Clinpath exam 3 (lectures 21-29)

hepatocellular injury

cholestasis

decreased hepatic functional mass

What are the categories of liver disease?

liver

What organ is often secondarily involved in systemic cases?

cytoplasmic and/or mitochondrial

What liver enzymes are leakage enzymes?

membrane bound

What liver enzymes are inducible enzymes?

hepatocellular injury

What does the presence of leakage enzymes indicate?

cholestasis

What does the presence of inducible enzymes indicate?

hepatocellular injury

What occurs when leakage enzymes leak from cytoplasm and are increased in the blood?

ALT, AST

SDH, GLDH, LDH

What biomarkers are used for hepatocellular injury?

mostly liver, little muscle

Where are is the tissue source of ALT in small animals?

muscle

Where are is the tissue source of ALT in large animals?

increased ALT

What level would you see with hepatocellular injury, muscle injury, drug therapy in dogs (glucocorticoids, anticonvulsants), hyperadrenocroticism in dogs, and feline hyperthyroidism?

AST

What level should be interpreted with CK and ALT?

Increased AST

What level would you see changed with hepatocellular injury, muscle injury, hemolysis, hyperadrenocorticism, and drug induction in dogs (glucocorticoids, anticonvulsants)?

cytoplasmic, mitochondrial from liver and muscle (potentially other tissues)

Where are is the tissue source of AST in animals?

AST due to shorter half-life

Which marker may provide a better indication of active liver injury?

cytoplasmic-liver

Where are is the tissue source of SDH in animals?

hepatocellular injury- sensitive and specific

When would you expect to see an increased SDH?

SDH

What is the hepatocellular injury enzyme of choice in large animals?

unstable enzyme-> impractical for mailed samples

Why is SDH not always available?

hepatocellular injury- sensitive and specific

When would you expect to see an increased GLDH?

mitochondrial-liver

Where are is the tissue source of GLDH in animals?

hepatocellular injury, muscle injury, hemolysis

When would you expect to see an increased LDH?

cytoplasmic- liver, muscle, RBCs

Where are is the tissue source of LDH in animals?

ALT, AST

What are the common hepatocellular injury enzymes used in small animal?

AST, SDH, GLDH, LDH

What are the common hepatocellular injury enzymes used in large animal?

carprofen, glucocorticoids, phenobarbital

What are some drugs that cause hepatocellular injury?

amanita mushroom, blue-green algae, copper toxicosis, sago palm, xylitol, pyrrolizidine alkaloids

What are some toxicities that cause hepatocellular injury?

mild

In hepatocellular injury, what is the magnitude of increase if the number is 2-3 times the upper range limit?

moderate

In hepatocellular injury, what is the magnitude of increase if the number is 4-10 times the upper range limit?

marked

In hepatocellular injury, what is the magnitude of increase if the number is >10 times the upper range limit?

considered insignificant

What does hepatocellular injury indicate if the number is less than the lower range limit?

Cholestasis

What is the interruption or obstruction of bile flow called?

intra-hepatic

What type of obstructive cholestasis affects the bile canaliculi and bile ductules?

extra-hepatic (post-hepatic)

What type of obstructive cholestasis affects the bile duct and gall bladder?

obstructive cholestasis and functional cholestasis

What are the two kinds of cholestasis?

hyperbilirubinemia

hypercholesterolemia

What are other indictors of cholestasis?

cholestasis

What leads to the induction and release of membrane-bound enzymes (induced enzymes)?

ALP and GGT

What markers are used to look for cholestasis (mostly obstructive cholestasis)?

intra-hepatic

What type of obstructive cholestasis can occur from hepatocyte swelling or necrosis, inflammation or neoplasia?

extra-hepatic

What type of obstructive cholestasis can occur from gall bladder mucoceles, pancreatitis, neoplasia, and choleslithiasis/chledocholithiasis?

liver, bone, corticosteroid

What are the sources for ALP in serum?

dogs

What animal has C-ALP: corticosteroid (hepatocytes)?

increased ALP

What level can be increased in cholestasis, bone (lesions, growing animals), drugs (glucocorticoids, anticonvulsants), and endocrine/metabolic (feline hyperthyroidism, hyperadrenocorticism)?

increased GGT

What level can be increased with cholestasis, biliary hyperplasia, drug therapy (glucocorticoids, anticonvulsants), and colostrum ingestion (not foals)?

urine

With GGT coming from the renal tubular epithelium, where does it enter?

milk

With GGT coming from mammary epithelium, where does it enter?

dogs

Which species has ALP being more sensitive than GGT for cholestasis?

cats and large animals

Which species has GGT being more sensitive than ALP for cholestasis?

cats

Which species has a characteristic pattern from hepatic lipidosis that often has an increase in ALP>GGT?

mixed hepatopathy

What is it caused when we se both hepatocellular injury and cholestasis together?

muscle injury

What is the disruption of myofiber membranes to allow leakage of cytoplasmic/mitochondrial enzymes?

degeneration, necrosis, inflammation, NOT atrophy

What processes cause muscle injury?

trauma, rhabsomyolysis, seizures, saddle thrombus, myositis, degenerative myopathies, toxins, neoplasia

What are the causes of muscle injury?

skeletal muscle injury

What is occurring if the following enzymes are increased: CK, AST, ALT, LDH?

creatinine kinase

What is the enzyme of choice for skeletal muscle injury?

rapid increase after injury, rapid decrease due to short half-life

What are the kinetics of creatinine kinase (CK)?

half life AST> CK in horses

What are the kinetics of creatinine kinase (CK) in horses?

pre-hepatic

What type of hyperbilirubinemia has an increased production of bilirubin?

hepatic

What type of hyperbilirubinemia has a decreased hepatic uptake or secretion of bilirubin?

post-hepatic

What type of hyperbilirubinemia is due to an obstruction of bile flow (cholestasis)-> reflux of bilirubin into blood?

more unconjugated bilirubin than conjugated bilirubin

During pre-hepatic hyperbilirubinemia, what will you see?

decrease liver functional mass: uncongugated and congugated bilirubin

During hepatic hyperbilirubinemia, what will you see?

anorexia: mostly uncongugated bilirubin

Why is the most common cause of hyperbilirubinemia in horses?

more conjugated bilirubin than uncongugated bilirubin

During post-hepatic hyperbilirubinemia, what will you see?

all fractions of bilirubin combined

What does total bilirubin (Bt) test for?

conjugated bilirubin

What does direct bilirubin (Bd) test for?

unconjugated bilirubin

What does indirect bilirubin (Bi) test for?

when Bt is ~1.5-2.0 mg/dL or greater

At what level will clinical icterus be seen?

increased bilirubin and globulins

What is seen if the clearance function of the liver is not working?

decreased glucose, albumin, BUN, cholesterol, and coagulation factors

What is seen if the synthetic products of the liver is not working?

70%

Liver products decrease when what percentage of function al mass is lost?

congenital portosystemic shunt or acquired portosystmic stunt

What can cause alterations of portal blood flow?

congenital portosystemic shunt

What can result in secondary loss in functional liver mass?

acquired portosystemic shunt

What can be secondary to chronic liver disease or decreased hepatic functional mass?

congenital portosystemic shunts

What type of shunts are seen in young patients, liver may be small but smooth edges, has increased bile acids and ammonia but less likely to be icteric?

acquired portosystemic shunts

What type of shunts are seen when the liver is often small but very nodular (cirrhosis), and has increased bile acids and ammonia, but also likely icteric with increased liver enzymes?

increased ammonia and bile acids

What other levels will increase with portosystemic shunts (PSS)?

GI microbes

What is ammonia produced by?

hyperammonemia

What lab level is seen with decreased hepatic functional mass, portosystemic shunts, feed additives in ruminants, intestinal disease in horses, and post-prandial?

collect-> immediately place on ice-> lab to run within 30 minutes

What are the requirements when testing for ammonia in the blood?

hepatocytes

What cells make bile acids?

increased bile acids

What laboratory finding occurs with decrease hepatic functional mass, portosystemic shunts, and cholestasis?

gallbladder contraction elevates fasting bile acids

What falsely elevates bile acids?

decreased bile acids

What are you likely to see with bile acids in GI disease?

horses

Which species does not have a gallbladder?

small animals

What species should you do the "challenge" step when measuring bile acids since feeding stimulates bile release form gall bladder?

decreased hepatic function

If you see these clinical signs, what should you be thinking about: hepatic encephalopathy, edema/ascites, PUPD, and hepatic photosensitivity?

hormone synthesis, excretion of waste, and conservation

What are the three roles of the kidneys?

Horses

Which species has no 1a-hydroxylase so Ca is diet dependent?

BUN: blood urea nitrogen

What is the product of protein catabolism either endogenous or increased protein digestion and is filtered at the glomerulus and reabsorption is related to GFR?

creatinine

What is produced in muscle and freely filtered at the glomerulus but NOT reabsorbed?

No! this indicates kidney problem

Should albumin be detected in urine?

gets reabsorbed back into the body

What happens to glucose and amino acids when they enter the nephron?

creatinine

What enters the nephron in the same amount as in the urine due to it neither being filtered or absorbed?

canine

Which species glucose renal threshold is 180-200 mg/dL?

feline

Which species glucose renal threshold is 270-290 mg/dL?

bovine

Which species glucose renal threshold is 100-140 mg/dL?

equine

Which species glucose renal threshold is 160-180 mg/dL?

erythropoietin

What hormone synthesis is affected and leads to a non-regenerative normocytic, normochromic anemia?

Vitamin D

What hormone synthesis is affected and leads to renal secondary hyperparathyroidism?