What is Amyloidosis?
Amyloidosis is a rare and serious disease characterized by the abnormal accumulation of amyloid proteins in various tissues and organs. These misfolded proteins form insoluble fibrils that deposit in extracellular spaces, disrupting normal tissue function and leading to a range of clinical manifestations.Amyloidosis involves the accumulation of misfolded proteins, known as amyloid, which aggregate into fibrils that deposit in extracellular spaces.
These deposits disrupt normal tissue structure and function by physically obstructing organ spaces and inducing chronic inflammation. The amyloid fibrils are resistant to proteolysis and can interfere with cellular processes, leading to organ dysfunction and systemic symptoms. The impact of amyloid deposits on tissue architecture varies by organ system, contributing to the wide range of clinical manifestations observed in amyloidosis.
Types of Amyloidosis
Primary (AL) Amyloidosis
- This type involves the deposition of amyloid proteins derived from abnormal plasma cells, which are cells in the bone marrow responsible for producing immune proteins. It is often linked with conditions affecting these cells and commonly affects the heart, kidneys, liver, and nervous system.
Secondary (AA) Amyloidosis
- Occurs due to the deposition of amyloid A protein, which is produced in response to chronic inflammation from diseases such as rheumatoid arthritis, chronic infections, or inflammatory bowel conditions. It primarily impacts the kidneys, liver, and spleen.
Hereditary (ATTR) Amyloidosis
- Caused by genetic mutations that lead to the production of abnormal transthyretin proteins. This type can be inherited from family members or occur with aging. It often affects the heart and nerves but can involve other organs as well.
Dialysis-Related (AD) Amyloidosis
- Associated with long-term kidney dialysis. The condition involves the accumulation of a protein called β2-microglobulin and is usually seen in the bones and joints, leading to issues like carpal tunnel syndrome.
Localized Amyloidosis
- Features amyloid deposits restricted to a specific area or organ without widespread systemic involvement. Examples include localized deposits in the skin, bladder, or lungs.
Risk Factors of Amyloidosis
- Primary (AL) Amyloidosis: Associated with disorders of the plasma cells, such as conditions that cause abnormal production of immune proteins.
- Secondary (AA) Amyloidosis: Linked to chronic inflammatory diseases or persistent infections that drive increased production of amyloid A protein.
- Hereditary (ATTR) Amyloidosis: Arises from genetic predispositions that lead to the abnormal production of transthyretin proteins. Family history can increase the risk.
- Dialysis-Related (AD) Amyloidosis: Affects individuals who undergo long-term dialysis, resulting in the accumulation of β2-microglobulin.
- Localized Amyloidosis: May occur without systemic disease and is not necessarily associated with any particular risk factors beyond localized deposition.
Symptoms of Amyloidosis
- Heart failure
- Irregular heart rhythms
- Shortness of breath
- General fatigue
- Protein in the urine
- Swelling (edema)
- High blood pressure
- Decreased kidney function
- Enlarged liver
- Jaundice (yellowing of the skin and eyes)
- Abdominal pain
- Numbness
- Tingling
- Pain in the extremities
- Digestive issues such as diarrhea, constipation, and bleeding
- Abdominal discomfort
Diagnosis
- Histological Examination: Diagnosis typically involves taking a tissue sample from the affected area and examining it under a microscope after staining it with specific dyes that highlight amyloid deposits.
- Serum and Urine Tests: Blood and urine tests can help detect abnormal proteins and assess kidney function, which are important for diagnosing certain types of amyloidosis.
- Genetic Testing: For hereditary forms, genetic testing can identify specific mutations that cause the condition.
- Imaging Studies: Various imaging techniques, such as ultrasound, MRI, or CT scans, help evaluate the extent of organ involvement and assess damage.
Treatment & Management
- Treatment focuses on addressing the underlying condition that is causing the abnormal protein production, often involving strategies to manage or reduce the production of these proteins.
- Management involves treating the underlying chronic inflammatory or infectious condition to reduce the production of amyloid A protein.
- Treatment may include strategies to stabilize the transthyretin protein or address the effects of its deposition. In severe cases, organ replacement may be considered.
- Improving dialysis methods and addressing symptoms through supportive measures can help manage this type.
- Depending on the location and extent of the deposits, localized treatments or procedures may be used to manage the condition.
Complications
Amyloidosis can lead to serious complications in the following organs:
Heart – Amyloid reduces the ability of your heart to fill with blood between heartbeats. As less blood is pumped with each beat, this can lead you to experience shortness of breath. If amyloidosis affects the electrical system of your heart, the heart rhythm may get disturbed. Heart problems which are related to amyloid can become life-threatening.
Nervous system – You might experience pain, numbness, or tingling on your fingers. You might also experience numbness, lack of feeling, or a burning sensation in your toes or the soles of your feet. If amyloid affects the nerves controlling your bowel function, you may experience periods of alternating constipation or even diarrhea. If it affects the nerves that control blood pressure, you may feel faint if you stand up too quickly.
Kidneys – Amyloid can harm the filtering system of the kidneys, and this can cause the protein to leak from your blood into your urine. The kidneys’ ability to remove waste from the body gets lowered, which can result in kidney failure and may require dialysis.