Lec 16: Intro To Liver

Question 1

The liver is located beneath and attached to the ______, protected by the _____, and held in
place by _____.

Answer 1

• Diaphragm
• lower rib cage
• ligamentous attachments

Question 2

The liver is divided unequally into two lobes by the ______________, or equally into two by the ______________

Answer 2

• Falciform ligament
• Line of Cantlie

Question 3

Liver is an extremely vascular organ that receives its blood
supply from what two major sources?

Answer 3

Hepatic portal vein (75% blood), hepatic artery (25%)

Question 4

Give the correct order of blood flow starting from the Portal triad until the systemic circulation

Answer 4

portal triad —> the sinusoids —> central vein —> hepatic veins —> inferior vena cava —> heart —> lungs —> heart —> the rest of the body

Question 5

1. Portal triad consists of ___.
2. Two major cell types (liver)

Answer 5

1. Hepatic artery, Portal vein, Bile duct
2. Hepatocytes, Kupffer cells

Question 6

4 major functions of Liver

Answer 6

• Excretion & secretion
• metabolism
• detoxification
• storage

Question 7

1. The pigment formed from the degradation of RBCs.
2. Lifespan of RBC.
3. The pigment released from RBC destruction/hemolysis.

Answer 7

1. Bilirubin
2. 120 days
3. Hemoglobin (main pigment of RBC)

Question 8

1. Hemoglobin is separated into ___ & heme.
2. Heme is separated into ___ by enzyme ___.
3. The main product of Heme is reduced by enzyme ___ into unconjugated Bilirubin.
4. What carrier protein does unconjugated bilirubin bind to in order to travel from blood to liver?
5. The protein that transports Unconjugated bilirubin into the hepatocytes.

Answer 8

1. Globin
2. Products: CO, Iron, porphyrin ring, biliverdin
   Enzyme: Heme oxygenase
3. Biliverdin reductase
4. Albumin
5. Ligandin

Question 9

1. The enzyme that conjugates the unconjugated bilirubin.
2. Product of conjugation
3. Conjugated bilirubin will be excreted in bile which will be stored in the ___.
4. The bilirubin released in the intestine is converted into a colorless pigment called ___ by ____.

Answer 9

1. UDPGT
   • adds glucuronic acid to bilirubin
2. Bilirubin diglucuronide / conjugated bilirubin
3. Gallbladder
4. Urobilinogen, GI trapped bacteria

Question 10

Urobilinogen (pathways)

Answer 10

1. Converted to stercobilin for feces color
2. Absorbed into blood and excreted in urine as urobilinogen
3. Converted to urobilin pigment
4. Enterohepatic Recirculation
   • reabsorbed in blood then returns to liver

Question 11

Differentiate Conjugated and Unconjugated bilirubin

1. Solubility
2. Toxicity

Answer 11

Unconjugated bilirubin
1. Fat soluble
2. Toxic
• Can cross fatty nervous tissue & blood-brain barrier
• especially to brain —> Kernicterus

Conjugated bilirubin
1. Water soluble
2. Not toxic

Question 12

• An unconjugated bilirubin that is covalently bound to albumin.
• It is seen in significant Hepatic obstruction.
• It reacts in lab methods as conjugated bilirubin.

Answer 12

Delta bilirubin

Question 13

Composition of Total bilirubin

Answer 13

• unconjugated bilirubin (a-bilirubin) (indirect)
• monoglucuronide bilirubin (b-bilirubin)
• conjugated/diglucuronide bilirubin (y-bilirubin) (direct)
• Delta bilirubin

Question 14

Liver metabolizes carbohydrates, FA or lipids, Amino acid & protein

Carbohydrate is broken down into glucose. What are the 3 methods/ways the liver can process glucose?

Answer 14

1. Glucose —> pyruvate —(enters)—> TCA or Krebs’s cycle = more ATP
2. Circulated throughout the body
3. Stored as glycogen

Question 15

Almost all proteins are synthesized by the liver except ___.

Answer 15

1. Immunoglobulin & antibodies
   • formed by lymphocytes
2. Adult hemoglobin
   • synthesized by precursor cells

Question 16

TRANSAMINATION

1. Alanine
   • enzyme
   • co-enzyme
   • products
2. Aspartate
   • enzyme
   • co-enzyme
   • products

Answer 16

1. Alanine
   • Alanine aminotransferase (ALT)
   • Pyridoxam-5-phosphate
   • pyruvate & glutamate
2. Aspartate
   • Aspartate aminotransferase (AST)
   • Pyridoxam-5-phosphate
   • oxaloacetate & glutamate

Question 17

1. Describe transamination reaction
2. After transamination, deamination degrades them to produce ________ ions that are consumed in the synthesis of ______, which is excreted by the ________.

Answer 17

1. Amino groups are transferred from amino acid to alpha-keto acid with the help of coenzyme PLP.
2. Ammonium ions
   Urea
   Kidneys

Question 18

Major blood supply of the liver

Answer 18

Hepatic portal vein

Question 19

FIRST PASS EFFECT

1. What is first pass effect?
2. End result.
3. How is this beneficial?
4. Drawbacks.

Answer 19

1. Any substance ingested will first pass through the liver before reaching the rest of the body.
2. Substances absorbed will have partial metabolism.
3. Harmful substances are screened before reaching the rest of the body.
4. In medications, the amount of agent absorbed is further reduced.

Question 20

DETOXIFICATION

1. Phase One is mediated primarily by ___.
2. Phase One product.
3. Phase One generally involves what reactions?
4. What occurs in Phase Two?
5. Phase Two end product.
6. Phase Two end product will be excreted via ___.

Answer 20

1. Cytochrome P-450 family of enzymes.
2. Polar, less toxic intermediates
3. Redox, hydrolysis, hydration, dehalogenation reaction
4. The addition of functional groups into the intermediate molecule.
5. Highly polar waste products
6. Bile, stool, urine

Question 21

DRUG ACTIVATION
How will the following drugs utilize the ability of the liver to metabolize the substance?

• Cortisone
• Prednisone

Answer 21

1. Cortisone
   Cortisone —> cortisol (active form)
   • via 11beta-hydroxysteroid dehydrogenase 1
2. Prednisone
   Prednisone —> Prednisolone (active form)
   • via 11beta-hydroxysteroid dehydrogenase 1

Question 22

SUMMARY OF COMMON LIVER FUNCTION TESTS: Total Bilirubin to Direct Bilirubin

1. Also known as ___.
2. Total and Direct bilirubin may be (a) ___ in disease states involving (b)___.

Answer 22

1. B1, B2 Test
2. a.) elevated
   b.) uptake, conjugation & excretion of bilirubin/bile

Question 23

SUMMARY OF COMMON LIVER FUNCTION TESTS:

AST & ALT
1. Elevated in disease states involving ___.

ALP
1. Is it specific to liver?
2. Elevated in disease states involving ___.

Gamma glutamyl transferase
1. A confirmatory test for ___.
2. Elevated in disease states involving ___.

Albumin
1. Low in ___.
2. Albumin is secreted in the kidneys because of the lost of negatively charged barrier of the glomerulus.

Answer 23

AST & ALT
1. Damage to hepatocytes

ALP
1. No
2. obstruction to biliary outflow

Gamma glutamyl transferase
1. ALP
2. Biliary tract

Albumin
1. Cirrhosis
2. Nephrotic syndrome

Question 24

1. What is Icterus or Ectertia?
2. What is Jaundice?
3. [True or False] The sclera of the eyes can be described as icterus sclera?
4. At what bilirubin level does jaundice become noticeable?

Answer 24

1. A serum or plasma sample with a yellowish discoloration due to elevated bilirubin level.
2. The yellow discoloration of the skin, sclera of eyes, and mucous membrane.
3. TRUE
4. 3 to 5 mg/dL

Question 25

**CAUSES OF JAUNDICE** 1. Destruction of RBCs; hemolysis. (Increase or decrease) 2. It is due to a blockage in the drainage system of the body. (Increase or decrease) 3. It is due to the problem with the hepatocytes. (Increase or decrease) 4. It may be due to the impairment in either the processing or excretion of bilirubin.

Answer 25

1. Pre-hepatic hyperbilirubinemia • increased unconjugated bilirubin 2. Post-hepatic/extrahepatic jaundice (Choledocholithiasis) • increased bilirubin 3. Hepatic jaundice • increased bilirubin 4. Cholestatic jaundice

Question 26

• causes Hepatic jaundice • mutation of UGT1A1 gene in chromosome 2 • UDPGT deficiency • a benign autosomal recessive hereditary disorder

Answer 26

Gilbert's syndrome

Question 27

• causes hepatic jaundice • non hemolytic unconjugated hyperbilirubinemia

Answer 27

Crigler-Najjar syndrome

Question 28

**Crigler-Najjar Syndrome** **Type 1** • Pathology: • Kernicterus: • Response to Barbiturates: • Treatment: **Type 2** • Pathology: • Kernicterus: • Response to Barbiturates: • Treatment:

Answer 28

**Type 1** • Pathology: _Complete absence of UDPGT_ • Kernicterus: _present_ • Response to Barbiturates: _NONE_ • Treatment: _Liver transplant_ **Type 2** • Pathology: _Partial deficiency of UDPGT_ • Kernicterus: _rare_ • Response to Barbiturates: _Mild improvement_ • Treatment: _Phenobarbitone & Liver transplant_

Question 29

Enumerate the conjugated and Unconjugated hyperbilirubinemia.

Answer 29

**Unconjugated:** Gilbert's syndrome & Crigler-Najjar syndrome **Conjugated:** Dubin-Johnson syndrome

Question 30

They are inducers of the CYP family of enzymes. They increase CYP enzyme production, thus increasing UDPGT activity

Answer 30

Barbiturates

Question 31

An autosomal recessive inherited disorder caused by the deficiency of the transport protein **MRP 2** (multi drug resistance protein) or **C Multispecific Organic Anionic Transporter Protein**.

Answer 31

**Dubin-Johnson's syndrome** • when MRP 2 doesn't work, conjugated bilirubin is stuck inside hepatocytes. It will leak into the bloodstream causing *Conjugated Hyperbilirubinemia*

Question 32

Distinguishing feature is the appearance of dark stained granules on liver biopsy samples.

Answer 32

Dubin-Johnson's syndrome

Question 33

**Rotor's Syndrome** 1. Who discovered this? 2. Rotor's syndrome is a disease caused by mutations in ___ and ___ genes on chromosome _? 3. Does it totally inhibit the uptake of bilirubin? 4. The ALP & GGT levels are ___ (decrease, normal, increase) 5. It can have high levels of ___ excretion. 6. The color of the liver.

Answer 33

1. Dr. Arturo Beliesa Rotor 2. **a.)** SLCO1B1 & SLCO1B3, **b.)** Chromosome 12 3. **NO**, because other transport proteins are still present. 4. **Normal** • while biliary obstruction has elevated levels 5. Urinary coproporphyrin 6. Normal • black color of liver is found in D-J syndrome

Question 34

**NEONATAL JAUNDICE** 1. Factors causing it. 2. Typical neonatal jaundice (physiologic in nature) occurs beyond ___ postpartum. 3. General treatment 4. Principle 5. Isomers of bilirubin

Answer 34

1. **a.** Relative immaturity of liver & relative deficiency of UDPGT **b.** Increased destruction of HBF-containing RBCs 2. **48 hours** • at least 2 days old baby will look yellow which is normal 3. Phototherapy • inexpensive 4. Using a light in the spectrum around the range of blue to violet which will cause photoisomerization of bilirubin. 5. **a.** 4Z 15E-bilirubin **b.** Z-lumirubin • water soluble • excreted without conjugation

Question 35

**BILIRUBIN CONCENTRATION in people with Jaundice** a.) conjugated (increase or decrease) b.) unconjugated (increase or decrease) 1. Pre-hepatic 2. Gilbert's disease 3. Crigler-Najjar syndrome 4. Dubin-Johnson's syndrome 5. Rotor's syndrome 6. Neonatal jaundice 7. Post-hepatic

Answer 35

**Pre-hepatic** • increased unconjugated bilirubin **Gilbert's disease** • *decreased* conjugating enzyme activity = increased unconjugated bilirubin **Crigler-Najjar syndrome** • *NO* conjugating enzyme activity = increased unconjugated bilirubin **Dubin-Johnson's syndrome** • increased _conjugated_ bilirubin **Rotor's syndrome** • increase in *either/both* conjugated and/or unconjugated bilirubin **Neonatal jaundice** • depends on the cause **Post-hepatic** • obstruction of biliary outflow drainage = increased _conjugated_ bilirubin

Question 36

**Urine color** 1. Pre-hepatic 2. Hepatic 3. Post-hepatic **Stool color** 1. Pre-hepatic 2. Hepatic 3. Post-hepatic **AST & ALT levels** 1. Pre-hepatic 2. Hepatic 3. Post-hepatic **ALP levels** 1. Pre-hepatic 2. Hepatic 3. Post-hepatic

Answer 36

**Urine color** 1. Pre-hepatic: _acholuric/normal_ 2. Hepatic: _Dark/choluric_ 3. Post-hepatic: _Dark/choluric_ **Stool color** 1. Pre-hepatic: _Dark brown_ 2. Hepatic: _Normal_ 3. Post-hepatic: _clay colored_ **AST & ALT levels** 1. Pre-hepatic: _Normal_ 2. Hepatic: _very high (100-1000x)_ 3. Post-hepatic: _increased_ **ALP levels** 1. Pre-hepatic: _normal_ 2. Hepatic: _increased (2-3x)_ 3. Post-hepatic: _increased (10-12x)_

Question 37

• a disease process that causes an alteration in the liver function • the scarring of the liver by chronic or prolonged damage.

Answer 37

Cirrhosis

Question 38

**Cirrhosis** 1. Signs and symptoms 2. Most common cause 3. Other causes included

Answer 38

**Signs and symptoms** • fatigue • nausea • weight loss • jaundice • GI bleeding • intense itching • swelling legs & abdomen **Most common cause** Chronic Alcoholism **Other causes** • chronic infection with Hepa B & C & D virus • autoimmune diseases • inherited Disorders

Question 39

1. This liver cancer begins in the hepatocytes. 2. This liver cancer occurs when tumors from other parts of the body will spread or metastasize.

Answer 39

1. Primary liver cancer 2. Metastatic liver cancer

Question 40

• develops with underlying cirrhosis and chronic liver inflammation • alpha fetoprotein is very high (reaching 400-500 ug/L)

Answer 40

Hepatocellular Carcinoma

Question 41

**Hepatocellular Carcinoma** 1. Alpha fetoprotein is very high, reaching ____ ug/L. 2. Major risk factors

Answer 41

1. **400-500 ug/L** • normal value: 0-15 2. **Major risk factors** • Hepa B & C infection • heavy alcohol consumption • aflatoxin B1 ingestion (mycotoxin) • tobacco smoking • non-alcoholic fatty liver disease • (may be) Cirrhosis

Question 42

• liver function alteration • typically occurring in children • Salicylate or Aspirin is used during viral infection in children leading to: (a) rapidly progressing hepatitis (b) liver failure

Answer 42

Reye's Syndrome

Question 43

**Alcohol related Disorders** 1. The alcohol substance typically found in alcoholic beverages 2. Negative effects of Acetaldehyde 3. The chemical that causes hangovers.

Answer 43

1. **Ethanol** Ethanol —(alcohol dehydrogenase)—> Acetaldehyde —(Aldehyde dehydrogenase)—> Acetate 2. **Negative effects of Acetaldehyde** • lipid accumulation of fatty liver • liver inflammation • cirrhosis 3. Acetaldehyde ✨