Wednesday, November 18, 2015

Early wrong ideas about how our glands work

Let's talk about glands! These highly specialized bits of tissue put together and pump out useful compounds to ensure we stay healthy and can do the things animals do (aim to reproduce, mostly). Exocrine glands release fluids such as sweat, saliva, milk, tears, mucous, and bile into segments of our digestive tract or onto the surface of our skin (and eyes). Endocrine glands toss hormones and other regulatory molecules into our bloodstream, to be carried to distant locales bearing instructions to stay the course (i.e. homeostasis). Our understanding of the human body is based upon the cumulative investigations of many scientists over many years. As part of this process, explanations for why or how sections of us work underwent multiple rewrites and occasionally were scrapped entirely. In the case of glands, until relatively recently their function was often mistaken because body investigators had no idea about their ability to produce hormones (you can't see tiny molecules when you cut open a cadaver). This post is about the folks who in earlier times tried valiantly but failed to correctly assign functions to some of the endocrine glands scattered throughout our bodies.

Andreas Vesalius (1514-1564) preparing to observe a gland or two

At the front of the neck, locked in a tight embrace with the windpipe, lies a fleshy hormone-making butterfly otherwise known as the thyroid gland. By secreting the hormones triiodothyronine, thyroxine, and calcitonin, the thyroid can broadly regulate our growth and development. Activities influenced by thyroid hormones include fundamental cell-based metabolic processes such as protein synthesis as well as the actions of other hormones (e.g. calcitonin counters the effects of parathyroid hormone). Thanks to goiter (having a super swollen neck due to your thyroid gland becoming enlarged), people indirectly knew about the existence of the thyroid gland thousands of years ago. Based on an early observation that the thyroid gland is often larger in women compared to men, anatomists wasted a couple of centuries believing the gland was purposefully (by God, obvs) enlarged in ladies to enhance their beauty ("giving grace to the contour of the neck"). Very silly. Andreas Vesalius (1514-1564) illustrated and described the human thyroid gland in his seminal anatomical text De humani corporis fabrica. At this time, the popular (and incorrect) notion was that the thyroid served to produce a lubricating fluid for the larynx (the part of the windpipe containing the vocal folds). This line of thinking was based on the close proximity of the thyroid to the larynx and the presence of a viscous fluid (later determined to be a concentrated solution of the protein thyroglobulin, used to make thyroid hormones) within follicles of the gland. In the 17th century, English anatomist Thomas Wharton gave the thyroid its name and speculated about its functions, which he erroneously thought included: (1) serving as a hub for the movement of fluids from nerves into veins, (2) warming the larynx (via two arteries supplying lots of blood to the gland), (3) lubricating the larynx so as to "render the voice more smooth, melodius, and agreeable", and (4) contributing to the shape of the neck (by filling in space around the larynx). After Wharton, some scientists came to believe the thyroid, given its location and excellent blood supply, helped to ensure a constant supply of blood to the brain. This idea was wrong.

Four bean-like parathyroid glands behind a larger butterfly-ish thyroid gland (Source)

Positioned right up against the back of the thyroid gland are pea-sized glands (usually four, although some individuals have as many as six or as few as one) appropriately called the parathyroid glands. Their eponymous hormone acts on bones, intestines, and kidneys to control the amount and distribution of calcium in the body. Due to their small size and nearness to the thyroid, they were the last major gland to be discovered in people. This discovery was made in 1880 by a Swedish med student by the name of Ivar Sandström. Sandström's finding was basically ignored for a decade until Eugène Gley (1857-1930), a French physiologist, came along. Gley realized people who died from involuntary muscle contractions (tetany) following the removal of their thyroid only did so because their parathryoid was inadvertently removed or damaged during the surgery. Based on this finding, Gley (wrongly) concluded that the role of the parathyroid was to supplement the actions of the thyroid. In reality, the removal of the parathyroid glands (and the hormone they secrete) brought about tetany due to a drop in blood calcium levels (since muscles require calcium to work properly).

The triangular adrenal glands have been known since ancient times. They sit atop the kidneys, producing a collection of hormones able to regulate everything from blood pressure to immune system activity to whatever it is that sex hormones do. The gland consists of two structurally and functionally distinct parts (medulla and cortex), which managed to confuse anatomists well into the 19th century. The first unambiguous and accurate description (and illustration) of the adrenal glands was made by Bartolomeo Eustachi (aka Eustachius), a 16th century Italian anatomist who had an ear tube named after him. Eustachius and other early investigators of the human body (wrongly) thought the adrenal glands assisted the kidneys in some way, given their close proximity. Moving onward in time, the 17th century was a golden age for European anatomists coming up with incorrect ideas about what the adrenal glands did:

  • Jan Baptista van Helmont suspected they released a substance capable of inhibiting the formation of kidney stones (calculi).
  • Adriaan van den Spiegel believed they had an entirely structural role which involved holding the stomach in place and filling up the space between the kidneys and the diaphragm.
  • Caspar Bartholin the Elder looked to Galen to explain the function of the adrenal glands. He believed them to be hollow structures capable of filling with "black bile" absorbed from blood leaving the liver and spleen, which was then passed to the kidneys for elimination.
  • Not content to focus on the thyroid, Thomas Wharton suggested the adrenal glands functioned to transfer an unknown material from the nerves of the neighbouring solar plexus into the bloodstream. All about nerve-vein transfer, Wharton was.
  • Antonius Molinetti figured they prevented a fetus from making urine by diverting blood away from the kidneys. This idea was based on the adrenal-to-kidney size ratio being relatively higher in a fetus compared to an adult. It's now known that fetuses freely urinate while inside the womb, cycling amniotic fluid through their bodies, but in Molinetti's time this was considered to be harmful to a pregnancy.

The 18th century brought a couple more subscribers to the false notion the adrenal glands exist solely for use by a fetus during its time in utero. Jean-Baptiste de Sénac reckoned the glands were responsible for making meconium, the first poop of a newborn baby. His contemporary, Giovanni Battista Morgagni, thought the adrenals drained fluid from the intestines while the fetus was in the womb.

The cute yellow kidney toques are the adrenal glands (Source)

Behind the stomach lies the pancreas, which is definitely a type A as far as glands go. It's an exocrine gland, dumping digestive enzymes into the duodenum to help break down food. Yet it's also an endocrine gland, producing the hormones insulin, glucagon, and somatostatin. These regulate blood glucose levels as well as the production of other hormones outside of the gland. The pancreas was first described and named by physicians in ancient Greece. Early European anatomists thought the pancreas served as a pillow of sorts to protect the stomach or nearby major blood vessels from harm. Franciscus Sylvius (1614-1672), a Dutch polymath, kind of but not quite figured out the digestion-aiding role of the exocrine pancreas. He believed the liquid secreted by the gland served to reduce the thickness of the mucous lining the intestine (thought at the time to originate from swallowed spit) and help ensure the useful components of ingested food made it to where they needed to be. I'll give him part marks.

Deep within the brain lies a cone-shaped and pea-sized gland. It secretes melatonin, which influences sleep patterns and may additionally be involved in all sorts of body processes. The pineal gland, as it's called, was viewed by the ancients as a portal connecting us with the spiritual world. Building on this idea, René Descartes (1596-1650) thought the gland was where our souls interact with our physical bodies. In the centuries that followed, scientists grew to believe the pineal gland was the brain's equivalent of the coccyx (tailbone), a leftover from evolution of no great importance. With the discovery of melatonin, this proved to be not quite the case.

A brain cut in half (sagittal style), with the pineal in red and the pituitary in yellow

At the base of the brain, not too far away from the pineal gland, hangs another pea-sized gland known as the pituitary. It's made up of two major lobes and is capable of synthesizing an impressive array of hormones. Aspects of human existence regulated by these hormones include growth, stress, sex, pregnancy, childbirth, lactation, and how often you have to pee. Hilariously and tragically (for those with pituitary hormone imbalances), up until the early 20th century folks believed the pituitary existed only to drain mucus (pituita is Latin for phlegm/mucus) from the brain to the nasal cavity. This idea is thought to have originated with the ancient Greeks, who apparently thought the brain made snot.


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