If you were to shrink down into a microscopic version of yourself and explore someone’s

alimentary canal, or gastrointestinal tract, you could tell exactly where you are based on the
tissue around you. Well, assuming you brought a microscopic flashlight at least.

[intro]

If you’re new here, welcome, my name is Patrick and this channel is all about anatomy and how
we learn about it. Today we’re going over the microscopic anatomy responsible for digestion,
and as always, notes for this lesson are linked in the description.

When you’re first learning digestion, I recommend separating it into two parts: mechanical
digestion which is the physical grinding and processing of food into smaller bits​1​, and chemical
digestion, all the enzymes and acids which break foods down further so we can get them ready
to pass into the bloodstream​2​. But there’s a caveat here: digestion is only the process that
breaks down food, while the products of digestion undergo absorption to enter the blood and
lymph​3​.

That’s why we emphasize digestive histology so much. Chemical digestion is microscopic, so

our anatomy of interest is microscopic as well.

That being said, let’s start in the oral cavity.

You already knew that the mouth was a big deal for mechanical digestion because chewing​4​.
But our saliva does a fair amount of chemical digestion too.

You’ve got a handful of major salivary glands — one is sublingual, under your tongue, one is
submandibular, under your jaw, and one is the parotid, it pumps in saliva from the side of your
face​5​. At the microscopic level, you might notice some familiar cuboidal epithelium and these
things are prime for secreting enzymes​6​. In particular, salivary amylase and lingual lipase​7​. And

1
Mechanical digestion involves physically breaking down food substances into smaller particles to more efficiently
undergo chemical digestion. ​https://www.ncbi.nlm.nih.gov/books/NBK544242/
2
The role of chemical digestion is to further degrade the molecular structure of the ingested compounds by digestive
enzymes into a form that is absorbable into the bloodstream. ​https://www.ncbi.nlm.nih.gov/books/NBK544242/
3
Lipids, proteins, and complex carbohydrates are broken down into small and absorbable units (digested), principally
in the small intestine. The products of digestion, including vitamins, minerals, and water, which cross the mucosa and
enter the lymph or the blood (Absorption). ​https://www.ncbi.nlm.nih.gov/books/NBK544242/
4
Mechanical digestion in the oral cavity consists of grinding of food into smaller pieces by the teeth, a process called
mastication. ​https://www.ncbi.nlm.nih.gov/books/NBK544242/
5
You have three pairs of major salivary glands under and behind your jaw — parotid, sublingual and submandibular.
https://www.mayoclinic.org/diseases-conditions/salivary-gland-cancer/symptoms-causes/syc-20354151#:~:text=You
%20have%20three%20pairs%20of%20major%20salivary%20glands%20under%20and,throughout%20your%20mout
h%20and%20throat​.
6
In humans, the striated ducts are larger in serous than mucous glands. Interlobar ducts have cuboidal epithelium,
and the main excretory ducts are lined by cuboidal cells that transition to stratified squamous (oral mucosa) at the
duct opening.
https://www.sciencedirect.com/topics/neuroscience/salivary-gland#:~:text=In%20humans%2C%20the%20striated%2
0ducts,mucosa​)
7
Chemical digestion in the mouth is minor but consists of salivary amylase (ptyalin, or alpha-amylase) and lingual
lipase, both contained in the saliva. ​https://www.ncbi.nlm.nih.gov/books/NBK544242/
pro tip, any time you see the suffix ​-ase​ at the end of a word, it’s an enzyme, a protein that
makes a chemical reaction happen faster. In this case, they’re helping to break bonds between
complex nutrients. And the prefix will tell you what it breaks down. Lipase breaks down lipids​8
while Amylase breaks down complex carbs into simpler carbs​9​.

At this point in digestion, the chewed up lump of what used to be food is called a ​bolus​10​ — cuz
unless you’re about to baby bird that thing into someone else’s mouth, it’s going down the
hatch.

Pardon my manners, I’m supposed to be a respectable anatomist. Down the esophagus.

It’s a thick muscular tube lined with a bunch of stratified squamous cells, which makes sense​11​.
It doesn’t break anything down, mechanically or chemically. It just moves the bolus to the
stomach​12​ with a ripple pattern called ​peristalsis​ — peri for around, stalsis for squeeze​13

Now, the tissue level anatomy of the stomach is important because it does both mechanical and
chemical digestion​14​.

The stomach is coated in smooth muscle, the type of muscle organized into big sheets which
lets it squeeze together. In the stomach, this squeezes the bolus towards the ​pylorus​, the tiny
hole that leads from the stomach into the small intestine​15​. Then this piece of the stomach, the
antrum keeps those ripply contractions coming, grinding the bolus against the pylorus which is
just clamped shut​16​. This grinding process breaks down food until it’s no larger than two
millimeters. Only then can it pass through the pylorus into the ​duodenum​, the first part of the
small intestine​17​. But the entire bolus isn’t immediately small enough to pass through. So your
stomach will move the bolus away from the pylorus, and keep grinding and chemically digesting
it until it’s small enough to pass​18​.

8
Lingual lipase, also contained in the saliva, hydrolyzes the ester bonds in triglycerides to form diacylglycerols and
monoacylglycerols. ​https://www.ncbi.nlm.nih.gov/books/NBK544242/
9
Salivary amylase is chemically identical to pancreatic amylase and digests starch into maltose and maltotriose,
working at a pH optimum of 6.7 to 7.0. ​https://www.ncbi.nlm.nih.gov/books/NBK544242/
10
​After sufficient digestion in the oral cavity, the partially digested foodstuff, or bolus, is swallowed into the
esophagus. ​https://www.ncbi.nlm.nih.gov/books/NBK544242/
11
The esophageal epithelium View Image is the non-keratinized stratified squamous type and is supported by a
connective tissue lamina propria.​https://histology.medicine.umich.edu/resources/pharynx-esophagus-stomach
12
No digestion occurs in the esophagus. After passage through the esophagus, the bolus will enter the stomach and
undergo mechanical and chemical digestion. ​https://www.ncbi.nlm.nih.gov/books/NBK544242/
13
from περιστέλλω (peristéllō, “to wrap around”), from περι- (peri-, “around”) +​ στέλλω (stéllō, “to make ready, to
prepare”). ​https://en.wiktionary.org/wiki/peristalsis
14
After passage through the esophagus, the bolus will enter the stomach and undergo mechanical and chemical
digestion. ​https://www.ncbi.nlm.nih.gov/books/NBK544242/
15
Mechanical digestion in the stomach occurs via peristaltic contractions of the smooth muscle from the fundus
towards the contracted pylorus, termed propulsion. ​https://www.ncbi.nlm.nih.gov/books/NBK544242/
16
Once the bolus is near the pylorus, the antrum functions to grind the material by forceful peristaltic contractions that
force the bolus against a tightly constricted pylorus. ​https://www.ncbi.nlm.nih.gov/books/NBK544242/
17
Only particles smaller than 2mm in diameter can pass through the contracted pylorus into the duodenum.
https://www.ncbi.nlm.nih.gov/books/NBK544242/
18
The rest of the bolus is pushed back towards the body of the stomach for further mechanical and chemical
digestion. This backward movement of the bolus from the pylorus to the body is termed retropulsion and also serves
And your stomach ​mucosa​, or mucous membrane, can throw a lot of chemical digestion at that
bolus​19​. Most of the epithelial cells are simple columnar cells, but there are also these little
gastric pits​20​ that have a few secreting glands — oxyntic glands and pyloric glands and they
both work together​21​.

Oxyntic glands are made of two cell types: ​parietal​ cells which pump out super concentrated
hydrochloric acid​22​ and ​chief​ cells which make a precursor to an important enzyme​23​. Not the
enzyme itself, but the thing that will become an enzyme.

What I love about these two cells is how they actually use each other to work. Like, hydrochloric
acid is powerful. It denatures or unfolds some of the protein we eat, but not all the way​24​.
Fortunately, that acid also helps turn pepsinogen, the precursor secreted by the chief cells, into
the active enzyme pepsin​25​. Then pepsin, in this acidic environment, can further break down the
peptide bonds between proteins to more completely digest them​26​.

And as great as this acid is for breaking down proteins, we’ve still got this delicate stomach
mucosa that we don’t want to burn holes into​27​. So the other type of glands, the pyloric glands,
have cells that secrete a mucous rich with bicarbonate, a more basic chemical that coats the
gastric mucosa to protect it​28​. Those glands also have G-cells that secrete ​gastrin​, which is a
hormone that stimulates the parietal cells to make more hydrochloric acid when needed​29​.

So by the time the bolus is done in the stomach, it’s more of a soupy acidic, partially digested
mess, and at this point we’d call it ​chyme​30​. And it’s about to see some serious chemical
digestion in the small intestine​31​.

to aid in mechanical digestion. This sequence of propulsion, grinding, and retropulsion repeats until the food particles
are small enough to pass through the pylorus into the duodenum. ​https://www.ncbi.nlm.nih.gov/books/NBK544242/
19
There is significant chemical digestion in the stomach. ​https://www.ncbi.nlm.nih.gov/books/NBK544242/
20
The mucosal surface is invaginated into numerous gastric pits, each of which opens freely onto the mucosal
surface ​http://www.siumed.edu/~dking2/erg/GI108b.htm
21
​ Two types of glands exist in the gastric mucosa that aid in chemical digestion: oxyntic glands and pyloric glands.
https://www.ncbi.nlm.nih.gov/books/NBK544242/
22
Parietal cells secrete hydrochloric acid, concentrated to approximately 160 mmol/L and a pH of 0.8.
https://www.ncbi.nlm.nih.gov/books/NBK544242/
23
Oxyntic glands also contain chief cells that secrete the zymogen pepsinogen.
https://www.ncbi.nlm.nih.gov/books/NBK544242/
24
Hydrochloric acid secreted by the parietal cells serves three main functions: to denature proteins and make them
more accessible for enzymatic degradation by pepsin ​https://www.ncbi.nlm.nih.gov/books/NBK544242/
25
Pepsinogen is the precursor to the proteolytic enzyme pepsin and must be activated to pepsin by the acidic pH of
the stomach (below 3.5) or from autoactivation by pepsin itself. ​https://www.ncbi.nlm.nih.gov/books/NBK544242/
26
Pepsin will then act on the internal peptide bonds of proteins at the optimal pH of 2 to 3.
https://www.ncbi.nlm.nih.gov/books/NBK544242/
27
The mucus covers the stomach wall with a protective coating. Together with the bicarbonate, this ensures that the
stomach wall itself is not damaged by the hydrochloric acid. ​https://www.ncbi.nlm.nih.gov/books/NBK279304/
28
Mucous cells secrete a bicarbonate-rich mucous onto the surface of the gastric mucosa to protect it from the acidic
contents of the stomach. ​https://www.ncbi.nlm.nih.gov/books/NBK544242/
29
The G-cells secrete gastrin, a hormone that acts in an endocrine fashion to stimulate the secretion of hydrochloric
acid by parietal cells. ​https://www.ncbi.nlm.nih.gov/books/NBK544242/
30
Chyme is a semi-fluid pulp formed in the stomach made of partly digested food and the secretions of the
gastrointestinal tract. ​https://biologydictionary.net/chyme/
31
The majority of chemical digestion occurs in the small intestine. ​https://www.ncbi.nlm.nih.gov/books/NBK544242/
After chyme passes through the pylorus it hits the first section of the small intestine called the
duodenum​32​. I imagine this thing like a little witch’s cauldron — it’s basically a mixing pot for
stomach contents and enzymes, including more amylase and lipase, but also enzyme
precursors like trypsinogen and proelastase sent from the pancreas​33​.

There’s an important reason why the pancreas sends precursors and not fully formed enzymes.

If the pancreas secreted active enzymes, it would digest itself, which is what happens during
pancreatitis​34​35​. Instead, it makes those precursors, and ships them to the duodenum where
they mix with another enzyme called enterokinase​36​ — entero- for intestine, -kine- for
movement, -ase for enzyme. It’s an intestinal enzyme that kickstarts other enzymes. First it
converts trypsinogen into trypsin​37​. Then trypsin can convert chymotrypsinogen into
chymotrypsin, procarboxypeptidase into carboxypeptidase, proelastase into elastase​38​. For all of
you noticing the pattern, yes, just drop the -ogen or pro- and you can figure out the name for the
active enzyme.

And a lot of these enzymes further break down the peptide bonds in proteins. But there are
more than just pancreatic enzymes in there.

The epithelial cells of the duodenum also secrete a dipeptidase, an enzyme that breaks down
peptide bonds in proteins​39​, and multiple disaccharidases, enzymes that break down compound
sugars into simple sugars. Like maltase is the enzyme that breaks down maltose into two
glucoses, but we’ve also got lactase for breaking down lactose, and sucrase for sucrose​40​.

I’ve said it before but I’ll say it again. Physiologists are the worst at naming things.
32
Digested chyme from the stomach passes through the pylorus and into the duodenum.
https://www.ncbi.nlm.nih.gov/books/NBK544242/
33
The pancreas produces many digestive enzymes, including pancreatic amylase, pancreatic lipase, trypsinogen,
chymotrypsinogen, procarboxypeptidase, and proelastase ​https://www.ncbi.nlm.nih.gov/books/NBK544242/
34
Pancreatitis is the inflammation and autodigestion of the pancreas. Autodigestion describes a process whereby
pancreatic enzymes destroy its own tissue leading to inflammation.
https://www.uchealth.com/en/conditions/pancreatitis#:~:text=Autodigestion%20describes%20a%20process%20where
by,the%20pancreas%20returns%20to%20normal​.
35
The pancreas does not secrete the active form of the peptidases; otherwise, autodigestion could occur, as is the
case in pancreatitis ​https://www.ncbi.nlm.nih.gov/books/NBK544242/
36
This conversion occurs as enterokinase, a duodenal enzyme, converts trypsinogen to trypsin.
https://www.ncbi.nlm.nih.gov/books/NBK544242/
37
Enterokinase is produced by the duodenal mucosa.1,2 It activates trypsin, a pancreatic proteolytic enzyme, which
in turn activates the remainder of the enzymes facilitating protein digestion
https://www.sciencedirect.com/topics/nursing-and-health-professions/enteropeptidase#:~:text=Enterokinase%20is%2
0produced%20by%20the%20duodenal%20mucosa.&text=It%20activates%20trypsin%2C%20a%20pancreatic,the%2
0enzymes%20facilitating%20protein%20digestion.&text=The%20pancreas%20releases%20other%20proteolytic,that
%20continue%20the%20digestive%20process​.
38
Trypsin can then convert chymotrypsinogen, procarboxypeptidase, and proelastase to their active forms.
https://www.ncbi.nlm.nih.gov/books/NBK544242/
39
Dipeptidase cleaves the peptide bond in dipeptides. ​https://www.ncbi.nlm.nih.gov/books/NBK544242/
40
The disaccharidases include maltase, lactase, and sucrase. Maltase cleaves the glycosidic bond in maltose,
producing two glucose monomers, lactase cleaves the glycosidic bond in lactose, producing glucose and galactose,
and sucrase cleaves the glycosidic bond in sucrose, producing glucose and fructose.
https://www.ncbi.nlm.nih.gov/books/NBK544242/
But you’ve still got a problem. You know how water and oil don’t mix? Well, the lipids, or fats
from your food aren’t mixing with the rest of that soupy, squishy chyme. So your liver and
gallbladder secrete a substance called ​bile​ into the duodenum​41​. It’s a mixture of cholesterol,
fatty acids, electrolytes, bile salts, and bilirubin that all act together to emulsify certain lipid
particles into the liquid​42​. We need to do that because some of our enzymes like pancreatic
lipase, work better if they can access more lipid surface area​43​.

At this point, you’ve digested food about as far as you can. Those big proteins have been
broken into amino acids and oligopeptides, and complex carbs into simple sugars​44​. Now we
can focus on absorption and excretion​45​.

The point here is to allow diffusion of nutrients through a really thin cellular layer made mostly of
enterocytes​, literally intestine cells. But there are also the awesomely named ​crypt cells that
supply the small intestine with stem cells and secrete chloride​46​47​48​. To help with that diffusion,
the small intestine is covered in all these wiggly projections called ​villi​ that increase surface
area available to absorb nutrients. Each of them are about half to one and half millimeters long
and covered in columnar epithelial cells​49​. Then those things have even tinier /micro/villi on them
that increase the surface area by a factor of 600​50​ and more surface area allows more diffusion
of nutrients from the small intestine.

I’m going to keep this video focused on histology, but I’ll dedicate a video to the absorption of
different nutrients in the future.

41
The common bile duct carries bile that was made in the liver and stored in the gallbladder.
https://www.ncbi.nlm.nih.gov/books/NBK544242/
42
Bile contains a mixture of bile salts, cholesterol, fatty acids, bilirubin, and electrolytes that help emulsify
hydrophobic lipids in the small intestine, which is necessary for access and action by pancreatic lipase, which is
hydrophilic. ​https://www.ncbi.nlm.nih.gov/books/NBK544242/
43
Bile salts enhance the efficiency of lipolysis by increasing the surface area of oil-water interfaces at which
water-soluble lipase is effective.
https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/pancreatic-lipase
44
At this point, the mouth, stomach, and small intestine have broken down fat in the form of triglycerides to fatty acids
and monoacylglycerol, carbohydrate in the form of starch and disaccharides to monosaccharides, and large proteins
into amino acids and oligopeptides. ​https://www.ncbi.nlm.nih.gov/books/NBK544242/
45
Thus, the digestive process has converted macronutrients into forms that are absorbable into the bloodstream for
bodily use. ​https://www.ncbi.nlm.nih.gov/books/NBK544242/
46
Chloride secretion occurs in the intestinal crypt cells throughout the small intestine, whereas chloride is generally
absorbed in the large intestine.
https://www.sciencedirect.com/topics/immunology-and-microbiology/crypt-cell#:~:text=Crypt%20cells%20of%20the%
20small,result%20in%20epithelial%20villus%20atrophy​.
47
Crypt cells of the small intestine provide stem cells for renewal of the intestinal epithelium, which turns over each 3
to 4 days.
https://www.sciencedirect.com/topics/immunology-and-microbiology/crypt-cell#:~:text=Crypt%20cells%20of%20the%
20small,result%20in%20epithelial%20villus%20atrophy​.
48
These are mostly absorptive cells, whereas crypt cells are generally regarded as secretory.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4956471/
49
Villi are approximately 0.5–1.6 mm in length and are covered with columnar epithelial cells at the tip
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4956471/
50
The surface area of the small intestine is significantly enhanced by the presence of villi and microvilli, which
increase the intestinal surface area by 30–600 fold, respectively.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4956471/
For now, suffice to say that all of the nutrients depend on electrolytes and diffusing through that
columnar epithelium to enter the bloodstream. Ohh, and 80% of your water is absorbed here.

By the time we’ve absorbed nutrients through the small intestine, we exit through a section
called the ​ileum​51​. For those familiar with skeletal anatomy, I’m sorry. It’s pronounced the same
as your pelvic bone but spelled differently. Anatomists suck.

From the ileum, we enter the large intestine where we absorb the rest of the water and get this
thing ready to ship out​52​. I said ship. With a P. Like for poop.

Overall, it’s shorter intestine and has a much larger lumen​53​. It has this segmented look because
of these pouch-like structures called ​haustra​, which on the inside, are separated by semilunar
folds​54​.

But we need some quick nomenclature since the large intestine has so many distinct sections.
The first chamber is the cecum​55​ — which I remember because, when it comes to contents from
the small intestine, this is the first section to see it coming.

Look, I know that’s a borderline dirty joke, but we’re almost at the anus so anything goes.

Hanging off the cecum is the appendix, which houses a bunch of good gut bacteria. Then
there’s the main section of the colon which gets divided into the ascending, transverse, and
descending colons, as well as the sigmoid colon​56​57​ which connects to the rectum subtext I
hardly knew him, and finally the anus.

That’s the big picture level, but what about the tissue level?

51
The last part of the small intestine. It connects to the cecum (first part of the large intestine).
https://www.cancer.gov/publications/dictionaries/cancer-terms/def/ileum
52
The large intestine performs an essential role by absorbing water, vitamins, and electrolytes from waste material
https://www.ncbi.nlm.nih.gov/books/NBK507857/
53
Unlike the small intestine, it has a shorter length but a much larger lumen.
https://www.ncbi.nlm.nih.gov/books/NBK470577/
54
Semilunar folds arise in the inner surface through muscle contractions. These are merely caused functionally and
therefore movable. These folds form pouches on the external surface (haustra).
https://www.kenhub.com/en/library/anatomy/the-colon
55
It begins at the terminal ileum with the cecum. ​https://www.ncbi.nlm.nih.gov/books/NBK470577/
56
The colon may be subdivided into four parts: ascending, transverse, descending and sigmoid colon.
https://www.kenhub.com/en/library/anatomy/the-colon
57
​The ascending colon runs superiorly on the right side of the abdomen from the right iliac fossa to the right lobe of
the liver. At this point, it makes a left turn at the right colic flexure (hepatic flexure). Ascending colon is a
retroperitoneal organ and has paracolic gutters on either side. The transverse colon is the third, most mobile, and
longest part of the large intestine. It is found between the right and left colic flexures. The left colic flexure is less
mobile than the right and is attached to the diaphragm through the phrenocolic ligament. The transverse colon is
attached to a mesentery, the transverse mesocolon, which has its root along the inferior border of the pancreas. The
transverse colon continues as the descending colon. The two are demarcated at the splenic flexure. The descending
colon is a retroperitoneal organ and related to paracolic gutters on either side. It terminates into the sigmoid colon,
which is the fifth part of the large intestine. The sigmoid colon links the descending colon to the rectum.
https://www.ncbi.nlm.nih.gov/books/NBK470577/
Well, it’s still lined with simple columnar epithelium with microvilli, and has a similar lamina
propria as the small intestine, but with a few unique features of its own​58​59​.

The colon has crypts, but no villi, it doesn’t secrete any digestive enzymes but does have a
bunch of goblet cells which secrete a protective mucus​60​61​. Which it uses to protect itself from
all the gut bacteria hanging out in the lumen.

If you move out from the lumen, you’ll see a much thicker muscular layer too, because that’s the
muscle that moves feces along the colon​62​. Eventually this transitions into the thick sphincters
around the anus​63​.

One of which is involuntary and almost always clamped shut, while one is under voluntary
control, holding back our poops.

But don’t let me hold you back from supporting me on Patreon.com/corporis, where for as low
as $2 a month you’ll get early access to videos, fully annotated scripts, and a direct line of
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good, thanks for watching.

58
The colon has the typical histological structure as the digestive tube: mucosa, submucosa, muscularis and
serosa/adventitia. The mucosa is lined by simple columnar epithelium (lamina epithelialis) with long microvilli.
https://www.kenhub.com/en/library/anatomy/the-colon
59
The lamina propria and submucosa are similar to the small intestine.
https://www.histology.leeds.ac.uk/digestive/large_intestine.php
60
The mucosa does not contain villi but many crypts of Lieberkuhn in which numerous goblet cells and
enteroendocrine cells are found. ​https://www.kenhub.com/en/library/anatomy/the-colon
61
It secretes large amounts of mucus, and some hormones, but no digestive enzymes…. The thick mucosa has deep
crypts, but there are no villi. The epithelium is formed of columnar absorptive cells with a striated border, many goblet
cells, endocrine cells and basal stem cells, but no Paneth cells.
https://www.histology.leeds.ac.uk/digestive/large_intestine.php
62
The inner circular musculature of the muscularis is strongly pronounced whereas the outer longitudinal musculature
is practically only found in the taeniae. ​https://www.kenhub.com/en/library/anatomy/the-colon
63
The longitudinal smooth muscle in the muscularis externa is arranged in three longitudinal bands called taenia coli.
At the anus, the circular muscle forms the internal anal sphincter.
https://www.histology.leeds.ac.uk/digestive/large_intestine.php