Amyloidosis

Learning objectives

Amyloidosis constitutes a group of diseases characterized by the extracellular deposition of insoluble protein aggregates
Precursor proteins, produced by various mechanisms, are deposited extracellularly as insoluble fibrils resulting in disruption of tissue architecture and organ dysfunction
The disease spectrum may be inherited or acquired and localized or systemic
May occur as its own entity or in association with dialysis-dependent renal failure, chronic infection, or inflammation
Diagnosed based on histological demonstration of amyloid deposits in affected tissues

Abbreviation	Protein type	Major Anaesthetic Considerations	Treatment
AL	Light chain (plasma cell-derived)	Airway difficulties, cardiomyopathy, arrhythmias, renal failure, hepatic failure, bleeding, autonomic/peripheral neuropathy, endocrine organ dysfunction, treatment-related complications	Symptomatic, chemotherapy, immunosuppression, endocrine supplementation, stem cell/organ transplantation
AA	Serum amyloid A (acute phase protein)	Features of underlying cause: Infection: TB, leprosy, Bronchiectasis Inflammation Autoimmune disease Malignancy: Hodgkin’s lymphoma Respiratory tract lesions Hepatic failure Renal failure Treatment-related complications	Treat underlying cause, surgical (localized disease)
Ab	b-Amyloid	Consent issues (Alzheimer’s dementia)	Supportive
Ab2M	b2-Microglobulin	Dialysis-dependent renal failure, difficult positioning (arthropathy)	Symptomatic, renal transplant
ATTR	Transthyretin Wild type (‘Senile’) Mutant type (Hereditary)	Heart failure (males, slow progressive) Autonomic/peripheral neuropathy, cardiomyopathy, gastrointestinal dysfunction	Symptomatic Symptomatic, liver transplant

	Associated complications
Airway and the respiratory system	Failed intubation Hemorrhage Obstruction Macroglossia predisposes to difficult intubation Laryngeal amyloid presents with hoarseness, dyspnea, cough, stridor, and odynophagia Tracheobronchial involvement is relatively uncommon Parenchymal amyloid may be unilateral or bilateral, diffuse or nodular
Cardiovascular system	Restrictive cardiomyopathy Diastolic heart failure Conduction disorders Ischaemic heart disease Arrhythmias Orthostatic hypotension Congestive heart failure
Hematological system	Microvascular fragility Platelet dysfunction Impaired fibrin formation Clotting factor deficiencies: factor X is most common, factors II, VI, VII, and IX also reported Impaired vasoconstriction Increased risk of hemorrhage
Neurological system	Autonomic and peripheral neuropathy
Other systems	Renal dysfunction: nephrotic syndrome & renal failure Visceral organomegalyy Early satiety Malabsorption Protein-losing enteropathy Ascites Dysmotility Gastrointestinal hemorrhage Deranged liver function Thyroid, adrenals, and testes infiltration

Class of drug	Caution
Anticholinergics	Blunted, or absent response
Anticoagulants	Use is contentious if bleeding risk evident
Benzylisoquinoliniums	Effect antagonized by anticholinesterase inhibitors
b-Blockers, Ca-channel blockers	Negative inotropic effects risk cardiac decompensation
Cardiac glycosides	Drug binding to protein fibrils risks toxicity at therapeutic levels
Depolarizing neuromuscular blocking agents	Potential for hyperkalaemic response in neurological dysfunction Prolonged action with anticholinesterase inhibitors
Halogenated volatile agents	Exposure increases in b-amyloid deposition in animal models
I.V. sedatives	Predictable haemodynamic depressant effects (except ketamine) Increased b-amyloid deposition not demonstrated with propofol, barbiturates and benzodiazepines