8.3.07 Amyloidosis Morrison

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AmyloidosisJenny Morrison

Morning Report8/3/2007


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Amyloidosis

Infiltration of organs with the deposit of extracellularinsoluble fibrillar protein.

Antiparallel beta-pleated sheet configuration on x-raydiffraction.

Straight and unbranching fibrils 8-10 nm in width on EM.

Binds Congo red leads to green birefringence under

polarized light.Binds thioflavine T yellow-green fluorescence.


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www.pathguy.com

Congo Red Stains of Heart

Infiltrated with Amyloid


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Amyloidosis- Subtypes

AL primary, Ig light chain deposits AA secondary, serum amyloid A deposits in

chronic diseases with inflammationDialysis beta-2 microglobulinHeritable multiple different mutations, ex. inTTRSenile Systemic Amyloidosis wt TTROrgan specific ex. Alzheimers disease


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Clinical Manifestations of Amyloidosis

Renal proteinuria, nephrotic syndrome, renal failure

GI hepatomegaly +/- splenomegaly, bleeding,gastroparesis, constipation, malabsorption

Neuro mixed sensory and motor peripheral

neuropathy, autonomic neuropathy, bowel/bladderdysfunction, orthostatic hypotension, dementia


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Clinical Manifestations of Amyloidosis

MSK pseudohypertrophy of muscles, macroglossia,arthropathy

Heme bleeding diathesis

Pulm pleural effusions, parenchymal nodules,tracheobronchial infiltration (hoarseness, stridor, airwayobstruction, dysphagia), rarely pulmonary HTN

Skin waxy thickening, nodules/plaques, easy bruising,purpura


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www.chemo.net

Amyloid Deposits in the Liver


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Cardiac Amyloidosis

Restrictive cardiomyopathyRight sided heart failure (both right and left sidedpressures are elevated)AnginaSyncope or pre-syncopeConduction diseaseRarely, cardiac tamponadeHypotensionSudden death


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K. B. Shah, et al . Archives of Internal Medicine. 2006.

Amyloid Deposits in the Heart


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K. B. Shah, et al . Archives of Internal Medicine. 2006.

Amyloid Deposits in the Heart


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www.chemo.net


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Diagnosis

Suspicion: unexplained heart failure, clinicalpicture (ex. proteinuria, hepatic dysfunction)TTE, EKGTissue biopsy (abd fat pad, rectal, salivary gland,endomyocardium)Check pro-BNP, CE, SPEP, UPEP

Consider bone marrow biopsyEvaluate for proteinuria, coagulopathy


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Cardiac Amyloidosis-Physical Exam

Elevated JVPHepatomegalyEdemaAbnormal heart sounds, murmurHypotensionSigns of other organ involvement


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Cardiac Amyloidosis-EKG Findings

Low voltage - especially in contrast todegree of hypertrophy

Conduction abnormalities (heart block)

Atrial fibrillation

Pseudoinfarct patterns


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Pseudoinfarct EKG Pattern

D. R. Booth, et al. Circulation. 1995.


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Amyloidosis-Echocardiographic Findings

LV and RV wall thickeningLV (and RV) diastolic dysfunction

Nondilated or small LV cavityBiatrial enlargementRV dilationThickened aortic and mitral valvesIncreased echogenicity granular, sparklingappearance of the myocardium


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Treatment

Treat underlying plasma cell disorder in AL orunderlying infectious or inflammatory disorder in

AA.Renal transplant or change dialysis mode fordialysis-related amyloidosis.

Hereditary liver transplantation +/-concomitant heart and renal transplant


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Amyloidosis:Take Home Points

Any organ system can be involved.Several different subtypes- look same under

microscope but behave differently and aretreated differently.Congo red stain apple-green birefring.Low voltage EKG but hypertrophy noted onTTE, restrictive pattern CM. think of cardiacamyloidosis.


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References

Booth, D. R., et al. A Novel Variant of Transthyretin Associated with Autosomal Dominant Cardiac Amyloidosis in an Italian Family.Circulation. 1995. 91: 962-967.

Gorevic, P. D. An overview of amyloidosis. UpToDate.com.

Rajkumar, S. V. and M. A. Gertz. Advances in the Treatment of Amyloidosis. NEJM. 2007. 356: 2413-2415.

Shah, K. B., et al. Amyloidosis and the Heart. Archives of Internal Medicine . 2006. 166: 1805-1813.

Simons, M., et al. Amyloid cardiomyopathy. UpToDate.com.Some pictures obtained from www.pathguy.com and www.chemo.net .
http://www.pathguy.com/http://www.chemo.net/http://www.chemo.net/http://www.pathguy.com/


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8.3.07 Amyloidosis Morrison

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