This document provides an overview of the role of liver enzymes in diagnostic pathology. It discusses the following key points in 3 sentences:
Liver enzymes are released into blood when liver cells are damaged and can indicate conditions affecting the liver such as viral hepatitis, alcohol damage, cirrhosis, and cancer. Common liver enzymes measured include ALT, AST, ALP, GGT, and LDH, which are elevated in different conditions and patterns depending on the type and location of liver injury. Interpretation of liver enzyme levels along with other clinical information can help diagnose liver diseases, monitor treatment response, and provide prognostic information.
The slides show the gastric and pancreatic function test along with the significance of these tests and the conditions in which the values of which increase.
ALT is an enzyme present in liver, heart skeletal muscles, highest concentration is present in Liver. it value increases when there is abnormality in liver, ALT is an amino transferase which transfer one amino group from an amino acid and transfer to another substance for production of non essential amino acid
GGT is one of a large group of enzymes “Peptidases”.
A membrane bound enzyme whose active site faces the external side of cell.
Hepatobiliary tract enzyme.
Test for pancreatic and intestinal functions are very important for clinical evaluation gastro intestinal disorders . So it will e useful for medical and allied professional students and practitioners.
Importance of enzymes : The two aminotransferases that are checked are the alanine aminotransferase (ALT or SGPT) and aspartate aminotransferase (AST or SGOT). These liver enzymes form a major constituent of the liver cells. They are present in lesser concentration in the muscle cells.
The slides show the gastric and pancreatic function test along with the significance of these tests and the conditions in which the values of which increase.
ALT is an enzyme present in liver, heart skeletal muscles, highest concentration is present in Liver. it value increases when there is abnormality in liver, ALT is an amino transferase which transfer one amino group from an amino acid and transfer to another substance for production of non essential amino acid
GGT is one of a large group of enzymes “Peptidases”.
A membrane bound enzyme whose active site faces the external side of cell.
Hepatobiliary tract enzyme.
Test for pancreatic and intestinal functions are very important for clinical evaluation gastro intestinal disorders . So it will e useful for medical and allied professional students and practitioners.
Importance of enzymes : The two aminotransferases that are checked are the alanine aminotransferase (ALT or SGPT) and aspartate aminotransferase (AST or SGOT). These liver enzymes form a major constituent of the liver cells. They are present in lesser concentration in the muscle cells.
One test can save your life. Know what an AST(SGOT) is, why you should have it, who should get it, and where can you get tested as well as get your results fast. If you want to read more about AST(SGOT), click the link below.
Visit: https://www.labfinder.com/labexams/ast-sgot/ and get tested now!
Gama GT is anzyme for the transfer of glumyle group form one peptide to another peptide group. its an specific hapatobilary enzyme which is elevated in biliary obstraction.
The liver is the largest organ in the body
It is located below the diaphragm in the right upper quadrant of the abdominal cavity and extended approximately from the right 5th rib to the lower border of the rib cage.
The multiple forms of an enzyme catalyzing the same chemical reaction are called isoenzmyes. They, however, differ in their physical and chemical properties.
Examples: Isozymes of numerous dehydrogenases, and several oxidases, transaminases, phosphatases, transphosphorylases, proteolytic enzymes, aldolases.
One test can save your life. Know what an AST(SGOT) is, why you should have it, who should get it, and where can you get tested as well as get your results fast. If you want to read more about AST(SGOT), click the link below.
Visit: https://www.labfinder.com/labexams/ast-sgot/ and get tested now!
Gama GT is anzyme for the transfer of glumyle group form one peptide to another peptide group. its an specific hapatobilary enzyme which is elevated in biliary obstraction.
The liver is the largest organ in the body
It is located below the diaphragm in the right upper quadrant of the abdominal cavity and extended approximately from the right 5th rib to the lower border of the rib cage.
The multiple forms of an enzyme catalyzing the same chemical reaction are called isoenzmyes. They, however, differ in their physical and chemical properties.
Examples: Isozymes of numerous dehydrogenases, and several oxidases, transaminases, phosphatases, transphosphorylases, proteolytic enzymes, aldolases.
Enzymology clinical significance of enzymes and isoenzymesrohini sane
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Objective: Provide comprehensive and compassionate care to infants, children, and adolescents in various healthcare settings (hospitals, clinics, etc.).
This includes tasks like:
Monitoring vital signs and physical condition.
Administering medications and treatments.
Performing procedures as directed by doctors.
Assisting with daily living activities (bathing, feeding).
Providing emotional support and pain management.
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Objective: Promote healthy behaviors and educate children, families, and communities about preventive healthcare.
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Administering vaccinations.
Providing education on nutrition, hygiene, and development.
Offering breastfeeding and childbirth support.
Counseling families on safety and injury prevention.
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Communicating effectively with healthcare teams.
Identifying and addressing potential risks to child welfare.
Educating families about their child's condition and treatment options.
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3. INTRODUCTION
ENZYMES : Complex protein catalysts, found in small amounts, cause specific chemical
change in all parts of the body.
• Present in all parts of the body including: blood, intestinal fluids, mouth (saliva),stomach
(gastric juice).
• Enzymes are present in virtually all organs but with slightly different forms in different
locations.
• Normally only small quantities of intracellular enzymes leak from cells into blood or
other body fluids.
intracellular
• Lysosome
• Nucleous
• Cytosol
• Mithochondria
Extracellular
• Are secreted
and function out
from the cell
4. • ENZYMES ARE OF TWO TYPES :
1. Functional plasma enzymes: Certain enzymes, proenzymes, and their
substrates are present at all times in the circulation of normal individuals
and perform a physiologic function in the blood.
Lipoprotein lipase
Plasmin
Choline esterase
Ceruloplasmin
2. Non-functional plasma enzymes: Plasma also contains numerous other
enzymes that perform no known physiologic function in blood.
Digestive Enzymes
Secretary Enzymes
Enzymes associated with metabolism
5. • RESPONSIBLE FOR INCREASED
SERUM LEVELS:-
A) Increased release
i. Necrosis of cell
ii. Increased permeability of cell
without gross cellular damage
iii. Increased production of enzyme
within the cell resulting in
increase in serum by overflow
iv. Increase in tissue source of enzyme
as in malignancy
B) Impaired disposition
i. Increased levels in obstructive
jaundice
ii. Increased levels in renal failure
• DECREASED SERUM LEVELS
A. Decreased formation which may
be
i. Genetic
ii. Acquired
B. Enzyme inhibition
C. Lack of cofactors
6. • Enzyme units are never expressed in terms of their concentration (as
mg or μg ) but are expressed as activity.
• To maintain uniformity world over enzyme activity.
International unit:-
• One IU is defined as the activity of the enzyme which transforms one
micro mole of substrate in to products per minute per liter of sample
under optimal conditions and at defined temperature .
• It is expressed as IU/L.
• IU / L = when one milli micro mole of substrate is transformed
7. CLINICAL ENZYMOLOGY
Clinical enzymology is the application of the science of enzymes in the
treatment and diagnosis of diseases.
CLINICAL SIGNIFICANCE
1) Helps in making the diagnosis/differential diagnosis/ early detection
of a disease.
2) Helps in ascertaining prognosis of a disease.
3) Helps in ascertaining the response to drugs in a disease.
4) Also help in ascertaining the time course of disease.
8. Enzymes routinely measured
Name of enzyme
• AST or Aspartate aminotransferase
• ALT or alanine aminotransferase
• ALP or Alkaline phosphatase
• Acid phosphate
• Gamma glutamyl transferase
• Creatinine Kinase
• LDH or lactate dehydrogenase
• Alpha amylase
Present in
• Heart and liver
• Heart and liver
• Bone, intestine and other tissues
• Prostate
• Liver
• Muscles (including cardiac)
• Heart, liver, muscle, RBC
• Pancreas
9. FACTORS AFFECTING THE RESULTS
1. Analytical Factors :
• These include the concentrations of the substrate and product, the pH and
temperature at which the reaction is carried out, the type of buffer, and the
presence of activators or inhibitors.
2. Physiological Factors :
a. Age: Plasma AST activity is moderately higher during the neonatal period than in
adults and plasma alkaline phosphatase activity is higher in children than in adults.
b. Sex: plasma γ-glutamyl transferase activity is higher in men than-in women.
c. physiological conditions: Plasma alkaline phosphatase activity rises during the
last trimester of pregnancy because of the presence of the placental isoenzyme.
10. Enzyme estimations are helpful in the diagnosis of –
1) Myocardial Infarction
2) Liver diseases
3) Muscle diseases
4) Bone diseases
5) Cancers
6) GI Tract diseases
13. AMINOTRANSFERASES
• Catalyze reversibly the transfer of the amino acids to the α keto group of ketoglutaric acid.
ALT
Alanine pyruvic acid
+ +
ketoglutarate glutamate
AST
Aspartate oxaloacetic acid
+ +
ketoglutarate glutamate
Serum Glutamate Oxaloacetic
Transaminase-SGOT
Serum Glutamic Pyruvate
Transaminase-SGPT
B6 B6
14. ALT
Cytosol
Liver
Half life – 47 hours
≤40IU/L
Detecting liver diseases in non-
alcoholic, asymptomatic patients.
AST
Cytosol + Mitochondria
Liver, Kidney, Skeletal, Cardiac
and Brain tissue
Half life – 17 hours (Mitochondrial
AST – 87 hours)
≤40IU/L
Monitoring therapy with
potentially hepatotoxic drugs.
18. >15 times
• Acute Viral Hepatitis, Toxin-induced hepatocellular
damage, Centrilobular Necrosis.
5-15
times
• Chronic Hepatitis, Autoimmune hepatitis, Alcoholic
Hepatitis, Acute Biliary tract obstruction, Drug induced
Hepatitis
1-3 times
• Cirrhosis, Non-Alcoholic Steatosis, Cholestasis.
19. • <1 s/o Acute Viral Hepatitis, Non Alcoholic
Steatohepatitis
• >1 s/o Acute Fulminant Hepatic Failure
• >2 s/o Alcoholic Hepatitis, Wilson’s Disease
AST/ALT Ratio
• Alcoholic Liver Disease
• Wilson’s Disease
Mitochondrial AST:
Total AST ratio
• long term haemodialysis
• Uremia
Falsely low
aminotransferase
levels
20. ALKALINE PHOSPHATASE
• Hydrolase
• Cleavage of phosphate-containing compounds and may facilitate the
movement of substances across cell membranes.
• Liver, bones, intestine, kidney and placenta.
• Optimal reaction pH – between 9 & 10.
• ALP requires Mg2+ as an activator.
• Liver isoenzyme
Canalicular surface of hepatocytes
Half life – 3 days.
21. • EDTA falsely lowers the ALP activity.
• OCPs, Blood Transfusions and Cardiopulmonary bypass decrease ALP.
• Smoking causes an average of 10% increase.
• ISOFORMS :
Heat Fractionation – Liver isoenzyme is moderately stable.
Inhibition Assay – Levamisole for liver – poorly reproducible.
High-resolution Electrophoresis using Polyacrylamide gel
High Performance Liquid Chromatography.
P-nitro
Phenyl Phosphate
P-nitro Phenoxide + Pi
Alkaline Phosphatase
410 nm
22. Causes of Increased ALP :
1. Hepatobiliary Disease
• Cholestatic type of Jaundice
• Bile Duct Obstruction
• Primary Biliary Cirrhosis
• Primary Sclerosing Cholangitis
• Infiltrative disease of liver (TB, Sarcoidosis, Cysts, Primary or Secondary
Cancer).
Simultaneous measurement of S. GGT & 5’NT – used to ascertain whether
increase of ALP is of hepatic origin.
2. Diseases of Bone : Children, Osteomalacia, Rickets, Hyperparathyroidism,
Paget’s Disease, Osteosarcoma and osteoblastic type of metastatic carcinoma.
3. Pregnancy.
23. γ-GLUTAMYL TRANSFERASE
• Catalyses the transfer of a glutamyl group from glutathione to a free
amino acid.
• Liver, pancreas, kidney and prostate.
• Half life - 10 days.
3-Carboxy, 4-
Nitroanilide of
gamma
glutamate
+ Glycylglycine
GGT
γ-glutamyl-
glycylglycine
5-amino-
2-nitro-
benzoate
+
410nm
24. Use of GGT Estimation :
1. ALCOHOLISM:
• Marked elevation in Acute Alcoholic Hepatitis.
• Suspected cases of Alcoholism (even in absence of ALD).
• Follow up of Chronic Alcoholics (levels decline slowly with abstinence and the half
life may be as long as 28 days).
2. Cholestasis.
3. Obstructive Disorders.
4. Space Occupying lesions.
5. GGT and Albuminuria – to predict the development of HTN.
25. 5’-NUCLEOTIDASE
• 5’-Ribonucleotide Phosphohydrolase.
5’-Ribonucleotide + H2O Ribonucleoside + Phosphate
• Widely distributed in the body, predominantly liver.
Measurement : large quantities of nonnucleoside substrates to
competitively inhibit ALP.
USES :
• Determine whether the source of elevated ALP is liver or bone.
• Cholestatic Disorders, Acute Hepatitis, Ovarian CA, Rheumatoid Arthritis.
• Second and third trimester of Pregnancy.
26. LACTATE DEHYDROGENASE
• Catalyses the reversible oxidation of lactate to pyruvate.
LACTATE + NAD+ PYRUVATE + NADH + H+
• LD is a tetramer of two subunits : H & M.
• Combinations of subunits produce five isoenzymes :
ISOENZYMES
LD1 HHHH LD2 HHHM LD3 HHMM
LD4
HMMM
LD5
MMMM
Myocardial tissue & RBCs Liver & Muscles
27. • LD4 & LD5 are major isoenzymes of liver.
• Half life – 4 to 6 hours.
• Upper reference limit for total LD activity in serum is 150 IU/L.
• The specific composition of elevated isoenzyme levels found in plasma will reflect
their tissue origin.
• Normally, 2 > 1 > 3 > 4 > 5.
• MEASUREMENT : either the forward (lactate-to-pyruvate) or the reverse
(pyruvate-to-lactate) direction of the reaction – 340nm.
• LD isoenzymes are separated by using agarose gel Electrophoresis.
28. INTERPRETATION OF LD ESTIMATION :
• Highly Non Specific test – relative levels of ALT, AST and CK provide clues.
• Elevated in Hepatitis.
– transient & return to normal by the time of clinical presentation ( due to low activity &
shorter half life).
• Elevated in Fulminant Liver Failure.
– ALT-LD Index predicts survival.
• Elevated in Space Occupying Lesions.
• Non Hepatic Causes – MI, Megaloblastic anemia, Hemolytic anemia, advanced
malignancies, Sepsis, Shock, Pneumocystis carinii, Biliary Pancreatitis (LD/AST ratio ) &
Cardiopulmonary arrest.
• Other uses – Prediction of response to therapy in Multiple Myeloma & overall survival in
metastatic Melanoma.
29. HEPATITIS
Direct virus induced or
immune response to virus
Inflammation/ Necrosis/
Apoptosis
Hepatocyte Damage
• Aminotransferases > 200IU/L, often
500IU/L or even 1000IU/L
• EXCEPTION : Hepatitis C – modest
elevation of ALT only.
• Mild elevation of LD (300-500 IU/L)
• Elevation of ALP (200-350 IU/L)
31. ALCOHOLIC HEPATITIS
Mitochondrial Damage
Release of mAST
(Half life of mAST >
cAST & ALT)
AST > ALT
• N or Low Aminotransferase [No B6]
After treatment
Elevated Aminotransferase (>200 IU/L)
• AST : ALT = 3-4 : 1 (DeRitis Ratio)
• Elevated ALT and GGT
32. CHRONIC PASSIVE CONGESTION
Back pressure from
IVC and Hepatic Vein
(secondary CCF)
Dilatation of Hepatic
Sinusoids
• Mild elevation of AST and ALT
• Other Enzymes - Normal
33. CIRRHOSIS
• Elevated Aminotransferase (ALT < AST)
AST > ALT
Normal or Low
• Elevated ALP + GGT + 5’-NT
Alcohol, Panhepatic
Hepatitis, Chronic Active
Hepatitis, Toxins, Drugs,
Biliary Tract Diseases,
Hemochromatosis
Parenchymal fibrosis &
hepatocytic nodular
regeneration
Fibrosis progresses
End Stage Cirrhosis (due to
massive tissue destruction)
34. POST HEPATIC BILIARY OBSTRUCTION
• Elevated ALP & GGT
• Incomplete obstruction
Partial flow of bile
Significant elevation of ALP + GGT + 5’NT
Cholelithiasis, Primary Biliary
Cirrhosis, Primary Sclerosing
Cholangitis, Neuroleptic Drugs,
CA Head of Pancreas, Lymphoma
Blockage of intra and extra –
hepatic ducts
Backflow of bile into Hepatocytes
Bile enters criculation
35. SPACE OCCUPYING LESION
Metastatic Tumors,
Lymphoma,
Hepatocellular
Carcinoma,
Angiosarcoma of Liver,
Hemangioma of Liver
Elevation of only
LD & ALP
• ALP – encroachment of masses on
canaliculi, cholangioles and main bile
ducts.
• LD – produced by liver or tumor (if
LD >500-1000IU/L and ALP > 500 IU/L).
• If tumor spreads widely – mild elevation
of Aminotransferase.
36. ACUTE FULMINANT LIVER FAILURE
• Rapid marked increase in AST + ALT
(AST > 20,000IU/L) with AST:ALT >1
after 1 week
AST & ALT return to low or undetectable
• Markedly elevated LD & ALP
Reye’s Syndrome, Acute
Hepatitis B with Hepatitis D
superinfection, Budd-Chiari
Syndrome, Vascular
Hypoperfusion of Liver, Fatty
liver of pregnancy
Massive destruction of liver
tissues
Complete liver failure
(Complete destruction
of all viable tissue)
37. CONDITION AST ALT LD ALP
1. Hepatitis H H H H
2. Cirrhosis N N N N – slightly H
3. Biliary Obstruction N N N H
4. Space Occupying lesion N or H N or H H H
5. Passive Congestion Slightly H Slightly H Slightly H N – slightly H
6. Fulminant Failure Very H H H H