Major Functions of the Liver

Question 1

What is the function of acute phase proteins?

Answer 1

Binding proteins opsonins (antibodies), such as C-reactive proteins (CRP) promote the phagocytosis of macromolecules released by: damaged tissue or infective agents

Question 2

What is the action of protease inhibitors (a1-antitrupsin and a1-antichymotrypsin)?

Answer 2

They inhibit proteolytic enzymes promoting the formation of fibroblast growth, production of connective tissue resulting in repair and resolution of injury

Question 3

What does the protease inhibitor a1-antitrypsin target? What happens if there is a genetic deficiency?

Answer 3

a1-antitrypsin, has macrophage-derived elastase as primary target

Infancy as liver disease (intrahepatic biliary atresia) — 10% of infants with a1-antitrypsin deficiency develop liver disease, which presents as jaundice, cholestasis, pruritus, growth retardation, and increased serum lipids

Adulthood as lung disease (develop between 20 and 50 yo)— shortness of breath, reduced ability to exercise, wheezing and emphysema, 15% of adults with a1-antitrypsin deficiency develop liver damage (cirrhosis) with risk of developing a type of liver cancer called hepatocellular carcinoma

Question 4

What happens in the deficiency of a1-antitrypsin?

Answer 4

Elastase causes tissue damage

Question 5

What is the role of ceruloplasmin? What happens in its deficiency?

Answer 5

It is a copper-carrying protein for the liver. It functions as an iron oxidizing (ferroxidase) enzyme

Ceruloplasmin deficiency due to liver function leads to anemia

Question 6

Why do anemia and diabetes occur together?

Answer 6

Mutation in ceruloplasmin leads to aceruloplasminemia (absence of ceruloplasmin). This leads to iron transport problems, leading to the iron accumulation in the tissues and organs

Iron deficiency in blood leads to anemia, damage to the pancreas leads to diabetes

Question 7

What is the function of a-fetoprotein (AFP)?

Elevated AFP levels can be a sign of what?

Answer 7

In the fetus, this serves as a physiological function similar to those of albumin in the adult. After the first year, AFP is replaced by albumin

ELEVATED AFP is a sign of hepatocellular carcinoma or ovarian and testicular teratocarcinomas

Question 8

What is acetaminophen conjugated to? How is it excreted? What happens to the excess?

Answer 8

Acetaminophen is a hepatotoxic compound at high doses. It is usually conjugated to glucuronic acid and excreted via the kidneys

The excess is oxidized by cytochrome P450 to N-acetyl-p-benzoquinone mine (NAPQI)

Question 9

Why is N-acetyl-p-benzoquinone mine (NAPQI) dangerous? What is a treatment for this?

Answer 9

This byproduct causes damage to cellular proteins and free-radical mediated perioxidation of the membrane’s fats, leading to the death of hepatocytes

N-acetyl cysteine (MUCOMYST; aka NAC) is an antidote to NAPQI-induced acetaminophen hepatotoxicity. IT restores intracellular glutathione (promotes detoxification), scavenger of free radicals, provide a glutathione substitute, it directly conjugates with NAPQI

Question 10

What can alcohol metabolism lead to?

Answer 10

Alcohol metabolism can lead to alcohol hepatitis, steatosis (deposition of fat in the liver), or cirrhosis, leading to liver failure

Question 11

Where and how is acetaldehyde synthesized? (Enzyme, cofactor, reactant)

Answer 11

Acetaldehyde is formed in the liver from ethanol using alcohol dehydrogenase. NAD+ is the cofactor

Question 12

What happens after acetaldehyde is synthesized in the liver? What is the cofactor and enzyme used in the reaction?

Answer 12

Acetate is formed. NAD+ is used using the enzyme acetaldehyde dehydrogenase (ALDH)

Question 13

What are the two forms of ADH found in individuals (difference from slow and fast metabolizers)?

Answer 13

Men with 2 genes for “slow enzyme” have a 30% reduction in heart attack risk and higher levels of HDL compared to fast metabolizers

Question 14

What is the use of glutamyl transferase (GGT)?

Answer 14

GGT is the most sensitive enzyme indicator of liver damage from alcohol

Question 15

What is the use of antabuse (disulfiram)?

Answer 15

Antabuse (disulfiram) is a long-term inhibitor of ALDH

Question 16

What does alcohol abuse lead to?

Answer 16

It leads to the accumulation of NADH and acetaldehyde. High levels of NADH inhibits the formation of OAA from pyruvate, leading to lactic acidosis, hypoglycemia, and the formation of ATP from NADH

Question 17

What can high levels of NADH lead to?

Answer 17

High levels of NADH inhibits the formation of OAA from pyruvate, leading to lactic acidosis, hypoglycemia, and the formation of ATP from NADH. IT can also lead to the inhibition of B-oxidatio of fat, promoting the synthesis of FA – fatty liver

Question 18

What is the action of pyruvate carboxylase? What inhibits it?

Answer 18

Pyruvate carboxylase is responsible for the formation of OAA from pyruvate and CO2

It is inhibited by acidic pH

Question 19

What is the action of malate dehydrogenase? What reverses it? What can one of its reactants lead to?

Answer 19

Malate dehydrogenase is responsible for the production of malate from OAA and NADH (reversible reaction). High NADH reverses malate dehydrogenase

Depletion of OAA leads to hypoglycemia

Question 20

What can hypoglycemia in pregnant women cause?

Answer 20

It can cause fetal alcohol syndrome, which is an irreversible mental and physical damage

Question 21

What happens with the increased activity of cytochrome P450 hydroxyls system?

Answer 21

Increased detoxification of hydrocarbon drugs, increased activation of carcinogens. Increased degradation of steroid hormones (gynecomastia and hypertrophy of testis leads to sterility. Increased estradiol formation leads to feminization)

Question 22

How does a sober alcoholic react to benzodiazepines and barbiturates?

Answer 22

They are insensitive to these drugs

Question 23

What happens with the intake of benzodiazapines and barbituates with alcohol?

Answer 23

Super sensitivity because of MEOS inhibition by ethanol leading to toxic overdose

Question 24

What disease is caused by thiamine deficiency secondary to alcohol antivitamin action. Results in the brain’s ability to use glucose, leading to encephalopathy, pophthalmoplegia, ataxia, stupor, coma, and death (if no thiamin injection)

Answer 24

Wernicke’s syndrome

Question 25

What disease is characterized by the inability to learn new material (anterograde amnesia), mild retrograde amnesia, impaired reasoning ability. If not severe, it may be corrected by thiamin therapy

Answer 25

Korsakoff’s syndrome

Question 26

What are the advantages of light alcohol intake?

Answer 26

Light intake, i.e., 1 drink for a woman, 2 drinks for a man per day, can be beneficial. Incidence of heart diseases is reduced due to antioxidant effects of flavonoid and polyphenol compounds (phytochemicals)

Low ethanol intake is believed to increase HDL levels in individuals with “slow” ADH

Question 27

What is catechin?

Answer 27

In red wine, the antioxidant is catechin. In vitro catechin inhibits the oxidation of cholesterol (LDL)

Question 28

What are the differences between AST and ALT?

Answer 28

AST is found especially in the heart, liver, and skeletal muscle

ALT is present primarily in the liver and to lesser extent in kidney and skeletal muscle, making it more “liver specific”

Question 29

What is the use of alkaline phosphatase (ALP)?

Answer 29

They are found in a number of tissues but used most often in the clinical diagnosis of bone and liver disease (different isozymes)

They have a moderate increase in hepatitis and cirrhosis. Two-fold increase of ALP in extrahepatic biliary obstruction

Question 30

What detoxifies xenobiotics?

Answer 30

Cytochrome P450