Mouth, oesophagus, and stomach.

Mouth, oesophagus, and stomach

Section I: Know thyself.

Blog 2: Mouth, oesophagus, and stomach.

Quote: “An army marches on its stomach.” Napoleon Bonaparte

The upper gastrointestinal tract, my beginning, is the composite organ of digestive anticipation and preparation of food for absorption. By upper gastrointestinal tract I mean the mouth, the pharynx, the oesophagus, the stomach, and sometimes we include the first part of the small bowel, due to shared pathology, symptomatology, embryological origin, and mode of investigation.

However, we’ll leave the first part of the small intestine, the duodenum, functionally the start of the major absorptive organ, to the next blog.

My stomach is all about preparation – preparing the food and preparing ourselves to absorb nutrients. The eyes, the nose, the ears, and even our mind – yes, even a mind devoid of sensory input with just a thought – all help prepare the gastrointestinal tract to receive the coming morsel or feast.

We are captivated by cooking shows from Masterchef to Maggie Beer, but, despite Willy Wonka’s attempts, television remains purely visual. But television food, and watching food preparation, remains nourishing to us; it piques our interest. Taste is important, but it is only a part of preparation, a deeply physiological, vital, and ancient process.

Food is part of some of our earliest and most intense memories. I remember food from sight, sound, smell, and touch, but also by how it made me feel, what was the emotion as much as what was the taste.

The texture of toasted coconut on the tongue, the earthy smell of rosemary, Digger’s rosemary, on resinous fingertips, the smell of the vine and the stalks of your own tomatoes, and the crackle of sherbet through a difficult licorice straw.

Any of you who have salivated by seeing, smelling, and thinking about food knows that eating is not just taste – digestion consumes all of one’s senses. Like medicine or science, cooking done well is thrilling.

As a thought experiment, try it now, just THINK about picking a heavy lemon from a tree. THINK of the smell of the released citrus oils spraying from the peel onto your hand when it is twisted from the tree. THINK about taking it into the kitchen and cutting a wedge.

Now, in your “mind’s nose” smell again the oils and the acids, bring it to your “mind’s mouth” and then, with one large bite, chomp down releasing the juice – the sour, sour juice – to coat your mouth and the sides of your tongue.

The saliva will flow, instantly. This digestive anticipation reflects the intimate connection between mind and the gut, not surprising given the many connections I have with my cerebral friend, but wonderful when contemplated.

We really have two brains, although Brian or Briana the brain doesn’t like to hear me say it. We of course have the brain, the familiar, walnut-shaped one (primarily in shape, although, occasionally, in size) at the top of our spinal cord, and a second massive concentration of neural circuitry within the gut, the enteric nervous system, that operates our digestive tract, what has been termed the second brain.

All the senses in concert with our “brains” help to prepare, to ensure that the food is gratefully and safely received to extract every nutrient. Saliva at the ready, check. Digestive juices primed, check. Getting the mesenteric (intestinal) blood flow ready to absorb, check.

Even though I am the bowel, I do contain memories of a sort. Have you heard of Pavlov’s experiments with dogs? Ivan Pavlov, Russian physiologist, who won the 1904 Nobel prize for physiology and medicine for his discovery of the conditioned reflex.

The conditioned reflex is a subconscious physiological response to an associated stimulus. His experiments were perfect, empirical evidence that food evokes a “memory” in the gut, not wholly contained within the gut perhaps, but “memory” with gut consequences nonetheless, just as the memory of the lemon wedge just made you salivate.

In Pavlov’s experiments, he proved that salivation could be induced without presentation of food, but merely through a secondary signal, a bell. The dog was “conditioned” to associate the peel of the dinner bell with, of course, dinner. This association was so strongly conditioned that the dog’s brain-gut axis “remembered” that the bell was followed by food, and thus the mere ringing of the bell led to salivation, and to several other physiological digestive responses as well.

This experiment has become entwined within common English, the term Pavlovian, to describe any conditioned, automatic response to a stimulus.

The mouth is the entrance to our second membrane, the seat of so many senses and sensations – taste, smell, touch, and kiss. It is the home of the smile that you receive instinctually from your newborn baby, and that you gave instinctually to your parents. The simple curl of the lips that makes each generation love the next completely.

The lips and the mouth also engage instinctually to suckle, the reflex, a pouting of the lips in response to a stimulus – the brush of a baby’s cheek against their mother’s nipple. This reflex is lost with maturation, but strangely may be rediscovered following brain injury in older age, by the tapping of the lips with a doctor’s finger to elicit a pout, termed the snout-pout reflex.

The mouth forms words with our wind, crafts laughter and song, and allows us to whisper breathy secrets. Biologically, however, the mouth is, above all, a voluntary aperture through which human nutrition is made possible.

The mouth reveals much about our health. A doctor is taught in a complete clinical examination to smell their patients’ breath (usually performed with a theatrical hand gesture, to waft their breath toward the examiner’s nostrils). But usually such signs of health or disease are self-evident in the mouth, and they do not require arcane hand gestures or expensive tests. It is the smell of cigarette smoke or alcohol at 10am in the morning, or stained, crooked, or absent teeth.

Poor dentition remains an immediate barometer of a patient’s overall health and, even in a rich country like Australia, signals patient need. A Pavlovian association for the doctor alerting them to all the risks to health that poverty brings to their patient.

In terms of preparation, the mouth receives the food, the drink, the drug. The teeth and tongue mechanically dissociate the food, chew it up with our strong cheek muscles, into a soft mass, wetted by saliva. The process of chemical digestion also begins with amylase produced by the salivary glands, starting the breakdown of carbohydrates.

The tongue and the oral muscles form the food into a swallowable packet, called a bolus. The bolus is then pushed consciously to the back of the mouth as one initiates a swallow and then, whooosh!

Thereafter, the gastrointestinal tract is placed on autopilot. It is too hard, too intricate with too many rapid and coordinated reflexes, and frankly far too important, to let us do it ourselves, as it were.

The bolus of food, at least in health, is rapidly passed as a unit through the muscular pharynx. The epiglottis covers the larynx as the upper oesophagus relaxes in turn, in perfect coordination, to receive the bolus, propelling it through the muscular pipe until it reaches the lower oesophageal sphincter.

This sphincter, the term given to any circular band of muscle, is usually closed. It has the very important job of keeping food and acid in the stomach. The lower oesophageal sphincter is usually contracted, but, of course, it must also be able to open when required, to permit nourishment. And thus, intermittently, it needs to relax to permit the passage of the next mouthful, the next bolus, into the stomach.

As we age, alas, the lower oesophageal sphincter may start to show transient lower oesophageal relaxations. Australian researchers were prominent in establishing the role of these intermittent relaxations[4]. When there are unnecessary and regular relaxations, and thus failures of the sphincter, acid can “reflux” (reverse flow) back up into the oesophagus, causing common reflux disease manifested by the symptoms of heartburn and regurgitation of bitter, acidic fluid into the back of our mouths. Many of you will be experiencing a little reflux now, particularly if you are reading this lying in bed, after a large or late dinner, particularly if combined with one too many glasses of wine.

From the oesophagus, the stomach then acts to further break up the meal, the bolus, into smaller pieces. Its strong muscular walls churning and mashing the steak and chips, the chick-peas and lentils, the hot dog served heavy on the mustard.

The stomach is also a very unusual environment, unusual at least for our bodies, because it is so very acidic. My stomach is at its essence a living sac of hydrochloric acid. “How acidic?” I don’t hear you ask. Well, on a scale of 1-14, because, frankly, that is the scale (called pH), with 1 very acidic and 14 very unacidic (or alkaline), stomach acid can be as low as 1.

Stomach acid is a very strong acid. To provide some contrast, lemon juice has a pH of 2.4 and vinegar a pH of 2.8. These are both less than 1/10th as acidic as stomach acid (pH is a logarithmic scale, meaning that every change of one represents a 10-fold change). But the stomach lining has evolved to manage this. Indeed, these conditions evolved through a selective advantage associated with a highly acidic stomach environment.

One of the stomach’s acid-defence mechanisms is the secretion of a thick mucous layer laced with bicarbonate, a snotty antacid barrier, to protect its lining from being eaten away by the acid within.

The acidic gastric environment is important for several reasons. Firstly, it helps to chemically breakdown food and to deactivate any toxins or kill pathogenic living micro-organisms that might be consumed. Of course, not everything is killed. In fact, although it was once thought that the stomach was too acidic to support micro-organisms, Robyn Warren and Barry Marshall, two scientific heroes of Australian research and gastroenterology, proved that this wasn’t the case, but more on that later.

The stomach is also a reservoir to help hold a meal and deliver it to the small intestine for further digestion and absorption when, and only when, the small intestine is primed and ready to receive it. At that point, the muscular bag starts to contract in a coordinated fashion, pushing the gastric bolus into the small intestine, where it is now referred to as chyme (pronounced kime, from the Gk: khymos, for juice; an apt description as it is the juice squeezed from the meal that we have just eaten).

It makes sense to now reflect on the stomach lining itself. What living stuff am I made of and how is that stuff arranged?

The gastrointestinal tract is a hollow tube, a tube arranged radially, as well as longitudinally. The gastrointestinal tract is comprised of concentric layers that tell the story of their function, just has a geologist can interpret the story of a valley, or a river, or a mountain range from the layers of rock eroded on view.

A cross-section of the tube, at any given site from the stomach to the rectum, with the oesophagus and anus, slightly different, will, more or less, begin with an outermost, surrounding fibrous connective tissue (serosa or adventitia, depending on the site) layer.

Beneath, deep to, closer to the lumen, there is a muscular layer. Automatic, non-conscious muscle, called smooth muscle. This layer provides the rhythmic contractions to churn and propel food from mouth to anus along the gut – a process called peristalsis.

The next layer, once again closer to my lumen, is called the submucosa. The submucosa is a layer of loose connective tissue, which means that the cells are less densely packed and connected by an interlacing web of extracellular molecules like collagen.

This layer is important, as it provides a connection between my outer muscle and my inner gut lining. The submucosa also permits the passage of important structures such as blood and lymphatic vessels and nerves. Think of the submucosa like a connecting sponge or foam that provides a space for other structures to run through as well as providing flexibility along my beautiful, boa constrictor-like, length.

Moving further inward to the lumen, the final layer that rests on the submucosa is, not surprisingly, called the mucosa. The mucosa, the innermost layer consists of a single layer of gastrointestinal cells, at least along the stomach, small and large intestines. This layer is made up of a type of cell called epithelium, because it is a single layer it is termed simple epithelium. One cell thick, roughly the width of a thin human hair, separating the sh*t from the fan. These cells must maintain all of the regional secretory, absorptive, barrier, metabolic, and immune functions required of me, the gut.

Epithelia are supreme “lining” cells, they form large sheets beautifully, with strong connections, and junctions, to their immediate neighbours, locking arms to form an imposing barrier. They are also connected by equally strong connections to the deeper structure of the basement membrane and the looser connective tissues beyond.

A single layer provides the opportunity for the first, a primary, axis of organisation. The epithelial cells lining the gut can be polarised, organised into a top and a bottom, or luminal and basal, parts.

That is, a bit like the Protozoa I mentioned in the first blog, different parts of the membrane can do different things. So the part of the cell that is next to the lumen, the luminal part, may be specialised for secretion of products like acid or digestive juices, mucus or absorbing nutrients. Whereas the lower part, basal part, adjacent to the basement membrane may be specialised for attachment and for passing nutrients within the cell more deeply to be absorbed and transported to the rest of the body.

The epithelia also have a secondary axis of organisation, beyond luminal and basal poles of the cells. The single cell layer of cells, the continuous sheet of cells that line my tube, are also folded into undulating microscopic peaks and valleys.

The arrangement of this folding provides discrete organisation, and, with it, functional units called glands. Glands have several important features.

Firstly, they are derived and sustained by distinct collections of dividing cells within the deeper part of the gland, called stem and progenitor cells. As a stem cell at the base of the gland divides, one cell becomes two and a new cell is born. By and large, one of these cells lives on as a stem cell, while the other matures into functional cells secreting or absorbing.

As this happens, the cell moves up its position in the gland towards the lumen. Until, towards the top of the gland, the cell finally is worn out, too old to do its job any longer, and it is sloughed and released into the lumen, to be replaced by a new cell, arising from the gland as it had done, biting at the heels of its elders.

This represents a continuous, and gland specific, conveyer belt of cellular birth, function, and death. The gland is a microscopic analogy of our life, and one “cell” in its time plays many parts.

The renewal, the lifespan, of the cells in each gastrointestinal gland varies, but it is a timeframe of days to weeks and only, very occasionally, longer. That is, the cells that made up my gastrointestinal lining a fortnight ago, have pretty much, with a few exceptions, done their job and died, sloughed-off like gut dandruff, gut dust, floating into my lumen, to be flushed away.

The glandular structure also allows functional compartmentalisation, so that different cells born within the gland can mature, or differentiate, into distinct functional cell types, to provide different roles. Under normal conditions the cellular birth rate, stem cell division, cellular maturation, differentiation, and programmed cellular death, known as apoptosis, are tightly coordinated.

The regulation is beautiful and precise, it must be, for when there is dysregulation, disease rapidly ensues. This concept of the gastrointestinal gland is important, as it can help us understand how diseases such as cancer occur and thus how they may be prevented.

The third, and I promise final, axis of gastrointestinal epithelial organisation is the longitudinal or regional organisation of the epithelial sheet. The glands of each section of the gastrointestinal tract, from proximal stomach to distal stomach, then small intestine and ultimately colon and rectum, each have a characteristic glandular organisation that house different types and combinations of functional cells.

A proximal stomach gland looks and is different from a distal stomach gland which is different from the small intestine, which is different again from a colorectal gland. But, in each region the presence of a gland provides an organisational unit, fit for its distinct organ-specific purpose.

The gastric glands in the first part of the stomach (the gastric body and gastric fundus) make mucus, acid, pepsinogen (a digestive enzyme), ghrelin (a hormone affecting appetite) and intrinsic factor (to help with absorption of vitamin B12). In the distal part of the stomach slightly different hormones and enzymes are made, including gastrin that works to regulate acid production in the first part of the stomach.

From the stomach the gastric contents are propelled through a little muscular channel, called the pylorus, that helps compartmentalise stomach from small intestine.

The food passes into the first part of the small intestine, called the duodenum, described a little above. This starts the major journey of absorption, facilitated by spurts of detergents and enzymes from my gallbladder and pancreas, to help me dissolve and extract every morsel of nourishment. Although in the age of fast and caloric food, that is, perhaps, not quite as important as it was when I was hunting and gathering for my supper.

That’s the first part of me: mouth, oesophagus, and stomach. The next instalment will be the small intestine, beginning with the duodenum.


In the series...

Section I: Know thyself

Blog 1. Introduction
Blog 2. Mouth, oesophagus, and stomach
Blog 3. Small intestine (coming soon)
Blog 4. Colon and appendix(coming soon)
Blog 5. Rectum and anus(coming soon)

Section II: Nothing to excess

Blog 6. Microbiome(coming soon)
Blog 7. Gut health(coming soon)

Section III: Surety brings ruin

Blog 8. Diseases of the upper me (gastrointestinal tract)(coming soon)
Blog 9. Colorectal cancer(coming soon)
Blog 10. Irritable bowel syndrome (IBS)(coming soon)
Blog 11. Inflammation: infections, coeliac disease and inflammatory bowel disease (IBD)(coming soon)

Section IV: Entrails

Blog 12. The future(coming soon)

Section V: Poo-st scriptum

Blog Poo & A. Questions, complaints, answers, and solutions(coming soon)

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