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Senescent RBCs
What is the main source of bilirubin?
F
T/F: Bilirubin is soluble in plasma
Albumin
This protein is responsible for carrying bilirubin in the bloodstream
B
QC: Expected total bilirubin in (1) Adults (2) Children
<0.3 mg/dL
Normal value of Direct Bilirubin in adults?
0.1-1 mg/dL
Normal value of Indirect Bilirubin in adults?
Ligandin
Upon entry of bilirubin in the hepatocyte, what protein is responsible for transporting it to the SER for glucuronidation?
UDP-glucuronyltransferase
Enzyme that facilitates the glucuronidation of bilirubin
Multidrug Resistant Protein (MRP) transporter
Transporter that excretes bilirubin glucuronides into the canalicular system
Gilbert Syndrome
This disease is associated with a defective transport protein found in the hepatocyte
Hemolytic Anemia
This disease is associated with an overwhelming synthesis of B1 from destroyed RBCs
Dubin Johnson Syndrome
This disease is associated with a defect in the MRP which prevents secretion of bilirubin glucuronides
Crigler-Najjar Syndrome
This disease is associated with a mutation in the UDP-glucuronyltransferase
A
QC: Gilbert Syndrome will elevate (1) B1 (2) B2
A
QC: Hemolysis will elevate (1) B1 (2) B2
A
QC: Crigler-Najjar Syndrome will elevate (1) B1 (2) B2
B
QC: Dubin Johnson Syndrome will elevate (1) B1 (2) B2
B
QC: Biliary Obstruction will elevate (1) B1 (2) B2
B
QC: Septic states will elevate (1) B1 (2) B2
2.5-3 mg/dL
Jaundice is a clinical manifestation that appears at what serum bilirubin levels?
F; B2
T/F: Tea-colored urine and acholic stools are clinical manifestations associated with an increase in B1
F; Arterial
T/F: Venous levels of ammonia correlate with the severity of encephalopathy
GABA
Ammonia is able to deplete what NT?
Ammonia
This is a product of protein metabolism that, when accumulated, causes encephalopathy
CPS1
This enzyme, which is the rate limiting step of the urea cycle, metabolizes ammonia
>80%
What percentage of the liver parenchyma would have to be damaged to see reduced urea cycle enzymes and increased ammonia levels
Depletes GABA, Toxic to astrocytes, and Neutrophil dysfunction
3 Mechanisms of ammonia toxicity
B
VR: (1) Cirrhosis (2) HDL3
A
VR: (1) Cirrhosis (2) TG
A
VR: (1) Cirrhosis (2) Phospholipids
A
VR: (1) Cirrhosis (2) Lecithin
A
VR: (1) Cirrhosis (2) VLDL
B
VR: (1) Cirrhosis (2) LCAT
B
VR: (1) Cirrhosis (2) LPL
A
VR: (1) Alcoholic Liver Injury (2) HDL3
A
VR: (1) Alcoholic Liver Injury (2) Alpha protein A1
A
VR: (1) Cholestasis (2) LpX
Proteins
This is the most important/obvious derangement when there is presence of liver disease
Immunoglobulins and vWF
What 2 proteins are not synthesized in the liver?
Factor 7
This is the first protein affected with liver damage
Plasma cells
What cells produce immunoglobulins?
Endothelium and Megakaryocytes
What cells produce vWF?
Albumin
This protein is responsible for colloid osmotic pressure, blood viscosity, and buffers blood pH
Ceruloplasmin, Haptoglobulin, Prothrombin
Enumerate the alpha globulins
Haptoglobulin
This alpha globulin transports hemoglobin released by dead RBCs
Ceruloplasmin
This alpha globulin transports copper
Prothrombin
This alpha globulin promotes blood clotting
Transferrin and Complement Proteins
Enumerate the beta globulins
Transferrin
This beta globulin transports iron
Complement Proteins
This beta globulin aids in the destruction of toxins and microorganisms
Fibrinogen
This gamma globulin becomes fibrin, a major component in blood clots
B
VR: (1) Liver Damage (2) Protein Synthesis
Beta-gamma bridging
This is a characteristic finding when doing serum protein electrophoresis in a cirrhotic patient
Albumin
Decrease of this portein serves as a prognostic factor for cirrhosis
2:1
Normal Albumin:Globulin Ration
DIC
Most common coagulopathy in liver failure
F; PT due to short half life of factor 7
T/F: aPTT is affected early in liver disease due to the short half life of factor 9
Cytoplasm
What compartment of the hepatocyte does Lactic acid Dehydrogenase belong in?
Cytoplasm
What compartment of the hepatocyte does Alanine Aminotransferase belong in?
Cytoplasm
What compartment of the hepatocyte does Aspartate Aminotransferase c belong in?
Mitochondria
What compartment of the hepatocyte does Aspartate Aminotransferase m belong in?
Canaliculi
What compartment of the hepatocyte does Alkaline Phosphatase belong in?
Canaliculi
What compartment of the hepatocyte does Gamma-Glutamyl Transferase belong in?
ASTm
In alcoholism, which liver enzyme is expected to be increased?
ALP and GGT
In cholestasis and biliary obstruction, which liver enzymes are expected to be increased?
Vitamin B6
Transaminases uses what vitamin as a cofactor?
Cori cycle
ALT participates in what cycle?
Malate Shuttle
AST participates in what biochemical process?
B
QC: Half life of (1) AST (2) ALT
T
T/F: AST is found both intramitochondrial and extramitochondrial
F; Extramitochondrial only
T/F: ALT is found both intramitochondrial and extramitochondrial
Ubiquitous in body tissues
Tissue sources of AST
Primary is liver with some in the kidney
Tissue sources of ALT
2.5:1
Hepatic fraction of AST:ALT
F; 1000 UI/L
T/F: Elevation of transaminase at approximately 300 UI/L is specific for hepatocellular injury
>2:1
Describe the ratio of AST:ALT in alcoholic hepatitis
C
QC: In chronic hepatocellular injury (1) ALT (2) AST
A
QC: In acute hepatocellular injury (1) ALT (2) AST
Cardiac, Kidney, and RBCs
LDH1 and LDH2 is found in what organs?
Lungs and Lymphocytes
LDH3 is found in what organs?
Liver and Skeletal Muscle
LDH4 and LDH5 is found in what organs?
Space Occupying Lesion
Elevated LDH and ALP with normal transaminases could indicate?
Liver and Bone
Majority of ALP is found in what organs?
Kidney, Intestine, Placenta, Germinal Tissues
Tissue-specific ALP is found in?
F
T/F: Rise in ALP correlates with the degree of obstruction
A
VR: (1) Pregnancy (2) ALP
Chronic cholestatis
GGT is highest during what condition?
F; ALP is non-specific while GGT is liver-specific
T/F: ALP is specific to the liver while GGT is non-specific
Alpha-fetoprotein
This protein in synthesized by embryonic hepatocytes and fetal yolk sac cells
A
VR: (1) Neural Tube defects (2) aFP
>400 ng/dL
At what amount of aFP in ng/dL indicates a high probability of HCC
Hepatitis B
This is the only type of hepatitis where the genome is made of dsDNA
ALP and GGT
In obstructive liver injury, which liver enzymes are expected to increase?
AST and ALT
In Hepatocellular liver injury, which liver enzymes are expected to increase?
T
T/F: HAV-RNA is present during the incubation period
T
T/F: Anti-HAV IgM is diagnostic of acute infection
F; Previous
T/F: Anti-HAV IgG is diagnostic of acute infection
2-3 weeks after infection
When does anti-HAV IgM usually develop?
3-6 months
How long does anti-HAV IgM persist?