts are whole herb extracts, and – ammonia tolerance test, coag tests these are hard to dose high enough to be – testing for hyperadrenocorticism & infectious dz effective – splenic portagram, thoracic/advanced imaging – liver biopsy, diagnostic surgery

Pattern Recognition Pattern Recognition Canine Liver Enzymes Canine Liver Enzymes • ALT is highest with: • Most common causes of increased ALKP – Acute hepatic necrosis – Hepatobiliary disease – Primary hepatic neoplasia (except lymphoma) – Glucocorticoids (Cushing’s, iatrogenic or stress) – Chronic inflammatory hepatitis – (Barbiturate anticonvulsant therapy) • Cushing’s Disease without elevated liver • Other Causes: enzymes is rare, especially ALKP – Cholestasis causing hepatotoxicity • GGT increases before ALKP in cholestasis – Systemic Causes of increased ALKP • Scotties can have very high liver enzymes • Sepsis, toxemia • Vacuolar Hepatopathy – glycogen or corticosteroid with no identifiable pathology • Systemic inflammation or infection

Pattern Recognition Significant Liver Disease that may Canine Liver Enzymes show Normal ALT & SAP

• GGT in dogs is less sensitive but more specific • End stage liver disease (cirrhosis) than ALKP for biliary disease in dogs • Hepatic Lymphoma ** – If GGT is high, the dog probably has biliary disease – If GGT is normal, the dog still might have biliary dz • Metastatic neoplasia • Albumin and BUN most often low with • Portasystemic shunt (especially if advanced) – chronic inflammatory hepatitis • Feline Cholangiohepatitis – PSS • FIP** – cirrhosis • Feline pancreatitis** • Histoplasma** **Not uncommon to cause icterus without elevated liver enzymes, in cats

6 5/28/2019

Diego Diego 5 yr male Chihuahua – 4.4 lbs Neurologic exam – declines referral to • Problems for 1-2 weeks neurologist • Acting weird - won’t go up and down the stairs, or • Tongue deviates to the right – lower brain stem through doors • CP deficits all 4 – L worse than R – R brain/upper neck • Starts wandering, then falls over with tremors • Seizures, dull mental state – cerebrum • Treated with Tramadol and Rimadyl by another vet • Blind (PLR, eyes normal, + dazzle) – forebrain (cortical – Gets “wired” after tramadol blindness) • Had a generalized seizure yesterday • Open fontanelle – Lasted 45-60 seconds – Several hours before back to normal Lesion Localization - Multifocal CNS Disease • Has always been thin, and a very picky eater Likely not an epileptic – neuro deficits between episodes

Diego Diego DDx – multifocal CNS Disease CBC, panel, lytes – ALT 160 U/L • Large or Metastatic neoplasia UA – SG 1.008 • Rickettsial, fungal, protozoal meningoencephalitis Thoracic rads, abdominal US – NSAF • Granulomatous meningoencephalitis BMBT – 1 min 30 sec • Hepatic encephalopathy Treatment Plan pending bile acids, and cytologies of • CDV, rabies unlikely liver and spleen: • Could be compounded by hydrocephalus • Levetiracetam (Keppra®) 40 mg (0.2cc) PO TID Diagnostic Plan: • Prednisone 2.5 mg PO x 3d, then 1.25 mg PO x 3d, then • CBC, panel, lytes, UA, HW Test 1.25 mg PO QOD x 3 doses, then as directed • Thoracic radiographs, abdominal ultrasound • Doxycycline 20 mg PO BID x 3 weeks • Fasting and post-prandial bile acids • 50cc LRS SC BID Check Bile acids in any small dog with neurologic dz

Diego Diego 3 days later – Recheck: Immediate Treatment Plan: • No seizures • Metronidazole 20 mg PO BID • Trouble seeing only at night – Will eventually transition to neomycin • Improving every day, eating better • Lactulose 1 cc PO TID • Still stumbles some – left side is still weaker – Can gradually increase, to effect for HE – Reduce if stools get too soft • “Personality coming back in little doses” • Continue Keppra® Neuro exam • Diet – L/D • Tongue is straight, more alert • Silymarin 80% (milk thistle) 15 mg PO BID • Little change in CP deficits Referral to Specialist for: Bile Acids – fasting 74, 2 hour post-prandial 177 • Splenic portagram – nuclear scintigraphy • Corrective or Diagnostic surgery, if indicated

7 5/28/2019

Splenic or Rectal Portagram Diego • Splenic is often preferred to rectal portagram Splenic portagram: 1. Radioactive isotope put into the rectum or injected into • Scintigraphy shows mild shunting the spleen • No single extrahepatic vessel visualized on scintigraphy or 2. Put dog on the camera ultrasound 3. See which lights up first – heart or liver • Surgery to explore for single shunt recommended • Liver first = normal – If found, ameroid constrictor will be placed • Heart first = PSS • If no single shunt found, liver biopsy for cause of HE • Big hubbub about whether to neuter him at the same time

Hospitalized for 1-3 days 3 weeks later: • Diego is feeling & eating better than he ever has • Finished with doxycycline, off prednisone • On silymarin, neomycin, lactulose, L/D, and Keppra®

Diego Diego Surgery: At the time of euthanasia: • No shunt found • CBC, panel, lytes normal • Histopath revealed microvascular dysplasia • He was not neutered • 2 weeks prior to euthanasia, Diego was at the deer lease, and grabbed a chocolate chip pancake and Outcome: downed it before they could get it away from him • Eventually weaned off neomycin/lactulose and did very • He had seizures all night, fell into HE and never came well on Keppra®, silymarin & multiple small meals of L/D out of it • Gained one pound in one month • A liver patient’s final episode is often precipitated by a • Bile acids 6 months later 0.9 fasting, 50 post-prandial stressful event • 12 months – episode of HE responded to therapy – Anesthesia • 20 months – HE unresponsive to treatment for 2 weeks – – Dietary indiscretion (high protein) owners elected euthanasia

Diego Portasystemic Shunt Lessons from Diego: • PSS dogs are not always diagnosed prior to 1-2 years of age – single intrahepatic shunts tend to present sooner – The milder the shunt, the older onset of symptoms • Some dogs with severe liver disease can do very well with medical/nutritional therapy for several years • Always check bile acids in small dogs with multifocal neurologic disease, cerebral signs, or seizures – Keep PSS on the differential diagnosis list • Euthanasia in PSS dogs is most often due to refractory Hyperechoic, Small Liver hepatic encephalopathy Hypoechoic spleen

8 5/28/2019

Portasystemic Shunt Pattern Recognition – PSS • Signalment & History Congenital – usually but not always a young dog who has been a poor doer 1. Single extrahepatic in small dogs and intermittently ill with any symptoms of hepatic disease • Yorkie, schnauzer, poodle, dachshund • may not have done well after first surgery • Corrected with ameroid constrictor over 4-5 weeks – Most common symptom in cats with PSS: • Hypersalivation • Other common signs – hepatic encephalopathy, GI upset • CBC – low MCV (Microcytosis) • Serum panel – usually a liver pattern, but could possibly be normal – Advanced PSS more likely to be normal than early PSS – Almost never icteric

Pattern Recognition – PSS Hepatic Microvascular Dysplasia • Urinalysis – ammonium biurate crystals or stones are 33- 50% sensitive for PSS aka HMD • Bile acids aka MVD (microvascular dysplasia) – usually markedly elevated – possible but unlikely to have intermittently normal bile acids aka portal vein hypoplasia • Ammonia – almost always elevated aka microscopic portasystemic shunt • Imaging – small liver + hyperechoic • Portal veins branch normally, but they are hypoplastic – Congenital – fails to receive trophic factors (80%) • Portal venules travel right through the liver, instead of – Acquired – fibrosis and cirrhosis (20%) breaking down to capillaries to be detoxified by the • Splenic Portagram hepatocytes – Extrahepatic and Intrahepatic shunts will show shunting which can be measured • All of the portal venules are dilated, and do small scale – Sometimes single shunts, if large, can be visualized on the scan shunting – Microvascular dysplasia will give variable scan results, but often normal • Yorkshire, Cairn Terriers predisposed

Hepatic Encephalopathy Hepatic Encephalopathy Abnormal mental status in patients with severe Things that can precipitate an HE episode: hepatic insufficiency • Increased protein intake, GI hemorrhage • Dehydration, diuretic therapy • Caused by neurotoxins that bypass a failing liver into • Barbiturates, benzodiazepines and other sedatives systemic circulation and hypoglycemia Do not give diazepam or phenobarbital to HE dogs • Severity of HE does not always correlate with severity Keppra is the anticonvulsant of choice of liver disease • Uremia • Infection, endotoxemia, constipation, increased anaerobes in the colon • Increased methionine intake

9 5/28/2019

Progression of Hepatic Encephalopathy Treatment of Hepatic Encephalopathy • IV fluids 1. Mildest form – anorexia and lethargy • Avoid drugs that exacerbate HE 2. May progress to weight loss, retarded growth, subtle – Benzodiazepines (diazepam, lorazepam, midazolam, etc.) behavior changes, inability to train, loss of training – CNS depressants – opiates, barbiturates, etc. 3. Neurologic abnormalities – Drugs metabolized by the liver – Ataxia • Consider ammonia trapping when significantly low – Confusion, stupor, loss/lack of training albumin, even if no HE – Pacing and wandering – ammonia prevents release of albumin from the – Twitching progressing to seizures hepatocytes 4. Vomiting, diarrhea • Ammonia trapping 5. Severe neurologic problems – Lactulose metabolized by colonic bacteria to lower colon – **Temporary blindness** pH + – Dementia, seizures, coma – Ammonia (NH3) is converted to ammonium (NH4 ) + – Multifocal deficits on neurologic exam – NH4 is less lipid soluble and trapped in the colon

Treatment of Hepatic Encephalopathy Treatment of Hepatic Encephalopathy • Cleansing enemas to decrease bacterial numbers • Lactulose also an osmotic cathartic – Moves bacteria that make ammonia out of the colon – Moves bacteria that make ammonia out of the colon – Warm soapy water 20-25 ml/kg up to q2hrs – 0.5 ml/kg PO TID (up to q 2-4 hrs in HE crisis) – Can add low dose Gentocin® to kill urease producing – Titrate up until stools soft bacteria (0.45 mg/lb daily) – Give as a retention enema if stupor prevents PO meds • Retention enema after the cleansing enema • Food Fast until crisis resolves • Anticonvulsants only if severe generalized seizures – Avoid proteins if feeding L/D precipitates HE – Often needed only for managing the crisis • Oral antibiotics – Keppra® first choice 20-60mg/kg IV, PO TID – Anaerobes and gram negatives (gut flora) make ammonia – Then zonisamide 5-10 mg/kg PO BID – Metronidazole 3-5 mg/lb BID-TID – Bromide likely won’t act fast enough to help, but can be used for long term control if Keppra® and zonisamide are not – Neomycin 9 mg/lb PO TID (not absorbed systemically) possible – Beta lactam if gram negative spectrum needed – Phenobarbital should be avoided due to hepatotoxicity – Add quinolone if severe HE • Eat L/D long term

Bile Acids Bile Acids • Things that decrease bile acids: 1. 12 hour fast – red top tube – Severe disease or resection of the ileum 2. Feed 1-2 Tablespoons a/d (not low fat – need – Prolonged anorexia gallbladder contraction) – Delayed gastric emptying and intestinal hypomotility 3. 2 hour post prandial red top tube (delayed delivery to the ileum) – Intestinal malabsorption Overfeeding can induce HE • Ursodiol increases bile acids • If not fasted, doing only the post-prandial can • Gallbladder removal makes bile acid assays inaccurate be a screen for liver insufficiency • “Backwards” bile acids (post-prandial higher) due to • Can’t run bile acids on a lipemic sample blocked enterohepatic circulation or dysbiosis • Don’t bother checking bile acids in an icteric animal – they are high

10 5/28/2019

Urine Bile Acid:Creatinine Ratio (UBAC) Protein C • Better than a single bile acid value, if you can’t • Plasma anticoagulant works at endothelial cell surface keep the patient for 2 hours, or can’t make a • Vitamin K dependent fractious animal eat – drops prior to PT, PTT with anticoagulant rodenticides • Treatment with ursodiol does not interfere • Low value identifies hypercoagulable state – Indicates need for Plavix® in chronic liver patients • Hematuria and hemoglobinuria my interfere • May help distinguish PSS from MVD – <70% for PSS – >70% for MVD • Rise in Protein C after shunt surgery can mean hepatic flow was re-established • Low in dogs with aflatoxin poisoning • Cornell – Do Not Confuse with C Reactive Protein

Pockets Pockets 12 year old F Yorkie: CBC, panel, lytes, UA - NSAF CC - GI upset while out of town HWTest, fecal, vaccines current • Bloodwork showed elevated liver Thoracic Rads: NSAF enzymes – owners wants work-up Abdominal US: • Regular vet said she was too small to spay • A+++ owner

Exam: 3lbs 11 ounces (ideal 5 lbs), BCS 3.5/5 • Has always been a very picky eater • 3 mammary nodules all < 2cm, mammary hyperplasia • Immature cataracts OU • G3 dental disease

Pockets Pockets CBC, panel, lytes, UA - NSAF CBC, panel, lytes, UA - NSAF HWTest, fecal, vaccines current HWTest, fecal, vaccines current

Thoracic Rads: NSAF Thoracic Rads: NSAF Abdominal US: Abdominal US: hyperechoic liver, liver mottled in echotexture, mild sludge in gall bladder

Bile Acids: Fasting normal, post prandial 55 Liver Cytology: Mild suppurative cholangiohepatitis, with cholestasis. No etiologic agents seen. None of the hepatocytes show the atypia associated with neoplasia. Mammary Mass Cytology: mammary cells with mild Right kidney atypia Inguinal Lymph node Cytology: reactive lymph node

11 5/28/2019

Pockets Pockets Tx 4 week recheck: • Denamarin® daily • Feeling better than she has in years • Metronidazole 20mg PO BID • Appetite has improved x 4 weeks • Gained 0.5 pounds 2 weeks - OHE, remove MGT, liver biopsy, then dental • Owner notes Denamarin® pills whole in the feces Liver histopath: moderate portal fibrosis, mild hepatic • Bile acids – fasting normal, 2 hour post prandial 62 vacuolar degeneration with cholestasis. Copper stains • Change to Denamarin® chewable subjectively normal – no quantitation indicated. COMMENT: The lesions are mild. Moderate fibrosis is • ursodiol 15 mg PO BID observed particularly in one portal area. Minimal numbers Refer for splenic portagram – no shunt of inflammatory cells are observed within portal areas. My interpretation: chronic inflammatory hepatitis MGT histopath: mixed mammary tumors, completely excised

Pockets Pockets 60 days later: 6 months later (regular vet): • Serum panel still normal • Doing very well • Bile acids – normal • Weaned off of liver meds • Mammary gland hyperplasia has resolved • CBC, panel, lytes - NSAF • Another mammary tumor <1cm • bile acids – post prandial >100 • 3 views thorax rads – NSAF Tx (regular vet) • Lymph node cytology - NSAF • Denamarin® chewable, Metronidazole again MGT removed Recheck 3 weeks: • histopath – mammary adenocarcinoma, completely • bile acids – fasting 105, post prandial 180 excised • Referred back to me for re-evaluation

Pockets Pockets • Now PU-PD with stranguria • Clavamox made her vomit • UA – USG 1.005 unmercifully • Urine culture – Staph • cephalexin 50 mg PO BID x 2 weeks • Thoracic rads – NSAF Recheck 1 week after stopping antibiotics • Abdominal US – liver mottled in echotexture, no sludge in gall gladder, kidneys and bladder NSAF • PU-PD and stranguria resolved • Liver cytology – suppurative cholangiohepatitis • UA – USG 1.020, sediment quiet • Inguinal LN cytology - NSAF • Urine culture – Klebsiella spp • NSAID panel - NSAF Tx • Clavamox 31mg PO BID x 2 weeks Tx - • Continue Denamarin® chewable for now, re-evaluate • Ampicillin 50 mg PO BID x 4 weeks liver when UTI resolved

12 5/28/2019

Pockets Pockets Recheck 1 week after stopping 60 days later Antibiotics • 30 day urine culture was negative • UA – USG 1.022, sediment quiet • NSAID panel – NSAF • Urine culture – negative • Bile acids - pre 2.1, post 73 • NSAID panel – NSAF • 60 day urine culture – negative • Bile acids - pre 1.6, post 114.1 Tx - Tx - • milk thistle and ursodiol, probably forever • milk thistle 50 mg PO BID, ursodiol 15mg PO BID • Start L/D diet • Recheck urine culture in 30 days, 60 days after that, • Recheck urine culture in 90 days and then twice yearly 90 days after that and then twice yearly • Dental went well, with antibiotics 1 week before and 1 • Yearly dental due (G2) – when bile acids improved week after (amoxicillin > metronidazole) • Extra UA and urine culture 1 week after antibiotics

Pockets Pockets 90 days recheck Rechecks • UA – bacteria (rods) on sediment • Pockets now 14 years old w/ minimal inflammation, USG 1.018 • Many UTIs and dental infections • NSAID panel – NSAF • she is deaf and has nearly mature cataracts • Bile acids - pre 2, post 62 (unchanged) • is overweight at 5 pounds 12 ounces • Abd US - unchanged • Liver enzymes, albumin, bile acids normal to almost normal for the rest of her life Tx - Continue milk thistle, ursodiol, L/D • Cleaned her teeth 3 times a year, with amoxicillin • Start serial urine culture recheck schedule again Developed CRF at 15 years of age • 1 week, 30 days, 60 days, 90 days, semi-annual Euthanized due to metastatic nasal melanoma at 16 • Start over at any positive culture • Died with almost no teeth in her head • Increase antibiotic therapy to 6-8 weeks if needed • Start bedtime antibiotics or midTx culture if stubborn

DDx Chronic Inflammatory Liver Dz Lessons from Pockets the disease formerly known as • Never underestimate the Chronic Active Hepatitis importance of controlling bacterial infections in chronic Infectious Canine Hepatitis (CAV2) liver patients Leptospirosis • Bacterial infection can cause decompensation Chronic GI Disease (Leaky Gut) • Always assume UTIs in chronic liver disease patients Autoimmune Disease are complicated, and can be silent • Never underestimate the importance of serial follow-up In many cases, etiology can not be determined, urine cultures in resolving complicated urinary tract and does not affect treatment choices infections, and dental antibiotics for liver patients Early detection and treatment are essential, • Early intervention can prevent cirrhosis to prevent cirrhosis • Significant liver disease can be present in the face of normal liver enzymes

13 5/28/2019

DDx Chronic Inflammatory Liver Dz Chronic Inflammatory Liver Dz the disease formerly known as Histopathology Chronic Active Hepatitis • Inflammation starts at the portal triads • Then extends to the hepatic lobule Copper Storage Disease • Eventual necrosis and bridging fibrosis between Fungal Hepatitis adjacent portal areas • Histoplasma, Blastomyces, Coccidiodes • Then nodular hyperplasia • Then cirrhosis Parasitic/Protozoal Hepatitis Other frequent characteristics: Heterobilharzia, Platynosomum, Pisthorcis, Amphimerus, • Inflammation predominantly mononuclear – prednisone Metorchis, Clonorchis, Capillaria • Suppurative inflammation suggests bacteria Many rickettsial and protozoon disease • Bile duct hyperplasia (reduplication) and cholestasis Determining etiology is important to treating – Treat with ursodiol these causes • Secondary copper accumulation can accelerate disease

Antibiotics for Liver Dz without HE Tx Chronic Inflammatory Liver Dz Dogs with chronic inflammatory liver disease are Antioxidants - Very important part of therapy, as free radical prone to bacterial hepatitis and sepsis (chicken/egg) positive feedback is a problem with this disease. » Kuppfer cells and hepatic reticuloepithelial – (Vitamin E – 7 U/lb PO BID) system remove pathogens from portal blood – Milk thistle – raises glutathione levels – SAMe – also raises glutathione levels – If septic, start with IV antibiotics for a few days, » Glutathione is depleted in about 50% of canine hepatopathies then SC/IM, then PO when not vomiting » 9 mg/lb PO divided BID – Gut bacteria are the offenders » Absorption is best given on an empty stomach, but less vomiting when given with food » gram negatives and anaerobes » Should not be used if there is hepatic encephalopathy, » Amoxicillin, metronidazole or both x 3 weeks because it contains methionine, which precipitates HE » If severe disease, add a quinilone x 3 weeks – Use antibiotics aggressively in liver patients

Tx Chronic Inflammatory Liver Dz Tx Chronic Inflammatory Liver Dz Ursodiol = ursodeoxycholic acid (Actigall®) Immunosuppression – if cholestasis or sludge in the gall bladder – Studies show mixed results in dogs – Bile acid with anti-inflammatory properties – More effective in cats – Dissolves gall stones at 1mm per month – Prednisolone (rather than prednisone) » Works best if stone < 2cm » Liver converts prednisone to prednisolone – Colorrhetic, for bile sludging » Start at 0.5-1 mg/lb/day for 3-4 weeks » Wean down to 0.2 mg/lb/day – 6-7 mg/lb/day, can divide BID » Then wean to lowest effective dose – Once mucocoele is organized, it is there to stay – Azathioprine (Imuran®) – Trade name $$$ 300mg caps - generic 250mg » 50 mg/m2 PO SID x 2 weeks, then QOD tabs affordable » Then wean to lowest effective dose

14 5/28/2019

Tx Chronic Inflammatory Liver Dz Bacterial Cholangiohepatitis Surgical correction of biliary obstruction if • Acute > chronic – cats present (remove the gallbladder) • Chronic > acute - dogs – Obstructive mucocoele • Leptospirosis (acute, chronic) – dogs – Cholecystoliths • Secondary to GI disease (leaky gut) or other infected – Gall bladder rupture or near rupture from abdominal organs which drain into the portal vein cholecystitis • GI signs, elevated liver enzymes + bile acids

• Ultrasound – thickened gallbladder wall & sludge, mottled liver echotexture

Bacterial Cholangiohepatitis Liver Aspiration Cytology • Acute > chronic – cats • Most helpful for: • Chronic > acute - dogs – Hepatic lipidosis • Leptospirosis (acute, chronic) – dogs – Histoplasma & other fungi, Cytauxzoon & other protozoa – Cholangiohepatitis – inflammation & cholestasis • Secondary to GI disease (leaky gut) or other infected • Can do bacterial culture & sensitivity if bacterial seen (cat) abdominal organs which drain into the portal vein – Some neoplasias • GI signs, elevated liver enzymes + bile acids • Good for histiocytic, aggressive carcinoma, MCT, metastasis • OK for LSA , moderate grade carcinoma • Ultrasound – thickened gallbladder wall & sludge, • Not good for hepatoma, low grade carcinoma, HSA mottled liver echotexture • Least helpful for Fibrosis, PSS • Acute bacterial cholangiohepatitis often associated with abdominal pain in dogs and cats

Liver Aspiration Cytology Liver Aspiration Cytology

fatty liver (steroid vacuolar Hepatopathy) bacterial cholangiohepatitis

normal hepatocytes cytauxzoonosis

histoplasmosis, fatty liver hepatic carcinoma hepatic lymphocytes

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Liver Aspiration Cytology Liver Aspiration Cytology

metastatic sarcoma

Glycogen vacuolar hepatopathy

histiocytic hepatic sarcoma mast cell tumor

hepatic lymphoma

Feline Cholangiohepatitis Feline Cholangiohepatitis Forms: Treatment: • Lymphocytic-plasmacytic – immune mediated • antioxidants • Eosinophilic – immune mediated, parasitic (deworm!) • Antibiotics x 1-3 months or more as needed • Suppurative - bacterial – use C&S to guide as necessary • End stage – biliary cirrhosis (rare) • corticosteroids if indicated by cytology or histopath • Ursodiol if bile sludging or cholestasis Concurrent Problems: • Surgery to correct biliary obstruction/rupture, hepatic • Triaditis – pancreatitis, IBD abscesses or necrotic gall bladder • Bile duct obstructions, cholelithiasis • Tube feeding for prolonged anorexia • Sepsis • Antiemetics as needed

Popcorn Popcorn Treatment for cirrhosis with ascites Popcorn did well for 8 months • Hetastarch 20 ml/kg IV over 30 min • She eventually did not respond as well to • Abdominocentesis to help breathing therapy, and was euthanized • Amoxicillin 40 mg PO BID x 3 wks • She never developed HE • Denamarin according to label dose • We did used lactulose for ammonia • Furosemide 4.125 mg PO BID trapping • Later added spironolactone • Euthanized due to uncontrollable ascites • Colchicine 0.014 mg/lb daily that resulted in dyspnea • If GI side effects, reduce dose by 25% • Gradually change diet to L/D over 5-7 days • Watch for signs of HE and treat • Repeat abdominocentesis and Hetastarch as needed

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Popcorn Max Lessons from Popcorn • 7 year old male Doberman • Patients with chronic liver disease often • Hx - Anorexia, weight loss 1 seem to become ill over a short period month in duration of time • Exam – ascites, splenomegaly • When liver disease progresses to • CBC – PCV 31% cirrhosis, pursuing the original etiology is seldom fruitful • Chemistries or helpful • ALT 789 U/L, ALP 1122 U/L • Long term prognosis of cirrhosis is dismal • Albumin 1.9 g/dl, globulins normal • Short term prognosis (1 year or so) is variable • Cholesterol 85 mg/dl • Some crashing patients continue to crash and die • Glucose 81 mg/dl • Some respond to supportive therapy up to several times • Bile Acids – fasting 88, 2 hour post-prandial – 144 • Urine P:C Ratio – 0.56

Max Max • Tap Abdomen • Tap Abdomen • 12cc whole blood • 12cc whole blood • PCV 30% - aspirated fluid • PCV 30% • Abdominal Ultrasound • Abdominal Ultrasound

Gall bladder

Max Max • Tap Abdomen • Tap Abdomen • 12cc whole blood • 12cc whole blood • PCV 30% • PCV 30% • Abdominal Ultrasound • Abdominal Ultrasound • Free fluid in the abdomen • Free fluid in the abdomen • Large spleen, hypoechoic • Large spleen, hypoechoic • Liver – mixed echogenicity, multiple hyperechoic • Liver – mixed echogenicity, multiple hyperechoic foci 1-2cm, irregular margins foci 1-2cm, irregular margins • Diagnostic Laparotomy • Diagnostic Laparotomy

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Max Lessons from Max • Liver Histopathology • If you get blood tapping the • Chronic inflammatory hepatitis abdomen on the left, consider with fibrosis that you may have hit the spleen • Cirrhotic areas • Especially if it is big – tap on right (HR site) • Spleen Histopathology • Ultrasound guidance or assistance into the fluid • Passive congestion • Liver biopsy on end stage liver can cause • Outcome decompensation • Max suffered hepatic encephalopathy after • Portal hypertension can cause splenomegaly surgery due to passive congestion • Owner elected euthanasia • Nodules in the liver are not always neoplastic • Liver dz can be asymptomatic until end stage

Gall Bladder Sludge Gall Bladder Sludge When is it clinically significant? When is it medically treatable? Gravity dependent (free falling) sludge is likely – Gravity dependent (free falling) insignificant, unless: – amorphous texture (is not yet organized into a mucocoele) – Clinical signs (abdominal pain, GI signs) – Not extensive and not highly organized – Abnormal gall bladder wall – decreases in response to therapy – Abnormal liver enzymes and/or bile acids – Treatable underlying disease – Cholestasis on cytology or histopath » Hyperlipidemia » Hypothyroidism » Cushing’s Disease » Bacterial Cholangiohepatitis » Pancreatitis

Gall Bladder Sludge Gall Bladder Sludge When is it surgically treatable? Treatment: – Sludge organizes into a mucocoele • Amoxicillin 10 mg/lb PO BID x 3 weeks – Symptoms stop responding to therapy in a way • Or based on C&S that is satisfactory to the owner • Actigall® 15 mg/kg PO divided BID – fluid around GB on ultrasound signals impending or recent rupture • Wedgewood Rx has reasonable 250mg quad tabs – Bile peritonitis from GB rupture is a life threatening immediate emergency • Denamarin® (milk thistle, SAMe) » bili in ascites >> serum • Pain meds » Fluid analysis chart • Low fat diet • Treat underlying cause

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Organizing sludge Amorphous unorganized sludge

Organized GB sludge, localized edema – impending rupture

Gall Bladder Aspiration Dottie • The only indication is culture and sensitivity – For chronic bacterial cholangiohepatitis/cholangitis • Easily performed with ultrasound guidance if gall bladder is enlarged • Deep sedation or short general anesthesia is required – To prevent gall bladder rupture – Rupture can happen even if all goes well – Rupture requires emergency surgery repair Gall bladder sludge before treatment with Vetoryl® and – Risky in practices without 24-hour care Ursodiol®

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Steroid Hepatopathy Dottie Pattern Recognition • Hyperechoic hepatomegaly • Normal liver margins • Liver enzymes almost always elevated (ALKP > ALT) • Bile acids rarely elevated, almost never icteric • Albumin normal • Liver FNA – steroid vacuolar hepatopathy • Adrenal US – mass(es) or both enlarged • Hypercoagulable rather than increased bleeding Gall bladder sludge after treatment with Vetoryl® and Ursodiol® • Gallbladder sludge not uncommon • Symptoms often resolve when treated

Poppie Poppie • 6 yr F Miniature Pinscher • 6 yr F Miniature Pinscher • CC: urine has been dark • CC: urine has been dark • Urinalysis: 4+ bilirubin, USG 1.024 • Urinalysis: 4+ bilirubin, USG 1.024 • CBC, panel: ALT 322, SAP 633, bili 1.8 • CBC, panel: ALT 322, SAP 633, bili 1.8 • Abdominal US: • Abdominal US: hyperechoic liver • BMBT: 1 minute 5 seconds • Liver Cytology: mild cholestasis • Tx: amoxicillin x 3 weeks, milk thistle, recheck 30 days

Poppie Poppie Recheck 2 weeks: urine Recheck 2 weeks: urine cleared up, now dark again cleared up, now dark again • Appetite has been a little off • Appetite has been a little off • Mild icterus noted on exam • Mild icterus noted on exam CBC, panel: ALT 752, SAP1433, bili 2.1 CBC, panel: ALT 752, SAP1433, bili 2.1 BMBT: 1 minute 10 seconds BMBT: 1 minute 10 seconds Abdominal US: Abdominal US:

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Poppie Lessons from Poppie Recheck: urine seemed to • Never hesitate to repeat clear up, now dark again • Appetite has been a little off the ultrasound, to check • Mild icterus noted on exam for progression of disease CBC, panel: ALT 752, SAP1433, bili 2.1 • Repeat FNA as well, even if no BMBT: 1 minute 10 seconds sonographic change Abdominal US: many nodules 1-30mm, rounded • Recheck as soon as 14-30 days if looking and bumpy liver margins for neoplasia Liver Cytology: histiocytic sarcoma • Poppie’s dam died of the same tumor, at the same age • Litter mate showed a similar sonogram recently

Scooter Scooter • 10 yr old SF Boxer • 10 yr old SF Boxer • CC: anorexia, lethargy • CC: anorexia, lethargy • over 30 days or so • over 30 days or so • Exam: no clinically significant abnormalities • Exam: no clinically significant abnormalities • CBC: mild neutrophilia 15,000/ul • CBC: mild neutrophilia 15,000/ul • Profile: ALT 532, ALP 986 • Profile: ALT 532, ALP 986 • Abdominal Ultrasound • Abdominal Ultrasound

Mottled echotexture liver, hypoechoic liver masses, liver hyperechoic to fat

Mixed echogenicity liver, *huge* gall bladder, hypoechoic Mottled echotexture liver at hepatic vein, liver hyperechoic to fat liver masses, local ascites between liver and right kidney

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Mixed echogenicity liver, hyperechoic liver mass; tail of the Mixed echogenicity liver with cystic lesion at stomach spleen normal echogenicity but enlarged, pleural effusion.

Liver mottled in echotexture; hypoechoic spleen (cranial body) Transverse - Large hepatic mass mixed echogenicity

Lessons from Scooter Scooter • Client declined further diagnostics • FNA of cystic liver tumors • Propensity to bleed • Treatment: • (Carprofen) & Yunnan Pai Yao daily for life • NSAIDs are probably a better choice then • Amoxicillin 500 mg PO BID x 2 weeks prednisone for palliative treatment of unresectable liver carcinomas/other cancers • Outcome: • Presence of metastatic cancer does not • Good response to therapy, returned to normal necessarily mean death will come soon • Scooter had 3 more similar episodes over a one year period of time • Sometimes there is a poor response to palliative therapy & survival is short • Response to therapy was good for all but the last episode, at which time owner elected euthanasia • Sometimes the pets return to good quality of life, and survival is as long as1-2 years

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Detecting Icterus Detecting Icterus

• Bilirubinuria • Icterus on exam – 2.0-3.0 mg/dl • Mild to moderate bilirubinuria can be normal in the – Can be seen at lower bili if cholestasis dog – More delta bilirubin that is not cleared by the kidneys – gets stored in SC/peripheral fat • Never normal in the cat – Cats have higher renal • Most common cause of icterus in the cat threshold for bili than dogs – Feline Cholangiohepatitis (bacterial) – Can be used to monitor • Most common cause of icterus in the dog cholestatic disease at home – canine inflammatory hepatitis (immune mediated)

DDx Icterus DDx Icterus

1. Pre-Hepatic (hemolysis) – RBC destroyed at a high rate, faster than the liver can Hepatic and post-hepatic icterus are difficult process the Hb & conjugate the bili (PCV <20%) to separate 2. Hepatic (hepatocellular disease) – Liver cells cannot conjugate the bili to be excreted by • Bile acids retained by obstruction are the gall bladder hepatotoxic – Happens when <10% of liver function remains • Ultrasound is the best test to determine cause 3. Post-Hepatic (bile duct obstruction) of hepatic and/or post-hepatic icterus – Bile duct obstructed – cannot excrete bili into the duodenum

DDx Hepatic Icterus DDx Hepatic Icterus

• Cats • Dogs – DDx acute hepatic failure 1. Hepatic Lipidosis (30%) – Sepsis – pyometra, prostatitis, GI obstruction, fight wounds, pneumonia, pyelonephritis, etc. 2. Cholangiohepatitis – bacterial, fungal (20%) – Leptospirosis 3. Lymphoma (20%) – Acute hepatic necrosis – idiopathic, toxins, pancreatitis, sepsis, hypoxia/ischemia/trauma – FIP – Toxicity (next slide) – Drug toxicity (methimazole, diazepam) – Exacerbation of chronic liver disease, leaky gut – Sepsis – Viral – infectious canine hepatitis (CAV2) – Protozoal – Cytauxzoon spp – SIRS

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Hepatotoxins Benzer • Acetaminophen • Itraconazole 5 year old male GSD • Aflatoxins • Kava Kava • Anabolic Steroids • Ketoconazole • Benzer was fine yesterday • Anticonvulsants • Mebendazole • Ate his dinner last night – then shared French • Antineoplastics • Mitotane fries from owner’s dinner, fine at bedtime • Arsenicals • Mushrooms (Amanita) • Early this morning, Benzer was weak an • Blue Green Algae • Oxabendazole unable to rise, vomited bile found nearby • Carprofen • Phenols (Lysol®) • Castor Beans (Ricin) • Sago Palm (seeds) • Immediately taken to the vet on call • Diazepam • Sulfonamides • Elevated liver enzymes & HCT, azotemia • Diethylcarbamazine • Thiabendazole • Vomiting and bloody diarrhea today • Griseofulvin • TMPS • No response to IV fluids, ampicillin, • Iron – chronic overdose • Xylitol enrofloxacin today

Benzer Benzer Exam CBC: neutrophils 15,000/ul, • Injected mucous membranes platelets 85,000/ul • T- 103.1F, P – 168, R – panting Panel: ALT 2100, SAP 1753, bili 8.3, TCO2 15 • Bounding pulses, CRT 3 sec, tacky mucous glucose 61, BUN 93, creat 3.0, phos 7.3 membranes Lytes: normal • Laterally recumbent UA: USG 1.012 (after fluid therapy) • Bloody diarrhea on fecal loop Fecal, HW test – negative • Rectal exam – prostate normal size, shape Coags – PT 16 sec (normal 3-7), PTT 21 sec and non-painful (normal 10-17), ACT normal, AT3 70%, FDPs normal

Benzer Benzer Suspected Acute Liver Failure, Diagnostic Plan: pancreatitis or both: • Thoracic x-rays - NSAF ALT 2100, SAP 1753, bili 8.3, • Abd ultrasound – diffusely hypoechoic liver neutrophils 15,000/ul, glucose 61 DDx – sepsis, gall bladder dz, other post-hepatic obstruction

DIC: platelets 85,000/ul, PT 16 sec, PTT 21 sec, AT3 70%

Possible Acute Renal Failure: BUN 73, creat 3.0, phos 7.3, USG 1.012 DDx – blood in gut + dehydration/hypovolemic shock + fluid therapy

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Benzer Benzer Diagnostic Plan: Treatment Plan: • LRS + 5% dextrose + 20 mEq/L KCl • Thoracic x-rays - NSAF 2x maint (calculator, K sliding scale) • Abd ultrasound – diffusely hypoechoic liver • IV ampicillin TID and enrofloxacin SID – Liver cytology - suppurative inflammation, • Heparin 75 U/kg SC TID cholestasis, no bacteria seen after antibiotics • Weigh BID • cPLI –normal Dx – azotemia, acute hepatic necrosis, DIC • Leptospirosis titers – negative • Urine culture - negative The next morning: • Benzer is laterally recumbent and breathing really hard, minimally responsive Dx – azotemia, acute hepatic necrosis, DIC • T 99.9F, P 120, R 80, mm pink and moist, CRT 1-2 sec, pulses normal, stools no longer bloody

Benzer Benzer Diagnostic Plan: Diagnostic Plan: • CBC –neutrophils 22,000/ul22,000/ul, • CBC –neutrophils 22,000/ul22,000/ul, platelets 145,000 platelets 145,000 • Panel/lytes – ALT 987, SAPSAP 1311,1311, bili bili 2323, BUN 43, creat • Panel/lytes – ALT 987, SAPSAP 1311,1311, bili bili 2323, BUN 43, creat

& phos normal, TCO2 99, glucose 153 & phos normal, TCO2 99, glucose 153 Why is Benzer worse when many tests are better? Why is Benzer worse when many tests are better? • The only vital sign not improved is RR • The only vital sign not improved is RR • Bicarbonate therapy may keep him alive over the next day or two while his liver continues to get better over the coming week or two

Benzer Lessons from Benzer Treatment Plan: • Acute hepatic necrosis has a guarded • Discontinue heparin – platelets normal short term prognosis, but an excellent • Continue IV fluids, antibiotics, weigh BID long term prognosis if survived – Reduce dextrose to 2.5% (glucose 153) • Acute hepatic necrosis often has no identifiable cause – Prevent bilirubin uremia (bili 23, BUN 43) • Panting in a severely ill animal can indicate acidosis • Bicarbonate therapy – 25% of base deficit over 20 min – a clue to check acid-base status • Bicarbonate therapy can be a life saving game changer Outcome: in fulminant acidosis • Benzer was sternal within 30 minutes with RR 30, and • DIC can be reversible if the cause can be reversed able to stand that afternoon • Liver failure patients are usually yellow when they go • Walked outside to eliminate the next morning home – urine clears  then serum  then tissues • gradually recovered during a 10 day stay in ICU – Delta bilirubin (conjugated) is not cleared by the kidneys • Died 5 years later of complications from megaesophagus – Values improve in this order – ALT  SAP  bilirubin

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DDx Post-Hepatic Icterus DDx Post-Hepatic Icterus

Most common: Less common causes of post-hepatic icterus 1. Pancreatitis (15%) - #1 • Pancreatic abscess, neoplasia or granuloma 2. Gall bladder mucocoele, cholecystitis – dogs #2 • Liver, Bile Duct, Duodenal Abscess or Granuloma, severe IBD 3. Neoplasia (10%) – liver, bile duct, pancreas, • Cholelithiasis or inspissated bile plugs duodenum – cats #2 • Duodenal foreign body • parasite migration, pancreatic or liver flukes

Icterus Work-Up Icterus Thumb Rules

1. MDB - CBC, panel • Danger value for bili >20 mg/dl for dogs (cats unknown) – Anemia, icterus  pursue hemolysis – kernicterus brain toxicity, renal toxicity) • <20% in the cat, <25% in the dog • Steroid hepatopathy and PSS patients are almost never icteric – No anemia – pursue liver dz, bile obstruction • Slight elevations in bili are rarely clinically significant – Remember that icteric cats can have ACID (non- regenerative – need a retic count to be sure) • Lipemia & hemolysis falsely elevate bili • Measurement of direct (conjugated) and indirect 2. Imaging - Abdominal rads & ultrasound – liver, pancreas (unconjugated) fractions is not useful because hemolytic, 3. Sample the liver + bile hepatic an biliary tract diseases have unpredictable – Cytology, histopathology, culture/sensitivity variation in each fraction 4. Syndrome specific diagnostics

What Can You Do for the Bleeding Treatment of Icterus Liver Patient? • IV fluid therapy • Fresh whole blood or plasma • Supportive treatment for underlying hepatic and post- • Heparinized plasma if DIC?? hepatic disease • Protect kidneys & brain from bilirubin toxicity • Vit K 5 mg/kg the first day and then 2.5 • Exposure to UV light reduces bilirubin by as much mg/kg/day, especially if cholestasis as 50% per hour • Heparin 75 U/kg SC TID if DIC • treat underlying cause • Treat GI ulceration (see vomiting section) • Hemolysis • Don’t do surgery or liver aspirates until • Hepatic/post-hepatic disease controlled • Treat the liver problem before it is too late

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Why Liver Patients Crash Hepatic Lipidosis • Something precipitates HE A significant problem for cats rather than dogs • Sepsis due to overwhelmed RE system • Overwhelming toxicity of hepatic necrosis, hepatic abscess Etiologies rupture or gall bladder rupture • Starvation or anorexia • Pulmonary edema due to low oncotic pressure • Predispositions: • Albumin <1.0 in most or <1.5 if CHF • Carnitine deficiency • Bleeding • Obesity • SIRS (Systemic Inflammatory Response Syndrome) • Diabetes mellitus • Cholangiohepatitis – bacterial endotoxins • Hypoxic injury • Triaditis – especially pancreatitis

Hepatic Lipidosis Hepatic Lipidosis Diagnosis Diagnosis • Usually anorectic, unless recovering • Usually anorectic, unless recovering • Often Icteric or at least bilirubinuric • Often Icteric or at least bilirubinuric • Hepatomegaly on abdominal palpation • Hepatomegaly on abdominal palpation • Liver aspiration cytology often diagnostic • Liver aspiration cytology often diagnostic • Liver enzymes • Liver enzymes • ALT, SAP, GGT often all elevated • ALT, SAP, GGT often all elevated • Only in hepatic lipidosis does ALKP elevation • Only in hepatic lipidosis does SAP elevation significantly exceed GGT elevation. significantly exceed GGT elevation. • Ultrasound • Ultrasound • Large, hyperechoic liver relative to fat • Large, hyperechoic liver relative to fat

Hepatic Lipidosis Summary Treatment – feed the cat PowerPoints - .pptx, .pdfs – 1 and 6 slides per page • Appetite stimulants – cyproheptadine, mirtazapine, low dose propofol (0.5 mg/kg IV) Vet Handouts • Usually requires a feeding tube • Blount - Bicarbonate administration • High protein, low carb diet • Blount - Fluid analysis diagnostic chart • Add carnitine, use antiemetics • Blount - IV potassium supplementation • Short term prognosis guarded • Blount – Adrenal Testing • Blount – Liver FNA • Long term prognosis can be excellent, if • Idexx – SNAP Bile Acids survives and no co-morbidities • If feeding precipitates hepatic encephalopathy, Articles – Liver Cytology prognosis is poor

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Summary Summary

Vet Handouts Client Handouts Excel Calculators • Willard – Algorithm for Increased ALT • Cholangiohepatitis • IV Fluid Rate Calculator • Willard – Algorithm for increased ALKP • Chronic Liver Disease • Percent Calories • Willard – Algorithm for increased Bili • Cytauxzoon Calculator • Willard – Algorithm for abnormal liver size • Fatty Liver • Willard – Algorithm for low albumin • Icterus Cornell Comparative Coag Lab – submission form, blood • Infectious Canine Hepatitis collection guidelines, electronic payment form, sample • Portasystemic Shunt labels, shipping guidelines, test price list, supply form

Summary Summary

Client Drug Handouts Sponsor Materials • Amoxicillin • Leviteracetam • Spironolactone • Denosyl® - Brochure, package insert • Azathioprine • Maropitant • Taurine • Denosyl® Chewable - package insert • Carnitine • Metronidazole • Ursodiol • Denamarin® - brochure, package insert • Colchicine • Milk Thistle • Yunnan Bai Yao • Denamarin® Chewable – package insert • Cyproheptadine • Mirtazapine • Zonisamide • Doxycycline • Neomycin • Furosemide • Phenobarbital • Hetastarch • Prednisone • Lactulose • SAMe

Acknowledgments Acknowledgments

• Dr. Adam Honeckman, ACVIM. “Icteric Cats – More • Stacy Simmonds, DVM, DACVECC than Just Lipidosis.” Mobile Veterinary Diagnostics, • Emergency Animal Hospital of Northwest Austin Orlando, FL. • Michael Connolly, DVM • DeNovo RC, Chapter 5, “Diseases of the Stomach,” in • Connolly Animal Clinic, Nacogdoches TX Todd R Tams Small Animal Gastroenterology, 2nd Edition. • Tam Garland, DVM, PhD, DABVTT • Richter KP, Chapter 9, “Diseases of the Liver and • Toxicology Consultant Hepatobiliary System,” in Todd R Tams Small Animal • Adam Honeckman, DACVIM nd • Gastroenterology, 2 Edition. • Mobile Veterinary Diagnostics, Orlando FL

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Acknowledgments Acknowledgements

Teleah Grand, DVM Animal Care Center at Stonebridge Ranch • Margie Scherck, DABVP, VIN Consultant Radiographs of Gall Bladder Mass • Willard MD and Tvedten H. Small Animal Clinical Connolly Animal Clinic Diagnosis by Laboratory Methods, 5th ed. Chapter 7 – Nacogdoches TX Gastrointestinal, Pancreatic and Hepatic Disorders. Eds Multiple Cases – Pockets, Max, Popcorn Willard MD and Tvedten H. 2014. Eastex Veterinary Clinic Nacogdoches TX Multiple Cases – Teaching Material, Jim Wilson, DVM The Ole Stirrin’ Stick God Bless His Soul Case - Popcorn