Enzymes: ACP, CPK, Amylase/Lipase

Acid Phosphatase (ACP)

• General Characteristics and Concentration

  • When evaluating enzymes, the primary concern is the anatomical location where they are found.
  • The highest concentration of acid phosphatase ($ACP$) is located within the prostate gland.
  • While the greatest concentration is in the prostate, it is present throughout various tissues in the body, including:
    • The spleen.
    • The liver.
    • Red blood cells ($RBCs$).
    • Platelets.
    • Bone marrow.

• Diagnostic Replacement and Modern Usage

  • Acid phosphatase is no longer typically included in a Comprehensive Metabolic Panel ($CMP$).
  • It has been largely replaced by the Prostate Specific Antigen ($PSA$) test.
  • The reason for this shift is that $PSA$ is both more sensitive and more specific than acid phosphatase.
  • Acid phosphatase was found to be an "okay" screening tool but often failed to detect prostate cancer until the disease had already metastasized to the bone.

• Mechanism of Elevation in Malignancy

  • $ACP$ levels elevate in instances of osteoclastic activity.
  • When prostate cancer metastasizes to the bone, it triggers increases in osteoclastic activity, which is the specific point at which clinicians would observe an elevation in acid phosphatase levels.

• Challenges with Prostate Specific Antigen ($PSA$)

  • While $PSA$ is highly sensitive, its propensity for false positives is a significant downside.
  • Potential causes for false elevations in $PSA$ include:
    • Ejaculation within the last $48$ hours prior to the test.
    • A large bowel movement occurring shortly before the test.
  • Clinical response to elevated $PSA$:
    • In older males (where this is used as a screening tool), providers may retest $PSA$ after a few months or up to a year, depending on the severity of the elevation.
    • If more information is needed, the patient may be referred for a digital rectal exam ($DRE$), a prostate ultrasound, or a biopsy of the prostate.

• Current Clinical Significance of ACP

  • Today, acid phosphatase is primarily used for:
    • Checking for the recurrence of prostate cancer.
    • Monitoring a patient's response to treatment.
  • Its clinical significance for initial screening is low; it is mostly associated with prostate cancer only after it has reached the bone (metz to bone).

Creatine Phosphokinase (CPK or CK)

• General Perspectives

  • Understanding enzymes often involves managing "alphabet soup" (three-letter delineations like $CPK$, $CK$, $ACP$, etc.).
  • Mastering this topic requires the memorization of these abbreviations and the specific pathologies that lead to their elevation.

• Isoenzymes Overview

  • Isoenzymes are variations of the same enzyme found in different specific tissues.
  • A lab report typically shows Total CPK.
  • If total $CPK$ is elevated, a follow-up test is needed to break out the isoenzymes. Many labs offer a reflexive order where the isoenzymes are automatically drawn if the total level is high.
  • Clinical determination of the cause of elevation involves using both the isoenzyme sub-fraction and the patient's history.

• Isoenzyme Categorization and Locations

  • CPK-1 (CPK-BB): Located in the brain.
    • Memory Tool: "One Big Brain" ($BB$).
  • CPK-2 (CPK-MB): Located in the heart and the diaphragm.
    • Memory Tool: "Two muscles that beat" ($MB$).
  • CPK-3 (CPK-MM): Located in the skeletal muscle.
    • Memory Tool: In anatomy, skeletal muscle is often shortened to "$\text{mm}$."

Clinical Significance of CPK Elevations

• CPK-1 (CPK-BB) Elevations

  • Elevations result from pathologies occurring within the brain.
  • Examples include:
    • Stroke.
    • Traumatic Brain Injury ($TBI$).
    • Cerebral hypoxia.
    • Seizures.
    • Certain neurodegenerative conditions (tending toward slow elevations).

• CPK-2 (CPK-MB) Elevations

  • The primary concern is Myocardial Infarct ($MI$) or heart attacks.
  • While $CPK-2$ is a modern cardiac panel component, it is often compared against troponins.
  • Troponins vs. CPK-2:
    • Troponins are the preferred standard because they elevate more quickly (within approximately $2$ hours) and stay elevated longer (for $1$ to $2$ weeks).
    • $CPK-2$ increases more slowly, taking $4$ to $6$ hours to elevate, and returns to normal more quickly within $2$ to $3$ days.
  • Clinicians use the "concert of information" from troponins and $CPK-2$ (plus other enzymes) to time the onset of the heart attack and determine its severity.

• CPK-3 (CPK-MM) Elevations

  • $CPK$ is considered the best indicator of skeletal muscle damage.
  • Pathologies include:
    • Muscular Dystrophy: Specifically Duchenne or Becker types.
    • Trauma: Crush injuries, fractures impacting surrounding muscle, or surgical interventions.
    • Prolonged or Intense Exercise: Exercise-induced elevations.
    • Hypothyroidism: Can lead to the death of muscle cells and subsequent elevation.
    • Drug-Induced Myopathy: Pharmaceuticals such as statins can cause muscle damage or increase the risk of rhabdomyolysis.

Rhabdomyolysis

• Pathophysiology

  • The name signifies "lysis of the muscles."
  • When muscle cells break down, myoglobin is released into the bloodstream and eventually ends up in the urine.

• Common Clinical Presentation

  • Can occur due to over-exercising (a factor to be aware of in chiropractic settings).
  • Myalgia: Muscle pain typically found in the thighs, low back, and shoulders.
  • Darkened Urine: Often described as "brown" or tea-colored urine due to the presence of myoglobin.
  • Other Symptoms: Fatigue and muscle weakness.

Differential Signs and Symptoms of Myocardial Infarct (MI)

• Male (Typical Presentation)

  • Chief finding: Intense, crushing chest pain often described as "an elephant sitting on the chest."
  • Radiation pattern: Most commonly to the left arm and sometimes traveling to the jaw.
  • Associated symptoms: Shortness of breath and sweating.

• Female ("Atypical" or Vague Presentation)

  • Chest pain is much less common and often mild, perceived as a feeling of "tightness" in the chest musculature during deep breaths.
  • Radiation pattern: More common in the neck, jaw, shoulders, and upper back.
  • Systemic/GI findings: Nausea, vomiting, and other GI symptoms.
  • Other findings: Unexplained and severe fatigue, dizziness, and lightheadedness.

• Clinical Illustration (Case Study)

  • A patient presented with mid-back pain, chest fluttering, and worsening fatigue over a week.
  • A cardiac panel (troponins, $CPK$, etc.) was normal, and the $EKG$ showed an arrhythmia, though the patient was eventually diagnosed with Hashimoto's.
  • Lesson: Vague symptoms in females must be taken seriously to rule out cardiac involvement.

Muscular Dystrophy

• Duchenne Muscular Dystrophy

  • More common and more severe.
  • Typical onset: $2$ to $5$ years of age.
  • Characterized by rapid progression and severe muscle weakness.

• Becker Muscular Dystrophy

  • Lesser frequency and milder presentation.
  • Typical onset: Between $5$ and $20$ years of age.
  • Characterized by slower progression and milder weakness.

• Clinical Presentation and Diagnostics

  • A muscle biopsy and genetic testing are required to differentiate the two definitively.
  • Common initial signs for both:
    • Delayed motor milestones: Delays in learning to walk, running, or climbing stairs.
    • Gowers Sign: A characteristic maneuver where a child uses their hands to "walk up" their own thighs to stand up from a seated or laying position.
    • Proximal Muscle Weakness: Usually impacts the pelvic girdle first, then moves to the shoulders.
    • Gait issues: Widened or waddling gait, clumsiness, and frequent falling.

Amylase and Lipase

• Functional Roles

  • Amylase: Responsible for breaking down carbohydrates.
  • Lipase: Responsible for breaking down lipids (fats).

• Anatomical Locations

  • Amylase is found in the pancreas and the salivary glands.
  • Lipase is primarily found in the pancreas and is considered more specific to the pancreas than amylase.

• Acute Pancreatitis

  • Characterized by reliable elevations in both amylase and lipase.
  • Clinical symptoms:
    • Severe, sudden, and constant epigastric pain.
    • Radiation of pain: Often "boring" through to the back or appearing as a "band-like" pain around the flank.
    • Exacerbating factors: Pain is worse after eating and worse when laying flat.
    • Other symptoms: Nausea, vomiting, fatigue, and fever.

• Pancreatic Carcinoma

  • Elevations in amylase and lipase are not reliable; the disease must be severe before elevations occur.
  • Symptoms: Epigastric pain radiating to the back, and the potential development of diabetes.
  • Red Flags: Weight loss and severe fatigue should be monitored.

• Other Causes for Elevation

  • Mumps or inflammation of the salivary glands will lead to elevations in amylase specifically, because of its presence in salivary tissue.

• Imaging Modalities for Pancreas

  • A CT scan is the preferred starting modality if acute pancreatitis or pancreatic carcinoma is suspected.
  • An MRI may follow after the initial $CT$.