L102b: evaluation of liver functions and analytes

what substances are evaluated in liver function tests?

1. substances produced by liver

2. substances metabolized and excreted by the liver

where does total bilirubin originate from?

breakdown of old RBC by macrophages

why is there very little unconjugated bilirubin in the blood?

degraded and bound to albumin to form delta bilirubin

what are the different ways icterus is classified?

1. pre-hepatic

2. hepatic (intra)

3. post hepatic

what are the causes of pre-hepatic hyperbilirubinemia?

1. extravascular hemolysis with marked anemia

2. massive internal hemorrhage

3. hypophosphatemia

how does hemolysis affect hepatocytes?

causes oxidative damage to hepatocytes which will interfere with bilirubin excretion and result in cholestasis

what typically occurs before jaundice?

bilirubinuria

how does massive internal hemorrhage lead to pre-hepatic hyperbilirubinemia?

marked increase of unconjugated hyperbilirubinemia 

what can cause extravascular hemolysis?

1. parasites

2. zinc

3. copper 

4. IMHA

what are the types of hepatic hyperbilirubinemia?

1. fasting

2. functional

3. obstructive intrahepatic or posthepatic

4. delta bilirubia

how does fasting lead to hyperbilirubinemia?

decreased uptake of unconjugated bilirubin by hepatocytes leads to regurgitation of bilirubin into the blood

what type of hyperbilirubinemia is sepsis associated cholestasis?

functional

what animal is functional hyperbilirubinemia common in?

sick cats

what is the pathogenesis of functional hyperbilirubinemia?

circulating inflammatory mediators such as TNF-alpha inhibit bile acid transport to canaliculi

what is the pathogenesis of obstructive intrahepatic hyperbilirubinemia?

hepatocyte swelling blocks bile canaliculi leading to decreased excretion

what is the pathogenesis of obstructive posthepatic hyperbilirubinemia?

impaired bile flow in canaliculi, bile ducts, or gall bladder

delta bilirubin

protein (albumin) bound part of conjugated total bilirubin in blood 

what is the half-life of albumin and what does this mean for delta bilirubin?

8-20 days meaning that it will remain in blood for longer and cholestasis can persist even if symptoms are gone

what type of bilirubin do labs typically only measure?

total bilirubin

what does the image show?

intercellular bile lakes showing accumulation of bile in canaliculi

what is the image showing>

leakage of bile due to rupture of gallbladder or bile duct; known as " regurgitation”

which animals have a low renal threshold for bilirubin and will get bilirubinuria?

dogs and rumininants

what value is considered normal in male dogs with concentrated urine in regards to bilirubinemia?

1-2 is normal and should not be considered hyperbilirubinemia

what percentage of cattle have bilirubinemia?

25%

what animals have a high renal threshold and what does this mean?

cats and horses; significant because bilirubinuria usually from cholestatic liver disease

MCQ: in what two species is bilirubinuria the least clinically significant?

dogs and ruminants

bile acids

cholesterol derived anionic acids

what are bile acids required for?

digestion of dietary lipids

when is the highest sensitivity for fasting bile acids?

in dogs with convenital circulatory anomalies and chronic hepatitis

what bile acid value is considered abnormal?

above 25 umol/L

what is important to know for bile acid samples?

does not matter if sample was fasting or post-prandial

what is considered a post-prandial serum sample for bile acid?

you fed animal a small meal of bland food and took sample 2 hours later

hypercholemia

increased bile acids due to decreased clearance from portal blood

what diagnostic tool can be used to measure bile acids?

SNAP-BAT

what can falsely increase bile acids in a sample?

lipemia

when is bile acid testing NOT useful?

if there is high bilirubin

what is the relationship between bile acid and liver malfunction?

degree of increase of bile acids not proportional to degree of liver malfunction

MCQ: what interferent has the most profound effect in artifactually increasing serum bile acids?

lipemia

what are shunts?

vascular anomaly that allows blood from the hepatic portal circulation to bypass the liver & is delivered directly into the systemic circulation

which animals are extrahepatic shunts common in?

small breed dogs

which animals are intrahepatic shunts common in?

large breed dogs

what does the radiograph show?

normal portogram showing hepatic vasculature

what does the radiograph show?

portosystemic shunt and loss of portal flow to liver

what does the portal vein drain?

1. intestines

2. stomach

3. pancreas

4. spleen

how are bile acids affected in animals with portosystemic shunts?

bile acids will be increased

what values will decrease if a portosystemic shunt leads to liver failure?

1. urea

2. glucose

3. cholesterol

4. albumin

5. coagulation factors

what can be seen on a CBC in animals with portosystemic shunts?

may see microcytic anemia hypoferremia due to abnormal iron sequestration

what are most dogs considered if they have hepatic microvascular dysplasia?

subclinical and rarely needs treatment; may see decrease in proteins

what is hepatic microvascular dysplasia?

congenital defect with abnormal development or absence of the portal microvasculature in the liver

what value will post prandial bile acids be in a dog with HMD?

35-60

what breeds are HMD more common in?

1. yorkies

2. sydney silkies

3. cairn terriers

what is important to know about bile acids in horses?

single bile acid is used

what will most horses with hepatobiliary disease have?

marked increase in bile acids

what will the value of cholesterol be in severe liver disease?

can have low cholesterol due to decreased production

will ammonimum be used over bile acids?

no due to many potential errors

what is the value of cholesterol in cholestasis?

increased due to decreased clearance

what causes a decreased production of cholesterol?

1. chronic liver disease

2. portosystemic shunts

what causes a loss of cholesterol?

1. malabsorption / maldigestion

2. protein losing enteropathy (PLE)

3. EPI

what plasma protein is made by the liver?

albumin

when will hypoalbuminemia be noted?

when 60-80% of the functional hepatic mass has been loss

what is an uncommon cause of low albumin?

liver failure unless it is a shunt

what is sometimes seen with plasma proteins in animals with severe liver disease?

polyclonal gammopathy and low albumin

what coagulation factor is NOT produced in the liver?

Factor VII

when would we recommend a coagulation screen to be conducted?

prior to liver FNA or biopsy

when will hepatic failure cause glucose values to decrease?

when there is reduced hepatic function

when will hepatic failure cause glucose levels to increase?

when there is decreased hepatic uptake

is it more common to see a decrease or increase in glucose levels with hepatic failure?

decrease

MCQ: what test result best detects liver malfunction?

increased concentrations of bile acids

what does the image show?

hepatocellular carcinoma

what is the cause of feline hepatic lipidosis?

massive accumulation of triglycerides in more than 50% of hepatocytes

what cats will we most commonly see hepatic lipidosis?

1. overweight cats

2. middle-aged females

what are clinical signs of hepatic lipidosis?

1. no appetite (1-2 weeks)

2. lost 25% of body weight

3. anorexia

4. lethargy

5. vomiting

6. diarrhea or constipation

what will be seen on a physical exam for hepatic lipidosis?

1. large non-painful liver

2. jaundice

3. mild-moderate dehydration

what type of anemia can be seen in cats with hepatic lipidosis?

non-regenerative normocytic normochromic anemia

is there a known association with hepatic lipidosis and FeLV or FIV?

no

MCQ: A 12-year-old Golden Retriever presents with chronic weight loss, polyuria/polydipsia, and mild ascites. Bloodwork as follows:

ALT: ↑↑ (moderate increase)

AST: ↑↑ (moderate increase)

ALP: ↑↑↑ (marked increase)

GGT: ↑ (mild increase)

Bile Acids: ↑↑↑ (marked increase)

Albumin: ↓ (low)

What is the most likely cause of these findings?

chronic hepatitis leading to hepatic insufiiciency

what can be used to confirm hepatic lipidosis?

1. ultrasound

2. FNA

3. biopsy

why is there an increase in ALP with hepatic lipidosis?

swelling of hepatocytes compresses bile canaliculi leading to induction of ALP

why is GGT normal with hepatic lipidosis?

nothing is happening in the biliary tree

what values will be increased in cats with hepatic lipidosis?

1. ALT

2. AST

3. ALP

4. bilirubin

what cell abnormalities may occur with hepatic lipidosis?

acanthocytes

what is the PCV value in cats with hepatic lipidosis?

WRI