Clin Chem - Q3 [Liver Functions]

Liver

Largest internal organ

synthesis
metabolism
digestion
detoxification

Liver play a biochemical role in: ______, ________, ________, ________

Vascular System

2 blood supplies

Hepatic artery
Portal vein

Two blood supply of the vascular system of the liver

Portal vein

(75%): supplies nutrient rich blood

Hepatic artery

(25%): supplies O2 rich blood

sinusoids

Blood flows into the ___________ which course between hepatocytes.

Excretory (Biliary) System

excretory system of the liver

1. Intrahepatic ducts (bile canaliculi & bile ductile) →
2. Right + hepatic ducts →
3. Common hepatic ducts + Cystic duct →
4. Common bile duct →
5. Duodenum

Excretory products of the cell drain to:

bile canaliculi
bile ductile

Two parts if the Intrahepatic ducts

Lobules

Six sided with central vein and portal triads
(hepatic artery, portal vein and a bile duct)

hepatic artery
portal vein
bile duct

Parts of the portal triads

Hepatocytes
Kupffer cells

Major cell types in the lobules

Excretory and Secretory Function

Eliminate heme waste products

Globin
Iron
Heme

Hemoglobin is broken down into:

bilirubin

Heme is converted to?

albumin (B1)

bilirubin is bound by ___________ and transported to the liver.

(sinusoids) B1

In the liver__________ is released from albumin

Ligandin

(sinusoids) B1 is picked up by?

smooth ER

Ligandin carries B1 to the _________ for conjugation

B2

B1 forms into _______ after conjugation

hepatocyte

B2 is secreted from the ______ to the intestine,

urobilinogen

In the intestine, bacteria metabolize B2 into ______

stercobilin (80%)

Urobilinogen is oxidized to _________

kidneys

stercobilin (80%) is recycled
through the liver (20%), & filtered in the ______.

Carbohydrates
Lipids
Proteins

Liver metabolizes: ______, _______ ,_______

Glycogenesis
Glycogenolysis
Gluconeogenesis

Liver is involve in which glucose pathways (Carbohydrates metab)

bile salts
lipids

Liver aids in the synthesis of what lipids?

albumin
α and β globulins
coagulation proteins

Liver aids in the synthesis of what proteins?

drugs and poisons

Liver can detoxify "First pass" of foreign materials (______&_______)

bilirubin & ammonia

Liver can detoxify metabolic products (_________ & _________)

"First pass" of foreign materials

Detoxification of the liver is also called?

Excretory and Secretory
Metabolism
Detoxification and Drug Metabolism

3 Biochemical Function of the Liver

Jaundice (Icterus)

Yellow discoloration of skin, eyes and mucous membranes (>3 mg/dL)

Pre-hepatic (uncojugated hyperbilirubinemia)

Excessive destruction of RBC
Acute and chronic hemolytic anemia

Hemolytic Disease of the Newborn
Hemolytic Transfusion Reaction
Malaria

Three diseases caused by Acute and chronic hemolytic anemia induced by Pre-hepatic (uncojugated hyperbilirubinemia)

Pre-hepatic (unconjugated hyperbilirubinemia)

↑ Total Bilirubin (↑ B1, Normal B2)

Gilbert Syndrome (Conjugation Deficit)
Crigler-Najjar Syndrome (Conjugation Deficit)
Dubin Johnson (Excretion Deficit)
Rotor Syndrome (Transport Deficit)
Physiologic Jaundice (Conjugation Deficit)

Hepatic Disease of the Liver?

Gilbert Syndrome (Conjugation Deficit)

Unconjugated hyperbilirubinemia due to defective conjugation system

UGT1A1

Gilbert Syndrome there is reduced expression of ___________ (20-30% of normal values)

Ligandin

In Gilbert Syndrome there is a deficiency of ________ (Transport Deficit)

Gilbert Syndrome (Conjugation Deficit)

↑ Total Bilirubin (↑ B1, Normal B2) - Hepatic Disease

Crigler-Najjar Syndrome (Conjugation Deficit)

Molecular defect of gene

Type 1 - Crigler-Najjar Syndrome

absence of conjugation

Type 2 - Crigler-Najjar Syndrome

severe deficiency of UDP-GT

Crigler-Najjar Syndrome

↑ Total Bilirubin (↑ B1, ↓ B2) - Hepatic Disease

Dubin Johnson (Excretion Deficit)

Defective removal of B2 from the liver cell and the excretion to bile

MDR2/cMOAT

In Dubin Johnson there is a deficiency of __________ proteins

Dubin Johnson

Hepatic disease that causes Hyperbilirunemia, Bilirubinuria

Delta Bilirubin

Presence of _______ is a marker for Dubin Johnson

Dark-stained

____________ granules on a liver biopsy is a marker of Dubin Johnson

Dubin Johnson

↑ Total Bilirubin (Normal B1, ↑B2) - Hepatic Disease

Rotor Syndrome (Transport Deficit)

Confused with Dubin-Johnson, but there is no dark pigmented granules in liver biopsy

Rotor Syndrome (Transport Deficit)

↑ Total Bilirubin (Normal B1, ↑B2) - Hepatic Disease

Physiologic Jaundice (Conjugation Deficit)

Deficiency in the glucoronyl transferase
Leads to Kernicterus

Physiologic Jaundice (Conjugation Deficit)

↑ Total Bilirubin (↑B1, Normal B2) - Hepatic Disease

Biliary obstructive disease (Cholestasis)

Physical obstructions which prevent flow of B2 into bile canal. (i. Gall stones, ii. Tumors)

Gall stones
Tumors

Can cause blockage of blood flow that leads to Biliary obstructive disease (Cholestasis)

clay colored

In Biliary Obstructive Disease, stool may appear as?

Biliary Obstructive Disease

↑ Total Bilirubin (↑B1, Normal B2) - Post Hepatic Disease

Cirrhosis

Scar tissue replaces liver tissue resulting to blockage of blood flow (Chronic alcoholism & Chronic Hepatitis C)

Chronic alcoholism
Chronic Hepatitis C

Can cause Cirrhosis

Tumors

Primary or Metastatic and Benign or Malignant

Reye's Syndrome

Disorders preceded by infectious (viral) or drug (aspirin) related disease in children.

Reye's Syndrome

Noninflammatory encephalopathy and fatty liver generation

Alcoholic Fatty Liver
Alcoholic Hepatitis
Alcoholic Cirrhosis

Alcohol Related Disorder

Acetaminophen
Tranquilizer
Antibiotics
Anti-inflammatory drugs

Drug Related Disorders

Unconjugated Bilirubin (Indirect Bili. or B1)

• Non-polar and water insoluble
• Found in plasma bound to albumin

Unconjugated Bilirubin (Indirect Bili. or B1)

Reacts w/ Diazo reagent w/ an accelerator

Conjugated Bilirubin (Direct Bili. or B2)

• Polar and water soluble
• Found in plasma in a free state

Conjugated Bilirubin (Direct Bili. or B2)

Reacts with Diazo reagent directly

Delta Bilirubin

Conjugated bilirubin bound to albumin

Diazotized Sulfanilic Acid

Bilirubin is measured using?

Direct Van den Bergh

• B2 + Diazo reagent → Azobilirubin
• Measures the Conjugated Bilirubin (B2)

Indirect Van den Bergh

• B1 + Diazo reagent → No reaction
• B1 + Diazo rgt. + Accelerator → Azobilirubin
• Measures the Total Bilirubin (B1 + B2)

B1 = Total Bilirubin - B2

Formula for B1

Malloy - Evelyn

Accelerator: 50% Methanol
Stopper: None
pH: Acidic (1.2)
End Color: Red-Purple (560 nm)

Jendrassik - Grof

Accelerator: Caffeine - Benzoate
Stopper: Ascorbic Acid
pH: Basic (Alkaline Tartrate)
End Color: Blue (600 nm)

Use serum

Specimen for Malloy-Evelyn

Fasting sample

Use this sample to avoid lipemia

False ↓

Hemolysis

↓ by 30-50% / hour

Protect from light

False ↑

Lipemia

1. Use Serum
2. Use fasting samples
3. Avoid hemolysis
4. Protect from light

Specimen and Collection Consideration

Aspartate Aminotransferase (AST)
Alanine Aminotransferase (ALT)

Enzyme Test in Liver Disease - Hepatocellular

Alkaline Phosphatase (ALP)
5'-Nucleotidase (5NT)
Gamma Glutamyl Transferase (GGT)

Enzyme Test in Liver Disease - Hepatobiliary

Kjeldahl
Refractometry
Biuret
Dye Binding
Electrophoresis
Serum Proteins

Measurement of Hepatic Synthetic Ability

Albumin

↓ in chronic liver disease

α1-globulins

↓ in α1- antitrypsin deficiency

γ-globulin

↑ in acute and chronic liver disease

Clotting factors

↑ Prothrombin Time (PT)

Ammonia

Test Measuring Nitrogen Metabolism

Ammonia

↑ in hepatic failure and in deficiencies of urea cycle