Practical Internal Medicine

Practical Internal Medicine
Liver Disease Wendy Blount, DVM Nacogdoches, TX

Elevated Liver Enzymes in the Cat
Cats are not little dogs Cats with persistently elevated enzymes should be worked up T1/2 of liver enzymes is hours in the cat, not days as in the dog cats have 1/3 the liver SAP compared to dogs Cats with significant cholangiohepatitis can have normal liver enzymes, though that problem often causes very high ALT GGT in cats has higher sensitivity but lower specificity for biliary disease GGT elevation significantly exceeds SAP elevation only in hepatic lipidosis High bile acids in the cat indicate liver disease nearly 100% of the time

Elevated Liver Enzymes in the Cat
Cats are not little dogs Any bilirubinuria in the cat is significant Cat have higher renal threshold for bili than dogs Can be used to monitor cholestatic disease at home DDx for cats with elevated bilirubin and normal liver enzymes (ALT & SAP) FIP, Hepatic lymphoma, Pancreatitis, Histoplasma Most common causes of SAP elevation in the cat Lymphoma Cholangiohepatitis Pancreatitis hyperthyroidism

Elevated Liver Enzymes in the Well Pet
Dogs… Grrrr… Expect SAP to be high in growing dogs Explore the history & exam for untreated problems that might cause reactive hepatopathy Treat empirically for reactive hepatopathy first Treat problems that can insult the liver Treat for subclinical cholangiohepatitis Amoxicillin 10 mg/lb PO BID x 3 weeks supplement to curtail hepatic inflammation Denosyl®, Denamarin® – dosage chart in package Now available in chewables (Denosyl®, Denamarin®) Be careful of SAMe supplements not in foil packages Milk thistle (Marin®) Combination antioxidants (VetriScience Cell Advance®)

Elevated Liver Enzymes in the Well Pet
Recheck Liver enzymes in 30 days Proceed with further diagnostics for liver disease if still significantly elevated (2-3x) Assess liver function with bile acids Abdominal ultrasound and liver cytology ACTH stimulation if signs of Cushing’s Disease If Step 4 reveals no significant problems, consider liver biopsy or referral for splenic portagram to rule out PSS Ultrasound guided liver biopsy (50% diagnostic) Surgical liver biopsy Scotties can have very high liver enzymes with no pathology

Problems Causing Reactive Hepatopathy
Occult infection Urinary tract, metritis, prostatitis, dental Disease Disease of organ drained by portal vein Gut, spleen, pancreas (ultrasound the best test) Hepatotoxicity due to cholestatic disease Hyperthyroidism in cats Severe muscle disease Hypoxia, passive congestion heart failure, respiratory disease, severe anemia

Pattern Recognition Canine Liver Enzymes
ALT is highest with: Acute hepatic necrosis Primary hepatic neoplasia (except lymphoma) Chronic inflammatory hepatitis Moderate elevation of ALT & SAP with reactive hepatopathy Cushing’s Disease without elevated liver enzymes is rare PSS without elevated bile acids if advanced Bone disease can also cause SAP elevation Neoplasia, osteomyelitis, hyperPTH, growth & healing

Drugs that induce SAP isoenzyme: Glucocorticoids, Phenobarbital, others Drug induced SAP does not necessarily indicate hepatic pathology Assess with bile acids if concerned Phenobarbital can also cause hepatotoxicity GGT increases markedly with corticosteroid enzyme induction Drug induced SAP takes weeks or months to resolve after stopping the drug

GGT increased before SAP in cholestasis GGT in dogs is less sensitive but more specific than SAP for biliary disease If GGT is high, the dog probably has biliary disease Albumin and BUN most often low with chronic inflammatory hepatitis PSS cirrhosis Steroid hepatopathy causes mild if any increase in bile acids

Significant Liver Disease that may show Normal ALT & SAP
End stage liver disease (cirrhosis) Hepatic Lymphoma Metastatic neoplasia Portasystemic shunt (especially if advanced) FIP Feline Cholangiohepatitis

Diego 5 yr male Chihuahua – 4.4 lbs Problems for 1-2 weeks
Acting weird - won’t go up and down the stairs, or through doors Starts wandering, then falls over with tremors Treated with Tramadol and Rimadyl by another vet Gets “wired” after tramadol Had a generalized seizure yesterday Lasted seconds Several hours before back to normal Has always been thin, and a very picky eater

Diego Neurologic exam – declines referral to neurologist
Tongue deviates to the right – lower brain stem CP deficits all 4 – L worse than R – R brain/upper neck Seizures, dull mental state – cerebrum Blind (PLR, eyes normal, + dazzle) – forebrain (cortical blindness) Open fontanelle Lesion Localization - Multifocal CNS Disease Likely not an epileptic – neuro deficits between episodes

Check Bile acids in any small dog with neurologic dz
Diego DDx – multifocal CNS Disease Large or Metastatic neoplasia Rickettsial, fungal, protozoal meningoencephalitis Granulomatous meningoencephalitis Hepatic encephalopathy CDV, rabies unlikely Could be compounded by hydrocephalus Diagnostic Plan: CBC, panel, lytes, UA, HW Test Thoracic radiographs, abdominal ultrasound Fasting and post-prandial bile acids Check Bile acids in any small dog with neurologic dz

Diego CBC, panel, lytes – ALT 160 U/L UA – SG 1.008
Thoracic rads, abdominal US – NSAF BMBT – 1 min 30 sec Treatment Plan pending bile acids, and cytologies of liver and spleen: Levetiracetam (Keppra®) 40 mg (0.2cc) PO TID Prednisone 2.5 mg PO x 3d, then 1.25 mg PO x 3d, then 1.25 mg PO QOD x 3 doses, then as directed Doxycycline 20 mg PO BID x 3 weeks 50cc LRS SC BID

Diego 3 days later – Recheck: No seizures Trouble seeing only at night
Improving every day, eating better Still stumbles some – left side is still weaker “Personality coming back in little doses” Neuro exam Tongue is straight, more alert Little change in CP deficits Bile Acids – fasting 74, 2 hour post-prandial 177

Diego Immediate Treatment Plan: Metronidazole 20 mg PO BID
Will eventually transition to neomycin Lactulose 1 cc PO TID Can gradually increase, to effect for HE Reduce if stools get too soft Continue Keppra® Diet – L/D Silymarin 80% (milk thistle) 15 mg PO BID Referral to Specialist for: Splenic portagram – nuclear scintigraphy Corrective or Diagnostic surgery, if indicated

Diego Splenic portagram: Scintigraphy shows mild shunting
No single extrahepatic vessel visualized on scintigraphy or ultrasound Surgery to explore for single shunt recommended If found, ameroid constrictor will be placed If no single shunt found, liver biopsy for cause of HE Big hubbub about whether to neuter him at the same time 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 Surgery: No shunt found
Histopath revealed microvascular dysplasia He was not neutered Outcome: Eventually weaned off neomycin/lactulose and did very well on Keppra®, silymarin & multiple small meals of L/D Gained one pound in one month Bile acids 6 months later 0.9 fasting, 50 post-prandial 12 months – episode of HE responded to therapy 20 months – HE unresponsive to treatment for 2 weeks – owners elected euthanasia

Diego At the time of euthanasia: CBC, panel, lytes normal
2 weeks prior to euthanasia, Diego was at the deer lease, and grabbed a chocolate chip pancake and downed it before they could get it away from him He had seizures all night, fell into HE and never came out of it A liver patient’s final episode is often precipitated by a stressful event Anesthesia Dietary indiscretion (high protein)

Diego 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 up to a few years Always check bile acids in small dogs with multifocal neurologic disease, cerebral signs, or seizures Keep PSS on the differential diagnosis list PSS dogs are rarely icteric & can have normal bloodwork Euthanasia in PSS dogs is most often due to refractory hepatic encephalopathy

Bile Acids 12 hour fast – red top tube Feed 1-2 Tablespoons a/d
2 hour post prandial red top tube Overfeeding can induce HE If not fasted, doing only the post-prandial can be a good screen for liver insufficiency Can’t run bile acids on a lipemic sample Don’t bother checking bile acids in an icteric animal – they are high

Bile Acids Bile acids >30-40 umol/L in the dog and >20-30 umol/L in the cat warrant further investigation Idexx SNAP test tells you <12 umol/L; umol/L; >25 umol/L Can tell you if a cat needs more work-up, but is of little use in the dog, other than to rule in really healthy liver function “Backwards” bile acids (post-prandial higher) due to blocked enterohepatic circulation or dysbiosis No need to check in icteric animals – they are high

Ammonia Normal in the dog 20-80 ug/dl Normal in the cat 20-120 ug/dl
Elevated resting ammonia is significant Idexx VetTest/Catalyst does ammonia assays Falsely increased by hemolysis Centrifuge and decant within 30 minutes Run assay within 2 hours Sending to outside lab can be difficult

Ammonia Ammonia Tolerance Test: 12 hour fast – red top tube
NH3Cl capsules 45 mg/lb max dose 3g PO 30 minutes later – red top tube DO NOT GIVE NH3Cl if resting ammonia elevated Can induce HE Increase should be <32% Nearly 100% sensitive for PSS

DDx Chronic Liver Disease
Immune Mediated Cholangiohepatitis Westie, Doberman, Skye terrier, cats Copper Storage Disease Dobermans, Bedlingtons Portasystemic Shunt Congenital or Acquired Extrahepatic – Yorkie, schnauzer, poodle, dachshund Intrahepatic – Doberman, Golden, Lab, Irish Setter, Samoyed, Irish Wolfhound Microvascular Dysplasia Yorkie, Cairn Terrier

DDx Chronic Liver Disease
Bacterial Cholangiohepatitis (cats) Fungal Hepatitis Histoplasma, Blastomyces, Coccidiodes Parasitic Hepatitis Heterobilharzia, Platynosomum, Pisthorcis, Amphimerus, Metorchis, Clonorchis, Capillaria Chronic Liver Disease usually Diagnosed by Liver Biopsy Fine needle aspiration cytology can be helpful in some cases Ultrasound guided biopsy 50% diagnostic The rest need wedge biopsy

Pockets 12 year old F Yorkie:
CC - GI upset while out of town Bloodwork showed elevated liver enzymes – owners wants work-up 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 CBC, panel, lytes, UA - NSAF HWTest, fecal, vaccines current
Thoracic Rads: NSAF Abdominal US:

Pockets CBC, panel, lytes, UA - NSAF HWTest, fecal, vaccines current
Thoracic Rads: NSAF Abdominal US: 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 atypia Inguinal Lymph node Cytology: reactive lymph node

Pockets Tx Denosyl daily Metronidazole 20mg PO BID x 4 weeks
2 weeks - OHE, remove MGT, liver biopsy, then dental Liver histopath: moderate portal fibrosis, mild hepatic vacuolar degeneration with cholestasis. COMMENT: The lesions are mild. Moderate fibrosis is observed particularly in one portal area. Minimal numbers of inflammatory cells are observed within portal areas. My interpretation: chronic inflammatory hepatitis MGT histopath: mixed mammary tumors, completely excised

Pockets 4 week recheck: Refer for splenic portagram – no shunt
Feeling better than she has in years Appetite has improved Gained 0.5 pounds Owner notes Denosyl pills whole in the feces Bile acids – fasting normal, 2 hour post prandial 62 Crush Denosyl just before giving Vitamin E 100 U daily Actigall 15 mg PO BID Refer for splenic portagram – no shunt

Pockets 60 days later: MGT removed Liver enzymes and albumin normal
Bile acids – normal Mammary gland hyperplasia has resolved Another mammary tumor <1cm 3 views thorax rads – NSAF Lymph node cytology - NSAF MGT removed histopath – mammary adenocarcinoma, completely excised

Pockets 6 months later (regular vet): Tx (regular vet) Doing very well
Weaned off of liver meds CBC, panel, lytes - NSAF bile acids – post prandial >100 Tx (regular vet) Denosyl, Vitamin E, Metronidazole again Recheck 3 weeks: bile acids – fasting 105, post prandial 180 Referred to me for re-evaluation

Pockets Tx Now PU-PD with stranguria UA – USG 1.005
Urine culture – Staph Thoracic rads – NSAF Abdominal US – liver mottled in echotexture, no sludge in gall gladder, kidneys and bladder NSAF Liver cytology – suppurative cholangiohepatitis Inguinal LN cytology - NSAF Tx Clavamox 31mg PO BID x 2 weeks Continue vitamin E and Denosyl for now, re-evaluate liver when UTI resolved

Pockets Recheck 1 week after stopping antibiotics Tx -
Clavamox made her vomit unmercifully cephalexin 50 mg PO BID x 2 weeks Recheck 1 week after stopping antibiotics PU-PD and stranguria resolved UA – USG 1.020, sediment quiet Urine culture – Klebsiella NSAID panel - NSAF Tx - Ampicillin 50 mg PO BID x 4 weeks

Pockets Recheck 1 week after stopping Antibiotics Tx -
UA – USG 1.022, sediment quiet Urine culture – negative NSAID panel – NSAF Bile acids - pre 1.6, post 114.1 Tx - milk thistle 50 mg PO BID Recheck urine culture in 30 days, 60 days after that, 90 days after that and then twice yearly Yearly dental due (G2) – when bile acids improved

Pockets 60 days later Tx - 30 day urine culture was negative
NSAID panel – NSAF Bile acids - pre 2.1, post 73 60 day urine culture – negative Tx - milk thistle 50 mg PO BID probably forever Start L/D diet Recheck urine culture in 90 days and then twice yearly Dental went well, with antibiotics 1 week before and 1 week after Extra UA and urine culture 1 week after antibiotics

Pockets 90 days recheck Tx - Continue milk thistle, L/D
UA – bacteria (rods) on sediment w/ minimal inflammation, USG 1.018 NSAID panel – NSAF Bile acids - pre 2, post 62 (unchanged) Abd US - unchanged Tx - Continue milk thistle, L/D Start serial urine culture recheck schedule again 1 week, 30 days, 60 days, 90 days, semi-annual Start over at any positive culture Increase antibiotic therapy to 6-8 weeks if needed Start bedtime antibiotics or midTx culture if stubborn

Pockets Rechecks Tx 1 week culture negative 30 day recheck
Pollakuria has returned NSAID panel – NSAF UA – USG 1.020 Urine culture: Klebsiella resistant to ampicillin Tx Marbofloxacin x 4 weeks Continue milk thistle, L/D Start serial urine culture recheck schedule again Recheck bile acids when UTI controlled

Pockets Rechecks Tx 1 week urine culture – feeling well UA – USG 1.010
NSAID panel – NSAF Urine culture - E coli resistant to Baytril and ampicillin Tx Cephalexin 50 mg PO BID x 6 weeks Continue milk thistle, L/D Start serial urine culture recheck schedule again Recheck bile acids when UTI under control

Pockets Rechecks Tx 1 week urine culture – negative UA – USG 1.035
30 day urine culture – negative UA – USG 1.042 NSAID panel – NSAF Bile acids - normal Tx Continue milk thistle, L/D Continue serial urine culture schedule 60 days, 90 days, semiannually Recheck bile acids semiannually

Pockets Rechecks All serial urine cultures negative
Pockets now 14 years old she is deaf and has nearly mature cataracts is overweight at 5 pounds 12 ounces G3 dental disease Liver enzymes, albumin, bile acids, UA normal Dental goes well Plan: Continue milk thistle, L/D (less) Semiannual rechecks (sooner if problems): CBC Panel, UA, bile acids, urine culture, chest rads, abd US Yearly dental as long as she is well enough

Pockets 6 months later Developed CRF at 15 years of age
All tests normal except bile acids fasting 10.6, post-prandial 35.5 Now is blind and has lens induced uveitis Needs a dental already Has 12 teeth left after this one amoxicillin 50 mg PO BID one week before and one week after dental Developed CRF at 15 years of age Euthanized due to metastatic nasal melanoma at 16

Lessons from Pockets Never underestimate the importance of controlling
bacterial infections in liver chronic liver patients Bacterial infection can cause decompensation Always assume UTIs in chronic liver disease patients are complicated Never underestimate the importance of serial follow-up urine cultures in resolving complicated urinary tract infections Early intervention can prevent cirrhosis

DDx Chronic Inflammatory Liver Dz formerly known as Chronic Active Hepatitis
Infectious Canine Hepatitis (CAV2) Leptospirosis Chronic GI Disease (Leaky Gut) **Copper Storage Disease** Autoimmune Disease In many cases, etiology can not be determined, and does not affect treatment choices Early detection is essential, to prevent cirrhosis

Popcorn 12 yr old SF Yorkie CC: Listless and panting for one week
Belly swelling over 2-3 weeks Decreased activity over 3-4 months PU-PD for more than a year History of collapsing trachea, medially luxating patellas

Popcorn Exam – RR 45-55/min Abdominal fluid wave – ascites
Bruising of the skin over abdomen Generalized muscle wasting Heart & lung sounds normal Difficult to palpate abdomen due to ascites Strong odor to the urine, like UTI Severe periodontal disease Nuclear sclerosis and iris atrophy OU Bilateral medially luxating patellas

Popcorn CBC – mild anemia (HCT 31.6%) Panel
albumin 1.1 g/dl (low) glucose 57.7 mg/dl (low) cholesterol 71.8 mg/dl (low) calcium 6.83 mg/dl (low) Corrected calcium (3.5 – 1.1 = 2.4) = 9.23 normal Lytes and Blood gases – normal UA – USG 1.008, bacteriuria, proteinuria 2+

Popcorn DDx hypoalbuminemia Bile Acids Urine protein:creatinine – 0.1
Liver disease** Protein losing nephropathy (protein losing enteropathy) (vasculitis, 3rd space loss) Bile Acids fasting 66 mmol/L 2 hr post-prandial 57.8 mmol/L Urine protein:creatinine – 0.1 BMBT – 1 minute

Popcorn Radiograph at another vet

Popcorn Radiograph at another vet Abdominal ultrasound
VHS = 9.5 (normal) Gastric axis shifted cranially Small liver Fluid in the abdomen Abdominal ultrasound normal

Popcorn Radiograph at another vet Abdominal ultrasound
VHS = 9.5 (normal) Gastric axis shifted cranially Small liver Fluid in the abdomen Abdominal ultrasound Very small, hyperechoic liver with irregular edges Mottled in echotexture Consistent with cirrhotic liver Anechoic fluid in the abdomen Hyperechoic gall bladder wall and bile duct

Popcorn Fluid analysis - colorless, clear fluid Liver cytology
WBC 980/ul, TP <2.5 g/dl, albumin 1.0 g/dl Pure transudate Pure transudate in the abdomen and not thorax is almost always due to portal hypertension Liver cytology Mild hepatic lipidosis Mild cholestasis Cytology from cirrhotic livers often not helpful Even histopath often not helpful, and patients can decompensate from anesthesia/surgery

Popcorn Treatment Hetastarch 20 ml/kg IV over 30 min
Abdominocentesis to help breathing Amoxicillin 40 mg PO BID x 3 wks Denamarin according to label dose Furosemide mg PO BID Some prefer spironolactone Colchicine mg/lb daily 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

Popcorn Popcorn did well for 8 months
She eventually did not respond as well to therapy, and was euthanized

Popcorn Lessons from Popcorn Patients with chronic liver disease often
seem to become ill over a short period of time When liver disease progresses to cirrhosis, pursuing the original etiology is seldom fruitful or helpful Long term prognosis of cirrhosis is dismal Short term prognosis (1 year or so) is variable Some crashing patients continue to crash and die Some respond to supportive therapy up to several times

Lessons from Pockets Never underestimate the importance of controlling
bacterial infections in liver chronic liver patients Bacterial infection can cause decompensation Always assume UTIs in chronic liver disease patients are complicated Never underestimate the importance of serial follow-up urine cultures in resolving complicated urinary tract infections Early intervention can prevent cirrhosis

Icterus Wendy Blount, DVM PracticalVetMed Seminars

Detecting Icterus Yellow to orange serum/plasma - >1 mg/dl bili
orange urine – renal threshold > 0.6=0.8 mg/dl bili

Detecting Icterus Bilirubinuria
Mild to moderate bilirubinuria can be normal in the dog Never normal in the cat

Detecting Icterus Icteric eyes, mucous membranes and skin
> 2-3 mg/dl

Detecting Icterus Icterus on exam – 2.0-3.0 mg/dl
Can ben seen at lower bili if cholestasis More delta bilirubin that is not cleared by the kidneys Most common cause of icterus in the dog Feline Cholangiohepatitis (bacterial) Most common cause of icterus in the cat canine inflammatory hepatitis (immune mediated)

DDx Icterus Pre-Hepatic (hemolysis) Hepatic (hepatocellular disease)
RBC destroyed at a high rate, faster than the liver can process the Hb & conjugate the bili Hepatic (hepatocellular disease) Liver cells cannot conjugate the bili to be excreted by the gall bladder Happens when <10% of liver function remains Post-Hepatic (bile duct obstruction) Bile duct obstructed – cannot excrete bili into the duodenum

DDx Pre-Hepatic Icterus
Cats Mycoplama haemofelis (fna Hemobartonella spp.) Hypophosphatemia (<1.5 – DKA) Heinz body anemia (feline Hb sensitive to oxidation) IMHA Pyruvate Kinase Deficiency

DDx Pre-Hepatic Icterus
Dogs IMHA

DDx Hepatic Icterus Cats Hepatic Lipidosis (30%)
Cholangiohepatitis – bacterial, fungal (20%) Lymphoma (20%) FIP Drug toxicity (methimazole, diazepam) Sepsis Protozoal – Cytauxzoon spp

DDx Hepatic Icterus Dogs – acute hepatic failure
Sepsis – pyometra, prostatitis, GI obstruction, fight wounds, pneumonia, pyelonephritis, etc. Leptospirosis Acute hepatic necrosis Toxicity Exacerbation of chronic liver disease Viral – infectious canine hepatitis (CAV2) SIRS

Hepatotoxins Acetaminophen Aflatoxins Anabolic Steroids
Anticonvulsants Antineoplastics Arsenicals Blue Green Algae Carprofen Castor Beans (Ricin) Diazepam Diethylcarbamazine Griseofulvin Iron – chronic overdose Itraconazole Kava Kava Ketoconazole Mebendazole Mitotane Mushrooms (Amanita) Oxabendazole Phenols (Lysol®) Sago Palm (seeds) Sulfonamides Thiabendazole TMPS Xylitol

Benzer 5 year old male GSD Benzer was fine yesterday
Ate his dinner last night – then shared French fries from owner’s dinner, fine at bedtime Early this morning, Benzer was weak an unable to rise, vomited bile found nearby Immediately taken to the vet on call Elevated liver enzymes & HCT, azotemia Vomiting and bloody diarrhea today No response to IV fluids, ampicillin, enrofloxacin today

Benzer Exam Injected mucous membranes T- 103.1F, P – 168, R – panting
Bounding pulses, CRT 3 sec, tacky mucous membranes Laterally recumbent Bloody diarrhea on fecal loop Rectal exam – prostate normal size, shape and non-painful

Benzer CBC: neutrophils 15,000/ul, platelets 85,000/ul
Panel: ALT 2100, SAP 1753, bili 8.3, TCO2 15 glucose 61, BUN 93, creat 3.0, phos 7.3 Lytes: normal UA: USG (after fluid therapy) Fecal, HW test – negative Coags – PT 16 sec (normal 3-7), PTT 21 sec (normal 10-17), ACT normal, AT3 70%, FDPs normal

Benzer Suspected Acute Liver Failure, pancreatitis or both:
ALT 2100, SAP 1753, bili 8.3, 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

Benzer Diagnostic Plan: Thoracic x-rays - NSAF
Abd ultrasound – diffusely hypoechoic liver

Abd ultrasound – diffusely hypoechoic liver DDx diffusely hypoechoic liver Cholangiohepatitis Bacterial, toxicity, acute necrosis Passive Congestion CHF, overhydration by IV fluid therapy Neoplasia Lymphoma

Abd ultrasound – diffusely hypoechoic liver Liver cytology - suppurative inflammation, cholestasis, no bacteria seen after antibiotics cPLI – normal Leptospirosis titers – negative Urine culture - negative Dx – azotemia, acute hepatic necrosis, DIC

Benzer Treatment Plan: Dx – azotemia, acute hepatic necrosis, DIC
LRS + 5% dextrose + 20 mEq/L KCl 2x maint (calculator, K sliding scale) IV ampicillin TID and enrofloxacin SID Heparin 75 U/kg SC TID Weigh BID Dx – azotemia, acute hepatic necrosis, DIC The next morning: Benzer is laterally recumbent and breathing really hard, minimally responsive T 99.9F, P 120, R 80, mm pink and moist, CRT 1-2 sec, pulses normal, stools no longer bloody

Benzer Diagnostic Plan:
CBC – neutrophils 22,000/ul, platelets 145,000 Panel/lytes – ALT 987, SAP 1311, bili 23, BUN 43, creat & phos normal, TCO2 9, glucose 153 Why is Benzer worse when many tests are better? The only vital sign not improved is RR neutrophils 22,000/ul SAP 1311, bili 23 TCO2 9

Benzer Diagnostic Plan:
CBC – neutrophils 22,000/ul, platelets 145,000 Panel/lytes – ALT 987, SAP 1311, bili 23, BUN 43, creat & phos normal, TCO2 9, glucose 153 Why is Benzer worse when many tests are better? 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 neutrophils 22,000/ul SAP 1311, bili 23 TCO2 9

Benzer Treatment Plan: Outcome: Discontinue heparin – platelets normal
Continue IV fluids, antibiotics, weigh BID Reduce dextrose to 2.5% (glucose 153) Prevent bilirubin uremia (bili 23, BUN 43) Bicarbonate therapy – 25% of base deficit over 20 min Outcome: Benzer was sternal within 30 minutes with RR 30, and able to stand that afternoon Walked outside to eliminate the next morning gradually recovered during a 10 day stay in ICU Died 5 years later of complications from megaesophagus

Lessons from Benzer Acute hepatic necrosis has a guarded
short term prognosis, but an excellent long term prognosis if survived Acute hepatic necrosis often has no identifiable cause Panting in a severely ill animal can indicate acidosis a clue to check acid-base status Bicarbonate therapy can be a life saving game changer in fulminant acidosis DIC can be reversible if the cause can be reversed Liver failure patients are usually yellow when they go home – urine clears  then serum  then tissues Delta bilirubin (conjugated) is not cleared by the kidneys Values improve in this order – ALT  SAP  bilirubin

DDx Post-Hepatic Icterus
Pancreatitis (15%) Gall bladder mucocoele, cholecystitis - dogs Neoplasia (10%) – liver, bile duct, pancreas, duodenum

DDx Post-Hepatic Icterus
Less common causes of post-hepatic icterus Pancreatic Abscess, or Granuloma Liver, Bile Duct, Duodenal Abscess or Granuloma Cholelithiasis or inspissated bile plugs Duodenal foreign body parasite migration, pancreatic or liver flukes Hepatic and post-hepatic icterus are difficult to separate Bile acids retained by obstruction are hepatotoxic Ultrasound is the best test to determine cause of hepatic or post-hepatic icterus

Icterus Work-Up MDB - CBC, panel Imaging Sample the liver + bile
Anemia, icterus – purse hemolysis <20% in the cat, <25% in the dog No anemia – pursue liver dz, bile obstruction Remember that icteric cats can have ACID Imaging Abdominal rads & ultrasound – liver, pancreas Sample the liver + bile Cytology, histopathology, culture/sensitivity Syndrome specific diagnostics

Abdominal Ultrasound Evidence of ExtraHepatic Bile Duct Obstruction (EHBDO) Common bile duct >4-5mm on ultrasound <4-5mm – consider hepatic causes of icterus Tortuous common bile duct Enlarged pancreas Hepatic parenchyma May or may not be abnormal Hepatic Lipidosis – diffusely hyperechoic Cholangiohepatitis – variable -

Abdominal Ultrasound Liver size and borders Evidence of pancreatitis
Ascites Cranial abdomen, around GB or diffuse Sample – green, high bili relative to serum Other signs of Triaditis Intestinal wall thickness, m:m ratio Complete abdomen is indicated (add US images)

Liver – Cytology vs. Histopath
FNA Cytology Advantages Less invasive – outpatient procedure Usually requires little or no sedation Decreased risk of bleeding Preliminary results may be immediately available Most useful for fatty liver > LSA

FNA Cytology Disadvantages Misses necroinflammatory disease of cholangitis Can miss lymphoma or inflammation which is patchy Not as accurate as histopath Benign is not a cytologic diagnosis Difficult to distinguish lymphocytic cholangiohepatitis from lymphocytic (small cell) lymphoma

FNA Cytology Wang et al 2004, Roth et al 2001, Bigge et al 2001 FNA agreed with histopath – 30-60% of the time Partial agreement 20% of the time Most likely to agree for fatty liver/vacuolar hepatopathy and lymphoma Disagreement 20% of the time Least likely to agree for inflammatory disease and fibrosis Also neoplasia in the dog (Blount)

Complication rate Wang et al 2004, Roth et al 2001, Bigge et al 2001 Major Complication rate for trucut biopsy 6% (bleed) Lower than complication from renal biopsy MCR for FNA probably much lower Complication more likely with: Thrombocytopenia Elevated PT (dogs) Elevated PTT (cats) Did not evaluate BMBT as a predictor

Wedge (Surgical) Biopsy
Indications for surgery Negative MiraVista Histoplasma spp antigen Evidence of EHBDO Focal mass needs resection FNA and TruCut have not successfully managed the case Evidence that biopsies of multiple organs are indicated Thickened gut wall, especially muscularis Suspect but have not confirmed pancreatitis (need biopsy) Other reason for laparotomy – bladder stones, spay, etc.

Cholangiohepatitis Liver ultrasound can be very boring – SAMPLE!!
Marolf et al 2012 (26 cats with cholangitis) Normal GB wall – 91% Normal bile duct size – 70% Normal liver size – 70% Normal GB contents – 62% Normal liver echogenicity - 54% Most frequent US abnormalities Enlarged pancreas – 39% Hyperechoic liver or GB contents (each 38%)

Choleliths May or may not be clinically significant
Look for evidence of mucocoele, obstruction, infection or impending rupture on imaging Correlate to clinical signs Anorexia, vomiting, diarrhea Icterus unexplained by hemolysis or liver disease X-ray (Beau Roberts)

Cats with elevated bili and normal liver nz (ALT & SAP)
DDx - FIP, Hepatic lymphoma, Pancreatitis, Histoplasma Diagnostic Trifecta for FIP Lymphopenia <1500/ul Titer 1:160 or greater Globulins >5.1 g/dl Positive predictive value 89% Negative predictive value 99% Histopath and fluid analysis supportive Fluid analysis chart – pancreatitis section

Icterus PSS and steroid hepatopathy patients are almost never icteric
Slight elevations in bili are rarely clinically significant Lipemia & hemolysis falsely elevate bili

Sebastian 9 year old neutered male pit bull
1 week ago ataxia and falling, and vocalizing every time he moves, after a dog fight 2 year history of relapsing neck pain Tx prednisone, methocarbamol, Tramadol, cage rest - no response for 4 days Sedated for radiographs 4 days ago Cervical & lumbar intervertebral disc calcification vomited large amount of fluid with coffee grounds after sedation Mid abdominal mass on x-rays?

Sebastian Exam Albumin 2.1 g/dl (2.2 g/dl low normal)
SAP 2119 U/L, ALT 1434 U/L, Bili 8.2 mg/dl HCT 30.8% Tx carafate, IV fluids, metronidazole, amoxicillin x 4 days Referred for ultrasound – the best test for assessing hepatic and post-hepatic icterus, and to evaluate possible mass Exam Can not walk - Muscle tremors and very jumpy Abdomen tense and difficult to palpate, very large urinary bladder Sclerae injected and icteric – owner says eyes have been red for 30 days

Sebastian Neuro Exam Unable to walk, unable to assess postural reflexes and CP Cranial nerves normal Spastic paresis in all 4 limbs (UMN reflexes) Conscious motor activity in all 4 limbs Lower cervical pain Dx - Lower cervical spinal cord disease Catheterized bladder and removed 1.5L of orange urine (bilirubin crystals) Hx – has been on clomipramine for some time, for anxiety

Sebastian Problem List Cervical myelopathy and tetraparesis
Surgery not an option for these owners Icterus – likely hepatic and/or post-hepatic but early hemolysis can not be ruled out Hematemesis – prednisone, liver failure, spinal cord injury Twitching – hepatic encephalopathy, metronidazole toxicity, serotonin syndrome Mid abdominal mass – will assess with ultrasound Mild anemia

Sebastian

Sebastian Radiographs Large amount of air in the stomach
Gastric axis shifted cranially Intestines appear distended with fluid Cervical and lumbar spondylosis Cervical and lumbar mineralized disc material Disc material in the cervical spinal foramina Dx – microhepatia Dx – degenerative disc disease

Sebastian Abdominal Ultrasound
Difficult because of the great amount of air in the stomach, due to aerophagia Small areas of the liver seen, hyperechoic, mottled in echotexture Gall bladder not seen Many fluid filled loops of bowel PT, PTT - normal

Sebastian Plan Discontinue prednisone, Tramadol, clomipramine, metronidazole Continue Carafate, IV fluids (LRS + 20 mEq/L KCl), ampicillin IV add milk thistle, famotidine Fast overnight and repeat ultrasound tomorrow Repeat CBC, panel, lytes tomorrow Send out Lepto titers Express bladder or catheterize to empty bladder TID

Sebastian Day 2 Ate chicken and drank water yesterday
Twitching stopped Skin appears less icteric, scleral injection improved HCT 17.7%, Hb 5.6 g/dl Albumin 1.6 g/dl, globulin 2.0 g/dl, Bili 5.4 mg/dl Neutrophilia 20K/ul No vomiting, no melena Urine is golden, not orange Eating chicken and drinking

Sebastian Ultrasound Liver small, mottled, hyperechoic
Liver cytology – suppurative hepatitis with cholestasis Gall bladder wall thickened - cholecystitis No fluid in the abdominal cavity

Sebastian Ultrasound Plan – add Baytril® & Vitamin K, monitor PCV
Liver small, mottled, hyperechoic Liver cytology – suppurative hepatitis with cholestasis Gall bladder wall thickened - cholecystitis No fluid in the abdominal cavity Plan – add Baytril® & Vitamin K, monitor PCV

Sebastian Day 3 Vomited overnight – chicken, melena on thermometer
HCT 14.9%, Hb 4.6% neutrophils 21.7K/ul Albumin 1.5 g/dl, globulins 1.9 g/dl Lytes normal Plan Whole blood transfusion Ate chicken & rice well that night, drinking water

Sebastian Day 4 Not feeling well, passed melena, fever 103.4F
Will not eat, licked lips when food offered Abdominal US – still no evidence of perforation, but deep ulcer seen in the duodenum PCV 25%, albumin 1.8 g/dl, lytes normal

Sebastian Day 5 Fever has resolved, feels better
Eating chicken, but not rice Urinating on own, but does not empty the bladder Can support weight on rear legs but not front legs If ulcer perforates, owners will not do surgery PCV 20%, albumin 1.8 g/dl

Sebastian Day 6 Will not eat, no fever
When put on feet, attempts to move forward, but can not move front legs well yet, can take a few steps Urinating on own neutrophils 75K, monocytes 1,100/ul No stools passed, but melena on thermometer Ultrasound

Sebastian Day 6 Will not eat, no fever
When put on feet, attempts to move forward, but can not move front legs well yet, can take a few steps Urinating on own neutrophils 75K, monocytes 1,100/ul, 6% bands No stools passed, but melena on thermometer Ultrasound Local peritonitis R Cranial abdomen

Sebastian Plan Drained fluid percutaneously
Discontinue catheterization Continue milk thistle, ampicillin, enrofloxacin, carafate, famotidine, Vit K, IV fluids Wrap front feet to prevent abrasions from knuckling

Sebastian Day 7 neutrophils 38K, monocytes normal, 3% bands HCT 20%
Albumin 1.6 g/dl, glob 5.3 g/dl SAP >4600 U/L, ALT 1868, bili 6.7 mg/dl Black tarry liquid stools Plan Barium 5ml/lb PO

Sebastian

Sebastian Day 8 Over the next 2 weeks
Owners came to visit – Sebastian ate a rib eye Can walk 5-10 feet without assistance Over the next 2 weeks Switched form injectable to oral meds Recovered well Recurrence of liver failure 1 year later Owners elected euthanasia

Lessons from “Pooper” Tramadol + some behavioral meds (SSRIs) can = serotonin syndrome (tremors) Dog with severe liver disease tend are predisposed to steroid GI side effects Barium is probably the best GI ulcer protectant on the planet Recovery from acute episodes of chronic liver disease can be very unpredictable Severe chronic inflammatory liver disease often ends in an acute liver failure episode Sedation can decompensate liver patients Pay attention to gastric axis on abdominal x-rays

Liver and Coag Tests Factors must be 30% of normal to elevate PT & PTT
AT3, albumin also low PIVKA more sensitive test for low Vit K than PT/PTT DIC dec platelets, AT3**, fibrinogen** inc FDP**, d-dimers, PT/PTT > ACT **AT3/fibrinogen made by the liver, FDP cleared by the liver **surgery can deplete fibrinogen Increased BMBT even if not DIC Factor deficiency low Vit K platelet dysfunction

Acknowledgments Dr. Adam Honeckman, ACVIM. “Icteric Cats – More than Just Lipidosis.” Mobile Veterinary Diagnostics, Orlando, FL.

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