Pathology Transcriber: Sara Sheppard

Pathology Transcriber: Sara Sheppard

08/21/08 52:39

Cell Adaptation and Cell Injury

Slide 1/2:

What we’re going to do today is talk about cell adaptation and cell injury. The objectives are in your hand out, so I won’t go through those, but we want to just get a basic idea and basic understanding of how all this fits together and how cells and tissues respond to stress.

Slide 3:

They respond to stress by adapting to it, or they respond to stress by dying. So, here is the diagram right out of your book. I tend to just follow along with what’s in the book and follow along with what’s in the laboratory module that Dr. Waites mentioned, the Interactive Pathology lab modules. A lot of the same pictures that I use in my lectures are the same ones we used to develop those online laboratories. That’s sort of to pull it all together for you and make it easier than having to learn a bunch of disparate facts and pull them all together at the end. So what we’re going to do today is to talk about basically how a normal cell responds to stress. And as I said they can respond to stress by adapting to that stress, and when they do that they change morphology and physiology. The other thing they can do is if they can’t adapt to the stress, if they are unable to adapt or if the injurious agent is too strong right from the beginning, then it could be unsurvivable and you’d end up with cell death.

Slide 4:

Let’s start with the easy stuff first. We won’t get too pathologic right away. We’ll start with the basic things--what happens to tissues and organs when there’s a stress. The way tissues and cells respond to stress is either by atrophy, hypertrophy, hyperplasia or metaplasia. Cells and tissues also respond through a process called dysplasia, which is mentioned in your book. We’ll talk about that more when we talk about neoplasia in the cancer section of the course. This is enough to start with right now.

Slide 5:

If you imagine a group of cells, the easiest way to imagine it is a layer of epithelial cells on a basement membrane. You have this layer of normal epithelial cells. This could be in the kidney, the urepitheila cells, the trachea, the bronchial epithelial cells, or the gall bladder, but just a layer of cells sitting on a basement membrane. If you either denervate them or put them in a situation where they don’t have to work as hard, the cells will atrophy. They will get smaller. They don’t have to do as much work, so they get smaller.

Another example is if you make them work harder, the cells get bigger. So that is hypertrophy.

Some tissues, depending upon what kind of tissue it is, can go through a process of hyperplasia where the cells divide and you end up with more cells. So you stress them, and in order to respond to that increased stress, they divide and make more cells. This group of cells can react to the stress.

The third (I think he meant fourth) kind of change that we see is a process called metaplasia. We’ll talk about that in a second. That’s a change from one cell type to a different cell type.

Slide 6:

Let’s go through the basic types of reactions. One is hyperplasia. That is an increased number of cells in an organ or tissue. Examples of this:

One thing that causes physiologic hyperplasia is a hormonally induced hyperplasia. In the breast after a baby is born and during lactation. You need proliferation, or increased numbers of breast cells, of mammary epithelial cells to produce the milk needed for the baby.

The other example is in the uterus, both during the normal menstrual cycle and/or during pregnancy where you have to produce an increased number of cells to respond to the hormonal stimulation.

There are some pathologic types of hyperplasia. The most classic one is in the prostate. Men as they get older and the hormones are altered may get benign prostatic hyperplasia.

The other classic example of hyperplasia is when you have a viral infection. Anyone who has had a wart knows this is just a proliferation of squamous epithelial cells stimulated by the virus that gives you a hyperplasia of the squamous epithelial cells, giving you a wart.

Slide 7:

Here’s prostatic hyperplasia. This is an autopsy specimen, and you see these nodules here, here, here (arrows on slide). This is because of an increased number of cells. If you have an organ this big and the cells start dividing, something has got to give, it’s got to expand.

Slide 8:

What’s happened is that each of these layers, which are actually glands within the prostate gland, are lined by single or doubled-layered epithelial cells. In this case, you can see there are so many they have had got to form these infoldings, or undulations, here because they are just stacked one on top of the other. When you do that at the cellular level, a nodule must form within the organ, which you saw in the previous slide. So that’s hyperplasia—increased proliferation of cells to give you increased numbers of cells within the organ, making the organ bigger.

Slide 9:

What happens if the cells can’t divide? The classic example is heart cells. Once you are an adult, you have all the heart cells you are going to have. The same is true with neurons. Once they are gone, they don’t come back. So cells that can’t divide, if they are stressed in some way, the only way they can react is to get bigger. The individual cells will get bigger.

An example of physiologic hypertrophy is again the uterus during pregnancy. The smooth muscle cells not only increase in number, but also in size. Arnold Schwarzenegger and weight lifters whose muscles get bigger are examples of hypertrophy. This example may be physiologic or pathologic. The pregnant uterus smooth muscle cells can divide and get bigger. So you have hypertrophy and hyperplasia in the uterus during pregnancy.

An example of pathologic hypertrophy is in the heart when you have a problem with one of the valves. The one that is often a problem is the aortic valve because old people get what’s called calcific aortic stenosis.

Slide 10:

This is a section of heart form an autopsy. We are looking down the aorta, which has been cut off. You are looking straight down onto the top of the aortic valve. If you remember, the aortic valve should have three cusps that all fold together during diastole and open during systole as the blood comes out. Those sometimes get calcified, which we’ll talk about in a minute. This is dystrophic calcification. The valves get calcified and turn into a rock, just like bone.

Slide 11:

What happens if you have a calcified valve right here? As the blood comes from the lungs and tries to squirt out through that calcified valve, the heart has to pump a lot harder. It’s like adding more weight to your barbell. What will happen is the heart has to work harder to pump that blood and the heart cells will hypertrophy.

Slide 12:

Here’s a heart from a patient who had left ventricular hypertrophy because of calcific aortic stenosis. This is a normal heart (on right) and this is a heart that has undergone pathologic hypertrophy because of a stenotic aortic valve (on left). Not only is the heart bigger, but each individual cell is bigger.

Slide 13:

Here is a high power view of a single myocyte from that hypertrophied heart, as compared to right here, this is a normal myocyte. You can see that each individual cell increases in size significantly and thus the whole organ gets a lot bigger. That is an example of pathologic hypertrophy.

Slide 14:

We talked about atrophy, and that is where you get shrinkage of the cells, and subsequently shrinkage of the whole organ. This can occur from decreased work load and loss of innervation. If your nerve gets damaged and there is no nerve stimulation, you will end up with loss of muscle. Diminished blood supply, inadequate nutrition, loss of endocrine stimulation, or aging. Some of us get bigger and some of us get smaller.

Slide 15:

The classic example of atrophy is when you have a broken leg and you can’t walk. The muscles of the leg atrophy, or get smaller. After you’ve had the cast and haven’t used the leg for awhile, what happens to the muscle? It will atrophy. This is disuse atrophy.

Slide 16:

This is a histological section looking at individual muscle fibers. You can see a lot of them look really little. See these little tiny ones here, compared to more normal size muscle cells over here. That is atrophy. The cells get smaller because of no hormone stimulation, no innervations, or whatever.

Slide 17:

Metaplasia is sometimes a difficult concept for people to grasp. It is pretty simple description. It is a reversible change in which one adult epithelial cell type is replaced by another adult epithelial cell type. Pretty straightforward.

Slide 18:

A classic example of metaplasia is in the bronchial epithelium of a smoker. Normal bronchial epithelium should be columnar ciliated epithelium. Nice tall cells with cilia on the end that wave back and forth to bring up all of the pollution. Columnar epithelium is the normal epithelium you’d expect in your trachea and your bronchioles. If you are a smoker, and all of the that gunk comes down the trachea and bronchi everyday, the ciliated columnar epithelium gets tired of that and they are injured by the material. So you are constantly injuring those cells. What is the body going to do? It will figure out a way to protect itself from this gunk that is coming down.

The way it does this is to develop a layer of squamous epithelial cells. Just like calluses you form on your hands when you lift weights, this is sort of what the lungs are trying to do. They are making a callus, or layer of skin on the inside of your bronchial epithelia to help protect the lung from all of the cigarette smoke. The concept here is easy. You get from columnar to squamous.

How do you get there? Does this cell turn into a squamous cell? No. It is terminally differentiated. It can’t do that. What has to happen is that signals from the dying cells send messenger molecules down to the reserve cells, the basal cells along the bottom of the epithelial layer. They tell those cells “Don’t grow up to be ciliated columnar epithelial cells, instead grow up to be smooth muscle cells” (I think he meant squamous epithelial cells).

You are really signaling the progenitor cells on the surface of the basement membrane to differentiate into a different cell type. You don’t go from one cell type to another cell type in the same cell; you go from one epithelial type to another epithelial type by stimulating the basal cells to differentiate into a different type of cell.

Another example of metaplasia is GERD (gastroesophageal reflux disease). The esophagus is usually squamous epithelia, but when the acid from your stomach splashes up on it, it is like putting acid on your hand. This is why you have heartburn. What the body does is switch from squamous epithelium to an epithelium just like the stomach, which is goblet cells producing mucus. So the bottom of your esophagus has a layer of cells producing mucus, so when the acid splashes up there, it hits the mucus and doesn’t hurt the epithelia. That is an example of not squamous metaplasia, but of metaplasia going from squamous to glandular as opposed to the example of the bronchus where you go from ciliated columnar to squamous epithelial. GERD is another great example of how you get metaplasia.

Answer to question: The change from fast to slow twitch muscle is not an example of metaplasia because the cell type is the same, just the makeup of actin/myosin/enzymes is changed. Also, it can’t be metaplasia because this term applies to epithelium only. So liver cells, kidney cells, muscle cells, bone, you won’t have metaplasia with those types of tissues.

Slide 19:

This is in your lab, but just real quickly. Another example besides smoking is if you have a kidney stone. That rock will rub against the epithelium in the kidney and irritate it.

Slide 20:

So you change from an urithelial lining, or transitional cell lining, to squamous epithelia.

Slide 21:

And instead of a single layer of urithelium or transitional epithelium, you have what looks almost exactly like skin. This is squamous metaplasia in the kidney due to a kidney stone.

****NOTE: At this point he started the second part of the handout, with a title slide “Cell Injury” and starting on page 8.

Slide 22/23:

So that‘s how tissues respond to stress. They can change phenotypes, proliferate, get smaller or bigger, and adapt to change.

Slide 24:

What happens if the injury is so bad that they can’t react to that change? When you get an injurious stimulus, you will get what is called reversible cell injury. In the case of reversible cell injury, it is similar to what we have been talking about where it damages or perturbates the cell, but it doesn’t kill it. That is initially.

If the injury continues, then you go past this point of irreversibility, or point of no return, and you end up with necrosis. Necrosis is what happens in tissues when you get cell death.

Another way of getting cell death is a process called apoptosis. Apoptosis is called programmed cell death where the tissue realizes that the jig is up. Instead of just sitting there waiting to die, the cells actually commit suicide. They go through a program of committing suicide in a nice way, a clean way. It is good for the betterment of the organ for them to get out of the way so that the tissue that does survive will be able to keep on going.

Slide 25:

Let’s go through an example of what we talk about when we say cell injury. Here is a case of a 65 year old man who comes to the ER because of a crushing sensation in his chest with pain radiating up his jaw.