In the gut there is a large network of nerve endings originating from the sympathetic and parasympathetic autonomic nervous system, especially the vagus nerve and spinal cord nerves, as well as an intrinsic neural network, called the enteric nervous system. These networks are interconnected. The vagus nerve is a cerebral nerve that runs down the neck and extends (or "wanders") virtually throughout the body, hence its name (not that it is a "lazy" nerve, as many people think). It is the main nerve of the parasympathetic system. At the intestinal level, it promotes the secretions of the digestive organs and the bowel movements that promote digestion and move the food bolus and faeces forward. It has about 20% of efferent fibres (carrying nerve messages from the brain to the gut) and 80% of afferent fibres (transmitting information from the gut to the brain). See figure 12. Thanks to this nerve, there is constant two-way communication between the brain and the gut. This communication takes place by means of chemical substances (neurotransmitters, short-chain fatty acids, peptides, hormones, cytokines, etc.) that are released by the vagus nerve into the gut in the case of efferent information or transmitted by the gut to the vagus nerve so that the information travels to the brain in the case of afferent messages. These chemicals can be produced both by nerve endings, intestinal or immune cells in the gut wall, and, to a large extent, by the microbiota. Thus, the microbiota plays a crucial role in gut-brain communication. I would like to clarify that the vagus nerve, while being the main communication pathway between the gut and the brain, is by no means the only one. Another important communication pathway is the blood pathway (hormones, cytokines or other chemicals produced in the brain travel to the gut via the blood, and vice versa). I won't go much further into the exciting world of the gut-brain axis, which would be enough to write several books, but, by way of example, I could say that it is more than proven that people suffering from psychiatric diseases such as depression or anxiety, neurodegenerative diseases such as Alzheimer's or Parkinson's or neurodevelopmental disorders (autism spectrum disorders for example) often have a profound alteration of their gut microbiota, which is known as "dysbiosis". If you want to know more about gut microbiota, I recommend you read this article: The role of the gut and its microbiota. Gut-brain axis.
Anatomy and function of the digestive system
The diagram below shows what the digestive system looks like and the function of each organ. Figure 13
The bladder's response to infection
In the bladder, defence mechanisms against infection are very complex and involve the immune system and other systems. Although not all of these mechanisms are known exactly, it is known that up to 1000 different genes involved in bladder defence can be activated in the urinary system when faced with a bacterial infection. Here is a summary of the broad outline of the bladder's defensive response.
The first line of resistance of the bladder to active infection is due both to the anatomical design of the bladder and to antimicrobial substances secreted by the urothelium (the cells of the bladder wall). Urothelial cells are covered by a layer of mucus and have defence proteins in their membrane called "uroplakins". These two mechanisms serve to prevent the adherence of some bacteria to their surface, although others, such as uropathogenic strains of Escherichia coliare able to use precisely these molecules to penetrate bladder cells. In fact, E. coliin addition to having the ability to multiply rapidly in urine, it has many mechanisms to evade the bladder's natural defences, which we will now discuss.
As I have already mentioned, the first line of defence against bladder infection is the urothelium with its mucus layer. The numerous bacterial receptors on its surface, called pattern recognition receptors (PRR), allow them to recognise different types of bacteria and immediately produce some pro-inflammatory cytokines, such as interleukin 6, interleukin 8 or interleukin 1β. These cytokines alert and attract immune cells to the urothelium. On the other hand, the epithelial cells themselves are able to directly produce some antimicrobial substances, called "antimicrobial peptides", such as cathelicidin LL-37, which starts to be secreted only five minutes after the onset of infection, β-defensin, ribonuclease 7, lipocalin 2, lactoferrin or pentraxin. Another way for the bladder to fight infection is to promote the death of urothelial cells and their shedding in the urine. This allows a large number of intracellular and surface-attached bacteria to be eliminated. The cells of the basal urothelium, where the stem cells are located, then begin to multiply rapidly in order to replace the sloughed cells. This prevents the underlying cells from being exposed for a long time to the aggression of urine and bacteria still present. In addition, the inflammation activates the urination reflex, which promotes frequent emptying of the bladder and thus the elimination of germs and infected cells.
Following the action of the first line of urothelial defence, the innate immune system goes into action to defend the bladder. The first immune cells to act in the inflammatory response are neutrophils, which emerge from the blood vessels and pass through multiple cellular and tissue layers to reach the bladder lumen to fight the infection. There, with the help of the antimicrobial peptide pentraxin, like that of urothelial cells, they will attract the bacteria and 'eat' them by a process called phagocytosis, destroying them once they are inside. The problem is that neutrophils, as they move into the bladder lumen, secrete a number of toxic substances, including a substance called "reactive oxygen species" or ROS, which is a very harmful product, causing a lot of tissue damage along the way.
Another type of immune cell that is very important in the defence of the bladder are mast cells. These cells reside in the bladder, mainly in the lamina propria, but also in the detrusor muscle. They can multiply and move wherever there is an infection. They come quickly, usually within the first hour after infection. They have granules inside them that are loaded with pro-inflammatory molecules, especially histamine, which they can release once they are activated. Mast cells regulate neutrophil activity. In addition to their role in initiating inflammation during infection, they also appear to be important in establishing homeostasis and accelerating tissue recovery after remission of infection by secreting anti-inflammatory cytokines such as interleukin-10. In some cases, if mast cells trigger this inflammation-resolving mechanism too early, premature and incomplete resolution of the inflammatory response may occur without complete eradication of the bacteria, leaving residual bacteria.
A third important cell type in bladder immunity is macrophages. These cells reside in the lamina propria of the bladder. When the inflammatory response is set in motion, they recruit other extravesical macrophages. Between the two types of macrophages, bladder and extravesical, a collaboration is established through the secretion of different cytokines, which ultimately results in the activation of neutrophils and the passage of neutrophils into the bladder lumen. In addition, they are responsible for clearing the cellular debris that remains after the "battle", thus promoting tissue recovery after inflammation. Like mast cells, macrophages are able to stop the inflammatory response. But if they do so earlier than they should, this may encourage some bacteria to persist in the bladder.
Finally, other cells involved in the innate inflammatory response in the bladder are natural killer cells, which are also indispensable for triggering the inflammatory response, mainly by recruiting neutrophils, although their exact role is not known. Figure 19
As for the adaptive immune response, very little is known about its role in UTIs. The adaptive response is that which occurs when immune cells of the innate system present antigens to lymphocytes so that the latter become activated and respond in a more specific way to the infection. The antigens are certain proteins from the invading bacteria that antigen-presenting cells (mainly dendritic cells and macrophages) pick up from the 'battlefield' and carry to the pelvic lymph nodes to show to the lymphocytes, which are located there. The lymphocytes are then activated, move to the bladder and specialise in fighting specifically that particular germ. This response, although slower than the innate response which is immediate, is much more precise and also allows the creation of "immunological memory". Thus, thanks to this memory, the next time the micro-organism in question attacks the bladder, the adaptive response will be activated much sooner and will allow the infection to be eliminated much more quickly and efficiently. This is the theory, but in the case of the bladder it is thought that lymphocytes do not play such a fundamental role in the defence response to infection, but rather in the immunomodulatory and tissue repair response, especially T-lymphocytes. Indeed, it is thought that the action of these T-lymphocytes could favour repeated urinary tract infections, as these cells would prioritise repair of the urothelium over complete elimination of bacteria, in order to prevent deep urothelial cells from being in contact with toxic substances in urine for too long after the superficial cells have been shed. These mechanisms would therefore favour the persistence of certain intracellular bacteria called "quiescent intracellular reservoirs" (QIR), which would remain "dormant" inside the urothelial cells and could reactivate some time later, causing a new urinary tract infection.
In summary, the bladder response to infection is very complex and takes place at several levels:
- the bladder mucosa with mainly urothelial cells and their antimicrobial peptides, as well as desquamation and activation of the micturition reflex to eliminate micro-organisms;
- the innate immune response with the activation of neutrophils, macrophages, mast cells and natural killer cells, where neutrophils are the cells primarily responsible for destroying bacteria, and macrophages, mast cells and natural killer cells are primarily responsible for activating the former, regulating their action and terminating the inflammatory response and repairing tissue damage after infection;
- the adaptive immune response, with T-lymphocyte activation mainly following antigen presentation by dendritic cells and macrophages, with an unclear role where the anti-inflammatory and reparative activity of T-cells seems to predominate.
Considering the existence of all these defence mechanisms, one might wonder how it is possible that uropathogenic bacteria are so often able to overcome them and so easily produce UTIs, especially recurrent UTIs. In addition to the negative influence of many external causes, such as the emergence of increasingly resistant or virulent bacteria, toxins, nutritional deficits due to poor diet, stress, etc., it should be known that individual susceptibility is also a risk factor for UTIs. There are many genetic polymorphisms, which, although they do not result in severe immune deficiencies, can alter certain stages of the triggering of the immune response. Some of the best known are those that occur in the PRRs (pattern recognition receptors), which we have already discussed, and in particular in one of them called TLR4. These mutations give a disadvantage to people who suffer from them, as less activation of these receptors triggers a much more discrete immune response. In addition, a link between the different blood groups (ABO and also the lesser-known Lewis groups) and the increased risk of repeated urinary tract infections has been shown for some time. People who do not have an O group would be more susceptible. Another susceptibility factor would be age, as it is well known that over time a phenomenon called immunosenescence occurs, which decreases the effectiveness of the immune response to aggressions. Among other things, the bactericidal activity and migration capacity of neutrophils, which is so important for fighting bacterial infections in the bladder, is reduced. The activity of sex hormones is also related to the response to infections. Oestrogens have a protective effect on the vaginal mucosa, promoting the development of a healthy microbiota, mainly composed of lactobacilli. But we also know that in the bladder, oestrogens act directly at the local level, via oestrogen receptors on urothelial cells. These hormones are able to regulate the desquamation of the urothelium in the presence of infection and also the magnitude of the inflammatory response. In post-menopausal patients, urothelial desquamation is known to be less and the inflammatory response more exaggerated. They also have a higher bacterial load during infections and more difficulty in clearing bacteria. As for testosterone, some studies suggest that it may have a deleterious effect on the innate immune response. Thus, although urinary tract infections are much more common in women, mainly due to anatomical factors, greater male exposure to testosterone may play a role in the severity of infections in men, particularly pyelonephritis (kidney infections).
As you can see, the complexity increases as we analyse more factors related to UTIs. In particular, the bladder immune response and interaction with uropathogenic bacteria, as well as their virulence mechanisms and individual susceptibility remain an enigma to scientists today. In addition to the genetic mechanisms involved, on which little action can be taken, new drugs are being developed based on the antimicrobial peptides secreted by urothelial cells, which will be discussed later. These drugs could serve to modulate the anti-infective response and could be an alternative to antibiotic treatment, especially in cases of multidrug-resistant bacteria.
The immune response
The immune system is ubiquitous throughout the body. It is composed of soluble molecules, spread throughout the body fluids (blood, lymph, extracellular fluid, etc.):
- complement proteins
- the antibodies
- antimicrobial peptides
- cytokines
- amines such as histamine
- etc.
Another of its components are immune cells, such as:
- neutrophils
- B and T lymphocytes
- eosinophils and basophils
- mast cells
- monocytes and macrophages
- dendritic cells
- natural killer cells
- microglial cells
These cells, in addition to being found in some lymphoid tissues and organs such as the spleen, thymus, lymph nodes, bone marrow and mucosa-associated lymphoid tissue (MALT), are also found throughout our fluids, tissues and organs, where they perform all the functions mentioned above.
I will not go into much detail about how the immune system works in the face of infection, but we can say that the immune response to micro-organism aggression is divided into an innate immune response and an adaptive immune response. The former is a response mediated by most immune cells, with the exception of lymphocytes, which destroy invading micro-organisms by different mechanisms, although in their wake they leave a significant inflammatory reaction that causes "collateral damage" to tissues. The second is a much more specific immune response that has memory. If our body has already been attacked by a micro-organism, the lymphocytes will have "taken note" of which germ it was and will have produced specific antibodies. It will take some time the first time, but on re-exposure, these antibodies will immediately recognise the offending agent and trigger a much more specific and effective response on entry.
Immune system functions and regulation
The immune system is a collection of organs, cells and molecules found throughout the body. Its best known function is to protect us against infections caused by viruses, bacteria, fungi, parasites and others. However, the immune system has many other very important functions for our body. On the one hand, it is responsible for immunosurveillance, i.e. the ability to detect and eliminate cells that have undergone malignant transformation. And if cancer has already occurred, it helps to fight it. It is also responsible for removing waste or toxic products from tissues and, through inflammation, is involved in repairing damaged tissues after illness or trauma. It is also responsible for guarding our body's borders, including the blood-brain barrier, which separates the central nervous system from the rest of our body. At the level of these barriers, and especially the intestinal barrier, it analyses each substance that passes through to decide whether or not it is allowed into the body. It is also involved in the development of all our organs, from the foetal stage to our old age. This is especially important in the brain, where cells of the immune system (resident and migrated), aided by other local cells called glial cells, are largely responsible for neuronal plasticity. This plasticity is the mechanism by which our brain adapts to our environment, the situations we experience, various requirements and the natural development of the body. Thanks to the action of all these cells, the connections between neurons are modified and specialised, and connections or cells that are not useful are eliminated. Finally, it also plays a very important role as a communication system in our body. Because of its ubiquity and its constant interaction with the external environment, and especially with our microbiota, the immune system is able to keep abreast of everything that is going on inside and outside our body. Thus, by manufacturing different substances (pro- and anti-inflammatory cytokines, peptides, amines and others) and releasing them into the extracellular fluid, blood or lymph, it is able to transmit this information to other parts of the body, especially the central nervous system. It is therefore in constant communication with our brain, but also with our endocrine system, and is influenced by hormone levels. Sex hormones, cortisol (stress hormone), thyroid hormones and others are able to regulate the activity of the immune system. This is why all the endocrine disrupting toxins, which we have discussed in other articles, can play a crucial role in the functioning of our body, and in the development of urinary tract infections, which is the subject of this article. Endocrine disruptors. The microbiota is also capable of regulating its function. This is why situations of dysbiosis can profoundly alter our health and our defence against infection, as well as all the other functions of this important system. Other mechanisms by which the activity of our immune system can be affected are sleep, emotional or physical stress, physical exercise and diet, especially if there is a deficit of certain vitamins, trace elements or other nutrients such as vitamin C, vitamin D, vitamin E, vitamin B12, zinc, magnesium, selenium, copper, iron, omega-3 fatty acids, etc.
How does the urinary system work?
Once urine is produced in the kidneys and collected by the calyces and renal pelvis, it flows down the ureters into the bladder. The ureters are very thin tubes, about 5 mm in diameter, which have peristaltic movements (like those of the intestine) that allow the urine to move more easily. Once it reaches the bladder, urine is stored in the bladder until it is expelled during urination.
The functioning of the bladder is very complex, as it depends on three different types of nerves, namely the hypogastric nerve belonging to the sympathetic nervous system, the pelvic nerve belonging to the parasympathetic and the pudendal nerve belonging to the voluntary or somatic nervous system. The sympathetic and parasympathetic nervous systems belong to the autonomic nervous system, which, as the name suggests, is a nervous system that is not under the voluntary control of the brain. It is not the aim of this article to explain in detail the complex micturition reflex, I will only point out that all these nerves start from neuron nuclei located in the spinal cord (T11-L2 for the hypogastric nerve, S2-S4 for the pelvic nerve and for the pudendal nerve), which in turn are regulated by higher brain structures. see figure 7. So you can imagine that when there are problems in the spine (a herniated disc for example) or there is a neurological disease (such as Parkinson's disease, Alzheimer's, multiple sclerosis or stroke, among many others) the micturition reflex can be affected. Under normal conditions, the coordinated work of these three nervous systems is essential for both micturition and continence to occur properly. Thus, during urination, the detrusor muscle of the bladder must contract thanks to the nerve impulse it receives from parasympathetic fibres, while the bladder neck (or internal sphincter) and the external sphincter relax, the former governed by sympathetic fibres and the latter by somatic fibres of the pudendal nerve. If this coordination does not occur properly, dyssynergic micturition or uncoordinated micturition will occur, with contractions of one or both sphincters during voiding, incomplete bladder emptying, or both. Outside of micturition, the detrusor muscle is at rest because there is a high sympathetic tone and low parasympathetic tone which allows its fibres to relax and give capacity to the bladder. At the same time, the bladder neck is contracted thanks to sympathetic tone and the external sphincter is contracted thanks to the action of the pudendal nerve. see figure 8. This situation allows us to be continent and not lose urine while the bladder is filling.
Having seen this, we can understand that any obstruction to the outflow of urine, whether of anatomical origin (hypertrophy of the prostate, cicatricial or congenital stenosis of the urethra) or of functional origin by which the sphincters do not relax properly during urination (uncoordinated urination, dyssynergia of neurological cause), can promote urine infections, dyssynergia of neurological cause), can promote urinary tract infections, as can any disease that causes a weakness of the bladder muscle that does not allow it to expel urine properly, even if there is no obstruction.
What is the famous prostate?
The prostate is an organ that belongs to the male genital system, but is located around the urethra, between the bladder neck and the external sphincter, like a "collar". Its main function is to manufacture seminal fluid, together with the seminal vesicles. This fluid contains many nutritive substances that serve as food for the spermatozoa. It also has an alkaline pH, which serves to counteract the acidic pH of the female vagina. In this way, when male ejaculation occurs, the seminal fluid is eliminated together with the spermatozoa, which "swim" in it, thus protecting them as they pass through the vagina and at the same time nourishing them so that they can advance to the uterus.
As for sperm, they are not produced in the prostate, but in the testicles. Once they are made, they leave the testicle and reach the prostate by travelling inside tubes called "vas deferens". The two vas deferens, one on each side, connect the testicles to the prostate. It is precisely these tubes that are cut when a vasectomy, one of the most effective methods of contraception, is performed. When, for various reasons (genetics, epigenetics, age, etc.), the prostate enlarges, it can compress the urethra and cause an obstruction, making it difficult to empty the bladder. Sometimes, this emptying is incomplete and leads to chronic urinary retention with a high postvoid residual, which is a risk factor for urinary tract infections, as stagnant urine is a great breeding ground for the development of the micro-organisms that cause them (see figure n°6).
Understanding the structure of the urinary system
Before we start looking at the different diseases that can occur in the urological sphere, we have to start at the beginning. First we need to have a good understanding of how our genitourinary system works, otherwise none of the following will make sense. The structure and functioning of the urinary system is very complex. I will therefore try to explain in a simple but logical way everything that happens around the excretory system and urination, so that you can later understand why all these recommendations and, with empowerment, make changes in your life that will lead you to suffer less often from uncomfortable cystitis or other more serious urinary conditions.
The urinary system consists of the kidneys, which are the urine-producing organs, and the pyelocaliceal system, the ureters, the urinary bladder and the urethra, which are the urine-excretory organs.see figure 1) The vast majority of urological diseases are based in the excretory system. I will therefore focus on this system to give a brief summary of the anatomy and physiology (how it functions under normal conditions), without dealing with the complex structure of the interior of the kidney, which is of little relevance to the topic at hand.
The urinary excretory system is made up of several layers of tissue (see figure 2). From the inside to the outside, and speaking in a very simplified way, we find the mucosa, which is the inner lining of the renal pelvis, ureters, bladder and urethra. Its function is to act as an impermeable barrier to the passage of urine. The cells lining this mucosa, called urothelial cells, have the particularity of having a series of proteins on their surface, the uroplakins, whose function, among others, is to protect the excretory system from infection. However, some germs, such as the bacterium Escherichia coliThe mucosa of the urothelial cells, a common cause of urinary tract infections, has "hairs" called fimbriae on its surface that allow it to attach to precisely these receptors (especially uroplakin Ia) and even penetrate inside the urothelial cells. The mucosa is also covered by a layer of mucus, mainly made up of complex sugars called glycosaminoglycans (GAGs), including hyaluronic acid and chondroitin sulphate, which protect it from physical, chemical or biological aggression and make it impermeable.
Under the mucosa, and separated from it by a thin layer called the basement membrane, on which the urothelial cells rest, we find the lamina propria, a tissue made up of different types of fibres (collagen, elastic fibres, etc.), blood and lymphatic vessels, nerve endings, some support cells such as fibroblasts, myofibroblasts or adipocytes (fat cells), and immune cells.
The function of the submucosa is to give structural support to the mucosa, as well as to provide immune defence if necessary, reinforcing the defence capacity that already exists in the urothelium. The resident immune system of the bladder consists mainly of cells of innate immunity (non-specialised cells, with no "immunological memory"), mainly mast cells and macrophages, as well as some natural killer (Nk) cells. These cells, together with secretory immunoglobulin A (the antibodies that usually reside in mucous membranes), uroplakins, the mucus layer and some bactericidal substances secreted into the urine from certain kidney or bladder cells (Tamm-Horsfall protein, β-defensin 1, NGAL, ribonuclease 7, cathelicidin, pentraxins, etc.), form the first defence against infection. If the innate immune response is activated by an infection, cytokines will be released by both immune cells and urothelial cells, which are substances that serve to "call for reinforcements", recruiting other immune cells that will help reinforce the innate immune response (neutrophils, more macrophages, lymphocytes, etc.).
After the lamina propria, we find the muscularis propria, a layer of muscle fibres arranged in different directions that allow movements to be created in these organs, so that urine can move from the kidneys to the bladder and then be expelled by the bladder during urination. In the bladder, this muscle is called the detrusor muscle. Its function is controlled by the autonomic nervous system (sympathetic and parasympathetic systems), which we will discuss in more detail in another article. The muscular layer, together with the submucosal layer and its elastic fibres, gives the bladder a large capacity to store about half a litre of urine, without the pressure inside it increasing at rest. This mechanism is very important for the proper functioning of the entire urinary system, as overpressure in the bladder could be transmitted retrograde to the kidneys, leading to kidney dysfunction, as the kidneys always need to work at low pressure. Also, during urination, when the bladder muscle contracts to expel urine and the pressure increases greatly, the special arrangement of smooth muscle fibres at the mouth of the ureters works as if it were a valve, so that this pressure is prevented from being transmitted to the kidneys (see figure 3). If this closure mechanism does not occur properly, a pathological situation known as "vesico-ureteral reflux" occurs. On the other hand, mention should be made of the sphincteric mechanism of the bladder and urethra, i.e. the muscles that "close" the end of the excretory system and prevent urine from constantly escaping to the outside (see figures 4 and 5). We can consider that there are two sphincters in the bladder, the internal sphincter or bladder neck and the external sphincter or striated sphincter. The internal sphincter is nothing more than the prolongation of the muscle fibres of the bladder wall, which become circular at the transition point between the bladder and the urethra. Thus, when they contract, they close the bladder outlet, while when they open, the bladder takes the shape of a funnel and urine can pass through. The external sphincter is not strictly speaking part of the urinary excretory system, but it is closely linked to it. It is a circular muscle that surrounds the middle urethra in women, and the membranous urethra in men (the part of the urethra just below the prostate). This muscle is part of a muscle group called the "pelvic floor", whose function is to give anatomical and functional support to the pelvic organs. Contraction of the external sphincter allows the urethra to be "strangulated" to prevent urine from passing. In this way, together with the help of the internal sphincter, correct continence is achieved. Unlike the bladder neck, whose function is governed by the autonomic nervous system, and which we cannot control voluntarily, the external sphincter works by means of fibres from the pudendal nerve, which belongs to the "voluntary" nervous system.
Continuing with the layered structure of the excretory system, we find the outermost layer known as the "serosa", composed mainly of connective tissue. This layer does not cover the entire outer surface of the organs, but provides vascular support for them by supplying numerous blood vessels. In the areas of the excretory system where there is no serosa, there is a layer of loose connective tissue called the adventitia, which has the same function.
Understanding the structure of the gut
The intestinal wall is made up of several layers of specialised tissues and cells whose arrangement in the form of small folds called intestinal villi allows it to facilitate digestion and absorption of nutrients. From the inside to the outside we find the mucosa, the submucosa, the muscular layer and the outermost serosa. The epithelium of the intestinal mucosa consists of a single layer of cells. It is lined with mucus, a substance that gives it protection and allows it to harbour numerous bacteria of the intestinal microbiota. The most numerous cells are the enterocytes, tall, narrow cells, which are responsible for the absorption of nutrients. The surface of the enterocytes that is in contact with the intestinal lumen and mucus is not smooth, but forms small protrusions called microvilli, which greatly increase the surface area for nutrient absorption. This is also known as the "brush border". In addition, these microvilli contain certain digestive enzymes such as lactase (which allows us to digest the lactose in milk), maltase (which digests maltose), sucrase (which digests sucrose) or aminopeptidase (which digests small proteins called di- or tripeptides and amino acids). Among the enterocytes are goblet cells, which are responsible for producing and secreting mucus. There are also endocrine cells, which release hormones such as secretin and cholecystokinin, which control the secretion of digestive enzymes by the pancreas and gallbladder. In the intestinal crypts, the deepest part of the villi, stem cells are located, which divide and differentiate as the surface cells die. These cells are responsible for the renewal and regeneration of the intestinal epithelium. Figure 10. Beneath the mucosa is the submucosa, which is made up of connective tissue and blood capillaries, and is responsible for supplying nutrients and oxygen to the cells of the intestine, and also for collecting and transporting the products of digestion through the bloodstream. The next layer is the muscle layer, which is divided into two sub-layers: the inner circular and the outer longitudinal. These layers are made up of smooth muscle cells, whose movement is governed by the nerves of the enteric nervous system (related to the sympathetic and parasympathetic autonomic nervous system) and are responsible for the movements of the intestine. These movements, such as peristalsis, segmentation, the migratory motor complex, colonic motility or reflexes, are what allow us to digest properly, as well as transport food along the gastrointestinal tract and eliminate it in the faeces. The outermost layer of the intestinal wall is the serosa, which is composed of connective tissue and epithelial cells. It contains blood vessels and is responsible for protecting and supporting the intestine. The gut has its own nervous system, known as the "enteric nervous system". It is made up of about 80 to 100 million neurons, as many as there are in the spinal cord. It has the capacity to function independently, but is also connected to the central nervous system via the autonomic (sympathetic and parasympathetic) nervous system. It has two main components, Meissner's submucosal plexus, located below the submucosa, and Auerbach's myenteric plexus, located between the circular and longitudinal muscle layers. Meissner's plexus is most developed in the small intestine and colon.
It is primarily concerned with regulating digestion and absorption at the level of the mucosa and blood vessels, depending on the stimulation produced by nutrients. Auerbach's plexus coordinates the activity of the muscle layers to enable the bowel movements I mentioned earlier.
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