Liver function

What is the liver apart of?

Reticuloendothelial system, active during an immune response

What proteins does the liver process?

• albumin and amino acids

• coagulation factors

• carrier proteins

• acute phase reactants

What other important substances does the liver metabolize?

• carbohydrates and lipids

• bilirubin 

What is albumin and amino acid turned into by the liver?

Alpha and beta globulins 

What are the functions of the liver?

• metabolism

• detoxification

• excretion and secretion

• storage

What is first pass conversion?

Substances absorbed from the GI tract pass through the liver and are often changed in the process

What happens during drug metabolism?

Substances are converted to more soluble or less toxic forms

What enzymatic processes go on in the liver?

• Hydrolysis, hydroxylation, oxidation, reduction, carboxylation and demethylation

• alcohol is converted to acetaldehyde and then to acetate by alcohol dehydrogenase

• conversion of ammonia to urea

What substances does the liver excrete/secrete?

• bile acids

• bilirubin

• metabolites: drugs, hormones  

What substances are stored in the liver?

• glycogen 

• Iron as ferritin

• fat soluble vitamins (A, E, D, K, B12)

• Albumin 

What components is hemoglobin broken down into?

• globulin

• iron

• porphyrin ring holding the iron molecule 

How is bilirubin transported?

• unconjugated bilirubin is loosely bound to albumin

• complex transported to liver via the blood stream

• bilirubin is converted to a conjugated form in the liver 

What is the anatomy of the liver?

• weighs 3 ½ lbs in an adult

• situated in the top right portion of the abdominal cavity just under the diaphragm

What sources does the liver receive blood through?

• Venous blood from the gastrointestinal tract (nutrient rich)

• Oxygenated from the hepatic artery 

How does blood leave the liver?

Via a central vein in each lobule that drains into the hepatic vein

What is lobule?

• the functional unit of the liver

• hexagonal shaped

• made up of hepatocytes

• arranged in thin layers

• contains small blood vessels called sinusoids

What kind of specialized cells are in the lobule?

Kupffer cells (macrophages)

What is at the corner of each lobule?

A branch of the hepatic portal vein, hepatic artery and bile duct

What do the bile canaluculi drain into?

The hepatic duct

What does the hepatic duct join?

The cystic duct which leads from the gallbladder to form the common bile duct, which then drains into the duodenum 

What does kupffer cells do?

Remove the bilirubin-albumin complex from the blood

Where is unconjugated bilirubin transported?

Into the microsomal region of the hepatocyte

What happens to unconjugated bilirubin in the hepatocyte?

• bilirubin-albumin complex broken down and albumin returned to circulation 

• bilirubin is conjugated to bilirubin diglucuronide within the hepatocyte 

What enzyme converts bilirubin to the conjugated form?

UDPG-transferase

How is conjugated bilirubin removed from the hepatocyte?

Actively into the bile canalicili and excreted in no the bile ducts

What is conjugated bilirubin excreted with?

Bile salts via the common bile ducts

What do anaerobic bacteria due to bilirubin?

Convert it to urobilinogen(colorless) and urobilin (brown)

What happens to 50% of urobilinogen?

Reabsorbed by the portal circulation and filtered by the kidney and eventually returned to the liver

What color does stool turn when there is an obstruction?

Chalky because conjugated bilirubin cannot be removed through the common bile duct and there is no conversation to urobilin

What is jaundice?

• yellow discoloration of the skin and white of the eyes

• caused by a build-up of bilirubin in the circulation and tissues

• a sign that the liver or bile duct system is not working normally 

Pre-hepatic jaundice is due to?

Increased breakdown of rbcs leading to an elevation in unconjugated bilirubin

What is hepatic jaundice due to?

Increased buildup of conjugated bilirubin due to damaged hepatocytes

What is post hepatic jaundice due to?

Increase in products of bilirubin metabolism due to decreased outflow from common bile duct 

What happens in pre hepatic/hemolytic jaundice?

• liver is presented with more unconjugated bilirubin than it has the capacity to handle

• unconjugated bilirubin builds up in the serum

• conjugated may increased because the liver has reserve capacity to conjugate bilirubin

• no bilirubin detection in urine (unconjugated bilirubin insoluble), increased urine urobilinogen   

What are the serum and urine bilirubin levels in prehepatic jaundice?

• Total bilirubin: Normal to increased

• Conjugated: Normal to increased

• Unconjugated: Increased

• Urine urobilinogen: Increased  

• Urine bilirubin: Normal

• LD: Increased 

What is the cause of neonatal physiological jaundice?

Immature liver, infant’s UPDG transferase not yet fully functioning

What are can result from increased hemolysis?

Kernicterus

What is kernicterus?

Deposition of bilirubin in lipid portion of brain tissue

What is Crigler-Najjar?

Congenital lack of UPDG transferase

What happens in type 1 and type 2 Crigler-Najjar?

• type 1: >50% motility rate and severe mental retardation if child lives, chronic persistent jaundice

• Type 2: milder form

What is gilbert’s disease?

• defect in ability to transport unconjugated bilirubin into the microsomal region of the hepatocyte 

• may have mild jaundice

• most individuals are asymptomatic 

What is Dubin-Johnson disease?

• Defect in transport system of conjugated bilirubin from microsomal region to bile canaliculi 

• may have upper right quadrant pain

• non-specific jaundice

• not life threatening 

What causes hepatic jaundice?

Diffuse hepatocellular damage or necrosis 

• viral or toxic hepatitis

• cirrhosis

• Intra-hepatic destruction from pressure or edema 

What happens in viral or toxic hepatitis?

Selective areas of hepatocytes are inflamed blocking the out flow of conjugated bilirubin into the bile canaliculi 

What happens in cirrhosis?

• nodular damage throughout the liver

• also blocks outflow of bilirubin into bille canaliculi 

What are the bilirubin results in hepatic jaundice?

• Total bilirubin: Increased

• Conjugated: Increased

• Unconjugated: Increased

• Urine urobilinogen: Increased 

• Urine bilirubin: Increased

• AST/ALT: greatly increased if hepatitis

• Alk phos: increased

• GGT: greatly increased in alcoholic cirrhosis

What are some causes of post hepatic jaundice?

Stones, spasms, strictures or neoplasms

What are the bilirubin results in post hepatic jaundice?

• Total bilirubin: Increased

• Conjugated: Increased

• Unconjugated: Increased

• Urine urobilinogen: Decreased

• Urine bilirubin: Increased

• AST/ALT: normal to increased

• ALK phos: greatly Increased 

How are sample for bilirubin testing handled?

• Pedi-tubes: brown

• UV light can cause 50% loss of bilirubin per an hour 

• large amounts of hgb can also interfere  

What is delta bilirubin?

Conjugated bilirubin bound to albumin

What is the Jendrassik Grof method used to measure?

• total bilirubin

• Direct bilirubin 

What are the reagents and reaction in the total bilirubin method?

• Diazonium salt + caffeine → Diazo bilirubin (pink) + Alkaline tartrate → green (shift in color spectrum due to pH change 

What is the reaction in the direct bilirubin method?

Direct bilirubin + diazonium salt + HCL → Diazo bilirubin + alkaline tartrate → green

How is indirect bilirubin calculated?

Total bilirubin - direct bilirubin

What is the original method of bilirubin testing?

Evelyn malloy method, tartrate step not added so hemolysis was a problem

What is the normal pattern for LD isoenzymes?

LD1<LD2

What is the pattern for LD isoenzymes in acute myocardial infraction?

LD1>LD2 the 1:2 flip 

What is the LD isoenzyme pattern in liver disease?

• LD5 is elevated

• LD3 and LD4 slight elevation 

What is seen in AMI with 2nd liver involvment?

• LD1 and LD2 elevate

• LD1>LD2

• LD 5 elevated 

What are alkaline phosphatase isoenzymes?

• heterogeneous group of enzymes from various tissues

• migrate with alpha-2 globulins

• hard to differentiate 

What is the best method to measure Alkaline phosphatase isoenzymes?

• Heat stability (10 minutes at 56C)

• Bone virtually destroyed (<20% activity remains) 

• Liver resistant to heat (>50% remains) 

What are some other heat stable AP isoenzymes?

• placental alkaline phosphatase

• tumor markers (Regan and Nagao AP)

When is intestine AP isoenzyme fraction increased?

• more frequently noted in patients with blood groups O and B who secrete H-blood group substance 

• Increased postprandially and after a fatty meal

• Increased In cirrhosis, malignancy, diabetes, and chronical renal failure

When is the placental AP isoenzyme fraction increased?

• during the later stages of pregnancy

• heat stable like liver alkaline phosphatase

• low levels of heat stable isoenzyme equal a poor prognosis for the fetus

When are bone AP isoenzymes increased?

• Elevated in osteoblastic activity

• Normally increased in growing children

• Increased in Paget’s disease or Renal Rickets

• Increased bone cancer or osteomalacia

• Decreased in children seen in cretinism or hypophosphatemia

When are increased liver AP isoenzymes seen?

• increased in acute hepatitis, cirrhosis, fatty liver, drug induced liver disease, obstruction, metastatic tumor

• increased fast fraction (macrohepatic isoenzyme) in metastatic carcinoma (sometimes seen in viral hepatitis and alcoholic cirrhosis