Liver Metabolism

Question 1

Blood Supply to the Liver is

Answer 1

IN
75% portal Vein (Nutrient rich) = enteric circulation
25% Hepatic A (O2 rich) = periphery circulation

OUT
Hepatic Veins and IVC

Question 2

How does the Hepatic A and Portal V get into the liver

Answer 2

They enter the Sinusoid lined by loose epithelial cells - bringing nutrients in to the hepatocytes (where the biochemistry is done)

Question 3

What canal is in the middle of the hepatocytes

Answer 3

The Bile Canniculus which run in the opposite direction of the blood

Question 4

Another name for the Hepatic Vein

Answer 4

Central Vein that exists the Liver

Question 5

Which cell can regenerate

Answer 5

Hepatocytes (60 % of liver)

Question 6

Kupffer Cells

Answer 6

Macrophage that remove RBCs if needed and secrete cytokines and phagocytos pathogens, many lysosomes

Question 7

hepatic Stellate Cells

Answer 7

Secrete ECF and stores VIT A and fat
Makes the liver flexible and healthy (contractile to of the sinusoids)

Liver Cirrosis: high secretion of ECF inflates liver and effects the hepatocytes

Question 8

Pit Cells

Answer 8

NKC against invasion of toxic agents like tumor cells or viruses

Question 9

Cholangiocytes

Answer 9

Line bile ducts

Control bile rate and bile pH

Question 10

Liver Functions

Answer 10

1. Carb metabolism (has glucose-6-phosphate = release free glucose)
2. Lipid metabolism (makes TAGS, cholesterol, bile acids, bile salts, ketone bodies, break down TAGS)
3. Protein, NA metabolism
4. Urea Cycle
5. MAKES BLOOD PROTEINS
6. BILIRUBIN METABOLISM
7. WASTE MANAGEMENT= inactivation, detoxification, of metabolites

Question 11

What blood proteins does the liver make

Answer 11

Albumin, IgG, blood coagulation, Acute phase protiens

C-Reactive proteins, a- Antitrypsin and a-1 Antichymotrypsin

Question 12

Major role of LIVER

Answer 12

Monitor what is coming into body and how much each organ has and needs
Recycles many metabolites from the periphery and GI

Question 13

How is the BP of the Liver

Answer 13

Very Low = increased accessibility of metabolites and toxins to be absorbed

Question 14

What makes up bile

Answer 14

1. Bile salt + Bile acid = emulsification of fats , absorption of fat and VITs, prevention of cholesterol precipitation, eliminate cholesterol, digest fat
2. Bile Pigment
3. Cholesterol
4. Phospholipids
5. Fatty acids
6. Proteins
7. Inorganic Salts
8. Strong Detergents = amphipathic form micelles around lipids to increase SA lipids are exposed to lipases

Question 15

How does the liver make bile salts and bile acids

Answer 15

From the hepatic cholesterol in the hepatocytes and released into the bile canuliculi —-> Gallbladder or Duodenum

Question 16

Bile Salt vs Bile Acid

Answer 16

Bile Acid = Protonated COOH

Bile Salt = De-Protonated Salt COO-

Question 17

After lipases break down TAGS in these micelles

Answer 17

The smaller FAs get absorbed in intestinal mucosa

Bile Salts also form Micelles

Question 18

What is the rate limiting step of making bile acids

Answer 18

Cholesterol and 7a-hydroxylase makes 7a-hyroxycholesterol by added another OH- at the 7th position (in ER of hepatocytes)

Then last step makes the Cholic Acid (3 OH- and 1 COOH groups) or Chenodeoxycholic Acid is made

Question 19

How is Cholic Acid activated to make other forms

Answer 19

Cholyl CoA by adding a Coenzyme = pH6 (similar to duodenum, so not a good emulsifier and detergent for making micelles)

CONJUGATE this - makes Taurocholic Acid and Glycocholic Acid (pH = 2 and 4 respectively) GOOD DETERGENT

Question 20

Chenodeoxycholic Acid conjugates to

Answer 20

Tauroenodeoxycholic Acid and Glycochenodeoxycholic acid

Question 21

Where are bile absorbed

Where are bile salts and acids deconjugated and dehydroxylated

Answer 21

Bile salts become these secondary bile acids and then absorbed in the Ileum ——> back to liver
Bacteria in the gut (this forms secondary bile acids - Deoxycholic Acid- from Cholic + Lithocholic Acid- from chenodeoxycholic)

Question 22

Secondary bile acid

Answer 22

Removed OH-, COOH, and Taurnine or Glycine group

Question 23

Cholesterol Lowering Drug

Answer 23

Based on Bile acid-binding RESINS
EX: Cholestyramine = causes large exertion of bile acids (so they don’t renter the liver) by binding to the bile and making it non-absorbable
= bile acid synthesis is increased
= lower liver cholesterol
= lower plasma cholesterol and higher uptake of LDL

Question 24

Gallstones

Answer 24

Crystals made of supersaturated by cholesterol bile
Cholelithiasis : low secretion of bile salts or phospholipids into gallbladder or excess cholesterol secretion into bile

IF CHRONIC = may-absorption syndrome (steatorrhea, low fat soluble vitamins)

Question 25

The Liver converts and degrades what

Answer 25

Xenobiotics (compounds from the outside with no nutritional value, can be toxic) = food colors, drugs,

Metabolites ( compounds made by my body during metabolism)

Question 26

What are the 2 phases of Detoxification and Xenobiotics

Answer 26

Phase 1: increase polarity (hydrophobic are more toxic beaux they can stick to plasma membrane) *Catalyzed by Cytochrome P450 (CYP) enzymes

Phase 2: Add functional groups or conjugate them to make them safe for secretion

Question 27

Give phase 1 and 2 for RH

Answer 27

1. R-OH

2. R-SO4

Question 28

Pro drugs and the liver

Answer 28

Get active only after the liver had done the detoxification

Question 29

CYPE

Answer 29

Low specificity, can bind to many drugs and molecules
Has a heme group
Work with CYPR to localiza NADPH
* CYP3A4 = 30%-40% most abundant and metabolizes the most drugs
*does PHASE 1

Question 30

When are CYPS present

Answer 30

When you ingest the substance they arise

Some drugs can form a complex with a CYP and inhibit metabolism of other substrates

Question 31

What hotel you think about when giving a patient a drug

Answer 31

Does he take another drug that is a CYP inhibitor, becuz then I need to de-prescribe the drug at a lower dosage so its concentration in the body will be right

Question 32

CYP inhibitor EX

Answer 32

Itraconozole and ckarithromycin and cyclosporine = CITRUS JUICE, GRAPEFRUIT

Question 33

CYP inducer EX

Answer 33

rifampicin, caramazepine, St. John’s Wort (mood enhancer)

Question 34

Reason for Personalized Medicine

Answer 34

Polymorphism in CYPs and they are differently sensitive and abundant in every person
= Genotyping CYPs can be relevant to personalized drugs given

Question 35

What happens with overdose of Tylenol or with Alcohol

Answer 35

Acetominophen becomes a different compound then what it is usually metabolizes to (free radical NAPQI)
= it reacts with proteins and hepatocytes in the liver and changes + damages them
=Neutralized by giving Acetyl Cysteine (since bodies glutathione (natural) is depleted)

Question 36

Diseases of the Liver

What usually happens and changes

Answer 36

1. Hepatocytes secrete fibrillar collagen = not flexible (high density membrane , substances can’t pass= fibrosis and cirrosis)
2. Hepatic vascular channels are stiffened = increased intra-sinusoid also BP = portal hypertension = materials are not exchanged as normal

Question 37

How to test Liver function and what the data means

Answer 37

1. Albumin = lower can mean edema
2. Transaminases (ALT, AST) = normally in liver cells, if in plasma ->damaged liver cells
3. PT (Prothrombin)
4. Urea, Glucose, TAGS, Alkaline Phosphate
5. Bilirubin
6. Cholesterol (VLDL, LDL, HDL)