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 $CT$.