Video: Parathyroid gland histology

Hello there! You're just in time. I'm looking for a group of pea-shaped endocrine glands, but I'm not quite sure where to find them. Yikes! Not down there. Let's try a bit higher up, shall we? Okay. Yes, we need to focus on the more superior part of the body. You got it! It's in the neck.

Next clue: It helps to regulate calcium levels in the blood. Well, that's technically correct. The thyroid gland does produce hormones that regulate blood calcium levels, but that's not what we're looking for. The tiny endocrine glands that we’re on the hunt for here are on the back of the thyroid gland – the parathyroid glands. Let's find out what they're really made of now as we explore the histology of the parathyroid glands.

Before we get started, here's a quick overview of what we'll cover today. We'll begin by looking at the macroscopic features of the parathyroid glands to remind ourselves about the anatomy without a microscope. We'll then dive into the good stuff and cover the histological features including the vasculature found in the parathyroid glands and cells that make up the gland’s parenchyma. Finally, we'll wrap up the tutorial by looking at some clinical notes related to the glands.

First up, however, a few quick facts about the gross anatomy of the parathyroid gland.

So, the parathyroid glands are small ovoid structures which are part of the endocrine system and are found on the posterior aspect of the thyroid gland. There are usually four – two superior and two inferior glands, or two left and two right glands, whichever way you prefer to look at it. Specific cells within this gland produce a hormone which is conveniently known as parathyroid hormone or PTH. This plays a role in regulating blood calcium levels. More specifically, when parathyroid cells detect a fall in calcium levels in our blood, the parathyroid glands synthesize and secrete PTH which basically causes bones to release calcium into the blood. The antagonist to this hormone is calcitonin, which reduces blood serum calcium levels.

All right, time to get down to the nitty-gritty of what actually makes up the parathyroid gland. Here we go.

This is a histological image of the parathyroid gland and this is the image we'll be focusing on throughout the tutorial. The section has been prepared with hematoxylin and eosin stain, often called the H&E stain. H&E is the most commonly used histological stain due to its simplicity and ability to clearly define the basic morphology of a tissue by staining nuclei and cytoplasm in different colors. The hematoxylin component is applied first and stains the nuclei blue in addition to parts of the cytoplasm that contain RNA. The sample is then counterstained with eosin, which stains proteins and cytoplasm varying shades of pink.

Like many organs, the parathyroid gland is surrounded by a thin, fibrous capsule which separates from the surrounding tissue of the thyroid gland. Connective tissue septa extend from the capsule into the gland roughly dividing it into smaller divisions known as lobules. These lobules are not very well-defined throughout the parathyroid gland, but serve to separate closely-packed cords of cells which we will see shortly.

Alright, time to switch gears and take a look at the various cells that make up the parathyroid gland.

There are two main types of cells that we'll explore today. The first are the chief cells, also known as the principal cells. These cells are the main, most numerous type of cell in the parathyroid gland. These are the cells that synthesize, store, and secrete parathyroid hormone. Chief cells are small, about seven to ten microns in diameter, present a centrally located nucleus, and contain vesicles of glycogen and lipid droplets. Their appearance, however, differs according to their level of activity which we'll see shortly.

Here are some active chief cells. When we say active, we mean they are actively producing parathyroid hormone. Just next to this bunch of active chief cells are inactive chief cells. As I'm sure you've already guessed, these cells are not actively producing PTH. Histologically, we can see differences between these types of chief cells. The active chief cells stain darker and are more densely packed. This is because they have large golgi complexes and many vesicles containing PTH. Inactive chief cells, however, appear more histologically clear. They don't have the large active golgi apparatuses, but do contain more glycogen granules than the active cells. There are generally more inactive cells than active chief cells – a ratio of about four to one.

The second major type of cell in the parathyroid glands are the oxyphil cells. These cells are slightly larger than chief cells at about twelve microns in diameter. They contain more cytoplasm, which helps them give a different staining color as you can see here. Oxyphil cells only begin to appear in the parathyroid glands around puberty and then increasing number with age. Their function, however, is still uncertain.

In parts of the parathyroid gland, we can find adipose tissue in the stroma. This is also something that begins around puberty increasing with age and is proportional to the amount of fat in the rest of the body. By adulthood, adipose tissue accounts for about one third of the mass of the parathyroid gland. It is a feature that can be used to help differentiate between sections of thyroid and parathyroid tissue.

When taking a look at chief cells around areas of adipose tissue, we can see they are arranged into cordlike cell clusters between adipocytes. Because adipose tissue appears in the parathyroid gland from puberty, this is an arrangement that will only really exist from then and into adulthood.

Like all endocrine organs, the parathyroid glands, of course, need blood supply, so let's take a look at how vascular structures appear within the gland. Richly oxygenated blood is delivered to the parathyroid glands mainly via branches of the inferior thyroid artery or from anastomosis with the superior thyroid artery above. We can see a cross-section of one of these small arterial branches highlighted now.

When looking for arteries in histological sections, start by finding a lumen typical of blood vessels, but one that is surrounded by a much thicker layer of tissue than, say, veins. Arteries have clearly distinguished layers – the tunica intima, media, and adventitia which can often be identified in histological images as well.

In order for gaseous exchange to occur, the blood needs to travel into capillaries – a few of which we can see now highlighted in green. They are also necessary for hormones produced by the parathyroid gland to be released into the bloodstream so they can be circulated around the body. You can see in the lower magnification part of the image that capillaries are less defined. They have much thinner walls and arteries at just a single cell-layer thick, so can be difficult to identify. However, if you can identify red blood cells on the slide which stain bright red in H&E sections, this can help to find the capillaries.

In the parathyroid glands, we find fenestrated capillaries which are typical of endocrine organs to ensure easy passage of hormones into the blood.

So, if we have arteries and capillaries, we must have veins as well, right? Highlighted now is a vein within the parathyroid gland. On histological images, veins can often be identified by their thin walls and relatively large lumens. Remember veins carry deoxygenated blood from various tissues back to the heart.

Another type of vessel that can be identified in this tissue is the lymphatic vessel we can now see highlighted in green. In the parathyroid glands, lymphatic vessels collect fluid and waste from the interstitial space and eventually return that fluid to the cardiovascular system.

Now that you've identified the cells and structure of the parathyroid gland, do you think you're able to notice if something was wrong? Time for a clinical note.

In this image, we're looking at what's called a parathyroid adenoma. An adenoma is a benign tumor developing in glandular tissue. In this case, that glandular tissue is of the parathyroid gland. We can see that the parathyroid adenoma is made up of chief and oxyphil cells. The additional chief cells will produce parathyroid hormone just like the normal chief cells of the parathyroid gland. This leads to a condition called hyperparathyroidism, which means there is too much activity in the parathyroid gland and too much parathyroid hormone being produced.

Because parathyroid hormone stimulates the body to increase its calcium levels, parathyroid adenomas will ultimately lead to a rise in blood calcium levels. To treat this problem, most commonly, parathyroid adenomas will be removed surgically.

And now you're an expert on the histology of the parathyroid gland. Before I let you go, here’s a quick review of what we looked at today.

We started by looking at a histological slide at the whole parathyroid gland and identifying a few larger structures – firstly, the capsule surrounding the gland itself and the intraglandular septa that project into the gland. Then we looked at poorly-defined lobules the septa divide the gland into. Our next port of call was the cells of the parathyroid gland starting with the most common ones – the chief cells. Chief cells can be in one of two forms – dark-staining active chief cells as highlighted in this image or pale-staining inactive chief cells. We saw that the chief cells sometimes build structures called pseudofollicles, which can look like follicles of the thyroid gland.

Another group of cells in the parathyroid gland are the oxyphil cells, which still don't have a fully understood function. We identified some adipose tissue which only begins to appear in the parathyroid glands around puberty and can cause the chief cells to take on a cordlike cell cluster appearance. Finally, we learned how to identify the vascular components within the parathyroid gland beginning with a thicker-walled artery. We then saw the very thin-walled capillaries where gas exchange occurs and parathyroid hormone enters the bloodstream, and we identified a vein which removes deoxygenated blood from the gland.

We also looked at a vessel of the lymphatic system which helps pick up extra fluid from the interstitial space. And the last thing we chatted about were parathyroid adenomas – benign tumors of the parathyroid glands that cause hyperparathyroidism increasing the levels of calcium in the blood.

And that brings us to the end of our tutorial on histology of the parathyroid gland. I hope you enjoyed it and thanks for joining me.