Liver

Question 1

Give the liver’s role in B5 metabolism

Answer 1

Responsible for forming acetyl CoA from panothenic acid

Question 2

Give the liver’s role in Vitamin D metabolism

Answer 2

Responsible for hydroxylation of vitamin D to 25-OHD3

Question 3

Give the liver’s role in folate metabolism

Answer 3

Responsible for formation of 5-methyl terthydrofolic acid (THFA)

Question 4

Give the liver’s role in niacin metabolism

Answer 4

Responsible for methylation of niacinamide

Question 5

Give the liver’s role in B6 metabolism

Answer 5

phosphorylation of pyridoxine

Question 6

Give the liver’s role in thiamin metabolism

Answer 6

Responsible for the dephosphoylation of thiamin

Question 7

Give the liver’s role in B12 metabolism

Answer 7

Formation of coenzyme B12

Question 8

Explain how alcohol acts as a disinfectant and lipid solvent

Answer 8

It has the ability to dissolve lipids out of cells and destroy cell structure

Question 9

What are the three pathways for alcohol oxidation in the hepatocytes?

Answer 9

1. ALCOHOL DEHYDROGENASE pathway in the hepatocyte cytosol (main pathway- generates free radicals)
2. ETHANOL OXIDIZING SYSTEM (MEOS) in the ER
3. CATALASE in peroxisomes (metabolizes <2% of alcohol)

Question 10

What is the product of all three ethanol metabolism pathways? Where does this happen?

Answer 10

Acetate

In the mitochondria (then goes into circulation)

Question 11

What is the end stage of chronic liver disease? What is the result?

Answer 11

Cirrhosis; results in hepatocyte destruction

Question 12

What are the three broad causes of hepatocyte destruction?

Answer 12

• physical destruction
• ischemia (lack of blood flow)
• infection

Question 13

Describe the changes of the liver in cirrhosis.

Answer 13

• Non-necrotic hepatocytes try to regenerate the liver but can’t get back to normal bc fibrotic bands of scar tissue get in the way
• multiply and form nodules of hepatocytes
• Don’t have normal vascularization, so don’t perform normally

Question 14

Where do nodules get their blood? Why is this an issue?

Answer 14

Nodules get their blood from the hepatic artery

•Sensitive from to decreases in its blood flow
• Hepatic artery is sensitive to sympathetic vasoconstriction from dehydration, shock, sepsis or general anesthesia
** Can see sudden decrease in hepatic function from these conditions

Question 15

What are some common s/s of liver cirrhosis?

Answer 15

Malaise, lethargy, dyspepsia, bloating, N/V and anorexia

••Cirrhosis requires presence of nodules throughout liver

Question 16

How does cirrhosis affect CHO metabolism?

Answer 16

Increased fasting and post-prandial insulin due to:
• Portal systemic shunting
• Increased peripheral resistance to insulin - both muscle and adipose tx
• Increased FFA
• Increased growth hormone

Question 17

List three sources of hyperglycemia in hepatic DM patients

Answer 17

• Reduced insulin extraction by damaged liver
• Portosystemic shunts
• Desensitized beta cells of pancreas

Question 18

What counter-regulatory hormones are increased in hepatic DM?

Answer 18

Glucagon

Growth hormone

Question 19

What is hepatic DM considered an indicator for?

Answer 19

Advanced liver damage

Question 20

Give two ways the presence of DM worsens the course of liver cirrhosis

Answer 20

• Accelerates liver fibrosis and inflammation

* Potentiates incidence of bacterial infections (white cells don’t work well in high glucose environments)

Question 21

Why is amount of alcohol consumed related to risk of hepatic DM?

Answer 21

• Ethanol ingestion reduces insulin-mediated glucose uptake (alcohol metabolized 1st, glucose 2nd)
• Chronic drinking results in pancreatic damage and injury to b-cells

Question 22

What is one way to differentiate between hepatic DM and T2DM?

Answer 22

Generally do not see microangiopathy in T2DM

**but challenging to differentiate

Question 23

How do you treat hepatic DM?

Answer 23

• Difficult - oral hypoglycemic drugs are hepatotoxic

* Monitor glucose levels - adjust CHO throughout the day, small meals

Question 24

Which proteins are elevated and which are increased in liver patients?

Answer 24

• Increased:

• aromatic AAs
• free tryptophan
• free methionine
• Decreased BCAA (decreased BCAA:AAA ratio)
• Increased ammonia

Question 25

Describe why a liver patient would have elevated ammonia levels

Answer 25

• Depressed plasma proteins synthesized in hepatic failure, so urea synthesis is depressed; blood ammonia levels rise
• Ammonia is from ingested protein, sloughed cells or internal bleeding
• Urine output can sometimes fall

Question 26

Describe lipid metabolism in liver cirrhosis. What is increased, what is decreased and why?

Answer 26

INCREASED:
•FFA - due to insulin resistance
•FA synthesis - elevated by NADH

DECREASED:
• FA oxidation - mitochondria using H+ from alcohol rather than oxidizing FFA to produce energy via TCA
• apolipoprotein synthesis and release from liver - lower serum cholesterol and less VLDL synthesis

Question 27

Give some clinical presentations of cirrhosis

Answer 27

• N/V/Anorexia
• Distention
• Edema
• Macrcytic anemia
• Steatorrhea

Question 28

Describe the cause of jaundice

Answer 28

Bilirubin binding to elastin in skin and mucus membranes
• Bilirubin is an end product of hemoglobin (Hbg) decomposition; is transported to liver and conjugated with glycine and taurine and excreted into intestine in the bile

Question 29

What can cause ascites? Give the pathophysiology.

Answer 29

Portal hypertension with decreased renal excretion