VM 704 (Pathology)- Cell and Tissue Injury, Regeneration, and Death

What are the 5 main players in cell injury?

1. ATP depletion

2. Calcium influx

3. Increased membrane permeability

4. Mitochondrial damage

5. Generation of Reactive oxygen species

What is used when cells run out of ATP?

Glycogen

What organelle generates reactive oxygen species?

The mitochondria

What 4 enzymes are activated with increased calcium in the cytosol?

1. ATPase

2. Phospholipase

3. Protease

4. Endonuclease

What is the definition of an infarct?

Damage to the cell from the absence of blood flow.

What 4 things happen when ATP is depleted in the cell?

1. Pi (inorganic phosphate increases)

2. Anaerobic glycolysis increases

3. pH drops

4. Sodium potassium pump shuts off

What is the medical term for cell swelling?

Hydropic change/degeneration

What does the cell look like when cell swelling occurs?

The cytoplasm becomes glassy/cloudy.

What 2 morphologic events indicate irreversible degeneration of cells? (hint: what happens to the organelles?)

1. Ribosomes are lost from RER

2. Mitochondrial swelling

What are 3 changes to the nucleus that result in IRREVERSIBLE injury and cell death?

1. Pyknosis (nucleus shrinks)

2. Karyorrhexis (nucleus fragments)

3. Karyolysis (enzymes in nucleus are digested)

What 2 things occur at the cellular level that cause reperfusion injury?

1. Excessive calcium influx into the cell

2. Generation of reactive oxygen species (damaging the membrane)

What does fatty change look like under a microscope?

Oil in water (immiscible)

How does lipid peroxidation occur?

The reaction of a lipid radical with oxygen, then generates ROS

What happens when the pneumotoxicant 3-MEIN enters the lungs?

The lung cells are flooded and damaged.

What are the 2 ways cell death can occur?

1. Necrosis

2. Apoptosis

What are the 4 morphologic patterns of necrosis?

1. Coagulative

2. Liquefactive

3. Caseous

4. Fat necrosis

What are the 2 main causes of liquefactive necrosis?

1. Bacterial

2. In tissues with little stroma

What occurs cellularly in dry gangrene?

Coagulated tissue dries out

What occurs cellularly in wet gangrene?

Tissue is digested and liquefied.

Which kinds of cell death produce inflammation?

1. Pyroptosis

2. Pyronecrosis

3. Ferroptosis

4. Oncosis

5. Necrosis

In what kinds of tissues does apoptosis occur?

1. Tissues undergoing physiologic involution or post-pathologic atrophy

2. Non-mature tissues (not fully developed)

3. Hematopoetic cell lines

4. Cells killed by T-lymphocytes

5. Cells with DNA damage/other injury

What disorders are associated with decreased apoptosis?

1. Neoplasia

2. Autoimmune disease

What disorders are associated with increased apoptosis?

1. Neurodegenerative disorders

2. Exacerbation of ischemic injury

3. Lymphocyte depletion (virus induced)

What happens to the cell when there is excessive glycogen storage?

Hydropic degeneration (water rushes into cell)

What hormone causes Cushing’s disease and how?

An excessive production of cortisol (hyperadrenocorticism)

What does the storage disease Locoism cause in cells?

Toxin causes buildup of sugars inside cells-- b/c enzyme that breaks the sugars down is destroyed.

What are the 2 types of calcification/mineralization of tissue?

1. Dystrophic (occurs in dead tissue)

2. Metastatic (occurs in healthy/live tissue)

What are the main causes of metastatic calcification?

1. Hypervitaminosis D

2. Renal disease

3. Hyperparathyroidism

4. Hypoadrenocorticism (Addison’s)

5. Paraneoplastic syndromes

What are the main types of antioxidants that terminate the generation of free radicals (ROS)?

1. Vitamin A,E,C

2. Selenium

3. Caeruloplasmin (binds Cu)

4. Fe binding compounds