Non-inflammatory Exocrine Pancreatic and SI Disorders (Maldigestion and Malabsorption)

Maldigestion(EPI)

Not enough enzymes to digest food as insufficient pancreas AND ↓ intrinsic factor

→ Impaired cobalamin absorption

→ Hypocobalaminemia(Low B12)

Malabsorption

Impaired intestinal absorption of improper / properly digested food – Loss of receptors → cannot absorb IF–Cobalamin complex

Dysbiosis / SIBO: Bacteria consume cobalamin → deficiency

Maldigestion (EPI) vs Malabsorption

Both manifested by Weight Loss and Chronic Diarrhea

Polyphagia

Causes of Exocrine Pancreatic Insufficiency EPI (Maldigestion): Non-Inflammatory disease

Mainly due to pancreatic acinar atrophy (wasting away)

Juvenile atrophy (immune mediated) – young GSD

Acquired (chronic pancreatitis / fibrosis), Iatrogenic or idiopathic

Causes of Exocrine Pancreatic Insufficiency EPI (Maldigestion): Rare Pancreatic neoplasia

exocrine pancreatic adenoma/adenocarcinoma (usually focal not diffuse – thus do not destroy enough exocrine tissue to cause EPI

EPI only develops when?

exocrine capacity < 10 – 15 % normal pancreas

Pathogenesis of maldigestion: Inherited: Pancreatic acinar atrophy

Acquired: GSD

idiopathic; neoplasia; chronic pancreatitis in cats

• >85 loss of acinar cells

Pathogenesis of maldigestion: Loss of pancreatic secretions

• ↓Lipase*

• ↓Amylase*

• ↓Protease

• ↓HCO3

Pathogenesis of maldigestion: maldigestion

Fecal loss of nutrients

Nutrients are used by gut pathogens

Clinical Presentation of EPI: Clinical signs

Severe weight loss, could be gradual

• Thin hair coat

Voluminous greasy malodorous feces - steatorrhea, Undigested fat in feces

Ravenous appetite, +/-coprophagia

EPI: Species and breed variation

More common in dogs than cats

• German shepherd, Cavelier King Charles Spaniels, Chows

Routine Clinical Pathology Abnormalities EPI

CBC: Usually within reference intervals

Serum Chemistry: Usually within reference intervals

Usually normal pancreatic enzymes (amylase & lipase) → Further testing: TLI

Trypsin-like Immunoreactivity (TLI): samples

• Serum preferred but heparin plasma may be used

• Fasting 12 - 18 hours

• TLI can be falsely increased by lipemia

TLI: analysis

ELISA (and RIA) species specific antibody

• Measures trypsin and trypsinogen (mostly)

TLI: diagnostic properties

Species-specific: cTLI, fTLI at TAMU & equine TLI

• Excellent sensitivity and specificity for EPI

TLI: Low values (Diagnostic)

x < 2.5μg/L

• Decreased exocrine pancreatic mass (EPI)

TLI: high values

Pancreatitis

Renal azotemia

Equivocal results - can be due to:

Recent feeding - Inadequate fasting < 12 hours

Recovering function, Heat exposure in transit, Early EPI

• Repeat in 1 month

Best practices for TLI testing: High TLI

Usually indicates pancreatitis – NOT used for this purpose

• PLI is the test of choice for the diagnosis of pancreatitis

Trypsin only enters blood via lymphatics or peritoneal fluid when pancreatic acinar cells are damaged:

Has a very short half-life

No greater advantage than serum lipase or amylase

Small Intestinal Disease(SID)(Gastro-intestinal Disease (GID / Gut disease)

Failure of the SI to absorb digested food: Malabsorption

What causes SID?

Damage to intestinal epithelium

• Decreased absorption surface

• Intestinal lymphangiectasia

SID: Location / Distribution

Inter-luminal, Intra-luminal, Extra-luminal

Lymphangiectasia

Interluminal vs intraluminal lesions

Intra vs extraluminal

SID differential list: Degenerative

Lymphangiectasia

SID differential list: A

Angiopathic: Includes torsion, thromboembolism, and hemorrhage.

Anomalous: (Congenital) primary lymphangiectasia

SID differential list: M

Metabolic: EPI, Small intestinal bacterial overgrowth (SIBO)

– Tylosin / antibiotic resp,

Endocrine : Addison’s, Hyperthyroidism

SID differential list: N

Neoplasia: Lymphoma, Gastric or adenocarcinoma, Leiomyoma / leiomyosarcoma, Mast Cell tumor (cats), Plasmacytoma

SID differential list: I

Infection: Salmonella, Giardia, histoplasmosis, Fungal, Viral, Worms,

Inflammation: Immune-mediated (eosinophilic, lymphocytic/ plasmacytic), IBD, idiopathic

SID differential list: T

Trauma: foreign body, Intussusception, Surgery

Toxic: Dietary indiscretion, Drugs (NSAIDs), Chemo agents

SID clinical signs

weight loss

vomiting +/-hematemesis

diarrhea +/-melena

Intestinal Malabsorption-Dysbiosis(SIBO) or antibiotic-responsive enteropathy

Abnormal quality and/ or quantity of intestinal microbiome

Bacteria produce excess folate → increase serum folate

Bacteria utilize cobalamin → decreased serum cobalamin

Causes of SIBO

EPI, antibiotics, abnormal GI motility

Canine microbiota dysbiosis index (DI): Quantifies 8 groups of gut bacteria using quantitative PCR

↑Strep, ↑E.coli, ↓clostridium, ↓Fusobacterium, ↓Turicibacter, etc..

<0 = normal gut microbiota

0-2 = ambiguous or mild change in the microbiome

>2 = intestinal dysbiosis

PLE: not a specific disease, but generally refers to

GI neoplasm (lymphoma), parasites, microorganisms; bacteria, rickettsia, Johne’s dz,

PLE test: Fecal α-1 protease inhibitor

Usually found in plasma, but not feces

• Presence in feces » leakage from blood to GI

Resists degradation by proteases - Inhibits activity of proteases including trypsin when in feces

Limitation: sample must be maintained under frozen conditions

Increased fecal α-1 protease inhibitor

Protein-losing enteropathy or chronic blood loss in GI; has the same molecular weight as albumin

False positive: sample collected using thermometer

SID hematology

SID: serum chem

Limitations of Routine Laboratory Tests in the Diagnosis of SID

low sensitivity in detecting SID → may be WRI in severe SID

low specificity for detecting SID → Non-SID can cause similar abnormal laboratory results

Diagnosis of SID requires additional specialized testing

Decreased serum cobalamin: Distal SID

Absorbed in ileum (lower SI or distal SI

Decreased serum cobalamin: EPI

Failure to release cobalamin from R-proteins due to lack of HCO3

Measure serum B12 in any dog with poor response to enzyme replacement therapy for EPI

Decreased serum cobalamin: Small intestinal bacterial overgrowth (SIBO)

Intestinal bacteria bind/ utilize cobalamin

Decreased serum cobalamin: Breeds

Giant schnauzers, Beagles, Shar Pei, Austr Shepherds, Border Collies

• Selective hereditary deficiency / cobalamin malabsorption

Increased serum cobalamin

Hepatocellular injury / neoplasia

Clinical signs of Cobalamin (B12) deficiency

Chronic wasting / failure to thrive/ weight loss

Inappetance and lethargy typically present at 3-6 months of age

● GIT signs - diarrhea

● Worsening outcome of chronic enteropathies

Cobalamin deficiency: Many cats with clinical signs of chronic GI disease (diarrhea)

have decreased serum cobalamin concentrations

• show good response to Vit B12 therapy

Serum Folate

Absorbed in duodenum (upper SI or proximal SI)

Decreased serum folate: Proximal SID

Dietary deficiency

Cobalamin deficiency required for conversion to N5 –methylhydro-folate

Increased serum folate

Small intestinal bacterial overgrowth (SIBO): Due to increased synthesis of folate

EPI: Impaired synthesis and secretion of HCO3 due to Low pH

Hemolysis: RBCs are rich in folate; spun serum sample of choice

Summary vit. B12 and folate patterns

Main Causes for Decreased Serum B12

1. EPI

2. Ileal disease - intestinal villus atrophy

3. intestinal bacterial overgrowth (IBO)

• Low B12 is an indication for checking serum TLI

• Not all dogs with these conditions will have a low B12 concentration