Lecture on Amyloid and Amyloidosis

Cellular Injury and the Role of Amyloid

  • Importance of Discussing Amyloid in Cellular Injury
    • Amyloid is a mechanism by which cells can become injured and eventually die.
    • Amyloid has the ability to damage tissues, leading to cell injury and tissue damage.

Definition of Amyloid

  • Amyloid:
    • A misfolded protein.
    • It deposits in the extracellular space.
    • This deposition leads to tissue damage as it contributes to the injury of cells.

Characteristics of Amyloid

  • Multiple Proteins as Amyloid

    • Amyloid is not a single protein; it is a broad category encompassing multiple proteins depositing in a specific way.

  • Misfolding and Structure

    • Misfolded proteins that deposit as amyloid typically exhibit a beta-pleated sheet configuration.

  • Staining Properties

    • Commonly, these proteins can be stained using Congo red.
    • Upon staining, amyloid turns red, indicating its presence in tissues.
    • Illustration Note:
      • Center represents a blood vessel, surrounded by dense pink material, which is amyloid.
      • Amyloid typically deposits around blood vessels, which is significant in diseases like Alzheimer's.

  • Birefringence

    • When Congo red stained amyloid is viewed under polarized light, it exhibits an apple-green birefringence.

Types of Amyloid Deposition

  • Systemic vs. Localized Amyloidosis
    • Systemic Amyloidosis: Deposits in multiple organ systems; characterized by diffuse deposition.
    • Localized Amyloidosis: Restricted to specific tissues or organs.

Systemic Amyloidosis

  • Primary Amyloidosis:

    • Characterized by systemic deposition of AL amyloid.
    • AL amyloid is derived from immunoglobulin light chains.
    • Occurs due to overproduction of light chains by plasma cells, leading to misfolding and deposition in various tissues.

  • Secondary Amyloidosis:

    • Often related to conditions that cause chronic inflammation, leading to the production of SAA (Serum Amyloid A) protein, which can misfold and deposit as AA amyloid.

Clinical Implications of Amyloidosis

  • Classic Clinical Findings:

    • Amyloid can deposit in multiple tissues, leading to various clinical manifestations.

  • Kidney Involvement:

    • The kidney is the most commonly involved organ.
    • Results in nephrotic syndrome: Characterized by a significant loss of protein via urine, typically greater than 3.5 grams over a 24-hour period.

  • Cardiac Involvement:

    • Restrictive Cardiomyopathy:
    • Heart becomes less compliant due to amyloid deposition, affecting its ability to fill and pump effectively.
    • This condition can lead to cardiac failure.

  • Familial Amyloid Cardiomyopathy:

    • Caused by mutated serum transthyretin that deposits in the heart, leading to restrictive cardiomyopathy.

Localized Amyloidosis Examples

  • Type 2 Diabetes Mellitus:

    • Characterized by insulin resistance in skeletal muscle and adipose tissues, leading to elevated insulin production.
    • Excess insulin leads to the production of amylin, which deposits in the pancreatic islets.

  • Alzheimer's Disease:

    • Characterized by amyloid plaques, which contain beta-amyloid, derived from beta-amyloid precursor protein (APP).
    • APP gene is located on chromosome 21, which is significant due its relation to MHC class I structural components.

  • Medullary Carcinoma of the Thyroid:

    • Originates from C cells in the thyroid that produce calcitonin.
    • Tumors lead to an overproduction of calcitonin, resulting in amyloid deposition.
    • Histological diagnosis can reveal tumor cells in an amyloid-rich background during fine needle aspiration biopsies.

Conclusion

  • Amyloidosis is a complex process involving the misfolding of proteins leading to harmful deposits that can affect various organs and cause significant clinical symptoms, emphasizing the necessity for understanding these processes in a medical context.