Extracellular Accumulations

Overview

Amyloid

Proteinaceous extracellular accumulation with charact. 2° structure causing insolubility

Many disease processes are now known to involve the deposition of amyloid protens

15 distinct proteins are known to compose different amyloids

the specific molecular species undergoing transformation into amyloid is specific to each disease process where amyloid deposition is seen

Calcification

Precipitation of insoluble salts of divalent cations in extraskeletal tissues
Distinct foms associated with various disease processes and provide pathological clues
Often seen and diagnosed by X-ray

Amyloid

"starch-like"; generic term for a family of insoluble extracell. protein accumulations

gross morphology: when grossly evident, causes enlargement of organ due to pure mass effect

cellular pathology: may be toxic at microscopic level

microscopic morphology:

amorphous, eosinophilic appearance on H and E stain
congo red staining used for identification (fibrillar struct. orients bound congo red molec)

brick red staining with unpolarized light
apple green staining with polarized light

unbranching filaments 70 to 100 Å diameter by electron microscopy

molecular pathology: specific amyloid proteins are assoc. with distinct disease entities

structures of amyloid precursor proteins: contain variable amounts of b sheet 2° struct.

Predisposing factors: excessive production, impaired clearance, or abnormal precursor; extreme longevity; cooperative self-assembly; abnormal post-translational processing

Formation in prion diseases:

Prion proteins (PrPc) are abundant in neurons of the CNS
In prion diseases, protein is converted to an abnormal form (PrPsc) that is resistant to proteinase K, coincident with deposition of prion amyloid (AScr)
Presence of PrPsc facilitates coversion of PrPc to PrPsc, which then aggregates as AScr

Molecular Structure: b sheets arranged perpendicular to fiber axis

Associated Subst: amyloid P component (tightly bound, salt-extractable, rich in b sheet 2° structure; unknown function); apolipoprotein E (interest as marker for Alzheimer disease); glycosaminoglycans (confer starch reaction with iodine solution)

Summary:

Family of extracell accum caused by deposition of various insoluble proteins

Physical and staining properties are caused by highly ordered b pleated sheet 2° struct

Specific amyloid proteins are assoc with different disease entities, systemic or focal

Contributing factors to deposition of amyloid: excessive production of protein, abnormal protein, extreme longevity, cooperative self assembly, abnormal protein processing

Pathologic Calcification

radiology: can distinguish 5 levels of contrast (air, fat, water, bone, metal); radio-opague: metal-like (whiter) areas; radiolucent: air-like (blacker) areas

deposition of insoluble calcium salts in soft tissue sites where they are normally not found
often visible in radiographs as extraskeletal "bone-like density"

chemistry:

Ca salts (Ca phosphate, Ca carbonate, Ca soaps, Ca pyrophosphate, Ca oxalate)
Affecting factors: Ca conc, counterion conc, pH, nucleating and inhibiting factors

types:

dystrophic calcification: calcif that follows tissue necrosis (ie calcif heart valves) metastatic calcif: systemic calcif. that is assoc with imbalances in plasma Ca conc (ie renal calcif in hyperparathyroidism, soft tissue calcif in hypoparathyroidism)

saponification: caused by in-situ hydrolysis of triglyceride, indicates release of lipase from a diseased exocrine pancreas, and deposits are composed of insoluble Ca salts of released FAs (ie sapon in pancreas, sapon in skin)

pathologic ossification: Calcif of abnormal deposits of osteoid bone matrix, occurs in both malignant and benign conditions (ie osteosarcoma of humerus, malignant osteoblasts in calcifying bone matrix)

summary:

distinct forms of abnormal calcif in soft tissue are distinguished by pathogenetic mech

imbalances in plasma Ca and phos conc (metastatic calcif)
following necrosis of tissue (dystrophic calcif)
following release of lipase from a diseased pancreas (saponification)
following abnormal deposition of bone matrix in benign or malignant processes (pathologic ossification)

calcified lesions are often detected with radiographs