Pathology - Lecture 4Tuesday 28/9/2010Done by: Hadeel Al-Kofahi

Cell Injury – Cellular Adaptations

In the last lecture, we've talked about hyperplasia, hypertrophy, atrophy, and so on, which are changes in growth, cell size, number of cells, and I’ve mentioned the different kinds of tissues that have different capacity to proliferate and replace any dead cells, okay ? :D We come now to another subject:

Metaplasia

(Meta-) means different. So metaplasia means: the cells have the ability to change from one type to another. It’s reversible, but not always, but usually it's a reversible change. It’s called “an adaptive change” in which one adult cell (it doesn't usually occur in the fetus, usually in adult cells) is replaced by another adult cell type that’s better suited to tolerate an abnormal environment or injury. For example, if some of you are pale, you put skin lotion to become a little bit dark; as a protection for the skin (so it's a protective mechanism). Metaplasia may also have a bad effect.

It can usually occur in the epithelial cells & the mesenchyme tissue. The usual types of cells which are changing are: bronchial, gastric, and cervical epithelium. The first part of the duodenum can also change and the bone in injured soft tissue. For example: you have some trauma to a muscle; a strong trauma becomes chronic and then it becomes somewhat calcified, and then in the calcification we find that there’s bone formation to make the soft tissue harder, okay?

What are the disadvantages? Now because of metaplasia, the normal protective mechanisms may be lost and the best example of this is in the bronchial mucosa.

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بسم الله الرحمن الرحيم

Now what type of bronchial mucosa do you have? It’s ciliated columnar epithelium, and what do the cilia do? They are protective against infection; they prevent any particle going down, so it's beneficial to the cells to have cilia in the respiratory tract.For example, cilia also occur around the fallopian tube, and this is good for the sperms and the ova and so on, so it's a beneficial factor here.

Let’s say somebody is a smoker, I guess many of you are (which is VERY wrong), now this protective mechanism is lost, what happens because of the smoke? The ciliated epithelium changes to squamous, and what is squamous epithelium? It’s just thick multi-layers (cell layers) and has no cilia. This can be the effect of smoke, the absence of cilia, and that’s why somebody who’s a smoker will continue to have a chest infection, especially if he has other chronic lung diseases. So metaplasia is sometimes beneficial and sometimes is bad.

The other point is that persistent of signals that results in metaplasia may at one point progress from metaplasia to dysplasia. We shall see in more details when we talk about tumors, that dysplasia may be one step before the occurrence of tumors. So dysplasia may progress to carcinoma, not in all cases but it does happen, so these are just some of the bad influences of metaplasia.

And here is an example: this is a ciliated columnar epithelium and then it’s being changed to squamous epithelium in the respiratory tract of a smoker! (The doctor admits “it’s not a very clear picture” :D )

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But this one (the picture below), shows the Gastric metaplasia in the esophagus. Now, sometimes you have gravitation of acid fluid from your stomach into the esophagus, this is called (Reflux) and as this acidity goes up, (or if you have a very short esophagus), then sometimes as a protective mechanism it becomes squamous and sometimes becomes columnar. And sometimes the gastric epithelium goes into the first part of the duodenum (acid secretion going to the

duodenum which is more neutral).

Dysplasia

What about dysplasia? We’ll take a short note about dysplasia but we’ll talk more about it when we talk about tumors.

It’s an abnormal change in the cell size, shape, appearance, and the organizational structure of the cells. It becomes very different. I’ll not talk in details about it; we’ll take about it later.

Dysplasia is caused by persistent injury or irritation. It often occurs in the cervix, oral cavity, gallbladder (not very much actually), respiratory tract, and other areas also, and it can occur in other tissues not just in an epithelium.

A student asked: Is dysplasia reversible or irreversible?

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Columnar (gastric) metaplasia in esophageal squamous

epithelium

The Doctor: some cases are reversible. You’ll see later on that dysplasia is graded; low-graded and high-graded. The low-graded ones sometimes are reversible, because they may also be related to infection. For example, in your mouth it could be related to bad dentures (teeth), it will continue to rub into the tooth mucosa. Treat the tooth, the mucosa may heal (if it’s low-graded). The same applies to the cervix, many of them are due to infection by human Papillomavirus. Treat the virus, this will heal.

This is a cervical dysplasia (picture below). If you see, these cells to the left are normal whereas the cells to the right are much more hyper chromatic and it’s very cellular as well!

Intracellular Accumulations & Deposits

Intracellular accumulations are sometimes an adaptive process, sometimes are a degenerative process, but in general we just call them accumulations & deposits.

They can occur in any of the following ways:(I mean, many types of tissues and cells accumulate various materials inside them, and usually these materials should not accumulate, why does it accumulate? Maybe it’s related to one of three things:

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1)Excessive production of a normal product but the metabolic function is inadequate: There’s such a heavy load of that substance coming to the organ or the cell & it can’t deal with it, just like a small room with a hundred patients inside, it’s not possible, they accumulate as they are in it. This is excess production of a normal product but the metabolic function is inadequate to deal with it and we shall see this in the fatty change in the liver: too much fat, although it’s a normal fat and a normal liver, but it’s too much!

2)Normal or abnormal substance accumulates but there’s a genetic or acquired defective enzyme mechanism for removal: The second type is a normal or abnormal substance, let’s say a lipid (you have normal lipids & abnormal lipids, abnormal glycogen, abnormal proteins, and so on ...) Whether it’s normal or abnormal, they accumulate and need to be moved out by an enzyme system, and that enzyme system is defective (maybe an inherited defect). For example: you have an enzyme which is Alpha 1-antitrypsin. This enzyme prevents the destruction of tissue like collagen. It’s synthesized in the liver and then released. If there are some defects in its production, it remains in the liver, accumulates in the hepatocytes, and causes a disease and a deficiency in the blood (anti-trypsin deficiency).

3)Abnormal exogenous substance accumulates because the cell doesn’t possess a mechanism for removal: Sometimes, the substance may be foreign to your body, and there’s no systematic mechanism to deal with it. For example: carbon that is generated from cigarette, or heavy smoke industrial areas. The majority of patients or abnormal people have carbon deposits in their lungs & there’s no enzyme system to get rid of that carbon.

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Accumulations include:1) Water: it is the easiest thing to accumulate, and this is a

picture (below) which’s called "hydropic degeneration" or "cloudy swelling". (Hydropic means from water), (cloudy swelling: the whole organ becomes heavier and the cell appear clouded). For example, when you have initial failure in the sodium pump, the water enters into the cells, and if the water is a lot, it will cause an enlargement of the cell and the organ.

These are the cells that are lining the renal tubule.(the picture above)

** Hyaline change: this is not really an accumulation, but it is sometimes included in this category. It’s really a change in the cytoplasm of the cell; it’s really a degenerative change and the cytoplasm takes a homogenous glassy appearance. This is a hyaline accumulation here in the kidney (maybe the doctor refers to the picture above), but it’s more typical in hypertension in the wall of the blood vessels. It’s not considered an accumulation; it’s just called a change.

2) Fatty change: Much more important than hyaline change is the fatty change. The abnormality of fatty change is steatosis. Steatosis occurs mainly in the liver, and the accumulation involves triglycerides.

3) Cholesterol and Cholesterol Esters is another type of lipid.

4) Proteins: different types of proteins.5)Glycogen6) Various kinds of Pigments7)Calcium 8) Amyloid deposits

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Hydropic degeneration

Fatty change

Fatty change is a very very common change. It can occur even in healthy people without any symptoms. It’s a reversible accumulation of excess lipid.

Hydropic degeneration is reversible, fatty change is reversible, & hyaline change is sometimes reversible.

In the fatty change the liver is the main organ. You may have it to a lesser extent in the heart or in the kidney, but it’s always mentioned in the liver. In little amount, it does not cause any damage or cause any changes in the gross appearance of the liver. But when it's in huge amounts, it causes liver enlargement.

What happens is that the fatty acids enter into the hepatocytes; there you have the triglycerides, and these are changed to cholesterol and phospholipids, and the result of the situation is ketones. The amount of ketones that are produced increases in cases of starvations, diabetes, and mutations (forms ketotic bone).

However, what remains of the triglyceride in the liver is usually linked to a carrier system of apoproteins, forming the lipoproteins, and then they exit the liver. Lipoproteins: are combinations of lipids and proteins.

If you have a protein deficiency, then the lipid will accumulate.

There are many enzyme systems involved; anything that can’t deal with the excess fat will lead to fat accumulation. So, the

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excess accumulation may result from a defect from any of the above components.

What are the causes of fatty change? The common causes are:1- Alcohol abuse: it is a very common cause in alcoholics. 2- Diabetes mellitus: these both of them are the most common types.3- Certain toxins (you see it in carbon tetrachloride poisoning). 4- Starvation and protein malnutrition 5- Any anemia, ischemia, or oxygen lack to the liver: are causes of accumulation of fat. 6- Drugs: certain drugs may cause it.7- Some types of fatty liver occur during Pregnancy, especially during the latter part of pregnancy “the 9th month”. This may be very dangerous, and the patient may pass into 'acute" liver damage and this is called "acute fatty liver of pregnancy", and there’s high mortality in that.

Small amounts of lipid accumulations are common and usually harmless. They are incidental bindings in the liver biopsy.

The morphology of the fatty liver (gross appearance of the liver) depends on the severity; either normal or very large. When it’s very large, the dark reddish color becomes yellowish and greasy, because of the presence of fat.

* Histological, there are two types of accumulations: 1- It accumulates in the hepatocytes as small vacuoles in the cytoplasm with a nucleus in the center, and that’s called micro-vesicular fatty change. You have many vacuoles not one, many small small vacuoles inside the individual hepatocytes, and this is seen in the acute fatty liver of pregnancy.

2- The second type is the macro-vesicular fatty change in that you have a single fat vacuole which pushes the cell to one side, as we shall see. The nucleus is pushed to one side almost like a signal cell (signal cells are cells in cancer). And these vacuoles are big vacuoles. This is what occurs in the usual steatosis. In steatosis especially in alcoholics, you find a lot of acute

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inflammatory changes as well. And this is called acute fatty liver, acute hepatitis, or acute alcoholic hepatitis.

Cholesterol and cholesterol esters

These accumulate in Macrophages which are also called "foam cells" ("foam cells" is not really the scientific term, a macrophage is), and in some cases these macrophages accumulate together and join to form a multinuclear foreign body giant cells. These cells are combinations of many epithelioid cells which are a type of macrophages. These macrophages take up the materials and engulf them. For example, in case of atherosclerosis or hereditary conditions, you can see multinucleated giant cells, containing what’s called "cholesterol crystals". During the procedure for preparing a slide, the slide passes into "xylene" ( مللشحو بيذُم ). It dissolves out the fat, and what we have is an empty space, and the cholesterol comes in crystals. *couldn't hear the rest clearly*

In hereditary conditions like acquired hyperlipidemia, some people have high lipids, they go to the hospital and they give blood samples for the assessment of the lipid profile. The lipid profile will tell you about the amount of cholesterol, free fatty acids, and so on that are present in the blood. Some families have very high contents of these components, and they are much more susceptible to atherosclerosis and myocardial infarction.

These patients, whether it’s acquired or it’s hereditary, they have yellow nodules especially on the skin around the eyes; you see many people have yellow patches around the eyes; these are full of fat. Also, cholesterol deposits in the intima of the aorta which makes it have yellow streaks in appearance.

Proteins accumulation

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A Fatty Liver

You know proteins are used by the body and some are passed into the urine, and there are certain conditions in the kidney or in the intestine which are protein-losing. For example, in cases of mal-absorption a lot of proteins will be lost, and there are syndromes in the kidney where much of the protein is lost instead of being reabsorbed in the tubules.Nephrotic syndrome: is when you lose a lot of proteins in the urine, and you can see proteins are accumulating in the renal tubular epithelium.

Plasma cells produce immunoglobulins as you know. In certain conditions there are some immunoglobulins more than others, and you see them accumulating inside the cytoplasm of plasma cells. And this is even seen in reactive plasma cells where they are called Russell bodies.Mallory bodies are another thing seen in the liver (in alcoholic liver disease) and these are eosinophilic intracellular hyaline bodies inside the liver related to damage in certain proteinous materials in the liver.

Glycogen accumulation

Glycogen usually accumulates as "glycogen storage disease". It accumulates in the osteocytes, in the liver, in the bone marrow, and other sites.

This is the liver (below), and these are the strands of Mallory bodies in alcoholic liver, and you can see the fat vacuoles. So both Mallory bodies and fat are seen in alcoholic liver disease.

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Finally, the doctor gave us information about the syllabus of pathology which you can find at the site (www.med4just.com/sama).

(Sorry for any mistakes ….. Best luck all! Do your best always! :D)

“Do not pray for easy lives. Pray to be stronger men! Do not pray for tasks equal to your powers. Pray for power equal to your

tasks.”

☺Done by: Hadeel Al-Kofahi☺

الحمد لله الذي بنعمته تتمالصالحات

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Mallory hyaline in the liver

(alcoholism)

fat