Exam #1: Cellular Adaptations and Accumulations II

Question 1

Review the process of lysosomal catabolism.

Answer 1

• Primary lysosomes bud from the golgi apparatus
• These organelles are filled with hydrolytic enzymes
• A primary lysosome will fuse with a phagocytic vesicle derived from invaginated plasma membrane to form a secondary lysosome

Question 2

What is a primary lysosome?

Answer 2

Small membrane found vesicle that buds from the Golgi apparatus

Question 3

What is a secondary lysosome?

Answer 3

• A primary lysosome that has fused with a phagocytic vesicle derived from invaginated plasma membrane
• Also called a phagolysosome

Question 4

What is heterophagy?

Answer 4

Materials from extracellular environment taken up through endocytosis

• Large= phagocytosis
• Small= pinocytosis

Question 5

What is autophagy?

Answer 5

Lysosomal digestion of cell’s down components; common in removal of senescent/damaged organelles & cellular remodeling association with cell differentation

Question 6

What are residual bodies?

Answer 6

Some lipids and other materials remain undigested in cells e.g. lipofuscin that is known as the “aging pigment”

Question 7

What are Hereditary Lyosomal Storage Disorders?

Answer 7

Abnormal accumulations of intermediate metabolites in lysosomes

*Note that drugs can disrupt the function of lysosome as well

Question 8

What happens in the p450 system?

Answer 8

Smooth ER is involved in metabolism of various chemicals/ compounds; synthesizes phospholipids & detox
- SER undergoes hypertrophy as adaptive response to drug abuse, esp. barbiturates

E.g. Barbituates & p450 mixed function oxidasde system

Question 9

What mitochondiral alterations are seen in alcoholic liver disease?

Answer 9

• Alcoholic liver disease can induce mitochondrial hypertrophy called “megalomitochondria”

Question 10

What is the cytoskeleton? What are the different functions of the components of the cytoskeleton?

Answer 10

• Thin filaments= movement & phagocytosis
• Microtubules= motility, phagocytosis, and mitotic spindle formation for mitotic spindle
• Intermediate filaments= intracellular scaffold, maintain cellular architecture–can accumulate and be pathologic e.g. Alzheimer’s Disease

Question 11

What are cytoskeletal proteins?

Answer 11

• Proteins of the cytoskeleton that are linked to cellular receptors
• These play an important role not only in membrane permeability, but also in how the cell functions

E.g. cytoskeletal proteins are active participants in signal transduction & lymphocyte receptors for antigens

Question 12

What are intracellular accumulations manifestations of?

Answer 12

Metabolic derangement–this is a storage of some product that cannot be degraded

Question 13

What are the three categories of intracellular accumulations?

Answer 13

1) Normal endogenous substances–produced at a normal or increased rate but the metabolism is inadequate to remove it
2) Normal or abnormal endogenous substance accumulates secondary to genetic of acquired defects in metabolism
3) Abnormal exogenous substance that cannot be removed

Question 14

What are the mechanisms that lead to intracellular accumulations?

Answer 14

1) Abnormal metabolism e.g. fatty liver (fat accumulates in vesicles within the cell)
2) Alterations in protein folding and transport
3) Deficiency of critical enzymes leading to accumulation of an insoluble intermediate
4) Inability to degrade phagocytosed particles

Question 15

Give an example of abnormal metabolism leading to intracellular accumulations.

Answer 15

Fatty Liver Disease

- Fatty acids enter the cell & the liver can’t keep up

Question 16

What is steatosis?

Answer 16

Abnormal accumulations of triglycerides within parenchymal cells

• Yellow discoloration
• Caused by toxins, protein malnutrition, obesity, DM, and alcohol

*This leads to cirrhosis

Question 17

Review fatty acid metabolism and the mechanism leading to accumulation of triglycerides.

Answer 17

A defect in any step of metabolism causes an accumulation of triglycerides

Question 18

What is athersclerosis?

Answer 18

Plaques, smooth muscle cells & macrophages form within intimal layer of aorta & large arteries fill with lipid vacuoles

• Lipid vacuoles= foam cell
• Aggregates produce yellow, cholesterol laden atheromas

Question 19

What is a cholesterol cleft?

Answer 19

Some foam cells rupture, releasing lipids in the extracellular space–>crystalize

Question 20

What are xanthomas? What patient population are they often seen in?

Answer 20

• Yellow discoloring accumulations around the eyes
• Foam cells
• Seen in familial hypercholesterolemia

Question 21

What is cholesterolosis of the gallbladder?

Answer 21

Foam cells in the gallbladder

Question 22

What causes protein accumulations?

Answer 22

• Point mutations interrupt protein folding and transport
• Accumulation occurs within vesicles

Specifically, there are diverse causes of protein accumulation e.g. reabsorption droplets in proteinuria

Question 23

How do protein accumulations appear?

Answer 23

Protein accumulations form a pink “hyaline” material in the cytoplasm

*Note that these are less common than lipid accumulations

Question 24

What can Nephrotic Syndrome lead to?

Answer 24

Nephrotic syndrome is a group of symptoms that include protein in the urine, low blood protein levels, high cholesterol levels, high triglyceride levels, and swelling.
- This syndrome will lead to the reabsorption of protein droplets in the proximal renal tubule

Question 25

What are russel bodies?

Answer 25

- Synthesis of excessive amounts of normal proteins can occur - One example is plasma cells that produce antibodies - Antibodies can accumulate in the plasma cell, which is referred to as a "Russel Body" Thus, this is not always a pathologic process

Question 26

What are mallory bodies?

Answer 26

In alcoholic liver disease, cell injury leads to a congregation of protein & keratin intermediate filament that stains very pink - These are called "Mallory Bodies" or alcoholic hyalin

Question 27

What is the function of chaperon proteins?

Answer 27

- Chaperones aid in proper folding & transport of proteins - Repair misfolded proteins - Facilitate degradation of damaged proteins by "flagging" them with ubiquitin

Question 28

What is alpha-1 antitrypsin deficiency?

Answer 28

- Alpha-1 antitrypsin is produced by the liver; it degrades trypsin - When deficient, there is an accumulation of this protein in the liver - Trypsin levels increase & can lead to the development of emphysema - Trypsin can also increase in liver, leading to cirrhosis

Question 29

What class of diseases does ER stress play a major role in?

Answer 29

Neurodegnerative disease

Question 30

What is amyloidosis?

Answer 30

Toxic, aggregated, abnormally folded protein that stains orang-red with Congo red staining

Question 31

What is a hyaline change?

Answer 31

Descriptive term for non-specific morphological changes that appear pink under H & E stain

Question 32

When there are abnormalities of metabolism of glucose or glycogen, how do excessive intracellular deposits appear on microscopy?

Answer 32

Clear

Question 33

In DM, where can glycogen be seen?

Answer 33

- Cytoplasm or renal tubular epithelium - Hepatocytes - Cardiac monocytes - B-cells of Islets of Langerhans

Question 34

What are glycogen storage diseases?

Answer 34

A class genetic enzymatic defects in synthesis or breakdown of glycogen that leads to a massive stockpiling that leads to cell injury and cell death

Question 35

What is glycogen storage disease type II?

Answer 35

Pompe's disease | - Acid alpha glyocsidase deficiency that effects the heart

Question 36

What is the most common exogenous pigment that is accumulated in the body?

Answer 36

Carbon i.e. coal dust that is picked up by macrophages

Question 37

What is anthracosis?

Answer 37

Darkening of lymph nodes from the accumulation of macrophages containing carbon pollution

Question 38

What is coal worker's penumoconiosis?

Answer 38

Heavy accumulations of coal dust i.e. carbon that leads to emphysema or fibroelastic reaction; a restrictive lung disease seen in coal miners

Question 39

What is tatooing in a pathologic sense?

Answer 39

Accumulation of exogenous pigmentation in the skin, specifically, in dermal macrophages

Question 40

What is lipofuscin?

Answer 40

- Lipofuscin is a brownish-yellow, granular intracellular material that is called the "wear and tear pigment, of the aging pigment" - It is difficult to breakdown lipids and phospholipids that leads to the formation of "Lipochrome"

Question 41

What is melanin? What is the function of melanin?

Answer 41

Brown pigment in the skin that protects from UV raidation

Question 42

What is hemosiderin?

Answer 42

- Gold-yellow-to-brown pigment that forms from excess iron locally or systemically - Represents aggregates of ferritin micelles *Heart failure cells

Question 43

What is hemosiderosis?

Answer 43

Systemic overload of iron i.e. deposition of iron in many organs and tissues