MORPHOLOGICAL FEATURES OF AMYLOIDOSIS OF ORGANS

Ans. is ‘b’ i.e., Rheumatoid arthritis

AA amyloid is secondary amyloidosis (for causes see previous explanations)

o Amyloid in familial mediterranean fever is also AA type.

Ans. is None

o It is also the most serious form of organ involvement.

• The size of kidney is characteristically normal or increased.
• The earliest pathological change seen in renal amyloidosis is mesangial expansion by amorphous hyaline material and thickning of the glomerular basment membrane.

o Amyloid is primarily deposited in the glomeruli, but interstitial peritubular tissue, arteries and arterioles are also affected.

• With time there is capillary narrowing and distortion of glomerular tufts.

o Eventually the glomerulus obliterated completely.

Clinical manifestations

             Nephrotic range proteinuria (most common)                             o Fanconi syndrome

         Edema (due to albuminemia)                                               o Nephrogenic diabetes insipidus

         Azotemia (when there is tubular involvement)                        o Renal tubular acidosis

         Urine may show RBC cast.                                                     o  Hypertension (in 20-50%)

         Renal vein thrombosis

Ans. is ‘c’ i.e., Renal Amyloidosis commonly presents with Hypertension

Most common presentation is proteinuria.

o Hypertension may occur but it is not common, it occurs in 20-50% of the patients.

“Although earlier it was thought that hypertension was an infrequent complication, more recently up to 50% of patients have been detected hypertensives”.

Ans. is ‘a’ i.e., Sinusoids of red pulp

Organs involved in Amyloidosis

Kidney Has been explained

Spleen

o One of the two patterns of deposition is seen ‑

1. Sago spleen —> Amyloid deposition is largely limited to splenic follicles, it produces topioca like granules on gross inspection.
2. Lardoceous spleen —> Amyloid depositon spares the follicles and instead involves the walls of the splenic sinuses and connective tissue framework in red pulp.

Heart

o Cardiac symptoms are the second most common presentation (after kidney).

o More common in primary amyloid (AL).

• Though the second most commonly affected organ, it is the leading cause of mortality

o It is also the major organ involved in senile systemic amyloidosis.

o There is focal subendocardial deposition and intermyocardial deposition (between myocardial fibres).

• Subendocardial deposits can damage conduction system.

Liver

o Amyloid appears first in space of Disse and then progressively encroaches on adjucent hepatic parenchymal cells and sinusoids.

o Normal liver functions are preserved despite sometimes quite severe involvement of the liver. Adrenal

• Deposits begin adjacent to the basement membranes of cortical cells, usually first in the zona glomarulosa. Tongue

o Deposition in Tongue cause macroglossia –> tumor forming amyloid of tongue.

Peripheral and automatic nerves

• In familial amyoloidotic neuropathies.

Carpal – tunnel

o Most prominant in hemodialysis associated amyloidosis, and can cause carpal tunnel syndrome. In brain

• In senile plaques of Alzheimer disease.

Ans. is ‘a’ i.e., Multiple myeloma-light chain; ‘b’ i.e., Chronic inflammation – AA; ‘c’ i.e., Cardiac­ATTR

o Option a & b have been explained so many times.

About other options

o ATTR is found in senile systemic amyloidosis and heart is the major organ to be involved in senile systemic amyloidosis.

o A _$2 m ($₂ microglobulin) is seen in hemodialysis associated amyloidosis.

o Neural amyloid is ATTR that is seen in familial amyloidotic neuropathies.

Ans. is ‘c’ i.e., Mutant transthyretin

Transthyretin (ATTR) amyloid

• Transthyretin (TTR) is normal serum protein that binds and transport thyroxine and retinol.

o TTR can cause following types of amyloidosis : ‑

1.   Mutant TTR : – Mutation in TTR can cause syndrome of familial amyloidotic polyneuropathy or familial amylodotic cardiotnyopathy.

2.   Wild (non-mutant) TTR : – There is no mutation of TTR and wild type TTR forms fibrils which results in senile systemic amyloidosis (senile cardiac amyloidosis).

Ans. is `d’ i.e., Transthyretin

Senile systemic amyloidosis (SSA)

• SSA is characterized by deposition of wild – type transthyretin (TTR) – based amyloid in parenchymal organs in elderly individuals.
• SSA is common disease, affecting approximately 25% of the population greater than 80 years old.
• SSA is characterized by amyloidosis clinically limited to heart; therefore, initially it was referred to as senile cardiac amyloidosis.

o This form of cardiac amyloidosis tends to run a benign clinical course and is not associated with extracardiac manifestations. However, some elderly male patients may have extensive amyloid deposits in the atria, ventricles or heart valves, producing CHF and death.

Ans. is ‘a’ i.e., Transthyretin

Ans. is ‘d’ i.e., Heart

Most common                –> Kidney

o Second most common —> Heart

Ans. is ‘b’ i.e., Primary amyloidosis & ‘c’ i.e., Multiple myeloma

Ans. is ‘a’ i.e., Medullary carcinoma thyroid

Note – `E’ in AE means endocrine. Endocrine amyloid is seen in medullary thyroid Ca & Type II DM.

Ans. is ‘a’ i.e., Knee joint

Hemodialysis associated amyloid is deposited in synovium, Joints and tendon sheath.

Ans. A: Space of disse

Ans. is ‘d’ i.e., Medullary 

Ans. is ‘c’ i.e., Medullary 

• Medullary carcinoma of thyroid has deposition of A cal amyloid (derived from calcitonin).