Aumento Enz Hepaticas EVC2009

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Proceedings of theEuropean Veterinary ConferenceVoorjaarsdagen

Amsterdam, the NetherlandsApr. 23-25, 2009

Next Meeting:

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2/14Abstracts European Veterinary Conference Voorjaarsdagen 20092

G A S T R O I N T E ST I N A L C A S E D I S C U S S I O N SHoffmann, Gaby, DVM,PhD, DECVIM, DACVIMUtrecht University, Faculty of Veterinary Medicine,Dept. of Clinical Sciences of Companion Animals,The [email protected]

Acute and chronic vomiting, chronicdiarrhea, abnormal behavior or painwhile eating are the topics that will

be addressed during the session.This interactive lecture will provide acase based, very practical step-by-step approach to the patient withgastrointestinal problems in order toprovide the practicing veterinarian

with a logical and easy to follow support in his/her deci-sion making.

In some patients a distinction between vomiting andregurgitation can be difficult, and it might not be im-mediately obvious whether behavioral problems orpain are the etiology of abnormal behavior of a pet.

During the presentation of example cases from the gas-troenterology service of the veterinary teaching hospi-tal in Utrecht these problems will be discussed with theaudience.

VomitingApart from toxicities differential diagnoses for vomitinginclude etiologies of the central nervous system (ex-cluded based on the results of a physical examination),etiologies within the gastrointestinal system, and extra-alimentary etiologies.Extra-alimentary etiologies for vomiting in dog as andcats are uremia, hepatic insufficiency, pancreatitis, peri-tonitis, pyometra, cholangitis, adrenal insufficiency, and

feline hyperthyroidism in cats older than 6 years of age.Gastrointestinal etiologies for vomiting include para-sites (including giardia), dietary indiscretion, gastritis,enteritis, colitis, ileus, IBD, and neoplasia (including py-loric stenosis).Due to the fact that parasites occur commonly in ani-mals the author recommends to exclude parasites bytreating the animal with fenbendazole for 5 days (pana-cur: 50mg/kg PO once daily) if the etiology remains un-solved after a clinical examination of the patient.If vomiting continues diagnostic imaging may aid toexclude intestinal ileus. In patients below 1-1.5 years ofage the 3 main differential diagnoses for vomiting and/

or diarrhea are parasites, dietary indiscretion, and intes-tinal ileus.

The patient can be assessed for dietary indiscretion bymanagement with a commercial diet containing a new

protein and a new carbohydrate source (e.g. d/d or sen-sitivity control), or by management with a home madediet (e.g. turkey and potato, turkey and rice, duck andpotato). Although the patient remains strictly on theprovided diet, improvement of clinical signs of the dis-ease may be seen after 10 days if the diet is effective.Once toxic and non-specific causes for vomiting havebeen excluded, the patient was treated for parasites,pyometra, abdominal neoplasia, and ileus were exclud-ed during diagnostic imaging, and good dietary man-agement was not successful to overcome the problem

of vomiting, blood and urinary examination can helpto asses for extra-gastrointestinal etiologies (ALT, bileacids for liverfunction testing, pancreatic lipase for pan-creatitis, blood urea/creatinine and specific gravity ofthe urine for uremia, total T4 in older cats).Endoscopy is indicated to assess the stomach, uppersmall intestine, and colon for immune-mediated in-flammatory or neoplastic changes.

DiarrheaGastrointestinal etiologies for diarrhea include para-sites (including giardia), dietary indiscretion, ileus,lymphangiectasia, antibiotic responsive diarrhea, IBD

(gastroenteritis, colitis), pancreatic insuffiency, andneoplasia.Due to the fact that parasites occur commonly in animalsthe author recommends to exclude parasites initially bytreating the animal with fenbendazole for 5 days (pana-cur : 50mg/kg PO once daily) if the etiology remains un-solved after a clinical examination of the patient. Addi-tional medication with metronidazole for 7-20 days (20mg/kg BID PO) can help to treat giardia strains that areresistant to fenbendazole. In addition the drug may beeffective to treat exclude antibiotic responsive diarrheafrom the list of differential diagnoses.If diarrhea continues diagnostic imaging may aid toexclude intestinal ileus. In patients below 1-1.5 years of

age the 3 most common reasons for diarrhea are para-sites, dietary indiscretion, and intestinal ileus. Thereforeas for vomiting the patient with diarrhea can be as-sessed for dietary indiscretion by management with acommercial diet containing a new protein and a newcarbohydrate source (e.g. d/d or sensitivity control), ahydrolyzed diet (e.g.hypoallergenic or z/d) or by man-agement with a home made diet (e.g. turkey and po-tato, turkey and rice, duck and potato). Although thepatient should remain strictly on the provided diet for 6weeks, improvement of clinical signs of the disease maybe seen after 10 days if the diet is effective.Once toxic and non-specific causes for diarrhea have

been excluded, the patient was treated for parasitesand antibiotic responsive diarrhea, abdominal neopla-sia, and ileus were excluded during diagnostic imaging,and careful dietary management was not successful to

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Scientific proceedings: companion animals programme

overcome the problem, blood examination can helpto asses for other etiologies (total protein and albuminfor severity of intestinal protein loss, ALT, bile acids forliverfunction testing, TLI and vitamin B12 for pancreaticinsufficiency and cobalamin deficiency, total T4 in oldercats).Endoscopy is indicated to assess the stomach, uppersmall intestine, and colon for immune-mediated in-flammatory changes or neoplasia.

A C U T E A B D O M E NHoffmann, Gaby, DVM,PhD, DECVIM, DACVIMUtrecht University, Faculty of Veterinary Medicine, Dept. ofClinical Sciences of Companion Animals, The [email protected]

The term acute abdomen is used to describe the syn-drome of peracute, acute or recurrent abdominal painof sudden onset. Further systemic signs of disease likefever, hypothermia, vomiting, diarrhea, depression, an-orexia and shock may be present.

Pain can be generated from serosal tension from dis-tended organs during dilatation or volvulus, as well ascapsular stretch of enlarged and/or inflamed organs(pancreas, spleen, kidney, liver, gallbladder). Further-more can intra-abdominal adhesions lead to serosaltraction which induces pain. Forceful contractions caninduce pain (obstructive ileus, hypersegmentation)Direct stimulation of nerve endings can occur from therelease of cytokines and vasoactive substances duringinflammation (pancreatitis, peritonitis) and ischemia(torsion, dilatation, rupture, thromboembolism).

Differential diagnosis for the acute abdomen

Surgery required Medical care

Gastric dilatation / volvulus

(GDV)

Gastroenteritis

Gastrointestinal perforation/

rupture/dehiscence

Colitis

Intestinal obstruction (foreign

body, neoplasia, intussuscep-

tion)/volvulus

Obstipation

Biliary rupture / bile peritonitis Gastrointestinal ulceration

Pancreatic abscess Acute pancreatitis

Pyometra, uterine torsion Hpatitis

Ovarian neoplasia Nephritis / pyelonephritis

Prostatic abscess/cyst prostatitis

Testicular torsion Blunt peritoneal trauma

Splenic mass / rupture / torsion Lymphadenopathy

Septic peritonitis Toxicities

Perforating abdominal trauma Hpoadrenocorticism

Uroabdomen Myositis

persistent abdominal bleeding Thromboembolism

free abdominal gas (if not

iatrogenic or from pneumo-

mediast)

Pleuritis / Pneumonia

Approach to the patient with acute abdominal pain

GDV and shock should be diagnosed and addressedbefore all further diagnostic investigations for a patientwith acute abdomen are initiated.

! Remember ! : Shock can be hyperdynamic or hy-podynamic. Capillary refill time (CRT) can therefore beshortened or prolonged, and the pulse quality can varybetween bounding and weak during shock !

Clinical signs of shockmucous membranes: pale (maybe hyperemic, brick

red to muddy during septicshock)

CRT : shortened (2 seconds)heart rate: fastpulse: bounding (hyperdynamic) or

weak (hypodynamic)attitude: depression, weaknessappendages: cold

Hypoperfusion during shock leads to deficits of tissueoxygenation, which has a major impact on the outcomeof the patient. Therefore infusion therapy should be ini-tiated as soon as possible in all patients in shock.

The shock dose of isotonic crystalloid solution for

dogs is 90 ml/kg.The shock dose of isotonic crystalloid solution forcats is 45 ml/kg.

Shock dose in ml of an isotonic crystalloid solutionfor

Species &

weight

Shock dose

[ml]

shock dose

[ml]

shock dose

[ml]

dog 10 kg 900 ml 225 450

12 kg 1080 ml 270 540

14 kg 1260 ml 315 630

16 kg 1440 ml 360 720

18 kg 1620 ml 405 810dog 20 kg 1800 ml 450 900

25 kg 2250 ml 563 1125





dog 30 kg 2700 ml 675 1350

dog 40 kg 3600 ml 900 1800

dog 50 kg 4500 ml 1125 2250

cat 2.5 kg 112 ml 28 56

cat 3.5 kg 158 ml 40 79

cat 4.5 kg 203 ml 51 102

cat 5.5 kg 248 ml 62 124

About half of this dosage should be given as fast as

possible (within 30 minutes), the other half after reassessment of the patient.

To avoid excessive fluid volumes in patients with intra-abdominal bleeding or cardiac failure re-assessmentmay be done earlier (after 15 minutes, when of theshock dose is given during fluid resuscitation), andthe absolute amount of fluid needed might be less inthese 2 conditions. Monitoring parameters may includecentral venous pressure, mean arterial blood pressure,urine production, body temperature, heart rate, respira-tory rate, CRT, mucous membrane color and moistness.

History of Clinical SignsThe history should provide information aboutthe duration of clinical signs (peracute, acute, chronicrecurrent)previous abdominal surgery (recently: intra-adominaltissue damage, abdominal contamination, foreignbody; longer than 10 days ago: adhesions, stictures,foreign body)earlier medical problems (chronic recurrent pancrea-titis, urolithiasis, cholelithiasis, neoplasia)castrated or intact male (testicular torsion) / female(peritonitis from pyometra)concurrent signs (vomiting and diarrhea in gastro-intestinal problems, anuria, hematuria, polyuria in

urinary involvement, gait abnormalities in spinal orskeletal problems, prostatic diseases, postoperativeadhesions)aggravating factors (eating, drinking, urinating, def-ecating)exposure to drugs, inappropriate diet (bone, toxici-ties)trauma

Physical examinationExtra-abdominal disorders should be excluded if pos-sible (intervertebral disc disease, discospondylitis, tho-racic diseases such as pleuritis, pneumonia).

Observation for shape changes, distensions, skin discol-oration/bruising.Careful abdominal palpation should be performed. Thismay reveal a localized process (ileus, painful kidneys,

organ enlargement). In cases where the urinary bladderis not palpable catheterization is indicated.

Emergency laboratory assessment available in practicePacked cell volume (PCV) and total protein (TP):

parallel increase indicates dehydrationparallel decrease indicates blood lossnormal to high PCV & normal to low TP indicates vas-cular protein loss (hemorrhagic gastroenteritis, peri-tonitis, acute hemorrhage in dogs from rupture of asplenic/ hepatic mass, gi ulceration)

A direct blood smear can be examined to assess forthrombocytopenia as aetiology for abdominal bleed-ing. Each platelet on a 100x magnification oil immersionfield represents about 15000 platelets per microliter.

Therefore platelet counts below 4-5 platelets per highpower oil immersion field can reveal thrombocytope-nia as aetiology for abdominal bleeding. Mild throm-bocytopenia can be an early indicator of disseminatedintravascular coagulopathy (DIC). During later DIC pro-longed coagulation times, and increased D-dimers willoccur.Blood glucose is measured to examine the patient for

sepsis which may lead to mild to moderate hypoglycae-mia. A differential diagnosis for hypoglycaemia fromsepsis is hypoadrenocorticism. High blood glucose ismost likely a result of stress, but may indicate diabetesmellitus secondary to pancreatitis.Increases of urea and/or creatinine may result fromprerenal, renal, or postrenal problems. Isolated increas-es in urea may be a result of gastrointestinal bleeding.

Diagnostic imaging:Abdominal radiographs should be investigated for:

free abdominal airskeletal changes (intervertebral changes, disc spacenarrowing, lytic bone lesions)

intact diaphragmintestinal gas patternsorgan enlargement/displacementpresence of the urinary bladderretroperitoneal enlargement/loss of detail (kidneys)loss of detail (focal: peritonitis, diffuse: abdominalfluid: peritonitis, blood, urine, bile, chyle)

Abdominal radiographs can be useful to diagnose freegas in the abdomen that may be found between dia-phragm and liver. The retroperitoneal space is assessedfor fluid accumulations and mass effects. Intestinal gaspatterns are assessed to diagnose localized or general-

ized ileus. Plicated bowel and teardrop shaped gas bub-bles may be seen if a linear foreign body is present.

Abnormal small intestinal distension is present if the





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gas filled intestines are larger than:twice the width of a vertebral bodyfour times the width of a ribcats: twice the height of L4cats: 12 mm

All loops of the small bowel should have about thesame diameter. Variations of 50% or larger in diameterbetween different loops of the small bowel may be anindication for disease.

Contrast studies with barium sulphate for the gastro-intestinal studies, or with iodine based contrast mediafor the urinary tract can be indicated in some patients.However, controversy exists about a possible contraindi-cation for barium sulphate in patients with esophageal,gastic or intestinal ulceration/perforation. Furthermoreshould barium contrast not be used in patients whereendoscopy is scheduled, because endoscopic equip-ment can be damaged.

Abdominal ultrasonography can be very helpful andspecific in the detection of organ changes and fluid ac-cumulations, as well as for the guidance of tissue sam-

pling. However, due to the fact that radiology is not thespecialty of the author this technique will not be de-scribed in detail during the lecture. For more informa-tion about abdominal ultrasonography please consultreference ( ) Burk, Ackerman Small Animal Radiologyand Ultrasonography, 2nd edition WB Saunders 1996.

Abdominocenthesis To answer the urgent question whether the patientwith acute abdominal pain requires immediate surgery,later surgery, or medical care abdominal fluid can becollected for diagnostic purposes.

The patient is aseptically prepared in an area of about

15 cm to all sides of the umbilicus. The Aspiration witha 18-20 gauge catheter with extra wholes might prefer-ably be performed in a standing patient, on the midline,immediately caudal to the umbilicus. Suction should beavoided. Instead the needle should be kept in place fora while in order to allow fluid to flow freely through theneedle (one droplet is enough for diagnostic puposes).If no fluid can be obtained with this first attempt, fourquadrant centesis can be tried after local anesthesiawith 0.5 ml lidocaine.

Diagnostic Peritoneal Lavage (DPL)With the patient in lateral or dorsal recumbency, and

after aseptical preparation, and local anesthesia with li-docaine, a small stab incision is made about 2 cm to theright of the umbilicus OR 2 cm caudal to the umbilicuswith a scalpel blade size 11. A peritoneal dialysis cath-

eter or 16 gauge catheter with extra wholes is insertedin caudal direction . If aspiration confirmed negative 20ml/kg of a warmed (37C), sterile, 0.9% sodium chloridesolution is infused through the catheter. Once the fluidis in the abdomen the patient is rolled from side to sidebefore the fluid is allowed to drain freely into the low-ered collection system. Fluid should be collected in anEDTA tube for cytological examination

Abdominal fluid analysis allows the diagnosis of:hemoperitoneum (>0.5ml unclotted blood, dpl fluid

PCV > 5%)uroabdomen (effusion creatinine : blood creati-nine ratio : > 2:1)uroabdomen (effusion K : blood K ratio: > 1.9:1)septic peritonitis: degenerated neutrophils, intrac-ellular bacteria, effusion glucose 20% below bloodglucose)biliary disease/ duodenal disease (bilirubin in effu-sion)pancreatitis or severe intestinal ischemia (effusionamylase > blood amylase)Dark printed letters are not readable under the tubewith dpl fluid : indicates serious hemorrhage, perito-

nitis, or leakage of gi contents.

ReferencesMalouin, Silverstein: Shock. In Bonagura, Twedt: Kirks Current Vet-

erinary Therpy XIV, Saunders 2009, 2-8.

Mann: Acute Abdomen: Evaluation and Emergency Treatment: In

Bonagura, Twedt: Kirks Current Veterinary Therpy XIV, Saunders

2009, 67-71.

Willard: Digestive System disorders. In: Small Animal Internal Medi-

cine, 3rd edition, Mosby, 2003, 343-365

Drobatz: Acute abdominal pain, In: Small Animal Critical Care Medi-

cine, Saunders Elsevier 2009, 534-536

I N C R E A S E D L I V E R E N Z Y M E S A N DH EPAT I T I SHoffmann, Gaby, DVM, PhD, DECVIM, DACVIMUtrecht University, Faculty of Veterinary Medicine, Dept. ofClinical Sciences of Companion Animals, The [email protected]

Increased Liver Chemistries in the AsymptomaticPatientIn a study of 1,022 blood samples taken from healthyand sick dogs and cats 39% had ALP increases and 17%had ALT increases. Liver biochemical test abnormalities

are common and can occur after 1% of liver tissue isdamaged. Furthermore no liver test is specific only tothe liver but all can be abnormal from primary non-he-patic disease. In addition the magnitude and duration





of increases do not relate to the irreversibility of a liverdisease and no single laboratory test reflects the com-plete functional state of the liver.

ALT / AST (hepatocellular leakage enzymes)Isolated elevations of alanine aminotransferase (ALT),the hepatocellular leakage enzyme. The plasma half-life of ALT is 12-24 hours, however ALT concentrationsmay take days to decrease following an acute insult.Persistent increases of only ALT are characteristic ofchronic hepatitis in the dog. AST will faster return tonormal (within hours - days) than ALT (days), because of

a shorter plasma half-life. Therefore improvement willbe seen earlier by measurement of AST.2

ALP / GGT (markers of cholestasis and drug-induction)Alkaline phosphatase (ALP) and gamma-glutamyltrans-ferase (GGT) increase in response to impaired bile flowor drug-induction. Impaired bile flow will be seen earlybecause ALP is associated with the canalicular mem-brane and GGT with bile ductular epithelial cells.3

ALPDiagnostically important alkaline phosphatase is pres-ent in bone and liver. The plasma half-life for hepatic

ALP in the dog is 66 hours in contrast to 6 hours for thecat and the magnitude of enzyme increase is greaterfor the dog than the cat. Bone source ALP from osteo-blasts is elevated in young growing dogs before theirepiphyseal plate closure as well as in some bone tumorsof adult dogs.

The most common reason for increases in ALP and GGTactivity are glucocorticoids (endogenous, topical orsystemic), and anticonvulsant medications in the dog.An increase in serum ALP activity without concurrenthyperbilirubinemia is most compatible with drug-in-duction or adrenal hyperfunction.

ALP steroid isoenzyme

The glucocorticoid-associated isoenzyme can also beassociated with hepatobiliary disease:A common condition observed in older dogs is an idio-pathic vacuolar hepatopathy associated with increasedALP steroid isoenzyme (Investigation for hyperadreno-corticism is negative). The diagnosis can be made cy-tologically.Scottish Terriers may have an unexplained increases inserum ALP.Benign hepatic nodular hyperplasia can lead to in-creases of ALP. Cytologic axamination of an ultrasoundguided fine needle aspirate can be performed to differ-entiate benign hyperplasia from neoplasia (adenoma,

adenocarcinoma or bile duct carcinoma).

GGTIncreased serum GGT activity is associated with im-

paired bile flow in the dog and cat and glucocorti-coid administration in the dog.3 Colostrum and milkhave high GGT activity and nursing animals developincreased serum GGT activity. As a marker of hepato-biliary disease, the measurement of serum GGT activ-ity does not appear to provide a diagnostic advantageover the serum ALP determination in the dog, howeverit is reported to be a more sensitive marker in cats hav-ing biliary tract disease.

Suggested Patient Approach:

If no explanation for the liver enzyme abnormalities canbe found and the patient is asymptomatic the authorrecommends to recheck the laboratory abnormalitiesafter 4 weeks (with the exception of Doberman Pin-schers, that require immediate investigation with a liverbiopsy as soon as possible). In case the decision to waitfor a month is not easy to make further work up at thispoint could be the measurement of bile acids.Abnormal bile acids indicate hepatic or circulatoryabnormalities. Such a patient should undergo furtherevaluation. In the cases where bile acids are normal inthe asymptomatic patient the animal can wait a monthbefore further workup.

Further WorkupRepeated abnormal liver enzymes should not be ig-nored, but investigated in a systematic manner, by per-formance of liver function testing, ultrasonography andretrieval of liver biopsies.

Liver Functionliver function tests include bilirubin, albumin, glucose,BUN, and cholesterol.Albumin is exclusively made in the liver and a low con-centration can indicate hepatic dysfunction (greaterthan 60% hepatic dysfunction, differential diagnosesfor low albumin are renal or gi loss, sequestration and

dilution).Clotting factors are made in the liver (except factor 8)therefore prolonged clotting time suggests hepaticdysfunction.

The fasting serum total bile acid concentration is a re-flection of the efficiency and integrity of the enterohe-patic circulation but non-specific for a particular typeof liver dysfunction.5 Pathology of the hepatobiliarysystem or the portal circulation results in an increasedfasted BA prior to the development of hyperbilirubine-mia.Occasionally higher fasted BA values occur comparedto postprandial BA values. Possible explanations could

be individual variations in the release of bileacids (in-dividual peaks by chance just before sampling), and asuboptimal stimulation from feeding.In Utrecht ammonia is measured for evaluation of liver





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function. Samples must be put on ice directly or im-mediately measured. (Feline plasma samples are lesssensitive). Erythrocytes contain two to three times theamount of ammonia as does plasma, therefore hemo-lysis will increases blood ammonia. The liver is respon-sible for the majority of ammonia detoxification. Am-monia is generated primarily in the GI tract by bacterialdegradation of amino acids. Failure of the liver to de-toxify ammonia or shunting of portal blood away fromthe liver results in hyperammonemia. To detect hepaticfailure liver dysfunction must be advanced for blood

ammonia concentrations to rise, but ammonia is verysensitive in the detection of shunting.In an ATT, a baseline blood ammonia value is deter-mined after a 12-hour fast. The animal is then given anexogenous load of ammonium per rectum and bloodammonia determined postchallenge (after 20 and after40 minutes). For the rectal ATT, 2mL/kg of 5% NH4Cl2 isvia a catheter inserted into the rectum. Blood ammoniashould not increase any more than twofold (maximum60 mg/kg, in Irish Wolfhound 120 mg/kg).

Ultrasonography is useful for identifying focal liver le-sions, diffuse liver disease or biliary disease. Although

fine needle aspiration (FNA) is safe and easy to perform,one must be cautious in the interpretation of results.The best correlation between FNA and liver biopsy canbe found with hepatic neoplasia and diffuse vacuolarhepatopathies, but for chronic hepatitis FNA is not reli-able!

After examination of a coagulation profile reveals nor-mal fibrinogen the method for liver biopsy may be sur-gery (skin punch device, NOT from an edge!), needlebiopsy or laparoscopy. Provision of the pathologist withsufficient data on the patient and personal discussionof results improve the accuracy of histology as a diag-nostic test !!!!

Increased Liver Chemistries in the Symptomatic PatientInflammatory diseases of the biliary system and theliver are relatively common and result from a wide di-versity of causes.

a) Non-Specific Reactive HepatitisReactive hepatitis represents a non-specific responseto a variety of extrahepatic disease processes, previousor ongoing febrile illnesses and/or inflammation some-where in the splanchnic area.The inflammatory infil-trate is mostly localized in the portal area during this

non-specific reaction of the liver.

b) Acute HepatitisAcute hepatitis is characterized morphologically by a

combination of inflammation, hepatocellular apoptosisand necrosis, and, in some instances, regeneration. Thedistinction from chronic hepatitis is NOT the durationof the disease but the absence of fibrosis (which is bydefinition present in chronic hepatitis).

Infectious causes of acute hepatocellular necrosis andinflammation

Septic diseases may lead to non-specific reactivehepatitis or may cause multifocal random and con-fluent necrosis with macrophage proliferation and/

or infiltration with neutrophils and in later stageslymphocytes and plasma cells. Many bacteria maycause hepatitis in dogs and cats, including E. coli,Streptococcus spp., Pasteurella spp., Salmonella spp.,and Brucella canis.

Toxoplasma gondii causes multisystemic disease in-volving the liver, lung, brain and other organs in thecat and dog. In the liver there is confluent to panlobu-lar necrosis often with neutrophils, macrophages andother inflammatory cells. Areas of necrosis and theadjacent parenchyma often contain free tachyzoitesand/or cysts containing bradyzoites. Canine and fe-line herpes viruses involve the liver, as well as other

organs.Infectious canine hepatitis causes a multisystemicdisease involving the liver, and other organs.Feline infectious peritonitis virus In the liver leads tomultifocal areas of necrosis.Clostridium piliformis are long bacilli within hepato-cytes in dogs and cats (Tyzzers disease).Leptospirosis occurs in dogs and various serovarsproduce an acute multisystemic disease leading todissociation and separation of liver cell plates (par-ticularly evident in postmortem material) and thepresence of many hepatocytes with mitotic figuresor binucleation.

In cases of known infectious causes of hepatitis treat-ment should be initiated against the diagnosed orsuspected organism. However, clinically most cases ofacute hepatitis are idiopathic, and therefore no causaltherapy is possible. Prednisolone is contraindicated inacute hepatitis ! Although no controlled studies coin-firm the effectiveness, the author would use ursodeoxy-cholic acid (ursochol, 7,5mg/kg BID PO for 3 months) fora suspected anti-inflammatory and hepatoprotectiveeffect.Control biopsies after 6-8 weeks in these patients willreveal self recovery in most cases. Unfortunately somepatients progress into chronic hepatitis and require

prednisolone treatment to avoid fibrosis of the liver. The liver of these patients will recover Therefore nocausal treatment is





c) Chronic Hepatitis / cirrhosisChronic hepatitis can ONLY be diagnosed histologi-cally, and is characterized by hepatocellular apoptosisor necrosis, a variable inflammatory infiltrate, regenera-tion and fibrosis. Cirrhosis is the end-stage of chronichepatitis.

The cause of many cases of canine chronic hepatitis isundetermined although a few cases have been associ-ated with leptospirosis, and infectious canine hepatitisvirus infection, aflatoxicosis and some dogs treated

with phenobarbital.

Treatment:In cases of chronic hepatitis from unknown reason thetreatment is prednisolone (1mg/kg once daily, for atleast 6 weeks). Chronic hepatitis and cirrhosis are rarelyseen in cats, although chronic cholangitis is common.

Copper-Associated Chronic HepatitisProgressive chronic hepatitis from accumulation ofcopper occurs as a breed related disease in Bedlingtonterriers, Labrador retrievers, West Highland White ter-riers, Dalmatians, Doberman Pinchers, and American

and English cocker spaniel. Copper continuously ac-cumulates in hepatocytes, starting in the centrolobularregions, and with progressive accumulation results inhepatocellular necrosis, inflammation with copper-laden macrophages and finally chronic hepatitis andcirrhosis.

Healthy dogs with normal livers may have copper lev-els up to 400 micrograms per gram dry weight. Hepaticcopper levels in breeds with primary copper storagedisease vary between individual animals and betweenbreeds from 600-2,200 micrograms per gram.Copper-induced chronic hepatitis and cirrhosis was re-cently observed in a cat and was characterized by severe

copper deposition in hepatocytes and macrophages inthe fibrotic areas and slight to moderate copper deposi-tion in the regenerative nodules.

Bedlington TerriersHepatic copper toxicity was first identified in Bedling-ton Terriers in 1975. It was subsequently shown thataffected Bedlington Terriers have an inherited au-tosomal recessive defect of the MURR1 gene, whichwas renamed to COMMD1 (copper metabolism murr1domain containing protein 1). The extent of hepaticdamage tends to parallel the increasing hepatic Cu con-centrations. The morphological changes extend from

focal necrosis to chronic hepatitis that may ultimatelylead to cirrhosis. In some cases, acute hepatic necrosisand Cu associated hemolytic anemia and acute liverfailure may occur.

Samples for analysis of quantitative copper should beplaced in a Cu free container (such as a serum bloodtube) for analysis. Normal canine hepatic Cu concen-trations are less than 400 g/g dry weight liver. The con-centration at which abnormal hepatic Cu contributesto hepatic damage is unknown. It is possible to takeadequate size biopsy sample embedded in paraffinfor histology and de-paraffinize the sample to obtaina quantitation of copper. Morphologic evidence of in-flammatory hepatic injury in Bedlington Terriers beginswhen concentrations reach approximately 2,000 g/g

dry weight. Homozygous affected dogs have increasedcopper concentrations but should be older than oneyear of age prior to having a biopsy. This is because theheterozygous carrier dogs normally increase in copperconcentrations out of the normal range until around6-9 months of age before concentrations fall back intothe normal range. Genetic testing is available for Bed-lington Terriers.

Doberman PinscherThe disease begins in young dogs (1-3 years) with in-creased ALT concentrations and having sub-clinicalhepatitis. Clinical evidence of liver disease usually be-

gins around 4-7 years of age with chronic hepatitis andcirrhosis. Copper appears to be associated with the dis-ease and recent studies suggest that copper is often in-creased prior to development of clinical hepatitis. Cop-per chelator (penicillamine, via tel +31-30-2531598, fax+31-30-2532065, in tablets of 150mg) therapy in sub-clinical dogs normalized copper concentrations withimprovement in the grade of histological damage.

DalmatiansA retrospective study summarizes 10 Dalmatians sus-pected of having hepatic copper toxicosis6. Two of thedogs were related and all presented for gastrointestinalclinical signs, had elevated liver enzymes and necroin-

flammatory hepatic changes. In 5 of these 9 dogs, he-patic copper concentrations exceeded 2,000 mg/kgdryweight liver with several dogs having copper levels ashigh as those observed in Bedlington Terriers.

West Highland White TerriersThe Westie breed has been associated with liver dis-ease and hepatic copper accumulation. Twenty-fourdogs described ranged from 3-7 years of age. Somedogs in this report had high copper concentrations butno evidence of liver disease while others did.9 While theBedlington Terrier tends to accumulate Cu with age itwas not apparent in this group of dogs.

Labrador RetrieverChronic hepatitis is reported to be common in this breedand copper accumulation is associated with about 75%,





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but not all the cases. Females are more commonly af-fected and the diagnosis is generally made arpound 7years of age (range 2-10 years) with non-specific clinicalsymptoms like anorexia, vomiting, and weightloss. He-patic copper concentrations generally range between650 to 3000 g/g dry weight liver (histologically above2+ by rubeanic acid stain). The histological location ofthe Cu being centrilobular suggests that Cu elevation isprimary and not secondary to cholestasis.Penicillamine treatment (10-15mg/kg BID PO for 6-12weeks), followed by dietary management with a diet

low in copper (hepatic from Royal Canin) were effec-tive against the disease in double blinded, placebo-controlled trials performed at the Veterinary Faculty inUtrecht.

Other Breeds The Skye Terrier, Anatolian Shepherd, and possiblythe Keeshond as well as other breeds have also beenreported with liver disease and increased copper accu-mulation. The exact mechanism or extensive descrip-tion in specific breeds is lacking.

Secondary Copper Accumulation

Copper may also concentrate in the liver secondary tocholestatic liver diseases. Because copper is excretedvia the bile, cholestatic liver disease often results incopper accumulation in another region of the liverlobule (the periportal areas). The copper accumulationoccurs in Kupffer cells and hepatocyte lysosomes. Themagnitude of Cu concentrations from cholestasis is notas high as those found in the breeds thought to havea genetic basis. In a Review of 17 liver biopsies frombreeds not yet identified to have inherited Cu copperassociated liver disease (including 2 Standard Poodles,2 Cocker Spaniels, 5 mixed breeds and the remaindersingle dogs of different breeds), the mean copper con-centration was 984 g/g dry weight liver.

References1. Comazzi S: Journal Small Animal Practice (2004) 45. 343-349.

2. Webster CRL. In: Ettinger SJ, et al. (editors). Textbook of Veteri-

nary Internal Medicine. St. Louis: Elsevier Saunders; 2005

3. Center SA, et al. JAVMA 1992; 201(8): 1258.

4. Bunch S. In: Nelson RW, et.al (editors). Small Animal Internal

Medicine. St. Louis: Mosby; 2003.

5. Trainor et.al., J Vet Int Med 17: 145-153, 2003

6. Webb CB, et al. J Vet Intern Med 2002; 16 (6):665.

7. Brewer GJ, et al. J Am Vet Assoc. 1992; 201(4):564.

I N T E R A C T I V E G A S T R O - I N T E S T I N A LC A S E S : C O M M O N G I D I S E A S E SChris L. Ludlow, DVM, MS Diplomate ACVIM (InternalMedicine), Animal Specialty Hospital, Rockledge, Fl, [email protected]

Case 1: Cindy Willey Helicobacter gastritisHelicobacter spp. are a class of gramnegative microaerophilic spiral-

shaped bacteria that are found inmany places in the body. H. pylorihas been identified as the underly-ing etiology for peptic ulcer diseasein humans. Much study has been

directed at the importance of Helicobacter-like organ-isms (GHLOs) commonly found in dogs and cats.Lymphoid follicles may bee seen in dogs and cats thatare not infected, but some suggest that those that aremore heavily infected have more prominent folliculardevelopment and more severe inflammation. It is im-portant to note that one significant difference from hu-mans with H. pylori is that we do not see ulcer disease

associated with infection in pets.A number of diagnostic tests have been developed todiagnose GHLOs. In a clinical setting, the last three arethe most relevant. There are a number of rapid ureasetests (e.g. the CLOtest). Cytology can be done on im-pression smears of gastric biopsies. Typically identifi-cation of GHLOs occurs on histopathology of gastricbiopsies. In dogs and cats the fundus is typically mostheavily colonized. PCR is the most sensitive of all tests,and is most often indicated when trying to determine ifinfection has been eradicated.When considering treatment, the first question weshould ask is do we treat? Since infection is so preva-lent, infection is not indication for treatment. I reserve

treatment when vomiting is a prominent part of thepresenting signs: 1) when colonization is very heavy; 2)when organisms are associated with regions of markedinflammation; or 3) when no other cause of vomitingcan be identified.A number of antibiotic combinations have been sug-gested for treatment of GHLOs in people and animals.At present the most frequently recommended is a com-bination of amoxicillin (20 mg/kg BID), metronidazole(10-15 mg/kg BID) and clarithromycin (7.5 mg/kg BID)used ideally for 3 weeks. I often also add omeprazole(0.5-1 mg/kg QD) to help reduce clinical signs. This treat-ment is intended to reduce bacterial numbers- no anti-

biotic protocol has been show to completely clear infec-tion based on PCR analysis of post-treatment biopsies.





Case 2: Cindy Willey Inflammatory bowel diseaseInflammatory bowel disease (IBD) is the most commonchronic gastrointestinal disease in cats and dogs. In-flammatory bowel disease is characterized by a diffuseinfiltration within the mucosal and the lamina propriaof the intestinal tract by various populations of inflam-matory cells. Changes in the small intestine are morecommon in cats, while in dogs changes are commonthroughout the GI tract

The cause of IBD in small animals remains elusive. Cer-tain nutrients are capable of causing direct damage to

the lining of the GI tract, and this may increase mucosalpermeability and lead to the inflammatory response.Diet therapy has always been one of the cornerstones intreatment of IBD, and several diet therapies have beenshown in humans to be effective in controlling cases ofsteroid refractory IBD. Autoimmunity has been foundas an underlying immune defect in humans. Foreigngut antigens (various bacterial antigens) have beenidentified that share antigenic similarity to self and arecross-reactive in laboratory testing. Regardless of thesource of antigenic stimulus, it is becoming increas-ing likely IBD is a failure to develop tolerance to anti-gen present in the GI tract. Failure of tolerance results

from a loss of or defect in T suppressor cell function andsubsequent immune amplification of the response toantigens. Increases in mucosal permeability result inincreased presentation of antigen to GALT. While thiscommonly occurs secondary to inflammation and GImucosal damage (alterations in GI permeability havebeen identified in a number of acute and chronic GI dis-eases), it may also be a primary defect. Human studieshave shown that relatives of individuals affected withIBD that are not suffering from signs of GI disease mayalso have increased GI mucosal permeability. A type Ihypersensitivity likely plays a role in the eosinophilicforms of the disease. Histologic changes in other formsmay be consistent with type II and III hypersensitivity

reactions.Definitive diagnosis of IBD requires biopsies of the GI.Be sure to biopsy multiple segments of the GI tract ifpossible. Results of histopathology must be interpret-ed carefully since mild mononuclear inflammation maybe present in the absence of clinical signs and overt GIdisease. The degree inflammation can vary significantlybetween segments of the GI tract, and those segmentsbiopsied may not reflect the severity of other seg-ments.

Treatment of IBD is usually based on dietary modifica-tion, antibiotics and immunosuppression. A therapeu-tic dietary trial can be performed with either: 1) a highly

digestible diet which is restricted in fat and gluten-free,2) a diet limited to a single novel protein source or pref-erentially 3) a hydrolyzed protein diet, to determine ifdietary sensitivity or intolerance are present. A response

is usually observed within 2-4 weeks. Oral prednisolone(1-2mg/kg PO BID) is the initial drug of choice. It is usu-ally administered at an immunosuppressive dose for 2-3wks and then decreased by 50% every 2-3wks, and thencontinued on an alternate day basis for 2-3 months. Ifclinical response is poor, the adverse effects of predni-solone are unacceptable, or if protein-losing enteropa-thy is present, then azathioprine should be added. Indogs it is usually given every day (2mg/kg PO SID) forfive days and then on alternate days. Budesonide (dogs1-2 mg/day, cats 1 mg/day) is a potent glucocorticoid

(15X more potent than prednisolone) with high topicalactivity. By delaying dissolution until reaching the duo-denum and subsequent controlled release of the drug,the drug can exert its topical anti-inflammatory activityin the intestines. It has a high first-pass metabolism ef-fect through the liver that reduces systemic blood lev-els. Cats are better managed with chlorambucil (6mg/m2 PO EOD- 2mg/5.3kg cat) and prednisone (5mg /cat/day). Cobalamin (dogs 1000 ug, cats 250 ug SC weeklyfor 4 weeks then once monthly) should also be given ifserum concentrations are low. Metronidazole (15mg/kgPO BID 10-14d then SID 10-14d) can also be used withprednisone and has antimicrobial effects and may sup-

press CMI.

Case 3 Squeaky WilliamsIntestinal lymphangiectasia is chronic small intestinaldisease characterized by dilation of lymphatic vessels(lacteals). In lymphangiectasia, these vessels becomedistended and begin to leak or even rupture. Clinicalsigns may be related to chronic diarrhea and proteinlosing enteropathy. In some cases GI signs are com-pletely absent, and only signs related to hypoproteine-mia are seen. Lymphangiectasia may be either primary(congenital), or more likely secondary to lymphatic ob-struction. There is a strong breed disposition in GermanShepherd Dogs, Lundehunds, and Yorkshire Terriers.

Diagnosis of lymphangiectasia is based on identifyingsigns of protein-losing enteropathy (PLE). Occasionallylaboratory results may show lymphopenia and hypoc-holesterolemia. GI protein loss may be distinguishedfrom renal since albumin and globulins are lost equally,leading to panhypoproteinemia. This is characteristicfor GI protein loss and not specific for lymphangiectasia.Definitive diagnosis must be made based on histologicexamination of the GI tract through either endoscopicor full-thickness intestinal biopsies. Endoscopy is oftenpreferred over laparotomy since panhypoproteinemiamay increase the risk of surgical dehiscence.

Therapy for lymphangiectasia is based at resolving

the underlying disease leading to lymphatic obstruc-tion. Prednisolone may be helpful (1-2mg/kg PO BID)may decrease lipogranulomatous inflammation. Sinceprednisolone can lead to protein catabolism, it should





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be tapered to the lowest effective dose quickly once re-mission is achieved.Dietary management is focused on providing highquality, highly digestible nutrients while at the sametime restricting fat intake to minimize lymphatic dila-tion. Ideally fat (long-chain triglyceride) content shouldbe below 10-12% DM, and in some cases may need tobe below 5% to control protein loss. Non-fat caloriesources may also need to be supplemented (pastas,breads, rice, potato). Medium chain triglyceride (MCToil, coconut oil 0.5-2ml/kg body weight per day added

to food) can be added to the diet to provide a easily ab-sorbed source of calories. In some cases, dietary fiberhas been shown to be help control GI signs without sig-nificantly impacting nutrient digestibility. Anorexia is apoor prognostic indicator.

Case 4: Maya GorbyFeline intestinal lymphoma is the most common neo-plasia in cats. Diffuse lymphoma is characterized byextensive infiltration of the lamina propria and submu-cosa with neoplastic lymphocytes. The nodular formcauses a segmental thickening of the bowel, most oftenin the ileocolic region, with resultant luminal narrow-

ing and partial intestinal obstruction. Metastasis to re-gional lymph nodes is common with both forms of thedisease. There are different grades of gastrointestinallymphoma commonly referred to as well differentiated(low-grade or lymphocytic), poorly differentiated (high-grade, lymphoblastic or immunoblastic), and intermedi-ate (or mixed). Studies have shown that cats previouslydiagnosed with lymphocytic plasmacytic enteritis havedown the road been diagnosed with lymphoma. Thereare definitely cases where the pathologists cannot dif-ferentiate between the two, especially on endoscopicbiopsies. Recently immunohistochemistry has been ofbenefit to help with this differentiation.Cats with gastrointestinal lymphoma are typically older

and FeLV negative. Estimates for incidence of FeLV ingastrointestinal lymphoma range from 12-30%. In arecent report of 39 cats with well differentiated gastro-intestinal lymphoma, the most common clinical signswere vomiting (87%), weight loss (79%), anorexia (53%),diarrhea (53%), and lethargy (47%). Nine percent hadneither vomiting nor diarrhea. An abdominal mass waspalpated in 26% of cats while 32% had thickened gas-trointestinal loops. Ultrasonographic examination ofthe abdominal cavity may reveal thickened intestinewith loss of normal layering, mesenteric lymphade-nopathy or additional masses or metastases to the liverand spleen. Definitive diagnosis is based on intestinal

biopsies. Studies have shown discordance between en-doscopic biopsies and full thickness biopsies obtainedat surgery.Chemotherapy is the mainstay treatment for lympho-

ma. The modified Wisconsin protocol (combinationprotocol consisting of L-asparaginase, vincristine, cyclo-phosphamide, doxorubricin, methotrexate, and predni-sone) is commonly recommended. The combinationof chlorambucil and prednisone offers a less intensiveprotocol with excellent results. Another alternative isto treat with chlorambucil (6mg/m2 2mg/5.3kg cat)every other day and prednisone (5mg /cat/day). Thisprotocol has been shown to have a dramatic and last-ing response (average 17-20 months) and has excel-lent owner compliance. As with IBD, cobalamin levels

should be supplemented if low.

Case 5: Bubba Williams The clinical signs of large bowel diarrhea, includemarked increased frequency, reduced fecal volume perdefecation, blood pigments and mucous in feces, andtenesmus.

The routine medical investigation of any dog or cataffected with chronic large bowel diarrhea should in-clude a CBC, chemistry and urinalysis. Also direct andindirect fecal examinations for helminth and protozoa,and bacterial culture of feces, may be required. Someorganisms appear to be of low pathogenicity, but it

should be emphasized that even commensal organ-isms may become pathogens given the appropriatecircumstance. Ultimately biopsies may be required fordefinitive diagnosis.Inflammatory or infectious disorders most commonlycause large bowel signs. Inflammatory bowel diseaseis a common cause. Neoplasia is another possible etiol-ogy. Polyps occur most commonly in the rectum anddescending colon of dogs, whereas they occur mostcommonly in the small intestine of cats.

Treatment for large bowel disease is based on the etiol-ogy. For IBD with primarily large bowel signs, aminosal-icylates are the drugs of choice. Sulfasalazine (dogs:12.5-30 mg/kg q8h until feces are normal for 4 weeks;

then same dose q12h for 24 weeks; then decreasedose by 50% every 2 weeks until discontinue; cats:1020 mg/kg q24h / oral suspension (50 mg/ml) easierdosing for cats) is a 5-aminosalicylic acid (mesalamine)

joined to sulfapyridine through an azo bond. Olsalazine(Dipentum dogs: 1022 mg/kg PO q8h) is 2 moleculesof 5-ASA linked by azo bond. Antibiotic therapy mayinclude metronidazole and tylosin. Histiocytic colitisin young to middle-aged Boxers and French Bulldogshas been shown to be caused by a variant of E. coli andwill resolve with ciprofloxacin (Baytril, 5 mg/kg/day).Resolution may take up to 6 weeks but they typicallyimprove within 1-2 weeks.





A N U P D A T E O N P A N C R E AT I T I SChris L. Ludlow, DVM, MS, Diplomate ACVIM (InternalMedicine), Animal Specialty Hospital, Rockledge, [email protected]

IntroductionOne study of findings at necropsy reported the inci-dence in dogs was 1.5% and in cats was 1.3%. This num-ber likely underestimates how common the disease is.One reason for this uncertainty is the difficulty in diag-

nosis. The inability to accurately diagnose pancreati-tis leads to difficulties in assessing the severity of thedisease. This in turn leads to difficulty in determiningresponse to therapy. This results in many unansweredquestions about pancreatitis and its treatment.

PathogenesisPancreatic digestive enzymes exist in the pancreas ininactive forms (zymogens) that are sequestered in lyso-somes. These enzymes are not activated until their se-cretion into the intestine. The initiating event in acutepancreatitis is the inappropriate activation of trypsin inthe pancreas. This leads to pancreatic autodigestion

and resulting inflammation, hemorrhage and poten-tially necrosis. Trypsin is an auto-catalyzing enzyme,so its presence in the acinar cells continues to cleavetrypsinogen (along with other zymogens) to the activeform, leading to a self-perpetuating process.Autodigestion is prevented in a number of ways. Zy-mogens (inactive forms of the enzymes) are packagedin lysosomes with protease inhibitors to bind activatedenzymes in the lysosome. Alpha-1 protease inhibitorand alpha1-macroglobulin are serum proteins that in-activate trypsin. Levels of these proteins in the pancre-as are dependent on adequate pancreatic blood. Theymay be rapidly consumed in pancreatitis. This may be-come an issue in hypotensive patients, either due to hy-

povolemia or shock, where blood flow to the pancreasis reduced. Pancreatitis can be readily exacerbated bydecreased pancreatic blood flow. Genetic abnormali-ties in the production of other protease inhibitors havebeen linked to a predisposition to developing pancrea-titis in people. Findings such as this may explain oneof the mechanisms of breed predisposition in animals.Additionally, inflammatory cytokines resulting frompancreatic damage alter pancreatic blood flow andmembrane permeability. They are chemotactic for leu-kocytes, which in turn produce more inflammatory me-diators and result in worsening of the process locally.Progression of pancreatitis from mild, self-limiting lo-

calized form to more severe systemic forms is the mostcommon cause for mortality in people and animals.Progression was historically thought to be mediatedby the release of proteases into the systemic circula-

tion and damage to or activation other proteins (e.g.clotting factors) leading to DIC. Recent work has re-vealed the importance of inflammatory mediators inthe systemic manifestations of pancreatitis. These maylead to the development of the systemic inflammatoryresponse syndrome (SIRS), circulatory and respiratorycollapse, and multiple organ failure (MOF). In humans,most fatalities from pancreatitis are due to SIRS andMOF. Early in the disease inflammation occurs in thepancreatic and peripancreatic tissue. In later stages ofthe disease, this process may occur secondary to infec-

tion associated with pancreatic necrosis and sepsis dueto bacterial translocation from the gut.

DiagnosisClinical signsRecent studies have shown that the presenting signs ofpancreatitis are very different in dogs and cats. Dogspresent with the more classic signs of vomiting (90%),abdominal pain (58%), dehydration (46%) and diarrhea(33%). Fever is common in more sever forms of the dis-ease. In contrast, cats rarely present with fevers, evenin the more sever cases. Clinical signs in cats tend tobe much more nonspecific including lethargy (100%),

anorexia (97%), dehydration (92%), hypothermia (68%),vomiting (35%), and diarrhea (15%).

Laboratory diagnosisIn dogs, CBC findings including a leukocytosis with aleft shift are present in about one half of the cases. Incats, leukocytosis is present in about one third, whileleukopenia can be seen in up to 15% of the cases andmay indicate a worse prognosis.Serum chemistry abnormalities may include eleva-tions in liver enzymes and bilirubin in both species.Azotemia may be present due to dehydration, but renalfailure rarely can result from pancreatitis. Hypocalce-mia is more common in cats than dogs (50% vs. 5%) and

suggests a worse prognosis

Pancreatic specific testsPancreatic enzymes have been used for years to diag-nose pancreatitis. It is important to recognize their limi-tations. Lipase may originate from other tissues (lipaseactivity remains in dogs and cats after pancreatectomy).Routine testing cannot differentiate these lipases frompancreatic lipase. Nonpancreatic disease including re-nal disease, hepatic disease, different types of cancer,heat stress and administration of corticosteriods mayresult in elevations of lipase. Sensitivity and specificityof serum lipase in the diagnosis of pancreatitis in dogs

has been reported as 73% and 55%. It should only beused as a screening tool in dogs, and only elevations of3-5 times the upper limit of normal should be consid-ered suggestive of pancreatitis. In cats, lipase had been





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shown to be normal with spontaneously occurring pan-creatitis. Amylase activity remains in dogs after pancre-atectomy, indicating other sites of synthesis. Dogs withspontaneously occurring pancreatitis have been shownto have amylase in the normal range, and nonpancre-atic diseases may result in elevations. Sensitivity andspecificity in dogs has been reported to be 62% and57%. In cats, amylase has been shown to decrease inexperimental pancreatitis. No difference in amylase hasbeen seen in pancreatitis vs. normal cats or nonpancre-atic disease.

Serum trypsin-like immunoreactivity (TLI)Serum TLI measures trypsinogen, trypsin and sometrypsin bound to proteinase inhibitors. Elevations mayoccur with pancreatitis, typically early in the disease,and resolve quickly. Elevations in dogs showed a sen-sitivity and specificity of 33% and 65% in one study. Incats, sensitivity and specificity varies depending on cut-off values (33% and 90% in one study using 100 ug/L asa cutoff value). TLI has been shown to elevate in non-pacreatic diseases including renal failure and intestinaldisease, which may result in false positives.

Serum pancreatic lipase immunoreactivity (PLI)Measurement of PLI allows specific quantification ofpancreatic lipase (vs lipase activity). It also appears tobe less affected by nonpancreatic disease (one studyshowed elevations with renal failure, but not above thediagnostic cutoff value for pancreatitis). In dogs, onestudy demonstrated a sensitivity of >80%. It appears tobe reliable in cats also. In experimentally induced pan-creatitis, rises occur similar to TLI, but elevations tendto persist longer. It has been suggested that PLI maybe more sensitive than other diagnostic tools includingimaging. Rurther studies evaluating PLI are warranted.

Diagnostic imaging

Radiographic findings in pancreatitis are very nonspe-cific. The use of CT in dogs has been very limited andadditional studies will be needed to determine theamount of information that can be obtained. In onestudy in cats, the sensitivity of CT was no better thanthat of ultrasonography.Sensitivity of ultrasound in dogs has been reported ashigh as 68%, though this is highly dependent on the op-erators skill level. Results in cats have not been as good,with a reported sensitivity of up to 35%. When changesare present, a specificity of up to 85% in diagnosingpancreatitis has been reported. Identifiable changesinclude pancreatic edema, fibrosis, calcification, and

peripancreatic fluid accumulation. Abscessation, cystformation, and neoplasia may also be detected.

TherapyTherapy for pancreatitis still remains largely supportive.Therapy centers on aggressive fluid therapy, antibiotics,and dietary therapy. Aggressive fluid therapy is criticalfor systemic cardiovascular support to prevent MOF.

The blood supply to the gut is often compromised inhypotensive, hypovolemic patients. Also rememberthat many of the protective mechanisms for the pan-creas are presented to or removed from the pancreas bythe circulatory system (antiproteases, leukocytes, wash-out of toxic metabolites and inflammatory mediators).

Antibiotic therapy There is a paucity of evidence showing bacterial in-volvement in canine or feline pancreatitis. Most evi-dence indicates that bacterial involvement, especiallyearly, is rare. One study in humans showed that theuse of prophylactic antibiotics increased the risk ofpancreatic necrosis and resultant infection. In animals,pancreatic necrosis, abscessation, and formation ofcysts are rarely reported. Certainly when evidence ofsystemic inflammation is present (fever, leukocytosiswith a left shift, etc.), antibiotic therapy is warranted.But one must question the routine use of antibiotics in

milder forms of pancreatitis. Proper selection is critical.Typically bacterial found in pancreatic lesions are of thegram-negative enteric form and aneorobes. Antibioticpenetration into the pancreas must be considered aswell. Clindamycin, metronidazole, and ciprofloxacinhave been shown to achieve therapeutic levels in thecanine pancreas.

Dietary therapy The paradigm of dietary therapy had been one ofwithholding food for pancreatic rest. The concept ofpancreatic rest is being challenged for a number of rea-sons. First, there is conflicting information regardingthe degree that feeding stimulates pancreatitic secre-

tions during pancreatitis. Whether the meal stimulatesprotease production vs. other secretions may also be ofrelevance. Meal feeding may increase pain associatedwith pancreatitis, but there is no definitive evidencethat feeding has a negative effect on the outcome inhumans or animals.In humans with more serious, protracted cases of acutepancreatitis, nutritional intervention has been shownto be beneficial. Benefits include improvement in nitro-gen balance, reduction in inflammatory mediators andincidence of SIRS and MOF, improvement in immunefunction (both systemically and at the level of the gut),decreased patient morbidity and mortality, decreased

surgical intervention, increased intestinal blood flow,decreased absorption of endotoxin and cytokines fromthe gut, and decreased risk of pancreatic infection andsepsis secondary to bacterial translocation from the




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gut. While the greatest benefits occur when it is insti-tuted early, studies show it is still beneficial when start-ed. At present, nutritional therapy is the standard ofcare in human patients with severe acute pancreatitis.Little information is available from naturally occurringanimal disease. Experimentally models of pancreatitisusing dogs and cats have shown similar.

The route of nutritional support is important. Totalparenteral nutrition has been used owing to the factthat nutrition could be provided without stimulatingpancreatic secretions. Comparison of enteral vs. paren-

teral nutrition in human pancreatitis shows the markedbenefits of the enteral route. Enteral feeding through a

jejunostomy tube (J-tube) is typically used. It has beenshown that enteral feeding downstream from the duo-denum (jejunostomy tubes) results in no more pancre-atic secretions that TPN. Should the animal require ab-dominal surgery for any reason, J-tubes may be easilyplaced at that time. One study in humans showed thatcontinuous enteral nutrition (CEN) provided through anasogastric tube did not exacerbate pancreatitis. Thisoffers the advantage of not requiring anesthesia andease of tube placement. There may also be a place forthe combination of CEN combined with peripheral par-

enteral nutrition (PPN). This would increase the chanceof meeting nutritional requirements while at the samenot over-stimulating the pancreas. This would also pro-vide nutrients for the GI tract and help prevent atrophyand bacterial translocation.Intact proteins and fats tend to have the greatest effecton pancreatic secretions. This may be minimized by theuse of diets that do not contain intact components. El-emental diets (amino acids, fatty acids, simple sugars)may cause less pancreatic stimulation. While no el-emental diets currently exist for animals, there are sev-eral human diets available. These are not nutritionallycomplete for animals but they would provide nutritionfor the GI tract and at least partially meet requirements.

Specific nutrients may help to modulate the inflamma-tory process and reduce complications associated withpancreatitis. These include glutamine and n-3 fatty ac-ids

Other therapiesThe use of plasma to replace naturally occurring anti-proteases has been recommended. While medicallysound in theory, these treatments have proven to beno benefit in pancreatitis in humans or animals. Onestudy in humans experiencing acute pancreatitisshowed faster resolution of signs and lower moralitywhen dexamethasone and Dextran 40 was added to

standard therapy. Perhaps it is time to reconsider therole of corticosteriods in pancreatitis during the initialacute inflammatory stages. Surgery continues to be asubject of debate. In human medicine, surgical therapy

is now reserved for those patients with CT evidence ofpancreatic necrosis, cyst formation, abscessation, orthose patients that are deteriorating in the face of ad-equate medical therapy. Animal studies have shown nobenefit in surgical intervention, though the numbers ofanimals have been small and criteria for surgery notwell defined.



Aumento Enz Hepaticas EVC2009

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