Biochemical Investigations and Muscle Damage

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Questions and Answers

Creatine kinase (CK) is found in high amounts in skeletal muscle and cardiac muscle.

True

Elevated plasma activities of CK in patients can indicate conditions like Duchenne muscular dystrophy.

True

Asymptomatic female carriers of the DMD gene have normal plasma CK activities.

False

CK is an enzyme that is consumed during the process of catalyzing reactions.

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Small amounts of enzyme leakage from damaged tissue can be detected with low sensitivity.

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Biochemical investigations are used only for monitoring disease progression.

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Enzymes have very high concentrations within cells as compared to plasma.

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Duchenne muscular dystrophy leads to the leakage of myocyte contents into the blood due to cell rupture.

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Common biochemical techniques are not used to measure analytes in body fluids.

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Biochemical tests can confirm or reject clinical diagnoses.

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Cellular damage does not affect the concentration of analytes in the plasma.

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Screening for subclinical diseases is one of the main uses of biochemical tests.

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The concepts of patient management do not include biochemical investigations.

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Creatine kinase is also known as CK.

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Myocardial infarction is caused by the removal of blood clots from arteries.

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The total CK assay measures all CK activity present in a plasma specimen.

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NADPH production is monitored by absorbance change at 240 nm.

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An infarct is a localized area of dead tissue due to loss of blood supply.

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Hexokinase is involved in the conversion of glucose to glucose-6-phosphate.

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NADP is produced during the reaction involving glucose-6-phosphate dehydrogenase.

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Creatine phosphate is a product of the creatine kinase reaction.

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Isoenzymes catalyze the same reaction but are different molecules.

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The presence of a specific isoenzyme in the plasma does not indicate any tissue damage.

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Isoenzymes are uniform throughout the body.

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Creatine kinase isoenzymes are formed from different combinations of subunits.

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Electrophoresis can reveal characteristic patterns of isoenzymes based on their mobility.

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CK-MM isoenzyme is primarily found in the heart.

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CK-MB isoenzyme is good for assessing cardiac damage.

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The brain contains the highest percentage of CK1 (BB) isoenzyme.

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ALT is more liver-specific than AST.

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Choleostasis refers to the failure of bile to reach the intestine.

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AST levels never exceed 10 times the upper limit of normal in acute hepatitis.

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γ-GT is less liver-specific than alkaline phosphatase (ALP).

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Increased prothrombin time can indicate synthetic function impairment of the liver.

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The presence of gallstones can cause choleostasis.

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Both ALT and AST are only found in the liver.

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Chronic hepatocellular disease tends to release more ALT than AST.

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CK is primarily found in large amounts within the liver cells.

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Elevated plasma CK activities can be more than 10 times higher than the normal reference range in some patients.

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Asymptomatic female carriers of the DMD gene have a 50% chance of having normal plasma CK activities.

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A small amount of enzyme can convert a much larger amount of substrate without being consumed in the reaction.

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Biochemical investigations are used exclusively for diagnosing diseases.

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In Duchenne muscular dystrophy, myocyte content leakage results from damage caused by excessive muscle growth.

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Excessive physical exercise does not lead to any elevation in CK levels in the blood.

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All analytes used in diagnosis have low concentrations within cells compared to plasma.

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Monitoring the natural history of a disease is not a function of biochemical tests.

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Isoenzymes are always identical and present uniformly across different tissues.

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Serum cholesterol can provide insight into the prognosis of coronary artery disease.

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Clinical biochemistry does not play a role in patient management and treatment decisions.

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Cellular damage from trauma or disease does not affect plasma concentrations of proteins and enzymes.

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Isoenzymes exhibit different activities towards different substrates.

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Isoenzymes are uniform throughout the entire body.

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The presence of CK-MB isoenzyme is primarily associated with skeletal muscle damage.

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The electrophoretic mobility of isoenzymes can provide a characteristic pattern for their identification.

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Creatine Kinase isoenzymes include MM, MB, and BB based on tissue origin.

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Isoenzymes can be detected using immunological methods for both active and inactive forms.

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Differential activity of isoenzymes remains constant under different reaction conditions.

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Cellular localization of isoenzymes is crucial for indicating specific tissue damage.

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Acid phosphatase is primarily associated with liver and skeletal muscle function.

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Lactate dehydrogenase is an enzyme useful for diagnosing myocardial infarction.

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Alkaline phosphatase (ALP) is primarily derived from the brain.

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Elevation of aspartate aminotransferase (AST) can indicate damage to the liver parenchyma.

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Cholinesterase assessments are commonly used to evaluate liver dysfunction.

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Increased γ-glutamyl transferase (GGT) levels are indicative of hepatobiliary disease.

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The primary clinical application of amylase is for diagnosing liver diseases.

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Plasma enzyme levels are influenced by both the rate of release from damaged cells and the extent of cell damage.

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Liver function includes processes such as gluconeogenesis and synthesis of plasma proteins.

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Cirrhosis results in an increase in functioning liver mass.

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ALT is less liver-specific than AST.

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In cholestasis, alkaline phosphatase levels increase due to the induction of enzyme synthesis.

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AST levels can reach more than 100 times the upper limit of normal in acute liver necrosis.

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Conjugated bilirubin is tested to assess the liver's enzymatic activity related to bile production.

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Hyperbilirubinaemia is not associated with liver dysfunction.

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γ-GT is primarily affected by bone disease rather than liver disease.

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The presence of a gallstone can lead to the failure of normal bile flow to the intestine.

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Increased prothrombin time can indicate normal synthetic function of the liver.

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Study Notes

Biochemical Investigation Uses

Biochemical investigations are useful for diagnosing and monitoring disease progression.
Principle uses include screening, diagnosis, monitoring, and prognosis.

Cellular Damage

Most analytes used in diagnosis rely on the difference in concentration between the cell and plasma.
Cellular damage releases the normally high concentration of intracellular analytes into the bloodstream.

Creatine Kinase (CK) and Duchenne Muscular Dystrophy

CK is an enzyme involved in energy production present in high amounts in skeletal and cardiac muscle.
Elevated plasma CK levels indicate muscle damage and can be more than 10 times higher than the reference range in Duchenne muscular dystrophy.
Asymptomatic female carriers of the DMD gene often (75%) have elevated plasma CK activity.

Muscle Damage

Causes of muscle damage include: excessive physical exercise, surgery, skeletal muscle trauma, drug-induced muscle damage (e.g., cocaine).

General Principles of Enzyme Measurement
Enzymes catalyze chemical reactions without being consumed, allowing for sensitive detection of small amounts in the bloodstream.
Coupled reactions and enzyme-coupled assays are used to monitor the production of NADPH, which is then measured by absorbance change at 340nm.

Myocardial Infarction (MI)

Infarction is the death of part or whole of an organ due to obstructed blood supply.
An infarct is a small, localized area of dead tissue.

Plasma Enzyme Activities Following MI

Enzyme levels rise following MI, indicating damage to cardiac tissue.

CK Isoenzymes

CK has several different molecular forms called isoenzymes.
Total CK assays measure all CK activity in a plasma sample, but do not distinguish between isoenzymes.
CK isoenzymes are tissue-specific, allowing for more targeted diagnosis of specific tissue damage.
CK-MB is primarily associated with cardiac muscle, while CK-MM is more associated with skeletal muscle.

Tests for Liver Disease

Liver function tests assess liver cell damage, synthetic function, conjugating capacity, and cholestasis.
Liver cell damage is indicated by elevated levels of AST and ALT.
Synthetic function is assessed by prothrombin time and albumin levels.
Conjugating capacity is indicated by conjugated bilirubin levels.
Cholestasis is indicated by elevated ALP and γ-GT levels, as well as serum bilirubin.

Hepatocellular Damage

AST and ALT are enzymes released into the bloodstream when liver cells are damaged.
ALT is more liver-specific than AST, which can be elevated in other tissues as well.

Choleostasis

Choleostasis is the failure of normal bile flow to the intestine.
ALP and γ-GT enzymes normally anchor to hepatocyte membranes but are released in choleostasis.
γ-GT is more liver-specific than ALP, which can also be elevated in bone disease.
Changes in γ-GT and ALP levels often parallel each other in choleostatic disease.

Causes of Increased Plasma AST

High AST levels, over 10 times the upper limit of normal (ULN), are often associated with acute hepatitis, liver necrosis, major crush injuries, severe tissue hypoxaemia, and myocardial infarction.
Moderate AST levels, 5-10 times ULN, can indicate skeletal muscle disease, cholestasis, chronic hepatitis, and physiological elevations (neonates).

Commonly Used Biochemical Techniques

Various methods and techniques are used to measure analytes in body fluids.

Biochemical Investigations For Diagnosis and Monitoring Disease Progression

Biochemical investigations play a crucial role in diagnosing and monitoring disease progression.
They can help detect subclinical disease, confirm or reject clinical diagnoses, monitor the natural history of a disease, and assess response to treatment.
Biochemical measurements depend on the high concentration of a substance within a cell relative to its concentration in plasma.
Levels of analytes such as proteins, enzymes, or other molecules in plasma can indicate cellular damage or dysfunction.

General Principles of Enzyme Measurement

Enzymes are biological catalysts that increase the rate of chemical reactions without being consumed themselves.
A small amount of enzyme released into the bloodstream can be detected with great sensitivity.
The activity of an enzyme is determined by its ability to convert a substrate into a product.
Coupled reactions are used to measure enzyme activity.
Isoenzymes are different molecules that catalyze the same reaction, but have different structures and tissue distributions.
Isoenzymes can be distinguished by their electrophoretic mobility, different activities towards different substrates, or other properties.

Creatine Kinase (CK) and Muscle Damage

Creatine kinase (CK) is an enzyme present in muscle tissue that catalyzes the conversion of creatine phosphate to creatine.
Increased CK levels in the blood may indicate muscle damage.
The CK-MB isoenzyme is specifically elevated in myocardial infarction.
Other causes of elevated CK levels include strenuous exercise, surgery, trauma, and drug use.

Distribution of Clinically Important Enzymes

Different enzymes are found in various tissues.
The distribution of an enzyme can help pinpoint the source of damage.
For example, increased levels of acid phosphatase indicate damage to the prostate gland.
Other enzymes like alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) are used to assess liver function.

Liver Enzymes

The liver plays a crucial role in metabolism, synthesis, and excretion.
Liver damage can be assessed by measuring levels of enzymes such as ALT, AST, ALP, and gamma-glutamyl transferase (GGT).
ALT, AST, and GGT are released into the bloodstream when liver cells are damaged.
Elevated ALP levels indicate cholestasis, a condition where bile flow is blocked.

Measuring Analytes in Body Fluids

Various techniques are used to measure analytes in body fluids.
Common methods include spectrophotometry, chromatography, and electrophoresis.
### Study Notes for "Common methods" Continued
Spectrophotometry measures the absorption of light by a substance.
Chromatography separates substances based on their physical properties.
Electrophoresis separates substances based on their charge and size.

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Description

This quiz explores the role of biochemical investigations in diagnosing diseases and monitoring conditions, particularly focusing on muscle damage. It covers key concepts like creatine kinase levels and their implications in Duchenne muscular dystrophy. Dive into the details of how cellular damage affects analyte concentrations and learn about the causes of muscle injury.