Liver Function (Liver-Syndrome) Flashcards
The chief metabolic organ of the body
Liver
A large organ divided unequally into two lobes by a falciform ligament
Liver
functional unit of the liver
Lobules
2 major cells
Hepatocytes (80%)
Hepatic macrophage (20%)
Most abundant cell
Hepatocytes (80%)
aka Kupffers cells
Hepatic macrophage (20%)
Liver blood supply: ________
1500 mL/min
2 blood supply of liver
Hepatic artery (25%)
Portal vein (75%)
Majority of the blood that is supplied to the liver.
Portal vein (75%)
Functions of the Liver
- Synthetic Function
- Conjugation Function
- Detoxification and Drug Metabolism
- Excretory and Secretory Function
- Storage Function
The capacity of liver to synthesize substances
Synthetic Function
Example of substances being synthesize by the liver
Proteins, cholesterol, carbohydrates, lipids, lipoproteins, enzymes, albumin (plasma protein)
Albumin rate of production
9-12 g/day
Involves the metabolism of bilirubin
Conjugation Function
Product of hemoglobin metabolism
Bilirubin
Liver conjugates bilirubin to ___________
200-300 mg/day
The liver protects the body from potential toxic substances absorbed from the intestine and toxic metabolic byproducts (eg. pharmaceutical drugs)
Detoxification and Drug Metabolism
Function of the liver that involves the bile
Excretory and Secretory Function
Emulsify fats (cholesterol) which is then excreted in the body
Bile
Liver is a storage site of glycogen, fat-soluble vitamins (A, D, E, K), and water-soluble vitamins
Storage Function
In storage function, Liver is a storage site of __________, ____-_______ (_, _, _, _), and ____-_____ _______
Glycogen
Fat-soluble vitamins (A, D, E, K)
Water-soluble vitamins
T/F: Storage Function is still assessed in the laboratory
FALSE: Not assessed in the laboratory; no diagnostic significance
T/F: All functions of the liver are assessed in the laboratory
FALSE: Out of the 5 functions of liver, only 4 functions are assessed in the laboratory (1-4)
enumerate which functions of the liver are assessed in the laboratory
- Synthetic Function
- Conjugation Function
- Detoxification and Drug Metabolism
- Excretory and Secretory Function
All functions of the liver are assessed in the laboratory EXCEPT:
Storage Function
Used to quantitate the severity of hepatic dysfunction
TESTS FOR LIVER SYNTHETIC FUNCTION
The more severe the hepatic dysfunction = the (less, more) the synthetic activity of liver
Less
TESTS FOR LIVER SYNTHETIC FUNCTION Measures:
Albumin (plasma protein)
Vitamin K-dependent clotting factors
Cholesterol (endogenous)
What are the Vitamin K-dependent clotting factors:
- Clotting Factors 2,7,9,10
What is Clotting Factor 2?
Prothrombin
What is Clotting Factor 7?
Stable Factor (Proconvertin)
What is Clotting Factor 9?
Plasma thromboplastic component (Christmas factor)
What is Clotting Factor 10?
Stuart-prower factor
What are the tests for liver synthetic function?
- Total Protein
- Albumin
- Albumin/Globulin Ratio
- Prothrombin Test
Assessment of nutritional status and presence of severe disease involving the liver, kidney and bone marrow
Total protein
Sample in Total Protein
Serum; NEVER plasma
Why is plasma never used in Total Protein?
Because all clotting factors are present and the majority is fibrinogen
Fibrinogen can increase total protein by _____________
0.2-0.4 g/dL
TOTAL PROTEIN
Interferences
hemolysis, ictericia
TOTAL PROTEIN
Reference value (serum)
6.5-8.3 g/dL
(CF to g/L: 10)
Methods for Total Protein
- Kjeldahl Method
- Biuret Method
- Folin-Ciocalteu (Lowry) Method
- UV Absorption Method
- Refractometry
- Turbidmetry and Nephelometry
- Salt Fractionation
- Coomasie Brilliant Blue Dye
- Ninhydrin
- Serum Protein Electrophoresis
Which method for Total is the MOST sensitive
Folin-Ciocalteu (Lowry) Method
Concentration is inversely proportional to the severity of hepatic disease.
ALBUMIN
ALBUMIN
T/F: Concentration is directly proportional to the severity of hepatic disease.
FALSE: Inversely proportional
↓albumin = (more, less) severe hepatic disease
more
Albumin is produced in the _______
Liver
Low albumin due to decrease synthesis
Hepatic cirrhosis
Nephrotic syndrome:
In hepatic cirrhosis and nephrotic syndrome, albumin and total protein are (increased, decreased)
Decreased
Why is total protein decreased in hepatic cirrhosis and nephrotic syndrome?
total protein is decreased because majority of total protein is albumin
ELECTROPHORETIC PATTERN
What is seen in hepatic cirrhosis?
β-γ bridging
ELECTROPHORETIC PATTERN
What is seen in Nephrotic syndrome?
α2 globulin spike
Methods in Albumin
Salt precipitation
Dye-binding
ALBUMIN
Reference value:
3.5 - 5.0 g/dL
ALBUMIN
Decreased reference value = (increased, decreased) total protein concentration
decreased
Used to validate if globulin is higher than the albumin
Albumin/Globulin Ratio
Globulin > Albumin
Inverted A/G ratio
Inverted A/G ratio occurs due to:
Hepatic cirrhosis
Multiple myeloma
Waldenström’s macroglobulinemia
ELECTROPHORETIC PATTERN
What is seen in Multiple myeloma?
gamma spike
ALBUMIN/GLOBULIN RATIO
Reference value:
1.3-3.1 g/dL
(CF to g/L: 10)
AG ratio =
Albumin/Globulin
Globulin =
Total protein - Albumin
Prothrombin test aka
Vitamin K Response Test
T/F: Prothrombin test is called as Vitamin K Response Test in case of laboratory liver synthetic function assessment
TRUE
What Vitamin K is being administered in Prothrombin Test?
phyloquinones
What is the method of administration in Prothrombin Test?
Intramuscularly
Dosage of Vitamin K administered in Prothrombin Test
10 mg for 1-3 days
T/F: Administration of Vitamin K in Prothrombin Test is done after the testing
FALSE: Prior the testing
Prolonged Prothrombin Time – liver cannot synthesize _______________
Clotting factors
It differentiates intrahepatic disorder from extrahepatic disorder
Prothrombin Test
PROTHROMBIN TEST
T/F: Intrahepatic disorder occurs in the liver
TRUE
PROTHROMBIN TEST
Intrahepatic disorder is due to (decreased, increased), (short, prolonged) prothrombin time
Increased
Prolonged
PROTHROMBIN TEST
T/F: Extrahepatic disorder occurs in the liver
FALSE: Outside the liver
PROTHROMBIN TEST
T/F: Extrahepatic disorder (normal, abnormal) prothrombin time
Normal
Prolonged prothrombin time signifies massive cellular damage.
Acute/Chronic Hepatitis
TESTS FOR CONJUGATION AND EXCRETION FUNCTION
- Bilirubin
- Delta Bilirubin
End product of hemoglobin metabolism (waste product)
Bilirubin
No function in the body; excreted
Bilirubin
Principal pigment in bile
Bilirubin
____ of bilirubin are from hemoglobin
85%
15% of bilirubin are from ____, _______,_______
myoglobin, cytochrome, peroxidase/catalase
Produced if RBCs are senescent
Bilirubin
How is Bilirubin Synthesized by the body?
- Happens in the Circulation
- Happens in the Liver
HAPPENS IN THE CIRCULATION
After ____ days, RBC will be transported to ______, which will then be destroyed, resulting to the release of __________.
120
Spleen
Hemoglobin
Three components of hemoglobin:
Ferrous Iron (Fe²⁺)
Heme
Globin
Ferrous iron (Fe²⁺) in hemoglobin are transported by _________ to the liver and bone marrow
Transferrin
HAPPENS IN THE CIRCULATION
When globins are degraded, amino acids will be
(excreted, reused)
reused
HAPPENS IN THE CIRCULATION
Heme will be converted to __________
Biliverdin
HAPPENS IN THE CIRCULATION
The conversion of heme to biliverdin is through the action of ____________
Heme oxygenase
HAPPENS IN THE CIRCULATION
Biliverdin, in the action of ____________ will be converted to bilirubin 1
Biliverdin reductase
HAPPENS IN THE LIVER
Albumin will release ___________
Bilirubin 1
HAPPENS IN THE LIVER
Bilirubin 1 will be bound to a transport protein called as ________
Ligandins
HAPPENS IN THE LIVER
Bilirubin 1 esterification/conjugation in the ligandins produces _________________________
Bilirubin monoglucuronide
HAPPENS IN THE LIVER
Conjugation of the other propionic acid by addition of another glucuronic acid to produce _____________________ _________________
bilirubin diglucuronide/bilirubin 2
The conjugation process is catalyzed by the enzyme
uridine diphosphate glucuronyl transferase (UDPGT)
In the intestine, the B2 will be reduced to __________, _________, and to ___________ in the intestines
mesobilirubin —> mesobilirubinogen –> urobilinogen
Urobilinogen fates:
80% - feces
20% - urine
Principal pigment of feces
Stercobilin
Principal pigment of urine
Urochrome
BILIRUBIN 1 other names
- Unconjugated Bilirubin
- Water insoluble
- Non-polar Bilirubin
- Indirect Bilirubin
- Hemobilirubin
- Slow reacting
- Pre-hepatic Bilirubin
BILIRUBIN 2 other names
- Conjugated Bilirubin
- Water soluble
- Polar Bilirubin
- Direct Bilirubin
- Cholebilirubin
- One-minute/Prompt Bilirubin (quickly reacts with)
- Post-hepatic / Hepatic / Obstuctuve / Regurtitative Bilirubn
Plasma concentration of bilirubin increases upon birth and reaches its peak on the ___ day.
5th
If bilirubin synthesis > liver clearance rate = (increased, decreased) bilirubin level
Increased
BILIRUBIN
Reference value for Conjugated Bilirubin (B2)
0 - 0.2 mg/dL (0-3 µmol/L)
Requires the most sensitive reagent because the normal value is zero
Conjugated Bilirubin (B2)
BILIRUBIN
Reference value for Unconjugated Bilirubin (B2)
0.2-0.8 mg/dL (3-14 µmol/L)
BILIRUBIN
Reference value for Total Bilirubin (B2 + B1)
0.2-1.0 mg/dL (3-17 µmol/L)
Must be conjugated to be excreted
Bilirubin 1
Common bilirubin found in the circulation
Bilirubin 1
Normally present in blood (formed in the circulation)
Bilirubin 1
Normally not present in serum
Bilirubin 2
Small amount of ____________ in the blood is because of minor leakage from ______________
Bilirubin 2
Hepatocytes
Formed in the liver
Bilirubin 2
Conjugated bilirubin bounded to albumin
Delta Bilirubin
DELTA BILIRUBIN
Helps in monitoring the decline of serum bilirubin following _____________
Cholecystectomy (Surgical removal of the gall bladder)
Prolonged elevation of conjugated bilirubin is due to the binding of albumin in serum/plasma
Delta Bilirubin
T/F: Delta Bilirubin has shorter life compared to other bilirubin
FALSE: Longer
Delta bilirubin reacts with what reagent?
Diazo reagent
DELTA BILIRUBIN
Reference Value:
<0.2 mg/dL
T/F: Delta bilirubin is computed, not measured
TRUE
Delta bilirubin is measured if patient is ________ (_________) due to high bilirubin
neonate (≤14 days)
Delta bilirubin =
TB - (IB+DB)
Condition where there is increase in bilirubin
Jaundice
_____________________ characterized by yellow discoloration of the skin, sclera, and mucus membranes.
Hyperbilirubinemia
Most common hyperbilirubinemia among adults?
Cholelithiasis (gallstones)
More commonly termed for serum or plasma with abnormal yellow discoloration due to hyperbilirubinemia.
Icterus
T/F: Icterus is always visible
FALSE: NOT always visible
ICTERUS
It will be visible if the bilirubin ________
> 25mg/dL (visible ictericia)
T/F: Icterus is still used interchangeably with jaundice
FALSE: BEFORE, but is now only referring to serum or plasma
Type of jaundice is not visible to the naked eyes (although with high bilirubin)
Overt Jaundice
Over jaundice has a bilirubin level of
1.0 - 1.5 mg/dL
Overt jaundice will only become visible if the bilirubin is ________
3.0 - 5.0 mg/dL
THREE TYPES OF JAUNDICE
- Pre-hepatic jaundice
- Post-hepatic jaundice
- Hepatic jaundice
aka Hemolytic jaundice, Unconjugated hyperbilirubinemia
PRE-HEPATIC JAUNDICE
Caused by too much red blood cell destruction
PRE-HEPATIC JAUNDICE
PRE-HEPATIC JAUNDICE
Conditions where there is too much RBC destruction
- Hemolytic disease of the newborn
- Hemolytic anemia
- Malaria
PRE-HEPATIC JAUNDICE
Very rare because bilirubin are removed by the placenta
Hemolytic disease of the newborn (HDN)
PRE-HEPATIC JAUNDICE
Cause of malaria
Plasmodium spp.
From most to least common, enumerate the Plasmodium spp.
P. falciparum
P. vivax
P. malariae
P. ovale
PRE-HEPATIC JAUNDICE
Increased destroyed RBCs = (increased, decreased) hemoglobin released
increased
PRE-HEPATIC JAUNDICE
Laboratory findings:
- Indirect Bilirubin: __________
- Direct Bilirubin: ________
- Urobilinogen: _________
- Urine bilirubin: ________
Increased
Normal
Normal
Negative
T/F: Increase indirect bilirubin is toxic (neurotoxic)
TRUE
Indirect bilirubin is neurotoxic because it can cross the blood brain barrier (BBB) causing __________
Kernicterus
bilirubin deposition in the brain causing severe motor dysfunction and retardation
Kernicterus
aka Obstructive jaundice
POST-HEPATIC JAUNDICE
Caused by failure of bile to flow to the intestine or impaired bilirubin excretion
POST-HEPATIC JAUNDICE
POST-HEPATIC JAUNDICE
Laboratory findings:
- Indirect Bilirubin: __________
- Direct Bilirubin: ________
- Urobilinogen: _________
- Urine bilirubin: ________
- Alkaline phosphatase: __________
Normal
Increased
Decreased
Positive
Increased
No.1 marker of the post-hepatic jaundice
Alkaline phosphatase:
It is increased due to increased excretion rate
Alkaline phosphatase:
aka Hepatocellular combined jaundice
HEPATIC JAUNDICE
Caused by disorders of bilirubin metabolism, transport defects, hepatocellular injury or destruction.
HEPATIC JAUNDICE
HEPATIC JAUNDICE
Laboratory findings:
- Indirect Bilirubin: __________
- Direct Bilirubin: ________
- Urobilinogen: _________
- Urine bilirubin: ________
Increased
Increased
Decreased
Positive
INHERITED DISORDERS OF BILIRUBIN METABOLISM (HEPATIC JAUNDICE)
- Gilbert’s Syndrome
- Crigler-Najjar Syndrome (Type 1 & 2)
- Dubin Johnson Syndrome
- Rotor Syndrome
- Lucey-Driscoll Syndrome
Bilirubin Transport Deficit
Gilbert’s Syndrome
Characterized by impaired cellular uptake of bilirubin due to genetic mutation in UGT1A1 gene (chromosome #2)
Gilbert’s Syndrome
GILBERT’S SYNDROME
Characterized by impaired cellular uptake of bilirubin due to genetic mutation in _______ gene (chromosome #2)
UGT1A1
GILBERT’S SYNDROME
Affected individuals may have no symptoms but may have mild _________ and predisposed ______________ (aka paracetamol) toxicity.
Icterus
Acetaminophen
GILBERT’S SYNDROME
Laboratory Findings:
- Indirect Bilirubin: ________
1.5-3.0 mg/dL
GILBERT’S SYNDROME
Indirect Bilirubin rarely increased to _______ as it maximizes its conjugation activity
4.5 mg/dL
Conjugation Deficit
Crigler-Najjar Syndrome
CRIGLER-NAJJAR SYNDROME
Problem: _______
conjugation process
CRIGLER-NAJJAR SYNDROME
Laboratory result:
Elevated indirect bilirubin
Complete deficiency of UDGPT
Crigler-Najjar Syndrome Type I
CRIGLER-NAJJAR SYNDROME TYPE 1
Complete deficiency of _______
UDGPT
CRIGLER-NAJJAR SYNDROME TYPE 1
Laboratory results:
- Indirect bilirubin: _______
- Direct bilirubin: _________
> 25 mg/dL
None
CRIGLER-NAJJAR SYNDROME TYPE 1
Symptoms:
kernicterus, colorless bile
Partial deficiency of UDGPT
CRIGLER-NAJJAR SYNDROME TYPE 2
CRIGLER-NAJJAR SYNDROME TYPE 2
(partial, complete) deficiency of UDGPT
Partial
CRIGLER-NAJJAR SYNDROME TYPE 2
Laboratory results:
- Indirect bilirubin: _______
- Direct bilirubin: _________
5-20 mg/dL
small amount
Diagnostic treatment for Crigler-Najjar Syndrome: ___________
Phototherapy
Bilirubin Excretion Deficit
Conjugated Hyperbilirubinemia
Dubin-Johnson Syndrome
Defective excretion of direct bilirubin into the canaliculi caused by hepatocyte membrane defect.
Dubin-Johnson Syndrome
DUBIN-JOHNSON SYNDROME
Characterized of an intense dark pigmentation of the liver due to accumulation of ________________
lipofuscin pigment
Accumulation of lipofuscin pigment is called as
Black liver (black discoloration of the liver)
DUBIN-JOHNSON SYNDROME
Laboratory findings:
- Elevation in direct bilirubin and total bilirubin (___________)
- Delta Bilirubin: __________
2-5 mg/dL
Increased
Similar with Dubin-Johnson Syndrome WITHOUT the “black liver”
Rotor Syndrome
Inherited disorders of bilirubin metabolism which cause is unknown
Rotor Syndrome
ROTOR SYNDROME
Laboratory findings:
- Elevation in direct bilirubin and total bilirubin (___________)
- Delta Bilirubin: __________
2-5 mg/dL
Increased
Familial form of unconjugated hyperbilirubinemia caused by a circulating inhibitor of bilirubin conjugation
Lucey-Driscoll Syndrome
LUCEY-DRISCOLL SYNDROME
________ (conjugation enzyme) are inhibited - no conjugation, no B2
UDPGT
LUCEY-DRISCOLL SYNDROME
Laboratory findings:
- Indirect bilirubin: _________
increased (2-3 weeks of life)
