Lec 16: Intro To Liver Flashcards
The liver is located beneath and attached to the ______, protected by the _____, and held in
place by _____.
- Diaphragm
- lower rib cage
- ligamentous attachments
The liver is divided unequally into two lobes by the ______________, or equally into two by the ______________
- Falciform ligament
- Line of Cantlie
Liver is an extremely vascular organ that receives its blood
supply from what two major sources?
Hepatic portal vein (75% blood), hepatic artery (25%)
Give the correct order of blood flow starting from the Portal triad until the systemic circulation
portal triad —> the sinusoids —> central vein —> hepatic veins —> inferior vena cava —> heart —> lungs —> heart —> the rest of the body
- Portal triad consists of ___.
- Two major cell types (liver)
- Hepatic artery, Portal vein, Bile duct
- Hepatocytes, Kupffer cells
4 major functions of Liver
- Excretion & secretion
- metabolism
- detoxification
- storage
- The pigment formed from the degradation of RBCs.
- Lifespan of RBC.
- The pigment released from RBC destruction/hemolysis.
- Bilirubin
- 120 days
- Hemoglobin (main pigment of RBC)
- Hemoglobin is separated into ___ & heme.
- Heme is separated into ___ by enzyme ___.
- The main product of Heme is reduced by enzyme ___ into unconjugated Bilirubin.
- What carrier protein does unconjugated bilirubin bind to in order to travel from blood to liver?
- The protein that transports Unconjugated bilirubin into the hepatocytes.
- Globin
-
Products: CO, Iron, porphyrin ring, biliverdin
Enzyme: Heme oxygenase - Biliverdin reductase
- Albumin
- Ligandin
- The enzyme that conjugates the unconjugated bilirubin.
- Product of conjugation
- Conjugated bilirubin will be excreted in bile which will be stored in the ___.
- The bilirubin released in the intestine is converted into a colorless pigment called ___ by ____.
- UDPGT
• adds glucuronic acid to bilirubin - Bilirubin diglucuronide / conjugated bilirubin
- Gallbladder
- Urobilinogen, GI trapped bacteria
Urobilinogen (pathways)
- Converted to stercobilin for feces color
- Absorbed into blood and excreted in urine as urobilinogen
- Converted to urobilin pigment
- Enterohepatic Recirculation
• reabsorbed in blood then returns to liver
Differentiate Conjugated and Unconjugated bilirubin
- Solubility
- Toxicity
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
- An unconjugated bilirubin that is covalently bound to albumin.
- It is seen in significant Hepatic obstruction.
- It reacts in lab methods as conjugated bilirubin.
Delta bilirubin
Composition of Total bilirubin
• unconjugated bilirubin (a-bilirubin) (indirect)
• monoglucuronide bilirubin (b-bilirubin)
• conjugated/diglucuronide bilirubin (y-bilirubin) (direct)
• Delta bilirubin
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?
- Glucose —> pyruvate —(enters)—> TCA or Krebs’s cycle = more ATP
- Circulated throughout the body
- Stored as glycogen
Almost all proteins are synthesized by the liver except ___.
- Immunoglobulin & antibodies
• formed by lymphocytes - Adult hemoglobin
• synthesized by precursor cells
TRANSAMINATION
- Alanine
• enzyme
• co-enzyme
• products - Aspartate
• enzyme
• co-enzyme
• products
-
Alanine
• Alanine aminotransferase (ALT)
• Pyridoxam-5-phosphate
• pyruvate & glutamate -
Aspartate
• Aspartate aminotransferase (AST)
• Pyridoxam-5-phosphate
• oxaloacetate & glutamate
- Describe transamination reaction
- After transamination, deamination degrades them to produce ________ ions that are consumed in the synthesis of ______, which is excreted by the ________.
- Amino groups are transferred from amino acid to alpha-keto acid with the help of coenzyme PLP.
- Ammonium ions
Urea
Kidneys
Major blood supply of the liver
Hepatic portal vein
FIRST PASS EFFECT
- What is first pass effect?
- End result.
- How is this beneficial?
- Drawbacks.
- Any substance ingested will first pass through the liver before reaching the rest of the body.
- Substances absorbed will have partial metabolism.
- Harmful substances are screened before reaching the rest of the body.
- In medications, the amount of agent absorbed is further reduced.
DETOXIFICATION
- Phase One is mediated primarily by ___.
- Phase One product.
- Phase One generally involves what reactions?
- What occurs in Phase Two?
- Phase Two end product.
- Phase Two end product will be excreted via ___.
- Cytochrome P-450 family of enzymes.
- Polar, less toxic intermediates
- Redox, hydrolysis, hydration, dehalogenation reaction
- The addition of functional groups into the intermediate molecule.
- Highly polar waste products
- Bile, stool, urine
DRUG ACTIVATION
How will the following drugs utilize the ability of the liver to metabolize the substance?
• Cortisone
• Prednisone
-
Cortisone
Cortisone —> cortisol (active form)
• via 11beta-hydroxysteroid dehydrogenase 1 -
Prednisone
Prednisone —> Prednisolone (active form)
• via 11beta-hydroxysteroid dehydrogenase 1
SUMMARY OF COMMON LIVER FUNCTION TESTS: Total Bilirubin to Direct Bilirubin
- Also known as ___.
- Total and Direct bilirubin may be (a) ___ in disease states involving (b)___.
- B1, B2 Test
-
a.) elevated
b.) uptake, conjugation & excretion of bilirubin/bile
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.
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
- What is Icterus or Ectertia?
- What is Jaundice?
- [True or False] The sclera of the eyes can be described as icterus sclera?
- At what bilirubin level does jaundice become noticeable?
- A serum or plasma sample with a yellowish discoloration due to elevated bilirubin level.
- The yellow discoloration of the skin, sclera of eyes, and mucous membrane.
- TRUE
- 3 to 5 mg/dL
CAUSES OF JAUNDICE
- Destruction of RBCs; hemolysis. (Increase or decrease)
- It is due to a blockage in the drainage system of the body. (Increase or decrease)
- It is due to the problem with the hepatocytes. (Increase or decrease)
- It may be due to the impairment in either the processing or excretion of bilirubin.
- Pre-hepatic hyperbilirubinemia
• increased unconjugated bilirubin - Post-hepatic/extrahepatic jaundice (Choledocholithiasis)
• increased bilirubin - Hepatic jaundice
• increased bilirubin - Cholestatic jaundice
• causes Hepatic jaundice
• mutation of UGT1A1 gene in chromosome 2
• UDPGT deficiency
• a benign autosomal recessive hereditary disorder
Gilbert’s syndrome
• causes hepatic jaundice
• non hemolytic unconjugated hyperbilirubinemia
Crigler-Najjar syndrome
Crigler-Najjar Syndrome
Type 1
• Pathology:
• Kernicterus:
• Response to Barbiturates:
• Treatment:
Type 2
• Pathology:
• Kernicterus:
• Response to Barbiturates:
• Treatment:
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
Enumerate the conjugated and Unconjugated hyperbilirubinemia.
Unconjugated:
Gilbert’s syndrome & Crigler-Najjar syndrome
Conjugated:
Dubin-Johnson syndrome
They are inducers of the CYP family of enzymes. They increase CYP enzyme production, thus increasing UDPGT activity
Barbiturates
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.
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
Distinguishing feature is the appearance of dark stained granules on liver biopsy samples.
Dubin-Johnson’s syndrome
Rotor’s Syndrome
- Who discovered this?
- Rotor’s syndrome is a disease caused by mutations in ___ and ___ genes on chromosome _?
- Does it totally inhibit the uptake of bilirubin?
- The ALP & GGT levels are ___ (decrease, normal, increase)
- It can have high levels of ___ excretion.
- The color of the liver.
- Dr. Arturo Beliesa Rotor
-
a.) SLCO1B1 & SLCO1B3,
b.) Chromosome 12 - NO, because other transport proteins are still present.
-
Normal
• while biliary obstruction has elevated levels - Urinary coproporphyrin
- Normal
• black color of liver is found in D-J syndrome
NEONATAL JAUNDICE
- Factors causing it.
- Typical neonatal jaundice (physiologic in nature) occurs beyond ___ postpartum.
- General treatment
- Principle
- Isomers of bilirubin
-
a. Relative immaturity of liver & relative deficiency of UDPGT
b. Increased destruction of HBF-containing RBCs -
48 hours
• at least 2 days old baby will look yellow which is normal - Phototherapy
• inexpensive - Using a light in the spectrum around the range of blue to violet which will cause photoisomerization of bilirubin.
-
a. 4Z 15E-bilirubin
b. Z-lumirubin
• water soluble
• excreted without conjugation
BILIRUBIN CONCENTRATION in people with Jaundice
a.) conjugated (increase or decrease)
b.) unconjugated (increase or decrease)
- Pre-hepatic
- Gilbert’s disease
- Crigler-Najjar syndrome
- Dubin-Johnson’s syndrome
- Rotor’s syndrome
- Neonatal jaundice
- Post-hepatic
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
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
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)
• a disease process that causes an alteration in the liver function
• the scarring of the liver by chronic or prolonged damage.
Cirrhosis
Cirrhosis
- Signs and symptoms
- Most common cause
- Other causes included
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
- This liver cancer begins in the hepatocytes.
- This liver cancer occurs when tumors from other parts of the body will spread or metastasize.
- Primary liver cancer
- Metastatic liver cancer
• develops with underlying cirrhosis and chronic liver inflammation
• alpha fetoprotein is very high (reaching 400-500 ug/L)
Hepatocellular Carcinoma
Hepatocellular Carcinoma
- Alpha fetoprotein is very high, reaching ____ ug/L.
- Major risk factors
-
400-500 ug/L
• normal value: 0-15 -
Major risk factors
• Hepa B & C infection
• heavy alcohol consumption
• aflatoxin B1 ingestion (mycotoxin)
• tobacco smoking
• non-alcoholic fatty liver disease
• (may be) Cirrhosis
• 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
Reye’s Syndrome
Alcohol related Disorders
- The alcohol substance typically found in alcoholic beverages
- Negative effects of Acetaldehyde
- The chemical that causes hangovers.
-
Ethanol
Ethanol —(alcohol dehydrogenase)—> Acetaldehyde —(Aldehyde dehydrogenase)—> Acetate -
Negative effects of Acetaldehyde
• lipid accumulation of fatty liver
• liver inflammation
• cirrhosis - Acetaldehyde ✨
