Ettinger GI And Hepatic Disease Flashcards
In what disease states is high or low serum folate seen?
- High folate - SIBO/dysbiosis
2. low folate - proximal small intestinal disease
How is folate absorbed and metabolized from diet?
Folate aka vit B9
Folate polyglutamate is found in food and is broken down to folate monoglutamate (by folate deconjugase) and absorbed by folate carriers
It is tough that serum folate can be increased during SIBO due to production by overproliferating bacteria
How is cobalamin (vitamin B12) absorbed from the diet?
Readily found in the diet bound to animal proteins
- Pepsin and HCL release cobalamin which is then bound to R proteins produced by the gastric mucosa.
- R proteins are broken down by pancreatic protease and then subsequently complexed by intrinsic factor by the exocrine pancreas.
- These complexed units are then transported across the mucosa at the ileum (Receptor mediated Endocytosis)
**In cats, intrinsic factor is only produced by the pancreas (none made by stomach). Cats also lack the binding protein transcobalamin 1 and thus can easily deplete their cobalamin stores within a month of malabsorptive disease
What is fecal alpha 1 proteinase inhibitor and why is it a potentially important biomarker of GI disease?
It is a marker of GI albumin loss
In cases where hypoalbuminemia exists, GI Loss can be confirmed by measuring alpha 1 proteinase inhibitor.
This marker is produced by the liver and has a rate of loss through the GI tract that is proportional to albumin. It is NOT hydrolyzed in the GI tract and therefore it is measurable in feces. To improve diagnostic accuracy, three samples should be evaluated and samples should be collected after voluntary evacuation
electrical burns may result in what change systemically that may cause respiratory distress?
Non-Cardiogenic pulmonary edema
What is the underlying pathophysiology of masticatory muscle myositis? How is it diagnosed?
Autoimmune response to 2M muscle fibers found in the temporal, massager and medial and lateral pterygoid muscle
Diagnostic workup - 2M Ab titer (demonstrate Ag-Ab complexes within muscle) and rule out other causes (e.g. CT head)
What are the most common canine oral tumors?
Malignant melanoma, SCC, fibrosarcoma, osteosarcoma and PNST
What are the most common feline oral tumors?
SCC and fibrosarcoma
What are the primary differentials for dysphagia in a cat?
Structural oropharyngeal lesions (e.g. mass or foreign body), ulcers, gingivostomatitis
What is Odynophagia and what might it indicate?
Painful swallowing, clinical sign of esophageal dysphagia
What comprises cricopharyngeal dysphagia?
Cricopharyngeal Achalasia (failure of upper esophageal sphincter relaxation) and cricopharyngeal dyssynchrony (lack of coordination between upper esophageal sphincter relaxation and pharyngeal relaxation)
What are potential causes of acquired secondary megaesophagus?
Myasthenia gravis (focal, generalized), hypoadrenocorticism, vascular ring anomalies, hypothyroidism, lupus myositis, polymyopathies, polyneuropathies, dysautonomia and severe esophagitis
Prognosis - ~50%
Prognosis of acquired idiopathic megaesophagus - poor, aspiration pneumonia common
What are the different types of hiatal hernia? Which is most common? How are hiatal hernias managed?
Type I - sliding, most common, especially in brachycephalic breeds (congenital) or with increases in intrathoracic pressure causing secondary/acquired hiatal hernia
Type II - paraesophageal (part of stomach displaced cranially with abdominal esophagus remaining fixed)
Type IV - liver, stomach and SI displaced cranially
Treatment - medical management, surgery (diaphragmatic crural apposition, esophagostopexy, gastropexy) when medical management fails
What are the most common primary esophageal tumors of dogs and cats?
Dogs - fibrosarcoma and osteosarcoma
Cats - SCC
What is granulomatous colitis?
Form of GI disease (predominates in Boxer and FRench Bulldogs) that is caused typically by a fluoroquinolone responsive E. Coli (adherent, invasive E. Coli)
What are common enteropathogenic bacteria?
Clostridium perfringens Clostridium difficile Clostridium jejuni Pathogenic E. Coli Salmonella
Risk factors for C. Difficile include antibiotics prior to hospitalization and immunosuppressive therapy during hospitalization
What are prebiotics?
Non digestible dietary carbohydrates that stimulate growth and metabolism of enteric protective bacteria
What are synbiotics?
Combination of probiotics and prebiotics
What are differentials for gastrin hypersecretion and vomiting, resulting in hypochloremia, hypokalemia, and metabolic alklaosis and paradoxical aciduria?
Gastrinoma (malignant transformation of somatostatin producing delta cells of the pancreas to gastrin producing cells) Mast cell tumor Renal failure (cat CKD) Proximal duodenal obstruction/ pyloric outflow tract obstruction
When unstimulated gastric pH is <3 and serum gastrin is elevated, gastrinoma can be diagnosed by secretin stimulation test, ultrasound (focused on liver and pancreas) and pentertreotide scintigraphy
What are potential differentials for chronic gastritis?
Systemic disease Ulcerogenic or irritant drugs Gastric foreign body Parasites (Physalloptera) Rare - fungal infection (Pythian or histoplasmosis)\ Dietary allergy/ intolerance Reaction to bacterial antigen/unknown pathogen Steroid responsive gastritis
Helicobacter? - role unknown, may play a role in some patients but generally considered a commensal organism
What is the most common gastric malignancy in dogs and cats?
Gastric lymphoma
Dog classifications: nodular and diffuse (more common)
Cat classifications: small (T cell) and large (B cell or T cell)
LP inflammation can coexist and precede lymphoma
What is required to diagnose clostridium perfringens overgrowth?
Fecal enterotoxin assay
What organism is Salmon poisoning caused by?
Aka rickettsial diarrhea
Caused by Neorickettsia helminthoeca or Neorickettsia elokominica found in a parasitic fluke (Nanophytes salmincola) found in salmon in norther California to Central Washington
What are clinical signs of Salmon poisoning?
Manifests one week following ingestion of salmon and results in high fever, HGE, vomiting, lethargy, anorexia, polydipsia, oculi nasal discharge and peripheral lymphadenopathy
How is salmon poisoning diagnosed?
History of raw fish ingestion in endemic areas, operculated fluke eggs in feces and intracytoplasmic inclusion bodies in the macrophages from lymph node aspirates
How is salmon poisoning treated?
Oxytetracycline 7 mg/kg IV q 8 for 5 days + praziquantel
In what breed might gluten sensitivity occur? What are clinical signs/ manifestations of gluten sensitivity in this breed?
Irish Setters
Disease manifests at weaning or introduction of gluten and causes poor weight gain and chronic intermittent diarrhea. Some dogs may become asymptomatic later in life
Gluten sensitivity causes direct toxicity to intestinal mucosa/ induces an adverse immune reaction
What are 4 suggested criteria for the diagnosis of antibiotic responsive diarrhea?
- Positive response to antibiotics
- Relapse on withdrawal of antibiotics
- Remission on reintroduction of antibiotics
- Elimination of other causes based on diagnostic testing and histopathologic assessment
How is antibiotic responsive diarrhea treated?
Oxytetracycline, tyrosine, metronidazole
Give initial 4-6 week course with change of antibiotic after 2 weeks if suboptimal response. Patient should be challenged at the end of the trial and intermittently during long term treatment (the condition may spontaneously resolve)
Much lower doses have been shown to be just as effect as recommended starting doses
What are the difference histologic subtypes of inflammatory bowel disease (in order from most to least prevalent)?
- Lymphoplasmacytic
- Eosinophilic enteritis
- Granulomatous enteritis
- Neutrophilic enteritis (mainly seen in cats)
What is feline sclerosis eosinophilic fibroplasia?
Histologic variant of IBD that occurs in middle aged cats and rag dolls.
Histologic ally there are eosinophils interspersed with fibroblasts, bands of collagen and bacteria. Affected cats typically respond well to steroids.
What is proliferative enteritis?
Rare form of IBD characterized by mucosal hypertrophy
Links have been drawn to infectious etiologies such as lawsonia intracellular is, campylobacter, and chlamydia
What are breed specific forms of inflammatory bowel disease?
- Basenji enteropathy
- Familial PLN/PLE of Soft coated Wheaten Terriers
- Lymphoplasmacytic enteritis and cobalamin deficiency in Chinese Shar peis
What is intestinal lymphangiectasia and what does it cause?
Marked dilation and dysfunction of intestinal lymphatics resulting in loss of protein, cholesterol and lymphocyte rich lymph resulting in a PLE, lymph open is, and predisposition to inflammation or neoplasia (gastritis or gastric carcinoma in Norwegian Lundehunds)
Primary lymphangiectasia - congenital
Secondary lymphangiectasia causes - 1) infiltration and obstruction of lacteals by inflammatory, neoplasticism or fibrosing processes, 2) thoracic duct obstruction c) R CHF or cardiac tamponade
What are the most common small intestinal tumors in cats?
Lymphoma —> adenocarcinoma —> mast cell tumors
What are the most common small intestinal tumors in dogs?
Adenocarcinoma —:> smooth muscle tumors (leiomyoma/sarcoma) —> stromal cell tumors ( GIST, etc)
What is crypt disease? How is it diagnosed?
Cause of PLE where crypt abscessation occurs without significant inflammation, lymphangiectasia, or neoplasia.
Diagnosis - full thickness biopsies
What are clinical forms of feline alimentary lymphoma?
- Intermediate to high grade T or B cell - usually focal mass, MST 7-10 months with multi agent chemo
- Low grade T cell - diffuse thickening, MSY 19-29 months with either multi agent chemo or oral only pred and chlorambucil - useful when IBD and lymphoma can’t be differentiated
- Large granular lymphocytes - present with focal intestinal mass +/- extra intestinal lymphoma - MST 17 days
What are phenotypic forms of feline alimentary lymphoma?
Mucosal T cell (small to intermediate cell) - MST 29 months
Transmural T cell (large cell) - MST 1.5 months (increasing prevalence among cats)
TRansmural B cell (MST 3.5 months )
What is a gastrointestinal stromal tumor (GIST)?
Tumor similar to tumors of smooth muscle origin but cells or origin are interstitial cells of cajal
There are two paraneoplastic syndromes that can occur with GIST: hypoglycemia (due to production of IGFII like peptide)
Erythrocytes is (due to production of EPO like molecule) nephrogenic DI
What breeds predisposed to copper storage hepatopathy?
Labs (female predisposition) Dobermans (females) Dalmatians Skye terriers WHWT Bedlington terriers - due to COMMD1 mutation
What breeds are predisposed to idiopathic chronic hepatitis?
Labs Standard poodle Doberman Cocker spaniel (American and English) English Springer Spaniel
What breeds ( dog and cat) are predisposed to hepatic amyloidosis?
Cat - Abyssinians, Orientals, Siamese
Dog - Shar pei
What degree of hyperbilirubinemia would be needed for clinical icterus to occur?What about discoloration of plasma hematocrit?
Clinical icterus - > 3-5 mg/dL
Plasma discoloration - ~> 0.5-1 mg/dL)
What is S-adenosine methionine (SAMe)?
Cytoprotective agent for hepatocytes that is thought to prevent depletion of hepatic glutathione
Used as adjunctive therapy for acute hepatic insult, chronic hepatitis, copper hepatopathy, hepatic lipidosis
What is N-acetylcysteine?
Formulation of L-cysteine - hypothesized to replenish intracellular cysteine and glutathione concentrations
Used in cases of acute hepatic insult and feline haptic lipidosis
What is Silymarin?
Mix of compounds from milk thistle plant that is hypothesized to scavenge free radicals and reduce lipid peroxidation.
Can be used during Amanita intoxication and during treatment with lomustine
Silymarin + phosphatidylcholine (increases bioavailability) = Denamarin
What role does Vitamin E play in liver disease?
Alpha tocopherol - most biologically active form of vitamin E, thought to have antioxidant effects.
Has a validated role as an antioxidant
What is the mechanism of action of ursodiol/ UDCA/ ursodeoxycholic acid?
Non-hepatotoxic, hydrophilic bile acid that is believed to be beneficial as 1) it replaces toxic hydrophobic bile acids, 2) it has a choloretic effect, 3) it prevents hepatocyte apoptosis and 4) it is immunomodulatory (blocks expression of IL2)
What is D-penicillamine?
Chelating agent combining with copper allowing excretion via the urine
IT is also an anti-fibrotic agent that has well established studies to support its use in copper associated chronic hepatitis
Side effects - predominantly GI upset, copper deficiency, copper associated hemolytic anemia, possible vitamin B6 (pyridoxine)
What is Trientine?
Second choice chelating agent to D-penicillamine when patients do not tolerate D-penicillamine side effects.
Poor evidence for use
What role does zinc supplementation play in regards to copper chelation?
Zinc acetate is used following chelation therapy in combination with dietary copper restriction to minimize copper absorption through increased upregulating synthesis of metallothionine in enterocytes, which binds copper and results in copper loss through sloughed enterocytes. Highly effective with minimal side effects. HAs been used as a sole therapy in Wilson’s disease
Dosed as elemental zinc at 5-10 mg/kg q 12 PO
When should copper chelating therapy be instituted?
When copper quantification is >1500 mcg/g (regardless of distribution) OR copper quantification is >750 mcg/g and the distribution is centrilobular
What is colchicine?
Hypothesized effect includes reduced inflammation and fibrosis following binding of tubulin thereby preventing mitosis. Causes significant GI upset, has questionable efficacy
What are the histopathologic categories of hepatitis?
Infectious Granulomatous Eosinophilic Lobular dissecting Idiopathic
What is the most common cause of INFECTIOUS canine hepatitis?
Leptospirosis
What are the four histopathological categories of cholangitis?
- Neutrophilic - cats
- Lymphocytic - cats
- Destructive - rare, in dogs
- Chronic (associated with liver fluke parasitism) - cats
Which dog breed can have high serum bile acids without liver dysfunction?
Maltese
What is glycogen like vacuolar hepatopathy of Scottish Terriers?
Poorly characterized hepatopathy occurring in middle aged Scottish Terriers in the USA and France
Individuals present with clinical and biochemical changes consistent with Cushings but ACTH stimulation, LDDST and response to therapy is not seen.
Treatment involves SAMe and closer monitoring, as these individuals are predisposed to hepatocellular carcinoma
What is superficial necrolytic dermatitis and how is it treated?
Aka hepatocutaneous syndrome
Characteristic hepatopathy predominantly of dogs
In humans, this disease is associated with glucagonoma and diabetes mellitus (secondary to hyperglucagonemia), though this does not seem to be definitively apparent in dogs
Affect dogs: usually older small breed male with possible link to phenobarbital usage
Clinical appearance: hyperkeratotic, erythematous skin lesions found on paw pads, nose, peri orbital and perinatal regions due to serum amino acid deficiency
Diagnosis - skin biopsy, minimum database, and ultrasound (characteristic Swiss cheese appearance or hypo echo is nodules with hyper echo is boders)
Treatment - high quality, high protein, highly digestible diet +/- egg yolks +/- parenteral amino acid supplementation and supportive skin treatments
Prognosis - poor, euthanasia generally within 6 months
What are the two forms of amyloid? Which form causes disease?
- Normal soluble form
2. Abrnormal auto-aggregated fibrillation form - accumulation of this form locally or generally causes disease
What is the most common source of amyloid?
Serum amyloid A - acute phase protein produced in large amounts during inflammatory disease
What feline breeds are predisposed to hepatic amyloidosis? What are other important organ sites of involvement in this disease process?
Abyssinian and Siamese
Renal involvement
What dog breed is predisposed to systemic amyloidosis?
Shar pei
How is amyloidosis treated? What is the prognosis?
Supportive care, colchicine
Poor prognosis
What is hemochromatosis?
Iron overload - primary or secondary to cholestasis (or iron ingestion?/toxicity)
What drug can be used safely at analgesic/antipyretic doses in dogs, but causes hepatotoxicity in cats?
Acetaminophen
Why is acetaminophen hepatotoxic in cats?
Cats do not have expression of glucuronidation enzyme UGT1A6
How does acetaminophen toxicity typically manifest in cats? How is toxicity treated?
Cyanosis and methemoglobinemia, then hepatotoxicity
Treatment - by glutathione N-acetylcyteine (glutathione precursor) and SAMe
Does phenobarbital cause dose dependent or idiosyncratic hepatotoxicity in dogs? By what mechanism?
Dose dependent, through up-regulation of CYP450 and subsequent increases in bio activation of other drugs, dietary and environmental toxins.
Toxicity can occur with chronic administration, regardless of dose, but c/s can be alleviated with dose reduction. Main treatment - switch to alternative AED
Do potentiated sulfonamides cause a dose dependent or idiosyncratic hepatotoxicity? What are other potential side effects of potentiated sulfonamides?
Idiosyncratic hepatotoxicity
Other side effects: fever, transient neutropenia, thrombocytopenia, hemolytic anemia, poly arthropod hypertension, proteinuria, KCS, skin lesions, uveitis
What is the incidence rate of carprofen associated idiosyncratic hepatotoxicity?
0.05%
