ASESSMENT OF LIVER FUNCTION & ENZYME INTRO Flashcards
High AST, ALT, LD, ALP, BILIRUBIN
Hepatitis
Coagulation test for monitoring of synthetic liver function
PT
Low total protein, albumin
High bilirubin, ammonia
Cirrhosis
Low TP and albumin, the rest is high - basta ABNORMAL LAHAT
Fulminant hepatic failure
High ALP and Bilirubin (B1)
Biliary obstruction
High LD and ALP
Space-occupying lesion
Normal total protein and albumin ; the rest is abnormal (Slightly high)
Passive congestion
Destruction of more than 80% of liver tissue with no regeneration
Panhepatic cirrhosis
Results from a VARIETY of causes e.g Reye syndrome, hepatitis, cirrhosis
Fulminant hepatic cirrhosis
Prehepatic / hemolytic
Unconjugated
Water-insoluble
Non-polar
Indirect reaction with diazo (requires accelerator)
Not excreted in urine
Has affinity for CNS
B1
Post hepatic / obstructive
Conjugated
Water-Soluble
Polar
Direct reaction with diazo
Excreted in urine
Has no affinity to CNS
B2
CONJUGATED bilirubin covalently bond to albumin ; long half life of 17 days ; seen in cases of bile duct obstruction ; direct reaction with diazo reagent ; separated from other fractions by HPLC
Delta bilirubin
High B1 due to increased production ; low delivery and uptake, or low conjugation
Unconjugated hyperbilirubinemia
High B2 due to intra or extra hepatic cholestasis
Conjugated hyperbilirubinemia
High B1 and B2 due to a combination of defects
Mixed hyperbilirubinemia
Serum bilirubin : high B1
Urine bilirubin : negative
Urine urobilinogen : 3+
Pre-hepatic/hemolytic jaundice
Serum bilirubin : high B1, high B2, or BOTH
Urine bilirubin : trace
Urine urobilinogen 2+
Hepatic jaundice
Serum bilirubin : high B2
Urine bilirubin : 3+
Urine urobilinogen : normal
Post-hepatic / obstructive
Conjugation of bilirubin happens in what organ
Liver
Form of bilirubin that undergoes recirculation to the liver via the portal system of enterohepatic circulation
Urobilinogen
Once urobilinogen is taken up by the liver after recirculation, it is now then reexcreted through the small intestine and becomes oxidized in the form of ____ giving feces its brown color
Urobilin
Type : unconjugated hyperbilirubinemia ; prehepatic
B1 : high
B2 : normal
Defect : increased rbc destruction = high bilirubin production
Hemolytic disease
Type : unconjugated hyperbilirubinemia, hepatic
B1 : high
B2 : normal
Defect : transport defect coupled with UDPGT deficiency
Gilbert Syndrome
Type : unconjugated hyperbilirubinemia, hepatic
B1 : high
B2 : normal
Defect : circulating inhibitor of bilirubin conjugation
Lucey-Driscoll syndrome
Ci(rculating) = (Lu)cey
Type : unconjugated hyperbilirubinemia, hepatic
B1 : high
B2 : normal
Defect : transient UDPGT deficiency ; no life
Physiologic jaundice of the newborn
Type : unconjugated hyperbilirubinemia, hepatic
B1 : high
B2 : normal
Defect : total or partial UDPGT deficiency ; survival is possible
Criggler-Najjar syndrome
How to prevent kernicterus
Phototherapy
Type : mixed hyperbilirubinemia
B1 : high
B2 : high
Defect : low conjugation ; bile flow interference ; intrahepatic cholestasis
Viral hepatitis or cirrhosis ; hepatic carcinoma
Type : conjugated/mixed hyperbilirubinemia ; hepatic
B1 : normal/high
B2 : high
Defect : secretory defect
Dubin-Johnson syndrome ; Rotor syndrome
Type : conjugated hyperbilirubinemia ; hepatic
B1 : normal
B2 : high
Defect : extra hepatic cholestasis , tumor, stricture
Biliary obstruction
Colorimetric and spectrophotometric measurement of bilirubin is based on the ____ reaction (diazotization with incorporated accelerator/solubilizer) ; 2 methods
Van Den Berg reaction ; Evelyn-Malloy and Jendrassik-Grof
Evelyn-Malloy : accelerator
Methanol
Evelyn-Malloy : pH
Acidic
Evelyn-Malloy : color reaction
Red purple
Evelyn-Malloy : maximum absorbance
560 nm
Jendrassik-Grof : accelerator
Caffeine sodium benzoate
Jendrassik-Grof : pH
Alkaline
Jendrassik-Grof : color reaction
Blue
Jendrassik-Grof : maximum absorbance
600 nm
Jendrassik-Grof : alkalizing agent
Fehlng’s reagent or Alkaline tartrate
Jendrassik-Grof : stopping reagent
Ascorbic acid
Bilirubin + diazo + accelerator —> Azodipyrroles (ALL FRACTIONS)
Total bilirubin
Bilirubin + diazo + accelerator —> Azodipyrroles (B2 and Delta bilirubin only)
Direct bilirubin
Calculated —> TB - DB
Indirect bilirubin
Over jaundice has a total bilirubin value of
3 mg/dL or above
Panic value for unconjugated hyperbilirubinemia
15 mg/dL or above
Based on the absorption of light by bilirubin at ___ nm ; correction for oxyhemoglobin is achieved by measuring absorbance at two wavelengths ; appropriate only for neonatal serum ; not done on serum due to the presence of carotenoid pigments
Direct spectrophotometry (Bilirubinometry)
Bilirubin reference value ; B1
0.2 - 0.8 mg/dL
Bilirubin reference value ; B2
0-0.2 mg/dL
Bilirubin reference value : total bilirubin
0.2 - 1.0 mg/dL
Biological catalysts that accelerate biochemical reactions without being consumed or changed in composition
Enzymology
Combines with only one substrate and catalyzes only the corresponding reaction
Absolute specificity
Combines with ALL substrates containing a particular chemical group
Group specificity
Breaks or forms a solitary type of covalent bond
Bond or reaction specificity
Combines with only one optical or geometric isomer of a compound
Stereoisomeric/geometric specificity
Oxidoreductases
LDH
G6PD
MDH
GLDH
TRANSFERASES & KINASES
AST
ALT
GGT
CK
HK
HYDROLASE (Estrases)
ACP
ALP
CHS
5-NT
LPS
HYDROLASE (PEPTIDASES)
TRYPSIN
PEPSIN
LAP (Leucine amino peptidase)
HYDROLASE (glycosidases)
AMS
GALACTOSIDASE
LYASE
Aldolase
Decarboxylase
EC code : 1
Oxidoreductases
EC code : 2
Transferases
EC code : 3
Hydrolases
EC code : 4
Lyases
EC code : 5
Isomerases
EC code : 7
Ligases
Enzymatic reaction/catalytic reaction
E + S <—> ES —> P + E
(E) > (S) - rate limiting component
First-order kinetics
(S) > (E)
Zero-order kinetics
Amount of enzyme that catalyzes the reaction of 1 UMOL of substrate per MINUTE
IU
Amount for enzyme that catalyzes the reaction of 1 MOL of substrates per SECOND
KATAL
1 IU = ___ukat
0.0167 ukat
0.0167 ukat = ____ nkat
16.7 nkat
1 kat = _____ IU
6X10^7 IU
End-point ; the reactions are combined, the reaction proceeds for a DESIGNATED TIME, the reaction is stopped followed by measurement of the amount of reaction that has occurred
Fixed-tome
Kinetic ; multiple measurements of absorbance change as a function of time, either at specific time intervals of continuously by a continuous recoding spectrophotometer
Continuous monitoring
Most enzymatic reactions occur at pH
pH 7-8 except ACP and ALP
Denaturation is usually significant at
Every 10C increase in temperature, the velocity (rate of reaction) doubles
Activators
Mg, Ca, Zn, and Cl
Coenzymes
NAD/NADH , NADP/NADPH
Prosthetic group
Pyridoxal phosphate (B6)
Inorganic ; may be essential for the reaction or may only enhance the reaction rate
Activators
Serve as second substrates for enzymatic reactions
Coenzymes
Bound tightly to enzyme
Prosthetic group
Competitive
Binding site:
Effect of adding substrate:
Lineweaver-Burk plot:
Active site ; reverse the inhibition ; same vmax and increased km
Noncompetitive
Binding site:
Effect of adding substrate:
Lineweaver-Burk plot:
Allosteric site ; no effect ; decreased vmax and same km
Uncompetitive
Binding site:
Effect of adding substrate:
Lineweaver-Burk plot:
Enzyme-substrate complex ; increases the inhibition ; low vmax and low km
High molecular-mass forms of the serum enzymes that can be bound to either an immunoglobulin or a nonimmunoglobulin substance ; long half life ; high in plasma/serum
Macroenzymes
Macroenzymes bound to an immunoglobulin
Macroenzymes type 1
Macroenzymes bound to a non immunoglobulin substance
Macroenzyme type 2
Enzymes with macroforms
CK
AMS
LD
AST
ALT
ALP
ACP
LPS
GGT