Amyloidosis Flashcards
What’s Amyloidosis?
Amyloidosis is a condition where abnormal proteins, known as amyloid fibrils, accumulate outside of cells (extracellularly) in various tissues and organs. These deposits can cause both structural damage and functional impairment of the affected tissues.
Formation of Abnormal Fibrils:
The abnormal amyloid fibrils result from proteins that misfold and aggregate. Normally, proteins fold into specific shapes to function correctly. When they misfold, they can stick together and form fibrils, which then deposit in tissues.
Amyloid fibrils tend to bind to certain molecules within the body, which are?
Proteoglycans and glycosaminoglycans: These are types of sugar-protein and sugar chains found in various tissues. Examples include heparin sulfate and dermatan sulfate.
Plasma proteins: Notably, the serum amyloid P component (SAP), which is a normal plasma protein, often associates with amyloid deposits.
Association with Other Disorders:
Amyloidosis can occur in conjunction with various inherited (genetic) and inflammatory conditions. This means it can either be passed down in families or arise due to chronic inflammatory diseases.
Staining Characteristics and Naming:
The amyloid deposits contain many charged sugar groups, which influence how they stain during microscopic examination. Historically, these deposits were thought to resemble starch (amylose) in their staining properties, leading to the name “amyloid.” However, amyloid deposits are not related to starch at all.
What are the types of Amyloidosis
Primary Amyloidosis
Plasma Cells: These are a type of white blood cell that produce antibodies, which are proteins that help fight infections.
Disorders of Plasma Cells: In primary amyloidosis, there is an abnormal production of proteins by plasma cells.
Multiple Myeloma: This is a specific type of cancer that affects plasma cells. In multiple myeloma, the cancerous plasma cells produce large amounts of an abnormal protein called light chains. These light chains can misfold and aggregate, forming amyloid fibrils that deposit in tissues, leading to primary amyloidosis.
Secondary Amyloidosis
Chronic Inflammatory or Tissue-Destructive Processes: These are long-term conditions that cause continuous inflammation or damage to tissues.
Examples of Conditions:
Long-term infections: Chronic infections like tuberculosis can lead to sustained inflammation.
Chronic Inflammatory Diseases: Conditions like rheumatoid arthritis involve ongoing inflammation of the joints and other tissues.
Prolonged Tissue Damage: Any condition that causes extended periods of tissue damage, such as certain autoimmune diseases, can contribute to secondary amyloidosis.
Mechanism: In secondary amyloidosis, the body’s response to chronic inflammation or tissue damage leads to the production of an abnormal protein called serum amyloid A (SAA). When produced in excess over a long period, SAA can misfold and form amyloid fibrils, which then deposit in various tissues and cause damage.
Hereditary or Familial Amyloidosis:
This type runs in families, meaning it’s passed down genetically. Different families might have different patterns of how and where these deposits form, like inheriting different blueprints for building problematic structures.
The pathogenesis of amyloidosis starts with proteins that fold incorrectly. Think of proteins as pieces of paper that need to be folded into specific shapes to fit into their designated spots. In amyloidosis, these papers are folded incorrectly, and instead of being disposed of, they accumulate and form insoluble clumps (fibrils) that deposit in the spaces between cells.
Normal type of protein Disposal:
Intracellular degradation: Proteins are broken down inside cells by structures called proteasomes, similar to a paper shredder destroying incorrect documents.
Extracellular degradation: Outside cells, macrophages (a type of immune cell) clean up misfolded proteins, like janitors cleaning up trash.
What are the Categories of Amyloid-Forming Proteins:
Normal Proteins Produced in Excess: These proteins are usually normal but are produced in large quantities, leading to a higher chance of misfolding. It’s like having too many papers to fold, increasing the likelihood of mistakes.
Mutant Proteins: These proteins have genetic mutations that make them more likely to misfold and clump together. Imagine having defective paper that’s harder to fold correctly, leading to more misfolding and aggregation.
What’s the most common types of amyloidosis?
Primary Amyloidosis
Most Common Form: Primary amyloidosis is the most frequently encountered type. It is often linked with disorders involving plasma cells (a type of white blood cell).
Whats the amyloid protein usually involved in primary amyloidosis
Systemic Distribution: Primary amyloidosis typically affects multiple organs (systemic distribution). The amyloid protein involved is usually of the AL type (amyloid light-chain).
What’s the cause of primary amyloidosis
Cause: The condition arises from a clonal proliferation of plasma cells, meaning a single group of plasma cells starts multiplying uncontrollably. These cells produce an abnormal immunoglobulin (Ig) that tends to misfold and form amyloid.
Multiple Myeloma causes what type of amyloidosis?
Multiple Myeloma:
About 5% to 15% of people with multiple myeloma (a type of cancer affecting plasma cells) develop amyloidosis. Multiple myeloma is characterized by multiple osteolytic lesions (bone damage) throughout the skeleton.
What’s Monoclonal Gammopathy?
Monoclonal Gammopathy: In multiple myeloma, the malignant plasma cells produce large amounts of a single type of immunoglobulin (Ig), known as monoclonal gammopathy. This is detected as an M protein spike on serum electrophoresis (a laboratory test that measures the presence of abnormal proteins in the blood).
What’s Secondary amyloidosis
Secondary amyloidosis, also known as reactive systemic amyloidosis, involves the systemic deposition of amyloid composed of AA protein. This form of amyloidosis arises secondary to chronic inflammatory conditions.
