Amyloidosis

Ninja Nerds!

In this lecture, Professor Zach Murphy delivers a comprehensive and high-yield breakdown of Amyloidosis, focusing on the pathophysiology, clinical manifestations, and diagnostic approach to this complex and multisystem protein deposition disorder.

We begin by explaining the biochemical basis of amyloid, including the misfolding of precursor proteins into beta-pleated sheet configurations that resist degradation and deposit extracellularly in various tissues. We then cover the major types of systemic amyloidosis, including AL (light chain) amyloidosis, AA (secondary) amyloidosis, and hereditary forms, such as those involving transthyretin (ATTR), with emphasis on their pathogenesis and associated conditions.

This lecture walks through the clinical presentations of amyloidosis based on organ involvement, including restrictive cardiomyopathy, nephrotic syndrome, hepatomegaly, peripheral neuropathy, macroglossia, and periorbital purpura—hallmark features that are often tested on board exams.

We provide an in-depth overview of the diagnostic workup, including serum and urine protein electrophoresis with immunofixation (SPEP/UPEP + IFE), fat pad biopsy with Congo red staining, and echocardiographic findings such as speckled myocardium. You’ll also learn to distinguish between the different types of amyloidosis using clinical clues, imaging findings, and lab data.

We conclude with a high-yield review of treatment strategies, from chemotherapy and stem cell transplantation in AL amyloidosis to targeted therapies like tafamidis in ATTR amyloidosis. Key differences between forms of amyloidosis are reinforced through tables, mnemonics, and clinical pearls tailored for the USMLE, COMLEX, and PANCE.

Table of Contents:
0:00 Lab
0:42 Pathophysiology of Amyloidosis
21:01 Complications of Amyloidosis
46:53 Diagnostic Approach to Amyloidosis
56:16 Treatment of Amyloidosis
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