Liver Clinical Chemistry

heparin

• metabolic function
• minerals
• proteins
• lipids
• glucose
• electrolytes

serum or heparinized plasma.

• fluid portion of whole blood in which cells are suspended.  
• 90% water, 10% dissolved proteins, carbohydrates, vitamins, hormones, enzymes, lipids, salt, waste, antibodies, ions, etc.

• plasma without fibrinogen.  
• plasma proteins
• When blood clots, fluid that remains is serum.

• Blood glucose
• BUN
• Creatinine
• Calcium
• Total Protein (no fibrinogen)
• Albumin
• Globulin
• Total Bilirubin
• Alkaline Phosphatase
• ALT (SGPT)
• Cholesterol
• Sodium
• Potassium
• Chloride

• dry reagent chemistry strips (whole blood, color change.  Glucose is one)
• Spectrophotometry (clinical chemistry)
• Electrochemical (electrolytes)

• biologically synthesized proteins that catalyze reactions (decrease energy of activation), acts on specific substrate.  
• Can be leakage or induced

normally present within cell, leaks across when cell is damaged.

Produced by cells irritated by inflammatory or toxic chemicals

Enzymes that are manufactured by several different organs, function identically but have variations of structure.

color interference with spectrophotometric assays causes false increases (K+ in horses and cattle)

• Happens in post-prandial
• visible turbidity, opaque to light, interferes with spectrophotometry
• false decrease due to dilution (electrolytes)

increased bilirubin in serum interferes with spectrophotometry.

• Synthesis, storage and metabolism of fats, carbs and protein
• Formation and secretion of bile
• synthesis of most coagulation factors
• detoxification and excretion of waste, drugs and toxic substances

• Liver is highly vascular.  
• Arterial blood from hepatic artery
• venous blood from portal vein (70-75% of blood flow)

portal vein, post-intestines

• secondary to metabolic disorders
• Circulatory
• biliary disorders
• Infections and parasites 
• toxicoses
• neoplastic disorders

• diabetes mellitus
• cushings
• malabsorption
• starvation (hepatic lipidosis)

shunts, anemia

cholangitis, obstruction, cholecysitis

infectious canine hepatitis, feline infectious peritonitis, equine infectious anemia, leptospirosis, ascarid migration

• abdominal pain
• ascites (lack of albumin stops pulling water into circulation so it goes into abdomen)
• persistent VD
• icterus, bilirubinemia, bilirubinuria
• hepatomegaly
• microhepatics

• results from the rupture or lysis of RBC WITHIN circulation
• hemolyzed intravascularly
• Hgb bound to haptoglobin, macrophage rapidly phagocytizes, hgb degraded

• iron, heme and globulin separated
• globulin and amino acids reutilized
• Iron stored in mononuclear phagocytic system  or combines with plasma protein and re-used in bone marrow
• heme biliverdin reduced to bilirubin in macrophage
• bilirubin released into plasma, binds to albumin, goes to liver

conjugation of bilirubin forms bilirubin glucuronide.  Conjugated bilirubin secreted into bile to enter intestine

reduce bilirubin glucuronide to urobilinogen, most excreted in feces, some returns to enterohepatic circulation.  Most reexcreted into bile, some bypasses liver, enters general circulation and excreted in urine.

The flow of bile acids from liver to intestine to portal blood to liver and back to intestine is known as enterohepatic circulation

• aid in digestion and absorption of fats in jejunum
• not absorbed until reach ileum, travel vial hepatic portal vein to liver.  
• Must enter hepatocyte to be recirculated
• HEPATIC UPTAKE REQUIRED for circualtion

• bile acids almost completely absorbed from portal blood
• no bile acids reach caudal vena cava.  LOW concentration in systemic circulation
• very slight increase postprandial.

• bile synthesis
• albumin synthesis
• synthesis of clotting factors
• detoxification (metabolites, drugs, toxins)
• NH3 to urea

in cells, leak out when cells are damaged (alterations in plasma membrane).  Rise very quickly after cell injury, like hit by car, much faster than induction enzymes.

overproduction of enzymes cells make.  Usually make very little, increase in production caused by stimuli.  Develops more slowly in blood than leakage.

Enzymes made only in a few organs or tissues.  Very important diagnostically.

• enzymes with similar catalytic abilities, produced in different places, but can vary in structure or half life.  If trying to identify a particular enzyme, get an idea of its half life.  
• Longer half lives are more likely to appear in serum

• Not directly correlated.  Dead cells can't leak but once.  Sub-lethal injuries make many more leakage enzymes.  
• necrosis or cirrhosis makes high serum enzymes, but less severe makes even higher.

• ALT
• AST
• SDH
• GLDH (or LDH)
• Hepatocellular damage, liver-specific enzymes.

• alanine aminotransferase, leakage enzyme
• liver specific in dog, cats and primates.  
• Not liver specific in horses, ruminants, pigs, birds.

• Aspartate Aminotransferase, leakage enzyme.
• Comes from liver, skeletal muscle, cardiac muscle, kidney, pancreas, erythrocytes
• caused by: liver disease, muscle inflammation or necrosis, hemolysis

• sorbitol dehydrogenase, leakage enzyme.  
• liver-specific in all domestic animals.  
• Used in large animals because ALT can't be.  
• sheep, horses, swine, goats, cattle).

• glutamate dehydrogenase, leakage enzyme
• cattle, sheep and goat hepatocytes.  
• caused by hepatocellular damage or necrosis
• standardized test not available.  Use SDH instead.

• Increased production in cells that usually produce a small amount
• ALKP (ALP)
• GGT
• Usually detecting cholestasis

• alkaline phosphatase-like enzymes can come from 
• osteoblast (bone)
• chondroblast (cartilage)
• intestine (short 1/2 life)
• placenta (short 1/2 life)
• renal (short 1/2 life)
• liver (hepatobiliary system, so evaluates cholestasis. Longer 1/2 life)

• alkaline phosphatase
• cholestasis in dogs, mostly
• serum or plasma ALP indicates liver bone or corticosteroid isoenzymes
• Increase caused by: cholestasis, bone growth in young or cancer, corticosteroids in dogs, severe periodontal disease

• ALP or ALKP
• comes from bone, liver, steriods
• common in young animals, stress, cushings, older dogs, cholestasis.

• Tested by ALP/ALKP, earliest indicator of biliary stasis in dog.  
• degenerative, by necrosis or hepatocyte swelling
• metabolic, by diabetes or hyperadrenocorticism (cushings)
• neoplastic by pancreatic carcinoma or lymphoma
• inflammatory by pancreatitis
• toxic diseases

ALP.  Serum ALP increases before serum bilirubin.

• gamma-glutamyltransferase, induced enzyme
• Liver is #1 source, found in several tissues.  
• Increased indicates liver disease, especially obstructive.  
• Increased with ALP in d/c indicates hepatobiliary disease
• Useful in detecting cholestasis in large animals, with SDH.  More sensitive to large animals than ALP.  
• Normal is <15, cholestasis = 200-300

• glucose
• albumin
• clotting factors

• glucose absorbed by small intestine, to liver via portal, to hepatocytes, converted from glucose to glycogen.  
• Hepatocytes can perform gluconeogenesis and glycogenolysis.  
• Up or down in liver disease, used as test of liver synthesis

• Test of hepatic synthesis.  
• Glucose can be up or down in liver disease
• increased glucose means decreased hepatic uptake, so prolonged postprandial hyperglycemia
• decreased glucose means reduced gluconeogenesis or glycogenolysis, most common in liver failure.

• test of hepatic synthesis
• If albumin in decreased in dogs, indicates 60%-80% loss of hepatic function.  
• Less common in horses.

• test of hepatic synthesis.  
• decreased clotting factors may present with bruising.  
• Liver synthesizes most coagulation factors and activates Vit K.  
• Blockage of bile flow reduces Vit K absorption and making of Vit K factors (2,7,9,10)

problem if liver coagulation factors are less than 30% of normal.  Can mean liver failure.

treat with Vit K.

• Bilirubin
• Ammonium
• Bile Acids

• Must evaluate liver, determine cause of icterus and assess bile obstruction.  
• From breakdown of hemoglobin by macrophage.  
• Small amounts in urine normal in dog.
• Conjugated in the liver, secreted in bile.  Can tell where problem is by conjugation etc, but rarely mentioned on tests.

accumulation of thick mucous bile from gallbladder inflammation

increase of bilirubin in serum.  Hemolysis (HCT, CBC), hepatocellular disease (ALT) or biliary obstruction (ALP, GGT)

• increase of bilirubin in urine.  Increased hemolysis, hepatocellular disease, biliary obstruction.  
• Small amount common in dog, not in cat.

• increase of urobilinogen in urine.  Clinically insignificant
• Unstable in urine, hard to detect.  
• hemolysis, mammal's with hepatic or biliary disease sometimes.

biliary obstruction

hemolysis, dark orange stool.

• biliary obstruction.  
• Clay colored stools.  No bile, so no dark color.

• increase of bilirubin in serum/blood (icterus)
• increase in urine bilirubin (orange urine)
• increase in fecal urobilin (orange stool)
• anemia
• hyperkalemia (false increase, leakage)
• hemoglobinemia
• hemoglobinuria (intravascular)

• increased bilirubin in blood (icteric)
• increased urine bilirubin (orange urine)
• NO orange stool due to not converting urobilogen
• Increase of bile acids in serum

• increase bilirubin in blood (icterus)
• increase urine bilirubin (orange urine)
• decrease urine urobilinogen
• decrease fecal urobilin (clay stools)
• Increase of bile acids in serum

• aka blood ammonia (NH3, plasma form NH4)
• produced in intestines by digestion of proteins or metabolism of bacteria
• enters liver through hepatic artery or portal vein, enters hepatocyte, converted into urea amino acids and protein (BUN) to be excreted by kidney.

• not removing from portal.  
• Hepatocellular disease, decreased production of urea (decreased BUN)
• portosystemic shunt (intrahepatic in large breed or extrahepatic in small breed)

• portosystemic shunt
• congenital or acquired, abnormal blood vessel allowing blood to bypass liver.
• NH4 and toxins not cleared from portal blood.  
• Intrahepatic, inside liver, in large breed dogs
• extrahepatic, outside liver, in small breed dogs.

• antibiotics to decrease bacteria which produce NH4
• lactulose to change pH to trap toxins and NH4 in feces and speed stool transit time
• Low protein diet to reduce substrates for ammonia
• surgery with ameroid ring closing over 6 weeks.

• aid in fat absorption and digestion
• synthesized by hepatocytes from cholesterol, conjugated, sent to duodenum.  
• reabsorbed by ileum, back into portal.  
• 90-95% reabsorbed in ileum, rest in feces
• Very efficient normally.

• should be very small.  
• hepatocellular disease, shunts, biliary obstruction

• decrease in reuptake and secretion
• more in circulation
• increase of acids in serum.

• Caused by severe cirrhosis, collateral circulation.  
• increased serum bilirubin
• normal to increased bile acids
• normal to increased blood ammonia
• normal to decreased blood glucose
• normal to decreased BUN
• normal to decreased Albumin serum
• prolonged coagulation test

• Increase in bile acids in serum.  >100
• normal or slight increase in leakage enzymes
• normal ALP and GGT
• normal bilirubin
• normal to increased ammonia
• normal to decreased albumen, BUN, glucose, cholesterol
• possible liver atrophy or microcytic anemia eventually

• lower bile acid excretion and subsequent regurgitation into systemic circulation--leakage from bile duct or gallbladder due to cholestasis
• increase of bile acids in serum.

• Bile Acids Response Test
• Gold standard for liver function.  
• d/c 2 samples, 2 hours apart.  1st after 12-hour fast, 2nd 2 hours after high-fat meal.
• normal is <5 pre and <15.5 post.   
• If icteric with hemolysis, no need for BART

• detects liver disease before clinical icterus, not specific for type or severity.  
• decrease in BA, ileum not absorbing (cats)
• increase in BA, liver disease in d/c (>20 pre and >25 post)

• single sample, normal is a pretty wide range.  
• Increase suggests liver disease, but assess in conjunction with other symptoms

• only way to definitively diagnose liver disease
• Use open laparotomy, laparoscopy (preferred, less invasive and can control bleeding), ultrasound-guided needle biopsy (tiny and can't see bleeding)

• hypoalbuminemia (less production from less area)
• decreased BUN (less urea to remove ammonia)
• increased or decreased glucose
• glucose increased or decreased, often decreased due to fewer cells to perform

• lactate dehydrogenase, leakage enzyme.  
• Marker of hepatic damage in all species.  Also increased by muscle damage or hemolysis.

• increased ALP and GGT
• increased serum bilirubin
• increased urine bilirubin
• decreased urobilinogen in urine
• decreased fecal urobilin and clay stool
• increased bile acids
• increased ALT and AST (due to pressure)
• If advanced, albumin, ammonia, BUN, cholesterol, coagulation tests, glucose involved.