Intracellular Accumulation

Intracellular, extracellular, pigmentation

What are the three general categories of cellular accumulations

true

True/false: cellular accumulations can be relatively harmless or promote cell degeneration and death.

lipidosis

__________ Accumulation of lipids within parenchyma cells

liver and kidney

lipidosis can occur in many organs and tissue but which two are 'classic'.

steatosis, fatty change

what are two other names for lipidosis

its role in lipid metabolism

why does lipidosis commonly occur in the liver?

liver,

adipose tissue or GI

lipids are transported to the ______ from ______ or _______

esterified to triglycerides, converted to cholesterol or phospholipids, oxidized to ketone bodies

within hepatocytes, free fatty acids can be __________ , ______________, or _______________

apoproteins,

lipoproteins,

an energy source

Triglycerides can be complexed with _______ to form low-density ________ for release into the plasma as _______ for tissue

increased mobilization of free fatty acids, abnormal hepatocellular metabolism, impaired release of lipoproteins

what are three causes of lipidosis?

high dietary fat, increased fat mobilization (starvation cat, diabetes, lactation)

what two main things can cause increased mobilization of free fatty acids?

free fatty acids, triglycerides, apoproteins

if there is abnormal hepatocellular metabolism, what do you expect to see>

hypoxia, cellular injury

what two things may cause abnormal hepatocellular metabolism

possible mechanisms that lead to lipid accumulation

What do these things all potentially have in common?

1.Excessive delivery of free fatty acids (FFAs) from fat stores or diet

2. Decreased oxidation or use of FFAs

3. Impaired synthesis of apoprotein

4. Impaired combination of protein and triglycerides to form lipoproteins

5. Impaired release of lipoproteins

from hepatocytes

macrovesicular (most common) , microvesicular

what are the two classifications of microscopic lipidosis? And which is more common?

macrovesicular lipidosis

Which type of lipidosis is this describing?

Large, clear, sharply defined vacuoles that are larger than the nucleus, distend the

cytoplasm, and displace the nucleus to the periphery of the cell

macrovesicular hepatic lipidosis

yellow arrow?

microvesicular hepatic lipidosis

blue arrow?

displaced nucleus

blue arrow

macrocytic lipidosis - large cytoplasmic vacuole

yellow circle?

oil red O stain (or Sudan Black B)

What stain is used to prove that an intracellular accumulation is lipid?

no! must use frozen samples

Can you do oil red O staining on tissue processed for the regular paraffin embedding?

oil red O stain, staining lipid inclusions

What the hell is happening to these cells???

swollen, yellow, greasy texture, maybe friable and floats in formalin, rounded margins

What are the characteristics grossly of an organ with lipidosis?

true

true/false: lipidosis can be physiologic and normal (its just like that sometimes)

late pregnancy, heavy lactation in ruminants, equine hyperlipidemia, feline hepatic lipidosis

what are some classic examples of hepatic lipidosis?

serum triglycerides

In equine hyperlipidemia, the negative energy balance leads to marked elevation of _________

feline fatty liver syndrome

what is the common term for feline hepratic lipidosis in an obese nutritionally stressed cat?

hepatic lipidosis

grossly.. what is this

hepatocytes , skeletal muscle

Glycogen is normally stored in _____ and __________

starvation or illness;

metabolic abnormalities, storage diseases, endocrine disorders

glycogen can be depleted in: _________ or ________

Excessive glycogen accumulation can occur with: __________-, _______ or _______

clear granules/vacuoles, "feathered cytoplasm", not displaced nuclei

what are the microscopic features of glycogen in the cytoplasm?

hepatocellular vacuolar change - glycogen type (glycogen in cytoplasm)

Both of these images are showing what?

amount of glycogen observed microscopically

What do all three of these things affects?:

Glycogen concentration, delay between death and fixation, type of fixation

periodic acid-Schiff (PAS)

which histochemical stain is sued to detect lgycogen?

false; its not

True/false: the PAS stain is specific to glycogen

diastase

what is PAS stain used in conjunction with in order to visualize glycogen?

right side sample has been treated with diastase

Both of these images are PAS stains to see glycogen... what's different about them?

swollen, pale brown, mottled

What are some gross characteristics of an organ (liver) with glycogen inclusions?

glycogen

glycogen or lipid inclusions?

lipid

glycogen or lipid inclusions?

glycogen

gycogen or lipid inclusions?

eosinophilic (pink/orange/red)

proteins are what color?

hyaline

What is the term for a proteinatious cellular inclusion? Often homogenous/eosinophilic/translucent substance that is internal or external to the cell.

Yes! Russel bodies are normal in plasma cells

can Hyaline inclusions be normal in any cells?

well, protein accumulation in proximal renal tubular epithelial cells is abnormal... so duh.

Oh, so russel bodies are normal protein accumulation in plasma cells... is hyaline inclusions ever abnormal?

Russel bodies in Mott cells

These are plasma cells. what is circled?

hyaline droplet

these are renal tubular epithelial cells... what is circled?

hyaline droplet

what are these bright esosinophilic 'dip dops'

can be extruded or remain as lipofuscin pigment

what is an important to know about autophagic vacuoles?

increase with age, common in hepatocytes/renal tubular epithelial cells

what are important to know about crystalline protein inclusions? (2)

intranuclear

Where are lead inclusions found in a renal tubular epithelial cell?

lead and protein mixture, acid-fast stains

What are lead inclusions made of? how best are they seen?

crystalline protein inclusions

What is the inclusion?

lead inclusions

what is the inclusion?

intracytoplasmic, intranuclear

what are the two types of viral inclusion bodies?

(location, not specific virus)

eosinophilic, basophilic, amphophilic, round to oval

the intranuclear DNA virus inclusions look... how? (variable)

herpesvirus, adenovirus, parvovirus

what three DNA virus inclusions are intranuclear? (that we were given at least)

poxviruses, large eosinophilic

What is the one viral cytoplasmic inclusion and what does it look like?

Rabies, canine distemper

what two RNA virus inclusions were we given as examples?

negri bodies

rabies inclusions are called?

both!

Is canine distemper a nuclear or cytoplasmic inclusion?

herpesvirus

which viral inclusion?

adenovirus

which viral inclusion

poxvirus

which viral inclusion?

rabies

which viral inclusion?

canine distemper virus

which viral inclusions?

storage diseases

Group of diseases characterized by mutations that result in the

accumulation of complex substrates or blockage of metabolic

pathways

lysosomal storage disease

which storage disease is characterized by a deficiency of lysosomal acid hydrolases

incomplete breakdown of substrates, accumulating partially degraded, insoluble metabolites

What shows up as a result of lysosomal storage diseases?

lysosomal

lysosomal galactocerebroside beta-galactosidase (sorry)

Globoid cell leukodystrophy is an example of what type of storage disease?

Specifically, it is a functional deficiency of ___________________________

galactocerebroside, macrophages of the CNS

Globoid cell leukodystrophy is an accumulation of __________ within the ________ cells of the _________ system

GM1 gangliosidosis, lysosomal, GM1 ganglioside

what storage disease is marked by a deficiency of GM1 ganglioside beta-galactosidase.

What type of storage disease is this and what accumulates?

hexosaminidase, tay-sachs disease, sandhoff disease

GM2 gangliosidosis is a deficiency or ______

If its a deficiency of the alpha subunit its called ________.

If its the beta subunit, it's called ___________

globoid cell leukodystrophy

What?

globoid cell leukodystrophy

what?

globoid cell leukodystrophy

what?

Tay-sachs disease

what?

an enzyme involved in synthesis or degradation of gylcogen (accumulates glycogen)

generally, glycogen storage diseases are characterized as a deficiency in _______________________________

Pompe disease, alpha-glucosidase enzyme

what is another name for glycogenesis type II?

Where is the deficiency?

Cori's disease,

function of amylo-1,6 glucosidase debranching enzyme (IM SORRY OKAY?)

Whta is another name for glycogenosis type III?

where is the deficiency?

Pompe disease

What?

induced storage diseases

What do you call an inhibition of enzymes due to outside sources like the ingestion of locoweed

lysosomal alpha mannosidase

what is inhibited in locoweed toxicosis?

proprioceptive defects and abnormal behavior

chronic consumption of locoweed causes _________ and __________

locoweed toxicosis

if you have a goat standing around like this, and this plant is in his habitat, and his cells look like this... what do we think this is?

viral inclusions

What is this?

(Options are like, glycogen, lipid, viral, iron inclusions.... options are all the inclusions a cell can have)