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What CBC abnormalities are common with liver disease? (5)
- blood loss anemia (GI ulcer) OR anemia of chronic disease (non-regenerative)
- microcytosis (PSS- abnormal iron metabolism)
- target cells
What biochem abnormalities might you see with liver disease? (9)
- increased liver enzymes (ALT, AST)
- low BUN
- low albumin
- low glucose
- low/high cholesterol
- increased bilirubin
- increased globulins (kupffer cells gone)
- low potassium
- low sodium
When are increased liver enzymes clinically significant?
accompanied by clinical signs; OR consistently >2-3 x normal limit even w/o clinical signs
Liver enzymes are NOT _____________ or ___________.
specific to the liver; liver function tests
What are some systemic diseases that can cause secondarily increased liver enzymes? (5)
- pancreatic disease
- intestinal disease
- endocrine diseases (hyperthyroidism, DM, Cushing's)
- heart failure
- sepsis and endotoxemia
What are the 3 general groups of liver enzymes?
- those that increase due to:
- -hepatocyte injury/leakage
- -cholestasis/increased synthesis
- -drug induction
What insults can cause hepatocyte leakage? (2) What enzymes fall under this category? (3)
necrosis, altered membrane permeability; ALT, AST, SDH
If you're doing a routine blood panel screening and find an elevated ALT value, how should you handle this?
check again in 14 days--> if still elevated, you must investigate further b/c some hepatic injury is ongoing
Disorders with increased ALT. (7)
hepatic necrosis, hepatitis, hepatic hypoxia, secondary to cholestasis, hepatocyte regeneration, enzyme induction (drugs), skeletal muscle disorders
What is different b/w ALT and AST?
AST is within mitochondria so it takes a larger injury to cause leakage
If AST is >> than ALT elevation, what are you thinking?
let's look at CK because it's likely from muscle injury
Cholestasis can be ________ or _________; examples of cholestatic enzymes include __(2)__.
intrahepatic; extrahepatic; ALP and GGT
What are the isotypes of ALP?
- liver ALP
- bone ALP
- corticosteroid ALP (DOGS ONLY)
What can increased ALP bone isoform be attributed to? (2)
- growing animal
- bony lysis (ex. osteosarc)
What can cause increased ALPCAP? (7)
- [corticosteroid induced ALP- "steroid hepatopathy"]
- individual variation
- liver disease
- chronic illness
Cats with cholangitis tend to have elevated ____________; cats with hepatic lipidosis tend to have elevated _____________.
ALP and GGT; ALP (normal GGT)
What liver enzymes may be induced by therapeutic corticosteroids?
ALP in dogs
What liver enzymes may be induced by administration of phenobarbitol?
increased ALP +/- ALT
What biochem values are decreased with liver synthetic failure? (4)
low BUN, albumin, glucose, and cholesterol
What may cause increased cholesterol and bilirubin? (3)
cholestasis, RBCs hemolysis, liver failure (not processing senescent RBCs)
What can cause increased globulins due to liver disease?
loss of Kupffer cells so more pathogens reach systemic circulation (not cleared in liver)
What UA abnormalities may result from liver disease? (3)
dilute urine, bilirubinuria (may be normally elevated in some dogs), NH4 crystals
What are the liver function tests? (2)
serum bile acids, blood ammonia levels
Serum bile acids are increased with ____________.
all types of liver disease
When should you NOT test serum bile acids?
when bilirubin is already elevated...waste of money
What will cause increased blood ammonia? (3)
portosystemic shunting, SEVERE hepatocellular dysfunction, urea cycle abnormality
With liver disease, what aspects of the clotting panel may be affected?
basically, any of them- OSPT, APTT, antithrombin, fibrinogen, FDPs, platelets, BMBT
What functional abnormalities usually characterize PSS? (3)
increased NH3, normal to increased fasting bile acids, increased post-prandial bile acids
What functional abnormalities often accompany cholestasis? (5)
hyperbilirubinemia, bilirubinuria, increased cholesterol, increased bile acids, Vit K responsive coagulopathy
What are causes of diffuse hepatomegaly? (6)
congestion, lipidosis, glycogen (steroids in dogs), neoplasia, inflammation, biliary obstruction
What are causes of focal hepatomegaly? (3)
regenerative nodules, cysts, neoplasia
What are indications for liver biopsy? (4)
persistent increased liver enzymes or serum bile acids, abnormal hepatic parenchyma (liver masses), obtain quantitative copper
What method of liver biopsy gives you the largest and most useful sample?
surgical biopsy (as opposed to US needle or laparoscopy)
What are pre-biopsy considerations? (3)
hemostasis screening, method of biopsy, pre-biopsy treatment (Vit K or plasma transfusion)
What are important additional points of the history for potential liver disease patients? (4)
diet and drug history, exposure history, environment history, vaccination history (Lepto, ICH)
What are clinical signs of liver disease? (11)
[very non-specific] anorexia, vomiting, hematemesis/melena (ulcers), PU/PD, dysuria/hematuria (urate stones), weight loss, stunted growth, ascites, jaundice, hepatic encephalopathy, bleeding tendencies
What questions should you ask yourself before giving a drug to a liver dz patient? (3)
- is it metabolized by the liver?
- it is potentially hepatotoxic?
- could is exacerbate signs of liver failure?
What are the big 4 classes of treatment for hepatobiliary disease?
antimicrobials, drug withdrawal, copper chelators, surgery (PSS, biliary obstruction, primary hepatic neoplasia)
Describe the general plan for supportive therapy of liver disease. (4)
fluid therapy, nutritional support, hepatoprotectants, control complications
What are your goals when providing fluid therapy to a liver patient? (4)
maintain fluid balance, low sodium fluids if ascites or effusion (avoid third spacing by minimizing Na+), add KCl and dextrose, avoid alkalosis and hypokalemia
With long-term cachexia, the better you maintain ___________, the better survival will be.
body and muscle condition
If an animal stops eating, how long will it be before they start breaking down muscle mass instead of body fat (cachexia)?
day 4 or 5
What are the general goals of nutritional support for a liver patient? (3)
maintain adequate nutrition to support hepatic regeneration, decrease protein with hepatic encephalopathy, DO NOT automatically restrict protein unless clinically indicated (HE)- keep a good plane of nutrition because it will increase survival (obesity paradox)
Describe "dietary supplements," such as hepatoprotectants. (6)
non-drug substance, given orally, required for normal body structure and function, "improve health and well-being," can't imply medical intent, not FDA regulated
What is SAMe?
glutithione precursor that provides protective metabolic impact; glutithione is an antioxidant
What diseases have a component of oxidative injury? (6) What drug is indicated in these cases?
heavy metal storage, drug-induced, cholestasis/ bile duct obstruction, feline hepatic lipidosis, necro-inflammatory liver disease, ischemia-reperfusion injury; SAMe
SAMe is absorbed from the ________; it has ________ safety level; it influences_________ levels, which is decreased in many spontaneous hepatobiliary disorders.
GI tract; very high; hepatic glutathione
How do you administer SAMe?
orally on an empty stomach (DO NOT crush/break- enterically coats to protect in stomach)
Vitamin E is __________, which is a(n) _________; it is a(n) __________, which is stored.
alpha-tocopherol; nutritional antioxidant; fat-soluble vitmain
What is milk thistle?
derived from Silybum plant- natural liver remedy; should be an adjunct txt, not a sole txt
What effects might milk thistle have? (4)
antioxidant, antifibrotic, anti-inflammatory, decreased hepatic uptake of amanita mushroom toxicity
What are the ingredients of the Nutramax neutriceutical Marin? (3)
Silybin (milk thistle), Vit E, zinc gluconate
What are the ingredients of Denamarin?
SAMe and Silybin (milk thistle)
What is Ursodiol?
primary hydrophilic bile acid marketed for dissolution of cholesterol gallstones in humans
What do we use Ursodiol for? (4)
hepatoprotective: anti-inflammatory, nti-fibrotic, immunomodulation, choleresis
What is the mechanism of action of Ursodiol?
replace hepatotoxic hydrophobic bile acids with less hepatotoxic hydrophilic bile acids
What are common complications of liver disease? (7)
- Intestinal and gastric ulcers
- eNdotoxemia and infection
How can you manage coagulopathies associated with liver disease? (3)
replace clotting factors with fresh or fresh-frozen plasma, Vit K supplementation, heparin (DIC)
How do you manage anemia associated with liver disease?
- ID mechanism:
- -Blood loss from GI ulcer, coagulopathy, post-biopsy, drugs: blood transfusion
- -Chronic disease: treat underlying cause
What are the 4 major causes of blood loss anemia with liver disease? How is each treated?
- GI ulcer: gastroprotectants, transfusion,
- Coagulopathy: transfusion, fresh plasma with clotting factors
- Post-biopsy: surgical correction
- Drugs: depends
How do you manage hepatic encephalopathy as a result of liver disease? (4)
correct precipitating events, restrict dietary protein, decrease colonic NH3 absorption (lactulose), alter intestinal bacteria
What are potential precipitating events of hepatic encephalopathy? (7)
high protein meal, GI bleeding, blood transfusion, constipation, dehydration, azotemia, alkalosis/ low K+
What drug therapies can be given to halt the precipitating event of hepatic encephalopathy? (6)
steroids, NSAIDs, tranquilizers, anticonvulsants, anesthetics, diuretics
What proteins should be given in a hepatic encephalopathy patient?
vegetable and dairy proteins (reduce meat proteins)
How do you decrease colonic NH3 absorption in a hepatic encephalopathy patient?
lactulose- not digested or absorbed in guy, metabolized by colonic bacteria to organic acids, decreasing pH and thus decreasing NH3 absorption from the colon
What is the mechanism of action of lactulose?
not digested or absorbed in guy, metabolized by colonic bacteria to organic acids, decreasing pH and thus decreasing NH3 absorption from the colon
What antibiotics are often used in conjunction with lactulose? (3)
amoxicillin, neomycin, metronidazole
How do infections and endotoxemia arise in liver failure? (2)
impaired Kupffer cell function, shunting of bacteria and endotoxin (not going through liver)
How do you treat ascites and edema associated with liver failure? (4)
diuretics, sodium restrictions, colloids, abdominocentesis (emergency)
What are differentials for hepatic hyperbili? (7)
inflammatory hepatitis, hepatic lipidosis, neoplasia, FIP, amyloidosis, sepsis, hepatotoxicity
What are post-hepatic causes of hyperbili? (5)
pancreatitis, cholecystitis, cholelithiasis, biliary mass [cholangitis]
What are the general mechanisms of hepatic lipidosis? (6)
nutritional [anorexic cat], metabolic, endocrine, toxic, drug-induced [more common in dogs], hypoxic
What is the prototypical patient that presents with hepatic lipidosis?
obese cat, anorexia or intentional weight loss
What are triggers for hepatic lipidosis? (8)
- Primary: stressful environment, diet change, boarding
- Secondary: IBD, cholangitis, neoplasia, pancreatitis, renal disease [anything that causes a cat to stop eating]
Why are cats unable to adaptto metabolism of fat for energy during catabolic stress and starvation?
obligate carnivores--> unique requirements for protein, essential amino acids, and essential fatty acids--> altered susceptibility
Historical findings common with feline hepatic lipidosis. (7)
middle-aged to older, obesity, prolonged anorexia/ weight loss, vomiting, lethargy, diarrhea/constipation, +/- hepatic encephalopathy
PE findings common with feline hepatic lipidosis. (5)
icterus, hepatomegaly, dehydration, muscle wasting, ventroflexion of head/neck (hypokalemia)
Laboratory findings common with hepatic lipidosis. (6)
high ALP, normal GGT, high-ish ALT, hyperbili, increased serum bile acids, Vit K responsive coagulopathy
How do you definitively diagnose feline hepatic lipidosis?
needle aspirate of liver finds fat vacuolation of hepatocytes [DO NOT GO TO BIOPSY UNLESS THE ANIMAL IS A NON-RESPONDER- treat based on presumptive diagnosis by history, PE, blood work]
How do you handle nutrition of a feline hepatic lipidosis case?
place a nasogastric tube for feeding immediately, once stable enough to go under anesthesia- place E tube so owner can feed at home; protein!!!, moderate to low in fat content, carbohydrate restricted
How do you fluid replace in a feline hepatic lipidosis case?
crystalloids (NO DEXTROSE, PREF NO LACTATE), K+ supplementation
What medications will you probably put a cat with hepatic lipidosis on? (2)
anti-emetics (Maropitant, Ondansetron, Metoclopramide), gastroprotectants (Famotidine)
What supplements should you give to a hepatic lipidosis cat? (3)
cobalamin (Vit B12), Vit K, +/- L- carnitine (rate-limiting step in FA oxidation)
What causes re-feeding syndrome?
food causes profound release of insulin and cell uptake of glucose, P, K, Mg, and water; likely occurs in first 48 hours
What are the 3 types of cholangitis?
neutrophilic (bacterial, acute, chronic), lymphocytic, chronic (fluke associated- on't worry about this one)
Signs of neutrophilic cholangitis. (5)
pyrexia, lethargy, variable jaundice, abdominal pain, hepatomegaly
What laboratory abnormalities are often associated with neutrophilic cholangitis? (8)
left shift leukogram, +/- ALP and GGT elevations, hyperbili, +/- azotemia; secondary hepatic necrosis markedly increased ALT; end-stage liver decreased synthetic function, inc ammonia
How do you diagnose neutrophilic cholangitis? (3)
liver biopsy, bacterial culture, +/- surgery if biliary obstruction
What are clinical signs associated with lymphocytic cholangitis? (4)
vomiting, diarrhea, jaundice, hepatomegaly
Lab abnormalities commonly associated with lymphocytic cholangitis. (10)
left shift leukogram, hyperglobulinemia, +/- ALP and GGT elevations, hyperbili, +/- azotemia; secondary hepatic necrosis markedly increased ALT; end-stage liver decreased synthetic function, inc ammonia
Describe treatment of neutrophilic cholangitis. (7)
amicillin/metronidazole, UDCA, SAMe, Vit K, Vit B complex, feeding, fluids
Describe treatment of lymphocytic cholangitis. (3)
immunosuppression, +/- metronidazole and chlorambucil
What are causes of biliary obstruction? (13)
- [biliary tract disease] GB mucoele (dogs), cholelithiasis, sludge bile, cholangitis, cholecystitis, neoplasia, flukes
- [pancreatic disease] inflammation, fibrosis, abscess, neoplasia
- [other] duodenal or hepatic neoplasia, diaphragmatic hernia
The most common cause of biliary obstruction in dogs is ___________; in cats, we think of __(2)__.
GB mucocele; inflammatory dz and masses/neoplasia
Diagnosis of biliary obstruction is reliant upon ___________.
imaging [dilated bile duct, GB mucocele, dilated GB, intrahepatic ducts dilated]
How do you manage biliary obstruction? (3)
Vit K1 for 24-48 hrs, antibiotics, surgery (relieve obstruction, bacterial culture, tissue biopsy)
What are the consequences of PSS? (3)
hepatic encephalopathy, urate urolithiasis, hepatic trophy
Clinical signs of PSS. (4)
CNS signs (encephalopathy, hypersalivation), vomiting/diarrhea, PU/PD, stunted growth
What lab abnormalities are associated with PSS? (4)
synthetic failure (low albumin, low BUN, low glucose, low cholesterol), normal to mildly increased liver enzymes, normal bili, increased serum bile acids
What will you see on imaging of a PSS patient?