Pancreas: new conceps

J. Pastor, DVM, PhD, Dipl ECVCP

Veterinary Faculty

Autonomous University of Barcelona

08193-Bellaterra (Spain)

Clinical case: PomaMiniature schnauzer, femalle, 9 y

old, spayed.

Client complaint

• Doing well since yesterday.

• Started to vomiting and diarrhea.

• Now, she is vomiting 7-8 times x day, she

is unable to stand or walk, very weak.

Physical examination

• Body score 4/5

• Tachycardia 120 ppm

• Weak femoral pulse.

• Slow capillary refill time ( over 2 secs).

• Tachypnea: 40 bpm

• Abdominal painfull palpation.

Key pointAlthough pancreatitis symptoms may be very unspecific, dogs with severe

pancreatitis usually present with vomiting and cranial abdominal pain. Pancreatitis

should be suspected in animals presenting with these clinical signs. Milder cases of

pancreatitis may not necessarily present with vomiting or abdominal pain.

Clinical signs in animals with

pancreatitis

• Vomiting: 90%

• Weakness: 79%

• Abdominal pain: 58%

• Dehydration: 46%

• Diarrhea: 33%

• Fever: 21%

• Hess et al. Clinical, clinicopathologic, radiographic, and ultrasonographic abnormalities in dogs with fatal acute pancreatitis: 70 cases (1986-1995). J Am Vet

Med Assoc. 1998 Sep ;213(5):665-70.

Differential diagnosis

• Gastrointestinal:

– Foreign bodies, neoplasia, IBD, alimentary...

• Extra-gastrointestinal:

– Pancreas.

– Liver.

– Kidney.

– Metabolic / Endocrine diseases.

– Other…

Diagnostic plan

• CBC.

• Biochemistry.

• Acid-base status.

• UA.

• Abdominal x-ray.

• Abdominal ultrasound.

CBC

• RBC (x10^6/µL): 8.22

• HCT (%): 45

• VCM (fl): 62.1

• CHCM (g/dl): 32,5

• WBC (/µL): 21470

– Lymp: 3006

– Mono: 429

– Band: 215

– Segm: 17391

– Eosin: 429

• PLT (x 10^3/µL): 120

• Coagulation profile:

– PT: 12 sec (6-8 sec)

– aPTT: 30 ( 8-16 sec)

– Fibrinogen: 150 mg/dl

(200-400)

– D-dimer: > 2000 (<200)

Biochemistry

• Creat (mg/dl): 3.1 (0.5-1.5)

• Urea (mg/dl): 120 (20-60)

• Cholesterol (mg/dl): 535 (135-270)

• Tryglicerides (mg/dl): 350 (50-100)

• Glucose (mg/dl): 150 (6-118)

• Total proteins (g/dL): 5.24

– Alb: 1.6 (2.6-3.3)

– Alfa 1: 0,15 (0,2-0,5)

– Alfa 2: 1.31 (0,3-1,1)

– Beta: 1,86 (0,9-1,6)

– Gamma: 0,33 (0,3-0,8)

• Total bil (mg/dl): 0.09 (0,1-0,5)

• ALP (UI/L): 2400 (20-156)

• GGT (UI/L): 21 (1,2-6,4)

• ALT (UI/L): 800 (21-102)

• Ca (mg/dl): 9.1 (9-11,3)

• K (mmol/L): 3,74 (4,37-5,35)

• NA (mmol/L): 138 (141-152)

• Cl (mmol/L): 107,8 (105-115)

• Phosphorus (mg/dl): 5,09 (2,6-6,2)

• Lipasa (UI/l): 577 (13-200)

Laboratory changes in animals with

pancreatitis

• ALP: 79%

• ALT: 61%

• Azotemia: 59%

• Bilirrubin: 53%

• Hipoalbuminemia: 50%

• Hipercholesterolemia: 48%

• Bleeding disorders: 68%

• Hess et al. Clinical, clinicopathologic, radiographic, and ultrasonographic abnormalities in dogs with fatal acute pancreatitis: 70 cases (1986-1995). J Am Vet Med Assoc. 1998 Sep ;213(5):665-

70.

Pancreatitis

Steiner, 2003, 2009

Key points

• The degree of elevations of lipase and amylase

do not correlate with severity of pancreatitis.

– At least 3 folds increase in lipase are needed to

suspect pancreatitis.

• At present, pancreatic lipase (cPLI) is the most

sensitive biochemistry test for diagnosing canine

pancreatitis.

• Laboratory changes in animals with pancreatitis

depend on the severity of the condition, and vary

greatly between one animal and another.

Normal 200 400

Pancreatic inflammation Pancreatitis

Pancreatitis

• Small number of animals.

• Retrospective study.

• Need a blinded study

Steiner, 2003, 2009

A Multi-Institutional Study Evaluating Diagnostic Utility of

Spec cPLI in the Diagnosis of Acute Pancreatitis in DogsACVIM 2009

K. McCord; J. Davis; F. Leyva; P.J. Armstrong; K.W. Simpson; M. Rishniw; M.A. Forman

• Multi-institutional blinded study.

– Cases:• with an initial differential diagnosis that included acute pancreatitis

(APS)

• did not include acute pancreatitis (CO)

– Information:• dog history, physical examination, laboratory findings (including total

amylase and lipase), abdominal ultrasound and the clinical course.

• Cases were categorized to one of five pre-defined groups (0-4): 0--not pancreatitis, 1--not primary pancreatitis, 2--possibly pancreatitis, 3--probably pancreatitis or 4--pancreatitis.

Conclusions ACVIM 2009

• Amylase and lipase activities did not differ

between groups.

• Spec cPL sensitivity and specificity for

cases with clinical score 0 (no

pancreatitis), and 2,3,4 (pancreatitis),

calculated using current cut off values of <

200µg/L as negative and >400 µg/L

positive:– 93% sensitivity and 78% specificity.

How we use spec cPLI

• If spec cPLI is < 200 µg/L is highly unlikely

to have acute pancreatitis.

• If spec cPLI is > 400 µg/L pancreatitis may

be present (could be pancreatitis).

Why a pancreatic lipase can be

increased without primary

pancreatitis?

Non pancreatic disease

Hypoxia

Cytokines

Endotoxins

Loss membrane permability

Increase enzimes

Other causes increase cPLI

• Gastritis.

• Chronic inflammatory bowel disease.

• Chronic renal failure.

• Drugs: bromide and phenobarbital.

Penninck, D. (2008). Atlas of Small

Animal Ultrasound. Blackwell publicing

Penninck, D. (2008). Atlas of Small

Animal Ultrasound. Blackwell publicing

Definitive diagnostic tool

• Pancreatic biopsy.

– Best technique.

– Animals with pancreatitis and many complications

have high anesthetics risks.

Poma

• Spec cPLI: 1800 µg/L

• Multiple organ compromise:

– Coagulation

– Liver

– Kidney

– Hematology

– Shock and hypotension

• PROGNOSIS

Poma

• Bad prognosis.

• Treatment

Treatment• 5 Strong evidence, 0 no evidence for its use.

Steiner, J.M. Y Rozanski, E.

Rationale treatment of

pancreatitis in small animals.

ACVIM 2006, pp 628-630

IV fluids (5) and plasma

• Fluidos: 5

– Crystalloid

– Colloids.

• Plasma: 2-4

– Colloids: 2

– Inhibitors Proteases: 2-1

– Coagulation factors: 4

Systemic inflammation

Analgesia (5)

• Evidence 5.

– Butrophanol: 0.1-1 mg/kg/SC/qid

– Fentanyl:

• 2-5 µg/kg/h CRI

– Ketamine (alone or with fentanyl):

• 0.2-0.6 mg/kg/h CRI

– Morphine + lidocaine+ketamine

• 0.24 mg/kg/h, 3 mg/kg/h and 0.6 mg/kg/h

Antiemetic treatment (4)

• Vomiting due to:– Local stimulus.

– Central.

• Metoclopramide: – central

• Dolansetron/ondansetron:– Central and peripheral.

• Maropitant (Cerenia):– Central and peripheral

– 1 mg/kg/SQ/24h

Nutrition (3-4)

• Parenteral nutrition (2-3):

– high cost, complications.

• Enteral feeding:

– free acces or using nasogastric tubes...

• New concept: start nutrition as soon as

possible it will improves survival.

Antibiotics (1-3)

• Evidence: 1-3

• If there are risk of sepsis or abscess

• Grave cases.

• Broad spectrum:

– Ampiciline o cefalexine + enrofloxacine

Poma• Bad prognosis

• Treatment.

Tomy, Husky, male, 7y old

• Acute presentation of vomiting.

• Not doing well for the last month.

• Physical examination:

– Abodminal pain and distensión.

• Located in craneal abdomen.

– Pale mucous membranes.

– Tachycardia and tachypnea.

– Hypotension

CBC

• RBC (x10^6/µL): 6.55

• HCT (%): 46

• VCM (fl): 70.2

• CHCM (g/dl): 36

• WBC (/µL): 20160

– Lymp: 403

– Mono: 1008

– Band: 0

– Segm: 18749

– Eosin: 0

• PLT (x 10^3/µL): 336

• Coagulation profile:

– PT: 7 sec (6-8 sec)

– aPTT: 15 ( 9-16 sec)

– Fibrinogen: 480 mg/dl

(200-400)

– D-dimer: 1000-2000 (<200)

Biochemistry

• Creat (mg/dl): 1.1 (0.5-1.5)

• Urea (mg/dl): 70 (20-60)

• Cholesterol (mg/dl): 180 (135-270)

• Trylicerides (mg/dl): 100 (50-100)

• Glucose (mg/dl): 68 (80-118)

• Total proteins (g/dL): 4.8

– Alb: 1.2 (2.6-3.3)

– Alfa 1: 0,15 (0,2-0,5)

– Alfa 2: 1.31 (0,3-1,1)

– Beta: 1,81 (0,9-1,6)

– Gamma: 0,33 (0,3-0,8)

• Total bil (mg/dl): 0.09 (0,1-0,5)

• ALP (UI/L): 250 (20-156)

• GGT (UI/L): 5 (1,2-6,4)

• ALT (UI/L): 150 (21-102)

• Ca (mg/dl): 9.1 (9-11,3)

• K (mmol/L): 4.4 (4,37-5,35)

• NA (mmol/L): 145 (141-152)

• Cl (mmol/L): 107,8 (105-115)

• Phosp (mg/dl): 5,09 (2,6-6,2)

• Lipase (UI/l): 800 (13-200)

• Spec cPLI: 850 µg/L (<100)

Is it a pancreatitis case?

• Do we need further investigation?.

Tomy

• Abdominal fluid:– Total proteins: 3 g/dl

– WBC: 127.490/µl• Lymp: 0

• Eosinop: 0

• Macropha: 14024

• Neutrop: 1134667

– Creat: 0.7 mg/dl

– Lipase: 5136 U/L

– Glucose:, 40 mg/dl

– LDH: >2800 UI/L.

DO YOU THINK IT STILL BE

A PANCREATITIS?

Acute Pancreatitis - Conclusion

• The diagnosis of pancreatitis does not only depend on laboratory test results, but also on careful interpretation of the animal's symptoms, results of physical examination, presence of predisposing factors, correct interpretation of changes in laboratory tests, and diagnostic imaging findings, especially ultrasound.

• Vomiting and cranial abdominal pain are the most common presentations for animals with acute pancreatitis. However, milder cases of pancreatitis may not necessarily present with vomiting or abdominal pain.

New conceps: acute or

chronic

Pancreatitis spectrum

Pancreatitis: classification

• Basically histopathology and clinical

course.

• Acute:

– Neutrophils, necrosis, edema. Reversible.

• Chronic:

– Mononuclear cells and fibrosis.ç

– Often subclinical phase that end with a agute

presentetion (acute on chronic)

• Chronic pancreatitis:

– 26-34%

• Acute pancreatitis:

– 2%

• Breeds:

– Cavalier king Charles,

boxer, collies (and

Cockers)

Sensitivity of test in chronic

cases• Ultrasound:

– 56%

• TLI:

– 25%

• cPLI:

– 58%

• Lipase (3x):

– 28%

• DECREASED SENSITIVY BECAUSE LESS

PANCREAS LEFT

Acute or acute on chronic is

important?• No for immediate treatment.

• Affects long term management:

– Risk of recurrence.

– Risk of diabetes or EPI.

• Get clues at history.

• Only biopsy will give the right answer.