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8. Liver metabolism

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What supplies the liver with blood?
Dual supply:
-portal vein rich in nutrients
-hepatic artery - for O2
What are the 2 important cell types in the liver?
What is the function of each?
-Kupffer's cells - phagocytic
-Parenchymal cells - hepatocytes
List the 5 categories of hepatic functions:
1. Metabolic
2. Synthetic
3. Catabolic
4. Metabolic
5. Storage
What are the metabolic processes that occur in the liver?
-Glycogen homeostasis
-Lipid metabolism
-Amino acid transamidation
What gets synthesized in the liver?
-Almost all plasma proteins
-Bile acids (from cholesterol)
What does the liver STORE?
Lipid soluble vitamins
Iron
Copper
Glycogen
Triglycerides
What does the liver catabolize?
Hormones
Proteins
Drugs/Toxins
How is stuff excreted from the liver?
In bile
Why is the gallbladder important?
It stores bile juice, which functions in digestion.
How does bile juice affect digestion?
1. Emulsifies fats/fatty acids
2. Allows fat-soluble vitamins to be absorbed
3. Neutralizes stomach acid
4. Allows drugs/toxin excretion
5. Allows body to rid of sterol ring
What are the hematologic functions of the liver?
1. Synthesis of clotting factors
2. Hematopoiesis in embryos occurs here.
3. Part of RES, gets rid of senescent RBCs.
How does the liver detoxify the body?
By catabolizing and excreting toxins through oxidation, reduction, hydrolysis, and conjugation.
What part of hematology does the liver always come up in, coming back to haunt me?
BILIRUBIN metabolism
What are the 4 steps in bilirubin metabolism?
1. Formation
2. Transport to liver
3. Conjugation
4. Excretion
What is urobilinogen?
The reduced product of diglucuronide (direct bilirubin) formed by intestinal bacteria; most is excreted by the liver.
What types of problems cause prehepatic jaundice?
Those that cause increased bilirubin production exceeding the liver's ability to conjugate it.
What are some specific causes of prehepatic jaundice?
1. Hereditary hemolytic anemias, HDN, transfusion reactions, Physiologic jaundice of Newborn, congestive heart failure...
Why does physiologic jaundice of the newborn develop?
B/c UDP-glucuronyltransferase is one of the last liver functions to mature.
What types of problems cause hepatitic jaundice?
Retention/Regurgitation jaundice
-Decreased bilirubin uptake by the liver cells.
What are some specific causes of hepatitic jaundice?
Gilbert's, Crijler/Najar, Dubin Johnson, and other liver diseases.
How is it that the direct bilirubin can be increased in hepatitic jaundice?
Glucuronyl transferase (the conjugating enzyme) leaks into the sinusoids from endothelial cells.
What type of problems cause post-hepatitic jaundice?
Obstruction of the biliary network, either intra or extrahepatic.
What are specific causes of post hepatic jaundice?
-Common bile duct stones
-Cancer of bile ducts/pancreas
-Bile duct stricture
What is the main problem in Gilbert's syndrome?
The hepatocytes are unable to take up bilirubin from the blood.
What is the main problem in Crigler-Najar and Physiologic Jaundice of Newborn?
Conjugation by the liver is impaired - i.e., glucuronyltransferase deficiency.
What is the main problem in Dubin-Johnson syndrome?
Hepatocytes can't secrete conjugated bilirubin - but they CAN conjugate it at least.
What builds up in Gilbert's syndrome then?
Unconjugated bilirubin in the blood; thus total bilirubin
What builds up in Crigler-najjar and Physiologic jaundice then?
Unconjugated bilirubin gets retained by the liver.
What builds up in Dubin Johnson then?
Conjugated bilirubin - gets spit back into the blood because it can't get secreted into bile.
Which form of bilirubin is water soluble?
Direct/conjugated
What is the classic method for bilirubin measurement?
Diazo reaction
Which bilirubin form reacts with diazo reagent?
Only water-soluble, conjugated.
How is total bilirubin measured then?
By adding a caffeine accelerator, allows both fractions to become H2O-soluble.
What 3 additional methods can be used for measuring bilirubin?
1. HPLC
2. Direct-reading bilirubinometer
3. Reflectance spectrophotometry (Ektachem)
What is a direct-reading bilirubinometer used for?
only neonates
What is the urine bilirubin a test for?
Conjugated hyperbilirubinemia - it's a qualitative screen only.
What specimens are tested for urobilinogen?
Urine and feces.
What is an important function of the pancreas?
Excretion of digestive enzymes.
the pancreas is described as a gland with what 2 types of functions?
-exocrine
-endocrine
What important enzymes are produced by the pancreas?
-Amylase
-Lipase
-Pepsin
-Trypsin/chymotrypsin/elastase
So what do the pancreatic enzymes break down?
-Starch
-Lipids
-Proteins
-Amino acids
What metabolic diseases can damage the liver?
1. Hemachromatosis
2. Wilson's disease (copper)
3. Reye's syndrome (chickenpox)
4. Alcoholism (cirrhosis)

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