Protein Losing Enteropathy Flashcards
Obj: Describe pathogenesis of PLE and difference between primary and secondary lymphagiectasia
Obj: Explain pathophysiology of common complications in patients w/ PLE and develop a management plan
Obj: Given a scenario, diagnose and recommend treatment for primary lymphangiectasia, including localization of protein loss
Obj: Contrast treatment, diagnostic test, and prognosis between primary lymphangiectasia and CE without protein loss
Obj: Given a patient scenario, evaluate risk factors for gastric ulceration and prioritize differentials for melena/hematochezia
Obj: Based on drug mechanisms and evidence of efficacy, develop a treatment plan for patients with GI ulceration
What are the different pathophysiologic causes behind Protein-losing enteropathy?
- Mucosal barrier injury
- Inflammation/infiltration
- Increased permeability
- Plasma protein leakage
- Mucosal erosions/ulcerations
- Lymphatic dysfunction
- Normal: ingestion of dietary fat packaged into chylomicrons → Chylomicrons enter lacteals → submucosal/mesenteric lymphatics → thoracic duct → Cranial vena cava
- Disruption of chyle flow → extravasation/leakage of protein-rich intestinal lymph
What are the specific etiologies of Protein-losing enteropathy?
- Mucosal Erosions/ulceration
- Intestinal Crypt Disease
- Lymphangiectasia
- Primary:
- idiopathic dilation of lacteals
- lymphatic dysfunction → chyle stasis -. lacteal rupture/leakage
- Breed-associations
- yorkshire - primary
- Maltese - primary
- Soft-coated wheaten terrier - Idiopathic IBD + PLE (primary) + PLN
- Norwegian lundehund - primary + idiopathic IBD
- Rottweiler - Primary + idiopathic IBD + crypt lesions
- idiopathic dilation of lacteals
- Secondary:
- Infiltrative disease
- Neoplasia (80% of patients with GI lymphoma)
- Severe inflammatory bowel disease (10% of patients with IBD)
- Infectious disease (histoplasmosis, pythium
- Infiltrative disease
- Primary:
What are the clinical signs of PLE?
- Diarrhea - 65-90%
- Effusion/Edema 50-80%
- Weight loss 80%
- Vomiting 30%
- Anorexia 20%
- Lethargy 20%
What are the consequences of PLE?
- Decreased Albumin (panhypoproteinemia)
- Decreased oncotic pressure
- cavitary effusions (Pure transudate)
- Edema
- Hypercoagulability
- loss of anti-coagulant proteins (i.e Antithrombin)
- Vit & Mineral deficiencies
- Fat Soluble Vitamins: ADEK
- Hypovitaminosis D
- low serum 25-hydroxycholecalciferol associated with more severe clinical signs and worse histopathologic scores
- Documented in cats w/ chronic diarrhea due to IBD & lymphoma
- serum concentrations correlate with albumin
- Hypovitaminosis D
- Fat Soluble Vitamins: ADEK
How is PLE diagnosed?
- CBC
- may be normal
- stress leukogram
- lymphopenia
- Anemia of chronic disease
- Chem
- Panhypoproteinemia
- Hypocholesterolemia
- Electrolyte abnormalities
- hypocalcemia
- total - due to ⇣ albumin
- ionized - due to ⇣ Vit D
- hypomagnesemia
- Hyponatremia, hypochloremia, +/- hyperkalemia (effusion-related)
- hypocalcemia
- UA
- normal unless concurrent disease
- Rule out concurrent PLN
- Tests for GI protein loss:
- Fecal alpha-proteinase inhibitor
- Similar size to albumin
- not degraded in feces → increased in fecal samples of dogs with PLE
- Helpful to localize low albumin to GI loss in patients w/out diarrhea
- Fecal occult blood
- stool based assay that detects heme, resulting in an oxidation reaction and color change
- Sensitive but non-specific test in dogs and cats (good rule out test)
- Fecal alpha-proteinase inhibitor
- Imaging - abdominal ultrasound
- Hyperechoic mucosal striations
- 75% sensitive, >90% specific
- GI mucosal thickening +/- loss wall layering
- Hyperechoic mucosal striations
- Biopsies
What is the treatment for PLE?
- Diet
- different for primary and secondary lymphangiectasia
- Anti-inflammatory/immunosuppressive therapy
- many options
- Vit D supplementation
- Calcitriol 0.03-0.06 ug/kg/day
- Calcium Carbonate
- 0.5-4g elemental calcium/day
- 1g calcium carb = 400mg elemental calcium
- Anticoagulant
- plavix 1-3mg/kg q24hr
- Cobalamin
- Dogs 250-1000 ug SQ q7d for 6wks then q30d
- Cats 2050 ug SQ q7d for 6wks then q30d
- OR daily oral dosing
What are the different diets for PLE?
- Primary Lymphangiectasia
- Low to ultra low fat
- Formulated - Hills, Royal Canin, Purina
- Home-cooked - Potato & whitefish, low-fat turkey, cottage cheese, cooked egg whites
- Low to ultra low fat
- Secondary Lymphangiectasia to sever IBD
- combination Low fat + novel protein/hydrolyzed
What are the options for Anti-inflammatory/immunosuppressive therapy for PLE treatment?
- Corticosteroids
- Chlorambucil
- Cyclosporine
- Mycophenolate
- Azathioprine - NEVER use in cats
- Octreotide (somatostatin analog)
- Mechanisms:
- ⇣ GI blood flow and fluid secretion
- ⇣ Triglyceride absorption
- ⇣ lymphatic flow
- Mechanisms:
What is the distribution of Protein-losing disease in Soft-coated Wheaten Terriers?
- PLE in 34%
- PLN in 40%
- Combined PLE + PLN 30%
What is the case of Protein-losing disease in Soft-coated Wheaten Terriers?
- Genetic mutation → immune dysregulation
- Complex mode of inheritance
What clinical signs of Protein-losing diseases are seen in Soft-coated Wheaten Terriers?
- Diarrhea (90%)
- Vomiting (65%)
- weight loss (55%)
- effusion (40%)
- thromboembolism (up to 20%)
What complications of Protein-losing disease are seen in Soft-coated Wheaten Terriers?
- PLE: Non-responsive effsion, thromboembolic disease
- PLN: Renal failure, systemic hypertension, thromboembolic disease
What is the prognosis of PLE in Yorkshire terriers?
- MST - 44 months in responsive animals, 12 months in non-responsive
- 40% - Complete response
- <15% - Partial response
- 50% - no response w/ diet and prednisone
What are the negative prognostic indicators for PLE in Yorkshire terriers?
- Clinical - vomiting
- Laboratory:
- monocytosis
- severe decrease in albumin
- Low BUN
- Villus blunting (survival <4mo)
What is the prognosis for protein-losing diseases in Soft-coated Wheaten terriers?
- PLE: 5mo MST
- PLN: 3mo MST
- PLE + PLN: 2mo MST
What is the prognosis for PLE? (overall not breed specific)
- >50% mortality in 3mo
What causes death in PLE cases?
- Thromboembolic disease
- (e.g. pulmonary thromboembolism)
- Non-responsive effusion
- Malnutrition
How can response to treatment for PLE be monitored?
- Responders:
- takes 14days (up to 80days) for Albumin to increase >2g/dL
What are the negative prognostic indictors for PLE? (overall not breed specific)
- Clinical:
- Ascites
- Chronic enteropathy activity index >12
- lack of clinical response at 4-8wks
- Laboratory:
- Albumin <½g/dL
- Hypocobalaminemia
- ⇡/⇣ BUN
- Histo: Crypt abscesses
What are the positive prognostic indicators for PLE?
- Normalization of canine inflammatory bowel disease activity index score and serum albumin with first 50 days of treatment
- Response to a diet trial
What are the clinical signs of GI Ulceration?
- Vomiting (90%)
- Hematemesis (30%) or Melena (30%)
- not observed in all patients
- Abdominal pain
- Hypersalivation
- Anemia-related if chronic or severe
What is melena?
- Black, tarry stool de to hemoglobin breakdown
What lab abnormalities are common with GI ulceration?
- Anemia: regenerative or non-regenerative depending on chronicity
- Microcytosis with chronicity and development of iron deficiency
- Elevated BUN:Creatinine
- Panhypoproteinemia
How are GI Ulcerations diagnosed?
- Rule-out toxins and systemic disease
- Other causes of melena:
- Hemoptysis, oral hemorrhage, epistaxis, congenital/acquired coagulopathies
- False-positive w/ bismuth and salicylate anti-diarrheal medications
- Other causes of melena:
- Abdominal imaging
- Rads: Normal unless GI perforation
- US: GI mural lesion, GI mucosal defect
- Both may be normal
- Endoscopy and biopsies
- Capsule endoscopy (pill camera)
What are the causes of Gastric (or gastroduodenal) ulcerations?
-
Drugs
- NSAID + steroid therapy **
- NSAIDS
- Steroids - usually w/ another high-risk disease process
- may produce sub-clinical gastric ulcerations
-
Increased Gastric acid secretion
- Mast cell disease
- Gastrinoma
- Liver failure - associated with portal hypertension with cirrhosis and patients with intrahepatic portosystemic shunts
-
Local disease
- Gastric neoplasia
- Chronic, severe gastritis
- Pyloric outflow obstruction
-
Hypoperfusion/”Stress”-related conditions
- Hypotension or hypovolemia (pancreatitis, anesthesia)
- Sepsis
- Spinal cord disease (intervertebral disc disease)
- Hypoadrenocorticism
- Exercise-induced (sled dogs)
What causes GI ulceration in cats?
- Neoplasia - gastric lymphoma*, mast cell tumors, gastrinoma
- Benign disease - IBD
- NSAIDS
- Liver Failure
What is the treatment for PLE?
- Treatment of underlying disease
- Gastroprotection
- Proton pump inhibitors
- omeprazole 1mg/kg q12h
- Mucosal barrier coating agents
- Sucralfate, barium
- Prostaglandin analogs if NSAID induced - Misoprostol
- Proton pump inhibitors
- Surgery if non-responsive to medical management or resectable neoplasiae
