What is an intracellular accumulation?
an accumulation of abnormal amounts of various substances
- manifestation of derangement in cells
what are the 3 categories of intracellular accumulations?
- normal cellular constituent in excess
- abnormal substance
- a pigment
what substances make up normal cellular intracellular accumulations?
too much water, lipid, protein, or carbohydrates
how are substances in intracellular accumulations produced?
may be produced by the cells or may be storing products of pathologic processes
What are the 3 events that most accumulations are attributable to?
- a normal endogenous substance is produced at a normal or increased rate, but metabolism rate is inadequate to remove it
- a normal or abnormal endogenous substance accumulates bc of genetic or acquired defects in the metabolism, packaging, transport, or secretion of these substances
- an abnormal exogenous substance is deposited and accumulates bc the cell has neither enzyme to degrade it nor the ability to transport it to other sites.
what is are some examples of a normal endogenous substance that is produce at a normal or increased rate, but metabolism rate is inadequate to remove it?
- fatty change in liver bc of intracellular accumulations of triglycerides
- reabsorption protein droplets in the epithelial cells of renal proximal tubules bc of increased leakage of protein from the glomerulus
What are some examples of accumulations of abnormal or normal substances bc of genetic or aquired defects in metabolism, packaging, transport, or secretion of these substances?
- storage disease: A-GM1 gangliosidosis.
- Defient enzyme B-galactosidase in
holsteins, beagles, english springer
spaniels, siamese cats
- storage disease: b-GM2 gangliosidosis
- deficient enzyme hexosaminidase in
german shorthair pointer and
- c-Globoid cell leukodystrophy
- defient enzyme galactosylceramidase
in cairn terrier, min poo, blue tick
hound, beagle, pomeranian, polled
- B-a-1 antitrypsin deficiency
What is B-a-1 antitrypsin deficiency?
single amino acid substitutuion in the enzyme results in defects in protein folding and accumulation of the enzyme in the ER of the liver seen as globular eosinophilic inclusion bodies
What are some examples of an accumulation of an abnormal exogenous substance?
carbon particles and non metabolizable chemical like silica
How do you differentiate between hemorrhage or melanoma?
check on white paper, hemorrhage will be red
In what types of cells are lipid accumulations most commonly observed?
hepatocytes and caradiomyocytes
- can also occur in skeletal muscle and kidney
What is lipidosis?
the accumulation of triglycerides and other lipid metabolites within the cytosol of the parenchymal cells
What does fat atrophy look like?
serous, gel-like substance in place of where fat was
- pale eosinophilic material histoloically
How does mitochondria injury affect fat metabolism?
decreases b-oxidation of fatty acids to ketones and other substances
What are some things that cause deceased apolipoprotein synthesis?
protein malnutrition, CCl4, aflatoxicosis
In ruminants, when is hepatic lipodosis a physiological process?
in late pregnancy (pregnancy toxemia) and heavy early lactosis (ketosis)
How are ketone bodies produced?
- produced in the liver by mitochondria
- conertin of acetyl CoA from fatty acids
In what nutritional disorders can hepatic lipidosis be seen?
obesity, imparied apolipoprotein synthesis (protein malnutrition), starvation
What is Niemann Pick disease?
- causes hepatic lipidosis
- caused by lacking enzyme that breaks down sphyngomyelin (fatty substance)
- sphyngomyelin then accumulates in cells
In what types of animals is glycogen found and stored in excessive amounts?
animals with abnormal glucose or glycogen metabolism:
- animals on corticosteroids
- animals with diabetes mellitus
In what cells is glycogen stored in animals with diabetes mellitus?
- hepatocytes, epithelial cell of renal proximal tubules, and B-cells of Islets of Langerhans
What are glycogenoses?
genetic disorder with enzymatic defects in the synthesis or breakdown of glycogen
What is type II?
- lysosomal metabolism defect
- deficient in the enzyme acid maltase
- seen in shorthorn and brahman beef cattle
- Laphund dog (pompe disease)
What is equine polysaccharide storage myopathy?
- excessive glycogen storage in skeletal muscle
- occurs in draft, warm blood, or quarter horses
What are the main muscles in which equine polysaccharide storage myopathy occurs?
Type II muscle fibers
-semimembranosus and semitendinosus
In equine polysaccharide storage myopathy, why does glycogen accumulate in type II muscle fibers?
- have high glycolytic capacity
- moderately fast contraction time and long term anaerobic activity
How do intracellular accumulations of proteins present?
- rounded eosinophilic droplets, vacuoles, and aggregates in cells
what are the 2 causes for protein accumulations in cells?
- excesses are presented to the cells
- cells synthesize excessive amounts
How do protein reabsorption droplets in renal proximal tubule cells present?
- hyaline, pink/ eosinophilic cytoplasmic droplets
- they have a granular appearance
When do reabsorption droplets in the proximal tubule cells of the kidney occur?
occurs during heavy protein leakage across the glomerular filter
normally, what happens if there is a defect in protein folding?
the protein is eliminated by the proteasome complex
What are lead inclusion bodies?
- lead and protein
- present in renal tubular epithelial cells
What are some hyaline substances?
- renal tubules in proteinuria
- serum or plasma
- plasma proteins in vessel walls
- scars/ collagen fibers
- thickened basement membranes
- membrane of alveolar walls
- microthrombi in DIC
What is amyloidosis?
condition associated with a number of inherited and inflammatory disorders in which extracellular deposits of fibrillar proteins are responsible for tissue damage and functional compromise
What are abnormal fibrils?
produced by aggregation of misfolded proteins and have beta-pleated sheet conformation
What is systemic amyloidosis?
involves components of the immune system
- probably related to abnormal protein folding and immunological abnormalities
How is amyloidosis caused by normal proteins?
they are normal proteins that have an inherent tendency to fold improperly, associate and for fibrils, and do so when they are produced in increased amounts
What is primary amyloidosis?
- Ig-light chain
- plasma cell proliferation
- uncommon in animals, common in humans
what is secondary amyloidosis?
- AA amyloid
- occurs in chronic inflammatory responses, presistant infections, or neoplastic conditions
- most common in animals
In what animals is amyloidosis most common?
- black-footed cat and cheetahs
- older dogs (idiopathic)
In old dogs, where does amyloidosis predominantly occur?
around the blood vessels in the heart and the brain
- no clinical signs
what is special when staining amyloid with congo red?
must use polarized light to prove it is amyloid
How does amyloid appear grossly when it is stained with Lugol's iodine and enhanced with dilute sulfuric acid?