Hepatobiliary System Flashcards
Cause of prehepatic hyperbilirubinemia
Hemolysis
Cause of hepatic hyperbilirubinemia
Inadequate uptake, conjugation and/or excretion
Cause of posthepatic hyperbilirubinemia
Abnormal biliary excretion of bilirubin
Most common type of PSS in cats
Extrahepatic
Cause of ascites in liver disease
Portal hypertension
Non-hepatic causes of liver enzyme elevation
- exogenous corticosteroid administration
- endogenous increase in corticosteroids
- phenobarbital
- injury to organs with portal venous drainage (esp. GI tract and pancreas)
Names of liver lobes
- left medial
- left lateral
- right medial
- right lateral
- caudate
- quadrate
Hepatic Lipidosis
OVERVIEW
- predisposing factors: obesity, anorexia, stree
- PRIMARY FORM: overweight cats fasted for prolonged period of time but have no identified underlying dz
- SECONDARY FORM: associated with another dz (DM, pancreatitis, renal dz, cholangitis, IBD, neoplasia, hyperthyroidism)
- To prevent FHL in dieting cats, recommend no more than 1lb or 10% of body weight loss per month
- Hepatic ketogenesis is noted with increased BHB levels compared to normal cats
- Healthy obese cats have excessive hepatic lipid accumulation (liver extracts fatty acids —> converts to triglycerides at greater rate than required for energy or lipoprotein dispersal); starvation exacerbates hepatic triglyceride accumulation due to release of large amounts of fatty acids from adipose stores during periods of rapid wt loss
- Lipoprotein synthesis limited due to reduced availability of nutrients during hypo- anorexia, promotes hepatic lipid (triglyceride) accumulation, which interferes with hepatic function and results in liver failure
- Marginal intake/syringe/force feeding of inadequate nutrition or admin of IV dextrose will worsen hepatic triglyceride storage; feeding balanced diet with sufficient calorie intake and protein content is CRUCIAL for FHL recovery
CLINICAL SIGNS
- totally or partially anorexic for days-weeks, resulting in sudden weight loss
- +/- jaundice
- +/- intermittent vomiting, diarrhea, constipation
- dehydration
- add’l c/s based on underlying dz process(es)
- severe FHL = head pressing, depression, ptyalism
DIAGNOSIS
- characterized by extensive vacuolation of hepatocytes
- in healthy cats: ~5% of liver tissue contains lipids, compared to greater than 50% in FHL
- CBC/chem = elevated ALP/ALT/AST, normal to low GGT (unless underlying Chloe static dz), elevated t bili (possibly with bilirubinuria/bilirubin crystalluria)
- AUS = hyperechoic liver (normal liver isoechoic to kidney and hypoechoic to surrounding fat)
- Cytology or histopath required for definitive dx (histopath/bx requires profound sedation or GA, and is preferred if FHL is questionable)
- cyto/histopath = highly vacuolated cytoplasm consistent with lipid accumulation, resulting in vacuolar hepatopathy (pathologist should grade as mild, mod, marked, or severe which aids as a prognostic inidicator)
TREATMENT
- IVFT for dehydration
- normal nutrition required to reverse dz (appetite stimulants may be enough if early), e-tube often needed
- treat underlying dz
- slow increase in food required due to villus atrophy and ileus in GIT, nausea common with reintroduction of food; antiemetics and GI motility agents can be helpful (cerenia, metoclopramide, ranitidine)
- once receiving 100% DER, split into 3 feedings, can be discharged from hospital; tube can be removed once cat is eating a normal amount of food on it’s own
- can recheck labs to ensure values have returned to normal
Hepatic Encephalopathy
OVERVIEW
- liver acts as filter of potential toxins from the gut
- vascular shunting allows toxins direct access to systemic circulation by bypassing liver detoxification
- CONGENITAL SHUNTS: vasculature bypasses liver
- ACQUIRED SHUNTS: caused by severe liver damage, secondary to infection or other insult
CLINICAL SIGNS
- depression, behavior abnormalities, pacing, head pressing, rarely seizures
- signs typically worse after eating
DIAGNOSIS
- CBC = mild, microcytic nonregenerative anemia
- chem = decreased BUN, albumin, cholesterol, glucose
- elevated ammonia
- severely elevated bile acids
- UA = urate crystalluria
- AXR = possibly microhepatica
- AUS = possible microhepatica
- definitive dx by CTA, bx required for microvascular dysplasia
TREATMENT
- medical management may be indicated prior to sx, or is exclusive treatment for microvascular disease
- fluid therapy to correct and maintain hydration, electrolyte abnormalities, glucose levels, metabolic acidosis
- lactulose PO or lactulose enema; metronidazole/ampicillin/neomycin (to reduce bacterial translocation); FFP/vitamin K for coagulopathies; GI protectants: famotidine/omeprazole/esomeprazole, misoprostal, sucralfate; seizure control: phenobarbital, KBr, keppra, AVOID BENZOS; mannitol if cerebral edema; hepatic protection: SAMe, ursodeoxycholic acid (ursodiol), milk thistle, L-carnitine (cats)
- surgical attenuation is the goal, partial shunt occlusion has a worse prognosis; however majority of pets have insufficient portal development at time of surgery and 30-50% of EHPSS and <15% of IHPSS tolerate complete attenuation. If portal hypertension acutely: ascites, intestinal congestion, diarrhea, hypoxemia, and possible bowel death; if portal hypertension chronically: multiple acquired EHPSS secondary to chronic portal hypertension
- amaroid constrictor devices (ACD) allow gradual closure of single EHPSS, eliminating concern for postoperative portal hypertension
NUTRITION
- HE results from loss of hepatic detoxification and subsequent accumulation of encephalotoxins within the systemic circulation and CNS
- low protein diet = K9: 3-4g protein per 100kcal of diet, cats: 6-7g protein per 100kcal of diet
- use of high quality protein
- branched-chain amino acids (BCAA) preferred over aromatic amino acids (AAA)
- feed several small meals, reducing ammonia load after each meal
Hepatic Vascular Anomalies
MACROVASCULAR PORTOSYSTEMIC SHUNTS (PSS)
- single PSS most common congenital macrovascular anomaly with communication between portal vein and systemic venous circulation (caudal vena cava or azygos vein)
- extrahepatic portosystemic shunts (EHPSS) = more common in small breeds; rarely two or more congenital communications possible; single portocaval EHPSS most common finding (66-75% of congenital vascular anomalies in cats and dogs)
- intrahepatic portosystemic shunts (IHPSS) = more common in large breeds
- abnormal vascular channels that divert blood from portal vein to other vessels (caudal vena cava, azygos vein)
- allows enteric toxins to bypass hepatic detoxification and enter systemic circulation
- results in elevated bile acids and ammonia
- NORMAL HEPATIC PORTAL VASCULATURE: portal vein drains blood from the abdominal viscera (spleen, intestines) and courses to liver; portal blood then flows through liver for metabolism and detoxification prior to distribution to systemic circulation
- PSS are named for the vessels that they join ex) portocaval shunt joins the portal vein to the caudal vena cava
CLINICAL SIGNS
- small body stature, failure to thrive, poor body condition
- neuro signs: depression, head pressing, lethargy, blindness, seizures more common after eating, and are secondary to hepatic encephalopathy
- PU/PD, lower urinary tract signs, and ptyalism also possible
DIAGNOSIS
- CBC: mild microcytic nonregenerative anemia
- chem: may be normal, but decreased BUN, glucose, cholesterol, creatinine, and albumin are common; mildly elevated ALP/ALT possibly but not always, total bilirubin normal or elevated
- UA: isosthenuria, ammonium urate or biurate crystalluria possible
- severely elevated bile acids (pre and post prandial) = best indicator
- elevated ammonia if HE
- AXR = microhepatica, possible renomegaly or cystic calculi (though majority or urate crystals are radiolucent)
- AUS = microhepatica, possible visualization of PSS
- gold standard = CTA; portal scinitigraphy and contrast portography also options
TREATMENT
- medical management: lactulose, antimicrobial therapy (ampicillin, metronidazole, neomycin), seizure therapy (see HE for txt)
- surgical attenuation: gradual constriction with amaroid constricting device preferred, complete ligation without sufficient pratap vasculature may lead to portal hypertension postoperatively
NUTRITION
- low protein diet, at least until medical or surgical management achieved
- mild copper restriction
- supplementation with antioxidants, vitamin K
PRIMARY PORTAL VEIN HYPOPLASIA (PVH)
- PVH with portal hypertension = formerly noncirrhotic portal hypertension
- PVH without portal hypertension = formerly microvascular dysplasia
ACQUIRED PORTOSYSTEMIC SHUNTS (APSS)
- caused by portal hypertension
- secondary to hepatic fibrosis (cirrhosis)
- secondary to hepatic arteriovenous malformations (HAVMs): formerly hepatic arteriovenous fistula; rare condition of multiple high-pressure arteries and low-pressure venous communications; typically congenital (both dogs and cats); typically branch of hepatic artery communicates with portal vein via dozens to hundreds of aberrant shunting vessels
Cholecystitis
OVERVIEW
- used to define both inflammatory conditions of the GB, and GB-related symptoms in the absence of gallstones
- encompasses wide variety of acute and chronic disease, with or without bacterial or parasitic infections
- predisposing factors include: bile stasis, GB mucoceles, ascending bacterial or parasitic dz, biliary neoplasia
- in cats bacterial infections thought to be 2nd to inflammation rather than inciting factor
- concurrent choleliths sometimes identified, causal relationship unknown
- may develop necrotizing cholecystitis —> considered separate dz due to severe manifestation, increased risk of complications, higher mortality rate
CLINICAL SIGS
- acute or chronic
- mild cases often asymptomatic
- moderate to severe acute cases: anorexia, vomiting, abdominal pain, fever, +/- icterus
- chronic cholecystitis more difficult to manage: intermittent anorexia, vomiting, progressive weight loss +/- abdominal pain; abdominal effusion with cholecystitis due to GB rupture and bile peritonitis
DIAGNOSIS
- cholestastic pattern: elevated ALP and GGT (these are bound to cell membranes of biliary epithelial cells); GGT more specific
- fluid analysis of abd effusion: yellow green fluid suggestive of bile, suppurative inflammation with or without bile pigments, intracellular and extracellular bacteria common, total protein 2.9-5.6 g/dL; if bilirubin is greater than twice that of peripheral blood = biliary rupture
- AXR = decreased serosal detail consistent w/ effusion, choleliths, emphysema of GB
- AUS = suspended sediment, choleliths, thickened GB wall, EHBO, emphysema of GB, CATS: hyperechoic sludge in GB or extrahepatic biliary tree indicative of cholecystitis (biliary sludge normal/common in older dogs); pericholecystic fluid and omental adhesions are suggestive of perforation
- cholecystocentesis can be diagnostic and therapeutic: less risk when drained completely; bile peritonitis and vasovagal collapse are known complications; C&S: E. coli, Entercoccus spp, Bacteroides spp, Streptococcus spp, Clostridium spp, and Helicobacter spp most common. Transhepatic approach preferred as liver will provide some pressure hemostatis
TREATMENT
- medical management: antimicrobials (80% isolates sensitive to ciprfloxacin and aminoglycosides) for minimum 1 month possibly longer, IVFT, analgesics
- surgical: cholecystectomy preferred in severe cases or with bile peritonitis
EMPHYSEMATOUS CHOLECYSTITIS
- rare management of acute cholecystitis complicated by gas-producing organisms
- gas may accumulate in lumen, wall, pericholecystic tissues
- AXR = spherical to ovoid gas opacity superimposed over hepatic silhouette
- AUS = gas interface in the area of the GB with variable distal shadowing; GB wall, echogenic sediment, fluid may be obscured; adhesions, pericholecystic fluid, general echogenic effusions correlate with biliary rupture
- CT ideal for dx
- surgical intervention most appropriate due to high risk of GB rupture and septic peritonitis
- anaerobes most common anaerobes, including E coli and Clostridium perfringens.
- fluoroquinolones, metronidazole, chloramphenicol commonly used
Gallbladder Mucocele (GBM)
OVERVIEW
- non inflammatory condition in which GB has become distended by abnormal accumulation of mucus and inspissated bile, which forms a gelatinous mass in GB lumen
- disease of dogs (one cat and one ferret), mostly middle-aged small to medium dogs (Shelties, mini schnauzers, and Cocker Spaniels predisposed)
- complications include: EHBO, cholecystitis, necrotizing cholecystitis, bile peritonitis, pancreatitis
- possibly related to heritable disorders like familial hyperlipidemia —> hyperlipidemia (through high biliary cholesterol levels) promotes more viscous bile and may stimulate mucin secretion —> increasing bile viscosity and potential for impaired GB emptying (both which predispose for GBM)
- possible association with HAC (+/- hypothyroidism as well)
- high-dose exogenous steroids = higher levels unconjugated bilirubin in extrahepatic biliary tree —> injury of biliary epithelium —> mucin secretion increases —> mutinous hyperplasia (one of the defining histologic features of GBM)
- 50% of patients with GBM have concurrent liver dz, could be coincidental or could be result of secondary cholestatic liver injury caused by GBM-related biliary obstruction
CLINICAL SIGNS
- many incidental findings
- C/S of acute abdomen associated with bile peritonitis, EHBO, pancreatitis
- vomiting, anorexia, lethargy, abdominal pain (fever if bacterial cholecystitis or bile peritonitis); icterus in 40% of patients
DIAGNOSIS
- CBC: leukocytosis seen in ~50% cases; neutrophilic leukocytosis with left shift occur most commonly with bile peritonitis, bacterial cholestasis, or bacterial cholangiohepatitis
- chem: indistinguishable from other hepatobiliary dz; elevated ALP, ALT, GGT (ALP predominant), hyperbilirubinemia
- AXR: useful to exclude other hepatobiliary dz, but not diagnostic for GBM; +/- hepatomegaly, +/- abdominal effusion, +/- mass effect in right cranioventral abdomen (distended GB)
- AUS: required for definitive dx; immobile echogenic material in GB lumen (characterized as striated or stellate “kiwi fruit” appearance); echogenic peritoneal fluid around GB if ruptured; focal thinning of discontinuity of GB wall is good indicator for rupture (but in many dogs rupture is not detectable on AUS)
- abdominocentesis (if ascites) to evaluate for bile peritonitis
- cPLI to assess for concurrent pancreatic disease
- aerobic and anaerobic culture of bile (via percutaneous cholecystocentesis or surgery) to direct abx txt
- histopath = cystic mucinous hyperplasia +/- thickening of GB wall; concurrent hepatitis or other hepatopathies are common
TREATMENT
- medical management: considered for asymptomatic or mildly affected; treat with choleretics (ursodiol) and SAMe, anaerobic antimicrobials (minimum 4-8 weeks) if C&S not available
- surgical intervention (cholecystectomy) is essential with rupture and bile peritonitis, also curative for less complicated GBM
NUTRITION
- low fat diet (7-15%)
- especially for patients with hyperlipidemia
Feline Cholangitis Complex
OVERVIEW
- feline inflammatory liver disease termed feline cholangitis complex
- primary cholangitis with inflammation centered on the intrahepatic biliary system; some cases inflammation extends to extrahepatic parenchyma (but is an extension of cholangitis)
- NEUTROPHILIC CHOLANGITIS: often associated with pancreatitis and/or IBD; can be acute or chronic
- LYMPHOCYTIC CHOLANGITIS: etiology unknown, immune-mediated mechanism is suspected
- CHRONIC CHOLANGITIS: associated with liver fluke infestation
CLINICAL SIGNS
- NEUTROPHILIC (ACUTE): middle-aged or older; fever, lethargy, anorexia, vomiting, +/- jaundice and abdominal pain
- LYMPHOCYTIC: young (50% < 4 yo); jaundice, +/- ascites (indicative of end-stage liver disease or cirrhosis)
- some cats have no c/s other than weight loss; hepatomegaly possibly, c/s of bruising/bleeding if concurrent coagulopathies
DIAGNOSIS
- CBC: normal or inflammatory neutrophilia, nonregenerative anemia (anemia of chronic disease) possible
- chem: elevated LE (ALT>ALP/GGT) ALP/GGT greater elevation if EHBO, hyperbilirubinemia; lymphcytic = hyperglobulinemia +/- hypoalbuminemia
- elevated bile acids (as with liver dysfunction)
- UA: bilirubinuria
- PT/PTT: possible prolongation due to vitamin K malabsorption or decreased hepatic production of coag factors
- AXR: hepatomegaly; less commonly ascites, cholelithiasis
- AUS: variable (or no) echogenicity changes to hepatic parenchyma; can differentiate between focal and diffuse disease; can assess other concurrent diseases (EHBO, pancreatitis, cholelithiasis, cholecystitis)
- definitive diagnosis through bx and cholecystocentesis: bx>FNA (assess coags first)
TREATMENT
- NEUTROPHILIC: abx; broad-spectrum until C&S, beta-lactam/fluoroquinolones or cephalosporins/metronidazole common; treat for AT LEAST 2 MONTHS; steroids indicated if no response to abx after 2-3 wk
- LMYPHOCYTIC: immunosuppressive doses of glucocorticoids, then tapered based on response +/- second agent
- choleretics (ursodiol) have immunomodulating, antifibrotic, and anti inflammatory effects as well DO NOT GIVE IN CASES WITH COMPLETE BILE DUCT OBSTRUCTION
- hospitalization and IVFT necessary for very ill cats; diuretics (furosemide, spironolactone) if ascites +/- therapeutic abdominocentesis
- treat any other underlying diseases
NUTRITION
- complete, balance, palatable, highly-digestible diet unless concurrent renal impairment or HE
- protein-restricted diet if renal impairment or HE
- feeding tube if anorectic
Copper-associated Chronic Hepatitis
OVERVIEW
- abnormal accumulation of copper in hepatocytes causes toxic injury and incites inflammation and hepatocellular necrosis —> progresses to chronic hepatitis and cirrhosis
- copper accumulation is the primary abnormality, not a consequence of hepatitis/hepatocellular dysfunction/cholestasis
- primarily disease of dogs
- Bedlington terrier (COMMD1 gene), Westies, Skye terriers, Labs, Dalmatians
CLINICAL SIGNS
- clinically normal early in disease while copper progressively accumulates
- waxing and waning inappetence, lethargy early in liver dysfunction
- intermittent to persistent anorexia, depression, vomiting, weight loss, diarrhea, PU/PD, icterus, ascites
- Bedlington terriers may present with acute fulminant disease from acute hepatic necrosis, precipitated by physiological stressful event (whelping, inter current disease); +/- hemolytic anemia
- +/- HE
DIAGNOSIS
- CBC: leukocytosis, thrombocytopenia, mild anemia
- chem: LE elevation (ALT predominant), +/ hypoalbuminemia, hyperbilirubinemia
- +/- elevated bile acids
- +/- prolonged coags
- UA: bilirubinuria, ammonium biurate crystals if severe dz
- blood copper levels NOT HELPFUL
- AXR/AUS non-specific
- bx and histopath with copper quantification required for definitive diagnosis: laparoscopic or surgical biopsies required to include 6-8 portal triads; special stains
TREATMENT
- chelating agents to reduce copper in hepatocytes: D-Penacillamine, trientene; may take months to years
- zinc (intestinal metallothionein) to reduce absorption of copper; need to monitor zinc levels to prevent toxicity
- reduced copper diet
- selected water sources
- antioxidants to reduce oxidative injury from copper (SAMe, silymarin, vitamin E)
NUTRITION
- exclude copper-rich foods: organ meat, eggs, shellfish, legumes, mushrooms
- commercial hepatic diets (supplement puppies with low-copper proteins: dairy-based, egg whites, white meat poultry)
