Cardiac & Skeletal Muscle Diseases

Cardiac & Skeletal Muscle Disease, and Muscle Biomarkers

• Presentation date: 17-18/12/2024
• Presenter: Dr. Halil Resmi

Muscle Anatomy and Function

• Three types of muscle: skeletal, cardiac, smooth
• Skeletal muscle: unbranched, cylindrical cells arranged in parallel bundles
• Skeletal muscle fibers: run the entire length of the muscle
• Skeletal muscle contraction: neurogenic (initiated by nerve impulses)
• Two skeletal muscle types: fast-twitch, slow-twitch (differ in biochemical nature)
• Cardiac muscle: found exclusively in the heart
• Cardiac muscle: contains actin and myosin filaments
• Cardiac muscle contraction: myogenic (involuntary control)

Cardiac Disorders

• Ischemia: inadequate blood supply to an organ
• Atherosclerosis: most common cause of ischemia
• Atherosclerosis: cholesterol deposits in arterial walls, occluding the artery
• Ischemic diseases: range from unstable angina (reversible myocardial cell injury) to frank myocardial infarction (large areas of necrosis).
• Acute Coronary Syndrome (ACS): block or severe reduction of blood flow to the heart muscle. Damages the heart muscle. Heart attack and unstable angina are types of ACS.
• Congestive Heart Failure (CHF): disease related to decreased blood pumping capability.
• CHF: spectrum of diseases from left ventricular dysfunction (LVD) to overt CHF.
• CHF therapy: angiotensin-converting enzyme (ACE) inhibitors.

Cardiomyopathy

• Cardiomyopathy: characterized by inadequate muscle contraction due to myocardial cell damage, resulting in heart failure.
• Cardiomyopathy manifestation: enlargement of all four heart chambers and heart failure.

Skeletal Muscle Disorders

• Skeletal muscle diseases: characterized by motor function issues like muscular weakness.
• Muscle disorders categories: neurogenic muscular atrophies, muscle fiber disorders (myopathies), disturbances of neuromuscular junctions.

Disorders of Muscle Fibers: Muscular Dystrophies

• Muscular dystrophy: group of genetic, chronic muscle diseases.
• Muscular dystrophy characteristics: progressive weakness and skeletal muscle degeneration without neural degeneration.
• Muscular dystrophy inheritance: varies among types.
• Muscular dystrophy factors: age of onset, disease course, fiber type effects vary among individual types.

Pseudohypertrophic Muscular Dystrophy (DMD)

• DMD: most common muscular dystrophy.
• DMD genetic defect: deletion in the dystrophin gene resulting in a defective dystrophin protein.
• DMD serum CK enzyme: greatly elevated even before symptoms appear.
• DMD treatment: currently no effective treatment, considered a prime candidate for gene therapy.

Changes of Analytes in Disease

Myocardiocyte Biomarkers

• Necrotic cardiac myocytes: lose membrane integrity, intracellular components enter the bloodstream.
• Cardiac biomarkers: collectively known molecules detectable in peripheral circulation
• Ideal cardiac biomarker: abundant in myocytes, low in blood, released early after injury, absent in nonmyocardial tissues.
• Direct relation: between plasma level of cardiac marker and myocardial injury effect.
• Marker persistence: sufficient length in blood for high-rate diagnosis, easy, inexpensive, and rapid measurement.

Definition of Myocardial Infarction (MI)

• MI: damaging process where ischemic injury is irreversible, leading to cell death and necrosis.
• MI diagnosis: clinical history, ECG interpretation, serum cardiac-specific biomarker measurement (cTnT and cTnI now cornerstone for MI detection).

Cardiac Biomarkers in MI

• CK-MB or troponin: elevated in blood 4 to 6 hours post-chest pain onset
• Biomarkers diagnostic value: 8 to 12 hours post-presentation
• Temporal pattern of CK-MB changes: helpful to distinguish uncomplicated MI from extension/reinfarction.

Creatine Kinase (CK) & Creatine Kinase MB (CK-MB)

• CK-MB: first cardiac biomarker to meet many criteria.
• CK-MB: one of three isoenzymes arising from total creatine kinase (CK).
• Total CK: dimeric enzyme composed of two subunits (“M” for muscle, “B” for brain).
• CK isoenzymes: CK-MM, CK-BB, CK-MB.
• CK-MB: high concentration in myocardium

Cardiac Biomarkers in MI (cont.)

• MI diagnosis: requires blood sample analysis at specific intervals (2-4 hours, 6-8 hours, 12 hours).
• Sampling intervals adjustments permitted: if early samples were negative and clinical suspicion index was high.
• Elevated CK-MB (normal total CK): possible in initial MI course.
• CK values rise and fall: in some cases, do not exceed the upper limit.

Cardiac Biomarkers in Coronary Disease

• Troponin (T&I): noticeably more sensitive and specific for cardiac injury than CK-MB.
• Troponins: preferred biomarker for cardiac disease.

Diagnostic Use of Cardiac Troponins

• Troponin: plays a vital role in diagnosis and risk assessment in ACS.
• Troponin release kinetics: similar to CK-MB after MI.
• Troponin: remains elevated in blood for 4 to 10 days after MI.
• Low troponin values (without cardiac disease): permit use of lower discriminatory values to determine MI.
• Troponin cardiac specificity: helps eliminate diagnostic uncertainty caused by increased CK-MB due to skeletal muscle injury.

Cardiac Troponin I (cTnI)

• cTnI: lower molecular weight than cTnT and CK-MB, similar release kinetics and early MI indicator.
• Clinical applications: similar to cTnT, measurement offers advantage over CK-MB.
• cTnI elevation duration: 3 to 7 days after acute MI.
• Diagnostic comparison (with CK-MB): comparable diagnostic sensitivity for initial (48-72 hours), cTnI improved sensitivity from 72 to 96 hours post MI.
• cTnI: not elevated in patients with extreme skeletal muscle injury.

Cardiac Troponin T (cTnT)

• cTnT: increases in serum after 4 hours of MI.
• cTnT peak/plateau: 1 to 6 days, with a second peak possible ("bound fraction").
• cTnT clinical sensitivity: similar to CK-MB in first 48 hours post-chest pain onset.
• cTnT extended life in serum: provides information on recent myocardial dysfunction history.

Sensitivity & Specificity of Cardiac Markers

• Chart of marker characteristics (first detection, duration of detection, sensitivities, specificities for Myocyte Necrosis.)
• Myoglobin: presence in both cardiac and skeletal muscle, limiting diagnostic specificity, early marker for MI, rise detectable 1 to 2 hours post-symptom onset.
• Myoglobin: not cardiac-specific (renal failure, injury, skeletal muscle disease); presence of myoglobinuria confirms muscle cell damage.

CK & CK Isoenzymes in Non-MI Conditions

• CK isoenzyme pattern (non-MI conditions): not a rise and fall pattern, but rather chronically elevated levels;
• Specific examples: Duchenne muscular dystrophy, polymyositis, rhabdomyositis demonstrate increased CK-MB levels in serum.
• Total CK levels in skeletal muscle: 5-10 fold higher than cardiac muscle, leading to significantly higher total CK levels in conditions other than MI compared to those observed in MI. Chart demonstrating CK value increases in various muscular pathology conditions.

This quiz covers the anatomy and function of skeletal and cardiac muscles, as well as common disorders associated with these muscle types. It also delves into muscle biomarkers and the implications of conditions like ischemia and atherosclerosis. Test your knowledge on how these diseases affect muscle physiology.