Accumulations & Deposits

Types of intracellular accumulations

• normal cellular component accumulated in excess

• abnormal substances (exogenous or endogenous)

• pigments

• may occur in cytoplasm or nucleus

Mechanisms of intracellular accumulation

• abnormal metabolism of a normal cellular substance

• abnormal endogenous substance due to defect in protein folding/transport

• lack of enzyme that metabolizes normal endogenous substances

• abnormal exogenous substance due to ingestion of indigestible material

Hyaline accumulations

• deposited homogenous eosinophilic (pink) protein

• nonspecific for changes, may be intra- or extracellular

• highlighted by PAS stain

Russell bodies

• hyaline bodies in cytoplasm of some plasma cells (Mott cells)

• made of accumulated immunoglobulin

Inclusion body types

• nuclear or cytoplasmic aggregates

• crystalline protein: occur in normal hepatocytes + renal tubular epithelium, large eosinophilic rhomboids

• viral: accumulations of viral proteins, incomplete or complete virions

Amyloid accumulation

• pathologic extracellular, insoluble, proteinaceous substance resistant to proteolysis, deposited between cells

• mechanically interfere with cell & organ function

Common sites of amyloid deposition

• always extracellular, often near vascular beds

  • kidney (glomeruli)

  • liver (space of Disse)

    • spleen

  • lymph nodes

  • adrenal cortex

Amyloid pathogenesis

• circulating precursor proteins are partially degraded, leading to misfolding

• misfolded proteins deposited in tissue & aggregate to form amyloid fibrils that displace + compress cells

Pathogenesis of reactive/secondary amyloidosis (AA)

• secondary to chronic antigen stimulation or may be genetic

• chronic inflammation increases acute phase proteins → increase of SAA (amyloid precursor) from liver → SAA proteins misfold into AA → amyloid deposition

• majority of amyloidosis cases

Islet amyloidosis

• co-secretion of insulin and amyloid precursor protein

• clinical significance unclear, tied to diabetes in humans

Gross features of amyloidosis

• organs appear firm, pale, waxy colored, & swollen/enlarged

• stain black wth Lugol’s iodine

Histologic features of amyloid

• eosinophilic (pink) amorphous “cotton candy-like” substance accumulating in extracellular spaces

• stains orange-red with Congo red

Gout

• deposition of sodium urate crystals in tissues (viscera + joints) due to lack of uricase enzyme

• seen in birds, reptiles, & humans

  • normally eliminate uric acid via kidneys

• caused by dehydration, high-protein diets, & kidney failure

Pathogenesis of gout

• occurs due to impaired excretion via kidney or overproduction via excess dietary protein & Ca2+

• high plasmic uric acid concentration → monosodium urate crystals on visceral + articular surface → chronic inflammation

Types of gout

• visceral: most common in birds + reptiles, affects visceral serosa of kidneys & pericardium

• articular: most common in humans, inflammatory reaction

Appearance of gout

• tophi - chalky white deposits on visceral or articular surfaces

• crystals seen as acicular clefts + birefringent crystals surrounded by inflammatory response

Calcium deposits

• abnormal deposition of calcium salts in soft tissues, usually with phosphate or carbonate

Metastatic calcification

• occurs in normal soft tissue due to hypercalcemia

• may be caused by excess PTH/PTH related protein secreting tumors (lymphoma, anal gland adenocarcinoma), bone destruction, vitamin D toxicosis, or renal diseases

• commonly found in small vessel walls/basement membranes of kidney, stomach, lung, vessel walls, intestinal mucosa

Dystrophic calcification

• affects visibly diseased/necrotic tissue

• caused by persistent irritants, serum calcium normal

• dead/dying cells release phosphates, can’t regulate calcium

• phosphate + calcium form “soap” deposits around central nidus of necrosis

Appearance of calcium deposits

• grossly gritty, hard, and white

• microscopically basophilic (purple/blue), black with von Kossa stain

  • dystrophic also appears with areas of necrosis

Cyanosis

• unoxygenated hemoglobin leads to blue color

Hemosiderin

• iron storage pigment mostly stored in spleen, golden-brown

• breakdown of erythrocytes (hemoglobin) at end of cell life

• “cleaned up” by macrophages