Liver Pseudo-Function Tests (copy)

True or False: terms like hepatic insufficiency, hepatic failure, decreased hepatic mass, and functional or synthetic liver failure all describe when the liver is unable to meet the metabolic needs of the body.

True!

Name at least FOUR things that can cause a decreased functional mass of the liver.

Infectious/inflammatory

Toxins

Necrosis

Metabolic disease

Portosystemic shunts

Neoplasia

Congenital liver disease

What cause of decreased functional liver mass can be caused by conditions like chronic hepatitis, cholangiohepatitis, or toxin exposure where there is a hepatocyte loss and architecture distortion?

What are the hepatocytes replaced with and what can this lead to in the liver over time?

Chronic progressive hepatic inflammation

Fibrosis; cirrhosis (fibrosis + regenerative nodules)

Toxins of the liver include drugs like —- or heavy metals like —-.

Acetaminophen

Copper

What cause of decreased functional mass is characterized with sudden loss of too many hepatocytes to maintain normal function with potential to regenerate with normal structure?

Massive necrosis

What cause of decreased functional mass sees hepatocytes fill up with lipid or glycogen?

Metabolic diseases

Name and describe the TWO types of portosystemic shunts.

Congenital: diversion of portal blood to liver in young animals; empties in vena cava so growth factors bypass liver; very small liver

Acquired: secondary to liver disease in older patients; hyperrtension from intrahepatic changes; increased portal resistance

Infiltrative neoplasia like —- may result in tissue necrosis and interfere with liver function.

Lymphoma

Name THREE major congenital diseases related to decreased liver function.

1. Congenital hepatic fibrosis/hepatic cysts (Persians; horses)

2. Copper hepatopathy (mutations in copper transport genes)

3. Hepatoportal microvascular dysplasia (similar to portosystemic shunts but no discernible large vessel)

Name THREE major clinical signs/physical exam findings suggestive of hepatic insufficiency.

1. Neurologic (seizures, behavior, stupor, coma)

2. Ascites (transudate)

3. Prolonged effect of drugs/anesthesia

Name FOUR pseudofunction tests/results that would indicate hepatic insufficiency on chemistry.

1. Hypoalbuminemia

2. Hypoglycemia

3. Low BUN

4. Hypocholesterolemia

What TWO things might you find on urinalysis to suggest liver insufficiency?

1. Ammonium urate crystals

2. Ammonium urate uroliths

What tests on a general serum chemistry panel that, taken together, can indicate liver insufficiency/functional liver failure?

Name the FOUR tests comprised in this.

Pseudo-function tests

1. Albumin

2. BUN

3. Glucose

4. Cholesterol

True or False: The liver additionally makes globulins and coagulation factors

True!

What serum proteins are synthesized by the liver?

Albumin and most globulins (acute phase proteins)

True or False: Abnormal patterns of serum proteins occur in animals with liver disease.

True!

What specific pseudofunction test would you expected to see decreased with chronic liver disease leading to hepatic insufficiency?

What other TWO might be seen?

Hypoalbuminemia

Hyperglobulinemia (inflammatory, producing acute phase proteins)

Hypoglobulinemia (decreased liver production of globulins)

What species often has hypoalbuminemia with hepatic insufficiency, where >60% are affected and must have 60-80% reduced functional mass?

What species is hypoalbuminemia not as commonly seen in with chronic liver disease, where 20% have hypoalbuminemia?

Would cats more likely have or not have hypoalbuminemia?

Dogs

Horses

More likely

Liver is responsible for —- uptake and its storage as —- after a meal and its synthesis, which is why it may be decreased with hepatic insufficiency.

Glucose

Glycogen

What are THREE other reasons you would see hypoglycemia outside of synthesis issues?

1. Decreased intake (neonates)

2. Pancreatic tumors (secrete insulin)

3. Iatrogenic (insulin)

The liver is responsible for —- synthesis from ammonia from the gut (—-%) or deamination of proteins (—-%).

It is a product of —- metabolism and a decreased BUN is mostly linked to decreased —-.

What is the secondary cause of decreased BUN?

Urea

90%

10%

Protein

Production

Low-protein diet

True or False: Cholesterol is always decreased with liver disease.

False! It can be HYPERCHOLESTEROLEMIA with cholestasis and HYPOCHOLESTEROLEMIA with hepatic insufficiency from production.

What is a major route of excretion of cholesterol, which is why interference with its flow results in (hypo/hyper)cholesterolemia?

Bile

Hypercholesterolemia

True or False: Patients with liver disease can also have a normal cholesterol concentration.

True!

Name TWO non-liver causes of hypoalbuminemia.

1. Decreased intake

2. Loss through GI/kidney (protein losing entero/nephropathy)

True or False: To know if your alterations are due to hepatic insufficiency or something else, correlate it with your clinical findings/diagnostics and examine the remainder of the bloodwork (enzymes, bilirubin, etc.)

True!

If a patient has —- —- that can be seen with liver insufficiency and —— of the pseudo-functional tests are decreased, this increases index of suspicion for liver insufficiency.

Clinical signs

2-4

If a liver biopsy is planned in order to put a name on the disease and determine prognosis, what must you do first? Why?

Coagulation testing

Can cause hemorrhage and hemostasis could be impaired with coagulation factor production from liver if insufficient

What kind of anemia is most likely seen with chronic liver disease?

What about portosystemic shunts and functional iron deficiency?

Normocytic, normochromic

Microcytic, normochromic

Acute severe intravascular hemolysis is most linked to what in horses? Sheep?

Horses: fulminant liver failure

Sheep: copper poisoning

What irregularity can be seen in RBCs without anemia in dogs with liver disease?

What kind of metabolism is it associated with?

Acanthocytes

Lipid/cholesterol

In what TWO situations would be see acanthrocytes with regenerative anemia in liver disease?

1. Erythrocyte fragmentation injury

2. Microangiopathic hemolysis

Red cell shape abnormalities can be caused by target cells, where —- and —- added equally to inner and outer leaflets or excess —-.

Cholesterol

Lipids

Membrane

Bile acids are synthesized by hepatocytes from —- and are excreted in —-.

Transport across the —- membrane is necessary for bile formation and they facilitate excretion of ——based compounds and their absorption in the gut.

Cholesterol

Bile

Canalicular

Lipid

What is the most specific test for decreased functional mass of the liver?

What is the basis of diagnostic testing with them?

Bile acids

Enterohepatic circulation

True or False: Liver must uptake, conjugate/re-conjugate, and excrete bile acids into bile.

True!

Total serum bile acid testing is indicated in what kind of animals?

Non-icteric suspected to have congenital or acquired portosystemic shunts or hepatic insufficiency

What tubes can be used for bile acid testing?

Red top (serum) or green top (plasma)

Name the TWO paired samples that are collected in bile acid testing and describe their names and when they are collected.

Pre-test: fasting bile acid; before eating small meal

Post-test: post-prandial; two hours after eating small meal

What is the purpose of feeding a small meal is the post-test sample of bile acid testing?

Why is it important to feed only about a teaspoon and not provide a large meal?

Cholecytokinin production/release and gallbladder contraction

Important not to produce lipemia with interferes with assay (causes false increase)

Why is there no useful information gained by testing bile acids in an icteric animal (bilirubin > 2.5 mg/dl)?

What is the rare exception?

Both samples collected will be expected to be increased

Pre-hepatic icterus without concurrent cholestasis

Bile acids will also be increased with MARKED increases in what TWO liver enzymes?

ALT (injury; not able to process bile acids)

ALP (cholestasis; downregulation of transport proteins on canalicular membranes; bile acids "regurgitated" into sinusoidal blood)

Describe what results you would expect to see in wither of your bile acid samplings with a patient with hepatic insufficiency or portosystemic shunts.

Pre/fasting: within RI or increased

Post/post-prandial: significant increase

A ———— is usually needed to identify cause or process of hepatic insufficiency, but —- can be done to diagnose portosystemic shunts.

Liver biopsy

Portocystogram

Name THREE of the four causes of a falsely low post bile acid test.

1. Meal does not cause gallbladder to empty

2. Delayed intestinal transit (bile acids do not reach ileum in 2 hours)

3. Rapid intestinal transit (already absorbed and partially handled)

4. Malabsorption due to concurrent intestinal disease

What might cause a pre-fasting bile acid to be higher than a post sample?

Spontaneous gallbladder emptying before meal (smelling food)

Name the FOUR major non-specific clinical signs of liver disease in horses.

1. Weight loss

2. Depression

3. Inappetence

4. Bizarre behavior

True or False: SDH, AST, or GGT are not helpful in chronic liver diseases of horses.

False! SDH and AST are not helpful (too few hepatocytes to leak or no aggressive active injury ongoing), but GGT CAN be increased in chronic liver disease in horses.

Fasting in horses causes an increase in —-, but little to no increase in ————.

Bilirubin

Bile acids

How does the number of sampling differ for bile acid testing in horses and why?

Only one sample (fasting- 12 hours); have no gallbladder for storage

What bile acid result would indicate high probability of liver disease and be indication for liver biopsy in a horse?

>2x RI

True or False: In horses, >25 umol/L is abnormal for bile acids in horses. usually, >20 would be questionable.

True!

What is the normal byproduct of protein metabolism and the product of catabolism of amino acids, nucleic acids, nitrogenous waste, and more?

What does it mainly circulate in the form of?

Ammonia

Ammonium

What converts amino acids and urea into ammonia in the gut?

What converts ammonia to urea in hepatocytes?

What TWO places is urea excreted?

GI microbes

Urea cycle

Urine and gut

(Hypo/hyper)ammonemia can result from hepatic insufficiency and significant changes can lead to —- signs.

Hyperammonemia

Neurologic

Name FOUR of the clinical signs of hepatic encephalopathy from hyperammonemia.

1. Behavior change

2. Seizures

3. Headpressing

4. Stupor

5. Coma

6. Death

What does an increased blood ammonia indicate about liver function?

Decreased hepatic functional mass and/or portosystemic shunts

True or False: Proper sample handling is essential to obtain reliable ammonia assay results.

True!

Do you have to fast a patient for blood ammonia samples?

What tubes should blood be collected in?

What should be harvested immediately?

Yes, at least 8 hours

Whole blood in EDTA or lithium green heparin tube

Plasma

Explain proper sample handling for blood ammonia in-house.

Take sample to lab immediately to spin and collect plasma -> Put in ice bath if delayed -> Assay within 1 hour or refrigerate for later +/- freezing

Describe what is needed for shipping blood ammonia samples.

Keep frozen and ship on dry ice -> Must NOT thaw during transit

Name THREE of the four reasons for a false increase in blood ammonia.

1. Hemolysis

2. Interferences (lipemia, hemolysis, icterus)

3. Contamination

4. Artifact (most common)

What is the primary cause of a false decrease in blood ammonia? Why?

Poor handling- air exposure allows ammonia to escape

True or False: Increased plasma ammonia can be seen in both portosystemic shunts and hepatic insufficiency.

True!

Name THREE of the six non-liver causes of issues with blood ammonia.

1. High-protein diet/meal

2. Recent strenuous exercise

3. Dysbiosis in gut (urease-producing microbes)

4. Urea toxicity in cattle

5. Colic, bacterial production in horses

6. Inherited disorder of urea cycle (young; neuro; liver/PSS ruled out)

Ammonia tolerance test:

—- the animal and collect a baseline sample. Administer —- —- solution at 100 mg/kg body weight via stomach tube not to exceed —- grams total dose. Collect sample —- minutes post-administration.

Fast

Ammonium chloride

3

30

When should you use an ammonia tolerance test?

When should you NOT use an ammonia tolerance test?

Use: animals suspected of PSS but fasting ammonia not increased

NOT: fasting/resting hyperammonemia (can kill patient)