Coupon Accepted Successfully!



  1. Pathologic proteinaceous substance, deposited between cells in various tissues and organs
  2. Amorphous, Eosinophilic, Hyaline, extracellular substance
  3. Progressive accumulation leads to pressure atrophy of adjacent cells
    1. Physical nature of Amyloid
      1. Non branching fibrils of indefinite length Q
      2. Diameter: 7.5 - 10 nm. Q
      3. X-ray crystallography and Infra red spectroscopy:
        1. Characteristic cross - pleated sheet confirmation Q.
        2. (Resp. for. Birefringence by polarizing microscope)
      4. Minor comp.:               
        1. Serum Amyloid P component    
        2. Proteoglycans     
        3. Glycosamine glycans
          a. 95% - fibril protein       
          b. 5% - P component and other glycoproteins
      5. 15 biochemically distinct forms 
    2. 3 more common.:
      1. AL (amyloid light chain) Q
        1. Derived from plasma cells (most AL-LAMBDA VI)       
        2. Contains Ig light chains
      2. AA (Amyloid associated): Q
        Non-immunoglobulin protein synthesized by liver
      3. Aβ amyloid: In cerebral lesion of Alzheimer disease

Clinicopathologic Category

Associated Diseases

Major Fibril Protein

Chemically Related Precursor Protein

Systemic (Generalized)

1. Amyloidosis




i. Immunocyte dyscrasias with amyloidosis (primary amyloidosis)

Multiple myeloma and other monoclonal B-cell proliferations


Immunoglobulin light chains, chiefly γtype

ii. Reactive systemic amyloidosis (secondary amyloidosis)

Chronic inflammatory conditions



iii. Hemodialysis-associated amyloidosis

Chronic renal failure


β2 microglobulin

2. Hereditary Amyloidosis




i. Familial Mediterranean fever




ii. Familial amyloidotic neuropathies (several types)




iii. Senile Amyloidosis




B. Localized Amyloidosis




i. Senile cerebral

Alzheimer disease


ii. Endocrine




iii. Medullary carcinoma of thyroid


A Cal


iv. Islets of Langerhans

Type 2 diabetes


Islet amyloid peptide

v. Isolated atrial amyloidosis



Atrial natriuretic factor

  1. Types ­
    1. Systemic         
    2. Localized
  1. Systemic
  1. Primary Amyloidosis/Immunocyte dyscrasias with:
    AL: Complete Ig light chain / - NH2 terminal fragment / both
  • Most common – are -
  • Lambda or kappa        
  • Associated with plasma cell dyscrasia
  • Systemic in nature
    5-15% of pts. With Multiple Myeloma develop AL Amyloidosis
  1. Reactive Systemic Amyloidosis (Secondary Amyloidosis:Q)
  • AA protein deposited   
  • Secondary to associated inflammations   
  • Systemic disorder


  1. Previously:
    TB, bronchiectasis, chronic osteomyelitis
  2. Now, Most common: are -
  • Rheumatoid Arthritis (13% of pts. dev, AA)
  • Ankylosing spondylitis   Heroine abuses   
  • Inflammatory bowel disease   RCC
  • Hodgkin's disease


Chronic inflammation → Macrophages Activation → IL-1, & IL-6

Liver cells → SAA protein Limited proteolysis → AA protein

  1. Hemodialysis associated amyloidosis:
  •  Deposition of β2 Microglobulin (component of MHC class I molecule)(Can't be filtered through cuprophane dialysis membranes)
  •  Deposits in Synovium, Joints & Tendon sheaths 
  1. Heredofamilial Amyloidosis
  • Familial Mediterranean fever: Fever with inflammation of serosal surface (pleura, peritoneum & synovial membrane) Q
  1. Deposits of AA proteins
  2. AR Gene product 'Pyrin':
  3. Exact function is not known – but known to Regulates acute inflammations 
  • Familial amyloidotic neuropathies (several types):
  1. Both peripheral & autonomic nerves- involved      
  2. AD
  3. Deposits of A TTR (Trans thyretin)  (Mutant form) 
  • Systemic senile Amyloidosis  
  1. Deposits of A TTR (structurally normal
  2. Deposits in heart of aged individuals (70-80 years) 
  1. Localized Amyloidosis:
    Nodular deposits most often in lung, larynx, skin, urinary bladder, tongue etc.   

i. Senile cerebral amyloidosis

  • Found in Alzheimer's disease
  • Deposits:β - amyloid protein (Aβ)Q
  • Precursor: Amyloid precursor protein

ii. Endocrine

  • Medullary carcinoma of thyroid, Deposits of A calQ , (Precursor: calcitonin)
  • Islet of Langerhans (in Type II DM)
  • Deposits: AIAPPQ , (Precursor: Islet Amyloid Peptide)
  • Isolated Atrial Amyloidosis: Deposits: AANF, (Precursor - Atrial Natriuretic factor) 


AA: M. severe systemic involvement

Kidneys, liver, Spleen, lymph nodes, Adrenals, Thyroid

AL: Heart, Kidney, GIT, Peripheral nerves, Skin, Tongue


Gross: Organ -+ enlarged, firm, waxy

Cut surface -

  1. Paint with H2SO4 ---
  2. Yellow color is obtained and then apply
  3. Iodine, Blue /  violet colour is produced. 

iii. Staining:

  • PAS +Q (:. of P component → glucoproteins)
  • Congo redQ on light Microscopy it appears light pink
    Polarized Light Green Birefringence
    After t/t with KMnO4----------------- AA protein losses its affinity
  • Crystal violet methyl violet Q
  • THIO flavin ‘T & ‘S'Q
  • Immunohistochemical staining Q
  • Electron Microscopy 
  1. Organs Affected
    1. Kidney:
      1. Most common and most serious form of organ involvement
      2. In interstitial, peritubular tissue, arteries & arterioles
    2. Spleen:
      1. Sago spleen: In splenic follicles
      2. On gross: tapioca like granules
      3. Lardaceous spleen: In walls of splenic sinuses & in red pulp
      4. On gross : large, map like areas 
    3. Liver:
      1. First in space of Disse and then leads to -
      2. => pressure atrophy
      3. Also vascular involvement & Kupffer cell deposition
    4. Heart:
      1. Focal subendocardial accumulation and between the muscle fibres.
      2. (May damage conduction
      3. Leads to ECG abnormalities)
      4. May present as CHF, arrhythmias
    5. Adrenals:
      1. Initially in zona glomerulosa 
    6. GIT:
      1. ​​Any level: Gingiva to anus
    7. Tongue:
      => macroglossia Q
      Tumor forming amyloid of the tongue
      (Clinically Asymptomatic difficulty in swallowing, malabsorption, etc.) 
    8. In long-term hemodialysis patients:
      1. Deposits in carpal ligament -+ carpal tunnel syndrome Prognosis:
      2. Poor for Generalized Amyloidosis 
      3. AL (not including MM) 
      4. Median ----------------- 2years Survival rate.
        In MM Worse Prognosis
        AA → Control the cause → Better Prognosis

Test Your Skills Now!
Take a Quiz now
Reviewer Name