Inguinal Region and Hernias PDF

Gastrointestinal System Inguinal Region and Hernias Welcome to this lecture which aims to explain the anatomy of hernias in three parts. In this 1st part we will discuss the general principles and describe a few specific types. About 10% of the population will have a hernia...

Gastrointestinal System Inguinal Region and Hernias Welcome to this lecture which aims to explain the anatomy of hernias in three parts. In this 1st part we will discuss the general principles and describe a few specific types. About 10% of the population will have a hernia at some point in their lifetime. Hernias can occur in many different locations, but the Inguinal Region is a particularly common site, so this is an important bit of anatomy to learn.  Learning Outcomes After this lecture you should be able to: ▪ Know the potential weaknesses in the abdominal wall and diaphragm ▪ List the differences between various abdominal hernias (inguinal, femoral, etc), and explain why they occur ▪ Know the boundaries and content of the inguinal and femoral canals ▪ Know how to distinguish between a femoral and inguinal hernia ▪ List the coverings of the spermatic cord, and give an account of their derivatives ▪ Know the boundaries of the inguinal triangle, and its relation to the superficial inguinal ring ▪ Distinguish the difference between a ‘direct’ and an ‘indirect’ inguinal hernia Here are the appropriate learning outcomes for this lecture.  Gastrointestinal System Inguinal Region and Hernias 1. Types of Hernia 2. The Inguinal and Femoral Canals 3. Inguinal Hernias The lecture is divided into 3 parts.  Gastrointestinal System Inguinal Region and Hernias Part 1: Types of Hernia In this 1st part we will discuss the general principles and describe a few specific types. About 10% of the population will have a hernia at some point in their lifetime. Hernias can occur in many different locations, but the Inguinal Region is a particularly common site, so this is an important bit of anatomy to learn.  Learning Outcomes After this lecture you should be able to: ▪ Know the potential weaknesses in the abdominal wall and diaphragm ▪ List the differences between various abdominal hernias (inguinal, femoral, etc), and explain why they occur ▪ Know the boundaries and content of the inguinal and femoral canals ▪ Know how to distinguish between a femoral and inguinal hernia ▪ List the coverings of the spermatic cord, and give an account of their derivatives ▪ Know the boundaries of the inguinal triangle, and its relation to the superficial inguinal ring ▪ Distinguish the difference between a ‘direct’ and an ‘indirect’ inguinal hernia As usual though we’ll deal with these two or three at a time. The outcomes for this section of the lecture are that you should be able to; ▪Know the potential weaknesses in the abdominal wall and diaphragm ▪List the differences between various abdominal hernias (inguinal, femoral, etc), and explain why they occur The remaining outcomes will be dealt with in the subsequent parts of the lecture.  Hernia Definition First of all, we need to define what a hernia is. The word comes from Latin meaning a rupture, but it is also from the Greek word meaning a bulge. Hence it is a bulge created by the rupture of a containing structure. It needn’t apply solely to the abdomen, but that is where most hernias are found. For example, it may apply to the herniation of the intervertebral disc of the vertebral column, colloquially called a “slipped disc”.  Abdominal Hernia Definition An abdominal hernia is a protrusion of the peritoneum through the abdominal walls, roof of the abdomen, or floor of the pelvis. An abdominal hernia involves a protrusion of peritoneum through the abdominal boundaries (roof, walls or floor). There are many types of abdominal hernias, and these arise in weakened areas. One such hernia is in the midline, since here we have the umbilicus there. The umbilicus was a region where the wall of the abdomen was breached during development in order to connect to the placenta. In the adult it remains a weak spot. In fact, the entire midline of the abdomen is at risk, because here lies the linea alba which is formed from a raphe of interdigitating tendon. This is mechanically weaker than elsewhere over the abdominal wall. Here you can see an example of such a hernia.  Content of a Hernia An abdominal hernia is a protrusion of the peritoneum through the abdominal walls, roof of the abdomen, or floor of the pelvis. This may just be a protrusion of the parietal peritoneum … or it may contain intestinal viscera If the viscera has its blood supply interrupted, then the hernia is said to be strangulated So, an abdominal hernia may just be a protrusion of the peritoneum, or It may also contain viscera, for example a loop of bowel. If the viscera have their blood supply compromised, then the organ will necrose due to a lack of oxygen and nutrients. The restriction of the blood vessel is called strangulation. This of course leads to severe complications of the hernia.  Midline Hernias Epigastric Paraumbilical Umbilical Hernias may occur when the pressure inside the abdominal cavity is greater than that outside, and there is a weakness of the wall. In addition to umbilical hernias, there can be paraumbilical and epigastric hernias in the midline. The example we have seen previously had all 3 of these together. We will discuss umbilical hernias further, but epigastric hernias account for between 2-5% of all hernias and are 2-3 times more common in men. Less commonly, there can be suprapubic hernias, also in the midline.  Umbilical Hernias Umbilical hernias account for 10-15% of all hernias. These can be congenital or acquired. Bearing in mind that approximately 10% of individuals have a hernia, this accounts for a large number of individuals. The umbilicus represents a natural hernia that occurs in utero, but an umbilical hernia after birth is usually a consequence of failure of closure of the umbilical scar Adult umbilical hernias are acquired. Multiparity (that is a women giving multiple births) and increased abdominal pressure (say through obesity, or abdominal pathologies) are known associations. Small umbilical hernias (less than 1cm) often repair spontaneously, others require surgical intervention. Most childhood umbilical hernias close spontaneously, but adult ones may require surgical repair. Umbilical hernia repair in adults is indicated in cases of entrapment of organs) or strangulation of the hernia.  Spegelian Hernias (Lateral Ventral) (this is not included in the lecture presentation) Spigelian Spigelian hernias occur in the region of the linea semilunaris but are very rare – accounting for between 1-2% of all hernias. Epigastric and spigelian hernias are mostly acquired, and due to excessive straining. Chronic prolonged strain on the abdominal muscles, as in constipation with straining at stool, chronic cough, vomiting, etc., may be a causative factor. Prolonged illness and emaciation are predisposing causes.  Lumbar Hernias (this is not included in the lecture presentation) Lumbar hernias are very rare. These are herniations through the lumbar fascia which is the deep fascia of the lumbar region of the back. At the lateral border of the quadratus lumborum muscle, this lumbar fascia is continuous with the transversalis fascia of the anterior abdominal wall. This area is devoid of muscle and is referred to as the superior lumbar triangle. This gives surgeons an opportunity to access the abdominal cavity without disrupting muscles. This approach is sometimes used to access abdominal organs at the back of the abdominal cavity, such as the kidneys. The superior lumbar triangle is bounded by the quadratus lumborum medially, the 12th rib superiorly and the internal oblique abdominis muscle infer-laterally. There is a second triangle called the inferior lumbar triangle, often simply referred to as the lumbar triangle (despite the fact that there is more than one). This is bounded by the muscles and bone as shown in the illustration. Lumbar hernias may emerge through either of the lumbar triangles, but more commonly through the superior one as this lacks muscle support entirely.  Incisional Hernias (this is not included in the lecture presentation) Incisional Incisional hernias are unfortunately all too common (with an incidence of up to 20%). These are caused by the surgical creation of a weakness in the wall, or by a stab wound to the abdomen. However, I will not discuss these further as they are beyond the scope of the lecture.  Hiatus Hernia (this is not included in the lecture presentation) Hiatal hernias are very common in those over 50 years of age. These are herniations through the diaphragm. Perhaps as many as 30% of the population will have one. One study put this figure at 60%. A hiatus hernia occurs through the oesophageal hiatus (or oesophageal opening) in the diaphragm. The oesophagus or gullet passes through the diaphragm to reach the stomach. If this opening is weak, then the stomach is able to herniate through the gap. There are two common types of these hernias, one is where the junction between the stomach and oesophagus slides up into the chest. This is a sliding hiatus hernia. The other type is where the top part of the stomach passes through the gap, leaving the gastro-oesophageal junction in the abdomen. This is a rolling hiatus hernia. Such pathologies risk inference with not only the normal sphincteric action at the oesophagus, but also may impede thoracic organs, such as the heart and lungs.  Inguinal and Femoral Hernias Femoral Inguinal The most common and important hernias for you to understand are inguinal and femoral, and these will be given due consideration later in this lecture.  Gastrointestinal System Inguinal Region and Hernias Part 2: The Inguinal and Femoral Canals In part two of the lecture on the Inguinal Region and Hernias, we will discuss the anatomy of the Inguinal and Femoral canals, through which hernias may occur.  Learning Outcomes After this lecture you should be able to: ▪ Know the potential weaknesses in the abdominal wall and diaphragm ▪ List the differences between various abdominal hernias (inguinal, femoral, etc), and explain why they occur ▪ Know the boundaries and content of the inguinal and femoral canals ▪ Know how to distinguish between a femoral and inguinal hernia ▪ List the coverings of the spermatic cord, and give an account of their derivatives ▪ Know the boundaries of the inguinal triangle, and its relation to the superficial inguinal ring ▪ Distinguish the difference between a ‘direct’ and an ‘indirect’ inguinal hernia ▪The objectives of this part of the lecture are that you should be able to: ▪Know the boundaries and content of the inguinal and femoral canals ▪Know how to distinguish between a femoral and inguinal hernia The remaining outcomes will be dealt with in the final part of the lecture.  Femoral Canal Behind the inguinal ligament, there is a neurovascular bundle going to and from the lower limb. The blood vessels and lymphatics are contained within a sheath called the femoral sheath. It is notable that the femoral nerve doesn’t pass through this sheath. It passes 4 cm below the inguinal ligament and disappears at this point by blending into the adventitia of the femoral vessels. The artery and vein are solidly contained within their respective compartments within the sheath; however, the lymphatics are thin vessels surrounded by fat. The space within the sheath where these are located is called the femoral canal. There is a lymph node here called Cloquet’s node, one of the few lymph nodes to be named. This canal is a weak spot where a femoral hernia may occur. Below the inguinal ligament there is an opening in the deep fascia where superficial veins and superficial lymphatics can join the deep vessels.  Femoral Hernia Hence, a femoral hernia is a protrusion through the femoral canal and subsequently through the saphenous opening. Such a hernia produces a bulge in the thigh. This type of hernia is more common in females than in males, due to the fact that females have a wider hip, and therefore a wider canal. At the medial end of the inguinal ligament is a ligament which turns back onto the pubis; this is the lacunar ligament. This ligament provides a harsh cutting edge to any femoral hernia and may compress the hernia at this point. It is then said to be a ‘strangulated femoral hernia’. This strangulation impedes the blood flow to any loops of bowel contained within the hernia, and this can lead to necrosis of that portion or at the very least occlude its lumen.  The Inguinal Canal This illustration allows us to see the layers of the inguinal region, where inguinal hernias occur. The reason the wall is weak here is because there is a gap created for the descent of the gonads (that is testes or ovaries). The ovaries never get to use this gap, but the exit was created before the gonad decided whether it would be male or female. The route taken by the testis ultimately is the inguinal canal. The canal is created in the deepest layer of the abdominal wall, the transversalis fascia. This is called the deep (or internal) inguinal ring. It is located just lateral to the origin of the inferior epigastric artery, 1.25 cm above the mid-point of the inguinal ligament. This is an important surface marking to remember. The exit point of the canal is an opening in the outer layer of the abdominal wall – the external oblique abdominis muscle. This opening is the superficial (or external) inguinal ring. The external oblique aponeurosis is attached to the pubic tubercle (via a lateral crus or leg) and the pubic crest (via a medial crus). The gap in between is the superficial inguinal ring. The function of the inguinal canal is to connect the spermatic cord from the testis in the scrotum to the pelvic cavity, and for the round ligament of the uterus to connect the labia majora of the external genitalia to the uterus within the pelvis.  Elongation of the Inguinal Canal In the fetus and in early infant life, the deep inguinal and superficial inguinal rings lie closer together. The round circle represents the deep ring and the triangle represents the superficial ring. The fetal position would offer more opportunity for herniation each time the intra- abdominal pressure was raised.  Elongation of the Inguinal Canal Compare that the adult position shown here where the inguinal canal is longer and hence the rings further apart. The obliquity of the canal in infancy and beyond, is one of the reasons why herniation is not inevitable beyond birth. When pressure in the abdomen rises, herniation is a threat. However, since the inguinal canal is oblique, an indirect hernia (the most common type) cannot go straight out - it will need to pass along the plane of the inguinal canal (which is in the abdominal wall itself). Since the wall is being compressed by the expanding abdomen, this is made more difficult. If the deep and superficial rings were in line, then the hernia could take a straight route out, and not have the interference of the abdominal wall hindering it.  Content of the Spermatic Cord The inguinal canal contains the ductus (vas) deferens in the male, or the round ligament of the uterus in the female. The ductus deferens in males is only one of a number structures that travel in or around the inguinal canal. The structures become wrapped in layers derived from the canal itself, and is then termed the spermatic cord. The cord contains neurovascular and reproductive structures that supply and drain the testes. You will learn the details of these in future lectures. On the surface of the spermatic cord, and on the surface of the round ligament of the uterus in females, lies the Ilioinguinal nerve. This contributes towards the sensory innervation of the external genitalia. This nerve though does not enter the deep ring – it joins the canal more laterally. Within the wall of the spermatic cord is the genital branch of the genitofemoral nerve – this supplies the cremaster muscle and anterior scrotal skin. In females it supplies the skin of the mons pubis and labia majora in females. We will come back to this in a later lecture.  Boundaries of the Inguinal Canal 1 The inguinal canal is illustrated in this diagram on the left by a dotted outline. In the diagram on the right, we can see the canal from behind. The canal itself has walls, a roof and a floor. The anterior wall is formed by the external oblique aponeurosis, and also by internal oblique abdominis in its lateral third. The posterior wall is formed by the fascia transversalis and by the conjoint tendon in its medial third. The floor is formed by the upturned lower border of the external oblique abdominis aponeurosis, which forms the inguinal ligament. The roof is formed by the arched fibres of the conjoint tendon.  Boundaries of the Inguinal Canal 2 We can see this perhaps better in this schematic representation. The spermatic cord is shown in black. It enters the inguinal region between the peritoneum and transversalis fascia. It then enters the deep inguinal ring, lateral to the inferior epigastric artery. This is a weak spot that could allow the peritoneum to enter the deep ring. At this lateral point there is protection provided in front by the internal oblique muscle and external oblique aponeurosis. The internal oblique and transversus abdominis then arch over the cord forming the roof of the canal. These layers unite forming the conjoint tendon, which forms the medial part of the posterior wall of the canal. The canal ends by a splitting of the external oblique aponeurosis forming the superficial inguinal ring. The spermatic cord exits this ring to reach the testis within the scrotum. In the female, the cord is replaced by the round ligament of the uterus and this terminates in the wall of the labia majora.  The Layers of the Inguinal Canal External oblique Conjoint Tendon Internal oblique Transversalis fascia This illustration allows us to see the 4 layers of the wall clearly. We have described the openings in them as holes, but the reality is that they are evaginations, much like the fingers of a glove. The ductus deferens takes a single and overlapping gloved finger from each of 3 layers of the anterior abdominal wall. The deepest layer (bottom right) is the fascia transversalis (which forms the deep ring) and the inner layer of the spermatic cord, the internal spermatic fascia. The internal oblique abdominis contributes both muscle and fascia to the formation of the spermatic cord. The muscle is the cremaster muscle, and this is supplied by the genital branch of the genitofemoral nerve. This is from the L2 spinal nerve. The fascia is the cremasteric fascia. The transversus abdominis together with internal oblique arch over the canal (forming the conjoint tendon), but transversus abdominis does not contribute to the layers of the spermatic cord. Finally, the external oblique forms the superficial ring and the outer covering of the spermatic cord, the external spermatic fascia.  Inguinal and Femoral Hernias Let’s turn our attention back to hernias. Both femoral and inguinal hernias take place in the lower part of the anterior abdominal wall. However, It can sometimes be difficult to differentiate them from each other. A femoral hernia emerges through the femoral canal, whilst an inguinal hernia emerges through the superficial inguinal ring. Femoral hernias are more common in females (with a ratio of about 3:1) due to the fact that females have wider hips and therefore wider femoral canals. Here though, we can see a femoral hernia in a male. Even so, femoral hernias only account for about 3-5% of all hernias. Inguinal hernias are more common in males due to a wider inguinal canal. They account for 75% of all hernias. Again, just to make sure you appreciate that the females also get these hernias, I’ve illustrated that here. Femoral hernias can be differentiated from an inguinal one, by noting the position of the root (base) of each hernia. The root of a femoral hernia lies below and lateral to the pubic tubercle, whilst an inguinal hernia lies above and medial to the pubic tubercle.  Gastrointestinal System Inguinal Region and Hernias Part 3: Inguinal Hernias So welcome to the final part of this lecture on the Inguinal Region and Hernias. Here we will review the coverings of the spermatic cord that we dealt with previously and learn of two types of inguinal hernias.  Learning Objectives After this lecture you should be able to: ▪ Know the potential weaknesses in the abdominal wall and diaphragm ▪ List the differences between various abdominal hernias (inguinal, femoral, etc), and explain why they occur ▪ Know the boundaries and content of the inguinal and femoral canals ▪ Know how to distinguish a femoral and inguinal hernia ▪ List the coverings of the spermatic cord, and give an account of their derivatives ▪ Know the boundaries of the inguinal triangle, and its relation to the superficial inguinal ring ▪ Distinguish the difference between a ‘direct’ and an ‘indirect’ inguinal hernia The learning outcomes for this part of the lecture are that you should be able to; List the coverings of the spermatic cord, and give an account of their derivatives ▪Know the boundaries of the inguinal triangle, and its relation to the superficial inguinal ring ▪Distinguish the difference between a ‘direct’ and an ‘indirect’ inguinal hernia  Descent of the Testes The testis develops high up on the posterior abdominal wall and is guided into the scrotum by a fibrous cord, called the gubernaculum. The testis moves along this cord, and the proximal part disintegrates as it moves. By the time the testis has reached its destination, only a small amount of the gubernaculum remains - this is the scrotal ligament and attaches the testis to the scrotal wall. For the gubernaculum (and the testis) to get into the scrotum, the layers of the anterior abdominal wall have had to be breached. As the deep inguinal and superficial inguinal rings are more aligned in the fetus, it is a straight passage for the testis to pass through.  Formation of the Inguinal Canal Firstly, there is an indentation into the fascia transversalis - this is the deep inguinal ring. It then passes UNDER the transversus abdominis tendon. The 2nd layer it must traverse is the internal oblique. Actually, it mostly passes under this layer also, but receives a fascial layer from it containing muscle. This is the cremasteric fascia and cremaster muscle. The final layer is the external oblique - the sleeve leaving the anterior abdominal wall so creates the superficial inguinal ring.  Formation of the Spermatic Cord The descended testis leaves a trail of these layers wrapped around the ductus (vas) deferens, and a neurovascular bundle. This is the spermatic cord. The wall of the spermatic cord is derived from the three layers of the abdominal wall as described. However, these layers are now known as the external, cremasteric and internal spermatic fascia.  Layers of the Spermatic Cord Camper’s fascia Scarpa’s fascia Dartos muscle Colles’ fascia We can see these layers very clearly in this diagram. On the outside deep to the skin we have Camper’s fascia, which is continuous in the scrotum as dartos fascia. Dartos has no fat as it needs to be kept cool, hence it is replaced by smooth muscle. Deep to that is Scarpa’s fascia which is continuous with Colles’ fascia in the scrotum.  Layers of the Spermatic Cord External spermatic fascia (derived from Ext Oblique) Cremasteric muscle and fascia (derived from Int Oblique) Internal spermatic fascia (derived from Transversalis fascia) Then we have the 3 layers derived from the anterior abdominal wall. External spermatic fascia derived from external oblique. Cremasteric muscle and fascia derived from internal oblique. And finally, Internal spermatic fascia derived from transversalis fascia. Processus Vaginalis and Tunica Vaginalis Processus vaginalis Tunica vaginalis Note that peritoneal fluid is shown in black at the top, but there is also some peritoneal fluid surrounding the testis. Although there is no good reason for the peritoneal cavity to pass into the inguinal canal during development (the testis does not have to pass through this layer) - it nevertheless does so. This forms a protrusion of the peritoneal membrane, called the processus vaginalis. A terminal portion of the processus buds off forming the tunica vaginalis, which acts as a cushion for the testis (the testis is embedded in it). The remainder of the processus regresses, isolating the tunica. This tunica vaginalis is therefore an isolated sac of serous fluid.  Hydrocele Testis Swelling enlarges when child coughs Normally the processus vaginalis closes leaving only a fibrous cord, however in some it may remain open, allowing for a connection between the peritoneal cavity and the tunica vaginalis. This is a patent processus vaginalis, and this will allow fluid to move into the tunica when intrabdominal pressure is increased, for example by coughing. It can also cause herniation of the abdominal content into the scrotum. The amount of serous fluid in the tunica vaginalis is often increased as a result of trauma to the scrotum or testis. It may also be caused by pressure caused by testicular cancer, or infection of the testis, scrotum or tunica itself. The enlargement of the serous sac is known as “hydrocele testis”. This can be felt as a painless swelling in the scrotum. There can sometimes be a hydrocele of the processus vaginalis which is isolated. This is shown on the lower right diagram and is usually harmless. In very rare cases, a hydrocele can be present in the labia majora of women. In these cases, the patent processus vaginalis in females is known as the canal of Nuck.  Support of the Inguinal Region With regard to inguinal hernias, it is important to appreciate the weaknesses in these layers of the wall, and to consider the possibility of an evagination (herniation) of the peritoneum. At the level of the deep ring, if the internal oblique and external oblique are weak they may allow the peritoneum to enter the ring. This might also happen if the internal pressures within the peritoneal cavity are high. If this happens the hernia will take an indirect route through the inguinal canal to exit via the superficial ring. This is an indirect inguinal hernia. Medial to the inferior epigastric artery there is a weak spot lateral to and underneath the conjoint tendon, where the only protection is the flimsy transversalis fascia and the external oblique aponeurosis. Of course the latter provides no support at the superficial inguinal ring. If the muscle fibres of the conjoint tendon contract then there will be extra protection provided as the gap under the tendon disappears. A hernia that passes straight through these layers (or exiting through the superficial ring) is called a direct inguinal hernia.  Inguinal Canal and Spermatic Cord A herniation through the inguinal canal is an indirect inguinal hernia. The hernia can often be felt emerging from the superficial inguinal ring by placing a finger into the scrotal wall. Indeed, a small hernia might be reduced by pushing it back in through the ring. However, not all inguinal hernias pass through the length of the inguinal canal, some emerge through the inguinal triangle instead.  Inguinal Triangle The inguinal triangle (Hesselbach's triangle) is an area of weakness in the anterior abdominal wall, where direct inguinal hernias can occur. This triangle has a medial, lateral and inferior border. The medial border is the lateral margin of the rectus abdominis muscle (linea semilunaris). The lateral border is the inferior epigastric artery and the inferior border is the inguinal ligament. Here we can see the inguinal triangle from behind. The upper half of the triangle contains the conjoint tendon (where the transversus abdominis and internal oblique aponeuroses join into one). The lower half contains the superficial inguinal ring (and therefore no external oblique aponeurosis). This lower half is particularly vulnerable therefore to herniation (direct inguinal hernia). The only protection comes form the fascia transversalis, which is thin. However, to prevent hernia, the conjoint tendon is pulled down like a shutter as it contracts. The muscles forming this tendon are supplied by the ilioinguinal and iliohypogastric nerves from L1, and their integrity is crucial for the maintenance of support for this weak spot.  Indirect Inguinal Hernias Deep ring Superficial ring A hernia will find the path of least resistance. The inguinal canal is one weak area. The deep ring is devoid of two layers, the transversalis fascia and transversus abdominis muscle. Once a hernia is in the deep ring, it will pass along the inguinal canal and exit via the superficial inguinal ring. This is an indirect inguinal hernia.  Inguinal Hernias At the superficial ring, the external layer of muscle is absent. In addition, the lateral part of the ring may not be covered by the conjoint tendon, since the latter arches over to join the pubic crest. The lateral part of the ring may therefore ONLY be covered by the transversalis fascia, and is therefore susceptible to direct herniation. This is a direct inguinal hernia. However, when the lower fibres of internal oblique and transversus abdominis contract, the conjoint tendon flattens, and come down like a shutter over the superficial ring, protecting against herniation. Direct herniation is however likely should the lower fibres of the conjoint muscle be paralysed. They are supplied by the ilioinguinal nerve (L1). Should there be a lesion at the L1 spinal nerve (e.g. slipped disc), then herniation of the abdominal wall is almost inevitable. Inguinal hernias account for the large majority of herniations of the abdomen (75%) and over 90% of inguinal hernias are of the indirect type.  Gastrointestinal System Inguinal Region and Hernias And with that we have come to the end of this section, and indeed this lecture on the inguinal region and hernias. In the next lecture, we will discuss the embryology of the gut.