histologically identifiable cytoplasmic or nuclear deposits caused by derangements of cellular function which may indicate either reversible or irreversible cell injury
normal intracellular constituent- but backs up and accumulates
product of deranged metabolism- normally absent
extracellular material taken up by the cell
infectious particles
General Mechanisms of Accumulation
disordered homeostasis:
Ý uptake from exogenous source, Ý endogenous synthesis, or ß breakdown or transport from cell
insolubility of accumulated material in water
Materials that Accumulate
(1) Protein
Russell bodies
: excess immunoglobulin production
Site
: reactive or malignant plasma cells
Mech
: synthesis of normal protein overwhelms export capacity
Mallory bodies
: alcoholic hepatitis (and other diseases)
Site
: hepatocytes
Mech
: abnormal aggregation of cytoskeletal proteins
a
1-antitrypsin deficiency
site
: hepatocytes
mech
: hepatocytes cannot efficiently export abnormal antitrypsin after synthesis
(2) Triglyceride
– Steatosis
sites
: liver, heart, kidney, skeletal muscle
mech
: often multiple
Ý
biosynthesis: excess substrates (obesity) or Ý demand (starvation)
ß
breakdown/export: ß production of proteins required for export (protein starvation) or impaired b -oxidation due to mitochondrial damage (toxins)
steatosis should NOT be confused with fatty infiltration (ingrowth of intact adipocytes within the stroma of a tissue)
(3) Cholesterol
site
: foamy macrophages (atherosclerotic vessels, gallbladder mucosa, other sites of necrosis)
mech
: uptake of oxidized LDL via the macrophage scavenger LDL receptor
cholesterol should NOT be confused with a # of other less common lipid accumulations (storage disease) caused by inherited defects in genes related to lipid metabolism or sites where oily foreign materials (mineral oil, silicone) are in contact with tissue
(4) Lipofuscin
– brown pigment derived from membrane lipids
Sites
: heart, liver
Mech
: Free radical-induced polymerization of polyunsaturated FAs
Despite its lipid origin, insoluble even in organic solvents, and presumably not metabolized further
Regarded as a "wear and tear" marker of aging
Often accompanied by atrophy ("brown atrophy"), lipofuscin does not itself appear to cause cellular dysfunction
: phagocytosis of particulate carbon by macrophages (carbon is biochemically inert)
carbon-laden macrophages are moved by lymphatic circulation, but last forever
anthracosis should NOT be confused with the uptake of other inert particulate pigments by macrophages, particularly in skin and mucosal locations, is called "tattooing"
(6) Hemosiderin
intracellular coalescence of the iron-containing protein ferritin in states of local or systemic overload
hemosiderosis and hemochromatosis: systemic iron overload leading to deposition of hemosiderin in tissues, and tissue damage (in hemochromatosis only)
: excess iron load (local hemorrhage, defective hematopoiesis, iron ingestion, multiple transfusions, Ý intestinal iron absorption), local or systemic ferritin excess, or aggregation of ferritin in molec
(7) Glycogen
pathologically significant glycogen deposits are related to inborn errors of metabolism of glycogen and sugars
site
: related to the site of the defect (liver, muscle, heart, brain)
numerous specific metabolic defects are known collectively as The Glycogenoses (blood, glucose, proteins, amino acids, liver cell, muscle cell, type V glycogenosis)
(8) Infectious Organisms
histologically identifiable intracellular inclusions sometimes prove to be infectious organisms from a wide range of taxa
both phagocytosis and intracell replication involoved (protozoa, fungi, bacteria, viruses)
can be thought of as "hijacked" cellular metabolism subverted for the reproduction of the pathogen
Summary
intracellular accumulations are often important clues to pathologic processes
accumulations result from derangements of cellular functions
increased uptake of exogenous material, decreased export of endogenous material, and synthesis of abnormal material can all contribute to the formation of intracellular accumulation
some intracellular accumulations can be specifically identified by special stains