Cell Injury and Adaption III

Question 1

How are ROS made in a cell (there are 6 ways)

Answer 1

1. Cell redox reactions
2. Radiation
3. Leukocytes make ROS during inflammation by generating hypchlorite (bleach) from myeloperoxidase
4. Metabolism of drugs by CP450
5. Transition metals from Fenton’s reaction.
6. Nitric Oxide

Question 2

Which one is the most detrimental radical. How does it causes damage to the cellular machinery?

Answer 2

Hydroxyl radical.

It causes damage by lipid peroxidation, reacts with proteins to cause a change in their 3D structure and change their morphology and finally it reacts with DNA to form single and double stranded breaks, form cross links and DNA adducts.

Question 3

How does an influx of Ca damages the cell

Answer 3

1. There is phospholipase activation leading to a loss of phospholipids
2. Protease activation leading to a loss of cytoskeletal structures
3. Oxygen goes down leading to an increase of ROS

Question 4

What happens in hypoxic conditions? How does the body respond?

Answer 4

Hypoxic conditions leads to the production of Hypoxic Inducible Factor I (HIF1). This leads to increased angiogenesis so the body starts to make more blood vessels and enhances glycolytic pathways for anaerobic metabolism.

However in diabetic people this leads to diabetic retinopathy which is increase in blood vessels right above the retina which can eventually lead to blindness.
Ophthalmologist deal with this by destroying these added blood vessels by laser.

Question 5

What are the ischemia-reperfusion injuries

Answer 5

1. Increases the risk of generation of ROS
2. Increase permeability of cell membrane to calcium (due to break down of pumps due to lack of ATP) leads to increase phospholipase and protease activity leading to loss of cell membranes and proteins. Also the permeability of mitochondria is affected leading to loss of production of ATP.
3. Ischemia leads to acute inflammation and repair pathways signalling neutrophils to move to the ischemic region by repsonding to danger signals called DAMPS

Question 6

Reperfusion and ischemia both leads to the production of ROS

Answer 6

Time is myocardium

Question 7

Added detail about apoptosis

Answer 7

Apoptopic bodies are formed which have organelles in them. These bodies are phagocytosed by the macrophages

Question 8

How does the extrinsic apoptotic pathway is executed?

Answer 8

The T cells in the body recognizes the cells. Those cells which are not identified as self are then signalled for apoptosis. This is done by the release of the ligand called FAS ligand. The cells have receptors on them which are called FAS which are a part of the TNF receptor family. These receptors then recruit scaffolding proteins (FADD) which then initiate capsases.

Question 9

Know how centrifuged samples of DNA look like from

1. Normal cell
2. Apoptotic cell
3. Necrotic cell

Answer 9

1. DNA usually on the top, doesn’t get very far in the agarose gel due to its high weight
2. DNA bands are seen along the length of the centrifuged sample as the DNA is carefully cut by the Caspase Activated DNAses.
3. DNA fragments are uniformly continuous along the length of the sample since this is a result of DNA dissolution by karyorrhexis and karyolysis

Question 10

What are common intracellular accumulation

Answer 10

1. Fat
2. Glycogen
3. Lysosomes
4. Iron
5. Lipofusin
6. Melanin
7. Hyaline
8. Exogenous pigments like carbon from smoking

Know how these look like

Question 11

What are the 2 kinds of pathologic calcification

Answer 11

Dystrophic calcification which occurs at any serum Ca conc. levels and usually occurs in injured tissue (remember his example of horse chewing the boob)

Metastatic calcification: occurs during hypercalcemia and is related to bone metastases. It can occur at any or all organs and occurs in normally functioning healthy tissues.

Question 12

How do you identify apoptotic bodies

Answer 12

They are segments of cytoplasm without any nucleus. (As far as I could see, I didn’t recognize any discrete organelles myself)