Chapter 1.5 AMYLOIDOSIS Flashcards
What is an amyloid?
Any type of misfolded protein that deposits in the EXTRACELLULAR SPACE, thereby damaging tissues
Also deposits characteristically around BLOOD VESSELS
What types or groups of proteins can deposit as amyloid?
Multiple proteins e.g-
- AL amyloid derived from Immunoglobulin light chain protein
- AA amyloid derived from SAA ( Serum amyloid associated protein)
What are the GENERAL FEATURES of amyloid proteins?
- Beta-pleated sheet configuration
- Congo-red staining
- Apple-green birefringence when viewed microscopically under polarized light
What are the 2 patterns of deposition of amyloidosis?
- Systemic
2. Localized
What are the types under Systemic amyloidosis?
- Primary systemic amyloidosis
2. Secondary systemic amyloidosis
What is primary systemic amyloidosis?
Systemic deposition of AL amyloid
AL amyloid is derived from light chain Ig.
Cause of 80% of systemic amyloidosis
Which disease is Primary Systemic Amyloidosis associated with?
Plasma cell dycrasias (i.e multiple myeloma)
Where there is disproportionate overproduction of light chain Ig—leaks into the blood—becomes misfolded—deposits in tissues.
What is secondary systemic amyloidosis?
Systemic deposition of AA amyloid
AA amyloid is derived from SAA (Serum associated Amyloid)
What is SSA? (Serum Associated Amyloid)
An acute phase reactant that is increased in:
- chronic inflammatory states (lupus, RA, crohn’s, ulcerative colitis, chronic osteomyelitis)
- Malignancy (ass with low grade chronic inflammatory state)
- Familial Mediterranean Fever
Chronic inflammation triggers and converts SAA—AA which is deposited in tissues.
What is Familial Mediterranean Fever?
Autosomal recessive
People of Mediterranean origin
Neutrophil dysfunction (incites inflammation even in absence of infection)
FEVER + acute SEROSAL INFLAMMATION (can mimic: APPENDICITIS, ARTHRITIS or MI)
During attacks, High SAA production—AA deposition in tissues
What are the clinical findings of systemic amyloidosis?
- Nephrotic syndrome (Kidneys-most common organ involved)
- Restrictive cardiomyopathy or arrhythmia
- Tongue enlargement(macroglossia), Gut enlargement (malabsorption), hepatosplenomegaly.
- Lung involvement—Cough and dyspnea
- Hematologic—Factor X def. (AL amyloid only absorbs factor X)
How can you diagnose Systemic amyloidosis?
- Tissue biopsy!
Abdominal fat pads (adipose tissue) and rectum- easy accessible biopsy targets
- Immunoelectrophoresis (SPEP- serum protein electrophoresis)
To detect light chains in AL amyloidosis
What is the definitive management of amyloidosis?
Organ transplantation.
Amyloid cannot be removed.
What is localized amyloidosis?
Amyloid deposition usually localized to a single organ.
Give examples of localized amyloidosis
- Senile cardiac amyloidosis
- Familial amyloid cardiomyopathy
- Non insulin dependent DM-type II (Amylin deposition)
- Alzheimer’s diseases (A-beta amyloid deposition)
- Dialysis associated amyloidosis (beta-2 microglobulin dep.)
- Medullary carcinoma of the thyroid (Calcitonin dep.)
What is senile cardiac amyloidosis?
Deposition of NON-MUTATED serum transthyretin in the cardiac ventricles of the elderly.
Usually asymptomatic (25% >80 years) but may result in:
- HF due to massive ventricular deposition
- Atrial fibrillation due to atrial deposition.
Transthyretin- 2nd most common protein in blood.
What is Familial Amyloid Cardiomyopathy?
Deposition of MUTATED serum transthyretin in the heart leading to restrictive cardiomyopathy.
5% of African Americans carry the mutated gene.
Autosomal dominant condition.
What is the association between Type II DM and localized amyloidosis?
AMYLIN (derived from excess insulin produced in type II DM to which tissues are resistant to) deposits in the ISLETS OF THE PANCREAS.
What is the association between Alzheimer’s disease and localized amyloidosis?
Deposition of A-BETA amyloid in the brain forming amyloid plaques.
A-BETA amyloid is derived from beta amyloid precursor protein.
Why are most people with Down syndrome prone to develop early onset Alzheimer’s? (40 years)
The gene for BETA-Amyloid precursor protein (BAPP) is found in chromosome 21.
A-Beta amyloid is derived from BAPP.
A-Beta amyloid deposits in the brain causing amyloid plaques
What is the association between dialysis and localized amyloidosis?
Chronic dialysis fails to filter off Beta-2 micro-globulin effectively—accumulation—deposition in JOINTS.
Beta-2 micro-globulin normally provides structural support for MHC-I on cells.
About 50% of dialysis related amyloidosis develop CARPAL TUNNEL SYNDROME due to a buildup of Beta-2 micro-globulin in the wrist
How is medullary carcinoma of the thyroid associated with localized amyloidosis?
Medullary carcinoma of thyroid (MCT) is derived from C cells
Tumor of C cells— overproduction of calcitonin
Overproduced calcitonin deposits within the tumor as amyloids
TUMOR CELLS IN AN AMYLOID BACKGROUND- MCT
How are amyloids characterized histologically?
Acellular eosinophilic deposits on traditional H&E staining
What is cerebral amyloid angiopathy?
Condition in which Beta-amyloid deposits in the walls of the CNS blood vessels—increased vascular fragility and hemorrhagic stroke
