Familial ATTR amyloidosis pathophysiology

Familial ATTR amyloidosis Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Familial ATTR amyloidosis from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Diagnostic Study of Choice
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
X-ray
Echocardiography and Ultrasound
CT scan
MRI
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Interventions
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Familial ATTR amyloidosis pathophysiology On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Familial ATTR amyloidosis pathophysiology All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Familial ATTR amyloidosis pathophysiology
CDC on Familial ATTR amyloidosis pathophysiology
Familial ATTR amyloidosis pathophysiology in the news
Blogs on Familial ATTR amyloidosis pathophysiology
Directions to Hospitals Treating Psoriasis
Risk calculators and risk factors for Familial ATTR amyloidosis pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:

Overview

The exact pathogenesis of [disease name] is not fully understood.

OR

It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].

OR

[Pathogen name] is usually transmitted via the [transmission route] route to the human host.

OR

Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.

OR

[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].

OR

The progression to [disease name] usually involves the [molecular pathway].

OR

The pathophysiology of [disease/malignancy] depends on the histological subtype.

Pathophysiology

Pathogenesis

• It is understood that amyloidosis is the result of deposition of Amyloid.
• Amyloid is an abnormal insoluble extracellular protein which may cause organic dysfunction and a wide variety of clinical syndromes.
• These abnormal amyloids are derived from misfolding and aggregation of normally soluble proteins.
• Amyloid deposition can disrupt tissue structure of involved organ and consequently leads to organ failure.

Genetics

• Familial ATTR amyloidosis is transmitted in autosomal dominant pattern but it can have a heterogeneous nature of presentation.

• Genes involved in the pathogenesis of Familial ATTR amyloidosis include:
  • Transthyretin (TTR) (most common inherited mutation)
  • Fibrinogen
  • Apolipoprotein A1
  • Apolipoprotein A2
  • Lysozyme
  • Gelsolin genes

Associated Conditions

Conditions associated with amyloidosis include:

• MEN2A

Gross Pathology

On gross pathology, the organs affected by amyloidosis can be characterized by the following features:

• Porcelain like or waxy appearance
• Enlargement

Images

Nodular deposits of amyloid on the pleural surfaces.

Cut section of an inguinal lymph node showing firm and waxy consistency.

A slice of the affected node (left) has turned black after treatment with Lugol's solution. A piece of normal myometrium (right) treated similarly with no reaction is also shown.

Microscopic Pathology

On microscopic histopathological analysis, amyloidosis is characterized by:

• Green birefringence under polarized light after Congo red staining (appears red under normal light)
• Linear non-branching fibrils (indefinite length with an approximately same diameter)
• Distinct X-ray diffraction pattern consistent with Pauling's model of a cross-beta fibril

Images

Small bowel duodenum with amyloid deposition Congo red.

Amyloidosis (black arrows) in a lymph node after staining with Congo Red.

Green birefringence under polarized light.