Have you read chapter 2 in Robbins? You’ll probably have to, if you’re taking a pathology course. Usually, pathology courses start with something on cell injury and cell death, and Robbins chapter 2 (Cell Injury, Cell Death, and Adaptations) is often the first reading assignment.

The cell death and adaptations sections of this chapter are pretty straightforward. It’s the cell injury part that is super detailed and frustrating. I thought it might be good to have a very general overview of the topic to give you a big picture of cell injury. So here it is – very short and sweet.

There are four structures within a cell that are particularly vulnerable to injury:
1. Mitochondria
2. Cell membranes
3. The protein synthesis apparatus
4. DNA.

Cell injury often starts with ATP depletion (this can happen with several types of injury, including hypoxic injury and chemical injury). When there’s not enough ATP around, the cell membrane pumps don’t work well, and sodium and calcium accumulate inside the cell. Too much cytoplasmic calcium is bad for 3 reasons:
1. It denatures proteins
2. It poisons mitochondria (makes them open little channels in their membranes which makes oxidative phosphorylation fail; also activates pathways that make the cell kill itself)
3. It activates a bunch of nasty cellular enzymes (like phospholipases, which break down membranes).

Cell injury can also be induced by free radicals (molecules that have a single, vicious unpaired electron). Several types of processes can increase the production of free radicals. Get enough free radicals, and the cell membrane will be damaged.

The bottom line is that there are two main reasons a cell dies:
1. Cytoplasmic calcium accumulation
2. Membrane damage.

There are some changes that you can actually see in injured cells. Some of the things you see (either with an electron microscope or a regular old light microscope) in reversibly injured cells include:
1. Mitochondrial densities
2. Cellular swelling
3. Cytoskeletal disruption (e.g., loss of microvilli, blebs).

Once you see any of the following things, a cell is considered irreversibly damaged:
1. Increased eosinophilia (pink color) in cells. Check out the image above of a myocardial infarction: the myocytes are brightly eosinophilic (remember: “red is dead!”).
2. Great big mitochondrial densities
3. Nuclear changes, such as pyknosis (a shrunken, dark nucleus), karyolysis (a fading of the nucleus), and karyorrhexis (fragmentation of the nucleus into little cookie-crumb-like pieces).

That’s it in a very small nutshell. You might also want to check out The six types of necrosis for a quick overview of that part of this chapter of Robbins.