Fundamentals of Pathology Amyloidosis PDF

Www.Medicalstudyzone.com IK * * 8 FUNDAMENTALS OF PATHOLOGY...

Www.Medicalstudyzone.com IK * * 8 FUNDAMENTALS OF PATHOLOGY AMYLOIDOSIS I. BASIC PRINCIPLES A. Amyloid is a misfolded protein that deposits in the extracellular space, thereby damaging tissues. B. Multiple proteins can deposit as amyloid. Shared features include 1. β- pleated sheet configuration 2. Congo red staining and apple-green birefringence when viewed microscopically under polarized light (Fig. 1.13) C. Deposition can be systemic or localized. II. SYSTEMIC AMYLOIDOSIS A. Amyloid deposition in multiple organs; divided into primary and secondary amyloidosis B. Primary amyloidosis is systemic deposition of AL amyloid, which is derived from immunoglobulin light chain. 1. Associated with plasma cell dyscrasias (e.g., multiple myeloma) C. Secondary amyloidosis is systemic deposition of AA amyloid, which is derived from serum amyloid-associated protein (SAA). 1. SAA is an acute phase reactant that is increased in chronic inflammatory states, malignancy, and Familial Mediterranean fever (FMF). 2. FMF is due to a dysfunction of neutrophils (autosomal recessive) and occurs in persons of Mediterranean origin. i. Presents with episodes of fever and acute serosal inflammation (can mimic appendicitis, arthritis, or myocardial infarction) ii. High SAA during attacks deposits as AA amyloid in tissues. D. Clinical findings of systemic amyloidosis are diverse since almost any tissue can be involved. Classic findings include 1. Nephrotic syndrome; kidney is the most common organ involved. 2. Restrictive cardiomyopathy or arrhythmia 3. Tongue enlargement, malabsorption, and hepatosplenomegaly E. Diagnosis requires tissue biopsy. Abdominal fat pad and rectum are easily accessible biopsy targets. F. Damaged organs must be transplanted. Amyloid cannot be removed. III. LOCALIZED AMYLOIDOSIS A. Amyloid deposition usually localized to a single organ. B. Senile cardiac amyloidosis 1. Non-mutated serum transthyretin deposits in the heart. 2. Usually asymptomatic; present in 25% of individuals > 80 years of age C. Familial amyloid cardiomyopathy I 'V % I.- r Pi * r 4 »' *r&i* r> » * ' -3ft ; te?. w wk:< £. i. - * V \ VN * * H. w > II B 1 \ At? *i i Fig.1.12 Fatty change of liver. Fig. 1.13 Amyloid. A, Congo red. B, Apple-green birefringence. (Courtesy of Ed Uthman, MD)  Www.Medicalstudyzone.com Growth Adaptations, Cellular Injury, and Cell Death 9 1. Mutated serum transthyretin deposits in the heart leading to restrictive cardiomyopathy. 2. 5% of African Americans carry the mutated gene. D. Non-insulin-dependent diabetes mellitus (type II) 1. Amylin (derived from insulin) deposits in the islets of the pancreas. E. Alzheimer disease 1. Aβ amyloid (derived from β-amyloid precursor protein) deposits in the brain forming amyloid plaques. 2. Gene for β-APP is present on chromosome 21. Most individuals with Down syndrome (trisomy 21) develop Alzheimer disease by the age of 40 (early-onset). F. Dialysis-associated amyloidosis 1. β2-microglobulin deposits in joints. G. Medullary carcinoma of the thyroid 1. Calcitonin (produced by tumor cells) deposits within the tumor ('tumor cells in an amyloid background'). I REMINDER Thank you for choosing Pathoma for your studies. We strive to provide the highest quality educational materials while keeping affordability in mind. A tremendous amount of time and effort has gone into developing these materials, so we appreciate your legitimate use of this program. It speaks to your integrity as a future physician and the high ethical standards that we all set forth for ourselves when taking the Hippocratic oath. Unauthorized use of Patho ma materials is contrary to the ethical standards of a training physician and is a violation of copyright. Pathoma videos are updated on a regular basis and the most current version, as well as a complete list of errata, can be accessed through your account at Pathoma.com. Sincerely, Dr. Sattar, MD