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CHOLANGIOHEPATITIS IN A TENNESSEE WALKING HORSE GELDING CHOLANGIOHEPATITIS IN A TENNESSEE WALKING HORSE GELDING

CHOLANGIOHEPATITIS IN A TENNESSEE WALKING HORSE GELDING - PowerPoint Presentation

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CHOLANGIOHEPATITIS IN A TENNESSEE WALKING HORSE GELDING - PPT Presentation

Becky Urion PO Box 1188 Crystal Beach FL 34681 727 4300060 Mentors Johanna Elfenbein DVM DACVIM Sarah Reuss VMD DACVIM University of Florida Veterinary Medical Center Gainesville Florida ID: 935326

amp liver equine normal liver amp normal equine diagnostic plan vet biopsy bile hepatic clinical additional referring performed durham

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Slide1

CHOLANGIOHEPATITIS IN A TENNESSEE WALKING HORSE GELDING

Becky UrionPO Box 1188Crystal Beach, FL 34681(727) 430-0060Mentors: Johanna Elfenbein, DVM, DACVIM; Sarah Reuss, VMD, DACVIMUniversity of Florida Veterinary Medical CenterGainesville, Florida

Slide2

SIGNALMENT & HISTORY

15 year old Tennessee Walking Horse gelding Trail horse living in central FloridaHistory of fever and anorexia in July 2010Evaluated by referring veterinarianSerum chemistry & Lyme titer performed at the timeTreated with month-long course of doxycyclineParameterResultNormal ValueTotal Protein

8.2 (H)5.7-8.0 g/dL

Globulins

5.2 (

H

)2.7-5.0 g/dLGGT71 (H)5-24 u/LIFA Titer12800 (H)>200 strongly suggestiveK-ELISA280>380 positive

Lyme’s disease suspected based on high titer

Clinical signs resolved with therapy

Slide3

RECENT HISTORY

Presented to referring veterinarian again for fever and anorexia of one week’s duration in March 2011Fever non-responsive to several oral doses of flunixin meglumine

On day of presentation:Owner noted passage of chocolate-colored urine

Bloodwork

performed by referring veterinarian

Referred to UF CVM for further diagnostics

Slide4

RECENT HISTORY

Biochemistry - performed by referring veterinarian on day of presentationParameterResultNormal ValueParameterResultNormal Value

Na+134126-146 mmol/L

AST

481 (

H

)175-340 U/LK+3.52.5-5.2 mmol/LT Bili10.4 (H)0.5-2.3 mg/dLTCO22720-33 mmol/LGGT

201 (H)5-24 u/LCPK

76120-470 u/LAlbumin3.42.2-3.7

g/

dL

Glucose

118

65-110 mg/

dL

T

Protein

7.7

5.7-8.0 g/dLCa+13.411.5-14.2 mg/dLHemolysis00BUN97-25 mg/dLLipemia00Creatinine1.00.6-2.2 mg/dLIcterus2+ (H)0

Slide5

RECENT HISTORY

Hematology - performed by referring veterinarian on day of presentationParameterResultNormal ValueParameterResult

Normal ValueWBC11.65.5-12.5

HGB

14.2

11-19 g/

dLLymphocyte %10.6HCT35.832-52%Monocyte %0.8MCV5436-52 flGranulocyte %88.6

MCH21.312.3-19.7 pgLymphocytes

1.2 1.8-5MCHC39.5

34-39 g/

dL

Monocytes

0

0.2-0.8

RDW

15.3

17-21%

Granulocytes

10.4 (H)3-7PLT278100-600RBC6.656.5-12.5MPV5.14-6 flFibrinogen600 (H)100-400 g/dLPCV38.535-45%

Slide6

CLINICAL FINDINGS

Bright, alert, responsiveBody condition score: 5/9Oral mucous membranes pink with yellow tingePale yellow scleraTemperature: 103.8 °F Pulse: 48 beats per minuteRespiratory rate: 36 breaths per minuteInappetance with no overt colic behavior and normal gastrointestinal borborygmi 500 mg of flunixin meglumine given intravenously

Slide7

DIAGNOSTIC PLAN

Urinalysis Additional bloodworkSDH Bile acids AmmoniaPT, PTTRebreathing examinationThoracic & abdominal ultrasound Liver biopsy

Fever likely hepatic in origin but additional diagnostics pursued in order to rule out extra-hepatic causes, e.g. peritonitis, pneumonia, neoplasia, abscesses

Slide8

LABORATORY FINDINGS

Urine Dipstick (free catch sample)ParameterResultpH8.5Urine Specific Gravity1.012

GlucoseNegativeBilirubin+++ LargeBlood

Negative

Protein*

+ (30 mg/

dL)UrobilinogenNormal (0.2 mg/dL)*Proteinuria considered spurious due to alkalinity of urine

Slide9

DIAGNOSTIC PLAN

Additional Laboratory TestingCytosolic enzyme with short half-life, making it ideal for evaluating ongoing disease; increased value indicates hepatocellular damageIncreased levels indicate decreased hepatic function and resulting inability of liver to clear ammonia from blood and convert to blood urea nitrogenMeasure of hepatic function; increased value indicates bile acids ineffectively cleared from blood by liver; may be due to failure of uptake, conjugation, or excretion, or regurgitation due to biliary obstruction

SDH

14.3

(

H

)Normal = 0-6 IU/LAmmonia30 Normal = 3-40 uMol/LBile Acids95.7 (H

)Normal = 0-6 uMol/L

Slide10

DIAGNOSTIC PLAN

Additional Laboratory TestingTests of extrinsic and intrinsic pathways of clotting cascade, respectivelyPerformed prior to biopsy to ensure adequate clotting abilityMildly prolonged PT was considered clinically insignificant as it represented <20% increase above normal reference range

ParameterResult

Normal Value

PT

13.7 seconds (

H)8.5-11.7 secondsPTT 51.2 seconds37.7-52.4 secondsRebreathing Exam & Thoracic UltrasoundPerformed to rule out non-hepatic causes of fever, e.g. pneumonia, neoplasia, abscessesBoth exams unremarkable

Slide11

DIAGNOSTIC PLAN

Trans-Abdominal UltrasoundEvaluation of liver shape, size, position, textureIdentification of abscesses, cysts, neoplastic masses, dilated bile ducts, choleliths, fibrosis, peritonitisLiver seen on right side, caudoventral to lung in 8th-14th intercostal spaces; can also be seen on left cranioventral abdomenAllows for biopsy instrument guidance

Liver edges roundedLikely indicates some degree of liver disease and fibrosisParenchymal pattern difficult to assess due to large abdominal fat storesNo evidence of biliary tree

distension,

choleliths

Does not entirely rule out presence

No other abnormalities noted

Slide12

PROBLEM LIST

Fever*Increased serum GGT, AST, SDH*Increased serum bile acids*Icterus, hyperbilirubinemia, bilirubinuria*Rounded liver edges*Hyperfibrinogenemia & neutrophilia

*InappetanceTachycardia *Denotes most significant problems

Slide13

DIFFERENTIAL DIAGNOSES

FeverInfectionInflammationNeoplasiaIncreased liver enzymes & bile acidsChronic active hepatitisHepatic abscessationPyrrolizidine alkaloid toxicityAflatoxicosis

CholangiohepatitisCholelithiasisSerum-associated hepatitisNeoplasia

Hemochromatosis

Icterus,

Bilirubinemia

& BilirubinuriaPre-HepaticAnorexiaHemolysisHepaticCholangiohepatitisPyrrolidizine alkaloid toxicityHepatic abscessationStreptococcus spp.,

Corynebacterium pseudotuberculosisSerum-associated hepatitisAcute or chronic hepatitis

NeoplasiaPost-HepaticCholelithiasisAnterior enteritis

Slide14

DIAGNOSTIC PLAN

Percutaneous Liver Biopsy – infectious or inflammatory process involving liver considered most likely

Performed to determine diagnosis & prognosis

(Durham 2003; Equine Vet J.;35:534-40)

Diffuse or zonal lesions (e.g. most

toxic, infectious, metabolic liver diseases) can usually be diagnosed by biopsyFocal lesions (e.g. abscesses, granulomas, neoplasias) easily missedBleeding is major complication; occurs in 13% of cases but is mostly subclinical (Johns 2008; J Vet Intern Med.;22:185-189)

Slide15

DIAGNOSTIC PLAN

Performed in right 9-14th ICS at intersection of line drawn from tuber coxae to mid-humerusSite aseptically prepared, anesthetized with lidocaineStab incision made with #15 blade before placement of 14-gauge Tru-cut biopsy instrumentUltrasound guidance usedAt least 4 samples takenOne for aerobic & anaerobic culturesRemainder fixed in formalin for histopathology

Percutaneous Liver Biopsy

Slide16

DIAGNOSTIC PLAN

Percutaneous Liver BiopsyHISTOPATHOLOGIC ANALYSISSuppurative cholangiohepatitis, multifocal, marked, with marked portal abscessation, chronicPortal fibrosis, biliary proliferation, periportal hepatocyte loss, multifocal, severe, chronicNodular hepatocellular regeneration, multifocal, marked, chronic

Gross samples greenish in color

Consistent with biliary stasis

Aerobic and anaerobic culture

No growth on either plate at 48 hours

Approximately 50% of bacterial

cholangiohepatitis

cultures yield no results

Normal hepatocytes

Inflammation

Fibrosis

H&E 20x; Photo courtesy of Dr. William Craft

Slide17

DIAGNOSIS

Common CausesPrimarySecondaryCholelithiasis or biliary stasisChronic active hepatitisDuodenal inflammationIntestinal obstructionNeoplasiaParasitismCertain toxinsOften ascending bacterial infectionCommon Clinical FindingsAnorexiaPyrexia

IcterusIntermittent signs of colicHyperammonemic hepatic encephalopathy possibleDiagnosis

S

upported By

Elevated

cholestatic & hepatocellular enzymes HyperbilirubinemiaInflammatory leukogramHyperfibrinogenemiaPRESUMPTIVE BACTERIAL CHOLANGIOHEPATITIS

Slide18

THERAPEUTIC PLAN

Enteric organisms commonSalmonella speciesEscherichia coliCitrobacterKlebsiellaAeromonasAcinetobacterCommonly used antibioticsTrimethoprim-sulfonamideCeftiofurEnrofloxacin

Penicillin and gentamicinAmpicillinChloramphenicol

*

Usually 4-6 weeks of antimicrobial therapy required based on culture & sensitivity results

Started one month course of chloramphenicol

(50 mg/kg TID)Empirical choice based on lack of positive cultureExcreted in bile ductsBroad spectrum of activityGood penetration of abscessesCan be given orally for long-term treatment**Owners warned to wear gloves while handling chloramphenicol because of potential for aplastic anemia in humans**

Slide19

ADDITIONAL THERAPEUTIC OPTIONS

Dietary ModificationGrain with high carbohydrates, low proteinEx: 2 parts beet pulp (or sorghum, bran, or milo), one part cracked corn in molassesDivide ration into multiple small mealsOat hay is best roughage, followed by other grass haysEncourage to graze in grass pasturesAlfalfa & legumes should be avoided if possible because of high protein (Can be included if more calories needed)Anti-inflammatories

Flunixin meglumineDimethyl sulfoxide

May help dissolve

interbiliary

sludge or small calcium

bilirubinate stonesPentoxifyllineProvides anti-endotoxic effects

Slide20

PROGNOSIS

Can be successfully treated but depends on long-term antimicrobial therapy and appropriate supportive care

Clinical signs usually not manifested until ~75% of liver function lostSevere periportal and bridging fibrosis generally poor prognostic indicators, with or without hyperammonemic encephalopathy

Leukocytosis associated with poorer prognoses

(Durham 2003; Equine Vet J.;35:542-547

)

Often result of neutrophilia due to systemic inflammatory response following loss of Kupffer cells or glucocorticoid-mediated stress response

Slide21

OUTCOME

Serum biochemistry repeated by referring veterinarian after one month of treatment with chloramphenicolTreatment recommended to continue until normalization of GGT levelsDecision made to pursue additional month of therapy with chloramphenicol with recheck of GGT & bile acid levels following completionTwo months after presentation, continues to do well at home with good appetite & no fevers

ParameterResultNormal Value

GGT

174

(

H)5-24 u/LAST181175-340 U/LT Bilirubin1.70.5-2.3 mg/dL*Clinical recovery often precedes normalization of biochemical values

All other parameters within normal limits

Slide22

REFERENCES & FURTHER READING

Durham, AE, Newton, JR, Smith, KC, et al. Retrospective analysis of historical, clinical, ultrasonographic, serum biochemical and haematological data in prognostic evaluation of equine liver disease. Equine Vet J. 2003;35:542-547.Durham, AE, Smith, KC, Newton, JR. An evaluation of diagnostic data in comparison to the results of liver biopsies in mature horses. Equine Vet J. 2003;35:554-559.Durham, AE, Smith, KC, Newton, JR, et al. Development and application of a scoring system for prognostic evaluation of equine liver biopsies. Equine Vet J. 2003;35:534-540.Johns, IC, Sweeney, RW. Coagulation abnormalities and complications after percutaneous liver biopsy in horses. J Vet Intern Med. 2008;22:185-189.Reed, SM, Bayly, WM, Sellon

, DC. Disorders of the liver. In: Equine Internal Medicine, 2nd ed. Ed: Fathman L, Elsevier, St Louis, MO. 2004. Pp. 951-994.Peek SF and

Tivers

TJ. Medical treatment of

cholangiohepatitis

and cholelithiasis in mature horses: 9 cases (1991-1998). Equine Vet J. 2000;32:301-306.

Slide23

ACKNOWLEDGMENTS

Photographs courtesy of Dr. Johanna Elfenbein and Dr. Sarah Reuss Thanks to both for their time, assistance, and patienceThanks to Drs. Barbara Sheppard and William Craft for histopathology evaluation