Cellular Accumulations Flashcards
two types of cellular accumulations
endogenous and exogenous
3 categories of cell accumulations
- normal cell constituent in excess (fats, carbs, protein)
- normal/abnormal substance due to genetic or acquired defects in cell processes
- a pigment
how does a normal cell constituent accumulate in excess?
endogenous substance produced at normal or increased rate and rate of metabolism is unable to remove it
3 common intracellular accumulations
- hepatic lipidosis
- glycogen in hepatocytes or muscles
- viral inclusions (aka viral proteins)
what is hepatic lipidosis and what is its pathogenesis?
= accumulations of triglycerides or other lipid metabolites (like neutral fats or cholesterol) in hepatocytes
pathogenesis: fat metabolism is impaired
why does lipidosis commonly manifest in the liver?
liver is most central organ in lipid metabolism and the clinical manifestation of cellular lipid accumulation is usually related to lipid function
where do we commonly see hepatic lipidosis in animals?
in animals where there is an increased demand for energy
found in obesity, starvation, diabetes mellitus, idiopathic in cats and cattle
gross changes associated with hepatic lipidosis
- enlarged
- yellow, soft, friable
- greasy texture
- broad, rounded edges
- floats in formalin
microscopic changes associated with hepatic lipidosis
highly vacuolated cytoplasm, can have sharply delineated borders
what is glycogen accumulation and what is its pathogenesis?
excessive amounts of glycogen, caused by an abnormal glucose or glycogen metabolism
can be a side effect of diabetes mellitus, Cushing’s disease, hyperglycemia, and can result from an animal being given too much steroids
give an example of a steroid-induced glycogen accumulation.
steroid-induced hepatopathy
- hepatocytes are highly permeable to glucose
- in steroid-induced hepatopathy we have a massive storage of glycogen
ways to distinguish hepatic lipidosis from steroid-induced hepatopathy
steroid-induced hepatopathy yields a swollen and pale liver, which is waxy as opposed to greasy, does not appear yellow like in hepatic lipidosis
microscopic changes associated with glycogen accumulation
- swelling and vacuolation of hepatocytes
- vacuoles are clear (like intracellular fat)
- vacuoles are more irregular with less distinct outlines (rarefaction)
what are viral inclusions?
these are accumulations of viral proteins; found in the nucleus, cytoplasm, or both
how do we use the presence of viral inclusions?
diagnostically these can confirm specific viral diseases
ex. herpesvirus, adenovirus, parvoviruses = intranuclear inclusions
ex. rabies = Negri bodies (in the cytoplasm of neurons)
ex. canine distemper = both cytoplasmic and intranuclear inclusions
what is ab/normal substance from genetic/acquired defects that we see? include pathogenesis.
diseases that occur when a certain enzyme is deficient. this missing enzyme usually breaks down certain products so there is a resulting accumulation of complex substrates
the buildup of these complex substrates cannot be exported or broken down further
mucopolysaccharidosis (MPS), what is it and what does it cause?
inherited metabolic disorders that result from a deficiency of lysosomal enzymes needed for catabolism of glycosaminoglycans (GAGs)
the buildup of GAGs causes progressive/irreversible cell damage affecting growth, morphology, mobility, organ function, neurodevelopment
MPS type 6 - accumulations in the joints which impair movement
MPS - histo characteristics
neutrophils have pink granules accumulating (which are GAGs)
muscle cells contain abundant cytoplasmic vacuoles
two examples of extracellular accumulations
amyloid
gout
what is amyloid and how is it formed?
amyloid is a pathologic proteinaceous substance deposited in extracellular space of various tissues
it is formed by the misfolding of soluble and functional peptides/proteins, which converts them into insoluble, rigid and non-functional aggregates
when misfolded, function is lost and the tissue containing this deposit is damaged (causes compression atrophy in adjacent/parenchymal cells)
there are two types of amyloidosis, localized and systemic. what are three examples of systemic (multi-organ) amyloidosis?
- primary amyloidosis (AL amyloid light chains)
- secondary amyloidosis (AA)
- hereditary/Familiar (AA) amyloidosis
what is primary / AL amyloidosis? where can it show up?
these affect the light chains of immunoglobulin molecules, which are produced in excess in neoplastic plasma cells (in B cell lymphoproliferative disorders), misfold and become AL proteins which build up in tissues like urine or serum
key distinction here is that it can show up inside and outside cells
what is secondary amyloidosis (AA)? what organs does it involve?
reactive form of systemic amyloidosis; caused by the abundance and buildup of serum amyloid A (“SAA” an acute-phase protein) from chronic inflammation
continual increase in SAA, and a small proportion will spontaneously misfold and accumulate in tissues
can involve kidneys, liver, spleen, lymph nodes
- most common in domestic animals *
what is the key distinguishing feature when observing AA amyloidosis? Gross/micro
Grossly: pale, beige, firm, waxy and UNIFORMLY DISTENDED
Microscopically: can see buildup of eosinophilic, hyaline material (aka amyloid)
