Exam 1 (Lecture 6) - Cellular Accumulations Flashcards

1
Q

What are the causes of intracellular accumulations?

A

1) Metabolism failure (cell overwhelmed with substrate)

2) Protein folding error (prions)

3) Lack of enzyme (fail to breakdown/metabolize substances)

4) Accumulation and storage of indigestible materials

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2
Q

What are examples of intracellular accumulations due to these causes?

A

1) Metabolism failure –> fatty liver (hepatic lipidosis)

2) Protein folding errors –> accumulation of abnormal proteins (causes other proteins to misfold)

3) Lack of enzyme –> accumulation of endogenous materials (Ex: lysosomal storage disease); alters shape/function of cell

4) Accumulation and storage of indigestible materials –> accumulation of exogenous materials (Ex: asbestos, carbon, silica); cell can’t get rid of these substances

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3
Q

What is lipofuscin?

A

Sign of wear and tear (old cells)

Appearance: fine light to dark brown pigment granules

Where: hepatocytes (cats most commonly), muscle cells, neurons

Significance: Usually just means its an older cell

  • Can look like iron/bile
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4
Q

What is fatty degeneration?

A

Fatty change (lipidosis/steatosis)

Accumulation of triglycerides in cytoplasm of cells.

Typical organs: liver, skeletal/cardiac muscle, kidneys (note: cats normally store lipids here so their kidneys appear yellow = totally normal)

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5
Q

What are the routes of fatty degeneration of the liver?

A

1) Excess delivery of FAs to liver
a) increased mobilization of fat
stores (caloric deficiency or
starvation, diabetes, pregnancy
toxemia)
b) increased FA from gut (high fat
(meal)

2) Blockage of FA oxidation (impaired metabolism)

3) Interference with export of triglycerides (due to mitochondrial damage; decreased protein synthesis)

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6
Q

What are the gross morphological changes seen with fatty degeneration of the liver?

A

1) Enlarged
2) Greasy
3) Yellow to tan in color
4) Soft/friable
5) Rounded edges
6) Will float in water

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7
Q

What are the microscopic morphological changes seen with fatty degeneration of the liver?

A

1) Cells are often swollen/vacuolated

2) Nucleus is displaced

3) Vacuoles are larger than with water or glycogen (can see lipid and glycogen storage in the same liver)

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8
Q

What is the microscopic morphology seen with glycogen degeneration in liver and kidneys (compared to fatty degeneration in liver)?

A

The nucleus of affected cells in centrally located with glycogen degeneration (it’s displaced to the side with fatty degeneration)

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9
Q

How do you confirm that it’s glycogen degeneration?

A

With PAS stain

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10
Q

What is the cause and mechanism of glycogen degeneration?

A

Hyperglycemia (prolonged increase of glucose in blood)

Increase in corticosteroids –> increased blood sugar –> increased glucose in blood –> glycogen storage in liver (confirm with PAS stain)

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11
Q

Differentiate microscopic morphology between spongiform encephalopathy (protein folding error) and lysosomal storage disease.

A

In spongiform encephalopathies (such as scrapie in sheep or BSE in cattle), neurons are vacuolated and appear white.

In lysosomal storage disease (excessive glycogen/CHOs in neurons), the neurons are storing a large amount of metabolite that appears white in the membrane along with the purple cell body.

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12
Q

What are the types of pathologic calcification?

A

1) Dystrophic calcification
2) Metastatic calcification

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13
Q

What is dystrophic calcification?

A

Deposition of calcium in tissues THAT ARE INJURED OR NECROTIC (ex: caseation necrosis or coagulation necrosis).

** Coagulation necrosis = intracellular
Caseous necrosis = extracellular

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14
Q

What is metastatic calcification?

A

Deposition of calcium (and/or phosphorus) in NORMAL tissue secondary to hypercalcemia.

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15
Q

What is the pathogenesis of dystrophic calcification?

A

Dying/dead cell –> denaturation of proteins –> binding by calcium –> mineral deposition

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16
Q

What is calcinosis circumscripta?

A

Dystrophic calcification that dogs get at different bony prominences/pressure points.

17
Q

What is the microscopic morphology of dystrophic calcification?

A

White lesions that are gritty or chalky.

18
Q

What markers do we look for to determine if a patient has metastatic calcification?

A

Need to do a serum chemistry analysis to determine if the calcium or phosphorus is high (or both are high).

If [Ca] x [P] > 70 = metastatic calcification; deposition of mineral in tissue.

19
Q

What are the causes of hypercalcemia?

A

1) High Ca2+ in diet
2) Vitamin D excess
3) Parathyroid tumor
4) Paraneoplastic –> parathyroid hormone
5) Renal failure

20
Q

What are the common locations we see metastatic calcification?

A

We will see precipitation of Ca2+ in organelles (mitochondria) in acidic environments.

1) Basement membranes of: kidneys and lungs
2) Blood vessels
3) Gastric mucosa