Clinical Biochemistry of Liver and Muscle Injury
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Questions and Answers

What primarily reflects liver injury as indicated by serum GLDH activity?

  • Cellular death
  • Decreased enzyme activity
  • Increased enzyme activity (correct)
  • No change in enzyme activity
  • Increased GLDH activity is a specific marker of the cause of liver injury.

    False

    What is the half-life of GLDH in dogs?

    8 hours

    SDH is considered to be a liver-specific enzyme due to its high concentrations in _______.

    <p>hepatocytes</p> Signup and view all the answers

    Which enzyme catalyzes the conversion of fructose to sorbitol?

    <p>SDH</p> Signup and view all the answers

    Cholestasis is associated with decreased levels of Alkaline Phosphatase (ALP).

    <p>False</p> Signup and view all the answers

    Match the following enzymes with their half-life in dogs:

    <p>GLDH = 8 hours SDH = 5 hours ALP = Not specified GOT = Not specified</p> Signup and view all the answers

    The half-life of SDH in the dog is approximately _______ hours.

    <p>5</p> Signup and view all the answers

    What is the normal recovery time for CK activity after acute muscle injury in horses?

    <p>24-48 hours</p> Signup and view all the answers

    AST activity decreases more rapidly than CK activity after muscle injury.

    <p>False</p> Signup and view all the answers

    What enzyme is released into the plasma following skeletal muscle injury?

    <p>Creatine Kinase (CK)</p> Signup and view all the answers

    Haemolysis will cause a false increase in CK activity due to the contribution of constituents within red blood cells or in their __________.

    <p>membranes</p> Signup and view all the answers

    Which condition does NOT typically result in high CK activity?

    <p>Normal muscle function</p> Signup and view all the answers

    Match the following terms with their descriptions:

    <p>CK = Catalyses the reversible reaction with creatine and creatine phosphate AST = Enzyme with a longer half-life after muscle injury Haemolysis = Can falsely increase CK activity Recumbent animals = Will have high CK activity due to muscle injury</p> Signup and view all the answers

    Increased CK levels in young puppies are four times higher than adult levels.

    <p>True</p> Signup and view all the answers

    List one physiological factor that may lead to increased CK activity.

    <p>Higher CK activity in young puppies</p> Signup and view all the answers

    What condition can lead to an increase in alkaline phosphatase (ALP) activity in dogs up to 22,000 U/L?

    <p>Adrenal dysfunction</p> Signup and view all the answers

    Elevated Gamma Glutamyl Transferase (GGT) levels primarily originate from the pancreas.

    <p>False</p> Signup and view all the answers

    What is commonly observed in dogs with osteosarcoma regarding ALP serum activity?

    <p>High ALP serum activities are observed, and it is a negative prognostic indicator.</p> Signup and view all the answers

    In cases of primary and secondary hyperparathyroidism, total serum ALP may increase due to the _____ isoform.

    <p>B-ALP</p> Signup and view all the answers

    Match the following conditions with their effect on ALP activity:

    <p>Adrenal dysfunction = Elevated ALP activity up to 22,000 U/L Osteosarcoma = High ALP with negative prognosis Primary hyperparathyroidism = 2-3x increase in ALP Non-hepatic neoplasia = Mild increases in ALP due to B-ALP</p> Signup and view all the answers

    Which enzyme is mainly used as a sensitive indicator of cholestasis?

    <p>GGT</p> Signup and view all the answers

    Which of the following is considered a major acute phase protein (APP) in dogs?

    <p>Serum amyloid A (SAA)</p> Signup and view all the answers

    GGT is primarily shed into the blood from the kidney.

    <p>False</p> Signup and view all the answers

    What metabolic process is GGT primarily involved in?

    <p>Glutathione metabolism and amino acid absorption.</p> Signup and view all the answers

    Positive acute phase proteins (APPs) increase in concentration during acute inflammation.

    <p>True</p> Signup and view all the answers

    What is the primary method used to measure total protein concentration in veterinary diagnostics?

    <p>Biuret method</p> Signup and view all the answers

    In cats, serum amyloid A (SAA) is a major APP, while ___ is a moderate APP.

    <p>Alpha-1 acid glycoprotein (AGP)</p> Signup and view all the answers

    Match the following species with their corresponding major and moderate acute phase proteins:

    <p>Dog = CRP; SAA (Major), Hp; AGP (Moderate) Cat = SAA (Major), AGP; Hp (Moderate) Horse = SAA (Major), Hp (Moderate) Pig = MAP (Major), Hp; CP (Moderate)</p> Signup and view all the answers

    Which cytokine is NOT part of the acute phase response?

    <p>Cytokine-5</p> Signup and view all the answers

    The refractometry method in veterinary diagnostics provides an estimate of ___ concentration.

    <p>plasma protein</p> Signup and view all the answers

    Fibrinogen is considered a major acute phase protein in horses.

    <p>False</p> Signup and view all the answers

    Which of the following conditions can lead to malabsorption in the small intestine?

    <p>Inflammation of the intestinal mucosa</p> Signup and view all the answers

    Increased renal retention of electrolytes occurs in healthy individuals.

    <p>False</p> Signup and view all the answers

    What is the primary role of electrolytes in the body?

    <p>Maintaining fluid balance and facilitating nerve and muscle function.</p> Signup and view all the answers

    In health, ECF is relatively rich in _____ and _____ but poor in K+, Ca2+, PO4, and Mg2+.

    <p>Na+</p> Signup and view all the answers

    Match the following electrolytes with their primary locations:

    <p>Na+ = Extracellular fluid K+ = Intracellular fluid Ca2+ = Bones and teeth Cl- = Extracellular fluid</p> Signup and view all the answers

    Which condition is associated with unexpectedly high or prolonged peak concentrations of glucose?

    <p>Diabetes mellitus</p> Signup and view all the answers

    What are the four processes that affect serum concentrations of electrolytes?

    <p>Decreased/increased intake, shifts between ICF and ECF, increased renal retention, and increased loss.</p> Signup and view all the answers

    Electrolytes enter the body only through oral intake of food or fluids.

    <p>False</p> Signup and view all the answers

    What is the primary hormone that affects renal potassium excretion?

    <p>Aldosterone</p> Signup and view all the answers

    Hypokalaemia occurs when the serum potassium concentration is greater than 5.1 mmol/L.

    <p>False</p> Signup and view all the answers

    What is the reference interval for normal serum potassium concentration?

    <p>3.6-5.1 mmol/L</p> Signup and view all the answers

    A serum potassium concentration exceeding _____ mmol/L is considered life-threatening.

    <p>7.5</p> Signup and view all the answers

    Which of the following conditions can cause hypokalaemia?

    <p>Chronic renal failure</p> Signup and view all the answers

    Match the following potassium conditions with their characteristics:

    <p>Hypokalaemia = Serum potassium &lt; 3.6 mmol/L Hyperkalaemia = Serum potassium &gt; 5.1 mmol/L Normal potassium levels = Serum potassium between 3.6-5.1 mmol/L Life-threatening hyperkalaemia = Serum potassium &gt; 7.5 mmol/L</p> Signup and view all the answers

    A decrease in potassium intake is usually the sole cause of hypokalaemia.

    <p>False</p> Signup and view all the answers

    What effect do insulin and β2-adrenergic catecholamines have on potassium levels?

    <p>They shift potassium into liver and muscle cells.</p> Signup and view all the answers

    Study Notes

    Clinical Biochemistry - Clinical Pathology 410

    • Course covers clinical enzymology, including the introduction to enzymology, explaining how different organs, tissues, or cells contain different enzymes. Some enzymes are specific to particular tissues, making them diagnostically helpful. Increased serum enzyme activity suggests either cell injury or increased enzyme production.
    • Enzymes catalyze biochemical reactions, converting a substrate into a product. Enzyme activity is directly proportional to its concentration, measured in units per liter (U/L).
    • Leakage enzymes are released when cell injury alters cell membranes, while induced enzymes result from increased production stimulated by a stimulus.
    • Enzyme half-life influences how long enzyme activity persists in the blood after leakage or induction.
    • Tissue specificity of enzymes helps determine the source of tissue injury or stimulation.
    • Proper handling and storage are essential for accurate serum enzyme assay results.

    Enzymes and Serum Activity

    • Increased serum enzyme activity results from leakage or induction. Leakage occurs when cell injury causes membrane damage, while induction involves increased production of an enzyme in response to a stimulus.
    • Leakage enzymes pass into the extracellular space and then into the serum.
    • Figures 1 and 2 in the text illustrate the mechanisms of leakage and induced enzyme release.
    • Various serum enzyme assays are used; accurate interpretation depends on proper handling and storage of samples.

    Enzyme Half-Life

    • Enzyme half-life determines how long an enzyme remains active after being released into the blood.
    • Knowledge of an enzyme's half-life is helpful for assessing when tissue injury or increased enzyme production occurred and whether the process is ongoing.

    Tissue Specificity

    • Tissue specificity of enzymes helps determine the tissue of origin of leakage. This includes the presence or absence of the enzyme in the tissue, its concentration, and where it goes after leakage or secretion.
    • Serum enzyme activity is not a reliable indicator of the severity or location of tissue injury.

    Isoenzymes and Isoforms

    • Isoenzymes are enzymes that catalyze the same reaction but have different structures.
    • Isoenzymes may differ in catalytic sites, activity, immunogenicity, and electrophoretic mobility.
    • Examples include alkaline phosphatase (ALP), with intestinal and tissue non-specific isoforms, and lactate dehydrogenase (LDH), with isoforms based on heart and muscle subunits.
    • Isoform measurement can be accomplished through various methods (electrophoresis, immunoassays, cellulose acetate electrophoresis, isoelectric focusing).

    Liver

    • Hepatocyte injury is assessed using Alanine aminotransferase (ALT).
    • ALT is found in the liver, muscle, kidneys, and erythrocytes.
    • Increased serum ALT activity commonly signals hepatocellular injury.
    • ALT is not a reliable indicator of liver disease in large animals.
    • Increased serum activity peaks about 48 hours post-injury, then decreases. The serum half-life of ALT is roughly 2–3 days in dogs.

    Aspartate Aminotransferase (AST)

    • AST is a cytoplasmic and mitochondrial enzyme found in various tissues, including skeletal, cardiac, and liver muscle, and erythrocytes.
    • Increased AST activity indicates liver or muscle injury.
    • The activity usually begins to increase around 24-36 hours after injury, and decreases more slowly than serum CK.

    Glutamate Dehydrogenase (GLDH)

    • GLDH is a mitochondrial indicator of liver injury and is found in several other organs.

    Alkaline Phosphatase (ALP)

    • ALP is a non-specific enzyme that hydrolyzes phosphate esters.
    • Liver and bone are the major sources of ALP.
    • Increased serum ALP activity is a sensitive indicator of cholestasis (gallbladder or extrahepatic bile duct obstruction) in dogs but is less useful in other species.

    Gamma-Glutamyl Transferase (GGT)

    • GGT is a membrane-bound enzyme involved in hepatic and biliary function.
    • GGT originates primarily from the liver and can indicate potential issues with the biliary system.
    • Increased serum GGT activity is commonly associated with cholestasis, and biliary hyperplasia.

    Pancreatic enzymes

    • Amylase activity is used to test for pancreatitis.
    • Pancreatic lipase activity plays a central role in fat digestion and is useful to identify potential pancreatic disorders.
    • Elevated lipase activity is often associated with pancreatitis in dogs, cats, and ruminants compared to amylase.
    • Testing for lipase is more sensitive for identification of pancreatitis in many species than testing for amylase, especially cats.

    Creatine Kinase (CK)

    • CK is an enzyme primarily found in skeletal and cardiac muscle.
    • Increased serum CK activity often indicates muscle injury or inflammation, as it is rapidly elevated and returns to normal within 24–48 hours after an acute insult.

    Serum Protein Electrophoresis (SPE)

    • SPE analysis separates serum proteins into albumin, alpha-1, alpha-2, beta-1, beta-2, and gamma fractions.
    • Albumin is the main serum protein, and the globulin fractions include diverse proteins, including immunoglobulins.
    • Increased or decreased concentrations of protein fractions indicate potential problems or underlying diseases.

    Acute Phase Proteins (APPs)

    • APPs are proteins whose concentrations change significantly (>25%) in response to inflammation and are used as markers for inflammatory conditions.
    • Increase in APPs occurs within 24–48 hours post-inflammation.

    Plasma Ammonia

    • Ammonia (ammonium) is produced in the gastrointestinal tract from microbial breakdown of proteins, and is converted in the liver to urea.
    • Ammonia is removed by the urea cycle, and elevated levels can be associated with liver insufficiency, or other non-hepatic causes.
    • Blood ammonia concentration is often elevated in animals with hepatic encephalopathy.

    Clinical evaluation of plasma proteins

    • Evaluation of A/G ratios and serum protein concentrations aids in diagnosing various diseases (i.e. acute phase response, overhydration, concurrent conditions).
    • Dehydration, increased water intake, may result in elevated protein levels.

    Tests of Carbohydrate Assimilation (Glucose Absorption Test)

    • Glucose absorption tests are useful for assessing carbohydrate absorption in monogastric mammals, but not ruminants.
    • Glucose is administered, and blood samples are collected at various time intervals.
    • Adequate intestinal absorption is indicated if the glucose concentration doubles at 120 minutes compared to basal levels.
    • This test is performed primarily in horses in cases of chronic weight loss.

    Electrolytes - Basic Concepts

    • Electrolytes include sodium (Na+), chloride (Cl-), potassium (K+), calcium (Ca2+), phosphate (PO4), and magnesium (Mg2+).
    • Electrolyte concentrations are measured in whole blood, plasma, or serum and these are determined by four processes : intake, shifts between ICF and ECF, increased renal retention, and increased loss via the kidneys, alimentary tract, skin, or airways.

    Liver Physiology and Diseases

    • The liver is a vital organ with many metabolic and excretory functions.
    • Liver disease encompasses various conditions affecting hepatocytes, bile ducts, or portal circulation.
    • Liver dysfunction can cause abnormalities in serum enzymes, bile acids, and other substances.

    Urinary System

    • Glomerular filtration rate (GFR) is the primary measure of renal function and is estimated using serum urea, serum creatinine, and symmetric dimethylarginine (SDMA).
    • Renal tubular function can also be tested through urine specific gravity (SG).
    • Urea is a byproduct of protein catabolism which is produced in the liver. Serum levels increase during renal dysfunction
    • Creatinine is predominantly produced by muscle metabolism, and serum levels increase in response to renal disease.

    Urine Analysis

    • Urine analysis involves physical (clarity, colour, odour) and chemical (e.g., pH, specific gravity, protein, glucose, ketones, blood) assessments.
    • Microscopic examination of the urine sediment assesses for cells, casts, and crystals.
    • These analyses are essential for diagnosing numerous urinary tract disorders, and assessing animal's health.

    Clinical Enzymology

    • Overview of enzymology topics in clinical pathology.
    • Detailed mechanisms about leakage versus induced and enzyme half-life's, importance and implications of tissue-specificity and proper handling/storage.
    • Specific serum enzyme assays and their clinical relevance (e.g. ALT, AST, GGT, GLDH, CK, lipase, amylase, bilirubin)
    • Methods to assess and interpret results of these tests.

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    Description

    Test your knowledge on liver and muscle injury biomarkers, including serum GLDH, SDH, and CK activities. This quiz explores the specific enzymes involved and their clinical implications. Perfect for students in veterinary biochemistry or clinical pathology courses.

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