BB007 – Fat digestion Basics

Schematisch overzicht macronutrienten
This is part three of the miniseries about macronutrient uptake. This time, I will discuss the break-down and uptake of fats. This blogpost will be longer than the previous ones, because fat absorption is far more complex that absorption of carbs and proteins. I made more figures to compensate for this and tried to cover all the critical concepts as best I could. Like last time, this information can be found in the book ‘Medical Physiology’ by Boron & Boulpaep, 2nd edition. My goal in this post was to let the figures speak for themselves and add as little extra text as possible. I hope you will let me know if I succeeded :). The text in the blog will not always be needed to understand the figures, but is mainly some extra information for those interested in it.
Take note: It will be useful for your understanding to have read the previous post on protein and carbohydrate digestion and uptake, since I will be using the same method of depicting things like salt ions and enzymes.
BP%2B007%2B %2B015  1%2B %2BLegenda%2BEN - BB007 - Fat digestion Basics
BP%2B007%2B %2B015 00%2B %2BIntro%2Bto%2Bfats%2BEN 00%2B %2BIntro%2Bto%2Bfats%2BEN - BB007 - Fat digestion Basics
BP%2B007%2B %2B015 01%2B %2BMechanical%2BEmulsification%2BEN - BB007 - Fat digestion Basics
BP%2B007%2B %2B015 02%2B %2BTAG%2Bstabil.%2BEN - BB007 - Fat digestion Basics
BP%2B007%2B %2B015 03%2B %2BTAG%2Bdigestion%2BEN - BB007 - Fat digestion Basics
BP%2B007%2B %2B015 04%2B %2BTAG%2Bdroplet%2Bevol.%2BEN - BB007 - Fat digestion Basics
BP%2B007%2B %2B015 05%2B %2BFat%2Babsorption%2B1%2BEN - BB007 - Fat digestion Basics
BP%2B007%2B %2B015 06%2B %2BFat%2Babsorption%2B2%2BEN - BB007 - Fat digestion Basics

And that’s all I can reasonably explain about the basics of fat digestion and absorption while still keeping it basic. With that, I have covered the absorption of all 3 macronutrients (the basics of it, at least)! YESSS! The next blogpost will be: MORE BASICS, because I like to know that stuff. After all, you are probably dying to know what happens after the macros have been absorbed. That’s when the real fun starts (and things get complicated … mostly complicated, so extra fun! (for me, maybe not for you (to bad ;-p)))!

BB006 – Protein digestion Basics

 This is part two of the miniseries about macronutrient uptake. This time, I will discuss the break-down and uptake of proteins. Like last time, this information can be found in the book ‘Medical Physiology’ by Boron & Boulpaep, 2nd edition. My goal in this post was to let the figures speak for themselves and add as little extra text as possible. I hope you will let me know if I succeeded :). The text in the blog will not always be needed to understand the figures, but is mainly some extra information for those interested in it.
Take note: It will be useful for your understanding to have read the previous post on carbohydrate digestion and uptake, since I will be using the same method of depicting things like salt ions and enzymes.
I forgot to mention in my previous post that the purple-tinted text blocks contain the most important information for understanding the process of protein digestion, while the green-tinted text block are extra, containing some facts that are not essential. For those people who would like some more depth.
BP%2B006%2B %2B006 01%2B %2BProtein%2BDig.%2BStomach%2BEN - BB006 - Protein digestion Basics
Proteins can be found in almost any type of food, unless it has been highly processed. Both plants and animals make proteins. Actually, all living organisms make proteins (with the exception of viruses, but you could argue viruses aren’t actually ‘alive’).
BP%2B006%2B %2B006 02%2B %2BProtein%2BDig.%2BSI%2BEN - BB006 - Protein digestion Basics
 For more info on pepsin: read the post about stomach acid regulation. (Basics – Advanced)
Pro-enzymes can often be activated by their already-active forms. For example: propepsine can be turned on by pepsin. This will cause an amplifying reaction: more active enzymes will activate more enzymes, which will activate more enzymes etc. This is called a positive feedback loop: the result of the reaction will stimulate the reaction.
A fact about trypsin: this enzyme is often used in laboratories when culturing cells (I know this from personal experience). Cells are cultured in dishes or flask. Some cells float in the medium (culturing liquid), while others stick to the bottom. Cells that stick to a surface can easily be released by adding trypsin. Trypsin cuts the anchors on the outside of the cells, which causes the cells to release from the dish or flask. Cells don’t really like this, so it is best not to do it too often or for too long.
BP%2B006%2B %2B006 03%2B %2BPept.%2BTrans%2BEN - BB006 - Protein digestion Basics
Salt ions drive the transport of oligopeptides and amino acids. This transport mechanism is used a lot by the body, so it is very important to understand it well. Please let me know if this is still unclear, so I can provide a better explanation of the mechanism if needed.
Unlike carbohydrates, proteins don’t need to be digested entirely to be absorbed by gut epithelial cells. This is due to oligopeptide transporters. According to Boron & Boulpaep, it is more efficient and faster for cells to take up 2-4 amino acids at a time as oligopeptides than to take up the same amount of amino acids individually.
The next and last post in this miniseries will cover the break-down and uptake of fats (my energy source of choice 😉 ). Of course I safe the best (and most complex) for last!

BB005 – Carbohydrate digestion Basics

Schematic carbohydrates

This is part 1 of a 3-part series about how the three macronutrients (carbohydrates – proteins – fats) are absorbed by the body. Here I explain how digestive enzymes break down food and how the intestines take up nutrients into the body. The textbook ‘Medical Physiology’ 2nd edition by Boron & Boulpaep is the source of this information.

The challenge of this series is to create complete figures that do not require much or any additional explanation. All essential info is listed in the figure itself in small text boxes. Interesting trivia or more detailed explanations are put in the blog post.
BP%2B005%2B %2BCarb%2BAbsorption Background%2Bpanel%2BEN - BB005 - Carbohydrate digestion Basics
 This is an overview of the different types of sugars commonly found in food and a legend of the schematic depictions thereof in the following figures.BP%2B005%2B %2BCarb%2BAbsorption Dig.%2BSaliv.%2BAmylase%2BEN - BB005 - Carbohydrate digestion Basics
Complex carbohydrates are mainly starches from plants and glycogen from animal meat. They are long carbohydrate chains (much longer than depicted here). Depending on the source, they can contain a million carbohydrate rings. 
BP%2B005%2B %2BCarb%2BAbsorption Dig.%2BLumen%2B %2BMonosacch.%2BEN - BB005 - Carbohydrate digestion Basics
The prefix ‘oligo-‘ is use to indicate ‘a few’ (I am not sure what the exact definition is in this context). The ‘mono-‘ prefix means ‘one’, so a monosaccharide indicates a single carbohydrate ring. Complex carbohydrates are also called polysaccharides, where ‘poly-‘ means ‘many / a lot’. 
The enzymes are named after the disaccharide (2 carbohydrate chains) they are able to cut. Lactase cuts lactose (milk sugar), which is made out of glucose and galactose. Sucrase cuts sucrose (table sugar), which is made out of glucose and fructose.
BP%2B005%2B %2BCarb%2BAbsorption Transepi.%2Btransport%2BEN - BB005 - Carbohydrate digestion Basics
 The use of sodium to improve the function of transporters is used in a lot of ways in the body, also for other transporters of other cell types. 
BTW: the transporter that exchanges sodium and potassium (Na-K exchanger) is needed to empty the cell of sodium, so it can be used to facilitate the uptake of glucose from the intestinal lumen. Of course, there are many other transporters used by intestinal epithelial cells, but I will keep things simple here ;). 
 
Part 2 of this series will be about proteins. In part 3 I will discuss fats. 

BB004 – Stomach acid Advanced

And now to continue with the second part of this mini project. This time with slightly more in-depth discussion regarding stomach acid regulations and protein digestion.
SB003%2B %2BStomach%2BAcid%2B033 Figure%2B3 - BB004 - Stomach acid Advanced
A brief summary:
– Inside the stomach, protein is broken down by the enzyme pepsin into smaller pieces, called peptones.
– Pepsin is derived from pepsinogen, which is made by chief cells in the stomach lining.
– Stomach acid made by parietal cells in the stomach lining transforms pepsinogen into pepsin and creates an acid environment to optimize the function of pepsin.
– The stomach lining is protected from stomach acid and pepsin by a layer of alkaline mucous made by mucous cells. The alkaline environment neutralizes the acid and inactivates the pepsin.
I will continue to discuss what other cell types and systems influence this proces. An important concept when studying the body is its ability to selectively activate or inactivate processes involved in maintaining a physiological balance (homeostasis). The body changes constantly and it is therefore required to compensate for outside (and inside) influences to maintain homeostasis. Homeostasis means maintaining an internal environment that is optimized for the body at that time. To this end, most critical processes are regulated to stay within tight boundaries. As the environment changes, however, these boundaries will change accordingly as well. And as the balance for any one factor falls outside of these boundaries, the body will act to return to a balanced internal environment. Homeostasis in an unconscious process, managed and monitored by the brain and nervous system.
The on-switch for the stomach is therefore also neurological. As soon as you see something to eat, smell something to eat, taste, chew and swallow, the stomach is made ready to digest. The autonomic nervous system has already sent a general signal to start digestion, since it knows that food will be/is being/has been eaten. The stomach starts producing acid and pepsinogen to initiate digestion, as well as extra mucous to protect itself.
Food entering the stomach provides an additional signal to promote the production of acid and digestive enzymes.
SB003%2B %2BStomach%2BAcid%2B033 Figure%2B4 - BB004 - Stomach acid Advanced
ECL cells (EnteroChromaffin-Like cells) are located close to parietal cells, but behind the layer of epithelial cells in the stomach lining (so they are not in direct contact with the stomach content). ECL cells produce histamine, which they release into their immediate environment. Parietal cells then produce more acid when they notice the presence of histamine.
ECL cells are so-called endocrine cells, because they release (crine) histamine inside (endo) the body, whereas parietal and chief cells release their product on the outside (exo) of the body. Technically, any part of the body that is not behind a layer of epithelium is internal. The digestive tract is technically a single long tube, which is lined by epithelium of some kind and is therefore considered external to the body.
Histamine may be familiar to some in a different context. Histamine is an important messenger for the immune system en is the main cause of allergic symptoms. Generally speaking, histamine signals for an increase in inflammation. But in the stomach it appears to have a different function.
Brief summary: ECL cells produce histamine, which makes parietal cells produce more acid. ECL cells therefore indirectly increase the acidity of the stomach content.
SB003%2B %2BStomach%2BAcid%2B033 Figure%2B5 - BB004 - Stomach acid Advanced
The next layer of complexity comes from the bottom of the stomach crypts, where the stomach endocrine cells are located. One type of endocrine cell, called G cells, produce gastrin and secrete it in their direct environment. Gastrin stimulates histamine production by ECL cells and acid production by parietal cells, thereby lowering the pH of the stomach indirectly.
SB003%2B %2BStomach%2BAcid%2B033 Figure%2B6 - BB004 - Stomach acid Advanced
Once protein digestion has started, a positive feedback loop kicks in. A positive feedback loop occurs when the result of process enhances the process it resulted from, effectively amplifying it. In this case, peptones (the small protein fragments) stimulate G and chief cells. G cells produce more gastrin, which increases acid production and chief cells produce more pepsinogen. Pepsinogen in the acidic environment becomes pepsin and breaks down more proteins into peptones, which amplifies the peptone signaling. This loop remains active as long as peptones are present. As soon as the stomach content is sufficiently digested, it will move on to the small intestines, thereby breaking the feedback loop.
SB003%2B %2BStomach%2BAcid%2B033 Figure%2B7 - BB004 - Stomach acid Advanced
The body regulates most processes at multiple levels. In the stomach, the second type of endocrine cell, D cells, provide more regulation for stomach acid production. D cells make somatostatin (Greek for: halting the body (or something like that)). D cells do very little when digestion has just gotten started, but start producing somatostatin once the pH gets lower and more gastrin is made by G cells. Somatostatin inhibits (stops) ECL, G and parietal cells from producing their products and thereby reduces the amount of acid that is being made directly and indirectly. Stronger activating signals for D cells result in higher amounts of somatostatin being released. This is known as a negative feedback loop, where the result of a process, inhibits that process.
Somatostatin is also made by cells in the small intestine (duodenum) as response to a lower pH when the stomach content gets enters the small intestine. Endocrine release of somatostatin can be transported by blood to provide signals elsewhere in the body, not just the immediate environment around the endocrine cell.
A final regulation of stomach acid, as mentioned before: the entire stomach is under the control of the nervous system, mainly the parasympathetic branch of the autonomous nervous system. This branch promotes digestion and rest. It used acetylcholine, locally made by nerve endings, to communicate with the stomach. Acetylcholine stimulates cells that produce digestive enzymes and acid, but it inhibits D cells. Given the effect of somatostatin produced by D cells, the inhibition of D cells by acetylcholine in this context, makes sense, since it results in more digestion. Of course, the inhibition of D cells by the nervous system can be overcome with sufficient stimulatory inputs.
SB003%2B %2BStomach%2BAcid%2B033 Figure%2B8 - BB004 - Stomach acid Advanced

That is some of the information I gathered from my book on human physiology regarding stomach acid regulation and protein digestion. My book is at least 5+ years old by now and mentioned that several unknown cells and signals are also suspected to affect the stomach. And, of course, my descriptions are simplified for your understanding ;).
Regardless, I hope you can now appreciate a bit more of the complexity involved in a seemingly simple process. This is a common theme, in my experience, when studying anything in-depth.

BB003 – Stomach acid Basics

Maagzuur regulatie simpel
I found some interesting facts about the stomach after rereading the book ‘Medical Physiology’ (Boron & Boulpaep, 2nd edition). Since this is quite a complex topic, I divided it into two parts. The first part is, in my mind, the basic knowledge required to get a general overview.

 

SB003%2B %2BStomach%2BAcid%2B029 Figure%2B1 - BB003 - Stomach acid Basics
Figure 1: Protein digestion
In figure 1 I depicted the a schematic version of the anatomy of the stomach and protein digestion.  Food that has been chewed and swallowed can only leave the stomach if it is smaller than 2 mm. Fluids can therefore pass through the stomach almost immediately. Muscles in the stomach wall mix and churn the food, grinding it against itself to reduce the size. Combined with digestive enzymes for carbohydrates, fats and proteins, the food is sufficiently digested in a few hours and can pass into the small intestine.

Digestion of carbohydrates and fats starts in the mouth by mixing in enzymes to break carbohydrate chains (amylases) or fats into fatty acids (lipases). These enzymes remain functional in the stomach, with the addition of enzymes to break proteins down into small amino acid chains (peptidases). The digestive enzymes are made by cells in the lining of the stomach (epithelium). The stomach lining contains many alcoves (crypts) and is covered by a thin layer of gel or slime (mucus).

I use pepsin here as an example of a cool digestive enzyme, a peptidase that plays an important role in protein digestion in the stomach. As shown in figure 1, pepsin breaks proteins down into small pieces, called peptones. Pepsin, unlike other types of peptidases, can break the middle of the peptide chain. This allows pepsin to rapidly break down any kind of protein it encounters.
SB003%2B %2BStomach%2BAcid%2B029 Figure%2B2 - BB003 - Stomach acid Basics
Figure 2: Pepsinogen and pepsin
However, pepsin is not made as such. Chief cells in the stomach lining make pepsinogen, a precursor of pepsin, and release it to the stomach content. Pepsinogen only becomes active if the pH is lower than 3.5. On the inside of cells, the pH is around 7, so pepsinogen remains inactive until it moves from the cell to into the stomach itself. Parietal cells produce the acid to lower the pH of the stomach. The acidic environment created by the parietal cells transforms pepsinogen into pepsin. The more acidic the environment, the faster the transformation and the faster pepsin can break down proteins.

 

SB003%2B %2BStomach%2BAcid%2B029 Figure%2B3 - BB003 - Stomach acid Basics
Figure 3: Pepsin inactivation
So pepsin in an acidic environment is very nice for digesting proteins in the stomach, but can be dangerous for the cells in the stomach lining. Pepsin is just as good at digesting cellular peptides and a pH of 2 or 3 can cause some severe acid burns. This is what the mucus layer protects from. Mucus is made by mucous cells at the entrance of a crypt, allowing the mucus to cover the crypt entrance and protect the underlying cells. The mucus layer can hardly be penetrated by the acid and and has a high pH. Even though pepsin works really well in an acidic environment, it stops working completely when the pH increases. The protection this alkaline mucus layer produces ensures that the stomach does not digest itself.
A small detail: the chief and parietal cells are located in the middle of the crypt. So the mucus layer lies between the crypt content and the stomach proper. How does the acid and pepsinogen get through the mucus? The book said: it is transported in a pressurized flow through the middle of the crypt. I cannot think of a better explaination myself 😉
Protein digestion by the stomach is pretty simple compared to my previous post. Of course, it gets more complex as you get further into it. There are a number of regulatory systems involved with digestion in general. I will discuss some in the next part, for enthusiasts. So I will cover the basics of stomach acid regulation in the next part. See you there 🙂